The thesis examines the activities of Cahiers d’Art as a magazine, gallery and publishing house active in Paris from 1926 to 1960 with special attention, and without particular regards to biography, to the intellectual development of its founder Christian Zervos from his early years in Alexandria at the beginning of the century to his professional establishment in the French capital. Its originality resides in the presentation of a significant corpus of unpublished archival information and the examination of the role that the network centred around Cahiers d’Art played in the institutionalisation of independent art in the first half of the century, the propagation of abstraction through the popularisation of European primitivism which was presented as a direct link to the modern era, and the passage from the Mechanist to the Atomic Age, its effects in the artistic domain and the ideological connotations it encased. The overall analysis focuses on particular transitional phenomena that marked the course of the 20th century. Particularly, the passage from analysis to synthesis which found diverse expressions in the contemporary artistic discourse since the beginning of the century giving birth to an increased interest in pragmatist approaches to art and architecture, social engagement, and a course towards formal simplification. The thesis observes the way in which the medieval and the primitive past contributed to the consecration of the international School of Paris and the conflicts of interest of their exponents. It furthermore pays close attention to Zervos’ position-taking with regards to these conflicts, his disdain for antiquity, its aftermath in western art, and the way that these positions affected his presentation of Picasso’s work in the voluminous catalogue raisonné of the artist’s work. Finally, it seeks to re-appreciate from the perspective of Cahiers d’Art, a significantly influential network of worldwide reputation, issues associated with the consecration and popularisation of international independent art in France and abroad, as well as the conflicting aspirations for decentralisation in a context dominated by Eurocentric attitudes and the formal and ideological projections of post Wold War Two liberal critique.

Le génome humain est constamment la cible d'agents qui endommagent l'ADN. Ces dommages sont multiples et variés tels que les cassures simple et double brin (DSB). Les DSBs sont des lésions très toxiques dont l'origine peut être multiple. Les cellules de mammifères réparent les DSBs en utilisant deux mécanismes principaux, la recombinaison homologue (RH) qui est dépendante du cycle cellulaire et utilise la chromatide sœur comme matrice de réparation et la jonction des extrémités non homologues (NHEJ) qui est indépendante du cycle cellulaire et consiste en la ligation des extrémités d'ADN endommagées. Cette réparation a lieu dans un contexte chromatinien qui nécessite un dynamisme pour rendre accessible les sites lésés aux différentes machineries de réparation. Lors de mes travaux, j'ai étudié le remodeleur de la chromatine p400 ainsi que le variant d'histone H2A.Z qui sont deux protéines impliquées dans la dynamique de la chromatine, afin de comprendre leur rôle dans les mécanismes de réparation des DSBs et la stabilité du génome. p400, une ATPase de la famille SWI2/SNF2 participe à l'incorporation du variant d'histone H2A.Z dans la chromatine. Au cours de ma thèse, j'ai montré que la déplétion par siRNA du variant d'histone H2A.Z, dans la lignée d'ostéosarcome humain (U2OS) et dans des fibroblastes humains immortalisées, n'a pas d'effets sur la réparation des DSBs. Ces résultats sont corrélés avec une absence de recrutement de H2A.Z au niveau des cassures après étude par micro irradiation laser ou par immunoprécipitation de chromatine. Cependant, la déplétion de H2A.Z affecte la prolifération cellulaire en influençant l'efficacité de clonage et le cycle cellulaire. L'autre partie de mes travaux a mis en évidence que l'ATPase p400 est un frein à l'utilisation de la voie alternative de jonction des extrémités (alt-EJ) qui est un processus de réparation des DSBs très mutagène. L'augmentation des événements du NHEJ-Alternatif et la génération d'instabilité génétique observés lors de la déplétion de p400 par siRNA semblent tributaires de la résection des DSBs par CtIP. Ces résultats indiquent que p400 joue un rôle post-résection dans les étapes plus tardives de la RH. De plus, la déplétion de p400 conduit au recrutement de la polyADP ribose polymérase (PARP) et de l'ADN ligase 3 à la DSB, ce qui provoque la mort sélective de ces cellules lors d'un traitement par des inhibiteurs de PARP. Ces résultats montrent que P400 agit comme un frein pour empêcher l'utilisation du NHEJ-Alternatif et donc l'instabilité génétique. / The human genome is constantly targeted by DNA damaging agents. These damages are many and varied, such as single and double strand breaks (DSBs). The DSB are highly toxic lesions whose origin can be multiple. Mammalian cells mainly use two DNA repair pathways to repair DSB, homologous recombination (RH), which is dependent on the presence of the intact homologous copy (the sister chromatid) and on the cell cycle stage and the non-homologous end joining (NHEJ) pathway, which is cell cycle independent and performs direct ligation of the two DNA ends. The repair of DNA damage takes place in a chromatin context that needs to be remodeled to give access to damaged sites. During my work, I studied the chromatin remodeler p400 and the histone variant H2A.Z both involved in chromatin remodeling, to understand their role in DSB repair and genome stability. p400, an ATPase of the SWI2/SNF2 family is involved in the incorporation of H2A.Z in chromatin. I have shown that H2A.Z depletion in the osteosarcoma cell line U2OS and in immortalized human fibroblasts did not alter DSB repair. These results are correlated with the lack of H2A.Z recruitment at DSB observed after local laser irradiation or Chromatin Immunoprecipitation. However, H2A.Z depletion affects cell proliferation and the cell cycle distribution. In addition, I have shown that the chromatin remodeler p400 is a brake to the use of alternative End Joining (alt-EJ) which is a highly mutagenic repair process. The increase in alt-EJ events observed in p400-depleted cells is dependent on CtIP- mediated resection of DNA ends. Moreover, p400 depletion leads to the recruitment of poly(ADP) ribose polymerase (PARP) and DNA ligase 3 at DSB, leading to selective cell killing by PARP inhibitors. Altogether these results show that p400 acts as a brake to prevent alt-EJ dependent genetic instability and underline its potential value as a clinical marker.

In this thesis I explore the role and significance of editorial illustration, developed in printed publications and evolving within online publishing structures. Editorial illustration has a long tradition of illustrating stories in news publications, but I argue that in current online news websites its particular role has all but failed. Online publishing has become the driving force within editorial publishing and this raises the question whether, and how, editorial illustration can continue to be a successful constituent in an online publishing environment? I argue that the continuation of editorial illustration lies within digitally native narrative forms, from online interactive documentaries, game-based storytelling, data-visualisation to memes: viral images spread through social media. Within these forms the significance and agency of illustration is not only clearly present but evolving, except here illustration is interwoven with the story. I argue that these forms of illustration, as well as printed illustration, are based on the same conceptual model and articulate editorial illustration’s inherent attributes. I propose a constellation of four attributes (manifestation, translation, reflection, and engagement) that together give rise to the key quality that illustration offers to the reader, deliberation. Illustration should not be understood as a separate artifact, positioned next to a text, but as a multimodal practice, always related to a story, enabled by the specific qualities of its contextualizing medium. As practice-led research, the thesis explores this proposition in practice and theory within printed and online forms of editorial illustration and in relation to online media technologies and material properties. Central is the development of a potential method of online editorial illustration that I call data driven illustration, a formation employing the material and semiotic expressive potential of live data and code. The research draws primarily from the ideas of media materiality (Hayles, Kittler, Manovich), but in doing so is supplemented with other relevant theories found in semiotics (Barthes, Hayles, Kress and van Leeuwen) and audience reception (Hall). This interdisciplinary approach is applied to the field of illustration through a historical study of wood-engraved news illustration in the Illustrated London News; through my own practice as an illustrator, in this case, work undertaken for the NRC newspaper; and explorations of various examples of online illustration. This thesis offers a first step in constructing a framework for editorial illustration, to move beyond the print paradigm and provide a language through which to explore illustration as an emergent practice.

Abstract : Regulation of transcription is crucial for the appropriate development and function of eukaryotic cells. In eukaryotes, DNA is organized into a dynamic, complex, nucleoprotein structure called chromatin. Chromatin structure provides markedly restricted access of transcription factors to regulatory sites. Several mechanisms have evolved to modulate chromatin dynamics in order to regulate proper gene expression. One of the most intriguing mechanisms that modulate chromatin structure is the exchange of canonical histones with histone variants by chromatin remodeling complexes. Among the histone variants, H2A.Z is an essential regulator of gene transcription. H2A.Z is enriched at regulatory regions but significant levels of the histone variant can also be found within gene bodies. However, the role of H2A.Z within the gene bodies is still not well understood. Recent evidence suggests that active recruitment of H2A.Z within gene bodies is required to induce gene repression. In contrast to this view, we show that global inhibition of transcription results in H2A.Z accumulation at gene transcription start sites, as well as within gene bodies. Our results indicate that accumulation of H2A.Z within repressed genes can also be a consequence of the absence of gene transcription rather than an active mechanism required to establish repression. The second part of my Ph.D. project was to investigate the potential role of BRD8 - a subunit of the p400/Tip60 complex - in p53-mediated signaling. We find that knockdown of BRD8 leads to p21 induction and concomitant cell cycle arrest in G1/S. We further demonstrate that the p53 transcriptional pathway is activated in BRD8-depleted cells, and this accounts for upregulation of not only p21 but also proapoptotic genes, an event that leads to consequent apoptosis. Importantly, the DNA damage response is induced upon depletion of BRD8 and DNA damage foci are detectable in BRD8-depleted cells under normal growth conditions, as indicated by immunostaining for γ-H2AX. Notably, H4K16 acetylation is reduced in BRD8-depleted cells suggesting that BRD8 may have a role in recruiting and/or stabilizing the p400/Tip60 complex within chromatin, thus facilitating DNA repair. Consistent with the activated DNA damage response, we find that in BRD8-depleted cells, CHK2 is activated but, surprisingly, CHK1 protein levels are severely reduced. Taken together, our results suggest that BRD8 is involved not only in mediating p53-dependant gene suppression, but also in mediating the DNA damage response. In the last part of my Ph.D. project, I investigated the possible mechanisms involved in recruitment of the p400 chromatin remodeler complex to chromatin. I showed that histone variant H2A.Z is essential for efficient recruitment of p53 and p400 to the distal p53 binding element of the p21 promoter. Furthermore, using double knockout (DKO) MEFs for p300/CBP I showed that the depletion of p300/CBP lead to a severe decrease in the recruitment of p400 at p21 promoter. Further studies are necessary to fully understand the role of p300/CBP in targeting p400 to chromatin. In conclusion, my studies provide insights into the molecular mechanisms involved in chromatin regulation by histone variant H2A.Z and chromatin remodeler complex p400. / Résumé : La régulation de la transcription est un mécanisme crucial pour le bon développement et fonctionnement des cellules eucaryotes. Chez les eucaryotes, l'ADN est organisé dans une structure dynamique de nucléoprotéines appelée chromatine. La structure de la chromatine forme une barrière qui contrôle l'accès des facteurs de transcription à leurs sites de fixation sur l’ADN. Plusieurs mécanismes ont été acquis au cours de l'évolution pour moduler la dynamique de la chromatine afin de réguler de manière adéquate l'expression des gènes. Un des mécanismes les plus intriguant qui module la structure de la chromatine est le remplacement des histones canoniques par des variants d'histones. Il est effectué par des complex de remodelage de la chromatine. Parmi les variants d'histones, H2A.Z est un régulateur essentiel de la transcription des gènes. H2A.Z est enrichi aux régions régulatrices des gènes, mais des niveaux significatifs de ce variant d'histone peuvent aussi être observés au cœur des gènes. Le rôle de H2A.Z localisé a lèintérieur gènes n'est, pour l'instant, pas bien compris. Des résultats récents suggèrent que le recrutement actif de H2A.Z dans les gènes est requis pour induire leur répression. En opposition à ces résultats, nous montrons que l'inhibition globale de la transcription conduit à l'accumulation de H2A.Z aux sites d'initiation de la transcription, mais aussi au cœur des gènes. Nos résultats indiquent que l'accumulation de H2A.Z dans les gènes réprimés serait une conséquence de l'absence de transcription plutôt qu'un mécanisme actif requit pour établir la répression. La seconde partie de mon doctorat a été dédiée à l'étude du rôle de BRD8 (une sous-unité du complexe p400/Tip60) dans la signalisation contrôlée par p53. Nous avons trouvé que la déplétion de BRD8 conduit à l'induction de p21 et à l'arrêt concomitant du cycle cellulaire en phase G1/S. Nous montrons aussi que le circuit transcriptionnel de p53 est activé dans les cellules déplétées en BRD8. Cela résulte en l'induction de p21, mais aussi de gènes proapoptotiques, ce qui conduit la cellule en apoptose. De manière marquante, la voie de réponse aux dommages de l'ADN est induite suite à la déplétion de BRD8, ce qui est observée par l'apparition de foci de dommages à l'ADN révélés par immunocoloration de γ-H2AX. De plus, l'acétylation de H4K16 est réduite dans les cellules déplétées en BRD8, suggérant que BRD8 pourrait avoir un rôle dans le recrutement et/ou la stabilisation du complexe p400/Tip60 dans la chromatine, et pourrait donc faciliter la réparation de l'ADN. En accord avec le fait que la réponse aux dommages de l'ADN soit activée, nous trouvons que dans les cellules déplétées en BRD8, CHK2 est activé mais étonnamment le niveau de la protéine CHK1 était fortement diminué. Ensemble, nos résultats suggèrent que BRD8 est impliqué non seulement dans la répression des gènes régulés par p53, mais aussi dans la réponse aux dommages de l'ADN. Finalement, dans la dernière partie de mon doctorat j'ai étudié le mécanisme qui pouvait être responsable du recrutement du complexe p400 au niveau de la chromatine. Nous avons montré que le variant d'histone H2A.Z est essentiel pour le recrutement de p53 et de p400 au site distal de fixation de p53 sur le promoteur de p21. De plus, en utilisant des cellules MEF DKO pour p300/CBP, nous avons montré que la déplétion de p300/CBP conduit à une diminution sévère du recrutement de p400 au promoteur de p21. En conclusion, mes études permettent de mieux comprendre les mécanismes moléculaires impliqués dans la régulation de la chromatine par l'histone H2A.Z et le complexe de remodelage de la chromatine p400.

Since the seminal work of Fritz Heider and Marienne Simmel (1944) the study of animacy perception, or the perception and attribution of life from the motion of simple geometrical shapes has intrigued researchers. The intrigue for psychologists and vision scientists then and today centered on the stark disconnect between the simplicity of the visual input and the universal richness of the resulting percept. Infant research in this domain has become critical in examining the ontological processes behind the formation of animated percepts. To date, little is known about how infants process these kinds of stimuli. While numerous habituation studies have shown sensitivity to animate motion in general, none to date has examined whether infants actually perceive animate displays as social interactions. The overarching goal of the present thesis is to answer this question and further augment knowledge about the mechanisms behind the formation of animated percepts in infancy. I, along with my collaborators, do so in three ways, in three separate studies. First, we examined visual attention during online observation of randomly moving geometrical shapes in adults and infants (Study I, using eye tracking). Second, we examine distribution of visual attention in infancy during online observation of non-contact causal interactions, focusing on the most ubiquitous, fitness relevant of interactions – chasing (Study II, using eye tracking). Third, we answer the question whether infants perceive social content in chasing displays by measuring the neural correlates in response to chasing (Study III, using EEG). The collective contribution of the present work is also three fold. First, it demonstrates that starting at the end of the first year of life, human visual system is sensitive to cues that efficiently predict an interaction. Second, at 5-months infants begins allocating attention differently across agents within interactions. Finally, attention to specific objects is not due to low-level saliency but the social nature of the interaction. Subsequently, I present the case that perception of social agents is fast, direct, and reflects the workings of a specialized learning mechanisms whose function is the detection of heat-seeking animates in motion.