407 research outputs found

    Sensitivity of Vertebrate Embryos to Heavy Metals as a Criterion of Water Quality, Phase I

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    Avian, amphibian and fish embryos were given continuous treatment with inorganic mercury, methyl mercury, cadmium and lead, to determine the sensitivity of embryogenesis to metallic poisoning. All metals produced substantial degrees of lethality and/or gross anatomical anomalies at 10 ppb or less. Treatment with inorganic mercury at 10 ppb produced 100% kill of frog embryos. Chick and rainbow trout embryos suffered 10-20% lethality when exposed to 1 ppb of either inorganic or methyl mercury. Lead and cadmium at 1 ppb produced 24-32% lethality in chick embryos. No significant differences were observed in the embryopathic effects of inorganic or methyl mercury. Concerning the toxic effects of mercury, cadmium and lead, the embryonic stage appears to constitute the critical sensitive link in the vertebrate life cycle. The reproductive potential of vertebrate populations may be severely restricted (e.g., embryonic mortality) by such pollutants at trace levels which may not prove hazardous to adult animals, and environmental standards based on tolerance levels for adult animals may not provide adequate protection for sensitive developmental stages

    Negative selection of chronic lymphocytic leukaemia cells using a bifunctional rosette-based antibody cocktail

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    <p>Abstract</p> <p>Background</p> <p>High purity of tumour samples is a necessity for accurate genetic and expression analysis and is usually achieved by positive selection in chronic lymphocytic leukaemia (CLL).</p> <p>Results</p> <p>We adapted a bifunctional rosette-based antibody cocktail for negative selection of B-cells for isolating CLL cells from peripheral blood (PB). PB samples from CLL patients were split into aliquots. One aliquot of each sample was enriched by density gradient centrifugation (DGC), while the other aliquot of each sample was incubated with an antibody cocktail for B-cell enrichment prior to DGC (RS+DGC). The purity of CLL cells after DGC averaged 74.1% (range: 15.9 – 97.4%). Using RS+DGC, the purity averaged 93.8% (range: 80.4 – 99.4%) with 23 of 29 (79%) samples showing CLL purities above 90%. RNA extracted from enriched CLL cells was of appropriately high quality for microarray analysis.</p> <p>Conclusion</p> <p>This study confirms the use of a bifunctional rosette-based antibody cocktail as an effective method for the purification of CLL cells from peripheral blood.</p

    Green engagement: An investigation into the relationship of Millennial engagement and an organization’s sustainable performance score

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    Since the start of the 21st century, the issue of sustainability in business and Human Resource practices has been a central topic of interest. More recently, human resources has come under considerable pressure to prove its worth, primarily by producing a more productive and engaged workforce. Sustainability has, thus, become an extremely interesting avenue of study for HR professionals as, at its core, sustainable practices aim to better all parts of an organization from the social, to the environmental, to the financial (the three components of the triple bottom line). This study will investigate the relationship between the extent to which Millennials are engaged in an organization and that organization’s score on sustainable performance measures

    Detection of NPM1 exon 12 mutations and FLT3 – internal tandem duplications by high resolution melting analysis in normal karyotype acute myeloid leukemia

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    <p>Abstract</p> <p>Background</p> <p>Molecular characterisation of normal karyotype acute myeloid leukemia (NK-AML) allows prognostic stratification and potentially can alter treatment choices and pathways. Approximately 45–60% of patients with NK-AML carry <it>NPM1 </it>gene mutations and are associated with a favourable clinical outcome when <it>FLT3</it>-internal tandem duplications (ITD) are absent. High resolution melting (HRM) is a novel screening method that enables rapid identification of mutation positive DNA samples.</p> <p>Results</p> <p>We developed HRM assays to detect <it>NPM1 </it>mutations and <it>FLT3</it>-ITD and tested diagnostic samples from 44 NK-AML patients. Eight were <it>NPM1 </it>mutation positive only, 4 were both <it>NPM1 </it>mutation and <it>FLT3</it>-ITD positive and 4 were <it>FLT3</it>-ITD positive only. A novel point mutation Y572C (c.1715A>G) in exon 14 of <it>FLT3 </it>was also detected. In the group with <it>de novo </it>NK-AML, 40% (12/29) were <it>NPM1 </it>mutation positive whereas <it>NPM1 </it>mutations were observed in 20% (3/15) of secondary NK-AML cases. Sequencing was performed and demonstrated 100% concordance with the HRM results.</p> <p>Conclusion</p> <p>HRM is a rapid and efficient method of screening NK-AML samples for both novel and known <it>NPM1 </it>and <it>FLT3 </it>mutations. <it>NPM1 </it>mutations can be observed in both primary and secondary NK-AML cases.</p

    The Australian Space Eye: studying the history of galaxy formation with a CubeSat

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    The Australian Space Eye is a proposed astronomical telescope based on a 6U CubeSat platform. The Space Eye will exploit the low level of systematic errors achievable with a small space based telescope to enable high accuracy measurements of the optical extragalactic background light and low surface brightness emission around nearby galaxies. This project is also a demonstrator for several technologies with general applicability to astronomical observations from nanosatellites. Space Eye is based around a 90 mm aperture clear aperture all refractive telescope for broadband wide field imaging in the i and z bands.Comment: 19 pages, 14 figures, submitted for publication as Proc. SPIE 9904, 9904-56 (SPIE Astronomical Telescopes & Instrumentation 2016

    Whole genome sequence association analysis of fasting glucose and fasting insulin levels in diverse cohorts from the NHLBI TOPMed program

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    The genetic determinants of fasting glucose (FG) and fasting insulin (FI) have been studied mostly through genome arrays, resulting in over 100 associated variants. We extended this work with high-coverage whole genome sequencing analyses from fifteen cohorts in NHLBI’s Trans-Omics for Precision Medicine (TOPMed) program. Over 23,000 non-diabetic individuals from five race-ethnicities/populations (African, Asian, European, Hispanic and Samoan) were included. Eight variants were significantly associated with FG or FI across previously identified regions MTNR1B, G6PC2, GCK, GCKR and FOXA2. We additionally characterize suggestive associations with FG or FI near previously identified SLC30A8, TCF7L2, and ADCY5 regions as well as APOB, PTPRT, and ROBO1. Functional annotation resources including the Diabetes Epigenome Atlas were compiled for each signal (chromatin states, annotation principal components, and others) to elucidate variant-to-function hypotheses. We provide a catalog of nucleotide-resolution genomic variation spanning intergenic and intronic regions creating a foundation for future sequencing-based investigations of glycemic traits

    Epigenomic assessment of cardiovascular disease risk and interactions with traditional risk metrics

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    Background Epigenome-wide association studies for cardiometabolic risk factors have discovered multiple loci associated with incident cardiovascular disease (CVD). However, few studies have sought to directly optimize a predictor of CVD risk. Furthermore, it is challenging to train multivariate models across multiple studies in the presence of study- or batch effects. Methods and Results Here, we analyzed existing DNA methylation data collected using the Illumina HumanMethylation450 microarray to create a predictor of CVD risk across 3 cohorts: Women's Health Initiative, Framingham Heart Study Offspring Cohort, and Lothian Birth Cohorts. We trained Cox proportional hazards-based elastic net regressions for incident CVD separately in each cohort and used a recently introduced cross-study learning approach to integrate these individual scores into an ensemble predictor. The methylation-based risk score was associated with CVD time-to-event in a held-out fraction of the Framingham data set (hazard ratio per SD=1.28, 95% CI, 1.10-1.50) and predicted myocardial infarction status in the independent REGICOR (Girona Heart Registry) data set (odds ratio per SD=2.14, 95% CI, 1.58-2.89). These associations remained after adjustment for traditional cardiovascular risk factors and were similar to those from elastic net models trained on a directly merged data set. Additionally, we investigated interactions between the methylation-based risk score and both genetic and biochemical CVD risk, showing preliminary evidence of an enhanced performance in those with less traditional risk factor elevation. Conclusions This investigation provides proof-of-concept for a genome-wide, CVD-specific epigenomic risk score and suggests that DNA methylation data may enable the discovery of high-risk individuals who would be missed by alternative risk metrics.This work was supported by the US Department of Agriculture, Agriculture Research Service (8050–51000-098-00D). Dr. Westerman was additionally supported by National Institutes of Health predoctoral training grant 5T32HL069772-14. The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services through contracts HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, and HHSN268201600004C. This article was prepared in collaboration with investigators of the WHI but has not been reviewed by the WHI and does not necessarily reflect the opinions of the WHI investigators or the National Heart, Lung, and Blood Institute. The Framingham Heart Study is conducted and supported by the National Heart, Lung, and Blood Institute in collaboration with Boston University (Contract No. N01-HC-25195 and HHSN268201500001I). This article was not prepared in collaboration with investigators of the Framingham Heart Study and does not necessarily reflect the opinions or views of the Framingham Heart Study, Boston University, or National Heart, Lung, and Blood Institute. The LBC 1936 is supported by Age UK (Disconnected Mind program) and the Medical Research Council (MR/M01311/1). Methylation typing in LBC 1936 was supported by Centre for Cognitive Ageing and Cognitive Epidemiology (Pilot Fund award), Age UK, The Wellcome Trust Institutional Strategic Support Fund, The University of Edinburgh, and The University of Queensland. LBC 1936 work was conducted in the Centre for Cognitive Ageing and Cognitive Epidemiology, which supported Dr. Deary and is supported by the medical Research Council and Biotechnology and Biological Sciences Research Council (MR/K026992/1).S

    Rise and Fall of a Multi-sheet Intrusive Complex, Elba Island, Italy

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    Elba Island intrusive complex: multisheet laccoliths, sheeted pluton, mafic dyke swarm. Laccolith magma fed from dykes and emplaced in crustal discontinuities (traps). Pluton growth by downward stacking of three magma pulses. Laccoliths and plutons: different outcomes of similar processes in different conditions. Emplacement of excess magma in a short time led to massive gravity slide
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