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Der Europäische Betriebsrat
(1995)
Plasticity and steric strain in a parallel beta-helix: Rational mutations in P22 tailspike protein
(2000)
By means of genetic screens, a great number of mutations that affect the folding and stability of the tailspike protein from Salmonella phage P22 have been identified. Temperature-sensitive folding (tsf) mutations decrease folding yields at high temperature, but hardly affect thermal stability of the native trimeric structure when assembled at low temperature. Global suppressor (su) mutations mitigate this phenotype. Virtually all of these mutations are located in the central domain of tailspike, a large parallel beta-helix. We modified tailspike by rational single amino acid replacements at three sites in order to investigate the influence of mutations of two types: (1) mutations expected to cause a tsf phenotype by increasing the side-chain volume of a core residue, and (2) mutations in a similar structural context as two of the four known su mutations, which have been suggested to stabilize folding intermediates and the native structure by the release of backbone strain, an effect well known for residues that are primarily evolved for function and not for stability or folding of the protein. Analysis of folding yields, refolding kinetics and thermal denaturation kinetics in vitro show that the tsf phenotype can indeed be produced rationally by increasing the volume of side chains in the beta-helix core. The high-resolution crystal structure of mutant T326F proves that structural rearrangements only take place in the remarkably plastic lumen of the beta-helix, leaving the arrangement of the hydrogen-bonded backbone and thus the surface of the protein unaffected. This supports the notion that changes in the stability of an intermediate, in which the beta-helix domain is largely formed, are the essential mechanism by which tsf mutations affect tailspike folding. A rational design of su mutants, on the other hand, appears to be more difficult. The exchange of two residues in the active site expected to lead to a drastic release of steric strain neither enhanced the folding properties nor the stability of tailspike. Apparently, side-chain interactions in these cases overcompensate for backbone strain, illustrating the extreme optimization of the tailspike protein for conformational stability. The result exemplifies the view arising from the statistical analysis of the distribution of backbone dihedral angles in known three-dimensional protein structures that the adoption of straight phi/psi angles other than the most favorable ones is often caused by side-chain interactions.
2-Amino-2-(hydroxymethyl)-1,3-propanediol (TRIS) and ethylenediaminetetraacetic acid ( EDTA) are key components of biological buffers and are frequently used as DNA stabilizers in irradiation studies. Such surface or liquid phase studies are done with the aim to understand the fundamental mechanisms of DNA radiation damage and to improve cancer radiotherapy. When ionizing radiation is used, abundant secondary electrons are formed during the irradiation process, which are able to attach to the molecular compounds present on the surface. In the present study we experimentally investigate low energy electron attachment to TRIS and methyliminodiacetic acid ( MIDA), an analogue of EDTA, supported by quantum chemical calculations. The most prominent dissociation channel for TRIS is through hydroperoxyl radical formation, whereas the dissociation of MIDA results in the formation of formic and acetic acid. These compounds are well-known to cause DNA modifications, like strand breaks. The present results indicate that buffer compounds may not have an exclusive protecting effect on DNA as suggested previously.
Temperature-related excess mortality in German cities at 2 °C and higher degrees of global warming
(2020)
Background: Investigating future changes in temperature-related mortality as a function of global mean temperature (GMT) rise allows for the evaluation of policy-relevant climate change targets. So far, only few studies have taken this approach, and, in particular, no such assessments exist for Germany, the most populated country of Europe.
Methods: We assess temperature-related mortality in 12 major German cities based on daily time-series of all-cause mortality and daily mean temperatures in the period 1993-2015, using distributed-lag non-linear models in a two-stage design. Resulting risk functions are applied to estimate excess mortality in terms of GMT rise relative to pre-industrial levels, assuming no change in demographics or population vulnerability.
Results: In the observational period, cold contributes stronger to temperature-related mortality than heat, with overall attributable fractions of 5.49% (95%CI: 3.82-7.19) and 0.81% (95%CI: 0.72-0.89), respectively. Future projections indicate that this pattern could be reversed under progressing global warming, with heat-related mortality starting to exceed cold-related mortality at 3 degrees C or higher GMT rise. Across cities, projected net increases in total temperature-related mortality were 0.45% (95%CI: -0.02-1.06) at 3 degrees C, 1.53% (95%CI: 0.96-2.06) at 4 degrees C, and 2.88% (95%CI: 1.60-4.10) at 5 degrees C, compared to today's warming level of 1 degrees C. By contrast, no significant difference was found between projected total temperature-related mortality at 2 degrees C versus 1 degrees C of GMT rise.
Conclusions: Our results can inform current adaptation policies aimed at buffering the health risks from increased heat exposure under climate change. They also allow for the evaluation of global mitigation efforts in terms of local health benefits in some of Germany's most populated cities.
Temperature-related excess mortality in German cities at 2 °C and higher degrees of global warming
(2020)
Background: Investigating future changes in temperature-related mortality as a function of global mean temperature (GMT) rise allows for the evaluation of policy-relevant climate change targets. So far, only few studies have taken this approach, and, in particular, no such assessments exist for Germany, the most populated country of Europe.
Methods: We assess temperature-related mortality in 12 major German cities based on daily time-series of all-cause mortality and daily mean temperatures in the period 1993-2015, using distributed-lag non-linear models in a two-stage design. Resulting risk functions are applied to estimate excess mortality in terms of GMT rise relative to pre-industrial levels, assuming no change in demographics or population vulnerability.
Results: In the observational period, cold contributes stronger to temperature-related mortality than heat, with overall attributable fractions of 5.49% (95%CI: 3.82-7.19) and 0.81% (95%CI: 0.72-0.89), respectively. Future projections indicate that this pattern could be reversed under progressing global warming, with heat-related mortality starting to exceed cold-related mortality at 3 degrees C or higher GMT rise. Across cities, projected net increases in total temperature-related mortality were 0.45% (95%CI: -0.02-1.06) at 3 degrees C, 1.53% (95%CI: 0.96-2.06) at 4 degrees C, and 2.88% (95%CI: 1.60-4.10) at 5 degrees C, compared to today's warming level of 1 degrees C. By contrast, no significant difference was found between projected total temperature-related mortality at 2 degrees C versus 1 degrees C of GMT rise.
Conclusions: Our results can inform current adaptation policies aimed at buffering the health risks from increased heat exposure under climate change. They also allow for the evaluation of global mitigation efforts in terms of local health benefits in some of Germany's most populated cities.
Strategisches Personalcontrolling als Unterstützungsfunktion des strategischen Personalmanagements
(1998)
Community Organizing in Deutschland : Eine "neue" Möglichkeit zur Vitalisierung Lokaler Demokratie?
(2010)
Als Instrument der Bürgerbeteiligung wurde Community Organizing von Saul D. Alinsky zum ersten Mal 1939 in Chicago/Illinois erfolgreich umgesetzt. Konzeptionell speist es sich aus der Stadtsoziologie, der sozialen Arbeit sowie einer interkulturell ausgerichteten, politischen Erwachsenenbildung. In den USA hat es sich seitdem auf lokaler und überregionaler Ebene etabliert und wird nun auch in Deutschland rezipiert und zunehmend projekthaft umgesetzt. Diese Arbeit beschreibt das Konzept des Community Organizing in Deutschland explorativ und zeigt fördernde und hemmende Faktoren für dessen Umsetzung auf. Zudem wird das Konzept für den deutschen Fall bezüglich partizipativer Demokratietheorien theoretisch diskutiert und verortet: Kann Community Organizing der Theorie der partizipativen Demokratie zugeordnet werden? Hierfür wurde die Ausprägung der Kriterien Deliberation, direkter Demokratie im weitesten Sinne, Dezentralisierung, Segmentierung und Delegation untersucht und bewertet. Die zweite Frage setzt sich mit der Wirksamkeit von umgesetzten Community Organizing-Projekten auseinander: Kann es als erfolgreiches Bürgerbeteiligungsinstrument auf lokaler Ebene betrachtet werden und inwiefern können dabei die demokratietheoretischen Kriterien Legitimität, Effektivität und Qualifizierung der Bürgerinnen und Bürger erfüllt werden?