Wohnen “in Goyas letztem Raum”: Eine intermediale Poetik des Entsetzens. Die Zitierung von Goyas Pinturas Negras in Ingeborg Bachmanns Roman Malina. [Living in “Goya’s Last Room”. An Intermedial Poetics of Dread. Ingeborg Bachmann’s use of Goya’s Pinturas Negras in her novel Malina]

Ingeborg Bachmann’s recurrent references to the Spanish painter Francisco de Goya have frequently been noted, but have so far never been investigated. After outlining, in chapter one, Bachmann’s references to Goya in her thesis on Wittgenstein as well as in the Franza-Fragment and in her only novel Malina, this thesis sets out to highlight the text-image relation between Bachmann’s novel Malina and Goya’s series of murals which are known as the so called „Black Paintings“. Chapter two focuses on the importance of intertextuality and intermediality in Bachmann’s novel and the importance of quotation for the female narrator, who relies on intertextual and intermedial references to express her traumatic experiences. After an introduction into the aesthetics of Goya, in chapter three, chapters four and five examine the text-image relation between Goya’s painting El Perro Semihundido and the first chapter in Bachmann’s novel. The double perspective contained in El Perro, of the subjective expression of the dog’s longing for rescue and the objective futility of this hope as expressed by the dog’s positioning against the abstract background setting, is transferred onto the female narrator and her longing to be rescued through love. Chapter five especially focuses on the (problematic) semantic shifts which occur in the course of this transformation from an abstract representation in the painting to the depiction of concrete and personalized experiences in the text. Chapter six investigates the correlations between Bachmann’s dream chapter and the aesthetics of Goya’s murals, and asks to what extent Bachmann succeeds in transferring the main motifs in Goya’s images into literary form. Chapter seven explores the similarities and media-specific differences in the strategies deployed for depicting madness, violence and destruction in Bachmann’s text and in Goya’s murals and his series of prints on the Desasters of War. Bachmann’s novel Malina shows an extraordinary richness in intertextual and intermedial references. Analysing the explicit as well as implicit references to Goya’s late works in the novel this thesis addresses one area on Ingeborg Bachmann which has not been researched in detail so far

Type I interferons as mediators of the innate immune response to gastrointestinal infection with Listeria monocytogenes

Listeria monocytogenes (Lm) ist ein Gram-positives, fakultativ intrazelluläres Bakterium, ein Humanpathogen und damit eine große Herausforderung für die Nahrungsmittelindustrie. Aufgrund seiner Fähigkeit einzigartige transkriptionelle Programme hochzuregulieren und sich dadurch an verschiedene Umweltbedingungen wie Temperatur, Säure oder Salz anzupassen kann Lm viele ökologische Nischen besetzen. Der natürliche Infektionsweg beim Menschen ist über den Magen-Darm-Trakt, wo sich das Bakterium adaptieren und den Wirt befallen kann. In der Naturwissenschaft ist Lm ein häufig verwendeter Modellorganismus, dessen molekulare Eigenschaften Einblicke in viele fundamentale Prinzipien der Immunologie und Zellbiologie ermöglichen. Die Synthese von Typ I Interferonen (IFN-I) ist eine der ersten Reaktionen des angeborenen Immunsystems auf Listerieninfektion. Um die Rolle von IFN-I nach oraler Verabreichung (i.g.) zu untersuchen, wurde in der vorliegenden Arbeit der murinisierte LO28InlA* Stamm verwendet, welcher mit murinem E-cadherin auf Epithelzellen interagieren kann. Dabei zeigte sich, dass IFN-I eine protektive Wirkung auf den Wirt haben, da Mäuse ohne IFN-I Rezeptorkette 1 (Ifnar1-/-) anfälliger sind als Wild-typ C57BL/6N Mäuse (Wt). Dies steht im Gegensatz zu früheren Aufzeichnungen, die IFN-I nach systemischer (i.p.) Infektion als nachteilig für den Wirt beschreiben. Histologische Untersuchungen des Darms ergaben, dass Lm nur stellenweise Zellen der Mucosa, unterhalb der Epithelschicht in Darm-assoziierten lymphoiden Geweben (GALT), infiziert. Jedoch waren Infektionsausmaß bzw. -verteilung zwischen Wt und Ifnar1-/- Mäusen sehr ähnlich. Diese Beobachtungen wurden durch histologische Untersuchungen, Genexpressions-analysen und Bestimmung von Bakterienmengen im Darm assoziierten Immungewebe, wie den Peyer’s patches (PP) und den mesenterialen Lymphknoten (MLN), bestätigt. Der unterschiedliche Phänotyp zwischen i.g. infizierten Wt und Ifnar1-/- Mäusen war am stärksten ausgeprägt in der Leber, einer wichtigen Replikationsnische von Lm am Weg zur systemischen Infektion. Zu Beginn der Infektion befindet sich Lm noch in Hepatozyten, gefolgt von Infiltrierung von Gr1+ myeloider Zellen und anderen Leukozyten. Kleinere Infiltrate enthielten auch F4/80+ Makrophagen, die Anzahl dieser Zellen nahm allerdings mit der Größe der Infiltrate ab. 48h nach i.g. Infektion waren die Infiltrate mit massiven Zelltod assoziiert, sowohl innerhalb als auch um das Infiltrat herum. 30% der Ifnar1-/- Mäuse zeigten diesen dramatischen Phänotyp, korrelierend mit der Letalität der Infektion. Dennoch überlebte der Großteil der Mäuse dieses Stadium, höchstwahrscheinlich wegen steigender IFNg Werte im Blut. Zytokinmessungen während der Infektion ergaben, dass das Expressionsprofile von frühem IL-6, IFNg und MCP-1 prognostisch für den Grad der Infektion sind da i.g infizierte Wt Mäuse hohe Werte dieser Zytokine zeigten. Vermutlich ist der Wirt durch eine besser regulierte Immunantwort, mit IFNα und IFNβ als Mediatoren, besser auf Bakterien aus dem Darm vorbereitet als auf solche die systemisch verabreicht werden, denn Ifnar1-/- Mäusen fehlt eine adäquate Immunantwort innerhalb der ersten 24h. In diesem Zeitfenster können Listerien Fuß fassen und replizieren. In welchem Organ/ Zellen die IFN-I Antwort die wichtigste Rolle spielt steht noch nicht fest. Wir können allerdings eine verstärkte Rolle für IFN-I an der intestinalen Eintrittsstelle ausschließen. Vielmehr vermuten wir eine wichtige Rolle der Typ III Interferone (IFN-III), da IRF9-/- Mäuse, die weder auf IFN-I noch IFN-III Interferone reagieren können, höhere Bakterienanzahlen aufzeigen als Ifnar1-/- Mäuse. Zusammengefasst öffnen die Ergebnisse meiner Arbeit neue Perspektiven im Hinblick auf die Rolle von IFN-I bei bakteriellen Infektionen. Sie unterstreichen eine herausragende Rolle der Infektionsroute durch den inversen Effekt eines Zytokins nach gastrointestinaler oder systemischer Verabreichung.Listeria monocytogenes (Lm), a Gram-positive facultatively intracellular bacterium, is a human pathogen and a major challenge to the food industry. It occurs ubiquitously due to its ability to upregulate unique transcriptional profiles under diverse environmental conditions, such as temperature, acid or salt. Its natural route of infection is through the gastrointestinal tract where it can adapt to and invade the host. In biological sciences Lm is a widely used model organism that has provided insight into many fundamental principles of immunology or cell biology. Synthesis of type I interferons (IFN-I) is one of the immediate innate responses to infection with Lm. Here, the mouse-adapted LO28InlA* strain, that is capable to interact with the murine epithelial junction protein E-cadherin, was used to study the impact of IFN-I responses on intragastric (i.g.) infection with Lm. IFN-I were shown to protect murine hosts in this situation, as mice lacking the IFN-I-receptor-chain 1 (Ifnar1-/-) were more susceptible than Wild-type C57BL/6N mice (Wt). This is in striking contrast with previous reports on systemic Lm infection, where IFN-I were described to be detrimental. Histological analysis of the gut revealed infected cell patches in the mucosal tissue underlying the epithelium and in the gut-associated lymphoid tissue (GALT), but the pattern or extent of infection was highly similar between Wt and Ifnar1-/- mice. This finding was corroborated by histological analysis, studies of gene expression and by the determination of bacterial burden with colony-forming-unit (CFU) assays of intestinal tissue including Peyer’s patches (PP) and mesenteric lymph nodes (MLN). The difference arising from i.g. infection between Wt and Ifnar1-/- mice was most pronounced in the liver, an early target organ of Lm on its way to systemic spread. Initially, Listeria resided in hepatocytes, following immune cell infiltration of Gr1+ myeloid cells and other leukocytes. In addition, smaller infiltrates containing F4/80+ macrophages were observed. Interestingly F4/80+ cells became increasingly rare as the size of inflammatory infiltrates increased. 48hrs after i.g. infection, massive cell death was found within the infiltrate as well as the surrounding hepatic tissue. About thirty percent of Ifnar1-/- mice displayed this dramatic liver phenotype and this correlated well with the lethality of infection. The majority of mice survived this stage, most likely due to a strong increase of IFNg production. Measurement of cytokine profiles during infection showed that the pattern of early IL-6, IFNg and MCP-1 production appears to be prognostic for the severity of infection. Wt mice infected i.g. displayed the highest levels of these cytokines early after infection. Speculatively, mammalian hosts are better adapted to gut-derived as opposed to systemic bacteria, resulting in a more regulated immune response with IFN-I as one of the first mediators. Ifnar1-/- mice seem to miss an adequate response within the first 24h, a timeframe for Lm to colonize its host and replicate. While our studies cannot definitively identify the relevant target organs or cells for IFN-I action after i.g. infection, they rule out a pronounced role for IFN-I at the site of intestinal entry. Interestingly, an impact of type III interferons (IFN-III) on the intestinal epithelium is suggested by the fact that IRF9-/- mice, that are unresponsive to both IFN-I and IFN-III, show an even higher bacterial burden than Ifnar1-/- mice upon i.g. infection. Taken together, the results presented in my thesis open a new perspective on the role of IFN-I in bacterial infections. They emphasize the importance of the infection route by demonstrating opposing roles of the cytokines upon infection via gastrointestinal or systemic administration

Spherical nanoindentation – advancements and prospects towards its application as a multifunctional testing technique

With the development of modern high-performance materials and components, cases increase where conventional testing techniques used for the mechanical characterization miss their target. Material fabrication at a bench scale, miniaturization and not least cost-effectiveness yearn for a highly reliable, fast and highly automatable testing technique. Even though uniaxial micromechanical tests on micro-pillars or -tensile samples are well suitable for the extraction of flow curves, they face the problem of elaborate specimen manufacturing. Spherical nanoindentation could be a candidate technique to overcome the mentioned drawbacks, since time needed for sample preparation is tremendously reduced. The present study will outline solutions of existing problems, which may lay the foundation for spherical nanoindentation to become a widely-used testing technique. Main objections concerning tip imperfections will be resolved by modifying the calibration procedure, and validated on a broad spectrum of materials independent of the indenter tip radius. Once the actual tip shape is available, displacement-time profiles can be designed to guarantee constant strain-rates during testing and thus permit the determination of the strain-rate sensitivity for rate-dependent materials. Finally, the comparison between nanoindentation flow curves and uniaxial tests will evidence that spherical indentation is a highly reliable technique for the extensive mechanical characterization of modern high-performance materials and show its high potential as a multifunctional standard testing technique. Please click Additional Files below to see the full abstract

ATP-dependent Remodelling of Linker Histone-Containing Nucleosomal Fibres

Eukaryotic genomes are condensed into a multilevel structure called chromatin which serves to organize and package the DNA, but at the same time needs to be flexible to permit regulated access to the stored information. ATP-dependent chromatin remodelling factors largely contribute to this dynamic nature of chromatin by catalysing processes such as the disruption of histone-DNA contacts, nucleosome repositioning and histone exchange. ATP-dependent remodelling has been well documented on a mononucleosomal level, but little is known about its regulation in a more physiological chromatin environment, where neighbouring nucleosomes and linker histones might interfere with the remodelling reaction. If and to what extent remodelling can work on chromatin bound by linker histones remains controversial, in spite of their high abundance and their strong influence on chromatin folding. We therefore investigated chromatin remodelling in the presence of linker histones H1 or H5 using regularly spaced, oligonucleosomal substrates reconstituted from purified components. Surprisingly, we found that both the remodelling complex ACF – consisting of the ATPase ISWI and the regulatory subunit ACF1 – and ISWI alone were able to catalyse the repositioning of entire chromatosomes (nucleosomes + H1). Linker histones inhibited their remodelling activity by only about 50%. In contrast, the related ATPase CHD1 remodelled chromatin only in the absence of linker histones, suggesting that linker histones allow remodelling by selected factors only. In addition, our data indicate that repositioning in the presence of H1 might be unidirectional. ACF1 is abundant during early Drosophila development, when H1 gradually replaces its early placeholder HMG-D. HMG-D binds to chromatin less tightly than H1 and unlike the latter, did not affect the remodelling activity of ACF in our assay. H1 was able to displace HMG-D from and bind to our reconstituted arrays without the help of cofactors. Strikingly, both H1 and HMG-D are more abundant in embryonic nuclei of acf1 null flies compared to the wild-type, raising the possibility that an ACF1-containing complex controls linker histone incorporation

Investigating thermally activated deformation mechanisms by high temperature nanoindentation – A Study on W-Re alloys

Since the advent of indentation at elevated temperatures the technique of high-temperature nanoindentation has been further developed, currently enabling testing temperatures above 1000 °C. Due to small sample sizes and a variety of different testing techniques this method provides the opportunity for alloy development at a new level regarding composition variety or efficiency. In this study the thermally activated deformation mechanisms in binary W-Re alloys will be investigated by using a high-end in-situ nanoindenter. For that purpose, three different materials were tested, namely commercially pure W, W5Re and W10Re, all of them in both, coarse grained and ultra-fine grained condition. Nanoindentation experiments were conducted from ambient temperatures up to 800 °C, thereby overcoming the critical temperature TC of tungsten at around 450 °C. With temperature increments of 100 °C a large range of the normalized temperature with respect to TC is covered, allowing general conclusions regarding the appearing deformation mechanisms in bcc metals. Additionally to constant indentation strain rate tests, strain rate jump tests were utilized to determine the mechanical properties and to evaluate the impact of temperature and microstructure on rate-dependent parameters. A strong influence of the alloying level with Re as well as the grain size on both, the thermal and athermal contribution to the flow stress, is observed. The origin and effects, such as solid solution softening for W5Re at temperatures far below TC, will be discussed in detail. Furthermore, the dominating deformation mechanisms in dependence of temperature and grain size are determined. In the coarse grained materials a change in deformation processes from kink-pair mechanism to dislocation-dislocation interaction at higher temperatures can be observed, while in ultra-fine grained materials grain boundary/dislocation interactions are responsible for the maintained time-dependent mechanical behavior

Phase transformations and local deformation mechanisms - A case study on Cu 20 m.% Sn

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Indentation unloading phase transformations in silicon: A new perspective

nanoindentation, silicon, Berkovich, contact pressure, continuous stiffness measuremen