Deutschsprachige Vampirfiktionen des 20. Jahrhunderts

Diese Arbeit untersucht deutschsprachige Vampirfiktionen des 20. Jahrhunderts, unter Betonung intermedialer, interkultureller und politisch gesellschaftlicher Aspekte. Anhand von Werken der deutschen Literatur und des deutschen Films zeigt sie die Wandlungsfähigkeit des Vampirs auf. Sie legt dar, wie sich die Vampirfigur historischen und gesellschaftlichen Veränderungen anzupassen versucht, dabei hingegen sämtliche Grenzen überschreitet. Vampirliteratur und -filme stehen seit dem Aufkommen des Films unter wechselseitigem Einfluss. Einen der wichtigsten Bezugspunkte für Vampirliteratur und -film gleichermaßen stellt Bram Stokers Dracula dar, dessen modellbildender Vampirgraf deshalb als ein zentrales Vergleichsobjekt herangezogen wird. Die Themen „Konflikte“, „Krieg“ und „Gewalt“ ziehen sich wie ein roter Faden durch die filmischen und literarischen Werke dieser Arbeit. Steht Nosferatu (1922) im Schatten des Ersten Weltkriegs und thematisiert die Ausländerfeindlichkeit in der Gesellschaft, so erahnte der ältere Text Vampir (1920) von Hanns Heinz Ewers bereits das nahende tyrannische Regime. Alfred Döblins Roman Hamlet oder Die lange Nacht nimmt ein Ende (1956) erzählt vom Zweiten Weltkrieg und lässt durchscheinen, dass die nationalsozialistische Herrschaft auch dem Vampir zum Verhängnis wurde. Die Resonanzfähigkeit des Vampirs für den Kampf der antikapitalistischen Studentenbewegung gegen das sogenannte ‚Establishment‘ zeigt sich an Hans Werner Geißendörfers Spielfilm Debüt Jonathan (1970). Doch ebenso die psychische Auseinandersetzung mit dem eigenen Ich, auf der Suche nach einer individuellen Identität jenseits konventioneller Lebensläufe, zu der Adolf Muschg die Leser in dem Roman Das Licht und der Schlüssel (1984) aufruft, führt uns die vampirische Hauptfigur meisterhaft vor. Zuletzt betreten in Elfriede Jelineks Theaterstück Krankheit oder Moderne Frauen (1987) weibliche Vampire die gesellschaftliche Bühne, um sich im Geschlechterkampf zu behaupten

Efficient Recovery of Attenuated Canine Distemper Virus from cDNA.

To provide insights into the biology of the attenuated canine distemper virus (CDV) Onderstepoort (OP) strain (large plaque forming variant), design next-generation multivalent vaccines, or further investigate its promising potential as an oncolytic vector, we employed contemporary modifications to establish an efficient OP-CDV-based reverse genetics platform. Successful viral rescue was obtained however only upon recovery of a completely conserved charged residue (V13E) residing at the N-terminal region of the large protein (L). Although L-V13 and L-V13E did not display drastic differences in cellular localization and physical interaction with P, efficient polymerase complex (P+L) activity was recorded only with L-V13E. Interestingly, grafting mNeonGreen to the viral N protein via a P2A ribosomal skipping sequence (OPneon) and its derivative V-protein-knockout variant (OPneon-Vko) exhibited delayed replication kinetics in cultured cells. Collectively, we established an efficient OP-CDV-based reverse genetics system that enables the design of various strategies potentially contributing to veterinary medicine and research

Nirmatrelvir-resistant SARS-CoV-2 is efficiently transmitted in female Syrian hamsters and retains partial susceptibility to treatment.

The SARS-CoV-2 main protease (3CLpro) is one of the promising therapeutic targets for the treatment of COVID-19. Nirmatrelvir is the first 3CLpro inhibitor authorized for treatment of COVID-19 patients at high risk of hospitalization. We recently reported on the in vitro selection of SARS-CoV-2 3CLpro resistant virus (L50F-E166A-L167F; 3CLprores) that is cross-resistant with nirmatrelvir and other 3CLpro inhibitors. Here, we demonstrate that the 3CLprores virus replicates efficiently in the lungs of intranasally infected female Syrian hamsters and causes lung pathology comparable to that caused by the WT virus. Moreover, hamsters infected with 3CLprores virus transmit the virus efficiently to co-housed non-infected contact hamsters. Importantly, at a dose of 200 mg/kg (BID) of nirmatrelvir, the compound was still able to reduce the lung infectious virus titers of 3CLprores-infected hamsters by 1.4 log10 with a modest improvement in the lung histopathology as compared to the vehicle control. Fortunately, resistance to Nirmatrelvir does not readily develop in clinical setting. Yet, as we demonstrate, in case drug-resistant viruses emerge, they may spread easily which may thus impact therapeutic options. Therefore, the use of 3CLpro inhibitors in combination with other drugs may be considered, especially in immunodeficient patients, to avoid the development of drug-resistant viruses

A Prevalence Estimation of Exstrophy and Epispadias in Germany From Public Health Insurance Data

Introduction: The prevalence of rare diseases is very important for health care research. According to the European Surveillance of Congenital Anomalies (EUROCAT) registers, the live prevalence for exstrophy and/or epispadias (grades 1–3) is reported with 1:23,255 (95% CI: 1:26,316; 1:20,000). A Europe-wide prevalence evaluation based on reports from excellence centers estimates a prevalence for exstrophies of 1:32,200 and for isolated epispadias of 1:96,800 in 2010. However, the frequency of exstrophy [International Statistical Classification of Diseases and Related Health Problems revision 10 (ICD-10): Q64.1] and epispadias (ICD-10: Q64.0) treated in different age groups in Germany remains unclear. Material and Method: Public health insurance data from 71 million people (approximately 87% of the population) were provided by the German Institute for Medical Documentation and Information (DIMDI) in accordance to the German Social Insurance Code for this research purpose. DIMDI analyzed the data source for the ICD diagnoses exstrophy and epispadias between 2009 and 2011. As provided data were robust over the years, averaged data are mentioned. Detailed subgroup analysis of small numbers was forbidden due to privacy protection. Results: Annually, 126 persons of all ages with epispadias and 244 with exstrophy are treated as inpatients. In the observed population, 34 infants (<1 year of age) with epispadias and 19 with exstrophy (58% male) are treated as outpatients each year. This corresponds to an estimated live prevalence of 1:11,000 (95% CI: 1:14,700; 1:8,400) for EEC (exstrophy–epispadias complex), more specifically a prevalence of 1:17,142 for epispadias and of 1:30,675 for exstrophy. The male-to-female ratio for exstrophy is 1.4:1 for infants and 1.6:1 for all minors. In children and adolescents, 349 epispadias and 393 exstrophies (up to the age of 17) are treated annually, whereas adults with exstrophy and even more with epispadias make comparatively less use of medical care. Conclusion: With the help of DIMDI data, the live prevalence of bladder exstrophy and epispadias in Germany could be estimated. The prevalence of epispadias was higher than in previous reports, in which milder epispadias phenotypes (grade 1 or 2) may not have been included. These analyses might enlighten knowledge about nationwide incidence and treatment numbers of rare diseases such as the EEC

A multicenter phase 4 geriatric assessment directed trial to evaluate gemcitabine +/− nab-paclitaxel in elderly pancreatic cancer patients (GrantPax)

Background: In the group of elderly patients (≥70 years) with metastatic pancreatic ductal adenocarcinoma (mPDAC), it is not known who benefits from intensive 1st line nab-paclitaxel/gemcitabine (nab-p/gem) combination chemotherapy or who would rather suffer from increased toxicity. We aim to determine whether treatment individualization by comprehensive geriatric assessments (CGAs) improves functional outcome of the patients. Methods/Design: GrantPax is a multicenter, open label phase 4 interventional trial. We use a CGA to stratify elderly patients into three parallel treatment groups (n = 45 per arm): 1) GOGO (nab-p/gem), 2) SLOWGO (gem mono) or 3) FRAIL (best supportive care). After the 1st cycle of chemotherapy (or 4 weeks in FRAIL group) another CGA and safety assessment is performed. CGA-stratified patients may not decline in their CGA performance in response to the first cycle of chemotherapy (primary objective), measured as a loss of 5 points or less in Barthels activities of daily living. Based on the second CGA, patients are re-assigned to their definite treatment arm and undergo further CGAs to monitor the course of treatment. Secondary endpoints include CGA scores during the course of therapy (CGA1–4), response rates, safety and survival rates. Discussion: GrantPax is the first trial implementing a CGA-driven treatment to personalize therapy for elderly patients with pancreatic cancer. This may lead to standardization of therapy decisions for elderly patients and may optimize standard of care for this increasing group of patients. Trial registration: NCT02812992 , registered 24.06.2016

Sorption und Abbau ausgewählter Pflanzenschutzmittel-Wirkstoffe (PSM) auf tiefgründigen Lößböden

Einträge von Pflanzenschutzmittel-Wirkstoffen (PSM) können erheblich zur Belastung von Grundwasser und Oberflächengewässern beitragen. Eine Identifizierung der Eintragsquellen ist jedoch oft problematisch, da zahlreiche Wirkstoffe sowohl in der Landwirtschaft als auch in Siedlungsbereichen eingesetzt werden (=duale Wirkstoffe). Bisherige Untersuchungen zeigten in den meisten Fällen keine Übereinstimmung zwischen der PSM-Anwendung in der Landwirtschaft und Wirkstoff-Funden im Oberflächengewässer. Belastbare, stoff- und standortspezifische Migrationsparameter, welche die Basis für eine gesicherte Stoffprognose darstellen, existieren für den Anwendungsfall bisher nicht. Um diese Informationen zur Mobilität und Persistenz der PSM zu gewinnen, werden im derzeit laufenden Projekt Laboruntersuchungen unter möglichst natürlichen Be-dingungen zum mikrobiellen Abbau relevanter Wirkstoffe im Boden (ungesättigte Zone) und im Wasser (Fließgewässer)sowie zur Sorption an der Bodenmatrix durchgeführt. Als Versuchsmethoden für die Untersuchungen dienen Bodensättigungs-extraktionsversuche (BSE) sowie klassische Batchversuche. Im Rahmen des Projektes wurden die folgenden umweltrelevanten PSM berücksichtigt: Glyphosat, MCPA, Diflufenican, Bentazon, Epoxiconazol, Terbutylazin, Metazachlor und Imidacloprid. Auf der Grundlage bisheriger Versuchsergebnisse der Abbauversuche konnte in der Regel ein höherer Abbau unter aeroben als unter anaeroben Bedingungen festgestellt werden. Dabei zeigten die PSM-Wirkstoffe MCPA (Halbwertszeit von ca. 3 d unter aero-ben Bedingungen), Glyphosat und Terbutylazin eine vergleichsweise gute biologische Abbaubarkeit und die Wirkstoffe Bentazon (Halbwertszeit von ca. 1.500 d unter aeroben Bedingungen) sowie Imidacloprid eine schlechte Abbaubarkeit. In Hinblick auf die Sorption ist ebenfalls ein stark stoffspezifisches Verhalten feststellbar. Für das Glyphosat konnte hier im Vergleich zu den anderen PSM eine deutliche höhere Sorptionsneigung für den Lößboden ermittelt werden

Live attenuated virus vaccine protects against SARS-CoV-2 variants of concern B.1.1.7 (Alpha) and B.1.351 (Beta).

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Establishment of well-differentiated camelid airway cultures to study Middle East respiratory syndrome coronavirus.

In 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in Saudi Arabia and was mostly associated with severe respiratory illness in humans. Dromedary camels are the zoonotic reservoir for MERS-CoV. To investigate the biology of MERS-CoV in camelids, we developed a well-differentiated airway epithelial cell (AEC) culture model for Llama glama and Camelus bactrianus. Histological characterization revealed progressive epithelial cellular differentiation with well-resemblance to autologous ex vivo tissues. We demonstrate that MERS-CoV displays a divergent cell tropism and replication kinetics profile in both AEC models. Furthermore, we observed that in the camelid AEC models MERS-CoV replication can be inhibited by both type I and III interferons (IFNs). In conclusion, we successfully established camelid AEC cultures that recapitulate the in vivo airway epithelium and reflect MERS-CoV infection in vivo. In combination with human AEC cultures, this system allows detailed characterization of the molecular basis of MERS-CoV cross-species transmission in respiratory epithelium