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

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

The effect of supplemented chestnut tannin to grass silage either at ensiling or at feeding on lamb performance, carcass characteristics and meat quality

This study was designed to investigate the effect of supplemented chestnut hydrolysable tannin (HT) both at ensiling and at feeding on lamb growth, carcass characteristic, and meat quality. Twenty tons of ryegrass (Lolium perenne) were used to produce silage. The ryegrass was treated at ensiling with one of three additives: 30 g kg-1 DM chestnut HT (GET), an inoculant as a positive control (GI), or water as a negative control (G). Another two treatments were made from ensiled grass by adding the 30 g kg-1 DM of chestnut HT to either positive (GI+T) or negative (GT) control. Forty Suffolk cross Mule lambs were used in this experiment and allocated to receive one of five experimental forage treatments with eight lambs per treatment. The diet consisted of two parts: concentrate and silage. Lambs were fed 215 g DM day-1 lamb of concentrate diet and ad libitum grass silage for seven weeks and then slaughtered. Back fat thickness tended to be lower (p= 0.07) for lambs fed the GT and GI+T treatments compared to lambs in the other experimental groups’ (10.0, 10.1, 9.8, 10.0, and 9.8 mm for GET, G, GT, GI, and GI+T, respectively). Feeding lambs GET tended to reduce (p= 0.06) meat lightness (L*) compared to the other treatments. Ammonia nitrogen concentration in rumen fluid was reduced significantly (p 0.05) on voluntary feed intake (914, 916, 899, 928, or 914 g day-1 for GET, G, GT, GI, and GI+T, respectively) or lamb performance

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

Measurements of Scintillation Efficiency and Pulse-Shape for Low Energy Recoils in Liquid Xenon

Results of observations of low energy nuclear and electron recoil events in liquid xenon scintillator detectors are given. The relative scintillation efficiency for nuclear recoils is 0.22 +/- 0.01 in the recoil energy range 40 keV - 70 keV. Under the assumption of a single dominant decay component to the scintillation pulse-shape the log-normal mean parameter T0 of the maximum likelihood estimator of the decay time constant for 6 keV < Eee < 30 keV nuclear recoil events is equal to 21.0 ns +/- 0.5 ns. It is observed that for electron recoils T0 rises slowly with energy, having a value ~ 30 ns at Eee ~ 15 keV. Electron and nuclear recoil pulse-shapes are found to be well fitted by single exponential functions although some evidence is found for a double exponential form for the nuclear recoil pulse-shape.Comment: 11 pages, including 5 encapsulated postscript figure