Benchmarking pKa prediction

Background: pKa values are a measure of the protonation of ionizable groups in proteins. Ionizable groups are involved in intra-protein, protein-solvent and protein-ligand interactions as well as solubility, protein folding and catalytic activity. The pKa shift of a group from its intrinsic value is determined by the perturbation of the residue by the environment and can be calculated from three-dimensional structural data. Results: Here we use a large dataset of experimentally-determined pKas to analyse the performance of different prediction techniques. Our work provides a benchmark of available software implementations: MCCE, MEAD, PROPKA and UHBD. Combinatorial and regression analysis is also used in an attempt to find a consensus approach towards pKa prediction. The tendency of individual programs to over- or underpredict the pKa value is related to the underlying methodology of the individual programs. Conclusion: Overall, PROPKA is more accurate than the other three programs. Key to developing accurate predictive software will be a complete sampling of conformations accessible to protein structures

Statistical deconvolution of enthalpic energetic contributions to MHC-peptide binding affinity

Background: MHC Class I molecules present antigenic peptides to cytotoxic T cells, which forms an integral part of the adaptive immune response. Peptides are bound within a groove formed by the MHC heavy chain. Previous approaches to MHC Class I-peptide binding prediction have largely concentrated on the peptide anchor residues located at the P2 and C-terminus positions. Results: A large dataset comprising MHC-peptide structural complexes was created by re-modelling pre-determined x-ray crystallographic structures. Static energetic analysis, following energy minimisation, was performed on the dataset in order to characterise interactions between bound peptides and the MHC Class I molecule, partitioning the interactions within the groove into van der Waals, electrostatic and total non-bonded energy contributions. Conclusion: The QSAR techniques of Genetic Function Approximation (GFA) and Genetic Partial Least Squares (G/PLS) algorithms were used to identify key interactions between the two molecules by comparing the calculated energy values with experimentally-determined BL50 data. Although the peptide termini binding interactions help ensure the stability of the MHC Class I-peptide complex, the central region of the peptide is also important in defining the specificity of the interaction. As thermodynamic studies indicate that peptide association and dissociation may be driven entropically, it may be necessary to incorporate entropic contributions into future calculations

Localized Flux Lines and the Bose Glass

Columnar defects provide effective pinning centers for magnetic flux lines in high--$T_{\rm c}$ superconductors. Utilizing a mapping of the statistical mechanics of directed lines to the quantum mechanics of two--dimensional bosons, one expects an entangled flux liquid phase at high temperatures, separated by a second--order localization transition from a low--temperature ``Bose glass'' phase with infinite tilt modulus. Recent decoration experiments have demonstrated that below the matching field the repulsive forces between the vortices may be sufficiently large to produce strong spatial correlations in the Bose glass. This is confirmed by numerical simulations, and a remarkably wide soft ``Coulomb gap'' at the chemical potential is found in the distribution of pinning energies. At low currents, the dominant transport mechanism in the Bose glass phase proceeds via the formation of double kinks between not necessarily adjacent columnar pins, similar to variable--range hopping in disordered semiconductors. The strong correlation effects originating in the long--range vortex interactions drastically reduce variable--range hopping transport.Comment: 10 pages, latex ("lamuphys.sty" file included), 6 figures can be obtained from the author ([email protected]); to appear in Proc. XIV Sitges conference on "Complex Behaviour of Glassy Systems" (Springer--Verlag

RADIATION-INDUCED CHROMOSOME ABERRATIONS AND LOSS OF REPRODUCTIVE INTEGRITY IN TRADESCANTIA

The reproductive integrity of single meristematic cells of Tradescantia occidentalis exposed to acute doses of x rays was investigated. The dose response curve was sigmoid and similar to that reported for a variety of mammaliand cell lines having a D/sub O/ of 149 r and and extrapolation number of 1.6. Detailed observations were also made of all forms of chromatid and chromosome aberrations induced after irradiating all stages of the mitotic cycle of these same meristematic cells. Attempts were then made to correlate these two sets of data and to equate loss of genetic information to loss of reproductive integrity. (auth

Properties of the Bose glass phase in irradiated superconductors near the matching field

Structural and transport properties of interacting localized flux lines in the Bose glass phase of irradiated superconductors are studied by means of Monte Carlo simulations near the matching field B_Phi, where the densities of vortices and columnar defects are equal. For a completely random columnar pin distribution in the xy-plane transverse to the magnetic field, our results show that the repulsive vortex interactions destroy the Mott insulator phase which was predicted to occur at B = B_Phi. On the other hand, for ratios of the penetration depth to average defect distance lambda/d <= 1, characteristic remnants of the Mott insulator singularities remain visible in experimentally accessible quantities as the magnetization, the bulk modulus, and the magnetization relaxation, when B is varied near B_Phi. For spatially more regular disorder, e.g., a nearly triangular defect distribution, we find that the Mott insulator phase can survive up to considerably large interaction range \lambda/d, and may thus be observable in experiments.Comment: RevTex, 17 pages, eps files for 12 figures include

Mantle wedge temperatures and their potential relation to volcanic arc location

The mechanisms underpinning the formation of a focused volcanic arc above subduction zones are debated. Suggestions include controls by: (i) where the subducting plate releases water, lowering the solidus in the overlying mantle wedge; (ii) the location where the mantle wedge melts to the highest degree; and (iii) a limit on melt formation and migration imposed by the cool shallow corner of the wedge. Here, we evaluate these three proposed mechanisms using a set of kinematically-driven 2D thermo-mechanical mantle-wedge models in which subduction velocity, slab dip and age, overriding-plate thickness and the depth of decoupling between the two plates are systematically varied. All mechanisms predict, on the basis of model geometry, that the arc-trench distance, D, decreases strongly with increasing dip, consistent with the negative D-dip correlations found in global subduction data. Model trends of sub-arc slab depth, H, with dip are positive if H is wedge-temperature controlled and overriding-plate thickness does not exceed the decoupling depth by more than 50 km, and negative if H is slab-temperature controlled. Observed global H-dip trends are overall positive. With increasing overriding plate thickness, the position of maximum melting shifts to smaller H and D, while the position of the trenchward limit of the melt zone, controlled by the wedge's cold corner, shifts to larger H and D, similar to the trend in the data for oceanic subduction zones. Thus, the limit imposed by the wedge corner on melting and melt migration seems to exert the first-order control on arc position

Interactions, Distribution of Pinning Energies, and Transport in the Bose Glass Phase of Vortices in Superconductors

We study the ground state and low energy excitations of vortices pinned to columnar defects in superconductors, taking into account the long--range interaction between the fluxons. We consider the ``underfilled'' situation in the Bose glass phase, where each flux line is attached to one of the defects, while some pins remain unoccupied. By exploiting an analogy with disordered semiconductors, we calculate the spatial configurations in the ground state, as well as the distribution of pinning energies, using a zero--temperature Monte Carlo algorithm minimizing the total energy with respect to all possible one--vortex transfers. Intervortex repulsion leads to strong correlations whenever the London penetration depth exceeds the fluxon spacing. A pronounced peak appears in the static structure factor $S(q)$ for low filling fractions $f \leq 0.3$. Interactions lead to a broad Coulomb gap in the distribution of pinning energies $g(\epsilon)$ near the chemical potential $\mu$, separating the occupied and empty pins. The vanishing of $g(\epsilon)$ at $\mu$ leads to a considerable reduction of variable--range hopping vortex transport by correlated flux line pinning.Comment: 16 pages (twocolumn), revtex, 16 figures not appended, please contact [email protected]

Compression ultrasonography for false femoral artery aneurysms: Hypocoagulability is a cause of failure

Objectives:false femoral artery aneurysm is an occasional complication of percutaneous cardiovascular radiological procedures. Compression ultrasonography causes thrombosis non-invasively, reducing need for operative intervention. The technique fails in a proportion of cases. Analysis was undertaken to identify causes of failure.Design:prospective open study.Materials and Methods:patients presenting with false femoral artery aneurysm since 1984 were identified from a computerised database (BIPAS). Since 1993 compression ultrasonography has been performed as first line treatment according to a standard protocol. Prospectively collected ultrasonographic data and case notes were reviewed to identify causes of failed compression.Results:false femoral artery aneurysm occurred as a complication in 32/26 687 (0.12%) cardiovascular radiological procedures. Eighteen aneurysms were treated by compression. The technique was successful in 11/18 (61%) cases but primary failure occurred in seven cases. Six out of seven had bleeding abnormalities (Chi-squared analysis with Yates correction 10.55, p=0.0012), four were anticoagulated and compression was subsequently successful following reversal of warfarin therapy in three of these patients. In 4/18 cases surgical repair was necessary.Conclusions:compression ultrasonography is an effective treatment of false femoral aneurysms, however, hypocoagulability is a significant cause of failure. For patients in whom anticoagulation cannot be reversed, primary surgical repair should be considered

Sticky stuff : redefining bedform prediction in modern and ancient environments

This work was funded by the UK Natural Environment Research Council (NERC) under the COHBED project (NE/1027223/1). Paterson was funded by the Marine Alliance for Science and Technology for Scotland (MASTS).The dimensions and dynamics of subaqueous bedforms are well known for cohesionless sediments. However, the effect of physical cohesion imparted by cohesive clay within mixed sand-mud substrates has not been examined, despite its recognized influence on sediment stability. Here we present a series of controlled laboratory experiments to establish the influence of substrate clay content on subaqueous bedform dynamics within mixtures of sand and clay exposed to unidirectional flow. The results show that bedform dimensions and steepness decrease linearly with clay content, and comparison with existing predictors of bedform dimensions, established within cohesionless sediments, reveals significant over-prediction of bedform size for all but the lowermost clay contents examined. The profound effect substrate clay content has on bedform dimensions has a number of important implications for interpretation in a range of modern and ancient environments, including reduced roughness and bedform heights in estuarine systems and the often cited lack of large dune cross-sets in turbidites. The results therefore offer a step change in our understanding of bedform formation and dynamics in these, and many other, sedimentary environments.Publisher PDFPeer reviewe

Effect of Workload History on Task Performance

Objective: This study investigated the effects of workload history (specifically, sudden shifts in workload) on performance. Background: In 1993 the National Research Council identified workload transition as an important concern for human factors researchers. The study of workload history suggests that what an individual has been doing prior to a point in time has an effect on subsequent performance. One trend emerging from workload history studies is that a general decrement in performance is most likely to occur following a decrease in task demand. Method: The 198 participants were randomly assigned to a high-to-low or low-to-high condition. Participants performed a version of the Bakan Vigilance Task while correct responses, response times, and total errors were recorded. Results: Results supported previous research suggesting a workload decrease results in a performance decrement. More importantly, this study reports that either a sudden increase or decrease could lead to a loss in accuracy and a slowing of response time in a longer time course. Conclusion: An explanation of the decrement is offered in terms of adaptation models. In addition, a follow-up study suggested that the decrement is a result of something inherent in the workload shift rather than an effect of fatigue. Application: Workload history (more specifically, a workload shift) has significant implications for many work environments. These implications are particularly salient in occupations where individuals are confronted with varying levels of workload demand, especially safety-sensitive occupations.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline