Das Handout erläutert anhand eines Suchbeispiels die Rechercheoberfläche der Datenbank World Biographical Information System (WBIS) - einer der wichtigsten Datenbanken zur Suche nach Personen. Dabei werden biographische und bibliographische Suchmöglichkeiten vorgestellt.
The main underlying mechanisms of chronic pain are still unclear. In this thesis, two new approaches targeting the excitability of peripheral nociceptive neurons were employed to examine processes leading to ongoing nociceptive discharge. Thereby we aimed to contribute to the understanding of peripherally driven spontaneous pain that leads to suffering in many patients with chronic pain. We used a new model of low extracellular potassium application that induces ongoing nociceptor activity at the sensory endings of skin nociceptors and a slow depolarizing ramp stimulus that preferentially activates C-fibres and is more closely related to the physiologic induction of action potentials in primary afferent neurons. Low potassium solution unexpectedly led to a rapid and transient depolarisation that is probably mediated by a loss of ion selectivity in 2 pore domain potassium channels. However, the dominant effect of low potassium was a massive increase of intracellular sodium mediated primarily by an influx of sodium ions via NaV1.9 channels. Moreover, primary afferents lacking NaV1.9 such as cold sensitive A-fibres of the cornea did not increase their discharge upon stimulation with low potassium. Slow depolarizing ramp stimuli (4 Hz sinusoidal) were found to be more effective at activating C-fibres during cooling whereas traditional rectangular stimulation became less effective. This differential effect could be explained by cold-induced closure of two pore domain potassium channels leading to increased membrane resistance. The increased membrane resistance increases the membrane time constant whereby the same transmembrane current will more effectively change membrane potential. This mechanism has major clinical importance for cold-induced pain. The voltage-sensitive sodium channel NaV1.7 would have the ideal characteristics to mediate the activation upon slow depolarizing ramps as it is known to amplify such stimuli via a “ramp current”. Activation of C-fibres by sinusoidal stimuli was not blocked by TTX suggesting that NaV1.7 is not the only NaV that can respond to slow depolarizing changes in membrane potential. Innovative excitability tests were used to investigate peripheral nerve fibres of rats that had received cisplatin to induce an acute nephropathy and potentially a peripheral neuropathy. In treated animals, unmyelinated fibres were found to be more sensitive to slow depolarizing stimuli suggesting hyper-excitability. However, the number of animals was low and it remains unclear how robust this effect is. In summary, the model of potassium free extracellular solution was used to identify NaV1.9 and 2 pore domain potassium channels as major determinants of small fibre excitability that have already been linked to clinical chronic pain states. Moreover, the cold-induced hyper-excitability of unmyelinated fibres in response to slow depolarizing ramp stimuli found in our study has important mechanistic implications for the generation of cold-induced pain and hypersensitivity in patients with neuropathic pain. It will be of major interest to use the newly developed tests for axonal excitability in pathophysiologic conditions and ultimately in human tissue in order to specify promising molecular targets that can lead to innovative analgesic treatment options in the future.
Es ist viel über den historischen Ursprung der Definition des Tensorproduktes von Matrizen geschrieben worden, so haben ihn einige Autoren Kronecker und anderen Autoren Zehfuss zugeschrieben. Aber bis jetzt waren bibliographische Informationen von Georg Zehfuss (1832-1901) knapp und die Liste seiner Veröffentlichungen unvollständig, so dass schwer zu verstehen ist, dass ein so unbekannter Mathematiker hier mitbestimmend war. Wir beabsichtigen hier diese Lücke auszufüllen, indem wir Daten aus verschiedenen bekannten und neuen Quellen sammeln, gruppieren, kategorisieren und kommentieren. Dies umfasst biographische Daten, seine Lehrer und Tutoren, viele seiner Publikationen und die Auswirkungen einiger seiner Errungenschaften in Mathematik und Physik. Die Schlussfolgerung ist, dass der Beitrag von Zehfuss zur Mathematik sich nicht auf die Definition vom Tensorprodukt von Matrizen beschränkt ist, da es weitere Beiträge zur Mathematik und nicht nur zur Determinantenttheorie, auch zur Physik von ihm gibt, und abgesehen von seinen Beiträgen zur Bildung von späteren Ingenieuren an höheren Gewerbeschulen mit seiner Lehrtätigkeit und mit seinen Büchern.
Zusammenstellung der von Moritz Cantor verfassten Publikationen.
Since the development of advanced mathematical modelling techniques in biology, thermodynamics (and therefore equilibrium statistical mechanics) has played a key role in mathematically quantifying biological activities. We use this underlying notion of thermodynamic ‘micro-states’ to attempt to uncover how the hormone hepcidin under the influence of two major signalling pathways maintains systemic iron homeostasis. Systemic iron homeostasis involves a negative feedback circuit in which the expression level of the peptide hormone hepcidin depends on and controls the iron blood levels. Hepcidin expression is regulated by the BMP6/SMAD and IL6/STAT signalling cascades. Deregulation of either pathway causes iron storage diseases such as hemochromatosis or anaemia of inflammation (AI). We quantitatively analyzed how BMP and IL6 control hepcidin expression in human hepatoma (HuH7) cells. We used data from our experimental collaborators who measured transcription factor phosphorylation and reporter gene expression under co-stimulation conditions and perturbed the promoter by mutagenesis. We applied statistical data analysis and mathematical modelling to reveal possible biological mechanisms that control hepcidin expression at the promoter level. Specifically we develop a thermodynamic modelling framework that is able to simulate and predict possible molecular mechanisms that might underlie iron homeostasis by hepcidin. Our results reveal that hepcidin cross- regulation primarily occurs by combinatorial transcription factor binding to the promoter, whereas signalling crosstalk is insignificant. We find that the presence of two BMP-responsive elements in the promoter ensures high sensitivity towards the iron-sensing BMP signalling axis, which promotes iron homeostasis in vivo. IL6 stimulation reduces the promoter sensitivity to the BMP signal that may explain the disturbance of iron homeostasis in AI. We get to understand why the iron homeostasis circuit is sensitive to certain perturbations implicated in disease. Taken together, our work reveals how mathematical quantification and modelling can aid in understanding biological phenomenon that underlies gene expression.
Zusammenstellung der von Ludwig Boltzmann verfassten Publikationen.
Der Artikel schildert kurz die Geschichte und Erscheinungsweise des Allgemeinen Künstlerlexikons (AKL), beschreibt sein auf HIDA/MIDAS basierendes Datenbanksystem, die Namensansetzung der verzeichneten Künstler und die Datenstruktur der Künstlereinträge.