40 research outputs found

    Status of UCN Source at WWR-M Reactor

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    The WWR-M reactor at PNPI is going to be equipped with an ultacold neutron source of high density. Method of UCN production is based on their accumulation in the super fluid helium due to particular qualities of that quantum liquid. The possibility of maintaining the temperature T = 1.371K with a thermal load of P = 60W was shown experimentally, while the theoretical load is expected to be P=30W. The project envisages the installation on UCN beams the experimental setups of various research projects such as searching for the nEDM, measure the neutron lifetime, and the observation of neutron to antineutron oscillation. In addition to UCN beams, three beams of cold and verycold neutrons are planned. Six experimental setups will be installed on these beams. At present, a vacuum container of the UCN source has been manufactured and the manufacture of low-temperature deuterium and helium parts of the source has been started

    Inhibitor recurrence after immune tolerance induction: a multicenter retrospective cohort study

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    Immune tolerance induction (ITI) in patients with congenital hemophilia A is successful in up to 70%. Although there is growing understanding of predictors of response to ITI, the probability and predictors of inhibitor recurrence following successful ITI are not well understood

    Zinc-Regulated DNA Binding of the Yeast Zap1 Zinc-Responsive Activator

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    The Zap1 transcription factor of Saccharomyces cerevisiae plays a central role in zinc homeostasis by controlling the expression of genes involved in zinc metabolism. Zap1 is active in zinc-limited cells and repressed in replete cells. At the transcriptional level, Zap1 controls its own expression via positive autoregulation. In addition, Zap1's two activation domains are regulated independently of each other by zinc binding directly to those regions and repressing activation function. In this report, we show that Zap1 DNA binding is also inhibited by zinc. DMS footprinting showed that Zap1 target gene promoter occupancy is regulated with or without transcriptional autoregulation. These results were confirmed using chromatin immunoprecipitation. Zinc regulation of DNA binding activity mapped to the DNA binding domain indicating other parts of Zap1 are unnecessary for this control. Overexpression of Zap1 overrode DNA binding regulation and resulted in constitutive promoter occupancy. Under these conditions of constitutive binding, both the zinc dose response of Zap1 activity and cellular zinc accumulation were altered suggesting the importance of DNA binding control to zinc homeostasis. Thus, our results indicated that zinc regulates Zap1 activity post-translationally via three independent mechanisms, all of which contribute to the overall zinc responsiveness of Zap1

    Requirement of TFIIH kinase subunit Mat1 for RNA Pol II C-terminal domain Ser5 phosphorylation, transcription and mRNA turnover

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    The relevance of serine 5 phosphorylation of RNA polymerase II carboxy-terminal domain during initiation has been difficult to determine in mammalian cells as no general in vivo Ser5 kinase has been identified. Here, we demonstrate that deletion of the TFIIH kinase subunit Mat1 in mouse fibroblasts leads to dramatically reduced Pol II Ser5 phosphorylation. This is associated with defective capping and reduced Ser2 phosphorylation, decreased Pol II progression into elongation and severely attenuated transcription detected through analysis of nascent mRNAs, establishing a general requirement for mammalian Mat1 in transcription. Surprisingly, the general defect in Pol II transcription in Mat1−/− fibroblasts is not reflected in the majority of steady-state mRNAs. This indicates widespread stabilization of mRNAs and points to the existence of a regulatory mechanism to stabilize mRNAs following transcriptional attenuation, thus revealing a potential caveat in similar studies limited to analysis of steady-state mRNAs

    Nature and forecast of regional zoning of dynamic phenomena in mines of Donbass

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    Principal propositions of the method and results of prediction of regional zones development of dynamic phenomena in the mines of Donets Basin are considered on the basis of geological environment mechanical stresses estimation caused by disturbance of the equilibrium state according to gravimetric data
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