The structure of the core NuRD repression complex provides insights into its interaction with chromatin

The NuRD complex is a multi-protein transcriptional corepressor that couples histone deacetylase and ATP-dependent chromatin remodelling activities. The complex regulates the higher-order structure of chromatin, and has important roles in the regulation of gene expression, DNA damage repair and cell differentiation. HDACs 1 and 2 are recruited by the MTA1 corepressor to form the catalytic core of the complex. The histone chaperone protein RBBP4, has previously been shown to bind to the carboxy-terminal tail of MTA1. We show that MTA1 recruits a second copy of RBBP4. The crystal structure reveals an extensive interface between MTA1 and RBBP4. An EM structure, supported by SAXS and crosslinking, reveals the architecture of the dimeric HDAC1:MTA1:RBBP4 assembly which forms the core of the NuRD complex. We find evidence that in this complex RBBP4 mediates interaction with histone H3 tails, but not histone H4, suggesting a mechanism for recruitment of the NuRD complex to chromati

Stress fracture of the thoracic spine in a male rugby player: a case report

This case reports a stress fracture of the thoracic spine in a professional rugby player. This is a rare anatomical location for this type of injury in this population and has not previously been described. Physicians should be aware that performance of rugby specific movements may lead to rare stress fractures in certain anatomic locations

Induction of leaf senescence in Arabidopsis thaliana by long days through a light-dosage effect

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74662/1/j.1399-3054.1996.tb00463.x.pd

Aharonov-Bohm cages in two-dimensional structures

We present an extreme localization mechanism induced by a magnetic field for tight-binding electrons in two-dimensional structures. This spectacular phenomenon is investigated for a large class of tilings (periodic, quasiperiodic, or random). We are led to introduce the Aharonov-Bohm cages defined as the set of sites eventually visited by a wavepacket that can, for particular values of the magnetic flux, be bounded. We finally discuss the quantum dynamics which exhibits an original pulsating behaviour.Comment: 4 pages Latex, 3 eps figures, 1 ps figur

The Ruderman-Kittel-Kasuya-Yosida (RKKY) interaction across a tunneling junction out of equilibrium

The Ruderman-Kittel-Kasuya-Yosida (RKKY) interaction between two magnetic $s$-$d$ spin impurities across a tunneling junction is studied when the system is driven out of equilibrium through biasing the junction. The nonequilibrium situation is handled with the Keldysh time-loop perturbation formalism in conjunction with appropriate coupling methods for tunneling systems due to Caroli and Feuchtwang. We find that the presence of a nonequilibrium bias across the junction leads to an interference of several fundamental oscillations, such that in this tunneling geometry, it is possible to tune the interaction between ferromagnetic and antiferromagnetic coupling at a fixed impurity configuration, simply by changing the bias across the junction. Furthermore, it is shown that the range of the RKKY interaction is altered out of equilibrium, such that in particular the interaction energy between two slabs of spins scales extensively with the thickness of the slabs in the presence of an applied bias.Comment: 38 pages revtex preprint; 5 postscript figures; submitted to Phys. Rev.

New Antarctic gravity anomaly grid for enhanced geodetic and geophysical studies in Antarctica

Gravity surveying is challenging in Antarctica because of its hostile environment and inaccessibility. Nevertheless, many ground-based, airborne, and shipborne gravity campaigns have been completed by the geophysical and geodetic communities since the 1980s. We present the first modern Antarctic-wide gravity data compilation derived from 13 million data points covering an area of 10 million km2, which corresponds to 73% coverage of the continent. The remove-compute-restore technique was applied for gridding, which facilitated leveling of the different gravity data sets with respect to an Earth gravity model derived from satellite data alone. The resulting free-air and Bouguer gravity anomaly grids of 10 km resolution are publicly available. These grids will enable new high-resolution combined Earth gravity models to be derived and represent a major step forward toward solving the geodetic polar data gap problem. They provide a new tool to investigate continental-scale lithospheric structure and geological evolution of Antarctica

Projecting Pharmaceutical Expenditure in EU5 to 2021: Adjusting for the Impact of Discounts and Rebates

Within (European) healthcare systems, the main goal for pharmaceutical expenditure is cost containment. This is due to a general belief among healthcare policy makers that pharmaceutical expenditure—driven by high prices—will be unsustainable unless further reforms are enacted.The aim of the research published in this paper is to provide more realistic expectations of pharmaceutical expenditure for all key stakeholder groups by estimating pharmaceutical expenditure at ‘net’ prices. We also aim to estimate any gaps developing between list and net pharmaceutical expenditure for the EU5 countries (i.e. France, Germany, Italy, Spain, and the UK). We adjusted an established forecast of pharmaceutical expenditure for the EU5 countries, from 2017 to 2021, by reflecting discounts and rebates not previously considered, i.e. we moved from ‘list’ to ‘net’ prices, as far as data were available.We found an increasing divergence between expenditure measured at list and net prices. When the forecasts for the five countries were aggregated, the EU5 (unweighted) average historical growth (2010–2016) rate fell from 3.4% compound annual growth rate at list to 2.5% at net. For the forecast, the net growth rate was estimated at 1.5 versus 2.9% at list.Our results suggest that future growth in pharmaceutical expenditure in Europe is likely to be (1) lower than previously understood from forecasts based on list prices and (2) below predicted healthcare expenditure growth in Europe and in line with long-term economic growth rates. For policy makers concerned about the sustainability of pharmaceutical expenditure, this study may provide some comfort, in that the perceived problem is not as large as expected

Performance of ab initio and density functional methods for conformational equilibria of CnH2n+2 alkane isomers (n=2-8)

Conformational energies of n-butane, n-pentane, and n-hexane have been calculated at the CCSD(T) level and at or near the basis set limit. Post-CCSD(T) contribution were considered and found to be unimportant. The data thus obtained were used to assess the performance of a variety of density functional methods. Double-hybrid functionals like B2GP-PLYP and B2K-PLYP, especially with a small Grimme-type empirical dispersion correction, are capable of rendering conformational energies of CCSD(T) quality. These were then used as a `secondary standard' for a larger sample of alkanes, including isopentane and the branched hexanes as well as key isomers of heptane and octane. Popular DFT functionals like B3LYP, B3PW91, BLYP, PBE, and PBE0 tend to overestimate conformer energies without dispersion correction, while the M06 family severely underestimates GG interaction energies. Grimme-type dispersion corrections for these overcorrect and lead to qualitatively wrong conformer orderings. All of these functionals also exhibit deficiencies in the conformer geometries, particularly the backbone torsion angles. The PW6B95 and, to a lesser extent, BMK functionals are relatively free of these deficiencies. Performance of these methods is further investigated to derive conformer ensemble corrections to the enthalpy function, $H_{298}-H_0$, and the Gibbs energy function, ${\rm gef}(T)\equiv - [G(T)-H_0]/T$, of these alkanes. While $H_{298}-H_0$ is only moderately sensitive to the level of theory, ${\rm gef}(T)$ exhibits more pronounced sensitivity. Once again, double hybrids acquit themselves very well.Comment: J. Phys. Chem. A, revised [Walter Thiel festschrift

Global hybrids from the semiclassical atom theory satisfying the local density linear response

We propose global hybrid approximations of the exchange-correlation (XC) energy functional which reproduce well the modified fourth-order gradient expansion of the exchange energy in the semiclassical limit of many-electron neutral atoms and recover the full local density approximation (LDA) linear response. These XC functionals represent the hybrid versions of the APBE functional [Phys. Rev. Lett. 106, 186406, (2011)] yet employing an additional correlation functional which uses the localization concept of the correlation energy density to improve the compatibility with the Hartree-Fock exchange as well as the coupling-constant-resolved XC potential energy. Broad energetical and structural testings, including thermochemistry and geometry, transition metal complexes, non-covalent interactions, gold clusters and small gold-molecule interfaces, as well as an analysis of the hybrid parameters, show that our construction is quite robust. In particular, our testing shows that the resulting hybrid, including 20\% of Hartree-Fock exchange and named hAPBE, performs remarkably well for a broad palette of systems and properties, being generally better than popular hybrids (PBE0 and B3LYP). Semi-empirical dispersion corrections are also provided.Comment: 12 pages, 4 figure