Genetic predisposition to mosaic Y chromosome loss in blood.

Mosaic loss of chromosome Y (LOY) in circulating white blood cells is the most common form of clonal mosaicism1-5, yet our knowledge of the causes and consequences of this is limited. Here, using a computational approach, we estimate that 20% of the male population represented in the UK Biobank study (n = 205,011) has detectable LOY. We identify 156 autosomal genetic determinants of LOY, which we replicate in 757,114 men of European and Japanese ancestry. These loci highlight genes that are involved in cell-cycle regulation and cancer susceptibility, as well as somatic drivers of tumour growth and targets of cancer therapy. We demonstrate that genetic susceptibility to LOY is associated with non-haematological effects on health in both men and women, which supports the hypothesis that clonal haematopoiesis is a biomarker of genomic instability in other tissues. Single-cell RNA sequencing identifies dysregulated expression of autosomal genes in leukocytes with LOY and provides insights into why clonal expansion of these cells may occur. Collectively, these data highlight the value of studying clonal mosaicism to uncover fundamental mechanisms that underlie cancer and other ageing-related diseases.This research has been conducted using the UK Biobank Resource under application 9905 and 19808. This work was supported by the Medical Research Council [Unit Programme number MC_UU_12015/2]. Full study-specific and individual acknowledgements can be found in the supplementary information

Uncertainty propagation in Surface Plate measurements

An easy applicable method for the evaluations of flatness measurements is given. The uncertainty is calculated using Monte-Carlo methods

Het schatten van onzekerheden bij (geometrische) metingen

Het berekenen van onzekerheden werd lange tijd beschouwd als een hobby van enkele specialisten van nationale standaardenlaboratoria. Sinds het verschijnen van erkende laboratoria en het opkomen van ‘kwaliteits’-denken is het ook in kalibratie-laboratoria een wezenlijk onderdeel van het verkrijgen van een erkenning en van de dagelijkse werkzaamheden. Bij het goed-of afkeuren van meetmiddelen en bij het toetsen van maten, zoals die bijvoorbeeld op een werktekening staan, is uiteraard ook de meetonzekerheid van belang. Lange tijd was dit nogal impliciet en werd er weinig acht op geslagen. De nieuwe norm ISO 14253-1 geeft echter eenduidig aan dat bij goed- of afkeur van werkstukken er rekening moet worden gehouden met de meetonzekerheid. In dit artikel zal gepoogd worden duidelijk te maken dat dit niet onnodig ingewikkeld behoeft te zijn

Uncertainty analysis of roughness standard calibration using stylus instruments

A stylus instrument was characterized and calibrated, including a dynamic calibration of the probe. This stylus instrument was used to calibrate ten roughness standards for six surface roughness parameters. The sensitivity of each parameter of each standard to such measurement conditions as stylus geometry, measurement force, cut-off wavelength, and so forth was determined experimentally. These results were used for an uncertainty evaluation of each parameter for each roughness standard. It is shown that the manufacturers’ specification for the stylus instrument (2% uncertainty in roughness parameters) is approximately correct for the most commonly used samples and parameters, but the uncertainty may range from 0.03% (for sinusoidal profiles) to 100% (for very fine surfaces), depending upon the standard and parameter to be calibrated

Evaluation of surface plate flatness measurements

The method of determining the flatness deviation of a surface plate, using differential measurements based on electronic levels, an autocollimator or laser interferometer, is well established. However, for the transformation of these measured values into absolute heights relative to a reference plane, various methods are used which do not utilize the redundancy of the measurements in a proper way. This paper gives the theoretical background for a proper calculation method and a treatment of the uncertainties in the results. This is illustrated by examples which have been met in practice

International comparison of roundness profiles with nanometric accuracy

Roundness profiles are compared which were obtained from measurements carried out at five national metrology laboratories. In the analysis, standard deviations and maximum deviations were calculated from point-by-point differences of the profiles with reference to one another or to the reference profile. Fourier analysis was used to select a spectral area for an analysis at the edge of the significance limit. The comparison shown that each participating laboratory is able to measure a roundness profile with a standard deviation in each data point of less than 2 nm

Design of a Calibration Platform for Scanning Probe Microscopes and Other Probing Systems

We designed a calibration platformthat enables the calibration of a scanning probe microscope (SPM

A scanning wafer thickness and flatness interferometer

Since the wafer industry in using an increasing amount of double side polished wafers, the future of wafer metrology is very likely to shift from capacitance gauging techniques to optical measurement techniques. Participating in an international project the Technical University of Eindhoven is developing a self calibrating, traceable double side wafer flatness and thickness measurement device.By using proper measurement principles and advanced software a robust traceble wafer thickness measurement instrument is created which combines high lateral resolution, nanometer accuracy, high speed and low cost. The data analysis used in this scanning interferometer involves multiple phase extraction methods, newly developed robust unwrapping methods, surface stitching and smart measuring strategies for the application of software compensation techniques

Design and calibration of a parallel-moving displacement generator for nano-metrology

A displacement generator is realized which enables the calibration of a wide variety of displacement-measuring probes, such as probes of roundness testers, roughness testers and stand-alone type scanning probe microscopes (SPMs), in the range of with a standard uncertainty below 1 nm. A digital piezo translator (DPT) drives a flat mirror which serves as the calibration platform. This mirror is locked to an elastic, hysteresis-free, monolithic parallel guide. Calibration of the platform displacement is carried out by various methods including tunable and stabilized lasers, Fabry-Pérot interferometry and laser interferometry. The system is calibrated with a standard uncertainty of about 0.1 nm using three independent methods. As an example the calibration of an SPM using generated steps is shown