Studies on the impact of job characteristics, social roles and gender

Bruijn, J.G.M. de [Promotor]Penninx, B.W.J.H. [Promotor]Smit, J.H. [Copromotor]Dyck, R. van [Copromotor

Structure-based predictions broadly link transcription factor mutations to gene expression changes in cancers

© 2014 The Author(s). Thousands of unique mutations in transcription factors (TFs) arise in cancers, and the functional and biological roles of relatively few of these have been characterized. Here, we used structure-based methods developed specifically for DNA-binding proteins to systematically predict the consequences of mutations in several TFs that are frequently mutated in cancers. The explicit consideration of protein-DNA interactions was crucial to explain the roles and prevalence of mutations in TP53 and RUNX1 in cancers, and resulted in a higher specificity of detection for known p53-regulated genes among genetic associations between TP53 genotypes and genome-wide expression in The Cancer Genome Atlas, compared to existing methods of mutation assessment. Biophysical predictions also indicated that the relative prevalence of TP53 missense mutations in cancer is proportional to their thermodynamic impacts on protein stability and DNA binding, which is consistent with the selection for the loss of p53 transcriptional function in cancers. Structure and thermodynamics-based predictions of the impacts of missense mutations that focus on specific molecular functions may be increasingly useful for the precise and large-scale inference of aberrant molecular phenotypes in cancer and other complex diseases

Using NuRadioMC to study the performance of UHE radio neutrino detectors

NuRadioMC is an open-source, Python-based simulation and reconstruction framework for radio detectors of ultra-high energy neutrinos and cosmic rays. Its modular design makes NuRadioMC suitable for use with a range of past, current and future detectors. In addition, the recent deployment of a complete documentation as well as a pip release make NuRadioMC relatively easy to learn and use. Here, we outline the features currently available and under development in NuRadioMC, with a focus on its usage to simulate and study in-ice radio neutrino detectors

Fatigue in laser shock peened open-hole thin aluminium specimens

An experimental study was performed in order to determine the influence of the sequence of operations on the effectiveness of Laser Shock Peening (LSP) treatment in increasing the fatigue performances of open-hole aluminium specimens. Residual stress measurements, fractographic analysis and FEM analysis were performed, indicating the presence of compressive residual stresses on the surface of the treated specimens and tensile residual stresses in the mid-section along the thickness of the specimens. Negative effects on fatigue lives were encountered on the specimens with the hole already present, while positive effect were observed in specimens in which the hole was drilled after LSP treatment. These results indicate that LSP can be a good solution for “in production” application, in which open holes are to be drilled after the LSP treatment. The application in which LSP is used “in service” on structures with pre-existing cut-outs, has proven to be impracticable in the investigated configuration