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Spätestens seit jener Entwicklung, die man heute als "Web 2.0" bezeichnet, verfließen die Grenzen zwischen Publizieren und partizipativem Interagieren im Netz. In unterschiedlicher Weise verstehen sich Blogs und Microblogging-Dienste als Medien der Wissenschaftskommunikation nach außen, als Werkzeuge interaktiver wissenschaftlicher Forschung oder als Möglichkeit der wissenschaftsinternen Vernetzung. Gemeinsam ist diesen verschiedenen Spielarten, dass sie in der traditionellen Anerkennungskultur des Faches bzw. der Geistes- und Kulturwissenschaften allgemein nach wie vor einen ungeklärten oder prekären Staus haben, so dass sich für die Akteure die Frage nach dem symbolischen "Ertrag" des investierten Aufwands stellt. Alexander Lasch problematisiert in seinem einführenden Beitrag zu Blogs in der Wissenschaft insbesondere, dass sich aktive Wissenschaftsblogger häufig einem "Prokrastinationsverdacht" aussetzen; in den auf Prestigeerwerb angelegten wissenschaftlichen Qualifikationswegen kann das Bloggen also sogar negativ wirksam werden.
No início da segunda parte das "Afinidades eletivas", de Johann Wolfgang von Goethe, o narrador traça um paralelo entre a vida e o artifício do poeta para substituir, na epopéia, os protagonistas por figuras até então pouco notadas, justificando assim a crescente importância do arquiteto na sequência da narrativa. Este jovem artista vincula à sua arte uma esperança de permanência, de sobrevida. Ottilie discordará em seus apontamentos de diário. Ela vê nas ruínas das igrejas e nos destroços das lápides não só uma prova da transitoriedade desta vida, mas também do apagamento de uma segunda existência post-mortem: "Assim como sobre os homens, também sobre os monumentos, o tempo não abdica de seu direito". Partindo do ensaio de Walter Benjamin sobre as "Afinidades eletivas" e trazendo para as reflexões outro magnum opus de Goethe, o "Fausto", o artigo tece considerações sobre os aspectos de arte, renúncia e morte na obra do poeta alemão.
Type 1 Diabetes (T1D) is an autoimmune disorder in which the own immune system attacks the insulin producing _-cells in the pancreas. Therapy of T1D with anti-CD3 antibodies (aCD3) leads to a blockade of the autoimmune process in animal models and patients resulting in reduced insulin need. Unfortunately, this effect is only temporal and the insulin need increases after a few years. In the first approach, I aimed at a blockade of the cellular re-entry into the islets of Langerhans after aCD3 treatment by neutralising the key chemokine CXCL10, which is important for the T cell migration. In the second approach I tried to block the transmigration of leukocytes trough the endothelial layer into inflamed tissue with an anti-JAM-C antibody (aJAM-C) after aCD3 treatment.
I used the well-established RIP-LCMV-GP mouse model of T1D. As target autoantigen in the _-cells, such mice express the glycoprotein (GP) of the lymphocytic choriomeningitis virus (LCMV) under control of the rat insulin promoter (RIP). These mice develop T1D within 10 to 14 days only after LCMV-infection. In the combination therapy (CT) I treated diabetic RIP-LCMV-GP mice with 3 5g aCD3 per mouse (3 injections in 3 days) followed by administration of a neutralising anti-CXCL10 (CT) or aJAM-C (CT-J) monoclonal antibody (8 injections of 100 5g per mouse over 2.5 weeks).
CT reverted T1D in RIP-LCMV-GP mice significantly (CT: 67 % reversion; control: 16 % reversion) and with superior efficacy to monotherapies with aCD3 (38 % reversion) and aCXCL10 (36 % reversion).
The CD8 T cells in the spleen have fully regenerated at day 31 after infection. However, the frequency of islet antigen (GP)-specific CD8 T-cells was significantly reduced by 73 % in the spleen after CT compared to isotype control treated mice. In contrast, in aCD3 treated mice the T cells were only reduced by 56 % of the frequency of isotype control treated mice. Flow cytometry and immunohistological examinations demonstrated a marked reduction of CD8 T cells in the pancreas of CT treated mice. Importantly, the number of GP-specific CD8 T cells was reduced dramatically by 78 % in the pancreas of CT treated mice, whereas aCD3 treatment led to a less pronounced reduction of the GP-specific CD8 T cell number (23 %). This reduction of infiltration was long lasting since in the pancreas of CT treated mice the _-cells produce insulin and there were almost no infiltrating T cells present at day 182 post-infection. aCD3 treated mice also showed many insulin producing cells after 182 days post-infection. Nevertheless, their pancreas displayed also some infiltrates around the islets.
In order to confirm my data I treated non-obese diabetic (NOD) mice with CT. In contrast to RIP-LCMV-GP mice, NOD mice develop spontaneous T1D within 15 to 30 weeks after birth, due to a mutation in the CTLA-4 gene. Strikingly CT cured 55 % of diabetic NOD mice, whereas only 30 % showed T1D reversion with aCD3 alone and none reverted after isotype control administration.
The impact of CT on GP-specific T cells (Teff) was stronger in the RIP LCMV-GP than in the NOD model. In contrast, regulatory T cells (Tregs) were induced predominantly in NOD mice rather than in RIP-LCMV-GP mice. However, looking at the Treg/Teff ratio and compared to isotype control antibody treated mice, I found a significant 4-fold increase in the pancreas of CT treated RIP LCMV-GP mice and a 17-fold increase in the PDLN of CT treated NOD mice. In addition, a tendency for an increase in Treg/Teff ratio was obtained in the spleen of CT-treated RIP LCMV-GP as well as NOD mice compared to aCD3 and isotype control antibody treated mice.
In the second combination therapy with neutralising aJAM-C, CT-J (51 % reversion) slightly improved the aCD3 therapy (41 % reversion). However, there was no significant difference between CT-J and aCD3 administration in terms of total CD8 and GP-specific CD8 T cells.
JAM-C also interacts with the integrin receptor macrophage-1 antigen (MAC-1), which is among others expressed by neutrophils. Accordingly, JAM-C could be involved in neutrophil transmigration to the pancreas. Indeed, I found a significant reduction for the infiltrating neutrophils into the pancreas of mice after CT-J compared to aCD3 monotherapy.
In summary the addition of aJAM-C to aCD3 monotherapy showed a small improvement, which was associated with a reduced neutrophil migration into the pancreas. However, JAM C seemed to play only a minor role in T1D development and some other adhesion molecules might be more important. Nevertheless, the combination of aCD3 and aCXCL10 resulted in a significant and long lasting reduction of aggressive T cells in the pancreas in two independent mouse models. Furthermore a protective immune balance was obtained. Since both antibodies are available for as well as tested in humans and the therapy is only for a short period of time after disease onset, this combination therapy might kick-start a novel therapy for T1D.
Along three transects of medium voltage power lines in the steppe of Central Kazakhstan, surveys for bird casualties were carried out in summer 2006 in order to estimate the quantitative and qualitative impact of power lines on bird mortality in this area. In total, 409 dead birds of 34 different species were found. Raptors represented 44 % of the total (179 individuals, 10 species). Most of them died due to electrocution. The proportion of raptors strongly varied between early and late summer, the increase in August suggests that especially young birds are prone to electrocution. The density of raptor casualties varied from 0.1 to 7.6 birds per line km and month. Adverse effects of power lines on bird life could be avoided by changing the pole construction (use of suspended insulators) or protective measures (e. g. caps).
Respiratory complex I in mitochondria and bacteria catalyzes the transfer of electrons from NADH to quinone (Q). The free energy available from the reaction is used to pump protons and to establish a membrane proton electrochemical gradient, which drives ATP synthesis. Even though several high-resolution structures of complex I have been resolved, how Q reduction is linked with proton pumping, remains unknown. Here, microsecond long molecular dynamics (MD) simulations were performed on Yarrowia lipolytica complex I structures where Q molecules have been resolved in the ~30 Å long Q tunnel. MD simulations of several different redox/protonation states of Q reveal the coupling between the Q dynamics and the restructuring of conserved loops and ion pairs. Oxidized quinone stabilizes towards the N2 FeS cluster, a binding mode not previously described in Yarrowia lipolytica complex I structures. On the other hand, reduced (and protonated) species tend to diffuse towards the Q binding sites closer to the tunnel entrance. Mechanistic and physiological relevance of these results are discussed.
Respiratory complex I in mitochondria and bacteria catalyzes the transfer of electrons from NADH to quinone (Q). The free energy available from the reaction is used to pump protons and to establish a membrane proton electrochemical gradient, which drives ATP synthesis. Even though several high-resolution structures of complex I have been resolved, how Q reduction is linked with proton pumping, remains unknown. Here, microsecond long molecular dynamics (MD) simulations were performed on Yarrowia lipolytica complex I structures where Q molecules have been resolved in the ~30 Å long Q tunnel. MD simulations of several different redox/protonation states of Q reveal the coupling between the Q dynamics and the restructuring of conserved loops and ion pairs. Oxidized quinone stabilizes towards the N2 FeS cluster, a binding mode not previously described in Yarrowia lipolytica complex I structures. On the other hand, reduced (and protonated) species tend to diffuse towards the Q binding sites closer to the tunnel entrance. Mechanistic and physiological relevance of these results are discussed.
Die vorliegende Arbeit beschäftigt sich mit der Ermittlung des Preises von Optionen. Optionen sind spezielle Derivate, die wiederum Hull in seinem Buch definiert als: Ein Derivat ist ein Finanzinstrument, dessen Wert von einem anderen, einfacheren zu Grunde liegenden Finanzinstrument (underlying) abhängt . Ein underlying kann unter anderem auch eine Anleihe, eine Aktie oder der Umtauschkurs zweier Währungen sein....
Die Befreiung : sechzehn Bilder aus dem Leben der deutschen und russischen Frauen ; 1914 - 1920
(1926)
Mit "Stirners Einzigem" ist das Buch 'Der Einzige und sein Eigentum' von Max Stirner gemeint, das gegen Ende des Vormärz erschien. Das Buch war ein Skandalon, ein paradoxes Skandalon allerdings, weil es ideengeschichtlich dort am eingreifendsten wirksam wurde, wo die Reaktion verborgen und indirekt blieb, bei Marx und Nietzsche. Ich habe den diffusen Status des 'Einzigen', der sich daraus ergab und den er, obwohl kein Mangel an Sekundärliteratur herrscht, im Grunde bis heute behielt, in einer Wirkungsgeschichte dargestellt und diese mit einem sprechenden Neologismus eine Re(pulsions- und De)zeptionsgeschichte genannt.
Auf die Repulsionsgeschichte des Einzigen gemünzt ist das "Vade retro!" im Titel, denn eine Reihe durchaus bedeutender Denker sahen in Stirners Ideen tatsächlich den Inbegriff des Bösen, Teuflischen bzw. "aufgeklärterweise" den Einbruch des Tierischen, Unmenschlichen, Barbarischen, Zerstörerischen in die kulturelle Welt. Einige waren dabei so entschieden, dass sie ihre philosophische Position wesentlich - wenngleich undeklariert - in Abwehr von Stirners Ideen entwickelten.
Ich werde - nach einer biografischen Skizze zu Leben und Werk Stirners - diese Repulsionsgeschichte in ihren markanteren Stationen wie in einem Parcours durchlaufen, um zu zeigen, dass diese Bezeichnung adäquat ist. Die mit ihr verwobene Dezeptionsgeschichte, also die das Inhaltliche betreffenden Täuschungen, Selbsttäuschungen und Verdrängungen der Abwehrenden, können hier nur beiläufig zur Sprache kommen.