The potential of electron beam radiation for simultaneous surface modification and bioresorption control of PLLA

Bioresorbable polymers have been widely investigated as materials exhibiting significant potential for successful application in the fields of tissue engineering and drug delivery. Further to the ability to control degradation, surface engineering of polymers has been highlighted as a key method central to their development. Previous work has demonstrated the ability of electron beam (e-beam) technology to control the degradation profiles and bioresorption of a number of commercially relevant bioresorbable polymers (poly-l-lactic acid (PLLA), Llactide/DL-lactide co-polymer (PLDL) and poly(lactic-co-glycolic acid (PLGA)). This work investigates the further potential of ebeam technology to impart added biofunctionality through the manipulation of polymer (PLLA) surface properties. PLLA samples were subjected to e-beam treatments in air, with varying beam energies and doses. Surface characterization was then performed using contact angle analysis, X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, and atomic force microscopy. Results demonstrated a significant increase in surface wettability post e-beam treatment. In correlation with this, XPS data showed the introduction of oxygen-containing functional groups to the surface of PLLA. Raman spectroscopy indicated chain scission in the near surface region of PLLA (as predicted). However, e-beam effects on surface properties were not shown to be dependent on beam energy or dose. E-beam irradiation did not seem to affect the surface roughness of PLLA as a direct consequence of the treatment.

Development of an Arcellacean (testate lobose amoebae) based transfer function for sedimentary phosphorous in lakes.

Arcellacea (testate lobose amoebae) communities were assessed from 73 sediment-water interface samples collected from 33 lakes in urban and rural settings within the Greater Toronto Area (GTA), Ontario, Canada, as well as from forested control areas in the Lake Simcoe area, Algonquin Park and eastern Ontario. The results were used to: (1) develop a statistically rigorous arcellacean-based training set for sedimentary phosphorus (Olsen P (OP)) loading; and (2) derive a transfer function to reconstruct OP levels during the post-European settlement era (AD1870s onward) using a chronologically well-constrained core from Haynes Lake on the environmentally sensitive Oak Ridges Moraine, within the GTA. Ordination analysis indicated that OP most influenced arcellacean assemblages, explaining 6.5% (p < 0.005) of total variance. An improved training set where the influence of other important environmental variables (e.g. total organic carbon, total nitrogen, Mg) was reduced, comprised 40 samples from 31 lakes, and was used to construct a transfer function for lacustrine arcellaceans for sedimentary phosphorus (Olsen P) using tolerance downweighted weighted averaging (WA-Tol) with inverse deshrinking (RMSEPjack-77pp; r2jack = 0.68). The inferred reconstruction indicates that OP levels remained near pre-settlement background levels from settlement in the late AD 1970s through to the early AD 1970s. Since OP runoff from both forests and pasture is minimal, early agricultural land use within the lake catchment was as most likely pasture and/or was used to grow perennial crops such as Timothy-grass for hay. A significant increase in inferred OP concentration beginning ~ AD 1972 may have been related to a change in crops (e.g. corn production) in the catchment resulting in more runoff, and the introduction of chemical fertilizers. A dramatic decline in OP after ~ AD 1985 probably corresponds to a reduction in chemical fertilizer use related to advances in agronomy, which permitted a more precise control over required fertilizer application. Another significant increase in OP levels after ~ AD 1995 may have been related to the construction of a large golf course upslope and immediately to the north of Haynes Lake in AD 1993, where significant fertilizer use is required to maintain the fairways. These results demonstrate that arcellaceans have great potential for reconstructing lake water geochemistry and will complement other proxies (e.g. diatoms) in paleolimnological research.

Off-central

Edited version of keynote address to AHRA 'Peripheries' conference, October 2011

Isolation basin records of late Quaternary sea-level change, central mainland British Columbia, Canada.

Isolation basin records from the Seymour-Belize Inlet Complex, a remote area of central mainland British Columbia, Canada are used to constrain post-glacial sea-level changes and provide a preliminary basis for testing geophysical model predictions of relative sea-level (RSL) change. Sedimentological and diatom data from three low-lying (<4 m elevation) basins record falling RSLs in late-glacial times and isolation from the sea by ~11,800–11,200 14C BP. A subsequent RSL rise during the early Holocene (~8000 14C BP) breached the 2.13 m sill of the lowest basin (Woods Lake), but the two more elevated basins (sill elevations of ~3.6 m) remained isolated. At ~2400 14C BP, RSL stood at 1.49 ± 0.34 m above present MTL. Falling RSLs in the late Holocene led to the final emergence of the Woods Lake basin by 1604 ± 36 14C BP. Model predictions generated using the ICE-5G model partnered with a small number of different Earth viscosity models generally show poor agreement with the observational data, indicating that the ice model and/or Earth models considered can be improved upon. The best data-model fits were achieved with relatively low values of upper mantle viscosity (5 × 1019 Pa s), which is consistent with previous modelling results from the region. The RSL data align more closely with observational records from the southeast of the region (eastern Vancouver Island, central Strait of Georgia), than the immediate north (Bella Bella–Bella Coola and Prince Rupert-Kitimat) and areas to the north-west (Queen Charlotte Sound, Hecate Strait), underlining the complexity of the regional response to glacio-isostatic recovery.

Unraveling the Structure and Function of G Protein-Coupled Receptors Through NMR Spectroscopy

G protein-coupled receptors (GPCRs) are a large superfamily of signaling proteins expressed on the plasma membrane. They are involved in a wide range of physiological processes and, therefore, are exploited as drug targets in a multitude of therapeutic areas. In this extent, knowledge of structural and functional properties of GPCRs may greatly facilitate rational design of modulator compounds. Solution and solid-state nuclear magnetic resonance (NMR) spectroscopy represents a powerful method to gather atomistic insights into protein structure and dynamics. In spite of the difficulties inherent the solution of the structure of membrane proteins through NMR, these methods have been successfully applied, sometimes in combination with molecular modeling, to the determination of the structure of GPCR fragments, the mapping of receptor-ligand interactions, and the study of the conformational changes associated with the activation of the receptors. In this review, we provide a summary of the NMR contributions to the study of the structure and function of GPCRs, also in light of the published crystal structures.

Modeled structure of a G-protein-coupled receptor:The cholecystokinin-1 receptor

The Cholecystokinin-1 receptor (CCK1R) mediates actions of CCK in areas of the central nervous system and of the gut. It is a potential target to treat a number of diseases. As for all G-protein-coupled receptors, docking of ligands into modeled CCK1R binding site should greatly help to understand intrinsic mechanisms of activation. Here, we describe the procedure we used to progressively build a structural model for the CCK1R, to integrated, and on the basis of site-directed mutagenesis data on its binding site. Reliability of the CCK1R model was confirmed by interaction networks that involved conserved and functionally crucial motifs in G-protein-coupled receptors, such as Glu/Asp-Arg-Tyr and Asn-Pro-Xaa-Xaa-Tyr motifs. In addition, the 3-D structure of CCK1R-bound CCK resembled that determined by NMR in a lipid environment. The derived computational model was also used for revealing binding modes of several nonpeptide ligands and for rationalizing ligand structure-activity relationships known from experiments. Our findings indeed support that our "validated CCK1R model" could be used to study the intrinsic mechanism of CCK1R activation and design new ligands.

2DRMP-G: Migrating a large-scale numerical mathematical application to a grid environment

We report on the migration of a traditional, single architecture application to a grid application using heterogeneous resources. We focus on the use of the UK e-Science Level 2 grid (UKL2G) which provides a heterogeneous collection of resources distributed within the UK. We discuss the solution architecture, the performance of our application, its future development as a grid-based application and comment on the lessons we have learned in using a grid infrastructure for large-scale numerical problems.

Review: G. De Búrca and J. Scott (eds.), Law and New Governance in the EU and the US (Hart, 2006)

Review of edited collection.

New anti-HIV aptamers based on tetra-end-linked DNA G-quadruplexes: effect of the base sequence on anti-HIV activity.

This communication reports on the synthesis and biophysical, biological and SAR studies of a small library of new anti-HIV aptamers based on the tetra-end-linked G-quadruplex structure. The new aptamers showed EC(50) values against HIV-1 in the range of 0.04-0.15 µM as well as affinities for the HIV-1 gp120 envelope in the same order of magnitude

INDEPENDENT EVALUATION OF THE PERFORMANCE OF THE CCITT G. 722 WIDEBAND CODING RECOMMENDATION.

The subjective performance of the G. 722 7-kHz wideband speech coding recommendation using music signals is described. A number of audible distortions specific to music signals were found to be present in real-time evaluations of the coder. As a result, three modifications are proposed which are found to improve the performance for music signals. These modifications are compatible with the G. 722 system configuration. Modifications made to G. 722 to alleviate the most serious aspects of the noise modulation are described: (1) an adaptive bit allocation scheme is used to reduce short and long-term nonoptimality; (2) spectral noise shaping is incorporated, significantly enhancing the subjective performance of certain modes; and (3) backward block adaptive prediction is used.

INDEPENDENT EVALUATION OF THE PERFORMANCE OF THE CCITT G. 722 WIDEBAND CODING RECOMMENDATION USING MUSIC SIGNALS.

The subjective performance of the G. 722 7-kHz wideband speech-coding recommendation using music signals is described. A number of audible distortions specific to music signals were found to be present in real-time evaluations of the coder. As a result, three modifications are proposed which are found to improve the performance for music signals. These modifications are compatible with the G. 722 system configuration. The results obtained clearly demonstrate the very high coding efficiency of subband ADPCM (adaptive differential pulse-code modulation) with comparison to digitally companding and ADM schemes when applied to music signals.

Late Quaternary tephrostratigraphy, Ahklun Mountains, SW Alaska

Radiocarbon-dated sediment cores from six lakes in the Ahklun Mountains, south-western Alaska, were used to interpolate the ages of late Quaternary tephra beds ranging in age from 25.4 to 0.4ka. The lakes are located downwind of the Aleutian Arc and Alaska Peninsula volcanoes in the northern Bristol Bay area between 159° and 161°W at around 60°N. Sedimentation-rate age models for each lake were based on a published spline-fit procedure that uses Monte Carlo simulation to determine age model uncertainty. In all, 62 C ages were used to construct the six age models, including 23 ages presented here for the first time. The age model from Lone Spruce Pond is based on 18 ages, and is currently the best-resolved Holocene age model available from the region, with an average 2s age uncertainty of about±109 years over the past 14.5ka. The sedimentary sequence from Lone Spruce Pond contains seven tephra beds, more than previously found in any other lake in the area. Of the 26 radiocarbon-dated tephra beds at the six lakes and from a soil pit, seven are correlated between two or more sites based on their ages. The major-element geochemistry of glass shards from most of these tephra beds supports the age-based correlations. The remaining tephra beds appear to be present at only one site based on their unique geochemistry or age. The 5.8ka tephra is similar to the widespread Aniakchak tephra [3.7±0.2 (1s) ka], but can be distinguished conclusively based on its trace-element geochemistry. The 3.1 and 0.4ka tephras have glass major- and trace-element geochemical compositions indistinguishable from prominent Aniakchak tephra, and might represent redeposited beds. Only two tephra beds are found in all lakes: the Aniakchak tephra (3.7±0.2ka) and Tephra B (6.1±0.3ka). The tephra beds can be used as chronostratigraphic markers for other sedimentary sequences in the region, including cores from Cascade and Sunday lakes, which were previously undated and were analyzed in this study to correlate with the new regional tephrostratigraphy. © 2012 John Wiley & Sons, Ltd.