514 research outputs found

    The Child - A View Across the Tweed

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    The Child - A View Across the Twee

    Tipping elements and amplified polar warming during the Last Interglacial

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    Irreversible shifts of large-scale components of the Earth system (so-called ‘tipping elements’) on policy-relevant timescales are a major source of uncertainty for projecting the impacts of future climate change. The high latitudes are particularly vulnerable to positive feedbacks that amplify change through atmosphere-ocean-ice interactions. Unfortunately, the short instrumental record does not capture the full range of past or projected climate scenarios (a situation particularly acute in the high latitudes). Natural archives from past periods warmer than present day, however, can be used to explore drivers and responses to forcing, and provide data against which to test models, thereby offering insights into the future. The Last Interglacial (129–116,000 years before present) — the warmest interglacial of the last 800,000 years — was the most recent period during which global temperatures were comparable with low-end 21st Century projections (up to 2 °C warmer, with temperature increase amplified over polar latitudes), providing a potentially useful analogue for future change. Substantial environmental changes happened during this time. Here we synthesise the nature and timing of potential high-latitude tipping elements during the Last Interglacial, including sea ice, extent of the boreal forest, permafrost, ocean circulation, and ice sheets/sea level. We also review the thresholds and feedbacks that likely operated through this period. Notably, substantial ice mass loss from Greenland, the West Antarctic, and possibly sectors of the East Antarctic drove a 6–9 m rise in global sea level. This was accompanied by reduced summer sea-ice extent, poleward-extended boreal forest, and reduced areas of permafrost. Despite current chronological uncertainties, we find that tipping elements in the high latitudes all experienced rapid and abrupt change (within 1–2 millennia of each other) across both hemispheres, while recovery to prior conditions took place over multi-millennia. Our synthesis demonstrates important feedback loops between tipping elements, amplifying polar and global change during the Last Interglacial. The high sensitivity and tight interconnections between polar tipping elements suggests that they could exhibit similar thresholds of vulnerability in the future, particularly if the aspirations of the Paris Agreement are not met

    A System-Wide Investigation of the Dynamics of Wnt Signaling Reveals Novel Phases of Transcriptional Regulation

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    Aberrant Wnt signaling has been implicated in a wide variety of cancers and many components of the Wnt signaling network have now been identified. Much less is known, however, about how these proteins are coordinately regulated. Here, a broad, quantitative, and dynamic study of Wnt3a-mediated stimulation of HEK 293 cells revealed two phases of transcriptional regulation: an early phase in which signaling antagonists were downregulated, providing positive feedback, and a later phase in which many of these same antagonists were upregulated, attenuating signaling. The dynamic expression profiles of several response genes, including MYC and CTBP1, correlated significantly with proliferation and migration (P<0.05). Additionally, their levels tracked with the tumorigenicity of colon cancer cell lines and they were significantly overexpressed in colorectal adenocarcinomas (P<0.05). Our data highlight CtBP1 as a transcription factor that contributes to positive feedback during the early phases of Wnt signaling and serves as a novel marker for colorectal cancer progression

    Tracing Cattle Breeds with Principal Components Analysis Ancestry Informative SNPs

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    The recent release of the Bovine HapMap dataset represents the most detailed survey of bovine genetic diversity to date, providing an important resource for the design and development of livestock production. We studied this dataset, comprising more than 30,000 Single Nucleotide Polymorphisms (SNPs) for 19 breeds (13 taurine, three zebu, and three hybrid breeds), seeking to identify small panels of genetic markers that can be used to trace the breed of unknown cattle samples. Taking advantage of the power of Principal Components Analysis and algorithms that we have recently described for the selection of Ancestry Informative Markers from genomewide datasets, we present a decision-tree which can be used to accurately infer the origin of individual cattle. In doing so, we present a thorough examination of population genetic structure in modern bovine breeds. Performing extensive cross-validation experiments, we demonstrate that 250-500 carefully selected SNPs suffice in order to achieve close to 100% prediction accuracy of individual ancestry, when this particular set of 19 breeds is considered. Our methods, coupled with the dense genotypic data that is becoming increasingly available, have the potential to become a valuable tool and have considerable impact in worldwide livestock production. They can be used to inform the design of studies of the genetic basis of economically important traits in cattle, as well as breeding programs and efforts to conserve biodiversity. Furthermore, the SNPs that we have identified can provide a reliable solution for the traceability of breed-specific branded products

    The Main Belt Comets and ice in the Solar System

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    We review the evidence for buried ice in the asteroid belt; specifically the questions around the so-called Main Belt Comets (MBCs). We summarise the evidence for water throughout the Solar System, and describe the various methods for detecting it, including remote sensing from ultraviolet to radio wavelengths. We review progress in the first decade of study of MBCs, including observations, modelling of ice survival, and discussion on their origins. We then look at which methods will likely be most effective for further progress, including the key challenge of direct detection of (escaping) water in these bodies

    NMR-Based Prostate Cancer Metabolomics

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    Author's accepted version (postprint).This is an Accepted Manuscript of an article published by Springer in Methods in Molecular Biology on 22 May 2018.Available online: https://doi.org/10.1007/978-1-4939-7845-8_14acceptedVersio

    Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

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    Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty
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