Regulation of anti-inflammatory gene expression in vascular endothelial cells by EPAC1

Suppressor of cytokine signalling 3 (SOCS3) is a potent inhibitor of pro-inflammatory pathways involved in atherogenesis and the development of neo-intimal hyperplasia (NIH), which contributes to the in-stent re-stenosis responsible for the failure of percutaneous coronary intervention (PCI) procedures. We have shown that cyclic AMP sensor EPAC1 triggers induction of the SOCS3 gene in vascular endothelial cells (VECs), thereby attenuating interleukin 6 (IL-6)-mediated pro-inflammatory signalling. We propose that EPAC1 localisation to the nuclear pore controls cyclic AMP-mediated activation of a C/EBPβ/c-Jun transcriptional complex, leading to SOCS3 induction and suppression of pro-inflammatory signalling. Future work in this area will involve an integrated approach to determine the wider significance of the EPAC1-C/EBPβ/c-Jun pathway in controlling human VEC function and identify new therapeutic targets for management of chronic inflammation in vascular settings

Modelling Hen Harrier Dynamics to Inform Human-Wildlife Conflict Resolution : A Spatially-Realistic, Individual-Based Approach

Peer reviewedPublisher PD

Research poster: GIS and Remote Sensing Core Lab for facilitating interdisciplinary research in climate change

Research poste

Learning from the children : exploring preschool children's encounters with ICT at home

This paper is an account of our attempts to understand preschool children's experiences with information and communication technologies (ICT) at home. Using case study data, we focus on what we can learn from talking directly to the children that might otherwise have been overlooked and on describing and evaluating the methods we adopted to ensure that we maximised the children's contributions to the research. By paying attention to the children's perspectives we have learned that they are discriminating users of ICT who evaluate their own performances, know what gives them pleasure and who differentiate between operational competence and the substantive activities made possible by ICT

A trait-based approach for predicting species responses to environmental change from sparse data : how well might terrestrial mammals track climate change?

Acknowledgements LS was supported by two STSMs by the COST Action ES1101 ”Harmonising Global Biodiversity Modelling“ (Harmbio), supported by COST (European Cooperation in Science and Technology). JMB and SMW were funded by CEH projects NEC05264 and NEC05100. JMJT and SCFP are grateful for the support of the Natural Environment Research Council UK (NE/J008001/1). LS, JAH and JMJT conceived the original idea. LS, JAH, JMB, TC & JMJT designed the study; LS collected the data; LS and TC performed the statistical analyses; LS conducted the integrodifference modelling assisted by JMB and SMW. LS conducted the individual-based modelling assisted by SCFP. LS led the writing supported by JMJT, JMB, SCFP, SMW, TC, JAH and GB.Peer reviewedPublisher PD

Spread rates on fragmented landscapes: the interacting roles of demography, dispersal and habitat availability

This work was supported by the award of the Natural Environment Research Council grant NE/J008001/1 to JMJT.Peer reviewedPublisher PD

A Complete Scheme of Ionization Cooling for a Muon Collider

A complete scheme for production and cooling a muon beam for three specified muon colliders is presented. Parameters for these muon colliders are given. The scheme starts with the front end of a proposed neutrino factory that yields bunch trains of both muon signs. Emittance exchange cooling in slow helical lattices reduces the longitudinal emittance until it becomes possible to merge the trains into single bunches, one of each sign. Further cooling in all dimensions is applied to the single bunches in further slow helical lattices. Final transverse cooling to the required parameters is achieved in 50 T solenoids using high Tc superconductor at 4 K. Preliminary simulations of each element are presented.Comment: 3 pages, 6 figure

Characterization of Organic Sulfur Compounds in Coals and Coal Macerals

Peroxyacetic acid oxidation has been used to investigate the type and distribution of organic sulfur species in samples of vitrinite, sporinite and inertinite, separated from the Herrin No.6 and an Indiana No.5 coal seam. It was established that organic sulfur species were selectively preserved during oxidation and their analysis led to some of the first sulfur-33 NMR spectra obtained for coal. The effects of maceral separation processes on model compounds were also studied. Results from our studies support the following conclusions: 1). Different macerals have different distributions and types of organic sulfur species. 2). Organic sulfur compounds in coal occur at the ends of macromolecular structures. 3). Maceral separation techniques do not affect organic sulfur species in coal. 4). Maceral separation is essential for the chemical characterization of coal. 5). GC-MS and sulfur-33 NMR data agree

Aspects of Sporinite Chemistry

With the recent advent of the ability to separate coal into maceral concentrates of high purity, the individual constituents of coal can now be analyzed separately, without their mutual interference, giving a much better understanding of the macromolecular structure of coal. The sporinites from two Pennsylvanian age coal samples (Illinois Basin, U.S.A.) were studied, one from a vitrinite-rich high-volatile bituminous coal, the other from a liptinite-rich high-volatile bituminous coal of slightly higher rank. Sporinites were isolated from each coal by density gradient centrifugation. The sporinite of the vitrinite-rich coal was compared chemically and petrographically with the parent coal and with the sporinite of the liptinite-rich coal. The fluorescence spectrum of the sporinite from the liptinite-rich coal is shifted to the red end of the spectrum, which may be accounted for by the somewhat higher rank of the sample and/or by differences in the original assemblage of spores. The lack of chemical differences between the extracts of the sporinite and its whole coal reinforce the concept of bitumen as an homogeneous mobile phase pervading the coal. Thus, extract chemistry seems an unsuitable technique for distinguishing between macerals from the same coal. Hopane and sterane distributions in the sporinite and parent coal pyrolyzates are very similar, but the two materials can be readily distinguished by the distribution of tetracyclic diterpanes of the phyllocladane type, which are biological marker compounds derived from higher plant material. Overall, the sporinite is considerably more paraffinic in character and has a greater preponderance of straight-chain alkane moieties than the coal as a whole. In the case of the vitrinite-rich coal, the whole-coal structure appears significantly more polyaromatic than the sporinite. The distributions of thiophenic compounds differ in the pyrolyzates of the two materials. The sporinite from the liptinite-rich coal is even less polycondensed than the sporinite from the vitrinite-rich sample. The chemical and petrographic differences of the two sporinites probably reflect the different assemblages of spores in the original peats and their different diagenetic histories

Achievement of combined goals of low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol with three different statins: Results from VOYAGER

AbstractBackgroundGuidelines suggest that the combination of low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) is the most clinically relevant goal for lipid-lowering treatments.MethodsData from VOYAGER, an individual patient data meta-analysis including 32,258 patients from 37 clinical trials, was used to determine the percentage of patients reaching combined goals of LDL-C and non-HDL-C following treatment with simvastatin, atorvastatin, or rosuvastatin. Paired comparisons were made between each dose of rosuvastatin and the same or higher doses of simvastatin and atorvastatin.ResultsEach dose of rosuvastatin brought significantly more patients to the combined goal of LDL-C < 100 mg/dL and non-HDL-C < 130 mg/dL than the same or double dose of atorvastatin; atorvastatin 80 mg was significantly superior to rosuvastatin 10 mg (all p < 0.001). Each dose of rosuvastatin helped significantly more patients reach the combined goal than any dose of simvastatin (all p < 0.001), except for rosuvastatin 10 mg versus simvastatin 80 mg (non-significant). Also, each dose of rosuvastatin helped significantly more patients to reach the combined goal of LDL-C < 70 mg/dL and non-HDL-C < 100 mg/dL than the same or double dose of atorvastatin (all p < 0.001). Every dose of rosuvastatin was significantly superior to all doses of simvastatin (all p ≤ 0.020), except for rosuvastatin 10 mg versus simvastatin 40 mg and 80 mg (non-significant).ConclusionsPhysicians' choice of statin and dose is important in helping patients achieve the combined LDL-C and non-HDL-C goals recommended in established guidelines