3,220 research outputs found

    The Antonine Wall: the current state of knowledge

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    The Antonine Wall: the current state of knowledge

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    Lawrence Keppie: an appreciation

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    A comparison of reference-based algorithms for correcting cell-type heterogeneity in Epigenome-Wide Association Studies.

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    BACKGROUND: Intra-sample cellular heterogeneity presents numerous challenges to the identification of biomarkers in large Epigenome-Wide Association Studies (EWAS). While a number of reference-based deconvolution algorithms have emerged, their potential remains underexplored and a comparative evaluation of these algorithms beyond tissues such as blood is still lacking. RESULTS: Here we present a novel framework for reference-based inference, which leverages cell-type specific DNAse Hypersensitive Site (DHS) information from the NIH Epigenomics Roadmap to construct an improved reference DNA methylation database. We show that this leads to a marginal but statistically significant improvement of cell-count estimates in whole blood as well as in mixtures involving epithelial cell-types. Using this framework we compare a widely used state-of-the-art reference-based algorithm (called constrained projection) to two non-constrained approaches including CIBERSORT and a method based on robust partial correlations. We conclude that the widely-used constrained projection technique may not always be optimal. Instead, we find that the method based on robust partial correlations is generally more robust across a range of different tissue types and for realistic noise levels. We call the combined algorithm which uses DHS data and robust partial correlations for inference, EpiDISH (Epigenetic Dissection of Intra-Sample Heterogeneity). Finally, we demonstrate the added value of EpiDISH in an EWAS of smoking. CONCLUSIONS: Estimating cell-type fractions and subsequent inference in EWAS may benefit from the use of non-constrained reference-based cell-type deconvolution methods

    Tissue-independent and tissue-specific patterns of DNA methylation alteration in cancer

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    BACKGROUND: There is growing evidence that DNA methylation alterations contribute to carcinogenesis. While cancer tissue exhibits widespread DNA methylation changes, the proportion of tissue-specific versus tissue-independent DNA methylation alterations in cancer is unclear. In addition, it is unknown which factors determine the patterns of aberrant DNA methylation in cancer. RESULTS: Using HumanMethylation450 BeadChips (450k), we here analyze genome-wide DNA methylation patterns of ten types of fetal tissue, in addition to matched normal-cancer data for corresponding tissue types, encompassing over 3000 samples. We demonstrate that the level of aberrant cancer DNA methylation in gene promoters and gene bodies is highly correlated between cancer types. We estimate that up to 60 % of the DNA methylation variation in a cancer genome of a given tissue type is explained by the corresponding variation in a cancer genome of another type, implying that much of the cancer DNA methylation landscape is tissue independent. We further show that histone marks in normal cells are better predictors of aberrant cancer DNA methylation than the corresponding signals in human embryonic stem cells. We build predictors of cancer DNA methylation patterns and show that although inclusion of three histone marks (H3K4me3, H3K27me3 and H3K36me3) improves model accuracy, the bivalent marks are the most predictive. Finally, we show that chromatin accessibility of gene promoters in normal tissue dictates the promoter's propensity to acquire aberrant DNA methylation in cancer in so far as it determines its level of DNA methylation in normal tissue. CONCLUSIONS: Our data show that a considerable fraction of the aberrant cancer DNA methylation landscape results from a mechanism that is largely tissue specific. Histone marks as specified in the normal cell of origin provide highly predictive models of aberrant cancer DNA methylation and outperform those derived from the same marks in hESCs

    Magnon-photon coupling in the noncollinear magnetic insulator Cu 2 OSeO 3

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    Anticrossing behavior between magnons in the noncollinear chiral magnet Cu2OSeO3 and a two-mode X-band microwave resonator was studied in the temperature range 5–100 K. In the field-induced ferrimagnetic phase, we observed a strong-coupling regime between magnons and two microwave cavity modes with a cooperativity reaching 3600. In the conical phase, cavity modes are dispersively coupled to a fundamental helimagnon mode, and we demonstrate that the magnetic phase diagram of Cu2OSeO3 can be reconstructed from the measurements of the cavity resonance frequency. In the helical phase, a hybridized state of a higher-order helimagnon mode and a cavity mode—a helimagnon polariton—was found. Our results reveal a class of magnetic systems where strong coupling of microwave photons to nontrivial spin textures can be observed

    Gelatine backing affects the performance of single-layer ballistic-resistant materials against blast fragments

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    Penetrating trauma by energized fragments is the most common injury from explosive devices, the main threat in the contemporary battlefield. Such devices produce projectiles dependent upon their design, including preformed fragments, casings, glass, or stones; these are subsequently energized to high velocities and cause serious injuries to the body. Current body armor focuses on the essential coverage, which is mainly the thoracic and abdominal area, and can be heavy and cumbersome. In addition, there may be coverage gaps that can benefit from the additional protection provided by one or more layers of lightweight ballistic fabrics. This study assessed the performance of single layers of commercially available ballistic protective fabrics such as Kevlar®, Twaron®, and Dyneema®, in both woven and knitted configurations. Experiments were carried out using a custom-built gas-gun system, with a 0.78-g cylindrical steel fragment simulating projectile (FSP) as the impactor, and ballistic gelatine as the backing material. FSP velocity at 50% risk of material perforation, gelatine penetration, and high-risk wounding to soft tissue, as well as the depth of penetration (DoP) against impact velocity and the normalized energy absorption were used as metrics to rank the performance of the materials tested. Additional tests were performed to investigate the effect of not including a soft-tissue simulant backing material on the performance of the fabrics. The results show that a thin layer of ballistic material may offer meaningful protection against the penetration of this FSP. Additionally, it is essential to ensure a biofidelic boundary condition as the protective efficacy of fabrics was markedly altered by a gelatine backing

    The neutral silicon-vacancy center in diamond: spin polarization and lifetimes

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    We demonstrate optical spin polarization of the neutrally-charged silicon-vacancy defect in diamond (SiV0\mathrm{SiV^{0}}), an S=1S=1 defect which emits with a zero-phonon line at 946 nm. The spin polarization is found to be most efficient under resonant excitation, but non-zero at below-resonant energies. We measure an ensemble spin coherence time T2>100 μsT_2>100~\mathrm{\mu s} at low-temperature, and a spin relaxation limit of T1>25 sT_1>25~\mathrm{s}. Optical spin state initialization around 946 nm allows independent initialization of SiV0\mathrm{SiV^{0}} and NV−\mathrm{NV^{-}} within the same optically-addressed volume, and SiV0\mathrm{SiV^{0}} emits within the telecoms downconversion band to 1550 nm: when combined with its high Debye-Waller factor, our initial results suggest that SiV0\mathrm{SiV^{0}} is a promising candidate for a long-range quantum communication technology

    A systematic review of methods to predict weight trajectories in health economic models of behavioral weight management programs : the potential role of psychosocial factors

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    Objectives. There is limited evidence on the long-term effectiveness of behavioral weight management interventions, and thus, when conducting health economic modeling, assumptions are made about weight trajectories. The aims of this review were to examine these assumptions made about weight trajectories, the evidence sources used to justify them, and the impact of assumptions on estimated cost-effectiveness. Given the evidence that some psychosocial variables are associated with weight-loss trajectories, we also aimed to examine the extent to which psychosocial variables have been used to estimate weight trajectories and whether psychosocial variables were measured within cited evidence sources. Methods. A search of databases (Medline, PubMed, Cochrane, NHS Economic Evaluation, Embase, PSYCinfo, CINAHL, EconLit) was conducted using keywords related to overweight, weight management, and economic evaluation. Economic evaluations of weight management interventions that included modeling beyond trial data were included. Results. Within the 38 eligible articles, 6 types of assumptions were reported (weight loss maintained, weight loss regained immediately, linear weight regain, subgroup-specific trajectories, exponential decay of effect, maintenance followed by regain). Fifteen articles cited at least 1 evidence source to support the assumption reported. The assumption used affected the assessment of cost-effectiveness in 9 of the 19 studies that tested this in sensitivity analyses. None of the articles reported using psychosocial factors to estimate weight trajectories. However, psychosocial factors were measured in evidence sources cited by 11 health economic models. Conclusions. Given the range of weight trajectories reported and the potential impact on funding decisions, further research is warranted to investigate how psychosocial variables measured in trials can be used within health economic models to simulate heterogeneous weight trajectories and potentially improve the accuracy of cost-effectiveness estimates
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