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Single long-chain omega-3 fatty acids (e.g. docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA)) are known for their neuroprotective properties associated with ischemic stroke. This pilot study aimed to test the effectiveness of an acute treatment with a long-chain omega-3 lipid emulsion (Omegaven 10%®, OGV) that contains fish oil (DHA 18 mg/ml; EPA 21 mg/ml) and α-tocopherol (0.2 mg/ml) in a transient middle cerebral artery occlusion (MCAO) model of ischemic stroke in mice. For this purpose, female CD-1 mice were anesthetized and subjected to 90 minutes of MCAO. To reflect a clinically relevant situation for an acute treatment, either after induction of stroke or after reperfusion, a single dose of OGV was injected intravenously into the tail vein (5 ml/kg b.w.). A neurological severity score was used to assess motor function and neurological outcome. Stroke-related parameters were determined 24 hours after MCAO. Microdialysis was used to collect samples from extracellular space of the striatum. Mitochondrial function was determined in isolated mitochondria or dissociated brain cells. Inflammation markers were measured in brain homogenate. According to control experiments, neuroprotective effects could be attributed to the long-chain omega-3 content of the emulsion. Intravenous injection of OGV reduced size and severity of stroke, restored mitochondrial function, and prevented excitotoxic glutamate release. Increases of pro-inflammatory markers (COX-2 and IL-6) were attenuated. Neurological severity scoring and neurochemical data demonstrated that acute OGV treatment shortly after induction of stroke was most efficient and able to improve short-term neurological outcome, reflecting the importance of an acute treatment to improve the outcome. Summarising, acute treatment of stroke with a single intravenous dose of OGV provided strong neuroprotective effects and was most effective when given immediately after onset of ischemia. As OGV is an approved fishoil emulsion for parenteral nutrition in humans, our results may provide first translational data for a possible early management of ischemic stroke with administration of OGV to prevent further brain damage.
Preserving a patient’s own teeth—even in a difficult situation—is nowadays preferable to surgical intervention and therefore promotes development of suitable dental repair materials. Biodentine®, a mineral trioxide aggregate substitute, has been used to replace dentine in a bioactive and biocompatible manner in both the dental crown and the root. The aim of our study was to evaluate the influence of Biodentine® on pulp fibroblasts in vitro. For this study, one to five Biodentine® discs with a diameter of 5.1mm were incubated in DMEM. To obtain Biodentine® suspensions the media were collected and replaced with fresh medium every 24h for 4 days. Primary pulp cells were isolated from freshly extracted wisdom teeth of 20–23 year old patients and incubated with the Biodentine® suspensions. Proliferation, cell morphology, cell integrity and cell viability were monitored. To evaluate the effect of Biodentine® on collagen type I synthesis, the secretion of the N-terminal domain of pro-collagen type I (P1NP) and the release of transforming growth factor-β1 (TGF-β1) were quantified. None of the Biodentine® suspensions tested influenced cell morphology, proliferation or cell integrity. The cell viability varied slightly depending on the suspension used. However, the concentrations of P1NP of all pulp fibroblast cultures treated for 24h with the moderate to high Biodentine® concentration containing suspensions of day 1 were reduced to 5% of the control. Furthermore, a significant TGF-β1 reduction was observed after treatment with these suspensions. It could be shown that Biodentine® is biocompatible. However, dissolved particles of the moderate to high concentrated Biodentine® suspensions 24h after mixing induce a significant reduction of TGF-β1 release and reduce the secretion of collagen type I of primary pulp fibroblasts.
It is long known that Kasugamycin inhibits translation of canonical transcripts containing a 5’-UTR with a Shine Dalgarno (SD) motif, but not that of leaderless transcripts. To gain a global overview of the influence of Kasugamycin on translation efficiencies, the changes of the translatome of Escherichia coli induced by a 10 minutes Kasugamycin treatment were quantified. The effect of Kasugamycin differed widely, 102 transcripts were at least twofold more sensitive to Kasugamycin than average, and 137 transcripts were at least twofold more resistant, and there was a more than 100-fold difference between the most resistant and the most sensitive transcript. The 5’-ends of 19 transcripts were determined from treated and untreated cultures, but Kasugamycin resistance did neither correlate with the presence or absence of a SD motif, nor with differences in 5’-UTR lengths or GC content. RNA Structure Logos were generated for the 102 Kasugamycin-sensitive and for the 137 resistant transcripts. For both groups a short Shine Dalgarno (SD) motif was retrieved, but no specific motifs associated with resistance or sensitivity could be found. Notably, this was also true for the region -3 to -1 upstream of the start codon and the presence of an extended SD motif, which had been proposed to result in Kasugamycin resistance. Comparison of the translatome results with the database RegulonDB showed that the transcript with the highest resistance was leaderless, but no further leaderless transcripts were among the resistant transcripts. Unexpectedly, it was found that translational coupling might be a novel feature that is associated with Kasugamycin resistance. Taken together, Kasugamycin has a profound effect on translational efficiencies of E. coli transcripts, but the mechanism of action is different than previously described.
The condensation phase transition and the number of solutions in random graph and hypergraph models
(2016)
This PhD thesis deals with two different types of questions on random graph and random hypergraph structures.
One part is about the proof of the existence and the determination of the location of the condensation phase transition. This transition will be investigated for large values of $k$ in the problem of $k$-colouring random graphs and in the problem of 2-colouring random $k$-uniform hypergraphs, where in the latter case we investigate a more general model with finite inverse temperature.
The other part deals with establishing the limiting distribution of the number of solutions in these structures in density regimes below the condensation threshold.
The three 'Materialienbände' - 'Schnitte'; 'Rom, Blicke'; and 'Erkundungen für die Präzisierung des Gefühls für einen Aufstand' - that Rolf Dieter Brinkmann produced in the early 1970s have, in the last decade, gradually come to be recognized as central statements of a radically new cultural formation. A peculiar feature of this recognition, though, is the relative puzzlement that lingers over the question as to the 'form' of these volumes. That the three objects resist generic classification is by now a truism of the Brinkmann literature; yet even the construction of a cultural field within which the volumes might be compared to other works has remained elusive. The essay that follows, based largely on a reading of 'Rom, Blicke', is an attempt to construct precisely that cultural field.
Wie kann man Gedichte verstehen, in denen die Rolle von Lesern nicht vorgesehen ist? Was erlebt man mit derartig abweisenden Texten, und wie findet man sich hinein - zumindest ein Stück weit? Von der großen amerikanischen Lyrikerin Emily Dickinson (1830-1886) sind zu ihren Lebzeiten nur zehn Gedichte gedruckt worden, noch dazu anonym und ohne ihre Zustimmung. Dabei hätte die Autorin durchaus Publikationsmöglichkeiten gehabt. Aber sie wollte die formalen und inhaltlichen Anpassungen an den Publikumsgeschmack, die ihr Mentor, der Essayist Thomas Higginson, empfohlen hatte, nicht vornehmen. Grundsätzlich wollte sie sich nicht auf den Marktplatz des Literaturbetriebs zerren lassen. In ihrer Schlafzimmerkommode hinterließ sie bei ihrem Tod ca. 1.800 Gedichte. Ein Drittel davon hatte sie zu Lebzeiten an Freunde und Bekannte weitergeschickt, aus denen sie sich selbst das Lesepublikum für ihre Lyrik schuf. Aber zwei Drittel ihrer Gedichte hatte sie an niemanden verschickt, niemandem gezeigt und vermutlich einzig für sich selbst geschrieben. Kein Wunder, dass diese Gedichte dunkel sind. Wenn die Dichterin selbst die einzige Leserin ihres Textes ist, braucht sie nichts zu erklären. Deshalb, und nicht weil die Gedichte - wie schon behauptet wurde - "von einer sehr fernen Glossolalie gestreift" sind, wirken viele ihrer Texte so rätselhaft.
Passionen der Ordnung
(2010)
In ihrer Schrift 'Über Revolution' (1963) bekennt sich Hannah Arendt zu einer politischen Passion des Mitfühlens - einer 'passion for compassion'. Die Wurzeln dieses Mitfühlens sind wesentlich dem semantischen wie begrifflichen Humus der schottischen Aufklärung entliehen. Der Text ergänzt jene von Arendt idealisierte Figur der griechischen 'polis' als Fundament einer guten, erstrebenswerten Ordnung. Die Resultante aus der Passion des Mitfühlens und der Figur der 'polis' - so will es scheinen - ist die Republik, wie sie sich idealerweise in den Institutionen der Amerikanischen Revolution niederschlägt; und dies in Kontrast zu der von Arendt wenig gelittenen Traditionslinie der Französischen Revolution, die ihrerseits von glühenden, indes wenig regulierten Passionen eines sich sozial begründenden Mitgefühls angefacht wird.
War die "Vernichtung der Sinnlichkeit" durch die "Civilisation" genannte dritte Stufe (nach "Wildheit" und "Barbarei") in der Kulturgeschichte der Menschheit der eine Impuls von Fouriers Sozialutopie, so stellte die Trennung von Körper und Geist, von 'sciences incertaines' und 'sciences fixes' den anderen, mathematisch und musikalisch imprägnierten Impuls dar. Demgegenüber bilden sowohl eine Theorie der Leidenschaften, der 'association passionnelle', als auch eine pädagogische Haus- und Lebensordnung für die Phalanstères - die idealen Wohn- und Produktionsgenossenschaften - in Fouriers Utopie die 'pivots', so der von ihm erfundene Begriff, das heißt die Grundpfeiler und Leitlinien.
Schon seit Ende der 1980er Jahre und bis heute setzt der Schweizer Künstler Thomas Hirschhorn Gesten in den öffentlichen Raum, aber auch in Museen und in Galerien, die das Wesen eines irrlichternden Mementos aufweisen, Zeichen einer kalkuliert in Szene gesetzten Hilflosigkeit. Dabei erfindet er sozusagen eine Kunstfigur, die seine Werke zu machen scheint. Seine wuchernden Objekte, Schrift- und Bildtafeln, entsprechen Handlungen, die ein Getriebener, ein Wahnsinniger gemacht haben könnte. Hirschhorn betätigt sich somit als Überbringer einer entfesselt leidenschaftlichen Emotionalität, die in krassem Kontrast steht zum kontrollierten, von der Vernunft gelenkten, von übertriebenen Affekten und Irrationalität geläuterten Idealbild des westlich aufgeklärten Kulturmenschen.
Thyroid hormone is a crucial regulator of gene expression in the developing and adult retina. Here we sought to map sites of thyroid hormone signaling at the cellular level using the transgenic FINDT3 reporter mouse model in which neurons express β-galactosidase (β-gal) under the control of a hybrid Gal4-TRα receptor when triiodothyronine (T3) and cofactors of thyroid receptor signaling are present. In the adult retina, nearly all neurons of the ganglion cell layer (GCL, ganglion cells and displaced amacrine cells) showed strong β-gal labeling. In the inner nuclear layer (INL), a minority of glycineric and GABAergic amacrine cells showed β-gal labeling, whereas the majority of amacrine cells were unlabeled. At the level of amacrine types, β-gal labeling was found in a large proportion of the glycinergic AII amacrines, but only in a small proportion of the cholinergic/GABAergic ‘starburst’ amacrines. At postnatal day 10, there also was a high density of strongly β-gal-labeled neurons in the GCL, but only few amacrine cells were labeled in the INL. There was no labeling of bipolar cells, horizontal cells and Müller glia cells at both stages. Most surprisingly, the photoreceptor somata in the outer nuclear layer also showed no β-gal label, although thyroid hormone is known to control cone opsin expression. This is the first record of thyroid hormone signaling in the inner retina of an adult mammal. We hypothesize that T3 levels in photoreceptors are below the detection threshold of the reporter system. The topographical distribution of β-gal-positive cells in the GCL follows the overall neuron distribution in that layer, with more T3-signaling cells in the ventral than the dorsal half-retina.