Despite the current understanding that sensorimotor circuits function through the action of transmitters and modulators, we have a limited understanding of how the nervous system directs the flow of information necessary to orchestrate complex behaviors. In this dissertation, I aimed to uncover how the nervous system coordinates these behaviors using the escape response of the soil nematode, Caenorhabditis elegans, as a paradigm. C. elegans exhibits a robust escape behavior in response to touch. The worm typically moves forward in a sinusoidal pattern, which is accompanied by exploratory head movements. During escape, the worm quickly retreats by moving backward from the point of stimulus while suppressing its head movements. It was previously shown that the biogenic amine tyramine played an important role in modulating the suppression of these head movmemetns in response to touch. We identified a novel tyramine-gated chloride channel, LGC-55, whose activation by tyramine coordinates motor programs essential for escape. Furthermore, we found that changing the electrical nature of a synapse within the neural circuit for escape behavior can reverse its behavioral output, indicating that the C. elegans connectome is established independent of the nature of synaptic activity or behavioral output. Finally, we characterized a unique mutant, zf35 , which is hyperactive in reversal behavior. This mutant was identified as a gain of function allele of the C. elegans P/Q/N-type voltage-gated calcium channel, UNC-2. Taken together, this work defines tyramine as a genuine neurotransmitter and completes the neural circuit that controls the initial phases of the C. elegans escape response. Additionally, this research further advances the understanding of how the interactions between transmitters and ion channels can precisely regulate neural circuit activity in the execution of a complex behavior.

Im Juli 2022 startet auf der Burg Mildenstein das Escape-Game »Der Schatz des Einäugigen«. Mittels einer analog-digitalen Schnitzeljagd durchrätseln Museumbesucher*innen die Burg, um sich dann final dem Escape-Room zu stellen. Der Beitrag gibt Einblick in die Projektarbeit, das Konzept und die zugrunde liegende Story des Spiels und hebt die Vorteile des Escape-Games als Vermittlungsformat im Bildungsbereich hervor. / Since July 2022 visitors to Mildenstein Castle are able to enjoy taking part in the Escape Game: »The Treasure of the One-Eyed Prince«. The game is a part-analogue, part-digital treasure hunt by means of which visitors can gain entry to the Escape Room itself. The following text gives an insight into the work of the project, the concept and to the story that lies behind it. It also highlights the value of the Escape Game format as an effective educational medium.

Doctor of Philosophy / Department of Diagnostic Medicine and Pathobiology / Kyeong-Ok Chang / Caliciviruses are important pathogens of humans and animals. Noroviruses are major causes of foodborne gastroenteritis cases, but their research is hindered due to the inability to grow human noroviruses in cell culture. Detailed studies on entry events of caliciviruses are lacking and may be crucial for development of cell culture models. We examined the entry events of caliciviruses using porcine enteric calicivirus (PEC), feline calicivirus (FCV) and murine norovirus-1 (MNV-1). PEC replication in LLC-PK cells requires bile acid in the medium, but the mechanism is not well understood. Our studies showed that bile acids are required in the early stage of virus replication, and while internalization of PEC is not dependent of them, they are required for endosomal escape and successful replication. Further examination on virus entry, we demonstrated that endosomal acidification and cathepsin L activity are essential in the replication of PEC, FCV and MNV-1. The results showed that inhibition of endosomal acidification or cathepsin L activity led to retention of viruses in the endosomes. Also we demonstrated that recombinant cathepsin L cleaved structural protein of PEC, FCV or MNV-1, which suggests that the enzyme may facilitate uncoating viruses in endosomes. In addition to bile acids, we found that a cold shock treatment during virus entry supported PEC replication by facilitating the endosomal escape. While PEC alone did not induce ceramide formation, bile acids or cold shock treatment induce ceramide formation on endosomes through activation acid sphingomyelinase (ASM), and this event was crucial for virus replication because inhibition of ASM blocked ceramide formation and significantly reduced PEC replication. Incubation of FCV or MNV-1 with cells led to ceramide formation during virus entry, and inhibition of ASM also significantly reduced their replication. Inhibition of ASM led to endosomal retention of PEC, FCV or MNV-1 during virus entry, which may be the reason for the reduction of viral replication. These studies revealed the important and common events during calicivirus entry for successful replication, including virus endosomal escape, cathepsin L activity and ASM/ceramide formation. This detailed information may provide clues for understanding the replication of fastidious caliciviruses and for potential therapeutic targets.

Le voyage chez Gadda représente toujours une fuite tendancielle de (son) monde, de (son) temps, de (son) espace et de ce que Gadda ressent comme son propre destin. En même temps, il est aussi un pèlerinage " religieux " vers des terres inconnues, il est la vérification gnoséologique et le témoignage qui en découle de la réalité du monde et de sa constitution historique et matérielle. Une réalité faite non de rêves, mais de pierres et d'hommes. Le voyage écrit de Gadda oscille donc, avec des composants variables et souvent conflictuelles, entre le voyage non éthique, fin en soi et " rêveur " des symbolistes, et le voyage éthique finalisé à la connaissance et à la construction du monde. Aux voyages pour la plus part " rêveurs " et lyriques correspond une signification de fuite tendancielle du monde, alors qu'aux voyages pour la plus part éthiques correspond la signification d'un pèlerinage finalisé à certifier et à témoigner de la réalité de l'œuvre humaine dans son devenir historique. Il n'y a pas de textes où est présente seulement l'une de ces deux composantes sous sa forme pure, mais textes où, avec une intensité variable, une composante, un registre ou une tendance, l'emporte sur l'autre. Il faudra dire en conclusion que le voyage lyrique sera fonda-mentalement dominant dans tout Gadda, tandis que le voyage éthique, subordonné à celui-ci, sera toujours le résultat d'un refoulement conscient et artistique de la première pulsion : une pulsion de rêve, lyrique et non éthique. / The travel in Gadda's work is always a tendencial escape from (his) world, from (his) time, from (his) space and from what he feels as (his) fate. But, at the same time, the travel is also a “religious” pilgrimage in foreign lands, it is the epistemological assessment and the subsequent testimony of the reality of the world and his historical and material form. A reality made of stones and men, not of dreams. The travel Gadda described fluctuates between the unetic travel that belongs to Symbolists, ending in itself and dreaming, and the etic travel which has the aim to know and built the world. To travel mostly dreamy and lyrical corresponds a sense of escape from the world, and to travel mainly ethical corresponds the meaning of a pilgrimage designed to certify and witness the reality of human work in its historical development. In this thesis I don't describe texts in which there is only one of these two components in the pure form; on the contrary there are texts in which prevails with greater or lesser intensity one of the two components. In conclusion the lyric travel tends to be dominant in Gadda and the etic travel is subject to the lyric and it will be always the result of a conscious and artistic repression of primal instinct: the dreamy, lyrical and unetic instinct.

This paper examines the power and limitations of historical analysis in regards to explaining the Holocaust and in particular the widespread consent to the Nazi program. One of the primary limitations that emerges is an inability of historians to fully engage other social sciences to offer a more comprehensive explanation as to why so many Germans engaged in what we would consider an “evil” enterprise. In that regard, I offer the work of Ernest Becker, a social anthropologist, whose work provides a framework for understanding history as a succession of attempts by man to create societies that generate meaning through various heroic quests that defy man's finite existence, yet often result in carnage. Combining Becker's theoretical framework with the rich historical evidence specific to the Holocaust provides a much richer understanding of both Becker's work and why the Holocaust happened.

and key words Mouse polyomavirus-derived virus-like particles composed from major capsid protein VP1 (MPyV VP1-VLPs) are interesting structures for use as a delivery system of various cargos into cells. VP1 protein self-assembles into icosahedral particles of 45 nm in diameter that are hollow highly regular nanoparticles. In this work, model small molecule cargo, Cyclodextrin-Based Bimodal Fluorescence/MRI Contrast Agent, was encapsidated into MPyV VP1-VLPs. The cargo was stably associated with VLPs and was delivered into mammalian cells using these VLPs. To prevent VLPs entrapment in endolysosomal compartments and increase the potential of VLPs applications, MPyV VP1 protein was modified by insertion of histidine-tag (6 histidine long sequence surrounded by glycine and serine) sequences into VP1 surface loop DE, because histidine modification of synthetic systems had enhancing effect on endosome escape and cargo delivery. With the use of in Bac-to-Bac® baculovirus expression system His-VP1 protein was expressed in insect cells and a variety of VP1-assemblies was obtained: long tubules and small 20nm VLPs formed from VP1 with 4 histidine-tags in DE loop, and novel VP1 nanostructure, which we named nano-jumpers, formed from VP1 with 2 histidine-tags. Nonetheless the endosome escape properties of...

Un territoire est indéniablement associé à Napoléon et à sa légende dans l'esprit des populations. Il ne s'agit pas de la Corse, lieu de naissance, mais bien de Sainte-Hélène, lieu d’exil, de mort mais aussi de construction de la légende napoléonienne. C'est sur cette île de l'Atlantique sud qu'entre 1815 et 1821 celui qui, pendant plus de vingt ans, a fait trembler l'Europe, vit les dernières années de son existence. Le captif pendant toutes les années de sa détention sur Sainte-Hélène n'est peut-être à aucun autre moment de sa vie si étroitement observé. Cependant, les Français, entre 1815 et 1821, ignorent ce qui se passe sur cette île perdue de l’Atlantique sud. Les nouvelles sur ce personnage sont rares sinon absentes et l'absence d'information véridique sur les événements de l'île est considérable. Ce constat est accentué par la situation de Sainte-Hélène. Il s'agit d'un lieu éloigné, inconnu et difficilement compréhensible pour la grandes majorités des Français du XIXe siècle. Cette absence d'information entraine les plus folles rumeurs. Effectivement, les fausses nouvelles parsèment l'exil de Napoléon, des Français répandent des bruits, prétendent connaître la vérité et la transmettre généralement oralement, plus rarement par l'écrit, aux autres. Si les bruits sont essentiellement émis entre 1815 et 1821 ils se poursuivent au cours des années 1820 et même au-delà par de multiples relais.Nombre de bruits et d'ouvrages offrent de multiples histoires toutes plus sensationnelles les unes par rapport aux autres sur l'exil de Napoléon. Parmi elles, Napoléon s'est évadé de Sainte‑Hélène. De véritables faits ont inspiré les nombreuses théories évasionistes qui fleurissent à partir de 1815. Ainsi, des projets d’enlèvement ont indéniablement été pensés. Néanmoins, aucun des plans n’est mis à exécution, amenant en conséquence un questionnement sur les raisons de l’absence de leur concrétisation, n'ont-ils pas simplement été de simples échanges verbaux entre Bonapartistes ?Enfin, les rumeurs perdurent après 1821 en partie grâce aux arts. En effet, l'internement de Napoléon a beaucoup été représenté par la littérature, la peinture et plus récemment par le cinéma. Par exemple, de très nombreux auteurs du XIXe siècle se sont inspirés du séjour de l'Empereur à Sainte-Hélène de façon plus ou moins évidente et ont réinvesti les éléments constitutifs de la légende.Toutes les rumeurs et les représentations artistiques de la captivité déforment les dernières années de Napoléon. Or, ces représentations altérées restent dans la mémoire collective car elles sont plus faciles à retenir, elles sont de meilleures histoires que la réalité... Et donc, la mythologie fini par altérer la réalité historique. Par exemple, l'idée d’un Napoléon humilié en permanence par les Anglais est ancrée dans la mentalité populaire comme parmi les élites. D'ailleurs cette distorsion de la réalité est une partie intégrante de la légende napoléonienne. Sans l'idée du calvaire de Napoléon à Sainte-Hélène prisonnier des puissances de la Sainte-Alliance et l’image négative de Hudson Lowe, la figure du captif auprès des libéraux et des nationalistes au XIXe siècle n’aurait pas été la même. La légende de Sainte-Hélène est donc une partie fondamentale de l’histoire napoléonienne. / A territory is undeniably associated with Napoleon and his legend in the minds of the peoples. It is not a question of Corsica, place of birth, but of Saint Helena, place of exile, of death but also of construction of the napoleonic legend. It is on this island of the South Atlantic that between 1815 and 1821 he who, during more than twenty years, made tremble Europe, saw the last years of its existence. The captive during all the years of his detention on St. Helena Napoléon is closely observed. However, the French, between 1815 and 1821, do not know what is happening on this lost island of the South Atlantic. News about this character is rare if not absent and the lack of truthful information about the events of the island is considerable. This observation is accentuated by the situation of St. Helena. It is a distant place, unknown and difficult to understand for the great majority of the French of the nineteenth century. This lack of information leads to the wildest rumors. Indeed, the false news strew the exile of Napoleon, French spread noises, claim to know the truth and to transmit it generally orally, more rarely in writing, to others. If the noises are essentially emitted between 1815 and 1821 they continue during the 1820s and even beyond by multiple relays. Many noises and books offer multiple stories all about Napoleon's exile. Among them, Napoleon escaped from Saint Helena. Real facts have inspired the many evasive theories that flourished from 1815. Thus, kidnapping projects have undeniably been thought out. Nevertheless, none of the plans are put into execution, leading consequently a questioning on the reasons of the absence of their concretization. Maybe, they were simple verbal exchanges between Bonapartists? Finally, rumors endure after 1821 partly thanks to the arts. Indeed, the internment of Napoleon was much represented by literature, painting and more recently by cinema. For example, many nineteenth-century writers drew inspiration from the Emperor's stay in Saint Helena in a more or less obvious way and re-invested the constituent elements of the legend. All the rumors and artistic representations of captivity distort the last years of Napoleon. However, these altered representations remain in the collective memory because they are easier to remember, they are better stories than reality ... And so, mythology ended up altering the historical reality. For example, the idea of ​​a Napoleon permanently humiliated by the British is rooted in the popular mentality as among the elites. Moreover this distortion of reality is an integral part of the Napoleonic legend. Without the idea of ​​Napoleon's ordeal on St. Helena prisoner of the Holy Alliance and the negative image of Hudson Lowe, the figure of the captive among liberals and nationalists in the nineteenth century would not have been the same. The legend of St. Helena is therefore a fundamental part of Napoleonic history.

This report documents the development of a concept and prototype for a mobile application with the purpose of making the megalith graves surrounding the town of Falköping more engaging and interactive for visitors. Because of the limitations of working with heritage sites that cannot be altered to support a gaming experience, the usage of escape room game mechanics is explored. Because escape room games depend on the user's observation and exploration of their environment, they serve as a usable inspiration for applications with the purpose of making visitors experience a location in a similar way. The prototype developed for the project contains puzzles designed for four different megalith grave sites which were then tested with groups of children and parents playing together.

Made available in DSpace on 2016-04-27T19:30:44Z (GMT). No. of bitstreams: 1 Edson Holanda Lima Barboza.pdf: 4849588 bytes, checksum: bb3c4e5e1c04717c71411b260f1a8c0d (MD5) Previous issue date: 2013-05-24 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / We will analyze interferences exerted by refugees from Ceará in the composition of migratory routes towards the provinces of the far North - Piauí, Maranhão, Pará and Amazonas. It interprets the impact of Diaspora of Ceará, between the years 1877 and 1880, due to drought, and how it was perceived by enslaved workers from Ceará and neighboring provinces as opportunities to reverse their identities and lifestyles, enabling captives or criminals to access denied projects of mobilization and social inclusion. The conflicting trajectories involved unruly captives and free paupers traversing provincial centers, public works and agricultural colonies. In this way, enslaved, national and foreign settlers formed contact zones in which it was possible to exchange experiences and solidarities. One main zone was the Núcleo Colonial de Nossa Senhora do Carmo de Benevides, next to Belém, a space planned by local elites to boost agricultural production in Pará, which, however, was a place of unexpected alliances joints that turned this core in place of riots and in focus of abolitionist struggles / Analisamos interferências exercidas por retirantes cearenses na composição de rotas migratórias em direção às províncias do extremo Norte Piauí, Maranhão, Pará e Amazonas. Interpretamos repercussões das Diásporas da população cearense, entre os anos de 1877 e 1880, em decorrência da seca, e como foram percebidas por parte de trabalhadores escravizados do Ceará e de províncias vizinhas, enquanto oportunidades para reverter suas identificações e modos de vida, possibilitando a cativos ou clandestinos acessos a projetos de mobilidade e inserção social até então negados. As trajetórias conflituosas, envolvendo cativos insubordinados e pobres livres, percorreram centros administrativos provinciais, frentes de trabalho e colônias agrícolas. Neste percurso, escravizados, colonos nacionais e estrangeiros formaram zonas de contato em que foi possível a troca de experiências e solidariedades. Um dos principais pontos de convergência foi o Núcleo Colonial de Nossa Senhora do Carmo de Benevides, nas proximidades de Belém, espaço planejado pelas elites locais para fomentar a produção agrícola no Pará, contudo, inesperadas articulações de alianças transformaram este núcleo em palco de motins e foco de lutas abolicionistas

Made available in DSpace on 2016-04-25T20:20:13Z (GMT). No. of bitstreams: 1 Marcelo Romani Peccioli.pdf: 560065 bytes, checksum: b6b607341098eef32b1933e85722788a (MD5) Previous issue date: 2011-05-27 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / The following dissertation intends to problematize the aesthetics of existence, the ones which have as central element the use of drugs, proposed by the writers Aldous Huxley and William Burroughs. . In order to address the problematization, the research goes back to the threaded discussion of Friedrich Nietzsche, Michel Foucault and Gilles Deleuze especially as a Spinoza reader -, as well as the control devices launched by the State since the disciplinary society s emergence, aiming the bodies docilization. To unfold these two thematic axes experimentation and control -, the research approaches the bodies and by doing a brief report on its dissemination in the urban society and the categorization of the drugs user as an abnormal who requires medical caring and police surveillance. Lastly, the dissertation approaches the works of Aldous Huxley and William Burroughs on the matters regarding drugs, their experiments, creations and confrontations. It is all brought up by the concepts developed by Deleuze and Foucault referencing one s aestheticization / A presente dissertação pretende problematizar estéticas de existência propostas pelos escritores Aldous Huxley e William Burroughs, as quais têm no uso de drogas um elemento central. Para isso, a pesquisa retoma a discussão feita por Friedrich Nietzsche, Michel Foucault, Gilles Deleuze especialmente como leitor de Espinosa , assim como os dispositivos de controle lançados pelo Estado desde o advento da sociedade disciplinar, visando ao adestramento dos corpos. Desdobrando esses dois eixos temáticos experimentação e controle , a pesquisa aborda os corpos e o agenciamento drogas, fazendo um breve relato sobre a sua disseminação na sociedade urbana e a caracterização do drogado como um anormal que requer cuidados médicos e atenção policial. Por fim, a dissertação discorre sobre as obras de Aldous Huxley e William Burroughs no que concerne às drogas, seus experimentos, suas produções e seus enfrentamentos, por meio dos conceitos desenvolvidos por Deleuze e Foucault, que fazem referência a uma estetização de si