75 research outputs found

    Simulation and the Fourth Industrial Revolution

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    Advancements in systems simulation over the past decade have propelled simulationinto a new position as a decision-making tool in Industry 4.0 applications. This paperaddresses the specific benefits of simulation which can be utilized to enable greaterflexibility in decision making in the Industry 4.0 environment. It is stressed thatboth discrete event simulation (DES) and agent-based simulation (ABS) can be usedto represent complex interactions in a fully integrated set of virtual and physicalsystems

    Scotland Registry for Ankylosing Spondylitis (SIRAS) – Protocol

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    Funding SIRAS was funded by unrestricted grants from Pfizer and AbbVie. The project was reviewed by both companies, during the award process, for Scientific merit, to ensure that the design did not compromise patient safety, and to assess the global regulatory implications and any impact on regulatory strategy.Publisher PD

    Listening In on the Past: What Can Otolith δ18O Values Really Tell Us about the Environmental History of Fishes?

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    Oxygen isotope ratios from fish otoliths are used to discriminate marine stocks and reconstruct past climate, assuming that variations in otolith δ18O values closely reflect differences in temperature history of fish when accounting for salinity induced variability in water δ18O. To investigate this, we exploited the environmental and migratory data gathered from a decade using archival tags to study the behaviour of adult plaice (Pleuronectes platessa L.) in the North Sea. Based on the tag-derived monthly distributions of the fish and corresponding temperature and salinity estimates modelled across three consecutive years, we first predicted annual otolith δ18O values for three geographically discrete offshore sub-stocks, using three alternative plausible scenarios for otolith growth. Comparison of predicted vs. measured annual δ18O values demonstrated >96% correct prediction of sub-stock membership, irrespective of the otolith growth scenario. Pronounced inter-stock differences in δ18O values, notably in summer, provide a robust marker for reconstructing broad-scale plaice distribution in the North Sea. However, although largely congruent, measured and predicted annual δ18O values of did not fully match. Small, but consistent, offsets were also observed between individual high-resolution otolith δ18O values measured during tag recording time and corresponding δ18O predictions using concomitant tag-recorded temperatures and location-specific salinity estimates. The nature of the shifts differed among sub-stocks, suggesting specific vital effects linked to variation in physiological response to temperature. Therefore, although otolith δ18O in free-ranging fish largely reflects environmental temperature and salinity, we counsel prudence when interpreting otolith δ18O data for stock discrimination or temperature reconstruction until the mechanisms underpinning otolith δ18O signature acquisition, and associated variation, are clarified

    Intellectual enrichment and genetic modifiers of cognition and brain volume in Huntington's disease

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    An important step towards the development of treatments for cognitive impairment in ageing and neurodegenerative diseases is to identify genetic and environmental modifiers of cognitive function and understand the mechanism by which they exert an effect. In Huntington’s disease, the most common autosomal dominant dementia, a small number of studies have identified intellectual enrichment, i.e. a cognitively stimulating lifestyle and genetic polymorphisms as potential modifiers of cognitive function. The aim of our study was to further investigate the relationship and interaction between genetic factors and intellectual enrichment on cognitive function and brain atrophy in Huntington’s disease. For this purpose, we analysed data from Track-HD, a multi-centre longitudinal study in Huntington’s disease gene carriers and focused on the role of intellectual enrichment (estimated at baseline) and the genes FAN1, MSH3, BDNF, COMT and MAPT in predicting cognitive decline and brain atrophy. We found that carrying the 3a allele in the MSH3 gene had a positive effect on global cognitive function and brain atrophy in multiple cortical regions, such that 3a allele carriers had a slower rate of cognitive decline and atrophy compared with non-carriers, in agreement with its role in somatic instability. No other genetic predictor had a significant effect on cognitive function and the effect of MSH3 was independent of intellectual enrichment. Intellectual enrichment also had a positive effect on cognitive function; participants with higher intellectual enrichment, i.e. those who were better educated, had higher verbal intelligence and performed an occupation that was intellectually engaging, had better cognitive function overall, in agreement with previous studies in Huntington’s disease and other dementias. We also found that intellectual enrichment interacted with the BDNF gene, such that the positive effect of intellectual enrichment was greater in Met66 allele carriers than non-carriers. A similar relationship was also identified for changes in whole brain and caudate volume; the positive effect of intellectual enrichment was greater for Met66 allele carriers, rather than for non-carriers. In summary, our study provides additional evidence for the beneficial role of intellectual enrichment and carrying the 3a allele in MSH3 in cognitive function in Huntington’s disease and their effect on brain structure

    Quantitative analysis of a footwall‐scarp degradation complex and syn‐rift stratigraphic architecture, Exmouth Plateau, NW Shelf, offshore Australia

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    Interactions between footwall‐, hangingwall‐ and axial‐derived depositional systems make syn‐rift stratigraphic architecture difficult to predict, and preservation of net‐erosional source landscapes is limited. Distinguishing between deposits derived from fault‐scarp degradation (consequent systems) and those derived from long‐lived catchments beyond the fault block crest (antecedent systems) is also challenging, but important for hydrocarbon reservoir prospecting. We undertake geometric and volumetric analysis of a fault‐scarp degradation complex and adjacent hangingwall‐fill associated with the Thebe‐2 fault block on the Exmouth Plateau, NW Shelf, offshore Australia, using high resolution 3D seismic data. Vertical and headward erosion of the complex and fault throw are measured. Seismic‐stratigraphic and seismic facies mapping allow us to constrain the spatial and architectural variability of depositional systems in the hangingwall. Footwall‐derived systems interacted with hangingwall‐ and axial‐derived systems, through diversion around topography, interfingering or successive onlap. We calculate the volume of footwall‐sourced hangingwall fans (VHW) for nine quadrants along the fault block, and compare this to the volume of material eroded from the immediately up‐dip fault‐scarp (VFW). This analysis highlights areas of sediment bypass (VFW > VHW) and areas fed by sediment sources beyond the degraded fault scarp (VHW > VFW). Exposure of the border fault footwall and adjacent fault terraces produced small catchments located beyond the fault block crest that fed the hangingwall basin. One source persisted throughout the main syn‐rift episode, and its location coincided with: (a) an intra‐basin topographic high; (b) a local fault throw minimum; (c) increased vertical and headward erosion within the fault‐scarp degradation complex; and (d) sustained clinoform development in the immediate hangingwall. Our novel quantitative volumetric approach to identify through‐going sediment input points could be applied to other rift basin‐fills. We highlight implications for hydrocarbon exploration and emphasize the need to incorporate interaction of multiple sediment sources and their resultant architecture in tectono‐stratigraphic models for rift basins

    Population differentiation of Southern Indian male lineages correlates with agricultural expansions predating the caste system

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    Christina J. Adler, Alan Cooper, Clio S.I. Der Sarkissian and Wolfgang Haak are contributors to the Genographic ConsortiumPrevious studies that pooled Indian populations from a wide variety of geographical locations, have obtained contradictory conclusions about the processes of the establishment of the Varna caste system and its genetic impact on the origins and demographic histories of Indian populations. To further investigate these questions we took advantage that both Y chromosome and caste designation are paternally inherited, and genotyped 1,680 Y chromosomes representing 12 tribal and 19 non-tribal (caste) endogamous populations from the predominantly Dravidian-speaking Tamil Nadu state in the southernmost part of India. Tribes and castes were both characterized by an overwhelming proportion of putatively Indian autochthonous Y-chromosomal haplogroups (H-M69, F-M89, R1a1-M17, L1-M27, R2-M124, and C5-M356; 81% combined) with a shared genetic heritage dating back to the late Pleistocene (10–30 Kya), suggesting that more recent Holocene migrations from western Eurasia contributed, <20% of the male lineages. We found strong evidence for genetic structure, associated primarily with the current mode of subsistence. Coalescence analysis suggested that the social stratification was established 4–6 Kya and there was little admixture during the last 3 Kya, implying a minimal genetic impact of the Varna(caste) system from the historically-documented Brahmin migrations into the area. In contrast, the overall Y-chromosomal patterns, the time depth of population diversifications and the period of differentiation were best explained by the emergence of agricultural technology in South Asia. These results highlight the utility of detailed local genetic studies within India, without prior assumptions about the importance of Varna rank status for population grouping, to obtain new insights into the relative influences of past demographic events for the population structure of the whole of modern India.GaneshPrasad ArunKumar, David F. Soria-Hernanz, Valampuri John Kavitha, Varatharajan Santhakumari Arun, Adhikarla Syama, Kumaran Samy Ashokan, Kavandanpatti Thangaraj Gandhirajan, Koothapuli Vijayakumar, Muthuswamy Narayanan, Mariakuttikan Jayalakshmi, Janet S. Ziegle, Ajay K. Royyuru, Laxmi Parida, R. Spencer Wells, Colin Renfrew, Theodore G. Schurr, Chris Tyler Smith, Daniel E. Platt, Ramasamy Pitchappan, The Genographic Consortiu
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