177 research outputs found

    Paid Content In The Internet : a literature study of researches and discussions in science and practice of journalistic paid content

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    Die vorliegende Arbeit geht der zentralen Fragestellung nach, ob Paid Content die Lösung der Finanzierungsproblematik von journalistischen Verlagen sein kann. Zur Beantwortung dieser Frage wurde eine umfangreiche Literaturstudie durchgeführt, in welcher wissenschaftliche Publikationen und Fachartikel ausgewertet wurden, um einen möglichst ganzheitlichen Überblick aus theoretischen und praktischen Erkenntnissen zu bekommen. Hierbei wurden die Bedeutung von Paid Content, mögliche Erfolgsfaktoren, Risiken und Zukunftsaussichten bewertet, um abschließend die zentrale Fragestellung zu beantworten

    Thermochemical sulfate reduction in fossil Ordovician deposits of the Majiang area: Evidence from a molecular-marker investigation

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    The main reservoirs of Majiang fossil deposits consist of the Silurian Wengxiang group, dominantly sandstones, and the Ordovician Honghuayuan formation, dominantly carbonate rocks, and the Lower Cambrian Niutitang Formation mudstones serve as the major source rocks. Thermochemical sulfate reduction (TSR) might have taken place in the Paleozoic marine carbonate oil pools, as indicated by high concentrations of dibenzothiophenes in the extracts (MDBT=0.27-4.32 µg/g extract, and MDBT/MPH= 0.71-1.38). Hydrocarbons in the Pojiaozhai Ordovician carbonate reservoirs have undergone severe TSR and are characterized by higher quantities of diamondoids and MDBT and heavier isotopic values (δ13C=-28.4‰). The very large amounts of dibenzothiophenes might be products of reactions between biphenyls and sulfur species associated with TSR

    A TNFR2-Specific TNF Fusion Protein With Improved In Vivo Activity

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    Tumor necrosis factor (TNF) receptor-2 (TNFR2) has attracted considerable interest as a target for immunotherapy. Indeed, using oligomeric fusion proteins of single chain-encoded TNFR2-specific TNF mutants (scTNF80), expansion of regulatory T cells and therapeutic activity could be demonstrated in various autoinflammatory diseases, including graft-versus-host disease (GvHD), experimental autoimmune encephalomyelitis (EAE) and collagen-induced arthritis (CIA). With the aim to improve the in vivo availability of TNFR2-specific TNF fusion proteins, we used here the neonatal Fc receptor (FcRn)-interacting IgG1 molecule as an oligomerizing building block and generated a new TNFR2 agonist with improved serum retention and superior in vivo activity.MethodsSingle-chain encoded murine TNF80 trimers (sc(mu)TNF80) were fused to the C-terminus of an in mice irrelevant IgG1 molecule carrying the N297A mutation which avoids/minimizes interaction with Fcγ-receptors (FcγRs). The fusion protein obtained (irrIgG1(N297A)-sc(mu)TNF80), termed NewSTAR2 (New selective TNF-based agonist of TNF receptor 2), was analyzed with respect to activity, productivity, serum retention and in vitro and in vivo activity. STAR2 (TNC-sc(mu)TNF80 or selective TNF-based agonist of TNF receptor 2), a well-established highly active nonameric TNFR2-specific variant, served as benchmark. NewSTAR2 was assessed in various in vitro and in vivo systems.ResultsSTAR2 (TNC-sc(mu)TNF80) and NewSTAR2 (irrIgG1(N297A)-sc(mu)TNF80) revealed comparable in vitro activity. The novel domain architecture of NewSTAR2 significantly improved serum retention compared to STAR2, which correlated with efficient binding to FcRn. A single injection of NewSTAR2 enhanced regulatory T cell (Treg) suppressive activity and increased Treg numbers by > 300% in vivo 5 days after treatment. Treg numbers remained as high as 200% for about 10 days. Furthermore, a single in vivo treatment with NewSTAR2 upregulated the adenosine-regulating ectoenzyme CD39 and other activation markers on Tregs. TNFR2-stimulated Tregs proved to be more suppressive than unstimulated Tregs, reducing conventional T cell (Tcon) proliferation and expression of activation markers in vitro. Finally, singular preemptive NewSTAR2 administration five days before allogeneic hematopoietic cell transplantation (allo-HCT) protected mice from acute GvHD.ConclusionsNewSTAR2 represents a next generation ligand-based TNFR2 agonist, which is efficiently produced, exhibits improved pharmacokinetic properties and high serum retention with superior in vivo activity exerting powerful protective effects against acute GvHD

    Brutbeobachtungen bei der Singdrossel, Turdus ericetorum philomelos Brehm, im Gebiete der Rominter Heide

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    von Otto Steinfatt, Jagdhaus Rominten/Pr
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