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Das im Jahr 2013 begonnene und für einen Zeitraum von 18 Jahren konzipierte Forschungsvorhaben zielt auf die Erstellung eines historisch-semantischen Wörterbuchs zum Denken der Schule von Salamanca und ihrer Bedeutung für politische Theorie und Recht in der Moderne. Als Grundlage dieses Wörterbuchs wird ein digitales Corpus von zentralen Texten der Schule von Salamanca aufgebaut, das mit der elektronischen Version des Wörterbuchs verknüpft ist und der internationalen und interdisziplinären Forschergemeinschaft direkten Zugriff auf die einschlägigen Quellentexte ermöglicht. Durch die Volltexterschließung der digitalen Quellen wird zugleich ein in seiner Funktionalität neuartiges elektronisches Arbeitsinstrument geschaffen, das einen wichtigen Fortschritt gegenüber allen bisherigen Digitalisierungsprojekten in diesem Bereich darstellt. Dieses Arbeitsinstrument wird auch über seine Funktionalität für das zu erstellende Wörterbuch hinaus qualitativ neue Forschungsmöglichkeiten eröffnen.
Beides – Wörterbuch und Quellencorpus – werden in einem repository erfasst und über eine Webseite als Forschungsinstrument der internationalen scientific community zur Verfügung gestellt. Das Wörterbuch wird zum Schluss der letzten Arbeitsphase zusätzlich in Buchform publiziert. Die weltweite Forschung zur Schule von Salamanca und zu ihrer Wirkungsgeschichte wird damit zum ersten Mal Zugriff auf ein gemeinsames Textcorpus haben und über einen intellektuellen Referenzrahmen für dessen historische Unter-suchung und interdisziplinäre Diskussion verfügen.
Dieser Beitrag soll Ausgangslage und Zielsetzung des Vorhabens zusammenfassen (1.), das geplante Quellencorpus (2.), das Wörterbuch (3.) und den Arbeitsplan (4.) vorstellen.
The article introduces a research project financed by the Academy of Sciences and Literature Mainz began in 2013 and will extend over an 18-year period. It aims at producing a historical-semantic dictionary elucidating central terms of the School of Salamanca's discourses and their significance for modern political theory and jurisprudence. The project's fundament will be a digital corpus of important texts from the School of Salamanca which will be linked up with the dictionary's online version. By making the source corpus accessible in searchable full text (as well as in high quality digital images), the project is creating a new research tool with exciting possibilities for further investigations. The dictionary will be a valuable source of information for the interdisciplinary research carried out in this field.
Inhibitor-kappaB kinase epsilon (IKKε) and TANK-binding kinase 1 (TBK1) are non-canonical IκB kinases, both described as contributors to tumor growth and metastasis in different cancer types. Several hints indicate that they are also involved in the pathogenesis of melanoma; however, the impact of their inhibition as a potential therapeutic measure in this “difficult-to-treat” cancer type has not been investigated so far. We assessed IKKε and TBK1 expression in human malignant melanoma cells, primary tumors and the metastasis of melanoma patients. Both kinases were expressed in the primary tumor and in metastasis and showed a significant overexpression in tumor cells in comparison to melanocytes. The pharmacological inhibition of IKKε/TBK1 by the approved drug amlexanox reduced cell proliferation, migration and invasion. Amlexanox did not affect the cell cycle progression nor apoptosis induction but significantly suppressed autophagy in melanoma cells. The analysis of potential functional downstream targets revealed that NF-кB and ERK pathways might be involved in kinase-mediated effects. In an in vivo xenograft model in nude mice, amlexanox treatment significantly reduced tumor growth. In conclusion, amlexanox was able to suppress tumor progression potentially by the inhibition of autophagy as well as NF-кB and MAP kinase pathways and might therefore constitute a promising candidate for melanoma therapy.
Alkylglycerol monooxygenase (AGMO) is a tetrahydrobiopterin (BH4)-dependent enzyme with major expression in the liver and white adipose tissue that cleaves alkyl ether glycerolipids. The present study describes the disclosure and biological characterization of a candidate compound (Cp6), which inhibits AGMO with an IC50 of 30–100 µM and 5–20-fold preference of AGMO relative to other BH4-dependent enzymes, i.e., phenylalanine-hydroxylase and nitric oxide synthase. The viability and metabolic activity of mouse 3T3-L1 fibroblasts, HepG2 human hepatocytes and mouse RAW264.7 macrophages were not affected up to 10-fold of the IC50. However, Cp6 reversibly inhibited the differentiation of 3T3-L1 cells towards adipocytes, in which AGMO expression was upregulated upon differentiation. Cp6 reduced the accumulation of lipid droplets in adipocytes upon differentiation and in HepG2 cells exposed to free fatty acids. Cp6 also inhibited IL-4-driven differentiation of RAW264.7 macrophages towards M2-like macrophages, which serve as adipocyte progenitors in adipose tissue. Collectively, the data suggest that pharmacologic AGMO inhibition may affect lipid storage.