Spectro-timing analysis of Cygnus X-1 during a fast state transition

We present the analysis of two long, quasi-uninterrupted RXTE observations of Cygnus X-1 that span several days within a 10 d interval. The spectral characteristics during this observation cover the region where previous observations have shown the source to be most dynamic. Despite that the source behavior on time scales of hours and days is remarkably similar to that on year time scales. This includes a variety of spectral/temporal correlations that previously had only been observed over Cyg X-1's long-term evolution. Furthermore, we observe a full transition from a hard to a soft spectral state that occurs within less than 2.5 hours - shorter than previously reported for any other similar Cyg X-1 transition. We describe the spectra with a phenomenological model dominated by a broken power law, and we fit the X-ray variability power spectra with a combination of a cutoff power law and Lorentzian components. The spectral and timing properties are correlated: the power spectrum Lorentzian components have an energy-dependent amplitude, and their peak frequencies increase with photon spectral index. Averaged over 3.2-10 Hz, the time lag between the variability in the 4.5-5.7 keV and 9.5-15 keV bands increases with decreasing hardness when the variability is dominated by the Lorentzian components during the hard state. The lag is small when there is a large power law noise contribution, shortly after the transition to the soft state. Interestingly, the soft state not only shows the shortest lags, but also the longest lags when the spectrum is at its softest and faintest. We discuss our results in terms of emission models for black hole binaries.Comment: 13 pages, 15 figures, accepted for publication in Astronomy and Astrophysic

A Cis-Regulatory Map of the Drosophila Genome

Systematic annotation of gene regulatory elements is a major challenge in genome science. Direct mapping of chromatin modification marks and transcriptional factor binding sites genome-wide1, 2 has successfully identified specific subtypes of regulatory elements3. In Drosophila several pioneering studies have provided genome-wide identification of Polycomb response elements4, chromatin states5, transcription factor binding sites6, 7, 8, 9, RNA polymerase II regulation8 and insulator elements10; however, comprehensive annotation of the regulatory genome remains a significant challenge. Here we describe results from the modENCODE cis-regulatory annotation project. We produced a map of the Drosophila melanogaster regulatory genome on the basis of more than 300 chromatin immunoprecipitation data sets for eight chromatin features, five histone deacetylases and thirty-eight site-specific transcription factors at different stages of development. Using these data we inferred more than 20,000 candidate regulatory elements and validated a subset of predictions for promoters, enhancers and insulators in vivo. We identified also nearly 2,000 genomic regions of dense transcription factor binding associated with chromatin activity and accessibility. We discovered hundreds of new transcription factor co-binding relationships and defined a transcription factor network with over 800 potential regulatory relationships

Modeling of MnS precipitation during the crystallization of grain oriented silicon steel

The process of manganese sulfide formation in the course of grain-oriented silicon steel solidification process is described in the paper. Fine dispersive MnS inclusions are grain growth inhibitors and apart from AlN inclusions they contribute to the formation of a privileged texture, i.e. Goss texture. A computer simulation of a high-silicon steel ingot solidification with the use of author’s software has been performed. Ueshima model was adapted for simulating the 3 % Si steel ingot solidification. The calculations accounted for the back diffusion effect according to Wołczyński equation. The computer simulation results are presented in the form of plots representing the process of steel components segregation in a solidifying ingot and curves illustrating the inclusion separation process

Modelling of non-metallic particles motion process in foundry alloys

The behaviour of non-metallic particles in the selected composites was analysed, in the current study. The calculations of particles floating in liquids differing in viscosity were performed. Simulations based on the Stokes equation were made for spherical SiC particles and additionally the particle size influence on Reynolds number was analysed.The movement of the particles in the liquid metal matrix is strictly connected with the agglomerate formation problem.Some of collisions between non-metallic particles lead to a permanent connection between them. Creation of the two spherical particles and a metallic phase system generates the adhesion force. It was found that the adhesion force mainly depends on the surface tension of the liquid alloy and radius of non-metallic particles

Valproic acid and fatalities in children: a review of individual case safety reports in VigiBase

Introduction Valproic acid is an effective first line drug for the treatment of epilepsy. Hepatotoxicity is a rare and potentially fatal adverse reaction for this medicine. Objective Firstly to characterise valproic acid reports on children with fatal outcome and secondly to determine reporting over time of hepatotoxicity with fatal outcome. Methods Individual case safety reports (ICSRs) for children ≤17 years with valproic acid and fatal outcome were retrieved from the WHO Global ICSR database, VigiBase, in June 2013. Reports were classified into hepatotoxic reactions or other reactions. Shrinkage observed-to-expected ratios were used to explore the relative reporting trend over time and for patient age. The frequency of polytherapy, i.e. reports with more than one antiepileptic medicine, was investigated. Results There have been 268 ICSRs with valproic acid and fatal outcome in children, reported from 25 countries since 1977. A total of 156 fatalities were reported with hepatotoxicity, which has been continuously and disproportionally reported over time. There were 31 fatalities with pancreatitis. Other frequently reported events were coma/encephalopathy, seizures, respiratory disorders and coagulopathy. Hepatotoxicity was disproportionally and most commonly reported in children aged 6 years and under (104/156 reports) but affected children of all ages. Polytherapy was significantly more frequently reported for valproic acid with fatal outcome (58%) compared with non-fatal outcome (34%). Conclusion Hepatotoxicity remains a considerable problem. The risk appears to be greatest in young children (6 years and below) but can occur at any age. Polytherapy is commonly reported and seems to be a risk factor for hepatotoxicity, pancreatitis and other serious adverse drug reactions with valproic acid

Genetic interaction screen for severe neurodevelopmental disorders reveals a functional link between Ube3a and Mef2 in Drosophila melanogaster

Neurodevelopmental disorders (NDDs) are clinically and genetically extremely heterogeneous with shared phenotypes often associated with genes from the same networks. Mutations in TCF4, MEF2C, UBE3A, ZEB2 or ATRX cause phenotypically overlapping, syndromic forms of NDDs with severe intellectual disability, epilepsy and microcephaly. To characterize potential functional links between these genes/proteins, we screened for genetic interactions in Drosophila melanogaster. We induced ubiquitous or tissue specific knockdown or overexpression of each single orthologous gene (Da, Mef2, Ube3a, Zfh1, XNP) and in pairwise combinations. Subsequently, we assessed parameters such as lethality, wing and eye morphology, neuromuscular junction morphology, bang sensitivity and climbing behaviour in comparison between single and pairwise dosage manipulations. We found most stringent evidence for genetic interaction between Ube3a and Mef2 as simultaneous dosage manipulation in different tissues including glia, wing and eye resulted in multiple phenotype modifications. We subsequently found evidence for physical interaction between UBE3A and MEF2C also in human cells. Systematic pairwise assessment of the Drosophila orthologues of five genes implicated in clinically overlapping, severe NDDs and subsequent confirmation in a human cell line revealed interactions between UBE3A/Ube3a and MEF2C/Mef2, thus contributing to the characterization of the underlying molecular commonalities