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Sample records for positioned nucleosomes flanking

  1. Nucleosome Positioning and Epigenetics

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    Schwab, David; Bruinsma, Robijn

    2008-03-01

    The role of chromatin structure in gene regulation has recently taken center stage in the field of epigenetics, phenomena that change the phenotype without changing the DNA sequence. Recent work has also shown that nucleosomes, a complex of DNA wrapped around a histone octamer, experience a sequence dependent energy landscape due to the variation in DNA bend stiffness with sequence composition. In this talk, we consider the role nucleosome positioning might play in the formation of heterochromatin, a compact form of DNA generically responsible for gene silencing. In particular, we discuss how different patterns of nucleosome positions, periodic or random, could either facilitate or suppress heterochromatin stability and formation.

  2. Disappearance of nucleosome positioning in mitotic chromatin in vivo.

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    Komura, Jun-ichiro; Ono, Tetsuya

    2005-04-15

    During mitosis, transcription is silenced and most transcription factors are displaced from their recognition sequences. By in vivo footprinting analysis, we have confirmed and extended previous studies showing loss of transcription factors from an RNA polymerase II promoter (c-FOS) and, for the first time, an RNA polymerase III promoter (U6) in HeLa cells. Because little was known about nucleosomal organization in mitotic chromosomes, we performed footprinting analysis for nucleosomes on these promoters in interphase and mitotic cells. During interphase, each of the promoters had a positioned nucleosome in the region intervening between proximal promoter elements and distal enhancer elements, but the strong nucleosome positioning disappeared during mitosis. Thus, the nucleosomal organization that appears to facilitate transcription in interphase cells may be lost in mitotic cells, and nucleosome positioning during mitosis does not seem to be a major component of the epigenetic mechanisms to mark genes for rapid reactivation after this phase.

  3. Prediction of nucleosome positioning based on transcription factor binding sites.

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    Xianfu Yi

    Full Text Available BACKGROUND: The DNA of all eukaryotic organisms is packaged into nucleosomes, the basic repeating units of chromatin. The nucleosome consists of a histone octamer around which a DNA core is wrapped and the linker histone H1, which is associated with linker DNA. By altering the accessibility of DNA sequences, the nucleosome has profound effects on all DNA-dependent processes. Understanding the factors that influence nucleosome positioning is of great importance for the study of genomic control mechanisms. Transcription factors (TFs have been suggested to play a role in nucleosome positioning in vivo. PRINCIPAL FINDINGS: Here, the minimum redundancy maximum relevance (mRMR feature selection algorithm, the nearest neighbor algorithm (NNA, and the incremental feature selection (IFS method were used to identify the most important TFs that either favor or inhibit nucleosome positioning by analyzing the numbers of transcription factor binding sites (TFBSs in 53,021 nucleosomal DNA sequences and 50,299 linker DNA sequences. A total of nine important families of TFs were extracted from 35 families, and the overall prediction accuracy was 87.4% as evaluated by the jackknife cross-validation test. CONCLUSIONS: Our results are consistent with the notion that TFs are more likely to bind linker DNA sequences than the sequences in the nucleosomes. In addition, our results imply that there may be some TFs that are important for nucleosome positioning but that play an insignificant role in discriminating nucleosome-forming DNA sequences from nucleosome-inhibiting DNA sequences. The hypothesis that TFs play a role in nucleosome positioning is, thus, confirmed by the results of this study.

  4. Nucleosome Positioning and NDR Structure at RNA Polymerase III Promoters

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    Helbo, Alexandra Søgaard; Lay, Fides D; Jones, Peter A

    2017-01-01

    Chromatin is structurally involved in the transcriptional regulation of all genes. While the nucleosome positioning at RNA polymerase II (pol II) promoters has been extensively studied, less is known about the chromatin structure at pol III promoters in human cells. We use a high...

  5. An in vitro-identified high-affinity nucleosome-positioning signal is capable of transiently positioning a nucleosome in vivo

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    Gracey Lia E

    2010-07-01

    Full Text Available Abstract Background The physiological function of eukaryotic DNA occurs in the context of nucleosomal arrays that can expose or obscure defined segments of the genome. Certain DNA sequences are capable of strongly positioning a nucleosome in vitro, suggesting the possibility that favorable intrinsic signals might reproducibly structure chromatin segments. As high-throughput sequencing analyses of nucleosome coverage in vitro and in vivo have become possible, a vigorous debate has arisen over the degree to which intrinsic DNA:nucleosome affinities orchestrate the in vivo positions of nucleosomes, thereby controlling physical accessibility of specific sequences in DNA. Results We describe here the in vivo consequences of placing a synthetic high-affinity nucleosome-positioning signal, the 601 sequence, into a DNA plasmid vector in mice. Strikingly, the 601 sequence was sufficient to position nucleosomes during an early phase after introduction of the DNA into the mice (when the plasmid vector transgene was active. This positioning capability was transient, with a loss of strong positioning at a later time point when the transgenes had become silent. Conclusions These results demonstrate an ability of DNA sequences selected solely for nucleosome affinity to organize chromatin in vivo, and the ability of other mechanisms to overcome these interactions in a dynamic nuclear environment.

  6. nuMap: a web platform for accurate prediction of nucleosome positioning.

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    Alharbi, Bader A; Alshammari, Thamir H; Felton, Nathan L; Zhurkin, Victor B; Cui, Feng

    2014-10-01

    Nucleosome positioning is critical for gene expression and of major biological interest. The high cost of experimentally mapping nucleosomal arrangement signifies the need for computational approaches to predict nucleosome positions at high resolution. Here, we present a web-based application to fulfill this need by implementing two models, YR and W/S schemes, for the translational and rotational positioning of nucleosomes, respectively. Our methods are based on sequence-dependent anisotropic bending that dictates how DNA is wrapped around a histone octamer. This application allows users to specify a number of options such as schemes and parameters for threading calculation and provides multiple layout formats. The nuMap is implemented in Java/Perl/MySQL and is freely available for public use at http://numap.rit.edu. The user manual, implementation notes, description of the methodology and examples are available at the site. Copyright © 2014 The Authors. Production and hosting by Elsevier Ltd.. All rights reserved.

  7. nuMap: A Web Platform for Accurate Prediction of Nucleosome Positioning

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    Bader A. Alharbi

    2014-10-01

    Full Text Available Nucleosome positioning is critical for gene expression and of major biological interest. The high cost of experimentally mapping nucleosomal arrangement signifies the need for computational approaches to predict nucleosome positions at high resolution. Here, we present a web-based application to fulfill this need by implementing two models, YR and W/S schemes, for the translational and rotational positioning of nucleosomes, respectively. Our methods are based on sequence-dependent anisotropic bending that dictates how DNA is wrapped around a histone octamer. This application allows users to specify a number of options such as schemes and parameters for threading calculation and provides multiple layout formats. The nuMap is implemented in Java/Perl/MySQL and is freely available for public use at http://numap.rit.edu. The user manual, implementation notes, description of the methodology and examples are available at the site.

  8. Understanding the connection between epigenetic DNA methylation and nucleosome positioning from computer simulations.

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    Guillem Portella

    Full Text Available Cytosine methylation is one of the most important epigenetic marks that regulate the process of gene expression. Here, we have examined the effect of epigenetic DNA methylation on nucleosomal stability using molecular dynamics simulations and elastic deformation models. We found that methylation of CpG steps destabilizes nucleosomes, especially when these are placed in sites where the DNA minor groove faces the histone core. The larger stiffness of methylated CpG steps is a crucial factor behind the decrease in nucleosome stability. Methylation changes the positioning and phasing of the nucleosomal DNA, altering the accessibility of DNA to regulatory proteins, and accordingly gene functionality. Our theoretical calculations highlight a simple physical-based explanation on the foundations of epigenetic signaling.

  9. Dynamic nucleosome organization at hox promoters during zebrafish embryogenesis.

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    Steven E Weicksel

    Full Text Available Nucleosome organization at promoter regions plays an important role in regulating gene activity. Genome-wide studies in yeast, flies, worms, mammalian embryonic stem cells and transformed cell lines have found well-positioned nucleosomes flanking a nucleosome depleted region (NDR at transcription start sites. This nucleosome arrangement depends on DNA sequence (cis-elements as well as DNA binding factors and ATP-dependent chromatin modifiers (trans-factors. However, little is understood about how the nascent embryonic genome positions nucleosomes during development. This is particularly intriguing since the embryonic genome must undergo a broad reprogramming event upon fusion of sperm and oocyte. Using four stages of early embryonic zebrafish development, we map nucleosome positions at the promoter region of 37 zebrafish hox genes. We find that nucleosome arrangement at the hox promoters is a progressive process that takes place over several stages. At stages immediately after fertilization, nucleosomes appear to be largely disordered at hox promoter regions. At stages after activation of the embryonic genome, nucleosomes are detectable at hox promoters, with positions becoming more uniform and more highly occupied. Since the genomic sequence is invariant during embryogenesis, this progressive change in nucleosome arrangement suggests that trans-factors play an important role in organizing nucleosomes during embryogenesis. Separating hox genes into expressed and non-expressed groups shows that expressed promoters have better positioned and occupied nucleosomes, as well as distinct NDRs, than non-expressed promoters. Finally, by blocking the retinoic acid-signaling pathway, we disrupt early hox gene transcription, but observe no effect on nucleosome positions, suggesting that active hox transcription is not a driving force behind the arrangement of nucleosomes at the promoters of hox genes during early development.

  10. Physical properties of naked DNA influence nucleosome positioning and correlate with transcription start and termination sites in yeast

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    Soler-López Montserrat

    2011-10-01

    Full Text Available Abstract Background In eukaryotic organisms, DNA is packaged into chromatin structure, where most of DNA is wrapped into nucleosomes. DNA compaction and nucleosome positioning have clear functional implications, since they modulate the accessibility of genomic regions to regulatory proteins. Despite the intensive research effort focused in this area, the rules defining nucleosome positioning and the location of DNA regulatory regions still remain elusive. Results Naked (histone-free and nucleosomal DNA from yeast were digested by microccocal nuclease (MNase and sequenced genome-wide. MNase cutting preferences were determined for both naked and nucleosomal DNAs. Integration of their sequencing profiles with DNA conformational descriptors derived from atomistic molecular dynamic simulations enabled us to extract the physical properties of DNA on a genomic scale and to correlate them with chromatin structure and gene regulation. The local structure of DNA around regulatory regions was found to be unusually flexible and to display a unique pattern of nucleosome positioning. Ab initio physical descriptors derived from molecular dynamics were used to develop a computational method that accurately predicts nucleosome enriched and depleted regions. Conclusions Our experimental and computational analyses jointly demonstrate a clear correlation between sequence-dependent physical properties of naked DNA and regulatory signals in the chromatin structure. These results demonstrate that nucleosome positioning around TSS (Transcription Start Site and TTS (Transcription Termination Site (at least in yeast is strongly dependent on DNA physical properties, which can define a basal regulatory mechanism of gene expression.

  11. Preferential 5-Methylcytosine Oxidation in the Linker Region of Reconstituted Positioned Nucleosomes by Tet1 Protein.

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    Kizaki, Seiichiro; Zou, Tingting; Li, Yue; Han, Yong-Woon; Suzuki, Yuki; Harada, Yoshie; Sugiyama, Hiroshi

    2016-11-07

    Tet (ten-eleven translocation) family proteins oxidize 5-methylcytosine (mC) to 5-hydroxymethylcytosine (hmC), 5-formylcytosine (fC), and 5-carboxycytosine (caC), and are suggested to be involved in the active DNA demethylation pathway. In this study, we reconstituted positioned mononucleosomes using CpG-methylated 382 bp DNA containing the Widom 601 sequence and recombinant histone octamer, and subjected the nucleosome to treatment with Tet1 protein. The sites of oxidized methylcytosine were identified by bisulfite sequencing. We found that, for the oxidation reaction, Tet1 protein prefers mCs located in the linker region of the nucleosome compared with those located in the core region. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Regulation of BAZ1A and nucleosome positioning in the nucleus accumbens in response to cocaine.

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    Sun, HaoSheng; Damez-Werno, Diane M; Scobie, Kimberly N; Shao, Ning-Yi; Dias, Caroline; Rabkin, Jacqui; Wright, Katherine N; Mouzon, Ezekiell; Kabbaj, Mohamed; Neve, Rachael; Turecki, Gustavo; Shen, Li; Nestler, Eric J

    2017-06-14

    Chromatin regulation, in particular ATP-dependent chromatin remodelers, have previously been shown to be important in the regulation of reward-related behaviors in animal models of mental illnesses. Here we demonstrate that BAZ1A, an accessory subunit of the ISWI family of chromatin remodeling complexes, is downregulated in the nucleus accumbens (NAc) of mice exposed repeatedly to cocaine and of cocaine-addicted humans. Viral-mediated overexpression of BAZ1A in mouse NAc reduces cocaine reward as assessed by conditioned place preference (CPP), but increases cocaine-induced locomotor activation. Furthermore, we investigate nucleosome repositioning genome-wide by conducting chromatin immunoprecipitation (ChIP)-sequencing for total H3 in NAc of control mice and after repeated cocaine administration, and find extensive nucleosome occupancy and shift changes across the genome in response to cocaine exposure. These findings implicate BAZ1A in molecular and behavioral plasticity to cocaine and offer new insight into the pathophysiology of cocaine addiction. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  13. Nucleosome Organization in Human Embryonic Stem Cells.

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    Puya G Yazdi

    Full Text Available The fundamental repeating unit of eukaryotic chromatin is the nucleosome. Besides being involved in packaging DNA, nucleosome organization plays an important role in transcriptional regulation and cellular identity. Currently, there is much debate about the major determinants of the nucleosome architecture of a genome and its significance with little being known about its role in stem cells. To address these questions, we performed ultra-deep sequencing of nucleosomal DNA in two human embryonic stem cell lines and integrated our data with numerous epigenomic maps. Our analyses have revealed that the genome is a determinant of nucleosome organization with transcriptionally inactive regions characterized by a "ground state" of nucleosome profiles driven by underlying DNA sequences. DNA sequence preferences are associated with heterogeneous chromatin organization around transcription start sites. Transcription, histone modifications, and DNA methylation alter this "ground state" by having distinct effects on both nucleosome positioning and occupancy. As the transcriptional rate increases, nucleosomes become better positioned. Exons transcribed and included in the final spliced mRNA have distinct nucleosome profiles in comparison to exons not included at exon-exon junctions. Genes marked by the active modification H3K4m3 are characterized by lower nucleosome occupancy before the transcription start site compared to genes marked by the inactive modification H3K27m3, while bivalent domains, genes associated with both marks, lie exactly in the middle. Combinatorial patterns of epigenetic marks (chromatin states are associated with unique nucleosome profiles. Nucleosome organization varies around transcription factor binding in enhancers versus promoters. DNA methylation is associated with increasing nucleosome occupancy and different types of methylations have distinct location preferences within the nucleosome core particle. Finally, computational

  14. Dissecting relative contributions of cis- and trans-determinants to nucleosome distribution by comparing Tetrahymena macronuclear and micronuclear chromatin.

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    Xiong, Jie; Gao, Shan; Dui, Wen; Yang, Wentao; Chen, Xiao; Taverna, Sean D; Pearlman, Ronald E; Ashlock, Wendy; Miao, Wei; Liu, Yifan

    2016-12-01

    The ciliate protozoan Tetrahymena thermophila contains two types of structurally and functionally differentiated nuclei: the transcriptionally active somatic macronucleus (MAC) and the transcriptionally silent germ-line micronucleus (MIC). Here, we demonstrate that MAC features well-positioned nucleosomes downstream of transcription start sites and flanking splice sites. Transcription-associated trans-determinants promote nucleosome positioning in MAC. By contrast, nucleosomes in MIC are dramatically delocalized. Nucleosome occupancy in MAC and MIC are nonetheless highly correlated with each other, as well as with in vitro reconstitution and predictions based upon DNA sequence features, revealing unexpectedly strong contributions from cis-determinants. In particular, well-positioned nucleosomes are often matched with GC content oscillations. As many nucleosomes are coordinately accommodated by both cis- and trans-determinants, we propose that their distribution is shaped by the impact of these nucleosomes on the mutational and transcriptional landscape, and driven by evolutionary selection. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  15. Co-Positivity for Anti-dsDNA, -Nucleosome and -Histone Antibodies in Lupus Nephritis Is Indicative of High Serum Levels and Severe Nephropathy.

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    Jinfeng Yang

    Full Text Available To characterize the significance of correlated autoantibodies in systemic lupus erythematosus (SLE and its complication lupus nephritis (LN in a large cohort of patients.Clinical data were statistically analyzed in 1699 SLE patients with or without nephritis who were diagnosed and treated during 2002-2013 in the northeast region of China. Reactivity to a list of 16 autoantibodies was detected by the serum test Euroline ANA profile (IgG. Serum titers of the anti-nucleosome autoantibodies were measured by ELISA assays. Kidney biopsies were examined by pathologists. Immune complex deposition was identified by immunohistochemistry stain.Simultaneous positivity of anti-dsDNA, -nucleosome and -histone antibodies (3-pos was prevalent in SLE patients with LN compared to Non-renal SLE patients (41% vs 11%, p< 0.001. Significant correlations were found between any two of the above three anti-nucleosome antibodies in LN patients. In comparison to non-3-pos cohorts, 3-pos patients with LN had significantly higher serum levels of the three antibodies and more active disease; was associated with type IV disease; suffered from more severe renal damages; received more intensive treatment and had worse disease outcome. The serum levels of these three autoantibodies in 3-pos LN patients were significantly decreased when they underwent clinical recovery.Simultaneous reactivity to anti-dsDNA, -nucleosome and -histone antibodies by Euroline ANA profile (IgG may indicate severe nephropathy in patients with SLE.

  16. PGC1α −1 Nucleosome Position and Splice Variant Expression and Cardiovascular Disease Risk in Overweight and Obese Individuals

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    Tara M. Henagan

    2014-01-01

    Full Text Available PGC1α, a transcriptional coactivator, interacts with PPARs and others to regulate skeletal muscle metabolism. PGC1α undergoes splicing to produce several mRNA variants, with the NTPGC1α variant having a similar biological function to the full length PGC1α (FLPGC1α. CVD is associated with obesity and T2D and a lower percentage of type 1 oxidative fibers and impaired mitochondrial function in skeletal muscle, characteristics determined by PGC1α expression. PGC1α expression is epigenetically regulated in skeletal muscle to determine mitochondrial adaptations, and epigenetic modifications may regulate mRNA splicing. We report in this paper that skeletal muscle PGC1α  −1 nucleosome (−1N position is associated with splice variant NTPGC1α but not FLPGC1α expression. Division of participants based on the −1N position revealed that those individuals with a −1N phased further upstream from the transcriptional start site (UP expressed lower levels of NTPGC1α than those with the −1N more proximal to TSS (DN. UP showed an increase in body fat percentage and serum total and LDL cholesterol. These findings suggest that the −1N may be a potential epigenetic regulator of NTPGC1α splice variant expression, and −1N position and NTPGC1α variant expression in skeletal muscle are linked to CVD risk. This trial is registered with clinicaltrials.gov, identifier NCT00458133.

  17. Skeletal Muscle PGC1α -1 Nucleosome Position and -260 nt DNA Methylation Determine Exercise Response and Prevent Ectopic Lipid Accumulation in Men.

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    Bajpeyi, Sudip; Covington, Jeffrey D; Taylor, Erin M; Stewart, Laura K; Galgani, Jose E; Henagan, Tara M

    2017-07-01

    Endurance exercise has been shown to improve lipid oxidation and increase mitochondrial content in skeletal muscle, two features that have shown dependence on increased expression of the peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α). It is also hypothesized that exercise-related alterations in PGC1α expression occur through epigenetic regulation of nucleosome positioning in association with differential DNA methylation status within the PGC1α promoter. In this study, we show that when primary human myotubes from obese patients with type 2 diabetes are exposed to lipolytic stimulus (palmitate, forskolin, inomycin) in vitro, nucleosome occupancy surrounding the -260 nucleotide (nt) region, a known regulatory DNA methylation site, is reduced. This finding is reproduced in vivo in the vastus lateralis from 11 healthy males after a single, long endurance exercise bout in which participants expended 650 kcal. Additionally, we show a significant positive correlation between fold change of PGC1α messenger RNA expression and -1 nucleosome repositioning away from the -260 nt methylation site in skeletal muscle tissue following exercise. Finally, we found that when exercise participants are divided into high and low responders based on the -260 nt methylation status, the -1 nucleosome is repositioned away from the regulatory -260 nt methylation site in high responders, those exhibiting a significant decrease in -260 nt methylation, but not in low responders. Additionally, high but not low responders showed a significant decrease in intramyocellular lipid content after exercise. These findings suggest a potential target for epigenetic modification of the PGC1α promoter to stimulate the therapeutic effects of endurance exercise in skeletal muscle. Copyright © 2017 Endocrine Society.

  18. Theoretical analysis of epigenetic cell memory by nucleosome modification

    DEFF Research Database (Denmark)

    Dodd, Ian B; Micheelsen, Mille A; Sneppen, Kim

    2007-01-01

    to involve positive feedback where modified nucleosomes recruit enzymes that similarly modify nearby nucleosomes. We developed a simplified stochastic model for dynamic nucleosome modification based on the silent mating-type region of the yeast Schizosaccharomyces pombe. We show that the mechanism can give...

  19. Comparative assessment of surgeons' task performance and surgical ergonomics associated with conventional and modified flank positions: a simulation study.

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    Fan, Yu; Kong, Gaiqing; Meng, Yisen; Tan, Shutao; Wei, Kunlin; Zhang, Qian; Jin, Jie

    2014-11-01

    Flank position is extensively used in retroperitoneoscopic urological practice. Most surgeons follow the patients' position in open approaches. However, surgical ergonomics of the conventional position in the retroperitoneoscopic surgery is poor. We introduce a modified position and evaluated task performance and surgical ergonomics of both positions with simulated surgical tasks. Twenty-one novice surgeons were recruited to perform four tasks: bead transfer, ring transfer, continuous suturing, and cutting a circle. The conventional position was simulated by setting an endo-surgical simulator parallel to the long axis of a surgical desk. The modified position was simulated by rotating the simulator 30° with respect to the long axis of the desk. The outcome measurements include task performance measures, kinematic measures for body alignment, surface electromyography, relative loading between feet, and subjective ratings of fatigue. We observed significant improvements in both task performance and surgical ergonomics parameters under the modified position. For all four tasks, subjects finished tasks faster with higher accuracy (p ergonomics part: (1) The angle between the upper body and the head was decreased by 7.4 ± 1.7°; (2) The EMG amplitude collected from shoulders and left lumber was significantly lower (p ergonomics. With a simulated surgery, we demonstrated that our modified position could significantly improve task performance and surgical ergonomics. Further studies are still warranted to validate these benefits for both patients and surgeons.

  20. Flank pain

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    ... how to do these exercises at home. Nonsteroidal anti-inflammatory drugs (NSAIDs) and physical therapy may be prescribed for flank pain caused by spinal arthritis. Antibiotics are used to treat most kidney infections. You ...

  1. Nucleosome-coupled expression differences in closely-related species

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    Gebbia Marinella

    2011-09-01

    Full Text Available Abstract Background Genome-wide nucleosome occupancy is negatively related to the average level of transcription factor motif binding based on studies in yeast and several other model organisms. The degree to which nucleosome-motif interactions relate to phenotypic changes across species is, however, unknown. Results We address this challenge by generating nucleosome positioning and cell cycle expression data for Saccharomyces bayanus and show that differences in nucleosome occupancy reflect cell cycle expression divergence between two yeast species, S. bayanus and S. cerevisiae. Specifically, genes with nucleosome-depleted MBP1 motifs upstream of their coding sequence show periodic expression during the cell cycle, whereas genes with nucleosome-shielded motifs do not. In addition, conserved cell cycle regulatory motifs across these two species are more nucleosome-depleted compared to those that are not conserved, suggesting that the degree of conservation of regulatory sites varies, and is reflected by nucleosome occupancy patterns. Finally, many changes in cell cycle gene expression patterns across species can be correlated to changes in nucleosome occupancy on motifs (rather than to the presence or absence of motifs. Conclusions Our observations suggest that alteration of nucleosome occupancy is a previously uncharacterized feature related to the divergence of cell cycle expression between species.

  2. Exploring the Link between Nucleosome Occupancy and DNA Methylation

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    Cecilia Lövkvist

    2018-01-01

    Full Text Available Near promoters, both nucleosomes and CpG sites form characteristic spatial patterns. Previously, nucleosome depleted regions were observed upstream of transcription start sites and nucleosome occupancy was reported to correlate both with CpG density and the level of CpG methylation. Several studies imply a causal link where CpG methylation might induce nucleosome formation, whereas others argue the opposite, i.e., that nucleosome occupancy might influence CpG methylation. Correlations are indeed evident between nucleosomes, CpG density and CpG methylation—at least near promoter sites. It is however less established whether there is an immediate causal relation between nucleosome occupancy and the presence of CpG sites—or if nucleosome occupancy could be influenced by other factors. In this work, we test for such causality in human genomes by analyzing the three quantities both near and away from promoter sites. For data from the human genome we compare promoter regions with given CpG densities with genomic regions without promoters but of similar CpG densities. We find the observed correlation between nucleosome occupancy and CpG density, respectively CpG methylation, to be specific to promoter regions. In other regions along the genome nucleosome occupancy is statistically independent of the positioning of CpGs or their methylation levels. Anti-correlation between CpG density and methylation level is however similarly strong in both regions. On promoters, nucleosome occupancy is more strongly affected by the level of gene expression than CpG density or CpG methylation—calling into question any direct causal relation between nucleosome occupancy and CpG organization. Rather, our results suggest that for organisms with cytosine methylation nucleosome occupancy might be primarily linked to gene expression, with no strong impact on methylation.

  3. Baculoviruses and nucleosome management

    International Nuclear Information System (INIS)

    Volkman, Loy E.

    2015-01-01

    Negatively-supercoiled-ds DNA molecules, including the genomes of baculoviruses, spontaneously wrap around cores of histones to form nucleosomes when present within eukaryotic nuclei. Hence, nucleosome management should be essential for baculovirus genome replication and temporal regulation of transcription, but this has not been documented. Nucleosome mobilization is the dominion of ATP-dependent chromatin-remodeling complexes. SWI/SNF and INO80, two of the best-studied complexes, as well as chromatin modifier TIP60, all contain actin as a subunit. Retrospective analysis of results of AcMNPV time course experiments wherein actin polymerization was blocked by cytochalasin D drug treatment implicate actin-containing chromatin modifying complexes in decatenating baculovirus genomes, shutting down host transcription, and regulating late and very late phases of viral transcription. Moreover, virus-mediated nuclear localization of actin early during infection may contribute to nucleosome management. - Highlights: • Baculoviruses have negatively-supercoiled, circular ds DNA. • Negatively-supercoiled DNA spontaneously forms nucleosomes in the nucleus. • Nucleosomes must be mobilized for replication and transcription to proceed. • Actin-containing chromatin modifiers participate in baculovirus replication

  4. Baculoviruses and nucleosome management

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    Volkman, Loy E., E-mail: lvolkman@berkeley.edu

    2015-02-15

    Negatively-supercoiled-ds DNA molecules, including the genomes of baculoviruses, spontaneously wrap around cores of histones to form nucleosomes when present within eukaryotic nuclei. Hence, nucleosome management should be essential for baculovirus genome replication and temporal regulation of transcription, but this has not been documented. Nucleosome mobilization is the dominion of ATP-dependent chromatin-remodeling complexes. SWI/SNF and INO80, two of the best-studied complexes, as well as chromatin modifier TIP60, all contain actin as a subunit. Retrospective analysis of results of AcMNPV time course experiments wherein actin polymerization was blocked by cytochalasin D drug treatment implicate actin-containing chromatin modifying complexes in decatenating baculovirus genomes, shutting down host transcription, and regulating late and very late phases of viral transcription. Moreover, virus-mediated nuclear localization of actin early during infection may contribute to nucleosome management. - Highlights: • Baculoviruses have negatively-supercoiled, circular ds DNA. • Negatively-supercoiled DNA spontaneously forms nucleosomes in the nucleus. • Nucleosomes must be mobilized for replication and transcription to proceed. • Actin-containing chromatin modifiers participate in baculovirus replication.

  5. Coupling of replisome movement with nucleosome dynamics can contribute to the parent-daughter information transfer.

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    Bameta, Tripti; Das, Dibyendu; Padinhateeri, Ranjith

    2018-06-01

    Positioning of nucleosomes along the genomic DNA is crucial for many cellular processes that include gene regulation and higher order packaging of chromatin. The question of how nucleosome-positioning information from a parent chromatin gets transferred to the daughter chromatin is highly intriguing. Accounting for experimentally known coupling between replisome movement and nucleosome dynamics, we propose a model that can obtain de novo nucleosome assembly similar to what is observed in recent experiments. Simulating nucleosome dynamics during replication, we argue that short pausing of the replication fork, associated with nucleosome disassembly, can be a event crucial for communicating nucleosome positioning information from parent to daughter. We show that the interplay of timescales between nucleosome disassembly (τp) at the replication fork and nucleosome sliding behind the fork (τs) can give rise to a rich 'phase diagram' having different inherited patterns of nucleosome organization. Our model predicts that only when τp ≥ τs the daughter chromatin can inherit nucleosome positioning of the parent.

  6. The Chd1 Chromatin Remodeler Shifts Nucleosomal DNA Bidirectionally as a Monomer

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    Qiu, Yupeng; Levendosky, Robert F.; Chakravarthy, Srinivas; Patel, Ashok; Bowman, Gregory D.; Myong, Sua

    2017-10-01

    Chromatin remodelers catalyze dynamic packaging of the genome by carrying out nucleosome assembly/disassembly, histone exchange, and nucleosome repositioning. Remodeling results in evenly spaced nucleosomes, which requires probing both sides of the nucleosome, yet the way remodelers organize sliding activity to achieve this task is not understood. Here, we show that the monomeric Chd1 remodeler shifts DNA back and forth by dynamically alternating between different segments of the nucleosome. During sliding, Chd1 generates unstable remodeling intermediates that spontaneously relax to a pre-remodeled position. We demonstrate that nucleosome sliding is tightly controlled by two regulatory domains: the DNA-binding domain, which interferes with sliding when its range is limited by a truncated linking segment, and the chromodomains, which play a key role in substrate discrimination. We propose that active interplay of the ATPase motor with the regulatory domains may promote dynamic nucleosome structures uniquely suited for histone exchange and chromatin reorganization during transcription.

  7. Links between DNA methylation and nucleosome occupancy in the human genome.

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    Collings, Clayton K; Anderson, John N

    2017-01-01

    DNA methylation is an epigenetic modification that is enriched in heterochromatin but depleted at active promoters and enhancers. However, the debate on whether or not DNA methylation is a reliable indicator of high nucleosome occupancy has not been settled. For example, the methylation levels of DNA flanking CTCF sites are higher in linker DNA than in nucleosomal DNA, while other studies have shown that the nucleosome core is the preferred site of methylation. In this study, we make progress toward understanding these conflicting phenomena by implementing a bioinformatics approach that combines MNase-seq and NOMe-seq data and by comprehensively profiling DNA methylation and nucleosome occupancy throughout the human genome. The results demonstrated that increasing methylated CpG density is correlated with nucleosome occupancy in the total genome and within nearly all subgenomic regions. Features with elevated methylated CpG density such as exons, SINE-Alu sequences, H3K36-trimethylated peaks, and methylated CpG islands are among the highest nucleosome occupied elements in the genome, while some of the lowest occupancies are displayed by unmethylated CpG islands and unmethylated transcription factor binding sites. Additionally, outside of CpG islands, the density of CpGs within nucleosomes was shown to be important for the nucleosomal location of DNA methylation with low CpG frequencies favoring linker methylation and high CpG frequencies favoring core particle methylation. Prominent exceptions to the correlations between methylated CpG density and nucleosome occupancy include CpG islands marked by H3K27me3 and CpG-poor heterochromatin marked by H3K9me3, and these modifications, along with DNA methylation, distinguish the major silencing mechanisms of the human epigenome. Thus, the relationship between DNA methylation and nucleosome occupancy is influenced by the density of methylated CpG dinucleotides and by other epigenomic components in chromatin.

  8. Abo1, a conserved bromodomain AAA?ATPase, maintains global nucleosome occupancy and organisation

    OpenAIRE

    Gal, Csenge; Murton, Heather E; Subramanian, Lakxmi; Whale, Alex J; Moore, Karen M; Paszkiewicz, Konrad; Codlin, Sandra; B?hler, J?rg; Creamer, Kevin M; Partridge, Janet F; Allshire, Robin C; Kent, Nicholas A; Whitehall, Simon K

    2015-01-01

    Maintenance of the correct level and organisation of nucleosomes is crucial for genome function. Here, we uncover a role for a conserved bromodomain AAA-ATPase, Abo1, in the maintenance of nucleosome architecture in fission yeast. Cells lacking abo1+ experience both a reduction and mis-positioning of nucleosomes at transcribed sequences in addition to increased intragenic transcription, phenotypes that are hallmarks of defective chromatin re-establishment behind RNA polymerase II. Abo1 is rec...

  9. Role of nucleosome remodeling in neurodevelopmental and intellectual disability disorders

    Directory of Open Access Journals (Sweden)

    Alberto J Lopez

    2015-04-01

    Full Text Available It is becoming increasingly important to understand how epigenetic mechanisms control gene expression during neurodevelopment. Two epigenetic mechanisms that have received considerable attention are DNA methylation and histone acetylation. Human exome sequencing and genome-wide association studies have linked several neurobiological disorders to genes whose products actively regulate DNA methylation and histone acetylation. More recently, a third major epigenetic mechanism, nucleosome remodeling, has been implicated in human developmental and intellectual disability disorders. Nucleosome remodeling is driven primarily through nucleosome remodeling complexes with specialized ATP-dependent enzymes. These enzymes directly interact with DNA or chromatin structure, as well as histone subunits, to restructure the shape and organization of nucleosome positioning to ultimately regulate gene expression. Of particular interest is the neuron-specific Brg1/hBrm Associated Factor (nBAF complex. Mutations in nBAF subunit genes have so far been linked to Coffin-Siris syndrome, Nicolaides-Baraitser syndrome, schizophrenia, and Autism Spectrum Disorder. Together, these human developmental and intellectual disability disorders are powerful examples of the impact of epigenetic modulation on gene expression. This review focuses on the new and emerging role of nucleosome remodeling in neurodevelopmental and intellectual disability disorders and whether nucleosome remodeling affects gene expression required for cognition independently of its role in regulating gene expression required for development.

  10. Role of nucleosome remodeling in neurodevelopmental and intellectual disability disorders.

    Science.gov (United States)

    López, Alberto J; Wood, Marcelo A

    2015-01-01

    It is becoming increasingly important to understand how epigenetic mechanisms control gene expression during neurodevelopment. Two epigenetic mechanisms that have received considerable attention are DNA methylation and histone acetylation. Human exome sequencing and genome-wide association studies have linked several neurobiological disorders to genes whose products actively regulate DNA methylation and histone acetylation. More recently, a third major epigenetic mechanism, nucleosome remodeling, has been implicated in human developmental and intellectual disability (ID) disorders. Nucleosome remodeling is driven primarily through nucleosome remodeling complexes with specialized ATP-dependent enzymes. These enzymes directly interact with DNA or chromatin structure, as well as histone subunits, to restructure the shape and organization of nucleosome positioning to ultimately regulate gene expression. Of particular interest is the neuron-specific Brg1/hBrm Associated Factor (nBAF) complex. Mutations in nBAF subunit genes have so far been linked to Coffin-Siris syndrome (CSS), Nicolaides-Baraitser syndrome (NBS), schizophrenia, and Autism Spectrum Disorder (ASD). Together, these human developmental and ID disorders are powerful examples of the impact of epigenetic modulation on gene expression. This review focuses on the new and emerging role of nucleosome remodeling in neurodevelopmental and ID disorders and whether nucleosome remodeling affects gene expression required for cognition independently of its role in regulating gene expression required for development.

  11. Identification of nucleosome assembly protein 1 (NAP1) as an interacting partner of plant ribosomal protein S6 (RPS6) and a positive regulator of rDNA transcription

    Energy Technology Data Exchange (ETDEWEB)

    Son, Ora [Department of Biological Science, Sookmyung Women' s University, Seoul 140-742 (Korea, Republic of); Kim, Sunghan [Department of Biological Science, Sookmyung Women' s University, Seoul 140-742 (Korea, Republic of); Department of Plant Science, Plant Genomics and Breeding Institute, Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 151-921 (Korea, Republic of); Shin, Yun-jeong [Department of Biological Science, Sookmyung Women' s University, Seoul 140-742 (Korea, Republic of); Kim, Woo-Young [College of Pharmacy, Sookmyung Women' s University, Seoul 140-742 (Korea, Republic of); Koh, Hee-Jong, E-mail: heejkoh@snu.ac.kr [Department of Plant Science, Plant Genomics and Breeding Institute, Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 151-921 (Korea, Republic of); Cheon, Choong-Ill, E-mail: ccheon@sookmyung.ac.kr [Department of Biological Science, Sookmyung Women' s University, Seoul 140-742 (Korea, Republic of)

    2015-09-18

    The ribosomal protein S6 (RPS6) is a downstream component of the signaling mediated by the target of rapamycin (TOR) kinase that acts as a central regulator of the key metabolic processes, such as protein translation and ribosome biogenesis, in response to various environmental cues. In our previous study, we identified a novel role of plant RPS6, which negatively regulates rDNA transcription, forming a complex with a plant-specific histone deacetylase, AtHD2B. Here we report that the Arabidopsis RPS6 interacts additionally with a histone chaperone, nucleosome assembly protein 1(AtNAP1;1). The interaction does not appear to preclude the association of RPS6 with AtHD2B, as the AtNAP1 was also able to interact with AtHD2B as well as with an RPS6-AtHD2B fusion protein in the BiFC assay and pulldown experiment. Similar to a positive effect of the ribosomal S6 kinase 1 (AtS6K1) on rDNA transcription observed in this study, overexpression or down regulation of the AtNAP1;1 resulted in concomitant increase and decrease, respectively, in rDNA transcription suggesting a positive regulatory role played by AtNAP1 in plant rDNA transcription, possibly through derepression of the negative effect of the RPS6-AtHD2B complex. - Highlights: • Nucleosome assembly protein 1 (AtNAP1) interacts with RPS6 as well as with AtHD2B. • rDNA transcription is regulated S6K1. • Overexpression or down regulation of AtNAP1 results in concomitant increase or decrease in rDNA transcription.

  12. Multiple distinct stimuli increase measured nucleosome occupancy around human promoters.

    Directory of Open Access Journals (Sweden)

    Chuong D Pham

    Full Text Available Nucleosomes can block access to transcription factors. Thus the precise localization of nucleosomes relative to transcription start sites and other factor binding sites is expected to be a critical component of transcriptional regulation. Recently developed microarray approaches have allowed the rapid mapping of nucleosome positions over hundreds of kilobases (kb of human genomic DNA, although these approaches have not yet been widely used to measure chromatin changes associated with changes in transcription. Here, we use custom tiling microarrays to reveal changes in nucleosome positions and abundance that occur when hormone-bound glucocorticoid receptor (GR binds to sites near target gene promoters in human osteosarcoma cells. The most striking change is an increase in measured nucleosome occupancy at sites spanning ∼1 kb upstream and downstream of transcription start sites, which occurs one hour after addition of hormone, but is lost at 4 hours. Unexpectedly, this increase was seen both on GR-regulated and GR-non-regulated genes. In addition, the human SWI/SNF chromatin remodeling factor (a GR co-activator was found to be important for increased occupancy upon hormone treatment and also for low nucleosome occupancy without hormone. Most surprisingly, similar increases in nucleosome occupancy were also seen on both regulated and non-regulated promoters during differentiation of human myeloid leukemia cells and upon activation of human CD4+ T-cells. These results indicate that dramatic changes in chromatin structure over ∼2 kb of human promoters may occur genomewide and in response to a variety of stimuli, and suggest novel models for transcriptional regulation.

  13. Deposition of nucleosomal antigens (histones and DNA) in the epidermal basement membrane in human lupus nephritis.

    NARCIS (Netherlands)

    Grootscholten, C.; Bruggen, M.C.J. van; Pijl, J.W. van der; Jong, E.M.G.J. de; Ligtenberg, G.; Derksen, R.H.W.M.; Berden, J.H.M.

    2003-01-01

    OBJECTIVE: Antinuclear autoantibodies complexed to nucleosomes can bind to heparan sulfate (HS) in the glomerular basement membrane. This binding is due to the binding of the positively charged histones to the strongly anionic HS. Nucleosomes and histones have been identified in glomerular deposits

  14. Multiple aspects of ATP-dependent nucleosome translocation by RSC and Mi-2 are directed by the underlying DNA sequence.

    Directory of Open Access Journals (Sweden)

    Joke J F A van Vugt

    Full Text Available BACKGROUND: Chromosome structure, DNA metabolic processes and cell type identity can all be affected by changing the positions of nucleosomes along chromosomal DNA, a reaction that is catalysed by SNF2-type ATP-driven chromatin remodelers. Recently it was suggested that in vivo, more than 50% of the nucleosome positions can be predicted simply by DNA sequence, especially within promoter regions. This seemingly contrasts with remodeler induced nucleosome mobility. The ability of remodeling enzymes to mobilise nucleosomes over short DNA distances is well documented. However, the nucleosome translocation processivity along DNA remains elusive. Furthermore, it is unknown what determines the initial direction of movement and how new nucleosome positions are adopted. METHODOLOGY/PRINCIPAL FINDINGS: We have used AFM imaging and high resolution PAGE of mononucleosomes on 600 and 2500 bp DNA molecules to analyze ATP-dependent nucleosome repositioning by native and recombinant SNF2-type enzymes. We report that the underlying DNA sequence can control the initial direction of translocation, translocation distance, as well as the new positions adopted by nucleosomes upon enzymatic mobilization. Within a strong nucleosomal positioning sequence both recombinant Drosophila Mi-2 (CHD-type and native RSC from yeast (SWI/SNF-type repositioned the nucleosome at 10 bp intervals, which are intrinsic to the positioning sequence. Furthermore, RSC-catalyzed nucleosome translocation was noticeably more efficient when beyond the influence of this sequence. Interestingly, under limiting ATP conditions RSC preferred to position the nucleosome with 20 bp intervals within the positioning sequence, suggesting that native RSC preferentially translocates nucleosomes with 15 to 25 bp DNA steps. CONCLUSIONS/SIGNIFICANCE: Nucleosome repositioning thus appears to be influenced by both remodeler intrinsic and DNA sequence specific properties that interplay to define ATPase

  15. The size of the nucleosome

    DEFF Research Database (Denmark)

    Bohr, Jakob; Olsen, Kasper

    2011-01-01

    is a necessity when allowing for transient tensile stresses during the reorganization of DNA, e.g., during the reposition, or sliding, of a nucleosome along the DNA double helix. The mathematical model we apply is based on a tubular description of double helices assuming hard walls. When the base...

  16. Nucleosome organizations in induced pluripotent stem cells reprogrammed from somatic cells belonging to three different germ layers.

    Science.gov (United States)

    Tao, Yu; Zheng, Weisheng; Jiang, Yonghua; Ding, Guitao; Hou, Xinfeng; Tang, Yitao; Li, Yueying; Gao, Shuai; Chang, Gang; Zhang, Xiaobai; Liu, Wenqiang; Kou, Xiaochen; Wang, Hong; Jiang, Cizhong; Gao, Shaorong

    2014-12-21

    Nucleosome organization determines the chromatin state, which in turn controls gene expression or silencing. Nucleosome remodeling occurs during somatic cell reprogramming, but it is still unclear to what degree the re-established nucleosome organization of induced pluripotent stem cells (iPSCs) resembles embryonic stem cells (ESCs), and whether the iPSCs inherit some residual gene expression from the parental fibroblast cells. We generated genome-wide nucleosome maps in mouse ESCs and in iPSCs reprogrammed from somatic cells belonging to three different germ layers using a secondary reprogramming system. Pairwise comparisons showed that the nucleosome organizations in the iPSCs, regardless of the iPSCs' tissue of origin, were nearly identical to the ESCs, but distinct from mouse embryonic fibroblasts (MEF). There is a canonical nucleosome arrangement of -1, nucleosome depletion region, +1, +2, +3, and so on nucleosomes around the transcription start sites of active genes whereas only a nucleosome occupies silent transcriptional units. Transcription factor binding sites possessed characteristic nucleosomal architecture, such that their access was governed by the rotational and translational settings of the nucleosome. Interestingly, the tissue-specific genes were highly expressed only in the parental somatic cells of the corresponding iPS cell line before reprogramming, but had a similar expression level in all the resultant iPSCs and ESCs. The re-established nucleosome landscape during nuclear reprogramming provides a conserved setting for accessibility of DNA sequences in mouse pluripotent stem cells. No persistent residual expression program or nucleosome positioning of the parental somatic cells that reflected their tissue of origin was passed on to the resulting mouse iPSCs.

  17. A species-specific nucleosomal signature defines a periodic distribution of amino acids in proteins.

    Science.gov (United States)

    Quintales, Luis; Soriano, Ignacio; Vázquez, Enrique; Segurado, Mónica; Antequera, Francisco

    2015-04-01

    Nucleosomes are the basic structural units of chromatin. Most of the yeast genome is organized in a pattern of positioned nucleosomes that is stably maintained under a wide range of physiological conditions. In this work, we have searched for sequence determinants associated with positioned nucleosomes in four species of fission and budding yeasts. We show that mononucleosomal DNA follows a highly structured base composition pattern, which differs among species despite the high degree of histone conservation. These nucleosomal signatures are present in transcribed and non-transcribed regions across the genome. In the case of open reading frames, they correctly predict the relative distribution of codons on mononucleosomal DNA, and they also determine a periodicity in the average distribution of amino acids along the proteins. These results establish a direct and species-specific connection between the position of each codon around the histone octamer and protein composition.

  18. Asymmetric binding of histone H1 stabilizes MMTV nucleosomes and the interaction of progesterone receptor with the exposed HRE.

    Science.gov (United States)

    Vicent, Guillermo P; Meliá, María J; Beato, Miguel

    2002-11-29

    Packaging of mouse mammary tumor virus (MMTV) promoter sequences in nucleosomes modulates access of DNA binding proteins and influences the interaction among DNA bound transcription factors. Here we analyze the binding of histone H1 to MMTV mononucleosomes assembled with recombinant histones and study its influence on nucleosome structure and stability as well as on progesterone receptor (PR) binding to the hormone responsive elements (HREs). The MMTV nucleosomes can be separated into three main populations, two of which exhibited precise translational positioning. Histone H1 bound preferentially to the 5' distal nucleosomal DNA protecting additional 27-28 nt from digestion by micrococcal nuclease. Binding of histone H1 was unaffected by prior crosslinking of protein and DNA in nucleosomes with formaldehyde. Neither the translational nor the rotational nucleosome positioning was altered by histone H1 binding, but the nucleosomes were stabilized as judged by the kinetics of nuclease cleavage. Unexpectedly, binding of recombinant PR to the exposed distal HRE-I in nucleosomes was enhanced in the presence of histone H1, as demonstrated by band shift and footprinting experiments. This enhanced PR affinity may contribute to the reported positive effect of histone H1 on the hormonal activation of MMTV reporter genes.

  19. Sequence periodicity in nucleosomal DNA and intrinsic curvature.

    Science.gov (United States)

    Nair, T Murlidharan

    2010-05-17

    Most eukaryotic DNA contained in the nucleus is packaged by wrapping DNA around histone octamers. Histones are ubiquitous and bind most regions of chromosomal DNA. In order to achieve smooth wrapping of the DNA around the histone octamer, the DNA duplex should be able to deform and should possess intrinsic curvature. The deformability of DNA is a result of the non-parallelness of base pair stacks. The stacking interaction between base pairs is sequence dependent. The higher the stacking energy the more rigid the DNA helix, thus it is natural to expect that sequences that are involved in wrapping around the histone octamer should be unstacked and possess intrinsic curvature. Intrinsic curvature has been shown to be dictated by the periodic recurrence of certain dinucleotides. Several genome-wide studies directed towards mapping of nucleosome positions have revealed periodicity associated with certain stretches of sequences. In the current study, these sequences have been analyzed with a view to understand their sequence-dependent structures. Higher order DNA structures and the distribution of molecular bend loci associated with 146 base nucleosome core DNA sequence from C. elegans and chicken have been analyzed using the theoretical model for DNA curvature. The curvature dispersion calculated by cyclically permuting the sequences revealed that the molecular bend loci were delocalized throughout the nucleosome core region and had varying degrees of intrinsic curvature. The higher order structures associated with nucleosomes of C.elegans and chicken calculated from the sequences revealed heterogeneity with respect to the deviation of the DNA axis. The results points to the possibility of context dependent curvature of varying degrees to be associated with nucleosomal DNA.

  20. Characterization of Dnmt1 Binding and DNA Methylation on Nucleosomes and Nucleosomal Arrays.

    Directory of Open Access Journals (Sweden)

    Anna Schrader

    Full Text Available The packaging of DNA into nucleosomes and the organisation into higher order structures of chromatin limits the access of sequence specific DNA binding factors to DNA. In cells, DNA methylation is preferentially occuring in the linker region of nucleosomes, suggesting a structural impact of chromatin on DNA methylation. These observations raise the question whether DNA methyltransferases are capable to recognize the nucleosomal substrates and to modify the packaged DNA. Here, we performed a detailed analysis of nucleosome binding and nucleosomal DNA methylation by the maintenance DNA methyltransferase Dnmt1. Our binding studies show that Dnmt1 has a DNA length sensing activity, binding cooperatively to DNA, and requiring a minimal DNA length of 20 bp. Dnmt1 needs linker DNA to bind to nucleosomes and most efficiently recognizes nucleosomes with symmetric DNA linkers. Footprinting experiments reveal that Dnmt1 binds to both DNA linkers exiting the nucleosome core. The binding pattern correlates with the efficient methylation of DNA linkers. However, the enzyme lacks the ability to methylate nucleosomal CpG sites on mononucleosomes and nucleosomal arrays, unless chromatin remodeling enzymes create a dynamic chromatin state. In addition, our results show that Dnmt1 functionally interacts with specific chromatin remodeling enzymes to enable complete methylation of hemi-methylated DNA in chromatin.

  1. Genome-wide nucleosome occupancy and DNA methylation profiling of four human cell lines

    Directory of Open Access Journals (Sweden)

    Aaron L. Statham

    2015-03-01

    Full Text Available DNA methylation and nucleosome positioning are two key mechanisms that contribute to the epigenetic control of gene expression. During carcinogenesis, the expression of many genes is altered alongside extensive changes in the epigenome, with repressed genes often being associated with local DNA hypermethylation and gain of nucleosomes at their promoters. However the spectrum of alterations that occur at distal regulatory regions has not been extensively studied. To address this we used Nucleosome Occupancy and Methylation sequencing (NOMe-seq to compare the genome-wide DNA methylation and nucleosome occupancy profiles between normal and cancer cell line models of the breast and prostate. Here we describe the bioinformatic pipeline and methods that we developed for the processing and analysis of the NOMe-seq data published by (Taberlay et al., 2014 [1] and deposited in the Gene Expression Omnibus with accession GSE57498.

  2. Nucleosome Repositioning: A Novel Mechanism for Nicotine- and Cocaine-Induced Epigenetic Changes.

    Directory of Open Access Journals (Sweden)

    Amber N Brown

    Full Text Available Drugs of abuse modify behavior by altering gene expression in the brain. Gene expression can be regulated by changes in DNA methylation as well as by histone modifications, which alter chromatin structure, DNA compaction and DNA accessibility. In order to better understand the molecular mechanisms directing drug-induced changes in chromatin structure, we examined DNA-nucleosome interactions within promoter regions of 858 genes in human neuroblastoma cells (SH-SY5Y exposed to nicotine or cocaine. Widespread, drug- and time-resolved repositioning of nucleosomes was identified at the transcription start site and promoter region of multiple genes. Nicotine and cocaine produced unique and shared changes in terms of the numbers and types of genes affected, as well as repositioning of nucleosomes at sites which could increase or decrease the probability of gene expression based on DNA accessibility. Half of the drug-induced nucleosome positions approximated a theoretical model of nucleosome occupancy based on physical and chemical characteristics of the DNA sequence, whereas the basal or drug naïve positions were generally DNA sequence independent. Thus we suggest that nucleosome repositioning represents an initial dynamic genome-wide alteration of the transcriptional landscape preceding more selective downstream transcriptional reprogramming, which ultimately characterizes the cell- and tissue-specific responses to drugs of abuse.

  3. Flank tectonics of Martian volcanoes

    International Nuclear Information System (INIS)

    Thomas, P.J.; Squyres, S.W.; Carr, M.H.

    1990-01-01

    On the flanks of Olympus Mons is a series of terraces, concentrically distributed around the caldera. Their morphology and location suggest that they could be thrust faults caused by compressional failure of the cone. In an attempt to understand the mechanism of faulting and the possible influences of the interior structure of Olympus Mons, the authors have constructed a numerical model for elastic stresses within a Martian volcano. In the absence of internal pressurization, the middle slopes of the cone are subjected to compressional stress, appropriate to the formation of thrust faults. These stresses for Olympus Mons are ∼250 MPa. If a vacant magma chamber is contained within the cone, the region of maximum compressional stress is extended toward the base of the cone. If the magma chamber is pressurized, extensional stresses occur at the summit and on the upper slopes of the cone. For a filled but unpressurized magma chamber, the observed positions of the faults agree well with the calculated region of high compressional stress. Three other volcanoes on Mars, Ascraeus Mons, Arsia Mons, and Pavonis Mons, possess similar terraces. Extending the analysis to other Martian volcanoes, they find that only these three and Olympus Mons have flank stresses that exceed the compressional failure strength of basalt, lending support to the view that the terraces on all four are thrust faults

  4. The DNA-encoded nucleosome organization of a eukaryotic genome.

    Science.gov (United States)

    Kaplan, Noam; Moore, Irene K; Fondufe-Mittendorf, Yvonne; Gossett, Andrea J; Tillo, Desiree; Field, Yair; LeProust, Emily M; Hughes, Timothy R; Lieb, Jason D; Widom, Jonathan; Segal, Eran

    2009-03-19

    Nucleosome organization is critical for gene regulation. In living cells this organization is determined by multiple factors, including the action of chromatin remodellers, competition with site-specific DNA-binding proteins, and the DNA sequence preferences of the nucleosomes themselves. However, it has been difficult to estimate the relative importance of each of these mechanisms in vivo, because in vivo nucleosome maps reflect the combined action of all influencing factors. Here we determine the importance of nucleosome DNA sequence preferences experimentally by measuring the genome-wide occupancy of nucleosomes assembled on purified yeast genomic DNA. The resulting map, in which nucleosome occupancy is governed only by the intrinsic sequence preferences of nucleosomes, is similar to in vivo nucleosome maps generated in three different growth conditions. In vitro, nucleosome depletion is evident at many transcription factor binding sites and around gene start and end sites, indicating that nucleosome depletion at these sites in vivo is partly encoded in the genome. We confirm these results with a micrococcal nuclease-independent experiment that measures the relative affinity of nucleosomes for approximately 40,000 double-stranded 150-base-pair oligonucleotides. Using our in vitro data, we devise a computational model of nucleosome sequence preferences that is significantly correlated with in vivo nucleosome occupancy in Caenorhabditis elegans. Our results indicate that the intrinsic DNA sequence preferences of nucleosomes have a central role in determining the organization of nucleosomes in vivo.

  5. Learning a weighted sequence model of the nucleosome core and linker yields more accurate predictions in Saccharomyces cerevisiae and Homo sapiens.

    Directory of Open Access Journals (Sweden)

    Sheila M Reynolds

    2010-07-01

    Full Text Available DNA in eukaryotes is packaged into a chromatin complex, the most basic element of which is the nucleosome. The precise positioning of the nucleosome cores allows for selective access to the DNA, and the mechanisms that control this positioning are important pieces of the gene expression puzzle. We describe a large-scale nucleosome pattern that jointly characterizes the nucleosome core and the adjacent linkers and is predominantly characterized by long-range oscillations in the mono, di- and tri-nucleotide content of the DNA sequence, and we show that this pattern can be used to predict nucleosome positions in both Homo sapiens and Saccharomyces cerevisiae more accurately than previously published methods. Surprisingly, in both H. sapiens and S. cerevisiae, the most informative individual features are the mono-nucleotide patterns, although the inclusion of di- and tri-nucleotide features results in improved performance. Our approach combines a much longer pattern than has been previously used to predict nucleosome positioning from sequence-301 base pairs, centered at the position to be scored-with a novel discriminative classification approach that selectively weights the contributions from each of the input features. The resulting scores are relatively insensitive to local AT-content and can be used to accurately discriminate putative dyad positions from adjacent linker regions without requiring an additional dynamic programming step and without the attendant edge effects and assumptions about linker length modeling and overall nucleosome density. Our approach produces the best dyad-linker classification results published to date in H. sapiens, and outperforms two recently published models on a large set of S. cerevisiae nucleosome positions. Our results suggest that in both genomes, a comparable and relatively small fraction of nucleosomes are well-positioned and that these positions are predictable based on sequence alone. We believe that the

  6. Learning a weighted sequence model of the nucleosome core and linker yields more accurate predictions in Saccharomyces cerevisiae and Homo sapiens.

    Science.gov (United States)

    Reynolds, Sheila M; Bilmes, Jeff A; Noble, William Stafford

    2010-07-08

    DNA in eukaryotes is packaged into a chromatin complex, the most basic element of which is the nucleosome. The precise positioning of the nucleosome cores allows for selective access to the DNA, and the mechanisms that control this positioning are important pieces of the gene expression puzzle. We describe a large-scale nucleosome pattern that jointly characterizes the nucleosome core and the adjacent linkers and is predominantly characterized by long-range oscillations in the mono, di- and tri-nucleotide content of the DNA sequence, and we show that this pattern can be used to predict nucleosome positions in both Homo sapiens and Saccharomyces cerevisiae more accurately than previously published methods. Surprisingly, in both H. sapiens and S. cerevisiae, the most informative individual features are the mono-nucleotide patterns, although the inclusion of di- and tri-nucleotide features results in improved performance. Our approach combines a much longer pattern than has been previously used to predict nucleosome positioning from sequence-301 base pairs, centered at the position to be scored-with a novel discriminative classification approach that selectively weights the contributions from each of the input features. The resulting scores are relatively insensitive to local AT-content and can be used to accurately discriminate putative dyad positions from adjacent linker regions without requiring an additional dynamic programming step and without the attendant edge effects and assumptions about linker length modeling and overall nucleosome density. Our approach produces the best dyad-linker classification results published to date in H. sapiens, and outperforms two recently published models on a large set of S. cerevisiae nucleosome positions. Our results suggest that in both genomes, a comparable and relatively small fraction of nucleosomes are well-positioned and that these positions are predictable based on sequence alone. We believe that the bulk of the

  7. Learning a Weighted Sequence Model of the Nucleosome Core and Linker Yields More Accurate Predictions in Saccharomyces cerevisiae and Homo sapiens

    Science.gov (United States)

    Reynolds, Sheila M.; Bilmes, Jeff A.; Noble, William Stafford

    2010-01-01

    DNA in eukaryotes is packaged into a chromatin complex, the most basic element of which is the nucleosome. The precise positioning of the nucleosome cores allows for selective access to the DNA, and the mechanisms that control this positioning are important pieces of the gene expression puzzle. We describe a large-scale nucleosome pattern that jointly characterizes the nucleosome core and the adjacent linkers and is predominantly characterized by long-range oscillations in the mono, di- and tri-nucleotide content of the DNA sequence, and we show that this pattern can be used to predict nucleosome positions in both Homo sapiens and Saccharomyces cerevisiae more accurately than previously published methods. Surprisingly, in both H. sapiens and S. cerevisiae, the most informative individual features are the mono-nucleotide patterns, although the inclusion of di- and tri-nucleotide features results in improved performance. Our approach combines a much longer pattern than has been previously used to predict nucleosome positioning from sequence—301 base pairs, centered at the position to be scored—with a novel discriminative classification approach that selectively weights the contributions from each of the input features. The resulting scores are relatively insensitive to local AT-content and can be used to accurately discriminate putative dyad positions from adjacent linker regions without requiring an additional dynamic programming step and without the attendant edge effects and assumptions about linker length modeling and overall nucleosome density. Our approach produces the best dyad-linker classification results published to date in H. sapiens, and outperforms two recently published models on a large set of S. cerevisiae nucleosome positions. Our results suggest that in both genomes, a comparable and relatively small fraction of nucleosomes are well-positioned and that these positions are predictable based on sequence alone. We believe that the bulk of the

  8. Functional conservation of nucleosome formation selectively biases presumably neutral molecular variation in yeast genomes.

    Science.gov (United States)

    Babbitt, Gregory A; Cotter, C R

    2011-01-01

    One prominent pattern of mutational frequency, long appreciated in comparative genomics, is the bias of purine/pyrimidine conserving substitutions (transitions) over purine/pyrimidine altering substitutions (transversions). Traditionally, this transitional bias has been thought to be driven by the underlying rates of DNA mutation and/or repair. However, recent sequencing studies of mutation accumulation lines in model organisms demonstrate that substitutions generally do not accumulate at rates that would indicate a transitional bias. These observations have called into question a very basic assumption of molecular evolution; that naturally occurring patterns of molecular variation in noncoding regions accurately reflect the underlying processes of randomly accumulating neutral mutation in nuclear genomes. Here, in Saccharomyces yeasts, we report a very strong inverse association (r = -0.951, P < 0.004) between the genome-wide frequency of substitutions and their average energetic effect on nucleosome formation, as predicted by a structurally based energy model of DNA deformation around the nucleosome core. We find that transitions occurring at sites positioned nearest the nucleosome surface, which are believed to function most importantly in nucleosome formation, alter the deformation energy of DNA to the nucleosome core by only a fraction of the energy changes typical of most transversions. When we examined the same substitutions set against random background sequences as well as an existing study reporting substitutions arising in mutation accumulation lines of Saccharomyces cerevisiae, we failed to find a similar relationship. These results support the idea that natural selection acting to functionally conserve chromatin organization may contribute significantly to genome-wide transitional bias, even in noncoding regions. Because nucleosome core structure is highly conserved across eukaryotes, our observations may also help to further explain locally elevated

  9. An advanced coarse-grained nucleosome core particle model for computer simulations of nucleosome-nucleosome interactions under varying ionic conditions.

    Directory of Open Access Journals (Sweden)

    Yanping Fan

    Full Text Available In the eukaryotic cell nucleus, DNA exists as chromatin, a compact but dynamic complex with histone proteins. The first level of DNA organization is the linear array of nucleosome core particles (NCPs. The NCP is a well-defined complex of 147 bp DNA with an octamer of histones. Interactions between NCPs are of paramount importance for higher levels of chromatin compaction. The polyelectrolyte nature of the NCP implies that nucleosome-nucleosome interactions must exhibit a great influence from both the ionic environment as well as the positively charged and highly flexible N-terminal histone tails, protruding out from the NCP. The large size of the system precludes a modelling analysis of chromatin at an all-atom level and calls for coarse-grained approximations. Here, a model of the NCP that include the globular histone core and the flexible histone tails described by one particle per each amino acid and taking into account their net charge is proposed. DNA wrapped around the histone core was approximated at the level of two base pairs represented by one bead (bases and sugar plus four beads of charged phosphate groups. Computer simulations, using a Langevin thermostat, in a dielectric continuum with explicit monovalent (K(+, divalent (Mg(2+ or trivalent (Co(NH(3(6 (3+ cations were performed for systems with one or ten NCPs. Increase of the counterion charge results in a switch from repulsive NCP-NCP interaction in the presence of K(+, to partial aggregation with Mg(2+ and to strong mutual attraction of all 10 NCPs in the presence of CoHex(3+. The new model reproduced experimental results and the structure of the NCP-NCP contacts is in agreement with available data. Cation screening, ion-ion correlations and tail bridging contribute to the NCP-NCP attraction and the new NCP model accounts for these interactions.

  10. Nucleosome dynamics: HMGB1 facilitates nucleosome restructuring and collaborates in estrogen-responsive gene expression

    Directory of Open Access Journals (Sweden)

    William M. Scovell

    2016-12-01

    Full Text Available The genome in the human cell is extraordinarily compacted in the nucleus. As a result, much of the DNA is inaccessible and functionally inert. Notwithstanding the highly efficient packaging, mechanisms have evolved to render DNA sites accessible that then enable a multitude of factors to carry out ongoing and vital functions. The compaction is derived from DNA complexation within nucleosomes, which can further consolidate into a higher-order chromatin structure. The nucleosome and nucleosomal DNA are not static in nature, but are dynamic, undergoing structural and functional changes as the cell responds to stresses and/or metabolic or environmental cues. We are only beginning to understand the forces and the complexes that engage the nucleosome to unearth the tightly bound and inaccessible DNA sequences and provide an opening to more accessible target sites. In many cases, current findings support a major role for the action of ATP-dependent chromatin remodeling complexes (CRCs in providing an avenue to factor accessibility that leads to the activation of transcription. The estrogen receptor α (ERα does not bind to the estrogen response element (ERE in the canonical nucleosome. However, evidence will be presented that HMGB1 restructures the nucleosome in an ATP-independent manner and also facilitates access and strong binding of ERα to ERE. The features that appear important in the mechanism of action for HMGB1 will be highlighted, in addition to the characteristic features of the restructured nucleosome. These findings, together with previous evidence, suggest a collaborative role for HMGB1 in the step-wise transcription of estrogen-responsive genes. In addition, alternate mechanistic pathways will be discussed, with consideration that “HMGB1 restructuring” of the nucleosome may generally be viewed as a perturbation of the equilibrium of an ensemble of nearly isoenergetic nucleosome states in an energy landscape that is driven by

  11. Low nucleosome occupancy is encoded around functional human transcription factor binding sites

    Directory of Open Access Journals (Sweden)

    Daenen Floris

    2008-07-01

    Full Text Available Abstract Background Transcriptional regulation of genes in eukaryotes is achieved by the interactions of multiple transcription factors with arrays of transcription factor binding sites (TFBSs on DNA and with each other. Identification of these TFBSs is an essential step in our understanding of gene regulatory networks, but computational prediction of TFBSs with either consensus or commonly used stochastic models such as Position-Specific Scoring Matrices (PSSMs results in an unacceptably high number of hits consisting of a few true functional binding sites and numerous false non-functional binding sites. This is due to the inability of the models to incorporate higher order properties of sequences including sequences surrounding TFBSs and influencing the positioning of nucleosomes and/or the interactions that might occur between transcription factors. Results Significant improvement can be expected through the development of a new framework for the modeling and prediction of TFBSs that considers explicitly these higher order sequence properties. It would be particularly interesting to include in the new modeling framework the information present in the nucleosome positioning sequences (NPSs surrounding TFBSs, as it can be hypothesized that genomes use this information to encode the formation of stable nucleosomes over non-functional sites, while functional sites have a more open chromatin configuration. In this report we evaluate the usefulness of the latter feature by comparing the nucleosome occupancy probabilities around experimentally verified human TFBSs with the nucleosome occupancy probabilities around false positive TFBSs and in random sequences. Conclusion We present evidence that nucleosome occupancy is remarkably lower around true functional human TFBSs as compared to non-functional human TFBSs, which supports the use of this feature to improve current TFBS prediction approaches in higher eukaryotes.

  12. Nucleosome Assembly Dynamics Involve Spontaneous Fluctuations in the Handedness of Tetrasomes

    Directory of Open Access Journals (Sweden)

    Rifka Vlijm

    2015-01-01

    Full Text Available DNA wrapping around histone octamers generates nucleosomes, the basic compaction unit of eukaryotic chromatin. Nucleosome stability is carefully tuned to maintain DNA accessibility in transcription, replication, and repair. Using freely orbiting magnetic tweezers, which measure the twist and length of single DNA molecules, we monitor the real-time loading of tetramers or complete histone octamers onto DNA by Nucleosome Assembly Protein-1 (NAP1. Remarkably, we find that tetrasomes exhibit spontaneous flipping between a preferentially occupied left-handed state (ΔLk = −0.73 and a right-handed state (ΔLk = +1.0, separated by a free energy difference of 2.3 kBT (1.5 kcal/mol. This flipping occurs without concomitant changes in DNA end-to-end length. The application of weak positive torque converts left-handed tetrasomes into right-handed tetrasomes, whereas nucleosomes display more gradual conformational changes. Our findings reveal unexpected dynamical rearrangements of the nucleosomal structure, suggesting that chromatin can serve as a “twist reservoir,” offering a mechanistic explanation for the regulation of DNA supercoiling in chromatin.

  13. Transcription factor binding sites prediction based on modified nucleosomes.

    Directory of Open Access Journals (Sweden)

    Mohammad Talebzadeh

    Full Text Available In computational methods, position weight matrices (PWMs are commonly applied for transcription factor binding site (TFBS prediction. Although these matrices are more accurate than simple consensus sequences to predict actual binding sites, they usually produce a large number of false positive (FP predictions and so are impoverished sources of information. Several studies have employed additional sources of information such as sequence conservation or the vicinity to transcription start sites to distinguish true binding regions from random ones. Recently, the spatial distribution of modified nucleosomes has been shown to be associated with different promoter architectures. These aligned patterns can facilitate DNA accessibility for transcription factors. We hypothesize that using data from these aligned and periodic patterns can improve the performance of binding region prediction. In this study, we propose two effective features, "modified nucleosomes neighboring" and "modified nucleosomes occupancy", to decrease FP in binding site discovery. Based on these features, we designed a logistic regression classifier which estimates the probability of a region as a TFBS. Our model learned each feature based on Sp1 binding sites on Chromosome 1 and was tested on the other chromosomes in human CD4+T cells. In this work, we investigated 21 histone modifications and found that only 8 out of 21 marks are strongly correlated with transcription factor binding regions. To prove that these features are not specific to Sp1, we combined the logistic regression classifier with the PWM, and created a new model to search TFBSs on the genome. We tested the model using transcription factors MAZ, PU.1 and ELF1 and compared the results to those using only the PWM. The results show that our model can predict Transcription factor binding regions more successfully. The relative simplicity of the model and capability of integrating other features make it a superior method

  14. Interaction of influenza virus proteins with nucleosomes

    International Nuclear Information System (INIS)

    Garcia-Robles, Inmaculada; Akarsu, Hatice; Mueller, Christoph W.; Ruigrok, Rob W.H.; Baudin, Florence

    2005-01-01

    During influenza virus infection, transcription and replication of the viral RNA take place in the cell nucleus. Directly after entry in the nucleus the viral ribonucleoproteins (RNPs, the viral subunits containing vRNA, nucleoprotein and the viral polymerase) are tightly associated with the nuclear matrix. Here, we have analysed the binding of RNPs, M1 and NS2/NEP proteins to purified nucleosomes, reconstituted histone octamers and purified single histones. RNPs and M1 both bind to the chromatin components but at two different sites, RNP to the histone tails and M1 to the globular domain of the histone octamer. NS2/NEP did not bind to nucleosomes at all. The possible consequences of these findings for nuclear release of newly made RNPs and for other processes during the infection cycle are discussed

  15. Routes to DNA Accessibility: Alternative Pathways for Nucleosome Unwinding

    OpenAIRE

    Schlingman, Daniel J.; Mack, Andrew H.; Kamenetska, Masha; Mochrie, Simon G.J.; Regan, Lynne

    2014-01-01

    The dynamic packaging of DNA into chromatin is a key determinant of eukaryotic gene regulation and epigenetic inheritance. Nucleosomes are the basic unit of chromatin, and therefore the accessible states of the nucleosome must be the starting point for mechanistic models regarding these essential processes. Although the existence of different unwound nucleosome states has been hypothesized, there have been few studies of these states. The consequences of multiple states are far reaching. Thes...

  16. Different nucleosomal architectures at early and late replicating origins in Saccharomyces cerevisiae.

    Science.gov (United States)

    Soriano, Ignacio; Morafraile, Esther C; Vázquez, Enrique; Antequera, Francisco; Segurado, Mónica

    2014-09-13

    Eukaryotic genomes are replicated during S phase according to a temporal program. Several determinants control the timing of origin firing, including the chromatin environment and epigenetic modifications. However, how chromatin structure influences the timing of the activation of specific origins is still poorly understood. By performing high-resolution analysis of genome-wide nucleosome positioning we have identified different chromatin architectures at early and late replication origins. These different patterns are already established in G1 and are tightly correlated with the organization of adjacent transcription units. Moreover, specific early and late nucleosomal patterns are fixed robustly, even in rpd3 mutants in which histone acetylation and origin timing have been significantly altered. Nevertheless, higher histone acetylation levels correlate with the local modulation of chromatin structure, leading to increased origin accessibility. In addition, we conducted parallel analyses of replication and nucleosome dynamics that revealed that chromatin structure at origins is modulated during origin activation. Our results show that early and late replication origins present distinctive nucleosomal configurations, which are preferentially associated to different genomic regions. Our data also reveal that origin structure is dynamic and can be locally modulated by histone deacetylation, as well as by origin activation. These data offer novel insight into the contribution of chromatin structure to origin selection and firing in budding yeast.

  17. Nature of the Nucleosomal Barrier to RNA Polymerase II | Center for Cancer Research

    Science.gov (United States)

    In the cell, RNA polymerase II (pol II) efficiently transcribes DNA packaged into nucleosomes, but in vitro encounters with the nucleosomes induce catalytic inactivation (arrest) of the pol II core enzyme. To determine potential mechanisms making nucleosomes transparent to transcription in vivo, we analyzed the nature of the nucleosome-induced arrest. We found that the arrests

  18. Local Nucleosome Dynamics Facilitate Chromatin Accessibility in Living Mammalian Cells

    Directory of Open Access Journals (Sweden)

    Saera Hihara

    2012-12-01

    Full Text Available Genome information, which is three-dimensionally organized within cells as chromatin, is searched and read by various proteins for diverse cell functions. Although how the protein factors find their targets remains unclear, the dynamic and flexible nature of chromatin is likely crucial. Using a combined approach of fluorescence correlation spectroscopy, single-nucleosome imaging, and Monte Carlo computer simulations, we demonstrate local chromatin dynamics in living mammalian cells. We show that similar to interphase chromatin, dense mitotic chromosomes also have considerable chromatin accessibility. For both interphase and mitotic chromatin, we observed local fluctuation of individual nucleosomes (∼50 nm movement/30 ms, which is caused by confined Brownian motion. Inhibition of these local dynamics by crosslinking impaired accessibility in the dense chromatin regions. Our findings show that local nucleosome dynamics drive chromatin accessibility. We propose that this local nucleosome fluctuation is the basis for scanning genome information.

  19. G+C content dominates intrinsic nucleosome occupancy

    Directory of Open Access Journals (Sweden)

    Hughes Timothy R

    2009-12-01

    Full Text Available Abstract Background The relative preference of nucleosomes to form on individual DNA sequences plays a major role in genome packaging. A wide variety of DNA sequence features are believed to influence nucleosome formation, including periodic dinucleotide signals, poly-A stretches and other short motifs, and sequence properties that influence DNA structure, including base content. It was recently shown by Kaplan et al. that a probabilistic model using composition of all 5-mers within a nucleosome-sized tiling window accurately predicts intrinsic nucleosome occupancy across an entire genome in vitro. However, the model is complicated, and it is not clear which specific DNA sequence properties are most important for intrinsic nucleosome-forming preferences. Results We find that a simple linear combination of only 14 simple DNA sequence attributes (G+C content, two transformations of dinucleotide composition, and the frequency of eleven 4-bp sequences explains nucleosome occupancy in vitro and in vivo in a manner comparable to the Kaplan model. G+C content and frequency of AAAA are the most important features. G+C content is dominant, alone explaining ~50% of the variation in nucleosome occupancy in vitro. Conclusions Our findings provide a dramatically simplified means to predict and understand intrinsic nucleosome occupancy. G+C content may dominate because it both reduces frequency of poly-A-like stretches and correlates with many other DNA structural characteristics. Since G+C content is enriched or depleted at many types of features in diverse eukaryotic genomes, our results suggest that variation in nucleotide composition may have a widespread and direct influence on chromatin structure.

  20. Nucleosome breathing and remodeling constrain CRISPR-Cas9 function

    Science.gov (United States)

    Isaac, R Stefan; Jiang, Fuguo; Doudna, Jennifer A; Lim, Wendell A; Narlikar, Geeta J; Almeida, Ricardo

    2016-01-01

    The CRISPR-Cas9 bacterial surveillance system has become a versatile tool for genome editing and gene regulation in eukaryotic cells, yet how CRISPR-Cas9 contends with the barriers presented by eukaryotic chromatin is poorly understood. Here we investigate how the smallest unit of chromatin, a nucleosome, constrains the activity of the CRISPR-Cas9 system. We find that nucleosomes assembled on native DNA sequences are permissive to Cas9 action. However, the accessibility of nucleosomal DNA to Cas9 is variable over several orders of magnitude depending on dynamic properties of the DNA sequence and the distance of the PAM site from the nucleosome dyad. We further find that chromatin remodeling enzymes stimulate Cas9 activity on nucleosomal templates. Our findings imply that the spontaneous breathing of nucleosomal DNA together with the action of chromatin remodelers allow Cas9 to effectively act on chromatin in vivo. DOI: http://dx.doi.org/10.7554/eLife.13450.001 PMID:27130520

  1. Studies of torsional properties of DNA and nucleosomes using angular optical trapping

    Science.gov (United States)

    Sheinin, Maxim Y.

    DNA in vivo is subjected to torsional stress due to the action of molecular motors and other DNA-binding proteins. Several decades of research have uncovered the fascinating diversity of DNA transformations under torsion and the important role they play in the regulation of vital cellular processes such as transcription and replication. Recent studies have also suggested that torsion can influence the structure and stability of nucleosomes---basic building blocks of the eukaryotic genome. However, our understanding of the impact of torsion is far from being complete due to significant experimental challenges. In this work we have used a powerful single-molecule experimental technique, angular optical trapping, to address several long-standing issues in the field of DNA and nucleosome mechanics. First, we utilized the high resolution and direct torque measuring capability of the angular optical trapping to precisely measure DNA twist-stretch coupling. Second, we characterized DNA melting under tension and torsion. We found that torsionally underwound DNA forms a left-handed structure, significantly more flexible compared to the regular B-DNA. Finally, we performed the first comprehensive investigation of the single nucleosome behavior under torque and force. Importantly, we discovered that positive torque causes significant dimer loss, which can have implications for transcription through chromatin.

  2. Acetylation curtails nucleosome binding, not stable nucleosome remodeling, by FoxO1

    International Nuclear Information System (INIS)

    Hatta, M.; Liu, F.; Cirillo, L.A.

    2009-01-01

    Transcriptional activity of FoxO factors is controlled through the actions of multiple growth factors signaling through protein kinase B, whereby phosphorylation of FoxO factors inhibits FoxO-mediated transactivation by promoting nuclear export. Phosphorylation of FoxO factors is enhanced by p300-mediated acetylation, which decreases their affinity for DNA. The negative effect of acetylation on FoxO DNA binding, together with nuclear FoxO mobility, is eliminated by over-expression of the de-acetylase Sirt1, suggesting that acetylation mobilizes FoxO factors in chromatin for inducible gene expression. Here, we show that acetylation significantly curtails the affinity of FoxO1 for its binding sites in nucleosomal DNA but has no effect on either stable nucleosome binding or remodeling by this factor. We suggest that, while acetylation provides a first, essential step toward mobilizing FoxO factors for inducible gene repression, additional mechanisms exist for overcoming their inherent capacity to stably bind and remodel nuclear chromatin.

  3. Electrostatic mechanism of nucleosomal array folding revealed by computer simulation.

    Science.gov (United States)

    Sun, Jian; Zhang, Qing; Schlick, Tamar

    2005-06-07

    Although numerous experiments indicate that the chromatin fiber displays salt-dependent conformations, the associated molecular mechanism remains unclear. Here, we apply an irregular Discrete Surface Charge Optimization (DiSCO) model of the nucleosome with all histone tails incorporated to describe by Monte Carlo simulations salt-dependent rearrangements of a nucleosomal array with 12 nucleosomes. The ensemble of nucleosomal array conformations display salt-dependent condensation in good agreement with hydrodynamic measurements and suggest that the array adopts highly irregular 3D zig-zag conformations at high (physiological) salt concentrations and transitions into the extended "beads-on-a-string" conformation at low salt. Energy analyses indicate that the repulsion among linker DNA leads to this extended form, whereas internucleosome attraction drives the folding at high salt. The balance between these two contributions determines the salt-dependent condensation. Importantly, the internucleosome and linker DNA-nucleosome attractions require histone tails; we find that the H3 tails, in particular, are crucial for stabilizing the moderately folded fiber at physiological monovalent salt.

  4. The nucleosome: orchestrating DNA damage signaling and repair within chromatin.

    Science.gov (United States)

    Agarwal, Poonam; Miller, Kyle M

    2016-10-01

    DNA damage occurs within the chromatin environment, which ultimately participates in regulating DNA damage response (DDR) pathways and repair of the lesion. DNA damage activates a cascade of signaling events that extensively modulates chromatin structure and organization to coordinate DDR factor recruitment to the break and repair, whilst also promoting the maintenance of normal chromatin functions within the damaged region. For example, DDR pathways must avoid conflicts between other DNA-based processes that function within the context of chromatin, including transcription and replication. The molecular mechanisms governing the recognition, target specificity, and recruitment of DDR factors and enzymes to the fundamental repeating unit of chromatin, i.e., the nucleosome, are poorly understood. Here we present our current view of how chromatin recognition by DDR factors is achieved at the level of the nucleosome. Emerging evidence suggests that the nucleosome surface, including the nucleosome acidic patch, promotes the binding and activity of several DNA damage factors on chromatin. Thus, in addition to interactions with damaged DNA and histone modifications, nucleosome recognition by DDR factors plays a key role in orchestrating the requisite chromatin response to maintain both genome and epigenome integrity.

  5. Structural Mechanisms of Nucleosome Recognition by Linker Histones.

    Science.gov (United States)

    Zhou, Bing-Rui; Jiang, Jiansheng; Feng, Hanqiao; Ghirlando, Rodolfo; Xiao, T Sam; Bai, Yawen

    2015-08-20

    Linker histones bind to the nucleosome and regulate the structure of chromatin and gene expression. Despite more than three decades of effort, the structural basis of nucleosome recognition by linker histones remains elusive. Here, we report the crystal structure of the globular domain of chicken linker histone H5 in complex with the nucleosome at 3.5 Å resolution, which is validated using nuclear magnetic resonance spectroscopy. The globular domain sits on the dyad of the nucleosome and interacts with both DNA linkers. Our structure integrates results from mutation analyses and previous cross-linking and fluorescence recovery after photobleach experiments, and it helps resolve the long debate on structural mechanisms of nucleosome recognition by linker histones. The on-dyad binding mode of the H5 globular domain is different from the recently reported off-dyad binding mode of Drosophila linker histone H1. We demonstrate that linker histones with different binding modes could fold chromatin to form distinct higher-order structures. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Reconstitution of Nucleosomes with Differentially Isotope-labeled Sister Histones.

    Science.gov (United States)

    Liokatis, Stamatios

    2017-03-26

    Asymmetrically modified nucleosomes contain the two copies of a histone (sister histones) decorated with distinct sets of Post-translational Modifications (PTMs). They are newly identified species with unknown means of establishment and functional implications. Current analytical methods are inadequate to detect the copy-specific occurrence of PTMs on the nucleosomal sister histones. This protocol presents a biochemical method for the in vitro reconstitution of nucleosomes containing differentially isotope-labeled sister histones. The generated complex can be also asymmetrically modified, after including a premodified histone pool during refolding of histone subcomplexes. These asymmetric nucleosome preparations can be readily reacted with histone-modifying enzymes to study modification cross-talk mechanisms imposed by the asymmetrically pre-incorporated PTM using nuclear magnetic resonance (NMR) spectroscopy. Particularly, the modification reactions in real-time can be mapped independently on the two sister histones by performing different types of NMR correlation experiments, tailored for the respective isotope type. This methodology provides the means to study crosstalk mechanisms that contribute to the formation and propagation of asymmetric PTM patterns on nucleosomal complexes.

  7. Flanking Variation Influences Rates of Stutter in Simple Repeats

    Directory of Open Access Journals (Sweden)

    August E. Woerner

    2017-11-01

    Full Text Available It has been posited that the longest uninterrupted stretch (LUS of tandem repeats, as defined by the number of exactly matching repeating motif units, is a better predictor of rates of stutter than the parental allele length (PAL. While there are cases where this hypothesis is likely correct, such as the 9.3 allele in the TH01 locus, there can be situations where it may not apply as well. For example, the PAL may capture flanking indel variations while remaining insensitive to polymorphisms in the repeat, and these haplotypic changes may impact the stutter rate. To address this, rates of stutter were contrasted against the LUS as well as the PAL on different flanking haplotypic backgrounds. This study shows that rates of stutter can vary substantially depending on the flanking haplotype, and while there are cases where the LUS is a better predictor of stutter than the PAL, examples to the contrary are apparent in commonly assayed forensic markers. Further, flanking variation that is 7 bp from the repeat region can impact rates of stutter. These findings suggest that non-proximal effects, such as DNA secondary structure, may be impacting the rates of stutter in common forensic short tandem repeat markers.

  8. Naturally occuring nucleosome positioning signals in human exons and introns

    DEFF Research Database (Denmark)

    Baldi, Pierre; Brunak, Søren; Chauvin, Yves

    1996-01-01

    We describe the structural implications of a periodic pattern found in human exons and introns by hidden Markov models. We show that exons (besides the reading frame) have a specific sequential structure in the form of a pattern with triplet consensus non-T(A/T)G, and a minimal periodicity of rou...

  9. Nucleosome Assembly Dynamics Involve Spontaneous Fluctuations in the Handedness of Tetrasomes

    NARCIS (Netherlands)

    Vlijm, R.; Lee, M.; Lipfert, J.; Lusser, A.; Dekker, C.; Dekker, N.H.

    2015-01-01

    DNA wrapping around histone octamers generates nucleosomes, the basic compaction unit of eukaryotic chromatin. Nucleosome stability is carefully tuned to maintain DNA accessibility in transcription, replication, and repair. Using freely orbiting magnetic tweezers, which measure the twist and length

  10. Routes to DNA accessibility: alternative pathways for nucleosome unwinding.

    Science.gov (United States)

    Schlingman, Daniel J; Mack, Andrew H; Kamenetska, Masha; Mochrie, Simon G J; Regan, Lynne

    2014-07-15

    The dynamic packaging of DNA into chromatin is a key determinant of eukaryotic gene regulation and epigenetic inheritance. Nucleosomes are the basic unit of chromatin, and therefore the accessible states of the nucleosome must be the starting point for mechanistic models regarding these essential processes. Although the existence of different unwound nucleosome states has been hypothesized, there have been few studies of these states. The consequences of multiple states are far reaching. These states will behave differently in all aspects, including their interactions with chromatin remodelers, histone variant exchange, and kinetic properties. Here, we demonstrate the existence of two distinct states of the unwound nucleosome, which are accessible at physiological forces and ionic strengths. Using optical tweezers, we measure the rates of unwinding and rewinding for these two states and show that the rewinding rates from each state are different. In addition, we show that the probability of unwinding into each state is dependent on the applied force and ionic strength. Our results demonstrate not only that multiple unwound states exist but that their accessibility can be differentially perturbed, suggesting possible roles for these states in gene regulation. For example, different histone variants or modifications may facilitate or suppress access to DNA by promoting unwinding into one state or the other. We anticipate that the two unwound states reported here will be the basis for future models of eukaryotic transcriptional control. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  11. Unfolding of core nucleosomes by PARP-1 revealed by spFRET microscopy

    Directory of Open Access Journals (Sweden)

    Daniel Sultanov

    2017-01-01

    Full Text Available DNA accessibility to various protein complexes is essential for various processes in the cell and is affected by nucleosome structure and dynamics. Protein factor PARP-1 (poly(ADP-ribose polymerase 1 increases the accessibility of DNA in chromatin to repair proteins and transcriptional machinery, but the mechanism and extent of this chromatin reorganization are unknown. Here we report on the effects of PARP-1 on single nucleosomes revealed by spFRET (single-particle Förster Resonance Energy Transfer microscopy. PARP-1 binding to a double-strand break in the vicinity of a nucleosome results in a significant increase of the distance between the adjacent gyres of nucleosomal DNA. This partial uncoiling of the entire nucleosomal DNA occurs without apparent loss of histones and is reversed after poly(ADP-ribosylation of PARP-1. Thus PARP-1-nucleosome interactions result in reversible, partial uncoiling of the entire nucleosomal DNA.

  12. Subnucleosomes and their relationships to the arrangement of histone binding sites along nucleosome deoxyribonucleic acid

    International Nuclear Information System (INIS)

    Nelson, D.A.; Mencke, A.J.; Chambers, S.A.; Oosterhof, D.K.; Rill, R.L.

    1982-01-01

    Micrococcal nuclease cleaves within nucleosomes at sites spaced about 10.4 base pairs (bp) apart. Cleavages at sites equivalent to 30-35 bp from the ends of 146-bp cores cause spontaneous loss of an H2a-H2b pair associated with 30-40 bp length DNA. Cleavages at certain other sites do not affect the nucleosome integrity unless a solvent perturbant such as urea is added. Chromatin moderately digested with micrococcal nuclease, when fractionated by sedimentation or electrophoresis in the presence of 3 M urea, yielded four previously unobserved subnucleosomes with the following histone/DNA compositions: (H3) 2 (H4) 2 (H2a)(H2b)/95-115 bp; (H3)(H4)/70-80 bp DNA; (H2a)(H2b)/50-60 bp DNA; and (H1)/60-70 bp DNA. All but the latter subnucleosome were also obtained upon DNase I digestion of purified nucleosome cores labeled on the 5' ends with 32 P. Only subnucleosomes that retained H2a and H2b also retained labeled ends. These results show that H2a and H2b are paired on the terminal 30-40 bp of core DNA, as suggested from analyses of histone-DNA cross-link products by Mirzabekov and coworkers. Considerations of the orgins and compositions of subnucleosomes and of cross-linking data suggest an expanded model for the locations of histone binding sites along nucleosome core DNA. The principal features of this model are (i) strong electrostatic binding sites of H2a and H2b occur at positions approximately 20-30 bp from the core ends, (ii) strong electrostatic binding sites of H3 and H4 occur primarily on the central 40 bp of core DNA, (iii) strong nonelectrostatic, urea-sensitive binding sites of H3 and H4 occur at positions approximately 30-50 bp from the core ends, and (iv) urea-sensitive binding sites of H2a or H2b may occur on the terminal 10-20 bp of core DNA

  13. Microsatellites grant more stable flanking genes

    Directory of Open Access Journals (Sweden)

    Joukhadar Reem

    2012-10-01

    Full Text Available Abstract Background Microsatellites, or simple sequence repeats (SSRs, are DNA sequences that include tandem copies of specific sequences no longer than six bases. SSRs are ubiquitous in all genomes and highly mutable. Presentation of the hypothesis Results from previous studies suggest that flanking regions of SSR are exhibit high stability in a wide range of organisms. We hypothesized that the SSRs ability to discard weak DNA polymerases could be responsible for this unusual stability. . When the weak polymerases are being decayed over SSRs, the flanking sequences would have higher opportunity to be replicated by more stable DNA polymerases. We present evidence of the molecular basis of our hypothesis. Testing the hypothesis The hypothesis could be tested by examining the activity of DNA polymerase during and after a number of PCRs. The PCR reactions should be run with the same SSR locus possessing differences in the SSR length. The hypothesis could also be tested by comparing the mutational rate of a transferred gene between two transformations. The first one has a naked T-DNA (transferred DNA, while the second one has the same T-DNA flanked with two SSRs. Implications of the hypothesis In any transformation experiment, flanking the T-DNA fragment with SSR sequences would result in more stably transferred genes. This process would decrease the unpredictable risks that may occur because of the mutational pressure on this foreign segment.

  14. Arginine-phosphate salt bridges between histones and DNA: Intermolecular actuators that control nucleosome architecture

    Science.gov (United States)

    Yusufaly, Tahir I.; Li, Yun; Singh, Gautam; Olson, Wilma K.

    2014-10-01

    Structural bioinformatics and van der Waals density functional theory are combined to investigate the mechanochemical impact of a major class of histone-DNA interactions, namely, the formation of salt bridges between arginine residues in histones and phosphate groups on the DNA backbone. Principal component analysis reveals that the configurational fluctuations of the sugar-phosphate backbone display sequence-specific directionality and variability, and clustering of nucleosome crystal structures identifies two major salt-bridge configurations: a monodentate form in which the arginine end-group guanidinium only forms one hydrogen bond with the phosphate, and a bidentate form in which it forms two. Density functional theory calculations highlight that the combination of sequence, denticity, and salt-bridge positioning enables the histones to apply a tunable mechanochemical stress to the DNA via precise and specific activation of backbone deformations. The results suggest that selection for specific placements of van der Waals contacts, with high-precision control of the spatial distribution of intermolecular forces, may serve as an underlying evolutionary design principle for the structure and function of nucleosomes, a conjecture that is corroborated by previous experimental studies.

  15. Nucleosome mediated crosstalk between transcription factors at eukaryotic enhancers

    International Nuclear Information System (INIS)

    Teif, Vladimir B; Rippe, Karsten

    2011-01-01

    A recent study of transcription regulation in Drosophila embryonic development revealed a complex non-monotonic dependence of gene expression on the distance between binding sites of repressor and activator proteins at the corresponding enhancer cis-regulatory modules (Fakhouri et al 2010 Mol. Syst. Biol. 6 341). The repressor efficiency was high at small separations, low around 30 bp, reached a maximum at 50–60 bp, and decreased at larger distances to the activator binding sites. Here, we propose a straightforward explanation for the distance dependence of repressor activity by considering the effect of the presence of a nucleosome. Using a method that considers partial unwrapping of nucleosomal DNA from the histone octamer core, we calculated the dependence of activator binding on the repressor–activator distance and found a quantitative agreement with the distance dependence reported for the Drosophila enhancer element. In addition, the proposed model offers explanations for other distance-dependent effects at eukaryotic enhancers. (communication)

  16. The Scc2/Scc4 complex acts in sister chromatid cohesion and transcriptional regulation by maintaining nucleosome-free regions

    Science.gov (United States)

    Lopez-Serra, Lidia; Kelly, Gavin; Patel, Harshil; Stewart, Aengus; Uhlmann, Frank

    2014-01-01

    The cohesin complex is at the heart of many chromosomal activities, including sister chromatid cohesion and transcriptional regulation1-3. Cohesin loading onto chromosomes depends on the Scc2/Scc4 cohesin loader complex4-6, but the chromatin features that form cohesin loading sites remain poorly understood. Here, we show that the RSC chromatin remodeling complex recruits budding yeast Scc2/Scc4 to broad nucleosome-free regions, that the cohesin loader itself helps to maintain. Consequently, inactivation of the cohesin loader or RSC complex have similar effects on nucleosome positioning, gene expression and sister chromatid cohesion. These results reveal an intimate link between local chromatin structure and higher order chromosome architecture. Our findings pertain to the similarities between two severe human disorders, Cornelia de Lange syndrome, caused by mutations in the human cohesin loader, and Coffin-Siris syndrome, resulting from mutations in human RSC complex components7-9. Both could arise from gene misregulation due to related changes in the nucleosome landscape. PMID:25173104

  17. Linker histones: novel insights into structure-specific recognition of the nucleosome.

    Science.gov (United States)

    Cutter, Amber R; Hayes, Jeffrey J

    2017-04-01

    Linker histones (H1s) are a primary component of metazoan chromatin, fulfilling numerous functions, both in vitro and in vivo, including stabilizing the wrapping of DNA around the nucleosome, promoting folding and assembly of higher order chromatin structures, influencing nucleosome spacing on DNA, and regulating specific gene expression. However, many molecular details of how H1 binds to nucleosomes and recognizes unique structural features on the nucleosome surface remain undefined. Numerous, confounding studies are complicated not only by experimental limitations, but the use of different linker histone isoforms and nucleosome constructions. This review summarizes the decades of research that has resulted in several models of H1 association with nucleosomes, with a focus on recent advances that suggest multiple modes of H1 interaction in chromatin, while highlighting the remaining questions.

  18. The Nucleosome Assembly Activity of NAP1 Is Enhanced by Alien▿

    OpenAIRE

    Eckey, Maren; Hong, Wei; Papaioannou, Maria; Baniahmad, Aria

    2007-01-01

    The assembly of nucleosomes into chromatin is essential for the compaction of DNA and inactivation of the DNA template to modulate and repress gene expression. The nucleosome assembly protein 1, NAP1, assembles nucleosomes independent of DNA synthesis and was shown to enhance coactivator-mediated gene expression, suggesting a role for NAP1 in transcriptional regulation. Here, we show that Alien, known to harbor characteristics of a corepressor of nuclear hormone receptors such as of the vitam...

  19. Understanding Etna flank instability through numerical models

    Science.gov (United States)

    Apuani, Tiziana; Corazzato, Claudia; Merri, Andrea; Tibaldi, Alessandro

    2013-02-01

    As many active volcanoes, Mount Etna shows clear evidence of flank instability, and different mechanisms were suggested to explain this flank dynamics, based on the recorded deformation pattern and character. Shallow and deep deformations, mainly associated with both eruptive and seismic events, are concentrated along recognised fracture and fault systems, mobilising the eastern and south-eastern flank of the volcano. Several interacting causes were postulated to control the phenomenon, including gravity force, magma ascent along the feeding system, and a very complex local and/or regional tectonic activity. Nevertheless, the complexity of such dynamics is still an open subject of research and being the volcano flanks heavily urbanised, the comprehension of the gravitative dynamics is a major issue for public safety and civil protection. The present research explores the effects of the main geological features (in particular the role of the subetnean clays, interposed between the Apennine-Maghrebian flysch and the volcanic products) and the role of weakness zones, identified by fracture and fault systems, on the slope instability process. The effects of magma intrusions are also investigated. The problem is addressed by integrating field data, laboratory tests and numerical modelling. A bi- and tri-dimensional stress-strain analysis was performed by a finite difference numerical code (FLAC and FLAC3D), mainly aimed at evaluating the relationship among geological features, volcano-tectonic structures and magmatic activity in controlling the deformation processes. The analyses are well supported by dedicated structural-mechanical field surveys, which allowed to estimate the rock mass strength and deformability parameters. To take into account the uncertainties which inevitably occur in a so complicated model, many efforts were done in performing a sensitivity analysis along a WNW-ESE section crossing the volcano summit and the Valle del Bove depression. This was

  20. Stabilization of Nucleosomes by Histone Tails and by FACT Revealed by spFRET Microscopy

    Directory of Open Access Journals (Sweden)

    Maria E. Valieva

    2017-01-01

    Full Text Available A correct chromatin structure is important for cell viability and is tightly regulated by numerous factors. Human protein complex FACT (facilitates chromatin transcription is an essential factor involved in chromatin transcription and cancer development. Here FACT-dependent changes in the structure of single nucleosomes were studied with single-particle Förster resonance energy transfer (spFRET microscopy using nucleosomes labeled with a donor-acceptor pair of fluorophores, which were attached to the adjacent gyres of DNA near the contact between H2A-H2B dimers. Human FACT and its version without the C-terminal domain (CTD and the high mobility group (HMG domain of the structure-specific recognition protein 1 (SSRP1 subunit did not change the structure of the nucleosomes, while FACT without the acidic C-terminal domains of the suppressor of Ty 16 (Spt16 and the SSRP1 subunits caused nucleosome aggregation. Proteolytic removal of histone tails significantly disturbed the nucleosome structure, inducing partial unwrapping of nucleosomal DNA. Human FACT reduced DNA unwrapping and stabilized the structure of tailless nucleosomes. CTD and/or HMG domains of SSRP1 are required for this FACT activity. In contrast, previously it has been shown that yeast FACT unfolds (reorganizes nucleosomes using the CTD domain of SSRP1-like Pol I-binding protein 3 subunit (Pob3. Thus, yeast and human FACT complexes likely utilize the same domains for nucleosome reorganization and stabilization, respectively, and these processes are mechanistically similar.

  1. Removal of histone tails from nucleosome dissects the physical mechanisms of salt-induced aggregation, linker histone H1-induced compaction, and 30-nm fiber formation of the nucleosome array

    International Nuclear Information System (INIS)

    Hizume, Kohji; Nakai, Tonau; Araki, Sumiko; Prieto, Eloise; Yoshikawa, Kenichi; Takeyasu, Kunio

    2009-01-01

    In order to reveal the roles of histone tails in the formation of higher-order chromatin structures, we employed atomic force microscopy (AFM), and an in vitro reconstitution system to examine the properties of reconstituted chromatin composed of tail-less histones and a long DNA (106-kb plasmid) template. The tail-less nucleosomes did not aggregate at high salt concentrations or with an excess amount of core histones, in contrast with the behavior of nucleosomal arrays composed of nucleosomes containing normal, N-terminal tails. Analysis of our nucleosome distributions reveals that the attractive interaction between tail-less nucleosomes is weakened. Addition of linker histone H1 into the tail-less nucleosomal array failed to promote the formation of 30 nm chromatin fibers that are usually formed in the normal nucleosomal array. These results demonstrate that the attractive interaction between nucleosomes via histone tails plays a critical role in the formation of the uniform 30-nm chromatin fiber.

  2. Hybridization Capture Using Short PCR Products Enriches Small Genomes by Capturing Flanking Sequences (CapFlank)

    DEFF Research Database (Denmark)

    Tsangaras, Kyriakos; Wales, Nathan; Sicheritz-Pontén, Thomas

    2014-01-01

    , a non-negligible fraction of the resulting sequence reads are not homologous to the bait. We demonstrate that during capture, the bait-hybridized library molecules add additional flanking library sequences iteratively, such that baits limited to targeting relatively short regions (e.g. few hundred...... nucleotides) can result in enrichment across entire mitochondrial and bacterial genomes. Our findings suggest that some of the off-target sequences derived in capture experiments are non-randomly enriched, and that CapFlank will facilitate targeted enrichment of large contiguous sequences with minimal prior...

  3. Increased Nucleosomes and Neutrophil Activation Link to Disease Progression in Patients with Scrub Typhus but Not Murine Typhus in Laos

    NARCIS (Netherlands)

    Paris, Daniel H.; Stephan, Femke; Bulder, Ingrid; Wouters, Diana; van der Poll, Tom; Newton, Paul N.; Day, Nicholas P. J.; Zeerleder, Sacha

    2015-01-01

    Cell-mediated immunity is essential in protection against rickettsial illnesses, but the role of neutrophils in these intracellular vasculotropic infections remains unclear. This study analyzed the plasma levels of nucleosomes, FSAP-activation (nucleosome-releasing factor), and neutrophil

  4. The nucleosome assembly activity of NAP1 is enhanced by Alien.

    Science.gov (United States)

    Eckey, Maren; Hong, Wei; Papaioannou, Maria; Baniahmad, Aria

    2007-05-01

    The assembly of nucleosomes into chromatin is essential for the compaction of DNA and inactivation of the DNA template to modulate and repress gene expression. The nucleosome assembly protein 1, NAP1, assembles nucleosomes independent of DNA synthesis and was shown to enhance coactivator-mediated gene expression, suggesting a role for NAP1 in transcriptional regulation. Here, we show that Alien, known to harbor characteristics of a corepressor of nuclear hormone receptors such as of the vitamin D receptor (VDR), binds in vivo and in vitro to NAP1 and modulates its activity by enhancing NAP1-mediated nucleosome assembly on DNA. Furthermore, Alien reduces the accessibility of the histones H3 and H4 for NAP1-promoted assembly reaction. This indicates that Alien sustains and reinforces the formation of nucleosomes. Employing deletion mutants of Alien suggests that different regions of Alien are involved in enhancement of NAP1-mediated nucleosome assembly and in inhibiting the accessibility of the histones H3 and H4. In addition, we provide evidence that Alien is associated with chromatin and with micrococcus nuclease-prepared nucleosome fractions and interacts with the histones H3 and H4. Furthermore, chromatin immunoprecipitation and reimmunoprecipitation experiments suggest that NAP1 and Alien localize to the endogenous CYP24 promoter in vivo, a VDR target gene. Based on these findings, we present here a novel pathway linking corepressor function with nucleosome assembly activity.

  5. Crowding-induced transcriptional bursts dictate polymerase and nucleosome density profiles along genes

    NARCIS (Netherlands)

    van den Berg, A.A.; Depken, S.M.

    2017-01-01

    During eukaryotic transcription, RNA polymerase (RNAP) translocates along DNA molecules covered with nucleosomes and other DNA binding proteins. Though the interactions between a single nucleosome and RNAP are by now fairly well understood, this understanding has not been synthesized into a

  6. Nucleosomes and histones are present in glomerular deposits in human lupus nephritis

    NARCIS (Netherlands)

    vanBruggen, MCJ; Kramers, C; Walgreen, B; Elema, JD; Kallenberg, CGM; vandenBorn, J; Smeenk, RJT; Assmann, KJM; Muller, S; Monestier, M; Berden, JHM

    Background. Recently we showed that antinuclear autoantibodies complexed to nucleosomes can bind to heparan sulphate (HS) in the glomerular basement membrane (GEM) via the histone part of the nucleosome. Histones have been identified in glomerular deposits in human and murine lupus nephritis. In

  7. Nitrated nucleosome levels and neuropsychiatric events in systemic lupus erythematosus;

    DEFF Research Database (Denmark)

    Ferreira, Isabel; Croca, Sara; Raimondo, Maria Gabriella

    2017-01-01

    BACKGROUND: In patients with systemic lupus erythematosus (SLE) there is no serological test that will reliably distinguish neuropsychiatric (NP) events due to active SLE from those due to other causes. Previously we showed that serum levels of nitrated nucleosomes (NN) were elevated in a small...... number of patients with NPSLE. Here we measured serum NN in samples from a larger population of patients with SLE and NP events to see whether elevated serum NN could be a marker for NPSLE. METHODS: We obtained serum samples from patients in the Systemic Lupus International Collaborative Clinics (SLICC...

  8. PARP-1 Interaction with and Activation by Histones and Nucleosomes.

    Science.gov (United States)

    Thomas, Colin; Kotova, Elena; Tulin, Alexei V

    2017-01-01

    Poly(ADP-ribose) Polymerase 1 (PARP-1) is an abundant chromatin associated protein, typical for most eukaryotic nuclei. The localization of PARP-1 in chromatin and its enzymatic activation involves multiple interactions of PARP-1 with nucleosomal histones, other proteins, and DNA. We report a set of methods designed to reconstitute PARP-1 regulation in vitro. These methods involve the expression of PARP-1 and PARP-1-regulating proteins using bacterial and eukaryotic systems, purification of these proteins using chromatography, testing of individual interactions in vitro, assembly of active complexes, and reconstitution of PARP-1 regulating reactions in vitro.

  9. Hybridization Capture Using Short PCR Products Enriches Small Genomes by Capturing Flanking Sequences (CapFlank)

    DEFF Research Database (Denmark)

    Tsangaras, Kyriakos; Wales, Nathan; Sicheritz-Pontén, Thomas

    2014-01-01

    nucleotides) can result in enrichment across entire mitochondrial and bacterial genomes. Our findings suggest that some of the off-target sequences derived in capture experiments are non-randomly enriched, and that CapFlank will facilitate targeted enrichment of large contiguous sequences with minimal prior...

  10. RPA binds histone H3-H4 and functions in DNA replication-coupled nucleosome assembly.

    Science.gov (United States)

    Liu, Shaofeng; Xu, Zhiyun; Leng, He; Zheng, Pu; Yang, Jiayi; Chen, Kaifu; Feng, Jianxun; Li, Qing

    2017-01-27

    DNA replication-coupled nucleosome assembly is essential to maintain genome integrity and retain epigenetic information. Multiple involved histone chaperones have been identified, but how nucleosome assembly is coupled to DNA replication remains elusive. Here we show that replication protein A (RPA), an essential replisome component that binds single-stranded DNA, has a role in replication-coupled nucleosome assembly. RPA directly binds free H3-H4. Assays using a synthetic sequence that mimics freshly unwound single-stranded DNA at replication fork showed that RPA promotes DNA-(H3-H4) complex formation immediately adjacent to double-stranded DNA. Further, an RPA mutant defective in H3-H4 binding exhibited attenuated nucleosome assembly on nascent chromatin. Thus, we propose that RPA functions as a platform for targeting histone deposition to replication fork, through which RPA couples nucleosome assembly with ongoing DNA replication. Copyright © 2017, American Association for the Advancement of Science.

  11. Circulatory nucleosome levels are significantly increased in early and late-onset preeclampsia.

    Science.gov (United States)

    Zhong, Xiao Yan; Gebhardt, Stefan; Hillermann, Renate; Tofa, Kashefa Carelse; Holzgreve, Wolfgang; Hahn, Sinuhe

    2005-08-01

    Elevations in circulatory DNA, as measured by real-time PCR, have been observed in pregnancies with manifest preeclampsia. Recent reports have indicated that circulatory nucleosome levels are elevated in the periphery of cancer patients. We have now examined whether circulatory nucleosome levels are similarly elevated in cases with preeclampsia. Maternal plasma samples were prepared from 17 cases with early onset preeclampsia (34 weeks gestation) with 10 matched normotensive controls. Levels of circulatory nucleosomes were quantified by commercial ELISA (enzyme-linked immunosorbant assay). The level of circulatory nucleosomes was significantly elevated in both study preeclampsia groups, compared to the matched normotensive control group (p = 0.000 and p = 0.001, respectively). Our data suggests that preeclampsia is associated with the elevated presence of circulatory nucleosomes, and that this phenomenon occurs in both early- and late-onset forms of the disorder. Copyright 2005 John Wiley & Sons, Ltd.

  12. Core nucleosomes by digestion of reconstructed histone-DNA complexes

    Energy Technology Data Exchange (ETDEWEB)

    Bryan, P N; Wright, E B; Olins, D E

    1979-04-01

    Reconstructed complexes of the inner histones (H2A, H2B, H3, H4) and a variety of DNAs were digested with micrococcal nuclease to yield very homogeneous populations of core nucleosomes (..nu../sub 1/). Nucleosomes containing Micrococcus luteus DNA (72% G+C); chicken DNA (43% G+C), Clostridium perfringens DNA (29% G+C); or poly(dA-dT).poly(dA-dT) have been examined by circular dichroism, thermal denaturation, electron microscopy, and DNAse I digestion. Circular dichroism spectra of all particles show a typically suppressed ellipticity at 260 to 280 nm and a prominent ..cap alpha..-helix signal at 222 nm. All particles show biphasic melting except ..nu../sub 1/(dA-dT), which show three prominent melting transitions at ionic strength less than or equal to 1 mM. DNAse I digestion of ..nu../sub 1/ (dA-dT) produces a ladder of DNA fragments differing in length by one base residue. ..nu../sub 1/ (dA-dT) contain 146 base pairs of DNA and exhibit an average DNA helix pitch of 10.4 to 10.5 bases per turn. There appear to be two regions of different DNA pitch within ..nu../sub 1/ (dA-dT). It is suggested that the two regions of DNA pitch might correspond to the two regions of the melting profiles.

  13. In silico evidence for sequence-dependent nucleosome sliding

    Energy Technology Data Exchange (ETDEWEB)

    Lequieu, Joshua; Schwartz, David C.; de Pablo, Juan J.

    2017-10-18

    Nucleosomes represent the basic building block of chromatin and provide an important mechanism by which cellular processes are controlled. The locations of nucleosomes across the genome are not random but instead depend on both the underlying DNA sequence and the dynamic action of other proteins within the nucleus. These processes are central to cellular function, and the molecular details of the interplay between DNA sequence and nudeosome dynamics remain poorly understood. In this work, we investigate this interplay in detail by relying on a molecular model, which permits development of a comprehensive picture of the underlying free energy surfaces and the corresponding dynamics of nudeosome repositioning. The mechanism of nudeosome repositioning is shown to be strongly linked to DNA sequence and directly related to the binding energy of a given DNA sequence to the histone core. It is also demonstrated that chromatin remodelers can override DNA-sequence preferences by exerting torque, and the histone H4 tail is then identified as a key component by which DNA-sequence, histone modifications, and chromatin remodelers could in fact be coupled.

  14. Nucleosomes correlate with in vivo progression pattern of de novo methylation of p16 CpG islands in human gastric carcinogenesis.

    Directory of Open Access Journals (Sweden)

    Zhe-Ming Lu

    Full Text Available BACKGROUND: The exact relationship between nucleosome positioning and methylation of CpG islands in human pathogenesis is unknown. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we characterized the nucleosome position within the p16 CpG island and established a seeding methylation-specific PCR (sMSP assay based on bisulfite modification to enrich the p16 alleles containing methylated-CpG at the methylation "seeding" sites within its intron-1 in gastric carcinogenesis. The sMSP-positive rate in primary gastric carcinoma (GC samples (36/40 was significantly higher than that observed in gastritis (19/45 or normal samples (7/13 (P<0.01. Extensive clone sequencing of these sMSP products showed that the density of methylated-CpGs in p16 CpG islands increased gradually along with the severity of pathological changes in gastric tissues. In gastritis lesions the methylation was frequently observed in the region corresponding to the exon-1 coding-nucleosome and the 5'UTR-nucleosome; the methylation was further extended to the region corresponding to the promoter-nucleosome in GC samples. Only few methylated-CpG sites were randomly detected within p16 CpG islands in normal tissues. The significantly inversed relationship between the p16 exon-1 methylation and its transcription was observed in GC samples. An exact p16 promoter-specific 83 bp-MSP assay confirms the result of sMSP (33/55 vs. 1/6, P<0.01. In addition, p16 methylation in chronic gastritis lesions significantly correlated with H. pylori infection; however, such correlation was not observed in GC specimens. CONCLUSIONS/SIGNIFICANCE: It was determined that de novo methylation was initiated in the coding region of p16 exon-1 in gastritis, then progressed to its 5'UTR, and ultimately to the proximal promoter in GCs. Nucleosomes may function as the basic extension/progression unit of de novo methylation of p16 CpG islands in vivo.

  15. Flanking signal and mature peptide residues influence signal peptide cleavage

    Directory of Open Access Journals (Sweden)

    Ranganathan Shoba

    2008-12-01

    Full Text Available Abstract Background Signal peptides (SPs mediate the targeting of secretory precursor proteins to the correct subcellular compartments in prokaryotes and eukaryotes. Identifying these transient peptides is crucial to the medical, food and beverage and biotechnology industries yet our understanding of these peptides remains limited. This paper examines the most common type of signal peptides cleavable by the endoprotease signal peptidase I (SPase I, and the residues flanking the cleavage sites of three groups of signal peptide sequences, namely (i eukaryotes (Euk (ii Gram-positive (Gram+ bacteria, and (iii Gram-negative (Gram- bacteria. Results In this study, 2352 secretory peptide sequences from a variety of organisms with amino-terminal SPs are extracted from the manually curated SPdb database for analysis based on physicochemical properties such as pI, aliphatic index, GRAVY score, hydrophobicity, net charge and position-specific residue preferences. Our findings show that the three groups share several similarities in general, but they display distinctive features upon examination in terms of their amino acid compositions and frequencies, and various physico-chemical properties. Thus, analysis or prediction of their sequences should be separated and treated as distinct groups. Conclusion We conclude that the peptide segment recognized by SPase I extends to the start of the mature protein to a limited extent, upon our survey of the amino acid residues surrounding the cleavage processing site. These flanking residues possibly influence the cleavage processing and contribute to non-canonical cleavage sites. Our findings are applicable in defining more accurate prediction tools for recognition and identification of cleavage site of SPs.

  16. Right psoas abscess following right flank trauma: a case report ...

    African Journals Online (AJOL)

    This is a case of 15 year old boy who presented with three weeks history of right flank pain, two weeks history of fever and five days history of inability to walk well. There was history of right flank trauma a week before the onset of right flank pain. He had earlier presented in two different hospitals before he was brought to our ...

  17. lncRNA-Induced Nucleosome Repositioning Reinforces Transcriptional Repression of rRNA Genes upon Hypotonic Stress

    Directory of Open Access Journals (Sweden)

    Zhongliang Zhao

    2016-03-01

    Full Text Available The activity of rRNA genes (rDNA is regulated by pathways that target the transcription machinery or alter the epigenetic state of rDNA. Previous work has established that downregulation of rRNA synthesis in quiescent cells is accompanied by upregulation of PAPAS, a long noncoding RNA (lncRNA that recruits the histone methyltransferase Suv4-20h2 to rDNA, thus triggering trimethylation of H4K20 (H4K20me3 and chromatin compaction. Here, we show that upregulation of PAPAS in response to hypoosmotic stress does not increase H4K20me3 because of Nedd4-dependent ubiquitinylation and proteasomal degradation of Suv4-20h2. Loss of Suv4-20h2 enables PAPAS to interact with CHD4, a subunit of the chromatin remodeling complex NuRD, which shifts the promoter-bound nucleosome into the transcriptional “off” position. Thus, PAPAS exerts a “stress-tailored” dual function in rDNA silencing, facilitating either Suv4-20h2-dependent chromatin compaction or NuRD-dependent changes in nucleosome positioning.

  18. Fortescue field, Gippsland basin: Flank potential realized

    Energy Technology Data Exchange (ETDEWEB)

    Hendrich, J.H.; Schwebel, D.A.; Palmer, I.D. (Esso Asustralia Ltd., Sydney, New South Wales (Australia))

    1990-09-01

    Fortescue field was the last major oil field to be discovered in the offshore Gippsland basin, southeastern Australia. The discovery well, 1 West Halibut, was drilled in 1978 on the basis of a 1-km seismic grid as a follow up to the dry 1 Fortescue wildcat. Data from this well were interpreted to indicate that there was a high probability of a stratigraphic trap occurring on the western flank of the giant Halibut-Cobia structure. The 2, 3, and 4 Fortescue wells were drilled by early 1979 to determine the limits of the field, delineate the stratigraphy, and define the hydrocarbon contacts. Cobia A had the dual purpose of developing the Cobia field and the southern extent of the Fortescue reservoirs that were inaccessible to the Fortescue A plat-form. At the conclusion of development drilling in early 1986, eight Cobia A wells and 20 Fortescue A wells were capable of producing from Fortescue reservoirs. The Fortescue reservoirs are Eocene sandstones that were deposited in coastal plain, upper shoreface, and lower shoreface environments. Integration of well log correlations, stratigraphic interpretations, reservoir pressure data, and seismic data indicates that these Fortescue reservoirs are stratigraphically younger than, and are hydraulically separated from, the underlying Halibut-Cobia fields. Pressure data acquired during development drilling and while monitoring subsequent production performance have conclusively demonstrated that there are at least three separate hydraulic systems active within the Fortescue field. Fortescue field dimensions are approximately 11 km x 4 km with a maximum relief of 100 m above the original oil-water contact. Reserves are estimated at 280,000 STB, based on original oil in place estimates of 415,000 STB and recovery factors in the 65-70% range. Production rate peaked in 1984 at 100 K BOPD from the combined development facilities and was sustained until late 1986. More than two-thirds of the reserves have been produced to date.

  19. Altered nucleosomes of active nucleolar chromatin contain accessible histone H3 in its hyperacetylated forms

    International Nuclear Information System (INIS)

    Johnson, E.M.; Sterner, R.; Allfrey, V.G.

    1987-01-01

    Chromatin of the organism Physarum polycephalum contains a class of conformationally altered nucleosomes previously localized to the transcribing regions of ribosomal genes in nucleoli. When nuclei are treated with 2-iodo[2-tritium]acetate, the histone H3 sulfhydryl group of the altered nucleosomes is derivatized while that of folded nucleosomes is not, and the labeled histones can then be identified by autoradiography of gels that separate H3 isoforms. The H3 derivatized is predominantly of tri- and tetraacetylated forms. In contrast, total free histone reacted with iodoacetate shows no preferential labeling of isoforms. Selective reaction of acetylated H3 is prevalent in both nucleolar and non-nucleolar chromatin. The results link specific patterns of H3 acetylation to changes in nucleosome conformation that occur during transcription

  20. Soft skills turned into hard facts: nucleosome remodelling at developmental switches.

    Science.gov (United States)

    Chioda, M; Becker, P B

    2010-07-01

    Nucleosome remodelling factors are regulators of DNA accessibility in chromatin and lubricators of all major functions of eukaryotic genomes. Their action is transient and reversible, yet can be decisive for irreversible cell-fate decisions during development. In addition to the well-known local actions of nucleosome remodelling factors during transcription initiation, more global and fundamental roles for remodelling complexes in shaping the epigenome during development are emerging.

  1. A role for FACT in repopulation of nucleosomes at inducible genes.

    Directory of Open Access Journals (Sweden)

    Warren P Voth

    Full Text Available Xenobiotic drugs induce Pleiotropic Drug Resistance (PDR genes via the orthologous Pdr1/Pdr3 transcription activators. We previously identified the Mediator transcription co-activator complex as a key target of Pdr1 orthologs and demonstrated that Pdr1 interacts directly with the Gal11/Med15 subunit of the Mediator complex. Based on an interaction between Pdr1 and the FACT complex, we show that strains with spt16 or pob3 mutations are sensitive to xenobiotic drugs and display diminished PDR gene induction. Although FACT acts during the activation of some genes by assisting in the nucleosomes eviction at promoters, PDR promoters already contain nucleosome-depleted regions (NDRs before induction. To determine the function of FACT at PDR genes, we examined the kinetics of RNA accumulation and changes in nucleosome occupancy following exposure to a xenobiotic drug in wild type and FACT mutant yeast strains. In the presence of normal FACT, PDR genes are transcribed within 5 minutes of xenobiotic stimulation and transcription returns to basal levels by 30-40 min. Nucleosomes are constitutively depleted in the promoter regions, are lost from the open reading frames during transcription, and the ORFs are wholly repopulated with nucleosomes as transcription ceases. While FACT mutations cause minor delays in activation of PDR genes, much more pronounced and significant defects in nucleosome repopulation in the ORFs are observed in FACT mutants upon transcription termination. FACT therefore has a major role in nucleosome redeposition following cessation of transcription at the PDR genes, the opposite of its better-known function in nucleosome disassembly.

  2. Anti-nucleosome antibodies complexed to nucleosomal antigens show anti-DNA reactivity and bind to rat glomerular basement membrane in vivo.

    Science.gov (United States)

    Kramers, C; Hylkema, M N; van Bruggen, M C; van de Lagemaat, R; Dijkman, H B; Assmann, K J; Smeenk, R J; Berden, J H

    1994-01-01

    Histones can mediate the binding of DNA and anti-DNA to the glomerular basement membrane (GBM). In ELISA histone/DNA/anti-DNA complexes are able to bind to heparan sulfate (HS), an intrinsic constituent of the GBM. We questioned whether histone containing immune complexes are able to bind to the GBM, and if so, whether the ligand in the GBM is HS. Monoclonal antibodies (mAbs) complexed to nucleosomal antigens and noncomplexed mAbs were isolated from culture supernatants of four IgG anti-nuclear mAbs. All noncomplexed mAbs showed strong anti-nucleosome reactivity in ELISA. One of them showed in addition anti-DNA reactivity in noncomplexed form. The other three mAbs only showed anti-DNA reactivity when they were complexed to nucleosomal antigens. After renal perfusion a fine granular binding of complexed mAbs to the glomerular capillary wall and activation of complement was observed in immunofluorescence, whereas noncomplexed mAbs did not bind. Immuno-electron microscopy showed binding of complexes to the whole width of the GBM. When HS in the GBM was removed by renal heparinase perfusion the binding of complexed mAb decreased, but did not disappear completely. We conclude that anti-nucleosome mAbs, which do not bind DNA, become DNA reactive once complexed to nucleosomal antigens. These complexed mAbs can bind to the GBM. The binding ligand in the GBM is partly, but not solely, HS. Binding to the GBM of immune complexes containing nucleosomal material might be an important event in the pathogenesis of lupus nephritis. Images PMID:8040312

  3. In vitro reconstitution and biochemical analyses of the Schizosaccharomyces pombe nucleosome

    International Nuclear Information System (INIS)

    Koyama, Masako; Nagakura, Wataru; Tanaka, Hiroki; Kujirai, Tomoya; Chikashige, Yuji; Haraguchi, Tokuko; Hiraoka, Yasushi; Kurumizaka, Hitoshi

    2017-01-01

    Schizosaccharomyces pombe, which has a small genome but shares many physiological functions with higher eukaryotes, is a useful single-cell, model eukaryotic organism. In particular, many features concerning chromatin structure and dynamics, including heterochromatin, centromeres, telomeres, and DNA replication origins, are well conserved between S. pombe and higher eukaryotes. However, the S. pombe nucleosome, the fundamental structural unit of chromatin, has not been reconstituted in vitro. In the present study, we established the method to purify S. pombe histones H2A, H2B, H3, and H4, and successfully reconstituted the S. pombe nucleosome in vitro. Our thermal stability assay and micrococcal nuclease treatment assay revealed that the S. pombe nucleosome is markedly unstable and its DNA ends are quite accessible, as compared to the canonical human nucleosome. These findings are important to understand the mechanisms of epigenetic genomic DNA regulation in fission yeast. - Highlights: • S. pombe histones were purified as recombinant proteins. • The recombinant S. pombe histones efficiently form nucleosomes in vitro. • The S. pombe nucleosome has distinct stability and DNA dynamics.

  4. Inducible nucleosome depletion at OREBP-binding-sites by hypertonic stress.

    Directory of Open Access Journals (Sweden)

    Edith H Y Tong

    Full Text Available BACKGROUND: Osmotic Response Element-Binding Protein (OREBP, also known as TonEBP or NFAT5, is a unique transcription factor. It is hitherto the only known mammalian transcription factor that regulates hypertonic stress-induced gene transcription. In addition, unlike other monomeric members of the NFAT family, OREBP exists as a homodimer and it is the only transcription factor known to bind naked DNA targets by complete encirclement in vitro. Nevertheless, how OREBP interacts with target DNA, also known as ORE/TonE, and how it elicits gene transcription in vivo, remains unknown. METHODOLOGY: Using hypertonic induction of the aldose reductase (AR gene activation as a model, we showed that OREs contained dynamic nucleosomes. Hypertonic stress induced a rapid and reversible loss of nucleosome(s around the OREs. The loss of nucleosome(s was found to be initiated by an OREBP-independent mechanism, but was significantly potentiated in the presence of OREBP. Furthermore, hypertonic induction of AR gene was associated with an OREBP-dependent hyperacetylation of histones that spanned the 5' upstream sequences and at least some exons of the gene. Nevertheless, nucleosome loss was not regulated by the acetylation status of histone. SIGNIFICANCE: Our findings offer novel insights into the mechanism of OREBP-dependent transcriptional regulation and provide a basis for understanding how histone eviction and transcription factor recruitment are coupled.

  5. Increased Nucleosomes and Neutrophil Activation Link to Disease Progression in Patients with Scrub Typhus but Not Murine Typhus in Laos.

    Science.gov (United States)

    Paris, Daniel H; Stephan, Femke; Bulder, Ingrid; Wouters, Diana; van der Poll, Tom; Newton, Paul N; Day, Nicholas P J; Zeerleder, Sacha

    2015-01-01

    Cell-mediated immunity is essential in protection against rickettsial illnesses, but the role of neutrophils in these intracellular vasculotropic infections remains unclear. This study analyzed the plasma levels of nucleosomes, FSAP-activation (nucleosome-releasing factor), and neutrophil activation, as evidenced by neutrophil-elastase (ELA) complexes, in sympatric Lao patients with scrub typhus and murine typhus. In acute scrub typhus elevated nucleosome levels correlated with lower GCS scores, raised respiratory rate, jaundice and impaired liver function, whereas neutrophil activation correlated with fibrinolysis and high IL-8 plasma levels, a recently identified predictor of severe disease and mortality. Nucleosome and ELA complex levels were associated with a 4.8-fold and 4-fold increased risk of developing severe scrub typhus, beyond cut off values of 1,040 U/ml for nucleosomes and 275 U/ml for ELA complexes respectively. In murine typhus, nucleosome levels associated with pro-inflammatory cytokines and the duration of illness, while ELA complexes correlated strongly with inflammation markers, jaundice and increased respiratory rates. This study found strong correlations between circulating nucleosomes and neutrophil activation in patients with scrub typhus, but not murine typhus, providing indirect evidence that nucleosomes could originate from neutrophil extracellular trap (NET) degradation. High circulating plasma nucleosomes and ELA complexes represent independent risk factors for developing severe complications in scrub typhus. As nucleosomes and histones exposed on NETs are highly cytotoxic to endothelial cells and are strongly pro-coagulant, neutrophil-derived nucleosomes could contribute to vascular damage, the pro-coagulant state and exacerbation of disease in scrub typhus, thus indicating a detrimental role of neutrophil activation. The data suggest that increased neutrophil activation relates to disease progression and severe complications, and

  6. Increasing Nucleosome Occupancy Is Correlated with an Increasing Mutation Rate so Long as DNA Repair Machinery Is Intact

    Science.gov (United States)

    Taylor, Jared F.; Khattab, Omar S.; Chen, Yu-Han; Chen, Yumay; Jacobsen, Steven E.; Wang, Ping H.

    2015-01-01

    Deciphering the multitude of epigenomic and genomic factors that influence the mutation rate is an area of great interest in modern biology. Recently, chromatin has been shown to play a part in this process. To elucidate this relationship further, we integrated our own ultra-deep sequenced human nucleosomal DNA data set with a host of published human genomic and cancer genomic data sets. Our results revealed, that differences in nucleosome occupancy are associated with changes in base-specific mutation rates. Increasing nucleosome occupancy is associated with an increasing transition to transversion ratio and an increased germline mutation rate within the human genome. Additionally, cancer single nucleotide variants and microindels are enriched within nucleosomes and both the coding and non-coding cancer mutation rate increases with increasing nucleosome occupancy. There is an enrichment of cancer indels at the theoretical start (74 bp) and end (115 bp) of linker DNA between two nucleosomes. We then hypothesized that increasing nucleosome occupancy decreases access to DNA by DNA repair machinery and could account for the increasing mutation rate. Such a relationship should not exist in DNA repair knockouts, and we thus repeated our analysis in DNA repair machinery knockouts to test our hypothesis. Indeed, our results revealed no correlation between increasing nucleosome occupancy and increasing mutation rate in DNA repair knockouts. Our findings emphasize the linkage of the genome and epigenome through the nucleosome whose properties can affect genome evolution and genetic aberrations such as cancer. PMID:26308346

  7. Increasing Nucleosome Occupancy Is Correlated with an Increasing Mutation Rate so Long as DNA Repair Machinery Is Intact.

    Directory of Open Access Journals (Sweden)

    Puya G Yazdi

    Full Text Available Deciphering the multitude of epigenomic and genomic factors that influence the mutation rate is an area of great interest in modern biology. Recently, chromatin has been shown to play a part in this process. To elucidate this relationship further, we integrated our own ultra-deep sequenced human nucleosomal DNA data set with a host of published human genomic and cancer genomic data sets. Our results revealed, that differences in nucleosome occupancy are associated with changes in base-specific mutation rates. Increasing nucleosome occupancy is associated with an increasing transition to transversion ratio and an increased germline mutation rate within the human genome. Additionally, cancer single nucleotide variants and microindels are enriched within nucleosomes and both the coding and non-coding cancer mutation rate increases with increasing nucleosome occupancy. There is an enrichment of cancer indels at the theoretical start (74 bp and end (115 bp of linker DNA between two nucleosomes. We then hypothesized that increasing nucleosome occupancy decreases access to DNA by DNA repair machinery and could account for the increasing mutation rate. Such a relationship should not exist in DNA repair knockouts, and we thus repeated our analysis in DNA repair machinery knockouts to test our hypothesis. Indeed, our results revealed no correlation between increasing nucleosome occupancy and increasing mutation rate in DNA repair knockouts. Our findings emphasize the linkage of the genome and epigenome through the nucleosome whose properties can affect genome evolution and genetic aberrations such as cancer.

  8. Chromatin Regulation of Estrogen-Mediated Transcription in Breast Cancer: Rules for Binding Sites in Nucleosomes and Modified Histones that Enhance ER Binding

    National Research Council Canada - National Science Library

    Chrivia, John C

    2005-01-01

    .... Using gel shift assays, we tested whether ER can bind these nucleosomes. We have also found that the non-histone chromatin protein HMOB2 enhances binding of ER to an ERE located at the center of the nucleosome...

  9. Modulation of the functional association between the HIV-1 intasome and the nucleosome by histone amino-terminal tails.

    Science.gov (United States)

    Benleulmi, Mohamed S; Matysiak, Julien; Robert, Xavier; Miskey, Csaba; Mauro, Eric; Lapaillerie, Delphine; Lesbats, Paul; Chaignepain, Stéphane; Henriquez, Daniel R; Calmels, Christina; Oladosu, Oyindamola; Thierry, Eloïse; Leon, Oscar; Lavigne, Marc; Andreola, Marie-Line; Delelis, Olivier; Ivics, Zoltán; Ruff, Marc; Gouet, Patrice; Parissi, Vincent

    2017-11-28

    Stable insertion of the retroviral DNA genome into host chromatin requires the functional association between the intasome (integrase·viral DNA complex) and the nucleosome. The data from the literature suggest that direct protein-protein contacts between integrase and histones may be involved in anchoring the intasome to the nucleosome. Since histone tails are candidates for interactions with the incoming intasomes we have investigated whether they could participate in modulating the nucleosomal integration process. We show here that histone tails are required for an optimal association between HIV-1 integrase (IN) and the nucleosome for efficient integration. We also demonstrate direct interactions between IN and the amino-terminal tail of human histone H4 in vitro. Structure/function studies enabled us to identify amino acids in the carboxy-terminal domain of IN that are important for this interaction. Analysis of the nucleosome-binding properties of catalytically active mutated INs confirmed that their ability to engage the nucleosome for integration in vitro was affected. Pseudovirus particles bearing mutations that affect the IN/H4 association also showed impaired replication capacity due to altered integration and re-targeting of their insertion sites toward dynamic regions of the chromatin with lower nucleosome occupancy. Collectively, our data support a functional association between HIV-1 IN and histone tails that promotes anchoring of the intasome to nucleosomes and optimal integration into chromatin.

  10. Cloning and characterization of the 5'-flanking region of the Ehox gene

    International Nuclear Information System (INIS)

    Lee, Woon Kyu; Kim, Yong-Man; Malik, Nasir; Ma Chang; Westphal, Heiner

    2006-01-01

    The paired-like homeobox-containing gene Ehox plays a role in embryonic stem cell differentiation and is highly expressed in the developing placenta and thymus. To understand the mechanisms of regulation of Ehox gene expression, the 5'-flanking region of the Ehox gene was isolated from a mouse BAC library. 5'-RACE analysis revealed a single transcriptional start site 130 nucleotides upstream of the translation initiation codon. Transient transfection with a luciferase reporter gene under the control of serially deleted 5'-flanking sequences revealed that the nt -84 to -68 region contained a positive cis-acting element for efficient expression of the Ehox gene. Mutational analysis of this region and oligonucleotide competition in the electrophoretic mobility shift assay revealed the presence of a CCAAT box, which is a target for transcription nuclear factor Y (NFY). NFY is essential for positive gene regulation. No tissue-specific enhancer was identified in the 1.9-kb 5'-flanking region of the Ehox gene. Ehox is expressed during the early stages of embryo development, specifically in Brain at 9.5 dpc, as well as during the late stages of embryo development. These results suggest that NFY is an essential regulatory factor for Ehox transcriptional activity, which is important for the post-implantation stage of the developing embryo

  11. Successful flank appraisal with a horizontal well: a Niger Delta example

    Energy Technology Data Exchange (ETDEWEB)

    Ohanele, C.; Emelumadu, U.

    1998-12-31

    Case study of a horizontal well successfully drilled in 1994 by Shell Oil in the Niger Delta is described. The well was drilled with the objectives of improving drainage of the major D3.1 reservoir and appraising the poorly defined eastern flank for structure and fluid content of the overlying D3.0 sand. The well was optimized by 3D reservoir and hydrocarbon modeling of these reservoirs. Combining the development and appraisal objectives in one horizontal well proved to be the optimal solution, both from a cost as well as a production consideration. The well proved up over 50 MMstb of additional reserves. The structural flank proved to be significantly shallower than previously mapped and had a positive effect not only on the D3.0 reserves, but also on the the D3.1. 6 figs.

  12. ATP-Dependent Chromatin Remodeling Factors and Their Roles in Affecting Nucleosome Fiber Composition

    Directory of Open Access Journals (Sweden)

    Alexandra Lusser

    2011-10-01

    Full Text Available ATP-dependent chromatin remodeling factors of the SNF2 family are key components of the cellular machineries that shape and regulate chromatin structure and function. Members of this group of proteins have broad and heterogeneous functions ranging from controlling gene activity, facilitating DNA damage repair, promoting homologous recombination to maintaining genomic stability. Several chromatin remodeling factors are critical components of nucleosome assembly processes, and recent reports have identified specific functions of distinct chromatin remodeling factors in the assembly of variant histones into chromatin. In this review we will discuss the specific roles of ATP-dependent chromatin remodeling factors in determining nucleosome composition and, thus, chromatin fiber properties.

  13. Genome-wide nucleosome map and cytosine methylation levels of an ancient human genome

    DEFF Research Database (Denmark)

    Pedersen, Jakob Skou; Valen, Eivind; Velazquez, Amhed Missael Vargas

    2014-01-01

    Epigenetic information is available from contemporary organisms, but is difficult to track back in evolutionary time. Here, we show that genome-wide epigenetic information can be gathered directly from next-generation sequence reads of DNA isolated from ancient remains. Using the genome sequence...... data generated from hair shafts of a 4000-yr-old Paleo-Eskimo belonging to the Saqqaq culture, we generate the first ancient nucleosome map coupled with a genome-wide survey of cytosine methylation levels. The validity of both nucleosome map and methylation levels were confirmed by the recovery...

  14. Flank solar wind interaction. Annual report, June 1991-July 1992

    International Nuclear Information System (INIS)

    Moses, S.L.; Greenstadt, E.W.

    1992-08-01

    This report summarizes the results of the first 12 months of our program to study the interaction of the Earth's magnetosphere with the solar wind on the far flanks of the bow shock. This study employs data from the ISEE-3 spacecraft during its traversals of the Earth's magnetotail and correlative data from spacecraft monitoring the solar wind upstream. Our main effort to date has involved assembling data sets and developing new plotting programs. Two talks were given at the Spring Meeting of the American Geophysical Union describing our initial results from analyzing data from the far flank foreshock and magnetosheath. The following sections summarize our results

  15. Single nucleotide polymorphisms in the 5'-flanking region of the ...

    African Journals Online (AJOL)

    Prolactin (PRL), a polypeptide hormone synthesized and secreted by the animal's anterior pituitary gland, plays an important role in the regulation of mammalian lactation and avian reproduction. Considering the significant association between single nucleotide polymorphisms (SNPs) in the 5'-flanking region of PRL and ...

  16. Evidence for magnocellular involvement in the identification of flanked letters

    NARCIS (Netherlands)

    Omtzigt, D.; Hendriks, A.W.C.J.; Kolk, H.H.J.

    2002-01-01

    Little is known about the role of the magno system in reading. One important hypothesis is that this system is involved in the allocation of attention. We reasoned that the presentation of a single letter automatically draws attention to this letter, whereas in the case of a flanked letter, an

  17. Dynamic Conformations of Nucleosome Arrays in Solution from Small-Angle X-ray Scattering

    Energy Technology Data Exchange (ETDEWEB)

    Howell, Steven C. [George Washington Univ., Washington, DC (United States)

    2016-01-31

    We set out to determine quantitative information regarding the dynamic conformation of nucleosome arrays in solution using experimental SAXS. Toward this end, we developed a CG simulation algorithm for dsDNA which rapidly generates ensembles of structures through Metropolis MC sampling of a Markov chain.

  18. Extracellular histones, cell-free DNA, or nucleosomes: differences in immunostimulation.

    Science.gov (United States)

    Marsman, Gerben; Zeerleder, Sacha; Luken, Brenda M

    2016-12-08

    In inflammation, extensive cell death may occur, which results in the release of chromatin components into the extracellular environment. Individually, the purified chromatin components double stranded (ds)DNA and histones have been demonstrated, both in vitro and in vivo, to display various immunostimulatory effects, for example, histones induce cytotoxicity and proinflammatory signaling through toll-like receptor (TLR)2 and 4, while DNA induces signaling through TLR9 and intracellular nucleic acid sensing mechanisms. However, DNA and histones are organized in nucleosomes in the nucleus, and evidence suggests that nucleosomes are released as such in inflammation. The cytotoxicity and proinflammatory signaling induced by nucleosomes have not been studied as extensively as the separate effects brought about by histones and dsDNA, and there appear to be some marked differences. Remarkably, little distinction between the different forms in which histones circulate has been made throughout literature. This is partly due to the limitations of existing techniques to differentiate between histones in their free or DNA-bound form. Here we review the current understanding of immunostimulation induced by extracellular histones, dsDNA and nucleosomes, and discuss the importance of techniques that in their detection differentiate between these different chromatin components.

  19. Extranuclear detection of histones and nucleosomes in activated human lymphoblasts as an early event in apoptosis.

    NARCIS (Netherlands)

    Gabler, C.; Blank, N.; Hieronymus, T.; Schiller, M.; Berden, J.H.M.; Kalden, J.R.; Lorenz, H.M.

    2004-01-01

    OBJECTIVE: To evaluate the presence of histones and nucleosomes in cell lysates of freshly isolated peripheral blood mononuclear cells (PBMC), fully activated lymphoblasts, or lymphoblasts after induction of apoptosis. METHODS: Each histone class (H1, H2A, H2B, H3, and H4) was detected by western

  20. Unilateral flank ovariohysterectomy in guinea pigs (Cavia porcellus).

    Science.gov (United States)

    Rozanska, D; Rozanski, P; Orzelski, M; Chlebicka, N; Putowska, K

    2016-11-01

    To describe a simple, minimally invasive method of ovariohysterectomy via a unilateral flank approach in guinea pigs, for use in routine desexing of healthy female guinea pigs or treatment of ovarian cysts. The subjects of this retrospective study were 41 client-owned guinea pigs submitted for routine desexing or treatment of ovarian cysts. They included 16 healthy female guinea pigs aged 8-12 months (Group 1), and 15 females aged from 9 months to 3 years (Group 2), and 10 females aged from 3 to 7 years (Group 3) with different-sized ovarian cysts. Prior to surgery, the animals received clinical examination, blood testing (complete blood count and serum biochemistry profile) and examination of the abdomen using ultrasonography, to assess the condition of the reproductive tract and ensure the guinea pigs were fit for surgery. Ovariohysterectomy was performed via a unilateral flank incision made close to the erector spinae muscle starting approximately 1 cm caudal to the last rib. Both ovaries, uterine horns, and the uterine cervix were localised, ligated, and dissected through this unilateral retroperitoneal incision. Ovariohysterectomy was successfully completed via a single flank incision in 38/41 (93%) guinea pigs. Three guinea pigs with ovarian cysts from Group 3, which were >6 years old died during surgery due to circulatory and respiratory failure under anaesthesia. In the remaining 38 cases, surgery proceeded without complications. A further two guinea pigs from Group 3 were reluctant to move or eat for the first 3 days after surgery but recovered after provision of supportive care. All 38 animals fully recovered and wound healing was normal. This is the first report of ovariohysterectomy via a unilateral flank incision in guinea pigs. This approach is a simple, minimally invasive and safe alternative to the midline or bilateral flank approaches currently used for surgery of the reproductive tract in guinea pigs.

  1. Complex exon-intron marking by histone modifications is not determined solely by nucleosome distribution.

    Directory of Open Access Journals (Sweden)

    Pawandeep Dhami

    2010-08-01

    Full Text Available It has recently been shown that nucleosome distribution, histone modifications and RNA polymerase II (Pol II occupancy show preferential association with exons ("exon-intron marking", linking chromatin structure and function to co-transcriptional splicing in a variety of eukaryotes. Previous ChIP-sequencing studies suggested that these marking patterns reflect the nucleosomal landscape. By analyzing ChIP-chip datasets across the human genome in three cell types, we have found that this marking system is far more complex than previously observed. We show here that a range of histone modifications and Pol II are preferentially associated with exons. However, there is noticeable cell-type specificity in the degree of exon marking by histone modifications and, surprisingly, this is also reflected in some histone modifications patterns showing biases towards introns. Exon-intron marking is laid down in the absence of transcription on silent genes, with some marking biases changing or becoming reversed for genes expressed at different levels. Furthermore, the relationship of this marking system with splicing is not simple, with only some histone modifications reflecting exon usage/inclusion, while others mirror patterns of exon exclusion. By examining nucleosomal distributions in all three cell types, we demonstrate that these histone modification patterns cannot solely be accounted for by differences in nucleosome levels between exons and introns. In addition, because of inherent differences between ChIP-chip array and ChIP-sequencing approaches, these platforms report different nucleosome distribution patterns across the human genome. Our findings confound existing views and point to active cellular mechanisms which dynamically regulate histone modification levels and account for exon-intron marking. We believe that these histone modification patterns provide links between chromatin accessibility, Pol II movement and co-transcriptional splicing.

  2. Genetic Recombination at the Buff Spore Color Locus in SORDARIA BREVICOLLIS. II. Analysis of Flanking Marker Behavior in Crosses between Buff Mutants

    OpenAIRE

    Sang, Helen; Whitehouse, Harold L K

    1983-01-01

    Aberrant asci containing one or more wild-type spores were selected from crosses between pairs of alleles of the buff locus in the presence of closely linked flanking markers. Data were obtained relating to the site of aberrant segregation and the position of any associated crossover giving recombination of flanking markers. Aberrant segregation at a proximal site within the buff gene may be associated with a crossover proximal to the site of aberrant segregation or, with equal frequency, wit...

  3. DISQUIETUDE ON THE EASTERN FLANK: AWAITING ALLIANCE RESPONSE

    Directory of Open Access Journals (Sweden)

    Octavian Manea

    2010-03-01

    Full Text Available The absence of significant and tangible military defensive infrastructure on the Eastern flank generated over time a breach of credibility in the security guarantee provided by NATO under its Article 5 commitment. The main argument of the countries in the New Europe now is that, in order to be credible enough, and not just a paper guarantee, a collective defence commitment must be backed by “boots on the ground” and by military tangible logistics.While assuming this perspective, the present article looks at some of the alarm signals coming from the countries on NATO’s Eastern flank, trying to explain the feeling of insecurity perceived by the states in the region as well as the options available to the Euro-Atlantic community in order to engage in a much-needed process of strategic reassurance.

  4. Force Modelling in Orthogonal Cutting Considering Flank Wear Effect

    Science.gov (United States)

    Rathod, Kanti Bhikhubhai; Lalwani, Devdas I.

    2017-05-01

    In the present work, an attempt has been made to provide a predictive cutting force model during orthogonal cutting by combining two different force models, that is, a force model for a perfectly sharp tool plus considering the effect of edge radius and a force model for a worn tool. The first force model is for a perfectly sharp tool that is based on Oxley's predictive machining theory for orthogonal cutting as the Oxley's model is for perfectly sharp tool, the effect of cutting edge radius (hone radius) is added and improve model is presented. The second force model is based on worn tool (flank wear) that was proposed by Waldorf. Further, the developed combined force model is also used to predict flank wear width using inverse approach. The performance of the developed combined total force model is compared with the previously published results for AISI 1045 and AISI 4142 materials and found reasonably good agreement.

  5. Economic method for helical gear flank surface characterisation

    Science.gov (United States)

    Koulin, G.; Reavie, T.; Frazer, R. C.; Shaw, B. A.

    2018-03-01

    Typically the quality of a gear pair is assessed based on simplified geometric tolerances which do not always correlate with functional performance. In order to identify and quantify functional performance based parameters, further development of the gear measurement approach is required. Methodology for interpolation of the full active helical gear flank surface, from sparse line measurements, is presented. The method seeks to identify the minimum number of line measurements required to sufficiently characterise an active gear flank. In the form ground gear example presented, a single helix and three profile line measurements was considered to be acceptable. The resulting surfaces can be used to simulate the meshing engagement of a gear pair and therefore provide insight into functional performance based parameters. Therefore the assessment of the quality can be based on the predicted performance in the context of an application.

  6. An unusual manifestation of acute appendicitis with left flank pain

    Directory of Open Access Journals (Sweden)

    Roland Talanow, MD, PhD

    2008-08-01

    Full Text Available The author presents a case with an unusual presentation of early appendicitis. The patient presented initially with left sided flank pain. Workup for nephrolithiasis, including non-contrast CT of the abdomen and pelvis was negative for renal stones or hydronephrosis. After discharge, the patient presented one week later in the ED with right lower quadrant pain. Contrast enhanced CT of the abdomen revealed perforated appendicitis.

  7. NATO’s Northeastern Flank: Emerging Opportunities for Engagement

    Science.gov (United States)

    2017-01-01

    escalation concerns. Engagement should also stress the importance of Polish support for and capabilities toward addressing NATO’s southern flank...in their response to the Ukraine crisis.8 Some countries are either cowed by the Russian threat or genuinely less concerned about it than might be...no small part due to Hungary’s dependence on Russian gas exports, which heat the homes of most Hungarians. It is also, however, due to political

  8. The hamster flank organ model: Is it relevant to man

    International Nuclear Information System (INIS)

    Franz, T.J.; Lehman, P.A.; Pochi, P.; Odland, G.F.; Olerud, J.

    1989-01-01

    The critical role that androgens play in the etiology of acne has led to a search for topically active antiandrogens and the frequent use of the flank organ of the golden Syrian hamster as an animal model. 17-alpha-propyltestosterone (17-PT) has been identified as having potent antiandrogenic activity in the hamster model, and this report describes its clinical evaluation. Two double-blind placebo controlled studies comparing 4% 17-PT in 80% alcohol versus vehicle alone were conducted. One study examined 17-PT sebosuppressive activity in 20 subjects. The second study examined its efficacy in 44 subjects having mild to moderate acne. A third study measured in vitro percutaneous absorption of 17-PT through hamster flank and monkey skin, and human face skin in-vivo, using radioactive drug. 17-PT was found to be ineffective in reducing either the sebum excretion rate or the number of inflammatory acne lesions. Failure of 17-PT to show clinical activity was not a result of poor percutaneous absorption. Total absorption in man was 7.7% of the dose and only 1.0% in the hamster. The sebaceous gland of hamster flank organ is apparently more sensitive to antiandrogens than the human sebaceous gland

  9. Optimization of turning process through the analytic flank wear modelling

    Science.gov (United States)

    Del Prete, A.; Franchi, R.; De Lorenzis, D.

    2018-05-01

    In the present work, the approach used for the optimization of the process capabilities for Oil&Gas components machining will be described. These components are machined by turning of stainless steel castings workpieces. For this purpose, a proper Design Of Experiments (DOE) plan has been designed and executed: as output of the experimentation, data about tool wear have been collected. The DOE has been designed starting from the cutting speed and feed values recommended by the tools manufacturer; the depth of cut parameter has been maintained as a constant. Wear data has been obtained by means the observation of the tool flank wear under an optical microscope: the data acquisition has been carried out at regular intervals of working times. Through a statistical data and regression analysis, analytical models of the flank wear and the tool life have been obtained. The optimization approach used is a multi-objective optimization, which minimizes the production time and the number of cutting tools used, under the constraint on a defined flank wear level. The technique used to solve the optimization problem is a Multi Objective Particle Swarm Optimization (MOPS). The optimization results, validated by the execution of a further experimental campaign, highlighted the reliability of the work and confirmed the usability of the optimized process parameters and the potential benefit for the company.

  10. It's fun to transcribe with Fun30: A model for nucleosome dynamics during RNA polymerase II-mediated elongation.

    Science.gov (United States)

    Lee, Junwoo; Choi, Eun Shik; Lee, Daeyoup

    2018-01-01

    The ability of elongating RNA polymerase II (RNAPII) to regulate the nucleosome barrier is poorly understood because we do not know enough about the involved factors and we lack a conceptual framework to model this process. Our group recently identified the conserved Fun30/SMARCAD1 family chromatin-remodeling factor, Fun30 Fft3 , as being critical for relieving the nucleosome barrier during RNAPII-mediated elongation, and proposed a model illustrating how Fun30 Fft3 may contribute to nucleosome disassembly during RNAPII-mediated elongation. Here, we present a model that describes nucleosome dynamics during RNAPII-mediated elongation in mathematical terms and addresses the involvement of Fun30 Fft3 in this process.

  11. In vitro molecular magnetic resonance imaging detection and measurement of apoptosis using superparamagnetic iron oxide + antibody as ligands for nucleosomes

    Science.gov (United States)

    Rapley, P. L.; Witiw, C.; Rich, K.; Niccoli, S.; Tassotto, M. L.; Th'ng, J.

    2012-11-01

    Recent research in cell biology as well as oncology research has focused on apoptosis or programmed cell death as a means of quantifying the induced effects of treatment. A hallmark of late-stage apoptosis is nuclear fragmentation in which DNA is degraded to release nucleosomes with their associated histones. In this work, a method was developed for detecting and measuring nucleosome concentration in vitro with magnetic resonance imaging (MRI). The indirect procedure used a commercially available secondary antibody-superparamagnetic iron oxide (SPIO) particle complex as a contrast agent that bound to primary antibodies against nucleosomal histones H4, H2A and H2B. Using a multiple-echo spin-echo sequence on a 1.5 T clinical MRI scanner, significant T2 relaxation enhancement as a function of in vitro nucleosomal concentration was measured. In addition, clustering or aggregation of the contrast agent was demonstrated with its associated enhancement in T2 effects. The T2 clustering enhancement showed a complex dependence on relative concentrations of nucleosomes, primary antibody and secondary antibody + SPIO. The technique supports the feasibility of using MRI measurements of nucleosome concentration in blood as a diagnostic, prognostic and predictive tool in the management of cancer.

  12. Mechanical properties of symmetric and asymmetric DNA A-tracts: implications for looping and nucleosome positioning

    Czech Academy of Sciences Publication Activity Database

    Dršata, Tomáš; Špačková, Naďa; Jurečka, P.; Zgarbová, M.; Šponer, Jiří; Lankaš, Filip

    2014-01-01

    Roč. 42, č. 11 (2014), s. 7383-7394 ISSN 0305-1048 R&D Projects: GA ČR(CZ) GA14-21893S Grant - others:GA MŠk(CZ) ED2.1.00/03.0058; GA MŠk(CZ) ED1.1.00/02.0068 Program:ED; ED Institutional support: RVO:61388963 ; RVO:68081707 Keywords : molecular dynamics simulations * sequence-directed curvature * adenine-thymine tract Subject RIV: BO - Biophysics Impact factor: 9.112, year: 2014 http://nar.oxfordjournals.org/content/42/11/7383

  13. Arabidopsis Chromatin Assembly Factor 1 is required for occupancy and position of a subset of nucleosomes

    Czech Academy of Sciences Publication Activity Database

    Munoz-Viana, R.; Wildhaber, T.; Trejo-Arellano, M.S.; Mozgová, Iva; Hennig, L.

    2017-01-01

    Roč. 92, č. 3 (2017), s. 363-374 ISSN 0960-7412 Institutional support: RVO:61388971 Keywords : Arabidopsis thaliana * chromatin * CAF-1 Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 5.901, year: 2016

  14. The H1 linker histones: multifunctional proteins beyond the nucleosomal core particle.

    Science.gov (United States)

    Hergeth, Sonja P; Schneider, Robert

    2015-11-01

    The linker histone H1 family members are a key component of chromatin and bind to the nucleosomal core particle around the DNA entry and exit sites. H1 can stabilize both nucleosome structure and higher-order chromatin architecture. In general, H1 molecules consist of a central globular domain with more flexible tail regions at both their N- and C-terminal ends. The existence of multiple H1 subtypes and a large variety of posttranslational modifications brings about a considerable degree of complexity and makes studying this protein family challenging. Here, we review recent progress in understanding the function of linker histones and their subtypes beyond their role as merely structural chromatin components. We summarize current findings on the role of H1 in heterochromatin formation, transcriptional regulation and embryogenesis with a focus on H1 subtypes and their specific modifications. © 2015 The Authors.

  15. Nucleosome–nucleosome interactions via histone tails and linker DNA regulate nuclear rigidity

    Science.gov (United States)

    Shimamoto, Yuta; Tamura, Sachiko; Masumoto, Hiroshi; Maeshima, Kazuhiro

    2017-01-01

    Cells, as well as the nuclei inside them, experience significant mechanical stress in diverse biological processes, including contraction, migration, and adhesion. The structural stability of nuclei must therefore be maintained in order to protect genome integrity. Despite extensive knowledge on nuclear architecture and components, however, the underlying physical and molecular mechanisms remain largely unknown. We address this by subjecting isolated human cell nuclei to microneedle-based quantitative micromanipulation with a series of biochemical perturbations of the chromatin. We find that the mechanical rigidity of nuclei depends on the continuity of the nucleosomal fiber and interactions between nucleosomes. Disrupting these chromatin features by varying cation concentration, acetylating histone tails, or digesting linker DNA results in loss of nuclear rigidity. In contrast, the levels of key chromatin assembly factors, including cohesin, condensin II, and CTCF, and a major nuclear envelope protein, lamin, are unaffected. Together with in situ evidence using living cells and a simple mechanical model, our findings reveal a chromatin-based regulation of the nuclear mechanical response and provide insight into the significance of local and global chromatin structures, such as those associated with interdigitated or melted nucleosomal fibers. PMID:28428255

  16. File list: InP.Emb.50.AllAg.Embryonic_flank [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Emb.50.AllAg.Embryonic_flank mm9 Input control Embryo Embryonic flank SRX804059... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Emb.50.AllAg.Embryonic_flank.bed ...

  17. Amyloidosis of the renal pelvis presenting as flank pain

    Directory of Open Access Journals (Sweden)

    Rachel Shikhman, D.O.

    2018-02-01

    Full Text Available Amyloidosis is a rare disease defined by accumulation of extracellular amyloid systemically or within a specific organ. Localized amyloidosis of the genitourinary system is extremely rare, with the predominate location being the bladder. The imaging findings are often nonspecific and mimic urothelial carcinoma. We present a 49-year-old woman with a chief complaint of flank pain. A filling defect was discovered on radiological imaging. The defect was subsequently biopsied and proven to be a primary amyloidosis of the renal pelvis. We then review the radiological findings of amyloidosis of the genitourinary system.

  18. Human renin 5'-flanking DNA to nucleotide-2750.

    Science.gov (United States)

    Smith, D L; Jeyapalan, S; Lang, J A; Guo, X H; Sigmund, C D; Morris, B J

    1995-01-01

    Renin is one of the most important factors in blood pressure and electrolyte regulation in mammals and the renin locus has been implicated in hypertension. To assist studies of promoter control we therefore determined the 5'-flanking sequence of the human gene (REN) to residue -2750 relative to the transcription start site (+1). Sites of homology to consensus sequences for binding of trans-acting factors involved in transcriptional control of other genes were identified, and functionality for two of these (a CRE and Pit-1 site) have so far been demonstrated.

  19. Unenhanced helical CT in the investigation of acute flank pain

    International Nuclear Information System (INIS)

    Colistro, Robert; Torreggiani, William C.; Lyburn, Iain D.; Harris, Alison C.; Al-Nakshabandi, Nizar A.; Nicolaou, Savvas; Munk, Peter L.

    2002-01-01

    Unenhanced helical CT has emerged as the imaging technique of choice for the investigation of patients presenting with acute flank pain and suspected nephroureteric stone disease. There are several signs identifiable on unenhanced CT that support a diagnosis of stone disease. However, there are many pitfalls, that may confound a correct diagnosis. Some of the common pitfalls, together with methods to avoid such occurrences, will be discussed. A review of some of the common alternative diagnoses that may mimic the symptoms of nephroureteric stone disease is illustrated. Colistro, R. et al (2002)

  20. Plasma Transport at the Magnetospheric Flank Boundary. Final report

    International Nuclear Information System (INIS)

    Otto, Antonius

    2012-01-01

    Progress is highlighted in these areas: 1. Model of magnetic reconnection induced by three-dimensional Kelvin Helmholtz (KH) modes at the magnetospheric flank boundary; 2. Quantitative evaluation of mass transport from the magnetosheath onto closed geomagnetic field for northward IMF; 3. Comparison of mass transfer by cusp reconnection and Flank Kelvin Helmholtz modes; 4. Entropy constraint and plasma transport in the magnetotail - a new mechanism for current sheet thinning; 5. Test particle model for mass transport onto closed geomagnetic field for northward IMF; 6. Influence of density asymmetry and magnetic shear on (a) the linear and nonlinear growth of 3D Kelvin Helmholtz (KH) modes, and (b) three-dimensional KH mediated mass transport; 7. Examination of entropy and plasma transport in the magnetotail; 8. Entropy change and plasma transport by KH mediated reconnection - mixing and heating of plasma; 9. Entropy and plasma transport in the magnetotail - tail reconnection; and, 10. Wave coupling at the magnetospheric boundary and generation of kinetic Alfven waves

  1. Southward flow on the western flank of the Florida Current

    Science.gov (United States)

    Soloviev, Alexander V.; Hirons, Amy; Maingot, Christopher; Dean, Cayla W.; Dodge, Richard E.; Yankovsky, Alexander E.; Wood, Jon; Weisberg, Robert H.; Luther, Mark E.; McCreary, Julian P.

    2017-07-01

    A suite of long-term in situ measurements in the Straits of Florida, including the ADCP bottom moorings at an 11-m isobath and 244-m isobath (Miami Terrace) and several ADCP ship transects, have revealed a remarkable feature of the ocean circulation - southward flow on the western, coastal flank of the Florida Current. We have observed three forms of the southward flow - a seasonally varying coastal countercurrent, an undercurrent jet attached to the Florida shelf, and an intermittent undercurrent on the Miami Terrace. According to a 13-year monthly climatology obtained from the near-shore mooring, the coastal countercurrent is a persistent feature from October through January. The southward flow in the form of an undercurrent jet attached to the continental slope was observed during five ship transects from April through September but was not observed during three transects in February, March, and November. This undercurrent jet is well mixed due to strong shear at its top associated with the northward direction of the surface flow (Florida Current) and friction at the bottom. At the same time, no statistically significant seasonal cycle has been observed in the undercurrent flow on the Miami Terrace. Theoretical considerations suggest that several processes could drive the southward current, including interaction between the Florida Current and the shelf, as well as forcing that is independent of the Florida Current. The exact nature of the southward flow on the western flank of the Florida Current is, however, unknown.

  2. Reverse time migration of prism waves for salt flank delineation

    KAUST Repository

    Dai, Wei; Schuster, Gerard T.

    2013-01-01

    In this paper, we present a new reverse time migration method for imaging salt flanks with prism wave reflections. It consists of four steps: (1) migrating the seismic data with conventional RTM to give the RTM image; (2) using the RTM image as a reflectivity model to simulate source-side reflections with the Born approximation; (3) zero-lag correlation of the source-side reflection wavefields and receiver-side wavefields to produce the prism wave migration image; and (4) repeating steps 2 and 3 for the receiver-side reflections. An advantage of this method is that there is no need to pick the horizontal reflectors prior to migration of the prism waves. It also separately images the vertical structures at a different step to reduce crosstalk interference. The disadvantage of prism wave migration algorithm is that its computational cost is twice that of conventional RTM. The empirical results with a salt model suggest that prism wave migration can be an effective method for salt flank delineation in the absence of diving waves.

  3. Reverse time migration of prism waves for salt flank delineation

    KAUST Repository

    Dai, Wei

    2013-09-22

    In this paper, we present a new reverse time migration method for imaging salt flanks with prism wave reflections. It consists of four steps: (1) migrating the seismic data with conventional RTM to give the RTM image; (2) using the RTM image as a reflectivity model to simulate source-side reflections with the Born approximation; (3) zero-lag correlation of the source-side reflection wavefields and receiver-side wavefields to produce the prism wave migration image; and (4) repeating steps 2 and 3 for the receiver-side reflections. An advantage of this method is that there is no need to pick the horizontal reflectors prior to migration of the prism waves. It also separately images the vertical structures at a different step to reduce crosstalk interference. The disadvantage of prism wave migration algorithm is that its computational cost is twice that of conventional RTM. The empirical results with a salt model suggest that prism wave migration can be an effective method for salt flank delineation in the absence of diving waves.

  4. Human platelet glycoprotein IX: An adhesive prototype of leucine-rich glycoproteins with flank-center-flank structures

    International Nuclear Information System (INIS)

    Hickey, M.J.; Williams, S.A.; Roth, G.J.

    1989-01-01

    The glycoprotein (GP) Ib-IX complex on the surface of human platelets functions as the von Willebrand factor receptor and mediates von Willebrand factor-dependent platelet adhesion to blood vessels. GPIX is a relatively small (M r , 17,000) protein that may provide for membrane insertion and orientation of the larger component of the complex. GPIb (M r , 165,000). Using antibody screening, the authors cloned a cDNA encoding GPIX from a human erythroleukemia cell cDNA library constructed in phage λgt11. Lacking a 5' untranslated region and start codon, the cDNA sequence includes 604 nucleotides, beginning with 495 bases at the 5' end coding for 165 amino acids, followed by a stop codon and 106 noncoding bases at the 3' end. By Northern blot analysis, the GPIX cDNA hybridizes with a single 1.0-kilobase species of platelet poly(A) + RNA. Translation of the cDNA sequence gives a predicted protein sequence beginning with a truncated putative signal sequence of 5 amino acids followed by a sequence of 17 amino acids matching that determined directly by Edman degradation of intact GPIX. GPIX contains a leucine-rich glycoprotein (LRG) sequence of 24 amino acids similar to conserved LRG sequences in GPIb and other proteins from humans, Drosophila, and yeast. The role of the flank-LRG center-flank structure in the evolution and function of the LRG proteins remains to be defined

  5. Surface waves on the tailward flanks of the Earth's magnetopause

    Science.gov (United States)

    Seon, J.; Frank, L. A.; Lazarus, A. J.; Lepping, R. P.

    1995-01-01

    Forty-three examples of ISEE 1 tailward flank side magnetopause crossings are examined and directly compared with upstream solar wind parameters. The crossings are classified into two groups. In the first group, a few sudden magnetopause crossings are observed, whereas repeated magnetopause crossings and oscillatory motions, often with boundary layer signatures, are observed in the second group. These distinctive characteristics of the two groups are interpreted in terms of the surface waves due to the Kelvin-Helmholtz instability. It is found that low solar wind speed tends to favor characteristics of the first group, whereas high solar wind speed yields those of the second group. However, no evident correlations between the groups and the interplanetary magnetic field directions are found.

  6. Geomorphology of the north flank of the Uinta Mountains

    Science.gov (United States)

    Bradley, W.H.

    1936-01-01

    The Uinta Mountains, whose northern margin is almost coincident with the southern boundary of Wyoming, extend from the Wasatch Range eastward across the northern part of Utah into northwestern Colorado. They were carved out of a large, simple anticlinal fold of sedimentary rocks arched up into essentially their present attitude at the end of the Cretaceous period. The Uinta Mountain group (Uinta quartzite of previous reports) a series of brick-red to purplish-red quartzite and sandstone beds of pre-Cambrian age, aggregating more than 12,000 feet in thickness, makes up the central mass of the range. Flanking the quartzite core and sharing its anticlinal structure are beds of limestone, sandstone, and shale ranging in age from Upper or Middle Cambrian to Upper Cretaceous. These rocks, which have a total thickness of about 15,000 feet, have been eroded from the higher part of the range, so the upturned edges of the harder

  7. Cluster observations of surface waves on the dawn flank magnetopause

    Directory of Open Access Journals (Sweden)

    C. J. Owen

    2004-03-01

    Full Text Available On 14 June 2001 the four Cluster spacecraft recorded multiple encounters of the dawn-side flank magnetopause. The characteristics of the observed electron populations varied between a cold, dense magnetosheath population and warmer, more rarified boundary layer population on a quasi-periodic basis. The demarcation between these two populations can be readily identified by gradients in the scalar temperature of the electrons. An analysis of the differences in the observed timings of the boundary at each spacecraft indicates that these magnetopause crossings are consistent with a surface wave moving across the flank magnetopause. When compared to the orientation of the magnetopause expected from models, we find that the leading edges of these waves are approximately 45° steeper than the trailing edges, consistent with the Kelvin-Helmholtz (KH driving mechanism. A stability analysis of this interval suggests that the magnetopause is marginally stable to this mechanism during this event. Periods in which the analysis predicts that the magnetopause is unstable correspond to observations of greater wave steepening. Analysis of the pulses suggests that the waves have an average wavelength of approximately 3.4 RE and move at an average speed of ~65km s-1 in an anti-sunward and northward direction, despite the spacecraft location somewhat south of the GSE Z=0 plane. This wave propagation direction lies close to perpendicular to the average magnetic field direction in the external magnetosheath, suggesting that these waves may preferentially propagate in the direction that requires no bending of these external field lines

    Key words. Magnetospheric physics (magnetospheric configuration and dynamics; MHD waves and unstabilities; solar wind-magnetosphere interactions

  8. Pore Pressure Distribution and Flank Instability in Hydrothermally Altered Stratovolcanoes

    Science.gov (United States)

    Ball, J. L.; Taron, J.; Hurwitz, S.; Reid, M. E.

    2015-12-01

    Field and geophysical investigations of stratovolcanoes with long-lived hydrothermal systems commonly reveal that initially permeable regions (such as brecciated layers of pyroclastic material) can become both altered and water-bearing. Hydrothermal alteration in these regions, including clay formation, can turn them into low-permeability barriers to fluid flow, which could increase pore fluid pressures resulting in flank slope instability. We examined elevated pore pressure conditions using numerical models of hydrothermal flow in stratovolcanoes, informed by geophysical data about internal structures and deposits. Idealized radially symmetric meshes were developed based on cross-sectional profiles and alteration/permeability structures of Cascade Range stratovolcanoes. We used the OpenGeoSys model to simulate variably saturated conditions in volcanoes heated only by regional heat fluxes, as well as 650°C intrusions at two km depth below the surface. Meteoric recharge was estimated from precipitation rates in the Cascade Range. Preliminary results indicate zones of elevated pore pressures form: 1) where slopes are underlain by continuous low-permeability altered layers, or 2) when the edifice has an altered core with saturated, less permeable limbs. The first scenario might control shallow collapses on the slopes above the altered layers. The second could promote deeper flank collapses that are initially limited to the summit and upper slopes, but could progress to the core of an edifice. In both scenarios, pore pressures can be further elevated by shallow intrusions, or evolve over longer time scales under forcing from regional heat flux. Geometries without confining low-permeability layers do not show these pressure effects. Our initial scenarios use radially symmetric models, but we are also simulating hydrothermal flow under real 3D geometries with asymmetric subsurface structures (Mount Adams). Simulation results will be used to inform 3D slope

  9. Regulation of Budding Yeast CENP-A levels Prevents Misincorporation at Promoter Nucleosomes and Transcriptional Defects.

    Directory of Open Access Journals (Sweden)

    Erica M Hildebrand

    2016-03-01

    Full Text Available The exclusive localization of the histone H3 variant CENP-A to centromeres is essential for accurate chromosome segregation. Ubiquitin-mediated proteolysis helps to ensure that CENP-A does not mislocalize to euchromatin, which can lead to genomic instability. Consistent with this, overexpression of the budding yeast CENP-A(Cse4 is lethal in cells lacking Psh1, the E3 ubiquitin ligase that targets CENP-A(Cse4 for degradation. To identify additional mechanisms that prevent CENP-A(Cse4 misincorporation and lethality, we analyzed the genome-wide mislocalization pattern of overexpressed CENP-A(Cse4 in the presence and absence of Psh1 by chromatin immunoprecipitation followed by high throughput sequencing. We found that ectopic CENP-A(Cse4 is enriched at promoters that contain histone H2A.Z(Htz1 nucleosomes, but that H2A.Z(Htz1 is not required for CENP-A(Cse4 mislocalization. Instead, the INO80 complex, which removes H2A.Z(Htz1 from nucleosomes, promotes the ectopic deposition of CENP-A(Cse4. Transcriptional profiling revealed gene expression changes in the psh1Δ cells overexpressing CENP-A(Cse4. The down-regulated genes are enriched for CENP-A(Cse4 mislocalization to promoters, while the up-regulated genes correlate with those that are also transcriptionally up-regulated in an htz1Δ strain. Together, these data show that regulating centromeric nucleosome localization is not only critical for maintaining centromere function, but also for ensuring accurate promoter function and transcriptional regulation.

  10. Chromatin associated mechanisms in base excision repair - nucleosome remodeling and DNA transcription, two key players.

    Science.gov (United States)

    Menoni, Hervé; Di Mascio, Paolo; Cadet, Jean; Dimitrov, Stefan; Angelov, Dimitar

    2017-06-01

    Genomic DNA is prone to a large number of insults by a myriad of endogenous and exogenous agents. The base excision repair (BER) is the major mechanism used by cells for the removal of various DNA lesions spontaneously or environmentally induced and the maintenance of genome integrity. The presence of persistent DNA damage is not compatible with life, since abrogation of BER leads to early embryonic lethality in mice. There are several lines of evidences showing existence of a link between deficient BER, cancer proneness and ageing, thus illustrating the importance of this DNA repair pathway in human health. Although the enzymology of BER mechanisms has been largely elucidated using chemically defined DNA damage substrates and purified proteins, the complex interplay of BER with another vital process like transcription or when DNA is in its natural state (i.e. wrapped in nucleosome and assembled in chromatin fiber is largely unexplored. Cells use chromatin remodeling factors to overcome the general repression associated with the nucleosomal organization. It is broadly accepted that energy-dependent nucleosome remodeling factors disrupt histones-DNA interactions at the expense of ATP hydrolysis to favor transcription as well as DNA repair. Importantly, unlike transcription, BER is not part of a regulated developmental process but represents a maintenance system that should be efficient anytime and anywhere in the genome. In this review we will discuss how BER can deal with chromatin organization to maintain genetic information. Emphasis will be placed on the following challenging question: how BER is initiated within chromatin? Copyright © 2017 Elsevier Inc. All rights reserved.

  11. The disequilibrium of nucleosomes distribution along chromosomes plays a functional and evolutionarily role in regulating gene expression

    KAUST Repository

    Cui, Peng

    2011-08-19

    To further understand the relationship between nucleosome-space occupancy (NO) and global transcriptional activity in mammals, we acquired a set of genome-wide nucleosome distribution and transcriptome data from the mouse cerebrum and testis based on ChIP (H3)-seq and RNA-seq, respectively. We identified a nearly consistent NO patterns among three mouse tissues-cerebrum, testis, and ESCs-and found, through clustering analysis for transcriptional activation, that the NO variations among chromosomes are closely associated with distinct expression levels between house-keeping (HK) genes and tissue-specific (TS) genes. Both TS and HK genes form clusters albeit the obvious majority. This feature implies that NO patterns, i.e. nucleosome binding and clustering, are coupled with gene clustering that may be functionally and evolutionarily conserved in regulating gene expression among different cell types. © 2011 Cui et al.

  12. The disequilibrium of nucleosomes distribution along chromosomes plays a functional and evolutionarily role in regulating gene expression.

    Directory of Open Access Journals (Sweden)

    Peng Cui

    Full Text Available To further understand the relationship between nucleosome-space occupancy (NO and global transcriptional activity in mammals, we acquired a set of genome-wide nucleosome distribution and transcriptome data from the mouse cerebrum and testis based on ChIP (H3-seq and RNA-seq, respectively. We identified a nearly consistent NO patterns among three mouse tissues--cerebrum, testis, and ESCs--and found, through clustering analysis for transcriptional activation, that the NO variations among chromosomes are closely associated with distinct expression levels between house-keeping (HK genes and tissue-specific (TS genes. Both TS and HK genes form clusters albeit the obvious majority. This feature implies that NO patterns, i.e. nucleosome binding and clustering, are coupled with gene clustering that may be functionally and evolutionarily conserved in regulating gene expression among different cell types.

  13. Analysis of the histone protein tail and DNA in nucleosome using molecular dynamics simulation

    Science.gov (United States)

    Fujimori, R.; Komatsu, Y.; Fukuda, M.; Miyakawa, T.; Morikawa, R.; Takasu, M.

    2013-02-01

    We study the effect of the tails of H3 and H4 histones in the nucleosomes, where DNA and histones are packed in the form of chromatin. We perform molecular dynamics simulations of the complex of DNA and histones and calculate the mean square displacement and the gyration radius of the complex of DNA and histones for the cases with tails intact and the cases with tails missing. Our results show that the H3 tails are important for the motion of the histones. We also find that the motion of one tail is affected by other tails, although the tails are distanced apart, suggesting the correlated motion in biological systems.

  14. Cluster observations of reconnection due to the Kelvin-Helmholtz instability at the dawnside magnetospheric flank

    Directory of Open Access Journals (Sweden)

    K. Nykyri

    2006-10-01

    Full Text Available On 3 July 2001, the four Cluster satellites traversed along the dawnside magnetospheric flank and observed large variations in all plasma parameters. The estimated magnetopause boundary normals were oscillating in the z-direction and the normal component of the magnetic field showed systematic  2–3 min bipolar variations for 1 h when the IMF had a small positive bz-component and a Parker-spiral orientation in the x,y-plane. Brief  33 s intervals with excellent deHoffman Teller frames were observed satisfying the Walén relation. Detailed comparisons with 2-D MHD simulations indicate that Cluster encountered rotational discontinuities generated by Kelvin-Helmholtz instability. We estimate a wave length of  6 RE and a wave vector with a significant z-component.

  15. Multi-stage volcanic island flank collapses with coeval explosive caldera-forming eruptions

    OpenAIRE

    Hunt, James E.; Cassidy, Michael; Talling, Peter J.

    2018-01-01

    Volcanic flank collapses and explosive eruptions are among the largest and most destructive processes on Earth. Events at Mount St. Helens in May 1980 demonstrated how a relatively small (<5 km3) flank collapse on a terrestrial volcano could immediately precede a devastating eruption. The lateral collapse of volcanic island flanks, such as in the Canary Islands, can be far larger (>300 km3), but can also occur in complex multiple stages. Here, we show that multistage retrogressive lands...

  16. Identification of genomic insertion and flanking sequence of G2-EPSPS and GAT transgenes in soybean using whole genome sequencing method

    Directory of Open Access Journals (Sweden)

    Bingfu Guo

    2016-07-01

    Full Text Available Molecular characterization of sequences flanking exogenous fragment insertions is essential for safety assessment and labeling of genetically modified organisms (GMO. In this study, the T-DNA insertion sites and flanking sequences were identified in two newly developed transgenic glyphosate-tolerant soybeans GE-J16 and ZH10-6 based on whole genome sequencing (WGS method. About 21 Gb sequence data (~21× coverage for each line was generated on Illumina HiSeq 2500 platform. The junction reads mapped to boundary of T-DNA and flanking sequences in these two events were identified by comparing all sequencing reads with soybean reference genome and sequence of transgenic vector. The putative insertion loci and flanking sequences were further confirmed by PCR amplification, Sanger sequencing, and co-segregation analysis. All these analyses supported that exogenous T-DNA fragments were integrated in positions of Chr19: 50543767-50543792 and Chr17: 7980527-7980541 in these two transgenic lines. Identification of the genomic insertion site of the G2-EPSPS and GAT transgenes will facilitate the use of their glyphosate-tolerant traits in soybean breeding program. These results also demonstrated that WGS is a cost-effective and rapid method of identifying sites of T-DNA insertions and flanking sequences in soybean.

  17. Predicting near-UV electronic circular dichroism in nucleosomal DNA by means of DFT response theory.

    Science.gov (United States)

    Norman, Patrick; Parello, Joseph; Polavarapu, Prasad L; Linares, Mathieu

    2015-09-14

    It is demonstrated that time-dependent density functional theory (DFT) calculations can accurately predict changes in near-UV electronic circular dichroism (ECD) spectra of DNA as the structure is altered from the linear (free) B-DNA form to the supercoiled N-DNA form found in nucleosome core particles. At the DFT/B3LYP level of theory, the ECD signal response is reduced by a factor of 6.7 in going from the B-DNA to the N-DNA form, and it is illustrated how more than 90% of the individual base-pair dimers contribute to this strong hypochromic effect. Of the several inter-base pair parameters, an increase in twist angles is identified as to strongly contribute to a reduced ellipticity. The present work provides first evidence that first-principles calculations can elucidate changes in DNA dichroism due to the supramolecular organization of the nucleoprotein particle and associates these changes with the local structural features of nucleosomal DNA.

  18. The Cac2 subunit is essential for productive histone binding and nucleosome assembly in CAF-1

    Energy Technology Data Exchange (ETDEWEB)

    Mattiroli, Francesca; Gu, Yajie; Balsbaugh, Jeremy L.; Ahn, Natalie G.; Luger, Karolin

    2017-04-18

    Nucleosome assembly following DNA replication controls epigenome maintenance and genome integrity. Chromatin assembly factor 1 (CAF-1) is the histone chaperone responsible for histone (H3-H4)2 deposition following DNA synthesis. Structural and functional details for this chaperone complex and its interaction with histones are slowly emerging. Using hydrogen-deuterium exchange coupled to mass spectrometry, combined with in vitro and in vivo mutagenesis studies, we identified the regions involved in the direct interaction between the yeast CAF-1 subunits, and mapped the CAF-1 domains responsible for H3-H4 binding. The large subunit, Cac1 organizes the assembly of CAF-1. Strikingly, H3-H4 binding is mediated by a composite interface, shaped by Cac1-bound Cac2 and the Cac1 acidic region. Cac2 is indispensable for productive histone binding, while deletion of Cac3 has only moderate effects on H3-H4 binding and nucleosome assembly. These results define direct structural roles for yeast CAF-1 subunits and uncover a previously unknown critical function of the middle subunit in CAF-1.

  19. A brief histone in time: understanding the combinatorial functions of histone PTMs in the nucleosome context.

    Science.gov (United States)

    Ng, Marlee K; Cheung, Peter

    2016-02-01

    It has been over 50 years since Allfrey et al. proposed that histone acetylation regulates RNA synthesis, and the study of histone modifications has progressed at an extraordinary pace for the past two decades. In this review, we provide a perspective on some key events and advances in our understanding of histone modifications. We also highlight reagents and tools from past to present that facilitated progress in this research field. Using histone H3 phosphorylation as an underlying thread, we review the rationale that led to the proposal of the histone code hypothesis, as well as examples that illustrate the concepts of combinatorial histone modifications and cross-talk pathways. We further highlight the importance of investigating these mechanisms in the context of nucleosomes rather than just at the histone level and present current and developing approaches for such studies. Overall, research on histone modifications has yielded great mechanistic insights into the regulation of genomic functions, and extending these studies using nucleosomes will further elucidate the complexity of these pathways in a more physiologically relevant context.

  20. Scutellarein antagonizes the tumorigenesis by modulating cytokine VEGF mediated neoangiogenesis and DFF-40 actuated nucleosomal degradation

    International Nuclear Information System (INIS)

    Thirusangu, Prabhu; Vigneshwaran, V.; Vijay Avin, B.R.; Rakesh, H.; Vikas, H.M.; Prabhakar, B.T.

    2017-01-01

    Neoplastic cells often reside in distinctive tumor hypoxia armed with a series of adaptive responses including oxidative stress, defective apoptotic machinery and neoangiogenesis, through that further confer cell survival improvement. Plants still acts as reservoir of natural chemicals to provide newer active pharmacophores. Scutellarein is flavones which has wide range of pharmacophoral effects. In our current research, scutellarein employed for targeting oxidative stress mediated tumor angiogenesis and apoptotic nuclear fragmentation. Experimental results revealed that scutellarein has antiproliferative index against multiple cancer cell lines and diminished the oxidative stress and tumor development of murine ascitic lymphoma & inflammatory hepatocellular carcinoma. Eventual consequences lead to reduced neovessel formation by abrogating angiogeneic factors cytokine-VEGF-A, Flt-1, HIF-1α, MMP-2 and MMP-9 and reversing of evading apoptosis by activating caspase-3 activated DNA fragmentation factor (DFF-40) mediated nucleosomal degradation. In summary, our experimental evidences suggest that scutellarein has strong potentiality to attenuate the tumor development by modulating sprouting neovasculature and DFF-40 mediated apoptosis. - Highlights: • Scutellarein exhibits potent neoplastic effect against ascitic and DEN-induced liver carcinoma in-vivo. • Scutellarein reticence the oxidative stress and angiogenesis on tumor and non-tumor models. • Scutellarein modulates tumor vasculature by altering tumor angiogenic factor’s expressions. • Scutellarein actuates the DFF-40 mediated nucleosomal degradation in DLA tumor.

  1. Scanning mutagenesis of the amino acid sequences flanking phosphorylation site 1 of the mitochondrial pyruvate dehydrogenase complex

    Directory of Open Access Journals (Sweden)

    Nagib eAhsan

    2012-07-01

    Full Text Available The mitochondrial pyruvate dehydrogenase complex is regulated by reversible seryl-phosphorylation of the E1α subunit by a dedicated, intrinsic kinase. The phospho-complex is reactivated when dephosphorylated by an intrinsic PP2C-type protein phosphatase. Both the position of the phosphorylated Ser-residue and the sequences of the flanking amino acids are highly conserved. We have used the synthetic peptide-based kinase client assay plus recombinant pyruvate dehydrogenase E1α and E1α-kinase to perform scanning mutagenesis of the residues flanking the site of phosphorylation. Consistent with the results from phylogenetic analysis of the flanking sequences, the direct peptide-based kinase assays tolerated very few changes. Even conservative changes such as Leu, Ile, or Val for Met, or Glu for Asp, gave very marked reductions in phosphorylation. Overall the results indicate that regulation of the mitochondrial pyruvate dehydrogenase complex by reversible phosphorylation is an extreme example of multiple, interdependent instances of co-evolution.

  2. Characterizing and controlling intrinsic biases of lambda exonuclease in nascent strand sequencing reveals phasing between nucleosomes and G-quadruplex motifs around a subset of human replication origins.

    Science.gov (United States)

    Foulk, Michael S; Urban, John M; Casella, Cinzia; Gerbi, Susan A

    2015-05-01

    Nascent strand sequencing (NS-seq) is used to discover DNA replication origins genome-wide, allowing identification of features for their specification. NS-seq depends on the ability of lambda exonuclease (λ-exo) to efficiently digest parental DNA while leaving RNA-primer protected nascent strands intact. We used genomics and biochemical approaches to determine if λ-exo digests all parental DNA sequences equally. We report that λ-exo does not efficiently digest G-quadruplex (G4) structures in a plasmid. Moreover, λ-exo digestion of nonreplicating genomic DNA (LexoG0) enriches GC-rich DNA and G4 motifs genome-wide. We used LexoG0 data to control for nascent strand-independent λ-exo biases in NS-seq and validated this approach at the rDNA locus. The λ-exo-controlled NS-seq peaks are not GC-rich, and only 35.5% overlap with 6.8% of all G4s, suggesting that G4s are not general determinants for origin specification but may play a role for a subset. Interestingly, we observed a periodic spacing of G4 motifs and nucleosomes around the peak summits, suggesting that G4s may position nucleosomes at this subset of origins. Finally, we demonstrate that use of Na(+) instead of K(+) in the λ-exo digestion buffer reduced the effect of G4s on λ-exo digestion and discuss ways to increase both the sensitivity and specificity of NS-seq. © 2015 Foulk et al.; Published by Cold Spring Harbor Laboratory Press.

  3. Flank pseudohernia following posterior rib fracture: a case report.

    Science.gov (United States)

    Butensky, Adam M; Gruss, Leah P; Gleit, Zachary L

    2016-10-01

    A pseudohernia is an abdominal wall bulge that may be mistaken for a hernia but that lacks the disruption of the abdominal wall that characterizes a hernia. Thus, the natural history and treatment of this condition differ from those of a hernia. This is the first report of a pseudohernia due to cough-associated rib fracture. A case of pseudohernia due to fractures of the 10 th and 11 th ribs in a 68-year-old white woman is presented. The patient suffered from a major coughing episode 1 year prior to her presentation, after which she noted a progressively enlarging bulge in her left flank. Computed tomography demonstrated a bulge in the abdominal wall containing bowel and spleen but with all muscle and fascial layers intact; in addition, lateral 10 th rib and posterior 11 th rib fractures were noted. As there was no defect in muscle or fascia, we diagnosed a pseudohernia, likely due to a denervation injury from the fractured ribs. Symptomatic treatment was recommended, including wearing a corset and referral to a pain management clinic. Symptomatic treatment is thought to be the mainstay of therapy for pseudohernias, as surgical intervention is unlikely to be of benefit.

  4. 3D FEM Simulation of Flank Wear in Turning

    Science.gov (United States)

    Attanasio, Aldo; Ceretti, Elisabetta; Giardini, Claudio

    2011-05-01

    This work deals with tool wear simulation. Studying the influence of tool wear on tool life, tool substitution policy and influence on final part quality, surface integrity, cutting forces and power consumption it is important to reduce the global process costs. Adhesion, abrasion, erosion, diffusion, corrosion and fracture are some of the phenomena responsible of the tool wear depending on the selected cutting parameters: cutting velocity, feed rate, depth of cut, …. In some cases these wear mechanisms are described by analytical models as a function of process variables (temperature, pressure and sliding velocity along the cutting surface). These analytical models are suitable to be implemented in FEM codes and they can be utilized to simulate the tool wear. In the present paper a commercial 3D FEM software has been customized to simulate the tool wear during turning operations when cutting AISI 1045 carbon steel with uncoated tungsten carbide tip. The FEM software was improved by means of a suitable subroutine able to modify the tool geometry on the basis of the estimated tool wear as the simulation goes on. Since for the considered couple of tool-workpiece material the main phenomena generating wear are the abrasive and the diffusive ones, the tool wear model implemented into the subroutine was obtained as combination between the Usui's and the Takeyama and Murata's models. A comparison between experimental and simulated flank tool wear curves is reported demonstrating that it is possible to simulate the tool wear development.

  5. Sodium Ion Dynamics in the Magnetospheric Flanks of Mercury

    Science.gov (United States)

    Aizawa, Sae; Delcourt, Dominique; Terada, Naoki

    2018-01-01

    We investigate the transport of planetary ions in the magnetospheric flanks of Mercury. In situ measurements from the MErcury Surface, Space ENvironment, GEochemistry, and Ranging spacecraft show evidences of Kelvin-Helmholtz instability development in this region of space, due to the velocity shear between the downtail streaming flow of solar wind originating protons in the magnetosheath and the magnetospheric populations. Ions that originate from the planet exosphere and that gain access to this region of space may be transported across the magnetopause along meandering orbits. We examine this transport using single-particle trajectory calculations in model Magnetohydrodynamics simulations of the Kelvin-Helmholtz instability. We show that heavy ions of planetary origin such as Na+ may experience prominent nonadiabatic energization as they E × B drift across large-scale rolled up vortices. This energization is controlled by the characteristics of the electric field burst encountered along the particle path, the net energy change realized corresponding to the maximum E × B drift energy. This nonadiabatic energization also is responsible for prominent scattering of the particles toward the direction perpendicular to the magnetic field.

  6. FACT, the Bur kinase pathway, and the histone co-repressor HirC have overlapping nucleosome-related roles in yeast transcription elongation.

    Directory of Open Access Journals (Sweden)

    Jennifer R Stevens

    Full Text Available Gene transcription is constrained by the nucleosomal nature of chromosomal DNA. This nucleosomal barrier is modulated by FACT, a conserved histone-binding heterodimer. FACT mediates transcription-linked nucleosome disassembly and also nucleosome reassembly in the wake of the RNA polymerase II transcription complex, and in this way maintains the repression of 'cryptic' promoters found within some genes. Here we focus on a novel mutant version of the yeast FACT subunit Spt16 that supplies essential Spt16 activities but impairs transcription-linked nucleosome reassembly in dominant fashion. This Spt16 mutant protein also has genetic effects that are recessive, which we used to show that certain Spt16 activities collaborate with histone acetylation and the activities of a Bur-kinase/Spt4-Spt5/Paf1C pathway that facilitate transcription elongation. These collaborating activities were opposed by the actions of Rpd3S, a histone deacetylase that restores a repressive chromatin environment in a transcription-linked manner. Spt16 activity paralleling that of HirC, a co-repressor of histone gene expression, was also found to be opposed by Rpd3S. Our findings suggest that Spt16, the Bur/Spt4-Spt5/Paf1C pathway, and normal histone abundance and/or stoichiometry, in mutually cooperative fashion, facilitate nucleosome disassembly during transcription elongation. The recessive nature of these effects of the mutant Spt16 protein on transcription-linked nucleosome disassembly, contrasted to its dominant negative effect on transcription-linked nucleosome reassembly, indicate that mutant FACT harbouring the mutant Spt16 protein competes poorly with normal FACT at the stage of transcription-linked nucleosome disassembly, but effectively with normal FACT for transcription-linked nucleosome reassembly. This functional difference is consistent with the idea that FACT association with the transcription elongation complex depends on nucleosome disassembly, and that the

  7. Airborne sound insulation evaluation and flanking path prediction of coupled room

    Science.gov (United States)

    Tassia, R. D.; Asmoro, W. A.; Arifianto, D.

    2016-11-01

    One of the parameters to review the acoustic comfort is based on the value of the insulation partition in the classroom. The insulation value can be expressed by the sound transmission loss which converted into a single value as weighted sound reduction index (Rw, DnTw) and also have an additional sound correction factor in low frequency (C, Ctr) .In this study, the measurements were performed in two positions at each point using BSWA microphone and dodecahedron speaker as the sound source. The results of field measurements indicate the acoustic insulation values (DnT w + C) is 19.6 dB. It is noted that the partition wall not according to the standard which the DnTw + C> 51 dB. Hence the partition wall need to be redesign to improve acoustic insulation in the classroom. The design used gypsum board, plasterboard, cement board, and PVC as the replacement material. Based on the results, all the material is simulated in accordance with established standards. Best insulation is cement board with the insulation value is 69dB, the thickness of 12.5 mm on each side and the absorber material is 50 mm. Many factors lead to increase the value of acoustic insulation, such as the thickness of the panel, the addition of absorber material, density, and Poisson's ratio of a material. The prediction of flanking path can be estimated from noise reduction values at each measurement point in the class room. Based on data obtained, there is no significant change in noise reduction from each point so that the pathway of flanking is not affect the sound transmission in the classroom.

  8. The incorporation of the novel histone variant H2AL2 confers unusual structural and functional properties of the nucleosome

    Czech Academy of Sciences Publication Activity Database

    Syed, S.H.; Boulard, M.; Shukla, M.S.; Gautier, T.; Travers, A.; Bednár, Jan; Faivre-Moskalenko, C.; Dimitrov, S.; Angelov, D.

    2009-01-01

    Roč. 37, č. 14 (2009), s. 4684-4695 ISSN 0305-1048 Grant - others:GA MŠk(CZ) LC535; GA ČR(CZ) GA304/05/2168 Program:LC Institutional research plan: CEZ:AV0Z50110509 Keywords : nucleosome * histone * variant Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 7.479, year: 2009

  9. Towards the theoretical bases of the folding of the 100-A nucleosome filament

    International Nuclear Information System (INIS)

    Chela Flores, J.

    1994-01-01

    We attempt to model DNA packaging at the various stages of ever increasing DNA folding from the 100-A nucleosome filament to various further stages leading up to the metaphase chromosome. We have assumed that a phase transition has induced chromatin into a condensed mode. The mean-field model allows the simultaneous discussion of chromatin with packaging ration η and DNA replication at various stages of folding. We derive a formula correlating (during the S phase of the cell cycle) the DNA polymerase velocity r f (measured in nucleotides per minute) in a relation of inverse proportionality with the degree of DNA packaging: r f = λη -1/2 , where the dimensional constant λ has been determined. This model suggests that in the heterochromatic regions of chromatin there is reduced activity of DNA polymerases. We discuss the possible relevance of our model to late replicating telomeres in yeast and several higher eukaryotes. (author). 28 refs, 3 tabs

  10. Thermomechanical damage of nucleosome by the shock wave initiated by ion passing through liquid water

    International Nuclear Information System (INIS)

    Yakubovich, Alexander V.; Surdutovich, Eugene; Solov’yov, Andrey V.

    2012-01-01

    We report on the results of full-atom molecular dynamics simulations of the heat spike in the water medium caused by the propagation of the heavy ion in the vicinity of its Bragg peak. High rate of energy transfer from an ion to the molecules of surrounding water environment leads to the rapid increase of the temperature of the molecules in the vicinity of ions trajectory. As a result of an abrupt increase of the temperature we observe the formation of the nanoscale shock wave propagating through the medium. We investigate the thermomechanical damage caused by the shock wave to the nucleosome located in the vicinity of heavy ion trajectory. We observe the substantial deformation of the DNA secondary structure. We show that the produced shock wave can lead to the thermomechanical breakage of the DNA backbone covalent bonds and present estimates for the number of such strand brakes per one cell nucleus.

  11. Brownian dynamics simulation of the cross-talking effect among modified histones on conformations of nucleosomes

    Science.gov (United States)

    Duan, Zhao-Wen; Li, Wei; Xie, Ping; Dou, Shuo-Xing; Wang, Peng-Ye

    2010-04-01

    Using Brownian dynamics simulation, we studied the effect of histone modifications on conformations of an array of nucleosomes in a segment of chromatin. The simulation demonstrated that the segment of chromatin shows the dynamic behaviour that its conformation can switch between a state with nearly all of the histones being wrapped by DNA and a state with nearly all of the histones being unwrapped by DNA, thus involving the “cross-talking" interactions among the histones. Each state can stay for a sufficiently long time. These conformational states are essential for gene expression or gene silence. The simulation also shows that these conformational states can be inherited by the daughter DNAs during DNA replication, giving a theoretical explanation of the epigenetic phenomenon.

  12. Brownian dynamics simulation of the cross-talking effect among modified histones on conformations of nucleosomes

    International Nuclear Information System (INIS)

    Zhao-Wen, Duan; Wei, Li; Ping, Xie; Shuo-Xing, Dou; Peng-Ye, Wang

    2010-01-01

    Using Brownian dynamics simulation, we studied the effect of histone modifications on conformations of an array of nucleosomes in a segment of chromatin. The simulation demonstrated that the segment of chromatin shows the dynamic behaviour that its conformation can switch between a state with nearly all of the histones being wrapped by DNA and a state with nearly all of the histones being unwrapped by DNA, thus involving the “cross-talking” interactions among the histones. Each state can stay for a sufficiently long time. These conformational states are essential for gene expression or gene silence. The simulation also shows that these conformational states can be inherited by the daughter DNAs during DNA replication, giving a theoretical explanation of the epigenetic phenomenon. (cross-disciplinary physics and related areas of science and technology)

  13. Unenhanced helical computed tomography in the evaluation of acute flank pain

    International Nuclear Information System (INIS)

    Ahmad, N.A.; Ather, M.H.; Rees, J.

    2003-01-01

    The purpose of this study was to determine the value of unenhanced helical computed tomography (UHCT) in the diagnosis of acute flank pain at our institution. Two hundred and thirty-three consecutive UHCT examinations, performed for suspected renal/ureteral colic between July 2000 and August 2001 were reviewed, along with pertinent medical records. Ureteral calculi were identified in 148 (64%) examinations, evidence of recent passage of calculi was found in 10 (4%) and no calculi were found in 75 (32%). Thirty-two of the conservatively managed patients were excluded for inadequate follow-up. In the remaining 201 patients, sensitivity of UHCT in diagnosing calculi was 99% and specificity was 98%, while the positive predictive value was 99% and negative positive predictive value was 98%. Overall, an alternative or additional diagnosis was established in 28 (12%) patients. Upon diagnosis of ureterolithiasis on UHCT, none of the patients required additional imaging studies for confirmation. UHCT is a highly sensitive imaging modality for the detection of urinary tract calculi and obstruction. (author)

  14. Wear evaluation of flank in burins of high speed steel modified with titanium ions

    Science.gov (United States)

    E Caballero, J.; V-Niño, E. D.

    2017-12-01

    This report shows the results obtained researching the flank wearing resistance performed by the high-speed steel (HSS) burins without any surface treatment (reference substrate) and others with surface treatment based on Titanium ions. The flank wearing was carried out by means of an industrial process by chip removal with repetitive tests of dry finished turning of AISI/SAE 1045 steel bars. The useful service life of the burins was evaluated according to ISO 3685:1993, and it was found that the burins treated with Titanium ions showed an increase in the flank wearing resistance with respect to the ones used as reference.

  15. Reconstruction of the eruptive activity on the NE sector of Stromboli volcano: timing of flank eruptions since 15 ka

    NARCIS (Netherlands)

    Calvari, S.; Branca, S.; Corsaro, R.A.; De Beni, E.; Miraglia, L.; Norini, G.; Wijbrans, J.R.; Boschi, E.

    2011-01-01

    A multidisciplinary geological and compositional investigation allowed us to reconstruct the occurrence of flank eruptions on the lower NE flank of Stromboli volcano since 15 ka. The oldest flank eruption recognised is Roisa, which occurred at ~15 ka during the Vancori period, and has transitional

  16. Imaging modalities and therapy options in patients with acute flank pain

    International Nuclear Information System (INIS)

    Grosse, A.; Grosse, C.

    2014-01-01

    The objective of this article is the description of imaging techniques for the evaluation of patients with acute flank pain and suspicion of urolithiasis and the impact of these techniques in the therapy management of patients with calculi. (orig.) [de

  17. Surface and Bottom Boundar Layer Dynamics on a Shallow Submarine Bank: Southern Flank of Georges Bank

    National Research Council Canada - National Science Library

    Werner, Sandra

    1999-01-01

    The thesis investigates the circulation at a 75-meter deep study site on the southern flank of Georges Bank, a shallow submarine bank located between the deeper Gulf of Maine and the continental slope...

  18. Magnocellular involvement in flanked-letter identification relates to the allocation of attention

    NARCIS (Netherlands)

    Omtzigt, D.; Hendriks, A.W.C.J.

    2004-01-01

    To verify the hypothesis that the magnocellular system is important to flanked-letter identification [Neuropsychologia 40 (2002) 1881] because it subserves attention allocation, we conducted three letter-naming experiments in which we manipulated magnocellular involvement (colour vs. luminance

  19. Relaxation of the south flank after the 7.2-magnitude Kalapana earthquake, Kilauea Volcano, Hawaii

    Science.gov (United States)

    Dvorak, John J.; Klein, Fred W.; Swanson, Donald A.

    1994-01-01

    An M = 7.2 earthquake on 29 November 1975 caused the south flank of Kilauea Volcano, Hawaii, to move seaward several meters: a catastrophic release of compression of the south flank caused by earlier injections of magma into the adjacent segment of a rift zone. The focal mechanisms of the mainshock, the largest foreshock, and the largest aftershock suggest seaward movement of the upper block. The rate of aftershocks decreased in a familiar hyperbolic decay, reaching the pre-1975 rate of seismicity by the mid-1980s. Repeated rift-zone intrusions and eruptions after 1975, which occurred within 25 km of the summit area, compressed the adjacent portion of the south flank, apparently masking continued seaward displacement of the south flank. This is evident along a trilateration line that continued to extend, suggesting seaward displacement, immediately after the M = 7.2 earthquake, but then was compressed during a series of intrusions and eruptions that began in September 1977. Farther to the east, trilateration measurements show that the portion of the south flank above the aftershock zone, but beyond the area of compression caused by the rift-zone intrusions and eruptions, continued to move seaward at a decreasing rate until the mid-1980s, mimicking the decay in aftershock rate. Along the same portion of the south flank, the pattern of vertical surface displacements can be explained by continued seaward movement of the south flank and development of two eruptive fissures along the east rift zone, each of which extended from a depth of ∼3 km to the surface. The aftershock rate and continued seaward movement of the south flank are reminiscent of crustal response to other large earthquakes, such as the 1966 M = 6 Parkfield earthquake and the 1983 M = 6.5 Coalinga earthquake.

  20. The enrichment of TATA box and the scarcity of depleted proximal nucleosome in the promoters of duplicated yeast genes.

    Science.gov (United States)

    Kim, Yuseob; Lee, Jang H; Babbitt, Gregory A

    2010-01-01

    Population genetic theory of gene duplication suggests that the preservation of duplicate copies requires functional divergence upon duplication. Genes that can be readily modified to produce new gene expression patterns may thus be duplicated often. In yeast, genes exhibit dichotomous expression patterns based on their promoter architectures. The expression of genes that contain TATA box or occupied proximal nucleosome (OPN) tends to be variable and respond to external signals. On the other hand, genes without TATA box or with depleted proximal nucleosome (DPN) are expressed constitutively. We find that recent duplicates in the yeast genome are heavily biased to be TATA box containing genes and not to be DPN genes. This suggests that variably expressed genes, due to the functional organization in their promoters, have higher duplicability than constitutively expressed genes.

  1. Carboniferous geology and uranium potential of the northeast flank of the Parana Basin and southwest flank of the Parnaiba Basin, Brazil

    International Nuclear Information System (INIS)

    Andrade, S.M. de; Camarco, P.E.N.

    1984-01-01

    The Carboniferous sequences of the northeast flank of the Parana Basin and those of the southwest flank of the Parnaiba Basin have been the subject of discussion and polemics for quite a long time, especially in terms of their stratigraphic relations and depositional environments. Thus, we reinforce our main objective, which is to furnish data for the definition of the uranium potential in these Carboniferous sediments, by adding recently acquired information that should aid in the clarification of the existing controversies. The Carboniferous along the northeast flank of the Parana Basin is represented by the Aquidauana Formation which has been informally divided into three members: lower, middle and upper members. The middle member, of marine origin, constitutes a prospective target for uranium and phosphate associations, in which sandstones interbedded with shales constitute the host rocks. On the other hand, the Carboniferous of the southwest margin of the Parnaiba Basin, which encompasses the Longa, Poti and Piaui Formations has shown very remote possibilities of uranium occurrences. The regional structural framework, as reflected by the Carboniferous rocks along both basin flanks, is characterized by homoclines cut by gravity faults. The faults along these weakness zones were occasionally intruded by basic rocks of Cretaceous age. Superimposed on the regional structure, open folds appear in the form of anticlines and domes. These folds are discontinuous structures resulting from uplift due to vertical stresses or result from differential subsidence along the limbs of the folds. (Author) [pt

  2. Effect of the bases flanking an abasic site on the recognition of nucleobase by amiloride.

    Science.gov (United States)

    Rajendran, Arivazhagan; Zhao, Chunxia; Rajendar, Burki; Thiagarajan, Viruthachalam; Sato, Yusuke; Nishizawa, Seiichi; Teramae, Norio

    2010-06-01

    We explain here the various non-covalent interactions which are responsible for the different binding modes of a small ligand with DNA. The combination of experimental and theoretical methods was used. The interaction of amiloride with thymine was found to depend on the bases flanking the AP site and different binding modes were observed for different flanking bases. Molecular modeling, absorption studies and binding constant measurements support for the different binding patterns. The flanking base dependent recognition of AP site phosphates was investigated by (31)P NMR experiments. The thermodynamics of the ligand-nucleotide interaction was demonstrated by isothermal titration calorimetry. The emission behavior of amiloride was found to depend on the bases flanking the AP site. Amiloride photophysics in the context of AP-site containing DNA is investigated by time-dependent density functional theory. Flanking bases affect the ground and excited electronic states of amiloride when binding to AP site, which causes flanking base-dependent fluorescence signaling. The various noncovalent interactions have been well characterized for the determination of nucleic acid structure and dynamics, and protein-DNA interactions. However, these are not clear for the DNA-small molecule interactions and we believe that our studies will bring a new insight into such phenomena. Copyright 2010 Elsevier B.V. All rights reserved.

  3. The Nucleosome Acidic Patch Regulates the H2B K123 Monoubiquitylation Cascade and Transcription Elongation in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Christine E Cucinotta

    2015-08-01

    Full Text Available Eukaryotes regulate gene expression and other nuclear processes through the posttranslational modification of histones. In S. cerevisiae, the mono-ubiquitylation of histone H2B on lysine 123 (H2B K123ub affects nucleosome stability, broadly influences gene expression and other DNA-templated processes, and is a prerequisite for additional conserved histone modifications that are associated with active transcription, namely the methylation of lysine residues in H3. While the enzymes that promote these chromatin marks are known, regions of the nucleosome required for the recruitment of these enzymes are undefined. To identify histone residues required for H2B K123ub, we exploited a functional interaction between the ubiquitin-protein ligase, Rkr1/Ltn1, and H2B K123ub in S. cerevisiae. Specifically, we performed a synthetic lethal screen with cells lacking RKR1 and a comprehensive library of H2A and H2B residue substitutions, and identified H2A residues that are required for H2B K123ub. Many of these residues map to the nucleosome acidic patch. The substitutions in the acidic patch confer varying histone modification defects downstream of H2B K123ub, indicating that this region contributes differentially to multiple histone modifications. Interestingly, substitutions in the acidic patch result in decreased recruitment of H2B K123ub machinery to active genes and defects in transcription elongation and termination. Together, our findings reveal a role for the nucleosome acidic patch in recruitment of histone modification machinery and maintenance of transcriptional integrity.

  4. Hypoxia-induced oxidative base modifications in the VEGF hypoxia-response element are associated with transcriptionally active nucleosomes.

    Science.gov (United States)

    Ruchko, Mykhaylo V; Gorodnya, Olena M; Pastukh, Viktor M; Swiger, Brad M; Middleton, Natavia S; Wilson, Glenn L; Gillespie, Mark N

    2009-02-01

    Reactive oxygen species (ROS) generated in hypoxic pulmonary artery endothelial cells cause transient oxidative base modifications in the hypoxia-response element (HRE) of the VEGF gene that bear a conspicuous relationship to induction of VEGF mRNA expression (K.A. Ziel et al., FASEB J. 19, 387-394, 2005). If such base modifications are indeed linked to transcriptional regulation, then they should be detected in HRE sequences associated with transcriptionally active nucleosomes. Southern blot analysis of the VEGF HRE associated with nucleosome fractions prepared by micrococcal nuclease digestion indicated that hypoxia redistributed some HRE sequences from multinucleosomes to transcriptionally active mono- and dinucleosome fractions. A simple PCR method revealed that VEGF HRE sequences harboring oxidative base modifications were found exclusively in mononucleosomes. Inhibition of hypoxia-induced ROS generation with myxathiozol prevented formation of oxidative base modifications but not the redistribution of HRE sequences into mono- and dinucleosome fractions. The histone deacetylase inhibitor trichostatin A caused retention of HRE sequences in compacted nucleosome fractions and prevented formation of oxidative base modifications. These findings suggest that the hypoxia-induced oxidant stress directed at the VEGF HRE requires the sequence to be repositioned into mononucleosomes and support the prospect that oxidative modifications in this sequence are an important step in transcriptional activation.

  5. Binding of ethidium to the nucleosome core particle. 2. Internal and external binding modes

    International Nuclear Information System (INIS)

    McMurray, C.T.; Small, E.W.; van Holde, K.E.

    1991-01-01

    The authors have previously reported that the binding of ethidium bromide to the nucleosome core particle results in a stepwise dissociation of the structure which involves the initial release of one copy each of H2A and H2B. In this report, they have examined the absorbance and fluorescence properties of intercalated and outside bound forms of ethidium bromide. From these properties, they have measured the extent of external, electrostatic binding of the dye versus internal, intercalation binding to the core particle, free from contribution by linker DNA. They have established that dissociation is induced by the intercalation mode of binding to DNA within the core particle DNA, and not by binding to the histones or by nonintercalative binding to DNA. The covalent binding of [ 3 H]-8-azidoethidium to the core particle clearly shows that < 1.0 adduct is formed per histone octamer over a wide range of input ratios. Simultaneously, analyses of steady-state fluorescence enhancement and fluorescence lifetime data from bound ethidium complexes demonstrate extensive intercalation binding. Combined analyses from steady-state fluorescence intensity with equilibrium dialysis or fluorescence lifetime data revealed that dissociation began when ∼14 ethidium molecules are bound by intercalation to each core particle and < 1.0 nonintercalated ion pair was formed per core particle

  6. DNA Replication Is Required for Circadian Clock Function by Regulating Rhythmic Nucleosome Composition.

    Science.gov (United States)

    Liu, Xiao; Dang, Yunkun; Matsu-Ura, Toru; He, Yubo; He, Qun; Hong, Christian I; Liu, Yi

    2017-07-20

    Although the coupling between circadian and cell cycles allows circadian clocks to gate cell division and DNA replication in many organisms, circadian clocks were thought to function independently of cell cycle. Here, we show that DNA replication is required for circadian clock function in Neurospora. Genetic and pharmacological inhibition of DNA replication abolished both overt and molecular rhythmicities by repressing frequency (frq) gene transcription. DNA replication is essential for the rhythmic changes of nucleosome composition at the frq promoter. The FACT complex, known to be involved in histone disassembly/reassembly, is required for clock function and is recruited to the frq promoter in a replication-dependent manner to promote replacement of histone H2A.Z by H2A. Finally, deletion of H2A.Z uncoupled the dependence of the circadian clock on DNA replication. Together, these results establish circadian clock and cell cycle as interdependent coupled oscillators and identify DNA replication as a critical process in the circadian mechanism. Published by Elsevier Inc.

  7. Interaction of nucleosome assembly proteins abolishes nuclear localization of DGKζ by attenuating its association with importins

    International Nuclear Information System (INIS)

    Okada, Masashi; Hozumi, Yasukazu; Ichimura, Tohru; Tanaka, Toshiaki; Hasegawa, Hiroshi; Yamamoto, Masakazu; Takahashi, Nobuya; Iseki, Ken; Yagisawa, Hitoshi; Shinkawa, Takashi; Isobe, Toshiaki; Goto, Kaoru

    2011-01-01

    Diacylglycerol kinase (DGK) is involved in the regulation of lipid-mediated signal transduction through the metabolism of a second messenger diacylglycerol. Of the DGK family, DGKζ, which contains a nuclear localization signal, localizes mainly to the nucleus but translocates to the cytoplasm under pathological conditions. However, the detailed mechanism of translocation and its functional significance remain unclear. To elucidate these issues, we used a proteomic approach to search for protein targets that interact with DGKζ. Results show that nucleosome assembly protein (NAP) 1-like 1 (NAP1L1) and NAP1-like 4 (NAP1L4) are identified as novel DGKζ binding partners. NAP1Ls constitutively shuttle between the nucleus and the cytoplasm in transfected HEK293 cells. The molecular interaction of DGKζ and NAP1Ls prohibits nuclear import of DGKζ because binding of NAP1Ls to DGKζ blocks import carrier proteins, Qip1 and NPI1, to interact with DGKζ, leading to cytoplasmic tethering of DGKζ. In addition, overexpression of NAP1Ls exerts a protective effect against doxorubicin-induced cytotoxicity. These findings suggest that NAP1Ls are involved in a novel molecular basis for the regulation of nucleocytoplasmic shuttling of DGKζ and provide a clue to examine functional significance of its translocation under pathological conditions.

  8. Dengue Virus Capsid Protein Binds Core Histones and Inhibits Nucleosome Formation in Human Liver Cells

    Science.gov (United States)

    Colpitts, Tonya M.; Barthel, Sebastian; Wang, Penghua; Fikrig, Erol

    2011-01-01

    Dengue virus (DENV) is a member of the Flaviviridae and a globally (re)emerging pathogen that causes serious human disease. There is no specific antiviral or vaccine for dengue virus infection. Flavivirus capsid (C) is a structural protein responsible for gathering the viral RNA into a nucleocapsid that forms the core of a mature virus particle. Flaviviral replication is known to occur in the cytoplasm yet a large portion of capsid protein localizes to the nucleus during infection. The reasons for the nuclear presences of capsid are not completely understood. Here, we expressed mature DENV C in a tandem affinity purification assay to identify potential binding partners in human liver cells. DENV C targeted the four core histones, H2A, H2B, H3 and H4. DENV C bound recombinant histones in solution and colocalized with histones in the nucleus and cytoplasm of liver cells during DENV infection. We show that DENV C acts as a histone mimic, forming heterodimers with core histones, binding DNA and disrupting nucleosome formation. We also demonstrate that DENV infection increases the amounts of core histones in livers cells, which may be a cellular response to C binding away the histone proteins. Infection with DENV additionally alters levels of H2A phosphorylation in a time-dependent manner. The interactions of C and histones add an interesting new role for the presence of C in the nucleus during DENV infection. PMID:21909430

  9. Evolution of high mobility group nucleosome-binding proteins and its implications for vertebrate chromatin specialization.

    Science.gov (United States)

    González-Romero, Rodrigo; Eirín-López, José M; Ausió, Juan

    2015-01-01

    High mobility group (HMG)-N proteins are a family of small nonhistone proteins that bind to nucleosomes (N). Despite the amount of information available on their structure and function, there is an almost complete lack of information on the molecular evolutionary mechanisms leading to their exclusive differentiation. In the present work, we provide evidence suggesting that HMGN lineages constitute independent monophyletic groups derived from a common ancestor prior to the diversification of vertebrates. Based on observations of the functional diversification across vertebrate HMGN proteins and on the extensive silent nucleotide divergence, our results suggest that the long-term evolution of HMGNs occurs under strong purifying selection, resulting from the lineage-specific functional constraints of their different protein domains. Selection analyses on independent lineages suggest that their functional specialization was mediated by bursts of adaptive selection at specific evolutionary times, in a small subset of codons with functional relevance-most notably in HMGN1, and in the rapidly evolving HMGN5. This work provides useful information to our understanding of the specialization imparted on chromatin metabolism by HMGNs, especially on the evolutionary mechanisms underlying their functional differentiation in vertebrates. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. A role for the nucleosome assembly proteins TAF-Iβ and NAP1 in the activation of BZLF1 expression and Epstein-Barr virus reactivation.

    Science.gov (United States)

    Mansouri, Sheila; Wang, Shan; Frappier, Lori

    2013-01-01

    The reactivation of Epstein-Barr virus (EBV) from latent to lytic infection begins with the expression of the viral BZLF1 gene, leading to a subsequent cascade of viral gene expression and amplification of the EBV genome. Using RNA interference, we show that nucleosome assembly proteins NAP1 and TAF-I positively contribute to EBV reactivation in epithelial cells through the induction of BZLF1 expression. In addition, overexpression of NAP1 or the β isoform of TAF-I (TAF-Iβ) in AGS cells latently infected with EBV was sufficient to induce BZLF1 expression. Chromatin immunoprecipitation experiments performed in AGS-EBV cells showed that TAF-I associated with the BZLF1 promoter upon lytic induction and affected local histone modifications by increasing H3K4 dimethylation and H4K8 acetylation. MLL1, the host protein known to dimethylate H3K4, was found to associate with the BZLF1 promoter upon lytic induction in a TAF-I-dependent manner, and MLL1 depletion decreased BZLF1 expression, confirming its contribution to lytic reactivation. The results indicate that TAF-Iβ promotes BZLF1 expression and subsequent lytic infection by affecting chromatin at the BZLF1 promoter.

  11. The association between maternal hydronephrosis and acute flank pain during pregnancy: a prospective pilot-study.

    Science.gov (United States)

    Farr, Alex; Ott, Johannes; Kueronya, Verena; Margreiter, Markus; Javadli, Elchin; Einig, Sabrina; Husslein, Peter W; Bancher-Todesca, Dagmar

    2017-10-01

    Maternal hydronephrosis may cause flank pain during pregnancy. We aimed to investigate the association between maternal hydronephrosis and flank pain intensity. From 2014 to 2015, all consecutive women with singleton pregnancies, who presented at our tertiary center due to acute flank pain, were prospectively evaluated by renal ultrasonography and pain questionnaires. A visual analogue scale was used to assess pain intensity. The study had 90% power to detect a significant correlation between hydronephrosis and flank pain (Spearman's test). A total of 51 consecutive women with left-sided (13.7%), right-sided (64.7%) or bilateral (21.6%) pain were enrolled. The mean gestational age of these women, who presented due to their pain, was 27.5 ± 6.8 weeks at the time of consultation. The mean VAS score was 7.6 ± 2.2. In 43/51 (84.3%) women, hydronephrosis was found on renal sonograms. No correlation was found between the grade of hydronephrosis and pain intensity (p = 0.466; r= -0.28). Women delivered at a mean gestational age of 38.1 ± 2.4 weeks and their infants had a mean birthweight of 3138 ± 677 g. Hydronephrosis is a common finding among pregnant women with acute flank pain. The grade of hydronephrosis does not affect pain intensity. This study suggests normal pregnancy outcomes in these women.

  12. Genetic Recombination at the Buff Spore Color Locus in SORDARIA BREVICOLLIS. II. Analysis of Flanking Marker Behavior in Crosses between Buff Mutants.

    Science.gov (United States)

    Sang, H; Whitehouse, H L

    1983-02-01

    Aberrant asci containing one or more wild-type spores were selected from crosses between pairs of alleles of the buff locus in the presence of closely linked flanking markers. Data were obtained relating to the site of aberrant segregation and the position of any associated crossover giving recombination of flanking markers. Aberrant segregation at a proximal site within the buff gene may be associated with a crossover proximal to the site of aberrant segregation or, with equal frequency, with a crossover distal to the site of the second mutant present in the cross. Similarly, segregation at a distal site may be associated with a crossover distal to the site or, with lower frequency, with a crossover proximal to the site of the proximal mutant present in the cross. Crossovers between the alleles were rare. This evidence for the relationship between hybrid DNA and crossing over is discussed in terms of current models for the mechanism of recombination.

  13. Nucleosome acidic patch promotes RNF168- and RING1B/BMI1-dependent H2AX and H2A ubiquitination and DNA damage signaling.

    Directory of Open Access Journals (Sweden)

    Justin W Leung

    2014-03-01

    Full Text Available Histone ubiquitinations are critical for the activation of the DNA damage response (DDR. In particular, RNF168 and RING1B/BMI1 function in the DDR by ubiquitinating H2A/H2AX on Lys-13/15 and Lys-118/119, respectively. However, it remains to be defined how the ubiquitin pathway engages chromatin to provide regulation of ubiquitin targeting of specific histone residues. Here we identify the nucleosome acid patch as a critical chromatin mediator of H2A/H2AX ubiquitination (ub. The acidic patch is required for RNF168- and RING1B/BMI1-dependent H2A/H2AXub in vivo. The acidic patch functions within the nucleosome as nucleosomes containing a mutated acidic patch exhibit defective H2A/H2AXub by RNF168 and RING1B/BMI1 in vitro. Furthermore, direct perturbation of the nucleosome acidic patch in vivo by the expression of an engineered acidic patch interacting viral peptide, LANA, results in defective H2AXub and RNF168-dependent DNA damage responses including 53BP1 and BRCA1 recruitment to DNA damage. The acidic patch therefore is a critical nucleosome feature that may serve as a scaffold to integrate multiple ubiquitin signals on chromatin to compose selective ubiquitinations on histones for DNA damage signaling.

  14. Mathematical description of tooth flank surface of globoidal worm gear with straight axial tooth profile

    Science.gov (United States)

    Połowniak, Piotr; Sobolak, Mariusz

    2017-12-01

    In this article, a mathematical description of tooth flank surface of the globoidal worm and worm wheel generated by the hourglass worm hob with straight tooth axial profile is presented. The kinematic system of globoidal worm gear is shown. The equation of globoid helix and tooth axial profile of worm is derived to determine worm tooth surface. Based on the equation of meshing the contact lines are obtained. The mathematical description of globoidal worm wheel tooth flank is performed on the basis of contact lines and generating the tooth side by the extreme cutting edge of worm hob. The presented mathematical model of tooth flank of TA worm and worm wheel can be used e.g. to analyse the contact pattern of the gear.

  15. Flank wear analysing of high speed end milling for hardened steel D2 using Taguchi Method

    Science.gov (United States)

    Hazza Faizi Al-Hazza, Muataz; Ibrahim, Nur Asmawiyah bt; Adesta, Erry T. Y.; Khan, Ahsan Ali; Abdullah Sidek, Atiah Bt.

    2017-03-01

    One of the main challenges for any manufacturer is how to decrease the machining cost without affecting the final quality of the product. One of the new advanced machining processes in industry is the high speed hard end milling process that merges three advanced machining processes: high speed milling, hard milling and dry milling. However, one of the most important challenges in this process is to control the flank wear rate. Therefore a analyzing the flank wear rate during machining should be investigated in order to determine the best cutting levels that will not affect the final quality of the product. In this research Taguchi method has been used to investigate the effect of cutting speed, feed rate and depth of cut and determine the best level s to minimize the flank wear rate up to total length of 0.3mm based on the ISO standard to maintain the finishing requirements.

  16. Mitigation of Flanking Noise Transmission in Periodic Structures of Lightweight Elements

    DEFF Research Database (Denmark)

    Domadiya, Parthkumar Gandalal

    through structural junctions and radiates into neighbouring rooms. To diminish the flanking transmission of sound, frames are usually designed with single or double studs or constructed with layers of foam or another viscoelastic material. This thesis is investigating the behaviour of flanking noise...... transmission in periodic structures of lightweight elements by employing various numerical, analytical and experimental methods. At first, three dimensional finite-element (FE) models of a Z-shaped lightweight panel structure based on various frame designs, inclusion of air and structural coupling between...... elements are considered for describing flanking noise transmission through panels. It is assumed that the ribs are fully fixed to the plates in case of various frame designs, and a parametric study is carried out on the centre panel with regard to various spacing between the ribs. Solid finite elements...

  17. Temperature and redox effect on mineral colonization in Juan de Fuca Ridge flank subsurface crustal fluids

    Directory of Open Access Journals (Sweden)

    Jean-Paul eBaquiran

    2016-03-01

    Full Text Available To examine microbe-mineral interactions in subsurface oceanic crust, we evaluated microbial colonization on crustal minerals that were incubated in borehole fluids for one year at the seafloor wellhead of a crustal borehole observatory (IODP Hole U1301A, Juan de Fuca Ridge flank as compared to an experiment that was not exposed to subsurface crustal fluids (at nearby IODP Hole U1301B. In comparison to previous studies at these same sites, this approach allowed assessment of the effects of temperature, fluid chemistry, and/or mineralogy on colonization patterns of different mineral substrates, and an opportunity to verify the approach of deploying colonization experiments at an observatory wellhead at the seafloor instead of within the borehole. The Hole U1301B deployment did not have biofilm growth, based on microscopy and DNA extraction, thereby confirming the integrity of the colonization design against bottom seawater intrusion. In contrast, the Hole U1301A deployment supported biofilms dominated by Epsilonproteobacteria (43.5% of 370 16S rRNA gene clone sequences and Gammaproteobacteria (29.3%. Sequence analysis revealed overlap in microbial communities between different minerals incubated at the Hole U1301A wellhead, indicating that mineralogy did not separate biofilm structure within the one-year colonization experiment. Differences in the Hole U1301A wellhead biofilm community composition relative to previous studies from within the borehole using similar mineral substrates suggest that temperature and the diffusion of dissolved oxygen through plastic components influenced the mineral colonization experiments positioned at the wellhead. This highlights the capacity of low abundance crustal fluid taxa to rapidly establish communities on diverse mineral substrates under changing environmental conditions such as from temperature and oxygen.

  18. Geologic setting of the proposed West Flank Forge Site, California: Suitability for EGS research and development

    Science.gov (United States)

    Sabin, Andrew; Blake, Kelly; Lazaro, Mike; Blankenship, Douglas; Kennedy, Mack; McCullough, Jess; DeOreo, S.B.; Hickman, Stephen H.; Glen, Jonathan; Kaven, Joern; Williams, Colin F.; Phelps, Geoffrey; Faulds, James E.; Hinz, Nicholas H.; Calvin, Wendy M.; Siler, Drew; Robertson-Tait, Ann

    2017-01-01

    The proposed West Flank FORGE site is within the China Lake Naval Air Weapons Station (NAWS), China Lake, CA. The West Flank is west of the Coso geothermal field, an area of China Lake NAWS dominated by the Quaternary Coso volcanic field largely comprised of rhyolite domes and their volcaniclastic and epiclastic horizons. The largest dome flow complex, Sugarloaf Mountain, marks the northwestern margin of the geothermal field. The West Flank is situated due west of Sugarloaf. The geologic setting of the West Flank was determined from one deep well (83-11) drilled as a potential production hole in 2009. The bottom-hole temperature (BHT) of well 83-11 approaches 600 oF (315˚C), but flow tests demonstrate very low, non-commercial permeabilities. With the exception of the upper 600 feet of volcaniclastic alluvium, well 83-11 is completed in granitic basement. The West Flank possesses the primary attributes of a FORGE site: non-commercial permeability (geothermal fieldThe Coso Mountains host the Coso volcanic field and are within a right-releasing stepover between the dextral Airport Lake (ALF) and Little Lake fault zones (LLFZ) and the Wild Horse Mesa and Owens Valley faults. Two distinct fault populations have been identified at Coso: WNW-trending and antithetical, NE-trending strike-slip faults and N- to NNE-trending normal faults. These faults are both high permeability drilling targets at depth within the main (productive) geothermal field and they locally segment the field into distinct hydrothermal regimes. The West Flank may be segmented from the rest of the field by one such northerly trending fault. The overall minimum principal stress orientation in the main geothermal field varies from 103˚ to 108˚; however, the minimum horizontal principal stress in 83-11 is rotated to 081˚.

  19. PGC1? ?1 Nucleosome Position and Splice Variant Expression and Cardiovascular Disease Risk in Overweight and Obese Individuals

    OpenAIRE

    Henagan, Tara M.; Stewart, Laura K.; Forney, Laura A.; Sparks, Lauren M.; Johannsen, Neil; Church, Timothy S.

    2014-01-01

    PGC1α, a transcriptional coactivator, interacts with PPARs and others to regulate skeletal muscle metabolism. PGC1α undergoes splicing to produce several mRNA variants, with the NTPGC1α variant having a similar biological function to the full length PGC1α (FLPGC1α). CVD is associated with obesity and T2D and a lower percentage of type 1 oxidative fibers and impaired mitochondrial function in skeletal muscle, characteristics determined by PGC1α expression. PGC1α expression is epigenetically re...

  20. Autoradiographic localization of tritiated dihydrotestosterone in the flank organ of the albino hamster

    International Nuclear Information System (INIS)

    Lucky, A.W.; Eisenfeld, A.J.; Visintin, I.

    1985-01-01

    In the hamster flank organ, the growth of hair and growth of sebaceous glands are androgen-dependent functions. Although dihydrotestosterone (DHT) is known to be a potent stimulator of flank organ growth, there is no information about localization of DHT receptor sites in this organ. The purpose of this study was to use steroid autoradiography to localize DHT receptors in the hamster flank organ. Because steroid hormones are functional when translocated to nuclear receptors, nuclear localization by autoradiography defines receptor sites. In order to be able to visualize autoradiographic grains from radiolabeled androgens around hair follicles, albino hamsters were studied to avoid confusion between the grains and pigment granules which are abundant in the more common Golden Syrian hamster. Mature male hamsters castrated 24 hours earlier were given tritium-labeled dihydrotestosterone ( [ 3 H]DHT). Using the technique of thaw-mount steroid autoradiography, 4-micron unfixed frozen sections were mounted in the dark onto emulsion-coated glass slides and allowed to develop for 4-6 months. [ 3 H]DHT was found to be concentrated over sebocyte nuclei. The label was present peripherally as well as in differentiating sebocytes. There was no nuclear localization of [ 3 H]DHT in animals pretreated with excessive quantities of unlabeled DHT. Steroid metabolites of [ 3 H] DHT were assessed by thin-layer chromatography in paired tissue samples. Most of the label remained with DHT. Uptake was inhibited in the flank organ of hamsters pretreated with unlabeled DHT

  1. Heme regulates the expression in Saccharomyces cerevisiae of chimaeric genes containing 5'-flanking soybean leghemoglobin sequences

    DEFF Research Database (Denmark)

    Jensen, E O; Marcker, K A; Villadsen, IS

    1986-01-01

    The TM1 yeast mutant was transformed with a 2 micron-derived plasmid (YEp24) which carries a chimaeric gene containing the Escherichia coli chloramphenicol acetyl transferase (CAT) gene fused to the 5'- and 3'-flanking regions of the soybean leghemoglobin (Lb) c3 gene. Expression of the chimaeric...

  2. Interphase FISH detection of BCL2 rearrangement in follicular lymphoma using breakpoint-flanking probes

    NARCIS (Netherlands)

    Vaandrager, J W; Schuuring, E; Raap, T; Philippo, K; Kleiverda, K; Kluin, P

    Rearrangement of the BCL2 gene is an important parameter for the differential diagnosis of non-Hodgkin lymphomas. Although a relatively large proportion of breakpoints is clustered, many are missed by standard PCR. A FISH assay is therefore desired. Up to now, a lack of probes flanking the BCL2 gene

  3. Forests of the tropical eastern Andean flank during the middle Pleistocene

    NARCIS (Netherlands)

    Cárdenas, M.L.; Gosling, W.D.; Pennington, R.T.; Poole, I.; Sherlock, S.C.; Mothes, P.

    2014-01-01

    Inter-bedded volcanic and organic sediments from Erazo (Ecuador) indicate the presence of four different forest assemblages on the eastern Andean flank during the middle Pleistocene. Radiometric dates (40Ar-39Ar) obtained from the volcanic ash indicate that deposition occurred between 620,000 and

  4. Flanking Magnitudes: Dissociation between Numerosity and Numerical Value in a Selective Attention Task

    Science.gov (United States)

    Naparstek, Sharon; Safadi, Ziad; Lichtenstein-Vidne, Limor; Henik, Avishai

    2015-01-01

    The current research examined whether peripherally presented numerical information can affect the speed of number processing. In 2 experiments, participants were presented with a target matrix flanked by a distractor matrix and were asked to perform a comparative judgment (i.e., decide whether the target was larger or smaller than the reference…

  5. Association of the polymorphism in the 5' flanking region of the ovine ...

    African Journals Online (AJOL)

    The insulin-like growth factor 1 (IGF-I) gene has been described in several studies as a candidate gene for growth traits in farm animals. The present preliminary study attempts to establish associations between growth traits and genetic polymorphisms at the 5' flanking region s IGF-I in the Baluchi sheep. The DNA of 102 ...

  6. Linkage disequilibrium in the insulin gene region: Size variation at the 5{prime} flanking polymorphism and bimodality among {open_quotes}Class I{close_quotes} alleles

    Energy Technology Data Exchange (ETDEWEB)

    McGinnis, R.E.; Spielman, R.S. [Univ. of Pennsylvania School of Medicine, Philadelphia, PA (United States)

    1994-09-01

    The 5{prime} flanking polymorphism (5{prime}FP), a hypervariable region at the 5{prime} end of the insulin gene, has {open_quotes}class 1{close_quotes} alleles (650-900 bp long) that are in positive linkage disequilibrium with insulin-dependent diabetes mellitus (IDDM). The authors report that precise sizing of the 5{prime}FP yields a bimodal frequency distribution of class 1 allele lengths. Class 1 alleles belonging to the lower component (650-750 bp) of the bimodal distribution were somewhat more highly associated with IDDM than were alleles from the upper component (760-900 bp), but the difference was not statistically significant. They also examined 5{prime}FP length variation in relation to allelic variation at nearby polymorphisms. At biallelic RFLPs on both sides of the 5{prime}FP, they found that one allele exhibits near-total association with the upper component of the 5FP class 1 distribution. Such associations represent a little-known but potentially wide-spread form of linkage disequilibrium. In this type of disequilibrium, a flanking allele has near-complete association with a single mode of VNTR alleles whose lengths represent consecutive numbers of tandem repeats (CNTR). Such extreme disequilibrium between a CNTR mode and flanking alleles may originate and persist because length mutations at some VNTR loci usually add or delete only one or two repeat units. 22 refs., 5 figs., 6 tabs.

  7. Implementing reverse genetics in Rosaceae: analysis of T-DNA flanking sequences of insertional mutant lines in the diploid strawberry, Fragaria vesca.

    Science.gov (United States)

    Oosumi, Teruko; Ruiz-Rojas, Juan Jairo; Veilleux, Richard E; Dickerman, Allan; Shulaev, Vladimir

    2010-09-01

    Reverse genetics is used for functional genomics research in model plants. To establish a model system for the systematic reverse genetics research in the Rosaceae family, we analyzed genomic DNA flanking the T-DNA insertions in 191 transgenic plants of the diploid strawberry, Fragaria vesca. One hundred and seventy-six T-DNA flanking sequences were amplified from the right border (RB) and 37 from the left border (LB) by thermal asymmetric interlaced PCR. Analysis of the T-DNA nick positions revealed that T-DNA was most frequently nicked at the cleavage sites. Analysis of 11 T-DNA integration sites indicated that T-DNA was integrated into the F. vesca genome by illegitimate recombination, as reported in other model plants: Arabidopsis, rice and tobacco. First, deletion of DNA was found at T-DNA integration target sites in all transgenic plants tested. Second, microsimilarities of a few base pairs between the left and/or right ends of the T-DNA and genomic sites were found in all transgenic plants tested. Finally, filler DNA was identified in four break-points. Out of 191 transgenic plants, T-DNA flanking sequences of 79 plants (41%) showed significant similarity to genes, elements or proteins of other plant species and 67 (35%) of the sequences are still unknown strawberry gene fragments. T-DNA flanking sequences of 126 plants (66%) showed homology to plant ESTs. This is the first report of T-DNA integration in a sizeable population of a rosaceous species. We have shown in this paper that T-DNA integration in strawberry is not random but directed by sequence microsimilarities in the host genome.

  8. Concurrent Preoperative Presence of Hydronephrosis and Flank Pain Independently Predicts Worse Outcome of Upper Tract Urothelial Carcinoma.

    Science.gov (United States)

    Yeh, Hsin-Chih; Jan, Hau-Chern; Wu, Wen-Jeng; Li, Ching-Chia; Li, Wei-Ming; Ke, Hung-Lung; Huang, Shu-Pin; Liu, Chia-Chu; Lee, Yung-Chin; Yang, Sheau-Fang; Liang, Peir-In; Huang, Chun-Nung

    2015-01-01

    To investigate the impact of preoperative hydronephrosis and flank pain on prognosis of patients with upper tract urothelial carcinoma. In total, 472 patients with upper tract urothelial carcinoma managed by radical nephroureterectomy were included from Kaohsiung Medical University Hospital Healthcare System. Clinicopathological data were collected retrospectively for analysis. The significance of hydronephrosis, especially when combined with flank pain, and other relevant factors on overall and cancer-specific survival were evaluated. Of the 472 patients, 292 (62%) had preoperative hydronephrosis and 121 (26%) presented with flank pain. Preoperative hydronephrosis was significantly associated with age, hematuria, flank pain, tumor location, and pathological tumor stage. Concurrent presence of hydronephrosis and flank pain was a significant predictor of non-organ-confined disease (multivariate-adjusted hazard ratio = 2.10, P = 0.025). Kaplan-Meier analysis showed significantly poorer overall and cancer-specific survival in patients with preoperative hydronephrosis (P = 0.005 and P = 0.026, respectively) and in patients with flank pain (P hydronephrosis and flank pain independently predicted adverse outcome (hazard ratio = 1.98, P = 0.016 for overall survival and hazard ratio = 1.87, P = 0.036 for and cancer-specific survival, respectively) in multivariate Cox proportional hazards models. In addition, concurrent presence of hydronephrosis and flank pain was also significantly predictive of worse survival in patient with high grade or muscle-invasive disease. Notably, there was no difference in survival between patients with hydronephrosis but devoid of flank pain and those without hydronephrosis. Concurrent preoperative presence of hydronephrosis and flank pain predicted non-organ-confined status of upper tract urothelial carcinoma. When accompanied with flank pain, hydronephrosis represented an independent predictor for worse outcome in patients with upper tract

  9. DMS-Seq for In Vivo Genome-wide Mapping of Protein-DNA Interactions and Nucleosome Centers.

    Science.gov (United States)

    Umeyama, Taichi; Ito, Takashi

    2017-10-03

    Protein-DNA interactions provide the basis for chromatin structure and gene regulation. Comprehensive identification of protein-occupied sites is thus vital to an in-depth understanding of genome function. Dimethyl sulfate (DMS) is a chemical probe that has long been used to detect footprints of DNA-bound proteins in vitro and in vivo. Here, we describe a genomic footprinting method, dimethyl sulfate sequencing (DMS-seq), which exploits the cell-permeable nature of DMS to obviate the need for nuclear isolation. This feature makes DMS-seq simple in practice and removes the potential risk of protein re-localization during nuclear isolation. DMS-seq successfully detects transcription factors bound to cis-regulatory elements and non-canonical chromatin particles in nucleosome-free regions. Furthermore, an unexpected preference of DMS confers on DMS-seq a unique potential to directly detect nucleosome centers without using genetic manipulation. We expect that DMS-seq will serve as a characteristic method for genome-wide interrogation of in vivo protein-DNA interactions. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  10. The role of viscous magma mush spreading in volcanic flank motion at Kīlauea Volcano, Hawai'i

    NARCIS (Netherlands)

    Plattner, C.; Amelung, F.; Baker, S.; Govers, R.; Poland, M.

    2013-01-01

    Multiple mechanisms have been suggested to explain seaward motion of the south flank of Kīlauea Volcano, Hawai'i. The consistency of flank motion during both waxing and waning magmatic activity at Kīlauea suggests that a continuously acting force, like gravity body force, plays a substantial role.

  11. High mobility group protein number17 cross-links primarily to histone H2A in the reconstituted HMG 17 - nucleosome core particle complex

    International Nuclear Information System (INIS)

    Cook, G.R.; Yau, P.; Yasuda, H.; Traut, R.R.; Bradbury, E.M.

    1986-01-01

    The neighbor relationship of lamb thymus High Mobility Group (HMG) protein 17 to native HeLa nucleosome core particle histones in the reconstituted complex has been studied. 125 I-labeled HMG 17 was cross-linking to core histones using the protein-protein cross-linking reagent 2-iminothiolane. Specific cross-linked products were separated on a two-dimensional Triton-acid-urea/SDS gel system, located by autoradiography, excised and quantified. Disulfide bonds in the cross links were then cleaved and the protein constituents were identified by SDS gel electrophoresis. HMG 17 cross-linked primarily to histone H2A while lower levels of cross-linking occurred between HMG 17 and the other histones. In contrast, cross-linking between two HMG 17 molecules bound on the same nucleosome was relatively rare. It is concluded that the same nucleosome was relatively rare. It is concluded that H2A comprises part of the HMG 17 binding site but that HMG 17 is sufficiently elongated and mobile to permit cross-linking to the other histones and to a second HMG 17 molecule. These results are in agreement with the current model for the structure of the nucleosome and the proposed binding sites for HMG 17

  12. Dissociation of nucleosomal particles by chemical modification. Equivalence of the two binding sites for H2A.H2B dimers

    International Nuclear Information System (INIS)

    Jordano, J.; Nieto, M.A.; Palacian, E.

    1985-01-01

    Treatment of nucleosomal particles with dimethylmaleic anhydride, a reagent for protein amino groups, is accompanied by a biphasic release of histones H2A plus H2B; one H2A.H2B dimer is more easily released than the other. This behavior allows the preparation of nucleosomal particles containing only one H2A.H2B dimer, which were complemented with 125 I-labeled H2A.H2B. These reconstituted particles, which contain one labeled and one unlabeled H2A.H2B dimer, were treated with the amount of reagent needed to release one of the two H2A.H2B dimers. Radioactivity was equally distributed between residual particles and released proteins, which is consistent with equivalent binding sites in the nucleosomal particle for H2A.H2B dimers, rather than with intrinsically different sites. The asymmetric release of H2A.H2B dimers would be caused by a change in the binding site of one dimer following the release of the other. This behavior might be related to the structural dynamics of nucleosomes

  13. Stability analysis of Western flank of Cumbre Vieja volcano (La Palma) using numerical modelling

    Science.gov (United States)

    Bru, Guadalupe; Gonzalez, Pablo J.; Fernandez-Merodo, Jose A.; Fernandez, Jose

    2016-04-01

    La Palma volcanic island is one of the youngest of the Canary archipelago, being a composite volcano formed by three overlapping volcanic centers. There are clear onshore and offshore evidences of past giant landslides that have occurred during its evolution. Currently, the active Cumbre Vieja volcano is in an early development state (Carracedo et al., 2001). The study of flank instability processes aim to assess, among other hazards, catastrophic collapse and potential tsunami generation. Early studies of the potential instability of Cumbre Vieja volcano western flank have focused on the use of sparse geodetic networks (Moss et al. 1999), surface geological mapping techniques (Day et al. 1999) and offshore bathymetry (Urgeles et al. 1999). Recently, a dense GNSS network and satellite radar interferometry results indicate ground motion consistent with deep-seated creeping processes (Prieto et al. 2009, Gonzalez et al. 2010). In this work, we present a geomechanical advanced numerical model that captures the ongoing deformation processes at Cumbre Vieja. We choose the Finite Elements Method (FEM) which is based in continuum mechanics and is the most used for geotechnical applications. FEM has the ability of using arbitrary geometry, heterogeneities, irregular boundaries and different constitutive models representative of the geotechnical units involved. Our main contribution is the introduction of an inverse approach to constrain the geomechanical parameters using satellite radar interferometry displacements. This is the first application of such approach on a large volcano flank study. We suggest that the use of surface displacements and inverse methods to rigorously constrain the geomechanical model parameter space is a powerful tool to understand volcano flank instability. A particular important result of the studied case is the estimation of displaced rock volume, which is a parameter of critical importance for simulations of Cumbre Vieja tsunamigenic hazard

  14. Hazard Potential of Volcanic Flank Collapses Raised by New Megatsunami Evidence

    Science.gov (United States)

    Ramalho, R. S.; Winckler, G.; Madeira, J.; Helffrich, G. R.; Hipólito, A.; Quartau, R.; Adena, K.; Schaefer, J. M.

    2015-12-01

    Large-scale gravitational flank collapses of steep volcanic islands are hypothetically capable of triggering megatsunamis with highly catastrophic effects. Yet evidence for the existence and impact of collapsed-triggered megatsunamis and their run-up heights remains scarce and/or is highly contentious. Therefore a considerable debate still exists over the potential magnitude of collapse-triggered tsunamis and their inherent hazard. In particular, doubts still remain whether or not large-scale flank failures typically generate enough volume flux to result in megatsunamis, or alternatively operate by slow-moving or multiple smaller episodic failures with much lower tsunamigenic potential. Here we show that one of the tallest and most active oceanic volcanoes on Earth - Fogo, in the Cape Verde Islands - collapsed catastrophically and triggered a megatsunami with devastating near-field effects ~73,000 years ago. Our deductions are based on the recent discovery and cosmogenic 3He dating of tsunamigenic deposits - comprising fields of stranded megaclasts, chaotic conglomerates, and sand sheets - found on the adjacent Santiago Island, which attest to the impact of this megatsunami and document wave run-up heights exceeding 270 m. The evidence reported here implies that Fogo's flank failure involved at least one sudden and voluminous event that resulted in a megatsunami, in contrast to what has been suggested before. Our work thus provides another line of evidence that large-scale flank failures at steep volcanic islands may indeed happen catastrophically and are capable of triggering tsunamis of enormous height and energy. This new line of evidence therefore reinforces the hazard potential of volcanic island collapses and stands as a warning that such hazard should not be underestimated, particularly in areas where volcanic island edifices are close to other islands or to highly populated continental margins.

  15. Automatic fitting of conical envelopes to free-form surfaces for flank CNC machining

    OpenAIRE

    Bo P.; Bartoň M.; Pottmann H.

    2017-01-01

    We propose a new algorithm to detect patches of free-form surfaces that can be well approximated by envelopes of a rotational cone under a rigid body motion. These conical envelopes are a preferable choice from the manufacturing point of view as they are, by-definition, manufacturable by computer numerically controlled (CNC) machining using the efficient flank (peripheral) method with standard conical tools. Our geometric approach exploits multi-valued vector fields that consist of vectors in...

  16. Simulation of flanking transmission in super-light structures for airborne and impact sound

    DEFF Research Database (Denmark)

    Christensen, Jacob Ellehauge; Hertz, Kristian Dahl; Brunskog, Jonas

    2012-01-01

    . Previously the airborne and impact sound insulation has been measured for a super-light deck element in a laboratory. This paper presents a flanking transmission analysis based on the measured results and are carried out for the Super-light deck elements by means of the acoustical software Bastian...... to design buildings with super-light deck elements while achieving a good acoustical environment in the building, fulfilling various acoustical requirements from the building regulations....

  17. Scarless and sequential gene modification in Pseudomonas using PCR product flanked by short homology regions

    Directory of Open Access Journals (Sweden)

    Liang Rubing

    2010-08-01

    Full Text Available Abstract Background The lambda Red recombination system has been used to inactivate chromosomal genes in various bacteria and fungi. The procedure consists of electroporating a polymerase chain reaction (PCR fragment containing antibiotic cassette flanked by homology regions to the target locus into a strain that can express the lambda Red proteins (Gam, Bet, Exo. Results Here a scarless gene modification strategy based on the Red recombination system has been developed to modify Pseudomonas genome DNA via sequential deletion of multiple targets. This process was mediated by plasmid pRKaraRed encoding the Red proteins regulated by PBAD promoter, which was functional in P. aeruginosa as well as in other bacteria. First the target gene was substituted for the sacB-bla cassette flanked by short homology regions (50 bp, and then this marker gene cassette could be replaced by the PCR fragment flanking itself, generating target-deleted genome without any remnants and no change happened to the surrounding region. Twenty genes involved in the synthesis and regulation pathways of the phenazine derivate, pyocyanin, were modified, including one single-point mutation and deletion of two large operons. The recombination efficiencies ranged from 88% to 98%. Multiple-gene modification was also achieved, generating a triple-gene deletion strain PCA (PAO1, ΔphzHΔphzMΔphzS, which could produce another phenazine derivate, phenazine-1-carboxylic acid (PCA, efficiently and exclusively. Conclusions This lambda Red-based technique can be used to generate scarless and sequential gene modification mutants of P. aeruginosa efficiently, using one-step PCR product flanked by short homology regions. Single-point mutation, scarless deletion of genes can be achieved easily in less than three days. This method may give a new way to construct genetically modified P. aeruginosa strains more efficiently and advance the regulatory network study of this organism.

  18. Reinforcing Deterrence on NATO’s Eastern Flank: Wargaming the Defense of the Baltics

    Science.gov (United States)

    2016-01-01

    SUMMARY ■ C O R P O R A T I O N Reinforcing Deterrence on NATO’s Eastern Flank Wargaming the Defense of the Baltics David A. Shlapak and Michael...and stability between Moscow and its Western neighbors and raised concerns about its larger intentions. From the perspective of the North Atlantic...After eastern Ukraine, the next most likely targets for an attempted Russian coercion are the Baltic Republics of Estonia, Latvia, and Lithuania

  19. Focused seismicity triggered by flank instability on Kīlauea's Southwest Rift Zone

    Science.gov (United States)

    Judson, Josiah; Thelen, Weston A.; Greenfield, Tim; White, Robert S.

    2018-03-01

    Swarms of earthquakes at the head of the Southwest Rift Zone on Kīlauea Volcano, Hawai´i, reveal an interaction of normal and strike-slip faulting associated with movement of Kīlauea's south flank. A relocated subset of earthquakes between January 2012 and August 2014 are highly focused in space and time at depths that are coincident with the south caldera magma reservoir beneath the southern margin of Kīlauea Caldera. Newly calculated focal mechanisms are dominantly dextral shear with a north-south preferred fault orientation. Two earthquakes within this focused area of seismicity have normal faulting mechanisms, indicating two mechanisms of failure in very close proximity (10's of meters to 100 m). We suggest a model where opening along the Southwest Rift Zone caused by seaward motion of the south flank permits injection of magma and subsequent freezing of a plug, which then fails in a right-lateral strike-slip sense, consistent with the direction of movement of the south flank. The seismicity is concentrated in an area where a constriction occurs between a normal fault and the deeper magma transport system into the Southwest Rift Zone. Although in many ways the Southwest Rift Zone appears analogous to the more active East Rift Zone, the localization of the largest seismicity (>M2.5) within the swarms to a small volume necessitates a different model than has been proposed to explain the lineament outlined by earthquakes along the East Rift Zone.

  20. Pancreatic Tail Cancer with Sole Manifestation of Left Flank Pain: A Very Rare Presentation

    Directory of Open Access Journals (Sweden)

    Hsing-Lin Lin

    2008-06-01

    Full Text Available Pancreatic cancer is sometimes called a “silent disease” because it often causes no symptoms in the early stage. The symptoms can be quite vague and various depending on the location of cancer in the pancreas. The anatomic site distribution is 78% in the head of the pancreas, 11% in the body, and 11% in the tail. Pancreatic cancer is rarely detected in the early stage, and it is very uncommon to diagnose pancreatic tail cancer during an emergency department visit. The manifestation of pancreatic tail cancer as left flank pain is very rare and has seldom been identified in the literature. We present a case of pancreatic tail cancer with the sole manifestation of dull left flank pain. Having negative findings on an ultrasound study initially, this female patient was misdiagnosed as having possible acute gastritis, urolithiasis or muscle strain after she received gastroendoscopy and colonofiberscopy. Her symptoms persisted for several months and she visited our emergency department due to an acute exacerbation of a persistent dull pain in the left flank area. Radiographic evaluation with computed tomography was performed, and pancreatic tail tumor with multiple metastases was found unexpectedly. We review the literature and discuss this rare presentation of pancreatic tail cancer.

  1. Method for Friction Force Estimation on the Flank of Cutting Tools

    Directory of Open Access Journals (Sweden)

    Luis Huerta

    2017-01-01

    Full Text Available Friction forces are present in any machining process. These forces could play an important role in the dynamics of the system. In the cutting process, friction is mainly present in the rake face and the flank of the tool. Although the one that acts on the rake face has a major influence, the other one can become also important and could take part in the stability of the system. In this work, experimental identification of the friction on the flank is presented. The experimental determination was carried out by machining aluminum samples in a CNC lathe. As a result, two friction functions were obtained as a function of the cutting speed and the relative motion of the contact elements. Experiments using a worn and a new insert were carried out. Force and acceleration were recorded simultaneously and, from these results, different friction levels were observed depending on the cutting parameters, such as cutting speed, feed rate, and tool condition. Finally, a friction model for the flank friction is presented.

  2. Radon measurements in the SE and NE flank of Mt. Etna (Italy)

    International Nuclear Information System (INIS)

    La Delfa, S.; Imme, G.; Lo Nigro, S.; Morelli, D.; Patane, G.; Vizzini, F.

    2007-01-01

    Soil Radon has been monitored at two fixed sites located in the northeastern and southeastern flank of Mt. Etna. In this study we report the comparison between in-soil Radon concentration trend recorded in the SE flank and that one recorded in the NE one, where an in-soil Radon detection system is operating since 2001. The aim of this work was to implement the investigation area finding a suitable radon detection site, in the south-east flank of Mt. Etna, in order to better understand possible links between Radon anomalies and volcano dynamic. Radon data collected in NE and SE sites were compared with the volcanic tremor, frequency of occurrence of earthquakes and seismic strain-release recorded at a fixed 3D digital seismic station placed in the NE site. Same general in-soil Radon trends and anomalies were found in both sites. These results have confirmed the suitability of the chosen southeastern site for the in-soil Radon monitoring at Mt. Etna. The comparison of the recorded Radon concentration anomalies with seismicity and volcanic tremor trends, has also verified a possible link with the volcanic activity, as observed in our previous published studies

  3. Multi-stage volcanic island flank collapses with coeval explosive caldera-forming eruptions.

    Science.gov (United States)

    Hunt, James E; Cassidy, Michael; Talling, Peter J

    2018-01-18

    Volcanic flank collapses and explosive eruptions are among the largest and most destructive processes on Earth. Events at Mount St. Helens in May 1980 demonstrated how a relatively small (300 km 3 ), but can also occur in complex multiple stages. Here, we show that multistage retrogressive landslides on Tenerife triggered explosive caldera-forming eruptions, including the Diego Hernandez, Guajara and Ucanca caldera eruptions. Geochemical analyses were performed on volcanic glasses recovered from marine sedimentary deposits, called turbidites, associated with each individual stage of each multistage landslide. These analyses indicate only the lattermost stages of subaerial flank failure contain materials originating from respective coeval explosive eruption, suggesting that initial more voluminous submarine stages of multi-stage flank collapse induce these aforementioned explosive eruption. Furthermore, there are extended time lags identified between the individual stages of multi-stage collapse, and thus an extended time lag between the initial submarine stages of failure and the onset of subsequent explosive eruption. This time lag succeeding landslide-generated static decompression has implications for the response of magmatic systems to un-roofing and poses a significant implication for ocean island volcanism and civil emergency planning.

  4. Predictive and prognostic value of circulating nucleosomes and serum biomarkers in patients with metastasized colorectal cancer undergoing Selective Internal Radiation Therapy

    International Nuclear Information System (INIS)

    Fahmueller, Yvonne Nadine; Nagel, Dorothea; Hoffmann, Ralf-Thorsten; Tatsch, Klaus; Jakobs, Tobias; Stieber, Petra; Holdenrieder, Stefan

    2012-01-01

    Selective Internal Radiation Therapy (SIRT) is a new and effective locoregional anticancer therapy for colorectal cancer patients with liver metastases. Markers for prediction of therapy response and prognosis are needed for the individual management of those patients undergoing SIRT. Blood samples were prospectively and consecutively taken from 49 colorectal cancer patients with extensive hepatic metastases before, three, six, 24 and 48 h after SIRT to analyze the concentrations of nucleosomes and further laboratory parameters, and to compare them with the response to therapy regularly determined 3 months after therapy and with overall survival. Circulating nucleosomes, cytokeratin-19 fragments (CYFRA 21-1), carcinoembryonic antigen (CEA), C-reactive protein (CRP) and various liver markers increased already 24 h after SIRT. Pretherapeutical levels of CYFRA 21-1, CEA, cancer antigen 19-9 (CA 19-9), asparate-aminotransferase (AST) and lactate dehydrogenase (LDH) as well as 24 h values of nucleosomes were significantly higher in patients suffering from disease progression (N = 35) than in non-progressive patients (N = 14). Concerning overall survival, CEA, CA 19-9, CYFRA 21-1, CRP, LDH, AST, choline esterase (CHE), gamma-glutamyl-transferase, alkaline phosphatase, and amylase (all 0 h, 24 h) and nucleosomes (24 h) were found to be prognostic relevant markers in univariate analyses. In multivariate Cox-Regression analysis, the best prognostic model was obtained for the combination of CRP and AST. When 24 h values were additionally included, nucleosomes (24 h) further improved the existing model. Panels of biochemical markers are helpful to stratify pretherapeutically colorectal cancer patients for SIR-therapy and to early estimate the response to SIR-therapy

  5. Genome-Wide Mapping Targets of the Metazoan Chromatin Remodeling Factor NURF Reveals Nucleosome Remodeling at Enhancers, Core Promoters and Gene Insulators.

    Directory of Open Access Journals (Sweden)

    So Yeon Kwon

    2016-04-01

    Full Text Available NURF is a conserved higher eukaryotic ISWI-containing chromatin remodeling complex that catalyzes ATP-dependent nucleosome sliding. By sliding nucleosomes, NURF is able to alter chromatin dynamics to control transcription and genome organization. Previous biochemical and genetic analysis of the specificity-subunit of Drosophila NURF (Nurf301/Enhancer of Bithorax (E(bx has defined NURF as a critical regulator of homeotic, heat-shock and steroid-responsive gene transcription. It has been speculated that NURF controls pathway specific transcription by co-operating with sequence-specific transcription factors to remodel chromatin at dedicated enhancers. However, conclusive in vivo demonstration of this is lacking and precise regulatory elements targeted by NURF are poorly defined. To address this, we have generated a comprehensive map of in vivo NURF activity, using MNase-sequencing to determine at base pair resolution NURF target nucleosomes, and ChIP-sequencing to define sites of NURF recruitment. Our data show that, besides anticipated roles at enhancers, NURF interacts physically and functionally with the TRF2/DREF basal transcription factor to organize nucleosomes downstream of active promoters. Moreover, we detect NURF remodeling and recruitment at distal insulator sites, where NURF functionally interacts with and co-localizes with DREF and insulator proteins including CP190 to establish nucleosome-depleted domains. This insulator function of NURF is most apparent at subclasses of insulators that mark the boundaries of chromatin domains, where multiple insulator proteins co-associate. By visualizing the complete repertoire of in vivo NURF chromatin targets, our data provide new insights into how chromatin remodeling can control genome organization and regulatory interactions.

  6. Experimental study of the interplay between magmatic rift intrusion and flank instability with application to the 2001 Mount Etna eruption

    KAUST Repository

    Le Corvec, Nicolas; Walter, Thomas R.; Ruch, Joel; Bonforte, Alessandro; Puglisi, Giuseppe

    2014-01-01

    Mount Etna volcano is subject to transient magmatic intrusions and flank movement. The east flank of the edifice, in particular, is moving eastward and is dissected by the Timpe Fault System. The relationship of this eastward motion with intrusions and tectonic fault motion, however, remains poorly constrained. Here we explore this relationship by using analogue experiments that are designed to simulate magmatic rift intrusion, flank movement, and fault activity before, during, and after a magmatic intrusion episode. Using particle image velocimetry allows for a precise temporal and spatial analysis of the development and activity of fault systems. The results show that the occurrence of rift intrusion episodes has a direct effect on fault activity. In such a situation, fault activity may occur or may be hindered, depending on the interplay of fault displacement and flank acceleration in response to dike intrusion. Our results demonstrate that a complex interplay may exist between an active tectonic fault system and magmatically induced flank instability. Episodes of magmatic intrusion change the intensity pattern of horizontal flank displacements and may hinder or activate associated faults. We further compare our results with the GPS data of the Mount Etna 2001 eruption and intrusion. We find that syneruptive displacement rates at the Timpe Fault System have differed from the preeruptive or posteruptive periods, which shows a good agreement of both the experimental and the GPS data. Therefore, understanding the flank instability and flank stability at Mount Etna requires consideration of both tectonic and magmatic forcing. Key Points Analyzing Mount Etna east flank dynamics during the 2001 eruption Good correlation between analogue models and GPS data Understanding the different behavior of faulting before/during/after an eruption © 2014. American Geophysical Union. All Rights Reserved.

  7. Experimental study of the interplay between magmatic rift intrusion and flank instability with application to the 2001 Mount Etna eruption

    KAUST Repository

    Le Corvec, Nicolas

    2014-07-01

    Mount Etna volcano is subject to transient magmatic intrusions and flank movement. The east flank of the edifice, in particular, is moving eastward and is dissected by the Timpe Fault System. The relationship of this eastward motion with intrusions and tectonic fault motion, however, remains poorly constrained. Here we explore this relationship by using analogue experiments that are designed to simulate magmatic rift intrusion, flank movement, and fault activity before, during, and after a magmatic intrusion episode. Using particle image velocimetry allows for a precise temporal and spatial analysis of the development and activity of fault systems. The results show that the occurrence of rift intrusion episodes has a direct effect on fault activity. In such a situation, fault activity may occur or may be hindered, depending on the interplay of fault displacement and flank acceleration in response to dike intrusion. Our results demonstrate that a complex interplay may exist between an active tectonic fault system and magmatically induced flank instability. Episodes of magmatic intrusion change the intensity pattern of horizontal flank displacements and may hinder or activate associated faults. We further compare our results with the GPS data of the Mount Etna 2001 eruption and intrusion. We find that syneruptive displacement rates at the Timpe Fault System have differed from the preeruptive or posteruptive periods, which shows a good agreement of both the experimental and the GPS data. Therefore, understanding the flank instability and flank stability at Mount Etna requires consideration of both tectonic and magmatic forcing. Key Points Analyzing Mount Etna east flank dynamics during the 2001 eruption Good correlation between analogue models and GPS data Understanding the different behavior of faulting before/during/after an eruption © 2014. American Geophysical Union. All Rights Reserved.

  8. MARCC (Matrix-Assisted Reader Chromatin Capture): an antibody-free method to enrich and analyze combinatorial nucleosome modifications

    Science.gov (United States)

    Su, Zhangli

    2016-01-01

    Combinatorial patterns of histone modifications are key indicators of different chromatin states. Most of the current approaches rely on the usage of antibodies to analyze combinatorial histone modifications. Here we detail an antibody-free method named MARCC (Matrix-Assisted Reader Chromatin Capture) to enrich combinatorial histone modifications. The combinatorial patterns are enriched on native nucleosomes extracted from cultured mammalian cells and prepared by micrococcal nuclease digestion. Such enrichment is achieved by recombinant chromatin-interacting protein modules, or so-called reader domains, which can bind in a combinatorial modification-dependent manner. The enriched chromatin can be quantified by western blotting or mass spectrometry for the co-existence of histone modifications, while the associated DNA content can be analyzed by qPCR or next-generation sequencing. Altogether, MARCC provides a reproducible, efficient and customizable solution to enrich and analyze combinatorial histone modifications. PMID:26131849

  9. North Kona slump: Submarine flank failure during the early(?) tholeiitic shield stage of Hualalai Volcano

    Science.gov (United States)

    Lipman, P.W.; Coombs, M.L.

    2006-01-01

    The North Kona slump is an elliptical region, about 20 by 60 km (1000-km2 area), of multiple, geometrically intricate benches and scarps, mostly at water depths of 2000–4500 m, on the west flank of Hualalai Volcano. Two dives up steep scarps in the slump area were made in September 2001, using the ROV Kaiko of the Japan Marine Science and Technology Center (JAMSTEC), as part of a collaborative Japan–USA project to improve understanding of the submarine flanks of Hawaiian volcanoes. Both dives, at water depths of 2700–4000 m, encountered pillow lavas draping the scarp-and-bench slopes. Intact to only slightly broken pillow lobes and cylinders that are downward elongate dominate on the steepest mid-sections of scarps, while more equant and spherical pillow shapes are common near the tops and bases of scarps and locally protrude through cover of muddy sediment on bench flats. Notably absent are subaerially erupted Hualalai lava flows, interbedded hyaloclastite pillow breccia, and/or coastal sandy sediment that might have accumulated downslope from an active coastline. The general structure of the North Kona flank is interpreted as an intricate assemblage of downdropped lenticular blocks, bounded by steeply dipping normal faults. The undisturbed pillow-lava drape indicates that slumping occurred during shield-stage tholeiitic volcanism. All analyzed samples of the pillow-lava drape are tholeiite, similar to published analyses from the submarine northwest rift zone of Hualālai. Relatively low sulfur (330–600 ppm) and water (0.18–0.47 wt.%) contents of glass rinds suggest that the eruptive sources were in shallow water, perhaps 500–1000-m depth. In contrast, saturation pressures calculated from carbon dioxide concentrations (100–190 ppm) indicate deeper equilibration, at or near sample sites at water depths of − 3900 to − 2800 m. Either vents close to the sample sites erupted mixtures of undegassed and degassed magmas, or volatiles were resorbed from

  10. Superficial deposits in northeast flank of Sierras Australes (Provincia de Buenos Aires, Republica Argentina)

    International Nuclear Information System (INIS)

    Gentile, R.; Fucks, E.; De Francesco, F.

    2004-01-01

    Pleistocene and Holocene superficial deposits, which have been recognized in an area of 1500 km2 in the northeast flank of Sierras Australes, are characterized. In divide they are underlain by silts and siltstone which are called Sediments Pampeanas. There, a lower sequence, consisting mainly of aeolian sediments (loess) with scarce fluvial deposits and diamictons, was recognized. In some places an upper sequence that is product of aeolian and anthropogenic activity, was also recognized. In the valley sequences, the loess deposits can not only be underlain by fluvial sediments but can also overlain them. The more recent fluvial deposits which have eroded loess sequences are of the post conquest age [es

  11. Geochemistry of summit fumarole vapors and flanking thermal/mineral waters at Popocatepetl Volcano, Mexico

    Energy Technology Data Exchange (ETDEWEB)

    Werner, C.; Goff, F. [Los Alamos National Lab., NM (United States); Janik, C.J. [Geological Survey, Menlo Park, CA (United States)] [and others

    1997-06-01

    Popocatepetl Volcano is potentially devastating to populations living in the greater Mexico City area. Systematic monitoring of fumarole gases and flanking thermal/mineral springs began in early 1994 after increased fumarolic and seismic activity were noticed in 1991. These investigations had two major objectives: (1) to determine if changes in magmatic conditions beneath Popocatepetl might be reflected by chemical changes in fumarolic discharges and (2) to determine if thermal/mineral spring waters in the vicinity of Popocatepetl are geochemically related to or influences by the magmatic system. This report summarizes results from these two discrete studies.

  12. Soil radon monitoring in the NE flank of Mt. Etna (Sicily)

    International Nuclear Information System (INIS)

    Imme, G.; La Delfa, S.; Lo Nigro, S.; Morelli, D.; Patane, G.

    2006-01-01

    Soil radon has been monitored at a fixed location on the northeastern flank of Mt. Etna, a high-risk volcano in Sicily. The aim of this study was to evaluate the effects of the recent volcanic activity on soil radon concentration. Continuous radon measurements have been performed since July 2001. While comparison between the trend in in-soil radon concentration and the acquired meteorological series (temperature, humidity and pressure) appear to confirm a general seasonal correlation, nevertheless particular anomalies suggest a possible dependence of the radon concentration on volcanic dynamics

  13. Flank wears Simulation by using back propagation neural network when cutting hardened H-13 steel in CNC End Milling

    Science.gov (United States)

    Hazza, Muataz Hazza F. Al; Adesta, Erry Y. T.; Riza, Muhammad

    2013-12-01

    High speed milling has many advantages such as higher removal rate and high productivity. However, higher cutting speed increase the flank wear rate and thus reducing the cutting tool life. Therefore estimating and predicting the flank wear length in early stages reduces the risk of unaccepted tooling cost. This research presents a neural network model for predicting and simulating the flank wear in the CNC end milling process. A set of sparse experimental data for finish end milling on AISI H13 at hardness of 48 HRC have been conducted to measure the flank wear length. Then the measured data have been used to train the developed neural network model. Artificial neural network (ANN) was applied to predict the flank wear length. The neural network contains twenty hidden layer with feed forward back propagation hierarchical. The neural network has been designed with MATLAB Neural Network Toolbox. The results show a high correlation between the predicted and the observed flank wear which indicates the validity of the models.

  14. Flank wears Simulation by using back propagation neural network when cutting hardened H-13 steel in CNC End Milling

    International Nuclear Information System (INIS)

    Al Hazza, Muataz Hazza F; Adesta, Erry Y T; Riza, Muhammad

    2013-01-01

    High speed milling has many advantages such as higher removal rate and high productivity. However, higher cutting speed increase the flank wear rate and thus reducing the cutting tool life. Therefore estimating and predicting the flank wear length in early stages reduces the risk of unaccepted tooling cost. This research presents a neural network model for predicting and simulating the flank wear in the CNC end milling process. A set of sparse experimental data for finish end milling on AISI H13 at hardness of 48 HRC have been conducted to measure the flank wear length. Then the measured data have been used to train the developed neural network model. Artificial neural network (ANN) was applied to predict the flank wear length. The neural network contains twenty hidden layer with feed forward back propagation hierarchical. The neural network has been designed with MATLAB Neural Network Toolbox. The results show a high correlation between the predicted and the observed flank wear which indicates the validity of the models

  15. Determining injuries from posterior and flank stab wounds using computed tomography tractography.

    Science.gov (United States)

    Bansal, Vishal; Reid, Chris M; Fortlage, Dale; Lee, Jeanne; Kobayashi, Leslie; Doucet, Jay; Coimbra, Raul

    2014-04-01

    Unlike anterior stab wounds (SW), in which local exploration may direct management, posterior SW can be challenging to evaluate. Traditional triple contrast computed tomography (CT) imaging is cumbersome and technician-dependent. The present study examines the role of CT tractography as a strategy to manage select patients with back and flank SW. Hemodynamically stable patients with back and flank SW were studied. After resuscitation, Betadine- or Visipaque®-soaked sterile sponges were inserted into each SW for the estimated depth of the wound. Patients underwent abdominal helical CT scanning, including intravenous contrast, as the sole abdominal imaging study. Images were reviewed by an attending radiologist and trauma surgeon. The tractogram was evaluated to determine SW trajectory and injury to intra- or retroperitoneal organs, vascular structures, the diaphragm, and the urinary tract. Complete patient demographics including operative management and injuries were collected. Forty-one patients underwent CT tractography. In 11 patients, tractography detected violation of the intra- or retroperitoneal cavity leading to operative exploration. Injuries detected included: the spleen (two), colon (one), colonic mesentery (one), kidney (kidney), diaphragm (kidney), pneumothorax (seven), hemothorax (two), iliac artery (one), and traumatic abdominal wall hernia (two). In all patients, none had negative CT findings that failed observation. In this series, CT tractography is a safe and effective imaging strategy to evaluate posterior torso SW. It is unknown whether CT tractography is superior to traditional imaging modalities. Other uses for CT tractography may include determining trajectory from missile wounds and tangential penetrating injuries.

  16. Identification of functional SNPs in the 5-prime flanking sequences of human genes

    Directory of Open Access Journals (Sweden)

    Lenhard Boris

    2005-02-01

    Full Text Available Abstract Background Over 4 million single nucleotide polymorphisms (SNPs are currently reported to exist within the human genome. Only a small fraction of these SNPs alter gene function or expression, and therefore might be associated with a cell phenotype. These functional SNPs are consequently important in understanding human health. Information related to functional SNPs in candidate disease genes is critical for cost effective genetic association studies, which attempt to understand the genetics of complex diseases like diabetes, Alzheimer's, etc. Robust methods for the identification of functional SNPs are therefore crucial. We report one such experimental approach. Results Sequence conserved between mouse and human genomes, within 5 kilobases of the 5-prime end of 176 GPCR genes, were screened for SNPs. Sequences flanking these SNPs were scored for transcription factor binding sites. Allelic pairs resulting in a significant score difference were predicted to influence the binding of transcription factors (TFs. Ten such SNPs were selected for mobility shift assays (EMSA, resulting in 7 of them exhibiting a reproducible shift. The full-length promoter regions with 4 of the 7 SNPs were cloned in a Luciferase based plasmid reporter system. Two out of the 4 SNPs exhibited differential promoter activity in several human cell lines. Conclusions We propose a method for effective selection of functional, regulatory SNPs that are located in evolutionary conserved 5-prime flanking regions (5'-FR regions of human genes and influence the activity of the transcriptional regulatory region. Some SNPs behave differently in different cell types.

  17. Flanking sequence determination and specific PCR identification of transgenic wheat B102-1-2.

    Science.gov (United States)

    Cao, Jijuan; Xu, Junyi; Zhao, Tongtong; Cao, Dongmei; Huang, Xin; Zhang, Piqiao; Luan, Fengxia

    2014-01-01

    The exogenous fragment sequence and flanking sequence between the exogenous fragment and recombinant chromosome of transgenic wheat B102-1-2 were successfully acquired using genome walking technology. The newly acquired exogenous fragment encoded the full-length sequence of transformed genes with transformed plasmid and corresponding functional genes including ubi, vector pBANF-bar, vector pUbiGUSPlus, vector HSP, reporter vector pUbiGUSPlus, promoter ubiquitin, and coli DH1. A specific polymerase chain reaction (PCR) identification method for transgenic wheat B102-1-2 was established on the basis of designed primers according to flanking sequence. This established specific PCR strategy was validated by using transgenic wheat, transgenic corn, transgenic soybean, transgenic rice, and non-transgenic wheat. A specifically amplified target band was observed only in transgenic wheat B102-1-2. Therefore, this method is characterized by high specificity, high reproducibility, rapid identification, and excellent accuracy for the identification of transgenic wheat B102-1-2.

  18. Sistema Faro, Isla de Mona, Puerto Rico: speleogenesis of the worlds largest flank margin cave

    International Nuclear Information System (INIS)

    Lace, M. J.; Kambesis, P. N.; Mylroie, J. E.

    2016-01-01

    Isla de Mona, a small, uplifted carbonate plateau jutting out of the waters of the Mona Passage, is an incredibly fragile and densely karstic environment. Expedition work was conducted by the Isla de Mona Project in cooperation with the Departamento Recursos Naturales y Ambientales de Puerto Rico (DRNA), including contributions from many researchers and cavers volunteering from across the U.S and Puerto Rico in the course of 12 separate expeditions, spanning a 14 year period (1998 to 2013). Over 200 caves have been documented on the island to date, the majority of this inventory is composed of flank margin caves but also includes sea caves, pit caves and talus caves. The most extensive example of cave development on the island is Sistema Faro - a sprawling maze-like series of chambers formed within the eastern point of the island with over 40 cliffside entrances overlooking the Caribbean Sea. Detailed cartography and analysis of the geomorphology and development of the Sistema Faro has helped form a complex model of carbonate island cave development as a function of tectonic uplift, lithology, sea level changes, karst hydrogeology and cliff retreat. This communication examines the roles these controls have played in the genesis of the world's largest flank margin cave. (Author)

  19. The value of HASTE MR urography in the diagnosis of the chronic nephrogenic flank pain

    International Nuclear Information System (INIS)

    Werel, D.; Tarasow, E.; Dzienis, W.; Ustymowicz, A.; Orzechowska-Bobkiewicz, A.; Walecki, J.; Darewicz, B.

    2004-01-01

    To asses the usefulness of the projectional HASTE sequence in the diagnosis of chronic flank pain caused by obstructive uropathy in comparison with conventional urography. 28 patients with chronic flank pain and hydronephrosis on ultrasound underwent conventional urography and HASTE sequence of static MR urography. The methods were evaluated for image quality, presence, agree, level and cause of urinary tract dilatation. The image quality of the urinary tract on HASTE was good in 57.1% and satisfactory in 42.9%; in conventional urography - good in 28.6%, satisfactory in 42.8% and poor in 28.6%. HASTE demonstrated hydronephrosis and degree of hydronephrosis in all the cases and conventional urography in 25 (83.3%). HASTE identified correctly the site of obstruction in 29 cases (96.7%), and conventional urography in 21 cases (70%). The sensitivity of HASTE in diagnosis of the intrinsic and extrinsic causes of obstruction was 73.7% and 80%, accuracy 73.3% and that of conventional urography 68.4%, 40% and 56.7%, respectively. HASTE is a valuable method in the diagnostics of chronic obstructive uropathy. It allows to evaluate the degree of hydronephrosis, the level and in many cases the cause of obstruction. When the urinary tract is not visualized in conventional urography, static MR urography is especially useful. (author)

  20. Characterization of Bovine 5′-flanking Region during Differentiation of Mouse Embryonic Stem Cells

    Directory of Open Access Journals (Sweden)

    Hye-Jeong Jang

    2015-12-01

    Full Text Available Embryonic stem cells (ESCs have been used as a powerful tool for research including gene manipulated animal models and the study of developmental gene regulation. Among the critical regulatory factors that maintain the pluripotency and self-renewal of undifferentiated ESCs, NANOG plays a very important role. Nevertheless, because pluripotency maintaining factors and specific markers for livestock ESCs have not yet been probed, few studies of the NANOG gene from domestic animals including bovine have been reported. Therefore, we chose mouse ESCs in order to understand and compare NANOG expression between bovine, human, and mouse during ESCs differentiation. We cloned a 600 bp (−420/+181 bovine NANOG 5′-flanking region, and tagged it with humanized recombinant green fluorescent protein (hrGFP as a tracing reporter. Very high GFP expression for bovine NANOG promoter was observed in the mouse ESC line. GFP expression was monitored upon ESC differentiation and was gradually reduced along with differentiation toward neurons and adipocyte cells. Activity of bovine NANOG (−420/+181 promoter was compared with already known mouse and human NANOG promoters in mouse ESC and they were likely to show a similar pattern of regulation. In conclusion, bovine NANOG 5-flanking region functions in mouse ES cells and has characteristics similar to those of mouse and human. These results suggest that bovine gene function studied in mouse ES cells should be evaluated and extrapolated for application to characterization of bovine ES cells.

  1. Sediment transport along the Cap de Creus Canyon flank during a mild, wet winter

    Directory of Open Access Journals (Sweden)

    J. Martín

    2013-05-01

    Full Text Available Cap de Creus Canyon (CCC is known as a preferential conduit for particulate matter leaving the Gulf of Lion continental shelf towards the slope and the basin, particularly in winter when storms and dense shelf water cascading coalesce to enhance the seaward export of shelf waters. During the CASCADE (CAscading, Storm, Convection, Advection and Downwelling Events cruise in March 2011, deployments of recording instruments within the canyon and vertical profiling of the water column properties were conducted to study with high spatial-temporal resolution the impact of such processes on particulate matter fluxes. In the context of the mild and wet 2010–2011 winter, no remarkable dense shelf water formation was observed. On the other hand, the experimental setup allowed for the study of the impact of E-SE storms on the hydrographical structure and the particulate matter fluxes in the CCC. The most remarkable feature in terms of sediment transport was a period of dominant E-SE winds from 12 to 16 March, including two moderate storms (maximum significant wave heights = 4.1–4.6 m. During this period, a plume of freshened, relatively cold and turbid water flowed at high speeds along the southern flank of the CCC in an approximate depth range of 150–350 m. The density of this water mass was lighter than the ambient water in the canyon, indicating that it did not cascade off-shelf and that it merely downwelled into the canyon forced by the strong cyclonic circulation induced over the shelf during the storms and by the subsequent accumulation of seawater along the coast. Suspended sediment load in this turbid intrusion recorded along the southern canyon flank oscillated between 10 and 50 mg L−1, and maximum currents speeds reached values up to 90 cm s−1. A rough estimation of 105 tons of sediment was transported through the canyon along its southern wall during a 3-day-long period of storm-induced downwelling. Following the veering of the wind

  2. Combination of Hypomorphic Mutations of the Drosophila Homologues of Aryl Hydrocarbon Receptor and Nucleosome Assembly Protein Family Genes Disrupts Morphogenesis, Memory and Detoxification

    OpenAIRE

    Kuzin, Boris A.; Nikitina, Ekaterina A.; Cherezov, Roman O.; Vorontsova, Julia E.; Slezinger, Mikhail S.; Zatsepina, Olga G.; Simonova, Olga B.; Enikolopov, Grigori N.; Savvateeva-Popova, Elena V.

    2014-01-01

    Aryl hydrocarbon receptor is essential for biological responses to endogenous and exogenous toxins in mammals. Its Drosophila homolog spineless plays an important role in fly morphogenesis. We have previously shown that during morphogenesis spineless genetically interacts with CG5017 gene, which encodes a nucleosome assembly factor and may affect cognitive function of the fly. We now demonstrate synergistic interactions of spineless and CG5017 in pathways controlling oxidative stress response...

  3. Lysine methyltransferase G9a is not required for DNMT3A/3B anchoring to methylated nucleosomes and maintenance of DNA methylation in somatic cells

    Directory of Open Access Journals (Sweden)

    Sharma Shikhar

    2012-01-01

    Full Text Available Abstract Background DNA methylation, histone modifications and nucleosome occupancy act in concert for regulation of gene expression patterns in mammalian cells. Recently, G9a, a H3K9 methyltransferase, has been shown to play a role in establishment of DNA methylation at embryonic gene targets in ES cells through recruitment of de novo DNMT3A/3B enzymes. However, whether G9a plays a similar role in maintenance of DNA methylation in somatic cells is still unclear. Results Here we show that G9a is not essential for maintenance of DNA methylation in somatic cells. Knockdown of G9a has no measurable effect on DNA methylation levels at G9a-target loci. DNMT3A/3B remain stably anchored to nucleosomes containing methylated DNA even in the absence of G9a, ensuring faithful propagation of methylated states in cooperation with DNMT1 through somatic divisions. Moreover, G9a also associates with nucleosomes in a DNMT3A/3B and DNA methylation-independent manner. However, G9a knockdown synergizes with pharmacologic inhibition of DNMTs resulting in increased hypomethylation and inhibition of cell proliferation. Conclusions Taken together, these data suggest that G9a is not involved in maintenance of DNA methylation in somatic cells but might play a role in re-initiation of de novo methylation after treatment with hypomethylating drugs, thus serving as a potential target for combinatorial treatments strategies involving DNMTs inhibitors.

  4. Distinct sources of particles near the cusp and the dusk flank of the magnetosphere

    Science.gov (United States)

    Escoubet, C. P.; Grison, B.; Berchem, J.; Trattner, K. J.; Lavraud, B.; Pitout, F.; Soucek, J.; Richard, R. L.; Laakso, H. E.; Masson, A.; Dunlop, M.; Dandouras, I. S.; Rème, H.; Fazakerley, A. N.; Daly, P. W.

    2015-12-01

    At the magnetopause, the location of the magnetic reconnection sites depends on the orientation of the interplanetary magnetic field (IMF) in the solar wind: on the dayside magnetosphere for an IMF southward, on the lobes for an IMF northward and on the flanks for an IMF in the East-West direction. Since most of observations of reconnection events have sampled a limited region of space simultaneously it is still not yet know if the reconnection line is extended over large regions of the magnetosphere or if is patchy and made of many reconnection lines. We report a Cluster crossing on 5 January 2002 near the exterior cusp on the southern dusk side where we observe multiple sources of reconnection/injections. The IMF was mainly azimuthal (IMF-By around -5 nT), the solar wind speed lower than usual around 280 km/s with the density of order 5 cm-3. The four Cluster spacecraft had an elongated configuration near the magnetopause. C4 was the first spacecraft to enter the cusp around 19:52:04 UT, followed by C2 at 19:52:35 UT, C1 at 19:54:24 UT and C3 at 20:13:15 UT. C4 and C1 observed two ion energy dispersions at 20:10 UT and 20:40 UT and C3 at 20:35 UT and 21:15 UT. Using the time of flight technique on the upgoing and downgoing ions, which leads to energy dispersions, we obtain distances of the ion sources between 14 and 20 RE from the spacecraft. The slope of the ion energy dispersions confirmed these distances. Using Tsyganenko model, we find that these sources are located on the dusk flank, past the terminator. The first injection by C3 is seen at approximately the same time as the 2nd injection on C1 but their sources at the magnetopause were separated by more than 7 RE. This would imply that two distinct sources were active at the same time on the dusk flank of the magnetosphere. In addition, a flow reversal was observed at the magnetopause on C4 which would be an indication that reconnection is also taking place near the exterior cusp quasi-simultaneously. A

  5. Cluster Observations of reconnection along the dusk flank of the magnetosphere

    Science.gov (United States)

    Escoubet, C.-Philippe; Grison, Benjamin; Berchem, Jean; Trattner, Karlheinz; Lavraud, Benoit; Pitout, Frederic; Soucek, Jan; Richard, Robert; Laakso, Harri; Masson, Arnaud; Dunlop, Malcolm; Dandouras, Iannis; Reme, Henri; Fazakerley, Andrew; Daly, Patrick

    2015-04-01

    Magnetic reconnection is generally accepted to be the main process that transfers particles and energy from the solar wind to the magnetosphere. The location of the reconnection site depends on the orientation of the interplanetary magnetic field (IMF) in the solar wind: on the dayside magnetosphere for an IMF southward, on the lobes for an IMF northward and on the flanks for an IMF in the East-West direction. Since most of observations of reconnection events have sampled a limited region of space simultaneously it is still not yet know if the reconnection line is extended over large regions of the magnetosphere or if is patchy and made of many reconnection lines. We report a Cluster crossing on 5 January 2002 near the exterior cusp on the southern dusk side where we observe multiple sources of reconnection/injections. The IMF was mainly azimuthal (IMF-By around -5 nT), the solar wind speed lower than usual around 280 km/s with the density of order 5 cm-3. The four Cluster spacecraft had an elongated configuration near the magnetopause. C4 was the first spacecraft to enter the cusp around 19:52:04 UT, followed by C2 at 19:52:35 UT, C1 at 19:54:24 UT and C3 at 20:13:15 UT. C4 and C1 observed two ion energy dispersions at 20:10 UT and 20:40 UT and C3 at 20:35 UT and 21:15 UT. Using the time of flight technique on the upgoing and downgoing ions, which leads to energy dispersions, we obtain distances of the ion sources between 14 and 20 RE from the spacecraft. The slope of the ion energy dispersions confirmed these distances. Using Tsyganenko model, we find that these sources are located on the dusk flank, past the terminator. The first injection by C3 is seen at approximately the same time as the 2nd injection on C1 but their sources at the magnetopause were separated by more than 7 RE. This would imply that two distinct sources were active at the same time on the dusk flank of the magnetosphere. In addition, a flow reversal was observed at the magnetopause on C4

  6. BAF53b, a Neuron-Specific Nucleosome Remodeling Factor, Is Induced after Learning and Facilitates Long-Term Memory Consolidation.

    Science.gov (United States)

    Yoo, Miran; Choi, Kwang-Yeon; Kim, Jieun; Kim, Mujun; Shim, Jaehoon; Choi, Jun-Hyeok; Cho, Hye-Yeon; Oh, Jung-Pyo; Kim, Hyung-Su; Kaang, Bong-Kiun; Han, Jin-Hee

    2017-03-29

    Although epigenetic mechanisms of gene expression regulation have recently been implicated in memory consolidation and persistence, the role of nucleosome-remodeling is largely unexplored. Recent studies show that the functional loss of BAF53b, a postmitotic neuron-specific subunit of the BAF nucleosome-remodeling complex, results in the deficit of consolidation of hippocampus-dependent memory and cocaine-associated memory in the rodent brain. However, it is unclear whether BAF53b expression is regulated during memory formation and how BAF53b regulates fear memory in the amygdala, a key brain site for fear memory encoding and storage. To address these questions, we used viral vector approaches to either decrease or increase BAF53b function specifically in the lateral amygdala of adult mice in auditory fear conditioning paradigm. Knockdown of Baf53b before training disrupted long-term memory formation with no effect on short-term memory, basal synaptic transmission, and spine structures. We observed in our qPCR analysis that BAF53b was induced in the lateral amygdala neurons at the late consolidation phase after fear conditioning. Moreover, transient BAF53b overexpression led to persistently enhanced memory formation, which was accompanied by increase in thin-type spine density. Together, our results provide the evidence that BAF53b is induced after learning, and show that such increase of BAF53b level facilitates memory consolidation likely by regulating learning-related spine structural plasticity. SIGNIFICANCE STATEMENT Recent works in the rodent brain begin to link nucleosome remodeling-dependent epigenetic mechanism to memory consolidation. Here we show that BAF53b, an epigenetic factor involved in nucleosome remodeling, is induced in the lateral amygdala neurons at the late phase of consolidation after fear conditioning. Using specific gene knockdown or overexpression approaches, we identify the critical role of BAF53b in the lateral amygdala neurons for

  7. Flank gland-secreted putative chemosignals pertaining to photoperiod, endocrine states, and sociosexual behavior in golden hamsters

    Directory of Open Access Journals (Sweden)

    Ying-Juan LIU, Da-Wei WANG, Lixing SUN, Jin-Hua ZHANG, Jian-Xu ZHANG

    2010-12-01

    Full Text Available Behavioral studies have shown that flank glands are involved in chemical communication in golden hamsters Mesocricetus auratus but little chemical analysis has been conducted on volatiles arising from these glands. Using gas chromatography-mass spectrometry, we detected compounds from the flank glands of males, only eight of which were also produced in females. Based on these chemical data we performed a number of further experiments. By manipulating light we found that males exposed to short-photoperiods developed smaller flank glands than those exposed to long-photoperiods. Six flank gland volatiles reduced in relative abundance, which possibly coded for reproductive status of males of this seasonally breeding hamster species. Through dyadic encounters, we were able to induce the formation of dominant-subordinate relationships and show that two glandular compounds became high in relative abundance and may function as dominance pheromones. Castration eliminated all male-specific compounds resulting from flank glands, but bilateral ovariectomies only affected one compound in females. Once these ovariectomized females were treated with testosterone, their glandular compounds resembled those of males, suggesting these compounds are under the main control of androgen. Two female putative pheromones, tetradecanoic acid and hexadecanoic acid, were used in binary choice tests and were both found to attract males over females. Applying a solution of these pheromone compounds to adult males also suppressed their agonistic behavior [Current Zoology 56 (6: 800–812, 2010].

  8. Transcription factor 19 interacts with histone 3 lysine 4 trimethylation and controls gluconeogenesis via the nucleosome-remodeling-deacetylase complex.

    Science.gov (United States)

    Sen, Sabyasachi; Sanyal, Sulagna; Srivastava, Dushyant Kumar; Dasgupta, Dipak; Roy, Siddhartha; Das, Chandrima

    2017-12-15

    Transcription factor 19 (TCF19) has been reported as a type 1 diabetes-associated locus involved in maintenance of pancreatic β cells through a fine-tuned regulation of cell proliferation and apoptosis. TCF19 also exhibits genomic association with type 2 diabetes, although the precise molecular mechanism remains unknown. It harbors both a plant homeodomain and a forkhead-associated domain implicated in epigenetic recognition and gene regulation, a phenomenon that has remained unexplored. Here, we show that TCF19 selectively interacts with histone 3 lysine 4 trimethylation through its plant homeodomain finger. Knocking down TCF19 under high-glucose conditions affected many metabolic processes, including gluconeogenesis. We found that TCF19 overexpression represses de novo glucose production in HepG2 cells. The transcriptional repression of key genes, induced by TCF19, coincided with NuRD (nucleosome-remodeling-deacetylase) complex recruitment to the promoters of these genes. TCF19 interacted with CHD4 (chromodomain helicase DNA-binding protein 4), which is a part of the NuRD complex, in a glucose concentration-independent manner. In summary, our results show that TCF19 interacts with an active transcription mark and recruits a co-repressor complex to regulate gluconeogenic gene expression in HepG2 cells. Our study offers critical insights into the molecular mechanisms of transcriptional regulation of gluconeogenesis and into the roles of chromatin readers in metabolic homeostasis. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Interaction of nucleosome assembly proteins abolishes nuclear localization of DGK{zeta} by attenuating its association with importins

    Energy Technology Data Exchange (ETDEWEB)

    Okada, Masashi; Hozumi, Yasukazu [Department of Anatomy and Cell Biology, Yamagata University School of Medicine, Yamagata 990-9585 (Japan); Ichimura, Tohru [Department of Chemistry, Graduate School of Sciences and Engineering, Tokyo Metropolitan University, Hachioji 192-0397 (Japan); Tanaka, Toshiaki; Hasegawa, Hiroshi; Yamamoto, Masakazu; Takahashi, Nobuya [Department of Anatomy and Cell Biology, Yamagata University School of Medicine, Yamagata 990-9585 (Japan); Iseki, Ken [Department of Emergency and Critical Care Medicine, Yamagata University School of Medicine, Yamagata 990-9585 (Japan); Yagisawa, Hitoshi [Laboratory of Biological Signaling, Graduate School of Life Science, University of Hyogo, Hyogo 678-1297 (Japan); Shinkawa, Takashi; Isobe, Toshiaki [Department of Chemistry, Graduate School of Sciences and Engineering, Tokyo Metropolitan University, Hachioji 192-0397 (Japan); Goto, Kaoru, E-mail: kgoto@med.id.yamagata-u.ac.jp [Department of Anatomy and Cell Biology, Yamagata University School of Medicine, Yamagata 990-9585 (Japan)

    2011-12-10

    Diacylglycerol kinase (DGK) is involved in the regulation of lipid-mediated signal transduction through the metabolism of a second messenger diacylglycerol. Of the DGK family, DGK{zeta}, which contains a nuclear localization signal, localizes mainly to the nucleus but translocates to the cytoplasm under pathological conditions. However, the detailed mechanism of translocation and its functional significance remain unclear. To elucidate these issues, we used a proteomic approach to search for protein targets that interact with DGK{zeta}. Results show that nucleosome assembly protein (NAP) 1-like 1 (NAP1L1) and NAP1-like 4 (NAP1L4) are identified as novel DGK{zeta} binding partners. NAP1Ls constitutively shuttle between the nucleus and the cytoplasm in transfected HEK293 cells. The molecular interaction of DGK{zeta} and NAP1Ls prohibits nuclear import of DGK{zeta} because binding of NAP1Ls to DGK{zeta} blocks import carrier proteins, Qip1 and NPI1, to interact with DGK{zeta}, leading to cytoplasmic tethering of DGK{zeta}. In addition, overexpression of NAP1Ls exerts a protective effect against doxorubicin-induced cytotoxicity. These findings suggest that NAP1Ls are involved in a novel molecular basis for the regulation of nucleocytoplasmic shuttling of DGK{zeta} and provide a clue to examine functional significance of its translocation under pathological conditions.

  10. [Norrie syndrome: identification of carriers by segregation analysis with flanking DNA markers].

    Science.gov (United States)

    Körner, J; Uhlhaas, S; Neugebauer, M; Gal, A

    1989-01-01

    Norrie disease is an X-linked recessive disorder. Affected males present with congenital blindness. Additionally, hearing loss and psychotic behavior may occur at any time. Since carriers are clinically healthy, they can only be identified by genetic means. Daughters of carriers or sisters of affected males have an à priori 50% risk of being carriers themselves. Close linkage has been found between the Norrie disease locus (NDP) and the DNA locus DXS7 mapped to Xp11.3. For genetic counselling, this linkage relationship allows carriers of the disease to be identified in informative families. We describe a large pedigree with Norrie disease. Segregation analysis was carried out with DXS7 and a second flanking marker, DXS255, both linked to NDP. In this way, three females at risk were identified who had a high probability of being carriers for Norrie disease.

  11. Whale phylogeny and rapid radiation events revealed using novel retroposed elements and their flanking sequences

    Directory of Open Access Journals (Sweden)

    Zhou Kaiya

    2011-10-01

    Full Text Available Abstract Background A diversity of hypotheses have been proposed based on both morphological and molecular data to reveal phylogenetic relationships within the order Cetacea (dolphins, porpoises, and whales, and great progress has been made in the past two decades. However, there is still some controversy concerning relationships among certain cetacean taxa such as river dolphins and delphinoid species, which needs to be further addressed with more markers in an effort to address unresolved portions of the phylogeny. Results An analysis of additional SINE insertions and SINE-flanking sequences supported the monophyly of the order Cetacea as well as Odontocete, Delphinoidea (Delphinidae + Phocoenidae + Mondontidae, and Delphinidae. A sister relationship between Delphinidae and Phocoenidae + Mondontidae was supported, and members of classical river dolphins and the genera Tursiops and Stenella were found to be paraphyletic. Estimates of divergence times revealed rapid divergences of basal Odontocete lineages in the Oligocene and Early Miocene, and a recent rapid diversification of Delphinidae in the Middle-Late Miocene and Pliocene within a narrow time frame. Conclusions Several novel SINEs were found to differentiate Delphinidae from the other two families (Monodontidae and Phocoenidae, whereas the sister grouping of the latter two families with exclusion of Delphinidae was further revealed using the SINE-flanking sequences. Interestingly, some anomalous PCR amplification patterns of SINE insertions were detected, which can be explained as the result of potential ancestral SINE polymorphisms and incomplete lineage sorting. Although a few loci were potentially anomalous, this study demonstrated that the SINE-based approach is a powerful tool in phylogenetic studies. Identifying additional SINE elements that resolve the relationships in the superfamily Delphinoidea and family Delphinidae will be important steps forward in completely resolving

  12. Whale phylogeny and rapid radiation events revealed using novel retroposed elements and their flanking sequences.

    Science.gov (United States)

    Chen, Zhuo; Xu, Shixia; Zhou, Kaiya; Yang, Guang

    2011-10-27

    A diversity of hypotheses have been proposed based on both morphological and molecular data to reveal phylogenetic relationships within the order Cetacea (dolphins, porpoises, and whales), and great progress has been made in the past two decades. However, there is still some controversy concerning relationships among certain cetacean taxa such as river dolphins and delphinoid species, which needs to be further addressed with more markers in an effort to address unresolved portions of the phylogeny. An analysis of additional SINE insertions and SINE-flanking sequences supported the monophyly of the order Cetacea as well as Odontocete, Delphinoidea (Delphinidae + Phocoenidae + Mondontidae), and Delphinidae. A sister relationship between Delphinidae and Phocoenidae + Mondontidae was supported, and members of classical river dolphins and the genera Tursiops and Stenella were found to be paraphyletic. Estimates of divergence times revealed rapid divergences of basal Odontocete lineages in the Oligocene and Early Miocene, and a recent rapid diversification of Delphinidae in the Middle-Late Miocene and Pliocene within a narrow time frame. Several novel SINEs were found to differentiate Delphinidae from the other two families (Monodontidae and Phocoenidae), whereas the sister grouping of the latter two families with exclusion of Delphinidae was further revealed using the SINE-flanking sequences. Interestingly, some anomalous PCR amplification patterns of SINE insertions were detected, which can be explained as the result of potential ancestral SINE polymorphisms and incomplete lineage sorting. Although a few loci were potentially anomalous, this study demonstrated that the SINE-based approach is a powerful tool in phylogenetic studies. Identifying additional SINE elements that resolve the relationships in the superfamily Delphinoidea and family Delphinidae will be important steps forward in completely resolving cetacean phylogenetic relationships in the future.

  13. Late Pleistocene flank collapse of Zempoala volcano (Central Mexico) and the role of fault reactivation

    Science.gov (United States)

    Arce, José Luis; Macías, Rodolfo; García Palomo, Armando; Capra, Lucia; Macías, José Luis; Layer, Paul; Rueda, Hernando

    2008-11-01

    Zempoala is an extinct Pleistocene (˜ 0.7-0.8 Ma) stratovolcano that together with La Corona volcano (˜ 0.9 Ma) forms the southern end of the Sierra de las Cruces volcanic range, Central Mexico. The volcano consists of andesitic and dacitic lava flows and domes, as well as pyroclastic and epiclastic sequences, and has had a complex history with several flank collapses. One of these collapses occurred during the late Pleistocene on the S-SE flank of the volcano and produced the Zempoala debris avalanche deposit. This collapse could have been triggered by the reactivation of two normal fault systems (E-W and NE-SW), although magmatic activity cannot be absolutely excluded. The debris avalanche traveled 60 km to the south, covers an area of 600 km 2 and has a total volume of 6 km 3, with a calculated Heim coefficient (H/L) of 0.03. Based on the textural characteristics of the deposit we recognized three zones: proximal, axial, and lateral distal zone. The proximal zone consists of debris avalanche blocks that develop a hummocky topography; the axial zone corresponds with the main debris avalanche deposit made of large clasts set in a sandy matrix, which transformed to a debris flow in the lateral distal portion. The deposit is heterolithologic in composition, with dacitic and andesitic fragments from the old edifice that decrease in volume as bulking of exotic clasts from the substratum increase. Several cities (Cuernavaca, Jojutla de Juárez, Alpuyeca) with associated industrial, agricultural, and tourism activities have been built on the deposit, which pose in evidence the possible impact in case of a new event with such characteristics, since the area is still tectonically active.

  14. Subseafloor seawater-basalt-microbe reactions: Continuous sampling of borehole fluids in a ridge flank environment

    Science.gov (United States)

    Wheat, C. Geoffrey; Jannasch, Hans W.; Fisher, Andrew T.; Becker, Keir; Sharkey, Jessica; Hulme, Samuel

    2010-07-01

    Integrated Ocean Drilling Program (IODP) Hole 1301A was drilled, cased, and instrumented with a long-term, subseafloor observatory (CORK) on the eastern flank of the Juan de Fuca Ridge in summer 2004. This borehole is located 1 km south of ODP Hole 1026B and 5 km north of Baby Bare outcrop. Hole 1301A penetrates 262 m of sediment and 108 m of the uppermost 3.5 Ma basaltic basement in an area of warm (64°C) hydrothermal circulation. The borehole was instrumented, and those instruments were recovered 4 years later. Here we report chemical data from two continuous fluid samplers (OsmoSamplers) and temperature recording tools that monitored changes in the state of borehole (formation) fluids. These changes document the effects of drilling, fluid overpressure and flow, seawater-basalt interactions, and microbial metababolic activity. Initially, bottom seawater flowed into the borehole through a leak between concentric CORK casing strings. Eventually, the direction of flow reversed, and warm, altered formation fluid flowed into the borehole and discharged at the seafloor. This reversal occurred during 1 week in September 2007, 3 years after drilling operations ceased. The composition of the formation fluid around Hole 1301A generally lies within bounds defined by springs on Baby Bare outcrop (to the south) and fluids that discharged from Hole 1026B (to the north); deviations likely result from reactions with drilling products. Simple conservative mixing of two end-member fluids reveals reactions occurring within the crust, including nitrate reduction presumably by denitrifying microbes. The observed changes in borehole fluid composition provide the foundation for a conceptual model of chemical and microbial change during recharge of a warm ridge-flank hydrothermal system. This model can be tested through future scientific ocean drilling experiments.

  15. Soil gases and SAR measurements reveal hidden faults on the sliding flank of Mt. Etna (Italy)

    Science.gov (United States)

    Bonforte, Alessandro; Federico, Cinzia; Giammanco, Salvatore; Guglielmino, Francesco; Liuzzo, Marco; Neri, Marco

    2013-02-01

    From October 2008 to November 2009, soil CO2, radon and structural field surveys were performed on Mt. Etna, in order to acquire insights into active tectonic structures in a densely populated sector of the south-eastern flank of the volcano, which is involved in the flank dynamics, as highlighted by satellite data (InSAR). The studied area extends about 150 km2, in a sector of the volcano where InSAR results detected several lineaments that were not well-defined from previous geological surveys. In order to validate and better constrain these features with ground data evidences, soil CO2 and soil radon measurements were performed along transects roughly orthogonal to the newly detected faults, with measurement points spaced about 100 m. In each transect, the highest CO2 values were found very close to the lineaments evidenced by InSAR observations. Anomalous soil CO2 and radon values were also measured at old eruptive fractures. In some portions of the investigated area soil gas anomalies were rather broad over transects, probably suggesting a complex structural framework consisting of several parallel volcano-tectonic structures, instead of a single one. Soil gas measurements proved particularly useful in areas at higher altitude on Mt. Etna (i.e. above 900 m asl), where InSAR results are not very informative/are fairly limited, and allowed recognizing the prolongation of some tectonic lineaments towards the summit of the volcano. At a lower altitude on the volcanic edifice, soil gas anomalies define the active structures indicated by InSAR results prominently, down to almost the coastline and through the northern periphery of the city of Catania. Coupling InSAR with soil gas prospecting methods has thus proved to be a powerful tool in detecting hidden active structures that do not show significant field evidences.

  16. Biophysical properties of regions flanking the bHLH-Zip motif in the p22 Max protein

    International Nuclear Information System (INIS)

    Pursglove, Sharon E.; Fladvad, Malin; Bellanda, Massimo; Moshref, Ahmad; Henriksson, Marie; Carey, Jannette; Sunnerhagen, Maria

    2004-01-01

    The Max protein is the central dimerization partner in the Myc-Max-Mad network of transcriptional regulators, and a founding structural member of the family of basic-helix-loop-helix (bHLH)-leucine zipper (Zip) proteins. Biologically important regions flanking its bHLH-Zip motif have been disordered or absent in crystal structures. The present study shows that these regions are resistant to proteolysis in both the presence and absence of DNA, and that Max dimers containing both flanking regions have significantly higher helix content as measured by circular dichroism than that predicted from the crystal structures. Nuclear magnetic resonance measurements in the absence of DNA also support the inferred structural order. Deletion of both flanking regions is required to achieve maximal DNA affinity as measured by EMSA. Thus, the previously observed functionalities of these Max regions in DNA binding, phosphorylation, and apoptosis are suggested to be linked to structural properties

  17. An experimental study of flank wear in the end milling of AISI 316 stainless steel with coated carbide inserts

    Science.gov (United States)

    Odedeyi, P. B.; Abou-El-Hossein, K.; Liman, M.

    2017-05-01

    Stainless steel 316 is a difficult-to-machine iron-based alloys that contain minimum of about 12% of chromium commonly used in marine and aerospace industry. This paper presents an experimental study of the tool wear propagation variations in the end milling of stainless steel 316 with coated carbide inserts. The milling tests were conducted at three different cutting speeds while feed rate and depth of cut were at (0.02, 0.06 and 01) mm/rev and (1, 2 and 3) mm, respectively. The cutting tool used was TiAlN-PVD-multi-layered coated carbides. The effects of cutting speed, cutting tool coating top layer and workpiece material were investigated on the tool life. The results showed that cutting speed significantly affected the machined flank wears values. With increasing cutting speed, the flank wear values decreased. The experimental results showed that significant flank wear was the major and predominant failure mode affecting the tool life.

  18. Lava-flow hazard on the SE flank of Mt. Etna (Southern Italy)

    Science.gov (United States)

    Crisci, G. M.; Iovine, G.; Di Gregorio, S.; Lupiano, V.

    2008-11-01

    A method for mapping lava-flow hazard on the SE flank of Mt. Etna (Sicily, Southern Italy) by applying the Cellular Automata model SCIARA -fv is described, together with employed techniques of calibration and validation through a parallel Genetic Algorithm. The study area is partly urbanised; it has repeatedly been affected by lava flows from flank eruptions in historical time, and shows evidence of a dominant SSE-trending fracture system. Moreover, a dormant deep-seated gravitational deformation, associated with a larger volcano-tectonic phenomenon, affects the whole south-eastern flank of the volcano. The Etnean 2001 Mt. Calcarazzi lava-flow event has been selected for model calibration, while validation has been performed by considering the 2002 Linguaglossa and the 1991-93 Valle del Bove events — suitable data for back analysis being available for these recent eruptions. Quantitative evaluation of the simulations, with respect to the real events, has been performed by means of a couple of fitness functions, which consider either the areas affected by the lava flows, or areas and eruption duration. Sensitivity analyses are in progress for thoroughly evaluating the role of parameters, topographic input data, and mesh geometry on model performance; though, preliminary results have already given encouraging responses on model robustness. In order to evaluate lava-flow hazard in the study area, a regular grid of n.340 possible vents, uniformly covering the study area and located at 500 m intervals, has been hypothesised. For each vent, a statistically-significant number of simulations has been planned, by adopting combinations of durations, lava volumes, and effusion-rate functions, selected by considering available volcanological data. Performed simulations have been stored in a GIS environment for successive analyses and map elaboration. Probabilities of activation, empirically based on past behaviour of the volcano, can be assigned to each vent of the grid, by

  19. Dynamics of gene expression with positive feedback to histone modifications at bivalent domains

    Science.gov (United States)

    Huang, Rongsheng; Lei, Jinzhi

    2018-03-01

    Experiments have shown that in embryonic stem cells, the promoters of many lineage-control genes contain “bivalent domains”, within which the nucleosomes possess both active (H3K4me3) and repressive (H3K27me3) marks. Such bivalent modifications play important roles in maintaining pluripotency in embryonic stem cells. Here, to investigate gene expression dynamics when there are regulations in bivalent histone modifications and random partition in cell divisions, we study how positive feedback to histone methylation/demethylation controls the transition dynamics of the histone modification patterns along with cell cycles. We constructed a computational model that includes dynamics of histone marks, three-stage chromatin state transitions, transcription and translation, feedbacks from protein product to enzymes to regulate the addition and removal of histone marks, and the inheritance of nucleosome state between cell cycles. The model reveals how dynamics of both nucleosome state transition and gene expression are dependent on the enzyme activities and feedback regulations. Results show that the combination of stochastic histone modification at each cell division and the deterministic feedback regulation work together to adjust the dynamics of chromatin state transition in stem cell regenerations.

  20. Chimeric polyomavirus-derived virus-like particles: the immunogenicity of an inserted peptide applied without adjuvant to mice depends on its insertion site and its flanking linker sequence

    OpenAIRE

    Lawatscheck, R.; Aleksaite, E.; Schenk, J.A.; Micheel, B.; Jandrig, B.; Holland, G.; Sasnauskas, K.; Gedvilaite, A.; Ulrich, R.G.

    2007-01-01

    We inserted the sequence of the carcinoembryonic antigen-derived T cell epitope CAP-1-6D (CEA) into different positions of the hamster polyomavirus major capsid protein VP1. Independently from additional flanking linkers, yeast-expressed VP1 proteins harboring the CEA insertion between VP1 amino acid residues 80 and 89 (site 1) or 288 and 295 (site 4) or simultaneously at both positions assembled to chimeric virus-like particles (VLPs). BALB/c mice immunized with adjuvant-free VLPs developed ...

  1. Landscape-scale drivers of glacial ecosystem change in the montane forests of the eastern Andean flank, Ecuador

    NARCIS (Netherlands)

    Loughlin, N.J.D.; Gosling, W.D.; Coe, A.L.; Gulliver, P.; Mothes, P.; Montoya, E.

    2018-01-01

    Understanding the impact of landscape-scale disturbance events during the last glacial period is vital in accurately reconstructing the ecosystem dynamics of montane environments. Here, a sedimentary succession from the tropical montane cloud forest of the eastern Andean flank of Ecuador provides

  2. Contrasting neogene denudation histories of different structural regions in the transantarctic mountains rift flank constrained by cosmogenic isotope measurements

    NARCIS (Netherlands)

    Wateren, F.M. van der; Dunai, T.J.; Balen, R.T. van; Klas, W.; Verbers, A.L.L.M.; Passchier, S.; Herpers, U.

    1999-01-01

    Separate regions within the Transantarctic Mountains, the uplifted flank of the West Antarctic rift system, appear to have distinct Neogene histories of glaciation and valley downcutting. Incision of deep glacial outlet valleys occurred at different times throughout central and northern Victoria

  3. Anatomy of the blood supply [by the circumflexa ilium profunda artery] to the flank of the sheep

    International Nuclear Information System (INIS)

    Zoltie, N.; Hynd, P.I.; Kuchel, T.

    1988-01-01

    The anatomy of the circumflexa ilium profunda artery supplying the flank of the sheep was investigated in 25 sheep. Two constant branches were identified by dissection and angiography, and the cutaneous areas they supply identified. The arterial system was used successfully in 2 separate experiments

  4. Changes in nucleosome repeat lengths precede replication in the early replicating metallothionein II gene region of cells synchronized in early S phase

    International Nuclear Information System (INIS)

    D'Anna, J.A.; Tobey, R.A.

    1989-01-01

    Previous investigations showed that inhibition of DNA synthesis by hydroxyurea, aphidicolin, or 5-fluorodeoxyuridine produced large changes in the composition and nucleosome repeat lengths of bulk chromatin. There the authors report results of investigations to determine whether the changes in nucleosome repeat lengths might be localized in the initiated replicons, as postulated. In most experiments, Chinese hamster (line CHO) cells were synchronized in G1, or they were synchronized in early S phase by allowing G1 cells to enter S phase in medium containing 1 mM hydroxyurea or 5 μg mL -1 aphidicolin, a procedure believed to produce an accumulation of initiated replicons that arise from normally early replicating DNA. Measurements of nucleosome repeat lengths of bulk chromatin, the early replicating unexpressed metallothionein II (MTII) gene region, and a later replicating repeated sequence indicate that the changes in repeat lengths occur preferentially in the early replicating MTII gene region as G1 cells enter and become synchronized in early S phase. During that time, the MTII gene region is not replicated nor is there any evidence for induction of MTII messenger RNA. Thus, the results are consistent with the hypothesis that changes in chromatin structure occur preferentially in the early replicating (presumably initiated) replicons at initiation or that changes in chromatin structure can precede replication during inhibition of DNA synthesis. The shortened repeat lengths that precede MTII replication are, potentially, reversible, because they become elongated when the synchronized early S-phase cells are released to resume cell cycle progression

  5. The Radical Flank Effect and Cross-occupational Collaboration for Technology Development during a Power Shift

    Science.gov (United States)

    Truelove, Emily; Kellogg, Katherine C.

    2016-01-01

    This 12-month ethnographic study of an early entrant into the U.S. car-sharing industry demonstrates that when an organization shifts its focus from developing radical new technology to incrementally improving this technology, the shift may spark an internal power struggle between the dominant engineering group and a challenger occupational group such as the marketing group. Analyzing 42 projects in two time periods that required collaboration between engineering and marketing during such a shift, we show how cross-occupational collaboration under these conditions can be facilitated by a radical flank threat, through which the bargaining power of moderates is strengthened by the presence of a more-radical group. In the face of a strong threat by radical members of a challenger occupational group, moderate members of the dominant engineering group may change their perceptions of their power to resist challengers’ demands and begin to distinguish between the goals of radical versus more-moderate challengers. To maintain as much power as possible and prevent the more-dramatic change in engineering occupational goals demanded by radical challengers, moderate engineers may build a coalition with moderate challengers and collaborate for incremental technology development. PMID:28424533

  6. A rhodanine flanked nonfullerene acceptor for solution-processed organic photovoltaics

    KAUST Repository

    Holliday, Sarah

    2015-01-21

    A novel small molecule, FBR, bearing 3-ethylrhodanine flanking groups was synthesized as a nonfullerene electron acceptor for solution-processed bulk heterojunction organic photovoltaics (OPV). A straightforward synthesis route was employed, offering the potential for large scale preparation of this material. Inverted OPV devices employing poly(3-hexylthiophene) (P3HT) as the donor polymer and FBR as the acceptor gave power conversion efficiencies (PCE) up to 4.1%. Transient and steady state optical spectroscopies indicated efficient, ultrafast charge generation and efficient photocurrent generation from both donor and acceptor. Ultrafast transient absorption spectroscopy was used to investigate polaron generation efficiency as well as recombination dynamics. It was determined that the P3HT:FBR blend is highly intermixed, leading to increased charge generation relative to comparative devices with P3HT:PC60BM, but also faster recombination due to a nonideal morphology in which, in contrast to P3HT:PC60BM devices, the acceptor does not aggregate enough to create appropriate percolation pathways that prevent fast nongeminate recombination. Despite this nonoptimal morphology the P3HT:FBR devices exhibit better performance than P3HT:PC60BM devices, used as control, demonstrating that this acceptor shows great promise for further optimization.

  7. Unusual presentation of cactus spines in the flank of an elderly man: a case report

    Directory of Open Access Journals (Sweden)

    Freeman Scott

    2010-05-01

    Full Text Available Abstract Introduction Splinters and spines of plant matter are common foreign bodies in skin wounds of the extremities, and often present embedded in the dermis or subcutaneous tissue. Vegetative foreign bodies are highly inflammatory and, if not completely removed, can cause infection, toxic reactions, or granuloma formation. Older patients are at increased risk for infection from untreated plant foreign bodies. The most common error in plant splinter and spine management is failure to detect their presence. Case presentation Here we report a case of cactus spines in an 84-year-old Caucasian man presenting on the right flank as multiple, red papules with spiny extensions. This presentation was unusual both in location and the spinous character of the lesions, and only after punch biopsy analysis was a diagnosis of cactus matter spines made. Conclusions Our patient presented with an unusual case of cactus spines that required histopathology for identification. Skin lesions with neglected foreign bodies are a common cause of malpractice claims. If not removed, foreign bodies of the skin, particularly in elderly individuals, can result in inflammatory and infectious sequela. This report underscores the importance of thoroughly evaluating penetrating skin lesions for the presence of foreign bodies, such as splinters and spines.

  8. Geologic map of the northeast flank of Mauna Loa volcano, Island of Hawai'i, Hawaii

    Science.gov (United States)

    Trusdell, Frank A.; Lockwood, John P.

    2017-05-01

    SummaryMauna Loa, the largest volcano on Earth, has erupted 33 times since written descriptions became available in 1832. Some eruptions were preceded by only brief seismic unrest, while others followed several months to a year of increased seismicity.The majority of the eruptions of Mauna Loa began in the summit area (>12,000-ft elevation; Lockwood and Lipman, 1987); yet the Northeast Rift Zone (NERZ) was the source of eight flank eruptions since 1843 (table 1). This zone extends from the 13,680-ft-high summit towards Hilo (population ~60,000), the second largest city in the State of Hawaii. Although most of the source vents are farther than 30 km away, the 1880 flow from one of the vents extends into Hilo, nearly reaching Hilo Bay. The city is built entirely on flows erupted from the NERZ, most older than that erupted in 1843.Once underway, Mauna Loa's eruptions can produce lava flows that reach the sea in less than 24 hours, severing roads and utilities in their path. For example, lava flows erupted from the Southwest Rift Zone (SWRZ) in 1950 advanced at an average rate of 9.3 km per hour, and all three lobes reached the ocean within approximately 24 hours (Finch and Macdonald, 1953). The flows near the eruptive vents must have traveled even faster.In terms of eruption frequency, pre-eruption warning, and rapid flow emplacement, Mauna Loa poses an enormous volcanic-hazard threat to the Island of Hawai‘i. By documenting past activity and by alerting the public and local government officials of our findings, we can anticipate the volcanic hazards and substantially mitigate the risks associated with an eruption of this massive edifice.From the geologic record, we can deduce several generalized facts about the geologic history of the NERZ. The middle to the uppermost section of the rift zone were more active in the past 4,000 years than the lower part, perhaps due to buttressing of the lower east rift zone by Mauna Kea and Kīlauea volcanoes. The historical flows

  9. The Radical Flank Effect and Cross-occupational Collaboration for Technology Development during a Power Shift.

    Science.gov (United States)

    Truelove, Emily; Kellogg, Katherine C

    2016-12-01

    This 12-month ethnographic study of an early entrant into the U.S. car-sharing industry demonstrates that when an organization shifts its focus from developing radical new technology to incrementally improving this technology, the shift may spark an internal power struggle between the dominant engineering group and a challenger occupational group such as the marketing group. Analyzing 42 projects in two time periods that required collaboration between engineering and marketing during such a shift, we show how cross-occupational collaboration under these conditions can be facilitated by a radical flank threat, through which the bargaining power of moderates is strengthened by the presence of a more-radical group. In the face of a strong threat by radical members of a challenger occupational group, moderate members of the dominant engineering group may change their perceptions of their power to resist challengers' demands and begin to distinguish between the goals of radical versus more-moderate challengers. To maintain as much power as possible and prevent the more-dramatic change in engineering occupational goals demanded by radical challengers, moderate engineers may build a coalition with moderate challengers and collaborate for incremental technology development.

  10. Spatial distribution of rolled up Kelvin-Helmholtz vortices at Earth's dayside and flank magnetopause

    Directory of Open Access Journals (Sweden)

    M. G. G. T. Taylor

    2012-06-01

    Full Text Available The Kelvin-Helmholtz Instability (KHI can drive waves at the magnetopause. These waves can grow to form rolled-up vortices and facilitate transfer of plasma into the magnetosphere. To investigate the persistence and frequency of such waves at the magnetopause we have carried out a survey of all Double Star 1 magnetopause crossings, using a combination of ion and magnetic field measurements. Using criteria originally used in a Geotail study made by Hasegawa et al. (2006 (forthwith referred to as H2006, 17 candidate events were identified from the entire TC-1 mission (covering ~623 orbits where the magnetopause was sampled, a majority of which were on the dayside of the terminator. The relationship between density and shear velocity was then investigated, to identify the predicted signature of a rolled up vortex from H2006 and all 17 events exhibited some level of rolled up behavior. The location of the events had a clear dawn-dusk asymmetry, with 12 (71% on the post noon, dusk flank suggesting preferential growth in this region.

  11. Soft sediment deformation structures in the Maastrichtian Ajali Formation Western Flank of Anambra Basin, Southern Nigeria

    Science.gov (United States)

    Olabode, Solomon Ojo

    2014-01-01

    Soft sediment deformation structures were recognized in the Maastrichtian shallow marine wave to tide influenced regressive sediments of Ajali Formation in the western flank of Anambra basin, southern Nigerian. The soft sediment deformation structures were in association with cross bedded sands, clay and silt and show different morphological types. Two main types recognised are plastic deformations represented by different types of recumbent folds and injection structure represented by clastic dykes. Other structures in association with the plastic deformation structures include distorted convolute lamination, subsidence lobes, pillars, cusps and sand balls. These structures are interpreted to have been formed by liquefaction and fluidization mechanisms. The driving forces inferred include gravitational instabilities and hydraulic processes. Facies analysis, detailed morphologic study of the soft sediment deformation structures and previous tectonic history of the basin indicate that the main trigger agent for deformation is earthquake shock. The soft sediment deformation structures recognised in the western part of Anambra basin provide a continuous record of the tectonic processes that acted on the regressive Ajali Formation during the Maastrichtian.

  12. Pre-analytical variables of circulating cell-free nucleosomes containing 5-methylcytosine DNA or histone modification H3K9Me3

    DEFF Research Database (Denmark)

    Rasmussen, Louise; Herzog, Marielle; Rømer, Eva

    2016-01-01

    Aim: To evaluate pre-analytical variables of circulating cell-free nucleosomes containing 5-methylcytosine DNA (5mC) or histone modification H3K9Me3 (H3K9Me3). Materials and methods: Six studies were designed to assess the possible influence of pre-analytical variables. Study 1: influence of stasis...... significantly lower levels of 5mC or H3K9Me3 compared to levels in healthy individuals. Conclusion: Levels of 5mC or H3K9Me3 appear stable in most pre-analytical settings if blood samples are stored at room temperature until centrifugation....

  13. Elements in the transcriptional regulatory region flanking herpes simplex virus type 1 oriS stimulate origin function.

    Science.gov (United States)

    Wong, S W; Schaffer, P A

    1991-05-01

    Like other DNA-containing viruses, the three origins of herpes simplex virus type 1 (HSV-1) DNA replication are flanked by sequences containing transcriptional regulatory elements. In a transient plasmid replication assay, deletion of sequences comprising the transcriptional regulatory elements of ICP4 and ICP22/47, which flank oriS, resulted in a greater than 80-fold decrease in origin function compared with a plasmid, pOS-822, which retains these sequences. In an effort to identify specific cis-acting elements responsible for this effect, we conducted systematic deletion analysis of the flanking region with plasmid pOS-822 and tested the resulting mutant plasmids for origin function. Stimulation by cis-acting elements was shown to be both distance and orientation dependent, as changes in either parameter resulted in a decrease in oriS function. Additional evidence for the stimulatory effect of flanking sequences on origin function was demonstrated by replacement of these sequences with the cytomegalovirus immediate-early promoter, resulting in nearly wild-type levels of oriS function. In competition experiments, cotransfection of cells with the test plasmid, pOS-822, and increasing molar concentrations of a competitor plasmid which contained the ICP4 and ICP22/47 transcriptional regulatory regions but lacked core origin sequences resulted in a significant reduction in the replication efficiency of pOS-822, demonstrating that factors which bind specifically to the oriS-flanking sequences are likely involved as auxiliary proteins in oriS function. Together, these studies demonstrate that trans-acting factors and the sites to which they bind play a critical role in the efficiency of HSV-1 DNA replication from oriS in transient-replication assays.

  14. Morphology and Doping Level of Electropolymerized Biselenophene-Flanked 3,4- Ethylenedioxythiophene Polymer: Effect of Solvents and Electrolytes

    International Nuclear Information System (INIS)

    Agrawal, Vikash; Shahjad; Bhardwaj, Dinesh; Bhargav, Ranoo; Sharma, Gauri Datt; Bhardwaj, Ramil Kumar; Patra, Asit; Chand, Suresh

    2016-01-01

    Highlights: • Biselenophene-flanked 3,4-ethylenedioxythiophene polymer films were obtained by electrochemical polymerization. • Supporting electrolyte has significant effect on the doping level, whereas electropolymerized solvent has a major effect on morphology of the polymer films. • Optoelectronic properties and morphology of the electropolymerized films were studied. • Density functional theory (DFT) calculation has been made for optoelectronic properties. - Abstract: Biselenophene-flanked 3,4-ethylenedioxythiophene (EDOT) based polymer films were obtained by electrochemical polymerization. The effects of polymerization conditions such as supporting electrolytes and solvents on doping level, optical property and morphology of the polymer films were systematically studied. Interestingly, we found that polymer prepared by using different supporting electrolytes (TBAPF 6 , TBABF 4 and TBAClO 4 ) has significant effects on the doping level of the polymer films, whereas electropolymerized solvents (acetonitrile and dichloromethane) has no such effects on doping level. The polymer films show reversible dedoping and doping behavior upon treatment with hydrazine hydrate and iodine respectively. Biselenophene-flanked EDOT polymer shows a band gap of about 1.6 eV which is comparable to poly(3,4- ethylenedioxythiophene) (PEDOT) and parent polyselenophene, whereas fine-tuning of HOMO and LUMO energy levels has been found. In contrast, we observed that electropolymerized solvent has a major effect on morphology of the polymer films, while supporting electrolyte has very minor effects on the morphology. The surface morphologies of the polymer films were characterized by scanning electron microscope (SEM) and atomic force microscope (AFM) techniques. We also present an efficient synthesis of bisthiophene-flanked bridged EDOT (ETTE), and biselenophene-flanked bridged EDOT (ESeSeE), and their electrochemical polymerization, characterizations and throughout comparison

  15. Modeling of Principal Flank Wear: An Empirical Approach Combining the Effect of Tool, Environment and Workpiece Hardness

    Science.gov (United States)

    Mia, Mozammel; Al Bashir, Mahmood; Dhar, Nikhil Ranjan

    2016-10-01

    Hard turning is increasingly employed in machining, lately, to replace time-consuming conventional turning followed by grinding process. An excessive amount of tool wear in hard turning is one of the main hurdles to be overcome. Many researchers have developed tool wear model, but most of them developed it for a particular work-tool-environment combination. No aggregate model is developed that can be used to predict the amount of principal flank wear for specific machining time. An empirical model of principal flank wear (VB) has been developed for the different hardness of workpiece (HRC40, HRC48 and HRC56) while turning by coated carbide insert with different configurations (SNMM and SNMG) under both dry and high pressure coolant conditions. Unlike other developed model, this model includes the use of dummy variables along with the base empirical equation to entail the effect of any changes in the input conditions on the response. The base empirical equation for principal flank wear is formulated adopting the Exponential Associate Function using the experimental results. The coefficient of dummy variable reflects the shifting of the response from one set of machining condition to another set of machining condition which is determined by simple linear regression. The independent cutting parameters (speed, rate, depth of cut) are kept constant while formulating and analyzing this model. The developed model is validated with different sets of machining responses in turning hardened medium carbon steel by coated carbide inserts. For any particular set, the model can be used to predict the amount of principal flank wear for specific machining time. Since the predicted results exhibit good resemblance with experimental data and the average percentage error is <10 %, this model can be used to predict the principal flank wear for stated conditions.

  16. Study of surface roughness and flank wear in hard turning of AISI 4140 steel with coated ceramic inserts

    Energy Technology Data Exchange (ETDEWEB)

    Das, Sudhansu Ranjan; Kuma, Amaresh [National Institute of Technology, Jamshedpur (India); Dhupal, Debabrata [Veer Surendra Sai University of Technology, Burla (India)

    2015-10-15

    This experimental investigation deals with dry hard turning of AISI 4140 steel using PVD-TiN coated Al{sub 2}O{sub 3}+TiCN mixed ceramic inserts. The combined effect of cutting parameters (cutting speed, feed and depth of cut) on performance characteristics such as surface roughness and flank wear is explored by Full factorial design (FFD) and analysis of variance (ANOVA). The results show that feed is the principal cutting parameter influencing surface roughness, followed by cutting speed. However, flank wear is affected by the cutting speed and interaction of feed-depth of cut, although depth of cut has not been found statistically significant, but flank wear is an increasing function of depth of cut. Observations are made on the machined surface, and worn tool by Scanning electron microscope (SEM) to establish the process. Abrasion was the major wear mechanism found during hard turning within the studied range. The effect of tool wear on surface roughness was also studied. The experimental data were analyzed to predict the optimal range of surface roughness and flank wear. Based on Response surface methodology (RSM), mathematical models were developed for surface roughness (Ra) and flank wear (VB) with 95% confidence level. Finally, under optimum cutting conditions (obtained by response optimization technique), tool life was evaluated to perform cost analysis for justifying the economic viability of coated ceramic inserts in hard turning. The estimated machining cost per part for TiN coated ceramic was found to be lower (Rs. 12.31) because of higher tool life (51 min), which results in the reduction of downtime and increase in savings.

  17. Study of surface roughness and flank wear in hard turning of AISI 4140 steel with coated ceramic inserts

    International Nuclear Information System (INIS)

    Das, Sudhansu Ranjan; Kuma, Amaresh; Dhupal, Debabrata

    2015-01-01

    This experimental investigation deals with dry hard turning of AISI 4140 steel using PVD-TiN coated Al_2O_3+TiCN mixed ceramic inserts. The combined effect of cutting parameters (cutting speed, feed and depth of cut) on performance characteristics such as surface roughness and flank wear is explored by Full factorial design (FFD) and analysis of variance (ANOVA). The results show that feed is the principal cutting parameter influencing surface roughness, followed by cutting speed. However, flank wear is affected by the cutting speed and interaction of feed-depth of cut, although depth of cut has not been found statistically significant, but flank wear is an increasing function of depth of cut. Observations are made on the machined surface, and worn tool by Scanning electron microscope (SEM) to establish the process. Abrasion was the major wear mechanism found during hard turning within the studied range. The effect of tool wear on surface roughness was also studied. The experimental data were analyzed to predict the optimal range of surface roughness and flank wear. Based on Response surface methodology (RSM), mathematical models were developed for surface roughness (Ra) and flank wear (VB) with 95% confidence level. Finally, under optimum cutting conditions (obtained by response optimization technique), tool life was evaluated to perform cost analysis for justifying the economic viability of coated ceramic inserts in hard turning. The estimated machining cost per part for TiN coated ceramic was found to be lower (Rs. 12.31) because of higher tool life (51 min), which results in the reduction of downtime and increase in savings.

  18. Analysis of gene order data supports vertical inheritance of the leukotoxin operon and genome rearrangements in the 5' flanking region in genus Mannheimia

    DEFF Research Database (Denmark)

    Larsen, Jesper; Kuhnert, Peter; Frey, Joachim

    2007-01-01

    subclades, thus reaffirming the hypothesis of vertical inheritance of the leukotoxin operon. The presence of individual 5' flanking regions in M. haemolytica + M. glucosida and M. granulomatis reflects later genome rearrangements within each subclade. The evolution of the novel 5' flanking region in M...

  19. Cost analysis of different protocols for imaging a patient with acute flank pain

    International Nuclear Information System (INIS)

    Grisi, G.; Stacul, F.; Cuttin, R.; Rimondini, A.; Meduri, S.; Dalla Palma, L.

    2000-01-01

    The aim of this study was to analyse the costs of different diagnostic approaches to patients with acute flank pain. Four different diagnostic approaches were considered: (a) spiral CT without contrast medium (CM); (b) plain film, ultrasonography (US) and intravenous urography (IVU) - the latter procedure is used in our department in cases still unsolved following the former investigations (28 % in our experience); (c) plain film, US and spiral CT without CM (as an alternative to IVU in 28 % of cases); and (d) IVU. The cost of each procedure in a university hospital was calculated, following analysis of the differential costs of each investigation (equipment, depreciation and maintenance costs, related materials and services, radiologists, radiographers, nurses) and their common costs (auxiliary personnel and indirect internal costs). Finally, we calculated the full cost of each procedure and applied it to the different diagnostic approaches. The full cost of each approach was: (a) spiral CT without CM = 74 Euro; (b) plain film, US and IVU (28 %) = 66.89 Euro; (c) plain film, US and spiral CT without CM (28 %) = 64.93 Euro; (d) IVU = 80.90 Euro. Intravenous urography alone or in unsolved cases is not to be considered because it provides higher costs and worse diagnostic results, whereas X-ray dose to patient is almost equal between IVU and spiral CT. Spiral CT integrated to plain film and US in unsolved cases could be preferred because of lower cost and dose to patient, though reaching a diagnostic conclusion may take longer than an immediate spiral CT. (orig.)

  20. Seismic Anisotropy Beneath the Eastern Flank of the Rio Grande Rift

    Science.gov (United States)

    Benton, N. W.; Pulliam, J.

    2015-12-01

    Shear wave splitting was measured across the eastern flank of the Rio Grande Rift (RGR) to investigate mechanisms of upper mantle anisotropy. Earthquakes recorded at epicentral distances of 90°-130° from EarthScope Transportable Array (TA) and SIEDCAR (SC) broadband seismic stations were examined comprehensively, via the Matlab program "Splitlab", to determine whether SKS and SKKS phases indicated anisotropic properties. Splitlab allows waveforms to be rotated, filtered, and windowed interactively and splitting measurements are made on a user-specified waveform segment via three independent methods simultaneously. To improve signal-to-noise and improve reliability, we stacked the error surfaces that resulted from grid searches in the measurements for each station location. Fast polarization directions near the Rio Grande Rift tend to be sub-parallel to the RGR but then change to angles that are consistent with North America's average plate motion, to the east. The surface erosional depression of the Pecos Valley coincides with fast polarization directions that are aligned in a more northerly direction than their neighbors, whereas the topographic high to the east coincides with an easterly change of the fast axis.The area above a mantle high velocity anomaly discovered separately via seismic tomography which may indicate thickened lithosphere, corresponds to unusually large delay times and fast polarization directions that are more closely aligned to a north-south orientation. The area of southeastern New Mexico that falls between the mantle fast anomaly and the Great Plains craton displays dramatically smaller delay times, as well as changes in fast axis directions toward the northeast. Changes in fast axis directions may indicate flow around the mantle anomaly; small delay times could indicate vertical or attenuated flow.

  1. Human terminal deoxyribonucleotidyltransferase: molecular cloning and structural analysis of the gene and 5' flanking region

    International Nuclear Information System (INIS)

    Riley, L.K.; Morrow, J.K.; Danton, M.J.; Coleman, M.S.

    1988-01-01

    Human terminal deoxyribonucleotidyltransferase cDNA contains an open reading frame of 1530 base pairs (bp) corresponding to a protein containing 510 amino acids. The encoded protein is a template-independent DNA polymerase found only in a restricted population of normal and malignant prelymphocytes. To begin to investigate the genetic elements responsible for the tissue-specific expression of terminal deoxyribonucleotidyltransferase, genomic clones, containing the entire human gene were isolated and characterized. Initially, cDNA clones were isolated from a library generated from the human lymphoblastoid cell line, MOLT-4R. A cDNA clone containing the entire coding region of the protein was used to isolate a series of overlapping clones from two human genomic libraries. The gene comprises 11 exons and 10 introns and spans 49.4 kilobases. The 5' flanking region (709 bp) including exon 1 was sequenced. Several putative transcription initiation sites were mapped. Within 500 nucleotides of the translation start site, a series of promoter elements was detected. TATA and CAAT sequences, respectively, were found to start at nucleotides -185 and -204, -328 and -370, and -465 and -505. Start sites were found for a cyclic AMP-dependent promoter analog at nucleotide -121, an eight-base sequence corresponding to the IgG promoter enhancer (cd) at nucleotide -455, and an analog of the IgG promoter (pd) at nucleotide -159. These findings suggest that transcripts coding for terminal deoxyribonucleotidyltransferase may be variable in length and that transcription may be influenced by a variety of genetic elements

  2. Integrated geophysical and hydrothermal models of flank degassing and fluid flow at Masaya Volcano, Nicaragua

    Science.gov (United States)

    Sanford, Ward E.; Pearson, S.C.P.; Kiyosugi, K.; Lehto, H.L.; Saballos, J.A.; Connor, C.B.

    2012-01-01

    We investigate geologic controls on circulation in the shallow hydrothermal system of Masaya volcano, Nicaragua, and their relationship to surface diffuse degassing. On a local scale (~250 m), relatively impermeable normal faults dipping at ~60° control the flowpath of water vapor and other gases in the vadose zone. These shallow normal faults are identified by modeling of a NE-SW trending magnetic anomaly of up to 2300 nT that corresponds to a topographic offset. Elevated SP and CO2 to the NW of the faults and an absence of CO2 to the SE suggest that these faults are barriers to flow. TOUGH2 numerical models of fluid circulation show enhanced flow through the footwalls of the faults, and corresponding increased mass flow and temperature at the surface (diffuse degassing zones). On a larger scale, TOUGH2 modeling suggests that groundwater convection may be occurring in a 3-4 km radial fracture zone transecting the entire flank of the volcano. Hot water rising uniformly into the base of the model at 1 x 10-5 kg/m2s results in convection that focuses heat and fluid and can explain the three distinct diffuse degassing zones distributed along the fracture. Our data and models suggest that the unusually active surface degassing zones at Masaya volcano can result purely from uniform heat and fluid flux at depth that is complicated by groundwater convection and permeability variations in the upper few km. Therefore isolating the effects of subsurface geology is vital when trying to interpret diffuse degassing in light of volcanic activity.

  3. A porous flow model of flank eruptions on Mt. Etna: second-order perturbation theory

    Directory of Open Access Journals (Sweden)

    N. Cenni

    1997-06-01

    Full Text Available A porous flow model for magma migration from a deep source within a volcanic edifice is developed. The model is based on the assumption that an isotropic and homogeneous system of fractures allows magma migration from one localized feeding dyke up to the surface of the volcano. The maximum level that magma can reach within the volcano (i.e., the «free surface» of magma, where fluid pressure equals the atmospheric pressure is reproduced through a second-order perturbation approach to the non-linear equations governing the migration of incompressible fluids through a porous medium. The perturbation parameter is found to depend on the ratio of the volumic discharge rate at the source (m3/s divided by the product of the hydraulic conductivity of the medium (m1/s times the square of the source depth. The second-order corrections for the free surface of Mt. Etna are found to be small but not negligible; from the comparison between first-order and second-order free surfaces it appears that the former is higher near the summit, slightly lower at intermediate altitudes and slightly higher far away from the axis of the volcano. Flank eruptions in the southern sector are found to be located in regions where the topography is actually lower than the theoretical free surface of magma. In this sector, modulations in the eruption site density correlate well with even minor differences between free surface and topography. In the northern and western sectors similar good fits are found, while the NE rift and the eastern sector seem to require mechanisms or structures respectively favouring and inhibiting magma migration.

  4. Mapping of the quasi-periodic oscillations at the flank magnetopause into the ionosphere

    Directory of Open Access Journals (Sweden)

    E. R. Dougal

    2013-11-01

    Full Text Available We have estimated the ionospheric location, area, and travel time of quasi-periodic oscillations originating from the magnetospheric flanks. This was accomplished by utilizing global and local MHD models and Tsyganenko semi-empirical magnetic field model on multiple published and four new cases believed to be caused by the Kelvin–Helmholtz Instability. Finally, we used auroral, magnetometer, and radar instruments to observe the ionospheric signatures. The ionospheric magnetic latitude determined using global MHD and Tsyganenko models ranged from 58.3–80.2 degrees in the Northern Hemisphere and −59.6 degrees to −83.4 degrees in the Southern Hemisphere. The ionospheric magnetic local time ranged between 5.0–13.8 h in the Northern Hemisphere and 1.3–11.9 h in the Southern Hemisphere. Typical Alfvén wave travel time from spacecraft location to the closest ionosphere ranged between 0.6–3.6 min. The projected ionospheric size calculated at an altitude of 100 km ranged from 47–606 km, the same order of magnitude as previously determined ionospheric signature sizes. Stationary and traveling convection vortices were observed in SuperDARN radar data in both hemispheres. The vortices were between 1000–1800 km in size. Some events were located within the ionospheric footprint ranges. Pc5 magnetic oscillations were observed in SuperMAG magnetometer data in both hemispheres. The oscillations had periods between 4–10 min with amplitudes of 3–25 nT. They were located within the ionospheric footprint ranges. Some ground magnetometer data power spectral density peaked at frequencies within one tenth of a mHz of the peaks found in the corresponding Cluster data. These magnetometer observations were consistent with previously published results.

  5. DDC and COBL, flanking the imprinted GRB10 gene on 7p12, are biallelically expressed.

    Science.gov (United States)

    Hitchins, Megan P; Bentley, Louise; Monk, David; Beechey, Colin; Peters, Jo; Kelsey, Gavin; Ishino, Fumitoshi; Preece, Michael A; Stanier, Philip; Moore, Gudrun E

    2002-12-01

    Maternal duplication of human 7p11.2-p13 has been associated with Silver-Russell syndrome (SRS) in two familial cases. GRB10 is the only imprinted gene identified within this region to date. GRB10 demonstrates an intricate tissue- and isoform-specific imprinting profile in humans, with paternal expression in fetal brain and maternal expression of one isoform in skeletal muscle. The mouse homolog is maternally transcribed. The GRB10 protein is a potent growth inhibitor and represents a candidate for SRS, which is characterized by pre- and postnatal growth retardation and a spectrum of additional dysmorphic features. Since imprinted genes tend to be grouped in clusters, we investigated the imprinting status of the dopa-decarboxylase gene (DDC) and the Cordon-bleu gene (COBL) which flank GRB10 within the 7p11.2-p13 SRS duplicated region. Although both genes were found to replicate asynchronously, suggestive of imprinting, SNP expression analyses showed that neither gene was imprinted in multiple human fetal tissues. The mouse homologues, Ddc and Cobl, which map to the homologous imprinted region on proximal Chr 11, were also biallelically expressed in mice with uniparental maternal or paternal inheritance of this region. With the intent of using mouse Grb10 as an imprinted control, biallelic expression was consistently observed in fetal, postnatal, and adult brain of these mice, in contrast to the maternal-specific transcription previously demonstrated in brain in inter-specific F1 progeny. This may be a further example of over-expression of maternally derived transcripts in inter-specific mouse crosses. GRB10 remains the only imprinted gene identified within 7p11.2-p13.

  6. Herpes simplex virus type 1 tegument protein VP22 interacts with TAF-I proteins and inhibits nucleosome assembly but not regulation of histone acetylation by INHAT.

    Science.gov (United States)

    van Leeuwen, Hans; Okuwaki, Mitsuru; Hong, Rui; Chakravarti, Debabrata; Nagata, Kyosuke; O'Hare, Peter

    2003-09-01

    Affinity chromatography was used to identify cellular proteins that interact with the herpes simplex virus (HSV) tegument protein VP22. Among a small set of proteins that bind specifically to VP22, we identified TAF-I (template-activating factor I), a chromatin remodelling protein and close homologue of the histone chaperone protein NAP-1. TAF-I has been shown previously to promote more ordered transfer of histones to naked DNA through a direct interaction with histones. TAF-I, as a subunit of the INHAT (inhibitor of acetyltransferases) protein complex, also binds to histones and masks them from being substrates for the acetyltransferases p300 and PCAF. Using in vitro assays for TAF-I activity in chromatin assembly, we show that VP22 inhibits nucleosome deposition on DNA by binding to TAF-I. We also observed that VP22 binds non-specifically to DNA, an activity that is abolished by TAF-I. However, the presence of VP22 does not affect the property of INHAT in inhibiting the histone acetyltransferase activity of p300 or PCAF in vitro. We speculate that this interaction could be relevant to HSV DNA organization early in infection, for example, by interfering with nucleosomal deposition on the genome. Consistent with this possibility was the observation that overexpression of TAF-I in transfected cells interferes with the progression of HSV-1 infection.

  7. Modulations of DNA Contacts by Linker Histones and Post-translational Modifications Determine the Mobility and Modifiability of Nucleosomal H3 Tails.

    Science.gov (United States)

    Stützer, Alexandra; Liokatis, Stamatios; Kiesel, Anja; Schwarzer, Dirk; Sprangers, Remco; Söding, Johannes; Selenko, Philipp; Fischle, Wolfgang

    2016-01-21

    Post-translational histone modifications and linker histone incorporation regulate chromatin structure and genome activity. How these systems interface on a molecular level is unclear. Using biochemistry and NMR spectroscopy, we deduced mechanistic insights into the modification behavior of N-terminal histone H3 tails in different nucleosomal contexts. We find that linker histones generally inhibit modifications of different H3 sites and reduce H3 tail dynamics in nucleosomes. These effects are caused by modulations of electrostatic interactions of H3 tails with linker DNA and largely depend on the C-terminal domains of linker histones. In agreement, linker histone occupancy and H3 tail modifications segregate on a genome-wide level. Charge-modulating modifications such as phosphorylation and acetylation weaken transient H3 tail-linker DNA interactions, increase H3 tail dynamics, and, concomitantly, enhance general modifiability. We propose that alterations of H3 tail-linker DNA interactions by linker histones and charge-modulating modifications execute basal control mechanisms of chromatin function. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. AMPLITUDES OF DISJUNCTIVE DISLOCATIONS IN THE KNIPOVICH RIDGE FLANKS (NORTHERN ATLANTIC AS AN INDICATOR OF MODERN REGIONAL GEODYNAMICS

    Directory of Open Access Journals (Sweden)

    S. Yu. Sokolov

    2017-01-01

    Full Text Available This article presents the first map showing the vertical amplitudes of modern disjunctive dislocations inNorthern Atlantic, based on the estimated phase shifts of reflected waves recorded by high-frequency seismic acoustic surveys. The amplitude distribution pattern is mosaic with alternating areas of compression and extension in the flanks of the Knipovich rift system. The modern structure of the Knipovich Ridge, including two strike-slip faults, represents a local rift in the pull-apart setting. The asymmetry of stresses and the presence of compression in the ridge flanks is evidenced by the distribution of the focal mechanisms of strong earthquakes related to reverse faults. In the southeastern Knipovich Ridge, tectonic activity is marked by the asymmetric pattern of the epicenters of small earthquakes.

  9. Sonographic Appearance of Abdominal Wall at the Left Flank of Laparotomy Incision Site in Ettawah Grade Does

    Directory of Open Access Journals (Sweden)

    M. F. Ulum

    2014-12-01

    Full Text Available The aim of this study was to describe the sonographic appearance of abdominal wall at the left flank of laparotomy incision site in 11 mated Ettawah grade does. Brightness-mode ultrasound examination by using transducer with frequency of 5.0-6.0 MHz was conducted to grouping the does based on their pregnancy statuses. The incision site of the abdominal wall at left flank laparotomy was transcutaneous-scanned as long as 8 cm vertically. The sonographic appearance of the laparotomy wall thickness showed that in all groups of does were similar and not different statistically. The thickness of oblique external and oblique internal abdominal muscles increased in the pregnant does as compared to non-pregnant does (P<0.05.

  10. Preliminary assessment of the state of CO2 soil degassing on the flanks of Gede volcano (West Java, Indonesia)

    Science.gov (United States)

    Kunrat, S. L.; Schwandner, F. M.

    2013-12-01

    Gede Volcano (West Java) is part of an andesitic stratovolcano complex consisting of Pangrango in the north-west and Gede in the south-east. The last recorded eruptive activity was a phreatic subvolcanian ash eruption in 1957. Current activity is characterized by episodic swarms at 2-4 km depth, and low-temperature (~160°C) crater degassing in two distinct summit crater fumarolic areas. Hot springs occur in the saddle between the Gede and Pangrango edifice, as well as on the NE flank base. The most recent eruptive events produced pyroclastic material, their flow deposits concentrate toward the NE. A collaborative effort between the Center for Volcanology and Geological Hazard Mitigation (CVGHM), Geological Agency and the Earth Observatory of Singapore (EOS) is since 2010 aimed at upgrading the geophysical and geochemical monitoring network at Gede Volcano. To support the monitoring instrumentation upgrades under way, surveys of soil CO2 degassing have been performed on the flanks of Gede, in circular and radial traverses.The goal was to establish a spatial distribution of flank CO2 fluxes, and to allow smart siting for continuous gas monitoring stations. Crater fluxes were not surveyed, as its low-temperature hydrothermal system is likely prone to large hydraulic changes in this tropical environment, resulting in variable permeability effects that might mask signals from deeper reservoir or conduit degassing. The high precipitation intensity in the mountains of tropical Java pose challenges to this method, since soil gas permeability is largely controlled by soil moisture content. Simultaneous soil moisture measurements were undertaken. The soil CO2 surveys were carried out using a LI-8100A campaign flux chamber instrument (LICOR Biosciences, Lincoln, Nebraska). This instrument has a very precise and highly stable sensor and an atmospheric pressure equilibrator, making it highly sensitive to low fluxes. It is the far superior choice for higher precision low

  11. Imaging modalities and therapy options in patients with acute flank pain; Bildgebungsmodalitaeten und Therapieoptionen bei Patienten mit akutem Flankenschmerz

    Energy Technology Data Exchange (ETDEWEB)

    Grosse, A.; Grosse, C. [Universitaet Bern, Bern (Switzerland)

    2014-07-15

    The objective of this article is the description of imaging techniques for the evaluation of patients with acute flank pain and suspicion of urolithiasis and the impact of these techniques in the therapy management of patients with calculi. (orig.) [German] Ziel der Arbeit ist die Eroerterung der bildgebenden Verfahren zur Abklaerung von Patienten mit akutem Flankenschmerz und Verdacht auf Urolithiasis und die Rolle dieser Verfahren im Therapiemanagement von Steinpatienten. (orig.)

  12. A new mathematical model of the surface degradation causing wear on the cutting tool`s flank land

    OpenAIRE

    Pаlmai, Z.

    2011-01-01

    Having reviewed the extensive literature on the wear of the cutting tool, we chose the theoretical description of flank wear as the subject matter of this paper. Based on the optical electron-optical and morphological studies of the physical characteristics of wear processes we came to the conclusion that the cutting distance need not only be taken into consideration in abrasive, adhesive processes but also in thermally activated diffusion, oxidation processes. Consequently, we propose the ap...

  13. Compartmentalization of the Coso East Flank geothermal field imaged by 3-D full-tensor MT inversion

    Science.gov (United States)

    Lindsey, Nathaniel J.; Kaven, Joern; Davatzes, Nicholas C.; Newman, Gregory A.

    2017-01-01

    Previous magnetotelluric (MT) studies of the high-temperature Coso geothermal system in California identified a subvertical feature of low resistivity (2–5 Ohm m) and appreciable lateral extent (>1 km) in the producing zone of the East Flank field. However, these models could not reproduce gross 3-D effects in the recorded data. We perform 3-D full-tensor inversion and retrieve a resistivity model that out-performs previous 2-D and 3-D off-diagonal models in terms of its fit to the complete 3-D MT data set as well as the degree of modelling bias. Inclusion of secondary Zxx and Zyy data components leads to a robust east-dip (60†) to the previously identified conductive East Flank reservoir feature, which correlates strongly with recently mapped surface faults, downhole well temperatures, 3-D seismic reflection data, and local microseismicity. We perform synthetic forward modelling to test the best-fit dip of this conductor using the response at a nearby MT station. We interpret the dipping conductor as a fractured and fluidized compartment, which is structurally controlled by an unmapped blind East Flank fault zone.

  14. Flanking sequence determination and event-specific detection of genetically modified wheat B73-6-1.

    Science.gov (United States)

    Xu, Junyi; Cao, Jijuan; Cao, Dongmei; Zhao, Tongtong; Huang, Xin; Zhang, Piqiao; Luan, Fengxia

    2013-05-01

    In order to establish a specific identification method for genetically modified (GM) wheat, exogenous insert DNA and flanking sequence between exogenous fragment and recombinant chromosome of GM wheat B73-6-1 were successfully acquired by means of conventional polymerase chain reaction (PCR) and thermal asymmetric interlaced (TAIL)-PCR strategies. Newly acquired exogenous fragment covered the full-length sequence of transformed genes such as transformed plasmid and corresponding functional genes including marker uidA, herbicide-resistant bar, ubiquitin promoter, and high-molecular-weight gluten subunit. The flanking sequence between insert DNA revealed high similarity with Triticum turgidum A gene (GenBank: AY494981.1). A specific PCR detection method for GM wheat B73-6-1 was established on the basis of primers designed according to the flanking sequence. This specific PCR method was validated by GM wheat, GM corn, GM soybean, GM rice, and non-GM wheat. The specifically amplified target band was observed only in GM wheat B73-6-1. This method is of high specificity, high reproducibility, rapid identification, and excellent accuracy for the identification of GM wheat B73-6-1.

  15. Heat flow, morphology, pore fluids and hydrothermal circulation in a typical Mid-Atlantic Ridge flank near Oceanographer Fracture Zone

    Science.gov (United States)

    Le Gal, V.; Lucazeau, F.; Cannat, M.; Poort, J.; Monnin, C.; Battani, A.; Fontaine, F.; Goutorbe, B.; Rolandone, F.; Poitou, C.; Blanc-Valleron, M.-M.; Piedade, A.; Hipólito, A.

    2018-01-01

    Hydrothermal circulation affects heat and mass transfers in the oceanic lithosphere, not only at the ridge axis but also on their flanks, where the magnitude of this process has been related to sediment blanket and seamounts density. This was documented in several areas of the Pacific Ocean by heat flow measurements and pore water analysis. However, as the morphology of Atlantic and Indian ridge flanks is generally rougher than in the Pacific, these regions of slow and ultra-slow accretion may be affected by hydrothermal processes of different regimes. We carried out a survey of two regions on the eastern and western flanks of the Mid-Atlantic Ridge between Oceanographer and Hayes fracture zones. Two hundred and eight new heat flow measurements were obtained along six seismic profiles, on 5 to 14 Ma old seafloor. Thirty sediment cores (from which porewaters have been extracted) have been collected with a Kullenberg corer equipped with thermistors thus allowing simultaneous heat flow measurement. Most heat flow values are lower than those predicted by purely conductive cooling models, with some local variations and exceptions: heat flow values on the eastern flank of the study area are more variable than on the western flank, where they tend to increase westward as the sedimentary cover in the basins becomes thicker and more continuous. Heat flow is also higher, on average, on the northern sides of both the western and eastern field regions and includes values close to conductive predictions near the Oceanographer Fracture Zone. All the sediment porewaters have a chemical composition similar to that of bottom seawater (no anomaly linked to fluid circulation has been detected). Heat flow values and pore fluid compositions are consistent with fluid circulation in volcanic rocks below the sediment. The short distances between seamounts and short fluid pathways explain that fluids flowing in the basaltic aquifer below the sediment have remained cool and unaltered

  16. Remote Sensing and Geodetic Measurements for Volcanic Slope Monitoring: Surface Variations Measured at Northern Flank of La Fossa Cone (Vulcano Island, Italy

    Directory of Open Access Journals (Sweden)

    Alessandro Bonforte

    2013-05-01

    Full Text Available Results of recent monitoring activities on potentially unstable areas of the NW volcano flank of La Fossa cone (Vulcano Island, Italy are shown here. They are obtained by integration of data by aerial photogrammetry, terrestrial laser scanning (TLS and GPS taken in the 1996–2011 time span. A comparison between multi-temporal models built from remote sensing data (photogrammetry and TLS highlights areas characterized by ~7–10 cm/y positive differences (i.e., elevation increase in the upper crown of the slope. The GPS measurements confirm these results. Areas characterized by negative differences, related to both mass collapses or small surface lowering, also exist. The higher differences, positive and negative, are always observed in zones affected by higher fumarolic activity. In the 2010–2012 time span, ground motions in the northern part of the crater rim, immediately above the upper part of observed area, are also observed. The results show different trends for both vertical and horizontal displacements of points distributed along the rim, with a magnitude of some centimeters, thus revealing a complex kinematics. A slope stability analysis shows that the safety factors estimated from these data do not indicate evidence of possible imminent failures. Nevertheless, new time series are needed to detect possible changes with the time of the stability conditions, and the monitoring has to go on.

  17. Crustal structure along the west flank of the Cascades, western Washington

    Science.gov (United States)

    Miller, K.C.; Keller, Gordon R.; Gridley, J.M.; Luetgert, J.H.; Mooney, W.D.; Thybo, H.

    1997-01-01

    Knowledge of the crustal structure of the Washington Cascades and adjacent Puget Lowland is important to both earthquake hazards studies and geologic studies of the evolution of this tectonically active region. We present a model for crustal velocity structure derived from analysis of seismic refraction/wide-angle reflection data collected in 1991 in western Washington. The 280-km-long north-south transect skirts the west flank of the Cascades as it crosses three tectonic provinces including the Northwest Cascades Thrust System (NWCS), the Puget Lowland, and the volcanic arc of the southern Cascades. Within the NWCS, upper crustal velocities range from 4.2 to 5.7 km s-1 and are consistent with the presence of a diverse suite of Mesozoic and Paleozoic metasediments and metavolcanics. In the upper 2-3 km of the Puget Lowland velocities drop to 1.7-3.5 km s-1 and reflect the occurrence of Oligocene to recent sediments within the basin. In the southern Washington Cascades, upper crustal velocities range from 4.0 to 5.5 km s-1 and are consistent with a large volume of Tertiary sediments and volcanics. A sharp change in velocity gradient at 5-10 km marks the division between the upper and middle crust. From approximately 10 to 35 km depth the velocity field is characterized by a velocity increase from ???6.0 to 7.2 km s-1. These high velocities do not support the presence of marine sedimentary rocks at depths of 10-20 km beneath the Cascades as previously proposed on the basis of magnetotelluric data. Crustal thickness ranges from 42 to 47 km along the profile. The lowermost crust consists of a 2 to 8-km-thick transitional layer with velocities of 7.3-7.4 km s-1. The upper mantle velocity appears to be an unusually low 7.6-7.8 km s-1. When compared to velocity models from other regions, this model most closely resembles those found in active continental arcs. Distinct seismicity patterns can be associated with individual tectonic provinces along the seismic transect. In

  18. Soil salinity data from Bayou Dupont and flanking marshes, New Orleans, LA, 2015-09-16 to 2016-03-30 (NCEI Accession 0151633)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The project restored both structural and habitat functions of Bayou Dupont and flanking marshes. The project created and nourished marsh and restored a ridge on the...

  19. Soil salinity data from Grand Liard Bayou and flanking marshes, New Orleans, LA, 2015-12-01 to 2016-03-30 (NCEI Accession 0151634)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The project restored both structural and habitat functions of Grand Liard Bayou and flanking marshes. The project created and nourished marsh and restored a ridge on...

  20. Development of a 3D numerical model to evaluate the Stromboli NW flank instability in relation to magma intrusion

    Science.gov (United States)

    Apuani, T.; Merri, A.

    2009-04-01

    by means of the National Institute for Geophysics and Volcanology (INGV)-National Civil Protection Department (DPC), monitoring system. The results are expressed in terms of deformations and shear strain increments. The much unstable portion of the Sciara depression is evidenced by the highest value of the shear strain increments and is located on its upper right portion. The strain distribution is coherent with the ground motion recorded by the GB-InSAR monitoring system installed by the University of Florence thanks to the INGV-DPC 2004-2006 research program. Superficial displacements of metric amount are developed in this sector and indicate local instability, but are not sufficient to expect deep seated collapse of the volcano's flanks. A mechanism for sub horizontal sill intrusion starting from a vertical dike was proposed, and modelled, to explain the formation of the eruptive vent appeared on the Sciara slope at an altitude of about 400 meters a.s.l.. The results indicate an highly stressed and disturbed band extended transversally to the Sciara at the same elevation; furthermore the maximum value of the shear strain increments is located in correspondence with the actual position of the eruptive vents. The obtained results are very coherent with the field evidences, and could represent one possible explanation of the observed 2007 events.

  1. Towards efficient 5-axis flank CNC machining of free-form surfaces via fitting envelopes of surfaces of revolution

    OpenAIRE

    Bo P.; Bartoň M.; Plakhotnik D.; Pottmann H.

    2016-01-01

    We introduce a new method that approximates free-form surfaces by envelopes of one-parameter motions of surfaces of revolution. In the context of 5-axis computer numerically controlled (CNC) machining, we propose a flank machining methodology which is a preferable scallop-free scenario when the milling tool and the machined free-form surface meet tangentially along a smooth curve. We seek both an optimal shape of the milling tool as well as its optimal path in 3D space and propose an optimiza...

  2. Exploring Microbial Processes with Thermal-Hydrological Models of the Eastern Flank of the Juan de Fuca Ridge

    Science.gov (United States)

    Weathers, T. S.; Fisher, A. T.; Winslow, D. M.; Stauffer, P. H.; Gable, C. W.

    2017-12-01

    The flanks of mid-ocean ridges experience coupled flows of fluid, heat, and solutes that are critical for a wide range of global processes, including the cycling of carbon and nutrients, which supports a vast crustal biosphere. Only a few ridge-flank sites have been studied in detail; hydrogeologic conditions and processes in the volcanic crust are best understood on the eastern flank of the Juan de Fuca Ridge. This area has been extensively explored with decades of drilling, submersible, observatory, and survey expeditions and experiments, including the first hole-to-hole tracer injection experiment in the ocean crust. This study describes the development of reactive transport simulations for this ridge-flank setting using three-dimensional coupled (thermal-hydrological) models of crustal-scale circulation, beginning with the exploration of tracer transport. The prevailing flow direction is roughly south to north as a result of outcrop-to-outcrop flow, with a bulk flow rate in the range of meters/year. However, tracer was detected 500 m south ("upstream") from the injection borehole during the first year following injection. This may be explained by local mixing and/or formation fluid discharge from the southern borehole during and after injection. The constraints and parameters required to fit the observed tracer behavior can be used as a basis for modeling reactive transport processes such as nutrient delivery or microbial community evolution as a function of fluid flow. For example, the sulfate concentration in fluid samples from Baby Bare outcrop ( 8 km south of the tracer transport experiment) was 17.8 mmol/kg, whereas at Mama Bare outcrop ( 8 km to north of the tracer transport experiment) the sulfate concentration was 16.3 mmol/mg. By integrating laboratory-derived sulfate reduction rates from microbial samples originating from Juan de Fuca borehole observatories into reactive transport models, we can explore the range of microbial activity that supports

  3. Emplacement controls for the basaltic-andesitic radial dikes of Summer Coon volcano and implications for flank vents at stratovolcanoes

    Science.gov (United States)

    Harp, A. G.; Valentine, G. A.

    2018-02-01

    Mafic flank eruptions are common events that pose a serious hazard to the communities and infrastructure often encroaching on the slopes of stratovolcanoes. Flank vent locations are dictated by the propagation path of their feeder dikes. The dikes are commonly thought to propagate either laterally from the central conduit or vertically from a deeper source. However, these interpretations are often based on indirect measurements, such as surface deformation and seismicity at active systems, and several studies at eroded volcanoes indicate the propagation paths may be more complex. We investigated the Oligocene age Summer Coon volcano (Colorado, USA), where erosion has exposed over 700 basaltic-andesitic radial dikes, to constrain the propagation directions, geometries, and spatial distributions of mafic dikes within a stratovolcano. The mean fabric angle of aligned plagioclase crystals was measured in oriented samples from the margins of 77 dikes. Of the 41 dikes with statistically significant flow fabrics, 85% had fabric angles that were inclined—plunging both inward and outward relative to the center of the volcano. After comparing fabric angles to those reported in other studies, we infer that, while most of the dikes with outward-plunging fabrics descended toward the flanks from a source within the edifice and near its axis, dikes with inward-plunging fabrics ascended through the edifice and toward the flanks from a deeper source. A possible control for the inclination of ascending dikes was the ratio between magma overpressure and the normal stress in the host rock. While higher ratios led to high-angle propagation, lower ratios resulted in inclined emplacement. Dikes crop out in higher frequencies within a zone surrounding the volcano axis at 2500 m radial distance from the center and may be the result of ascending dikes, emplaced at similar propagation angles, intersecting the current level of exposure at common distances from the volcano axis. The process

  4. Experimental Evaluation and Optimization of Flank Wear During Turning of AISI 4340 Steel with Coated Carbide Inserts Using Different Cutting Fluids

    Science.gov (United States)

    Lawal, S. A.; Choudhury, I. A.; Nukman, Y.

    2015-01-01

    The understanding of cutting fluids performance in turning process is very important in order to improve the efficiency of the process. This efficiency can be determined based on certain process parameters such as flank wear, cutting forces developed, temperature developed at the tool chip interface, surface roughness on the work piece, etc. In this study, the objective is to determine the influence of cutting fluids on flank wear during turning of AISI 4340 with coated carbide inserts. The performances of three types of cutting fluids were compared using Taguchi experimental method. The results show that palm kernel oil based cutting fluids performed better than the other two cutting fluids in reducing flank wear. Mathematical models for cutting parameters such as cutting speed, feed rate, depth of cut and cutting fluids were obtained from regression analysis using MINITAB 14 software to predict flank wear. Experiments were conducted based on the optimized values to validate the regression equations for flank wear and 5.82 % error was obtained. The optimal cutting parameters for the flank wear using S/N ratio were 160 m/min of cutting speed (level 1), 0.18 mm/rev of feed (level 1), 1.75 mm of depth of cut (level 2) and 2.97 mm2/s palm kernel oil based cutting fluid (level 3). ANOVA shows cutting speed of 85.36 %; and feed rate 4.81 %) as significant factors.

  5. Sistema Faro, Isla de Mona, Puerto Rico: speleogenesis of the worlds largest flank margin cave; Sistema Faro, Isla de Mona, Puerto Rico: espeleogenesis de la cueva del tipo flank margin mas grande del mundo

    Energy Technology Data Exchange (ETDEWEB)

    Lace, M. J.; Kambesis, P. N.; Mylroie, J. E.

    2016-07-01

    Isla de Mona, a small, uplifted carbonate plateau jutting out of the waters of the Mona Passage, is an incredibly fragile and densely karstic environment. Expedition work was conducted by the Isla de Mona Project in cooperation with the Departamento Recursos Naturales y Ambientales de Puerto Rico (DRNA), including contributions from many researchers and cavers volunteering from across the U.S and Puerto Rico in the course of 12 separate expeditions, spanning a 14 year period (1998 to 2013). Over 200 caves have been documented on the island to date, the majority of this inventory is composed of flank margin caves but also includes sea caves, pit caves and talus caves. The most extensive example of cave development on the island is Sistema Faro - a sprawling maze-like series of chambers formed within the eastern point of the island with over 40 cliffside entrances overlooking the Caribbean Sea. Detailed cartography and analysis of the geomorphology and development of the Sistema Faro has helped form a complex model of carbonate island cave development as a function of tectonic uplift, lithology, sea level changes, karst hydrogeology and cliff retreat. This communication examines the roles these controls have played in the genesis of the world's largest flank margin cave. (Author)

  6. Neuraminidase-mediated haemagglutination of recent human influenza A(H3N2) viruses is determined by arginine 150 flanking the neuraminidase catalytic site.

    Science.gov (United States)

    Mögling, Ramona; Richard, Mathilde J; Vliet, Stefan van der; Beek, Ruud van; Schrauwen, Eefje J A; Spronken, Monique I; Rimmelzwaan, Guus F; Fouchier, Ron A M

    2017-06-01

    Over the last decade, an increasing proportion of circulating human influenza A(H3N2) viruses exhibited haemagglutination activity that was sensitive to neuraminidase inhibitors. This change in haemagglutination as compared to older circulating A(H3N2) viruses prompted an investigation of the underlying molecular basis. Recent human influenza A(H3N2) viruses were found to agglutinate turkey erythrocytes in a manner that could be blocked with either oseltamivir or neuraminidase-specific antisera, indicating that agglutination was driven by neuraminidase, with a low or negligible contribution of haemagglutinin. Using representative virus recombinants it was shown that the haemagglutinin of a recent A(H3N2) virus indeed had decreased activity to agglutinate turkey erythrocytes, while its neuraminidase displayed increased haemagglutinating activity. Viruses with chimeric and mutant neuraminidases were used to identify the amino acid substitution histidine to arginine at position 150 flanking the neuraminidase catalytic site as the determinant of this neuraminidase-mediated haemagglutination. An analysis of publicly available neuraminidase gene sequences showed that viruses with histidine at position 150 were rapidly replaced by viruses with arginine at this position between 2005 and 2008, in agreement with the phenotypic data. As a consequence of neuraminidase-mediated haemagglutination of recent A(H3N2) viruses and poor haemagglutination via haemagglutinin, haemagglutination inhibition assays with A(H3N2) antisera are no longer useful to characterize the antigenic properties of the haemagglutinin of these viruses for vaccine strain selection purposes. Continuous monitoring of the evolution of these viruses and potential consequences for vaccine strain selection remains important.

  7. Plasma wave profiles of Earth's bow shock at low Mach number: ISEE 3 observations on the far flank

    International Nuclear Information System (INIS)

    Greenstadt, E.W.; Coroniti, F.V.; Moses, S.L.; Smith, E.J.

    1992-01-01

    The Earth's bow shock is weak along its distant flanks where the projected component of solar wind velocity normal to the hyperboloidal surface is only a fraction of the total free stream velocity, severely reducing the local Mach number. The authors present a survey of selected crossings far downstream from the subsolar shock, delineating the overall plasma wave (pw) behavior of a selected set of nearly perpendicular crossings and another set of limited Mach number but broad geometry; they include their immediate upstream regions. The result is a generalizable pw signature, or signatures, of low Mach number shocks and some likely implications of those signatures for the weak shock's plasma physical processes on the flank. They find the data consistent with the presence of ion beam interactions producing noise ahead of the shock in the ion acoustic frequency range. One subcritical case was found whose pw noise was presumably related to a reflected ion population just as in stronger events. The presence or absence, and the amplitudes, of pw activity are explainable by the presence or absence of a population of upstream ions controlled by the component of interplanetary magnetic field normal to the solar wind flow

  8. The phylogeny of the social wasp subfamily Polistinae: evidence from microsatellite flanking sequences, mitochondrial COI sequence, and morphological characters

    Directory of Open Access Journals (Sweden)

    Strassmann Joan E

    2004-03-01

    Full Text Available Abstract Background Social wasps in the subfamily Polistinae (Hymenoptera: Vespidae have been important in studies of the evolution of sociality, kin selection, and within colony conflicts of interest. These studies have generally been conducted within species, because a resolved phylogeny among species is lacking. We used nuclear DNA microsatellite flanking sequences, mitochondrial COI sequence, and morphological characters to generate a phylogeny for the Polistinae (Hymenoptera using 69 species. Results Our phylogeny is largely concordant with previous phylogenies at higher levels, and is more resolved at the species level. Our results support the monophyly of the New World subgenera of Polistini, while the Old World subgenera are a paraphyletic group. All genera for which we had more than one exemplar were supported as monophyletic except Polybia which is not resolved, and may be paraphyletic. Conclusion The combination of DNA sequences from flanks of microsatellite repeats with mtCOI sequences and morphological characters proved to be useful characters establishing relationships among the different subgenera and species of the Polistini. This is the first detailed hypothesis for the species of this important group.

  9. Influence of the cutting parameters on flank wear of coated inserts during turning of AISI 316L

    Directory of Open Access Journals (Sweden)

    Yusimit Zamora Hernández

    2015-03-01

    Full Text Available (Received: 2015/01/20 - Accepted: 2015/03/25The continuous improvement of manufacturing processes is critical to achieve optimum levels of productivity, quality and cut production of components and products. This research aims to determine the cutting tool flank wearing progression, during a high speed dry turning, for AISI 316L steel parts. Experimental data were acquired using two cutting feed levels, two material levels, three cutting speeds, and four principal cutting times. A scanning electron microscope (SEM was used to measure and analyze the wear of the cutting tools. Results were compared using analysis of variance and multiple regression for describing the relation between the variables used in the study. The analysis showed that the three layers coating insert did not exceed the end of life wearing criterion, while the one layer insert suffered a catastrophic wearing at the highest cutting speed. It was found that a relation exists between the experimental data and the predicted values for flank wear with a general average error of 4.1182%.

  10. Association between DNA methylation in the miR-328 5'-flanking region and inter-individual differences in miR-328 and BCRP expression in human placenta.

    Directory of Open Access Journals (Sweden)

    Jumpei Saito

    Full Text Available MicroRNA (miRNA are non-coding small RNA that regulate gene expression. MiR-328 is reported to influence breast cancer resistance protein (BCRP expression in cancer cells. As a large inter-individual difference in BCRP levels is observed in various human tissues, the contribution of miR-328 to these differences is of interest. We hypothesized that DNA methylation in the miR-328 promoter region is responsible for the difference in miR-328 levels, leading to inter-individual variability in BCRP levels in human placenta. The association between placental miR-328 and BCRP levels was analyzed, and then DNA methylation in the miR-328 5'-flanking region and regulatory mechanisms causing inter-individual differences in miR-328 and BCRP levels were examined. MiR-328 expression was significantly correlated with BCRP mRNA (Rs = -0.560, P < 0.01 and protein (Rs = -0.730, P < 0.01 levels. It was also up-regulated by the demethylating agent 5-aza-2'-deoxycytidine in BCRP-expressing cells. Luciferase assays with differentially methylated reporter constructs indicated that methylation in the miR-328 5'-flanking region including a predicted CpG island remarkably decreased transcriptional activity compared to that in unmethylated constructs. We selected CCAAT/enhancer binding protein α (C/EBPα, located within the predicted CpG island, by in silico analysis. To elucidate the role of C/EBPα in miR-328 expression, a chromatin immunoprecipitation assay, promoter deletion analysis, and electrophoretic mobility shift assay (EMSA were performed. C/EBPα-binding site-truncated constructs showed significantly decreased promoter activity, and EMSA indicated that the C/EBPα-binding sites were located in the CpG island. Finally, the methylation patterns of several CpG dinucleotides proximal to two C/EBPα-binding sites in the miR-328 5'-flanking region were correlated negatively with miR-328 levels, and positively with BCRP levels in human placental samples. These

  11. Mitigation of Flanking Noise in Double-Plate Panel Structures by Periodic Stiffening

    DEFF Research Database (Denmark)

    Domadiya, Parthkumar Gandalal; Dickow, Kristoffer Ahrens; Andersen, Lars

    2011-01-01

    , the air enclosed in the cavities within the structure is taken into consideration, whereas the external air has been disregarded. A fully coupled analysis is performed in which solid finite elements are adopted for the structure, whereas the acoustic medium within the panel is discretized into fluid...... continuum elements. The computations are carried out in frequency domain in the range below 500 Hz and the load acts as a concentrated force on one side of one of the panels. The responses of the same panel as well as the adjacent wall are studied. The position of the load relative to the stiffeners...

  12. Vasopressin-dependent flank marking in golden hamsters is suppressed by drugs used in the treatment of obsessive-compulsive disorder

    Directory of Open Access Journals (Sweden)

    Messenger Tara

    2001-08-01

    Full Text Available Abstract Background Alterations in arginine vasopressin regulation and secretion have been proposed as one possible biochemical abnormality in patients with obsessive-compulsive disorder. In golden hamsters, arginine vasopressin microinjections into the anterior hypothalamus trigger robust grooming and flank marking, a stereotyped scent marking behaviors. The intensity and repetition of the behaviors induced by arginine vasopressin is somewhat reminiscent of Obsessive Compulsive Disorder in humans. The present experiments were carried out to test whether pharmacological agents used to alleviate obsessive compulsive disorder could inhibit arginine vasopressin-induced flank marking and grooming. Results Male golden hamsters were treated daily for two weeks with either vehicle, fluoxetine, clomipramine, or desipramine (an ineffective drug, before being tested for arginine vasopressin-induced flank marking and grooming. Flank marking was significantly inhibited in animals treated with fluoxetine or clomipramine but unaffected by treatment with desipramine. Grooming behavior was not affected by any treatment. Conclusion These data suggest that arginine vasopressin-induced flank marking may serve as an animal model for screening drugs used in the control of Obsessive Compulsive Disorder.

  13. Finite Element Analysis Of Influence Of Flank Wear Evolution On Forces In Orthogonal Cutting Of 42CrMo4 Steel

    Directory of Open Access Journals (Sweden)

    Madajewski Marek

    2017-01-01

    Full Text Available This paper presents analysis of flank wear influence on forces in orthogonal turning of 42CrMo4 steel and evaluates capacity of finite element model to provide such force values. Data about magnitude of feed and cutting force were obtained from measurements with force tensiometer in experimental test as well as from finite element analysis of chip formation process in ABAQUS/Explicit software. For studies an insert with complex rake face was selected and flank wear was simulated by grinding operation on its flank face. The aim of grinding inset surface was to obtain even flat wear along cutting edge, which after the measurement could be modeled with CAD program and applied in FE analysis for selected range of wear width. By comparing both sets of force values as function of flank wear in given cutting conditions FEA model was validated and it was established that it can be applied to analyze other physical aspects of machining. Force analysis found that progression of wear causes increase in cutting force magnitude and steep boost to feed force magnitude. Analysis of Fc/Ff force ratio revealed that flank wear has significant impact on resultant force in orthogonal cutting and magnitude of this force components in cutting and feed direction. Surge in force values can result in transfer of substantial loads to machine-tool interface.

  14. Finite Element Analysis Of Influence Of Flank Wear Evolution On Forces In Orthogonal Cutting Of 42CrMo4 Steel

    Science.gov (United States)

    Madajewski, Marek; Nowakowski, Zbigniew

    2017-01-01

    This paper presents analysis of flank wear influence on forces in orthogonal turning of 42CrMo4 steel and evaluates capacity of finite element model to provide such force values. Data about magnitude of feed and cutting force were obtained from measurements with force tensiometer in experimental test as well as from finite element analysis of chip formation process in ABAQUS/Explicit software. For studies an insert with complex rake face was selected and flank wear was simulated by grinding operation on its flank face. The aim of grinding inset surface was to obtain even flat wear along cutting edge, which after the measurement could be modeled with CAD program and applied in FE analysis for selected range of wear width. By comparing both sets of force values as function of flank wear in given cutting conditions FEA model was validated and it was established that it can be applied to analyze other physical aspects of machining. Force analysis found that progression of wear causes increase in cutting force magnitude and steep boost to feed force magnitude. Analysis of Fc/Ff force ratio revealed that flank wear has significant impact on resultant force in orthogonal cutting and magnitude of this force components in cutting and feed direction. Surge in force values can result in transfer of substantial loads to machine-tool interface.

  15. Application of response surface methodology on investigating flank wear in machining hardened steel using PVD TiN coated mixed ceramic insert

    Directory of Open Access Journals (Sweden)

    Ashok Kumar Sahoo

    2013-10-01

    Full Text Available The paper presents the development of flank wear model in turning hardened EN 24 steel with PVD TiN coated mixed ceramic insert under dry environment. The paper also investigates the effect of process parameter on flank wear (VBc. The experiments have been conducted using three level full factorial design techniques. The machinability model has been developed in terms of cutting speed (v, feed (f and machining time (t as input variable using response surface methodology. The adequacy of model has been checked using correlation coefficients. As the determination coefficient, R2 (98% is higher for the model developed; the better is the response model fits the actual data. In addition, residuals of the normal probability plot lie reasonably close to a straight line showing that the terms mentioned in the model are statistically significant. The predicted flank wear has been found to lie close to the experimental value. This indicates that the developed model can be effectively used to predict the flank wear in the hard turning. Abrasion and diffusion has been found to be the dominant wear mechanism in machining hardened steel from SEM micrographs at highest parametric range. Machining time has been found to be the most significant parameter on flank wear followed by cutting speed and feed as observed from main effect plot and ANOVA study.

  16. Can comodulation masking release occur when frequency changes could promote perceptual segregation of the on-frequency and flanking bands?

    DEFF Research Database (Denmark)

    Verhey, Jesko L; Epp, Bastian; Stasiak, Arkadiusz

    2013-01-01

    A common characteristic of natural sounds is that the level fluctuations in different frequency regions are coherent. The ability of the auditory system to use this comodulation is shown when a sinusoidal signal is masked by a masker centred at the signal frequency (on-frequency masker, OFM......) and one or more off-frequency components, commonly referred to as flanking bands (FBs). In general, the threshold of the signal masked by comodulated masker components is lower than when masked by masker components with uncorrelated envelopes or in the presence of the OFM only. This effect is commonly...... referred to as comodulation masking release (CMR). The present study investigates if CMR is also observed for a sinusoidal signal embedded in the OFM when the centre frequencies of the FBs are swept over time with a sweep rate of one octave per second. Both a common change of different frequencies...

  17. Identification and characterization of a silencer regulatory element in the 3'-flanking region of the murine CD46 gene.

    Science.gov (United States)

    Nomura, M; Tsujimura, A; Begum, N A; Matsumoto, M; Wabiko, H; Toyoshima, K; Seya, T

    2000-01-01

    The murine membrane cofactor protein (CD46) gene is expressed exclusively in testis, in contrast to human CD46, which is expressed ubiquitously. To elucidate the mechanism of differential CD46 gene expression among species, we cloned entire murine CD46 genomic DNA and possible regulatory regions were placed in the flanking region of the luciferase reporter gene. The reporter gene assay revealed a silencing activity not in the promoter, but in the 3'-flanking region of the gene and the silencer-like element was identified within a 0.2-kb region between 0.6 and 0.8 kb downstream of the stop codon. This silencer-like element was highly similar to that of the pig MHC class-I gene. The introduction of a mutation into this putative silencer element of murine CD46 resulted in an abrogation of the silencing effect. Electrophoretic mobility-shift assay indicated the presence of the binding molecule(s) for this silencer sequence in murine cell lines and tissues. A size difference of the protein-silencer-element complex was observed depending upon the solubilizers used for preparation of the nuclear extracts. A mutated silencer sequence failed to interact with the binding molecules. The level of the binding factor was lower in the testicular germ cells compared with other organs. Thus the silencer element and its binding factor may play a role in transcriptional regulation of murine CD46 gene expression. These results imply that the effects of the CD46 silencer element encompass the innate immune and reproductive systems, and in mice may determine the testicular germ-cell-dominant expression of CD46. PMID:11023821

  18. A Tooth Flank Crowning Method by Applying a Novel Crossed Angle Function Between the Hob Cutter and Work Gear in the Gear Hobbing Process

    Directory of Open Access Journals (Sweden)

    Wu Yu-Ren

    2016-01-01

    Full Text Available In this paper, a novel longitudinal tooth flank crowning method is proposed by setting the crossed angle between the hob cutter and work gear as a linear function of hob’s traverse feed movement in the gear hobbing process. However, this method makes twisted tooth flanks on the hobbed work gear. Therefore, a variable pressure angle hob cutter is applied to obtain an anti-twist tooth flank of hobbed work gear. A computer simulation example is performed to verify the superiority of the proposed novel hobbing method by comparing topographies of the crowned work gear surfaces hobbed by a standard hob cutter and a variable pressure angle hob cutter.

  19. Outline of a genome navigation system based on the properties of GA-sequences and their flanks.

    Directory of Open Access Journals (Sweden)

    Guenter Albrecht-Buehler

    Full Text Available Introducing a new method to visualize large stretches of genomic DNA (see Appendix S1 the article reports that most GA-sequences [1] shared chains of tetra-GA-motifs and contained upstream poly(A-segments. Although not integral parts of them, Alu-elements were found immediately upstream of all human and chimpanzee GA-sequences with an upstream poly(A-segment. The article hypothesizes that genome navigation uses these properties of GA-sequences in the following way. (1 Poly(A binding proteins interact with the upstream poly(A-segments and arrange adjacent GA-sequences side-by-side ('GA-ribbon', while folding the intervening DNA sequences between them into loops ('associated DNA-loops'. (2 Genome navigation uses the GA-ribbon as a search path for specific target genes that is up to 730-fold shorter than the full-length chromosome. (3 As to the specificity of the search, each molecule of a target protein is assumed to catalyze the formation of specific oligomers from a set of transcription factors that recognize tetra-GA-motifs. Their specific combinations of tetra-GA motifs are assumed to be present in the particular GA-sequence whose associated loop contains the gene for the target protein. As long as the target protein is abundant in the cell it produces sufficient numbers of such oligomers which bind to their specific GA-sequences and, thereby, inhibit locally the transcription of the target protein in the associated loop. However, if the amount of target protein drops below a certain threshold, the resultant reduction of specific oligomers leaves the corresponding GA-sequence 'denuded'. In response, the associated DNA-loop releases its nucleosomes and allows transcription of the target protein to proceed. (4 The Alu-transcripts may help control the general background of protein synthesis proportional to the number of transcriptionally active associated loops, especially in stressed cells. (5 The model offers a new mechanism of co-regulation of

  20. Effect of Saw Palmetto Supplements on Androgen-Sensitive LNCaP Human Prostate Cancer Cell Number and Syrian Hamster Flank Organ Growth

    Directory of Open Access Journals (Sweden)

    Alexander B. Opoku-Acheampong

    2016-01-01

    Full Text Available Saw palmetto supplements (SPS are commonly consumed by men with prostate cancer. We investigated whether SPS fatty acids and phytosterols concentrations determine their growth-inhibitory action in androgen-sensitive LNCaP cells and hamster flank organs. High long-chain fatty acids-low phytosterols (HLLP SPS ≥ 750 nM with testosterone significantly increased and ≥500 nM with dihydrotestosterone significantly decreased LNCaP cell number. High long-chain fatty acids-high phytosterols (HLHP SPS ≥ 500 nM with dihydrotestosterone and high medium-chain fatty acids-low phytosterols (HMLP SPS ≥ 750 nM or with androgens significantly decreased LNCaP cell number (n=3; p<0.05. Five- to six-week-old, castrated male Syrian hamsters were randomized to control (n=4, HLLP, HLHP, and HMLP SPS (n=6 groups. Testosterone or dihydrotestosterone was applied topically daily for 21 days to the right flank organ; the left flank organ was treated with ethanol and served as the control. Thirty minutes later, SPS or ethanol was applied to each flank organ in treatment and control groups, respectively. SPS treatments caused a notable but nonsignificant reduction in the difference between left and right flank organ growth in testosterone-treated SPS groups compared to the control. The same level of inhibition was not seen in dihydrotestosterone-treated SPS groups (p<0.05. Results may suggest that SPS inhibit 5α-reductase thereby preventing hamster flank organ growth.

  1. Effect of Saw Palmetto Supplements on Androgen-Sensitive LNCaP Human Prostate Cancer Cell Number and Syrian Hamster Flank Organ Growth.

    Science.gov (United States)

    Opoku-Acheampong, Alexander B; Penugonda, Kavitha; Lindshield, Brian L

    2016-01-01

    Saw palmetto supplements (SPS) are commonly consumed by men with prostate cancer. We investigated whether SPS fatty acids and phytosterols concentrations determine their growth-inhibitory action in androgen-sensitive LNCaP cells and hamster flank organs. High long-chain fatty acids-low phytosterols (HLLP) SPS ≥ 750 nM with testosterone significantly increased and ≥500 nM with dihydrotestosterone significantly decreased LNCaP cell number. High long-chain fatty acids-high phytosterols (HLHP) SPS ≥ 500 nM with dihydrotestosterone and high medium-chain fatty acids-low phytosterols (HMLP) SPS ≥ 750 nM or with androgens significantly decreased LNCaP cell number (n = 3; p < 0.05). Five- to six-week-old, castrated male Syrian hamsters were randomized to control (n = 4), HLLP, HLHP, and HMLP SPS (n = 6) groups. Testosterone or dihydrotestosterone was applied topically daily for 21 days to the right flank organ; the left flank organ was treated with ethanol and served as the control. Thirty minutes later, SPS or ethanol was applied to each flank organ in treatment and control groups, respectively. SPS treatments caused a notable but nonsignificant reduction in the difference between left and right flank organ growth in testosterone-treated SPS groups compared to the control. The same level of inhibition was not seen in dihydrotestosterone-treated SPS groups (p < 0.05). Results may suggest that SPS inhibit 5α-reductase thereby preventing hamster flank organ growth.

  2. Radiation therapy for favorable histology Wilms tumor: Prevention of flank recurrence did not improve survival on National Wilms Tumor Studies 3 and 4

    International Nuclear Information System (INIS)

    Breslow, Norman E.; Beckwith, J. Bruce; Haase, Gerald M.; Kalapurakal, John A.; Ritchey, Michael L.; Shamberger, Robert C.; Thomas, Patrick; D'Angio, Giulio J.; Green, Daniel M.

    2006-01-01

    Purpose: To determine whether radiation therapy (RT) of patients with Wilms tumor of favorable histology prevented flank recurrence and thereby improved the survival outcomes. Methods and Materials: Recurrence and mortality risks were compared among groups of patients with Stage I-IV/favorable histology Wilms tumor enrolled in the third (n = 1,640) and fourth (n = 2,066) National Wilms Tumor Study Group studies. Results: Proportions of patients with flank recurrence were 0 of 513 = 0.0% for 20 Gy, 12 of 805 = 1.5% for 10 Gy, and 44 of 2,388 = 1.8% for no flank RT (p trend 0.001 adjusted for stage and doxorubicin); for intra-abdominal (including flank) recurrence they were 5 of 513 = 1.0%, 30 of 805 = 3.7%, and 58 of 2,388 = 2.4%, respectively (p trend = 0.02 adjusted). Survival percentages at 8 years after intra-abdominal recurrence were 0 of 5 = 0% for 20 Gy, 10 of 30 = 33% for 10 Gy, and 34 of 58 = 56% for no RT (p trend = 0.0001). NWTS-4 discontinued use of 20 Gy RT, and the 8-year flank recurrence risk increased to 2.1% from 1.0% on NWTS-3 (p = 0.013). However, event-free survival was unaltered (88% vs. 86%, p = 0.39), and overall survival was better (93.8% vs. 90.8%, p = 0.036) on NWTS-4. Conclusions: Partly because of lower postrecurrence mortality among nonirradiated patients, prevention of flank recurrence by RT did not improve survival. It is important to evaluate entire treatment policies with regard to long-term outcomes

  3. Combination of hypomorphic mutations of the Drosophila homologues of aryl hydrocarbon receptor and nucleosome assembly protein family genes disrupts morphogenesis, memory and detoxification.

    Science.gov (United States)

    Kuzin, Boris A; Nikitina, Ekaterina A; Cherezov, Roman O; Vorontsova, Julia E; Slezinger, Mikhail S; Zatsepina, Olga G; Simonova, Olga B; Enikolopov, Grigori N; Savvateeva-Popova, Elena V

    2014-01-01

    Aryl hydrocarbon receptor is essential for biological responses to endogenous and exogenous toxins in mammals. Its Drosophila homolog spineless plays an important role in fly morphogenesis. We have previously shown that during morphogenesis spineless genetically interacts with CG5017 gene, which encodes a nucleosome assembly factor and may affect cognitive function of the fly. We now demonstrate synergistic interactions of spineless and CG5017 in pathways controlling oxidative stress response and long-term memory formation in Drosophila melanogaster. Oxidative stress was induced by low doses of X-ray irradiation of flies carrying hypomorphic mutation of spineless, mutation of CG5017, and their combination. To determine the sensitivity of these mutants to pharmacological modifiers of the irradiation effect, we irradiated flies growing on standard medium supplemented by radiosensitizer furazidin and radioprotector serotonin. The effects of irradiation were investigated by analyzing leg and antenna morphological structures and by using real-time PCR to measure mRNA expression levels for spineless, Cyp6g1 and Gst-theta genes. We also examined long-term memory in these mutants using conditioned courtship suppression paradigm. Our results show that the interaction of spineless and CG5017 is important for regulation of morphogenesis, long-term memory formation, and detoxification during oxidative stress. Since spineless and CG5017 are evolutionary conserved, these results must be considered when evaluating the risk of combining similar mutations in other organisms, including humans.

  4. Combination of hypomorphic mutations of the Drosophila homologues of aryl hydrocarbon receptor and nucleosome assembly protein family genes disrupts morphogenesis, memory and detoxification.

    Directory of Open Access Journals (Sweden)

    Boris A Kuzin

    Full Text Available Aryl hydrocarbon receptor is essential for biological responses to endogenous and exogenous toxins in mammals. Its Drosophila homolog spineless plays an important role in fly morphogenesis. We have previously shown that during morphogenesis spineless genetically interacts with CG5017 gene, which encodes a nucleosome assembly factor and may affect cognitive function of the fly. We now demonstrate synergistic interactions of spineless and CG5017 in pathways controlling oxidative stress response and long-term memory formation in Drosophila melanogaster. Oxidative stress was induced by low doses of X-ray irradiation of flies carrying hypomorphic mutation of spineless, mutation of CG5017, and their combination. To determine the sensitivity of these mutants to pharmacological modifiers of the irradiation effect, we irradiated flies growing on standard medium supplemented by radiosensitizer furazidin and radioprotector serotonin. The effects of irradiation were investigated by analyzing leg and antenna morphological structures and by using real-time PCR to measure mRNA expression levels for spineless, Cyp6g1 and Gst-theta genes. We also examined long-term memory in these mutants using conditioned courtship suppression paradigm. Our results show that the interaction of spineless and CG5017 is important for regulation of morphogenesis, long-term memory formation, and detoxification during oxidative stress. Since spineless and CG5017 are evolutionary conserved, these results must be considered when evaluating the risk of combining similar mutations in other organisms, including humans.

  5. MARINE CONGLOMERATE AND REEF MEGACLASTS AT MAURITUS ISLAND: Evidences of a tsunami generated by a flank collapse of the PITON DE LA Fournaise volcano, Reunion Island?

    Directory of Open Access Journals (Sweden)

    R. Paris

    2014-05-01

    Full Text Available Tsunamis related to volcano flank collapse are typically a high-magnitude, low frequency hazard for which evaluation and mitigation are difficult to address. In this short communication, we present field evidences of a large tsunami along the southern coast of Mauritius Island ca. 4400 years ago. Tsunami deposits described include both marine conglomerates and coral boulders up to 90 m3 (> 100 tons. The most probable origin of the tsunami is a flank collapse of Piton de la Fournaise volcano, Réunion Island.

  6. Pre-Carboniferous sedimentary sequences of the northeastern flank of the Parana basin and southwestern of the Parnaiba basin and its uraniferous possibilites

    International Nuclear Information System (INIS)

    Andrade, S.M. de; Camarco, P.E.N.

    1982-01-01

    The analyses of the already existent geological data of the northeastern flank of the Parana Basin and the Southwestern flank of the Parnaiba Basin, added to new data from drilling and geological mapping allowed a better knowledge of the stratigraphy of the pre-carboniferous sedimentary sequences (silurian and devonian ages) as well as provided subsidies for the definition of its uranium possibilites. Besides the already known uranium deposits of the Ponta Grossa Formation, is should be considered as worth while of prospecting the Pimenteiras Formation. (Author) [pt

  7. Leakage of active crater lake brine through the north flank at Rincon de la Vieja volcano, northwest Costa Rica, and implications for crater collapse

    Science.gov (United States)

    Kempter, K.A.; Rowe, G.L.

    2000-01-01

    The Active Crater at Rincon de la Vieja volcano, Costa Rica, reaches an elevation of 1750 m and contains a warm, hyper-acidic crater lake that probably formed soon after the eruption of the Rio Blanco tephra deposit approximately 3500 years before present. The Active Crater is buttressed by volcanic ridges and older craters on all sides except the north, which dips steeply toward the Caribbean coastal plains. Acidic, above-ambient-temperature streams are found along the Active Crater's north flank at elevations between 800 and 1000 m. A geochemical survey of thermal and non-thermal waters at Rincon de la Vieja was done in 1989 to determine whether hyper-acidic fluids are leaking from the Active Crater through the north flank, affecting the composition of north-flank streams. Results of the water-chemistry survey reveal that three distinct thermal waters are found on the flanks of Rincon de la Vieja volcano: acid chloride-sulfate (ACS), acid sulfate (AS), and neutral chloride (NC) waters. The most extreme ACS water was collected from the crater lake that fills the Active Crater. Chemical analyses of the lake water reveal a hyper-acidic (pH ~ 0) chloride-sulfate brine with elevated concentrations of calcium, magnesium, aluminum, iron, manganese, copper, zinc, fluorine, and boron. The composition of the brine reflects the combined effects of magmatic degassing from a shallow magma body beneath the Active Crater, dissolution of andesitic volcanic rock, and evaporative concentration of dissolved constituents at above-ambient temperatures. Similar cation and anion enrichments are found in the above-ambient-temperature streams draining the north flank of the Active Crater. The pH of north-flank thermal waters range from 3.6 to 4.1 and chloride:sulfate ratios (1.2-1.4) that are a factor of two greater than that of the lake brine (0.60). The waters have an ACS composition that is quite different from the AS and NC thermal waters that occur along the southern flank of Rincon

  8. Position Information

    Data.gov (United States)

    Social Security Administration — The Position Information Data Asset provides the ability to search for active SSA position descriptions using various search criteria. An individual may search by PD...

  9. Positive Psychology

    Science.gov (United States)

    Peterson, Christopher

    2009-01-01

    Positive psychology is a deliberate correction to the focus of psychology on problems. Positive psychology does not deny the difficulties that people may experience but does suggest that sole attention to disorder leads to an incomplete view of the human condition. Positive psychologists concern themselves with four major topics: (1) positive…

  10. Preliminary Mineralogic and Stable Isotope Studies of Altered Summit and Flank Rocks and Osceola Mudflow Deposits on Mount Rainier, Washington

    Science.gov (United States)

    Rye, Robert O.; Breit, George N.; Zimbelman, David R.

    2003-01-01

    About 5600 years ago part of Mount Rainier?s edifice collapsed with the resultant Osceola Mudflow traveling more than 120 km and covering an area of at least 505 km2. Mineralogic and stable isotope studies were conducted on altered rocks from outcrops near the summit and east flank of the volcano and samples of clasts and matrix from the Osceola Mudflow. Results of these analyses are used to constrain processes responsible for pre-collapse alteration and provide insight into the role of alteration in edifice instability prior to the Osceola collapse event. Jarosite, pyrite, alunite, and kaolinite occur in hydrothermally altered rock exposed in summit scarps formed by edifice collapse events and in altered rock within the east-west structural zone (EWSZ) of the volcano?s east flank. Deposits of the Osceola Mudflow contain clasts of variably altered and unaltered andesite within a clay-rich matrix. Minerals detected in samples from the edifice are also present in many of the clasts. The matrix includes abundant smectite, kaolinite and variably abundant jarosite. Hydrothermal fluid compositions calculated from hydrogen and oxygen isotope data of alunite, and smectite on Mount Rainier reflect mixing of magmatic and meteoric waters. The range in the dD values of modern meteoric water on the volcano (-85 to 155?) reflect the influence of elevation on the dD of precipitation. The d34S and d18OSO4 values of alunite, gypsum and jarosite are distinct but together range from 1.7 to 17.6? and -12.3 to 15.0?, respectively; both parameters increase from jarosite to gypsum to alunite. The variations in sulfur isotope composition are attributed to the varying contributions of disproportionation of magmatic SO2, the supergene oxidation of hydrothermal pyrite and possible oxidation of H2S to the parent aqueous sulfate. The 18OSO4 values of jarosite are the lowest recorded for the mineral, consistent with a supergene origin. The mineralogy and isotope composition of alteration

  11. Ubiquitous positioning

    CERN Document Server

    Mannings, Robin

    2008-01-01

    This groundbreaking resource offers a practical, in-depth understanding of Ubiquitous Positioning - positioning systems that identify the location and position of people, vehicles and objects in time and space in the digitized networked economy. The future and growth of ubiquitous positioning will be fueled by the convergence of many other areas of technology, from mobile telematics, Internet technology, and location systems, to sensing systems, geographic information systems, and the semantic web. This first-of-its-kind volume explores ubiquitous positioning from a convergence perspective, of

  12. Flank Collapse Assessment At Kick-'em-Jenny Submarine Volcano (Lesser Antilles): A Combined Approach Using Modelling and Experiments

    Science.gov (United States)

    Dondin, F. J. Y.; Heap, M. J.; Robertson, R. E. A.; Dorville, J. F. M.; Carey, S.

    2016-12-01

    In the Lesser Antilles over 52 volcanic landslide episodes have been identified. These episodes serve as a testament to the hazard posed by volcanic landslides to a region composed of many islands that are small independent countries with vulnerable local economies. This study presents a relative slope stability analysis (RIA) to investigate the stability condition of the only active submarine volcano of the Lesser Antilles Arc: Kick-'em-Jenny Submarine Volcano (KeJ). Thus we hope to provide better constraint on the landslide source geometry to help mitigate volcanic landslide hazards at a KeJ. KeJ is located ca. 8 km north of Grenada island. KeJ lies within a collapse scar from a prehistorical flank collapse. This collapse was associated with a voluminous landslide deposit of about 4.4km3 with a 14 km runout. Numerial simulations showed that this event could generate a regional tsunami. We aim to quantify potential initial volumes of collapsed material using a RIA. The RIA evaluates the critical potential failure surface associated with factor of safety (Fs) inferior to unity and compares them to areas of deficit/surplus of mass/volume obtained from the comparison of an high resolution digital elevation model of the edifice with an ideal 3D surface. We use freeware programs VolcanoFit 2.0 and SSAP 4.7. and produce a 3D representation of the stability map. We report, for the first time, results of a Limit Equilibrium Method performed using geomechanical parameters retrieved from rock mechanics tests performed on two rock basaltic-andesite rock samples collected from within the crater of the volcano during the 1-18 November 2013 NA039 E/V Nautilus cruise. We performed triaxial and uniaxial deformation tests to obtain values of strength at the top and bottom of the edifice. We further characterized the permeability and P-wave velocity of the samples collected. The chosen internal structure for the model is composed of three bodies: (i) a body composed of basaltic

  13. Positioning consumption

    DEFF Research Database (Denmark)

    Halkier, Bente; Keller, Margit

    2014-01-01

    positionings emerges based on empirical examples of research in parent–children consumption. Positionings are flexible discursive fixations of the relationship between the performances of the practitioner, other practitioners, media discourse and consumption activities. The basic positioning types...... are the practice maintenance and the practice change position, with different sorts of adapting in between. Media discourse can become a resource for a resistant position against social control or for an appropriating position in favour of space for action. Regardless of the current relation to a particular media......This article analyses the ways in which media discourses become a part of contested consumption activities. We apply a positioning perspective with practice theory to focus on how practitioners relate to media discourse as a symbolic resource in their everyday practices. A typology of performance...

  14. The N-Terminal Flanking Region of the Invariant Chain Peptide Augments the Immunogenicity of a Cryptic “Self” Epitope from a Tumor-Associated Antigen

    NARCIS (Netherlands)

    Hess, A.D.; Thoburn, C.; Chen, W.; Miura, Y.; Wall, E. van der

    2001-01-01

    The N-terminal flanking region of the invariant chain peptide termed CLIP appears to have superagonistic properties interacting with the T cell receptor and the MHC class II molecule at or near the binding site for the bacterial superantigen Staphylococcal enterotoxin B (SEB). The present studies

  15. Tool Wear Analysis on Five-Axis Flank Milling for Curved Shape Part – Full Flute and Ground Shank End Mill

    Directory of Open Access Journals (Sweden)

    Syahrul Azwan Sundi

    2017-01-01

    Full Text Available This paper is a study on full flute (extra-long tool and ground shank end mill wear analysis by utilizing five-axis CNC to implement flank milling strategy on curved shape part. Five-axis machining eases the user to implement variations of strategy such as flank milling. Flank milling is different from point milling. Point milling cuts materials by using the tip of the tool whereas the flank milling uses the cutting tool body to cut material. The type of cutting tool used was end mill 10 mm diameter with High Speed Steel (HSS material. One factor at a time was utilized to analyze the overall data. Feed rate and spindle speed were the two main factors that been set up equally for both full flute and ground shank end mill. At the end of this research, the qualitative analysis based on tool wear between full flute and ground shank end mill is observed. Generally, both types of cutting tools showed almost the same failure indication such as broken edge or chipped off edge, formation of pinned hole on the surface and serration formation or built-up edge (BUE on the primary flute. However, the results obtained from the enlarged images which were captured by Optical Microscope indicated that, the ground shank end mill is better than the full flute end mill.

  16. Erratum: Correction to: Emplacement controls for the basaltic-andesitic radial dikes of Summer Coon volcano and implications for flank vents at stratovolcanoes

    Science.gov (United States)

    Harp, A. G.; Valentine, G. A.

    2018-06-01

    In the article "Emplacement controls for the basaltic-andesitic radial dikes of Summer Coon volcano and implications for flank vents at stratovolcanoes", the vertical axis for Fig. 8 a was incorrectly labeled (i.e., the value for dikes per km2).

  17. Visit to valuable water springs. 22. ; Kanazawa spring and springs at the mountain flank of Iwate volcano. Meisui wo tazunete. 22. ; Kanazawa shimizu to Iwate sanroku yusuigun

    Energy Technology Data Exchange (ETDEWEB)

    Itadera, K. (Kanagawa Hot Springs Research Institute, Kanagawa (Japan)); Shimano, Y. (Utsunomiya Bunsei Junior College, Tochigi (Japan))

    1993-06-30

    This paper describes the following matters on the springs at the mountain flank of Iwate volcano in Iwate Prefecture, with the Kanazawa spring as the main subject: The new and old Iwate volcanos have rock-bed flow deposits which resulted from mountain disintegration, distributed over their south, east and north flanks, and most of the spring water wells up in these areas; the south, east and north flanks have about 80 springs, about 30 springs, and about 10 springs, respectively; the number of springs and the water well-up scale show a trend of inverse proportion; the Kanazawa spring is a generic name of the several springs located on the north flank in the Kanazawa area; its main spring forms a spring pond with an area of about 100 m[sup 2] with a spring water temperature of about 11.5[degree]C, electric conductivity of 200 [mu] S/cm or higher, and a flow-out rate of 500 l/s or more; the Kanazawa spring is characterized by having as large total dissolved component amount as 170 mg/l or more and abundant amount of SO4[sup 2-] and Cl[sup -]; and the spring presents properties different from those in other springs. 10 refs., 5 figs., 1 tab.

  18. Pigs suffering from injurious behaviours like flank biting and tail biting are more interested to manipulate a novel rope than uninjured control animals

    NARCIS (Netherlands)

    Bracke, M.B.M.; Ettema, K.

    2014-01-01

    Injurious behaviours in pigs may involve persistent or forceful biting in specific body parts and may result in wounds of the pigs’ tails, ears, flanks and legs. Such behaviours, which may lead to progressive tissue damage, are difficult to counteract. On a commercial farm 22 groups of pigs with

  19. King's Trough Flank: geological and geophysical investigations of its suitability for high-level radioactive waste disposal

    International Nuclear Information System (INIS)

    Kidd, R.B.; Searle, R.C.; Weaver, P.P.E.; Jacobs, C.L.; Huggett, Q.J.; Noel, M.J.; Schultheiss, P.J.

    1983-01-01

    The King's Trough Flank study area in the Northeast Atlantic Ocean was chosen in 1979 as a location at which to examine the suitability of pelagic carbonate sequences for sub-seabed disposal of high-level radioactive waste. This report summarises investigations up to the end of 1982; following visits by four research ships to the area during which geophysical data and sediment samples were collected. The region is a characteristically rugged portion of the deep ocean floor with hills and scarps 10 to 30 km apart and slopes around the hills ranging from 18 deg to 30 deg. Areas of relatively smooth seafloor occur, however, up to 35 km across, where slopes no greater than 2 deg are recorded. At this stage an apparent discrepancy between the geophysical and sediment core data leaves some uncertainty regarding the stability of the sediment cover and the likelihood of current erosion in these areas. The general suitability of the area is discussed by comparing our present geological and geophysical data with the set of 'desirable characteristics' for a sub-seabed disposal site first outlined in 1979. The difficulties involved in extrapolating findings from presently-sampled depths of up to 10 metres to depths envisaged for shallow waste disposal are emphasised. (author)

  20. Insulin increases transcription of rat gene 33 through cis-acting elements in 5[prime]-flanking DNA

    Energy Technology Data Exchange (ETDEWEB)

    Cadilla, C.; Isham, K.R.; Lee, K.L.; Ch' ang, L.Y.; Kenney, F.T. (Oak Ridge National Lab., TN (United States)); Johnson, A.C. (National Cancer Institute, Bethesda, MD (United States). Lab. of Molecular Biology)

    1992-01-01

    Gene 33 is a multihormonally-regulated rat gene whose transcription is rapidly and markedly enhanced by insulin in liver and cultured hepatoma cells. To examine the mechanism by which insulin regulates transcription, the authors have constructed chimeric plasmids in which expression of the bacterial cat gene, encoding chloramphenicol acetyltransferase (CAT), is governed by gene 33 promoter elements and contiguous sequence in DNA flanking the transcription start point (tsp). When transfected into H4IIE hepatoma cells, these constructs gave rise to stably transformed cell lines producing the bacterial CAT enzyme. This expression was increased by insulin treatment in a fashion resembling the effect of this hormone on transcription of the native gene. In vitro transcription assays in nuclear extracts also revealed increased transcription of the chimeric plasmids when the extracts were prepared from insulin-treated rat hepatoma cells. The results demonstrate that induction by insulin is mediated by cis-acting nucleotide sequences located between bp [minus]480 to +27 relative to the tsp.

  1. Changes in Bottom Water Physical Properties Above the Mid-Atlantic Ridge Flank in the Brazil Basin

    Science.gov (United States)

    Zhao, Jian; Thurnherr, Andreas M.

    2018-01-01

    Warming of abyssal waters in recent decades has been widely documented around the global ocean. Here repeat hydrographic data collected in 1997 and 2014 near a deep fracture zone canyon in the eastern Brazil Basin are used to quantify the long-term change. Significant changes are found in the Antarctic Bottom Water (AABW) within the canyon. The AABW in 2014 was warmer (0.08 ± 0.06°C), saltier (0.01 ± 0.005), and less dense (0.005 ± 0.004 kg m-3) than in 1997. In contrast, the change in the North Atlantic Deep Water has complicated spatial structure and is almost indistinguishable from zero at 95% confidence. The resulting divergence in vertical displacement of the isopycnals modifies the local density stratification. At its peak, the local squared buoyancy frequency (N2) near the canyon is reduced by about 20% from 1997 to 2014. Similar reduction is found in the basinwide averaged profiles over the Mid-Atlantic Ridge flank along 25°W in years 1989, 2005, and 2014. The observed changes in density stratification have important implications for internal tide generation and dissipation.

  2. On the main anhydrite scenario, illustrated by the example of the NE flank of the Stassfurt saddle

    International Nuclear Information System (INIS)

    Schwandt, A.; Schilder, C.; Rauche, H.; Franzke, H.J.

    1991-09-01

    The non-chloride successions embedded in the salt of the Zechstein with their geomechanical behaviour which is completely different from that of the salt rock play an important part in the assessment of the concrete safety situation in the salt mine destined to serve as a repository. The literature study of this report presents a safety-related assessment of the main anhydrite using the example of the NE flank of the Stassfurt saddle, on the basis of exploratory data and experience and documented data obtained by the authors of this report. The tectonic effects on the main anhydrite are studied in detail. It is found that geomechanical impacts can lead to healed or closed joints getting damaged and thus loose their tightness to water or gas. The most intensive geomechanical stress on the main anhydrite results from the flooding of mines. It is stated that, making pin-pointed investigations of the geological and hydrogeological conditions, natural or man-made hazards to the safety of a repository can be well recognized, characterized, and mastered. (orig./HP) [de

  3. Revealing the hidden faults in the SE flank of Mt. Etna using radon in-soil gas measurement.

    Science.gov (United States)

    Johnová, K; Thinová, L; Giammanco, S

    2014-07-01

    Although there are many methods for investigating tectonic structures, many faults remain hidden, and they can endanger the life and property of people living along them. The slopes of volcanoes are covered with such hidden faults, near which strong earthquakes and gas releases can appear. Revealing hidden faults can therefore contribute significantly to the protection of people living in volcanic areas. In the study, seven different techniques were used for making measurements of in-soil radon concentrations in order to search for hidden faults on the SE flank of the Mt. Etna volcano. These reported methods had previously been proved to be useful tools for investigating fault structures. The main aim of the experiment presented here was to evaluate the usability of these methods in the geological conditions of the Mt. Etna region, and to find the best place for continual radon monitoring using a permanent station in the near future. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. Friend of GATA (FOG interacts with the nucleosome remodeling and deacetylase complex (NuRD to support primitive erythropoiesis in Xenopus laevis.

    Directory of Open Access Journals (Sweden)

    Mizuho S Mimoto

    Full Text Available Friend of GATA (FOG plays many diverse roles in adult and embryonic hematopoiesis, however the mechanisms by which it functions and the roles of potential interaction partners are not completely understood. Previous work has shown that overexpression of FOG in Xenopus laevis causes loss of blood suggesting that in contrast to its role in mammals, FOG might normally function to repress erythropoiesis in this species. Using loss-of-function analysis, we demonstrate that FOG is essential to support primitive red blood cell (RBC development in Xenopus. Moreover, we show that it is specifically required to prevent excess apoptosis of circulating primitive RBCs and that in the absence of FOG, the pro-apoptotic gene Bim-1 is strongly upregulated. To identify domains of FOG that are essential for blood development and, conversely, to begin to understand the mechanism by which overexpressed FOG represses primitive erythropoiesis, we asked whether FOG mutants that are unable to interact with known co-factors retain their ability to rescue blood formation in FOG morphants and whether they repress erythropoiesis when overexpressed in wild type embryos. We find that interaction of FOG with the Nucleosome Remodeling and Deacetylase complex (NuRD, but not with C-terminal Binding Protein, is essential for normal primitive RBC development. In contrast, overexpression of all mutant and wild type constructs causes a comparable repression of primitive erythropoiesis. Together, our data suggest that a requirement for FOG and its interaction with NuRD during primitive erythropoiesis are conserved in Xenopus and that loss of blood upon FOG overexpression is due to a dominant-interfering effect.

  5. Friend of GATA (FOG) interacts with the nucleosome remodeling and deacetylase complex (NuRD) to support primitive erythropoiesis in Xenopus laevis.

    Science.gov (United States)

    Mimoto, Mizuho S; Christian, Jan L

    2012-01-01

    Friend of GATA (FOG) plays many diverse roles in adult and embryonic hematopoiesis, however the mechanisms by which it functions and the roles of potential interaction partners are not completely understood. Previous work has shown that overexpression of FOG in Xenopus laevis causes loss of blood suggesting that in contrast to its role in mammals, FOG might normally function to repress erythropoiesis in this species. Using loss-of-function analysis, we demonstrate that FOG is essential to support primitive red blood cell (RBC) development in Xenopus. Moreover, we show that it is specifically required to prevent excess apoptosis of circulating primitive RBCs and that in the absence of FOG, the pro-apoptotic gene Bim-1 is strongly upregulated. To identify domains of FOG that are essential for blood development and, conversely, to begin to understand the mechanism by which overexpressed FOG represses primitive erythropoiesis, we asked whether FOG mutants that are unable to interact with known co-factors retain their ability to rescue blood formation in FOG morphants and whether they repress erythropoiesis when overexpressed in wild type embryos. We find that interaction of FOG with the Nucleosome Remodeling and Deacetylase complex (NuRD), but not with C-terminal Binding Protein, is essential for normal primitive RBC development. In contrast, overexpression of all mutant and wild type constructs causes a comparable repression of primitive erythropoiesis. Together, our data suggest that a requirement for FOG and its interaction with NuRD during primitive erythropoiesis are conserved in Xenopus and that loss of blood upon FOG overexpression is due to a dominant-interfering effect.

  6. Researcher positioning

    DEFF Research Database (Denmark)

    Mørck, Line Lerche; Khawaja, Iram

    2009-01-01

    abstract  This article focuses on the complex and multi-layered process of researcher positioning, specifically in relation to the politically sensitive study of marginalised and ‘othered' groups such as Muslims living in Denmark. We discuss the impact of different ethnic, religious and racial...... political and personal involvement by the researcher, which challenges traditional perspectives on research and researcher positioning. A key point in this regard is the importance of constant awareness of and reflection on the multiple ways in which one's positioning as a researcher influences the research...

  7. The Rock Engineering System (RES) applied to landslide susceptibility zonation of the northeastern flank of Etna: methodological approach and results

    Science.gov (United States)

    Apuani, Tiziana; Corazzato, Claudia

    2015-04-01

    Ground deformations in the northeastern flank of Etna are well known. Despite only a few landslide events have been documented, these have significantly involved and damaged lifelines and buildings. These events are mainly related to the activity of the volcano-tectonic structures and associated seismicity, as in the case of the 2002 reactivation of the Presa landslide during an increased activity of the Pernicana fault system. In order to highlight the areal distribution of potentially unstable slopes based on a detailed, site-specific study of the factors responsible for landslide, and to ultimately contribute to risk management, a landslide susceptibility analysis of the northeastern flank of Etna in the Pernicana area was carried out, and a susceptibility map at 1:10.000 scale was produced, extending over an area of 168 km2. Different methods are proposed in the literature to obtain the regional distribution of potentially unstable slopes, depending on the problem scale, the slope dynamic evolution in the geological context, and the availability of data. Among semi-quantitative approaches, the present research combines the Rock Engineering System (RES) methodology with parameter zonation mapping in a GIS environment. The RES method represents a structured approach to manage a high number of interacting factors involved in the instability problem. A numerically coded, site-specific interaction matrix (IM) analyzes the cause-effect relationship in these factors, and calculates the degree of interactivity of each parameter, normalized by the overall interactivity of the system (weight factor). In the specific Etna case, the considered parameters are: slope attitude, lithotechnical properties (lithology, structural complexity, soil and rock mass quality), land use, tectonic structures, seismic activity (horizontal acceleration) and hydrogeological conditions (groundwater and drainage). Thematic maps are prepared at 1:10.000 scale for each of these parameters, and

  8. An extended study of the low-latitude boundary layer on the dawn and dusk flanks of the magnetosphere

    International Nuclear Information System (INIS)

    Mitchell, D.G.; Kutchko, F.; Williams, D.J.; Eastman, T.E.; Frank, L.A.; Russell, C.T.

    1987-01-01

    The authors present a study of the low-latitude boundary layer (LLBL) using ISEE 1 energetic particle, plasma, and magnetic field data obtained during numerous traversals of the LLBL that occurred on 66 ISEE 1 passes through the magnetospheric flank LLBL region. They use energetic particle distributions to determine dawn and dusk LLBL behavior and topology for varying orientations of the magnetosheath and/or interplanetary magnetic field (M/IMF), for different local times, and for changing levels of geomagnetic activity (Kp). This study corroborates and extends the earlier work of Williams et al. (1985) who presented a detailed study of two (dusk and dawn) ISEE 1 passes through the LLBL region for the case of northward M/IMF. They find that the dawn and dusk LLBL are on closed geomagnetic field lines for northward M/IMF but are on a combination of closed and open field lines for a southward M/IMF. The energetic particle distributions show that cases of reverse-draped field lines in the LLBL are consistent with an open field line topology. In addition, they find that the LLBL is thicker (thinner) for northward (southward) M/IMF and becomes thicker with increasing distance from the subsolar point. LLBL electric fields nominally are in the few (3-5) millivolts per meter range and display an apparent maximum value of ∼10mV/m. These electric fields capture magnetospherically drifting particles as they approach the LLBL and propel them tailward. In this way, the plasma sheet is the dominant source of energetic (approx-gt 10 keV) particles in the LLBL while the magnetosheath appears to be the dominant source for lower-energy (approx-lt 10 keV) LLBL particles

  9. Seismic characteristics and identification of negative flower structures, positive flower structures, and positive structural inversion

    Energy Technology Data Exchange (ETDEWEB)

    Harding, T.P.

    1985-04-01

    Negative and positive flower structures and positive inverted structures imply specific modes of formation, and their distinctive characteristics make them important criteria for the identification of certain structural styles. A negative flower structure from the Andaman Sea consists of a shallow synform bounded by upward-spreading strands of a wrench fault that have mostly normal separations. Paralleling monoclines and oblique, en echelon normal faults flank the divergent wrench fault. A positive flower structure from the Ardmore basin, Oklahoma, consists of a shallow antiform displaced by the upward diverging strands of a wrench fault that have mostly reverse separations. En echelon folds are present on either side of this convergent wrench fault. Positive structural inversion at the Rambutan oil field, South Sumatra basin, has formed a shallow anticlinorium and has partly uplifted the underlying graben. Deeper fault segments bounding the graben have retained their normal fault profiles, but at shallow levels some of these faults have reverse separations.

  10. Radiographic positioning

    International Nuclear Information System (INIS)

    Eisenberg, R.L.; Dennis, C.A.; May, C.

    1989-01-01

    This book concentrates on the routine radiographic examinations commonly performed. It details the wide variety of examinations possible and their place in initial learning and in the radiology department as references for those occasions when an unusual examination is requested. This book provides information ranging from basic terminology to skeletal positioning to special procedures. Positions are discussed and supplemented with a picture of a patient, the resulting radiograph, and a labeled diagram. Immobilization and proper shielding of the patient are also shown

  11. Position encoder

    International Nuclear Information System (INIS)

    Goursky, Vsevolod

    1975-01-01

    A circuitry for deriving the quotient of signal delivered by position-sensitive detectors is described. Digital output is obtained in the form of 10- to 12-bit words. Impact position may be determined with 0.25% accuracy when the dynamic range of the energy signal is less 1:10, and 0.5% accuracy when the dynamic range is 1:20. The division requires an average time of 5μs for 10-bit words

  12. Position encoder

    International Nuclear Information System (INIS)

    Goursky, V.

    1975-05-01

    This paper describes circuitry for deriving the quotient of signals delivered by position-sensitive detectors. Digital output is obtained in the form of 10 to 12 bit words. Impact position may be determined with 0.25% accuracy when the dynamic range of the energy signal is less than 1:10, and 0.5% accuracy when the dynamic range is 1:20. The division requires an average time of 5μs for 10-bit words [fr

  13. Positional games

    CERN Document Server

    Hefetz, Dan; Stojaković, Miloš; Szabó, Tibor

    2014-01-01

    This text serves as a thorough introduction to the rapidly developing field of positional games. This area constitutes an important branch of combinatorics, whose aim it is to systematically develop an extensive mathematical basis for a variety of two-player perfect information games. These range from such popular games as Tic-Tac-Toe and Hex to purely abstract games played on graphs and hypergraphs. The subject of positional games is strongly related to several other branches of combinatorics such as Ramsey theory, extremal graph and set theory, and the probabilistic method. These notes cover a variety of topics in positional games, including both classical results and recent important developments. They are presented in an accessible way and are accompanied by exercises of varying difficulty, helping the reader to better understand the theory. The text will benefit both researchers and graduate students in combinatorics and adjacent fields.

  14. Fusion primer and nested integrated PCR (FPNI-PCR: a new high-efficiency strategy for rapid chromosome walking or flanking sequence cloning

    Directory of Open Access Journals (Sweden)

    Wang Zhen

    2011-11-01

    Full Text Available Abstract Background The advent of genomics-based technologies has revolutionized many fields of biological enquiry. However, chromosome walking or flanking sequence cloning is still a necessary and important procedure to determining gene structure. Such methods are used to identify T-DNA insertion sites and so are especially relevant for organisms where large T-DNA insertion libraries have been created, such as rice and Arabidopsis. The currently available methods for flanking sequence cloning, including the popular TAIL-PCR technique, are relatively laborious and slow. Results Here, we report a simple and effective fusion primer and nested integrated PCR method (FPNI-PCR for the identification and cloning of unknown genomic regions flanked known sequences. In brief, a set of universal primers was designed that consisted of various 15-16 base arbitrary degenerate oligonucleotides. These arbitrary degenerate primers were fused to the 3' end of an adaptor oligonucleotide which provided a known sequence without degenerate nucleotides, thereby forming the fusion primers (FPs. These fusion primers are employed in the first step of an integrated nested PCR strategy which defines the overall FPNI-PCR protocol. In order to demonstrate the efficacy of this novel strategy, we have successfully used it to isolate multiple genomic sequences namely, 21 orthologs of genes in various species of Rosaceace, 4 MYB genes of Rosa rugosa, 3 promoters of transcription factors of Petunia hybrida, and 4 flanking sequences of T-DNA insertion sites in transgenic tobacco lines and 6 specific genes from sequenced genome of rice and Arabidopsis. Conclusions The successful amplification of target products through FPNI-PCR verified that this novel strategy is an effective, low cost and simple procedure. Furthermore, FPNI-PCR represents a more sensitive, rapid and accurate technique than the established TAIL-PCR and hiTAIL-PCR procedures.

  15. Diagnosis of acute flank pain caused by ureteral stones: value of combined direct and indirect signs on IVU and unenhanced helical CT

    International Nuclear Information System (INIS)

    Wang, Li-Jen; Wong, Yon-Cheong; Ng, Chip-Jin; Chen, Jih-Chang; Chiu, Te-Fa

    2004-01-01

    The aim of this study was to assess the usefulness of combined direct and indirect signs on intravenous urography (IVU) and unenhanced helical computed tomography (UHCT) for the diagnosis of ureteral stones in emergency patients with acute flank pain. During an 8-month period, 82 emergency patients with acute flank pain undergoing IVU and UHCT with sufficient clinical follow-up formed the study group. The presence or absence of direct sign (visualization of ureteral stones) and indirect signs on IVU and UHCT was recorded. The diagnostic accuracy of each direct/indirect sign and their combination for the diagnosis of ureteral stones on IVU and UHCT were analyzed and compared. Of the 82 patients, 66 had ureteral stones, four had passed urinary stones prior to imaging and 12 had other diseases. The diagnostic accuracies of direct signs on IVU and UHCT for the diagnosis of ureteral stones were 79.3 and 98.8%, respectively, which was more accurate than that of any single indirect sign on IVU and UHCT. However, the diagnostic accuracy of ureteral stones by IVU increased to 90.2% when using diagnostic criteria requiring the presence of a direct sign or at least three indirect signs, and by UHCT, it increased to 100% when using diagnostic criteria requiring the presence of a direct sign with at least one indirect sign. Therefore, for emergency patients with acute flank pain, the use of the above combinations of direct/indirect signs is useful as the diagnostic criterion for ureteral stones. (orig.)

  16. WE-E-BRE-11: New Method to Simulate DNA Damage Using Ionization Cross-Sections and a Geometrical Nucleosome Model

    International Nuclear Information System (INIS)

    Pater, P; Seuntjens, J; El Naqa, I

    2014-01-01

    Purpose: To obtain probability distributions of various DNA damage types as a function of the incident electron kinetic energy. Methods: Using Geant4-DNA electron ionization cross-sections, we calculated path length distributions for electrons of energies between 10 eV and 1 MeV, defined as the length between two subsequent interactions. These path lengths were then convolved with probability distributions for the creation of same-strand damage, opposite-strand damage, clustered damage, isolated damage, and same DNA strand target damage. These probability distributions of DNA damage were obtained by a Monte Carlo routine calculating probabilities of interaction in DNA targets inside a nucleosome geometrical model. Results represent the probability of a secondary electron, initially created inside a DNA strand target, of undergoing its next interaction: (1) in the opposite strand (DSB), (2) in the same strand (SSB+), (3) in either the opposite or same-strand (clustered), (4) in the same DNA target (multiple-hit) or (5) more than 10 base pairs away (isolated). Results: Electrons with kinetic energy between 50 and 250 eV have a maximal probability of creating DSB, SSB+, clustered damage and multiple-hits in the same target The probabilities for these damage patterns have values of 2.5%, 4.3%, 6.7% and 5.4%, respectively. Isolated damage is most probable between 700 eV to 900 eV with a probability of 0.2%. Conclusion: We obtained DNA damage probability distributions as a function of electron incident energy. We showed that electrons with kinetic energies between 50 and 250 eV have the highest probability of producing complex forms of DNA damage (DSB, SSB+). We also showed that a double ionization within the same DNA target is the most frequent outcome occurring 5% of the time. It is expected that electron slowing down spectra can be convolved with our formalism to calculate source specific DNA damage patterns. Research grants from governments of Canada and Quebec. PP

  17. Researcher Positioning

    DEFF Research Database (Denmark)

    Khawaja, Iram; Mørck, Line Lerche

    2009-01-01

    involvement by the researcher, which challenges traditional perspectives onresearch and researcher positioning. A key point in this regard is the importance ofconstant awareness of and reflection on the multiple ways in which one's positioningas a researcher influences the research process. Studying the other...

  18. Position detector

    International Nuclear Information System (INIS)

    Hayakawa, Toshifumi.

    1985-01-01

    Purpose: To enable to detect the position of an moving object in a control rod position detector, stably in a digital manner at a high accuracy and free from the undesired effects of circumstantial conditions such as the reactor temperature. Constitution: Coils connected in parallel with each other are disposed along the passage of a moving object and variable resistors and relays are connected in series with each of the coils respectively. Light emitting diodes is connected in series with the contacts of the respective relays. The resistance value of the variable resistors are adjusted depending on the changes in the circumstantial conditions and temperature distribution upon carrying out the positional detection. When the object is inserted into a coils, the relevant relay is deenergized, by which the relay contacts are closed to light up the diode. In the same manner, as the object is successively inserted into the coils, the diodes are lighted-up successively thereby enabling highly accurate and stable positional detection in a digital manner, free from the undesired effects of the circumstantial conditions. (Horiuchi, T.)

  19. A 15 Mb large paracentric chromosome 21 inversion identified in Czech population through a pair of flanking duplications.

    Science.gov (United States)

    Drabova, Jana; Trkova, Marie; Hancarova, Miroslava; Novotna, Drahuse; Hejtmankova, Michaela; Havlovicova, Marketa; Sedlacek, Zdenek

    2014-01-01

    Inversions are balanced structural chromosome rearrangements, which can influence gene expression and the risk of unbalanced chromosome constitution in offspring. Many examples of inversion polymorphisms exist in human, affecting both heterochromatic regions and euchromatin. We describe a novel, 15 Mb long paracentric inversion, inv(21)(q21.1q22.11), affecting more than a third of human 21q. Despite of its length, the inversion cannot be detected using karyotyping due to similar band patterns on the normal and inverted chromosomes, and is therefore likely to escape attention. Its identification was aided by the repeated observation of the same pair of 150 kb long duplications present in cis on chromosome 21 in three Czech families subjected to microarray analysis. The finding prompted us to hypothesise that this co-occurrence of two remote duplications could be associated with an inversion of the intervening segment, and this speculation turned out to be right. The inversion was confirmed in a series of FISH experiments which also showed that the second copy of each of the duplications was always located at the opposite end of the inversion. The presence of the same pair of duplications in additional individuals reported in public databases indicates that the inversion may also be present in other populations. Three out of the total of about 4000 chromosomes 21 examined in our sample carried the duplications and were inverted, corresponding to carrier frequency of about 1/660. Although the breakpoints affect protein-coding genes, the occurrence of the inversion in normal parents and siblings of our patients and the occurrence of the duplications in unaffected controls in databases indicate that this rare variant is rather non-pathogenic. The inverted segment carried an identical shared haplotype in the three families studied. The haplotypes, however, diverged very rapidly in the flanking regions, possibly pointing to an ancient founder event at the origin of the

  20. Identification of an estrogen response element in the 3'-flanking region of the murine c-fos protooncogene.

    Science.gov (United States)

    Hyder, S M; Stancel, G M; Nawaz, Z; McDonnell, D P; Loose-Mitchell, D S

    1992-09-05

    We have used transient transfection assays with reporter plasmids expressing chloramphenicol acetyltransferase, linked to regions of mouse c-fos, to identify a specific estrogen response element (ERE) in this protooncogene. This element is located in the untranslated 3'-flanking region of the c-fos gene, 5 kilobases (kb) downstream from the c-fos promoter and 1.5 kb downstream of the poly(A) signal. This element confers estrogen responsiveness to chloramphenicol acetyltransferase reporters linked to both the herpes simplex virus thymidine kinase promoter and the homologous c-fos promoter. Deletion analysis localized the response element to a 200-base pair fragment which contains the element GGTCACCACAGCC that resembles the consensus ERE sequence GGTCACAGTGACC originally identified in Xenopus vitellogenin A2 gene. A synthetic 36-base pair oligodeoxynucleotide containing this c-fos sequence conferred estrogen inducibility to the thymidine kinase promoter. The corresponding sequence also induced reporter activity when present in the c-fos gene fragment 3 kb from the thymidine kinase promoter. Gel-shift experiments demonstrated that synthetic oligonucleotides containing either the consensus ERE or the c-fos element bind human estrogen receptor obtained from a yeast expression system. However, the mobility of the shifted band is faster for the fos-ERE-complex than the consensus ERE complex suggesting that the three-dimensional structure of the protein-DNA complexes is different or that other factors are differentially involved in the two reactions. When the 5'-GGTCA sequence present in the c-fos ERE is mutated to 5'-TTTCA, transcriptional activation and receptor binding activities are both lost. Mutation of the CAGCC-3' element corresponding to the second half-site of the c-fos sequence also led to the loss of receptor binding activity, suggesting that both half-sites of this element are involved in this function. The estrogen induction mediated by either the c-fos or

  1. Maintaining positive

    OpenAIRE

    Gheorghe Gh. IONESCU; Adina Letitia NEGRUSA

    2004-01-01

    Maintaining positive work-force relationships includes in effective labor-management relations and making appropriate responses to current employee issues. Among the major current employee issues are protection from arbitrary dismissal, drug and alcohol abuse, privacy rights and family maters and they impact work. In our paper we discus two problems: first, the meanings of industrial democracy; second, the three principal operational concepts of industrial democracy (1) industrial democracy t...

  2. Comparison of the diagenetic and reservoir quality evolution between the anticline crest and flank of an Upper Jurassic carbonate gas reservoir, Abu Dhabi, United Arab Emirates

    Science.gov (United States)

    Morad, Daniel; Nader, Fadi H.; Gasparrini, Marta; Morad, Sadoon; Rossi, Carlos; Marchionda, Elisabetta; Al Darmaki, Fatima; Martines, Marco; Hellevang, Helge

    2018-05-01

    This petrographic, stable isotopic and fluid inclusion microthermometric study of the Upper Jurassic limestones of an onshore field, Abu Dhabi, United Arab Emirates (UAE) compares diagenesis in flanks and crest of the anticline. The results revealed that the diagenetic and related reservoir quality evolution occurred during three phases, including: (i) eogenesis to mesogenesis 1, during which reservoir quality across the field was either deteriorated or preserved by calcite cementation presumably derived from marine or evolved marine pore waters. Improvement of reservoir quality was due to the formation of micropores by micritization of allochems and creation of moldic/intragranular pores by dissolution of peloids and skeletal fragments. (ii) Obduction of Oman ophiolites and formation of the anticline of the studied field was accompanied by cementation by saddle dolomite and blocky calcite. High homogenization temperatures (125-175 °C) and high salinity (19-26 wt% NaCl eq) of the fluid inclusions, negative δ18OVPDB values (-7.7 to -2.9‰), saddle shape of dolomite, and the presence of exotic cements (i.e. fluorite and sphalerite) suggest that these carbonates were formed by flux of hot basinal brines, probably related to this tectonic compression event. (iii) Mesogenesis 2 during subsidence subsequent to the obduction event, which resulted in extensive stylolitization and cementation by calcite. This calcite cement occluded most of the remaining moldic and inter-/intragranular pores of the flank limestones (water zone) whereas porosity was preserved in the crest. This study contributes to: (1) our understanding of differences in the impact of diagenesis on reservoir quality evolution in flanks and crests of anticlines, i.e. impact of hydrocarbon emplacement on diagenesis, and (2) relating various diagenetic processes to burial history and tectonic events of foreland basins in the Arabian Gulf area and elsewhere.

  3. The 16 November 2006 flank collapse of the south-east crater at Mount Etna, Italy: Study of the deposit and hazard assessment

    Science.gov (United States)

    Norini, Gianluca; de Beni, Emanuela; Andronico, Daniele; Polacci, Margherita; Burton, Mike; Zucca, Francesco

    2009-02-01

    On 16 November 2006 a flank collapse affected the unstable eastern slope of the South-East Crater (SEC) of Mount Etna. The collapse occurred during one of the paroxysmal events with sustained strombolian activity that characterized the August-December 2006 eruption and was triggered by erosion of loose, hydrothermally altered material of the steep south-east sector of SEC from the outpour of lava. The collapse produced a debris avalanche that involved both lithic and juvenile material and resulted in a deposit emplaced on the eastern flank of the volcano up to 1.2 km away from the source. The total volume of the deposit was estimated to be in the order of 330,000-413,000 m3. The reconstruction of the collapse event was simulated using TITAN2D software designed to model granular avalanches and landslides. This approach can be used to estimate areas that may be affected by similar collapse events in the future. The area affected by the 16 November 2006 lateral collapse of SEC was a small portion of the Mount Etna summit area, but the fact that no one was killed or injured should be considered fortuitous. The summit and adjacent areas of the volcano, in fact, are usually visited by many tourists who are not prepared to face this type of danger. The 16 November 2006 collapse points to the need to be prepared for similar events through scientific investigation (analysis of flank instability, numerical simulation of flows) and development of specific civil protection plans.

  4. Genotyping of the 19-bp insertion/deletion polymorphism in the 5' flank of beta-hydroxylase gene by dissociation analysis of allele-specific PCR products

    DEFF Research Database (Denmark)

    Rasmussen, Henrik Berg; Werge, Thomas

    2005-01-01

    The 19-bp insertion/deletion polymorphism in the 5' flank of the dopamine beta-hydroxylase (DBH) gene has been associated with psychiatric disorders. We have developed a simple, reliable and inexpensive closed-tube assay for genotyping of this polymorphism based upon T(m) determination of amplified...... and a conventional approach based upon agarose gel electrophoresis of amplified fragments revealed complete concordance between the two procedures. The insights obtained in this study may be utilized to develop assays based upon dissociation analysis of PCR products for genotyping of other insertion...

  5. Structural analysis of the 5' flanking region of the β-globin gene in African sickle cell anemia patients: Further evidence for three origins of the sickle cell mutation in Africa

    International Nuclear Information System (INIS)

    Chebloune, Y.; Pagnier, J.; Trabuchet, G.; Faure, C.; Verdier, G.; Labie, D.; Nigon, V.

    1988-01-01

    Haplotype analysis of the β-globin gene cluster shows two regions of DNA characterized by nonrandom association of restriction site polymorphisms. These regions are separated by a variable segment containing the repeated sequences (ATTTT) n and (AT) x T y , which might be involved in recombinational events. Studies of haplotypes linked to the sickle cell gene in Africa provide strong argument for three origins of the mutation: Benin, Senegal, and the Central African Republic. The structure of the variable segment in the three African populations was studied by S1 nuclease mapping of genomic DNA, which allows a comparison of several samples. A 1080-base-pair DNA segment was sequenced for one sample from each population. S1 nuclease mapping confirmed the homogeneity of each population with regard to both (ATTTT) n and (AT) x T y repeats. The authors found three additional structures for (AT) x T y correlating with the geographic origin of the patients. Ten other nucleotide positions, 5' and 3' to the (AT) x T y copies, were found to be variable when compared to homologous sequences from human and monkey DNAs. These results allow us to propose an evolutionary scheme for the polymorphisms in the 5' flanking region of the β-globin gene. The results strongly support the hypothesis of three origins for the sickle mutation in Africa

  6. A recurrent deletion syndrome at chromosome bands 2p11.2-2p12 flanked by segmental duplications at the breakpoints and including REEP1.

    Science.gov (United States)

    Stevens, Servi J C; Blom, Eveline W; Siegelaer, Ingrid T J; Smeets, Eric E J G L

    2015-04-01

    We identified an identical and recurrent 9.4-Mbp deletion at chromosome bands 2p11.2-2p12, which occurred de novo in two unrelated patients. It is flanked at the distal and proximal breakpoints by two homologous segmental duplications consisting of low copy repeat (LCR) blocks in direct orientation, which have >99% sequence identity. Despite the fact that the deletion was almost 10 Mbp in size, the patients showed a relatively mild clinical phenotype, that is, mild-to-moderate intellectual disability, a happy disposition, speech delay and delayed motor development. Their phenotype matches with that of previously described patients. The 2p11.2-2p12 deletion includes the REEP1 gene that is associated with spastic paraplegia and phenotypic features related to this are apparent in most 2p11.2-2p12 deletion patients, but not in all. Other hemizygous genes that may contribute to the clinical phenotype include LRRTM1 and CTNNA2. We propose a recurrent but rare 2p11.2-2p12 deletion syndrome based on (1) the identical, non-random localisation of the de novo deletion breakpoints in two unrelated patients and a patient from literature, (2) the patients' phenotypic similarity and their phenotypic overlap with other 2p deletions and (3) the presence of highly identical LCR blocks flanking both breakpoints, consistent with a non-allelic homologous recombination (NAHR)-mediated rearrangement.

  7. SARS-coronavirus spike S2 domain flanked by cysteine residues C822 and C833 is important for activation of membrane fusion

    International Nuclear Information System (INIS)

    Madu, Ikenna G.; Belouzard, Sandrine; Whittaker, Gary R.

    2009-01-01

    The S2 domain of the coronavirus spike (S) protein is known to be responsible for mediating membrane fusion. In addition to a well-recognized cleavage site at the S1-S2 boundary, a second proteolytic cleavage site has been identified in the severe acute respiratory syndrome coronavirus (SARS-CoV) S2 domain (R797). C-terminal to this S2 cleavage site is a conserved region flanked by cysteine residues C822 and C833. Here, we investigated the importance of this well conserved region for SARS-CoV S-mediated fusion activation. We show that the residues between C822-C833 are well conserved across all coronaviruses. Mutagenic analysis of SARS-CoV S, combined with cell-cell fusion and pseudotyped virion infectivity assays, showed a critical role for the core-conserved residues C822, D830, L831, and C833. Based on available predictive models, we propose that the conserved domain flanked by cysteines 822 and 833 forms a loop structure that interacts with components of the SARS-CoV S trimer to control the activation of membrane fusion.

  8. A Boy with an LCR3/4-Flanked 10q22.3q23.2 Microdeletion and Uncommon Phenotypic Features

    Science.gov (United States)

    Petrova, E.; Neuner, C.; Haaf, T.; Schmid, M.; Wirbelauer, J.; Jurkutat, A.; Wermke, K.; Nanda, I.; Kunstmann, E.

    2014-01-01

    The recurrent 10q22.3q23.2 deletion with breakpoints within low copy repeats 3 and 4 is a rare genomic disorder, reported in only 13 patients to date. The phenotype is rather uncharacteristic, which makes a clinical diagnosis difficult. A phenotypic feature described in almost all patients is a delay in speech development, albeit systematic studies are still pending. In this study, we report on a boy with an LCR3/4-flanked 10q22.3q23.2 deletion exhibiting an age-appropriate language development evaluated by a standardized test at an age of 2 years and 3 months. The boy was born with a cleft palate – a feature not present in any of the patients described before. Previously reported cases are reviewed, and the role of the BMPR1A gene is discussed. The phenotype of patients with an LCR3/4-flanked 10q22.3q23.2 deletion can be rather variable, so counseling the families regarding the prognosis of an affected child should be done with caution. Long-term studies of affected children are needed to delineate the natural history of this rare disorder. PMID:24550761

  9. Quinoline-Flanked Diketopyrrolopyrrole Copolymers Breaking through Electron Mobility over 6 cm2 V-1 s-1 in Flexible Thin Film Devices.

    Science.gov (United States)

    Ni, Zhenjie; Dong, Huanli; Wang, Hanlin; Ding, Shang; Zou, Ye; Zhao, Qiang; Zhen, Yonggang; Liu, Feng; Jiang, Lang; Hu, Wenping

    2018-03-01

    Herein, the design and synthesis of novel π-extended quinoline-flanked diketopyrrolopyrrole (DPP) [abbreviated as QDPP] motifs and corresponding copolymers named PQDPP-T and PQDPP-2FT for high performing n-type organic field-effect transistors (OFETs) in flexible organic thin film devices are reported. Serving as DPP-flankers in backbones, quinoline is found to effectively tune copolymer optoelectric properties. Compared with TDPP and pyridine-flanked DPP (PyDPP) analogs, widened bandgaps and strengthened electron deficiency are achieved. Moreover, both hole and electron mobility are improved two orders of magnitude compared to those of PyDPP analogs (PPyDPP-T and PPyDPP-2FT). Notably, featuring an all-acceptor-incorporated backbone, PQDPP-2FT exhibits electron mobility of 6.04 cm 2 V -1 s -1 , among the highest value in OFETs fabricated on flexible substrates to date. Moreover, due to the widened bandgap and strengthened electron deficiency of PQDPP, n-channel on/off ratio over 10 5 with suppressed hole transport is first realized in the ambipolar DPP-based copolymers. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Estimation and optimization of flank wear and tool lifespan in finish turning of AISI 304 stainless steel using desirability function approach

    Directory of Open Access Journals (Sweden)

    Lakhdar Bouzid

    2018-10-01

    Full Text Available The wear of cutting tools remains a major obstacle. The effects of wear are not only antagonistic at the lifespan and productivity, but also harmful with the surface quality. The present work deals with some machinability studies on flank wear, surface roughness, and lifespan in finish turning of AISI 304 stainless steel using multilayer Ti(C,N/Al2O3/TiN coated carbide inserts. The machining experiments are conducted based on the response surface methodology (RSM. Combined effects of three cutting parameters, namely cutting speed, feed rate and cutting time on the two performance outputs (i.e. VB and Ra, and combined effects of two cutting parameters, namely cutting speed and feed rate on lifespan (T, are explored employing the analysis of variance (ANOVA. The relationship between the variables and the technological parameters is determined using a quadratic regression model and optimal cutting conditions for each performance level are established through desirability function approach (DFA optimization. The results show that the flank wear is influenced principally by the cutting time and in the second level by the cutting speed. In addition, it is indicated that the cutting time is the dominant factor affecting workpiece surface roughness followed by feed rate, while lifespan is influenced by cutting speed. The optimum level of input parameters for composite desirability was found Vc1-f1-t1 for VB, Ra and Vc1-f1 for T, with a maximum percentage of error 6.38%.

  11. “Scanning mutagenesis” of the amino acid sequences flanking phosphorylation site 1 of the mitochondrial pyruvate dehydrogenase complex

    Science.gov (United States)

    The mitochondrial pyruvate dehydrogenase complex is regulated by reversible seryl-phosphorylation of the E1alpha subunit by a dedicated, intrinsic kinase. The phospho-complex is reactivated when dephosphorylated by an intrinsic PP2C-type protein phosphatase. Both the position of the phosphorylated...

  12. Europe’s Exposed Right Flank: Countering The Bonds Between Russia And Europe’s Radical Right

    Science.gov (United States)

    2017-04-06

    seeking to bolster national unity and restore societal stability, while simultaneously supporting a liberal capitalist economy .10 However, these parties...global access.11 Meanwhile, while some, but not all, radical right parties advocate socially conservative positions on things such as abortion and...traditional morality, including supporting the patriarchal family, the banning of abortion and a “war against moral depravity.”23 On defense and

  13. Type of faulting and orientation of stress and strain as a function of space and time in Kilauea's south flank, Hawaii

    Science.gov (United States)

    Gillard, D.; Wyss, M.; Okubo, P.

    1996-01-01

    Earthquake focal mechanisms of events occurring between 1972 and 1992 in the south flank of Kilauea volcano, Hawaii, are used to infer the state of stress and strain as a function of time and space. We have determined 870 fault plane solutions from P wave first motion polarities for events with magnitudes ML ??? 2.5 and depth ranging between 6 and 12 km. Faulting is characterized by a mixture of decollement, reverse, and normal faults. Most large earthquakes with magnitude M 7 rupture the decollement plane, since it is the only surface large enough to generate magnitude 7 or larger earthquakes. The percentage of reverse faulting events is high compared to the decollement and normal faulting mechanisms for the period 1972-1983. The percentage of decollement type focal mechanisms becomes dominant after 1983. This pattern of faulting activity suggests that pressure was building up within Kilauea's rift zone prior to the 1983 Puu'Oo eruption. Overall, a single stress orientation with the maximum compressive stress oriented SE perpendicular to the rift and dipping at 45?? is compatible with the coeval existence of decollement, reverse, and normal faults. However, in a crustal volume east of longitude 155??10'W, we find a change of the orientation of ??1 from nearly horizontal to plunging 45?? SE occurring in 1979. This stress rotation suggests magma movements within the aseismic part of Kilauea's east rift zone. The strain and stress orientations are coaxial in the south flank except within the volume where the stress rotation is observed. We observe a change in the relationship between stress and strain directions caused either by the shifting of seismic activity from reverse faults to decollements, while stress stays constant, or by a rotation of stress, while strain remains constant. Assuming that the model of a noncohesive Coulomb wedge is appropriate for Kilauea's south flank, we find that high pore pressures are prevalent along the decollement and within the wedge

  14. Varicella-zoster virus (VZV) origin of DNA replication oriS influences origin-dependent DNA replication and flanking gene transcription.

    Science.gov (United States)

    Khalil, Mohamed I; Sommer, Marvin H; Hay, John; Ruyechan, William T; Arvin, Ann M

    2015-07-01

    The VZV genome has two origins of DNA replication (oriS), each of which consists of an AT-rich sequence and three origin binding protein (OBP) sites called Box A, C and B. In these experiments, the mutation in the core sequence CGC of the Box A and C not only inhibited DNA replication but also inhibited both ORF62 and ORF63 expression in reporter gene assays. In contrast the Box B mutation did not influence DNA replication or flanking gene transcription. These results suggest that efficient DNA replication enhances ORF62 and ORF63 transcription. Recombinant viruses carrying these mutations in both sites and one with a deletion of the whole oriS were constructed. Surprisingly, the recombinant virus lacking both copies of oriS retained the capacity to replicate in melanoma and HELF cells suggesting that VZV has another origin of DNA replication. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Study of Tool Wear Mechanisms and Mathematical Modeling of Flank Wear During Machining of Ti Alloy (Ti6Al4V)

    Science.gov (United States)

    Chetan; Narasimhulu, A.; Ghosh, S.; Rao, P. V.

    2015-07-01

    Machinability of titanium is poor due to its low thermal conductivity and high chemical affinity. Lower thermal conductivity of titanium alloy is undesirable on the part of cutting tool causing extensive tool wear. The main task of this work is to predict the various wear mechanisms involved during machining of Ti alloy (Ti6Al4V) and to formulate an analytical mathematical tool wear model for the same. It has been found from various experiments that adhesive and diffusion wear are the dominating wear during machining of Ti alloy with PVD coated tungsten carbide tool. It is also clear from the experiments that the tool wear increases with the increase in cutting parameters like speed, feed and depth of cut. The wear model was validated by carrying out dry machining of Ti alloy at suitable cutting conditions. It has been found that the wear model is able to predict the flank wear suitably under gentle cutting conditions.

  16. The primary structures of two yeast enolase genes. Homology between the 5' noncoding flanking regions of yeast enolase and glyceraldehyde-3-phosphate dehydrogenase genes.

    Science.gov (United States)

    Holland, M J; Holland, J P; Thill, G P; Jackson, K A

    1981-02-10

    Segments of yeast genomic DNA containing two enolase structural genes have been isolated by subculture cloning procedures using a cDNA hybridization probe synthesized from purified yeast enolase mRNA. Based on restriction endonuclease and transcriptional maps of these two segments of yeast DNA, each hybrid plasmid contains a region of extensive nucleotide sequence homology which forms hybrids with the cDNA probe. The DNA sequences which flank this homologous region in the two hybrid plasmids are nonhomologous indicating that these sequences are nontandemly repeated in the yeast genome. The complete nucleotide sequence of the coding as well as the flanking noncoding regions of these genes has been determined. The amino acid sequence predicted from one reading frame of both structural genes is extremely similar to that determined for yeast enolase (Chin, C. C. Q., Brewer, J. M., Eckard, E., and Wold, F. (1981) J. Biol. Chem. 256, 1370-1376), confirming that these isolated structural genes encode yeast enolase. The nucleotide sequences of the coding regions of the genes are approximately 95% homologous, and neither gene contains an intervening sequence. Codon utilization in the enolase genes follows the same biased pattern previously described for two yeast glyceraldehyde-3-phosphate dehydrogenase structural genes (Holland, J. P., and Holland, M. J. (1980) J. Biol. Chem. 255, 2596-2605). DNA blotting analysis confirmed that the isolated segments of yeast DNA are colinear with yeast genomic DNA and that there are two nontandemly repeated enolase genes per haploid yeast genome. The noncoding portions of the two enolase genes adjacent to the initiation and termination codons are approximately 70% homologous and contain sequences thought to be involved in the synthesis and processing messenger RNA. Finally there are regions of extensive homology between the two enolase structural genes and two yeast glyceraldehyde-3-phosphate dehydrogenase structural genes within the 5

  17. Computed tomography versus intravenous urography in diagnosis of acute flank pain from urolithiasis: a randomized study comparing imaging costs and radiation dose

    International Nuclear Information System (INIS)

    Thomson, J.M.Z.; Maling, T.M.J.; Glocer, J.; Mark, S.; Abbott, C.

    2001-01-01

    The equivalent sensitivity of non-contrast computed tomography (NCCT) and intravenous urography (IVU) in the diagnosis of suspected ureteric colic has been established. Approximately 50% of patients with suspected ureteric colic do not have a nephro-urological cause for pain. Because many such patients require further imaging studies, NCCT may obviate the need for these studies and, in so doing, be more cost effective and involve less overall radiation exposure. The present study compares the total imaging cost and radiation dose of NCCT versus IVU in the diagnosis of acute flank pain. Two hundred and twenty-four patients (157 men; mean age 45 years; age range 19-79 years) with suspected renal colic were randomized either to NCCT or IVU. The number of additional diagnostic imaging studies, cost (IVU A$ 136; CTU A$ 173), radiation exposure and imaging times were compared. Of 119(53%) patients with renal obstruction, 105 had no nephro-urological causes of pain. For 21 (20%) of these patients an alternative diagnosis was made at the initial imaging, 10 of which were significant. Of 118 IVU patients, 28 (24%) required 32 additional imaging tests to reach a diagnosis, whereas seven of 106 (6%) NCCT patients required seven additional imaging studies. The average total diagnostic imaging cost for the NCCT group was A$181.94 and A$175.46 for the IVU group (P< 0.43). Mean radiation dose to diagnosis was 5.00 mSv (NCCT) versus 3.50 mSv (IVU) (P < 0.001). Mean imaging time was 30 min (NCCT) versus 75 min (IVU) (P < 0.001). Diagnostic imaging costs were remarkably similar. Although NCCT involves a higher radiation dose than IVU, its advantages of faster diagnosis, the avoidance of additional diagnostic imaging tests and its ability to diagnose other causes makes it the study of choice for acute flank pain at Christchurch Hospital. Copyright (2001) Blackwell Science Pty Ltd

  18. Geomicrobiology of Archaeal Communities Isolated from an Off-axis Abyssal Hill Fault Scarp on the East Pacific Rise Flank at 9° 27'N

    Science.gov (United States)

    Ehrhardt, C. J.; Haymon, R.; Holden, P.; Lamontagne, M.

    2003-12-01

    Although heat flow studies suggest that ~70% of the hydrothermal heat loss in the oceans occurs in the abyssal hill terrain on the flanks of mid-ocean ridges, very few off-axis hydrothermal sites have been discovered. In May 2002, sedimentary blowout structures of probable hydrothermal origin were discovered along East Pacific Rise at 9° 27'N on an off-axis abyssal hill bounded by a fault scarp covered with orange-brown microbial flocculations. Recovered samples of these flocculations have presented an opportunity to study the unknown nature and role of thermophilic and hyperthermophilic microbial communities on the ridge flanks. Furthermore, the archaeal communities that we have identified in the samples are useful "microbial tracers" which can be used to locate off-axis areas of moderate-to-high temperature fluid flow (>50° C). In this study, we used molecular techniques to isolate, amplify, and sequence community archaeal RNA sequences from fault scarp flocculations collected with a slurp pump system mounted in the Alvin basket. Molecular phylogenies based on 16S rRNA were constructed. Phylogenetic relationships of isolated clones were used to infer temperature preferences of archaeal communities. We identified 12 clones that clustered within thermophilic or hyperthermophilic clades within Archaea suggesting that moderately high temperature fluid (>50° C) exited the seafloor along this abyssal hill fault scarp. Our studies also suggest that these communities mediate the formation of Fe-sulfide mineral phases. Analysis of the samples with an Environmental Scanning Electron Microscope (ESEM) and X-ray energy dispersive analysis (EDS) revealed unique iron sulfide mineral phases with anomalously low Fe/S ratios in direct association with microbial communities.

  19. The association of SNPs in Hsp90β gene 5' flanking region with thermo tolerance traits and tissue mRNA expression in two chicken breeds.

    Science.gov (United States)

    Chen, Zhuo-Yu; Gan, Jian-Kang; Xiao, Xiong; Jiang, Li-Yan; Zhang, Xi-Quan; Luo, Qing-Bin

    2013-09-01

    Thermo stress induces heat shock proteins (HSPs) expression and HSP90 family is one of them that has been reported to involve in cellular protection against heat stress. But whether there is any association of genetic variation in the Hsp90β gene in chicken with thermo tolerance is still unknown. Direct sequencing was used to detect possible SNPs in Hsp90β gene 5' flanking region in 3 chicken breeds (n = 663). Six mutations, among which 2 SNPs were chosen and genotypes were analyzed with PCR-RFLP method, were found in Hsp90β gene in these 3 chicken breeds. Association analysis indicated that SNP of C.-141G>A in the 5' flanking region of the Hsp90β gene in chicken had some effect on thermo tolerance traits, which may be a potential molecular marker of thermo tolerance, and the genotype GG was the thermo tolerance genotype. Hsp90β gene mRNA expression in different tissues detected by quantitative real-time PCR assay were demonstrated to be tissue dependent, implying that different tissues have distinct sensibilities to thermo stress. Besides, it was shown time specific and varieties differences. The expression of Hsp90β mRNA in Lingshan chickens in some tissues including heart, liver, brain and spleen were significantly higher or lower than that of White Recessive Rock (WRR). In this study, we presume that these mutations could be used in marker assisted selection for anti-heat stress chickens in our breeding program, and WRR were vulnerable to tropical thermo stress whereas Lingshan chickens were well adapted.

  20. What happens along the flank and corner of a continental indenter? Insights from the easternmost Himalayan orogen and constraints on the models of the India-Asia collision

    Science.gov (United States)

    Haproff, P. J.; Yin, A.; Zuza, A. V.

    2017-12-01

    Investigations of continental collisions often focus on thrust belts oriented perpendicular to the plate-convergence direction and exclude belts that bound the flanks of a continental indenter despite being crucial to understanding the collisional process. Research of the Himalayan orogen, for example, has mostly centered on the east-trending thrust belt between the eastern and western syntaxes, resulting in inadequate examination of the north-trending Indo-Burma Ranges located along the eastern margin of India. To better understand the development of the entire Himalayan orogenic system, we conducted field mapping across the Northern Indo-Burma Range (NIBR), situated at the intersection of the eastern Himalaya and Indo-Burma Ranges. Our research shows that major lithologic units and thrust faults of the Himalaya extend to the NIBR, suggesting a shared geologic evolution. The structural framework of the NIBR consists of a southwest-directed thrust belt cored by a hinterland-dipping duplex, like the Himalaya. However, the Northern Indo-Burma orogen is distinct based on (1) the absence of the Tethyan Himalayan Sequence and southern Gangdese batholith, (2) the absence of the South Tibetan detachment, (3) crustal shortening greater than 80%, (4) an incredibly narrow orogen width of 7-33 km, (5) exposure of an ophiolitic mélange complex as a klippe, (6) and right-slip shear along the active range-bounding thrust fault. Furthermore, lithospheric deformation along the flank and northeast corner of India is characterized by right-slip transpression partitioned between the thrust belt and right-slip faults. Such a regime is interpreted to accommodate both contraction and clockwise rotation of Tibetan lithosphere around India, consistent with existing continuum deformation and rotation models.

  1. Investigation of the 5' flanking region and exon 3 polymorphisms of IGF-1 gene showed moderate association with semen quality in Sanjabi breed rams.

    Science.gov (United States)

    Bakhtiar, R; Abdolmohammadi, A; Hajarian, H; Nikousefat, Z; Kalantar-Neyestanaki, D

    2017-12-01

    In this study, semen samples were collected from 96 Sanjabi rams in order to investigate the IGF-1 gene polymorphisms and their relationship with the characteristics of semen quality and testicular size. The dimensions of scrotal length, width and circumference were measured during autumn and spring over two years. Blood samples were simultaneously collected from jugular vein to extract DNA. PCR was performed using specific primers to amplify 294 and 272bp fragments including 5' regulatory region and exon 3 of IGF-1 gene, respectively. PCR products were digested by BFOI and Eco88l restriction enzymes, respectively. Two genotypes including AA (194 and 100bp), AB (294, 194 and 100bp) and all possible genotypes including CC (182 and 90bp), CT (272, 182, and 90bp) and TT (272bp) were observed for 5' flanking region and exon 3 of IGF-1 gene, respectively. The significant differences among IGF-1 genotypes for testicular dimensions were not observed. However, the polymorphism of 5' flanking region in the studied population had significant effect on individual motility and percent morphology traits. Animals with AB genotype had significantly higher individual motility compared with AA genotype (P IGF-1 gene had significant effect on individual motility, concentration, morphology and water test traits. Animals with CT genotype had the highest sperm concentration (P IGF-1 genotypes. It might be concluded that polymorphisms in IGF-1gene can be considered to develop male fertility in future and for using in selection process of better animals under masker assisted selection programs. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Frictional processes during flank motion at Mount Etna (Italy): experimental characterisation of slip on similar and dissimilar volcanic and sedimentary rocks.

    Science.gov (United States)

    Rozanski, Wojciech; Lavallee, Yan; Kendrick, Jackie; Castagna, Angela; Mitchell, Thomas; Heap, Michael; Vinciguerra, Sergio; Hirose, Takehiro; Dingwell, Donald

    2015-04-01

    The edifice of Mount Etna (Italy) is structurally unstable, exhibiting a near continuous ESE seaward sliding along a set of faults due to interplay between regional tectonics, gravity instability and magma intrusion. Continuous seismic and ground deformation monitoring reveals the resulting large-scale flank motion at variable rates. The mechanisms controlling this faulting kinetic remains, however, poorly constrained. Examination of the fault zones reveals a range of rock types along the different fault segments: fresh and altered basalt, clay and limestone. As lithological contrasts can jeopardise the structural stability of an edifice, we experimentally investigate the frictional properties of these rocks using low- to high-velocity-rotary shear tests on similar and dissimilar rocks to better understand episodes of slow flank motion as well as rapid and catastrophic sector collapse events. The first set of experiments was performed at velocities up to 1.2 m/s and at normal stresses of 1.5 MPa, commensurate with depths of the contacts seen in the Etna edifice. Friction experiments on clay gouge shows the strong rate-weakening dependence of slip in this material as well as the release of carbon dioxide. Friction experiments on solid rocks show a wider range of mechanical behaviour. At high velocity (>0.6 m/s) volcanic rocks tend to melt whereas the clay and limestone do not; rather they decarbonate, which prevents the rock from achieving the temperature required for melting. Experiments on dissimilar rocks clearly show that composition of host rocks affects the composition and viscosity of the resultant frictional melt, which can have a dramatic effect on shear stress leading to fault weakening or strengthening depending on the combination of host rock samples. A series of low- to moderate-slip velocity experiments is now being conducted to complement our dataset and provide a more complete rock friction model applicable to Mount Etna.

  3. Benign positional vertigo

    Science.gov (United States)

    Vertigo - positional; Benign paroxysmal positional vertigo; BPPV: dizziness- positional ... Benign positional vertigo is also called benign paroxysmal positional vertigo (BPPV). It is caused by a problem in the inner ear. ...

  4. Estimating volume of deposits associated with landslides on volcanic landscapes in the SW flank of the volcano Pico de Orizaba, Puebla-Veracruz

    Directory of Open Access Journals (Sweden)

    Gabriel Legorreta Paulín

    2017-03-01

    Full Text Available Landslides that occur along river systems are very common and have the potential to cause harm to human, to its infrastructure or affect their socio-economic activity. This dynamic is magnified in territories where morphological contrasts are very marked; as in the border between the mountains and subhorizontal land. This is especially true for volcanic terrains where volcanic activity can trigger voluminous landslides along stream systems by sector and flank collapse and where high seasonal rainfall on terrains covered by poorly consolidated materials produces small but hazardous landslides and debris flows that occur continually along stream systems during the volcanic repose periods. Those type of landslides can deliver volumes of hundreds and millions cubic meters that create a potentially hazardous situation for people and property down the valleys. The study of landslides in volcanic terrains through a Geographic Information System (GIS and under a geomorphological criterion, have allowed to develop a comprehensive methodology linked to the development of multi-temporal inventory, with susceptibility and volume estimation of displaced material. The aim of this research is to develop a method (protocol for landslide susceptibility and landslide volume assessment of potentially unstable volcanic landscapes in order to be helpful in mitigating landslide damages to human settlements. Pico de Orizaba volcano is the highest volcano in Mexico. The volcano has been affected by large flank collapse landslides throughout its geological history. These events have partially destroyed the cone as it happened in Bezymianny volcano and St. Elena volcano. In this volcano, the risk associated with landslide and debris flows, is increased by the growing of human settlements along the hillslopes and by the subsistence agriculture, and deforestation. This situation is favored by a volcanic calm that has lasted 147 years, approximate. These conditions create a

  5. Supine Percutaneous Nephrolithotripsy in Double-S Position.

    Science.gov (United States)

    Giusti, Giuseppe; De Lisa, Antonello

    2018-01-01

    At present, the percutaneous nephrolithotripsy (PCNL) is performed both in supine and in prone position. The aim of this paper is to describe an innovative position during PCNL. We describe a supine position. The patient's legs are slightly abducted at the hips. The thorax is laterally tilted (inclination 30°-35°) and kept in the right position by one or two gel pads placed between the scapula and the vertebrae. External genitalia can be accessed at any time, so that it is always possible to use flexible instruments in the upper urinary tract. We used this position for a period of 12 months to treat with PCNL 45 patients with renal lithiasis. All the procedures were successfully completed without complications, using the position we are describing. The following are some of its benefits: an easier positioning of the patient; a better exposure of the flank for an easier access to the posterior renal calyces of the kidney; a lower risk of pressure injuries compared to positions foreseeing the use of knee crutches; the possibility of combined procedures (ECIRS) through the use of flexible instruments; and a good fluoroscopic visualization of the kidney not overlapped by the vertebrae. This position is effective, safe, easy, and quick to prepare and allows for combined anterograde/retrograde operations.

  6. Supine Percutaneous Nephrolithotripsy in Double-S Position

    Directory of Open Access Journals (Sweden)

    Giuseppe Giusti

    2018-01-01

    Full Text Available Background. At present, the percutaneous nephrolithotripsy (PCNL is performed both in supine and in prone position. The aim of this paper is to describe an innovative position during PCNL. Methods. We describe a supine position. The patient’s legs are slightly abducted at the hips. The thorax is laterally tilted (inclination 30°–35° and kept in the right position by one or two gel pads placed between the scapula and the vertebrae. External genitalia can be accessed at any time, so that it is always possible to use flexible instruments in the upper urinary tract. We used this position for a period of 12 months to treat with PCNL 45 patients with renal lithiasis. Results. All the procedures were successfully completed without complications, using the position we are describing. The following are some of its benefits: an easier positioning of the patient; a better exposure of the flank for an easier access to the posterior renal calyces of the kidney; a lower risk of pressure injuries compared to positions foreseeing the use of knee crutches; the possibility of combined procedures (ECIRS through the use of flexible instruments; and a good fluoroscopic visualization of the kidney not overlapped by the vertebrae. Conclusions. This position is effective, safe, easy, and quick to prepare and allows for combined anterograde/retrograde operations.

  7. Two large-scale analyses of Ty1 LTR-retrotransposon de novo insertion events indicate that Ty1 targets nucleosomal DNA near the H2A/H2B interface

    Directory of Open Access Journals (Sweden)

    Bridier-Nahmias Antoine

    2012-12-01

    Full Text Available Abstract Background Over the years, a number of reports have revealed that Ty1 integration occurs in a 1-kb window upstream of Pol III-transcribed genes with an approximate 80-bp periodicity between each integration hotspot and that this targeting requires active Pol III transcription at the site of integration. However, the molecular bases of Ty1 targeting are still not understood. Findings The publications by Baller et al. and Mularoni et al. in the April issue of Genome Res. report the first high-throughput sequencing analysis of Ty1 de novo insertion events. Their observations converge to the same conclusion, that Ty1 targets a specific surface of the nucleosome at he H2A/H2B interface. Conclusion This discovery is important, and should help identifying factor(s involved in Ty1 targeting. Recent data on transposable elements and retroviruses integration site choice obtained by large-scale analyses indicate that transcription and chromatin structure play an important role in this process. The studies reported in this commentary add a new evidence of the importance of chromatin in integration selectivity that should be of interest for everyone interested in transposable elements integration.

  8. Deposition of newly synthesized histones: new histones H2A and H2B do not deposit in the same nucleosome with new Histones H3 and H4

    International Nuclear Information System (INIS)

    Jackson, V.

    1987-01-01

    The authors have developed procedures to study histone-histone interactions during the deposition of histones in replicating cells. Cells are labeled for 60 min with dense amino acids, and subsequently, the histones within the nucleosomes are cross-linked into an octameric complex with formaldehyde. These complexes are sedimented to equilibrium in density gradients and octamer and dioctamer complexes separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. With reversal of the cross-link, the distribution of the individual density-labeled histones in the octamer is determined. Newly synthesized H3 and H4 deposits as a tetramer and are associated with old H2A and H2B. Newly synthesized H2A and H2B deposit as a dimer associated with old H2A, H2B, H3, and H4. The significance of these results with respect to the dynamics of histone interactions in the nucleus is discussed. Control experiments are presented to test for artifactual formation of these complexes during preparative procedures. In addition, reconstitution experiments were performed to demonstrate that the composition of these octameric complexes can be determined from their distribution of density gradients

  9. Unenhanced helical computed tomography vs intravenous urography in patients with acute flank pain: accuracy and economic impact in a randomized prospective trial

    International Nuclear Information System (INIS)

    Pfister, S.A.; Deckart, A.; Laschke, S.; Gasser, T.C.; Dellas, S.; Otto, U.; Buitrago, C.; Wiesner, W.; Bongartz, G.; Roth, J.

    2003-01-01

    Unenhanced helical computed tomography (UHCT) has evolved into a well-accepted alternative to intravenous urography (IVU) in patients with acute flank pain and suspected ureterolithiasis. The purpose of our randomized prospective study was to analyse the diagnostic accuracy of UHCT vs IVU in the normal clinical setting with special interest on economic impact, applied radiation dose and time savings in patient management. A total of 122 consecutive patients with acute flank pain suggestive of urolithiasis were randomized for UHCT (n=59) or IVU (n=63). Patient management (time, contrast media), costs and radiation dose were analysed. The films were independently interpreted by four radiologists, unaware of previous findings, clinical history and clinical outcome. Alternative diagnoses if present were assessed. Direct costs of UHCT and IVU are nearly identical (310/309 Euro). Indirect costs are much lower for UHCT because it saves examination time and when performed immediately initial abdominal plain film (KUB) and sonography are not necessary. Time delay between access to the emergency room and start of the imaging procedure was 32 h 7 min for UHCT and 36 h 55 min for IVU. The UHCT took an average in-room time of 23 min vs 1 h 21 min for IVU. Mild to moderate adverse reactions for contrast material were seen in 3 (5%) patients. The UHCT was safe, as no contrast material was needed. The mean applied radiation dose was 3.3 mSv for IVU and 6.5 mSv for UHCT. Alternative diagnoses were identified in 4 (7%) UHCT patients and 3 (5%) IVU patients. Sensitivity and specificity of UHCT and IVU was 94.1 and 94.2%, and 85.2 and 90.4%, respectively. In patients with suspected renal colic KUB and US may be the least expensive and most easily accessable modalities; however, if needed and available, UHCT can be considered a better alternative than IVU because it has a higher diagnostic accuracy and a better economic impact since it is more effective, faster, less expensive and less

  10. Evolution of a behavior-linked microsatellite-containing element in the 5' flanking region of the primate AVPR1A gene.

    Science.gov (United States)

    Donaldson, Zoe R; Kondrashov, Fyodor A; Putnam, Andrea; Bai, Yaohui; Stoinski, Tara L; Hammock, Elizabeth A D; Young, Larry J

    2008-06-23

    The arginine vasopressin V1a receptor (V1aR) modulates social cognition and behavior in a wide variety of species. Variation in a repetitive microsatellite element in the 5' flanking region of the V1aR gene (AVPR1A) in rodents has been associated with variation in brain V1aR expression and in social behavior. In humans, the 5' flanking region of AVPR1A contains a tandem duplication of two approximately 350 bp, microsatellite-containing elements located approximately 3.5 kb upstream of the transcription start site. The first block, referred to as DupA, contains a polymorphic (GT)25 microsatellite; the second block, DupB, has a complex (CT)4-(TT)-(CT)8-(GT)24 polymorphic motif, known as RS3. Polymorphisms in RS3 have been associated with variation in sociobehavioral traits in humans, including autism spectrum disorders. Thus, evolution of these regions may have contributed to variation in social behavior in primates. We examined the structure of these regions in six ape, six monkey, and one prosimian species. Both tandem repeat blocks are present upstream of the AVPR1A coding region in five of the ape species we investigated, while monkeys have only one copy of this region. As in humans, the microsatellites within DupA and DupB are polymorphic in many primate species. Furthermore, both single (lacking DupB) and duplicated alleles (containing both DupA and DupB) are present in chimpanzee (Pan troglodytes) populations with allele frequencies of 0.795 and 0.205 for the single and duplicated alleles, respectively, based on the analysis of 47 wild-caught individuals. Finally, a phylogenetic reconstruction suggests two alternate evolutionary histories for this locus. There is no obvious relationship between the presence of the RS3 duplication and social organization in primates. However, polymorphisms identified in some species may be useful in future genetic association studies. In particular, the presence of both single and duplicated alleles in chimpanzees provides a

  11. Modeling growth of Atlantic cod larvae on the southern flank of Georges Bank in the tidal-front circulation during May 1999

    Science.gov (United States)

    Lough, R. G.; Broughton, E. A.; Buckley, L. J.; Incze, L. S.; Pehrson Edwards, K.; Converse, R.; Aretxabaleta, A.; Werner, F. E.

    2006-11-01

    Cruises were conducted in spring 1999 to describe the interaction between tidal-front processes and the transport, retention, and growth of cod larvae and their prey during the seasonal transition to a stratified water-column along the southern flank of Georges Bank. All the physical and biological observations were integrated in coupled circulation-trophodynamic simulations. The three-dimensional circulation fields were modeled using data assimilation methods described in Aretxabaleta et al. [2005. Data assimilative hindcast on the Southern Flank of Georges Bank during May 1999: frontal circulation and implications. Continental Shelf Research 25, 849-874]. The individual-based model (IBM) of Lough et al. [2005. A general biophysical model of larval cod growth applied to populations on Georges Bank. Fisheries Oceanography 14, 241-262] was used to consider trophodynamic effects on the growth and survival of larval cod. Prey fields were specified for mixed and stratified water columns from field surveys and allowed to adjust in the circulation model. Encounter and ingestion rates of larvae were functions of prey concentration, larval search patterns, light, swimming speeds of predator and prey, and turbulence. Model outputs provide hourly depth-dependent estimates of growth rates, prey biomass ingested, and larval length and weight. Simulations were conducted along a 2-D transect across the tidal front, from mixed to stratified water columns, before and after a wind event. Pre-storm, observed larval cod growth rates, based on RNA-DNA analysis, were highest in the surface 20 m at the stratified and front stations. Post-storm, larval growth rates decreased 1-2% d -1 at the stratified and front stations, corresponding with a <1 °C decrease in temperature. At the mixed station, there was no apparent difference in growth rates with depth, either before or after the storm. Simulations indicate that maximum larval growth rates can occur at the tidal-mixing front due to the

  12. Sequencing analysis of ghrelin gene 5' flanking region: relations between the sequence variants, fasting plasma total ghrelin concentrations, and body mass index.

    Science.gov (United States)

    Vartiainen, Johanna; Kesäniemi, Y Antero; Ukkola, Olavi

    2006-10-01

    Ghrelin is a 28-amino-acid peptide with several functions linked to energy metabolism. Low ghrelin plasma concentrations are associated with obesity, hypertension, and type 2 diabetes mellitus, whereas high concentrations reflect states of negative energy balance. Several studies addressing the hormonal and neural regulation of ghrelin gene expression have been carried out, but the role of genetic factors in the regulation of ghrelin plasma levels remains unclear. To elucidate the role of genetic factors in the regulation of ghrelin expression, we screened 1657 nucleotides of the ghrelin gene 5' flanking region (promoter and possible regulatory sites) for new sequential variations from patient samples with low (n = 50) and high (n = 50) fasting plasma total ghrelin concentrations (low- and high-ghrelin groups). Eleven single nucleotide polymorphisms (SNPs), 3 of which were rare variants (allelic frequency less than 1%) were found in our population. The genotype distribution patterns of the SNPs did not differ between the study groups, except for SNP-501A>C (P = .039). In addition, the SNP-01A>C was associated with body mass index (BMI) (P = .018). This variant was studied further in our large and well-defined Oulu Project Elucidating Risk for Atherosclerosis (OPERA) cohort (n = 1045) by the restriction fragment length polymorphism (RFLP) technique. No significant association of SNP-501A>C genotypes with fasting ghrelin plasma concentrations was found in the whole OPERA population. However, the association of this SNP with BMI and with waist circumference reached statistical significance in OPERA (P = .047 and .049, respectively), remaining of borderline significance for BMI after adjustments (P = .055). The results indicate that factors other than the 11 SNPs found in this study in the 5' flanking region of ghrelin gene are the main determinants of ghrelin plasma levels. However, SNP-501 A>C genotype distribution seems to be different in subjects having the highest

  13. Evolution of a behavior-linked microsatellite-containing element in the 5' flanking region of the primate AVPR1A gene

    Directory of Open Access Journals (Sweden)

    Bai Yaohui

    2008-06-01

    Full Text Available Abstract Background The arginine vasopressin V1a receptor (V1aR modulates social cognition and behavior in a wide variety of species. Variation in a repetitive microsatellite element in the 5' flanking region of the V1aR gene (AVPR1A in rodents has been associated with variation in brain V1aR expression and in social behavior. In humans, the 5' flanking region of AVPR1A contains a tandem duplication of two ~350 bp, microsatellite-containing elements located approximately 3.5 kb upstream of the transcription start site. The first block, referred to as DupA, contains a polymorphic (GT25 microsatellite; the second block, DupB, has a complex (CT4-(TT-(CT8-(GT24 polymorphic motif, known as RS3. Polymorphisms in RS3 have been associated with variation in sociobehavioral traits in humans, including autism spectrum disorders. Thus, evolution of these regions may have contributed to variation in social behavior in primates. We examined the structure of these regions in six ape, six monkey, and one prosimian species. Results Both tandem repeat blocks are present upstream of the AVPR1A coding region in five of the ape species we investigated, while monkeys have only one copy of this region. As in humans, the microsatellites within DupA and DupB are polymorphic in many primate species. Furthermore, both single (lacking DupB and duplicated alleles (containing both DupA and DupB are present in chimpanzee (Pan troglodytes populations with allele frequencies of 0.795 and 0.205 for the single and duplicated alleles, respectively, based on the analysis of 47 wild-caught individuals. Finally, a phylogenetic reconstruction suggests two alternate evolutionary histories for this locus. Conclusion There is no obvious relationship between the presence of the RS3 duplication and social organization in primates. However, polymorphisms identified in some species may be useful in future genetic association studies. In particular, the presence of both single and duplicated

  14. Inherited discontinuities and fault kinematics of a multiphase, non-colinear extensional setting: Subsurface observations from the South Flank of the Golfo San Jorge basin, Patagonia

    Science.gov (United States)

    Paredes, José Matildo; Aguiar, Mariana; Ansa, Andrés; Giordano, Sergio; Ledesma, Mario; Tejada, Silvia

    2018-01-01

    We use three-dimensional (3D) seismic reflection data to analyze the structural style, fault kinematics and growth fault mechanisms of non-colinear normal fault systems in the South Flank of the Golfo San Jorge basin, central Patagonia. Pre-existing structural fabrics in the basement of the South Flank show NW-SE and NE-SW oriented faults. They control the location and geometry of wedge-shaped half grabens from the "main synrift phase" infilled with Middle Jurassic volcanic-volcaniclastic rocks and lacustrine units of Late Jurassic to Early Cretaceous age. The NE-striking, basement-involved normal faults resulted in the rapid establishment of fault lenght, followed by gradual increasing in displacement, and minor reactivation during subsequent extensional phases; NW-striking normal faults are characterized by fault segments that propagated laterally during the "main rifting phase", being subsequently reactivated during succesive extensional phases. The Aptian-Campanian Chubut Group is a continental succession up to 4 km thick associated to the "second rifting stage", characterized by propagation and linkage of W-E to WNW-ESE fault segments that increase their lenght and displacement in several extensional phases, recognized by detailed measurement of current throw distribution of selected seismic horizons along fault surfaces. Strain is distributed in an array of sub-parallel normal faults oriented normal to the extension direction. A Late Cretaceous-Paleogene (pre-late Eocene) extensional event is characterized by high-angle, NNW-SSE to NNE-SSW grabens coeval with intraplate alkali basaltic volcanism, evidencing clockwise rotation of the stress field following a ∼W-E extension direction. We demonstrate differences in growth fault mechanisms of non-colinear fault populations, and highlight the importance of follow a systematic approach to the analysis of fault geometry and throw distribution in a fault network, in order to understand temporal-spatial variations

  15. Geomorphic evidence for post-10 Ma uplift of the western flank of the central Andes 18°30'-22°S

    Science.gov (United States)

    Hoke, Gregory D.; Isacks, Bryan L.; Jordan, Teresa E.; Blanco, NicoláS.; Tomlinson, Andrew J.; Ramezani, Jahandar

    2007-10-01

    The western Andean mountain front forms the western edge of the central Andean Plateau. Between 18.5° and 22°S latitude, the mountain front has ˜3000 m of relief over ˜50 km horizontal distance that has developed in the absence of major local Neogene deformation. Models of the evolution of the plateau, as well as paleoaltimetry estimates, all call for continued large-magnitude uplift of the plateau surface into the late Miocene (i.e., younger than 10 Ma). Longitudinal river profiles from 20 catchments that drain the western Andean mountain front contain several streams with knickpoint-bounded segments that we use to reconstruct the history of post-10 Ma surface uplift of the western flank of the central Andean Plateau. The generation of knickpoints is attributed to tectonic processes and is not a consequence of base level change related to Pacific Ocean capture, eustatic change, or climate change as causes for creating the knickpoint-bounded stream segments observed. Minor valley-filling alluvial gravels intercalated with the 5.4 Ma Carcote ignimbrite suggest uplift related river incision was well under way by 5.4 Ma. The maximum age of river incision is provided by the regionally extensive, approximately 10 Ma El Diablo-Altos de Pica paleosurface. The river profiles reveal that relative surface uplift of at least1 km occurred after 10 Ma.

  16. Linear and exponential TAIL-PCR: a method for efficient and quick amplification of flanking sequences adjacent to Tn5 transposon insertion sites.

    Science.gov (United States)

    Jia, Xianbo; Lin, Xinjian; Chen, Jichen

    2017-11-02

    Current genome walking methods are very time consuming, and many produce non-specific amplification products. To amplify the flanking sequences that are adjacent to Tn5 transposon insertion sites in Serratia marcescens FZSF02, we developed a genome walking method based on TAIL-PCR. This PCR method added a 20-cycle linear amplification step before the exponential amplification step to increase the concentration of the target sequences. Products of the linear amplification and the exponential amplification were diluted 100-fold to decrease the concentration of the templates that cause non-specific amplification. Fast DNA polymerase with a high extension speed was used in this method, and an amplification program was used to rapidly amplify long specific sequences. With this linear and exponential TAIL-PCR (LETAIL-PCR), we successfully obtained products larger than 2 kb from Tn5 transposon insertion mutant strains within 3 h. This method can be widely used in genome walking studies to amplify unknown sequences that are adjacent to known sequences.

  17. The uncharacterized gene 1700093K21Rik and flanking regions are correlated with reproductive isolation in the house mouse, Mus musculus.

    Science.gov (United States)

    Kass, David H; Janoušek, Václav; Wang, Liuyang; Tucker, Priscilla K

    2014-06-01

    Reproductive barriers exist between the house mouse subspecies, Mus musculus musculus and M. m. domesticus, members of the Mus musculus species complex, primarily as a result of hybrid male infertility, and a hybrid zone exists where their ranges intersect in Europe. Using single nucleotide polymorphisms (SNPs) diagnostic for the two taxa, the extent of introgression across the genome was previously compared in these hybrid populations. Sixty-nine of 1316 autosomal SNPs exhibited reduced introgression in two hybrid zone transects suggesting maladaptive interactions among certain loci. One of these markers is within a region on chromosome 11 that, in other studies, has been associated with hybrid male sterility of these subspecies. We assessed sequence variation in a 20 Mb region on chromosome 11 flanking this marker, and observed its inclusion within a roughly 150 kb stretch of DNA showing elevated sequence differentiation between the two subspecies. Four genes are associated with this genomic subregion, with two entirely encompassed. One of the two genes, the uncharacterized 1700093K21Rik gene, displays distinguishing features consistent with a potential role in reproductive isolation between these subspecies. Along with its expression specifically within spermatogenic cells, we present various sequence analyses that demonstrate a high rate of molecular evolution of this gene, as well as identify a subspecies amino acid variant resulting in a structural difference. Taken together, the data suggest a role for this gene in reproductive isolation.

  18. Paleoarchean bedrock lithologies across the Makhonjwa Mountains of South Africa and Swaziland linked to geochemical, magnetic and tectonic data reveal early plate tectonic genes flanking subduction margins

    Directory of Open Access Journals (Sweden)

    Maarten de Wit

    2018-05-01

    Full Text Available The Makhonjwa Mountains, traditionally referred to as the Barberton Greenstone Belt, retain an iconic Paleoarchean archive against which numerical models of early earth geodynamics can be tested. We present new geologic and structural maps, geochemical plots, geo- and thermo-chronology, and geophysical data from seven silicic, mafic to ultramafic complexes separated by major shear systems across the southern Makhonjwa Mountains. All reveal signs of modern oceanic back-arc crust and subduction-related processes. We compare the rates of processes determined from this data and balance these against plate tectonic and plume related models. Robust rates of both horizontal and vertical tectonic processes derived from the Makhonjwa Mountain complexes are similar, well within an order of magnitude, to those encountered across modern oceanic and orogenic terrains flanking Western Pacific-like subduction zones. We conclude that plate tectonics and linked plate-boundary processes were well established by 3.2–3.6 Ga. Our work provides new constraints for modellers with rates of a ‘basket’ of processes against which to test Paleoarchean geodynamic models over a time period close to the length of the Phanerozoic. Keywords: Paleoarchean, Barberton Greenstone Belt, Onverwacht Suite, Geologic bedrock and structural maps, Geochemistry and geophysics, Plate tectonics

  19. Position automatic determination technology

    International Nuclear Information System (INIS)

    1985-10-01

    This book tells of method of position determination and characteristic, control method of position determination and point of design, point of sensor choice for position detector, position determination of digital control system, application of clutch break in high frequency position determination, automation technique of position determination, position determination by electromagnetic clutch and break, air cylinder, cam and solenoid, stop position control of automatic guide vehicle, stacker crane and automatic transfer control.

  20. Positive Psychology: Positive Emotions and Emotional Intelegence

    OpenAIRE

    Miloseva, Lence

    2008-01-01

    The paper focuses on the and emotional intelligence. We try to answer on some questions regarding the role which positive emotions have in our life’s. The broaden-and-build theory (Fredrickson, 1998; 2001) predicts that positive emotions are useful in several ways. They guide present behavior, by broadening one’s attention and cognition, setting the stage for creative, explorative, and innovative pursuits. As well, positive emotions build personal and social resources to help individuals achi...

  1. Methyl CpG level at distal part of heat-shock protein promoter HSP70 exhibits epigenetic memory for heat stress by modulating recruitment of POU2F1-associated nucleosome-remodeling deacetylase (NuRD) complex.

    Science.gov (United States)

    Kisliouk, Tatiana; Cramer, Tomer; Meiri, Noam

    2017-05-01

    Depending on its stringency, exposure to heat in early life leads to either resilience or vulnerability to heat stress later in life. We hypothesized that epigenetic alterations in genes belonging to the cell proteostasis pathways are attributed to long-term responses to heat stress. Epigenetic regulation of the mRNA expression of the molecular chaperone heat-shock protein (HSP) 70 (HSPA2) was evaluated in the chick hypothalamus during the critical period of thermal-control establishment on day 3 post-hatch and during heat challenge on day 10. Both the level and duration of HSP70 expression during heat challenge a week after heat conditioning were more pronounced in chicks conditioned under harsh versus mild temperature. Analyzing different segments of the promoter in vitro indicated that methylation of a distal part altered its transcriptional activity. In parallel, DNA-methylation level of this segment in vivo was higher in harsh- compared to mild-heat-conditioned chicks. Hypermethylation of the HSP70 promoter in high-temperature-conditioned chicks was accompanied by a reduction in both POU Class 2 Homeobox 1 (POU2F1) binding and recruitment of the nucleosome remodeling deacetylase (NuRD) chromatin-remodeling complex. As a result, histone H3 acetylation levels at the HSP70 promoter were higher in harsh-temperature-conditioned chicks than in their mild-heat-conditioned counterparts. These results suggest that methylation level of a distal part of the HSP70 promoter and POU2F1 recruitment may reflect heat-stress-related epigenetic memory and may be useful in differentiating between individuals that are resilient or vulnerable to stress. © 2017 International Society for Neurochemistry.

  2. Want Positive Behavior? Use Positive Language

    Science.gov (United States)

    Wood, Chip; Freeman-Loftis, Babs

    2012-01-01

    Positive adult language is the professional use of words and tone of voice to enable students to learn in an engaged, active way. This includes learning social skills. To guide children toward choosing and maintaining positive behaviors, adults need to carefully choose the words and tone of voice used when speaking to them. Learning to use…

  3. Benign positional vertigo - aftercare

    Science.gov (United States)

    Vertigo - positional - aftercare; Benign paroxysmal positional vertigo - aftercare; BPPV - aftercare; Dizziness - positional vertigo ... Your health care provider may have treated your vertigo with the Epley maneuver . These are head movements ...

  4. Mini-flank supra-12th rib incision for open partial nephrectomy for renal tumor with RENAL nephrometry score ≥10: an innovation of traditional open surgery.

    Science.gov (United States)

    Wang, Hang; Sun, Li-an; Wang, Yiwei; Xiang, Zhuoyi; Zhou, Lin; Guo, Jianming; Wang, Guomin

    2015-04-01

    The skill of supra-12th rib mini-flank approach for open partial nephrectomy (MI-OPN) provides an advanced operative method for renal tumor. Compared with laparoscopic and robotic surgery, it may be a feasible selection for the complex renal tumors. We describe our techniques and results of MI-OPN in complex renal tumors with high RENAL nephrometry score (RENAL nephrometry score ≥10). Fifty-five patients diagnosed with renal tumors between January 2009 and July 2013 were included in this study. Eligibility criteria comprised of patients with complex renal tumor (RENAL score ≥10) being candidates for partial nephrectomy (PN). All patients received MI-OPN and all surgeries were performed by a single urologist. The preoperative workup comprised of medical history, physical examination, and routine laboratory tests. Serum creatinine was recorded preoperatively and 2 to 3 months after operation. Operative time, ischemia time, blood loss, operative and postoperative complications, renal function, and pathology parameters were recorded. MI-OPN was successfully performed in all cases. Mean tumor size was 4.7 cm (range: 2.5-8.1). Mean warm ischemia time was 28.1 minutes (range: 21-39), mean operative time was 105 minutes (range: 70-150) and mean estimated blood loss was 68 mL (range: 10-400). Mean postoperative hospital stay was 6.5 days (range: 5-12). Postoperative complications were found in 3 patients (5.5%). The mean pre- and postoperative serum creatinine levels were 76.2 μmol/L (range: 47-132) and 87.1 μmol/L (range: 61-189) with significant difference (P = 0.004). The mean pre- and postoperative estimated glomerular filtration rate (eGFR) were 91.5 (range: 34-133) and 82.5 (range: 22-126.5), respectively with significant difference (P = 0.024). In an average follow-up of 19.9 months (range: 8-50), no local recurrence or systemic progression occurred. In conclusion, MI-OPN can combine the benefits of both minimal invasive and traditional open

  5. Determining the Extent of Hydrothermal Interaction on the Southern Costa Rica Rift Ridge Flank During the Past 8 Ma from Joint Inversion of Geophysical Data

    Science.gov (United States)

    Wilson, D. J.; Moorkamp, M.; Hobbs, R. W.; Peirce, C.; Harris, R. N.; Morgan, J. V.

    2017-12-01

    Advective hydrothermal systems preferentially develop in zones of high porosity and permeability, driven by a local heat source. Associated chemical reactions lead to changes in the bulk physical properties, so variations in velocity and density, and the relationship connecting them, may provide a record of alteration by hydrothermal fluids. Oceanic crust accreted at intermediate rate ridges displays a range of characteristics between those typical for fast and slow spreading rates so changes in crustal porosity and permeability are sensitive to the interplay between tectonic stretching, magmatic supply and plate motions. Hence, changes in spreading style and sediment cover will influence the extent of the hydrothermal interaction that occurs and the mode of heat loss as evidenced by heat flow measurements. Using a variety of geophysical data we determine where hydrothermal circulation has been active in young oceanic crust that was accreted at an intermediate spreading rate. Results from traveltime tomography along a 300 km profile across the southern flank of the Costa Rica Rift reveal several variations in the P-wave velocity structure of the upper crust (layer 2). Following an initial increase in P-wave velocity near the ridge axis there is a section of the model 80 km in length that has lower P-wave velocity (up to 0.5 km s-1) compared to adjacent crust. This section has shallower bathymetry, by up to 500 m, than predicted by the subsidence curve and the top basement surface is rougher with a greater amount of faulting and larger throws. This zone is preceded by crust with significantly faster P-wave velocities (up to 1.0 km s-1) that was sampled by DSDP/ODP 504B. We characterise these changes in the shallow crustal structure by jointly inverting travel-time data and gravity data with deeper control from coincident magnetotelluric data. Using a cross-gradient approach allows us to search for models with a structural match, thus determining the relationship

  6. Peak-valley-peak pattern of histone modifications delineates active regulatory elements and their directionality

    DEFF Research Database (Denmark)

    Pundhir, Sachin; Bagger, Frederik Otzen; Lauridsen, Felicia Kathrine Bratt

    2016-01-01

    Formation of nucleosome free region (NFR) accompanied by specific histone modifications at flanking nucleosomes is an important prerequisite for enhancer and promoter activity. Due to this process, active regulatory elements often exhibit a distinct shape of histone signal in the form of a peak......-valley-peak (PVP) pattern. However, different features of PVP patterns and their robustness in predicting active regulatory elements have never been systematically analyzed. Here, we present PARE, a novel computational method that systematically analyzes the H3K4me1 or H3K4me3 PVP patterns to predict NFRs. We show...... four ENCODE cell lines and four hematopoietic differentiation stages, we identified several enhancers whose regulatory activity is stage specific and correlates positively with the expression of proximal genes in a particular stage. In conclusion, our results demonstrate that PVP patterns delineate...

  7. Multi-technology positioning

    CERN Document Server

    Lohan, Elena-Simona; Wymeersch, Henk; Seco-Granados, Gonzalo; Nykänen, Ossi

    2017-01-01

    This book provides an overview of positioning technologies, applications and services in a format accessible to a wide variety of readers. Readers who have always wanted to understand how satellite-based positioning, wireless network positioning, inertial navigation, and their combinations work will find great value in this book. Readers will also learn about the advantages and disadvantages of different positioning methods, their limitations and challenges. Cognitive positioning, adding the brain to determine which technologies to use at device runtime, is introduced as well. Coverage also includes the use of position information for Location Based Services (LBS), as well as context-aware positioning services, designed for better user experience. • Brings understanding of positioning technology to readers from a variety of disciplines • Reviews multiple techniques, providing insight on the pros, cons and challenges related to each • Designed to be a tutorial on basic principles, avoiding unnecessary de...

  8. Navicular bone position determined by positional MRI

    DEFF Research Database (Denmark)

    Hansen, Philip; Johannsen, Finn E; Hangaard, Stine

    2016-01-01

    -scanner). Scanning was performed in supine and standing position, respectively. Two radiologists evaluated the images in a blinded manner. Reliability and agreement were assessed by calculation of intraclass correlation coefficient (ICC) and 95 % limits of agreement as a percentage of the mean (LOA%). RESULTS...

  9. Percutaneous nephrolithotomy in semisupine position: a modified approach for renal calculus.

    Science.gov (United States)

    Xu, Ke-Wei; Huang, Jian; Guo, Zheng-Hui; Lin, Tian-Xin; Zhang, Cai-Xai; Liu, Hao; Chun, Jian; Yao, You-Sheng; Han, Jin-Li; Huang, Hai

    2011-12-01

    Conventional percutaneous nephrolithotomy (PCNL) is usually performed in a prone position, which compresses the thorax and results in difficulty in rescue during operation. When PCNL is performed in a supine position, the flank renal puncture area is limited, so it is difficult to treat disseminated and complex renal calculi. Herein, we introduce a modified semisupine position for performing PCNL, which has numerous benefits as well as safe and effective. Between May 2002 and May 2009, a total of 452 patients with renal calculi were treated with semisupine PCNL. The patient was placed in 45° semisupine position during the procedure, with the affected flank arched as much as possible. In this series, no one converted to open surgery. The average operating time was (115.2 ± 44.5) min. Single tract PCNL was performed for 80.97% of the cases, two tracts 13.94%, three tracts 4.65%, and four tracts 0.44%. The upper, middle, and lower calix tracts accounted for 12.1, 63.0, and 24.9%, of procedures, respectively. Stone-free rate was 85.7% overall, 92.2% for single calculus (83/90), and 72.9% for staghorn calculi (78/107). Major postoperative complications occurred in 3.3% of the cases. This study demonstrated PCNL in a semisupine position is an effective alternative for treating renal calculi, which combines the advantages of PCNL in a prone position, and PCNL in a supine position. The semisupine position allows easier irrigation of stone fragments, is more comfortable for the patient, and facilitates monitoring of anesthesia.

  10. Initiation of long-term coupled microbiological, geochemical, and hydrological experimentation within the seafloor at North Pond, western flank of the Mid-Atlantic Ridge

    Science.gov (United States)

    Edwards, K.J.; Backert, N.; Bach, W.; Becker, K.; Klaus, A.; Griffin, Dale W.; Anderson, L.; Haddad, A.G.; Harigane, Y.; Campion, P.L.; Hirayama, H.; Mills, H.J.; Hulme, S.M.; Nakamura, K.; Jorgensen, S.L.; Orcutt, B.; Insua, T.L.; Park, Y.-S.; Rennie, V.; Salas, E.C.; Rouxel, O.; Wang, F.; Russel, J.A.; Wheat, C.G.; Sakata, K.; Brown, M.; Magnusson, J.L.; Ettlinger, Z.

    2012-01-01

    Integrated Ocean Drilling Program (IODP) Expedition 336 successfully initiated subseafloor observatory science at a young mid-ocean-ridge flank setting. All of the drilled sites are located in the North Pond region of the Atlantic Ocean (22??45'N, 46??05'W) in 4414-4483 m water depth. This area is known from previous ocean drilling and site survey investigations as a site of particularly vigorous circulation of seawater in permeable 8 Ma basaltic basement underlying a logged in Holes U1382A and U1383C. Upper oceanic crust in Hole U1382A, which is only 50 m west of Deep Sea Drilling Project (DSDP) Hole 395A, recovered 32 m of core between 110 and 210 meters below seafloor (mbsf). Core recovery in basement was 32%, yielding a number of volcanic flow units with distinct geochemical and petrographic characteristics. A unit of sedimentary breccia containing clasts of basalt, gabbroic rocks, and mantle peridotite was found intercalated between two volcanic flow units and was interpreted as a rock slide deposit. From Hole U1383C we recovered 50.3 m of core between 69.5 and 331.5 mbsf (19%). The basalts are aphyric to highly plagioclase-olivine-phyric tholeiites that fall on a liquid line of descent controlled by olivine fractionation. They are fresh to moderately altered, with clay minerals (saponite, nontronite, and celadonite), Fe oxyhydroxide, carbonate, and zeolite as secondary phases replacing glass and olivine to variable extents. In addition to traditional downhole logs, we also used a new logging tool for detecting in situ microbial life in ocean floor boreholes-the Deep Exploration Biosphere Investigative tool (DEBI-t). Sediment thickness was ???90 m at Sites U1382 and U1384 and varied between 38 and 53 m at Site U1383. The sediments are predominantly nannofossil ooze with layers of coarse foraminiferal sand and occasional pebble-size clasts of basalt, serpentinite, gabbroic rocks, and bivalve debris. The bottommost meters of sections cored with the advanced

  11. The East Pacific Rise and its flanks 8 18° N: History of segmentation, propagation and spreading direction based on SeaMARC II and Sea Beam studies

    Science.gov (United States)

    MacDonald, Ken C.; Fox, Paul J.; Miller, Steve; Carbotte, Suzanne; Edwards, Margo H.; Eisen, Mark; Fornari, Daniel J.; Perram, Laura; Pockalny, Rob; Scheirer, Dan; Tighe, Stacey; Weiland, Charles; Wilson, Doug

    1992-12-01

    SeaMARC II and Sea Beam bathymetric data are combined to create a chart of the East Pacific Rise (EPR) from 8°N to 18°N reaching at least 1 Ma onto the rise flanks in most places. Based on these data as well as SeaMARC II side scan sonar mosaics we offer the following observations and conclusions. The EPR is segmented by ridge axis discontinuities such that the average segment lengths in the area are 360 km for first-order segments, 140 km for second-order segments, 52 km for third-order segments, and 13 km for fourth-order segments. All three first-order discontinuities are transform faults. Where the rise axis is a bathymetric high, second-order discontinuities are overlapping spreading centers (OSCs), usually with a distinctive 3:1 overlap to offset ratio. The off-axis discordant zones created by the OSCs are V-shaped in plan view indicating along axis migration at rates of 40 100 mm yr-1. The discordant zones consist of discrete abandoned ridge tips and overlap basins within a broad wake of anomalously deep bathymetry and high crustal magnetization. The discordant zones indicate that OSCs have commenced at different times and have migrated in different directions. This rules out any linkage between OSCs and a hot spot reference frame. The spacing of abandoned ridges indicates a recurrence interval for ridge abandonment of 20,000 200,000 yrs for OSCs with an average interval of approximately 100,000 yrs. Where the rise axis is a bathymetric low, the only second-order discontinuity mapped is a right-stepping jog in the axial rift valley. The discordant zone consists of a V-shaped wake of elongated deeps and interlocking ridges, similar to the wakes of second-order discontinuities on slow-spreading ridges. At the second-order segment level, long segments tend to lengthen at the expense of neighboring shorter segments. This can be understood if segments can be approximated by cracks, because the propagation force at a crack tip is directly proportional to crack

  12. Pretty Easy Pervasive Positioning

    DEFF Research Database (Denmark)

    Hansen, Rene; Wind, Rico; Jensen, Christian Søndergaard

    2009-01-01

    With the increasing availability of positioning based on GPS, Wi-Fi, and cellular technologies and the proliferation of mobile devices with GPS, Wi-Fi and cellular connectivity, ubiquitous positioning is becoming a reality. While offerings by companies such as Google, Skyhook, and Spotigo render...... positioning possible in outdoor settings, including urban environments with limited GPS coverage, they remain unable to offer accurate indoor positioning. We will demonstrate a software infrastructure that makes it easy for anybody to build support for accurate Wi-Fi based positioning in buildings. All...... that is needed is a building with Wi-Fi coverage, access to the building, a floor plan of the building, and a Wi-Fi enabled device. Specifically, we will explain the software infrastructure and the steps that must be completed to obtain support for positioning. And we will demonstrate the positioning obtained...

  13. Positive criminology in practice.

    Science.gov (United States)

    Ronel, Natti; Segev, Dana

    2014-11-01

    The discourse regarding offender rehabilitation has been criticized by various scholars who have claimed that reducing negative causes and managing risk will not automatically prompt positive human development and elements that are associated with desistance. Positive criminology is an innovative concept that challenges the common preoccupation with negative elements, by placing emphasis on human encounters and forces of inclusion that are experienced positively by target individuals and that can promote crime desistance. However, as the concept is relatively new, there are still no guiding principles for the practice of positive criminology that could direct research and the criminal justice system. This article attempts to fill that gap by providing principles that could be practiced by criminal justice personnel and examples of different interventions that reflect positive criminology. The article also provides ideological explanations for adopting the concept of positive criminology in practice. © The Author(s) 2013.

  14. Den positive psykologis metoder

    DEFF Research Database (Denmark)

    Andersen, Frans Ørsted; Mørck, Line Lerche; Nissen, Poul Erik

    En antologi der giver en introduktion til en række af de metoder der anvendes til forskning, assessment, test, udviklingsarbejde og intervention indenfor den positive psykologi.......En antologi der giver en introduktion til en række af de metoder der anvendes til forskning, assessment, test, udviklingsarbejde og intervention indenfor den positive psykologi....

  15. Modern management positions

    Directory of Open Access Journals (Sweden)

    Jovanović Petar M.

    2015-01-01

    Full Text Available In this paper we analyze contemporary managerial positions such as program manager, project portfolio manager, crisis manager and others. The idea is to promote managerial positions in Serbia, which is quite unjustifiably undervalued, primarily because of the lack of knowledge in the field of management and other issues related to management education.

  16. Positioning and locking apparatus

    Science.gov (United States)

    Hayward, M.L.; Harper, W.H.

    1985-06-19

    A positioning and locking apparatus including a fixture having a rotatable torque ring provided with a plurality of cam segments for automatically guiding a container into a desired location within the fixture. Rotation of the ring turns the container into a final position in pressure sealing relation against a hatch member.

  17. Positioning health professional identity

    DEFF Research Database (Denmark)

    Lund, Ole; Krogh Christensen, Mette; Mørcke, Anne Mette

    2017-01-01

    Drawing on positioning theory, the purpose of this paper is to characterize the activities and positions of students and supervisors at workplaces and on-campus skills training sites across the higher health professional educations of medicine, sports science, and nursing. Furthermore, the study ...... explored the impact of work-based learning (WBL) and skills training on students’ personal professional identity development....

  18. Phantom position dependence

    International Nuclear Information System (INIS)

    Thorson, M.R.; Endres, G.W.R.

    1981-01-01

    Sensitivity of the Hanford dosimeter response to its position relative to the phantom and the neutron source has always been recognized. A thorough investigation was performed to quantify dosimeter response according to: (a) dosimeter position on phantom, (b) dosimeter distance from phantom, and (c) angular relationship of dosimeter relative to neutron source and phantom. Results were obtained for neutron irradiation at several different energies

  19. Position display device

    International Nuclear Information System (INIS)

    Nishizawa, Yukio.

    1974-01-01

    Object: To provide a device capable of easily and quickly reading mutual mounting relations of control bodies such as control rods mounted on a nuclear reactor and positions to which the control bodies are driven. Structure: A scanning circuit is provided to scan positions of controllably mounted control bodies such as control rods. Values detected by scanning the positions are converted into character signals according to the values and converted into preranked color signals. The character signals and color signals are stored in a memory circuit by synchronous signals in synchronism with the scanning in the scanning circuit. Outputs of the memory circuit are displayed by a display unit such as a color Braun tube in accordance with the synchronous signals to provide color representations according to positions to which control bodies are driven in the same positional relation as the mounting of the control bodies. (Kamimura, M.)

  20. Review of Positional Nystagmus

    Directory of Open Access Journals (Sweden)

    José Ignacio BENITO-OREJAS

    2018-01-01

    Full Text Available Introduction and objective: Any change of position of the head (dynamic or static can trigger a nystagmus or increase the spontaneous. This nystagmus we call it positional. We intend to review in this chapter its definition, clinical features, etiology and the way of exploring it. Method: narrative review. Results: Positional vertigo is the most frequent vestibular disorder, and most of the times of peripheral cause. Characteristics of nystagmus or its association with other neurological symptoms are sufficient grounds to request a magnetic resonance, which will provide additional information on very few occasions. Discussion: The study of the positional nystagmus as a procedure to rule out central pathology has lost much of its relevance. Signs that Nylén defined mixed findings peripheral and central, making complex classification. Conclusion: Regardless of how to bring the patient change position (very slow or fast, if it appears an atypical nystagmus should rule out a central origin.

  1. POSITIONING STRATEGIES DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    Shakhshir Ghassan

    2014-07-01

    Full Text Available The positioning strategy has suffered serious changes in the last few decades, being influenced by the rapid development of competition and the growing focus on specific traits belonging to the market, to the consumer or to the product. The purpose of this paper is to present the developments of theoretical positioning strategies and the orientation from more simple, product oriented strategies, to ones more oriented towards the client and with a briefer period of time. The world is moving in a much faster pace than in the past, thanks to communication development so companies are obliged to adopt more specific strategies in order for them to be effective. This essay represents a literary review presenting a documentary research within the scientific articles and strategy and positioning books. The paper begins with the analysis of company strategies and the marketing strategies in general. The first author to group the product positioning strategies is Porter with his three generic strategies. Following the development of brands and because of the lack of competitiveness in the simple generic positioning strategies, this paper has also presented the newer positioning strategies proposed by Kotler, Treacy & Wiersema, and also more complex ones such as Bowman's Strategy Clock and Blankson and Kalafatis positioning strategy based on the type of the consumer. The fast expansion of local brands in all categories has led to mistakes in positioning strategies, categories also presented in the current essay. The results of this study show that new positioning strategies are more and more based on the consumer and market segments and on the product specification - which have also evolved in the last decades. Adaptability to fast changes in the competitive market will represent the future positioning strategies.

  2. Identification of DNA-binding proteins that interact with the 5'-flanking region of the human D-amino acid oxidase gene by pull-down assay coupled with two-dimensional gel electrophoresis and mass spectrometry.

    Science.gov (United States)

    Tran, Diem Hong; Shishido, Yuji; Chung, Seong Pil; Trinh, Huong Thi Thanh; Yorita, Kazuko; Sakai, Takashi; Fukui, Kiyoshi

    2015-12-10

    D-Amino acid oxidase (DAO) is a flavoenzyme that metabolizes D-amino acids and is expected to be a promising therapeutic target of schizophrenia and glioblastoma. The study of DNA-binding proteins has yielded much information in the regulation of transcription and other biological processes. However, proteins interacting with DAO gene have not been elucidated. Our assessment of human DAO promoter activity using luciferase reporter system indicated the 5'-flanking region of this gene (-4289 bp from transcription initiation site) has a regulatory sequence for gene expression, which is regulated by multi-protein complexes interacting with this region. By using pull-down assay coupled with two-dimensional gel electrophoresis and mass spectrometry, we identified six proteins binding to the 5'-flanking region of the human DAO gene (zinc finger C2HC domain-containing protein 1A; histidine-tRNA ligase, cytoplasmic; molybdenum cofactor biosynthesis protein; 60S ribosomal protein L37; calponin-1; calmodulin binding protein and heterogeneous nuclear ribonucleoprotein A2/B1). These preliminary results will contribute to the advance in the understanding of the potential factors associated with the regulatory mechanism of DAO expression. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. A Thieno[2,3-b]pyridine-Flanked Diketopyrrolopyrrole Polymer as an n-Type Polymer Semiconductor for All-Polymer Solar Cells and Organic Field-Effect Transistors

    KAUST Repository

    Chen, Hung-Yang

    2017-12-28

    A novel fused heterocycle-flanked diketopyrrolopyrrole (DPP) monomer, thieno[2,3-b]pyridine diketopyrrolopyrrole (TPDPP), was designed and synthesized. When copolymerized with 3,4-difluorothiophene using Stille coupling polymerization, the new polymer pTPDPP-TF possesses a highly planar conjugated polymer backbone due to the fused thieno[2,3-b]pyridine flanking unit that effectively alleviates the steric hindrance with both the central DPP core and the 3,4-difluorothiophene repeat unit. This new polymer exhibits a high electron affinity (EA) of −4.1 eV and was successfully utilized as an n-type polymer semiconductor for applications in organic field-effect transistors (OFETs) and all polymer solar cells. A promising n-type charge carrier mobility of 0.1 cm2 V–1 s–1 was obtained in bottom-contact, top-gate OFETs, and a power conversion efficiency (PCE) of 2.72% with a high open-circuit voltage (VOC) of 1.04 V was achieved for all polymer solar cells using PTB7-Th as the polymer donor.

  4. A Thieno[2,3-b]pyridine-Flanked Diketopyrrolopyrrole Polymer as an n-Type Polymer Semiconductor for All-Polymer Solar Cells and Organic Field-Effect Transistors

    KAUST Repository

    Chen, Hung-Yang; Nikolka, Mark; Wadsworth, Andrew; Yue, Wan; Onwubiko, Ada; Xiao, Mingfei; White, Andrew J. P.; Baran, Derya; Sirringhaus, Henning; McCulloch, Iain

    2017-01-01

    A novel fused heterocycle-flanked diketopyrrolopyrrole (DPP) monomer, thieno[2,3-b]pyridine diketopyrrolopyrrole (TPDPP), was designed and synthesized. When copolymerized with 3,4-difluorothiophene using Stille coupling polymerization, the new polymer pTPDPP-TF possesses a highly planar conjugated polymer backbone due to the fused thieno[2,3-b]pyridine flanking unit that effectively alleviates the steric hindrance with both the central DPP core and the 3,4-difluorothiophene repeat unit. This new polymer exhibits a high electron affinity (EA) of −4.1 eV and was successfully utilized as an n-type polymer semiconductor for applications in organic field-effect transistors (OFETs) and all polymer solar cells. A promising n-type charge carrier mobility of 0.1 cm2 V–1 s–1 was obtained in bottom-contact, top-gate OFETs, and a power conversion efficiency (PCE) of 2.72% with a high open-circuit voltage (VOC) of 1.04 V was achieved for all polymer solar cells using PTB7-Th as the polymer donor.

  5. Positional Concerns and Institutions

    DEFF Research Database (Denmark)

    Landes, Xavier

    2013-01-01

    that invoking envy or subjective well-being is not fully satisfying for regulating positional concerns. More compelling reasons seem, in complement with efficiency, to be related to considerations for equality. In other words, if institutions could have strong reasons to pay attention to and regulate positional...... their implications for economics, positional concerns imply important normative dimensions. There have been presumed to be a symptom of envy, reduce people’s happiness, and create problems of social interaction or economic inefficiencies. Individuals are, for instance, prone to pick states of the world that improve...... concerns, it would be in virtue of their impact on the social product and individuals’ conditions of living....

  6. Stress Management: Positive Thinking

    Science.gov (United States)

    Healthy Lifestyle Stress management Positive thinking helps with stress management and can even improve your health. Practice overcoming negative self-talk ... with optimism is a key part of effective stress management. And effective stress management is associated with ...

  7. Den positive psykologis metoder

    DEFF Research Database (Denmark)

    Bogen introducerer til de mange metoder, som anvendes i positiv psykologi. dette sker ud fra en reflekteret tilgang, der ligeledes rummer bidrag fra kritisk psykologi med det formål at nuancere den positive psykologis forståelser...

  8. Clinical Positioning Space

    DEFF Research Database (Denmark)

    Williams, Lars Peter Hedegaard; Christensen, Mette Krogh; Rytter, Carsten

    2014-01-01

    In this article, we present a case study of residents’ clinical experiences and communication in outpatient oncology consultations. We apply positioning theory, a dynamic alternative to role theory, to investigate how oncology residents and patients situate themselves as persons with rights...... and duties. Drawing from seven qualitative interviews and six days of observation, we investigate the residents’ social positioning and their conversations with patients or supervisors. Our focus is on how (a) relational shifts in authority depend on each situation and its participants; (b) storylines...... establish acts and positions and narratively frame what participants can expect from a medical consultation viewed as a social episode; and (c) the positioning of rights and duties can lead to misunderstandings and frustrations. We conclude that residents and patients locate themselves in outpatient...

  9. Fluorescent optical position sensor

    Science.gov (United States)

    Weiss, Jonathan D.

    2005-11-15

    A fluorescent optical position sensor and method of operation. A small excitation source side-pumps a localized region of fluorescence at an unknown position along a fluorescent waveguide. As the fluorescent light travels down the waveguide, the intensity of fluorescent light decreases due to absorption. By measuring with one (or two) photodetectors the attenuated intensity of fluorescent light emitted from one (or both) ends of the waveguide, the position of the excitation source relative to the waveguide can be determined by comparing the measured light intensity to a calibrated response curve or mathematical model. Alternatively, excitation light can be pumped into an end of the waveguide, which generates an exponentially-decaying continuous source of fluorescent light along the length of the waveguide. The position of a photodetector oriented to view the side of the waveguide can be uniquely determined by measuring the intensity of the fluorescent light emitted radially at that location.

  10. POSITIONING STRATEGIES DEVELOPMENT

    OpenAIRE

    Shakhshir Ghassan

    2014-01-01

    The positioning strategy has suffered serious changes in the last few decades, being influenced by the rapid development of competition and the growing focus on specific traits belonging to the market, to the consumer or to the product. The purpose of this paper is to present the developments of theoretical positioning strategies and the orientation from more simple, product oriented strategies, to ones more oriented towards the client and with a briefer period of time. The world is moving in...

  11. Position measuring device

    International Nuclear Information System (INIS)

    Maeda, Kazuyuki; Takahashi, Shuichi; Maruyama, Mayumi

    1998-01-01

    The present invention provides a device capable of measuring accurate position and distance easily even at places where operator can not easily access, such as cell facilities for vitrifying radioactive wastes. Referring to a case of the vitrifying cell, an objective equipment settled in the cell is photographed by a photographing device. The image is stored in a position measuring device by way of an image input device. After several years, when the objective equipment is exchanged, a new objective equipment is photographed by a photographing device. The image is also stored in the position measuring device. The position measuring device compares the data of both of the images on the basis of pixel unit. Based on the image of the equipment before the exchange as a reference, extent of the displacement of the installation position of the equipment on the image after the exchange caused by installation error and manufacturing error is determined to decide the position of the equipment after exchange relative to the equipment before exchange. (I.S.)

  12. Plasma position control device

    International Nuclear Information System (INIS)

    Takase, Haruhiko.

    1987-01-01

    Purpose: To conduct position control stably to various plasmas and reduce the burden on the control coil power source. Constitution: Among the proportional, integration and differentiation controls, a proportional-differentiation control section and an integration control section are connected in parallel. Then, a signal switching circuit is disposed to the control signal input section for the proportional-differentiation control section such that either a present position of plasmas or deviation between the present plasma position and an aimed value can be selected as a control signal depending on the control procedures or the state of the plasmas. For instance, if a rapid response is required for the control, the deviation between the present plasma position and the aimed value is selected as the input signal to conduct proportional, integration and differentiation controls. While on the other hand, if it is intended to reduce the burden on the control coil power source, it is adapted such that the control signal inputted to the proportional-differentiation control section itself can select the present plasma position. (Yoshihara, H.)

  13. Uncharged positive electrode composition

    Science.gov (United States)

    Kaun, Thomas D.; Vissers, Donald R.; Shimotake, Hiroshi

    1977-03-08

    An uncharged positive-electrode composition contains particulate lithium sulfide, another alkali metal or alkaline earth metal compound other than sulfide, e.g., lithium carbide, and a transition metal powder. The composition along with a binder, such as electrolytic salt or a thermosetting resin is applied onto an electrically conductive substrate to form a plaque. The plaque is assembled as a positive electrode within an electrochemical cell opposite to a negative electrode containing a material such as aluminum or silicon for alloying with lithium. During charging, lithium alloy is formed within the negative electrode and transition metal sulfide such as iron sulfide is produced within the positive electrode. Excess negative electrode capacity over that from the transition metal sulfide is provided due to the electrochemical reaction of the other than sulfide alkali metal or alkaline earth metal compound.

  14. Position indication apparatus

    Energy Technology Data Exchange (ETDEWEB)

    Masuda, T

    1964-02-24

    A plurality of magnetically operated switches are spaced equally in the hollow tube of a control rod actuating mechanism. One side of each switch is connected, via a low resistance, to a corresponding tap of a low resistance voltage divider network consisting of an equivalent number of low resistance sections with the opposite side of each switch connected to a common conducting wire A. To both ends of the voltage dividing network are connected, respectively, conducting wires B and C. Wires A, B, and C are further coupled to a fuel rod position indicator comprising a voltmeter and power source external to the control rod actuating member. The control rod actuating member is adapted to slide in the hollow tube so that switches passing a position facing a magnet secured to the lower end of the actuating member are rendered closed. Hence, the position of the control rod may be read by reading the voltage off the meter.

  15. Positioning devices for patients

    International Nuclear Information System (INIS)

    Heavens, M.

    1981-01-01

    It has been suggested that it is very important to position patients reproducibly at different stages of radiotherapy treatment planning and treatment, or similar procedures. Devices have been described for positioning a patient's upper and lower thorax. This invention provides reproducible positioning for a female patient's breasts, for example in planning treatment of and treating breast tumours. The patient is placed prone, using for example an upper thorax device. A support device is placed central to and beneath her breasts to partially displace them outwards. The device may be triangular in section with one apex contacting the chest wall at the sternum. Restraining straps may be provided to hold the breasts against the support device. Means may be provided to take a healthy breast from the path of radiation through the tumour. (author)

  16. Positioning and applications

    Directory of Open Access Journals (Sweden)

    Rogowski Jerzy B.

    2015-12-01

    Full Text Available The paper presents national report of Poland for IAG on positioning and applications. The selected research presented was carried out at leading Polish research institutions and concern precise multi-GNSS satellite positioning - relative and absolute - and also GNSS-based ionosphere and troposphere modelling and studies. The research resulted in noticeable advancements in these subjects confirmed by the development of new algorithms and methods. New and improved methods of precise GNSS positioning were developed, and also GNSS metrology was studied. New advanced troposphere models were presented and tested. In particular, these models allowed testing IPW variability on regional and global scales. Also, new regional ionosphere monitoring web-based services were developed and launched.

  17. Massive Galileon positivity bounds

    Science.gov (United States)

    de Rham, Claudia; Melville, Scott; Tolley, Andrew J.; Zhou, Shuang-Yong

    2017-09-01

    The EFT coefficients in any gapped, scalar, Lorentz invariant field theory must satisfy positivity requirements if there is to exist a local, analytic Wilsonian UV completion. We apply these bounds to the tree level scattering amplitudes for a massive Galileon. The addition of a mass term, which does not spoil the non-renormalization theorem of the Galileon and preserves the Galileon symmetry at loop level, is necessary to satisfy the lowest order positivity bound. We further show that a careful choice of successively higher derivative corrections are necessary to satisfy the higher order positivity bounds. There is then no obstruction to a local UV completion from considerations of tree level 2-to-2 scattering alone. To demonstrate this we give an explicit example of such a UV completion.

  18. Prospective Internally Controlled Blind Reviewed Clinical Evaluation of Cryolipolysis Combined With Multipolar Radiofrequency andVaripulseTechnology for Enhanced Subject Results in Circumferential Fat Reduction and Skin Laxity of the Flanks.

    Science.gov (United States)

    Few, Julius; Gold, Michael; Sadick, Neil

    2016-11-01

    Increasing demand for non-invasive skin tightening and body contouring procedures has led to several technological in- novations in energy-based devices such as ultrasound, radiofrequency and cryolipolysis. An emerging trend in the eld is to evaluate whether combination therapies for skin laxity/body contouring using energy-based devices can deliver superior clinical results and patient satisfaction. As such, the objective of this prospective, internal-controlled, blind clinical study was to assess the safety and efficacy of cryolipolysis followed by multipolar radiofrequency with pulsed electromagnetic elds (PEMF) and adjustable pulsed suction for the treatment of skin laxity in the flanks. Ten subjects with focal adiposities in the anks were enrolled in the study. All subjects received one session of cryolipolysis treatment and after randomization received two sessions of radiofrequency with PEMF (spaced two weeks apart), followed by another two sessions of radiofrequency with PEMF and adjustable pulsed suction (spaced two weeks apart). Clinical photography was used to monitor the subject's results at baseline, one week, three, and six months post treatment. Blinded reviewers and the treating inves- tigator assessed the clinical outcomes using the Global Aesthetic Improvement (GAI) scale. Side effects were recorded at every visit and patient satisfaction was noted at the one week, three and six-month follow-up using a 5-scale subject satisfaction assessment questionnaire. Analysis of the blinded investigator ratings demonstrated statistical significant enhanced skin laxity mean improvement of 1 grade on the GAI scale in subject treated with the combination treatment (cryolipolysis+RF/PEMF/suction) compared with the cryolipolysis treatment alone. The unblinded investigator GAI ratings also showed enhanced (20%) mean improvement of laxity in the combination treated subjects versus those receiving cryolipolysis alone. Over half of the participants reported

  19. Perceptual learning eases crowding by reducing recognition errors but not position errors.

    Science.gov (United States)

    Xiong, Ying-Zi; Yu, Cong; Zhang, Jun-Yun

    2015-08-01

    When an observer reports a letter flanked by additional letters in the visual periphery, the response errors (the crowding effect) may result from failure to recognize the target letter (recognition errors), from mislocating a correctly recognized target letter at a flanker location (target misplacement errors), or from reporting a flanker as the target letter (flanker substitution errors). Crowding can be reduced through perceptual learning. However, it is not known how perceptual learning operates to reduce crowding. In this study we trained observers with a partial-report task (Experiment 1), in which they reported the central target letter of a three-letter string presented in the visual periphery, or a whole-report task (Experiment 2), in which they reported all three letters in order. We then assessed the impact of training on recognition of both unflanked and flanked targets, with particular attention to how perceptual learning affected the types of errors. Our results show that training improved target recognition but not single-letter recognition, indicating that training indeed affected crowding. However, training did not reduce target misplacement errors or flanker substitution errors. This dissociation between target recognition and flanker substitution errors supports the view that flanker substitution may be more likely a by-product (due to response bias), rather than a cause, of crowding. Moreover, the dissociation is not consistent with hypothesized mechanisms of crowding that would predict reduced positional errors.

  20. Attitude and position tracking

    CSIR Research Space (South Africa)

    Candy, LP

    2011-01-01

    Full Text Available Several applications require the tracking of attitude and position of a body based on velocity data. It is tempting to use direction cosine matrices (DCM), for example, to track attitude based on angular velocity data, and to integrate the linear...

  1. Logotherapy and positive psychology

    Directory of Open Access Journals (Sweden)

    Oscar R. Oro

    2015-09-01

    Full Text Available Psychology omitted to approach, during almost a century, the positive aspects from persons, like creativity, humor, optimism, hope, forgiveness, life meaning, and happiness. These themes are approached by Positive Psychology, with Seligman like the principal exponent. Psychology was dedicated to explore the negative aspects from human beings improving human health. Nevertheless, this pathogenic model could not prevent mental disease. Concepts of Positive Psychology have a solid antecedent in Víktor Frankl ́s studies, which is the Logotherapy founder. This allows incorporating another perspective to approach positive aspects, from a philosophical and anthropological focus. Although the ways adopted by Frank and Seligman are different, both considered main aspects of human existence. Nevertheless, they investigated in different countries (from Europe and EE.UU.; in different circumstances (concentration camps, deaths, tortures; vs. academic context; in different historical periods and different social contexts (a country that lost the war and other that gave freedom to Europeans. In this work is used the concept life sense as the focus in professional formation and psychotherapy approach. 

  2. Delegation. Position Statement. Revised

    Science.gov (United States)

    Board, Connie; Bushmiaer, Margo; Davis-Alldritt, Linda; Fekaris, Nina; Morgitan, Judith; Murphy, M. Kathleen; Yow, Barbara

    2010-01-01

    It is the position of the National Association of School Nurses (NASN) that the delegation of nursing tasks in the school setting can be a valuable tool for the school nurse, when based on the nursing definition of delegation and in compliance with state nursing regulations and guidance. Delegation in school nursing is a complex process in which…

  3. Precise Point Positioning

    DEFF Research Database (Denmark)

    Zhang, Xiaohong

    the airborne lidar system misalignment angle by automating the matching of lidar data with ground truth. Kinematic GPS positioning has been widely used, but the available commercial software systems are normally only suitable for the short or medium range kinematic baseline. However, in polar areas, airborne...

  4. Positionality at the Center

    Directory of Open Access Journals (Sweden)

    Catherine Vanner

    2015-11-01

    Full Text Available As a Western feminist supporting and researching gender equality in education in postcolonial contexts, I often wonder: Am I doing more harm than good? The privilege of my social location means that my efforts to support education in postcolonial contexts risk being patronizing, insulting, threatening, imperialist, and recolonizing. Yet neglecting and ignoring postcolonial contexts similarly reflects and reproduces a privileged position. I provide a tentative framework designed to address positionality, power, and privilege while creating an ethical research process for working in a postcolonial context. Beginning with an identification of positionality, the objectives of research, and guiding theoretical frameworks to situate the research in relation to the participants and context, I proceed to establish a methodology designed to minimize the negative effects of power and maximize participants’ empowerment. I position myself as a bricoleur, layering feminist standpoint theory and postcolonial theory, and propose the collaborative data collection and analysis techniques, with particular attention to ethical and cultural sensitivity, using a social constructivist approach to grounded theory. This article highlights the need for Western researchers to reflect upon the power dynamics of their research in postcolonial contexts and develop a strategy for conducting empowering research that prevents the misrepresentation and exploitation of participants. Observations from my doctoral thesis data collection provide examples of how these concepts were operationalized in practice as well as reflections on the disconnect between theorizing and conducting ethical research in postcolonial contexts.

  5. Immunizations. Position Statement. Revised

    Science.gov (United States)

    Bobo, Nichole; Garrett, Jennifer; Teskey, Carmen; Duncan, Kay; Strasser, Kathy; Burrows-Mezu, Alicia L.

    2015-01-01

    It is the position of the National Association of School Nurses (NASN) that immunizations are essential to primary prevention of disease from infancy through adulthood. Promotion of immunizations by the registered professional school nurse (hereinafter referred to as school nurse) is central to the public health focus of school nursing practice…

  6. Net positive energy buildings

    International Nuclear Information System (INIS)

    Romero, A.; Barreiro, E.; Sanchez Zabala, V.

    2010-01-01

    Buildings are great consumers of energy, being responsible for almost 36% of CO2 emissions in Europe. Though there are many initiatives towards the reduction of energy consumption and CO2 emissions in buildings, many of the alternatives are diminished due to a lack of a unique and holistic approach to the problem. This paper reports a new innovative concept of Positive Energy Buildings (EB+), as well as an integral methodology that covers the overall design process for achieving them. The methodology evaluates energy efficiency solutions at different scales, from building site to generation systems. An educational building design in Navarra serves as a case study to check the feasibility of the proposed methodology. The study concludes that the key to achieve a Positive Energy Building is a minimized energy demand, complemented by efficient facilities and enhanced by distributed power generation from renewable sources. (Author).

  7. Conflict, Memory, and Positioning

    DEFF Research Database (Denmark)

    Brescó, Ignacio

    2016-01-01

    The aim of this paper was to bring the dialogical and multivoiced dimension of conflict to the fore in the study of how people remember a particular event in the past. Drawing from different case studies, it contains analyses of how subjects identifying with different political actors in the Basque...... conflict adopted their respective positions, and interpretation of the conflict, and how, in light of same, they reconstruct the failed peace process that took place in 2006 between the terrorist group ETA (Euzkadi ta Azcatasuna, or Basque Country and Freedom in English) and the Spanish government. Results...... show that the positioning adopted by participants gives rise to a certain form of interpreting the conflict, which, in turn, affects how the peace process is remembered. This occurs within a particular argumentative context in which each version constitutes an implicit response to a competing...

  8. Are Parton Distributions Positive?

    CERN Document Server

    Forte, Stefano; Ridolfi, Giovanni; Altarelli, Guido; Forte, Stefano; Ridolfi, Giovanni

    1999-01-01

    We show that the naive positivity conditions on polarized parton distributions which follow from their probabilistic interpretation in the naive parton model are reproduced in perturbative QCD at the leading log level if the quark and gluon distribution are defined in terms of physical processes. We show how these conditions are modified at the next-to-leading level, and discuss their phenomenological implications, in particular in view of the determination of the polarized gluon distribution

  9. Are parton distributions positive?

    International Nuclear Information System (INIS)

    Forte, Stefano; Altarelli, Guido; Ridolfi, Giovanni

    1999-01-01

    We show that the naive positivity conditions on polarized parton distributions which follow from their probabilistic interpretation in the naive parton model are reproduced in perturbative QCD at the leading log level if the quark and gluon distribution are defined in terms of physical processes. We show how these conditions are modified at the next-to-leading level, and discuss their phenomenological implications, in particular in view of the determination of the polarized gluon distribution

  10. Spatial Search, Position Papers

    OpenAIRE

    Center for Spatial Studies, UCSB

    2014-01-01

    The Spatial Search specialist meeting in Santa Barbara (December 2014) brought together 35 academic and industry representatives from computational, geospatial, and cognitive sciences with interest in focused discussions on the development of an interdisciplinary research agenda to advance spatial search from scientific and engineering viewpoints. The position papers from participants represent the shared expertise that guided discussions and the formulation of research questions about proces...

  11. Barebacking and sexual position

    OpenAIRE

    Grundy-Bowers, M.; Hardy, S.; McKeown, E.

    2015-01-01

    Bareback sex continues to fuel the HIV epidemic among men who have sex with men but despite the fact that much academic attention has been focused on the sexual behaviour of this population few authors have considered the significance of sexual position. In order to explore this relatively under-examined factor, interviews were conducted with 13 HIV-negative and unknown status gay men who had recently engaged in bareback sex. Using Interpretative Phenomenological Analysis and through the lens...

  12. The strategic research positioning:

    DEFF Research Database (Denmark)

    Viala, Eva Silberschmidt

    to provide new insights into ‘immigrant’ parents’ perspective on home/school partnership in Denmark. The majority of the immigrant parents came from non-Western countries, and they had already been ‘labelled’ difficult in terms of home/school partnership. This calls for what I call ‘strategic research...... positioning’, meaning critical reflections about the relationship and power balance between the researcher and the researched. The paper focus' on challenges and dilemmas linked to this position....

  13. Review of HRP Positions

    Energy Technology Data Exchange (ETDEWEB)

    Center for Reliability Studies

    2007-01-01

    The Department of Energy (DOE) Human Reliability Program (HRP), published as 10 CFR Part 712, is currently being reviewed and revised to address concerns identified during its implementation. Although these ''page changes'' primarily incorporate clarification of terms and language, the following discussion relates to broadening the definition of positions that require HRP certification that is found in {section}712.10.

  14. Position indicating device

    International Nuclear Information System (INIS)

    Fellchenfeld, M.M.; Connors, G.R.

    1987-01-01

    This patent describes a position indicating device for producing an indication of the position of a displaceable structure comprising: a position representing member mounted for movement in response to displacement of the structure; sensing elements spaced apart along the defined path such that each element is associated with a respective location along the defined path; means operatively coupling the elements into respective pairs of elements, having, for each pair of elements, an output producing a signal only when a single element of its respective pair is responding to the presence of the member; signal producing members each operative for producing a signal representing a predetermined logic state in response to a predetermined input signal, the number of the signal producing members being smaller than the number of the sensing elements; and circuit means operatively connecting the outputs to the signal producing members for causing a signal at each output to produce a predetermined input signal at a corresponding signal producing member and for causing a predetermined input signal to be produced at least one the signal producing member whenever a signal is present at either one of at least two of the outputs

  15. Photon beam position monitor

    Science.gov (United States)

    Kuzay, Tuncer M.; Shu, Deming

    1995-01-01

    A photon beam position monitor for use in the front end of a beamline of a high heat flux and high energy photon source such as a synchrotron radiation storage ring detects and measures the position and, when a pair of such monitors are used in tandem, the slope of a photon beam emanating from an insertion device such as a wiggler or an undulator inserted in the straight sections of the ring. The photon beam position monitor includes a plurality of spaced blades for precisely locating the photon beam, with each blade comprised of chemical vapor deposition (CVD) diamond with an outer metal coating of a photon sensitive metal such as tungsten, molybdenum, etc., which combination emits electrons when a high energy photon beam is incident upon the blade. Two such monitors are contemplated for use in the front end of the beamline, with the two monitors having vertically and horizontally offset detector blades to avoid blade "shadowing". Provision is made for aligning the detector blades with the photon beam and limiting detector blade temperature during operation.

  16. Beam Position Monitor Engineering

    International Nuclear Information System (INIS)

    Smith, Stephen R.

    1996-07-01

    The design of beam position monitors often involves challenging system design choices. Position transducers must be robust, accurate, and generate adequate position signal without unduly disturbing the beam. Electronics must be reliable and affordable, usually while meeting tough requirements on precision. accuracy, and dynamic range. These requirements may be difficult to achieve simultaneously, leading the designer into interesting opportunities for optimization or compromise. Some useful techniques and tools are shown. Both finite element analysis and analytic techniques will be used to investigate quasi-static aspects of electromagnetic fields such as the impedance of and the coupling of beam to striplines or buttons. Finite-element tools will be used to understand dynamic aspects of the electromagnetic fields of beams, such as wake-fields and transmission-line and cavity effects in vacuum-to-air feed through. Mathematical modeling of electrical signals through a processing chain will be demonstrated, in particular to illuminate areas where neither a pure time-domain nor a pure frequency-domain analysis is obviously advantageous. Emphasis will be on calculational techniques, in particular on using both time-domain and frequency domain approaches to the applicable parts of interesting problems

  17. Position reconstruction in LUX

    Science.gov (United States)

    Akerib, D. S.; Alsum, S.; Araújo, H. M.; Bai, X.; Bailey, A. J.; Balajthy, J.; Beltrame, P.; Bernard, E. P.; Bernstein, A.; Biesiadzinski, T. P.; Boulton, E. M.; Brás, P.; Byram, D.; Cahn, S. B.; Carmona-Benitez, M. C.; Chan, C.; Currie, A.; Cutter, J. E.; Davison, T. J. R.; Dobi, A.; Druszkiewicz, E.; Edwards, B. N.; Fallon, S. R.; Fan, A.; Fiorucci, S.; Gaitskell, R. J.; Genovesi, J.; Ghag, C.; Gilchriese, M. G. D.; Hall, C. R.; Hanhardt, M.; Haselschwardt, S. J.; Hertel, S. A.; Hogan, D. P.; Horn, M.; Huang, D. Q.; Ignarra, C. M.; Jacobsen, R. G.; Ji, W.; Kamdin, K.; Kazkaz, K.; Khaitan, D.; Knoche, R.; Larsen, N. A.; Lenardo, B. G.; Lesko, K. T.; Lindote, A.; Lopes, M. I.; Manalaysay, A.; Mannino, R. L.; Marzioni, M. F.; McKinsey, D. N.; Mei, D.-M.; Mock, J.; Moongweluwan, M.; Morad, J. A.; Murphy, A. St. J.; Nehrkorn, C.; Nelson, H. N.; Neves, F.; O'Sullivan, K.; Oliver-Mallory, K. C.; Palladino, K. J.; Pease, E. K.; Rhyne, C.; Shaw, S.; Shutt, T. A.; Silva, C.; Solmaz, M.; Solovov, V. N.; Sorensen, P.; Sumner, T. J.; Szydagis, M.; Taylor, D. J.; Taylor, W. C.; Tennyson, B. P.; Terman, P. A.; Tiedt, D. R.; To, W. H.; Tripathi, M.; Tvrznikova, L.; Uvarov, S.; Velan, V.; Verbus, J. R.; Webb, R. C.; White, J. T.; Whitis, T. J.; Witherell, M. S.; Wolfs, F. L. H.; Xu, J.; Yazdani, K.; Young, S. K.; Zhang, C.

    2018-02-01

    The (x, y) position reconstruction method used in the analysis of the complete exposure of the Large Underground Xenon (LUX) experiment is presented. The algorithm is based on a statistical test that makes use of an iterative method to recover the photomultiplier tube (PMT) light response directly from the calibration data. The light response functions make use of a two dimensional functional form to account for the photons reflected on the inner walls of the detector. To increase the resolution for small pulses, a photon counting technique was employed to describe the response of the PMTs. The reconstruction was assessed with calibration data including 83mKr (releasing a total energy of 41.5 keV) and 3H (β- with Q = 18.6 keV) decays, and a deuterium-deuterium (D-D) neutron beam (2.45 MeV) . Within the detector's fiducial volume, the reconstruction has achieved an (x, y) position uncertainty of σ = 0.82 cm and σ = 0.17 cm for events of only 200 and 4,000 detected electroluminescence photons respectively. Such signals are associated with electron recoils of energies ~0.25 keV and ~10 keV, respectively. The reconstructed position of the smallest events with a single electron emitted from the liquid surface (22 detected photons) has a horizontal (x, y) uncertainty of 2.13 cm.

  18. Flank wear study of coating carbides and cermet inserts during the dry high speed turning of AISI 1045 steel; Estudio del desgaste del flanco de carburos recubiertos y cermet durante el torneado de alta velocidad en seco del acero AISI 1045

    Energy Technology Data Exchange (ETDEWEB)

    Hernandez-Gonzalez, L. W.; Perez-Rodriguez, R.; Zambrano-Robledo, P.; Guerrero-Mata, M.; Dumitrescu, L.

    2011-07-01

    This work deals with the experimental study of the flank wear evolution of two coating carbide inserts and a cermet insert during the dry finishing turning of AISI 1045 steel with 400, 500 and 600 m/min cutting speeds. The results were analyzed using the variance analysis and lineal regression analysis in order to describe the relationship between the flank wear and machining time, obtaining the adjusted model equation. The investigation demonstrated a significant effect of cutting speed and machining time on the flank wear at high speed machining. The three coating layers insert showed the best performance while the two layers insert had the worst behaviour of the cutting tool wear at high cutting speeds. (Author) 19 refs.

  19. Expression of wheat high molecular weight glutenin subunit 1Bx is affected by large insertions and deletions located in the upstream flanking sequences.

    Directory of Open Access Journals (Sweden)

    Yuke Geng

    Full Text Available To better understand the transcriptional regulation of high molecular weight glutenin subunit (HMW-GS expression, we isolated four Glu-1Bx promoters from six wheat cultivars exhibiting diverse protein expression levels. The activities of the diverse Glu-1Bx promoters were tested and compared with β-glucuronidase (GUS reporter fusions. Although all the full-length Glu-1Bx promoters showed endosperm-specific activities, the strongest GUS activity was observed with the 1Bx7OE promoter in both transient expression assays and stable transgenic rice lines. A 43 bp insertion in the 1Bx7OE promoter, which is absent in the 1Bx7 promoter, led to enhanced expression. Analysis of promoter deletion constructs confirmed that a 185 bp MITE (miniature inverted-repeat transposable element in the 1Bx14 promoter had a weak positive effect on Glu-1Bx expression, and a 54 bp deletion in the 1Bx13 promoter reduced endosperm-specific activity. To investigate the effect of the 43 bp insertion in the 1Bx7OE promoter, a functional marker was developed to screen 505 Chinese varieties and 160 European varieties, and only 1Bx7-type varieties harboring the 43 bp insertion in their promoters showed similar overexpression patterns. Hence, the 1Bx7OE promoter should be important tool in crop genetic engineering as well as in molecular assisted breeding.

  20. Positively deflected anomaly mediation

    International Nuclear Information System (INIS)

    Okada, Nobuchika

    2002-01-01

    We generalize the so-called 'deflected anomaly mediation' scenario to the case where threshold corrections of heavy messengers to the sparticle squared masses are positive. A concrete model realizing this scenario is also presented. The tachyonic slepton problem can be fixed with only a pair of messengers. The resultant sparticle mass spectrum is quite different from that in the conventional deflected anomaly mediation scenario, but is similar to the one in the gauge mediation scenario. The lightest sparticle is mostly B-ino

  1. Structural features of an exocyclic adduct positioned opposite an abasic site in a DNA duplex

    International Nuclear Information System (INIS)

    Kouchakdjian, M.; Patel, D.J.; Eisenberg, M.; Johnson, F.; Grollman, A.P.

    1991-01-01

    Structural studies have been extended to dual lesions where an exocyclic adduct is positioned opposite an abasic site in the center of a DNA oligomer duplex. NMR and energy minimization studies were performed on the 1,N 2 -propanodeoxyguanosine exocyclic adduct (X) positioned opposite a tetrahydrofuran abasic site (F) with the dual lesions located in the center of the (C1-A2-T3-G4-X5-G6-T7-A8-C9)·(G10-T11-A12-C13-F14-C15-A16-T17-G18) X·F 9-mer duplex. Two-dimensional NMR experiments establish that the X·F 9-mer helix is right-handed with Watson-Crick A·T and G·C base pairing on either side of the lesion site. NOEs are detected from the methylene protons of the exocyclic ring of X5 to the imino protons of G4·C15 and G6·C13 which flank the lesion site, as well as to the H1' and H1 double-prime protons of the cross strand F14 tetrahydrofuran moiety. These NMR results establish that the exocyclic adduct X5 is positioned between flanking G4·C15 and G6·C13 base pairs and directed toward the abasic lesion F14 on the partner strand. These studies establish that the exocyclic ring of the 1,N 2 -propanodeoxyguanosine adduct fits into the cavity generated by the abasic site

  2. Triangulation positioning system network

    Directory of Open Access Journals (Sweden)

    Sfendourakis Marios

    2017-01-01

    Full Text Available This paper presents ongoing work on localization and positioning through triangulation procedure for a Fixed Sensors Network - FSN.The FSN has to work as a system.As the triangulation problem becomes high complicated in a case with large numbers of sensors and transmitters, an adequate grid topology is needed in order to tackle the detection complexity.For that reason a Network grid topology is presented and areas that are problematic and need further analysis are analyzed.The Network System in order to deal with problems of saturation and False Triangulations - FTRNs will have to find adequate methods in every sub-area of the Area Of Interest - AOI.Also, concepts like Sensor blindness and overall Network blindness, are presented. All these concepts affect the Network detection rate and its performance and ought to be considered in a way that the network overall performance won’t be degraded.Network performance should be monitored contentiously, with right algorithms and methods.It is also shown that as the number of TRNs and FTRNs is increased Detection Complexity - DC is increased.It is hoped that with further research all the characteristics of a triangulation system network for positioning will be gained and the system will be able to perform autonomously with a high detection rate.

  3. Positive void reactivity

    International Nuclear Information System (INIS)

    Diamond, D.J.

    1992-09-01

    This report is a review of some of the important aspects of the analysis of large loss-of-coolant accidents (LOCAs). One important aspect is the calculation of positive void reactivity. To study this subject the lattice physics codes used for void worth calculations and the coupled neutronic and thermal-hydraulic codes used for the transient analysis are reviewed. Also reviewed are the measurements used to help validate the codes. The application of these codes to large LOCAs is studied with attention focused on the uncertainty factor for the void worth used to bias the results. Another aspect of the subject dealt with in the report is the acceptance criteria that are applied. This includes the criterion for peak fuel enthalpy and the question of whether prompt criticality should also be a criterion. To study the former, fuel behavior measurements and calculations are reviewed. (Author) (49 refs., 2 figs., tab.)

  4. Conference - La discipline positive

    CERN Multimedia

    Staff Association

    2018-01-01

    Eduquer avec fermeté et bienveillance Véronique Genevay Jeudi 31 mai à 19h00 CERN Meyrin, Salle du Conseil 503-1-001 Venez vous familiariser avec la pensée et le positionnement développé dans la discipline positive. Une approche ni permissive, ni punitive, qui vise à enseigner aux enfants des compétences comme la confiance en soi, l’autonomie, le respect de soi-même et le respect mutuel, la responsabilité, la coopération… Inscrivez-vous : https://indico.cern.ch/e/disciplinepositive   Pour plus d’informations : staff.association@cern.ch ou (+41) 022 766 37 38

  5. Position paper on mesotherapy.

    Science.gov (United States)

    Sarkar, Rashmi; Garg, Vijay Kumar; Mysore, Venkataram

    2011-01-01

    Mesotherapy is a controversial cosmetic procedure which has received publicity among the lay people, in the internet and in the media. It refers to minimally invasive techniques which consist of the use of intra- or subcutaneous injections containing liquid mixture of compounds (pharmaceutical and homeopathic medications, plant extracts, vitamins and other ingredients) to treat local medical and cosmetic conditions. This position paper has examined the available evidence and finds that acceptable scientific evidence for its effectiveness and safety is lacking. IADVL taskforce, therefore would like to state that the use of this technique remains controversial at present. Further research and well-designed controlled scientific studies are required to substantiate the claims of benefit of this mode of therapy.

  6. Position paper on mesotherapy

    Directory of Open Access Journals (Sweden)

    Rashmi Sarkar

    2011-01-01

    Full Text Available Mesotherapy is a controversial cosmetic procedure which has received publicity among the lay people, in the internet and in the media. It refers to minimally invasive techniques which consist of the use of intra- or subcutaneous injections containing liquid mixture of compounds (pharmaceutical and homeopathic medications, plant extracts, vitamins and other ingredients to treat local medical and cosmetic conditions. This position paper has examined the available evidence and finds that acceptable scientific evidence for its effectiveness and safety is lacking. IADVL taskforce, therefore would like to state that the use of this technique remains controversial at present. Further research and well-designed controlled scientific studies are required to substantiate the claims of benefit of this mode of therapy.

  7. Galileo positioning technology

    CERN Document Server

    Lohan, Elena; Sand, Stephan; Hurskainen, Heikki

    2015-01-01

    This book covers multi-band Galileo receivers (especially E1-E5 bands of Galileo) and addresses all receiver building blocks, from the antenna and front end, through details of the baseband receiver processing blocks, up to the navigation processing, including the Galileo message structure and Position, Velocity, Time (PVT) computation. Moreover, hybridization solutions with communications systems for improved localization are discussed and an open-source GNSS receiver platform (available for download) developed at Tampere University of Technology (TUT) is addressed in detail. • Takes a holistic approach to GALILEO and related systems, such as EGNOS and hybrid solutions on mobile phones; • Provides an invaluable reference to Binary Offset Carrier modulations and related families, which are some of the trademarks of GALILEO; • Includes a detailed survey of GALILEO receiver research in Europe and existing software-defined radio (SDR) GALILEO receiver implementations; • Addresses the multiple challen...

  8. ISSP Position Stand

    DEFF Research Database (Denmark)

    Ryba, Tatiana; Stambulova, Natalia; Si, Gangyan

    2013-01-01

    The multicultural landscape of contemporary sport sets a challenge to rethink sport and exercise psychology research and practice through a culturally re␣exive lens. This ISSP Position Stand provides a rigorous synthesis and engagement with existing scholarship to outline a roadmap for future work...... in the ␣eld. The shift to culturally competent sport and exercise psychology implies: (a) recognizing hidden ethnocentric philosophical assumptions permeating much of the current theory, research, and practice; (b) transitioning to professional ethics in which difference is seen as not inherent and ␣xed...... but as relational and ␣uid; and (c) focusing on meaning (instead of cause) in cross-cultural and cultural research projects, and cultural praxis work. In the paper, we ␣rst provide an overview of the concepts of cultural competence and ethics of difference. Second, we present a step-by-step approach for developing...

  9. Amygdala responses to unpleasant pictures are influenced by task demands and positive affect trait

    Directory of Open Access Journals (Sweden)

    Tiago Arruda Sanchez

    2015-03-01

    Full Text Available The role of attention in emotional processing is still the subject of debate. Recent studies have found that high positive affect in approach motivation narrows attention. Furthermore, the positive affect trait has been suggested as an important component for determining human variability in threat reactivity. We employed fMRI to investigate whether different states of attention control would modulate amygdala responses to highly unpleasant pictures relative to neutral and whether this modulation would be influenced by the positive affect trait. Participants (n=22, 12 male were scanned while viewing neutral (people or unpleasant pictures (mutilated bodies flanked by two peripheral bars. They were instructed to (a judge the picture content as unpleasant or neutral or (b to judge the difference in orientation between the bars in an easy condition (0º or 90º orientation difference or (c in a hard condition (0º or 6º orientation difference. Whole brain analysis revealed a task main effect of brain areas related to the experimental manipulation of attentional control, including the amygdala, dorsolateral prefrontal cortex and posterior parietal cortex. ROI analysis showed an inverse correlation (r = -0.51, p < 0.01 between left amygdala activation and positive affect level when participants viewed unpleasant stimuli and judged bar orientation in the easy condition. This result suggests that subjects with high positive affect exhibit lower amygdala reactivity to distracting unpleasant pictures. In conclusion, the current study suggests that positive affect modulates attention effect on unpleasant pictures, therefore attenuating emotional responses.

  10. Serological biomarkers in triage of FIT-positive subjects?

    DEFF Research Database (Denmark)

    Nielsen, Hans J; Christensen, Ib Jarle; Andersen, Berit

    2017-01-01

    with neoplastic lesions missed by increased cut-off levels appears to be much higher than expected. Therefore, tests that identify those patients missed by increased FIT cut-off levels must be developed. Preliminary results of determination of one of several biomarker entities currently under investigation show...... that nucleosome blood tests may be one option for identifying some of these patients. Implementation of a triage test consisting of FIT, blood-based biomarkers and plus/minus colonoscopy is suggested to identify subjects with FIT levels between the initial and the increased cut-off level that must be offered...

  11. The Power of Positive Emotions

    Science.gov (United States)

    ... Safe Videos for Educators Search English Español The Power of Positive Emotions KidsHealth / For Teens / The Power ... great one. 2. Practice Positivity Every Day Building habits that encourage us to feel more positive emotions ...

  12. Detecting positive quadrant dependence and positive function dependence

    NARCIS (Netherlands)

    Janic-Wróblewska, A.; Kallenberg, W.C.M.; Ledwina, T.

    2004-01-01

    There is a lot of interest in positive dependence going beyond linear correlation. In this paper three new rank tests for testing independence against positive dependence are introduced. The first one is directed on positive quadrant dependence, the second and third one concentrate on positive

  13. Detecting positive quadrant dependence and positive function dependence

    NARCIS (Netherlands)

    Janic-Wróblewska, A.; Kallenberg, W.C.M.; Ledwina, T.

    2003-01-01

    There is a lot of interest in positive dependence going beyond linear correlation. In this paper three new rank tests for testing independence against positive dependence are introduced. The first one is directed on positive quadrant dependence, the second and third one concentrate on positive

  14. Relationship of condylar position to disc position and morphology

    Energy Technology Data Exchange (ETDEWEB)

    Incesu, L.; Taskaya-Yilmaz, N. E-mail: nergizy@omu.edu.tr; Oeguetcen-Toller, M.; Uzun, E

    2004-09-01

    Introduction/objective: The purpose of this study was to assess whether condylar position, as depicted by magnetic resonance imaging, was an indicator of disc morphology and position. Methods and material: One hundred and twenty two TMJs of 61 patients with temporomandibular joint disorder were examined. Condylar position, disc deformity and degree of anterior disc displacement were evaluated by using magnetic resonance imaging. Results and discussion: Posterior condyle position was found to be the main feature of temporomandibular joints with slight and moderate anterior disc displacement. No statistical significance was found between the condylar position, and reducing and nonreducing disc positions. On the other hand, superior disc position was found to be statistically significant for centric condylar position. Conclusion: It was concluded that posterior condyle position could indicate anterior disc displacement whereas there was no relation between the position of condyle and the disc deformity.

  15. SQUID position sensor development

    Science.gov (United States)

    Torii, Rodney

    1996-11-01

    I describe the development of an inductance position sensor for the STEP (satellite test of the equivalence principle) accelerometer. I have measured the inductance (with an experimental error of 0.5%) of a single-turn thin-film niobium pick-up coil as a function of the distance from a thin-film niobium disc (both at 4.2 K and superconducting). The circular pick-up coil had a diameter of 4 cm with a track width of 0264-9381/13/11A/022/img1. The disc (mock test mass) had a diameter of 4 cm. The distance range between the coil and disc was set by the range of a low-temperature differential capacitance sensor: 0 - 2 mm with a resolution of 0264-9381/13/11A/022/img2. The full range of the low-temperature translation stage was 0 - 4 mm. The inductance was measured using an LCR meter in a four-wire configuration. The measured inductance was compared to the inductance of a circular loop above a superconducting plane. Due to the fact that the thin-film disc is of finite size, the calculation differed from experiment by as much as 12%. I have also calculated the inductance by segmenting the thin-film niobium disc into 500 concentric rings (each with a width of 0264-9381/13/11A/022/img3). A discrepancy between calculation and experiment of approximately 3% was found.

  16. Gathering positive experience

    CERN Document Server

    2009-01-01

    Last Monday, the new CERN Machine Advisory Committee (CMAC) met for the first time, and we had good news to tell its members. Over the weekend, injection tests for both LHC beams were successfully carried out. In other words, we’ve had beam in the LHC for the first time since September 2008. That’s a good feeling, but it’s no reason for complacency. There’s still a long way to go before first physics at the new energy frontier. As the Bulletin has reported over recent weeks, we’re gathering a lot of positive experience with the new quench detection and protection system (QPS), which is already allowing us to monitor the LHC far better than we were able to in the past. So far, the QPS for three of the LHC’s eight sectors has been put through its paces, and we’ve also power tested those sectors to 2000 amperes, the equivalent of around 1.2 TeV per beam. The next step is to slowly increase the current to 4000 amperes, and...

  17. Climate change policy position

    International Nuclear Information System (INIS)

    2002-11-01

    The Canadian Association of Petroleum Producers (CAPP) is a firm believer in the need to take action to mitigate the risks associated with climate change, and that clear government policy is called for. The principles of sustainable development must guide this policy development effort. The initiatives required to address greenhouse gas emissions over both the short and long term must be carefully considered, and it is up to industries to ensure their production efficiency and emission intensity. Promoting improved performance of industries in Canada and developing technology that can be deployed internationally for larger global effects represents Canada's best contribution to progress on greenhouse gas emissions. The increase in energy demand along with increases in population and economic growth have contributed to an increase in greenhouse gas emissions despite improved energy efficiency in industry. Significant damage to the economy will result if Canada is to meet its commitment under the Kyoto Protocol, forcing the country to buy large quantities of foreign credits instead of using those funds for increased research and development. CAPP indicated that an effective plan must be: balanced, equitable, responsible, competitive, focused on technology and innovation, and based on agreements on sectoral plans. Each of these principles were discussed, followed by the fundamentals of approach for upstream oil and gas. The framework for climate change policy was described as well as the elements of a sector plan. CAPP wants to work with all levels of government on an appropriate plan for Canada, that considers our unique circumstances. Canada can play a significant role on the international stage by properly implementing the policy position proposed by the CAPP without unnecessary risks to the economy. refs

  18. Exposing Position Uncertainty in Middleware

    DEFF Research Database (Denmark)

    Langdal, Jakob; Kjærgaard, Mikkel Baun; Toftkjær, Thomas

    2010-01-01

    Traditionally, the goal for positioning middleware is to provide developers with seamless position transparency, i.e., providing a connection between the application domain and the positioning sensors while hiding the complexity of the positioning technologies in use. A key part of the hidden com...

  19. Thruster allocation for dynamical positioning

    NARCIS (Netherlands)

    Poppe, K.; van den Berg, J.B.; Blank, E.; Archer, C.; Redeker, M.; Kutter, M.; Hemker, P.

    2010-01-01

    Positioning a vessel at a fixed position in deep water is of great importance when working offshore. In recent years a Dynamical Positioning (DP) system was developed at Marin [2]. After the measurement of the current position and external forces (like waves, wind etc.), each thruster of the vessel

  20. Positive Technologies for Understanding and Promoting Positive Emotions.

    Science.gov (United States)

    Baños, Rosa María; Carrillo, Alba; Etchemendy, Ernestina; Botella, Cristina

    2017-10-26

    Information and Communication Technologies (ICTs) have become increasingly present in our lives, and their use has spread considerably. This paper presents a review of the way ICTs can help practitioners and researchers to study, promote, and train positive emotions. It is framed within the field of Positive Technologies: the applied scientific approach to the study of the use of technology to improve the quality of personal experience, with the goal of increasing wellbeing. First, the article presents an introduction to the topic of technologies and positive emotions. Then, it describes how ICTs can aid in monitoring, assessing, promoting, modifying, and training positive emotions. Finally, implications and future directions of the role of Positive Technologies in positive emotions are discussed. The authors conclude that, in the near future, Positive Technologies and the field of positive emotions will interact synergistically, producing an exponential growth in the understanding and promotion of positive emotions.

  1. Neural correlates of an early attentional capture by positive distractor words.

    Science.gov (United States)

    Hinojosa, José A; Mercado, Francisco; Albert, Jacobo; Barjola, Paloma; Peláez, Irene; Villalba-García, Cristina; Carretié, Luis

    2015-01-01

    Exogenous or automatic attention to emotional distractors has been observed for emotional scenes and faces. In the language domain, however, automatic attention capture by emotional words has been scarcely investigated. In the current event-related potentials study we explored distractor effects elicited by positive, negative and neutral words in a concurrent but distinct target distractor paradigm. Specifically, participants performed a digit categorization task in which task-irrelevant words were flanked by numbers. The results of both temporo-spatial principal component and source location analyses revealed the existence of early distractor effects that were specifically triggered by positive words. At the scalp level, task-irrelevant positive compared to neutral and negative words elicited larger amplitudes in an anterior negative component that peaked around 120 ms. Also, at the voxel level, positive distractor words increased activity in orbitofrontal regions compared to negative words. These results suggest that positive distractor words quickly and automatically capture attentional resources diverting them from the task where attention was voluntarily directed.

  2. Neural correlates of an early attentional capture by positive distractor words

    Directory of Open Access Journals (Sweden)

    José Antonio Hinojosa

    2015-01-01

    Full Text Available Exogenous or automatic attention to emotional distractors has been observed for emotional scenes and faces. In the language domain, however, automatic attention capture by emotional words has been scarcely investigated. In the current event-related potentials study we explored distractor effects elicited by positive, negative and neutral words in a concurrent but distinct target distractor paradigm. Specifically, participants performed a digit categorization task in which task-irrelevant words were flanked by numbers. The results of both temporo-spatial principal component and source location analyses revealed the existence of early distractor effects that were specifically triggered by positive words. At the scalp level, task-irrelevant positive compared to neutral and negative words elicited larger amplitudes in an anterior negative component that peaked around 120 ms. Also, at the voxel level, positive distractor words increased activity in orbitofrontal regions compared to negative words. These results suggest that positive distractor words quickly and automatically capture attentional resources diverting them from the task where attention was voluntarily directed.

  3. Secure positioning in wireless networks

    DEFF Research Database (Denmark)

    Capkun, Srdjan; Hubaux, Jean-Pierre

    2006-01-01

    So far, the problem of positioning in wireless networks has been studied mainly in a non-adversarial settings. In this work, we analyze the resistance of positioning techniques to position and distance spoofing attacks. We propose a mechanism for secure positioning of wireless devices, that we call...... Verifiable Multilateration. We then show how this mechanism can be used to secure positioning in sensor networks. We analyze our system through simulations....

  4. Rapid identification of 11 human intestinal Lactobacillus species by multiplex PCR assays using group- and species-specific primers derived from the 16S-23S rRNA intergenic spacer region and its flanking 23S rRNA.

    Science.gov (United States)

    Song, Y; Kato, N; Liu, C; Matsumiya, Y; Kato, H; Watanabe, K

    2000-06-15

    Rapid and reliable two-step multiplex polymerase chain reaction (PCR) assays were established to identify human intestinal lactobacilli; a multiplex PCR was used for grouping of lactobacilli with a mixture of group-specific primers followed by four multiplex PCR assays with four sorts of species-specific primer mixtures for identification at the species level. Primers used were designed from nucleotide sequences of the 16S-23S rRNA intergenic spacer region and its flanking 23S rRNA gene of members of the genus Lactobacillus which are commonly isolated from human stool specimens: Lactobacillus acidophilus, Lactobacillus crispatus, Lactobacillus delbrueckii (ssp. bulgaricus and ssp. lactis), Lactobacillus fermentum, Lactobacillus gasseri, Lactobacillus jensenii, Lactobacillus paracasei (ssp. paracasei and ssp. tolerans), Lactobacillus plantarum, Lactobacillus reuteri, Lactobacillus rhamnosus and Lactobacillus salivarius (ssp. salicinius and ssp. salivarius). The established two-step multiplex PCR assays were applied to the identification of 84 Lactobacillus strains isolated from human stool specimens and the PCR results were consistent with the results from the DNA-DNA hybridization assay. These results suggest that the multiplex PCR system established in this study is a simple, rapid and reliable method for the identification of common Lactobacillus isolates from human stool samples.

  5. Evidence for the Association of a Deleted Variant in the 5′-Flanking Region of the Chicken serotonin transporter (5-HTT Gene with a Temporary Increase in Feed Intake and Growth Rate

    Directory of Open Access Journals (Sweden)

    Joergen B. Kjaer

    2016-10-01

    Full Text Available The serotonergic system has been shown to be implicated in the regulation of mood and feeding behavior. Previous studies have identified a polymorphism in the 5′-flanking region of the serotonin transporter ( 5 - HTT gene of Lohmann Brown (LB laying hens. The deleted variant D was found to be associated with increased body weight. The objective of this study was to address whether the increased body weight may be due to an increased feed intake. After hatching, hens were kept under ad libitum feeding conditions, and their body weight and feed intake were weekly determined. From 5 weeks of age, the body weight of hens with the D/D and W/D genotypes was significantly greater than that of W/W carrying hens. Interestingly, we found that the feed intake of D/D carrying hens, relative to body weight, was transiently increased only between 4 and 7 weeks of age ( p < 0.05, leading to a higher growth rate ( p < 0.05, compared with that of W/W carrying hens. These results suggest that the presence of variant D may be correlated with a transiently increased appetite of D/D carrying hens.

  6. Exceptional recurrence of flank destabilizations in the recent activity of the Colima volcanic complex, Mexico; Recurrence exceptionnelle de destabilisations de flanc dans l`activite recente du complexe volcanique du Colima, Mexique

    Energy Technology Data Exchange (ETDEWEB)

    Komorowski, J C [IPGP, (Mexico); Siebe, C [Institut de Geofisica, UNAM (Mexico); Rodriguez, S [Institut de Geologia, UNAM (Mexico); Cortes, A; Navarro, C; Gavilanes, J C

    1997-12-31

    This short paper reports on new {sup 14}C datings of debris flow units from the Nevado de Colima and Fuego de Colima volcanoes in Mexico. These new datings in connection with a detailed stratigraphic study in the deep canyons around the volcanoes has revealed an exceptional recurrence of flank destabilizations of the Fuego de Colima during the last 45000 years. The cumulated volume of debris in the whole Colima massif is estimated to 60-100 km{sup 3}. The correlation between Landsat satellite pictures and the distribution and age of the debris flows shows that both volcanoes are made of several post-destabilization remaining structures, and that both volcanoes were active and simultaneously collapsed 18500 years ago. The numerous fluvial-lacustrine sequences intercalated between the successive flows indicate that the debris flow were partially sedimented under water and could have led to catastrophic tsunamis towards the Pacific coast. Implications of this work are important because a population of more than 200000 inhabitants is living in a zone covered by several debris flows. (J.S.).

  7. Influence of Cutting Fluid Flow Rate and Cutting Parameters on the Surface Roughness and Flank Wear of TiAlN Coated Tool In Turning AISI 1015 Steel Using Taguchi Method

    Directory of Open Access Journals (Sweden)

    Moganapriya C.

    2017-09-01

    Full Text Available This paper presents the influence of cutting parameters (Depth of cut, feed rate, spindle speed and cutting fluid flow rate on the surface roughness and flank wear of physical vapor deposition (PVD Cathodic arc evaporation coated TiAlN tungsten carbide cutting tool insert during CNC turning of AISI 1015 mild steel. Analysis of Variance has been applied to determine the critical influence of cutting parameters. Taguchi orthogonal test design has been employed to optimize the process parameters affecting surface roughness and tool wear. Depth of cut was found to be the most dominant factor contributing to high surface roughness (67.5% of the inserts. However, cutting speed, feed rate and flow rate of cutting fluid showed minimal contribution to surface roughness. On the other hand, cutting speed (45.6% and flow rate of cutting fluid (23% were the dominant factors influencing tool wear. The optimum cutting conditions for desired surface roughness constitutes the following parameters such as medium cutting speed, low feed rate, low depth of cut and high cutting fluid flow rate. Minimal tool wear was achieved for the following process parameters such as low cutting speed, low feed rate, medium depth of cut and high cutting fluid flow rate.

  8. Exceptional recurrence of flank destabilizations in the recent activity of the Colima volcanic complex, Mexico; Recurrence exceptionnelle de destabilisations de flanc dans l`activite recente du complexe volcanique du Colima, Mexique

    Energy Technology Data Exchange (ETDEWEB)

    Komorowski, J.C. [IPGP, (Mexico); Siebe, C. [Institut de Geofisica, UNAM (Mexico); Rodriguez, S. [Institut de Geologia, UNAM (Mexico); Cortes, A.; Navarro, C.; Gavilanes, J.C.

    1996-12-31

    This short paper reports on new {sup 14}C datings of debris flow units from the Nevado de Colima and Fuego de Colima volcanoes in Mexico. These new datings in connection with a detailed stratigraphic study in the deep canyons around the volcanoes has revealed an exceptional recurrence of flank destabilizations of the Fuego de Colima during the last 45000 years. The cumulated volume of debris in the whole Colima massif is estimated to 60-100 km{sup 3}. The correlation between Landsat satellite pictures and the distribution and age of the debris flows shows that both volcanoes are made of several post-destabilization remaining structures, and that both volcanoes were active and simultaneously collapsed 18500 years ago. The numerous fluvial-lacustrine sequences intercalated between the successive flows indicate that the debris flow were partially sedimented under water and could have led to catastrophic tsunamis towards the Pacific coast. Implications of this work are important because a population of more than 200000 inhabitants is living in a zone covered by several debris flows. (J.S.).

  9. Replication origins oriGNAI3 and oriB of the mammalian AMPD2 locus nested in a region of straight DNA flanked by intrinsically bent DNA sites.

    Science.gov (United States)

    Balani, Valério Américo; de Lima Neto, Quirino Alves; Takeda, Karen Izumi; Gimenes, Fabrícia; Fiorini, Adriana; Debatisse, Michelle; Fernandez, Maria Aparecida

    2010-11-01

    The aim of this work was to determine whether intrinsically bent DNA sites are present at, or close to, the mammalian replication origins oriGNAI3 and oriB in the Chinese hamster AMPD2 locus. Using an electrophoretic mobility shift assay and in silico analysis, we located four intrinsically bent DNA sites (b1 to b4) in a fragment that contains the oriGNAI3 and one site (b5) proximal to oriB. The helical parameters show that each bent DNA site is curved in a left-handed superhelical writhe. A 2D projection of 3D fragment trajectories revealed that oriGNAI3 is located in a relatively straight segment flanked by bent sites b1 and b2, which map in previously identified Scaffold/Matrix Attachment Region. Sites b3 and b4 are located approximately 2 kb downstream and force the fragment into a strong closed loop structure. The b5 site is also located in an S/MAR that is found just downstream of oriB.

  10. Flank hernia secondary to phenol nerve block.

    LENUS (Irish Health Repository)

    Al-Hilli, Z

    2010-09-01

    The management of patients with chronic pain is challenging. The aim of treatment is alleviation of symptoms in an attempt to increase functional capacity. Interventional procedures, such as chemical neurolysis are adopted when other techniques fail to provide adequate pain control.

  11. Position detectors, methods of detecting position, and methods of providing positional detectors

    Science.gov (United States)

    Weinberg, David M.; Harding, L. Dean; Larsen, Eric D.

    2002-01-01

    Position detectors, welding system position detectors, methods of detecting various positions, and methods of providing position detectors are described. In one embodiment, a welding system positional detector includes a base that is configured to engage and be moved along a curved surface of a welding work piece. At least one position detection apparatus is provided and is connected with the base and configured to measure angular position of the detector relative to a reference vector. In another embodiment, a welding system positional detector includes a weld head and at least one inclinometer mounted on the weld head. The one inclinometer is configured to develop positional data relative to a reference vector and the position of the weld head on a non-planar weldable work piece.

  12. False Position, Double False Position and Cramer's Rule

    Science.gov (United States)

    Boman, Eugene

    2009-01-01

    We state and prove the methods of False Position (Regula Falsa) and Double False Position (Regula Duorum Falsorum). The history of both is traced from ancient Egypt and China through the work of Fibonacci, ending with a connection between Double False Position and Cramer's Rule.

  13. Positive Psychology and Positive Education: Old Wine in New Bottles?

    Science.gov (United States)

    Kristjansson, Kristjan

    2012-01-01

    The recently fashionable theories of positive psychology have educational ramifications at virtually every level of engagement, culminating in the model of positive education. In this critical review, I scrutinize positive education as a potential theory in educational psychology. Special attention is given to conceptual controversies and…

  14. Mechanical ventilation with lower tidal volumes and positive end-expiratory pressure prevents pulmonary inflammation in patients without preexisting lung injury.

    Science.gov (United States)

    Wolthuis, Esther K; Choi, Goda; Dessing, Mark C; Bresser, Paul; Lutter, Rene; Dzoljic, Misa; van der Poll, Tom; Vroom, Margreeth B; Hollmann, Markus; Schultz, Marcus J

    2008-01-01

    Mechanical ventilation with high tidal volumes aggravates lung injury in patients with acute lung injury or acute respiratory distress syndrome. The authors sought to determine the effects of short-term mechanical ventilation on local inflammatory responses in patients without preexisting lung injury. Patients scheduled to undergo an elective surgical procedure (lasting > or = 5 h) were randomly assigned to mechanical ventilation with either higher tidal volumes of 12 ml/kg ideal body weight and no positive end-expiratory pressure (PEEP) or lower tidal volumes of 6 ml/kg and 10 cm H2O PEEP. After induction of anesthesia and 5 h thereafter, bronchoalveolar lavage fluid and/or blood was investigated for polymorphonuclear cell influx, changes in levels of inflammatory markers, and nucleosomes. Mechanical ventilation with lower tidal volumes and PEEP (n = 21) attenuated the increase of pulmonary levels of interleukin (IL)-8, myeloperoxidase, and elastase as seen with higher tidal volumes and no PEEP (n = 19). Only for myeloperoxidase, a difference was found between the two ventilation strategies after 5 h of mechanical ventilation (P volumes and PEEP may limit pulmonary inflammation in mechanically ventilated patients without preexisting lung injury. The specific contribution of both lower tidal volumes and PEEP on the protective effects of the lung should be further investigated.

  15. Continuous Positive Airway Pressure (CPAP)

    Science.gov (United States)

    ... ENT Doctor Near You Continuous Positive Airway Pressure (CPAP) Continuous Positive Airway Pressure (CPAP) Patient Health Information ... relations staff at newsroom@entnet.org . What Is CPAP? The most common and effective nonsurgical treatment for ...

  16. Amygdala responses to unpleasant pictures are influenced by task demands and positive affect trait.

    Science.gov (United States)

    Sanchez, Tiago A; Mocaiber, Izabela; Erthal, Fatima S; Joffily, Mateus; Volchan, Eliane; Pereira, Mirtes G; de Araujo, Draulio B; Oliveira, Leticia

    2015-01-01

    The role of attention in emotional processing is still the subject of debate. Recent studies have found that high positive affect in approach motivation narrows attention. Furthermore, the positive affect trait has been suggested as an important component for determining human variability in threat reactivity. We employed functional magnetic resonance imaging to investigate whether different states of attention control would modulate amygdala responses to highly unpleasant pictures relative to neutral and whether this modulation would be influenced by the positive affect trait. Participants (n = 22, 12 male) were scanned while viewing neutral (people) or unpleasant pictures (mutilated bodies) flanked by two peripheral bars. They were instructed to (a) judge the picture content as unpleasant or neutral or (b) to judge the difference in orientation between the bars in an easy condition (0 or 90(∘) orientation difference) or (c) in a hard condition (0 or 6(∘) orientation difference). Whole brain analysis revealed a task main effect of brain areas related to the experimental manipulation of attentional control, including the amygdala, dorsolateral prefrontal cortex, and posterior parietal cortex. Region of interest analysis showed an inverse correlation (r = -0.51, p pictures. In conclusion, the current study suggests that positive affect modulates attention effect on unpleasant pictures, therefore attenuating emotional responses.

  17. Collective Behaviour: Physiology Determines Position.

    Science.gov (United States)

    Krause, Jens; Seebacher, Frank

    2018-04-23

    An animal's position within a group affects feeding - front positions generally offer richer pickings. However, a new study shows that position can be influenced by feeding because big meals reduce scope for locomotion. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

  18. Introducing Positive Psychology to SLA

    Science.gov (United States)

    MacIntyre, Peter D.; Mercer, Sarah

    2014-01-01

    Positive psychology is a rapidly expanding subfield in psychology that has important implications for the field of second language acquisition (SLA). This paper introduces positive psychology to the study of language by describing its key tenets. The potential contributions of positive psychology are contextualized with reference to prior work,…

  19. Navicular bone position determined by positional MRI: a reproducibility study

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, Philip; Nybing, Janus D. [Copenhagen University Hospital Frederiksberg and Bispebjerg, Department of Radiology, Frederiksberg (Denmark); Johannsen, Finn E.; Stallknecht, Sandra E. [Copenhagen University Hospital Bispebjerg, Institute of Sports Medicine Copenhagen, Copenhagen, NV (Denmark); Hangaard, Stine; Hansen, Bjarke B. [Copenhagen University Hospital Frederiksberg, Parker Institute, Department of Rheumatology, Frederiksberg (Denmark); Boesen, Mikael [Copenhagen University Hospital Frederiksberg and Bispebjerg, Department of Radiology, Frederiksberg (Denmark); Copenhagen University Hospital Frederiksberg, Parker Institute, Department of Rheumatology, Frederiksberg (Denmark)

    2016-02-15

    To examine intraobserver, interobserver and between-day reproducibility of positional MRI for evaluation of navicular bone height (NVH) and medial navicular position (MNP). Positional MRI (pMRI) of the foot was performed on ten healthy participants (0.25 T G-scanner). Scanning was performed in supine and standing position, respectively. Two radiologists evaluated the images in a blinded manner. Reliability and agreement were assessed by calculation of intraclass correlation coefficient (ICC) and 95 % limits of agreement as a percentage of the mean (LOA%). Intraobserver and interobserver reliability was ''substantial'' in both supine and standing position (ICC 0.86-0.98) and showed good agreement (LOA% 4.9-14.7 %). Between-day reliability of navicular height and medial navicular position in standing position remained substantial (ICC 0.85-0.92) with adequate agreement (LOA% 8.3-19.8 %). In supine position between-day reliability was ''moderate'' for NVH (ICC 0.72) and ''slight'' for MNP (ICC 0.39). Agreement remained adequate between-days for MNP in supine position (LOA% 17.7 %), but it was less than adequate for NVH in supine position (LOA% 24.2 %). Navicular height and medial navicular position can be measured by pMRI in a very reproducible manner within and between observers. Increased measurement variation is observed between-days in supine position, which may be due to small positional differences or other unknown biomechanical factors. (orig.)

  20. Navicular bone position determined by positional MRI: a reproducibility study

    International Nuclear Information System (INIS)

    Hansen, Philip; Nybing, Janus D.; Johannsen, Finn E.; Stallknecht, Sandra E.; Hangaard, Stine; Hansen, Bjarke B.; Boesen, Mikael

    2016-01-01

    To examine intraobserver, interobserver and between-day reproducibility of positional MRI for evaluation of navicular bone height (NVH) and medial navicular position (MNP). Positional MRI (pMRI) of the foot was performed on ten healthy participants (0.25 T G-scanner). Scanning was performed in supine and standing position, respectively. Two radiologists evaluated the images in a blinded manner. Reliability and agreement were assessed by calculation of intraclass correlation coefficient (ICC) and 95 % limits of agreement as a percentage of the mean (LOA%). Intraobserver and interobserver reliability was ''substantial'' in both supine and standing position (ICC 0.86-0.98) and showed good agreement (LOA% 4.9-14.7 %). Between-day reliability of navicular height and medial navicular position in standing position remained substantial (ICC 0.85-0.92) with adequate agreement (LOA% 8.3-19.8 %). In supine position between-day reliability was ''moderate'' for NVH (ICC 0.72) and ''slight'' for MNP (ICC 0.39). Agreement remained adequate between-days for MNP in supine position (LOA% 17.7 %), but it was less than adequate for NVH in supine position (LOA% 24.2 %). Navicular height and medial navicular position can be measured by pMRI in a very reproducible manner within and between observers. Increased measurement variation is observed between-days in supine position, which may be due to small positional differences or other unknown biomechanical factors. (orig.)