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

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

Survey of Sensor Technology for Aircraft Cabin Environment Sensing

The aircraft cabin environment is unique due to the proximity of the passengers, the need for cabin pressurization, and the low humidity. All of these aspects are complicated by the fact that the aircraft is a semi-enclosed structure. There is an increased desire to monitor the aircraft cabin environment with various sensors for comfort and safety. However, the aircraft cabin environment is composed of a large number of factors. Some of these factors can include air quality, temperature, level of pressurization, and motion of the aircraft. Therefore, many types of sensors must be used to monitor aircraft environments. A variety of technology options are often available for each sensor. Consequently, a fair number of tradeoffs need to be carefully considered when designing a sensor monitoring system for the aircraft cabin environment. For instance, a system designer may need to decide if the increased accuracy of a sensor using a particular technology is worth the increased power consumption over a similar sensor employing a more efficient, less accurate technology. In order to achieve a good solution, a designer needs to understand the tradeoffs and general operation for all of the different sensor technologies that could be used in the design. The purpose of this paper is to provide a survey of the current sensor technology. The primary focus of this paper is on sensors and technologies that cover the most common aspects of aircraft cabin environment monitoring. The first half of this paper details the basic operation of different sensor technologies. The second half covers the individual environmental conditions which need to be sensed. This will include the benefits, limitations, and applications of the different technologies available for each particular type of sensor

Angiotensin II causes b-cell dysfunction through an ER stress-induced proinflammatory response

The metabolic syndrome is associated with an increase in the activation of the renin angiotensin system, whose inhibition reduces the incidence of new-onset diabetes. Importantly, angiotensin II (AngII), independently of its vasoconstrictor action, causes b-cell inflammation and dysfunction, which may be an early step in the development of type 2 diabetes. The aim of this study was to determine how AngII causes b-cell dysfunction. Islets of Langerhans were isolated from C57BL/6J mice that had been infused with AngII in the presence or absence of taurineconjugated ursodeoxycholic acid (TUDCA) and effects on endoplasmic reticulum (ER) stress, inflammation, and b-cell function determined. The mechanism of action of AngII was further investigated using isolated murine islets and clonal b cells. We show that AngII triggers ER stress, an increase in the messenger RNA expression of proinflammatory cytokines, and promotes b-cell dysfunction in murine islets of Langerhans both in vivo and ex vivo. These effects were significantly attenuated by TUDCA, an inhibitor of ER stress. We also show that AngII-induced ER stress is required for the increased expression of proinflammatory cytokines and is caused by reactive oxygen species and IP3 receptor activation. These data reveal that the induction of ER stress is critical for AngII-induced b-cell dysfunction and indicates how therapies that promote ER homeostasis may be beneficial in the prevention of type 2 diabetes. © 2017 Endocrine Society

An investigation into minichromosomal maintenance proteins (MCMs) for the diagnosis of prostate cancer, as a possible alternative to prostate specific antigen (PSA)

The current strategy for the diagnosis of prostate cancer includes serum prostate specific antigen (PSA) measurement. There is however debate into its specificity and sensitivity, so new diagnostic markers are under investigation. Minichromosomal maintenance proteins (MCMs) are potential markers for the diagnosis of neoplasia, as they are involved in cellular replication. The aim of this study is to assess MCM2, 5 and 7 as new diagnostic markers for prostate cancer, to compare the clinical usefulness of PSA and to develop a less invasive technique for diagnosis. PSA specificity was investigated in several human cellular lines, and a clinical study was performed to assess expression in prostatic tissue and blood serum. MCM2, 5 and 7 was investigated by translational and transcriptional means in two prostate cell lines PNT1A and PC-3. In addition, a clinical study was performed to assess the expression of MCM2, 5 and 7 in prostate tissue, urine and blood The results suggest that PSA is not prostate specific, as it is synthesised and secreted by several non-prostatic cell lines. In addition PSA testing does not conclusively indicate neoplastic tissue and serum testing only has 63% sensitivity and 60% specificity in accurately identifying prostate cancer. The in vitro results suggest that the PC-3 cells express less MCM2, 5 and 7 on both the protein and mRNA level compared to the PNT1A cells, suggesting that MCM2, 5 and 7 maybe performing a bigger role than just replication of DNA. The tissue results indicate that there is an increase in MCM2, 5 and 7 epithelial nuclei staining for neoplastic condition compared to BPH. While the clinical study on urine sediment indicates increased MCM2, 5 and 7 staining in prostatic neoplasia compared to BPH and the transcriptional study on MCM5 can identify neoplastic tissue from BPH as 11/12 cancerous patients expressed MCM5 compared to only 3/23 BPH patients. Finally the transcriptional study on the blood samples is inconclusive and need to be repeated These results suggest that serum PSA testing is not ideal for the diagnosis of prostate cancer, that MCM2, 5 and 7 appear to have potential as new diagnostic markers and may aid the histopathologist to allocate Gleason score. Also the MCMs may have potential in the development of a less invasive technique through the use of urine sediment.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

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

Coronary artery endothelial dysfunction is positively correlated with low density lipoprotein and inversely correlated with high density lipoprotein subclass particles measured by nuclear magnetic resonance spectroscopy.

OBJECTIVE: The association between cholesterol and endothelial dysfunction remains controversial. We tested the hypothesis that lipoprotein subclasses are associated with coronary endothelial dysfunction. METHODS AND RESULTS: Coronary endothelial function was assessed in 490 patients between November 1993 and February 2007. Fasting lipids and nuclear magnetic resonance (NMR) lipoprotein particle subclasses were measured. There were 325 females and 165 males with a mean age of 49.8+/-11.6 years. Coronary endothelial dysfunction (epicardial constriction>20% or increase in coronary blood flow<50% in response to intracoronary acetylcholine) was diagnosed in 273 patients, the majority of whom (64.5%) had microvascular dysfunction. Total cholesterol and LDL-C (low density lipoprotein cholesterol) were not associated with endothelial dysfunction. One-way analysis and multivariate methods adjusting for age, gender, diabetes, hypertension and lipid-lowering agent use were used to determine the correlation between lipoprotein subclasses and coronary endothelial dysfunction. Epicardial endothelial dysfunction was significantly correlated with total (p=0.03) and small LDLp (LDL particles) (p<0.01) and inversely correlated with total and large HDLp (high density lipoprotein particles) (p<0.01). CONCLUSIONS: Epicardial, but not microvascular, coronary endothelial dysfunction was associated directly with LDL particles and inversely with HDL particles, suggesting location-dependent impact of lipoprotein particles on the coronary circulation

The centre cannot (always) hold : examining pathways towards energy system de-centralisation

‘Energy decentralisation’ means many things to many people. Among the confusion of definitions and practices that may be characterised as decentralisation, three broad causal narratives are commonly (implicitly or explicitly) invoked. These narratives imply that the process of decentralisation: i) will result in appropriate changes to rules and institutions, ii) will be more democratic and iii) is directly and causally linked to energy system decarbonisation. The principal aim of this paper is to critically examine these narratives. By conceptualising energy decentralisation as a distinct class of socio-technical transition pathway, we present a comparative analysis of energy decentralisation in Cornwall, South West UK, the French island of Ushant and the National Electricity Market in Australia. We show that, while energy decentralisation is often strongly correlated with institutional change, increasing citizen agency in the energy system, and enhanced environmental performance, these trends cannot be assumed as given. Indeed, some decentralisation pathways may entrench incumbent actors' interests or block rapid decarbonisation. In particular, we show how institutional context is a key determinant of the link between energy decentralisation and normative goals such as democratisation and decarbonisation. While institutional theory suggests that changes in rules and institutions are often incremental and path-dependent, the dense legal and regulatory arrangements that develop around the electricity sector seem particularly resistant to adaptive change. Consequently, policymakers seeking to pursue normative goals such as democratisation or decarbonisation through energy decentralisation need to look beyond technology towards the rules, norms and laws that constitute the energy governance system