August von Kotzebue et le Siècle de Frédéric II. Histoire d’un succès inachevé

Après son installation à Berlin en 1802, August von Kotzebue lança différents projets pour circonscrire et par ailleurs pour mettre en valeur la culture de la Prusse, en particulier celle de la capitale. Afin d’atteindre cet objectif, il conçut ces projets de telle sorte qu’on les perçoive comme un contrepoids à ce foyer des muses toujours plus influent qu’était la cour de Weimar. Il prit pour modèle la culture française qui, en Prusse, servait d’exemple à suivre depuis Frédéric II. Kotzebue se référait aussi bien au classicisme français qu’à la France postrévolutionnaire qui avait fondé à Paris des musées somptueux. Le projet qu’il nourrit de rassembler et d’exposer des antiquités prussiennes dans un musée central ainsi que la création de la revue Der Freimüthige reposaient sur l’idée commune de donner à la Prusse et à sa capitale une mémoire culturelle. La fondation de ce musée et la publication d’une revue visaient à institutionnaliser une culture du souvenir et à élargir la mémoire culturelle. Les projets de Kotzebue échouèrent parce qu’il sous-estima la complexité du paysage culturel de Berlin et qu’il ne vit pas que toutes personnes cultivées n’étaient pas prêtes à accepter son programme éclairé et classiciste, prônant le classicisme français comme système de référence. Mais la raison la plus importante est le revirement de nature politique qui se produisit à l’époque des guerres antinapoléoniennes, quand la « Prusse française » à l’esprit cosmopolite fut définitivement refoulée par une Prusse patriotique.Nachdem sich August von Kotzebue 1802 in Berlin niedergelassen hatte, initiierte er verschiedene Projekte, um die preußische Kultur, insbesondere, die der Hauptstadt, zu konturieren und weithin sichtbar zu machen. Dieses Sichtbarmachen erreichte er vor allem, indem er diese Projekte so gestaltete, dass sie als Gegengewicht zu dem immer einflussreicher werdenden Weimarer Musenhof wahrgenommen wurden. Vorbild war ihm die französische Kultur, die in Preußen seit Friedrich II. eine Leitfunktion ausübte. Kotzebue bezog sich sowohl auf die Französische Klassik als auch auf das nachrevolutionäre Frankreich mit seinen glanzvollen Pariser Museumsgründungen. Sowohl seinem Plan, die preußischen Altertümer in einem zentralen Museum zu versammeln und auszustellen, als auch der Gründung der Kulturzeitschrift Der Freimüthige lag die gemeinsame Idee zugrunde, Preußen und seiner Hauptstadt Berlin ein kulturelles Gedächtnis zu stiften. Museums-Gründung und Zeitschriften-Projekt zielten darauf ab, Erinnerungskultur zu institutionalisieren und das kulturelle Gedächtnis zu erweitern. Kotzebues Projekte scheiterten, weil er die Komplexität der Berliner Kulturlandschaft unterschätzte und nicht erkannte, dass sich nicht alle Gebildeten auf sein aufklärerisch-klassizistisches Programm, das die französische Klassik als Referenzsystem aufstellte, festlegen ließen. Entscheidend aber war der politisch motivierte Umschwung, der sich in der Zeit der Befreiungskriege ereignete; denn die kosmopolitische Prusse française wurde endgültig durch ein patriotisches Preußen verdrängt.After he settled in Berlin in 1802, August von Kotzebue initiated various projects aimed at profiling Prussian culture – and especially that of the capital – and expanding its visibility to a far greater extent. He achieved this above all by designing these projects to be perceived as a counterbalance to the “Weimarer Musenhof” whose influence was ever increasing. French culture, which had played a key role in Prussia since the reign of Frederick II, served as his model. Kotzebue referenced French classicism as well as post-revolutionary France and the grand museum founded in Paris during this period. Both Kotzebue’s plan for collecting and exhibiting Prussian antiquities in a central museum as well as his founding of the cultural journal Der Freimüthige are based on the same idea: to endow Prussia and its capital of Berlin with a cultural memory. The objective of both projects – to found a museum and to found a journal – was to institutionalize a culture of remembrance and to enhance cultural memory. Kotzebue’s projects failed, in part because he underestimated the complexity of Berlin’s cultural landscape and didn’t recognize that not all of his well-educated compatriots wanted to commit themselves to a program drawing upon the principles of the Enlightenment and classicism, with French classicism as its reference system. But the deciding factor was the politically motivated turnaround that occurred during the German campaign; the cosmopolitan Prusse française was supplanted by a patriotic Prussia, and there would be no turning back

Coexpression of GM-CSF and antigen in DNA prime-adenoviral vector boost immunization enhances polyfunctional CD8+ T cell responses, whereas expression of GM-CSF antigen fusion protein induces autoimmunity

<p>Abstract</p> <p>Background</p> <p>Granulocyte-macrophage colony-stimulating factor (GM-CSF) has shown promising results as a cytokine adjuvant for antiviral vaccines and in various models of tumor gene therapy. To explore whether the targeting of antigens to GM-CSF receptors on antigen-presenting cells enhances antigen-specific CD8 T-cell responses, fusion proteins of GM-CSF and ovalbumin (OVA) were expressed by DNA and adenoviral vector vaccines. In addition, bicistronic vectors allowing independent expression of the antigen and the cytokine were tested in parallel.</p> <p>Results</p> <p><it>In vitro</it>, the GM-CSF ovalbumin fusion protein (GM-OVA) led to the better stimulation of OVA-specific CD8+ T cells by antigen-presenting cells than OVA and GM-CSF given as two separate proteins. However, prime-boost immunizations of mice with DNA and adenoviral vector vaccines encoding GM-OVA suppressed CD8+ T-cell responses to OVA. OVA-specific IgG2a antibody levels were also reduced, while the IgG1 antibody response was enhanced. Suppression of CD8+ T cell responses by GM-OVA vaccines was associated with the induction of neutralizing antibodies to GM-CSF. In contrast, the coexpression of GM-CSF and antigens in DNA prime adenoviral boost immunizations led to a striking expansion of polyfunctional OVA-specific CD8+ T cells without the induction of autoantibodies.</p> <p>Conclusion</p> <p>The induction of autoantibodies suggests a general note of caution regarding the use of highly immunogenic viral vector vaccines encoding fusion proteins between antigens and host proteins. In contrast, the expansion of polyfunctional OVA-specific CD8+ T cells after immunizations with bicistronic vectors further support a potential application of GM-CSF as an adjuvant for heterologous prime-boost regimens with genetic vaccines. Since DNA prime adenoviral vector boost regimenes are presently considered as one of the most efficient ways to induce CD8+ T cell responses in mice, non-human primates and humans, further enhancement of this response by GM-CSF is a striking observation.</p

A Novel In Vitro Method for the Detection and Characterization of Photosensitizers

Photoactivation and binding of photoactive chemicals to proteins is a known prerequisite for the formation of immunogenic photoantigens and the induction of photoallergy. The intensive use of products and the availability of new chemicals, along with an increasing exposure to sun light contribute to the risk of photosensitizing adverse reactions. Dendritic cells (DC) play a pivotal role in the induction of allergic contact dermatitis. Human peripheral blood monocyte derived dendritic cells (PBMDC) were thus perceived as an obvious choice for the development of a novel in vitro photosensitization assay using the modulation of cell surface protein expression in response to photosensitizing agents. In this new protocol, known chemicals with photosensitizing, allergenic or non-allergenic potential were pre-incubated with PBMDCs prior to UVA irradiation (1 J/cm2). Following a 48 h incubation, the expression of the cell surface molecules CD86, HLA-DR and CD83 was measured by flow cytometry. All tested photosensitizers induced a significant and dose-dependent increase of CD86 expression after irradiation compared to non-irradiated controls. Moreover, the phototoxicity of the chemicals could also be determined. In contrast, (i) CD86 expression was not affected by the chosen irradiation conditions, (ii) increased CD86 expression induced by allergens was independent of irradiation and (iii) no PBMDC activation was observed with the non-allergenic control. The assay proposed here for the evaluation of the photoallergenic potential of chemicals includes the assessment of their allergenic, phototoxic and toxic potential in a single and robust test system and is filling a gap in the in vitro photoallergenicity test battery

A genetic validation study reveals a role of vitamin D metabolism in the response to interferon-alfa-based therapy of chronic hepatitis C

Background: To perform a comprehensive study on the relationship between vitamin D metabolism and the response to interferon-α-based therapy of chronic hepatitis C. Methodology/Principal Findings: Associations between a functionally relevant polymorphism in the gene encoding the vitamin D 1α-hydroxylase (CYP27B1-1260 rs10877012) and the response to treatment with pegylated interferon-α (PEG-IFN-α) and ribavirin were determined in 701 patients with chronic hepatitis C. In addition, associations between serum concentrations of 25-hydroxyvitamin D3 (25[OH]D3) and treatment outcome were analysed. CYP27B1-1260 rs10877012 was found to be an independent predictor of sustained virologic response (SVR) in patients with poor-response IL28B genotypes (15% difference in SVR for rs10877012 genotype AA vs. CC, p = 0.02, OR = 1.52, 95% CI = 1.061–2.188), but not in patients with favourable IL28B genotype. Patients with chronic hepatitis C showed a high prevalence of vitamin D insufficiency (25[OH]D3<20 ng/mL) during all seasons, but 25(OH)D3 serum levels were not associated with treatment outcome. Conclusions/Significance: Our study suggests a role of bioactive vitamin D (1,25[OH]2D3, calcitriol) in the response to treatment of chronic hepatitis C. However, serum concentration of the calcitriol precursor 25(OH)D3 is not a suitable predictor of treatment outcome

Pilot study: potential transcription markers for adult attention-deficit hyperactivity disorder in whole blood

Attention-deficit hyperactivity disorder (ADHD) is a common behavioural disorder that affects not only children and adolescents but also adults; however, diagnosis of adult ADHD is difficult because patients seem to have reduced externalized behaviour. ADHD is a multifactorial disorder in which many genes, all with small effects, are thought to cause the disorder in the presence of unfavourable environmental conditions. Therefore, in this pilot study, we explored the expression profile of a list of previously established candidate genes in peripheral blood samples from adult ADHD subjects (n=108) and compared these results with those of healthy controls (n=35). We demonstrate that combining the gene expression levels of dopamine transporter (SLC6A3), dopamine D5 receptor, tryptophan hydroxylase-1, and SNAP25 as predictors in a regression model resulted in sensitivity and specificity of over 80% (ROC: max R 2=0.587, AUC=0.917, P<0.001, 95% CI: 0.900-0.985). In conclusion, the combination of these four genes could represent a potential method for estimating risk and could be of diagnostic value for ADHD. Nevertheless, further investigation in a larger independent population including different subtypes of ADHD (inattentive, hyperactive, or combined type) patients is required to obtain more specific sets of biomarkers for each subtype as well as to differentiate between child, adolescent, and adulthood form

5-hydroxyindolacetic acid (5-HIAA), a main metabolite of serotonin, is responsible for complete Freund's adjuvant-induced thermal hyperalgesia in mice

<p>Abstract</p> <p>Background</p> <p>The role of serotonin (5-hydroxytrptamine, 5-HT) in the modulation of pain has been widely studied. Previous work led to the hypothesis that 5-hydroxyindolacetic acid (5-HIAA), a main metabolite of serotonin, might by itself influence pain thresholds.</p> <p>Results</p> <p>In the present study, we investigated the role of 5-HIAA in inflammatory pain induced by intraplantar injection of complete Freund's adjuvant (CFA) into the hind paw of mice. Wild-type mice were compared to mice deficient of the 5-HT transporter (5-HTT-/- mice) using behavioral tests for hyperalgesia and high-performance liquid chromatography (HPLC) to determine tissue levels of 5-HIAA. Wild-type mice reproducibly developed thermal hyperalgesia and paw edema for 5 days after CFA injection. 5-HTT-/- mice treated with CFA had reduced thermal hyperalgesia on day 1 after CFA injection and normal responses to heat thereafter. The 5-HIAA levels in spinal cord and sciatic nerve as measured with HPLC were lower in 5-HTT-/- mice than in wild-type mice after CFA injection. Pretreatment of wild-type mice with intraperitoneal injection of para-chlorophenylalanine (p-CPA), a serotonin synthesis inhibitor, resulted in depletion of the 5-HIAA content in spinal cord and sciatic nerve and decrease in thermal hyperalgesia in CFA injected mice. The application of exogenous 5-HIAA resulted in potentiation of thermal hyperalgesia induced by CFA in 5-HTT-/- mice and in wild-type mice pretreated with p-CPA, but not in wild-type mice without p-CPA pretreatment. Further, methysergide, a broad-spectrum serotonin receptor antagonist, had no effect on 5-HIAA-induced potentiation of thermal hyperalgesia in CFA-treated wild-type mice.</p> <p>Conclusion</p> <p>Taken together, the present results suggest that 5-HIAA plays an important role in modulating peripheral thermal hyperalgesia in CFA induced inflammation, probably via a non-serotonin receptor mechanism.</p

Chemical interaction at the buried silicon/zinc oxide thin-film solar cell interface as revealed by hard x-ray photoelectron spectroscopy

Hard X-ray photoelectron spectroscopy (HAXPES) is used to identify chemical interactions (such as elemental redistribution) at the buried silicon /aluminum-doped zinc oxide thin-film solar cell interface. Expanding our study of the interfacial oxidation of silicon upon its solid-phase crystallization (SPC), in which we found zinc oxide to be the source of oxygen, in this investigation we address chemical interaction processes involving zinc and aluminum. In particular, we observe an increase of zinc- and aluminum-related HAXPES signals after SPC of the deposited amorphous silicon thin films. Quantitative analysis suggests an elemental redistribution in the proximity of the silicon/aluminum-doped zinc oxide interface – more pronounced for aluminum than for zinc – as explanation. Based on these insights the complex chemical interface structure is discussed

Understanding an empirically optimized contact

The electronic structure of the interface between the boron-doped oxygenated amorphous silicon “window layer” (a-SiOx:H(B)) and aluminum-doped zinc oxide (ZnO:Al) was investigated using hard x-ray photoelectron spectroscopy and compared to that of the boron-doped microcrystalline silicon (μc- Si:H(B))/ZnO:Al interface. The corresponding valence band offsets have been determined to be (−2.87 ± 0.27) eV and (−3.37 ± 0.27) eV, respectively. A lower tunnel junction barrier height at the μc-Si:H(B)/ZnO:Al interface compared to that at the a-SiOx:H(B)/ZnO:Al interface is found and linked to the higher device performances in cells where a μc-Si:H(B) buffer between the a-Si:H p-i-n absorber stack and the ZnO:Al contact is employed