Plasmons and Interband Transitions of Ca11_{11}Sr3_3Cu24_{24}O41_{41} investigated by Electron Energy-Loss Spectroscopy

Electron energy-loss spectroscopy studies have been performed in order to get a deeper insight into the electronic structure and elementary excitations of the two-leg ladder system Ca$_{11}$Sr$_3$Cu$_{24}$O$_{41}$. We find a strong anisotropy of the loss function for momentum transfers along the a and c-crystallographic axis, and a remarkable linear plasmon dispersion for a momentum transfer parallel to the legs of the ladders. The investigated spectral features are attributed to localized and delocalized charge-transfer excitations and the charge carrier plasmon. The charge carrier plasmon position and dispersion in the long wave-length limit agree well with expectations based upon the band structure of the two-leg ladder, while the observed quasi-linear plasmon dispersion might be related to the peculiar properties of underdoped cuprates in general.Comment: 16 pages, 8 figure

Mitigating Water Crossover by Crosslinked Coating of Cation‐Exchange Membranes for Brine Concentration

Undesired water crossover through ion-exchange membranes is a significant limitation in electrically driven desalination processes. The effect of mitigating water crossover is twofold: 1) The desalination degree is less reduced due to the unwanted removal of water, and 2) the brine concentration is increased due to decreased dilution by an unwanted crossover of water molecules. Hence, water crossover limits the desalination and concentration efficiency of the processes, while the energy demand to achieve a certain level of desalination or concentration increases. This effect is especially pronounced when treating high salinity solutions, which goes hand in hand with the crossover of many ions through the ion-exchange membranes. A crosslinked coating for cation-exchange membranes (CEMs) is presented in this work, which can significantly mitigate such undesired water crossover. The efficacy is demonstrated using the flow-electrode capacitive deionization process applied for desalination and concentration of saline brines at feed concentrations of 60 and 120 g L−1 NaCl. With just a single coated CEM, the water crossover was reduced by up to 54%

The Adaptive Evolution Database (TAED): a phylogeny based tool for comparative genomics

From 138 662 embryophyte (higher plant) and 348 142 chordate genes, 4216 embryophyte and 15 452 chordate gene families were generated. For each of these gene families, multiple sequence alignments, phylogenetic trees, ratios of non-synonymous to synonymous nucleotide substitution rates (K(a)/K(s)), mappings from gene trees to the NCBI taxonomy and structural links to solved three-dimensional protein structures in the Protein Data Bank (PDB) with Grantham-weighted mutational factors were all calculated. Of the ‘gene family trees’, 173 embryophyte and 505 chordate branches show K(a)/K(s) ≫ 1 and are candidates for functional adaptation. The calculated information is available both as a gene family database and as a phylogenetically indexed resource, called ‘The Adaptive Evolution Database’ (TAED), available at http://www.bioinfo.no/tools/TAED

An unexpected co-crystal structure of the calpain PEF(S) domain with Hfq reveals a potential chaperone function of Hfq

Calpain is a Ca2+-activated, heterodimeric cysteine protease consisting of a large catalytic subunit and a small regulatory subunit. Dysregulation of this enzyme is involved in a range of pathological conditions such as cancer, Alzheimer's disease and rheumatoid arthritis, and thus calpain I is a drug target with potential therapeutic applications. Difficulty in the production of this enzyme has hindered structural and functional investigations in the past, although heterodimeric calpain I can be generated by Escherichia coli expression in low yield. Here, an unexpected structure discovered during crystallization trials of heterodimeric calpain I (CAPN1C115S + CAPNS1ΔGR) is reported. A novel co-crystal structure of the PEF(S) domain from the dissociated regulatory small subunit of calpain I and the RNA-binding chaperone Hfq, which was likely to be overproduced as a stress response to the recombinant expression conditions, was obtained, providing unexpected insight in the chaperone function of Hfq

The Leeway of Shipping Containers at Different Immersion Levels

The leeway of 20-foot containers in typical distress conditions is established through field experiments in a Norwegian fjord and in open-ocean conditions off the coast of France with wind speed ranging from calm to 14 m/s. The experimental setup is described in detail and certain recommendations given for experiments on objects of this size. The results are compared with the leeway of a scaled-down container before the full set of measured leeway characteristics are compared with a semi-analytical model of immersed containers. Our results are broadly consistent with the semi-analytical model, but the model is found to be sensitive to choice of drag coefficient and makes no estimate of the cross-wind leeway of containers. We extend the results from the semi-analytical immersion model by extrapolating the observed leeway divergence and estimates of the experimental uncertainty to various realistic immersion levels. The sensitivity of these leeway estimates at different immersion levels are tested using a stochastic trajectory model. Search areas are found to be sensitive to the exact immersion levels, the choice of drag coefficient and somewhat less sensitive to the inclusion of leeway divergence. We further compare the search areas thus found with a range of trajectories estimated using the semi-analytical model with only perturbations to the immersion level. We find that the search areas calculated without estimates of crosswind leeway and its uncertainty will grossly underestimate the rate of expansion of the search areas. We recommend that stochastic trajectory models of container drift should account for these uncertainties by generating search areas for different immersion levels and with the uncertainties in crosswind and downwind leeway reported from our field experiments.Comment: 25 pages, 11 figures and 5 tables; Ocean Dynamics, Special Issue on Advances in Search and Rescue at Sea (2012

Structural insight into industrially relevant glucoamylases : flexible positions of starch-binding domains

Glucoamylases are one of the most important classes of enzymes in the industrial degradation of starch biomass. They consist of a catalytic domain and a carbohydrate-binding domain (CBM), with the latter being important for the interaction with the polymeric substrate. Whereas the catalytic mechanisms and structures of the individual domains are well known, the spatial arrangement of the domains with respect to each other and its influence on activity are not fully understood. Here, the structures of three industrially used fungal glucoamylases, two of which are full length, have been crystallized and determined. It is shown for the first time that the relative orientation between the CBM and the catalytic domain is flexible, as they can adopt different orientations independently of ligand binding, suggesting a role as an anchor to increase the contact time and the relative concentration of substrate near the active site. The flexibility in the orientations of the two domains presented a considerable challenge for the crystallization of the enzymes

Dynamic modeling of uteroplacental blood flow in IUGR indicates vortices and elevated pressure in the intervillous space - a pilot study

Ischemic placental disease is a concept that links intrauterine growth retardation (IUGR) and preeclampsia (PE) back to insufficient remodeling of uterine spiral arteries. The rheological consequences of insufficient remodeling of uterine spiral arteries were hypothesized to mediate the considerably later manifestation of obstetric disease. However, the micro-rheology in the intervillous space (IVS) cannot be examined clinically and rheological animal models of the human IVS do not exist. Thus, an in silico approach was implemented to provide in vivo inaccessible data. The morphology of a spiral artery and the inflow region of the IVS were three-dimensionally reconstructed to provide a morphological stage for the simulations. Advanced high-end supercomputing resources were used to provide blood flow simulations at high spatial resolution. Our simulations revealed turbulent blood flow (high-velocity jets and vortices) combined with elevated blood pressure in the IVS and increased wall shear stress at the villous surface in conjunction with insufficient spiral artery remodeling only. Post-hoc histological analysis of uterine veins showed evidence of increased trophoblast shedding in an IUGR placenta. Our data support that rheological alteration in the IVS is a relevant mechanism linking ischemic placental disease to altered structural integrity and function of the placenta

Congenital cervical spine malformation due to bi-allelicRIPPLY2 variants in spondylocostal dysostosis type 6

RIPPLY2 is an essential part of the formation of somite patterning during embryogenesis and in establishment of rostro-caudal polarity. Here, we describe three individuals from two families with compound-heterozygous variants in RIPPLY2 (NM_001009994.2): c.238A > T, p.(Arg80*) and c.240-4 T > G, p.(?), in two 15 and 20-year-old sisters, and a homozygous nonsense variant, c.238A > T, p.(Arg80*), in an 8 year old boy. All patients had multiple vertebral body malformations in the cervical and thoracic region, small or absent rib involvement, myelopathies, and common clinical features of SCDO6 including scoliosis, mild facial asymmetry, spinal spasticity and hemivertebrae. The nonsense variant can be classified as likely pathogenic based on the ACMG criteria while the splice variants must be classified as a variant of unknown significance. With this report on two further families, we confirm RIPPLY2 as the gene for SCDO6 and broaden the phenotype by adding myelopathy with or without spinal canal stenosis and spinal spasticity to the symptom spectrum

Substrate Engagement and Catalytic Mechanisms of N-Acetylglucosaminyltransferase v

α-Mannoside β-1,6-N-acetylglucosaminyltransferase V (MGAT5) is a mammalian glycosyltransferase involved in complex N-glycan formation, which strongly drives cancer when overexpressed. Despite intense interest, the catalytic mechanism of MGAT5 is not known in detail, precluding therapeutic exploitation. We solved structures of MGAT5 complexed to glycosyl donor and acceptor ligands, revealing an unforeseen role for donor-induced loop rearrangements in controlling acceptor substrate engagement. QM/MM metadynamics simulations of MGAT5 catalysis highlight the key assisting role of Glu297 and reveal considerable conformational distortions imposed upon the glycosyl donor during transfer. Detailed mechanistic characterization of MGAT5 will aid inhibitor development to correct cancer-associated N-glycosylation