Characterizing Dynamic Changes in the Human Blood Transcriptional Network

Gene expression data generated systematically in a given system over multiple time points provides a source of perturbation that can be leveraged to infer causal relationships among genes explaining network changes. Previously, we showed that food intake has a large impact on blood gene expression patterns and that these responses, either in terms of gene expression level or gene-gene connectivity, are strongly associated with metabolic diseases. In this study, we explored which genes drive the changes of gene expression patterns in response to time and food intake. We applied the Granger causality test and the dynamic Bayesian network to gene expression data generated from blood samples collected at multiple time points during the course of a day. The simulation result shows that combining many short time series together is as powerful to infer Granger causality as using a single long time series. Using the Granger causality test, we identified genes that were supported as the most likely causal candidates for the coordinated temporal changes in the network. These results show that PER1 is a key regulator of the blood transcriptional network, in which multiple biological processes are under circadian rhythm regulation. The fasted and fed dynamic Bayesian networks showed that over 72% of dynamic connections are self links. Finally, we show that different processes such as inflammation and lipid metabolism, which are disconnected in the static network, become dynamically linked in response to food intake, which would suggest that increasing nutritional load leads to coordinate regulation of these biological processes. In conclusion, our results suggest that food intake has a profound impact on the dynamic co-regulation of multiple biological processes, such as metabolism, immune response, apoptosis and circadian rhythm. The results could have broader implications for the design of studies of disease association and drug response in clinical trials

Temperature Dependent Electron Beam Induced Current Study of Defects in Silicon

A new computer-aided electron beam induced current system was developed which makes it possible to obtain two-dimensional mapping of the absolute magnitudes of electron beam induced current signals over the temperature range 15 K-400 K. Electronic states of defects in cast silicon and deformation-induced dislocations in float-zone silicon were investigated from the analyses of temperature dependencies of electron beam induced current contrasts of the defects measured with the system. Electron beam induced current active defects in cast Si were identified to be Fe impurity atoms or Fe-B pairs incorporated at the dislocation core depending on the cooling rate of a crystal. Dislocations in float-zone silicon were shown to have an energy level for carrier recombination in the lower half of the band gap

Mechanical properties of 20% cold-worked 316 stainless steel irradiated at low dose rate.

To assess the effects of long-term, low-dose-rate neutron exposure on mechanical strength and ductility, tensile properties were measured on irradiated 20% cold-worked Type 316 stainless steel. Samples were prepared from reactor core components retrieved from the EBR-II reactor following final shutdown. Sample locations were chosen to cover a dose range of 1-47 dpa at temperatures from 371-385 C and dose rates from 0.8-2.8 x 10{sup -7} dpa/s. These dose rates are about one order of magnitude lower than those of typical EBR-II in-core experiments. Irradiation caused hardening, with the yield strength (YS) following approximately the same trend as the ultimate tensile strength (UTS). At higher dose, the difference between the UTS and YS decreases, suggesting the work-hardening capability of the material is decreasing with increasing dose. Both the uniform elongation and total elongation decrease up to the largest dose. Unlike the strength data, the ductility reduction showed no signs of saturated at 20 dpa. While the material retained respectable ductility at 20 dpa, the uniform and total elongation decreased to <1 and <3%, respectively, at 47 dpa. Fracture in the 30 dpa specimen is mainly ductile but with local regions of mixed-mode failure, consisting of dimples and microvoids. The fracture surface of the higher-exposure 47 dpa specimen displays significantly more brittle features. The fracture consists of mainly small facets and slip bands that suggest channel fracture.The hardening in these low-dose-rate components differs from that measured in test samples irradiated in EBR-II at higher-dose-rate. The material irradiated at higher dose rate loses work hardening capacity faster than the lower dose rate material, although this effect could be due to compositional differences