GPCR structure, function, drug discovery and crystallography: report from Academia-Industry International Conference (UK Royal Society) Chicheley Hall, 1-2 September 2014

G-protein coupled receptors (GPCRs) are the targets of over half of all prescribed drugs today. The UniProt database has records for about 800 proteins classified as GPCRs, but drugs have only been developed against 50 of these. Thus, there is huge potential in terms of the number of targets for new therapies to be designed. Several breakthroughs in GPCRs biased pharmacology, structural biology, modelling and scoring have resulted in a resurgence of interest in GPCRs as drug targets. Therefore, an international conference, sponsored by the Royal Society, with world-renowned researchers from industry and academia was recently held to discuss recent progress and highlight key areas of future research needed to accelerate GPCR drug discovery. Several key points emerged. Firstly, structures for all three major classes of GPCRs have now been solved and there is increasing coverage across the GPCR phylogenetic tree. This is likely to be substantially enhanced with data from x-ray free electron sources as they move beyond proof of concept. Secondly, the concept of biased signalling or functional selectivity is likely to be prevalent in many GPCRs, and this presents exciting new opportunities for selectivity and the control of side effects, especially when combined with increasing data regarding allosteric modulation. Thirdly, there will almost certainly be some GPCRs that will remain difficult targets because they exhibit complex ligand dependencies and have many metastable states rendering them difficult to resolve by crystallographic methods. Subtle effects within the packing of the transmembrane helices are likely to mask and contribute to this aspect, which may play a role in species dependent behaviour. This is particularly important because it has ramifications for how we interpret pre-clinical data. In summary, collaborative efforts between industry and academia have delivered significant progress in terms of structure and understanding of GPCRs and will be essential for resolving problems associated with the more difficult targets in the future.

Material Waste in the Northern Ireland Construction Industry: On-Site Management Causes and Methods of Prevention

The construction industry in Northern Ireland is one of the major contributors of construction waste to landfill each year. The aim of this research paper is to identify the core on-site management causes of material waste on construction sites in Northern Ireland and to illustrate various methods of prevention which can be adopted. The research begins with a detailed literature review and is complemented with the conduction of semi-structured interviews with 6 professionals who are experienced and active within the Northern Ireland construction industry. Following on from the literature review and interviews analysis, a questionnaire survey is developed to obtain further information in relation to the subject area. The questionnaire is based on the key findings of the previous stages to direct the research towards the most influential factors. The analysis of the survey responses reveals that the core causes of waste generation include a rushed program, poor handling and on-site damage of materials, while the principal methods of prevention emerge as the adequate storage, the reuse of material on-site and efficient material ordering. Furthermore, the role of the professional background in the shaping of perceptions relevant to waste management is also investigated and significant differences are identified. The findings of this research are beneficial for the industry as they enhance the understanding of construction waste generation causes and highlight the practices required to reduce waste on-site in the context of sustainable development.

Reducing SCADA System Nuisance Alarms in the Water Industry in Northern Ireland

The advancement of telemetry control for the water industry has increased the difficulty of 14 managing large volumes of nuisance alarms (i.e. alarms that do not require a response). The aim 15 of this study was to identify and reduce the number of nuisance alarms that occur for Northern 16 Ireland (NI) Water by carrying-out alarm duration analysis to determine the appropriate length of 17 persistence (an advanced alarm management tool) that could be applied. All data was extracted 18 from TelemWeb (NI Water’s telemetry monitoring system) and analysed in Excel. Over a 6 19 week period, an average of 40,000 alarms occurred per week. The alarm duration analysis, which 20 has never been implemented before by NI Water, found that an average of 57% of NI Water 21 alarms had a duration of <5 minutes. Applying 5 minute persistence; therefore, could prevent an 22 average 26,816 nuisance alarms per week. Most of these alarms were from wastewater assets.

Environmental Operations Management and its links with Proactivity and Performance: A study of the UK Food Industry

Two important strands of research within the literature on Environmental Operations Management (EOM) relate to environmental approach and performance. Often in this research the links between environmental approach, environmental performance and EOM are considered separately with little consideration given to the interrelationships between them. This study develops and tests a theoretical framework that combines these two strands to explore how UK food manufacturers approach EOM. The framework considers the relationships between an environmentally pro-active strategic orientation, EOM and environmental and cost performance. A cross-sectional survey was developed to collect data from a sample of 1200 food manufacturing firms located within the UK. Responses were sought from production and operations managers who are knowledgeable about the environmental operations practices within their firms. A total of 149 complete and useable responses were obtained. The reliability and validity of the scales used in the survey were tested using exploratory factor analysis, prior to the testing of the hypotheses underpinning the theoretical framework using hierarchical regression analysis. Our results generate support for a link between environmental proactivity, environmental practices and performance, consistent with the natural resource-based view (NRBV) and a number of studies in the extant literature. In considering environmental proactivity as a standalone concept that influences the implementation of environmental practices outlined in the NRBV, our study generates some novel insights into these links. Further our results provide some interesting insights for managers within the food industry who can identify the potential benefits of certain practices for performance within this unique context.