63 research outputs found

    The Reliability of Test Discriminations

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66658/2/10.1177_001316445501500404.pd

    Measuring single cell divisions in human tissues from multi-region sequencing data.

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    Both normal tissue development and cancer growth are driven by a branching process of cell division and mutation accumulation that leads to intra-tissue genetic heterogeneity. However, quantifying somatic evolution in humans remains challenging. Here, we show that multi-sample genomic data from a single time point of normal and cancer tissues contains information on single-cell divisions. We present a new theoretical framework that, applied to whole-genome sequencing data of healthy tissue and cancer, allows inferring the mutation rate and the cell survival/death rate per division. On average, we found that cells accumulate 1.14 mutations per cell division in healthy haematopoiesis and 1.37 mutations per division in brain development. In both tissues, cell survival was maximal during early development. Analysis of 131 biopsies from 16 tumours showed 4 to 100 times increased mutation rates compared to healthy development and substantial inter-patient variation of cell survival/death rates

    Low rates of mutation in clinical grade human pluripotent stem cells under different culture conditions

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    Abstract: The occurrence of repetitive genomic changes that provide a selective growth advantage in pluripotent stem cells is of concern for their clinical application. However, the effect of different culture conditions on the underlying mutation rate is unknown. Here we show that the mutation rate in two human embryonic stem cell lines derived and banked for clinical application is low and not substantially affected by culture with Rho Kinase inhibitor, commonly used in their routine maintenance. However, the mutation rate is reduced by >50% in cells cultured under 5% oxygen, when we also found alterations in imprint methylation and reversible DNA hypomethylation. Mutations are evenly distributed across the chromosomes, except for a slight increase on the X-chromosome, and an elevation in intergenic regions suggesting that chromatin structure may affect mutation rate. Overall the results suggest that pluripotent stem cells are not subject to unusually high rates of genetic or epigenetic alterations

    The assessment of partial knowledge

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    http://deepblue.lib.umich.edu/bitstream/2027.42/4404/5/bab7835.0001.001.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/4404/4/bab7835.0001.001.tx

    The assessment of partial knowledge in objective testing

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    http://deepblue.lib.umich.edu/bitstream/2027.42/4405/5/bab7836.0001.001.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/4405/4/bab7836.0001.001.tx

    1984: Abilene Christian College Bible Lectures - Full Text

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    CALLED TO BE SERVANTS Being the Abilene Christian University Annual Bible Lectures 1984 Published by Abilene Christian University Book Store ACU Station Abilene, Texas 7969
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