Human identification & forensic analyses of degraded or low level DNA

DNA-based human identification is employed in varying situations, such as disaster victim identification, relationship testing and forensic analyses. When DNA is of low quality and/or quantity, standard methods for DNA profiling may not suffice. The research described in this thesis is aimed at the development of additional or alternative methods to extract information from a person__s DNA. The explored methods include: optimised sampling, the use of smaller and/or other types of DNA markers, increased analysis sensitivity, DNA repair, and combining marker sets. These studies have been performed to get closer to the answer regarding the question: __To whom belongs this body?__The research described in this thesis has been performed within the R&D group of the Human biological traces department of the Netherlands Forensic Institute. Part of this work was supported by a grant from the Netherlands Genomics Initiative / Netherlands Organization for Scientific Research (NWO) within the framework of the Forensic Genomics Consortium Netherlands. Publication of this thesis was financially supported by the Netherlands Forensic Institute.UBL - phd migration 201

Identification of Allosteric Modulators of Metabotropic Glutamate 7 Receptor Using Proteochemometric Modeling

Proteochemometric modeling (PCM) is a computational approach that can be considered an extension of quantitative structure–activity relationship (QSAR) modeling, where a single model incorporates information for a family of targets and all the associated ligands instead of modeling activity versus one target. This is especially useful for situations where bioactivity data exists for similar proteins but is scarce for the protein of interest. Here we demonstrate the application of PCM to identify allosteric modulators of metabotropic glutamate (mGlu) receptors. Given our long-running interest in modulating mGlu receptor function we compiled a matrix of compound-target bioactivity data. Some members of the mGlu family are well explored both internally and in the public domain, while there are much fewer examples of ligands for other targets such as the mGlu7 receptor. Using a PCM approach mGlu7 receptor hits were found. In comparison to conventional single target modeling the identified hits were more diverse, had a better confirmation rate, and provide starting points for further exploration. We conclude that the robust structure–activity relationship from well explored target family members translated to better quality hits for PCM compared to virtual screening (VS) based on a single target.FWN – Publicaties zonder aanstelling Universiteit Leide

特集 生活習慣病

Molecular Technology and Informatics for Personalised Medicine and Healt

Human identification & forensic analyses of degraded or low level DNA

DNA-based human identification is employed in varying situations, such as disaster victim identification, relationship testing and forensic analyses. When DNA is of low quality and/or quantity, standard methods for DNA profiling may not suffice. The research described in this thesis is aimed at the development of additional or alternative methods to extract information from a person__s DNA. The explored methods include: optimised sampling, the use of smaller and/or other types of DNA markers, increased analysis sensitivity, DNA repair, and combining marker sets. These studies have been performed to get closer to the answer regarding the question: __To whom belongs this body?_

Stimulus level effects on neural excitation and eCAP amplitude

Disorders of the head and nec

Improved analysis of long STR amplicons from degraded single source and mixed DNA

Genomics, epigenetics, population genetics and bioinformatic

Assessment of the stochastic threshold, back- and forward stutter filters and low template techniques for NGM

Genomics, epigenetics, population genetics and bioinformatic

Combining results of forensic STR kits: HDplex validation including allelic association and linkage testing with NGM and Identifiler loci

Genomics, epigenetics, population genetics and bioinformatic

Scanning electron microscopic assessment of coating irregularities and their precursors in unexpanded durable polymer-based drug-eluting stents

Objectives: To assess and quantify coating irregularities on unexpanded and expanded durable polymer-based drug-eluting stents (DES) to gain insights into the origin of coating irregularities. Background: Previous scanning electron microscopy (SEM) studies in various expanded DES revealed differences in frequency and size of coating irregularities between DES types and specific distribution patterns, however, the origin of these irregularities is unclear. Methods: We assessed at bench side a total of 1,200 SEM images obtained in 30 DES samples (15 expanded and 15 unexpanded) of Cypher Select Plus, Taxus Liberté, Endeavor, Xience V, and resolute. Results: For most coating irregularities seen on expanded DES (72%; 23/32), a matching irregularity (n = 18/23) and/or its precursor (n = 11/23) was observed in unexpanded DES. Unexpanded Cypher select showed (small) crater lesions and cracks together with precursors of “peeling.” On unexpanded Taxus Liberté, thinning of polymer, small bare metal areas, wrinkles, and one precursor type were found. Unexpanded endeavor showed cracks, small bare metal areas, crater lesions, and precursors of the latter. Unexpanded Xience V and resolute mainly revealed crater lesions and their precursors. On unexpanded versus expanded DES, there was no difference in measured frequency of coating irregularities and precursors (P = ns) with the exception of more bare metal areas on expanded Taxus Liberte (P = 0.01). Conclusions: Most coating irregularities, or the potential to develop them, are inherent to the unexpanded DES. Important determinants of the formation of coating irregularities may be the stent geometry and the physical properties of the coating, while stent-balloon interaction plays no major role