Biomedical subjects

Ron Wehrens

Publications and source records attributed to Ron Wehrens.

3 recordsLinked to original sources

PubMed2005

Representing structural databases in a self-organizing map.

This paper presents a way to accomodate large numbers of crystal structures, as present in e.g. the Cambridge Structural Database (CSD), in a self-organizing map. The structures are represented by their calculated powder diffraction patterns. The use of a recently introduced similarity criterion is essential: the weighted cross-correlation. This accurately reflects the similarities of the powder patterns and therefore, indirectly measures the resemblance of crystal packings. It will be shown that good results are obtained, even if the network is trained with a small subset of a complete database. This makes it possible to construct the map on common hardware in a few hours. Such a map provides several possibilities for two-dimensional visualization, but additionally has a number of important applications. Two such applications are fast and easy screening of a database, and providing an overview of the contents of a database in terms of structural diversity of specific chemical classes of compounds, e.g. steroids or peptides. A third is the selection of archetypical structures, covering the complete structural space.

Algorithms↗

PubMed2005

Spatial variability and uncertainty in ecological risk assessment: a case study on the potential risk of cadmium for the little owl in a Dutch river flood plain.

This paper outlines a procedure that quantifies the impact of different sources of spatial variability and uncertainty on ecological risk estimates. The procedure is illustrated in a case study that estimates the risks of cadmium for a little owl (Athene noctua vidalli) living in a Dutch river flood plain along the river Rhine. A geographical information system (GIS) was used to quantify spatial variability in contaminant concentrations and habitats. It was combined with an exposure and effect model that uses Monte Carlo simulation to quantify parameter uncertainty. Spatial model uncertainty was assessed by the application of two different spatial interpolation methods (classification and kriging) and foraging ranges. The results of the case study show that parameter uncertainty is the main type of uncertainty influencing the risk estimate, and to a lesser extent spatial variability, while spatial model uncertainty was of minor importance. Compared to the deterministically calculated hazard index for the little owl (0.9), inclusion of spatial variability resulted in a median hazard index that can vary between 0.8 and 1.4. It is concluded that a single estimator for a whole flood plain may over- or underestimate risks for specific parts within the flood plain. Further research that expands the procedure presented in this paper is necessary to improve the incorporation of spatial factors in ecological risk assessment.

Animals↗

PubMed2004

Identification of novel regulators associated with early-phase osteoblast differentiation.

UNLABELLED: Key regulatory components of the BMP-induced osteoblast differentiation cascade remain to be established. Microarray and subsequent expression analyses in mice identified two transcription factors, Hey1 and Tcf7, with in vitro and in vivo expression characteristics very similar to Cbfa1. Transfection studies suggest that Tcf7 modulates BMP2-induced osteoblast differentiation. This study contributes to a better definition of the onset of BMP-induced osteoblast differentiation. INTRODUCTION: Elucidation of the genetic cascade guiding mesenchymal stem cells to become osteoblasts is of extreme importance for improving the treatment of bone-related diseases such as osteoporosis. The aim of this study was to identify regulators of the early phases of bone morphogenetic protein (BMP)2-induced osteoblast differentiation. MATERIALS AND METHODS: Osteoblast differentiation of mouse C2C12 cells was induced by treatment with BMP2, and regulation of gene expression was studied during the subsequent 24 h using high-density microarrays. The regulated genes were grouped by means of model-based clustering, and protein functions were assigned. Real-time quantitative RT-PCR analysis was used to validate BMP2-induced gene expression patterns in C2C12 cells. Osteoblast specificity was studied by comparing these expression patterns with those in C3H10T1/2 and NIH3T3 cells under similar conditions. In situ hybridization of mRNA in embryos at embryonic day (E)14.5 and E16.5 of gestation and on newborn mouse tails were used to study in vivo expression patterns. Cells constitutively expressing the regulated gene Tcf7 were used to investigate its influence on BMP-induced osteoblast differentiation. RESULTS AND CONCLUSIONS: A total of 184 genes and expressed sequence tags (ESTs) were differentially expressed in the first 24 h after BMP2 treatment and grouped in subsets of immediate early, intermediate early, and late early response genes. Signal transduction regulatory factors mainly represented the subset of immediate early genes. Regulation of expression of these genes was direct, independent of de novo protein synthesis and independent of the cell type studied. The intermediate early and late early genes consisted primarily of genes related to processes that modulate morphology, basement membrane formation, and synthesis of extracellular calcified matrix. The late early genes require de novo protein synthesis and show osteoblast specificity. In vivo and in vitro experiments showed that the transcription factors Hey1 and Tcf7 exhibited expression characteristics and cell type specificity very similar to those of the osteoblast specific transcription factor Cbfa1, and constitutive expression of Tcf7 in C2C12 cells differentially regulated osteoblast differentiation marker genes.

Animals↗