Off-stoichiometric softening and polytypic transformations in the plastic deformation of the C14 Fe2_2Nb Laves phase

Plastic deformation of the brittle C14-Fe$_2$Nb Laves phase occurs mostly by basal slip due to the complex crystal structure. Here, we compare the barriers for basal slip for the known mechanisms of direct slip, synchroshear and undulating slip using density functional theory calculations. According to our calculated generalized stacking fault (SF) energies, the most favorable mechanisms are synchroshear and undulating slip. Both mechanisms lead to stable SF with a formation energy of 50 $mJ/m^2$ through the same unstable SF configuration at the transition. The energy barrier of approximately 3 $J/m^2$ indicates a low dislocation mobility as expected from the brittle character. We also determine the influence of vacancies and antisite defects on the formation energy of stable and unstable SF. Both kinds of point defects tend to lower the energy barrier on both sides of 2:1 stoichiometry. This explains the experimentally observed off-stoichiometric softening of C14-Fe$_2$Nb. The small energy differences between the Fe$_2$Nb Laves phase polytypes raises the question if there are further deformation mechanisms with low barrier. Therefore, we additionally consider transformations between C14, C15 and C36 Laves phases as further deformation mechanism. Our calculations for polytypic transformations by successive synchroshear steps show that the corresponding energy barriers are in fact very similar to the energy barrier for basal slip in C14. This suggests that the energy needed to create a stable SF in C14 by synchroshear is also sufficient to initiate polytypic transformations where existing SFs in C14 are further transformed to form C15 or C36 Laves phases

Heterologous Overexpression and Mutagenesis of the Human Bile Salt Export Pump (ABCB11) Using DREAM (Directed REcombination-Assisted Mutagenesis)

Homologous recombination in Saccharomyces cerevisiae is a well-studied process. Here, we describe a yeast-recombination-based approach to construct and mutate plasmids containing the cDNA of the human bile salt export pump (BSEP) that has been shown to be unstable in E. coli. Using this approach, we constructed the necessary plasmids for a heterologous overexpression of BSEP in the yeast Pichia pastoris. We then applied a new site-directed mutagenesis method, DREAM (Directed REcombination-Assisted Mutagenesis) that completely bypasses E. coli by using S. cerevisiae as the plasmid host with high mutagenesis efficiency. Finally, we show how to apply this strategy to unstable non-yeast plasmids by rapidly turning an existing mammalian BSEP expression construct into a S. cerevisiae-compatible plasmid and analyzing the impact of a BSEP mutation in several mammalian cell lines

Overview : Integrative and Comprehensive Understanding on Polar Environments (iCUPE) - concept and initial results

The role of polar regions is increasing in terms of megatrends such as globalization, new transport routes, demography, and the use of natural resources with consequent effects on regional and transported pollutant concentrations. We set up the ERA-PLANET Strand 4 project "iCUPE - integrative and Comprehensive Understanding on Polar Environments" to provide novel insights and observational data on global grand challenges with an Arctic focus. We utilize an integrated approach combining in situ observations, satellite remote sensing Earth observations (EOs), and multi-scale modeling to synthesize data from comprehensive long-term measurements, intensive campaigns, and satellites to deliver data products, metrics, and indicators to stakeholders concerning the environmental status, availability, and extraction of natural resources in the polar areas. The iCUPE work consists of thematic state-of-the-art research and the provision of novel data in atmospheric pollution, local sources and transboundary transport, the characterization of arctic surfaces and their changes, an assessment of the concentrations and impacts of heavy metals and persistent organic pollutants and their cycling, the quantification of emissions from natural resource extraction, and the validation and optimization of satellite Earth observation (EO) data streams. In this paper we introduce the iCUPE project and summarize initial results arising out of the integration of comprehensive in situ observations, satellite remote sensing, and multi-scale modeling in the Arctic context.Peer reviewe

Overview: Integrative and Comprehensive Understanding on Polar Environments (iCUPE) – concept and initial results

The role of polar regions is increasing in terms of megatrends such as globalization, new transport routes, demography, and the use of natural resources with consequent effects on regional and transported pollutant concentrations. We set up the ERA-PLANET Strand 4 project “iCUPE – integrative and Comprehensive Understanding on Polar Environments” to provide novel insights and observational data on global grand challenges with an Arctic focus. We utilize an integrated approach combining in situ observations, satellite remote sensing Earth observations (EOs), and multi-scale modeling to synthesize data from comprehensive long-term measurements, intensive campaigns, and satellites to deliver data products, metrics, and indicators to stakeholders concerning the environmental status, availability, and extraction of natural resources in the polar areas. The iCUPE work consists of thematic state-of-the-art research and the provision of novel data in atmospheric pollution, local sources and transboundary transport, the characterization of arctic surfaces and their changes, an assessment of the concentrations and impacts of heavy metals and persistent organic pollutants and their cycling, the quantification of emissions from natural resource extraction, and the validation and optimization of satellite Earth observation (EO) data streams. In this paper we introduce the iCUPE project and summarize initial results arising out of the integration of comprehensive in situ observations, satellite remote sensing, and multi-scale modeling in the Arctic context

A comprehensive analysis of common genetic variation around six candidate loci for intrahepatic cholestasis of pregnancy.

OBJECTIVES: Intrahepatic cholestasis of pregnancy (ICP) has a complex etiology with a significant genetic component. Heterozygous mutations of canalicular transporters occur in a subset of ICP cases and a population susceptibility allele (p.444A) has been identified in ABCB11. We sought to expand our knowledge of the detailed genetic contribution to ICP by investigation of common variation around candidate loci with biological plausibility for a role in ICP (ABCB4, ABCB11, ABCC2, ATP8B1, NR1H4, and FGF19). METHODS: ICP patients (n=563) of white western European origin and controls (n=642) were analyzed in a case-control design. Single-nucleotide polymorphism (SNP) markers (n=83) were selected from the HapMap data set (Tagger, Haploview 4.1 (build 22)). Genotyping was performed by allelic discrimination assay on a robotic platform. Following quality control, SNP data were analyzed by Armitage's trend test. RESULTS: Cochran-Armitage trend testing identified six SNPs in ABCB11 together with six SNPs in ABCB4 that showed significant evidence of association. The minimum Bonferroni corrected P value for trend testing ABCB11 was 5.81×10(-4) (rs3815676) and for ABCB4 it was 4.6×10(-7)(rs2109505). Conditional analysis of the two clusters of association signals suggested a single signal in ABCB4 but evidence for two independent signals in ABCB11. To confirm these findings, a second study was performed in a further 227 cases, which confirmed and strengthened the original findings. CONCLUSIONS: Our analysis of a large cohort of ICP cases has identified a key role for common variation around the ABCB4 and ABCB11 loci, identified the core associations, and expanded our knowledge of ICP susceptibility

Towards A Lightweight Incentive Scheme for Peer-to-Peer Systems

Peer-to-peer (p2p) systems rely on the contributions of peers to operate. In order to not only depend on the altruism of individual peers, a number of incentive systems have been proposed. However many of them are complex and suffer from high overhead. In this work we propose BioTrust, a lightweight incentive scheme. In contrast to other approaches, it does not require reputation histories and can operate with minimal overhead in terms of bandwidth, infrastructure, memory and computation. BioTrust is based on observations of cooperation as observed in biological systems, which show that individuals try to ally themselves with others that can best increase their own standing. Such observations are prevalent in evolutionary systems where individuals must weigh off their own individual needs against the need for cooperation to survive. Using these models, BioTrust has been developed to extract and modify some of the most useful properties of biological systems to work effectively in a p2p environment. It is shown through simulation that this scheme encourages honest peers, which leads to a close to optimal behavior in the system context as well as for single peers

Novel (imino-η6-arene)chromium-complexes and their diastereoselective intramolecular hetero-Diels-Alder reactions

Novel (imino-η6-arene)chromium complexes 3 with nonactivated olefins tethered to the 2-azadiene system were prepared and further used in a new diastereoselective intramolecular Lewis-acid-catalyzed hetero-Diels-Alder reaction to give (η6-octahydroacridine)chromium complexes 4. The trans selectivity of the cyclization reaction is mainly controlled by the Cr- (CO)3 fragment and to a minor extent by the catalyst, solvent, and substituents. Complexes 4 also could be obtained by a one-pot reaction starting from aldehyde 1, (o-toluidine)Cr(CO)3 (2), and Lewis acid. The stereochemistry of 4a was established by single-crystal X-ray structure analysis

Crystal-Structure Analysis with Moments of the Density-of-States: Application to Intermetallic Topologically Close-Packed Phases

The moments of the electronic density-of-states provide a robust and transparent means for the characterization of crystal structures. Using d-valent canonical tight-binding, we compute the moments of the crystal structures of topologically close-packed (TCP) phases as obtained from density-functional theory (DFT) calculations. We apply the moments to establish a measure for the difference between two crystal structures and to characterize volume changes and internal relaxations. The second moment provides access to volume variations of the unit cell and of the atomic coordination polyhedra. Higher moments reveal changes in the longer-ranged coordination shells due to internal relaxations. Normalization of the higher moments leads to constant (A15,C15) or very similar (χ, C14, C36, μ, and σ) higher moments of the DFT-relaxed TCP phases across the 4d and 5d transition-metal series. The identification and analysis of internal relaxations is demonstrated for atomic-size differences in the V-Ta system and for different magnetic orderings in the C14-Fe 2 Nb Laves phase