Les cellules souches somatiques présentent habituellement un comportement très différent des cellules souches pluripotentes. Les bases moléculaires de l’auto-renouvellement des cellules souches embryonnaires ont été récemment déchiffrées grâce à la facilité avec laquelle nous pouvons maintenant les purifier et les maintenir en culture durant de longues périodes de temps. Par contre, il en va tout autrement pour les cellules souches hématopoïétiques. Dans le but d’en apprendre davantage sur le fonctionnement moléculaire de l’auto-renouvellement des cellules souches hématopoïétiques, j’ai d’abord conçu une nouvelle méthode de criblage gain-de-fonction qui répond aux caprices particuliers de ces cellules. Partant d’une liste de plus de 700 facteurs nucléaires et facteurs de division asymétrique candidats, j’ai identifié 24 nouveaux facteurs qui augmentent l’activité des cellules souches hématopoïétiques lorsqu’ils sont surexprimés. J’ai par la suite démontré que neuf de ces facteurs agissent de manière extrinsèque aux cellules souches hématopoïétiques, c’est-à-dire que l’effet provient des cellules nourricières modifiées en co-culture. J’ai également mis à jour un nouveau réseau de régulation de transcription qui implique cinq des facteurs identifiés, c’est-à-dire PRDM16, SPI1, KLF10, FOS et TFEC. Ce réseau ressemble étrangement à celui soutenant l’ostéoclastogénèse. Ces résultats soulèvent l’hypothèse selon laquelle les ostéoclastes pourraient aussi faire partie de la niche fonctionnelle des cellules souches hématopoïétiques dans la moelle osseuse. De plus, j’ai identifié un second réseau de régulation impliquant SOX4, SMARCC1 et plusieurs facteurs identifiés précédemment dans le laboratoire, c’est-à-dire BMI1, MSI2 et KDM5B. D’autre part, plusieurs indices accumulés tendent à démontrer qu’il existe des différences fondamentales entre le fonctionnement des cellules souches hématopoïétiques murines et humaines. / Somatic stem cells usually exhibit a very different behavior compared to pluripotent stem cells. The molecular basis of embryonic stem cell self-renewal was recently decrypted by the relative straightforwardness with which we can now purify and maintain these cells in culture for long periods of time. However, this is not the case with hematopoietic stem cells. In order to elucidate the molecular mechanisms of hematopoietic stem cell self-renewal, I developed a novel gain-of-function screening strategy, which bypasses some constraints found with these cells. Starting from a list of more than 700 candidate nuclear factors and asymmetric division factors, I have identified 24 new factors that increase hematopoietic stem cell activity when overexpressed. I have also found that nine of these factors act extrinsically to hematopoietic stem cells, i.e., the effect comes from the engineered feeder cells in co-culture. Moreover, I have revealed a new transcriptional regulatory network including five of the factors identified, i.e., PRDM16, SPI1, KLF10, FOS and TFEC. This network is particularly similar to that involved in osteoclastogenesis. These results raise the hypothesis that osteoclasts might also be part of the functional hematopoietic stem cell niche in the bone marrow. Furthermore, I have identified a second regulatory network involving SOX4, SMARCC1 and several factors previously identified in the laboratory, i.e., BMI1, MSI2 and KDM5B. Besides, several lines of evidence tend to show that there are fundamental differences between mouse and human hematopoietic stem cells.

Les surfaces tactiles ayant connu un grand essor ces dernières années, le grand public les utilise quotidiennement pour de multiples tâches, telles que la consultation d'e-mail, la manipulation de photos, etc. En revanche, très peu d'applications 3D existent sur ces dispositifs, alors que de telles applications pourraient avoir un grand potentiel dans des domaines variés, telles que la culture, l'architecture, ou encore l'archéologie. La difficulté majeure pour ce type d'applications est d'interagir avec un espace défini en trois dimensions à partir d'une modalité d'interaction définie en deux dimensions. Les travaux effectués dans cette thèse explorent l'association entre surfaces tactiles et manipulation de contenu 3D pour le grand public. Les premières études ont été réalisées afin de comprendre comment l'utilisateur réagit pour manipuler un objet virtuel 3D avec une surface tactile sans lui imposer de techniques d'interaction particulières. De par les connaissances acquises sur les utilisateurs, les travaux suivants présentent l'élaboration de nouvelles techniques d'interaction ainsi que leur évaluation. / Since the emergence of tactile surfaces in recent years, the general public uses them every day for multiple tasks, such as checking email, photo manipulation, and so on. However, very few 3D applications on these devices exist, although such applications may have great potential in various fields, such as culture, architecture, or archeology. The major difficulty for such applications is to interact with a defined space in three dimensions from an interaction modality defined in two dimensions. Work in this thesis explores the association between tactile surfaces and manipulation of 3D content for the general public. The first studies were conducted to understand how the user tends to manipulate a 3D virtual object with a touch surface without imposing specific interaction techniques. Throughout knowledge gained by users, the following works are developing new interaction techniques and their evaluation.

The diploma thesis named "Do we need more information? Using of multiple media at the same time" examines the phenomen of simultaneous media usage in young audience aged 18-35 years. This thesis is based on the hypotheses of international surveys that demonstrate a new trend in consumption of media by which people use multiple media simultaneously. The aim of the thesis is to provide an insight into this issue. The first part defines basic concepts such as the media, media audience and related theories. Furthermore, international studies and their conclusions are presented, serving as a starting point for my own research. The second part presents the research methodology. The thesis makes use of a combination of a quantitative and qualitative approach, the so-called mixed research. The methodological section briefly describes the selected method - survey and an semi-structured interview. The next two sections deal with the implementation of the research itself. The sample consisted of 103 young people for the quantitative part of the survey, and 15 young people for the qualitative analysis section. The conclusion summarizes the research results and approaches each thematic area, including the possible hypotheses.

Quel type d’expérience faisons-nous quand nous « regardons un film » ? Si cette formulation se montre impropre du fait de la double implication sensorielle d’un voir/entendre qu’engage l’expérience spectatorielle, elle signale d’emblée une forme d’équivocité à propos de ce qu’on « regarde » comme de ce qu’engage le rapport que nous établissons avec ce que nous percevons d’un film. Il s’offre en effet comme une expérience de mimèsis singulière, dont l’examen est l’enjeu du présent travail. La méthode retenue a consisté à mener notre réflexion à partir de l’étude attentive d’un corpus de six films : Valse avec Bachir, d’Ari Folman, Caché, de Michael Haneke, le diptyque Mulholland drive/Lost highway, de David Lynch, Le mystère Picasso, de Henri-Georges Clouzot, et Eût-elle été criminelle…, de Jean-Gabriel Périot. Cette méthode nous a permis de nous interroger sur le type d’opérations que le visionnage d’un film requiert chez le spectateur, comme de nous demander quelle est la nature des objets perçus par le biais du dispositif cinématographique. Nous avons mis à jour le statut équivoque de ce que le spectateur perçoit, en distinguant trois aspects de l’image filmique : profigurant, figuratif, figural. Cette distinction met en évidence l’ambiguïté de l’image filmique quant à ce qu’elle image : monde représenté, complexe d’images et de sons, ensemble d’événements issus du monde réel. Ceci dans un second temps nous a conduit à étudier en quoi la réalisation engage des opérations productives de sens et de prescriptions pour le spectateur. A quelles conditions peut-on la penser comme écriture ? Et qu’est-ce qui est ainsi « réalisé » par ces opérations ? Enfin il s’agissait de s’interroger sur le rôle singulier que le cinéma réserve au spectateur : cette expérience particulière engage des activités tant perceptives, que cognitives et affectives, des immersions dans des temporalités hétérogènes, et un mode de croyance qui n’exclut pas le savoir de ce qui s’y joue. / What exactly do we experience when we “watch a movie” ? This phrase may seem ill-chosen since, in this “spectatorial experience” the viewer not only watches but he also listens. However it announces straightaway a form of equivocity between what we watch and what we connect with, while watching a movie. It appears as a unique experience of mimesis whose analysis is the aim of this study.The chosen method consisted in carrying out our reflection starting from the attentive study of a corpus of six films: Waltz with Bachir, by Ari Folman, Hidden, by Michael Haneke, the diptych Mulholland drive/Lost highway, by David Lynch, the Mystery Picasso, by Henri-Georges Clouzot, and Even if she had been a criminal…, by Jean-Gabriel Périot. This method enabled us to study the type of operations which the watching of a film requires from the spectator, and led us to ask ourselves which is the nature of the objects perceived by the means of the cinematographic device. We’ve highlighted the equivocity of what the spectator perceives, by distinguishing three aspects of the filmic image : profigurant, figurative, figural. This distinction underlines the ambiguity of the filmic image in what it actually shows : a representation of the world, a mixing of images and sounds, a set of events resulting from the real world. This, in a second time, led us to study to what extent the director’s choices engages productive operations of direction and regulations for the spectator. On which conditions can we consider it as writing? And what is thus « realized » by these operations? At last, we have tried to analyse the singular role that the cinema offers to the spectator : this particular experience involves perceptive, cognitive and emotional activities, immersions in heterogeneous temporalities, and a mode of belief in which the viewer is aware of what is at stake.

Capteur électrochimique basé sur des matériaux carbonés fonctionnalisés, pour la détection de deux micropolluants faisant partie des substances prioritaires de la Directive Cadre européenne sur l’Eau (DCE2000/60/CE) : le plomb et l’anthracène. Les capteurs électrochimiques permettent d’atteindre des limites de détection et une sélectivité adéquates pour l’analyse de micropolluants dont les concentrations sont de l’ordredu μg/L, et sont simples d’utilisation pour des analyses in situ à moindre coût comparés aux appareils d’analyses conventionnels. Leur robustesse est un paramètre important afin de permettre des mesures en continu ou semi-continu dans les eaux. Cette thèse propose tout d’abord le développement du capteur pour la détection du plomb. La formulation d’une encre conductrice de carbone est étudiée pour la sérigraphie de ’électrode réceptrice, permettant ainsi de contrôler la composition de l’encre et d’étudier l’influence de la phase carbonée sur les propriétés électrocatalytiques des électrodes. La fonctionnalisation des électrodes par greffage électrochimique d’un sel de diazonium est également étudiée afin de maîtriser la sensibilité et la reproductibilité des électrodes greffées, en contrôlant l’épaisseur et la qualité des couches. Avec cet objectif, la fonctionnalisation dans un liquide ionique protique qui permet le contrôle de la monocouche en modulant la viscosité de ce milieu a été étudiée. Les électrodes greffées montrent des performances analytiques améliorées notamment en termes de répétabilité et de reproductibilité. Enfin ce travail de thèse porte également sur le développement du capteur pour la détection électrochimique de l’anthracène, molécule sans fonctions chimiques. Les électrodes sont, dans ce cas, fonctionnalisées par un polymère à empreinte moléculaire, matériau connu pour sa très grande sélectivité. Les performances de ce capteur, dont la sélectivité est basée uniquement sur le facteur de forme de la molécule, pour la détection de l’anthracène sont alors mises en évidence. / Electrochemical sensor based on functionalized carbon materials, for the detection of two micropollutants, lead and anthracene, which are among of the priority substances of the European Framework Directive on Water(DCE 2000/60 / EC). Electrochemical sensors allow to achieve detection limits and selectivities for the analysis of micropollutants whose concentrations are of the order of μg/L. They are easy to use for in situ analyzes at lower costs compared to those of the conventional analysis equipment. Their robustness is an important parameter in order to allow continuous or semi-continuous measurements in water. First of all, this thesis proposes the development of a sensor for lead detection. The conductive carbon ink formulation is studied for the screen-printing of the receiving electrode, thus allowing to control the ink composition and to study the influence of the carbon phase on the electrocatalytic properties of electrodes. Functionalization of electrodes by electrochemical grafting of a diazonium salt is also studied in order to control the sensitivity and reproducibility of grafted electrodes, by controlling the thickness and the quality of the layers. With this aim it has been studied the functionalization in a protic ionic liquid in order to allow the control of the monolayer bymodulating the viscosity of this medium. The grafted electrodes show improved analytical performance especially in terms of repeatability and reproducibility. Finally, this work reports the development of a sensor for the electrochemical detection of anthracene, a molecule without chemical functions. In this case, a molecularly imprinted polymer, a material known for its very high selectivity, functionalizes the electrodes.Having a selectivity is only based on the form factor of the molecule, the performance of the sensor developed for the detection of anthracene is also highlighted.

La présente thèse cartographie et condense l'histoire des relations entre l'art et la télévision au cours du demi-siècle environ durant lequel la télévision maintint sa position de média de masse par excellence dans la société, des années 1950 au tournant du millénaire, jusqu'à la phase de vaporisation des médias récemment apportée par la profusion des technologies numériques et d'Internet. La centaine d'artistes étudiés appartient à différentes générations, des pionniers des années 1960 tels que Nam June Paik, Andy Warhol et divers collectifs de la guerilla television aux figures postmodernistes telles que Dara Birnbaum et General Idea, des artistes issus des années 1990 comme Phil Collins, Christian Jankowski et Matthieu Laurette aux figures émergées au XXIe siècle comme Keren Cytter, Hito Steyerl, Ryan Trecartin et les Yes Men.Les travaux abordés sont des vidéos, installations, performances, interventions et programmes télévisés conçus comme des formes de résistance, d'appropriation et de parodie de la télévision grand public, qui exposent les mécanismes par lesquels le média de masse influence notre perception de la réalité et de nous-mêmes. Les genres et les formats télévisuels les plus populaires sont ciblés : les informations, publicités, soap operas, talk-shows, émissions pour enfants, vidéoclips, téléréalité, divertissements éducatifs et séries télévisées. En permettant de « voir à distance », la télévision produit chez le spectateur un sentiment étrange de déplacement physique. Les travaux étudiés mettent en évidence et tentent de surmonter cette séparation entre les corps factuels et télévisés, qui est aussi une séparation entre réalité et représentation. / The present study maps and condenses the history of the relationships between art and television during the rough half century in which television maintained its position as society’s quintessential mass medium, from the 1950s to the turn of the millennium, through to the phase of vaporization of media recently brought by the profusion of digital technologies and the Internet. The close to one hundred artists discussed belong to different generations, from 1960s pioneers such as Nam June Paik, Andy Warhol and various guerrilla television collectives to postmodernist figures such as Dara Birnbaum and General Idea, from artists emerged in the 1990s such as Phil Collins, Christian Jankowski, and Matthieu Laurette up to figures emerged in in this early XXI century such as Keren Cytter, Hito Steyerl, Ryan Trecartin, and the Yes Men.The works discussed are videos, installations, performances, interventions and television programs conceived as forms of resistance, appropriation and parody of mainstream television, that expose the mechanisms through which the mass medium influences our perception of both reality and ourselves. To be targeted are the most popular television genres and formats including news, commercials, soap operas, talk shows, children's programs, music videos, reality shows, edutainment, and TV series. By allowing to “see at distance,” television produces in the viewer an uncanny feeling of physical displacement. What the works discussed highlight and try to overcome, is that split between factual and televised bodies, that is also a split between reality and representation.

O presente trabalho trata do desenvolvimento de sensores eletroquímicos que possuam características descartáveis e ao uso destes dispositivos para a determinação de diferentes analitos em amostras biológicas, farmacêuticas e de interesse ambiental. O desenvolvimento e a aplicação dos sensores foram divididos em seis capítulos. O primeiro capítulo corresponde a fabricação de conjuntos de microeletrodos em suporte de CD-RW e placa fenolite utilizando impressão com tinta toner. Os conjuntos de microeletrodos foram fabricados por meio da deposição de duas máscaras de toner em um substrato de cobre ou ouro. Os eletrodos fabricados neste capítulo foram caracterizados e aplicados nos capítulos subsequentes. Os resultados da aplicação do conjunto de microeletrodos de cobre (DCRM) foram descritos no segundo capítulo. Os dispositivos foram aplicados para a determinação de peróxido de hidrogênio em amostras de antisséptico bucal e clareadores dentais. As determinações foram realizadas em solução de tampão fosfato (pH 7.0) por meio da técnica de amperometria (E = -0,2 V). Estes sensores foram também aplicados para determinação de ácido acetilsalítico (AAS) em amostras farmacêuticas em solução de hidróxido de sódio 0,1 mol L-1 por amperometria (E = 0,6 V). A determinação de nitrato em amostra de água de rio foi realizada por amperometria (E = -0,45V) em solução de sulfato de sódio 0,1 mol L-1 (pH = 2,0). Os resultados obtidos com o sensor demonstraram o sucesso das aplicações. As principais vantagens deste dispositivo dizem respeito à simplicidade de fabricação, baixo custo do equipamento e rapidez das análises. A caracterização eletroquímica do sensor e a determinação de ciclopirox olamina em solução de tampão BR 0,1 mol L-1 (pH = 5,0) utilizando o conjunto de microeletrodos de ouro (CD-RW) foi apresentada no terceiro capítulo. Os resultados obtidos mostraram que é possível realizar a determinação desta espécie de interesse em soluções oftalmológicas. O desenvolvimento, a caracterização e aplicação de um novo conjunto de microeletrodos de ouro fabricados a partir da redução eletroquímica da 5-bromo-1,10-fenantrolina em solução de dimetilformalmida (DMF) foi investidada no quarto capítulo. A superfície foi bloqueada com um filme isolante de 1,10-fenantrolina e o sensor foi caracterizado como um conjunto de microeletrodos de ouro. O sensor foi aplicado para a determinação de peróxido de hidrogênio, nas condições descritas anteriormente a fim de avaliar a aplicabilidade deste dispositivo. Os resultados obtidos foram promissores. A utilização de um eletrodo de microbanda impresso na configuração \"back-to-back\" foi descrita no quinto capítulo. A configuração faz uso da impressão de um novo eletrodo nas costas de um eletrodo impresso \"tradicional\", aumentando com isso a sensibilidade do sensor. O eletrodo impresso na configuração \"back-to-back\" foi utilizado para a determinação de íons Pb(II) em amostras de água potável por meio da técnica de voltametria de redissolução anódica por onda quadrada e os resultados obtidos foram concordantes com os encontrados utilizando espectrometria de emissão atômica por plasma acoplado. Os eletrodos de microbanda impressos na configuração \"back-to-back\" modificados com nanotubos de carbono para a determinação de capsaicina e dopamina e com ftalocianina de cobalto (II) para determinação de hidrazina foram investigados no sexto capítulo. Os resultados obtidos foram concordantes com aqueles descritos em outros trabalhos encontrados na literatura. / This work presents results on the fabrication of disposable electrochemical sensors and the use of such devices for the determination of different analytes in biological, pharmaceutical and environmental samples. The development and application of these sensors have been divided into six chapters. The first chapter describes the fabrication of a microelectrode ensemble (CD-RW) using ink toner. The sensor was fabricated by deposition of two toner pattern masks on copper and gold substrates. The electrodes fabricated according this procedure were characterized and applied in subsequent chapters. The second chapter describes the use of a disposable copper random microarrays (DCRM) for the amperometric determination of three analytes: hydrogen peroxide in real samples (oral antiseptic and dental whitening) at -0.2 V in phosphate buffer (pH 7.0) solution, acetylsalicylic acid (ASA) in pharmaceutical formulations at 0.6 V in 0.10 mol L-1 NaOH solution and nitrate in river samples at -0.45V in a 0.10 mol L-1 sodium sulfate solution (pH 2.0). The good results obtained with the DCRM demonstrated the successful application of this new sensor. The main advantages of the proposed manufacturing procedure are the simplicity, low cost of equipment and the high speed of production. The third chapter presents results on the use of a gold random microarray (GRM) for the determination of ciclopirox olamine in 0.10 mol L-1 Britton Robinson buffer solution (pH 5.0). Following the optimization of the experimental parameters, the proposed sensor presented excellent analytical properties for the amperometric detection of ciclopirox olamine at +0.85 V. The usefulness of the GRM sensor was confirmed by determining ciclopirox olamine in commercial products and the results obtained agreed well with those found by potentiometric titration and the labeled values. The fourth chapter describes the fabrication of a random assembly of microelectrodes (RAMs) by electrochemical reduction of 5-bromo-1,10- phenathroline in N,N-dimethylformamide (DMF), generating the 1,10-phenanthroline radical, which was covalently grafted on gold electrodes. After several potential cycles, the gold surface was partially blocked with an insulating film of 1,10-phenanthroline and the resulting modified electrode exhibited the characteristics of RAMs for the electrochemical reduction of the reversible probe 1,4-benzoquinone in DMF. This sensor was applied for hydrogen peroxide detection at -0.2 V in phosphate buffer (pH 7.0) solution. The fifth chapter reports on the use of screen-printed back-to-back microband electroanalytical sensors for quantification of lead(II) ions in drinking water samples in 0.01 mol L-1 HCl and the validation of the results by ICP-OES. The sixth chapter shows results on the use of back-to-back screen-printed microband electrodes modified with single-walled carbon nanotubes and cobalt phthalocyanine. The electroanalytical applications of this novel electrode configuration were exemplified towards the sensing of dopamine, capsaicin and hydrazine.

As technology evolves, new devices and interaction techniques are developed. These transformations create several challenges in terms of usability and user experience. Our research faces some challenges for data input or content exploration in scenarios with restrictions. It is not our intention to investigate all possible scenarios, but we deeply explore a broad range of devices and restrictions. We start with a discussion about the use of an interactive coffee table for exploration of personal photos and videos, also considering a TV set as an additional screen. In a second scenario, we present an architecture that offers to interactive digital TV (iDTV) applications the possibility of receiving multimodal data from multiple devices. Our third scenario concentrates on supporting text input for iDTV applications using a remote control, and presents an interface model based on multiple input modes as a solution. In the last two scenarios, we continued investigating better ways to provide text entry; however, our restriction becomes not using the hands, which is the kind of challenge faced by severely motor-disabled individuals. First, we present a text entry method based on two input symbols and an interaction technique based on detecting internal and external heel rotations using an accelerometer, for those who keep at least a partial movement of a leg and a foot. In the following scenario, only the eyes are required. We present an eye-typing technique that recognizes the intended word by weighting length and frequency of all possible words formed by filtering extra letters from the sequence of letters gazed by the user. The exploration of each scenario in depth was important to achieve the relevant results and contributions. On the other hand, the wide scope of this dissertation allowed the student to learn about several technologies and techniques. / Com a evolução da tecnologia, novos dispositivos e técnicas de interação são desenvolvidas. Essas transformações criam desafios em termos de usabilidade e experiência do usuário. Essa pesquisa enfrenta alguns desafios para a entrada de dados e exploração de conteúdo em cenários com restrições. Não foi intenção da pesquisa investigar todos os possíveis cenários, mas sim a exploração em profundidade de uma ampla gama de dispositivos e restrições. Ao todo cinco cenários são investigados. Primeiramente é apresentada uma discussão sobre o uso de uma mesa de centro interativa para a exploração de fotos e vídeos pessoais, a qual também considera um aparelho de TV como tela adicional. Com base no segundo cenário, uma arquitetura que oferece a aplicações de TV digital interativa (TVDI) a possibilidade de receber dados multimodais de múltiplos dispositivos é apresentada. O terceiro cenário se concentra no suporte a entrada de texto para aplicações de TVDI usando o controle remoto, resultando na apresentação de um modelo de interface baseado em múltiplos modos de entrada como solução. Os dois últimos cenários permitem continuar a investigação por melhores formas de entrada de texto, porém, a restrição se torna a impossibilidade de usar as mãos, um dos desafios enfrentados por indivíduos com deficiência motora severa. No primeiro deles, são apresentados um método de entrada de texto baseado em dois símbolos de entrada e uma técnica de interação baseada na detecção de rotações do pé apoiado sobre o calcanhar usando acelerômetro, para aqueles que mantêm pelo menos um movimento parcial de uma perna e um pé. No senário seguinte, apenas os movimentos dos olhos são exigidos. Foi apresentada uma técnica de escrita com o olho que reconhece a palavra desejada ponderando o comprimento de a frequência de ocorrência de todas as palavras que podem ser formadas filtrando letras excedentes da lista de letras olhadas pelo usuário. A exploração de cada cenário em profundidade foi importante para a obtenção de resultados e contribuições relevantes. Por outro lado, o amplo escopo da dissertação permitiu ao estudante o aprendizado de diversas técnicas e tecnologias.

C/EBPα und C/EBPβ sind Transkriptionsfaktoren, die die Zellproliferation und Zelldifferenzierung in vielen Geweben regulieren. C/EBPα und C/EBPβ spielen auch eine onkogene Rolle in akuter myeloischer Leukämie und anaplastisch-großzelligen Lymphomen (ALCL). In dieser Studie wird C/EBPα auf neue posttranslationale Modifikationen, wie z. B. Arginin-Methylierungen und Citrullinierungen, sowie Lysin-Methylierungen und Acetylierungen, mit massenspektrometrischen Mitteln untersucht. Es werden eine modifizierbare C/EBPα-Arginin-Citrullinierungsposition und die C/EBPα-Lysinsumoylierung eingehend auf ihren Einfluss auf C/EBPα-Proteininteraktionsnetzwerk überprüft. Außerdem wurde im Verlauf dieser Studie ein Hochdurchsatz-Screening-Verfahren entwickelt, das wir Protein Interaktions-Screening auf einer Peptid Matrix (PrISMa) nennen. Dieses Verfahren dient der Aufklärung des modifikationsabhängigen Proteininteraktionsnetzwerkes von C/EBPβ. PrISMa basiert auf einer Peptidmembran, auf der C/EBPβ-Peptide synthetisiert sind. Viele dieser Peptide enthalten methylierte Arginine und Lysine, acetylierte Lysine, citrullinierte Arginine und phosphorylierte Serine, Tyrosine und Threonine. Mittels PrISMa konnten Interaktionen von C/EBPβ mit Histonacetyltransferasen, dem Mediatorkomplex, Proteinen des nukleären Transports und RNA bindenden und spleißenden Proteinen verifiziert und kartiert werden. Des Weiteren konnte mit Hilfe von PrISMa eine große Anzahl von publizierten C/EBPβ Interaktionspartner spezifischen C/EBPβ-Sequenzen zugeordnet werden. C/EBPβ wird in ALCL in hohem Maße exprimiert und ist für die Zellproliferation dieser Krebsart wichtig. In dieser Studie wird das Proteininteraktionsnetzwerk C/EBPβ in einer ALCL Zelllinie aufgeklärt, um tiefere Einsichten über die Funktion von C/EBPβ als Onkogen zu erlangen. / C/EBPα and C/EBPβ regulate cell proliferation and differentiation in multiple cell types. Moreover, C/EBPα and C/EBPβ are known to play oncogenic roles in acute myeloid leukemia and anaplastic large cell lymphomas (ALCLs). In this study C/EBPα is screened for novel posttranslational modifications (PTMs), such as arginine methylation and citrullination, as well as lysine methylation and acetylation by using mass spectrometry. A in this survey identified C/EBPα site of arginine citrullination and the C/EBPα lysine sumoylation are scrutinized for their impact on C/EBPα protein interaction network. A new high-throughput method named Protein Interaction Screen on peptide Matrices (PrISMa) is introduced in this study. This method was developed to determine the C/EBPβ protein interaction network in a PTM dependent manner. The PrISMa survey is based on a peptide membrane spotted with C/EBPβ peptides. Many of these C/EBPβ peptide sequences contain amino acid sequences comprising arginine and lysine methylation, lysine acetylation, arginine citrullination and serine, tyrosine and threonine phosphorylation. By means of PrISMa the C/EBPβ interplay with histone acetyltransferases, the mediator complex, proteins of the nucleoplasmic transport and RNA processing proteins is verified and specified by mapping these interactions to C/EBPβ amino acid sequences. Furthermore, PrISMa provides a map of C/EBPβ protein interaction patterns for a great number of the up to date published C/EBPβ protein interaction partners. C/EBPβ is highly expressed in ALCL cell lines and is essential for the cell proliferation of this type of cancer. In this study the C/EBPβ protein-protein interaction pattern in an ALCL cell line is unraveled providing valuable insight into the protein interaction network of C/EBPβ as an oncogene.

<div>This project engages in an intersectional and interdisciplinary tracing of the emerging field of feminist game studies and the epistemologies and methodologies that exist within this field. Through such tracing, this project asks—what are feminist game studies’ epistemological goals and frameworks? What methodologies can the field draw from in order to achieve these epistemological goals? Ultimately, this project argues that feminist game studies enacts an epistemology of feminist worldbuilding—that is, an inclusive, embodied, space-claiming mode of producing knowledge—and achieves this worldbuilding through methodologies of intersectional disruption in order to perform disruptive feminist interventions into video game culture. </div><div><br></div><div>In the first chapter of this project, I make use of a methodology of narrative autoethnography to discuss my experience with online harassment as an inroad into interrogating the bodies at risk in gaming spaces in order to make a case for the need for feminist interventions to disrupt the violent structures within video game culture. The second chapter traces the ways hegemonic, patriarchal frameworks in game studies epistemologically deprivilege material, representational analyses of bodies and culture in the study of games and, instead, argues for the implementation of intersectional approaches to video game culture. The third chapter maps the intersectional feminist methodologies that can be implemented in feminist game studies in order to perform generative and disruptive interventions into video game culture and build feminist worlds. </div><div><br></div><div>In the fourth chapter, I apply some of these methodologies of disruption to the alienation of mothers in the gaming industry’s workplace culture and representations of mothers in the games Among the Sleep and Horizon Zero Dawn in order to intervene into video game culture’s prejudicial attitudes regarding labor, mothers, and women. The final chapter continues my autoethnographic work through the connection of my experiences with online harassment to previous experiences with gendered violence and trauma in order to underscore the stakes of feminist game studies praxis. In all these ways, I argue that feminist game studies builds worlds by performing interventions into video game culture through intersectional and pluralistic methodologies of disruption, for such methodologies imagine new, inclusive models of existence and futurity in video game culture.</div>