Description: We introduce the improved Freie Universität Berlin (FUB) high-resolution radiation scheme FUBRad and compare it to the 4-band standard ECHAM5 SW radiation scheme of Fouquart and Bonnel (FB). Both schemes are validated against the detailed radiative transfer model libRadtran. FUBRad produces realistic heating rate variations during the solar cycle. The SW heating rate response with the FB scheme is about 20 times smaller than with FUBRad and cannot produce the observed temperature signal. A reduction of the spectral resolution to 6 bands for solar irradiance and ozone absorption cross sections leads to a degradation (reduction) of the solar SW heating rate signal by about 20%. The simulated temperature response agrees qualitatively well with observations in the summer upper stratosphere and mesosphere where irradiance variations dominate the signal. Comparison of the total short-wave heating rates under solar minimum conditions shows good agreement between FUBRad, FB and libRadtran up to the middle mesosphere (60–70 km) indicating that both parameterizations are well suited for climate integrations that do not take solar variability into account. The FUBRad scheme has been implemented as a sub-submodel of the Modular Earth Submodel System (MESSy).

Description: Inhibition of the ternary protein complex of the synaptic scaffolding protein postsynaptic density protein-95 (PSD-95), neuronal nitric oxide synthase (nNOS), and the N-methyl-d-aspartate (NMDA) receptor is a potential strategy for treating ischemic brain damage, but high-affinity inhibitors are lacking. Here we report the design and synthesis of a novel dimeric inhibitor, Tat-NPEG4(IETDV)2 (Tat-N-dimer), which binds the tandem PDZ1-2 domain of PSD-95 with an unprecedented high affinity of 4.6 nM, and displays extensive protease-resistance as evaluated in vitro by stability-measurements in human blood plasma. X-ray crystallography, NMR, and small-angle X-ray scattering (SAXS) deduced a true bivalent interaction between dimeric inhibitor and PDZ1-2, and also provided a dynamic model of the conformational changes of PDZ1-2 induced by the dimeric inhibitor. A single intravenous injection of Tat-N-dimer (3 nmol/g) to mice subjected to focal cerebral ischemia reduces infarct volume with 40% and restores motor functions. Thus, Tat-N-dimer is a highly efficacious neuroprotective agent with therapeutic potential in stroke.

Description: Multiple lines of evidence implicate chromatin in the regulation of premessenger RNA (pre-mRNA) splicing. However, the influence of chromatin factors on cotranscriptional splice site usage remains unclear. Here we investigated the function of the highly conserved histone variant H2A.Z in pre-mRNA splicing using the intron-rich model yeast Schizosaccharomyces pombe . Using epistatic miniarray profiles (EMAPs) to survey the genetic interaction landscape of the Swr1 nucleosome remodeling complex, which deposits H2A.Z, we uncovered evidence for functional interactions with components of the spliceosome. In support of these genetic connections, splicing-specific microarrays show that H2A.Z and the Swr1 ATPase are required during temperature stress for the efficient splicing of a subset of introns. Notably, affected introns are enriched for H2A.Z occupancy and more likely to contain nonconsensus splice sites. To test the significance of the latter correlation, we mutated the splice sites in an affected intron to consensus and found that this suppressed the requirement for H2A.Z in splicing of that intron. These data suggest that H2A.Z occupancy promotes cotranscriptional splicing of suboptimal introns that may otherwise be discarded via proofreading ATPases. Consistent with this model, we show that overexpression of splicing ATPase Prp16 suppresses both the growth and splicing defects seen in the absence of H2A.Z.

Description: We introduce the improved Freie Universität Berlin (FUB) high-resolution radiation scheme FUBRad and compare it to the 4-band standard ECHAM5 SW radiation scheme of Fouquart and Bonnel (FB). Both schemes are validated against the detailed radiative transfer model libRadtran. FUBRad produces realistic heating rate variations during the solar cycle. The SW heating rate response with the FB scheme is about 20 times smaller than with FUBRad and cannot produce the observed temperature signal. A reduction of the spectral resolution to 6 bands for solar irradiance and ozone absorption cross sections leads to a degradation (reduction) of the solar SW heating rate signal by about 20%. The simulated temperature response agrees qualitatively well with observations in the summer upper stratosphere and mesosphere where irradiance variations dominate the signal. Comparison of the total short-wave heating rates under solar minimum conditions shows good agreement between FUBRad, FB and libRadtran up to the middle mesosphere (60–70 km) indicating that both parameterizations are well suited for climate integrations that do not take solar variability into account. The FUBRad scheme has been implemented as a sub-submodel of the Modular Earth Submodel System (MESSy).

Description: A rockfall dataset for Germany is analysed with the objective of identifying the meteorological and hydrological (pre-)conditions that change the probability for such events in central Europe. The factors investigated in the analysis are precipitation amount and intensity, freeze–thaw cycles, and subsurface moisture. As there is no suitable observational dataset for all relevant subsurface moisture types (e.g. water in rock pores and cleft water) available, simulated soil moisture and a proxy for pore water are tested as substitutes. The potential triggering factors were analysed both for the day of the event and for the days leading up to it. A logistic regression model was built, which considers individual potential triggering factors and their interactions. It is found that the most important factor influencing rockfall probability in the research area is the precipitation amount at the day of the event, but the water content of the ground on that day and freeze–thaw cycles in the days prior to the event also influence the hazard probability. Comparing simulated soil moisture and the pore-water proxy as predictors for rockfall reveals that the proxy, calculated as accumulated precipitation minus potential evaporation, performs slightly better in the statistical model. Using the statistical model, the effects of meteorological conditions on rockfall probability in German low mountain ranges can be quantified. The model suggests that precipitation is most efficient when the pore-water content of the ground is high. An increase in daily precipitation from its local 50th percentile to its 90th percentile approximately doubles the probability for a rockfall event under median pore-water conditions. When the pore-water proxy is at its 95th percentile, the same increase in precipitation leads to a 4-fold increase in rockfall probability. The occurrence of a freeze–thaw cycle in the preceding days increases the rockfall hazard by about 50 %. The most critical combination can therefore be expected in winter and at the beginning of spring after a freeze–thaw transition, which is followed by a day with high precipitation amounts and takes place in a region preconditioned by a high level of subsurface moisture.