Eine Generationenbilanz für Österreich. Exemplarische Analyse der intergenerativen Umverteilungswirkungen der öffentlichen Haushalte

Angesichts der massiven Finanzierungsproblematik, der sich die öffentliche Hand kurz- und mittelfristig aufgrund der geschilderten Herausforderungen gegenübersieht, ist zu thematisieren, in welcher Art und Weise die Lasten der Sanierung der öffentlichen Haushalte fair auf die Bevölkerung aufgeteilt werden sollten. In diesem Zusammenhang ist zu bemerken, dass in der öffentlichen Debatte sehr wohl die vertikale Umverteilung zwischen verschiedenen Einkommenshöhen angesprochen wird. Demgegenüber fehlt jedoch das Bewusstsein, dass Konsolidierungsmaßnahmen auch die Verteilungswirkung des Staatshaushalts zwischenverschiedenen Generationen verändert. Das Studienvorhaben zielt darauf ab, eine wesentliche empirische Grundlage zur Beurteilung der intergenerativen Umverteilungswirkung der öffentlichen Haushalte zu generieren

Thermostable designed ankyrin repeat proteins (DARPins) as building blocks for innovative drugs

Designed ankyrin repeat proteins (DARPins) are antibody mimetics with high and mostly unexplored potential in drug development. By using in silico analysis and a rationally guided Ala scanning, we identified position 17 of the N-terminal capping repeat to play a key role in overall protein thermostability. The melting temperature of a DARPin domain with a single full-consensus internal repeat was increased by 8 °C to 10 °C when Asp17 was replaced by Leu, Val, Ile, Met, Ala, or Thr. We then transferred the Asp17Leu mutation to various backgrounds, including clinically validated DARPin domains, such as the vascular endothelial growth factor-binding domain of the DARPin abicipar pegol. In all cases, these proteins showed improvements in the thermostability on the order of 8 °C to 16 °C, suggesting the replacement of Asp17 could be generically applicable to this drug class. Molecular dynamics simulations showed that the Asp17Leu mutation reduces electrostatic repulsion and improves van-der-Waals packing, rendering the DARPin domain less flexible and more stable. Interestingly, this beneficial Asp17Leu mutation is present in the N-terminal caps of three of the five DARPin domains of ensovibep, a SARS-CoV-2 entry inhibitor currently in clinical development, indicating this mutation could be partly responsible for the very high melting temperature (>90 °C) of this promising anti-COVID-19 drug. Overall, such N-terminal capping repeats with increased thermostability seem to be beneficial for the development of innovative drugs based on DARPins. Keywords: DARPin; N-terminal capping repeat; abicipar pegol; designed ankyrin repeat protein; drug development; drug engineering; ensovibep; molecular dynamics; thermostabilit

A Rapid, Highly Sensitive and Open-Access SARS-CoV-2 Detection Assay for Laboratory and Home Testing

RT-qPCR-based diagnostic tests play important roles in combating virus-caused pandemics such as Covid-19. However, their dependence on sophisticated equipment and the associated costs often limits their widespread use. Loop-mediated isothermal amplification after reverse transcription (RT-LAMP) is an alternative nucleic acid detection method that overcomes these limitations. Here, we present a rapid, robust, and sensitive RT-LAMP-based SARS-CoV-2 detection assay. Our 40-min procedure bypasses the RNA isolation step, is insensitive to carryover contamination, and uses a colorimetric readout that enables robust SARS-CoV-2 detection from various sample types. Based on this assay, we have increased sensitivity and scalability by adding a nucleic acid enrichment step (Bead-LAMP), developed a version for home testing (HomeDip-LAMP), and identified open-source RT-LAMP enzymes that can be produced in any molecular biology laboratory. On a dedicated website, rtlamp.org (DOI: 10.5281/zenodo.6033689), we provide detailed protocols and videos. Our optimized, general-purpose RT-LAMP assay is an important step toward population-scale SARS-CoV-2 testing.MK was supported by the Vienna Science and Technology Fund (WWTF) through project COV20-031 (to JZ) and a Cambridge Trust LMB Cambridge Scholarship. Research in the AP lab is supported by the Austrian Science Fund (START Projekt Y 1031-B28, SFB “RNA-Deco” F 80) and EMBO-YIP; research in the JB lab is supported by the European Research Council (ERC- 2015-CoG - 682181). The IMP receives generous institutional funding from Boehringer Ingelheim and the Austrian Research Promotion Agency (Headquarter grant FFG-852936); IMBA is generously supported by the Austrian Academy of Sciences. Work in the LM-A laboratory is supported by grant PID2019- 104176RB-I00/AEI/10.13039/501100011033 of the Spanish Ministry of Science and Innovation, and an institutional grant of the Fundación Ramón Areces.Peer reviewe

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Complexity Analysis of Term Rewriting Based on Matrix and Context Dependent Interpretations

For a given (terminating) term rewriting system one can often estimate its derivational complexity indirectly by looking at the proof method that established termination. In this spirit we investigate two instances of the interpretation method: matrix interpretations and context dependent interpretations. We introduce a subclass of matrix interpretations, denoted as triangular matrix interpretations, which induce polynomial derivational complexity and establish tight correspondence results between a subclass of context dependent interpretations and restricted triangular matrix interpretations. The thus obtained new results are easy to implement and considerably extend the analytic power of existing results. We provide ample numerical data for assessing the viability of the method

Serbia Functional Review: Efficiency Analysis of the National Employment Service

Introduction; Technical Approach and Methodology; Results; Executive Summary; Details for individual branch offices; Literature

Dental Students’ Oral Health-Related Quality of Life and Temporomandibular Dysfunction-Self-Rating versus Clinical Assessment

The aim of this study was to compare dental students’ self-perception of oral health with the results of a clinical examination of the masticatory system. Seventy-four dental students (38 (51.4%) females and 36 (48.6%) males) completed the Oral Health Impact Profile questionnaire (OHIP-G-14) and underwent a clinical examination according to the Graz Dysfunction Index (GDI). Data were analyzed with descriptive and comparative statistics. Median OHIP-G-14 scores were 3 (IQR 0–6) in the total collective, 4 (1–11) in females, and 2 (0–4) in males (p = 0.072). A score of 0 was found in 29.7% of the sample. The results of the GDI were 50% “normal function”, 43.2% “adaptation”, 5.4% “compensation”, and 1.4% “dysfunction”. The comparison of OHIP-G-14 scores and DGI groups showed a significant difference (p = 0.031). Based on the questionnaire, less than one third of the sample indicated maximum oral health-related quality of life. In contrast, the GDI revealed “normal function” or “adaptation” in 93.2%. Dental students underappreciated their oral health condition. Health assessments should not be solely questionnaire-based, especially in health professionals (-to-be). To establish a valid diagnosis of the state of health, self-assessment must be complemented by an objective clinical examination, e.g., GDI

Dentists’ Working Conditions during the First COVID-19 Pandemic Lockdown: An Online Survey

The aim of this study was to investigate the operating conditions of dentists in Central Europe during the first coronavirus disease 2019 (COVID-19) lockdown. A survey including 24 questions was emailed to dentists in Austria, Germany, Switzerland and South Tyrol (Italy). Questions regarding dentists’ field of work, working hours, treatments performed, personal protective equipment and protocols, and economic consequences were asked. 1731 participants were included. 30.4% of participants worked mainly in Austria, 60.8% in Germany, 6% in Switzerland and 2.1% in South Tyrol. A country-specific analysis for the situation of South Tyrol was not possible due to the low participation; 53.7% of German, 45.5% of Austrian, and 11.7% of Swiss respondents reduced their working hours; 42.8% of Austrian, 41.5% of Swiss, and 17.3% of German participants closed their offices temporarily; 52.2% of respondents provided emergency service including pain management, restorations/temporaries, and denture repairs. A lack of access to FFP2/FFP3 (filtering facepiece) respirators was indicated by 59.4% Austrian, 38.0% German, and 11.7% Swiss dentists (p < 0.001). FFP2/FFP3 respirators were, when available, most frequently used in Austria (86.9%), followed by Switzerland (61.2%) and Germany (56.7%) (p < 0.001). Financial consequences could not be conclusively quantified by 58.6% of the participants. Most respondents in all partaking countries made use of governmental support. A lack of blueprints/guidelines resulted in heterogeneous working conditions. In consideration of a potentially high risk of infection in the dental setting, non-emergency dental treatments were largely suspended in all participating countries

A rapid, highly sensitive and open-access SARS-CoV-2 detection assay for laboratory and home testing

Global efforts to combat the Covid-19 pandemic caused by the beta coronavirus SARS-CoV-2 are currently based on RT-qPCR-based diagnostic tests. However, their high cost, moderate throughput and reliance on sophisticated equipment limit widespread implementation. Loop-mediated isothermal amplification after reverse transcription (RT-LAMP) is an alternative detection method that has the potential to overcome these limitations. Here we present a rapid, robust, highly sensitive and versatile RT-LAMP based SARS-CoV-2 detection assay. Our forty-minute procedure bypasses a dedicated RNA isolation step, is insensitive to carry-over contamination, and uses a hydroxynaphthol blue (HNB)-based colorimetric readout, which allows robust SARS-CoV-2 detection from various sample types. Based on this assay, we have substantially increased sensitivity and scalability by a simple nucleic acid enrichment step (bead-LAMP), established a pipette-free version for home testing (HomeDip-LAMP), and developed a version with open source enzymes that can be produced in any molecular biology setting. Our advanced, universally applicable RT-LAMP assay is a major step towards population-scale SARS-CoV-2 testing.N