The turnover number for band 3-mediated sulfate transport in phosphatidylcholine bilayers

AbstractThe anion transport system of the human erythrocyte membrane was reconstituted in unilamellar phosphatidylcholine vesicles, and a vesicle subpopulation of a narrow size distribution was isolated from the sample by gel filtration. In this subpopulation, the turnover number of the transport protein (the band 3 protein) for sulfate transport was determined. It was found that, in the reconstituted system, the protein transports sulfate 5–10-times faster than in the human erythrocyte membrane

Massive X-ray screening reveals two allosteric drug binding sites of SARS-CoV-2 main protease

The coronavirus disease (COVID-19) caused by SARS-CoV-2 is creating tremendous health problems and economical challenges for mankind. To date, no effective drug is available to directly treat the disease and prevent virus spreading. In a search for a drug against COVID-19, we have performed a massive X-ray crystallographic screen of repurposing drug libraries containing 5953 individual compounds against the SARS-CoV-2 main protease (Mpro), which is a potent drug target as it is essential for the virus replication. In contrast to commonly applied X-ray fragment screening experiments with molecules of low complexity, our screen tested already approved drugs and drugs in clinical trials. From the three-dimensional protein structures, we identified 37 compounds binding to Mpro. In subsequent cell-based viral reduction assays, one peptidomimetic and five non-peptidic compounds showed antiviral activity at non-toxic concentrations. Interestingly, two compounds bind outside the active site to the native dimer interface in close proximity to the S1 binding pocket. Another compound binds in a cleft between the catalytic and dimerization domain of Mpro. Neither binding site is related to the enzymatic active site and both represent attractive targets for drug development against SARS-CoV-2. This X-ray screening approach thus has the potential to help deliver an approved drug on an accelerated time-scale for this and future pandemics

X-ray screening identifies active site and allosteric inhibitors of SARS-CoV-2 main protease

The coronavirus disease (COVID-19) caused by SARS-CoV-2 is creating tremendous human suffering. To date, no effective drug is available to directly treat the disease. In a search for a drug against COVID-19, we have performed a high-throughput X-ray crystallographic screen of two repurposing drug libraries against the SARS-CoV-2 main protease (M^(pro)), which is essential for viral replication. In contrast to commonly applied X-ray fragment screening experiments with molecules of low complexity, our screen tested already approved drugs and drugs in clinical trials. From the three-dimensional protein structures, we identified 37 compounds that bind to M^(pro). In subsequent cell-based viral reduction assays, one peptidomimetic and six non-peptidic compounds showed antiviral activity at non-toxic concentrations. We identified two allosteric binding sites representing attractive targets for drug development against SARS-CoV-2

<scp>ReSurveyEurope</scp>: A database of resurveyed vegetation plots in Europe

AbstractAimsWe introduce ReSurveyEurope — a new data source of resurveyed vegetation plots in Europe, compiled by a collaborative network of vegetation scientists. We describe the scope of this initiative, provide an overview of currently available data, governance, data contribution rules, and accessibility. In addition, we outline further steps, including potential research questions.ResultsReSurveyEurope includes resurveyed vegetation plots from all habitats. Version 1.0 of ReSurveyEurope contains 283,135 observations (i.e., individual surveys of each plot) from 79,190 plots sampled in 449 independent resurvey projects. Of these, 62,139 (78%) are permanent plots, that is, marked in situ, or located with GPS, which allow for high spatial accuracy in resurvey. The remaining 17,051 (22%) plots are from studies in which plots from the initial survey could not be exactly relocated. Four data sets, which together account for 28,470 (36%) plots, provide only presence/absence information on plant species, while the remaining 50,720 (64%) plots contain abundance information (e.g., percentage cover or cover–abundance classes such as variants of the Braun‐Blanquet scale). The oldest plots were sampled in 1911 in the Swiss Alps, while most plots were sampled between 1950 and 2020.ConclusionsReSurveyEurope is a new resource to address a wide range of research questions on fine‐scale changes in European vegetation. The initiative is devoted to an inclusive and transparent governance and data usage approach, based on slightly adapted rules of the well‐established European Vegetation Archive (EVA). ReSurveyEurope data are ready for use, and proposals for analyses of the data set can be submitted at any time to the coordinators. Still, further data contributions are highly welcome.</jats:sec

Betreuungsqualität insulinpflichtiger Diabetiker in der zentralen Diabetesambulanz eines nordostdeutschen Stadtkreises im Verlauf von 6 Jahren

HINTERGRUND: Ziel der Studie war es, die Betreuungsqualität einer diabetologisch spezialisierten ambulanten Arztpraxis im zeitlichen Verlauf zu untersuchen und Möglichkeiten eines Qualitässicherungsmonitorings zu evaluieren. - METHODE: ES wurde retrospektiv eine Klientel von 303 nicht selektierten Diabetikern mit Insulintherapie (32,7 % Typ 1) eines Stadtkreise von 91.068 Einwohnern für die Jahre 1987, 1990 und 1993 untersucht. - ERGEBNISSE: Ausgewählte Ergebnisse im Vergleich 1987 zu 1993: ärztliche Konsultationen pro Jahr: 8,0 vs. 7,9. Intensivierte Insulintherapie: 77,8 % vs. 84,8 % (Typ 1) bzw. 2,1 % vs. 2,5 % (Typ 2). Gewichtsbezogene Insulindosis pro Tag: 0,64 vs. 0,65 (Typ 1) bzw. 0,48 vs. 0,58 (Typ 2) IU*kg'1*d"1. Mittlere non-fasting-Blutglukose [mmol/1]: 11,3 vs. 10,1 (Verbesserung um 10,6 %; p < 0,05). Mittleres HbAlc [%]: 9,0 vs. 8,6 (Verbesserung um 4,5 %) untersucht bei 12,2 vs. 94,1 % aller Patienten. Patienten mit Glykohämoglobinwerten im Normbereich: 5 % vs. 21,8 % (Verbesserung um 16,8 %). Mittleres Cholesterol [mmol/1]: 7,0 vs. 6,1 (p < 0,05) untersucht bei 22,1 vs. 94,1 % aller Patienten. Mittlerer arterieller Blutdruck [mmHg]: 156 vs. 149 systolisch bzw. 92 vs. 85 diastolisch (p < 0,05). Mittlerer Body-Mass-Index [kg*(m)~2]: 27,3 vs. 27,9. Prävalenz einer proliferativen Retinopathie: 9,1 vs. 11,1 % beim Typ 1 (untersucht bei 67,7 vs. 84,8 % aller Patienten) bzw. 1,0 vs. 7,5 % beim Typ 2 (untersucht bei 52,2 vs. 80,9 % aller Patienten). Prävalenz einer Nephropathie (Stadien III bis V nach MORGENSON): 27,3 vs. 68,7 % (Typ 1) bzw. 20,6 vs. 70,0 % (Typ 2). Prävalenz von Fußkomplikationen (Ulzerationen und Amputationen): 2,0 vs. 3,0 % (Typ 1) bzw. 1.5 vs. 1,5 % (Typ2). - SCHLUSSFOLGERUNGEN: Die Betreuungsqualität der untersuchten Arztpraxis war durchgehend Leitlinien-gerecht bezüglich der Prozessqualität und akzeptabel bezüglich der meisten Indikatoren der Ergebnisqualität. Aufgrund, der gewöhnlichen Inzidenzen der Spätkomplikationen wie Erblindungen, Nierenversagen, Amputationen, KHK und perinataler Komplikationen, sind signifikante Aussagen nur im Rahmen territorial übergreifender Netzwerke mit Benchmarking möglich. SCHLÜSSELWÖRTER: Betreuungsqualität, Diabetes mellitus, Glykohämoglobine, HbAlc, Spätkomplikationen, Retinopathie, Nephropathie, Fußkomplikationen, Koronare Herzkrankheit, perinatale Komplikationen, St. Vincent DeklarationBACKGROUND: The objective of this study was to examine the quality of health care in time dependent course and to evaluate possibilities for a monitoring of quality in concerning in a diabetes specialized outpatient setting. - METHODS: We studied retrospective a clientele of 303 non selected diabetic patients with insulin-treatment (32,7 % type 1) in 1987, 1990 and 1993 in a township of 91,068 inhabitants. - RESULTS: Selected results in comparison 1987 to 1993: visits per year: 8,0 vs. 7,9. Intensified insulin treatment: 77,8 % vs. 84,8 % (type 1) respectively 2,1 % vs. 2,5 % (type 2). They were on 2,9 vs. 3,7 (type 1) / 2,1 vs. 2,5 (type 2) injections per day applying doses of 0,64 vs. 0,65 (type 1) / 0,48 vs. 0,58 (type 2) IU*kg"1*d"1. Mean non fasting blood glucose [mmol/1]: 11,3 vs. 10,1 (improvement 10,6 %; p < 0,05). Mean HbAlc [%]: 9,0 vs. 8,6 (improvement 4,5 %) was checked by 12,2 vs. 94,1 % of all patients. Patients with glycohemoglobin results inside the normal range: 5 % vs. 21,8 % (improvement 16,8 %). Mean cholesterol [mmol/1]: 7,0 vs. 6,1 (p< 0,05) was checked by 22,1 vs. 94,1 % of all patients. Mean blood pressure [mmHg]: 156 vs. 149 systolic respectively 92 vs. 85 diastolic (p < 0,05). Mean body mass index [kg*(m)'2]: 27,3 vs. 27,9. Proliferative retinopathy prevalence: 9,1 vs. 11,1 % in type 1 (was checked by 67,7 vs. 84,8 % of all patients) respectively 1,0 vs. 7,5 % in type 2 (was checked by 52,2 vs. 80,9 % of all patients). Nephropathy prevalence (stage III to V by MORGENSEN): 27,3 vs. 68,7 % (type 1) / 20,6 vs. 70,0 % (type 2). Foot complications prevalence (ulcers and amputations): 2,0 vs. 3,0 % (type 1) / 1,5 vs. 1,5 % (type 2). - CONCLUSIONS: The quality of care in the described outpatient setting was throughout conform with guidelines for indicators of process-quality and acceptable for most indicators of outcome-quality. Because of the low incidences of late complications diabetic associated blindness, renal failure, amputations, coronary heart disease and perinatal complications, significant testimony could only be given in over-territorial networks for benchmarking. KEY WORDS: quality of health care, diabetes mellitus, glycohemogloblins, HbAlc, late complications, retinopathy, nephropathy, microalbuminuria, foot complications, coronary heart disease, perinatal complications, St. Vincent Declaratio

Multi-level Architecture of object-oriented Operating Systems

Applications should be provided with optimal infrastructures at their run time. The proposed architecture encourages to structure a system into sets of interacting instances supported by optimal infrastructures at multiple levels. Infrastructures are organized as sets of instances as well, but of more elementary quality. Thus, a recursive architecture results with related infrastructures and instance areas that forms an n-ary tree. Each instance area provides the infrastructure for higher instance areas and needs itself a lower level infrastructure. Processing is considered as performing services among instances. Object-orientation is proved to be suitable for structuring instance areas and infrastructures. Instances performing services are objects. A discussion of general principles of object-orientation gives the background to apply it to this architecture. Most existing object-oriented systems only consider one kind or &quot;quality&quot; of objects, which is however inadequate for operating..

Cost Efficacy of Tazobactam/Piperacillin versus Imipenem/Cilastatin in the Treatment of Intra-Abdominal Infection

Objective: To compare the cost, efficacy and cost efficacy of tazobactam/ piperacillin and imipenem/cilastatin in the treatment of intra-abdominal infection. Design: The analysis was retrospective and based on a decision tree. Effectiveness data were obtained from 19 published clinical trials. Direct costs were quantified per patient from the time the decision was made to administer the antibacterial to the end of the first course of treatment or the end of a subsequent course of treatment, if required. The primary end-point was the cost per successfully treated patient. The cost per life saved was also analysed. Various follow-up times were taken into account. Perspective: German National Health Insurance funds. Study population: 1744 patients with intra-abdominal infection. Interventions: Tazobactam/piperacillin (total daily dosage of 13.5 g/day) and imipenem/cilastatin (total daily dosage of 1.5 to 4 g/day). The mean duration of treatment varied from 5.5 to 8.2 days for tazobactam/piperacillin and 5 to 9.4 days for imipenem/cilastatin. Main outcome measure and results: Compared with imipenem/cilastatin, treatment with tazobactam/piperacillin was more effective and the overall treatment costs were lower. In the base-case analysis, the cost-efficacy ratio (cost per successfully treated patient) was 7881 German deutschmarks (DM) for tazobactam/ piperacillin and DM11 390 for imipenem/cilastatin. The incremental cost-efficacy ratio (per life saved) varied between -DM72 567 and -DM350 738 for tazobactam/ piperacillin. Sensitivity analyses revealed that the results were robust against various assumptions on cost parameters, clinical outcomes and length of treatment. All costs reflect 1998 values; $US1 = DM1.85. Conclusions: This study suggests that compared with imipenem/cilastatin, tazobactam/piperacillin is more cost efficacious in the treatment of intra-abdominal infections and that it offers a cost advantage through fewer relapses and lower daily therapeutic costs.Antibacterials, Cost analysis, Imipenem/cilastatin, Intra abdominal infections, Pharmacoeconomics, Tazobactam/piperacillin

Zur kulturellen Bedeutung des Wohnungsbauprogramms der Sozialistischen Einheitspartei Deutschlands bei der Gestaltung der entwickelten sozialistischen Gesellschaft in der Deutschen Demokratischen Republik

HUB(11) - 92 HB 3263 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman