370 research outputs found

    The existence of an inverse limit of inverse system of measure spaces - a purely measurable case

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    The existence of an inverse limit of an inverse system of (probability) measure spaces has been investigated since the very beginning of the birth of the modern probability theory. Results from Kolmogorov [10], Bochner [2], Choksi [5], Metivier [14], Bourbaki [3] among others have paved the way of the deep understanding of the problem under consideration. All the above results, however, call for some topological concepts, or at least ones which are closely related topological ones. In this paper we investigate purely measurable inverse systems of (probability) measure spaces, and give a sucient condition for the existence of a unique inverse limit. An example for the considered purely measurable inverse systems of (probability) measure spaces is also given

    Diverse roles of androgen receptor (AR) domains in AR-mediated signaling

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    Androgens control male sexual development and maintenance of the adult male phenotype. They have very divergent effects on their target organs like the reproductive organs, muscle, bone, brain and skin. This is explained in part by the fact that different cell types respond differently to androgen stimulus, even when all these responses are mediated by the same intracellular androgen receptor. To understand these tissue- and cell-specific readouts of androgens, we have to learn the many different steps in the transcription activation mechanisms of the androgen receptor (NR3C4). Like all nuclear receptors, the steroid receptors have a central DNA-binding domain connected to a ligand-binding domain by a hinge region. In addition, all steroid receptors have a relatively large amino-terminal domain. Despite the overall structural homology with other nuclear receptors, the androgen receptor has several specific characteristics which will be discussed here. This receptor can bind two types of androgen response elements (AREs): one type being similar to the classical GRE/PRE-type elements, the other type being the more divergent and more selective AREs. The hormone-binding domain has low intrinsic transactivation properties, a feature that correlates with the low affinity of this domain for the canonical LxxLL-bearing coactivators. For the androgen receptor, transcriptional activation involves the alternative recruitment of coactivators to different regions in the amino-terminal domain, as well as the hinge region. Finally, a very strong ligand-induced interaction between the amino-terminal domain and the ligand-binding domain of the androgen receptor seems to be involved in many aspects of its function as a transcription factor. This review describes the current knowledge on the structure-function relationships within the domains of the androgen receptor and tries to integrate the involvement of different domains, subdomains and motifs in the functioning of this receptor as a transcription factor with tissue- and cell-specific readouts

    Multifragment production in Au+Au at 35 MeV/u

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    Multifragment disintegration has been measured with a high efficiency detection system for the reaction Au+AuAu + Au at E/A=35 MeVE/A = 35\ MeV. From the event shape analysis and the comparison with the predictions of a many-body trajectories calculation the data, for central collisions, are compatible with a fast emission from a unique fragment source.Comment: 9 pages, LaTex file, 4 postscript figures available upon request from [email protected]. - to appear in Phys. Lett.

    Hydrological Behaviour of Tritium on the Former Semipalatinsk Nuclear Test Site (Kazakhstan) Determined using Stable Isotope Measurements

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    Tritium and stable isotope (deuterium 2H and 18O) concentrations have been determined in natural waters collected from shallow lakes, wells, streams and rivers inside and in the vicinity of the former Semipalatinsk Nuclear Test Site (NE Kazakhstan). The Semipalatinsk Test Site (STS) was one of the main proving grounds for the testing of nuclear weapons by the former Soviet Union. Tritium activity concentrations have been determined by liquid scintillation counting, while hydrogen isotopic composition have been determined using a GV-Isoprime mass spectrometer coupled to an elemental analyzer. Tritium activity concentrations recorded in lake waters (in most cases >10 Bq L-1) were significantly higher than those in well, stream and the Irtysh River waters. In lake waters, enrichments in deuterium and 18O (δD and δ18O varying between –5 and –64 ‰ V-SMOW and –8.4 and +5.5 ‰ V-SMOW, respectively), and high salt concentrations, strongly suggest that significant evaporation has occurred. In contrast, deuterium and tritium signatures of ‘common’ surface and underground waters at the STS were mostly typical of present-day isotope backgrounds of natural waters in NE Kazakhstan. In STS, come salt lakes like Bajansor and Tumatsor with elevated tritium activity from 12 to 15 Bq L-1 lie close to the Global Meteoric Water Line. The potential tritium source for these lakes is residual concentration of tritium after former nuclear test in STS. The study provides evidence to show that export of tritium from underground nuclear test areas and tritium enrichment produced by evaporation are both important determinants of tritium concentrations in standing waters on the Semipalatinsk test site

    Dynamics of nuclear receptor target gene regulation

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    Ligand-regulated nuclear receptors, such as estrogen receptors, glucocorticoid receptor, vitamin D receptor, and peroxisome proliferator-activated receptors, belong to the most widely studied and best understood transcription factors. Therefore, the dynamic nature of transcriptional regulation was observed first with different members of the nuclear receptor superfamily, but is now also extended to other transcription factors, such as nuclear factor κB. Dynamic and in part cyclical processes were observed on the level of translocation into the nucleus, association with genomic binding sites, exchange of co-regulators and chromatin modifiers, occurrence of chromatin marks, and activities of RNA polymerase II resulting in mRNA synthesis. In this review, we summarize recent findings on the dynamic regulation of nuclear receptor target genes in the chromatin context

    Large Deviations for the Stochastic Shell Model of Turbulence

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    In this work we first prove the existence and uniqueness of a strong solution to stochastic GOY model of turbulence with a small multiplicative noise. Then using the weak convergence approach, Laplace principle for so- lutions of the stochastic GOY model is established in certain Polish space. Thus a Wentzell-Freidlin type large deviation principle is established utilizing certain results by Varadhan and Bryc.Comment: 21 pages, submitted for publicatio

    Retinoic Acid Mediates Long-Paced Oscillations in Retinoid Receptor Activity: Evidence for a Potential Role for RIP140

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    Mechanisms that underlie oscillatory transcriptional activity of nuclear receptors (NRs) are incompletely understood. Evidence exists for rapid, cyclic recruitment of coregulatory complexes upon activation of nuclear receptors. RIP140 is a NR coregulator that represses the transactivation of agonist-bound nuclear receptors. Previously, we showed that RIP140 is inducible by all-trans retinoic acid (RA) and mediates limiting, negative-feedback regulation of retinoid signaling.Here we report that in the continued presence of RA, long-paced oscillations of retinoic acid receptor (RAR) activity occur with a period ranging from 24 to 35 hours. Endogenous expression of RIP140 and other RA-target genes also oscillate in the presence of RA. Cyclic retinoid receptor transactivation is ablated by constitutive overexpression of RIP140. Further, depletion of RIP140 disrupts cyclic expression of the RA target gene HOXA5. Evidence is provided that RIP140 may limit RAR signaling in a selective, non-redundant manner in contrast to the classic NR coregulators NCoR1 and SRC1 that are not RA-inducible, do not cycle, and may be partially redundant in limiting RAR activity. Finally, evidence is provided that RIP140 can repress and be induced by other nuclear receptors in a manner that suggests potential participation in other NR oscillations.We provide evidence for novel, long-paced oscillatory retinoid receptor activity and hypothesize that this may be paced in part, by RIP140. Oscillatory NR activity may be involved in mediating hormone actions of physiological and pathological importance

    Dimer formation and conformational flexibility ensure cytoplasmic stability and nuclear accumulation of Elk-1

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    The ETS (E26) protein Elk-1 serves as a paradigm for mitogen-responsive transcription factors. It is multiply phosphorylated by mitogen-activated protein kinases (MAPKs), which it recruits into pre-initiation complexes on target gene promoters. However, events preparatory to Elk-1 phosphorylation are less well understood. Here, we identify two novel, functional elements in Elk-1 that determine its stability and nuclear accumulation. One element corresponds to a dimerization interface in the ETS domain and the second is a cryptic degron adjacent to the serum response factor (SRF)-interaction domain that marks dimerization-defective Elk-1 for rapid degradation by the ubiquitin–proteasome system. Dimerization appears to be crucial for Elk-1 stability only in the cytoplasm, as latent Elk-1 accumulates in the nucleus and interacts dynamically with DNA as a monomer. These findings define a novel role for the ETS domain of Elk-1 and demonstrate that nuclear accumulation of Elk-1 involves conformational flexibility prior to its phosphorylation by MAPKs
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