Nutritional Manipulation of One-Carbon Metabolism: Effects on Arsenic Methylation and Toxicity

Exposure to arsenic (As) through drinking water is a substantial problem worldwide. The methylation of As, a reactive metalloid, generates monomethyl- (MMA) and dimethyl-arsenical (DMA) species. The biochemical pathway that catalyzes these reactions, one-carbon metabolism, is regulated by folate and other micronutrients. Arsenic methylation exerts a critical influence on both its urinary elimination and chemical reactivity. Mice having the As methyltransferase null genotype show reduced urinary As excretion, increased As retention, and severe systemic toxicity. The most toxic As metabolite in vitro is MMAIII, an intermediate in the generation of DMAV, a much less toxic metabolite. These findings have raised the question of whether As methylation is a detoxification or bioactivation pathway. Results of population-based studies suggest that complete methylation of inorganic As to DMA is associated with reduced risk for As-induced health outcomes, and that nutrients involved in one-carbon metabolism, such as folate, can facilitate As methylation and elimination

94 GHz Beam Scanning Dual-Reflector Antenna with a Sub-Reflectarray

A Cassegrain dual-reflector antenna which employs a flat reflectarray subreflector was analysed in a recent paper [1]. It was shown that the antenna beam can be scanned by introducing an appropriate progressive phase distribution across the reflectarray surface. This configuration is very attractive for steerable beam applications, because it combines the high gain and broad bandwidth properties of the parabolic main reflector with the simplicity of manufacturing a small electronically reconfigurable microstrip reflectarray antenna. The subreflector could be constructed on a thin liquid crystal (LC) substrate, and control of the phase distribution across the aperture would be achieved by applying a bias voltage to the individual elements in the patch array [2, 3]. In addition to the simplicity of this biasing arrangement, phase shifters based on LC materials can be designed to operate with no upper limit on the operating frequency range, thereby removing the main disadvantage of many existing active control technologies. Moreover precision micromachining processes and a quasi–optical measurement technique which are suitable for manufacturing and characterising sub mm wavelength phase agile reflectarrays, have recently been demonstrated at frequencies up to 170 GHz [4]. In this paper we present the design of a dual-reflector antenna which could use an ‘active’ sub-reflectarray based on liquid crystals to produce the required Earth scene scan profile of a limbsounder radiometric instrument [5]. The validity of the beam scanning concept has been demonstrated by designing, manufacturing and measuring the radiation patterns of a 120mm diameter offset parabolic reflector at 94 GHz. In the first phase of the project we have used three planar solid metal subreflectors of diameter 28-mm to generate a focussed beam in the boresight direction, and at offset scan angles of 2.5° and 5°. Experimental results are shown to be in reasonably good agreement with numerical simulations. In the second phase of the work, the solid metal subreflectors are replaced by a passive microstrip patch subreflectarray which is designed to scan the beam to an angle of 5º. The final stage of the project will employ an electronically controllable LC reflectarray subreflector which will be used to scan the beam over the angular range 0 º to 5º

The Conservatives and the Union: The 'New English Toryism' and the Origins of Anglo-Britishness

The Union has for over a century been one of the cornerstones of Conservative politics, but with the changes to the old union state in the last 20 years, its value has been increasingly questioned. While the Conservative Party remains committed to maintaining the Union, a new English Toryism is emerging, which has a strong continuity with an older English Toryism which was partially buried by the ascendancy of Unionism. English Tories have always considered the Union to be desirable, but it comes second in their thinking to the need to protect the sovereignty of the British state, the core of which is England and its traditional institutions. What is new about the contemporary Conservative Party is that there is within it the revival of an English Toryism which is happy to discard the older clothes of Empire and Union once so important to Conservative identity and which is unabashedly English in its focus. For an increasing number of contemporary Conservatives, there no longer seems to be any passion about defending the Union or even of continuing to think about the United Kingdom in Unionist terms

Arctic air pollution: Challenges and opportunities for the next decade

The Arctic is a sentinel of global change. This region is influenced by multiple physical and socio-economic drivers and feedbacks, impacting both the natural and human environment. Air pollution is one such driver that impacts Arctic climate change, ecosystems and health but significant uncertainties still surround quantification of these effects. Arctic air pollution includes harmful trace gases (e.g. tropospheric ozone) and particles (e.g. black carbon, sulphate) and toxic substances (e.g. polycyclic aromatic hydrocarbons) that can be transported to the Arctic from emission sources located far outside the region, or emitted within the Arctic from activities including shipping, power production, and other industrial activities. This paper qualitatively summarizes the complex science issues motivating the creation of a new international initiative, PACES (air Pollution in the Arctic: Climate, Environment and Societies). Approaches for coordinated, international and interdisciplinary research on this topic are described with the goal to improve predictive capability via new understanding about sources, processes, feedbacks and impacts of Arctic air pollution. Overarching research actions are outlined, in which we describe our recommendations for 1) the development of trans-disciplinary approaches combining social and economic research with investigation of the chemical and physical aspects of Arctic air pollution; 2) increasing the quality and quantity of observations in the Arctic using long-term monitoring and intensive field studies, both at the surface and throughout the troposphere; and 3) developing improved predictive capability across a range of spatial and temporal scales

A study protocol of qualitative data sharing practices in clinical trials in the UK and Ireland: towards the production of good practice guidance [version 2; peer review: 2 approved]

BACKGROUND: Data sharing enables researchers to conduct novel research with previously collected data sets, thus maximising scientific findings and cost effectiveness, and reducing research waste. The value of sharing anonymised data from clinical trials is well recognised with a moderated access approach recommended. While substantial challenges to data sharing remain, there are additional challenges for qualitative data. Qualitative data including videos, interviews, and observations are often more readily identifiable than quantitative data. Existing guidance from UK Economic and Social Research Council applies to sharing qualitative data but does not address the additional challenges related to sharing qualitative data collected within trials, including the need to incorporate the necessary information and consent into already complex recruitment processes, with the additional sensitive nature of health-related data. METHODS: Work package 1 will involve separate focus group interviews with members of each stakeholder group: trial managers, clinical trialists, qualitative researchers, members of research funding bodies and trial participants who have been involved in qualitative research. Data will be analysed using thematic analysis and managed within QSR NVivo to enhance transparency. Work package 2 will involve a documentary analysis of current consent procedures for qualitative data collected as part of the conduct of clinical trials. We will include documents such as participant information leaflets and consent forms for the qualitative components in trials. We will extract data such as whether specific clauses for data sharing are included in the consent form. Content analysis will be used to analyse whether and how consent is being obtained for qualitative data sharing. CONCLUSIONS: This study will provide insight into the existing practice of sharing of qualitative data in clinical trials and the current issues and opportunities, to help shape future research and development of guidance to encourage maximum learning to be gained from this valuable dat

The ZEPLIN-III dark matter detector: instrument design, manufacture and commissioning

We present details of the technical design and manufacture of the ZEPLIN-III dark matter experiment. ZEPLIN-III is a two-phase xenon detector which measures both the scintillation light and the ionisation charge generated in the liquid by interacting particles and radiation. The instrument design is driven by both the physics requirements and by the technology requirements surrounding the use of liquid xenon. These include considerations of key performance parameters, such as the efficiency of scintillation light collection, restrictions placed on the use of materials to control the inherent radioactivity levels, attainment of high vacuum levels and chemical contamination control. The successful solution has involved a number of novel design and manufacturing features which will be of specific use to future generations of direct dark matter search experiments as they struggle with similar and progressively more demanding requirements.Comment: 25 pages, 19 figures. Submitted to Astropart. Phys. Some figures down sampled to reduce siz

Advancements in cortisol detection: from conventional methods to next-generation technologies for enhanced hormone monitoring.

The hormone cortisol, released as the end-product of the hypothalamic-pituitary-adrenal (HPA) axis, has a wellcharacterized circadian rhythm that enables an allostatic response to external stressors. When the pattern of secretion is disrupted, cortisol levels are chronically elevated, contributing to diseases such as heart attacks, strokes, mental health disorders, and diabetes. The diagnosis of chronic stress and stress related disorders depends upon accurate measurement of cortisol levels; currently, it is quantified using mass spectroscopy or immunoassay, in specialized laboratories with trained personnel. However, these methods are time-consuming, expensive and are unable to capture the dynamic biorhythm of the hormone. This critical review traces the path of cortisol detection from traditional laboratory-based methods to decentralised cortisol monitoring biosensors. A complete picture of cortisol biology and pathophysiology is provided, and the importance of precision medicine style monitoring of cortisol is highlighted. Antibody-based immunoassays still dominate the pipeline of development of point-of-care biosensors; new capture molecules such as aptamers and molecularly imprinted polymers (MIPs) combined with technologies such as microfluidics, wearable electronics, and quantum dots offer improvements to limit of detection (LoD), specificity, and a shift toward rapid or continuous measurements. While a variety of different sensors and devices have been proposed, there still exists a need to produce quantitative tests for cortisol - using either rapid or continuous monitoring devices that can enable a personalized medicine approach to stress management. This can be addressed by synergistic combinations of technologies that can leverage low sample volumes, relevant limit of detection and rapid testing time, to better account for cortisol’s shifting biorhythm. Trends in cortisol diagnostics toward rapid and continuous monitoring of hormones are highlighted, along with insights into choice of sample matrix