Der Zweite Weltkrieg in der Literatur : österreichische Beispiele

Das Interesse an den literarischen Antworten auf den Krieg war in Österreich nicht besonders ausgeprägt, sonst hätte die Literatur zum Krieg einen größeren Stellenwert als sie hatte und hat – bei den Lesern wie bei den Literaturhistorikern. Es gibt zwar Aufsätzen zu einzelnen Werken, doch es existiert – mit Ausnahme einer Monographie zur Dramatik – bis heute keine umfassende Arbeit zum Thema. Die Ausstellung ‚Verbrechen der Wehrmacht’, die sie begleitende wissenschaftliche Debatte und die durch beide ausgelösten öffentlichen Kontroversen haben unseren Blick auf den Zweiten Weltkrieg entscheidend verändert. Sie haben ihn geschärft für das, was den anderen angetan werden sollte und tatsächlich angetan wurde. Das lässt auch eine Lektüre der Literatur über diesen Krieg nicht unberührt. Was ist vom nationalsozialistischen Vernichtungskrieg gegen diese Personengruppen in der österreichischen Literatur sichtbar? Der folgende Bericht bezieht sich auf die unmittelbare Nachkriegszeit bis zum Abschluss der Staatsvertragsverhandlungen 1955. Dieses politische Datum bildet, wie sich zeigen wird, einen auffallenden Einschnitt

Endothelin receptor antagonists influence cardiovascular morphology in uremic rats

Endothelin receptor antagonists influence cardiovascular morphology in uremic rats.BackgroundIt is generally held that renal failure results in blood pressure (BP)-independent structural changes of the myocardium and the vasculature. The contribution, if any, of endothelin (ET) to these changes has been unknown.MethodsWe morphometrically studied random samples of the left ventricle myocardium and small intramyocardial arteries in subtotally (5/6) nephrectomized (SNx) male Sprague-Dawley rats treated with either the selective ETA receptor antagonist BMS182874 (30mg/kg/day) or the nonselective ETA/ETB receptor antagonist Ro46-2005 (30mg/kg/day) in comparison with either sham-operated rats, untreated SNx, or SNx rats treated with the angiotensin-converting enzyme inhibitor trandolapril (0.1mg/kg/day).ResultsEight weeks later, systolic BP was lower in trandolapril-treated SNx compared with untreated SNx animals. No decrease in BP was seen following either ET receptor antagonist at the dose used. A significantly increased volume density of the myocardial interstitium was found in untreated SNx rats as compared with sham-operated controls. Such interstitial expansion was prevented by trandolapril and either ET receptor antagonist. SNx caused a substantial increase in the wall thickness of small intramyocardial arteries. The increase was prevented by trandolapril or BMS182874 treatment. The arteriolar wall:lumen ratio was significantly lower in all treated groups when compared with untreated SNx. In contrast, only trandolapril, but not the ET receptor antagonists, attenuated thickening of the aortic media in SNx animals.ConclusionsThe ETA-selective and ETA/ETB-nonselective receptor antagonists appear to prevent development of myocardial fibrosis and structural changes of small intramyocardial arteries in experimental chronic renal failure. This effect is independent of systemic BP

Case Report: Pediatric Renal Sarcoidosis and Prognostic Factors in Reviewed Cases

Background: Pediatric sarcoidosis is a complex inflammatory disorder with multisystemic manifestations. Kidney involvement in children is rare, and prognostic factors are unknown. Case Report and Methods: We report the case of a 16-year-old girl with multiorgan sarcoidosis and renal involvement. The patient presented with tubulointerstitial nephritis, acute kidney injury (AKI), chest CT disseminated noduli, granulomatous iridocyclitis, giant-cell sialadenitis, and arthralgia. The kidney biopsy revealed non-granulomatous interstitial nephritis. Treatment consisted of initial high-dose methylprednisolone pulse followed by oral prednisolone and methotrexate. Full remission was achieved. In addition, we performed a literature review using PubMed and analyzed data on pediatric renal sarcoidosis cases. Results: We identified 36 cases of pediatric sarcoidosis with renal involvement on presentation and data on the end-of-follow-up glomerular filtration rate (GFR). The data from the literature review showed that renal involvement was slightly more prevalent in males (60%). AKI was present in most of the described patients (84%). Oral prednisolone was used in 35 of 36 cases; in more severe cases, other immunosuppressants were used. We newly identified renal concentration impairment and granulomatous interstitial nephritis as factors with a clear trend toward GFR loss at the end of follow-up, emphasizing the importance of kidney biopsy in symptomatic patients. In contrast, higher GFR at presentation and hypercalcemia were rather favorable factors. According to the identified predictive factors, our patient has a good prognosis and is in remission. Conclusion: The factors indicating a trend toward an unfavorable renal outcome in pediatric sarcoidosis are renal concentration impairment and granulomatous interstitial nephritis at presentation, while a higher GFR is beneficial

Precursors for cytochrome P450 profiling breath tests from an in silico screening approach

The family of cytochrome P450 enzymes (CYPs) is a major player in the metabolism of drugs and xenobiotics. Genetic polymorphisms and transcriptional regulation give a complex patient-individual CYP activity profile for each human being. Therefore, personalized medicine demands easy and non-invasive measurement of the CYP phenotype. Breath tests detect volatile organic compounds (VOCs) in the patients’ exhaled air after administration of a precursor molecule. CYP breath tests established for individual CYP isoforms are based on the detection of 13CO2 or 14CO2 originating from CYP-catalyzed oxidative degradation reactions of isotopically labeled precursors. We present an in silico work-flow aiming at the identification of novel precursor molecules, likely to result in VOCs other than CO2 upon oxidative degradation as we aim at label-free precursor molecules. The ligand-based work-flow comprises five parts: (1) CYP profiling was encoded as a decision tree based on 2D molecular descriptors derived from established models in the literature and validated against publicly available data extracted from the DrugBank. (2) Likely sites of metabolism were identified by reactivity and accessibility estimation for abstractable hydrogen radical. (3) Oxidative degradation reactions (O- and N-dealkylations) were found to be most promising in the release of VOCs. Thus, the CYP-catalyzed oxidative degradation reaction was encoded as SMIRKS (a programming language style to implement reactions based on the SMARTS description) to enumerate possible reaction products. (4) A quantitative structure property relation (QSPR) model aiming to predict the Henry constant H was derived from data for 488 organic compounds and identifies potentially VOCs amongst CYP reaction products. (5) A blacklist of naturally occurring breath components was implemented to identify marker molecules allowing straightforward detection within the exhaled air.peer-reviewe

Effect of pitchfork bifurcations on the spectral statistics of Hamiltonian systems

We present a quantitative semiclassical treatment of the effects of bifurcations on the spectral rigidity and the spectral form factor of a Hamiltonian quantum system defined by two coupled quartic oscillators, which on the classical level exhibits mixed phase space dynamics. We show that the signature of a pitchfork bifurcation is two-fold: Beside the known effect of an enhanced periodic orbit contribution due to its peculiar $\hbar$-dependence at the bifurcation, we demonstrate that the orbit pair born {\em at} the bifurcation gives rise to distinct deviations from universality slightly {\em above} the bifurcation. This requires a semiclassical treatment beyond the so-called diagonal approximation. Our semiclassical predictions for both the coarse-grained density of states and the spectral rigidity, are in excellent agreement with corresponding quantum-mechanical results.Comment: LaTex, 25 pp., 14 Figures (26 *.eps files); final version 3, to be published in Journal of Physics

Complement Activation in Kidneys of Patients With COVID-19

Most patients who became critically ill following infection with COVID-19 develop severe acute respiratory syndrome (SARS) attributed to a maladaptive or inadequate immune response. The complement system is an important component of the innate immune system that is involved in the opsonization of viruses but also in triggering further immune cell responses. Complement activation was seen in plasma adsorber material that clogged during the treatment of critically ill patients with COVID-19. Apart from the lung, the kidney is the second most common organ affected by COVID-19. Using immunohistochemistry for complement factors C1q, MASP-2, C3c, C3d, C4d, and C5b-9 we investigated the involvement of the complement system in six kidney biopsies with acute kidney failure in different clinical settings and three kidneys from autopsy material of patients with COVID-19. Renal tissue was analyzed for signs of renal injury by detection of thrombus formation using CD61, endothelial cell rarefaction using the marker E-26 transformation specific-related gene (ERG-) and proliferation using proliferating cell nuclear antigen (PCNA)-staining. SARS-CoV-2 was detected by in situ hybridization and immunohistochemistry. Biopsies from patients with hemolytic uremic syndrome (HUS, n = 5), severe acute tubular injury (ATI, n = 7), zero biopsies with disseminated intravascular coagulation (DIC, n = 7) and 1 year protocol biopsies from renal transplants (Ctrl, n = 7) served as controls. In the material clogging plasma adsorbers used for extracorporeal therapy of patients with COVID-19 C3 was the dominant protein but collectin 11 and MASP-2 were also identified. SARS-CoV-2 was sporadically present in varying numbers in some biopsies from patients with COVID-19. The highest frequency of CD61-positive platelets was found in peritubular capillaries and arteries of COVID-19 infected renal specimens as compared to all controls. Apart from COVID-19 specimens, MASP-2 was detected in glomeruli with DIC and ATI. In contrast, the classical pathway (i.e. C1q) was hardly seen in COVID-19 biopsies. Both C3 cleavage products C3c and C3d were strongly detected in renal arteries but also occurs in glomerular capillaries of COVID-19 biopsies, while tubular C3d was stronger than C3c in biopsies from COVID-19 patients. The membrane attack complex C5b-9, demonstrating terminal pathway activation, was predominantly deposited in COVID-19 biopsies in peritubular capillaries, renal arterioles, and tubular basement membrane with similar or even higher frequency compared to controls. In conclusion, various complement pathways were activated in COVID-19 kidneys, the lectin pathway mainly in peritubular capillaries and in part the classical pathway in renal arteries whereas the alternative pathway seem to be crucial for tubular complement activation. Therefore, activation of the complement system might be involved in the worsening of renal injury. Complement inhibition might thus be a promising treatment option to prevent deregulated activation and subsequent collateral tissue injury

Socio-Informatics

Contents Editorial Thematic Focus: Socio-Informatics Introduction to the Thematic Focus “Socio-Informatics” / Claudia Müller Digitalisation in Small German Metal-Working Companies. Appropriation of Technology in a “Traditional” Industrial Domain / Bernhard Nett, Jennifer Bönsch Travelling by Taxi Brousse in Madagascar: An Investigation into Practices of Overland Transportation / Volker Wulf, Kaoru Misaki, Dave Randall, and Markus Rohde Mobile and Interactive Media in the Store? Design Case Study on Bluetooth Beacon Concepts for Food Retail / Christian Reuter, Inken Leopold Facebook and the Mass Media in Tunisia / Konstantin Aal, Marén Schorch, Esma Ben Hadj Elkilani, Volker Wulf Book Review Symposium Charles Goodwin Charles Goodwin’s Co-Operative Action: The Idea and the Argument / Erhard Schüttpelz, Christian Meyer Multi-Modal Interaction and Tool-Making: Goodwin’s Intuition / Christian Meyer, Erhard Schüttpelz Co-Operation is a Feature of Sociality, not an Attribute of People : “We inhabit each other’s actions.” (Goodwin, cover) / Jutta Wiesemann, Klaus Amann The Making of the World in Co-Operative Action. From Sentence Construction to Cultural Evolution / Jürgen Streeck On Goodwin and his Co-Operative Action / Jörg R. Bergman

Time-resolved cryo-EM (TR-EM) analysis of substrate polyubiquitination by the RING E3 anaphase-promoting complex/cyclosome (APC/C)

Substrate polyubiquitination drives a myriad of cellular processes, including the cell cycle, apoptosis and immune responses. Polyubiquitination is highly dynamic, and obtaining mechanistic insight has thus far required artificially trapped structures to stabilize specific steps along the enzymatic process. So far, how any ubiquitin ligase builds a proteasomal degradation signal, which is canonically regarded as four or more ubiquitins, remains unclear. Here we present time-resolved cryogenic electron microscopy studies of the 1.2MDa E3 ubiquitin ligase, known as the anaphase-promoting complex/cyclosome (APC/C), and its E2 co-enzymes (UBE2C/UBCH10 and UBE2S) during substrate polyubiquitination. Using cryoDRGN (Deep Reconstructing Generative Networks), a neural network-based approach, we reconstruct the conformational changes undergone by the human APC/C during polyubiquitination, directly visualize an active E3-E2 pair modifying its substrate, and identify unexpected interactions between multiple ubiquitins with parts of the APC/C machinery, including its coactivator CDH1. Together, we demonstrate how modification of substrates with nascent ubiquitin chains helps to potentiate processive substrate polyubiquitination, allowing us to model how a ubiquitin ligase builds a proteasomal degradation signal

Prevention and treatment of renal osteodystrophy in children on chronic renal failure: European guidelines

Childhood renal osteodystrophy (ROD) is the consequence of disturbances of the calcium-regulating hormones vitamin D and parathyroid hormone (PTH) as well as of the somatotroph hormone axis associated with local modulation of bone and growth cartilage function. The resulting growth retardation and the potentially rapid onset of ROD in children are different from ROD in adults. The biochemical changes of ROD as well as its prevention and treatment affect calcium and phosphorus homeostasis and are directly associated with the development of cardiovascular disease in pediatric renal patients. The aims of the clinical and biochemical surveillance of pediatric patients with CRF or on dialysis are prevention of hyperphosphatemia, avoidance of hypercalcemia and keeping the calcium phosphorus product below 5 mmol(2)/l(2). The PTH levels should be within the normal range in chronic renal failure (CRF) and up to 2–3 times the upper limit of normal levels in dialysed children. Prevention of ROD is expected to result in improved growth and less vascular calcification