Wiedervereinigung, Aufholprozess Ost und Nachhaltigkeit

Zwölf Jahre nach der Wiedervereinigung muss für Ostdeutschland eine ernüchternde Bilanz gezogen werden. Der Osten ist durch geringe privatwirtschaftliche Investitionen, eine hohe Arbeitslosigkeit und einen ungünstigen Altersaufbau gekennzeichnet. Wie wirkt sich die Anpassungsgeschwindigkeit Ostdeutschlands auf die fiskalische Nachhaltigkeit aus? --

The histone deacetylase (HDAC) Rpd3 antagonizes heterochromatin formation at telomeres in Saccharomyces cerevisiae

In Saccharomyces cerevisiae, spreading of the telomeric SIR heterochromatin complexes into centromere-proximal euchromatic regions is prevented by the activity of boundary elements. So far, these boundaries have been associated with chromatin opening activities, like histone acetyltransferases (HATs) or histone methyltransferases. Here, we show that the opposite enzymatic activity, the histone deacetylase (HDAC) Rpd3, was necessary to prevent the encroachment of heterochromatin into euchromatin at telomeres in S. cerevisiae. We found by ChIP analysis that in the absence of Rpd3, the SIR complexes were mislocalized to more centromere-proximal regions, showing that Rpd3 was necessary to restrict SIR complexes to the telomere. Furthermore, quantitative RT-PCR showed that SIR proteins repressed subtelomeric genes in rpd3Δ cells, suggesting a role for Rpd3 in the restriction of telomeric heterochromatin. When combined with the absence of the known boundary factor, the HAT SAS-I, rpd3Δ caused inappropriate SIR spreading that was lethal to yeast cells. Significantly, the lethality between sas2Δ rpd3Δ was suppressed by sir deletions, suggesting parallel functions for the two enzymes in restricting SIR proteins to heterochromatin despite their opposing enzymatic activity. In addition, Rpd3 was capable of creating a boundary when targeted to the heterochromatic loci, indicating a boundary function for Rpd3. Further analysis showed that Rpd3 in essence functioned by removing acetyl groups, such that they were no longer available for NAD+-dependent deacetylation via Sir2. This further suggested that prevention of O-acetyl-ADP-ribose (OAADPR) production during deacetylation by Sir2 in effect prevented SIR propagation. This hypothesis was strengthened by the notion that inhibition of OAADPR binding to Sir3 created a halt to SIR spreading. In further experiments, we found that Rpd3 interacted in vivo with Cac1, the largest subunit of the chromatin assembly complex CAF-I, suggesting that it deacetylated cytoplasmic histone acetylation marks in a replication-coupled fashion. Thus, Rpd3 likely performed its function in SIR restriction through a transient contact to chromatin, rather than being permanently located at subtelomeric regions. In summary, our data indicated that Rpd3 effectively removed acetyl groups in subtelomeric regions and therefore deprived Sir2 of its ability to perform the deacetylation reaction and in doing so to produce OAADPR. This in essence prevented SIR propagation and created a boundary against heterochromatin spreading

27 W 2.1 µm OPCPA system for coherent soft X-ray generation operating at 10 kHz

© 2020 Optical Society of America. Users may use, reuse, and build upon the article, or use the article for text or data mining, so long as such uses are for non-commercial purposes and appropriate attribution is maintained. All other rights are reserved.We developed a high power optical parametric chirped-pulse amplification (OPCPA) system at 2.1 µm harnessing a 500 W Yb:YAG thin disk laser as the only pump and signal generation source. The OPCPA system operates at 10 kHz with a single pulse energy of up to 2.7 mJ and pulse duration of 30 fs. The maximum average output power of 27 W sets a new record for an OPCPA system in the 2 µm wavelength region. The soft X-ray continuum generated through high harmonic generation with this driver laser can extend to around 0.55 keV, thus covering the entire water window (284 eV - 543 eV). With a repetition rate still enabling pump-probe experiments on solid samples, the system can be used for many applications.EC/H2020/654148/EU/The Integrated Initiative of European Laser Research Infrastructures/LASERLAB-EUROP

27 W 2.1 µm OPCPA system for coherent soft X-ray generation operating at 10 kHz

We developed a high power optical parametric chirped-pulse amplification (OPCPA) system at 2.1 µm harnessing a 500 W Yb:YAG thin disk laser as the only pump and signal generation source. The OPCPA system operates at 10 kHz with a single pulse energy of up to 2.7 mJ and pulse duration of 30 fs. The maximum average output power of 27 W sets a new record for an OPCPA system in the 2 µm wavelength region. The soft X-ray continuum generated through high harmonic generation with this driver laser can extend to around 0.55 keV, thus covering the entire water window (284 eV - 543 eV). With a repetition rate still enabling pump-probe experiments on solid samples, the system can be used for many applications. © 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreemen

Fiskalische Wirkungen der Einführung eines gesetzlichen Mindestlohns

Der BMAS Forschungsbericht "Fiskalische Wirkungen der Einführung eines gesetzlichen Mindestlohns" quantifiziert die mindestlohnbedingten Veränderungen von Einnahmen- und Ausgaben des öffentlichen Gesamthaushalts, also im Steuer- und Transfersystem sowie auf der Ebene der Gesetzlichen Sozialversicherungen. Ausgangspunkt für die Berechnungen stellt ein Literaturüberblick zum aktuellen Stand der quantitativ orientierten Forschung zu den Wirkungen des gesetzlichen Mindestlohns in Deutschland dar. Die durchgeführten Berechnungen erfolgen dann mit Hilfe des Mikrosimulationsmodells der Prognos auf Basis der Daten des sozio-oekonomischen Panels. Zur Abgrenzung mindestlohninduzierter Lohneffekte werden im Datensatz verschiedene Beschäftigtengruppen identifiziert. Für diese Gruppen werden kontrafaktische Stundenlöhne und Arbeitszeiten bestimmt, die als Grundlage für die Modellrechnungen "ohne Mindestlohn" genutzt werden. Abschließend erfolgt die Abschätzung der Mindestlohneffekte auf die fiskalischen Einnahmen und Ausgaben für unterschiedliche Szenarien, um die mögliche Spannbreite der Effekte aufzuzeigen.The BMAS research report "Fiscal Effects of the Introduction of a Statutory Minimum Wage" quanti-fies the minimum wage-related changes in income and expenditure in the overall public budget, i.e. in the tax and transfer system and the statutory social insurance scheme. The starting point for these calculations is an overview of the literature on the latest quantitative research into the impact of the statutory minimum wage in Germany. The calculations are then carried out with the help of Prognos‘ microsimulation model based on data from the Socio-Economic Panel. In the data set, various em-ployee groups are identified to differentiate minimum wage effects. Counterfactual hourly wages and working hours are determined for these groups, which are then used as the basis for the "without minimum wages" model calculations. Finally, the minimum wage effects on fiscal income and ex-penditure are estimated for different scenarios to show the possible range of effects

Extensive Therapeutic Drug Monitoring of Colistin in Critically Ill Patients Reveals Undetected Risks

(1) Background: With the rise of multi-/pan-drug resistant (MDR/PDR) pathogens, the less utilized antibiotic Colistin has made a comeback. Colistin fell out of favor due to its small therapeutic range and high potential for toxicity. Today, it is used again as a last resort substance in treating MDR/PDR pathogens. Although new guidelines with detailed recommendations for Colistin dosing are available, finding the right dose in critically ill patients with renal failure remains difficult. Here, we evaluate the efficiency of the current guidelines’ recommendations by using high resolution therapeutic drug monitoring of Colistin. (2) Methods: We analyzed plasma levels of Colistin and its prodrug colisthimethate sodium (CMS) in 779 samples, drawn from eight PDR-infected ICU patients, using a HPLC-MS/MS approach. The impact of renal function on proper Colistin target levels was assessed. (3) Results: CMS levels did not correlate with Colistin levels. Over-/Underdosing occurred regardless of renal function and mode of renal replacement therapy. Colistin elimination half-time appeared to be longer than previously reported. (4) Conclusion: Following dose recommendations from the most current guidelines does not necessarily lead to adequate Colistin plasma levels. Use of Colistin without therapeutic drug monitoring might be unsafe and guideline adherence does not warrant efficient target levels in critically ill patients