Molecular mechanisms regulating perivascular adipose tissue - potential pharmacological targets?

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An investigation of the antiplatelet effects of succinobucol (AGI-1067)

Succinobucol is a phenolic antioxidant with anti-inflammatory and antiplatelet effects. Given the importance of oxidant stress in modulating platelet–platelet and platelet–vessel wall interactions, the aim of this study was to establish if antioxidant activity was responsible for the antiplatelet activity of succinobucol. Platelet aggregation in response to collagen and adenosine diphosphate (ADP) was studied in rabbit whole blood and platelet-rich plasma using impedance aggregometry. The effect of oxidant stress on aggregation, platelet lipid peroxides, and vascular tone was studied by incubating platelets, washed platelets or preconstricted rabbit iliac artery rings respectively with a combination of xanthine and xanthine oxidase (X/XO). To study the effect of succinobucol in vivo, anaesthetized rats were injected with up to 150 mg/kg succinobucol and aggregation measured in blood removed 15 mins later. Succinobucol (10−5–10−4 M) significantly attenuated platelet aggregation to collagen and ADP in whole blood and platelet-rich plasma. X/XO significantly increased aggregation to collagen and platelet lipid peroxides and this was reversed by succinobucol. Addition of X/XO to denuded rabbit iliac arteries caused a dose-dependent relaxation which was significantly inhibited by succinobucol. In vivo administration up to 150 mg/kg had no effect on heart rate or mean arterial blood pressure but significantly inhibited platelet aggregation to collagen ex vivo. In conclusion, succinobucol displays anti-platelet activity in rabbit and rat blood and reverses the increase in platelet aggregation in response to oxidant stress

Trading efficiency in water quality markets

A crucial factor in the success of any water quality trading market is its ability to cost-effectively reallocate nutrient allowances from initial holders to those users who find them most valuable; the market's trading efficiency. We explore causes of and solutions to trading inefficiency by assessing the impact on participant transaction costs and the tradeoffs that occur as a result of policy design decisions. Differing impacts of baseline-credit and cap-and-trade markets, the impact of trading rules and monitoring regimes are discussed in this endeavour. Possible solutions of increased information flows and regulatory certainty are also discussed. We then apply this framework to three existing water quality trading schemes; two from the US, and one from New Zealand. We use this experience to extract general recommendations for policy makers looking to maximise trading efficiency when designing future water quality trading markets.Nutrient trading, trading efficiency, water quality markets, transaction costs, Community/Rural/Urban Development, Environmental Economics and Policy, Health Economics and Policy, International Relations/Trade,

Investigations into the assembly behaviour of a 'rigidified': P-carboxylatocalix[4]arene

The p-carboxylatocalix[4]arenes have been shown to be versatile supramolecular building blocks capable of forming a range of bi-layers, capsules and nanoscale tubules in the solid state. Here we report the synthesis of a new 'rigidified' analogue, as well as investigations into its self-assembly and related coordination chemistry. These behaviours are reminiscent of other p-carboxylatocalix[4]arenes despite the presence of rigidifying groups at the lower-rim, suggesting that this building block may be further exploited in the assembly of a range of new metal-organic cages and coordination polymers

PEA‐15 (Phosphoprotein Enriched in Astrocytes 15) Is a Protective Mediator in the Vasculature and Is Regulated During Neointimal Hyperplasia

This work was supported by a grant from the Medical Research Council, UK (MR/K012789/1). Additional information can be downloaded from the publisher's websitePeer reviewedPublisher PD

Simulating Drug-Eluting Stents: Progress Made and the Way Forward

Drug-eluting stents have significantly improved the treatment of coronary artery disease. Compared with their bare metal predecessors, they offer reduced rates of restenosis and thus represent the current gold standard in percutaneous coronary interventions. Drug-eluting stents have been around for over a decade, and while progress is continually being made, they are not suitable in all patients and lesion types. Furthermore there are still real concerns over incomplete healing and late stent thrombosis. In this paper, some modelling approaches are reviewed and the future of modelling and simulation in this field is discussed

A polymer coated cicaprost-eluting stent increases neointima formation and impairs vessel function in the rabbit iliac artery

Drug-eluting stents have been successful in reducing in-stent restenosis but are not suitable for all lesion types and have been implicated in causing late stent thrombosis due to incomplete regeneration of the endothelial cell layer. In this study we implanted stents coated with cicaprost, a prostacyclin analogue with a long plasma half-life and antiproliferative effects on vascular smooth muscle cells, into the iliac arteries of rabbits. At 28-day follow-up we compared neointima formation within the stented vessels and vascular function in adjacent vessels, to assess if cicaprost could reduce restenosis without impairing vessel function. Arteries implanted with cicaprost eluting stents had significantly more neointima compared to bare metal stents. In adjacent segments of artery, endothelium-dependent relaxation was impaired by the cicaprost-eluting stent but vasodilation to an endothelium-independent vasodilator was maintained. We conclude that the presence of the polymer and sub-optimal release of cicaprost from the stent may be responsible for the increased neointma and impaired functional recovery of the endothelium observed. Further experiments should be aimed at optimising release of cicaprost and exploring different stent polymer coatings

Diagnostic framework and health check tool for engineering and technology projects

Purpose: Development of a practitioner oriented diagnostic framework and health check tool to support the robust assessment of engineering and technology projects. Design/methodology/approach: The research is based on a literature review that draws together insights on project assessment and critical success factors to establish an integrated systems view of projects. This is extended to allow a comprehensive diagnostic framework to be developed along with a high-level health check tool that can be readily deployed on projects. The utility of the diagnostic framework and health check tool are explored through three illustrative case studies, with two from Canada and one from the United Kingdom. Findings and Originality/value: The performance of engineering and technology projects can be viewed through a systems perspective and being a function of six contributing subsystems that are: process, technology, resources, impact, knowledge and culture. The diagnostic framework that is developed through this research integrates these sub-systems to provide a robust assessment methodology for projects, which is linked to existing best practice for project reviews, performance management and maturity models. The case studies provide managerial insights that are related to the diagnostic framework but crucially also position the approach in the context of industrial applications for construction engineering and technology management.Research limitations/implications: The case study approach includes two case studies from the construction and facilities development sector with the third case study from the research and technology sector. Further work is required to investigate the use of the diagnostic framework and health check tool in other sectors. Practical implications: The health check tool will be of practical benefit to new projects managers that require access to a robust and convenient project review methodology for assessing the status and health of a given portfolio of projects. The tool can also be used periodically and throughout the project lifecycle in order to track the performance of projects. Originality/value: This paper provides a unique view and supporting management framework to help project managers assess the status and health of projects. Value can be associated with an extension to the literature on diagnostic tools for engineering project management as well as the insights provided in the three international case studies, which explore the scope and applicability of the health check tool to be used in support of projects that have encountered difficulties and which require implementation of project recovery strategies.Peer Reviewe

NaGdF4:Eu3+ Nanoparticles for Enhanced X-ray Excited Optical Imaging.

X-ray luminescent nanoparticles (NPs), including lanthanide fluorides, have been evaluated for application to deep tissue in vivo molecular imaging using optical tomography. A combination of high material density, higher atomic number and efficient NIR luminescence from compatible lanthanide dopant ions indicates that particles that consist of ALnF4 (A = alkaline, Ln = lanthanide element) may offer a very attractive class of materials for high resolution, deep tissue imaging with X-ray excitation. NaGdF4:Eu3+ NPs produced an X-ray excited luminescence that was among the most efficient of nanomaterials that have been studied thus far. We have systematically studied factors such as (a) the crystal structure that changes the lattice environment of the doped Eu3+ ions within the unit cell; and extrinsic factors such as (b) a gold coating (with attendant biocompatibility) that couples to a plasmonic excitation, and (c) changes in the NPs surface properties via changes in the pH of the suspending medium-all with a significant impact on the X-ray excited luminescence of NaGdF4:Eu3+NPs. The luminescence from an optimally doped hexagonal phase NaGdF4:Eu3+ nanoparticle was 25% more intense compared to that of a cubic structure. We observed evidence of plasmonic reabsorption of midwavelength emission by a gold coating on hexagonal NaGdF4:Eu3+ NPs; fortunately, the NaGdF4:Eu3+ @Au core-shell NPs retained the efficient 5D0→7F4 NIR (692 nm) luminescence. The NaGdF4:Eu3+ NPs exhibited sensitivity to the ambient pH when excited by X-rays, an effect not seen with UV excitation. The sensitivity to the local environment can be understood in terms of the sensitivity of the excitons that are generated by the high energy X-rays (and not by UV photons) to crystal structure and to the surface state of the particles

Discovery of new dipper stars with K2 : a window into the inner disc region of T Tauri stars

In recent years, a new class of young stellar object (YSO) has been defined, referred to as dippers, where large transient drops in flux are observed. These dips are too large to be attributed to stellar variability, last from hours to days and can reduce the flux of a star by 10-50 per cent. This variability has been attributed to occultations by warps or accretion columns near the inner edge of circumstellar discs. Here, we present 95 dippers in the Upper Scorpius association and ρ Ophiuchus cloud complex found in K2 Campaign 2 data using supervised machine learning with a random forest classifier. We also present 30 YSOs that exhibit brightening events on the order of days, known as bursters. Not all dippers and bursters are known members, but all exhibit infrared excesses and are consistent with belonging to either of the two young star-forming regions. We find 21.0 ± 5.5 per cent of stars with discs are dippers for both regions combined. Our entire dipper sample consists only of late-type (KM) stars, but we show that biases limit dipper discovery for earlier spectral types. Using the dipper properties as a proxy, we find that the temperature at the inner disc edge is consistent with interferometric results for similar and earlier type stars