2,160 research outputs found
Targeting cell envelope synthesis of Streptococcus pneumoniae and microfluidic diagnostic tool development
No full textEvolving antibiotic resistance warrants the development of new therapeutic and diagnostic approaches as part of the strategies to secure future antibacterial therapies and preserve the compounds currently available. Work constituting the thesis characterized small molecules yielded from a screen for autolysis inducing compounds on Streptococcus pneumoniae. Two compound classes were characterized, and their targets identified.The alkylated di-cyclohexyl carboxylic acid 2CCA-1 was identified as a fatty acid mimetic, that is incorporated into pneumococcal phospholipids via the polyunsaturated host fatty acid metabolism pathway. The formed 2CCA-1 containing lipids alter membrane fluidity, and treatment with 3 μM 2CCA-1 resulted in decreased pneumococcal viability and cell wall hydrolase mediated lysis. Deletion of the fatty acid binding protein FakB3 rendered pneumococci resistant to 2CCA-1, which could explain the inherent 2CCA-1 resistance of Staphylococcus aureus as FakB3 homologues are predominantly absent in bacteria of the Bacillales order. The involvement of the transcriptional repressor of the endogenous fatty acid synthesis machinery FabT in 2CCA-1 resistance, showed that FakB3 dependent host fatty acid incorporation is regulated depending on extracellular fatty acid availability.The second compound class comprised analogs of 1-amino substituted Tetrahydrocarbazoles (THCz). THCz analogs are active in the low micromolar range against an array of gram-positive bacteria as well as mycobacteria, Neisseria gonorrhoeae and Moraxella catarrhalis. Mode of action studies identified the pyrophosphate moiety of undecaprenyl pyrophosphate as the minimal binding motif for THCz, which depended on the central diamino moiety for activity. THCz analogs consequently inhibited cell wall, teichoic acid and capsular biosynthesis. Reduction of the polysaccharide capsule increased pneumococcal tolerance to the compound, but resistant mutants could not be obtained.Furthermore, we developed a microfluidic based sample preparation method for decomplexation of bacteria containing whole blood. First, blood cells were selectively lysed while preserving bacterial viability. For the reduction of the small, below micrometer sized debris, gradient acoustic focusing was developed, that allowed separation of bacteria from the blood lysate in a microfluidic channel. The so purified sample might facilitate further microfluidic downstream operations to accelerate antimicrobial susceptibility determination of the sepsis causing pathogen. In conclusion, the thesis work identifies the target of two new compounds with bactericidal activity and presents a microfluidic based method for sample preparation as tool in sepsis diagnosis.List of scientific papersI. Reithuber E., Nannapaneni P., Rzhepishevska O., Lindgren AEG., Illchenko O., Normark S., Almqvist F., Henriques-Normark B., Mellroth P. The bactericidal fatty acid mimetic 2CCA-1 selectively targets pneumococcal extracellular polyunsaturated fatty acid metabolism. mBio. 2020 Dec 15; 11(6):e03027-20. https://doi.org/10.1128/mBio.03027-20 II. Reithuber E., Wixe T., Ludwig K.C., Müller A., Uvell H., Grein F., Lindgren AEG., Muschiol S., Nannapaneni P., Eriksson A., Schneider T., Normark S., Henriques-Normark B., Almqvist F., Mellroth P. THCz – A small molecule with antimicrobial activity that blocks cell wall lipid intermediates. [Manuscript]III. Van Assche D., Reithuber E., Qiu W., Laurell T., Henriques-Normark B., Mellroth P., Ohlsson P., Augustsson P. Gradient acoustic focusing of sub-micron particles for separation of bacteria from blood lysate. Sci Rep. 2020 Feb 28; 10(1):3670. https://doi.org/10.1038/s41598-020-60338-2 </p
Dr. Elisabeth Gruner - Faculty Author Interview
No full textDr. Elisabeth Gruner, Associate Professor of English, discusses her new book, Constructing the Adolescent Reader in Contemporary Young Adult Fiction, published recently by Palgrave Macmillan. The book considers a range of contemporary titles in order to explore the types of reading sparked through various forms of adolescent fiction
Inter-generational family support provided by older people in Indonesia
No full textMost social research on ageing in Asia has focused on the support provided by adult children to their parents, and thereby suggests that as a matter of course older people are in need of support. This paper offers a different perspective. Drawing on ethnographic and quantitative data from a village in East Java, it examines the extent of older people's dependence on others and highlights the material and practical contributions that they make to their families. It is shown that only a minority of older people are reliant on children or grandchildren for their daily survival. In the majority of cases, the net flow of inter-generational support is either downwards – from old to young – or balanced. Far from merely assisting with childcare and domestic tasks, older people are often the economic pillars of multi-generational families. Pension and agricultural incomes serve to secure the livelihoods of whole family networks, and the accumulated wealth of older parents is crucial for launching children into economic independence and underwriting their risks. Parental generosity does not generally elicit commensurate reciprocal support when it is needed, leaving many people vulnerable towards the end of their lives
Ambiguity of Scale:Thomas Mann's The Magic Mountain — an Anthropocene Novel?
No full textThomas Mann’s The Magic Mountain is obsessed with questions of scale. Whether in its incessant reflection on days, weeks, months, years, minutes, or depths of fathoms and meters of altitude, the novel is driven by questions of the measurability of time and space. At the same time, one would hardly want to speak of measurability with regard to The Magic Mountain, either in terms of time or space. What, then, is this obsession with scale? The Magic Mountain, Strowick will argue, generates literary scales beyond measurability that address what the novel calls the ‘dual nature’ [Zwienatur] of time and space. The talk will explore this ambiguity of scale and its consequences for the question of narrative and the form of the novel. About 100 years after the publication of Thomas Mann’s novel, questions of scale are often discussed in theories of the Anthropocene. In fact, ‘scale critique’ is one of the most promising ways to analyse the Anthropocene. Is The Magic Mountain a setting for ‘scale critique’, an Anthropocene novel avant la lettre? Elisabeth Strowick is a Professor of German in the Department of German at New York University. Before joining NYU, she was Professor of German and Humanities, Chair of the Department of German and Romance Languages and Literatures, and Co-Director of the Max Kade Center for Modern German Thought at Johns Hopkins University. Elisabeth Strowick has held numerous academic positions, including visiting professorships, at universities in the United States, Germany (FU Berlin, Zentrum für Literatur- und Kulturforschung Berlin, University of Hamburg), and Switzerland (University of Zurich, University of Basel). She was awarded a Feodor Lynen Fellowship by the Alexander von Humboldt Foundation (Yale, Johns Hopkins, 2004-2006). Her areas of expertise are German literature, culture, and thought from the 19th century to the present, with special emphasis on literary theory, psychoanalysis, aesthetics, the poetics of knowledge, and ecocriticism. She is the author of Passagen der Wiederholung: Kierkegaard — Lacan — Freud (Metzler, 1999), Sprechende Körper — Poetik der Ansteckung (Fink, 2009), Gespenster des Realismus. Zur literarischen Wahrnehmung von Wirklichkeit (Fink, 2019) and has (co-)edited numerous volumes and special issues of peer-reviewed journals. Elisabeth Strowick is currently working on a book on ‘Literary Scale Critique: The Anthropocene as Deep War Time’.00:00 Introduction by Claudia Peppel07:29 Talk by Elisabeth Strowick1:09:48 Discussio
St. Elisabeth Heritage Garden: Refurbish of St. Elisabeth complex
No full textSt. Elisabeth complex is located at the edge of Nieuwstad. The site includes valuable heritages such as Berkelpoort, city wall and tower from the 14th century. However St. Elisabeth building has separated these monuments from the public since 1993, and these cultural assets are not being properly maintained. Is cultural property justified by means of private use?Heritages are a national asset. Everyone has the right to learn history through heritage. Therefore, when the circumstances allow it, heritage must be shared in public. The historical elements in this complex can provide great future opportunities to Nieuwstad. In this project, I suggest a ‘Heritage garden’ as a cultural hub of the Nieuwstad. Architecture, Urbanism and Building Science
Detection of rare mutations using bead emulsion amplification : optimization of water-in-oil emulsion stability for simultaneous detection of rare mutations
No full textAuthor Elisabeth Palzenberger, B.Sc.Abstract in deutscher und englischer SpracheMasterarbeit Universität Linz 201
"Harmonious coexistence" - St. Elisabeth nursing home renovation project
No full textThe renovation project of St. Elisabeth in Zutphen is guided by the concept of "sustainable city". Meanwhile as a graduation project in the studio of heritage and architecture, how to deal with the relation between historic relics and modern architectures is important. During the whole process of my project, I started my design assignment with previous analysis and research.Architecture, Urbanism and Building Science
Zagłada, ofiara i zwierzęta w myśli Elisabeth de Fontenay
No full textThe Shoah, the Sacrifice, and the Animal in Elisabeth de Fontenay’s ThoughtThe article aims at presenting the views of a French philosopher Elisabeth de Fontanay on the issue of proximity between the Shoah and the inhuman, industrial treatment of animals.The author not only explains the history of such a contextualisation of the problem, but also tackles the question of the meaning of a sacrifice, which is a term often used to define both the extermination of the Jews and the mass animal slaughter.
Key words: Elisabeth de Fontenay, Shoah, sacrifice, animals, mass slaughte
Conference: Prof. Elisabeth Kaske
No full textOn 7 February 2020, the ENP-China project will receive Prof. Elisabeth Kaske (Leipzig University), a foremost historian of late Qing China in Germany with a broad range of academic interests. She is the author of The Politics of Language in Chinese Education: 1895 - 1919, which underpins the conference she will give at Aix-Marseille University. The First Congress: The 1913 Conference for the Unification of Reading Pronunciations and its Significance for the May Fourth Movement 7 Februa..
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