Examination of Msh6- and Msh3-deficient Mice in Class Switching Reveals Overlapping and Distinct Roles of MutS Homologues in Antibody Diversification

Somatic hypermutation and class switch recombination (CSR) contribute to the somatic diversification of antibodies. It has been shown that MutS homologue (Msh)6 (in conjunction with Msh2) but not Msh3 is involved in generating A/T base substitutions in somatic hypermutation. However, their roles in CSR have not yet been reported. Here we show that Msh6−/− mice have a decrease in CSR, whereas Msh3−/− mice do not. When switch regions were analyzed for mutations, deficiency in Msh6 was associated with an increase in transition mutations at G/C basepairs, mutations at RGYW/WRCY hotspots, and a small increase in the targeting of G/C bases. In addition, Msh6−/− mice exhibited an increase in the targeting of recombination sites to GAGCT/GGGGT consensus repeats and hotspots in Sγ3 but not in Sμ. In contrast to Msh2−/− mice, deficiency in Msh6 surprisingly did not change the characteristics of Sμ-Sγ3 switch junctions. However, Msh6−/− mice exhibited a change in the positioning of Sμ and Sγ3 junctions. Although none of these changes were seen in Msh3−/− mice, they had a higher percentage of large inserts in their switch junctions. Together, our data suggest that MutS homologues Msh2, Msh3, and Msh6 play overlapping and distinct roles during antibody diversification processes

Zur selbsttätig sicheren Begrenzung von nuklearer Leistung und Brennstofftemperatur in innovativen Kernreaktoren

Nuclear energy probably will not contribute significantly to the future worldwide energysupply until it can be made catastrophefree. Therefore it has to be shown, that theconsequences of even largest accidents will have no major impact to the environmentof a power plant.In this paper one of the basic conditions for such a nuclear technology is discussed.Using mainly the modular pebble-bed high-temperature reactor as an example, thedesign principles, analytical methods and the level of knowledge as given today incontrolling reactivity accidents by inherent safety features of innovative nuclear reactorsare described. Complementary possibilities are shown to reach this goal with systems ofdifferent types of construction . Questions open today and resulting requirements forfuture activities are discussed .Today's knowledge credibly supports the possibility of a catastrophefree nucleartechnology with respect to reactivity event

Potential climatic transitions with profound impact on Europe

We discuss potential transitions of six climatic subsystems with large-scale impact on Europe, sometimes denoted as tipping elements. These are the ice sheets on Greenland and West Antarctica, the Atlantic thermohaline circulation, Arctic sea ice, Alpine glaciers and northern hemisphere stratospheric ozone. Each system is represented by co-authors actively publishing in the corresponding field. For each subsystem we summarize the mechanism of a potential transition in a warmer climate along with its impact on Europe and assess the likelihood for such a transition based on published scientific literature. As a summary, the ‘tipping’ potential for each system is provided as a function of global mean temperature increase which required some subjective interpretation of scientific facts by the authors and should be considered as a snapshot of our current understanding. <br/

Diversity Promotes Temporal Stability across Levels of Ecosystem Organization in Experimental Grasslands

The diversity–stability hypothesis states that current losses of biodiversity can impair the ability of an ecosystem to dampen the effect of environmental perturbations on its functioning. Using data from a long-term and comprehensive biodiversity experiment, we quantified the temporal stability of 42 variables characterizing twelve ecological functions in managed grassland plots varying in plant species richness. We demonstrate that diversity increases stability i) across trophic levels (producer, consumer), ii) at both the system (community, ecosystem) and the component levels (population, functional group, phylogenetic clade), and iii) primarily for aboveground rather than belowground processes. Temporal synchronization across studied variables was mostly unaffected with increasing species richness. This study provides the strongest empirical support so far that diversity promotes stability across different ecological functions and levels of ecosystem organization in grasslands

A comparison of the strength of biodiversity effects across multiple functions

In order to predict which ecosystem functions are most at risk from biodiversity loss, meta-analyses have generalised results from biodiversity experiments over different sites and ecosystem types. In contrast, comparing the strength of biodiversity effects across a large number of ecosystem processes measured in a single experiment permits more direct comparisons. Here, we present an analysis of 418 separate measures of 38 ecosystem processes. Overall, 45% of processes were significantly affected by plant species richness, suggesting that, while diversity affects a large number of processes not all respond to biodiversity. We therefore compared the strength of plant diversity effects between different categories of ecosystem processes, grouping processes according to the year of measurement, their biogeochemical cycle, trophic level and compartment (above- or belowground) and according to whether they were measures of biodiversity or other ecosystem processes, biotic or abiotic and static or dynamic. Overall, and for several individual processes, we found that biodiversity effects became stronger over time. Measures of the carbon cycle were also affected more strongly by plant species richness than were the measures associated with the nitrogen cycle. Further, we found greater plant species richness effects on measures of biodiversity than on other processes. The differential effects of plant diversity on the various types of ecosystem processes indicate that future research and political effort should shift from a general debate about whether biodiversity loss impairs ecosystem functions to focussing on the specific functions of interest and ways to preserve them individually or in combinatio

Numerical Simulation of Severe Water Ingress Accidents in a ModularHigh Temperature Gas Cooled Reactor

This report analyzes severe water ingress accidents in the SIEMENS 200MW Modular Pebble-Bed High Temperature Gas Cooled Reactor (HTR-MODULE) under the assumption of no active safety protection systems in order to find the safety margins of the current HTR-MODULE design and to realize a catastrophe-free nuclear technology. A water, steam and helium multi-phase cavity model is developed and implemented in the DSNP simulation system. The DSNP system is then used to simulate the primary and secondary circuit of a HTR-MODULE power plant. Comparisons of the model with experiments and with TIN1M calculations serve as validation of the simulation. The analysis of the primary circuit tries to answer the question how fast the water enters the reactor core. It was found that the maximum H$_{2}$O concentration increase in the reactor core is smaller than 0.3 kg/(m$^{3}$s) The liquid water vaporization in the steam generator and H$_{2}$O transport from the steam generator to the reactor core reduce the ingress velocity of the H$_{2}$O into the reactor core. In order to answer the question haw much water enters the primary circuit, the full cavitationof the feed water pumps is analyzed. It is found that if the secondary circuit is depressurized enough, the feed water pumps will be inherently stopped by the full cavitation. This limits the water to be pumped from the deaerator to the steam generator. A comprehensive simulation of the MODUL-HTR power plant then shows that the H$_{2}$O inventory in the primary circuit can be limited to about 3000 kg. The nuclear reactivity increase caused by the water ingress leads to a fast power excursion, which, however, is inherently counterbalanced by negative feedback effects. Concerning the integrity of the fuel elements, the safety relevant temperature limit of 1600 °C was not reached in any case

Die Behandlung der Nachzerfallswärme im Reaktordynamikprogramm TINTE

The TINTE code system deals with the nuclear and the thermal transient behaviour of the primary circuit of an 1-lTGR tatting into consideration the mutual feedback effects in two-dimensional r-z-geometry. In this paper an update of the treatment of delayed heat production is presented. It is based on the german norm DIN 15485, the rules ofwhich had to be adjusted for use in a dynamics code. For the description of the fuel element power history a substitutehistogram has been constructed from local burnup and optionally from information about shuffling of the fuel bails. As an example the depressurisation accident of a MODUL-1-ITR is calculated. The results obtained are very similar to others previously reported

Analysis of the gas diffusion process during a hypothetical air ingress accident in a modular high temperature gas cooled reactor

In order to simulate the diffusion process during a hypothetical air ingress accident in a modular high temperature gas cooled reactor, a one-dimensional coupled diffusion-convection model has been established. In this analysis it is shown first, that experiments performed at the Japan Atomic Energy Research Institute (JAERI) have been recalculated successfully, thus validating the new model. Applying this model to the NACOK facility, now under construction at the Institute for Safety Research and Reactor Technology (ISR) of the KFA Research Center Jiilich, a delay time until the onset of natural circulation was found to be 14 hours. For the 200MW HTR-MODULE designed by the SIEMENS company about 39 hours are predicted. It was found that pressure disturbances, e.g. caused by environmental noise could significantly shorten the time delay until the onset of natural circulation. The onset time delay remains constant below 40 dB noise, reaches half of its value at 80 dB and tends to zero at 120 dB. Thus, the relevance of the delay effect with respect to safety related questions is reduced

Studie zur Untersuchung der Wirksamkeit einer zentralen Neutronenquelle für das 300-MWe-THTR-Kernkraftwerk Schmehausen

The loading and starting phase of the THTR-3oo is eontrolled by an external neutron source. The possible positions of this source result from the requirement to fulfil certain criteria concerning the intensity and the interpretation of the detector-Signal. In this study it is investigated, how far a source centrally inserted into the reactor can be equal to this tack and whether it is possible to go over to a non-central position at a later point of time. lt is shown that the central source can fulfil all discussed demands. A source position lying in the vicinity of the side reflector demands a special choice of the detector position, which can be exactly determined only by further three-dimensional caIculations. Beyond that this study shows that during the loading phase in the subcritical range the spatial neutron flux distribution is expected as to be completely different from that of the critical reactor