There is a significant body of literature stating that caffeine is the most widely consumed drug in the world, yet its effects on operant behavior are little understood. Some of the current research on caffeine suggests that it may play a role in altering motivational states related to transitions between previous and upcoming work requirements. The purpose of the current study was to examine the effects of caffeine on postreinforcement pausing during transitions between small and large fixed ratio rudiments. Eight rats were exposed to five doses of caffeine and and a two-component multiple schedule. We found that caffeine does systematically alter the length of pausing during transitions between fixed ratio requirements, however the magnitude of the effect may be dependent on the baseline rate of responding.

Koordinierte Phosphorylierung der C-terminale Domäne von RNA Polymerase II (RNAPII) ist essentiell für eine effiziente Kupplung von naszierender RNA Synthese und co-transkriptionalem RNA Prozessierens. Zirkuläre RNAs (circRNAs) sind eine neue Klasse von RNA Molekülen mit hoher Prävalenz in neuronalen Zelltypen. Die Biogenese von circRNAs ist noch ungeklärt, insbesondere die Frage warum das Intron upstream der circRNA während der Transkription des circRNA Exons zurückbehalten wird um Rück-Spleißen zu ermöglichen. Verschiede Belege suggerieren, dass unzulängliche Rekrutierung des Spleiceosoms zur circRNA Formation führen kann. In dieser Arbeit untersuche ich die Mechanismen die zu Defekten in der Erkennung und des Spleißens des Introns upstream der circRNA führen. Mit diesem Ziel erfasste ich die genomweite Verteilung von chromatinassoziierter RNAPII mit verschiedenen Phosphorylierungen, sowie Spleißfaktoren und Transkriptionsreglern mittels ChIP-seq in neuronaler Differenzierung von murinen embryonalen Stammzellen zu dopaminergen und Motoneuronen. Während der gesamten Differenzierung, aber insbesondere in den differenzieren Neuronen, konnten circRNAs detektiert werden. In meiner Arbeit finde ich, dass circRNAs detektiert werden, wenn Gene hohe Levels an mRNA exprimieren und, dass die Produktion von circRNA mit einer Dysbalance zwischen dem Laden der RNA-Polymerase II auf die DNA und dem Rekruitieren der Splice-Maschinerie zusammen hängt. Um funktionell mit den Pausier-Mechanismen der RNA-Polymerase II zu interferieren, habe ich einen ''promotor-proximal-pausing'' Faktor depletiert. Dabei stellte ich fest, dass diese Depletion genügt, um die circRNA Levels in embryonalen Stamzellen zu erhöhen. Die Ergebnisse die in dieser Arbeit gezeigt werden, beschreiben die Beteiligung des Pausierens der RNA-Polymerase II and der Formierung von circRNAs. / Coordinated phosphorylation of RNA polymerase II (RNAPII) C-terminal domain is essential for efficient coupling of nascent RNA synthesis with co-transcriptional RNA processing events. Circular RNAs (circRNAs) are a novel class of RNAs whose biogenesis remains ill understood, namely why the upstream intron is not spliced before the circRNA-exon is fully transcribed. Indirect evidence suggests that altered spliceosome recruitment can lead to circRNA formation. To investigate the mechanisms that may be involved in deficient recognition and splicing of introns upstream of exons included in circRNAs, I mapped the chromatin occupancy of RNAPII phosphorylated forms, splicing factors, and transcription regulators by ChIP-seq during mouse ESC differentiation to dopaminergic and spinal motor neurons. CircRNAs are detected throughout differentiation, peaking in differentiated neurons, as expected. I found that circRNAs are detected when genes express high levels of mRNA, and that circRNA production is associated with an imbalance between RNAPII loading and recruitment of the splicing machinery. To mechanistically interfere with pausing mechanisms, I depleted an RNAPII promoter-proximal pausing factor, and found that it was sufficient to increase the formation of circRNAs in stem cells. Results shown in this work implicate RNAPII regulation mechanisms in the formation of circRNAs.

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The study explores pausing in action is, within the ambit of Strategy-as-practice (s-ap) as an emergent school of thought. Pausing is thus discerned during the implementation phase of the strategy of a credit risk system within a South African bank, as strategy is known to take shape during implementation. Different sites of the bank’s systems – change, strategy practitioners, and their times of pausing, form the unit of analysis. Strategy-making and engagement are explored by understanding the influence of pausing on enabling or disenabling the strategic outcome of the risk system. Pausing is situated in an applied and theoretical gap as an intangible under-theorised strategy practice. Practitioners, as champions or non-champions of strategy, pause in various ways, and attribute meaning to this ‘action’. Their account of pausing is recognised for its value-adding or diminishing dimensions to strategy-making. The study follows a comprehensive literature review which shows limited theoretical positions on embodied, latent practices, such as pausing, as strategic practices. The body of knowledge provides a challenge for scholars to consider perceived ‘silences’ or the ‘receding’ of strategists as un-remarked dimensions of strategy, which could nevertheless be instrumental in the nature of the strategic outcome. The contribution of the current study identifies pausing as a strategic practice, especially when considered within the structure of engagement and social learning / Business Management / M. Com. (Business Management)

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