Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Tox(ukn) and STOP-Tox(ukk) tests

Stem cell-based in vitro test systems can recapitulate specific phases of human development. In the UKK test system, human pluripotent stem cells (hPSCs) randomly differentiate into cells of the three germ layers and their derivatives. In the UKN1 test system, hPSCs differentiate into early neural precursor cells. During the normal differentiation period (14 days) of the UKK system, 570 genes [849 probe sets (PSs)] were regulated > fivefold; in the UKN1 system (6 days), 879 genes (1238 PSs) were regulated. We refer to these genes as 'developmental genes'. In the present study, we used genome-wide expression data of 12 test substances in the UKK and UKN1 test systems to understand the basic principles of how chemicals interfere with the spontaneous transcriptional development in both test systems. The set of test compounds included six histone deacetylase inhibitors (HDACis), six mercury-containing compounds ('mercurials') and thalidomide. All compounds were tested at the maximum non-cytotoxic concentration, while valproic acid and thalidomide were additionally tested over a wide range of concentrations. In total, 242 genes (252 PSs) in the UKK test system and 793 genes (1092 PSs) in the UKN1 test system were deregulated by the 12 test compounds. We identified sets of 'diagnostic genes' appropriate for the identification of the influence of HDACis or mercurials. Test compounds that interfered with the expression of developmental genes usually antagonized their spontaneous development, meaning that up-regulated developmental genes were suppressed and developmental genes whose expression normally decreases were induced. The fraction of compromised developmental genes varied widely between the test compounds, and it reached up to 60 %. To quantitatively describe disturbed development on a genome-wide basis, we recommend a concept of two indices, 'developmental potency' (D (p)) and 'developmental index' (D (i)), whereby D (p) is the fraction of all developmental genes that are up- or down-regulated by a test compound, and D (i) is the ratio of overrepresentation of developmental genes among all genes deregulated by a test compound. The use of D (i) makes hazard identification more sensitive because some compounds compromise the expression of only a relatively small number of genes but have a high propensity to deregulate developmental genes specifically, resulting in a low D (p) but a high D (i). In conclusion, the concept based on the indices D (p) and D (i) offers the possibility to quantitatively express the propensity of test compounds to interfere with normal development

First Experience with the Standard Diagnostics at the European XFEL Injector

International audienceThe injector of the European XFEL is in operation since December 2015. It includes, beside the gun and the accelerating section, containing 1.3 and a 3.9 GHz accelerating module, a variety of standard diagnostics systems specially designed for this facility. With very few exceptions, all types of diagnostics systems are installed in the injector. Therefore the operation of the injector is served to validate and prove the diagnostics characteristics for the complete European XFEL. Most of the standard diagnostics has been available for the start of beam operation and showed the evidence of first beam along the beam line. In the following months the diagnostics has been optimized and used for improvements of beam quality. First operational experiences and results from the standard beam diagnostics in the injector of the European XFEL will be reported in this contribution

Status of the Standard Electron Beam Diagnostics of the EU-XFEL

Outline• Setup and status accelerator• Diagnostics• BPMs• Toroids• Beam Loss Monitors• Wirescanner• Dosimetry• Summar

First Experience with the Standard Diagnostics at the European XFEL Injector

The injector of the European XFEL started beam operation in December 2015. Besides the gun and the accelerating section, containing a 1.3 and a 3.9 GHz accelerating module, it contains a variety of standard diagnostics systems specially designed for this facility. With very few exceptions, all types of diagnostics systems of the whole XFEL are installed in the injector. Therefore the injector operation allows validating and proving of the diagnostics performances for the entire facility. Most of the standard diagnostics have been available from the very beginning of the beam operation and have been used for the monitoring of the first beam. In the following months the diagnostics have been optimized and used for improvements of beam quality. In this contribution, the first results and the operation experience of the standard beam diagnostics of the European XFEL are reported