BioMagResBank (BMRB) as a partner in the Worldwide Protein Data Bank (wwPDB): new policies affecting biomolecular NMR depositions

We describe the role of the BioMagResBank (BMRB) within the Worldwide Protein Data Bank (wwPDB) and recent policies affecting the deposition of biomolecular NMR data. All PDB depositions of structures based on NMR data must now be accompanied by experimental restraints. A scheme has been devised that allows depositors to specify a representative structure and to define residues within that structure found experimentally to be largely unstructured. The BMRB now accepts coordinate sets representing three-dimensional structural models based on experimental NMR data of molecules of biological interest that fall outside the guidelines of the Protein Data Bank (i.e., the molecule is a peptide with 23 or fewer residues, a polynucleotide with 3 or fewer residues, a polysaccharide with 3 or fewer sugar residues, or a natural product), provided that the coordinates are accompanied by representation of the covalent structure of the molecule (atom connectivity), assigned NMR chemical shifts, and the structural restraints used in generating model. The BMRB now contains an archive of NMR data for metabolites and other small molecules found in biological systems

The generalised NMSSM at one loop: fine tuning and phenomenology

We determine the degree of fine tuning needed in a generalised version of the NMSSM that follows from an underlying Z4 or Z8 R symmetry. We find that it is significantly less than is found in the MSSM or NMSSM and extends the range of Higgs mass that have acceptable fine tuning up to Higgs masses of mh ~ 130 GeV. For universal boundary conditions analogous to the CMSSM the phenomenology is rather MSSM like with the singlet states typically rather heavy. For more general boundary conditions the singlet states can be light, leading to interesting signatures at the LHC and direct detection experiments.Comment: 20 pages, 9 figures, matches published versio

Developmental seizures and mortality result from reducing GABAᴀ receptor α2-subunit interaction with collybistin

Fast inhibitory synaptic transmission is mediated by γ-aminobutyric acid type A receptors (GABAARs) that are enriched at functionally diverse synapses via mechanisms that remain unclear. Using isothermal titration calorimetry and complementary methods we demonstrate an exclusive low micromolar binding of collybistin to the α2-subunit of GABAARs. To explore the biological relevance of collybistin-α2-subunit selectivity, we generate mice with a mutation in the α2-subunit-collybistin binding region (Gabra2-1). The mutation results in loss of a distinct subset of inhibitory synapses and decreased amplitude of inhibitory synaptic currents. Gabra2–1 mice have a striking phenotype characterized by increased susceptibility to seizures and early mortality. Surviving Gabra2-1 mice show anxiety and elevations in electroencephalogram δ power, which are ameliorated by treatment with the α2/α3-selective positive modulator, AZD7325. Taken together, our results demonstrate an α2-subunit selective binding of collybistin, which plays a key role in patterned brain activity, particularly during development

NLTE analysis of Co I/Co II lines in spectra of cool stars with new laboratory hyperfine splitting constants

We investigate the statistical equilibrium of Co in the atmospheres of cool stars, and the influence of NLTE and HFS (hyperfine splitting) on the formation of Co lines and abundances. Significant departures from LTE level populations are found for Co I, also number densities of excited states in Co II differ from LTE at low metallicity. The NLTE abundance of Co in solar photosphere is 4.95 +/- 0.04 dex, which is in agreement with that in C I meteorites within the combined uncertainties. The spectral lines of Co I were calculated using the results of recent measurements of hyperfine interaction constants by UV Fourier transform spectrometry. For Co II, the first laboratory measurements of hyperfine structure splitting A and B factors were performed. A differential abundance analysis of Co is carried out for 18 stars in the metallicity range -3.12 < [Fe/H] < 0. The abundances are derived by method of spectrum synthesis. At low [Fe/H], NLTE abundance corrections for Co I lines are as large as +0.6 >... +0.8 dex. Thus, LTE abundances of Co in metal-poor stars are severely underestimated. The stellar NLTE abundances determined from the single UV line of Co II are lower by ~0.5-0.6 dex. The discrepancy might be attributed to possible blends that have not been accounted for in the solar Co II line and its erroneous oscillator strength. The increasing [Co/Fe] trend in metal-poor stars, as calculated from the Co I lines under NLTE, can be explained if Co is overproduced relative to Fe in massive stars. The models of galactic chemical evolution are wholly inadequate to describe this trend suggesting that the problem is in SN yields.Comment: submitted to MNRAS, 15 page

Lattice potentials and fermions in holographic non Fermi-liquids: hybridizing local quantum criticality

We study lattice effects in strongly coupled systems of fermions at a finite density described by a holographic dual consisting of fermions in Anti-de-Sitter space in the presence of a Reissner-Nordstrom black hole. The lattice effect is encoded by a periodic modulation of the chemical potential with a wavelength of order of the intrinsic length scales of the system. This corresponds with a highly complicated "band structure" problem in AdS, which we only manage to solve in the weak potential limit. The "domain wall" fermions in AdS encoding for the Fermi surfaces in the boundary field theory diffract as usually against the periodic lattice, giving rise to band gaps. However, the deep infrared of the field theory as encoded by the near horizon AdS2 geometry in the bulk reacts in a surprising way to the weak potential. The hybridization of the fermions bulk dualizes into a linear combination of CFT1 "local quantum critical" propagators in the bulk, characterized by momentum dependent exponents displaced by lattice Umklapp vectors. This has the consequence that the metals showing quasi-Fermi surfaces cannot be localized in band insulators. In the AdS2 metal regime, where the conformal dimension of the fermionic operator is large and no Fermi surfaces are present at low T/\mu, the lattice gives rise to a characteristic dependence of the energy scaling as a function of momentum. We predict crossovers from a high energy standard momentum AdS2 scaling to a low energy regime where exponents found associated with momenta "backscattered" to a lower Brillioun zone in the extended zone scheme. We comment on how these findings can be used as a unique fingerprint for the detection of AdS2 like "pseudogap metals" in the laboratory.Comment: 42 pages, 5 figures; v2, minor correction, to appear in JHE

Cavitation of Electrons Bubbles in Liquid Helium Below saturation Pressure

We have used a Hartree-type electron-helium potential together with a density functional description of liquid $^4$He and $^3$He to study the explosion of electron bubbles submitted to a negative pressure. The critical pressure at which bubbles explode has been determined as a function of temperature. It has been found that this critical pressure is very close to the pressure at which liquid helium becomes globally unstable in the presence of electrons. It is shown that at high temperatures the capillary model overestimates the critical pressures. We have checked that a commonly used and rather simple electron-helium interaction yields results very similar to those obtained using the more accurate Hartree-type interaction. We have estimated that the crossover temperature for thermal to quantum nucleation of electron bubbles is very low, of the order of 6 mK for $^4$He.Comment: 22 pages, 9 figure

Heme oxygenase-1 derived carbon monoxide suppresses Aβ1-42 toxicity in astrocytes

Neurodegeneration in Alzheimer’s disease (AD) is extensively studied, and the involvement of astrocytes and other cell types in this process has been described. However, the responses of astrocytes themselves to amyloid β peptides ((Aβ; the widely accepted major toxic factor in AD) is less well understood. Here, we show that Aβ(1-42) is toxic to primary cultures of astrocytes. Toxicity does not involve disruption of astrocyte Ca2+ homeostasis, but instead occurs via formation of the toxic reactive species, peroxynitrite. Thus, Aβ(1-42) raises peroxynitrite levels in astrocytes, and Aβ(1-42) toxicity can be inhibited by antioxidants, or by inhibition of nitric oxide (NO) formation (reactive oxygen species (ROS) and NO combine to form peroxynitrite), or by a scavenger of peroxynitrite. Increased ROS levels observed following Aβ(1-42) application were derived from NADPH oxidase. Induction of heme oxygenase-1 (HO-1) protected astrocytes from Aβ(1-42) toxicity, and this protective effect was mimicked by application of the carbon monoxide (CO) releasing molecule CORM-2, suggesting HO-1 protection was attributable to its formation of CO. CO suppressed the rise of NADPH oxidase-derived ROS caused by Aβ(1-42). Under hypoxic conditions (0.5% O2, 48h) HO-1 was induced in astrocytes and Aβ(1-42) toxicity was significantly reduced, an effect which was reversed by the specific HO-1 inhibitor, QC-15. Our data suggest that Aβ(1-42) is toxic to astrocytes, but that induction of HO-1 affords protection against this toxicity due to formation of CO. HO-1 induction, or CO donors, would appear to present attractive possible approaches to provide protection of both neuronal and non-neuronal cell types from the degenerative effects of AD in the central nervous system

The effect of statin therapy on heart failure events: a collaborative meta-analysis of unpublished data from major randomized trials

The effect of statins on risk of heart failure (HF) hospitalization and HF death remains uncertain. We aimed to establish whether statins reduce major HF events.We searched Medline, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized controlled endpoint statin trials from 1994 to 2014. Collaborating trialists provided unpublished data from adverse event reports. We included primary- and secondary-prevention statin trials with >1000 participants followed for >1 year. Outcomes consisted of first non-fatal HF hospitalization, HF death and a composite of first non-fatal HF hospitalization or HF death. HF events occurring <30 days after within-trial myocardial infarction (MI) were excluded. We calculated risk ratios (RR) with fixed-effects meta-analyses. In up to 17 trials with 132 538 participants conducted over 4.3 [weighted standard deviation (SD) 1.4] years, statin therapy reduced LDL-cholesterol by 0.97 mmol/L (weighted SD 0.38 mmol/L). Statins reduced the numbers of patients experiencing non-fatal HF hospitalization (1344/66 238 vs. 1498/66 330; RR 0.90, 95% confidence interval, CI 0.84-0.97) and the composite HF outcome (1234/57 734 vs. 1344/57 836; RR 0.92, 95% CI 0.85-0.99) but not HF death (213/57 734 vs. 220/57 836; RR 0.97, 95% CI 0.80-1.17). The effect of statins on first non-fatal HF hospitalization was similar whether this was preceded by MI (RR 0.87, 95% CI 0.68-1.11) or not (RR 0.91, 95% CI 0.84-0.98).In primary- and secondary-prevention trials, statins modestly reduced the risks of non-fatal HF hospitalization and a composite of non-fatal HF hospitalization and HF death with no demonstrable difference in risk reduction between those who suffered an MI or not

Technology readiness level assessment of composites recycling technologies

Composite materials made of glass and carbon fibres have revolutionised many industries. Demand for composites is experiencing rapid growth and global demand is expected to double. As demand for composites grows it is clear that waste management will become an important issue for businesses. Technically composite materials evoke difficult recycling challenges due to the heterogeneity of their composition. As current waste management practices in composites are dominated by landfilling, governments and businesses themselves foresee that this will need to change in the future. The recycling of composites will play a vital role in the future especially for the aerospace, automotive, construction and marine sectors. These industries will require different recycling options for their products based on compliance with current legislation, the business model as well as cost effectiveness. In order to be able to evaluate waste management strategies for composites, a review of recycling technologies has been conducted based on technology readiness levels and waste management hierarchy. This paper analyses 56 research projects to identify growing trends in composite recycling technologies with pyrolysis, solvolysis and mechanical grinding as the most prominent technologies. These recycling technologies attained high scores on the waste management hierarchy (either recycling or reuse applications) suggesting potential development as future viable alternatives to composite landfilling. The research concluded that recycling as a waste management strategy is most popular exploration area. It was found mechanical grinding to be most mature for glass fibre applications while pyrolysis has been most mature in the context of carbon fibre. The paper also highlights the need to understand the use of reclaimed material as important assessment element of recycling efforts. This paper contributes to the widening and systematising knowledge on maturity and understanding composites recycling technologies