156 research outputs found

    From tacit knowledge to visual expertise: Eye-tracking support in maritime education and training

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    The maritime pilot is an expert with knowledge on a specific navi- gational route. The maritime pilot cadet undergoes maritime education and training in classrooms, onboard vessels and in simulators. Developing visual expertise is a basic objective. Transferring knowledge from experienced mar- itime pilots to maritime pilot cadets is challenging since some of this knowledge is tacit. The transference is achieved by externalization and socialization pro- cesses. The objective of this pre-study was to assess eye-tracking methodology as a tool to support maritime education and training, and for transferring tacit knowledge. The study was performed in an explorative way during simulator sessions, by interviews, questionnaires and observations. The result shows that eye-tracking methodology is useful for transferring tacit knowledge in simulator settings, but not during other parts of the education and training. The results also show that situational awareness of maritime pilot instructors and maritime pilot cadets increases when utilizing eye-tracking methodology

    Defending the genome from the enemy within:mechanisms of retrotransposon suppression in the mouse germline

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    The viability of any species requires that the genome is kept stable as it is transmitted from generation to generation by the germ cells. One of the challenges to transgenerational genome stability is the potential mutagenic activity of transposable genetic elements, particularly retrotransposons. There are many different types of retrotransposon in mammalian genomes, and these target different points in germline development to amplify and integrate into new genomic locations. Germ cells, and their pluripotent developmental precursors, have evolved a variety of genome defence mechanisms that suppress retrotransposon activity and maintain genome stability across the generations. Here, we review recent advances in understanding how retrotransposon activity is suppressed in the mammalian germline, how genes involved in germline genome defence mechanisms are regulated, and the consequences of mutating these genome defence genes for the developing germline

    Mutational signatures in esophageal adenocarcinoma define etiologically distinct subgroups with therapeutic relevance

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    Esophageal adenocarcinoma (EAC) has a poor outcome, and targeted therapy trials have thus far been disappointing owing to a lack of robust stratification methods. Whole-genome sequencing (WGS) analysis of 129 cases demonstrated that this is a heterogeneous cancer dominated by copy number alterations with frequent large-scale rearrangements. Co-amplification of receptor tyrosine kinases (RTKs) and/or downstream mitogenic activation is almost ubiquitous; thus tailored combination RTK inhibitor (RTKi) therapy might be required, as we demonstrate in vitro. However, mutational signatures showed three distinct molecular subtypes with potential therapeutic relevance, which we verified in an independent cohort (n = 87): (i) enrichment for BRCA signature with prevalent defects in the homologous recombination pathway; (ii) dominant T>G mutational pattern associated with a high mutational load and neoantigen burden; and (iii) C>A/T mutational pattern with evidence of an aging imprint. These subtypes could be ascertained using a clinically applicable sequencing strategy (low coverage) as a basis for therapy selection

    Authentication and characterisation of a new oesophageal adenocarcinoma cell line: MFD-1.

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    New biological tools are required to understand the functional significance of genetic events revealed by whole genome sequencing (WGS) studies in oesophageal adenocarcinoma (OAC). The MFD-1 cell line was isolated from a 55-year-old male with OAC without recombinant-DNA transformation. Somatic genetic variations from MFD-1, tumour, normal oesophagus, and leucocytes were analysed with SNP6. WGS was performed in tumour and leucocytes. RNAseq was performed in MFD-1, and two classic OAC cell lines FLO1 and OE33. Transposase-accessible chromatin sequencing (ATAC-seq) was performed in MFD-1, OE33, and non-neoplastic HET1A cells. Functional studies were performed. MFD-1 had a high SNP genotype concordance with matched germline/tumour. Parental tumour and MFD-1 carried four somatically acquired mutations in three recurrent mutated genes in OAC: TP53, ABCB1 and SEMA5A, not present in FLO-1 or OE33. MFD-1 displayed high expression of epithelial and glandular markers and a unique fingerprint of open chromatin. MFD-1 was tumorigenic in SCID mouse and proliferative and invasive in 3D cultures. The clinical utility of whole genome sequencing projects will be delivered using accurate model systems to develop molecular-phenotype therapeutics. We have described the first such system to arise from the oesophageal International Cancer Genome Consortium project.Cancer Research UK, Medical Research CouncilThis is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/srep3241

    Are homeowners willing to adapt to and mitigate the effects of climate change?

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    The need to adapt to climate change impacts, whilst simultaneously limiting greenhouse gas emissions, requires that the government’s efforts are joined by public action. In England and Wales, housing contributes significantly to the emissions and many properties are at risk of flooding. This paper investigates the preparedness of homeowners in England and Wales to make changes to their homes in response to the predicted effects of climate change. A telephone survey of 961 homeowners investigated their interest in purchasing mitigation and adaptation improvements against their concern about climate change, awareness of flood risk and attribution of responsibility for action. Whilst the majority of homes had some energy-saving improvements, few were found to have property-level flood protection. The high levels of awareness about climate change and flooding were coupled with the perception of risks as low. Whilst some respondents accepted personal responsibility for action, most believed that the authorities were responsible for flood protection, and would not pay the costs required to make their home more energy-efficient and better prepared for the eventuality of floods. The results suggest that there is scope for further improvement of energy-saving measures, and that the levels of adoption of flood-protection measures are very low. Multi-faceted strategies, including more effective communication of risks and responsibilities, incentives, and material support for the poorest, will need to be developed to overcome the current reluctance by homeowners to invest in flood-protection measures and further energy conservation solutions in the futur

    Bioinorganic Chemistry of Alzheimer’s Disease

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    The Atacama Cosmology Telescope: A Catalog of >4000 Sunyaev–Zel’dovich Galaxy Clusters

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    We present a catalog of 4195 optically confirmed Sunyaev–Zel'dovich (SZ) selected galaxy clusters detected with signal-to-noise ratio >4 in 13,211 deg2 of sky surveyed by the Atacama Cosmology Telescope (ACT). Cluster candidates were selected by applying a multifrequency matched filter to 98 and 150 GHz maps constructed from ACT observations obtained from 2008 to 2018 and confirmed using deep, wide-area optical surveys. The clusters span the redshift range 0.04 1 clusters, and a total of 868 systems are new discoveries. Assuming an SZ signal versus mass-scaling relation calibrated from X-ray observations, the sample has a 90% completeness mass limit of M500c > 3.8 × 1014 M⊙, evaluated at z = 0.5, for clusters detected at signal-to-noise ratio >5 in maps filtered at an angular scale of 2farcm4. The survey has a large overlap with deep optical weak-lensing surveys that are being used to calibrate the SZ signal mass-scaling relation, such as the Dark Energy Survey (4566 deg2), the Hyper Suprime-Cam Subaru Strategic Program (469 deg2), and the Kilo Degree Survey (825 deg2). We highlight some noteworthy objects in the sample, including potentially projected systems, clusters with strong lensing features, clusters with active central galaxies or star formation, and systems of multiple clusters that may be physically associated. The cluster catalog will be a useful resource for future cosmological analyses and studying the evolution of the intracluster medium and galaxies in massive clusters over the past 10 Gyr

    Pregnancy-related pelvic girdle pain: an update

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    A large number of scientists from a wide range of medical and surgical disciplines have reported on the existence and characteristics of the clinical syndrome of pelvic girdle pain during or after pregnancy. This syndrome refers to a musculoskeletal type of persistent pain localised at the anterior and/or posterior aspect of the pelvic ring. The pain may radiate across the hip joint and the thigh bones. The symptoms may begin either during the first trimester of pregnancy, at labour or even during the postpartum period. The physiological processes characterising this clinical entity remain obscure. In this review, the definition and epidemiology, as well as a proposed diagnostic algorithm and treatment options, are presented. Ongoing research is desirable to establish clear management strategies that are based on the pathophysiologic mechanisms responsible for the escalation of the syndrome's symptoms to a fraction of the population of pregnant women
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