Conformational Dependence of a Protein Kinase Phosphate Transfer Reaction

Atomic motions and energetics for a phosphate transfer reaction catalyzed by the cAMP-dependent protein kinase (PKA) are calculated by plane-wave density functional theory, starting from structures of proteins crystallized in both the reactant conformation (RC) and the transition-state conformation (TC). In the TC, we calculate that the reactants and products are nearly isoenergetic with a 0.2 eV barrier; while phosphate transfer is unfavorable by over 1.2 eV in the RC, with an even higher barrier. With the protein in the TC, the motions involved in reaction are small, with only P$_\gamma$ and the catalytic proton moving more than 0.5 \AA. Examination of the structures reveals that in the RC the active site cleft is not completely closed and there is insufficient space for the phosphorylated serine residue in the product state. Together, these observations imply that the phosphate transfer reaction occurs rapidly and reversibly in a particular conformation of the protein, and that the reaction can be gated by changes of a few tenths of an \AA in the catalytic site.Comment: revtex4, 7 pages, 4 figures, to be submitted to Scienc

Direct characterisation of tuneable few-femtosecond dispersive-wave pulses in the deep UV

Dispersive wave emission (DWE) in gas-filled hollow-core dielectric waveguides is a promising source of tuneable coherent and broadband radiation, but so far the generation of few-femtosecond pulses using this technique has not been demonstrated. Using in-vacuum frequency-resolved optical gating, we directly characterise tuneable 3fs pulses in the deep ultraviolet generated via DWE. Through numerical simulations, we identify that the use of a pressure gradient in the waveguide is critical for the generation of short pulses.Comment: 5 pages, 4 figure

Children with new onset seizures: A prospective study of parent variables, child behavior problems, and seizure occurrence

OBJECTIVE: Parent variables (stigma, mood, unmet needs for information and support, and worry) are associated with behavioral difficulties in children with seizures; however, it is not known how this relationship is influenced by additional seizures. This study followed children (ages 4-14 years) and their parents over a 24-month period (with data collected at baseline and 6, 12, and 24 months) and investigated the effect of an additional seizure on the relationship between parenting variables and child behavior difficulties. METHODS: The sample was parents of 196 children (104 girls and 92 boys) with a first seizure within the past 6 weeks. Child mean age at baseline was 8 years, 3 months (SD 3 years). Data were analyzed using t-tests, chi-square tests, and repeated measures analyses of covariance. RESULTS: Relationships between parent variables, additional seizures, and child behavior problems were consistent across time. Several associations between parent variables and child behavior problems were stronger in the additional seizure group than in the no additional seizure group. CONCLUSIONS: Findings suggest that interventions that assist families to respond constructively to the reactions of others regarding their child's seizure condition and to address their needs for information and support could help families of children with continuing seizures to have an improved quality of life

Measurement of sulfur L2,3 and carbon K edge XANES in a polythiophene film using a high harmonic supercontinuum

We use a high harmonic generated supercontinuum in the soft X-ray region to measure X-ray absorption near edge structure (XANES) spectra in polythiophene (poly(3-hexylthiophene)) films at multiple absorption edges. A few-cycle carrier-envelope phase-stable laser pulse centered at 1800 nm was used to generate a stable soft X-ray supercontinuum, with amplitude gating limiting the generated pulse duration to a single optical half-cycle. We report a quantitative transmission measurement of the sulfur L2,3 edge over the range 160-200 eV and the carbon K edge from 280 to 330 eV. These spectra show all the features previously reported in the XANES spectra of polythiophene, but for the first time they are measured with a source that has an approximately 1 fs pulse duration. This study opens the door to measurements that can fully time-resolve the photoexcited electronic dynamics in these systems

Predicting tree distributions in an East African biodiversity hotspot : model selection, data bias and envelope uncertainty

The Eastern Arc Mountains (EAMs) of Tanzania and Kenya support some of the most ancient tropical rainforest on Earth. The forests are a global priority for biodiversity conservation and provide vital resources to the Tanzanian population. Here, we make a first attempt to predict the spatial distribution of 40 EAM tree species, using generalised additive models, plot data and environmental predictor maps at sub 1 km resolution. The results of three modelling experiments are presented, investigating predictions obtained by (1) two different procedures for the stepwise selection of predictors, (2) down-weighting absence data, and (3) incorporating an autocovariate term to describe fine-scale spatial aggregation. In response to recent concerns regarding the extrapolation of model predictions beyond the restricted environmental range of training data, we also demonstrate a novel graphical tool for quantifying envelope uncertainty in restricted range niche-based models (envelope uncertainty maps). We find that even for species with very few documented occurrences useful estimates of distribution can be achieved. Initiating selection with a null model is found to be useful for explanatory purposes, while beginning with a full predictor set can over-fit the data. We show that a simple multimodel average of these two best-model predictions yields a superior compromise between generality and precision (parsimony). Down-weighting absences shifts the balance of errors in favour of higher sensitivity, reducing the number of serious mistakes (i.e., falsely predicted absences); however, response functions are more complex, exacerbating uncertainty in larger models. Spatial autocovariates help describe fine-scale patterns of occurrence and significantly improve explained deviance, though if important environmental constraints are omitted then model stability and explanatory power can be compromised. We conclude that the best modelling practice is contingent both on the intentions of the analyst (explanation or prediction) and on the quality of distribution data; generalised additive models have potential to provide valuable information for conservation in the EAMs, but methods must be carefully considered, particularly if occurrence data are scarce. Full results and details of all species models are supplied in an online Appendix. (C) 2008 Elsevier B.V. All rights reserved

Thin liquid water clouds: their importance and our challenge

Many clouds important to the Earth’s energy balance contain small amounts of liquid water, yet despite many improvements, large differences in retrievals of their liquid water amount and particle size still must be resolved

Predicting habitat suitability for basking sharks (Cetorhinus maximus) in UK waters using ensemble ecological niche modelling

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.The basking shark (Cetorhinus maximus) is an endangered species in the north-east Atlantic, having been historically over exploited. Whilst near-shore aggregation hotspots in the UK have been identified, robust knowledge on species distribution and abundance outside these areas remains limited. Research techniques, such as habitat modelling, could however be used to gain a greater knowledge of the species distribution to inform management plans to aid population recovery. For large mobile species gathering wide-scale distribution data can be financially and logistically challenging. In lieu of conducting a UK-wide expensive strategic survey for basking sharks, we use data from two regional-scale surveys, which were conducted in southwest England and western Scotland, and use an Ensemble Ecological Niche Model (EENM) to produce a spatially explicit map of habitat suitability. When compared against a ~20-year database of public sightings of basking sharks across UK coastal seas (to 6 nautical miles offshore), patterns of habitat suitability yielded a statistically significant agreement with areas known to support basking shark sightings. EENMs could be used to advise Marine Protected Area (MPA) selection, as well as to inform environmental impact assessments for offshore developments. The application of EENM outputs could be wide-reaching and benefit not only basking sharks but other large mobile marine species in the north-east Atlantic

Direct measurement of room-temperature nondiffusive thermal transport over micron distances in a silicon membrane

The >textbook> phonon mean free path of heat carrying phonons in silicon at room temperature is ~40 nm. However, a large contribution to the thermal conductivity comes from low-frequency phonons with much longer mean free paths. We present a simple experiment demonstrating that room-temperature thermal transport in Si significantly deviates from the diffusion model already at micron distances. Absorption of crossed laser pulses in a freestanding silicon membrane sets up a sinusoidal temperature profile that is monitored via diffraction of a probe laser beam. By changing the period of the thermal grating we vary the heat transport distance within the range ~1-10 ¿m. At small distances, we observe a reduction in the effective thermal conductivity indicating a transition from the diffusive to the ballistic transport regime for the low-frequency part of the phonon spectrum. © 2013 American Physical Society.This work was supported as part of the S3TEC Energy Frontier Research Center funded by the U.S. Department of Energy, Office of Basic Energy Sciences under Award No. DE-SC0001299/DE-FG02-09ER46577 (experimental setup and data analysis). This work was also partially supported by projects NANOPOWER, Contract No. 256959; TAILPHOX, Contract No. 233883; NANOFUNCTION, Contract No. 257375; ACPHIN, Contract No. FIS2009-150; and AGAUR, 2009-SGR-150.Peer Reviewe