Synthesis, biological evaluation, and SAR studies of 14β-phenylacetyl substituted 17-cyclopropylmethyl-7, 8-dihydronoroxymorphinones derivatives : Ligands with mixed NOP and opioid receptor profile

© 2018 Kumar, Polgar, Cami-Kobeci, Thomas, Khroyan, Toll and Husbands.A series of 14β-acyl substituted 17-cyclopropylmethyl-7,8-dihydronoroxymorphinone compounds has been synthesized and evaluated for affinity and efficacy for mu (MOP), kappa (KOP), and delta (DOP) opioid receptors and nociceptin/orphanin FQ peptide (NOP) receptors. The majority of the new ligands displayed high binding affinities for the three opioid receptors, and moderate affinity for NOP receptors. The affinities for NOP receptors are of particular interest as most classical opioid ligands do not bind to NOP receptors. The predominant activity in the [35S]GTPγS assay was partial agonism at each receptor. The results are consistent with our prediction that an appropriate 14β side chain would access a binding site within the NOP receptor and result in substantially higher affinity than displayed by the parent compound naltrexone. Molecular modeling studies, utilizing the recently reported structure of the NOP receptor, are also consistent with this interpretation.Peer reviewedFinal Published versio

Risk governance in organizations

Dieses Buch dokumentiert 10 Jahre Risk-Governance-Forschung an der Universität Siegen. In 50 Beiträgen reflektieren Forscher und Praktiker Risk Governance vor dem Hintergrund ihrer eigenen Forschungen und/oder Erfahrungen und geben jeweils einen Entwicklungsimpuls für die Zukunft der Risk Governance. Das Buch zeigt die große Bandbreite und Tiefe des Forschungsgebietes auf und diskutiert Grundannahmen, Implementierungsfragen, die Rolle der Risk Governance als Transformationsmotor, ihre Wirkung in den verschiedenen betrieblichen Funktionen, Entwicklungsperspektiven und den Beitrag der Risk Governance zu einer nachhaltigen Ausrichtung von Unternehmen.This book documents 10 years of risk governance research at the University of Siegen. In 50 contributions, researchers and practitioners reflect on risk governance against the background of their own research and/or experience and provide a development impetus for the future of risk governance. The book shows the wide range and depth of the research field and discusses basic assumptions, implementation issues, the role of risk governance as transformation engine, its impact in the various operational functions, development perspectives, and the contribution of risk governance to a sustainable orientation of companies

[Costüme]

[COSTÜME] [Costüme] ( - ) Einband ( - ) Titelseite ( - ) Maria Theresia (1) Franciscvs Stephanvs (2) 3. Ein Obrister der Tolpatschen, Ein Hußaren Rittmeister (3) 4. Ein Fähndrich der Tolpatschen, Ein Tolpatschen Tambour (4) 5. Ein nachhauender Tolpatsch, Ein in action begriffener Tolpatsch (5) 6. Ein Morlack oder Dalmatier, Ein Ungarischer Hannack (6) 7. Ein Croat auf dem Vorposten, Ein gemeiner Ungrischer Pandur (7) 8. Ein Ungarischer Pantzer Stecher, Ein Ungarischer Stängel Reuter (8) 9. Ein Wallachischer Tolpatsch, Ein Croat auf der Schildwacht, Ein Morlack mit seiner Rüstung (9) 10. Ein Sclavonischer Pandur, Ein gemeiner Pandur, Ein sich Defendirender Pandur (9) 11. Ein Ungarischer Tolpatsch, Ein Croatischer Tolpatsch, Ein Stängel Reuter (11) 12. Ein Panduren Obrister, Ein Fähndrich der Panduren, Ein Panduren Obrist Wachtmeister (12) 13. Ein Hannack, Ein Wallach, Ein Raizischer Tolpatsch (13) 14. Johann Daniel von Menzel (14) 15. Ein Feld Pfeiffer by den Panduren, ein Trom[m]elschläger, Ein Warasdiner Panduren Corporal (15

Intraday Pricing of ETFs and Certificates Replicating the German DAX Index

The market for the leading German equity index DAX comprises electronically traded futures contracts, fully replicated and swap-based exchange-traded funds (ETFs), and certificates. This paper reveals that DAX futures contracts contribute an economically and statistically significant proportion to contemporaneous price quotes of ETFs and certificates. This finding is surprising because the prospectus of ETFs and certificates claim to follow the stock index solely, but not the index futures contract. Exploring further the short-run dynamics, our results suggest that fully replicated ETFs cope better with adjusting their prices to the DAX index than swap-based ETFs and certificates

The real benchmark of DAX index products and the influence of information dissemination: A natural experiment

Analysing 5 exchange traded funds (ETFs) and 26 index certificates, this is a comprehensive intraday study combining the perspective of information dissemination and pricing quality. We focus on the Volkswagen extreme event day on 28 October 2008, where a breakdown of the futures-cash arbitrage relationship offered the unique opportunity to identify the true benchmark of index-related products free from market microstructure noise. Although product information prospectuses promise to follow the DAX, we discover that the price quote level of DAX futures contracts became the one-on-one benchmark for all ETFs and for nearly all index certificates. We identify deviations between ETFs and their fair value exceeding 4 per cent. This is striking because the creation redemption process is assumed to restrict deviations. Analysing price information dynamics, we find that the revelation of new information to the market does not determine the price quote setting strategy of market makers during the extreme event. Hedging opportunities deliver a substantive argument to support the benchmark position of DAX futures

Towards a Theory on Dominant Business Model Emergence of Marketplace Lending in Germany

In this paper, we analyze the business models of Germany’s biggest lending platforms smava, auxmoney, and Lendico to identify a standard business model as a dominant design in this industry. We use a mixed method approach in which a case study at firm level is conducted to analyze and contrast the business models together with their business model components. This qualitative analysis is complemented with a quantitative test of their total asset annual growth rates to triangulate the qualitative analysis. The results indicate that all three companies started with a similar approach but evolved over time into entirely different business model variants. This seems to contradict the previous theory of the emergence of standard business models and dominant designs. At first glance, an increasing convergence of business models over time into a standard business model in the German lending platform industry was not consistent with our results. However, we suggest to explain this contradiction by taking a closer look at the global context of the industry. The origin of lending platforms was pioneered outside the German market by firms such as Zopa (UK) or later Prosper and Lending Club (USA). We hypothesize based on initial evidence that the German lending platforms have largely adopted the business models of the early movers and later modified them according to their local value network such as local market, regulation, and competition conditions. Thereby we propose that the deficient standard business model as a dominant design or a winner takes all market outcome in the lending platform industry might depend on localized demand and regulative heterogeneity