Increased nitric oxide activity compensates for increased oxidative stress to maintain endothelial function in rat aorta in early type 1 diabetes

Hyperglycaemia and oxidative stress are known to acutely cause endothelial dysfunction in vitro, but in the initial stages of diabetes, endothelium-dependent relaxation is preserved. The aim of this study was to investigate how endothelium-dependent relaxation is maintained in the early stages of type 1 diabetes. Diabetes was induced in Sprague-Dawley rats with a single injection of streptozotocin (48 mg/kg, i.v.), and after 6 weeks, endothelium-dependent and endothelium-independent relaxations were examined in the thoracic aorta in vitro. Lucigenin-enhanced chemiluminescence was used to measure superoxide generation from the aorta. Diabetes increased superoxide generation by the aorta (2,180 +/- 363 vs 986 +/- 163 AU/mg dry tissue weight)

Auctions for the support of renewable energy in the UK: updated results and lessons learnt

This is the final version. Available from AURES II via the link in this recordBackground to this study. This report serves to restate and update the findings of AURES report D4.1-UK published in March 2016 (Fitch-Roy and Woodman 2016)1 . While the fundamental design of the UK auctions system remains largely unchanged, substantial shifts in the policy context and the additional experience and data from two further auction processes (one completed, another in progress at the time of writing) warrant an updated evaluation and report. The UK has been a frontrunner in the use of RES auctions. From early experiences with the Non Fossil-Fuel Obligation (NFFO) auctions in the 1990s to the current auction system, first announced in 2011, the use of competitive allocation mechanisms has been central to the UK’s approach to supporting new renewable electricity generation projects. However, the use and design of renewable auctions remain a source of policy debate and discussion in the UK. For example, the potential for a combination of auction dynamics and the application of a cap on the volume of ‘fuelled’ renewable technologies led to higher than necessary support costs being awarded to some projects has been the subject of an enquiry by the national audit office (NAO 2018). This remainder of this report adopts the following structure: Section 2 provides an updated overview of the UK electricity sector Section 3 outlines the key features of the UK RES auction system, including recent rule changes Section 4 updates our earlier evaluation of the programme in light of recent auctions Section 5 concludesEuropean Commissio

Defining incumbency: considering the UK heat sector

This is the final version of the article. Available from UKERC via the link in this record.This is working paper 1/3 from the Heat, Incumbency and Transformations (HIT) project.Incumbency is frequently considered as a barrier to the transformation of unsustainable socio-technical systems such as energy systems. However, despite wide use of the term, ‘incumbency’ has never been fully or adequately defined within the sustainable transitions literature. This working paper considers the use and meaning of the term incumbency in relation to sustainable transformations, specifically in relation to the UK’s heat system. It takes ideas of incumbency from other disciplines including economics, politics and innovation. Synthesising these literatures, the paper proposes a number of characteristics of incumbency. Finally we propose a definition of incumbency in relation to sustainability transformations, which suggests that incumbents are actors already present in a specific socio-technical system, who are likely to be involved with unsustainable practices, and who possess the capacity to affect system change.UKERC is funded by The Research Councils UK Energy Programme

Inhibition of platelet mediated arterial thrombosis and platelet granule exocytosis by 3'4'-dihydroxyflavonol and quercetin

Flavonols are polyphenolic compounds with broad-spectrum kinase inhibitory, as well as potent anti-oxidant and anti-inflammatory properties. Anti-platelet potential of quercetin (Que) and several related flavonoids have been reported; however, few studies have assessed the ability of flavonols to inhibit exocytosis of different platelet granules or to inhibit thrombus formation in vivo. 3′,4′-Dihydroxyflavonol (DiOHF) is a flavonol which is structurally related to Que and has been shown to have greater anti-oxidant capacity and to improve the endothelial function in the context of diabetes and ischaemia/reperfusion injury. While the structural similarity to Que suggests DiOHF may have a potential to inhibit platelet function, no studies have assessed the anti-platelet potential of DiOHF. We therefore investigated platelet granule inhibition and potential to delay arterial thrombosis by Que and DiOHF. Both Que and DiOHF showed inhibition of collagen, adenosine diphosphate and arachidonic acid stimulated platelet aggregation, agonist-induced GPIIb/IIIa activation as demonstrated by PAC-1 and fibrinogen binding. While both flavonols inhibited agonist-induced granule exocytosis, greater inhibition of dense granule exocytosis occurred with DiOHF as measured by both ATP release and flow cytometry. In contrast, while Que inhibited agonist-induced P-selectin expression, as measured by both platelet surface P-selectin expression and upregulation of surface GPIIIa expression, inhibition by DiOHF was not significant for either parameter. C57BL/6 mice treated with 6 mg kg-1 IV Que or DiOHF maintained greater blood flow following FeCl3-induced carotid artery injury when compared to the vehicle control. We provide evidence that Que and DiOHF improve blood flow following arterial injury in part by attenuating platelet granule exocytosis

The flavonols quercetin and 3', 4'-dihydroxyflavonol reduce platelet function and delay thrombus formation in a model of type 1 diabetes.

Diabetes is associated with increased cardiovascular risk. We have recently shown that the naturally occurring flavonol quercetin (Que) or the synthetic flavonol 3,4-dihydroxyflavonol (DiOHF) inhibits platelet function and delays thrombus formation in healthy mice. Therefore, the aim of this study was to investigate the effect of Que or DiOHF treatment on platelet function and ferric chloride-induced carotid artery thrombosis in a mouse model of type 1 diabetes. Diabetic mice treated with Que or DiOHF maintained blood flow at a significantly higher level than untreated diabetic mice at the end of the recording period. In addition, treatment with Que or DiOHF significantly reduced diabetes-induced platelet hyper-aggregability in response to platelet agonist stimulation. Furthermore, treatment with Que or DiOHF significantly inhibited dense, but not alpha, granule exocytosis in diabetic and control mice. Our demonstration that flavonols delay thrombus formation in diabetes suggests a potential clinical role for these compounds in anti-platelet therapy

The future of renewable energy auctions: scenarios and pathways

This is the final version. Available from AURES II via the link in this recordEuropean Commissio

3',4'-Dihydroxyflavonol antioxidant attenuates aiastolic dysfunction and cardiac remodeling in streptozotocin-induced diabetic m(Ren2)27 rats

Background Diabetic cardiomyopathy (DCM) is an increasingly recognized cause of chronic heart failure amongst diabetic patients. Both increased reactive oxygen species (ROS) generation and impaired ROS scavenging have been implicated in the pathogenesis of hyperglycemia-induced left ventricular dysfunction, cardiac fibrosis, apoptosis and hypertrophy. We hypothesized that 3',4'-dihydroxyflavonol (DiOHF), a small highly lipid soluble synthetic flavonol, may prevent DCM by scavenging ROS, thus preventing ROS-induced cardiac damage. Methodology/Principal Findings Six week old homozygous Ren-2 rats were randomized to receive either streptozotocin or citrate buffer, then further randomized to receive either DiOHF (1 mg/kg/day) by oral gavage or vehicle for six weeks. Cardiac function was assessed via echocardiography and left ventricular cardiac catheterization before the animals were sacrificed and hearts removed for histological and molecular analyses. Diabetic Ren-2 rats showed evidence of diastolic dysfunction with prolonged deceleration time, reduced E/A ratio, and increased slope of end-diastolic pressure volume relationship (EDPVR) in association with marked interstitial fibrosis and oxidative stress (all P<0.05 vs control Ren-2). Treatment with DiOHF prevented the development of diastolic dysfunction and was associated with reduced oxidative stress and interstitial fibrosis (all P<0.05 vs untreated diabetic Ren-2 rats). In contrast, few changes were seen in non-diabetic treated animals compared to untreated counterparts. Conclusions Inhibition of ROS production and action by DiOHF improved diastolic function and reduced myocyte hypertrophy as well as collagen deposition. These findings suggest the potential clinical utility of antioxidative compounds such as flavonols in the prevention of diabetes-associated cardiac dysfunction

Environmental Hazard Analysis - a Variant of Preliminary Hazard Analysis for Autonomous Mobile Robots

© 2014, Springer Science+Business Media Dordrecht. Robot manufacturers will be required to demonstrate objectively that all reasonably foreseeable hazards have been identified in any robotic product design that is to be marketed commercially. This is problematic for autonomous mobile robots because conventional methods, which have been developed for automatic systems do not assist safety analysts in identifying non-mission interactions with environmental features that are not directly associated with the robot’s design mission, and which may comprise the majority of the required tasks of autonomous robots. In this paper we develop a new variant of preliminary hazard analysis that is explicitly aimed at identifying non-mission interactions by means of new sets of guidewords not normally found in existing variants. We develop the required features of the method and describe its application to several small trials conducted at Bristol Robotics Laboratory in the 2011–2012 period

Tocotrienol-rich tocomin attenuates oxidative stress and improves endothelium-dependent relaxation in aortae from rats fed a high-fat Western diet

We have previously reported that tocomin, a mixture high in tocotrienol content and also containing tocopherol, acutely preserves endothelial function in the presence of oxidative stress. In this study, we investigated whether tocomin treatment would preserve endothelial function in aortae isolated from rats fed a high-fat diet known to cause oxidative stress. Wistar hooded rats were fed a western diet (WD, 21% fat) or control rat chow (standard diet, 6% fat) for 12 weeks. Tocomin (40 mg/kg/day sc) or its vehicle (peanut oil) was administered for the last 4 weeks of the feeding regime. Aortae from WD rats showed an impairment of endothelium-dependent relaxation that was associated with an increased expression of the NADPH oxidase Nox2 subunit and an increase in the vascular generation of superoxide measured using L-012 chemiluminescence. The increase in vascular oxidative stress was accompanied by a decrease in basal NO release and impairment of the contribution of NO to ACh-induced relaxation. The impaired relaxation is likely contributed to by a decreased expression of eNOS, calmodulin, and phosphorylated Akt and an increase in caveolin. Tocotrienol rich tocomin, which prevented the diet-induced changes in vascular function, reduced vascular superoxide production and abolished the diet-induced changes in eNOS and other protein expression. Using selective inhibitors of nitric oxide synthase (NOS), soluble guanylate cyclase (sGC) and calcium-activated potassium (KCa) channels we demonstrated that tocomin increased NO-mediated relaxation, without affecting the contribution of endothelium-dependent hyperpolarization type relaxation to the endothelium-dependent relaxation. The beneficial actions of tocomin in this diet-induced model of obesity suggest that it may have potential to be used as a therapeutic agent to prevent vascular disease in obesity

33rd New England Intercollegiate Geological Conference: October 8, 9 and 10, 1937, New York City

Excursion A-2: A Geological Traverse from the Hudson River to Long Island Sound; Excursion B-3: Paleontological Trip to the New Jersey Coastal Plain; Excursion C-1: Progressive Metamorphism of the Hudson River Series; Excursion C-2: Glacial Geology of Long Island; Excursion C-3: Engineering Projects in New York City