16 research outputs found

    Towards good practice guidelines for the contour method of residual stress measurement

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    Accurate measurement of residual stress in metallic components using the contour method relies on the achievement of a good quality cut, on the appropriate measurement of the deformed cut surface and on the robust analysis of the measured data. There is currently no published standard or code of practice for the contour method. As a first step towards such a standard, this study draws on research investigations addressing the three main steps in the method: how best to cut the specimens; how to measure the deformation contour of the cut surface; and how to analyse the data. Good practice guidance is provided throughout the text accompanied by more detailed observations and advice tabulated in Appendi

    The Science Case for 4GLS

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    YY1 Haploinsufficiency Causes an Intellectual Disability Syndrome Featuring Transcriptional and Chromatin Dysfunction

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    Yin and yang 1 (YY1) is a well-known zinc-finger transcription factor with crucial roles in normal development and malignancy. YY1 acts both as a repressor and as an activator of gene expression. We have identified 23 individuals with de novo mutations or deletions of YY1 and phenotypic features that define a syndrome of cognitive impairment, behavioral alterations, intrauterine growth restriction, feeding problems, and various congenital malformations. Our combined clinical and molecular data define "YY1 syndrome" as a haploinsufficiency syndrome. Through immunoprecipitation of YY1-bound chromatin from affected individuals' cells with antibodies recognizing both ends of the protein, we show that YY1 deletions and missense mutations lead to a global loss of YY1 binding with a preferential retention at high-occupancy sites. Finally, we uncover a widespread loss of H3K27 acetylation in particular on the YY1-bound enhancers, underscoring a crucial role for YY1 in enhancer regulation. Collectively, these results define a clinical syndrome caused by haploinsufficiency of YY1 through dysregulation of key transcriptional regulators
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