Prenatal screening of sialic acid storage disease and confirmation in cultured fibroblasts by LC-MS/MS

Sialic acid storage disease (SASD) is an inborn error resulting from defects in the lysosomal membrane protein sialin. The SASD phenotypical spectrum ranges from a severe presentation, infantile sialic acid storage disease (ISSD) which may present as hydrops fetalis, to a relatively mild form, Salla disease. Screening for SASD is performed by determination of free sialic acid (FSA) in urine or amniotic fluid supernatant (AFS). Subsequent diagnosis of SASD is performed by quantification of FSA in cultured fibroblasts and by mutation analysis of the sialin gene, SLC17A5. We describe simple quantitative procedures to determine FSA as well as conjugated sialic acid in AFS, and FSA in cultured fibroblasts, using isotope dilution (13C3-sialic acid) and multiple reaction monitoring LC-ESI-MS/MS. The whole procedure can be performed in 2–4 h. Reference values in AFS were 0–8.2 μmol/L for 15–25 weeks of gestation and 3.2-12.0 μmol/L for 26–38 weeks of gestation. In AFS samples from five fetuses affected with ISSD FSA was 23.9-58.9 μmol/L demonstrating that this method is able to discriminate ISSD pregnancies from normal ones. The method was also validated for determination of FSA in fibroblast homogenates. FSA in SASD fibroblasts (ISSD; 20–154 nmol/mg protein, intermediate SASD; 12.9-15.1 nmol/mg, Salla disease; 5.9-7.4 nmol/mg) was clearly elevated compared to normal controls (0.3-2.2 nmol/mg). In conclusion, we report simple quantitative procedures to determine FSA in AFS and cultured fibroblasts improving both prenatal diagnostic efficacy for ISSD as well as confirmatory testing in cultured fibroblasts following initial screening in urine or AFS

Beyond ecosystem modeling: a roadmap to community cyberinfrastructure for ecological data‐model integration

In an era of rapid global change, our ability to understand and predict Earth's natural systems is lagging behind our ability to monitor and measure changes in the biosphere. Bottlenecks to informing models with observations have reduced our capacity to fully exploit the growing volume and variety of available data. Here, we take a critical look at the information infrastructure that connects ecosystem modeling and measurement efforts, and propose a roadmap to community cyberinfrastructure development that can reduce the divisions between empirical research and modeling and accelerate the pace of discovery. A new era of data‐model integration requires investment in accessible, scalable, transparent tools that integrate the expertise of the whole community, including both modelers and empiricists. This roadmap focuses on five key opportunities for community tools: the underlying foundationsof community cyberinfrastructure; data ingest; calibration of models to data; model‐data benchmarking; and data assimilation and ecological forecasting. This community‐driven approach is key to meeting the pressing needs of science and society in the 21st century

UvA-DARE (Digital Academic Repository) PrimaVera Working Paper Series

Abstract Information governance as an approach to better govern the use of information within and outside an organization is rapidly gaining popularity. A common and scientific ground for this approach has not yet been formulated. In this report the authors describe a unific definition for information governance, extending the common, one-dimensional approach into a more generic statement. Starting from the wellknown principles of IT-governance the authors further explore the aspects of both information and governance. Five hypotheses are proposed to give ground to the use of information governance. These hypotheses will be basis for further research

Application of the Implicitly Updated Arnoldi Method with a Complex Shift-and-Invert Strategy in Mhd

The implicitly updated Arnoldi method introduced by Sorensen with an internal QR-iteration is a very useful eigenvalue solver for nonsymmetric eigenvalue problems. To make this method rigorous in finding internal eigenvalues, a complex shift-and-invert strategy is used. Therefore a complex variant of the method has been constructed and the method has been compared with a Lanczos method, as implemented by Cullum at al., for a practical problem in magnetohydrodynamics. (c) 1995 Academic Press, Inc