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Sample records for regulates higher-order chromatin

  1. Higher order chromatin organization in cancer

    Science.gov (United States)

    Reddy, Karen L.; Feinberg, Andrew P.

    2013-01-01

    In spite of our increased understanding of how genomes are dysregulated in cancer and a plethora of molecular diagnostic tools, the front line and ‘gold standard’ detection of cancer remains the pathologist’s detection of gross changes in cellular and tissue structure, most strikingly nuclear dis-organization. In fact, for over 140 years it has been noted that nuclear morphology is often disrupted in cancer. Even today, nuclear morphology measures include nuclear size, shape, DNA content (ploidy) and ‘chromatin organization’. Given the importance of nuclear shape to diagnoses of cancer phenotypes, it is surprising and frustrating that we currently lack a detailed understanding to explain these changes and how they might arise and relate to molecular events in the cell. It is an implicit hypothesis that perturbation of chromatin and epigenetic signatures may lead to alterations in nuclear structure (or vice versa) and that these perturbations lie at the heart of cancer genesis. In this review, we attempt to synthesize research leading to our current understanding on how chromatin interactions at the nuclear lamina, epigenetic modulation and gene regulation may intersect in cancer and offer a perspective on critical experiments that would help clarify how nuclear architecture may contribute to the cancerous phenotype. We also discuss the historical understanding of nuclear structure in normal cells and as a diagnostic in cancer. PMID:23266653

  2. Neutron scattering studies on chromatin higher-order structure

    Energy Technology Data Exchange (ETDEWEB)

    Graziano, V.; Gerchman, S.E.; Schneider, D.K.; Ramakrishnan, V. [Brookhaven National Laboratory, Upton, NY (United States)

    1994-12-31

    We have been engaged in studies of the structure and condensation of chromatin into the 30nm filament using small-angle neutron scattering. We have also used deuterated histone H1 to determine its location in the chromatin 30nm filament. Our studies indicate that chromatin condenses with increasing ionic strength to a limiting structure that has a mass per unit length of 6-7 nucleosomes/11 nm. They also show that the linker histone H1/H5 is located in the interior of the chromatin filament, in a position compatible with its binding to the inner face of the nucleosome. Analysis of the mass per unit length as a function of H5 stoichiometry suggests that 5-7 contiguous nucleosomes need to have H5 bound before a stable higher order structure can exist.

  3. Neutron scattering studies on chromatin higher-order structure

    International Nuclear Information System (INIS)

    Graziano, V.; Gerchman, S.E.; Schneider, D.K.; Ramakrishnan, V.

    1994-01-01

    We have been engaged in studies of the structure and condensation of chromatin into the 30nm filament using small-angle neutron scattering. We have also used deuterated histone H1 to determine its location in the chromatin 30nm filament. Our studies indicate that chromatin condenses with increasing ionic strength to a limiting structure that has a mass per unit length of 6-7 nucleosomes/11 nm. They also show that the linker histone H1/H5 is located in the interior of the chromatin filament, in a position compatible with its binding to the inner face of the nucleosome. Analysis of the mass per unit length as a function of H5 stoichiometry suggests that 5-7 contiguous nucleosomes need to have H5 bound before a stable higher order structure can exist

  4. Higher-order structure of Saccharomyces cerevisiae chromatin

    International Nuclear Information System (INIS)

    Lowary, P.T.; Widom, J.

    1989-01-01

    We have developed a method for partially purifying chromatin from Saccharomyces cerevisiae (baker's yeast) to a level suitable for studies of its higher-order folding. This has required the use of yeast strains that are free of the ubiquitous yeast killer virus. Results from dynamic light scattering, electron microscopy, and x-ray diffraction show that the yeast chromatin undergoes a cation-dependent folding into 30-nm filaments that resemble those characteristic of higher-cell chromatin; moreover, the packing of nucleosomes within the yeast 30-nm filaments is similar to that of higher cells. These results imply that yeast has a protein or protein domain that serves the role of the histone H 1 found in higher cells; physical and genetic studies of the yeast activity could help elucidate the structure and function of H 1. Images of the yeast 30-nm filaments can be used to test crossed-linker models for 30-nm filament structure

  5. H2O2-induced higher order chromatin degradation: A novel ...

    Indian Academy of Sciences (India)

    Unknown

    mediator of oxidative stress, can also cause genomic damage indirectly. Thus, H2O2 at pathologically relevant concentrations rapidly induces higher order chromatin degradation (HOCD), i.e. enzymatic ... clease works through a single strand scission mechanism ... a great mutagenic risk to the surviving cells, because en-.

  6. The effect of higher order chromatin structure on DNA damage and repair

    International Nuclear Information System (INIS)

    Yasui, L.S.; Warters, R.L.; Higashikubo, R.

    1985-01-01

    Alterations in chromatin structure are thought to play an important role in various radiobiological end points, i.e., DNA damage, DNA damage repair and cell survival. The authors use here the isoleucine deprivation technique to decondense higher order chromatin structure and asses X-ray induced DNA damage, DNA damage repair and cell survival on cells with decondensed chromatin as compared to controls. This chromatin decondensation manifests itself as a 30 fold decrease in nuclear area occupied by heterochromatin, an increased rate of Micrococcal nuclease digestion, 15% increased ethidium bromide intercalation and an altered binding capacity of Hl histone. These chromatin/nuclear changes do not affect X-ray induced DNA damage as measured by the alkaline elution technique or cell survival but slows DNA damage repair by 2 fold. Therefore, even though the chromatin appears more accessible to DNA damage and repair processes, these particular nuclear changes do not affect the DNA damaging effects of X-rays and in addition, repair is not enhanced by the ''relaxed'' state of chromatin. It is proposed that the altered metabolic state of isoleucine deprived cells provides a less efficient system for the repair of X-ray induced DNA damage

  7. Modulation of Higher Order Chromatin Conformation in Mammalian Cell Nuclei Can Be Mediated by Polyamines and Divalent Cations.

    Directory of Open Access Journals (Sweden)

    Ashwat Visvanathan

    Full Text Available The organisation of the large volume of mammalian genomic DNA within cell nuclei requires mechanisms to regulate chromatin compaction involving the reversible formation of higher order structures. The compaction state of chromatin varies between interphase and mitosis and is also subject to rapid and reversible change upon ATP depletion/repletion. In this study we have investigated mechanisms that may be involved in promoting the hyper-condensation of chromatin when ATP levels are depleted by treating cells with sodium azide and 2-deoxyglucose. Chromatin conformation was analysed in both live and permeabilised HeLa cells using FLIM-FRET, high resolution fluorescence microscopy and by electron spectroscopic imaging microscopy. We show that chromatin compaction following ATP depletion is not caused by loss of transcription activity and that it can occur at a similar level in both interphase and mitotic cells. Analysis of both live and permeabilised HeLa cells shows that chromatin conformation within nuclei is strongly influenced by the levels of divalent cations, including calcium and magnesium. While ATP depletion results in an increase in the level of unbound calcium, chromatin condensation still occurs even in the presence of a calcium chelator. Chromatin compaction is shown to be strongly affected by small changes in the levels of polyamines, including spermine and spermidine. The data are consistent with a model in which the increased intracellular pool of polyamines and divalent cations, resulting from depletion of ATP, bind to DNA and contribute to the large scale hyper-compaction of chromatin by a charge neutralisation mechanism.

  8. Higher-order chromatin structure in DSB induction, repair and misrepair

    Czech Academy of Sciences Publication Activity Database

    Falk, Martin; Lukášová, Emilie; Kozubek, Stanislav

    2010-01-01

    Roč. 704, 1-3 (2010), s. 88-100 ISSN 1383-5742 R&D Projects: GA MŠk ME 919; GA AV ČR(CZ) IAA500040802; GA AV ČR(CZ) 1QS500040508 Grant - others:GA MŠk(CZ) LC535 Program:LC Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : DNA double strand breaks * DSB repair * higher-order chromatin structure Subject RIV: BO - Biophysics Impact factor: 8.741, year: 2010

  9. Common themes and cell type specific variations of higher order chromatin arrangements in the mouse

    Directory of Open Access Journals (Sweden)

    Cremer Thomas

    2005-12-01

    Full Text Available Abstract Background Similarities as well as differences in higher order chromatin arrangements of human cell types were previously reported. For an evolutionary comparison, we now studied the arrangements of chromosome territories and centromere regions in six mouse cell types (lymphocytes, embryonic stem cells, macrophages, fibroblasts, myoblasts and myotubes with fluorescence in situ hybridization and confocal laser scanning microscopy. Both species evolved pronounced differences in karyotypes after their last common ancestors lived about 87 million years ago and thus seem particularly suited to elucidate common and cell type specific themes of higher order chromatin arrangements in mammals. Results All mouse cell types showed non-random correlations of radial chromosome territory positions with gene density as well as with chromosome size. The distribution of chromosome territories and pericentromeric heterochromatin changed during differentiation, leading to distinct cell type specific distribution patterns. We exclude a strict dependence of these differences on nuclear shape. Positional differences in mouse cell nuclei were less pronounced compared to human cell nuclei in agreement with smaller differences in chromosome size and gene density. Notably, the position of chromosome territories relative to each other was very variable. Conclusion Chromosome territory arrangements according to chromosome size and gene density provide common, evolutionary conserved themes in both, human and mouse cell types. Our findings are incompatible with a previously reported model of parental genome separation.

  10. Distribution of segmental duplications in the context of higher order chromatin organisation of human chromosome 7

    DEFF Research Database (Denmark)

    Ebert, Grit; Steininger, Anne; Weißmann, Robert

    2014-01-01

    of the Williams-Beuren syndrome locus we demonstrate by cross-species comparison that these SDs have inserted at the borders of a topological domain and that they flank regions with distinct DNA conformation. CONCLUSIONS: Our study suggests a link of nuclear architecture and the propagation of SDs across......BACKGROUND: Segmental duplications (SDs) are not evenly distributed along chromosomes. The reasons for this biased susceptibility to SD insertion are poorly understood. Accumulation of SDs is associated with increased genomic instability, which can lead to structural variants and genomic disorders...... chromosome 7, either by promoting regional SD insertion or by contributing to the establishment of higher order chromatin organisation themselves. The latter could compensate for the high risk of structural rearrangements and thus may have contributed to their evolutionary fixation in the human genome....

  11. Local changes of higher-order chromatin structure during DSB-repair

    International Nuclear Information System (INIS)

    Falk, M; Lukasova, E; Gabrielova, B; Ondrej, V; Kozubek, S

    2008-01-01

    We show that double-strand breaks (DSBs) induced in DNA of human cells by γ-radiation arise mainly in active, gene-rich, decondensed chromatin. We demonstrate that DSBs show limited movement in living cells, occasionally resulting in their permanent clustering, which poses a risk of incorrect DNA rejoining. In addition, some DSBs remain unrepaired for several days after irradiation, forming lesions repairable only with difficulty which are hazardous for genome stability. These 'late' DSBs colocalize with heterochromatin markers (dimethylated histone H3 at lysine 9, HP1 and CENP-A proteins), despite the low density of the surrounding chromatin. This indicates that there is epigenetic silencing of loci close to unrepaired DSBs and/or stabilization of damaged decondensed chromatin loops during repair and post-repair reconstitution of chromatin structure

  12. Phosphorylation-dependent regulation of plant chromatin and chromatin-associated proteins

    KAUST Repository

    Bigeard, Jean; Rayapuram, Naganand; Pflieger, Delphine; Hirt, Heribert

    2014-01-01

    In eukaryotes, most of the DNA is located in the nucleus where it is organized with histone proteins in a higher order structure as chromatin. Chromatin and chromatin-associated proteins contribute to DNA-related processes such as replication and transcription as well as epigenetic regulation. Protein functions are often regulated by PTMs among which phosphorylation is one of the most abundant PTM. Phosphorylation of proteins affects important properties, such as enzyme activity, protein stability, or subcellular localization. We here describe the main specificities of protein phosphorylation in plants and review the current knowledge on phosphorylation-dependent regulation of plant chromatin and chromatin-associated proteins. We also outline some future challenges to further elucidate protein phosphorylation and chromatin regulation.

  13. Phosphorylation-dependent regulation of plant chromatin and chromatin-associated proteins

    KAUST Repository

    Bigeard, Jean

    2014-07-10

    In eukaryotes, most of the DNA is located in the nucleus where it is organized with histone proteins in a higher order structure as chromatin. Chromatin and chromatin-associated proteins contribute to DNA-related processes such as replication and transcription as well as epigenetic regulation. Protein functions are often regulated by PTMs among which phosphorylation is one of the most abundant PTM. Phosphorylation of proteins affects important properties, such as enzyme activity, protein stability, or subcellular localization. We here describe the main specificities of protein phosphorylation in plants and review the current knowledge on phosphorylation-dependent regulation of plant chromatin and chromatin-associated proteins. We also outline some future challenges to further elucidate protein phosphorylation and chromatin regulation.

  14. A new non-catalytic role for ubiquitin ligase RNF8 in unfolding higher-order chromatin structure

    DEFF Research Database (Denmark)

    Luijsterburg, Martijn S; Acs, Klara; Ackermann, Leena

    2012-01-01

    The ubiquitin ligases RNF8 and RNF168 orchestrate DNA damage signalling through the ubiquitylation of histone H2A and the recruitment of downstream repair factors. Here, we demonstrate that RNF8, but not RNF168 or the canonical H2A ubiquitin ligase RNF2, mediates extensive chromatin decondensation....... Our data show that CHD4, the catalytic subunit of the NuRD complex, interacts with RNF8 and is essential for RNF8-mediated chromatin unfolding. The chromatin remodelling activity of CHD4 promotes efficient ubiquitin conjugation and assembly of RNF168 and BRCA1 at DNA double-strand breaks....... Interestingly, RNF8-mediated recruitment of CHD4 and subsequent chromatin remodelling were independent of the ubiquitin-ligase activity of RNF8, but involved a non-canonical interaction with the forkhead-associated (FHA) domain. Our study reveals a new mechanism of chromatin remodelling-assisted ubiquitylation...

  15. A component of DNA double-strand break repair is dependent on the spatial orientation of the lesions within the higher-order structures of chromatin

    Energy Technology Data Exchange (ETDEWEB)

    Johnston, P.J.; Bryant, P.E. (Saint Andrews Univ. (United Kingdom))

    1994-11-01

    By the use of a modified neutral filter elution procedure variations in the repair of DNA dsb have been observed between the ionising radiation sensitive mutant xrs-5 and the parent cell line CHO-K1. Conventional neutral filter elution requires harsh lysis conditions to remove higher-order chromatin structures which interfere with elution of DNA containing dsb. By lysing cells with non-ionic detergent in the presence of 2 mol dm[sup -3] salt, histone-depleted structures that retain the higher-order nuclear matrix organization, including chromatin loops, can be produced. Elution from these structures will only occur if two or more dsb lie within a single-looped domain delineated by points of attachment to the nuclear matrix. Repair experiments indicate that in CHO cells repair of dsb in loops containing multiple dsb are repaired with slow kinetics whilst dsb occurring in loops containing single dsb are repaired with fast kinetics. Xrs-5 cells are defective in the repair of multiply damaged loops. This work indicates that the spatial orientation of dsb in the higher-order structures of chromatin are a possible factor in the repair of these lesions. (Author).

  16. A component of DNA double-strand break repair is dependent on the spatial orientation of the lesions within the higher-order structures of chromatin

    International Nuclear Information System (INIS)

    Johnston, P.J.; Bryant, P.E.

    1994-01-01

    By the use of a modified neutral filter elution procedure variations in the repair of DNA dsb have been observed between the ionising radiation sensitive mutant xrs-5 and the parent cell line CHO-K1. Conventional neutral filter elution requires harsh lysis conditions to remove higher-order chromatin structures which interfere with elution of DNA containing dsb. By lysing cells with non-ionic detergent in the presence of 2 mol dm -3 salt, histone-depleted structures that retain the higher-order nuclear matrix organization, including chromatin loops, can be produced. Elution from these structures will only occur if two or more dsb lie within a single-looped domain delineated by points of attachment to the nuclear matrix. Repair experiments indicate that in CHO cells repair of dsb in loops containing multiple dsb are repaired with slow kinetics whilst dsb occurring in loops containing single dsb are repaired with fast kinetics. Xrs-5 cells are defective in the repair of multiply damaged loops. This work indicates that the spatial orientation of dsb in the higher-order structures of chromatin are a possible factor in the repair of these lesions. (Author)

  17. Heterochromatinization associated with cell differentiation as a model to study DNA double strand break induction and repair in the context of higher-order chromatin structure

    International Nuclear Information System (INIS)

    Falk, Martin; Lukášová, Emilie; Štefančíková, Lenka; Baranová, Elena; Falková, Iva; Ježková, Lucie; Davídková, Marie; Bačíková, Alena; Vachelová, Jana; Michaelidesová, Anna; Kozubek, Stanislav

    2014-01-01

    Cell differentiation is associated with extensive gene silencing, heterochromatinization and potentially decreasing need for repairing DNA double-strand breaks (DSBs). Differentiation stages of blood cells thus represent an excellent model to study DSB induction, repair and misrepair in the context of changing higher-order chromatin structure. We show that immature granulocytes form γH2AX and 53BP1 foci, contrary to the mature cells; however, these foci colocalize only rarely and DSB repair is inefficient. Moreover, specific chromatin structure of granulocytes probably influences DSB induction. - Highlights: ► DSB repair is absent in mature granulocytes with condensed chromatin. ► Repair proteins and γH2AX appear in immature stages but rarely colocalize. ► γH2AX persist long times in these cells and DSB repair is inefficient. ► Even though, γH2AX foci “move” out of the dense chromatin. ► 53BP1 enters HP1β domains only after their decondensation

  18. Oligomer formation and G-quadruplex binding by purified murine Rif1 protein, a key organizer of higher-order chromatin architecture.

    Science.gov (United States)

    Moriyama, Kenji; Yoshizawa-Sugata, Naoko; Masai, Hisao

    2018-03-09

    Rap1-interacting protein 1 (Rif1) regulates telomere length in budding yeast. We previously reported that, in metazoans and fission yeast, Rif1 also plays pivotal roles in controlling genome-wide DNA replication timing. We proposed that Rif1 may assemble chromatin compartments that contain specific replication-timing domains by promoting chromatin loop formation. Rif1 also is involved in DNA lesion repair, restart after replication fork collapse, anti-apoptosis activities, replicative senescence, and transcriptional regulation. Although multiple physiological functions of Rif1 have been characterized, biochemical and structural information on mammalian Rif1 is limited, mainly because of difficulties in purifying the full-length protein. Here, we expressed and purified the 2418-amino-acid-long, full-length murine Rif1 as well as its partially truncated variants in human 293T cells. Hydrodynamic analyses indicated that Rif1 forms elongated or extended homo-oligomers in solution, consistent with the presence of a HEAT-type helical repeat segment known to adopt an elongated shape. We also observed that the purified murine Rif1 bound G-quadruplex (G4) DNA with high specificity and affinity, as was previously shown for Rif1 from fission yeast. Both the N-terminal (HEAT-repeat) and C-terminal segments were involved in oligomer formation and specifically bound G4 DNA, and the central intrinsically disordered polypeptide segment increased the affinity for G4. Of note, pulldown assays revealed that Rif1 simultaneously binds multiple G4 molecules. Our findings support a model in which Rif1 modulates chromatin loop structures through binding to multiple G4 assemblies and by holding chromatin fibers together. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. A model of photon cell killing based on the spatio-temporal clustering of DNA damage in higher order chromatin structures.

    Directory of Open Access Journals (Sweden)

    Lisa Herr

    Full Text Available We present a new approach to model dose rate effects on cell killing after photon radiation based on the spatio-temporal clustering of DNA double strand breaks (DSBs within higher order chromatin structures of approximately 1-2 Mbp size, so called giant loops. The main concept of this approach consists of a distinction of two classes of lesions, isolated and clustered DSBs, characterized by the number of double strand breaks induced in a giant loop. We assume a low lethality and fast component of repair for isolated DSBs and a high lethality and slow component of repair for clustered DSBs. With appropriate rates, the temporal transition between the different lesion classes is expressed in terms of five differential equations. These allow formulating the dynamics involved in the competition of damage induction and repair for arbitrary dose rates and fractionation schemes. Final cell survival probabilities are computable with a cell line specific set of three parameters: The lethality for isolated DSBs, the lethality for clustered DSBs and the half-life time of isolated DSBs. By comparison with larger sets of published experimental data it is demonstrated that the model describes the cell line dependent response to treatments using either continuous irradiation at a constant dose rate or to split dose irradiation well. Furthermore, an analytic investigation of the formulation concerning single fraction treatments with constant dose rates in the limiting cases of extremely high or low dose rates is presented. The approach is consistent with the Linear-Quadratic model extended by the Lea-Catcheside factor up to the second moment in dose. Finally, it is shown that the model correctly predicts empirical findings about the dose rate dependence of incidence probabilities for deterministic radiation effects like pneumonitis and the bone marrow syndrome. These findings further support the general concepts on which the approach is based.

  20. Getting in (and out of) the loop: regulating higher order telomere structures.

    Science.gov (United States)

    Luke-Glaser, Sarah; Poschke, Heiko; Luke, Brian

    2012-01-01

    The DNA at the ends of linear chromosomes (the telomere) folds back onto itself and forms an intramolecular lariat-like structure. Although the telomere loop has been implicated in the protection of chromosome ends from nuclease-mediated resection and unscheduled DNA repair activities, it potentially poses an obstacle to the DNA replication machinery during S-phase. Therefore, the coordinated regulation of telomere loop formation, maintenance, and resolution is required in order to establish a balance between protecting the chromosome ends and promoting their duplication prior to cell division. Until recently, the only factor known to influence telomere looping in human cells was TRF2, a component of the shelterin complex. Recent work in yeast and mouse cells has uncovered additional regulatory factors that affect the loop structure at telomeres. In the following "perspective" we outline what is known about telomere looping and highlight the latest results regarding the regulation of this chromosome end structure. We speculate about how the manipulation of the telomere loop may have therapeutic implications in terms of diseases associated with telomere dysfunction and uncontrolled proliferation.

  1. Getting in (and out of the loop: regulating higher order telomere structures

    Directory of Open Access Journals (Sweden)

    Sarah eLuke-Glaser

    2012-11-01

    Full Text Available The DNA at the ends of linear chromosomes (the telomere folds back onto itself and forms an intramolecular lariat-like structure. Although the telomere loop has been implicated in the protection of chromosome ends from nuclease-mediated resection and unscheduled DNA repair activities, it potentially poses an obstacle to the DNA replication machinery during S phase. Therefore, the coordinated regulation of telomere loop formation, maintenance and resolution is required in order to establish a balance between protecting the chromosome ends and promoting their duplication prior to cell division. Until recently, the only factor know to influence telomere looping in human cells was TRF2, a component of the shelterin complex. Recent work in yeast and mouse cells has uncovered additional regulatory factors that affect the loop structure at telomeres. In the following perspective we will outline what is known about telomere looping and highlight the latest results regarding the regulation of this chromosome end structure. We will speculate about how the manipulation of the telomere loop may have therapeutic implications in terms of diseases associated with telomere dysfunction and uncontrolled proliferation.

  2. New mitotic regulators released from chromatin

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    Hideki eYokoyama

    2013-12-01

    Full Text Available Faithful action of the mitotic spindle segregates duplicated chromosomes into daughter cells. Perturbations of this process result in chromosome mis-segregation, leading to chromosomal instability and cancer development. Chromosomes are not simply passengers segregated by spindle microtubules but rather play a major active role in spindle assembly. The GTP bound form of the Ran GTPase (RanGTP, produced around chromosomes, locally activates spindle assembly factors. Recent studies have uncovered that chromosomes organize mitosis beyond spindle formation. They distinctly regulate other mitotic events, such as spindle maintenance in anaphase, which is essential for chromosome segregation. Furthermore, the direct function of chromosomes is not only to produce RanGTP but, in addition, to release key mitotic regulators from chromatin. Chromatin-remodeling factors and nuclear pore complex proteins, which have established functions on chromatin in interphase, dissociate from mitotic chromatin and function in spindle assembly or maintenance. Thus, chromosomes actively organize their own segregation using chromatin-releasing mitotic regulators as well as RanGTP.

  3. Chromatin Regulation of Neuronal Maturation and Plasticity.

    Science.gov (United States)

    Gallegos, David A; Chan, Urann; Chen, Liang-Fu; West, Anne E

    2018-05-01

    Neurons are dynamic cells that respond and adapt to stimuli throughout their long postmitotic lives. The structural and functional plasticity of neurons requires the regulated transcription of new gene products, and dysregulation of transcription in either the developing or adult brain impairs cognition. We discuss how mechanisms of chromatin regulation help to orchestrate the transcriptional programs that underlie the maturation of developing neurons and the plasticity of adult neurons. We review how chromatin regulation acts locally to modulate the expression of specific genes and more broadly to coordinate gene expression programs during transitions between cellular states. These data highlight the importance of epigenetic transcriptional mechanisms in postmitotic neurons. We suggest areas where emerging methods may advance understanding in the future. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Localization of ultraviolet-induced excision repair in the nucleus and the distribution of repair events in higher order chromatin loops in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Mullenders, L.H.F.; Zeeland, A.A. van; Natarajan, A.T.

    1987-01-01

    Several lines of evidence indicate that eukaryotic DNA is arranged in highly supercoiled domains or loops, and that the repeating loops are constrained by attachment to a nuclear skeletal structure termed the nuclear matrix. We have investigated whether the repair of DNA damage occurs in the nuclear matrix compartment. Normal human fibroblasts, ultraviolet (u.v.)-irradiated with 30 J m/sup -2/ and post-u.v. incubated in the presence of hydroxyurea, did not show any evidence for the occurrence of repair synthesis at the nuclear matrix. 5 J m/sup -2/ repair synthesis seems to initiate at the nuclear matrix, although only part of the total repair could be localized there. In u.v.-irradiated (30 J m/sup -2/) normal human fibroblast post-u.v. incubated in the presence of hydroxyurea and arabinsosylcytosine for 2h, multiple single-stranded regions are generated in a DNA loop as a result of the inhibition of the excision repair process. Preferential repair of certain domains in the chromatin was shown to occur in xeroderma pigmentosum cells of complementation group C (XP-C) in contrast to XP-D cells and Syrian hamster embryonic cells.

  5. The localization of ultraviolet-induced excision repair in the nucleus and the distribution of repair events in higher order chromatin loops in mammalian cells

    International Nuclear Information System (INIS)

    Mullenders, L.H.F.; Zeeland, A.A. van; Natarajan, A.T.

    1987-01-01

    Several lines of evidence indicate that eukaryotic DNA is arranged in highly supercoiled domains or loops, and that the repeating loops are constrained by attachment to a nuclear skeletal structure termed the nuclear matrix. We have investigated whether the repair of DNA damage occurs in the nuclear matrix compartment. Normal human fibroblasts, ultraviolet (u.v.)-irradiated with 30 J m -2 and post-u.v. incubated in the presence of hydroxyurea, did not show any evidence for the occurrence of repair synthesis at the nuclear matrix. 5 J m -2 repair synthesis seems to initiate at the nuclear matrix, although only part of the total repair could be localized there. In u.v.-irradiated (30 J m -2 ) normal human fibroblast post-u.v. incubated in the presence of hydroxyurea and arabinsosylcytosine for 2h, multiple single-stranded regions are generated in a DNA loop as a result of the inhibition of the excision repair process. Preferential repair of certain domains in the chromatin was shown to occur in xeroderma pigmentosum cells of complementation group C (XP-C) in contrast to XP-D cells and Syrian hamster embryonic cells. (author)

  6. FGF signalling regulates chromatin organisation during neural differentiation via mechanisms that can be uncoupled from transcription.

    Directory of Open Access Journals (Sweden)

    Nishal S Patel

    Full Text Available Changes in higher order chromatin organisation have been linked to transcriptional regulation; however, little is known about how such organisation alters during embryonic development or how it is regulated by extrinsic signals. Here we analyse changes in chromatin organisation as neural differentiation progresses, exploiting the clear spatial separation of the temporal events of differentiation along the elongating body axis of the mouse embryo. Combining fluorescence in situ hybridisation with super-resolution structured illumination microscopy, we show that chromatin around key differentiation gene loci Pax6 and Irx3 undergoes both decompaction and displacement towards the nuclear centre coincident with transcriptional onset. Conversely, down-regulation of Fgf8 as neural differentiation commences correlates with a more peripheral nuclear position of this locus. During normal neural differentiation, fibroblast growth factor (FGF signalling is repressed by retinoic acid, and this vitamin A derivative is further required for transcription of neural genes. We show here that exposure to retinoic acid or inhibition of FGF signalling promotes precocious decompaction and central nuclear positioning of differentiation gene loci. Using the Raldh2 mutant as a model for retinoid deficiency, we further find that such changes in higher order chromatin organisation are dependent on retinoid signalling. In this retinoid deficient condition, FGF signalling persists ectopically in the elongating body, and importantly, we find that inhibiting FGF receptor (FGFR signalling in Raldh2-/- embryos does not rescue differentiation gene transcription, but does elicit both chromatin decompaction and nuclear position change. These findings demonstrate that regulation of higher order chromatin organisation during differentiation in the embryo can be uncoupled from the machinery that promotes transcription and, for the first time, identify FGF as an extrinsic signal that

  7. A role for chromatin topology in imprinted domain regulation.

    Science.gov (United States)

    MacDonald, William A; Sachani, Saqib S; White, Carlee R; Mann, Mellissa R W

    2016-02-01

    Recently, many advancements in genome-wide chromatin topology and nuclear architecture have unveiled the complex and hidden world of the nucleus, where chromatin is organized into discrete neighbourhoods with coordinated gene expression. This includes the active and inactive X chromosomes. Using X chromosome inactivation as a working model, we utilized publicly available datasets together with a literature review to gain insight into topologically associated domains, lamin-associated domains, nucleolar-associating domains, scaffold/matrix attachment regions, and nucleoporin-associated chromatin and their role in regulating monoallelic expression. Furthermore, we comprehensively review for the first time the role of chromatin topology and nuclear architecture in the regulation of genomic imprinting. We propose that chromatin topology and nuclear architecture are important regulatory mechanisms for directing gene expression within imprinted domains. Furthermore, we predict that dynamic changes in chromatin topology and nuclear architecture play roles in tissue-specific imprint domain regulation during early development and differentiation.

  8. RNA polymerase III transcription - regulated by chromatin structure and regulator of nuclear chromatin organization.

    Science.gov (United States)

    Pascali, Chiara; Teichmann, Martin

    2013-01-01

    RNA polymerase III (Pol III) transcription is regulated by modifications of the chromatin. DNA methylation and post-translational modifications of histones, such as acetylation, phosphorylation and methylation have been linked to Pol III transcriptional activity. In addition to being regulated by modifications of DNA and histones, Pol III genes and its transcription factors have been implicated in the organization of nuclear chromatin in several organisms. In yeast, the ability of the Pol III transcription system to contribute to nuclear organization seems to be dependent on direct interactions of Pol III genes and/or its transcription factors TFIIIC and TFIIIB with the structural maintenance of chromatin (SMC) protein-containing complexes cohesin and condensin. In human cells, Pol III genes and transcription factors have also been shown to colocalize with cohesin and the transcription regulator and genome organizer CCCTC-binding factor (CTCF). Furthermore, chromosomal sites have been identified in yeast and humans that are bound by partial Pol III machineries (extra TFIIIC sites - ETC; chromosome organizing clamps - COC). These ETCs/COC as well as Pol III genes possess the ability to act as boundary elements that restrict spreading of heterochromatin.

  9. The chromatin remodeler SPLAYED regulates specific stress signaling pathways.

    Directory of Open Access Journals (Sweden)

    Justin W Walley

    2008-12-01

    Full Text Available Organisms are continuously exposed to a myriad of environmental stresses. Central to an organism's survival is the ability to mount a robust transcriptional response to the imposed stress. An emerging mechanism of transcriptional control involves dynamic changes in chromatin structure. Alterations in chromatin structure are brought about by a number of different mechanisms, including chromatin modifications, which covalently modify histone proteins; incorporation of histone variants; and chromatin remodeling, which utilizes ATP hydrolysis to alter histone-DNA contacts. While considerable insight into the mechanisms of chromatin remodeling has been gained, the biological role of chromatin remodeling complexes beyond their function as regulators of cellular differentiation and development has remained poorly understood. Here, we provide genetic, biochemical, and biological evidence for the critical role of chromatin remodeling in mediating plant defense against specific biotic stresses. We found that the Arabidopsis SWI/SNF class chromatin remodeling ATPase SPLAYED (SYD is required for the expression of selected genes downstream of the jasmonate (JA and ethylene (ET signaling pathways. SYD is also directly recruited to the promoters of several of these genes. Furthermore, we show that SYD is required for resistance against the necrotrophic pathogen Botrytis cinerea but not the biotrophic pathogen Pseudomonas syringae. These findings demonstrate not only that chromatin remodeling is required for selective pathogen resistance, but also that chromatin remodelers such as SYD can regulate specific pathways within biotic stress signaling networks.

  10. Chromatin regulation at the frontier of synthetic biology

    Science.gov (United States)

    Keung, Albert J.; Joung, J. Keith; Khalil, Ahmad S.; Collins, James J.

    2016-01-01

    As synthetic biology approaches are extended to diverse applications throughout medicine, biotechnology and basic biological research, there is an increasing need to engineer yeast, plant and mammalian cells. Eukaryotic genomes are regulated by the diverse biochemical and biophysical states of chromatin, which brings distinct challenges, as well as opportunities, over applications in bacteria. Recent synthetic approaches, including `epigenome editing', have allowed the direct and functional dissection of many aspects of physiological chromatin regulation. These studies lay the foundation for biomedical and biotechnological engineering applications that could take advantage of the unique combinatorial and spatiotemporal layers of chromatin regulation to create synthetic systems of unprecedented sophistication. PMID:25668787

  11. Rapid and reversible epigenome editing by endogenous chromatin regulators.

    Science.gov (United States)

    Braun, Simon M G; Kirkland, Jacob G; Chory, Emma J; Husmann, Dylan; Calarco, Joseph P; Crabtree, Gerald R

    2017-09-15

    Understanding the causal link between epigenetic marks and gene regulation remains a central question in chromatin biology. To edit the epigenome we developed the FIRE-Cas9 system for rapid and reversible recruitment of endogenous chromatin regulators to specific genomic loci. We enhanced the dCas9-MS2 anchor for genome targeting with Fkbp/Frb dimerizing fusion proteins to allow chemical-induced proximity of a desired chromatin regulator. We find that mSWI/SNF (BAF) complex recruitment is sufficient to oppose Polycomb within minutes, leading to activation of bivalent gene transcription in mouse embryonic stem cells. Furthermore, Hp1/Suv39h1 heterochromatin complex recruitment to active promoters deposits H3K9me3 domains, resulting in gene silencing that can be reversed upon washout of the chemical dimerizer. This inducible recruitment strategy provides precise kinetic information to model epigenetic memory and plasticity. It is broadly applicable to mechanistic studies of chromatin in mammalian cells and is particularly suited to the analysis of endogenous multi-subunit chromatin regulator complexes.Understanding the link between epigenetic marks and gene regulation requires the development of new tools to directly manipulate chromatin. Here the authors demonstrate a Cas9-based system to recruit chromatin remodelers to loci of interest, allowing rapid, reversible manipulation of epigenetic states.

  12. A SWI/SNF Chromatin Remodelling Protein Controls Cytokinin Production through the Regulation of Chromatin Architecture

    KAUST Repository

    Jé gu, Teddy; Domenichini, Sé verine; Blein, Thomas; Ariel, Federico; Christ, Auré lie; Kim, SoonKap; Crespi, Martin; Boutet-Mercey, Sté phanie; Mouille, Gré gory; Bourge, Mickaë l; Hirt, Heribert; Bergounioux, Catherine; Raynaud, Cé cile; Benhamed, Moussa

    2015-01-01

    Chromatin architecture determines transcriptional accessibility to DNA and consequently gene expression levels in response to developmental and environmental stimuli. Recently, chromatin remodelers such as SWI/SNF complexes have been recognized as key regulators of chromatin architecture. To gain insight into the function of these complexes during root development, we have analyzed Arabidopsis knock-down lines for one sub-unit of SWI/SNF complexes: BAF60. Here, we show that BAF60 is a positive regulator of root development and cell cycle progression in the root meristem via its ability to down-regulate cytokinin production. By opposing both the deposition of active histone marks and the formation of a chromatin regulatory loop, BAF60 negatively regulates two crucial target genes for cytokinin biosynthesis (IPT3 and IPT7) and one cell cycle inhibitor (KRP7). Our results demonstrate that SWI/SNF complexes containing BAF60 are key factors governing the equilibrium between formation and dissociation of a chromatin loop controlling phytohormone production and cell cycle progression.

  13. A SWI/SNF Chromatin Remodelling Protein Controls Cytokinin Production through the Regulation of Chromatin Architecture

    KAUST Repository

    Jégu, Teddy

    2015-10-12

    Chromatin architecture determines transcriptional accessibility to DNA and consequently gene expression levels in response to developmental and environmental stimuli. Recently, chromatin remodelers such as SWI/SNF complexes have been recognized as key regulators of chromatin architecture. To gain insight into the function of these complexes during root development, we have analyzed Arabidopsis knock-down lines for one sub-unit of SWI/SNF complexes: BAF60. Here, we show that BAF60 is a positive regulator of root development and cell cycle progression in the root meristem via its ability to down-regulate cytokinin production. By opposing both the deposition of active histone marks and the formation of a chromatin regulatory loop, BAF60 negatively regulates two crucial target genes for cytokinin biosynthesis (IPT3 and IPT7) and one cell cycle inhibitor (KRP7). Our results demonstrate that SWI/SNF complexes containing BAF60 are key factors governing the equilibrium between formation and dissociation of a chromatin loop controlling phytohormone production and cell cycle progression.

  14. Higher-Order Hierarchies

    DEFF Research Database (Denmark)

    Ernst, Erik

    2003-01-01

    This paper introduces the notion of higher-order inheritance hierarchies. They are useful because they provide well-known benefits of object-orientation at the level of entire hierarchies-benefits which are not available with current approaches. Three facets must be adressed: First, it must be po...

  15. HDAC up-regulation in early colon field carcinogenesis is involved in cell tumorigenicity through regulation of chromatin structure.

    Directory of Open Access Journals (Sweden)

    Yolanda Stypula-Cyrus

    Full Text Available Normal cell function is dependent on the proper maintenance of chromatin structure. Regulation of chromatin structure is controlled by histone modifications that directly influence chromatin architecture and genome function. Specifically, the histone deacetylase (HDAC family of proteins modulate chromatin compaction and are commonly dysregulated in many tumors, including colorectal cancer (CRC. However, the role of HDAC proteins in early colorectal carcinogenesis has not been previously reported. We found HDAC1, HDAC2, HDAC3, HDAC5, and HDAC7 all to be up-regulated in the field of human CRC. Furthermore, we observed that HDAC2 up-regulation is one of the earliest events in CRC carcinogenesis and observed this in human field carcinogenesis, the azoxymethane-treated rat model, and in more aggressive colon cancer cell lines. The universality of HDAC2 up-regulation suggests that HDAC2 up-regulation is a novel and important early event in CRC, which may serve as a biomarker. HDAC inhibitors (HDACIs interfere with tumorigenic HDAC activity; however, the precise mechanisms involved in this process remain to be elucidated. We confirmed that HDAC inhibition by valproic acid (VPA targeted the more aggressive cell line. Using nuclease digestion assays and transmission electron microscopy imaging, we observed that VPA treatment induced greater changes in chromatin structure in the more aggressive cell line. Furthermore, we used the novel imaging technique partial wave spectroscopy (PWS to quantify nanoscale alterations in chromatin. We noted that the PWS results are consistent with the biological assays, indicating a greater effect of VPA treatment in the more aggressive cell type. Together, these results demonstrate the importance of HDAC activity in early carcinogenic events and the unique role of higher-order chromatin structure in determining cell tumorigenicity.

  16. Citrullination regulates pluripotency and histone H1 binding to chromatin

    DEFF Research Database (Denmark)

    Christophorou, Maria A; Castelo-Branco, Gonçalo; Halley-Stott, Richard P

    2014-01-01

    citrullination of core histones has been linked to transcriptional regulation and the DNA damage response. PADI4 (also called PAD4 or PADV), the only PADI with a nuclear localization signal, was previously shown to act in myeloid cells where it mediates profound chromatin decondensation during the innate immune...... and activating their expression. Its inhibition lowers the percentage of pluripotent cells in the early mouse embryo and significantly reduces reprogramming efficiency. Using an unbiased proteomic approach we identify linker histone H1 variants, which are involved in the generation of compact chromatin, as novel...... PADI4 substrates. Citrullination of a single arginine residue within the DNA-binding site of H1 results in its displacement from chromatin and global chromatin decondensation. Together, these results uncover a role for citrullination in the regulation of pluripotency and provide new mechanistic...

  17. Higher Order Mode Fibers

    DEFF Research Database (Denmark)

    Israelsen, Stine Møller

    This PhD thesis considers higher order modes (HOMs) in optical fibers. That includes their excitation and characteristics. Within the last decades, HOMs have been applied both for space multiplexing in optical communications, group velocity dispersion management and sensing among others......-radial polarization as opposed to the linear polarization of the LP0X modes. The effect is investigated numerically in a double cladding fiber with an outer aircladding using a full vectorial modesolver. Experimentally, the bowtie modes are excited using a long period grating and their free space characteristics...... and polarization state are investigated. For this fiber, the onset of the bowtie effect is shown numerically to be LP011. The characteristics usually associated with Bessel-likes modes such as long diffraction free length and selfhealing are shown to be conserved despite the lack of azimuthal symmetry...

  18. Epigenetic regulation of open chromatin in pluripotent stem cells

    Science.gov (United States)

    Kobayashi, Hiroshi; Kikyo, Nobuaki

    2014-01-01

    The recent progress in pluripotent stem cell research has opened new avenues of disease modeling, drug screening, and transplantation of patient-specific tissues that had been unimaginable until a decade ago. The central mechanism underlying pluripotency is epigenetic gene regulation; the majority of cell signaling pathways, both extracellular and cytoplasmic, eventually alter the epigenetic status of their target genes during the process of activating or suppressing the genes to acquire or maintain pluripotency. It has long been thought that the chromatin of pluripotent stem cells is globally open to enable the timely activation of essentially all genes in the genome during differentiation into multiple lineages. The current article reviews descriptive observations and the epigenetic machinery relevant to what is supposed to be globally open chromatin in pluripotent stem cells. This includes microscopic appearance, permissive gene transcription, chromatin remodeling complexes, histone modifications, DNA methylation, noncoding RNAs, dynamic movement of chromatin proteins, nucleosome accessibility and positioning, and long-range chromosomal interactions. Detailed analyses of each element, however, have revealed that the globally open chromatin hypothesis is not necessarily supported by some of the critical experimental evidence, such as genome-wide nucleosome accessibility and nucleosome positioning. Further understanding of the epigenetic gene regulation is expected to determine the true nature of the so-called globally open chromatin in pluripotent stem. PMID:24695097

  19. Chromatin Regulation and the Histone Code in HIV Latency
.

    Science.gov (United States)

    Turner, Anne-Marie W; Margolis, David M

    2017-06-01

    The formation of a latent reservoir of Human Immunodeficiency Virus (HIV) infection hidden from immune clearance remains a significant obstacle to approaches to eradicate HIV infection. Towards an understanding of the mechanisms of HIV persistence, there is a growing body of work implicating epigenetic regulation of chromatin in establishment and maintenance of this latent reservoir. Here we discuss recent advances in the field of chromatin regulation, specifically in our understanding of the histone code, and how these discoveries relate to our current knowledge of the chromatin mechanisms linked to HIV transcriptional repression and the reversal of latency. We also examine mechanisms unexplored in the context of HIV latency and briefly discuss current therapies aimed at the induction of proviral expression within latently infected cells. We aim to emphasize that a greater understanding of the epigenetic mechanisms which govern HIV latency could lead to new therapeutic targets for latency reversal and clearance cure strategies.

  20. Epigenetic regulation and chromatin remodeling in learning and memory.

    Science.gov (United States)

    Kim, Somi; Kaang, Bong-Kiun

    2017-01-13

    Understanding the underlying mechanisms of memory formation and maintenance has been a major goal in the field of neuroscience. Memory formation and maintenance are tightly controlled complex processes. Among the various processes occurring at different levels, gene expression regulation is especially crucial for proper memory processing, as some genes need to be activated while some genes must be suppressed. Epigenetic regulation of the genome involves processes such as DNA methylation and histone post-translational modifications. These processes edit genomic properties or the interactions between the genome and histone cores. They then induce structural changes in the chromatin and lead to transcriptional changes of different genes. Recent studies have focused on the concept of chromatin remodeling, which consists of 3D structural changes in chromatin in relation to gene regulation, and is an important process in learning and memory. In this review, we will introduce three major epigenetic processes involved in memory regulation: DNA methylation, histone methylation and histone acetylation. We will also discuss general mechanisms of long-term memory storage and relate the epigenetic control of learning and memory to chromatin remodeling. Finally, we will discuss how epigenetic mechanisms can contribute to the pathologies of neurological disorders and cause memory-related symptoms.

  1. Chromatin-regulating proteins as targets for cancer therapy

    International Nuclear Information System (INIS)

    Oike, Takahiro; Ogiwara, Hideaki; Kohno, Takashi; Amornwichet, Napapat; Nakano, Takashi

    2014-01-01

    Chromatin-regulating proteins represent a large class of novel targets for cancer therapy. In the context of radiotherapy, acetylation and deacetylation of histones by histone acetyltransferases (HATs) and histone deacetylases (HDACs) play important roles in the repair of DNA double-strand breaks generated by ionizing irradiation, and are therefore attractive targets for radiosensitization. Small-molecule inhibitors of HATs (garcinol, anacardic acid and curcumin) and HDACs (vorinostat, sodium butyrate and valproic acid) have been shown to sensitize cancer cells to ionizing irradiation in preclinical models, and some of these molecules are being tested in clinical trials, either alone or in combination with radiotherapy. Meanwhile, recent large-scale genome analyses have identified frequent mutations in genes encoding chromatin-regulating proteins, especially in those encoding subunits of the SWI/SNF chromatin-remodeling complex, in various human cancers. These observations have driven researchers toward development of targeted therapies against cancers carrying these mutations. DOT1L inhibition in MLL-rearranged leukemia, EZH2 inhibition in EZH2-mutant or MLL-rearranged hematologic malignancies and SNF5-deficient tumors, BRD4 inhibition in various hematologic malignancies, and BRM inhibition in BRG1-deficient tumors have demonstrated promising anti-tumor effects in preclinical models, and these strategies are currently awaiting clinical application. Overall, the data collected so far suggest that targeting chromatin-regulating proteins is a promising strategy for tomorrow's cancer therapy, including radiotherapy and molecularly targeted chemotherapy. (author)

  2. Regulation of chromatin structure by poly(ADP-ribosylation

    Directory of Open Access Journals (Sweden)

    Sascha eBeneke

    2012-09-01

    Full Text Available The interaction of DNA with proteins in the context of chromatin has to be tightly regulated to achieve so different tasks as packaging, transcription, replication and repair. The very rapid and transient post-translational modification of proteins by poly(ADP-ribose has been shown to take part in all four. Originally identified as immediate cellular answer to a variety of genotoxic stresses, already early data indicated the ability of this highly charged nucleic acid-like polymer to modulate nucleosome structure, the basic unit of chromatin. At the same time the enzyme responsible for synthesizing poly(ADP-ribose, the zinc-finger protein poly(ADP-ribose polymerase-1 (PARP1, was shown to control transcription initiation as basic factor TFIIC within the RNA-polymerase II machinery. Later research focused more on PARP-mediated regulation of DNA repair and cell death, but in the last few years, transcription as well as chromatin modulation has re-appeared on the scene. This review will discuss the impact of PARP1 on transcription and transcription factors, its implication in chromatin remodeling for DNA repair and probably also replication, and its role in controlling epigenetic events such as DNA methylation and the functionality of the insulator protein CCCTC-binding factor.

  3. Chromatin regulators, phenotypic robustness and autism risk

    Directory of Open Access Journals (Sweden)

    Reut eSuliman

    2014-04-01

    Full Text Available Though extensively characterized clinically, the causes of autism spectrum disorder (ASD remain a mystery. ASD is known to have a strong genetic basis, but it is genetically very heterogeneous. Recent studies have estimated that de novo disruptive mutations in hundreds of genes may contribute to ASD. However, it is unclear how it is possible for mutations in so many different genes to contribute to ASD. Recent findings suggest that many of the mutations disrupt genes involved in transcription regulation that are expressed prenatally in the developing brain. De novo disruptive mutations are also more frequent in girls with ASD, despite the fact that ASD is more prevalent in boys. In this paper, we hypothesize that loss of robustness may contribute to ASD. Loss of phenotypic robustness may be caused by mutations that disrupt capacitors that operate in the developing brain. This may lead to the release of cryptic genetic variation that contributes to ASD. Reduced robustness is consistent with the observed variability in expressivity and incomplete penetrance. It is also consistent with the hypothesis that the development of the female brain is more robust, and it may explain the higher rate and severity of disruptive de novo mutations in girls with ASD.

  4. Transcriptional and chromatin regulation during fasting – The genomic era

    Science.gov (United States)

    Goldstein, Ido; Hager, Gordon L.

    2015-01-01

    An elaborate metabolic response to fasting is orchestrated by the liver and is heavily reliant upon transcriptional regulation. In response to hormones (glucagon, glucocorticoids) many transcription factors (TFs) are activated and regulate various genes involved in metabolic pathways aimed at restoring homeostasis: gluconeogenesis, fatty acid oxidation, ketogenesis and amino acid shuttling. We summarize the recent discoveries regarding fasting-related TFs with an emphasis on genome-wide binding patterns. Collectively, the summarized findings reveal a large degree of co-operation between TFs during fasting which occurs at motif-rich DNA sites bound by a combination of TFs. These new findings implicate transcriptional and chromatin regulation as major determinants of the response to fasting and unravels the complex, multi-TF nature of this response. PMID:26520657

  5. Poly(ADP-ribosyl)ation of Methyl CpG Binding Domain Protein 2 Regulates Chromatin Structure*

    Science.gov (United States)

    Becker, Annette; Zhang, Peng; Allmann, Lena; Meilinger, Daniela; Bertulat, Bianca; Eck, Daniel; Hofstaetter, Maria; Bartolomei, Giody; Hottiger, Michael O.; Schreiber, Valérie; Leonhardt, Heinrich; Cardoso, M. Cristina

    2016-01-01

    The epigenetic information encoded in the genomic DNA methylation pattern is translated by methylcytosine binding proteins like MeCP2 into chromatin topology and structure and gene activity states. We have shown previously that the MeCP2 level increases during differentiation and that it causes large-scale chromatin reorganization, which is disturbed by MeCP2 Rett syndrome mutations. Phosphorylation and other posttranslational modifications of MeCP2 have been described recently to modulate its function. Here we show poly(ADP-ribosyl)ation of endogenous MeCP2 in mouse brain tissue. Consequently, we found that MeCP2 induced aggregation of pericentric heterochromatin and that its chromatin accumulation was enhanced in poly(ADP-ribose) polymerase (PARP) 1−/− compared with wild-type cells. We mapped the poly(ADP-ribosyl)ation domains and engineered MeCP2 mutation constructs to further analyze potential effects on DNA binding affinity and large-scale chromatin remodeling. Single or double deletion of the poly(ADP-ribosyl)ated regions and PARP inhibition increased the heterochromatin clustering ability of MeCP2. Increased chromatin clustering may reflect increased binding affinity. In agreement with this hypothesis, we found that PARP-1 deficiency significantly increased the chromatin binding affinity of MeCP2 in vivo. These data provide novel mechanistic insights into the regulation of MeCP2-mediated, higher-order chromatin architecture and suggest therapeutic opportunities to manipulate MeCP2 function. PMID:26772194

  6. Scaffold Attachment Factor B1: A Novel Chromatin Regulator of Prostate Cancer Metabolism

    Science.gov (United States)

    2016-10-01

    AWARD NUMBER: W81XWH-14-1-0152 TITLE: Scaffold Attachment Factor B1: A Novel Chromatin Regulator of Prostate Cancer Metabolism PRINCIPAL...TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-14-1-0152 Scaffold Attachment Factor B1: A Novel Chromatin Regulator of Prostate Cancer Metabolism... chromatin immunoprecipitation-next generation DNA sequencing (ChIP-seq) and integrative network modeling to identify the SAFB1 cistrome and the extent of

  7. A Paraconsistent Higher Order Logic

    DEFF Research Database (Denmark)

    Villadsen, Jørgen

    2004-01-01

    of paraconsistent logics in knowledge-based systems, logical semantics of natural language, etc. Higher order logics have the advantages of being expressive and with several automated theorem provers available. Also the type system can be helpful. We present a concise description of a paraconsistent higher order...... of the logic is examined by a case study in the domain of medicine. Thus we try to build a bridge between the HOL and MVL communities. A sequent calculus is proposed based on recent work by Muskens. Many non-classical logics are, at the propositional level, funny toys which work quite good, but when one wants...

  8. Nonlocal higher order evolution equations

    KAUST Repository

    Rossi, Julio D.; Schö nlieb, Carola-Bibiane

    2010-01-01

    In this article, we study the asymptotic behaviour of solutions to the nonlocal operator ut(x, t)1/4(-1)n-1 (J*Id -1)n (u(x, t)), x ∈ ℝN, which is the nonlocal analogous to the higher order local evolution equation vt(-1)n-1(Δ)nv. We prove

  9. Higher-Order Program Generation

    DEFF Research Database (Denmark)

    Rhiger, Morten

    for OCaml, a dialect of ML, that provides run-time code generation for OCaml programs. We apply these byte-code combinators in semantics-directed compilation for an imperative language and in run-time specialization using type-directed partial evaluation. Finally, we present an approach to compiling goal......This dissertation addresses the challenges of embedding programming languages, specializing generic programs to specific parameters, and generating specialized instances of programs directly as executable code. Our main tools are higher-order programming techniques and automatic program generation....... It is our thesis that they synergize well in the development of customizable software. Recent research on domain-specific languages propose to embed them into existing general-purpose languages. Typed higher-order languages have proven especially useful as meta languages because they provide a rich...

  10. Nonlocal higher order evolution equations

    KAUST Repository

    Rossi, Julio D.

    2010-06-01

    In this article, we study the asymptotic behaviour of solutions to the nonlocal operator ut(x, t)1/4(-1)n-1 (J*Id -1)n (u(x, t)), x ∈ ℝN, which is the nonlocal analogous to the higher order local evolution equation vt(-1)n-1(Δ)nv. We prove that the solutions of the nonlocal problem converge to the solution of the higher order problem with the right-hand side given by powers of the Laplacian when the kernel J is rescaled in an appropriate way. Moreover, we prove that solutions to both equations have the same asymptotic decay rate as t goes to infinity. © 2010 Taylor & Francis.

  11. Classical higher-order processes

    DEFF Research Database (Denmark)

    Montesi, Fabrizio

    2017-01-01

    Classical Processes (CP) is a calculus where the proof theory of classical linear logic types processes à la Π-calculus, building on a Curry-Howard correspondence between session types and linear propositions. We contribute to this research line by extending CP with process mobility, inspired...... by the Higher-Order Π-calculus. The key to our calculus is that sequents are asymmetric: one side types sessions as in CP and the other types process variables, which can be instantiated with process values. The controlled interaction between the two sides ensures that process variables can be used at will......, but always respecting the linear usage of sessions expected by the environment....

  12. Resilience and Higher Order Thinking

    Directory of Open Access Journals (Sweden)

    Ioan Fazey

    2010-09-01

    Full Text Available To appreciate, understand, and tackle chronic global social and environmental problems, greater appreciation of the importance of higher order thinking is required. Such thinking includes personal epistemological beliefs (PEBs, i.e., the beliefs people hold about the nature of knowledge and how something is known. These beliefs have profound implications for the way individuals relate to each other and the world, such as how people understand complex social-ecological systems. Resilience thinking is an approach to environmental stewardship that includes a number of interrelated concepts and has strong foundations in systemic ways of thinking. This paper (1 summarizes a review of educational psychology literature on PEBs, (2 explains why resilience thinking has potential to facilitate development of more sophisticated PEBs, (3 describes an example of a module designed to teach resilience thinking to undergraduate students in ways conducive to influencing PEBs, and (4 discusses a pilot study that evaluates the module's impact. Theoretical and preliminary evidence from the pilot evaluation suggests that resilience thinking which is underpinned by systems thinking has considerable potential to influence the development of more sophisticated PEBs. To be effective, however, careful consideration of how resilience thinking is taught is required. Finding ways to encourage students to take greater responsibility for their own learning and ensuring close alignment between assessment and desired learning outcomes are particularly important.

  13. The importance of topoisomerases for chromatin regulated genes

    DEFF Research Database (Denmark)

    Fredsøe, Jacob Christian; Pedersen, Jakob Madsen; Rødgaard, Morten Terpager

    2013-01-01

    DNA topoisomerases are enzymes, which function to relieve torsional stress in the DNA helix by introducing transient breaks into the DNA molecule. By use of Saccharomyces cerevisiae and microarray technology we have previously shown that topoisomerases are required for the activation of chromatin...... topoisomerases for optimal activation, but in contrast to the PHO5 gene, topoisomerases are not required for chromatin remodeling of the GAL1/10 promoter region, indicating a different role of the enzymes. We are currently performing a detailed investigation of the GAL genes to elucidate the precise role...

  14. SAGA, TFIID and regulation of transcription through chromatin

    NARCIS (Netherlands)

    Schram, A.W.

    2013-01-01

    Chromatin has an important role in eukaryotic transcription. Research into this role is ongoing and genome-wide analysis has correlated various histone modifications to multiple elements in active and silent genes, such as enhancers, promoters and coding regions. Modifications often serve to recruit

  15. Modulation of chromatin structure by the FACT histone chaperone complex regulates HIV-1 integration.

    Science.gov (United States)

    Matysiak, Julien; Lesbats, Paul; Mauro, Eric; Lapaillerie, Delphine; Dupuy, Jean-William; Lopez, Angelica P; Benleulmi, Mohamed Salah; Calmels, Christina; Andreola, Marie-Line; Ruff, Marc; Llano, Manuel; Delelis, Olivier; Lavigne, Marc; Parissi, Vincent

    2017-07-28

    Insertion of retroviral genome DNA occurs in the chromatin of the host cell. This step is modulated by chromatin structure as nucleosomes compaction was shown to prevent HIV-1 integration and chromatin remodeling has been reported to affect integration efficiency. LEDGF/p75-mediated targeting of the integration complex toward RNA polymerase II (polII) transcribed regions ensures optimal access to dynamic regions that are suitable for integration. Consequently, we have investigated the involvement of polII-associated factors in the regulation of HIV-1 integration. Using a pull down approach coupled with mass spectrometry, we have selected the FACT (FAcilitates Chromatin Transcription) complex as a new potential cofactor of HIV-1 integration. FACT is a histone chaperone complex associated with the polII transcription machinery and recently shown to bind LEDGF/p75. We report here that a tripartite complex can be formed between HIV-1 integrase, LEDGF/p75 and FACT in vitro and in cells. Biochemical analyzes show that FACT-dependent nucleosome disassembly promotes HIV-1 integration into chromatinized templates, and generates highly favored nucleosomal structures in vitro. This effect was found to be amplified by LEDGF/p75. Promotion of this FACT-mediated chromatin remodeling in cells both increases chromatin accessibility and stimulates HIV-1 infectivity and integration. Altogether, our data indicate that FACT regulates HIV-1 integration by inducing local nucleosomes dissociation that modulates the functional association between the incoming intasome and the targeted nucleosome.

  16. Systematic dissection of roles for chromatin regulators in a yeast stress response.

    Directory of Open Access Journals (Sweden)

    Assaf Weiner

    Full Text Available Packaging of eukaryotic genomes into chromatin has wide-ranging effects on gene transcription. Curiously, it is commonly observed that deletion of a global chromatin regulator affects expression of only a limited subset of genes bound to or modified by the regulator in question. However, in many single-gene studies it has become clear that chromatin regulators often do not affect steady-state transcription, but instead are required for normal transcriptional reprogramming by environmental cues. We therefore have systematically investigated the effects of 83 histone mutants, and 119 gene deletion mutants, on induction/repression dynamics of 170 transcripts in response to diamide stress in yeast. Importantly, we find that chromatin regulators play far more pronounced roles during gene induction/repression than they do in steady-state expression. Furthermore, by jointly analyzing the substrates (histone mutants and enzymes (chromatin modifier deletions we identify specific interactions between histone modifications and their regulators. Combining these functional results with genome-wide mapping of several histone marks in the same time course, we systematically investigated the correspondence between histone modification occurrence and function. We followed up on one pathway, finding that Set1-dependent H3K4 methylation primarily acts as a gene repressor during multiple stresses, specifically at genes involved in ribosome biosynthesis. Set1-dependent repression of ribosomal genes occurs via distinct pathways for ribosomal protein genes and ribosomal biogenesis genes, which can be separated based on genetic requirements for repression and based on chromatin changes during gene repression. Together, our dynamic studies provide a rich resource for investigating chromatin regulation, and identify a significant role for the "activating" mark H3K4me3 in gene repression.

  17. The Chromatin Regulator Brpf1 Regulates Embryo Development and Cell Proliferation*

    Science.gov (United States)

    You, Linya; Yan, Kezhi; Zou, Jinfeng; Zhao, Hong; Bertos, Nicholas R.; Park, Morag; Wang, Edwin; Yang, Xiang-Jiao

    2015-01-01

    With hundreds of chromatin regulators identified in mammals, an emerging issue is how they modulate biological and pathological processes. BRPF1 (bromodomain- and PHD finger-containing protein 1) is a unique chromatin regulator possessing two PHD fingers, one bromodomain and a PWWP domain for recognizing multiple histone modifications. In addition, it binds to the acetyltransferases MOZ, MORF, and HBO1 (also known as KAT6A, KAT6B, and KAT7, respectively) to promote complex formation, restrict substrate specificity, and enhance enzymatic activity. We have recently showed that ablation of the mouse Brpf1 gene causes embryonic lethality at E9.5. Here we present systematic analyses of the mutant animals and demonstrate that the ablation leads to vascular defects in the placenta, yolk sac, and embryo proper, as well as abnormal neural tube closure. At the cellular level, Brpf1 loss inhibits proliferation of embryonic fibroblasts and hematopoietic progenitors. Molecularly, the loss reduces transcription of a ribosomal protein L10 (Rpl10)-like gene and the cell cycle inhibitor p27, and increases expression of the cell-cycle inhibitor p16 and a novel protein homologous to Scp3, a synaptonemal complex protein critical for chromosome association and embryo survival. These results uncover a crucial role of Brpf1 in controlling mouse embryo development and regulating cellular and gene expression programs. PMID:25773539

  18. Higher order mode optical fiber Raman amplifiers

    DEFF Research Database (Denmark)

    Rottwitt, Karsten; Friis, Søren Michael Mørk; Usuga Castaneda, Mario A.

    2016-01-01

    We review higher order mode Raman amplifiers and discuss recent theoretical as well as experimental results including system demonstrations.......We review higher order mode Raman amplifiers and discuss recent theoretical as well as experimental results including system demonstrations....

  19. Ascl1 Coordinately Regulates Gene Expression and the Chromatin Landscape during Neurogenesis

    Directory of Open Access Journals (Sweden)

    Alexandre A.S.F. Raposo

    2015-03-01

    Full Text Available The proneural transcription factor Ascl1 coordinates gene expression in both proliferating and differentiating progenitors along the neuronal lineage. Here, we used a cellular model of neurogenesis to investigate how Ascl1 interacts with the chromatin landscape to regulate gene expression when promoting neuronal differentiation. We find that Ascl1 binding occurs mostly at distal enhancers and is associated with activation of gene transcription. Surprisingly, the accessibility of Ascl1 to its binding sites in neural stem/progenitor cells remains largely unchanged throughout their differentiation, as Ascl1 targets regions of both readily accessible and closed chromatin in proliferating cells. Moreover, binding of Ascl1 often precedes an increase in chromatin accessibility and the appearance of new regions of open chromatin, associated with de novo gene expression during differentiation. Our results reveal a function of Ascl1 in promoting chromatin accessibility during neurogenesis, linking the chromatin landscape at Ascl1 target regions with the temporal progression of its transcriptional program.

  20. Challenges in higher order mode Raman amplifiers

    DEFF Research Database (Denmark)

    Rottwitt, Karsten; Nielsen, Kristian; Friis, Søren Michael Mørk

    2015-01-01

    A higher order Raman amplifier model that take random mode coupling into account ispresented. Mode dependent gain and signal power fluctuations at the output of the higher order modeRaman amplifier are discussed......A higher order Raman amplifier model that take random mode coupling into account ispresented. Mode dependent gain and signal power fluctuations at the output of the higher order modeRaman amplifier are discussed...

  1. Large-scale chromatin remodeling at the immunoglobulin heavy chain locus: a paradigm for multigene regulation.

    Science.gov (United States)

    Bolland, Daniel J; Wood, Andrew L; Corcoran, Anne E

    2009-01-01

    complementary processes involved in this large-scale locus organisation. We will examine the structure of the Igh locus and the large-scale and higher-order chromatin remodelling processes associated with V(D)J recombination, at the level of the locus itself, its conformational changes and its dynamic localisation within the nucleus.

  2. Undifferentiated Embryonic Cell Transcription Factor 1 Regulates ESC Chromatin Organization and Gene Expression

    NARCIS (Netherlands)

    Kooistra, Susanne M.; van den Boom, Vincent; Thummer, Rajkumar P.; Johannes, Frank; Wardenaar, Rene; Tesson, Bruno M.; Veenhoff, Liesbeth M.; Fusetti, Fabrizia; O'Neill, Laura P.; Turner, Bryan M.; de Haan, Gerald; Eggen, Bart J. L.; O’Neill, Laura P.

    2010-01-01

    Previous reports showed that embryonic stem (ES) cells contain hyperdynamic and globally transcribed chromatin-properties that are important for ES cell pluripotency and differentiation. Here, we demonstrate a role for undifferentiated embryonic cell transcription factor 1 (UTF1) in regulating ES

  3. Chromatin looping and epigenetic regulation at the maize b1 locus

    NARCIS (Netherlands)

    Louwers, M.L.D.

    2008-01-01

    In this thesis, the effect of epigenetic regulation on long-range chromatin looping is studied. As a model system we used two maize b1 epialleles involved in paramutation. Paramutation entails a trans-interaction between two alleles whereby one allele heritably changes the expression level of the

  4. Phosphorylation of linker histones regulates ATP-dependent chromatin remodeling enzymes.

    NARCIS (Netherlands)

    Horn, P.J.; Carruthers, L.M.; Logie, C.; Hill, D.A.; Solomon, M.J.; Wade, P.A.; Imbalzano, A.N.; Hansen, J.; Peterson, C.L.

    2002-01-01

    Members of the ATP-dependent family of chromatin remodeling enzymes play key roles in the regulation of transcription, development, DNA repair and cell cycle control. We find that the remodeling activities of the ySWI/SNF, hSWI/SNF, xMi-2 and xACF complexes are nearly abolished by incorporation of

  5. Higher Order Expectations in Asset Pricing

    OpenAIRE

    Philippe BACCHETTA; Eric VAN WINCOOP

    2004-01-01

    We examine formally Keynes' idea that higher order beliefs can drive a wedge between an asset price and its fundamental value based on expected future payoffs. Higher order expectations add an additional term to a standard asset pricing equation. We call this the higher order wedge, which depends on the difference between higher and first order expectations of future payoffs. We analyze the determinants of this wedge and its impact on the equilibrium price. In the context of a dynamic noisy r...

  6. Higher order harmonics of reactor neutron equation

    International Nuclear Information System (INIS)

    Li Fu; Hu Yongming; Luo Zhengpei

    1996-01-01

    The flux mapping method using the higher order harmonics of the neutron equation is proposed. Based on the bi-orthogonality of the higher order harmonics, the process and formulas for higher order harmonics calculation are derived via the source iteration method with source correction. For the first time, not only any order harmonics for up-to-3-dimensional geometry are achieved, but also the preliminary verification to the capability for flux mapping have been carried out

  7. A Functional Switch of NuRD Chromatin Remodeling Complex Subunits Regulates Mouse Cortical Development

    Directory of Open Access Journals (Sweden)

    Justyna Nitarska

    2016-11-01

    Full Text Available Histone modifications and chromatin remodeling represent universal mechanisms by which cells adapt their transcriptional response to rapidly changing environmental conditions. Extensive chromatin remodeling takes place during neuronal development, allowing the transition of pluripotent cells into differentiated neurons. Here, we report that the NuRD complex, which couples ATP-dependent chromatin remodeling with histone deacetylase activity, regulates mouse brain development. Subunit exchange of CHDs, the core ATPase subunits of the NuRD complex, is required for distinct aspects of cortical development. Whereas CHD4 promotes the early proliferation of progenitors, CHD5 facilitates neuronal migration and CHD3 ensures proper layer specification. Inhibition of each CHD leads to defects of neuronal differentiation and migration, which cannot be rescued by expressing heterologous CHDs. Finally, we demonstrate that NuRD complexes containing specific CHDs are recruited to regulatory elements and modulate the expression of genes essential for brain development.

  8. Undifferentiated embryonic cell transcription factor 1 regulates ESC chromatin organization and gene expression

    DEFF Research Database (Denmark)

    Kooistra, Susanne M; van den Boom, Vincent; Thummer, Rajkumar P

    2010-01-01

    Previous reports showed that embryonic stem (ES) cells contain hyperdynamic and globally transcribed chromatin-properties that are important for ES cell pluripotency and differentiation. Here, we demonstrate a role for undifferentiated embryonic cell transcription factor 1 (UTF1) in regulating ES...... cell chromatin structure. Using chromatin immunoprecipitation-on-chip analysis, we identified >1,700 UTF1 target genes that significantly overlap with previously identified Nanog, Oct4, Klf-4, c-Myc, and Rex1 targets. Gene expression profiling showed that UTF1 knock down results in increased expression...... of a large set of genes, including a significant number of UTF1 targets. UTF1 knock down (KD) ES cells are, irrespective of the increased expression of several self-renewal genes, Leukemia inhibitory factor (LIF) dependent. However, UTF1 KD ES cells are perturbed in their differentiation in response...

  9. Chromatin-Bound MDM2 Regulates Serine Metabolism and Redox Homeostasis Independently of p53.

    Science.gov (United States)

    Riscal, Romain; Schrepfer, Emilie; Arena, Giuseppe; Cissé, Madi Y; Bellvert, Floriant; Heuillet, Maud; Rambow, Florian; Bonneil, Eric; Sabourdy, Frédérique; Vincent, Charles; Ait-Arsa, Imade; Levade, Thierry; Thibaut, Pierre; Marine, Jean-Christophe; Portais, Jean-Charles; Sarry, Jean-Emmanuel; Le Cam, Laurent; Linares, Laetitia K

    2016-06-16

    The mouse double minute 2 (MDM2) oncoprotein is recognized as a major negative regulator of the p53 tumor suppressor, but growing evidence indicates that its oncogenic activities extend beyond p53. Here, we show that MDM2 is recruited to chromatin independently of p53 to regulate a transcriptional program implicated in amino acid metabolism and redox homeostasis. Identification of MDM2 target genes at the whole-genome level highlights an important role for ATF3/4 transcription factors in tethering MDM2 to chromatin. MDM2 recruitment to chromatin is a tightly regulated process that occurs during oxidative stress and serine/glycine deprivation and is modulated by the pyruvate kinase M2 (PKM2) metabolic enzyme. Depletion of endogenous MDM2 in p53-deficient cells impairs serine/glycine metabolism, the NAD(+)/NADH ratio, and glutathione (GSH) recycling, impacting their redox state and tumorigenic potential. Collectively, our data illustrate a previously unsuspected function of chromatin-bound MDM2 in cancer cell metabolism. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. PHF6 regulates phenotypic plasticity through chromatin organization within lineage-specific genes.

    Science.gov (United States)

    Soto-Feliciano, Yadira M; Bartlebaugh, Jordan M E; Liu, Yunpeng; Sánchez-Rivera, Francisco J; Bhutkar, Arjun; Weintraub, Abraham S; Buenrostro, Jason D; Cheng, Christine S; Regev, Aviv; Jacks, Tyler E; Young, Richard A; Hemann, Michael T

    2017-05-15

    Developmental and lineage plasticity have been observed in numerous malignancies and have been correlated with tumor progression and drug resistance. However, little is known about the molecular mechanisms that enable such plasticity to occur. Here, we describe the function of the plant homeodomain finger protein 6 (PHF6) in leukemia and define its role in regulating chromatin accessibility to lineage-specific transcription factors. We show that loss of Phf6 in B-cell leukemia results in systematic changes in gene expression via alteration of the chromatin landscape at the transcriptional start sites of B-cell- and T-cell-specific factors. Additionally, Phf6 KO cells show significant down-regulation of genes involved in the development and function of normal B cells, show up-regulation of genes involved in T-cell signaling, and give rise to mixed-lineage lymphoma in vivo. Engagement of divergent transcriptional programs results in phenotypic plasticity that leads to altered disease presentation in vivo, tolerance of aberrant oncogenic signaling, and differential sensitivity to frontline and targeted therapies. These findings suggest that active maintenance of a precise chromatin landscape is essential for sustaining proper leukemia cell identity and that loss of a single factor (PHF6) can cause focal changes in chromatin accessibility and nucleosome positioning that render cells susceptible to lineage transition. © 2017 Soto-Feliciano et al.; Published by Cold Spring Harbor Laboratory Press.

  11. ELF4 Regulates GIGANTEA Chromatin Access through Subnuclear Sequestration

    Directory of Open Access Journals (Sweden)

    Yumi Kim

    2013-03-01

    Full Text Available Many organisms, including plants, use the circadian clock to measure the duration of day and night. Daily rhythms in the plant circadian system are generated by multiple interlocked transcriptional/translational loops and also by spatial regulations such as nuclear translocation. GIGANTEA (GI, one of the key clock components in Arabidopsis, makes distinctive nuclear bodies like other nuclear-localized circadian regulators. However, little is known about the dynamics or roles of GI subnuclear localization. Here, we characterize GI subnuclear compartmentalization and identify unexpected dynamic changes under diurnal conditions. We further identify EARLY FLOWERING 4 (ELF4 as a regulator of GI nuclear distribution through a physical interaction. ELF4 sequesters GI from the nucleoplasm, where GI binds the promoter of CONSTANS (CO, to discrete nuclear bodies. We suggest that the subnuclear compartmentalization of GI by ELF4 contributes to the regulation of photoperiodic flowering.

  12. Higher-order (non-)modularity

    DEFF Research Database (Denmark)

    Appel, Claus; van Oostrom, Vincent; Simonsen, Jakob Grue

    2010-01-01

    We show that, contrary to the situation in first-order term rewriting, almost none of the usual properties of rewriting are modular for higher-order rewriting, irrespective of the higher-order rewriting format. We show that for the particular format of simply typed applicative term rewriting...... systems modularity of confluence, normalization, and termination can be recovered by imposing suitable linearity constraints....

  13. Difference equations in massive higher order calculations

    International Nuclear Information System (INIS)

    Bierenbaum, I.; Bluemlein, J.; Klein, S.; Schneider, C.

    2007-07-01

    The calculation of massive 2-loop operator matrix elements, required for the higher order Wilson coefficients for heavy flavor production in deeply inelastic scattering, leads to new types of multiple infinite sums over harmonic sums and related functions, which depend on the Mellin parameter N. We report on the solution of these sums through higher order difference equations using the summation package Sigma. (orig.)

  14. Noncoding transcription by alternative rna polymerases dynamically regulates an auxin-driven chromatin loop

    KAUST Repository

    Ariel, Federico D.; Jé gu, Teddy; Latrasse, David; Romero-Barrios, Natali; Christ, Auré lie; Benhamed, Moussa; Crespi, Martí n D.

    2014-01-01

    The eukaryotic epigenome is shaped by the genome topology in three-dimensional space. Dynamic reversible variations in this epigenome structure directly influence the transcriptional responses to developmental cues. Here, we show that the Arabidopsis long intergenic noncoding RNA (lincRNA) APOLO is transcribed by RNA polymerases II and V in response to auxin, a phytohormone controlling numerous facets of plant development. This dual APOLO transcription regulates the formation of a chromatin loop encompassing the promoter of its neighboring gene PID, a key regulator of polar auxin transport. Altering APOLO expression affects chromatin loop formation, whereas RNA-dependent DNA methylation, active DNA demethylation, and Polycomb complexes control loop dynamics. This dynamic chromatin topology determines PID expression patterns. Hence, the dual transcription of a lincRNA influences local chromatin topology and directs dynamic auxin-controlled developmental outputs on neighboring genes. This mechanism likely underscores the adaptive success of plants in diverse environments and may be widespread in eukaryotes. © 2014 Elsevier Inc.

  15. DNA breaks and chromatin structural changes enhance the transcription of autoimmune regulator target genes.

    Science.gov (United States)

    Guha, Mithu; Saare, Mario; Maslovskaja, Julia; Kisand, Kai; Liiv, Ingrid; Haljasorg, Uku; Tasa, Tõnis; Metspalu, Andres; Milani, Lili; Peterson, Pärt

    2017-04-21

    The autoimmune regulator (AIRE) protein is the key factor in thymic negative selection of autoreactive T cells by promoting the ectopic expression of tissue-specific genes in the thymic medullary epithelium. Mutations in AIRE cause a monogenic autoimmune disease called autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. AIRE has been shown to promote DNA breaks via its interaction with topoisomerase 2 (TOP2). In this study, we investigated topoisomerase-induced DNA breaks and chromatin structural alterations in conjunction with AIRE-dependent gene expression. Using RNA sequencing, we found that inhibition of TOP2 religation activity by etoposide in AIRE-expressing cells had a synergistic effect on genes with low expression levels. AIRE-mediated transcription was not only enhanced by TOP2 inhibition but also by the TOP1 inhibitor camptothecin. The transcriptional activation was associated with structural rearrangements in chromatin, notably the accumulation of γH2AX and the exchange of histone H1 with HMGB1 at AIRE target gene promoters. In addition, we found the transcriptional up-regulation to co-occur with the chromatin structural changes within the genomic cluster of carcinoembryonic antigen-like cellular adhesion molecule genes. Overall, our results suggest that the presence of AIRE can trigger molecular events leading to an altered chromatin landscape and the enhanced transcription of low-expressed genes. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Noncoding transcription by alternative rna polymerases dynamically regulates an auxin-driven chromatin loop

    KAUST Repository

    Ariel, Federico D.

    2014-08-01

    The eukaryotic epigenome is shaped by the genome topology in three-dimensional space. Dynamic reversible variations in this epigenome structure directly influence the transcriptional responses to developmental cues. Here, we show that the Arabidopsis long intergenic noncoding RNA (lincRNA) APOLO is transcribed by RNA polymerases II and V in response to auxin, a phytohormone controlling numerous facets of plant development. This dual APOLO transcription regulates the formation of a chromatin loop encompassing the promoter of its neighboring gene PID, a key regulator of polar auxin transport. Altering APOLO expression affects chromatin loop formation, whereas RNA-dependent DNA methylation, active DNA demethylation, and Polycomb complexes control loop dynamics. This dynamic chromatin topology determines PID expression patterns. Hence, the dual transcription of a lincRNA influences local chromatin topology and directs dynamic auxin-controlled developmental outputs on neighboring genes. This mechanism likely underscores the adaptive success of plants in diverse environments and may be widespread in eukaryotes. © 2014 Elsevier Inc.

  17. Higher-order techniques in computational electromagnetics

    CERN Document Server

    Graglia, Roberto D

    2016-01-01

    Higher-Order Techniques in Computational Electromagnetics explains 'high-order' techniques that can significantly improve the accuracy, computational cost, and reliability of computational techniques for high-frequency electromagnetics, such as antennas, microwave devices and radar scattering applications.

  18. Higher-order rewriting and partial evaluation

    DEFF Research Database (Denmark)

    Danvy, Olivier; Rose, Kristoffer H.

    1998-01-01

    We demonstrate the usefulness of higher-order rewriting techniques for specializing programs, i.e., for partial evaluation. More precisely, we demonstrate how casting program specializers as combinatory reduction systems (CRSs) makes it possible to formalize the corresponding program...

  19. Chromatin remodeling, development and disease

    International Nuclear Information System (INIS)

    Ko, Myunggon; Sohn, Dong H.; Chung, Heekyoung; Seong, Rho H.

    2008-01-01

    Development is a stepwise process in which multi-potent progenitor cells undergo lineage commitment, differentiation, proliferation and maturation to produce mature cells with restricted developmental potentials. This process is directed by spatiotemporally distinct gene expression programs that allow cells to stringently orchestrate intricate transcriptional activation or silencing events. In eukaryotes, chromatin structure contributes to developmental progression as a blueprint for coordinated gene expression by actively participating in the regulation of gene expression. Changes in higher order chromatin structure or covalent modification of its components are considered to be critical events in dictating lineage-specific gene expression during development. Mammalian cells utilize multi-subunit nuclear complexes to alter chromatin structure. Histone-modifying complex catalyzes covalent modifications of histone tails including acetylation, methylation, phosphorylation and ubiquitination. ATP-dependent chromatin remodeling complex, which disrupts histone-DNA contacts and induces nucleosome mobilization, requires energy from ATP hydrolysis for its catalytic activity. Here, we discuss the diverse functions of ATP-dependent chromatin remodeling complexes during mammalian development. In particular, the roles of these complexes during embryonic and hematopoietic development are reviewed in depth. In addition, pathological conditions such as tumor development that are induced by mutation of several key subunits of the chromatin remodeling complex are discussed, together with possible mechanisms that underlie tumor suppression by the complex

  20. The Fanconi anemia proteins FANCD2 and FANCJ interact and regulate each other's chromatin localization.

    Science.gov (United States)

    Chen, Xiaoyong; Wilson, James B; McChesney, Patricia; Williams, Stacy A; Kwon, Youngho; Longerich, Simonne; Marriott, Andrew S; Sung, Patrick; Jones, Nigel J; Kupfer, Gary M

    2014-09-12

    Fanconi anemia is a genetic disease resulting in bone marrow failure, birth defects, and cancer that is thought to encompass a defect in maintenance of genomic stability. Mutations in 16 genes (FANCA, B, C, D1, D2, E, F, G, I, J, L, M, N, O, P, and Q) have been identified in patients, with the Fanconi anemia subtype J (FA-J) resulting from homozygous mutations in the FANCJ gene. Here, we describe the direct interaction of FANCD2 with FANCJ. We demonstrate the interaction of FANCD2 and FANCJ in vivo and in vitro by immunoprecipitation in crude cell lysates and from fractions after gel filtration and with baculovirally expressed proteins. Mutation of the monoubiquitination site of FANCD2 (K561R) preserves interaction with FANCJ constitutively in a manner that impedes proper chromatin localization of FANCJ. FANCJ is necessary for FANCD2 chromatin loading and focus formation in response to mitomycin C treatment. Our results suggest not only that FANCD2 regulates FANCJ chromatin localization but also that FANCJ is necessary for efficient loading of FANCD2 onto chromatin following DNA damage caused by mitomycin C treatment. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Regulation of chromatin states by drugs of abuse.

    Science.gov (United States)

    Walker, Deena M; Cates, Hannah M; Heller, Elizabeth A; Nestler, Eric J

    2015-02-01

    Drug addiction involves long-term behavioral abnormalities and gene expression changes throughout the mesolimbic dopamine system. Epigenetic mechanisms establish/maintain alterations in gene expression in the brain, providing the impetus for investigations characterizing how epigenetic processes mediate the effects of drugs of abuse. This review focuses on evidence that epigenetic events, specifically histone modifications, regulate gene expression changes throughout the reward circuitry. Drugs of abuse induce changes in histone modifications throughout the reward circuitry by altering histone-modifying enzymes, manipulation of which reveals a role for histone modification in addiction-related behaviors. There is a complex interplay between these enzymes, resulting in a histone signature of the addicted phenotype. Insights gained from these studies are key to identifying novel targets for diagnosis and therapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Phosphorylation of histone H3 at threonine 11 establishes a novel chromatin mark for transcriptional regulation

    OpenAIRE

    Metzger, Eric; Yin, Na; Wissmann, Melanie; Kunowska, Natalia; Fischer, Kristin; Friedrichs, Nicolaus; Patnaik, Debasis; Higgins, Jonathan M.G.; Potier, Noelle; Scheidtmann, Karl-Heinz; Buettner, Reinhard; Schüle, Roland

    2007-01-01

    Posttranslational modifications of histones such as methylation, acetylation, and phosphorylation regulate chromatin structure and gene expression. Here we show that protein kinase C-related kinase 1 (PRK1) phosphorylates histone H3 at threonine 11 (H3T11) upon ligand-dependent recruitment to androgen receptor (AR) target genes. PRK1 is pivotal to AR function since PRK1 knockdown or inhibition impedes AR-dependent transcription. Blocking PRK1 function abrogates androgen-induced H3T11 phosphor...

  3. Identification of chromatin-associated regulators of MSL complex targeting in Drosophila dosage compensation.

    Directory of Open Access Journals (Sweden)

    Erica Larschan

    Full Text Available Sex chromosome dosage compensation in Drosophila provides a model for understanding how chromatin organization can modulate coordinate gene regulation. Male Drosophila increase the transcript levels of genes on the single male X approximately two-fold to equal the gene expression in females, which have two X-chromosomes. Dosage compensation is mediated by the Male-Specific Lethal (MSL histone acetyltransferase complex. Five core components of the MSL complex were identified by genetic screens for genes that are specifically required for male viability and are dispensable for females. However, because dosage compensation must interface with the general transcriptional machinery, it is likely that identifying additional regulators that are not strictly male-specific will be key to understanding the process at a mechanistic level. Such regulators would not have been recovered from previous male-specific lethal screening strategies. Therefore, we have performed a cell culture-based, genome-wide RNAi screen to search for factors required for MSL targeting or function. Here we focus on the discovery of proteins that function to promote MSL complex recruitment to "chromatin entry sites," which are proposed to be the initial sites of MSL targeting. We find that components of the NSL (Non-specific lethal complex, and a previously unstudied zinc-finger protein, facilitate MSL targeting and display a striking enrichment at MSL entry sites. Identification of these factors provides new insight into how MSL complex establishes the specialized hyperactive chromatin required for dosage compensation in Drosophila.

  4. HIGHER ORDER THINKING IN TEACHING GRAMMAR

    Directory of Open Access Journals (Sweden)

    Citra Dewi

    2017-04-01

    Full Text Available The aim of this paper discussed about how to enhance students’ higher order thinking that should be done by teacher in teaching grammar. Usually teaching grammar was boring and has the same way to learn like change the pattern of sentence into positive, negative and introgative while the students’ need more various way to develop their thinking. The outcome of students’ competence in grammar sometimes not sufficient enough when the students’ occured some test international standart like Test of English Foreign Language, International English Language Testing. Whereas in TOEFL test it needed higher order thinking answer, so teacher should develop students’ higher order thingking in daily teaching grammar in order to make the students’ enhance their thinking are higher. The method was used in this paper by using field study based on the experience of teaching grammar. It can be shown by students’ toefl score was less in stucture and written expression. The result of this paper was after teacher gave some treatments to enhance students’ higher order thinking in teaching grammar, the students’ toefl scores are sufficient enough as a part of stucture and written expression. It can concluded that it needed some strategies to enhancce students higher order thinking by teaching grammar it can make students’ higher toefl score. Teachers should be creative and inovative to teach the students’ started from giving the students’ question or test in teaching grammar.

  5. Interplay between chromatin modulators and histone acetylation regulates the formation of accessible chromatin in the upstream regulatory region of fission yeast fbp1.

    Science.gov (United States)

    Adachi, Akira; Senmatsu, Satoshi; Asada, Ryuta; Abe, Takuya; Hoffman, Charles S; Ohta, Kunihiro; Hirota, Kouji

    2018-05-03

    Numerous noncoding RNA transcripts are detected in eukaryotic cells. Noncoding RNAs transcribed across gene promoters are involved in the regulation of mRNA transcription via chromatin modulation. This function of noncoding RNA transcription was first demonstrated for the fission yeast fbp1 gene, where a cascade of noncoding RNA transcription events induces chromatin remodeling to facilitate transcription factor binding. We recently demonstrated that the noncoding RNAs from the fbp1 upstream region facilitate binding of the transcription activator Atf1 and thereby promote histone acetylation. Histone acetylation by histone acetyl transferases (HATs) and ATP-dependent chromatin remodelers (ADCRs) are implicated in chromatin remodeling, but the interplay between HATs and ADCRs in this process has not been fully elucidated. Here, we examine the roles played by two distinct ADCRs, Snf22 and Hrp3, and by the HAT Gcn5 in the transcriptional activation of fbp1. Snf22 and Hrp3 redundantly promote disassembly of chromatin in the fbp1 upstream region. Gcn5 critically contributes to nucleosome eviction in the absence of either Snf22 or Hrp3, presumably by recruiting Hrp3 in snf22∆ cells and Snf22 in hrp3∆ cells. Conversely, Gcn5-dependent histone H3 acetylation is impaired in snf22∆/hrp3∆ cells, suggesting that both redundant ADCRs induce recruitment of Gcn5 to the chromatin array in the fbp1 upstream region. These results reveal a previously unappreciated interplay between ADCRs and histone acetylation in which histone acetylation facilitates recruitment of ADCRs, while ADCRs are required for histone acetylation.

  6. Electromagnetic cloaking in higher order spherical cloaks

    Science.gov (United States)

    Sidhwa, H. H.; Aiyar, R. P. R. C.; Kulkarni, S. V.

    2017-06-01

    The inception of transformation optics has led to the realisation of the invisibility devices for various applications, one of which is spherical cloaking. In this paper, a formulation for a higher-order spherical cloak has been proposed to reduce its physical thickness significantly by introducing a nonlinear relation between the original and transformed coordinate systems and it has been verified using the ray tracing approach. Analysis has been carried out to observe the anomalies in the variation of refractive index for higher order cloaks indicating the presence of poles in the relevant equations. Furthermore, a higher-order spherical cloak with predefined values of the material characteristics on its inner and outer surfaces has been designed for practical application.

  7. Higher-order force gradient symplectic algorithms

    Science.gov (United States)

    Chin, Siu A.; Kidwell, Donald W.

    2000-12-01

    We show that a recently discovered fourth order symplectic algorithm, which requires one evaluation of force gradient in addition to three evaluations of the force, when iterated to higher order, yielded algorithms that are far superior to similarly iterated higher order algorithms based on the standard Forest-Ruth algorithm. We gauge the accuracy of each algorithm by comparing the step-size independent error functions associated with energy conservation and the rotation of the Laplace-Runge-Lenz vector when solving a highly eccentric Kepler problem. For orders 6, 8, 10, and 12, the new algorithms are approximately a factor of 103, 104, 104, and 105 better.

  8. Frontiers of higher order fuzzy sets

    CERN Document Server

    Tahayori, Hooman

    2015-01-01

    Frontiers of Higher Order Fuzzy Sets, strives to improve the theoretical aspects of general and Interval Type-2 fuzzy sets and provides a unified representation theorem for higher order fuzzy sets. Moreover, the book elaborates on the concept of gradual elements and their integration with the higher order fuzzy sets. This book also introduces new frameworks for information granulation based on general T2FSs, IT2FSs, Gradual elements, Shadowed sets and rough sets. In particular, the properties and characteristics of the new proposed frameworks are studied. Such new frameworks are shown to be more capable to be exploited in real applications. Higher order fuzzy sets that are the result of the integration of general T2FSs, IT2FSs, gradual elements, shadowed sets and rough sets will be shown to be suitable to be applied in the fields of bioinformatics, business, management, ambient intelligence, medicine, cloud computing and smart grids. Presents new variations of fuzzy set frameworks and new areas of applicabili...

  9. Higher-order tensors in diffusion imaging

    NARCIS (Netherlands)

    Schultz, T.; Fuster, A.; Ghosh, A.; Deriche, R.; Florack, L.M.J.; Lim, L.H.; Westin, C.-F.; Vilanova, A.; Burgeth, B.

    2014-01-01

    Diffusion imaging is a noninvasive tool for probing the microstructure of fibrous nerve and muscle tissue. Higher-order tensors provide a powerful mathematical language to model and analyze the large and complex data that is generated by its modern variants such as High Angular Resolution Diffusion

  10. Analogy, higher order thinking, and education.

    Science.gov (United States)

    Richland, Lindsey Engle; Simms, Nina

    2015-01-01

    Analogical reasoning, the ability to understand phenomena as systems of structured relationships that can be aligned, compared, and mapped together, plays a fundamental role in the technology rich, increasingly globalized educational climate of the 21st century. Flexible, conceptual thinking is prioritized in this view of education, and schools are emphasizing 'higher order thinking', rather than memorization of a cannon of key topics. The lack of a cognitively grounded definition for higher order thinking, however, has led to a field of research and practice with little coherence across domains or connection to the large body of cognitive science research on thinking. We review literature on analogy and disciplinary higher order thinking to propose that relational reasoning can be productively considered the cognitive underpinning of higher order thinking. We highlight the utility of this framework for developing insights into practice through a review of mathematics, science, and history educational contexts. In these disciplines, analogy is essential to developing expert-like disciplinary knowledge in which concepts are understood to be systems of relationships that can be connected and flexibly manipulated. At the same time, analogies in education require explicit support to ensure that learners notice the relevance of relational thinking, have adequate processing resources available to mentally hold and manipulate relations, and are able to recognize both the similarities and differences when drawing analogies between systems of relationships. © 2015 John Wiley & Sons, Ltd.

  11. Higher-Order Components for Grid Programming

    CERN Document Server

    Dünnweber, Jan

    2009-01-01

    Higher-Order Components were developed within the CoreGRID European Network of Excellence and have become an optional extension of the popular Globus middleware. This book provides the reader with hands-on experience, describing a collection of example applications from various fields of science and engineering, including biology and physics.

  12. Higher order antibunching in intermediate states

    International Nuclear Information System (INIS)

    Verma, Amit; Sharma, Navneet K.; Pathak, Anirban

    2008-01-01

    Since the introduction of binomial state as an intermediate state, different intermediate states have been proposed. Different nonclassical effects have also been reported in these intermediate states. But till now higher order antibunching is predicted in only one type of intermediate state, which is known as shadowed negative binomial state. Recently we have shown that the higher order antibunching is not a rare phenomenon [P. Gupta, P. Pandey, A. Pathak, J. Phys. B 39 (2006) 1137]. To establish our earlier claim further, here we have shown that the higher order antibunching can be seen in different intermediate states, such as binomial state, reciprocal binomial state, hypergeometric state, generalized binomial state, negative binomial state and photon added coherent state. We have studied the possibility of observing the higher order subpoissonian photon statistics in different limits of intermediate states. The effects of different control parameters on the depth of non classicality have also been studied in this connection and it has been shown that the depth of nonclassicality can be tuned by controlling various physical parameters

  13. Certified higher-order recursive path ordering

    NARCIS (Netherlands)

    Koprowski, A.; Pfenning, F.

    2006-01-01

    The paper reports on a formalization of a proof of wellfoundedness of the higher-order recursive path ordering (HORPO) in the proof checker Coq. The development is axiom-free and fully constructive. Three substantive parts that could be used also in other developments are the formalizations of the

  14. Higher-Order Minimal Functional Graphs

    DEFF Research Database (Denmark)

    Jones, Neil D; Rosendahl, Mads

    1994-01-01

    We present a minimal function graph semantics for a higher-order functional language with applicative evaluation order. The semantics captures the intermediate calls performed during the evaluation of a program. This information may be used in abstract interpretation as a basis for proving...

  15. Chromatin landscaping in algae reveals novel regulation pathway for biofuels production

    Energy Technology Data Exchange (ETDEWEB)

    Ngan, Chew Yee; Wong, Chee-Hong; Choi, Cindy; Pratap, Abhishek; Han, James; Wei, Chia-Lin

    2013-02-19

    The diminishing reserve of fossil fuels calls for the development of biofuels. Biofuels are produced from renewable resources, including photosynthetic organisms, generating clean energy. Microalgae is one of the potential feedstock for biofuels production. It grows easily even in waste water, and poses no competition to agricultural crops for arable land. However, little is known about the algae lipid biosynthetic regulatory mechanisms. Most studies relied on the homology to other plant model organisms, in particular Arabidopsis or through low coverage expression analysis to identify key enzymes. This limits the discovery of new components in the biosynthetic pathways, particularly the genetic regulators and effort to maximize the production efficiency of algal biofuels. Here we report an unprecedented and de novo approach to dissect the algal lipid pathways through disclosing the temporal regulations of chromatin states during lipid biosynthesis. We have generated genome wide chromatin maps in chlamydomonas genome using ChIP-seq targeting 7 histone modifications and RNA polymerase II in a time-series manner throughout conditions activating lipid biosynthesis. To our surprise, the combinatory profiles of histone codes uncovered new regulatory mechanism in gene expression in algae. Coupled with matched RNA-seq data, chromatin changes revealed potential novel regulators and candidate genes involved in the activation of lipid accumulations. Genetic perturbation on these candidate regulators further demonstrated the potential to manipulate the regulatory cascade for lipid synthesis efficiency. Exploring epigenetic landscape in microalgae shown here provides powerful tools needed in improving biofuel production and new technology platform for renewable energy generation, global carbon management, and environmental survey.

  16. Chromatin remodeling regulates catalase expression during cancer cells adaptation to chronic oxidative stress.

    Science.gov (United States)

    Glorieux, Christophe; Sandoval, Juan Marcelo; Fattaccioli, Antoine; Dejeans, Nicolas; Garbe, James C; Dieu, Marc; Verrax, Julien; Renard, Patricia; Huang, Peng; Calderon, Pedro Buc

    2016-10-01

    Regulation of ROS metabolism plays a major role in cellular adaptation to oxidative stress in cancer cells, but the molecular mechanism that regulates catalase, a key antioxidant enzyme responsible for conversion of hydrogen peroxide to water and oxygen, remains to be elucidated. Therefore, we investigated the transcriptional regulatory mechanism controlling catalase expression in three human mammary cell lines: the normal mammary epithelial 250MK primary cells, the breast adenocarcinoma MCF-7 cells and an experimental model of MCF-7 cells resistant against oxidative stress resulting from chronic exposure to H 2 O 2 (Resox), in which catalase was overexpressed. Here we identify a novel promoter region responsible for the regulation of catalase expression at -1518/-1226 locus and the key molecules that interact with this promoter and affect catalase transcription. We show that the AP-1 family member JunB and retinoic acid receptor alpha (RARα) mediate catalase transcriptional activation and repression, respectively, by controlling chromatin remodeling through a histone deacetylases-dependent mechanism. This regulatory mechanism plays an important role in redox adaptation to chronic exposure to H 2 O 2 in breast cancer cells. Our study suggests that cancer adaptation to oxidative stress may be regulated by transcriptional factors through chromatin remodeling, and reveals a potential new mechanism to target cancer cells. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. A Higher-Order Colon Translation

    DEFF Research Database (Denmark)

    Danvy, Olivier; Nielsen, Lasse Reichstein

    2001-01-01

    A lambda-encoding such as the CPS transformation gives rise to administrative redexes. In his seminal article ``Call-by-name, call-by-value and the lambda-calculus'', 25 years ago, Plotkin tackled administrative reductions using a so-called ``colon translation.'' 10 years ago, Danvy and Filinski...... integrated administrative reductions in the CPS transformation, making it operate in one pass. The technique applies to other lambda-encodings (e.g., variants of CPS), but we do not see it used in practice--instead, Plotkin's colon translation appears to be favored. Therefore, in an attempt to link both...... techniques, we recast Plotkin's proof of Indifference and Simulation to the higher-order specification of the one-pass CPS transformation. To this end, we extend his colon translation from first order to higher order...

  18. XY model with higher-order exchange.

    Science.gov (United States)

    Žukovič, Milan; Kalagov, Georgii

    2017-08-01

    An XY model, generalized by inclusion of up to an infinite number of higher-order pairwise interactions with an exponentially decreasing strength, is studied by spin-wave theory and Monte Carlo simulations. At low temperatures the model displays a quasi-long-range-order phase characterized by an algebraically decaying correlation function with the exponent η=T/[2πJ(p,α)], nonlinearly dependent on the parameters p and α that control the number of the higher-order terms and the decay rate of their intensity, respectively. At higher temperatures the system shows a crossover from the continuous Berezinskii-Kosterlitz-Thouless to the first-order transition for the parameter values corresponding to a highly nonlinear shape of the potential well. The role of topological excitations (vortices) in changing the nature of the transition is discussed.

  19. Higher-Order and Symbolic Computation

    DEFF Research Database (Denmark)

    Danvy, Olivier; Mason, Ian

    2008-01-01

    a series of implementaions that properly account for multiple invocations of the derivative-taking opeatro. In "Adapting Functional Programs to Higher-Order Logic," Scott Owens and Konrad Slind present a variety of examples of terminiation proofs of functional programs written in HOL proof systems. Since......-calculus programs, historically. The anaylsis determines the possible locations of ambients and mirrors the temporla sequencing of actions in the structure of types....

  20. Lagrangian procedures for higher order field equations

    International Nuclear Information System (INIS)

    Bollini, C.G.

    1987-01-01

    A Lagrangian procedure for a pedagogical way is presented for the treatment of higher order field equations. The energy-momentum tensor and the conserved density current are built. In particular the case in which the derivatives appear only in the invariant D'Alembertian operator is discussed. Some examples are discussed. The fields are quantized and the corresponding Hamilonian which is shown not to be positive defructed. Rules are given to write the causal propagators. (author) [pt

  1. Lagrangian procedures for higher order field equations

    International Nuclear Information System (INIS)

    Bollini, C.G.; Giambiagi, J.J.

    1986-01-01

    We present in a pedagogical way a Lagrangian procedure for the treatment of higher order field equations. We build the energy-momentum tensor and the conserved density current. In particular we discuss the case in which the derivatives appear only in the invariant D'Alembertian operator. We discuss some examples. We quantize the fields and construct the corresponding Hamiltonian which is shown not to be positive definite. We give the rules for the causal propagators. (Author) [pt

  2. Higher order correlations in computed particle distributions

    International Nuclear Information System (INIS)

    Hanerfeld, H.; Herrmannsfeldt, W.; Miller, R.H.

    1989-03-01

    The rms emittances calculated for beam distributions using computer simulations are frequently dominated by higher order aberrations. Thus there are substantial open areas in the phase space plots. It has long been observed that the rms emittance is not an invariant to beam manipulations. The usual emittance calculation removes the correlation between transverse displacement and transverse momentum. In this paper, we explore the possibility of defining higher order correlations that can be removed from the distribution to result in a lower limit to the realizable emittance. The intent is that by inserting the correct combinations of linear lenses at the proper position, the beam may recombine in a way that cancels the effects of some higher order forces. An example might be the non-linear transverse space charge forces which cause a beam to spread. If the beam is then refocused so that the same non-linear forces reverse the inward velocities, the resulting phase space distribution may reasonably approximate the original distribution. The approach to finding the location and strength of the proper lens to optimize the transported beam is based on work by Bruce Carlsten of Los Alamos National Laboratory. 11 refs., 4 figs

  3. Chromatin-associated regulation of sorbitol synthesis in flower buds of peach.

    Science.gov (United States)

    Lloret, Alba; Martínez-Fuentes, Amparo; Agustí, Manuel; Badenes, María Luisa; Ríos, Gabino

    2017-11-01

    PpeS6PDH gene is postulated to mediate sorbitol synthesis in flower buds of peach concomitantly with specific chromatin modifications. Perennial plants have evolved an adaptive mechanism involving protection of meristems within specialized structures named buds in order to survive low temperatures and water deprivation during winter. A seasonal period of dormancy further improves tolerance of buds to environmental stresses through specific mechanisms poorly known at the molecular level. We have shown that peach PpeS6PDH gene is down-regulated in flower buds after dormancy release, concomitantly with changes in the methylation level at specific lysine residues of histone H3 (H3K27 and H3K4) in the chromatin around the translation start site of the gene. PpeS6PDH encodes a NADPH-dependent sorbitol-6-phosphate dehydrogenase, the key enzyme for biosynthesis of sorbitol. Consistently, sorbitol accumulates in dormant buds showing higher PpeS6PDH expression. Moreover, PpeS6PDH gene expression is affected by cold and water deficit stress. Particularly, its expression is up-regulated by low temperature in buds and leaves, whereas desiccation treatment induces PpeS6PDH in buds and represses the gene in leaves. These data reveal the concurrent participation of chromatin modification mechanisms, transcriptional regulation of PpeS6PDH and sorbitol accumulation in flower buds of peach. In addition to its role as a major translocatable photosynthate in Rosaceae species, sorbitol is a widespread compatible solute and cryoprotectant, which suggests its participation in tolerance to environmental stresses in flower buds of peach.

  4. Higher order modes of coupled optical fibres

    International Nuclear Information System (INIS)

    Alexeyev, C N; Yavorsky, M A; Boklag, N A

    2010-01-01

    The structure of hybrid higher order modes of two coupled weakly guiding identical optical fibres is studied. On the basis of perturbation theory with degeneracy for the vector wave equation expressions for modes with azimuthal angular number l ≥ 1 are obtained that allow for the spin–orbit interaction. The spectra of polarization corrections to the scalar propagation constants are calculated in a wide range of distances between the fibres. The limiting cases of widely and closely spaced fibres are studied. The obtained results can be used for studying the tunnelling of optical vortices in directional couplers and in matters concerned with information security

  5. Ward identities of higher order Virasoro algebra

    International Nuclear Information System (INIS)

    Zha Chaozeng; Dolate, S.

    1994-11-01

    The general formulations of primary fields versus quasi-primary ones in the context of high order Virasoro algebra (HOVA) and the corresponding Ward identity are explored. The primary fields of conformal spins up to 8 are given in terms of quasi-primary fields, and the general features of the higher order expressions are also discussed. It is observed that the local fields, either primary of quasi-primary, carry the same numbers of central charges, and not all the primary fields contribute to the anomalies in the Ward identities. (author). 6 refs

  6. Theorem Proving In Higher Order Logics

    Science.gov (United States)

    Carreno, Victor A. (Editor); Munoz, Cesar A.; Tahar, Sofiene

    2002-01-01

    The TPHOLs International Conference serves as a venue for the presentation of work in theorem proving in higher-order logics and related areas in deduction, formal specification, software and hardware verification, and other applications. Fourteen papers were submitted to Track B (Work in Progress), which are included in this volume. Authors of Track B papers gave short introductory talks that were followed by an open poster session. The FCM 2002 Workshop aimed to bring together researchers working on the formalisation of continuous mathematics in theorem proving systems with those needing such libraries for their applications. Many of the major higher order theorem proving systems now have a formalisation of the real numbers and various levels of real analysis support. This work is of interest in a number of application areas, such as formal methods development for hardware and software application and computer supported mathematics. The FCM 2002 consisted of three papers, presented by their authors at the workshop venue, and one invited talk.

  7. Higher order cumulants in colorless partonic plasma

    Energy Technology Data Exchange (ETDEWEB)

    Cherif, S. [Sciences and Technologies Department, University of Ghardaia, Ghardaia, Algiers (Algeria); Laboratoire de Physique et de Mathématiques Appliquées (LPMA), ENS-Kouba (Bachir El-Ibrahimi), Algiers (Algeria); Ahmed, M. A. A. [Department of Physics, College of Science, Taibah University Al-Madinah Al-Mounawwarah KSA (Saudi Arabia); Department of Physics, Taiz University in Turba, Taiz (Yemen); Laboratoire de Physique et de Mathématiques Appliquées (LPMA), ENS-Kouba (Bachir El-Ibrahimi), Algiers (Algeria); Ladrem, M., E-mail: mladrem@yahoo.fr [Department of Physics, College of Science, Taibah University Al-Madinah Al-Mounawwarah KSA (Saudi Arabia); Laboratoire de Physique et de Mathématiques Appliquées (LPMA), ENS-Kouba (Bachir El-Ibrahimi), Algiers (Algeria)

    2016-06-10

    Any physical system considered to study the QCD deconfinement phase transition certainly has a finite volume, so the finite size effects are inevitably present. This renders the location of the phase transition and the determination of its order as an extremely difficult task, even in the simplest known cases. In order to identify and locate the colorless QCD deconfinement transition point in finite volume T{sub 0}(V), a new approach based on the finite-size cumulant expansion of the order parameter and the ℒ{sub m,n}-Method is used. We have shown that both cumulants of higher order and their ratios, associated to the thermodynamical fluctuations of the order parameter, in QCD deconfinement phase transition behave in a particular enough way revealing pronounced oscillations in the transition region. The sign structure and the oscillatory behavior of these in the vicinity of the deconfinement phase transition point might be a sensitive probe and may allow one to elucidate their relation to the QCD phase transition point. In the context of our model, we have shown that the finite volume transition point is always associated to the appearance of a particular point in whole higher order cumulants under consideration.

  8. Finding Higher Order Differentials of MISTY1

    Science.gov (United States)

    Tsunoo, Yukiyasu; Saito, Teruo; Kawabata, Takeshi; Nakagawa, Hirokatsu

    MISTY1 is a 64-bit block cipher that has provable security against differential and linear cryptanalysis. MISTY1 is one of the algorithms selected in the European NESSIE project, and it is recommended for Japanese e-Government ciphers by the CRYPTREC project. In this paper, we report on 12th order differentials in 3-round MISTY1 with FL functions and 44th order differentials in 4-round MISTY1 with FL functions both previously unknown. We also report that both data complexity and computational complexity of higher order differential attacks on 6-round MISTY1 with FL functions and 7-round MISTY1 with FL functions using the 46th order differential can be reduced to as much as 1/22 of the previous values by using multiple 44th order differentials simultaneously.

  9. Three weights higher order Hardy type inequalities

    Directory of Open Access Journals (Sweden)

    Aigerim A. Kalybay

    2006-01-01

    Full Text Available We investigate the following three weights higher order Hardy type inequality (0.1 ‖g‖q,u≤  C‖Dρkg‖p,v where Dρi denotes the following weighted differential operator: {dig(tdti,i=0,1,...,m−1,di−mdti−m(p(tdmg(tdtm,i=m,m+1,...,k, for a weight function ρ(⋅. A complete description of the weights u, v and ρ so that (0.1 holds was given in [4] for the case 1

  10. Epigenetic Regulation of Centromere Chromatin Stability by Dietary and Environmental Factors.

    Science.gov (United States)

    Hernández-Saavedra, Diego; Strakovsky, Rita S; Ostrosky-Wegman, Patricia; Pan, Yuan-Xiang

    2017-11-01

    The centromere is a genomic locus required for the segregation of the chromosomes during cell division. This chromosomal region together with pericentromeres has been found to be susceptible to damage, and thus the perturbation of the centromere could lead to the development of aneuploidic events. Metabolic abnormalities that underlie the generation of cancer include inflammation, oxidative stress, cell cycle deregulation, and numerous others. The micronucleus assay, an early clinical marker of cancer, has been shown to provide a reliable measure of genotoxic damage that may signal cancer initiation. In the current review, we will discuss the events that lead to micronucleus formation and centromeric and pericentromeric chromatin instability, as well transcripts emanating from these regions, which were previously thought to be inactive. Studies were selected in PubMed if they reported the effects of nutritional status (macro- and micronutrients) or environmental toxicant exposure on micronucleus frequency or any other chromosomal abnormality in humans, animals, or cell models. Mounting evidence from epidemiologic, environmental, and nutritional studies provides a novel perspective on the origination of aneuploidic events. Although substantial evidence exists describing the role that nutritional status and environmental toxicants have on the generation of micronuclei and other nuclear aberrations, limited information is available to describe the importance of macro- and micronutrients on centromeric and pericentromeric chromatin stability. Moving forward, studies that specifically address the direct link between nutritional status, excess, or deficiency and the epigenetic regulation of the centromere will provide much needed insight into the nutritional and environmental regulation of this chromosomal region and the initiation of aneuploidy. © 2017 American Society for Nutrition.

  11. JMJD1C demethylates MDC1 to regulate the RNF8 and BRCA1-mediated chromatin response to DNA breaks

    DEFF Research Database (Denmark)

    Watanabe, Sugiko; Watanabe, Kenji; Akimov, Vyacheslav

    2013-01-01

    Chromatin ubiquitylation flanking DNA double-strand breaks (DSBs), mediated by RNF8 and RNF168 ubiquitin ligases, orchestrates a two-branch pathway, recruiting repair factors 53BP1 or the RAP80-BRCA1 complex. We report that human demethylase JMJD1C regulates the RAP80-BRCA1 branch of this DNA...

  12. Local chromatin structure of heterochromatin regulates repeated DNA stability, nucleolus structure, and genome integrity

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Jamy C. [Univ. of California, Berkeley, CA (United States)

    2007-01-01

    Heterochromatin constitutes a significant portion of the genome in higher eukaryotes; approximately 30% in Drosophila and human. Heterochromatin contains a high repeat DNA content and a low density of protein-encoding genes. In contrast, euchromatin is composed mostly of unique sequences and contains the majority of single-copy genes. Genetic and cytological studies demonstrated that heterochromatin exhibits regulatory roles in chromosome organization, centromere function and telomere protection. As an epigenetically regulated structure, heterochromatin formation is not defined by any DNA sequence consensus. Heterochromatin is characterized by its association with nucleosomes containing methylated-lysine 9 of histone H3 (H3K9me), heterochromatin protein 1 (HP1) that binds H3K9me, and Su(var)3-9, which methylates H3K9 and binds HP1. Heterochromatin formation and functions are influenced by HP1, Su(var)3-9, and the RNA interference (RNAi) pathway. My thesis project investigates how heterochromatin formation and function impact nuclear architecture, repeated DNA organization, and genome stability in Drosophila melanogaster. H3K9me-based chromatin reduces extrachromosomal DNA formation; most likely by restricting the access of repair machineries to repeated DNAs. Reducing extrachromosomal ribosomal DNA stabilizes rDNA repeats and the nucleolus structure. H3K9me-based chromatin also inhibits DNA damage in heterochromatin. Cells with compromised heterochromatin structure, due to Su(var)3-9 or dcr-2 (a component of the RNAi pathway) mutations, display severe DNA damage in heterochromatin compared to wild type. In these mutant cells, accumulated DNA damage leads to chromosomal defects such as translocations, defective DNA repair response, and activation of the G2-M DNA repair and mitotic checkpoints that ensure cellular and animal viability. My thesis research suggests that DNA replication, repair, and recombination mechanisms in heterochromatin differ from those in

  13. Chd1 remodelers maintain open chromatin and regulate the epigenetics of differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Persson, Jenna [Department of Biosciences and Nutrition, Center for Biosciences, Karolinska Institutet (Sweden); Ekwall, Karl, E-mail: karl.ekwall@ki.se [Department of Biosciences and Nutrition, Center for Biosciences, Karolinska Institutet (Sweden); School of Life Sciences, University College Sodertorn, NOVUM, Huddinge (Sweden)

    2010-05-01

    Eukaryotic DNA is packaged around octamers of histone proteins into nucleosomes, the basic unit of chromatin. In addition to enabling meters of DNA to fit within the confines of a nucleus, the structure of chromatin has functional implications for cell identity. Covalent chemical modifications to the DNA and to histones, histone variants, ATP-dependent chromatin remodelers, small noncoding RNAs and the level of chromatin compaction all contribute to chromosomal structure and to the activity or silencing of genes. These chromatin-level alterations are defined as epigenetic when they are heritable from mother to daughter cell. The great diversity of epigenomes that can arise from a single genome permits a single, totipotent cell to generate the hundreds of distinct cell types found in humans. Two recent studies in mouse and in fly have highlighted the importance of Chd1 chromatin remodelers for maintaining an open, active chromatin state. Based on evidence from fission yeast as a model system, we speculate that Chd1 remodelers are involved in the disassembly of nucleosomes at promoter regions, thus promoting active transcription and open chromatin. It is likely that these nucleosomes are specifically marked for disassembly by the histone variant H2A.Z.

  14. Chd1 remodelers maintain open chromatin and regulate the epigenetics of differentiation

    International Nuclear Information System (INIS)

    Persson, Jenna; Ekwall, Karl

    2010-01-01

    Eukaryotic DNA is packaged around octamers of histone proteins into nucleosomes, the basic unit of chromatin. In addition to enabling meters of DNA to fit within the confines of a nucleus, the structure of chromatin has functional implications for cell identity. Covalent chemical modifications to the DNA and to histones, histone variants, ATP-dependent chromatin remodelers, small noncoding RNAs and the level of chromatin compaction all contribute to chromosomal structure and to the activity or silencing of genes. These chromatin-level alterations are defined as epigenetic when they are heritable from mother to daughter cell. The great diversity of epigenomes that can arise from a single genome permits a single, totipotent cell to generate the hundreds of distinct cell types found in humans. Two recent studies in mouse and in fly have highlighted the importance of Chd1 chromatin remodelers for maintaining an open, active chromatin state. Based on evidence from fission yeast as a model system, we speculate that Chd1 remodelers are involved in the disassembly of nucleosomes at promoter regions, thus promoting active transcription and open chromatin. It is likely that these nucleosomes are specifically marked for disassembly by the histone variant H2A.Z.

  15. Chromatin replication and epigenome maintenance

    DEFF Research Database (Denmark)

    Alabert, Constance; Groth, Anja

    2012-01-01

    Stability and function of eukaryotic genomes are closely linked to chromatin structure and organization. During cell division the entire genome must be accurately replicated and the chromatin landscape reproduced on new DNA. Chromatin and nuclear structure influence where and when DNA replication...... initiates, whereas the replication process itself disrupts chromatin and challenges established patterns of genome regulation. Specialized replication-coupled mechanisms assemble new DNA into chromatin, but epigenome maintenance is a continuous process taking place throughout the cell cycle. If DNA...

  16. Multivalent Chromatin Engagement and Inter-domain Crosstalk Regulate MORC3 ATPase

    Directory of Open Access Journals (Sweden)

    Forest H. Andrews

    2016-09-01

    Full Text Available MORC3 is linked to inflammatory myopathies and cancer; however, the precise role of MORC3 in normal cell physiology and disease remains poorly understood. Here, we present detailed genetic, biochemical, and structural analyses of MORC3. We demonstrate that MORC3 is significantly upregulated in Down syndrome and that genetic abnormalities in MORC3 are associated with cancer. The CW domain of MORC3 binds to the methylated histone H3K4 tail, and this interaction is essential for recruitment of MORC3 to chromatin and accumulation in nuclear bodies. We show that MORC3 possesses intrinsic ATPase activity that requires DNA, but it is negatively regulated by the CW domain, which interacts with the ATPase domain. Natively linked CW impedes binding of the ATPase domain to DNA, resulting in a decrease in the DNA-stimulated enzymatic activity. Collectively, our studies provide a molecular framework detailing MORC3 functions and suggest that its modulation may contribute to human disease.

  17. Transcriptional regulation by histone modifications: towards a theory of chromatin re-organization during stem cell differentiation

    International Nuclear Information System (INIS)

    Binder, Hans; Steiner, Lydia; Przybilla, Jens; Rohlf, Thimo; Prohaska, Sonja; Galle, Jörg

    2013-01-01

    Chromatin-related mechanisms, as e.g. histone modifications, are known to be involved in regulatory switches within the transcriptome. Only recently, mathematical models of these mechanisms have been established. So far they have not been applied to genome-wide data. We here introduce a mathematical model of transcriptional regulation by histone modifications and apply it to data of trimethylation of histone 3 at lysine 4 (H3K4me3) and 27 (H3K27me3) in mouse pluripotent and lineage-committed cells. The model describes binding of protein complexes to chromatin which are capable of reading and writing histone marks. Molecular interactions of the complexes with DNA and modified histones create a regulatory switch of transcriptional activity. The regulatory states of the switch depend on the activity of histone (de-) methylases, the strength of complex-DNA-binding and the number of nucleosomes capable of cooperatively contributing to complex-binding. Our model explains experimentally measured length distributions of modified chromatin regions. It suggests (i) that high CpG-density facilitates recruitment of the modifying complexes in embryonic stem cells and (ii) that re-organization of extended chromatin regions during lineage specification into neuronal progenitor cells requires targeted de-modification. Our approach represents a basic step towards multi-scale models of transcriptional control during development and lineage specification. (paper)

  18. Concerted action of the PHD, chromo and motor domains regulates the human chromatin remodelling ATPase CHD4.

    Science.gov (United States)

    Morra, Rosa; Lee, Benjamin M; Shaw, Heather; Tuma, Roman; Mancini, Erika J

    2012-07-30

    CHD4, the core subunit of the Nucleosome Remodelling and Deacetylase (NuRD) complex, is a chromatin remodelling ATPase that, in addition to a helicase domain, harbors tandem plant homeo finger and chromo domains. By using a panel of domain constructs we dissect their roles and demonstrate that DNA binding, histone binding and ATPase activities are allosterically regulated. Molecular shape reconstruction from small-angle X-ray scattering reveals extensive domain-domain interactions, which provide a structural explanation for the regulation of CHD4 activities by intramolecular domain communication. Our results demonstrate functional interdependency between domains within a chromatin remodeller. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  19. Concerted action of the PHD, chromo and motor domains regulates the human chromatin remodelling ATPase CHD4

    OpenAIRE

    Morra, Rosa; Lee, Benjamin M; Shaw, Heather; Tuma, Roman; Mancini, Erika J

    2012-01-01

    CHD4, the core subunit of the Nucleosome Remodelling and Deacetylase (NuRD) complex, is a chromatin remodelling ATPase that, in addition to a helicase domain, harbors tandem plant homeo finger and chromo domains. By using a panel of domain constructs we dissect their roles and demonstrate that DNA binding, histone binding and ATPase activities are allosterically regulated. Molecular shape reconstruction from small-angle X-ray scattering reveals extensive domain-domain interactions, which prov...

  20. A fast, open source implementation of adaptive biasing potentials uncovers a ligand design strategy for the chromatin regulator BRD4

    OpenAIRE

    Dickson, Bradley M.; de Waal, Parker W; Ramjan, Zachary H; Xu, H Eric; Rothbart, Scott B.

    2016-01-01

    In this communication we introduce an efficient implementation of adaptive biasing that greatly improves the speed of free energy computation in molecular dynamics simulations. We investigated the use of accelerated simulations to inform on compound design using a recently reported and clinically relevant inhibitor of the chromatin regulator BRD4 (bromodomain-containing protein 4). Benchmarking on our local compute cluster, our implementation achieves up to 2.5 times more force calls per day ...

  1. RISC-mediated control of selected chromatin regulators stabilizes ground state pluripotency of mouse embryonic stem cells.

    Science.gov (United States)

    Pandolfini, Luca; Luzi, Ettore; Bressan, Dario; Ucciferri, Nadia; Bertacchi, Michele; Brandi, Rossella; Rocchiccioli, Silvia; D'Onofrio, Mara; Cremisi, Federico

    2016-05-06

    Embryonic stem cells are intrinsically unstable and differentiate spontaneously if they are not shielded from external stimuli. Although the nature of such instability is still controversial, growing evidence suggests that protein translation control may play a crucial role. We performed an integrated analysis of RNA and proteins at the transition between naïve embryonic stem cells and cells primed to differentiate. During this transition, mRNAs coding for chromatin regulators are specifically released from translational inhibition mediated by RNA-induced silencing complex (RISC). This suggests that, prior to differentiation, the propensity of embryonic stem cells to change their epigenetic status is hampered by RNA interference. The expression of these chromatin regulators is reinstated following acute inactivation of RISC and it correlates with loss of stemness markers and activation of early cell differentiation markers in treated embryonic stem cells. We propose that RISC-mediated inhibition of specific sets of chromatin regulators is a primary mechanism for preserving embryonic stem cell pluripotency while inhibiting the onset of embryonic developmental programs.

  2. Chromatin organization regulated by EZH2-mediated H3K27me3 is required for OPN-induced migration of bone marrow-derived mesenchymal stem cells.

    Science.gov (United States)

    Liu, Lingling; Luo, Qing; Sun, Jinghui; Ju, Yang; Morita, Yasuyuki; Song, Guanbin

    2018-03-01

    Osteopontin (OPN) is a chemokine-like extracellular matrix-associated protein involved in the migration of bone marrow-derived mesenchymal stem cells (BMSCs). An increasing number of studies have found that chromatin organization may affect cellular migration. However, whether OPN regulates chromatin organization is not understood, nor are the underlying molecular mechanisms. In this study, we investigated the link between chromatin organization and BMSC migration and demonstrated that OPN-mediated BMSC migration leads to elevated levels of heterochromatin marker histone H3 lysine 27 trimethylation (H3K27me3) through the methyltransferase EZH2. The expression of EZH2 reorganizes the chromatin structure of BMSCs. Pharmacological inhibition or depletion of EZH2 blocks BMSC migration. Moreover, using an atomic force microscope (AFM), we found that chromatin decondensation alters the mechanical properties of the nucleus. In addition, inhibition of extracellular signal-regulated kinase 1/2 (ERK1/2) signals represses OPN-promoted chromatin condensation and cell migration. Thus, our results identify a mechanism by which ERK1/2 signalling drives specific chromatin modifications in BMSCs, which alters chromatin organization and thereby enables OPN-mediated BMSC migration. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Identification of potential target genes for the tomato fruit-ripening regulator RIN by chromatin immunoprecipitation

    Directory of Open Access Journals (Sweden)

    Nakano Toshitsugu

    2011-01-01

    Full Text Available Abstract Background During ripening, climacteric fruits increase their ethylene level and subsequently undergo various physiological changes, such as softening, pigmentation and development of aroma and flavor. These changes occur simultaneously and are caused by the highly synchronized expression of numerous genes at the onset of ripening. In tomatoes, the MADS-box transcription factor RIN has been regarded as a key regulator responsible for the onset of ripening by acting upstream of both ethylene- and non-ethylene-mediated controls. However, except for LeACS2, direct targets of RIN have not been clarified, and little is known about the transcriptional cascade for ripening. Results Using immunoprecipitated (IPed DNA fragments recovered by chromatin immunoprecipitation (ChIP with anti-RIN antibody from ripening tomato fruit, we analyzed potential binding sites for RIN (CArG-box sites in the promoters of representative ripening-induced genes by quantitative PCR. Results revealed nearly a 5- to 20-fold enrichment of CArG boxes in the promoters of LeACS2, LeACS4, PG, TBG4, LeEXP1, and LeMAN4 and of RIN itself, indicating direct interaction of RIN with their promoters in vivo. Moreover, sequence analysis and genome mapping of 51 cloned IPed DNAs revealed potential RIN binding sites. Quantitative PCR revealed that four of the potential binding sites were enriched 4- to 17-fold in the IPed DNA pools compared with the controls, indicating direct interaction of RIN with these sites in vivo. Near one of the four CArG boxes we found a gene encoding a protein similar to thioredoxin y1. An increase in the transcript level of this gene was observed with ripening in normal fruit but not in the rin mutant, suggesting that RIN possibly induces its expression. Conclusions The presented results suggest that RIN controls fruit softening and ethylene production by the direct transcriptional regulation of cell-wall-modifying genes and ethylene biosynthesis genes

  4. Identification of potential target genes for the tomato fruit-ripening regulator RIN by chromatin immunoprecipitation.

    Science.gov (United States)

    Fujisawa, Masaki; Nakano, Toshitsugu; Ito, Yasuhiro

    2011-01-30

    During ripening, climacteric fruits increase their ethylene level and subsequently undergo various physiological changes, such as softening, pigmentation and development of aroma and flavor. These changes occur simultaneously and are caused by the highly synchronized expression of numerous genes at the onset of ripening. In tomatoes, the MADS-box transcription factor RIN has been regarded as a key regulator responsible for the onset of ripening by acting upstream of both ethylene- and non-ethylene-mediated controls. However, except for LeACS2, direct targets of RIN have not been clarified, and little is known about the transcriptional cascade for ripening. Using immunoprecipitated (IPed) DNA fragments recovered by chromatin immunoprecipitation (ChIP) with anti-RIN antibody from ripening tomato fruit, we analyzed potential binding sites for RIN (CArG-box sites) in the promoters of representative ripening-induced genes by quantitative PCR. Results revealed nearly a 5- to 20-fold enrichment of CArG boxes in the promoters of LeACS2, LeACS4, PG, TBG4, LeEXP1, and LeMAN4 and of RIN itself, indicating direct interaction of RIN with their promoters in vivo. Moreover, sequence analysis and genome mapping of 51 cloned IPed DNAs revealed potential RIN binding sites. Quantitative PCR revealed that four of the potential binding sites were enriched 4- to 17-fold in the IPed DNA pools compared with the controls, indicating direct interaction of RIN with these sites in vivo. Near one of the four CArG boxes we found a gene encoding a protein similar to thioredoxin y1. An increase in the transcript level of this gene was observed with ripening in normal fruit but not in the rin mutant, suggesting that RIN possibly induces its expression. The presented results suggest that RIN controls fruit softening and ethylene production by the direct transcriptional regulation of cell-wall-modifying genes and ethylene biosynthesis genes during ripening. Moreover, the binding of RIN to its own

  5. The global relationship between chromatin physical topology, fractal structure, and gene expression

    DEFF Research Database (Denmark)

    Almassalha, Luay M; Tiwari, A; Ruhoff, P T

    2017-01-01

    in an empty space, but in a highly complex, interrelated, and dense nanoenvironment that profoundly influences chemical interactions. We explored the relationship between the physical nanoenvironment of chromatin and gene transcription in vitro. We analytically show that changes in the fractal dimension, D...... show that the increased heterogeneity of physical structure of chromatin due to increase in fractal dimension correlates with increased heterogeneity of gene networks. These findings indicate that the higher order folding of chromatin topology may act as a molecular-pathway independent code regulating...

  6. Conceptualizing and Assessing Higher-Order Thinking in Reading

    Science.gov (United States)

    Afflerbach, Peter; Cho, Byeong-Young; Kim, Jong-Yun

    2015-01-01

    Students engage in higher-order thinking as they read complex texts and perform complex reading-related tasks. However, the most consequential assessments, high-stakes tests, are currently limited in providing information about students' higher-order thinking. In this article, we describe higher-order thinking in relation to reading. We provide a…

  7. Higher-Order Chromatin Organisation in Cell Nuclei: Structure and Function

    Czech Academy of Sciences Publication Activity Database

    Kozubek, Stanislav; Lukášová, Emilie; Bártová, Eva; Kozubek, Michal; Skalníková, M.; Jirsová, Pavla; Koutná, I.

    2000-01-01

    Roč. 17, - (2000), s. 1145 ISSN 0739-1102. [Mendel - Brno 2000. DNA Structure and Interactions. Their Biological Roles and Implications in Biomedicine and Biotechnologies. 19.07.2000-23.07.2000, Brno] Institutional research plan: CEZ:A17/98:Z5-004-9-ii Subject RIV: BO - Biophysics

  8. Heterogeneous chromatin target model

    International Nuclear Information System (INIS)

    Watanabe, Makoto

    1996-01-01

    The higher order structure of the entangled chromatin fibers in a chromosome plays a key role in molecular control mechanism involved in chromosome mutation due to ionizing radiations or chemical mutagens. The condensed superstructure of chromatin is not so rigid and regular as has been postulated in general. We have proposed a rheological explanation for the flexible network system ('chromatin network') that consists of the fluctuating assembly of nucleosome clusters linked with supertwisting DNA in a chromatin fiber ('Supertwisting Particulate Model'). We have proposed a 'Heterosensitive Target Model' for cellular radiosensitivity that is a modification of 'Heterogeneous Target Model'. The heterogeneity of chromatin target is derived from the highly condensed organization of chromatin segments consist of unstable and fragile sites in the fluctuating assembly of nucleosome clusters, namely 'supranucleosomal particles' or 'superbeads'. The models have been principally supported by our electron microscopic experiments employing 'surface - spreading whole - mount technique' since 1967. However, some deformation and artifacts in the chromatin structure are inevitable with these electron microscopic procedures. On the contrary, the 'atomic force microscope (AFM)' can be operated in liquid as well as in the air. A living specimen can be examined without any preparative procedures. Micromanipulation of the isolated chromosome is also possible by the precise positional control of a cantilever on the nanometer scale. The living human chromosomes were submerged in a solution of culture medium and observed by AFM using a liquid immersion cell. The surface - spreading whole - mount technique was applicable for this observation. The particulate chromatin segments of nucleosome clusters were clearly observed within mitotic human chromosomes in a living hydrated condition. These findings support the heterogeneity of chromatin target in a living cell. (J.P.N.)

  9. TOPBP1 regulates RAD51 phosphorylation and chromatin loading and determines PARP inhibitor sensitivity

    DEFF Research Database (Denmark)

    Moudry, Pavel; Watanabe, Kenji; Wolanin, Kamila M.

    2016-01-01

    to chromatin and formation of RAD51 foci, but without affecting the upstream HR steps of DNA end resection and RPA loading. Furthermore, TOPBP1 BRCT domains 7/8 are essential for RAD51 foci formation. Mechanistically, TOPBP1 physically binds PLK1 and promotes PLK1 kinase-mediated phosphorylation of RAD51...

  10. Histone Variant Regulates DNA Repair via Chromatin Condensation | Center for Cancer Research

    Science.gov (United States)

    Activating the appropriate DNA repair pathway is essential for maintaining the stability of the genome after a break in both strands of DNA. How a pathway is selected, however, is not well understood. Since these double strand breaks (DSBs) occur while DNA is packaged as chromatin, changes in its organization are necessary for repair to take place. Numerous alterations have

  11. Reprogramming chromatin

    DEFF Research Database (Denmark)

    Ehrensberger, Andreas Hasso; Svejstrup, Jesper Qualmann

    2012-01-01

    attributed to high kinetic barriers that affect all cells equally and can only be overcome by rare stochastic events. The barriers to reprogramming are likely to involve transformations of chromatin state because (i) inhibitors of chromatin-modifying enzymes can enhance the efficiency of reprogramming...... and (ii) knockdown or knock-out of chromatin-modifying enzymes can lower the efficiency of reprogramming. Here, we review the relationship between chromatin state transformations (chromatin reprogramming) and cellular reprogramming, with an emphasis on transcription factors, chromatin remodeling factors...

  12. Genome-wide identification of physically clustered genes suggests chromatin-level co-regulation in male reproductive development in Arabidopsis thaliana.

    Science.gov (United States)

    Reimegård, Johan; Kundu, Snehangshu; Pendle, Ali; Irish, Vivian F; Shaw, Peter; Nakayama, Naomi; Sundström, Jens F; Emanuelsson, Olof

    2017-04-07

    Co-expression of physically linked genes occurs surprisingly frequently in eukaryotes. Such chromosomal clustering may confer a selective advantage as it enables coordinated gene regulation at the chromatin level. We studied the chromosomal organization of genes involved in male reproductive development in Arabidopsis thaliana. We developed an in-silico tool to identify physical clusters of co-regulated genes from gene expression data. We identified 17 clusters (96 genes) involved in stamen development and acting downstream of the transcriptional activator MS1 (MALE STERILITY 1), which contains a PHD domain associated with chromatin re-organization. The clusters exhibited little gene homology or promoter element similarity, and largely overlapped with reported repressive histone marks. Experiments on a subset of the clusters suggested a link between expression activation and chromatin conformation: qRT-PCR and mRNA in situ hybridization showed that the clustered genes were up-regulated within 48 h after MS1 induction; out of 14 chromatin-remodeling mutants studied, expression of clustered genes was consistently down-regulated only in hta9/hta11, previously associated with metabolic cluster activation; DNA fluorescence in situ hybridization confirmed that transcriptional activation of the clustered genes was correlated with open chromatin conformation. Stamen development thus appears to involve transcriptional activation of physically clustered genes through chromatin de-condensation. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  13. Higher-Order Generalized Invexity in Control Problems

    Directory of Open Access Journals (Sweden)

    S. K. Padhan

    2011-01-01

    Full Text Available We introduce a higher-order duality (Mangasarian type and Mond-Weir type for the control problem. Under the higher-order generalized invexity assumptions on the functions that compose the primal problems, higher-order duality results (weak duality, strong duality, and converse duality are derived for these pair of problems. Also, we establish few examples in support of our investigation.

  14. Skinner-Rusk unified formalism for higher-order systems

    Science.gov (United States)

    Prieto-Martínez, Pedro Daniel; Román-Roy, Narciso

    2012-07-01

    The Lagrangian-Hamiltonian unified formalism of R. Skinner and R. Rusk was originally stated for autonomous dynamical systems in classical mechanics. It has been generalized for non-autonomous first-order mechanical systems, first-order and higher-order field theories, and higher-order autonomous systems. In this work we present a generalization of this formalism for higher-order non-autonomous mechanical systems.

  15. Nil Bohr-sets and almost automorphy of higher order

    CERN Document Server

    Huang, Wen; Ye, Xiangdong

    2016-01-01

    Two closely related topics, higher order Bohr sets and higher order almost automorphy, are investigated in this paper. Both of them are related to nilsystems. In the first part, the problem which can be viewed as the higher order version of an old question concerning Bohr sets is studied: for any d\\in \\mathbb{N} does the collection of \\{n\\in \\mathbb{Z}: S\\cap (S-n)\\cap\\ldots\\cap (S-dn)\

  16. Higher-Order Hybrid Gaussian Kernel in Meshsize Boosting Algorithm

    African Journals Online (AJOL)

    In this paper, we shall use higher-order hybrid Gaussian kernel in a meshsize boosting algorithm in kernel density estimation. Bias reduction is guaranteed in this scheme like other existing schemes but uses the higher-order hybrid Gaussian kernel instead of the regular fixed kernels. A numerical verification of this scheme ...

  17. Higher-order Jordan Osserman pseudo-Riemannian manifolds

    International Nuclear Information System (INIS)

    Gilkey, Peter B; Ivanova, Raina; Zhang Tan

    2002-01-01

    We study the higher-order Jacobi operator in pseudo-Riemannian geometry. We exhibit a family of manifolds so that this operator has constant Jordan normal form on the Grassmannian of subspaces of signature (r, s) for certain values of (r, s). These pseudo-Riemannian manifolds are new and non-trivial examples of higher-order Osserman manifolds

  18. Higher-order Jordan Osserman pseudo-Riemannian manifolds

    Energy Technology Data Exchange (ETDEWEB)

    Gilkey, Peter B [Mathematics Department, University of Oregon, Eugene, OR 97403 (United States); Ivanova, Raina [Mathematics Department, University of Hawaii - Hilo, 200 W Kawili St, Hilo, HI 96720 (United States); Zhang Tan [Department of Mathematics and Statistics, Murray State University, Murray, KY 42071 (United States)

    2002-09-07

    We study the higher-order Jacobi operator in pseudo-Riemannian geometry. We exhibit a family of manifolds so that this operator has constant Jordan normal form on the Grassmannian of subspaces of signature (r, s) for certain values of (r, s). These pseudo-Riemannian manifolds are new and non-trivial examples of higher-order Osserman manifolds.

  19. Exact solutions to two higher order nonlinear Schroedinger equations

    International Nuclear Information System (INIS)

    Xu Liping; Zhang Jinliang

    2007-01-01

    Using the homogeneous balance principle and F-expansion method, the exact solutions to two higher order nonlinear Schroedinger equations which describe the propagation of femtosecond pulses in nonlinear fibres are obtained with the aid of a set of subsidiary higher order ordinary differential equations (sub-equations for short)

  20. Neural classifiers for learning higher-order correlations

    International Nuclear Information System (INIS)

    Gueler, M.

    1999-01-01

    Studies by various authors suggest that higher-order networks can be more powerful and biologically more plausible with respect to the more traditional multilayer networks. These architecture make explicit use of nonlinear interactions between input variables in the form of higher-order units or product units. If it is known a priori that the problem to be implemented possesses a given set of invariances like in the translation, rotation, and scale invariant recognition problems, those invariances can be encoded, thus eliminating all higher-order terms which are incompatible with the invariances. In general, however, it is a serious set-back that the complexity of learning increases exponentially with the size of inputs. This paper reviews higher-order networks and introduces an implicit representation in which learning complexity is mainly decided by the number of higher-order terms to be learned and increases only linearly with the input size

  1. Neural Classifiers for Learning Higher-Order Correlations

    Science.gov (United States)

    Güler, Marifi

    1999-01-01

    Studies by various authors suggest that higher-order networks can be more powerful and are biologically more plausible with respect to the more traditional multilayer networks. These architectures make explicit use of nonlinear interactions between input variables in the form of higher-order units or product units. If it is known a priori that the problem to be implemented possesses a given set of invariances like in the translation, rotation, and scale invariant pattern recognition problems, those invariances can be encoded, thus eliminating all higher-order terms which are incompatible with the invariances. In general, however, it is a serious set-back that the complexity of learning increases exponentially with the size of inputs. This paper reviews higher-order networks and introduces an implicit representation in which learning complexity is mainly decided by the number of higher-order terms to be learned and increases only linearly with the input size.

  2. let-7 Modulates Chromatin Configuration and Target Gene Repression through Regulation of the ARID3B Complex

    Directory of Open Access Journals (Sweden)

    Tsai-Tsen Liao

    2016-01-01

    Full Text Available Let-7 is crucial for both stem cell differentiation and tumor suppression. Here, we demonstrate a chromatin-dependent mechanism of let-7 in regulating target gene expression in cancer cells. Let-7 directly represses the expression of AT-rich interacting domain 3B (ARID3B, ARID3A, and importin-9. In the absence of let-7, importin-9 facilitates the nuclear import of ARID3A, which then forms a complex with ARID3B. The nuclear ARID3B complex recruits histone demethylase 4C to reduce histone 3 lysine 9 trimethylation and promotes the transcription of stemness factors. Functionally, expression of ARID3B is critical for the tumor initiation in let-7-depleted cancer cells. An inverse association between let-7 and ARID3A/ARID3B and prognostic significance is demonstrated in head and neck cancer patients. These results highlight a chromatin-dependent mechanism where let-7 regulates cancer stemness through ARID3B.

  3. Analysis of MVP and VPARP promoters indicates a role for chromatin remodeling in the regulation of MVP.

    Science.gov (United States)

    Emre, Nil; Raval-Fernandes, Sujna; Kickhoefer, Valerie A; Rome, Leonard H

    2004-04-16

    Multi-drug-resistant cancer cells frequently express elevated levels of ribonucleoprotein complexes termed vaults. The increased expression of vault proteins and their mRNAs has led to the suggestion that vaults may play a direct role in preventing drug toxicity. To further understand vault component up-regulation, the three proteins that comprise the vault, the major vault protein (MVP), vault poly(ADP-ribose) polymerase (VPARP), and telomerase-associated protein-1 (TEP1), were examined with respect to gene amplification and drug-induced chromatin remodeling. Gene amplification was not responsible for increased vault component levels in multi-drug-resistant cancer cell lines. The TATA-less murine MVP and human VPARP promoters were identified and functionally characterized. There was no significant activation of either the MVP or VPARP promoters in drug-resistant cell lines in comparison to their parental, drug-sensitive counterparts. Treatment of various cell lines with sodium butyrate, an inhibitor of histone deacetylase (HDAC), led to an increase in vault component protein levels. Furthermore, treatment with trichostatin A (TSA), a more specific inhibitor of HDAC, caused an increase in MVP protein, mRNA, and promoter activity. These results suggest that up-regulation of MVP in multi-drug resistance (MDR) may involve chromatin remodeling.

  4. Transcription initiation patterns indicate divergent strategies for gene regulation at the chromatin level.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Rach

    2011-01-01

    Full Text Available The application of deep sequencing to map 5' capped transcripts has confirmed the existence of at least two distinct promoter classes in metazoans: "focused" promoters with transcription start sites (TSSs that occur in a narrowly defined genomic span and "dispersed" promoters with TSSs that are spread over a larger window. Previous studies have explored the presence of genomic features, such as CpG islands and sequence motifs, in these promoter classes, but virtually no studies have directly investigated the relationship with chromatin features. Here, we show that promoter classes are significantly differentiated by nucleosome organization and chromatin structure. Dispersed promoters display higher associations with well-positioned nucleosomes downstream of the TSS and a more clearly defined nucleosome free region upstream, while focused promoters have a less organized nucleosome structure, yet higher presence of RNA polymerase II. These differences extend to histone variants (H2A.Z and marks (H3K4 methylation, as well as insulator binding (such as CTCF, independent of the expression levels of affected genes. Notably, differences are conserved across mammals and flies, and they provide for a clearer separation of promoter architectures than the presence and absence of CpG islands or the occurrence of stalled RNA polymerase. Computational models support the stronger contribution of chromatin features to the definition of dispersed promoters compared to focused start sites. Our results show that promoter classes defined from 5' capped transcripts not only reflect differences in the initiation process at the core promoter but also are indicative of divergent transcriptional programs established within gene-proximal nucleosome organization.

  5. Higher order Lie-Baecklund symmetries of evolution equations

    International Nuclear Information System (INIS)

    Roy Chowdhury, A.; Roy Chowdhury, K.; Paul, S.

    1983-10-01

    We have considered in detail the analysis of higher order Lie-Baecklund symmetries for some representative nonlinear evolution equations. Until now all such symmetry analyses have been restricted only to the first order of the infinitesimal parameter. But the existence of Baecklund transformation (which can be shown to be an overall sum of higher order Lie-Baecklund symmetries) makes it necessary to search for such higher order Lie-Baecklund symmetries directly without taking recourse to the Baecklund transformation or inverse scattering technique. (author)

  6. The differential geometry of higher order jets and tangent bundles

    International Nuclear Information System (INIS)

    De Leon, M.; Rodrigues, P.R.

    1985-01-01

    This chapter is devoted to the study of basic geometrical notions required for the development of the main object of the text. Some facts about Jet theory are reviewed. A particular case of Jet manifolds is considered: the tangent bundle of higher order. It is shown that this jet bundle possesses in a canonical way a certain kind of geometric structure, the so called almost tangent structure of higher order, and which is a generalization of the almost tangent geometry of the tangent bundle. Another important fact examined is the extension of the notion of 'spray' to higher order tangent bundles. (Auth.)

  7. Higher-order harmonics of general limited diffraction Bessel beams

    International Nuclear Information System (INIS)

    Ding De-Sheng; Huang Jin-Huang

    2016-01-01

    In this paper, we extensively study the higher-order harmonic generation of the general limited diffraction m -th-order Bessel beam. The analysis is based on successive approximations of the Khokhlov–Zabolotskaya–Kuznetsov (KZK) equation. Asymptotic expansions are presented for higher-order harmonic Bessel beams in near and far fields. The validity of asymptotic approximation is also analyzed. The higher-order harmonic of the Bessel beam with the lowest zero-order is taken as a special example. (special topic)

  8. Higher-order harmonics of general limited diffraction Bessel beams

    Science.gov (United States)

    Ding, De-Sheng; Huang, Jin-Huang

    2016-12-01

    In this paper, we extensively study the higher-order harmonic generation of the general limited diffraction m-th-order Bessel beam. The analysis is based on successive approximations of the Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation. Asymptotic expansions are presented for higher-order harmonic Bessel beams in near and far fields. The validity of asymptotic approximation is also analyzed. The higher-order harmonic of the Bessel beam with the lowest zero-order is taken as a special example. Project supported by the National Natural Science Foundation of China (Grant Nos. 11074038 and 11374051).

  9. Elucidation of Chromatin Remodeling Machinery Involved in Regulation of Estrogen Receptor Alpha Expression in Human Breast Cancer Cells

    National Research Council Canada - National Science Library

    Sharma, Dipali

    2005-01-01

    .... Using chromatin immunoprecipitation (ChIP), we examined the chromatin status and repressor complex associated with silenced ER and changes in the key regulatory factors during reactivation by inhibitors of DNMT...

  10. Protein scaffolds and higher-order complexes in synthetic biology

    NARCIS (Netherlands)

    den Hamer, A.; Rosier, B.J.H.M.; Brunsveld, L.; de Greef, T.F.A.; Ryadnov, M.; Brunsveld, L.; Suga, H.

    2017-01-01

    Interactions between proteins control molecular functions such as signalling or metabolic activity. Assembly of proteins via scaffold proteins or in higher-order complexes is a key regulatory mechanism. Understanding and functionally applying this concept requires the construction, study, and

  11. Generating superpositions of higher order bessel beams [Conference paper

    CSIR Research Space (South Africa)

    Vasilyeu, R

    2009-10-01

    Full Text Available An experimental setup to generate a superposition of higher-order Bessel beams by means of a spatial light modulator and ring aperture is presented. The experimentally produced fields are in good agreement with those calculated theoretically....

  12. Higher-order curvature terms and extended inflation

    International Nuclear Information System (INIS)

    Wang Yun

    1990-01-01

    We consider higher-order curvature terms in context of the Brans-Dicke theory of gravity, and investigate the effects of these terms on extended inflationary theories. We find that the higher-order curvature terms tend to speed up inflation, although the original extended-inflation solutions are stable when these terms are small. Analytical solutions are found for two extreme cases: when the higher-order curvature terms are small, and when they dominate. A conformal transformation is employed in solving the latter case, and some of the subtleties in this technique are discussed. We note that percolation is less likely to occur when the higher-order curvature terms are present. An upper bound on α is expected if we are to avoid excessive and inadequate percolation of true-vacuum bubbles

  13. Unambiguous formalism for higher order Lagrangian field theories

    International Nuclear Information System (INIS)

    Campos, Cedric M; De Leon, Manuel; De Diego, David MartIn; Vankerschaver, Joris

    2009-01-01

    The aim of this paper is to propose an unambiguous intrinsic formalism for higher order field theories which avoids the arbitrariness in the generalization of the conventional description of field theories, and implies the existence of different Cartan forms and Legendre transformations. We propose a differential-geometric setting for the dynamics of a higher order field theory, based on the Skinner and Rusk formalism for mechanics. This approach incorporates aspects of both the Lagrangian and the Hamiltonian description, since the field equations are formulated using the Lagrangian on a higher order jet bundle and the canonical multisymplectic form on its affine dual. As both of these objects are uniquely defined, the Skinner-Rusk approach has the advantage that it does not suffer from the arbitrariness in conventional descriptions. The result is that we obtain a unique and global intrinsic version of the Euler-Lagrange equations for higher order field theories. Several examples illustrate our construction.

  14. Higher-order RANS turbulence models for separated flows

    Data.gov (United States)

    National Aeronautics and Space Administration — Higher-order Reynolds-averaged Navier-Stokes (RANS) models are developed to overcome the shortcomings of second-moment RANS models in predicting separated flows....

  15. A simplified parsimonious higher order multivariate Markov chain model

    Science.gov (United States)

    Wang, Chao; Yang, Chuan-sheng

    2017-09-01

    In this paper, a simplified parsimonious higher-order multivariate Markov chain model (SPHOMMCM) is presented. Moreover, parameter estimation method of TPHOMMCM is give. Numerical experiments shows the effectiveness of TPHOMMCM.

  16. A tridiagonal parsimonious higher order multivariate Markov chain model

    Science.gov (United States)

    Wang, Chao; Yang, Chuan-sheng

    2017-09-01

    In this paper, we present a tridiagonal parsimonious higher-order multivariate Markov chain model (TPHOMMCM). Moreover, estimation method of the parameters in TPHOMMCM is give. Numerical experiments illustrate the effectiveness of TPHOMMCM.

  17. Application of Mass Lumped Higher Order Finite Elements

    International Nuclear Information System (INIS)

    J. Chen, H.R. Strauss, S.C. Jardin, W. Park, L.E. Sugiyama, G. Fu, J. Breslau

    2005-01-01

    There are many interesting phenomena in extended-MHD such as anisotropic transport, mhd, 2-fluid effects stellarator and hot particles. Any one of them challenges numerical analysts, and researchers are seeking for higher order methods, such as higher order finite difference, higher order finite elements and hp/spectral elements. It is true that these methods give more accurate solution than their linear counterparts. However, numerically they are prohibitively expensive. Here we give a successful solution of this conflict by applying mass lumped higher order finite elements. This type of elements not only keep second/third order accuracy but also scale closely to linear elements by doing mass lumping. This is especially true for second order lump elements. Full M3D and anisotropic transport models are studied

  18. The role of formative feedback in promoting higher order thinking ...

    African Journals Online (AJOL)

    The role of formative feedback in promoting higher order thinking skills in ... activities, task characteristics, validating students' thinking, and providing feedback. ... Keywords: classroom environment, formative assessment, formative feedback, ...

  19. Asymptotic Expansions for Higher-Order Scalar Difference Equations

    Directory of Open Access Journals (Sweden)

    Ravi P. Agarwal

    2007-04-01

    Full Text Available We give an asymptotic expansion of the solutions of higher-order Poincaré difference equation in terms of the characteristic solutions of the limiting equation. As a consequence, we obtain an asymptotic description of the solutions approaching a hyperbolic equilibrium of a higher-order nonlinear difference equation with sufficiently smooth nonlinearity. The proof is based on the inversion formula for the z -transform and the residue theorem.

  20. Asymptotic Expansions for Higher-Order Scalar Difference Equations

    Directory of Open Access Journals (Sweden)

    Pituk Mihály

    2007-01-01

    Full Text Available We give an asymptotic expansion of the solutions of higher-order Poincaré difference equation in terms of the characteristic solutions of the limiting equation. As a consequence, we obtain an asymptotic description of the solutions approaching a hyperbolic equilibrium of a higher-order nonlinear difference equation with sufficiently smooth nonlinearity. The proof is based on the inversion formula for the z -transform and the residue theorem.

  1. Higher order aberrations of the eye: Part one

    Directory of Open Access Journals (Sweden)

    Marsha Oberholzer

    2016-06-01

    Full Text Available This article is the first in a series of two articles that provide a comprehensive literature review of higher order aberrations (HOAs of the eye. The present article mainly explains the general principles of such HOAs as well as HOAs of importance, and the measuring apparatus used to measure HOAs of the eye. The second article in the series discusses factors contributing to variable results in measurements of HOAs of the eye. Keywords: Higher order aberrations; wavefront aberrations; aberrometer

  2. All-fiber Raman Probe using Higher Order Modes

    DEFF Research Database (Denmark)

    Larsen, Stine Højer Møller; Rishøj, Lars Søgaard; Rottwitt, Karsten

    2013-01-01

    We demonstrate the first all-fiber Raman probe utilizing higher order modes for the excitation. The spectrum of cyclohexane is measured using both the fundamental mode as well as in-fiber-generated Bessel-like modes.......We demonstrate the first all-fiber Raman probe utilizing higher order modes for the excitation. The spectrum of cyclohexane is measured using both the fundamental mode as well as in-fiber-generated Bessel-like modes....

  3. Linear matrix differential equations of higher-order and applications

    Directory of Open Access Journals (Sweden)

    Mustapha Rachidi

    2008-07-01

    Full Text Available In this article, we study linear differential equations of higher-order whose coefficients are square matrices. The combinatorial method for computing the matrix powers and exponential is adopted. New formulas representing auxiliary results are obtained. This allows us to prove properties of a large class of linear matrix differential equations of higher-order, in particular results of Apostol and Kolodner are recovered. Also illustrative examples and applications are presented.

  4. Chromatin dynamics in genome stability

    DEFF Research Database (Denmark)

    Nair, Nidhi; Shoaib, Muhammad; Sørensen, Claus Storgaard

    2017-01-01

    Genomic DNA is compacted into chromatin through packaging with histone and non-histone proteins. Importantly, DNA accessibility is dynamically regulated to ensure genome stability. This is exemplified in the response to DNA damage where chromatin relaxation near genomic lesions serves to promote...... access of relevant enzymes to specific DNA regions for signaling and repair. Furthermore, recent data highlight genome maintenance roles of chromatin through the regulation of endogenous DNA-templated processes including transcription and replication. Here, we review research that shows the importance...... of chromatin structure regulation in maintaining genome integrity by multiple mechanisms including facilitating DNA repair and directly suppressing endogenous DNA damage....

  5. Proteomic interrogation of human chromatin.

    Directory of Open Access Journals (Sweden)

    Mariana P Torrente

    Full Text Available Chromatin proteins provide a scaffold for DNA packaging and a basis for epigenetic regulation and genomic maintenance. Despite understanding its functional roles, mapping the chromatin proteome (i.e. the "Chromatome" is still a continuing process. Here, we assess the biological specificity and proteomic extent of three distinct chromatin preparations by identifying proteins in selected chromatin-enriched fractions using mass spectrometry-based proteomics. These experiments allowed us to produce a chromatin catalog, including several proteins ranging from highly abundant histone proteins to less abundant members of different chromatin machinery complexes. Using a Normalized Spectral Abundance Factor approach, we quantified relative abundances of the proteins across the chromatin enriched fractions giving a glimpse into their chromosomal abundance. The large-scale data sets also allowed for the discovery of a variety of novel post-translational modifications on the identified chromatin proteins. With these comparisons, we find one of the probed methods to be qualitatively superior in specificity for chromatin proteins, but inferior in proteomic extent, evidencing a compromise that must be made between biological specificity and broadness of characterization. Additionally, we attempt to identify proteins in eu- and heterochromatin, verifying the enrichments by characterizing the post-translational modifications detected on histone proteins from these chromatin regions. In summary, our results provide insights into the value of different methods to extract chromatin-associated proteins and provide starting points to study the factors that may be involved in directing gene expression and other chromatin-related processes.

  6. Sigma-1 receptor mediates cocaine-induced transcriptional regulation by recruiting chromatin-remodeling factors at the nuclear envelope.

    Science.gov (United States)

    Tsai, Shang-Yi A; Chuang, Jian-Ying; Tsai, Meng-Shan; Wang, Xiao-Fei; Xi, Zheng-Xiong; Hung, Jan-Jong; Chang, Wen-Chang; Bonci, Antonello; Su, Tsung-Ping

    2015-11-24

    The sigma-1 receptor (Sig-1R) chaperone at the endoplasmic reticulum (ER) plays important roles in cellular regulation. Here we found a new function of Sig-1R, in that it translocates from the ER to the nuclear envelope (NE) to recruit chromatin-remodeling molecules and regulate the gene transcription thereof. Sig-1Rs mainly reside at the ER-mitochondrion interface. However, on stimulation by agonists such as cocaine, Sig-1Rs translocate from ER to the NE, where Sig-1Rs bind NE protein emerin and recruit chromatin-remodeling molecules, including lamin A/C, barrier-to-autointegration factor (BAF), and histone deacetylase (HDAC), to form a complex with the gene repressor specific protein 3 (Sp3). Knockdown of Sig-1Rs attenuates the complex formation. Cocaine was found to suppress the gene expression of monoamine oxidase B (MAOB) in the brain of wild-type but not Sig-1R knockout mouse. A single dose of cocaine (20 mg/kg) in rats suppresses the level of MAOB at nuclear accumbens without affecting the level of dopamine transporter. Daily injections of cocaine in rats caused behavioral sensitization. Withdrawal from cocaine in cocaine-sensitized rats induced an apparent time-dependent rebound of the MAOB protein level to about 200% over control on day 14 after withdrawal. Treatment of cocaine-withdrawn rats with the MAOB inhibitor deprenyl completely alleviated the behavioral sensitization to cocaine. Our results demonstrate a role of Sig-1R in transcriptional regulation and suggest cocaine may work through this newly discovered genomic action to achieve its addictive action. Results also suggest the MAOB inhibitor deprenyl as a therapeutic agent to block certain actions of cocaine during withdrawal.

  7. TADs are 3D structural units of higher-order chromosome organization in Drosophila

    Science.gov (United States)

    Szabo, Quentin; Jost, Daniel; Chang, Jia-Ming; Cattoni, Diego I.; Papadopoulos, Giorgio L.; Bonev, Boyan; Sexton, Tom; Gurgo, Julian; Jacquier, Caroline; Nollmann, Marcelo; Bantignies, Frédéric; Cavalli, Giacomo

    2018-01-01

    Deciphering the rules of genome folding in the cell nucleus is essential to understand its functions. Recent chromosome conformation capture (Hi-C) studies have revealed that the genome is partitioned into topologically associating domains (TADs), which demarcate functional epigenetic domains defined by combinations of specific chromatin marks. However, whether TADs are true physical units in each cell nucleus or whether they reflect statistical frequencies of measured interactions within cell populations is unclear. Using a combination of Hi-C, three-dimensional (3D) fluorescent in situ hybridization, super-resolution microscopy, and polymer modeling, we provide an integrative view of chromatin folding in Drosophila. We observed that repressed TADs form a succession of discrete nanocompartments, interspersed by less condensed active regions. Single-cell analysis revealed a consistent TAD-based physical compartmentalization of the chromatin fiber, with some degree of heterogeneity in intra-TAD conformations and in cis and trans inter-TAD contact events. These results indicate that TADs are fundamental 3D genome units that engage in dynamic higher-order inter-TAD connections. This domain-based architecture is likely to play a major role in regulatory transactions during DNA-dependent processes. PMID:29503869

  8. A fast, open source implementation of adaptive biasing potentials uncovers a ligand design strategy for the chromatin regulator BRD4

    Science.gov (United States)

    Dickson, Bradley M.; de Waal, Parker W.; Ramjan, Zachary H.; Xu, H. Eric; Rothbart, Scott B.

    2016-10-01

    In this communication we introduce an efficient implementation of adaptive biasing that greatly improves the speed of free energy computation in molecular dynamics simulations. We investigated the use of accelerated simulations to inform on compound design using a recently reported and clinically relevant inhibitor of the chromatin regulator BRD4 (bromodomain-containing protein 4). Benchmarking on our local compute cluster, our implementation achieves up to 2.5 times more force calls per day than plumed2. Results of five 1 μs-long simulations are presented, which reveal a conformational switch in the BRD4 inhibitor between a binding competent and incompetent state. Stabilization of the switch led to a -3 kcal/mol improvement of absolute binding free energy. These studies suggest an unexplored ligand design principle and offer new actionable hypotheses for medicinal chemistry efforts against this druggable epigenetic target class.

  9. PTIP chromatin regulator controls development and activation of B cell subsets to license humoral immunity in mice

    DEFF Research Database (Denmark)

    Su, Dan; Vanhee, Stijn; Soria, Rebeca

    2017-01-01

    B cell receptor signaling and downstream NF-κB activity are crucial for the maturation and functionality of all major B cell subsets, yet the molecular players in these signaling events are not fully understood. Here we use several genetically modified mouse models to demonstrate that expression...... of the multifunctional BRCT (BRCA1 C-terminal) domain-containing PTIP (Pax transactivation domain-interacting protein) chromatin regulator is controlled by B cell activation and potentiates steady-state and postimmune antibody production in vivo. By examining the effects of PTIP deficiency in mice at various ages during...... ontogeny, we demonstrate that PTIP promotes bone marrow B cell development as well as the neonatal establishment and subsequent long-term maintenance of self-reactive B-1 B cells. Furthermore, we find that PTIP is required for B cell receptor- and T:B interaction-induced proliferation, differentiation...

  10. Interactions, strings and isotopies in higher order anisotropic superspaces

    CERN Document Server

    Vacaru, Sergiu Ion

    2001-01-01

    The monograph summarizes the author's results on the geometry of anholonomic and locally anisotropic interactions, published in J. Math. Phys., Nucl. Phys. B, Ann. Phys. (NY), JHEP, Rep. Math. Phys., Int. J. Theor. Phys. and in some former Soviet Union and Romanian scientific journals. The main subjects are in the theory of field interactions, strings and diffusion processes on spaces, superspaces and isospaces with higher order anisotropy and inhomogeneity. The approach proceeds by developing the concept of higher order anisotropic (super)space which unifies the logical and manthematical aspects of modern Kaluza--Klein theories and generalized Lagrange and Finsler geometry and leads to modeling of physical processes on higher order fiber (super)bundles provided with nonlinear and distinguished connections and metric structures. This book can be also considered as a pedagogical survey on the mentioned subjects.

  11. Higher-order modulation instability in nonlinear fiber optics.

    Science.gov (United States)

    Erkintalo, Miro; Hammani, Kamal; Kibler, Bertrand; Finot, Christophe; Akhmediev, Nail; Dudley, John M; Genty, Goëry

    2011-12-16

    We report theoretical, numerical, and experimental studies of higher-order modulation instability in the focusing nonlinear Schrödinger equation. This higher-order instability arises from the nonlinear superposition of elementary instabilities, associated with initial single breather evolution followed by a regime of complex, yet deterministic, pulse splitting. We analytically describe the process using the Darboux transformation and compare with experiments in optical fiber. We show how a suitably low frequency modulation on a continuous wave field induces higher-order modulation instability splitting with the pulse characteristics at different phases of evolution related by a simple scaling relationship. We anticipate that similar processes are likely to be observed in many other systems including plasmas, Bose-Einstein condensates, and deep water waves. © 2011 American Physical Society

  12. Higher Order Lagrange Finite Elements In M3D

    International Nuclear Information System (INIS)

    Chen, J.; Strauss, H.R.; Jardin, S.C.; Park, W.; Sugiyama, L.E.; Fu, G.; Breslau, J.

    2004-01-01

    The M3D code has been using linear finite elements to represent multilevel MHD on 2-D poloidal planes. Triangular higher order elements, up to third order, are constructed here in order to provide M3D the capability to solve highly anisotropic transport problems. It is found that higher order elements are essential to resolve the thin transition layer characteristic of the anisotropic transport equation, particularly when the strong anisotropic direction is not aligned with one of the Cartesian coordinates. The transition layer is measured by the profile width, which is zero for infinite anisotropy. It is shown that only higher order schemes have the ability to make this layer converge towards zero when the anisotropy gets stronger and stronger. Two cases are considered. One has the strong transport direction partially aligned with one of the element edges, the other doesn't have any alignment. Both cases have the strong transport direction misaligned with the grid line by some angles

  13. Practical implementation of a higher order transverse leakage approximation

    International Nuclear Information System (INIS)

    Prinsloo, Rian H.; Tomašević

    2011-01-01

    Transverse integrated nodal diffusion methods currently represent the standard in full core neutronic simulation. The primary shortcoming in this approach, be it via the Analytic Nodal Method or Nodal Expansion Method, is the utilization of the quadratic transverse leakage approximation. This approach, although proven to work well for typical LWR problems, is not consistent with the formulation of nodal methods and can cause accuracy and convergence problems. In this work an improved, consistent quadratic leakage approximation is formulated, which derives from the class of higher order nodal methods developed some years ago. In this new approach, only information relevant to describing the transverse leak- age terms in the zero-order nodal equations are obtained from the higher order formalism. The method yields accuracy comparable to full higher order methods, but does not suffer from the same computational burden which these methods typically incur. (author)

  14. Role of the BAHD1 Chromatin-Repressive Complex in Placental Development and Regulation of Steroid Metabolism.

    Directory of Open Access Journals (Sweden)

    Goran Lakisic

    2016-03-01

    Full Text Available BAHD1 is a vertebrate protein that promotes heterochromatin formation and gene repression in association with several epigenetic regulators. However, its physiological roles remain unknown. Here, we demonstrate that ablation of the Bahd1 gene results in hypocholesterolemia, hypoglycemia and decreased body fat in mice. It also causes placental growth restriction with a drop of trophoblast glycogen cells, a reduction of fetal weight and a high neonatal mortality rate. By intersecting transcriptome data from murine Bahd1 knockout (KO placentas at stages E16.5 and E18.5 of gestation, Bahd1-KO embryonic fibroblasts, and human cells stably expressing BAHD1, we also show that changes in BAHD1 levels alter expression of steroid/lipid metabolism genes. Biochemical analysis of the BAHD1-associated multiprotein complex identifies MIER proteins as novel partners of BAHD1 and suggests that BAHD1-MIER interaction forms a hub for histone deacetylases and methyltransferases, chromatin readers and transcription factors. We further show that overexpression of BAHD1 leads to an increase of MIER1 enrichment on the inactive X chromosome (Xi. In addition, BAHD1 and MIER1/3 repress expression of the steroid hormone receptor genes ESR1 and PGR, both playing important roles in placental development and energy metabolism. Moreover, modulation of BAHD1 expression in HEK293 cells triggers epigenetic changes at the ESR1 locus. Together, these results identify BAHD1 as a core component of a chromatin-repressive complex regulating placental morphogenesis and body fat storage and suggest that its dysfunction may contribute to several human diseases.

  15. Higher order multipoles and splines in plasma simulations

    International Nuclear Information System (INIS)

    Okuda, H.; Cheng, C.Z.

    1978-01-01

    The reduction of spatial grid effects in plasma simulations has been studied numerically using higher order multipole expansions and the spline method in one dimension. It is found that, while keeping the higher order moments such as quadrupole and octopole moments substantially reduces the grid effects, quadratic and cubic splines in general have better stability properties for numerical plasma simulations when the Debye length is much smaller than the grid size. In particular the spline method may be useful in three-dimensional simulations for plasma confinement where the grid size in the axial direction is much greater than the Debye length. (Auth.)

  16. Higher-order multipoles and splines in plasma simulations

    International Nuclear Information System (INIS)

    Okuda, H.; Cheng, C.Z.

    1977-12-01

    Reduction of spatial grid effects in plasma simulations has been studied numerically using higher order multipole expansions and spline method in one dimension. It is found that, while keeping the higher order moments such as quadrupole and octopole moments substantially reduces the grid effects, quadratic and cubic splines in general have better stability properties for numerical plasma simulations when the Debye length is much smaller than the grid size. In particular, spline method may be useful in three dimensional simulations for plasma confinement where the grid size in the axial direction is much greater than the Debye length

  17. Multilevel Fast Multipole Method for Higher Order Discretizations

    DEFF Research Database (Denmark)

    Borries, Oscar Peter; Meincke, Peter; Jorgensen, Erik

    2014-01-01

    The multi-level fast multipole method (MLFMM) for a higher order (HO) discretization is demonstrated on high-frequency (HF) problems, illustrating for the first time how an efficient MLFMM for HO can be achieved even for very large groups. Applying several novel ideas, beneficial to both lower...... order and higher order discretizations, results from a low-memory, high-speed MLFMM implementation of a HO hierarchical discretization are shown. These results challenge the general view that the benefits of HO and HF-MLFMM cannot be combined....

  18. The Cauchy problem for higher order abstract differential equations

    CERN Document Server

    Xiao, Ti-Jun

    1998-01-01

    This monograph is the first systematic exposition of the theory of the Cauchy problem for higher order abstract linear differential equations, which covers all the main aspects of the developed theory. The main results are complete with detailed proofs and established recently, containing the corresponding theorems for first and incomplete second order cases and therefore for operator semigroups and cosine functions. They will find applications in many fields. The special power of treating the higher order problems directly is demonstrated, as well as that of the vector-valued Laplace transforms in dealing with operator differential equations and operator families. The reader is expected to have a knowledge of complex and functional analysis.

  19. Chromatin-remodeling SWI/SNF complex regulates coenzyme Q6 synthesis and a metabolic shift to respiration in yeast.

    Science.gov (United States)

    Awad, Agape M; Venkataramanan, Srivats; Nag, Anish; Galivanche, Anoop Raj; Bradley, Michelle C; Neves, Lauren T; Douglass, Stephen; Clarke, Catherine F; Johnson, Tracy L

    2017-09-08

    Despite its relatively streamlined genome, there are many important examples of regulated RNA splicing in Saccharomyces cerevisiae Here, we report a role for the chromatin remodeler SWI/SNF in respiration, partially via the regulation of splicing. We find that a nutrient-dependent decrease in Snf2 leads to an increase in splicing of the PTC7 transcript. The spliced PTC7 transcript encodes a mitochondrial phosphatase regulator of biosynthesis of coenzyme Q 6 (ubiquinone or CoQ 6 ) and a mitochondrial redox-active lipid essential for electron and proton transport in respiration. Increased splicing of PTC7 increases CoQ 6 levels. The increase in PTC7 splicing occurs at least in part due to down-regulation of ribosomal protein gene expression, leading to the redistribution of spliceosomes from this abundant class of intron-containing RNAs to otherwise poorly spliced transcripts. In contrast, a protein encoded by the nonspliced isoform of PTC7 represses CoQ 6 biosynthesis. Taken together, these findings uncover a link between Snf2 expression and the splicing of PTC7 and establish a previously unknown role for the SWI/SNF complex in the transition of yeast cells from fermentative to respiratory modes of metabolism. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. IRAK-M regulates chromatin remodeling in lung macrophages during experimental sepsis.

    Directory of Open Access Journals (Sweden)

    Kenneth Lyn-Kew

    2010-06-01

    Full Text Available Sepsis results in a profound state of immunosuppression, which is temporally associated with impaired leukocyte function. The mechanism of leukocyte reprogramming in sepsis is incompletely understood. In this study, we explored mechanisms contributing to dysregulated inflammatory cytokine expression by pulmonary macrophages during experimental sepsis. Pulmonary macrophages (PM recovered from the lungs of mice undergoing cecal ligation and puncture (CLP display transiently reduced expression of some, but not all innate genes in response to LPS. Impaired expression of TNF-alpha and iNOS was associated with reduced acetylation and methylation of specific histones (AcH4 and H3K4me3 and reduced binding of RNA polymerase II to the promoters of these genes. Transient impairment in LPS-induced cytokine responses in septic PM temporally correlated with induction of IRAK-M mRNA and protein, which occurred in a MyD88-dependent fashion. PM isolated from IRAK-M(-/- mice were largely refractory to CLP-induced impairment in cytokine expression, chromatin remodeling, recruitment of RNA polymerase II, and induction of histone deacetylase-2 observed during sepsis. Our findings indicate that systemic sepsis induces epigenetic silencing of cytokine gene expression in lung macrophages, and IRAK-M appears to be a critical mediator of this response.

  1. The Role of Formative Feedback in Promoting Higher Order ...

    African Journals Online (AJOL)

    DrNneka

    An International Multi-disciplinary Journal, Ethiopia. AFRREV ... make contribution to this research gap by proposing a theoretical feedback model that can promote higher order thinking skills in the classroom. The proposed ..... process; students provided with tasks that are novel, complex, creative, and non- algorithmic ...

  2. Developing Higher-Order Thinking Skills through WebQuests

    Science.gov (United States)

    Polly, Drew; Ausband, Leigh

    2009-01-01

    In this study, 32 teachers participated in a year-long professional development project related to technology integration in which they designed and implemented a WebQuest. This paper describes the extent to which higher-order thinking skills (HOTS) and levels of technology implementation (LoTI) occur in the WebQuests that participants designed.…

  3. Hamiltonian formulation of theory with higher order derivatives

    International Nuclear Information System (INIS)

    Gitman, D.M.; Lyakhovich, S.L.; Tyutin, I.V.

    1983-01-01

    A method of ''hamiltonization'' of a special theory with higher order derivatives is described. In a nonspecial case the result coincides with the known Ostrogradsky formulation. It is shown that in the nonspecial theory the lagrange equations of motion are reduced to the normal form

  4. Numerical methods of higher order of accuracy for incompressible flows

    Czech Academy of Sciences Publication Activity Database

    Kozel, K.; Louda, Petr; Příhoda, Jaromír

    2010-01-01

    Roč. 80, č. 8 (2010), s. 1734-1745 ISSN 0378-4754 Institutional research plan: CEZ:AV0Z20760514 Keywords : higher order methods * upwind methods * backward-facing step Subject RIV: BK - Fluid Dynamics Impact factor: 0.812, year: 2010

  5. First Measurements of Higher Order Optics Parameters in the LHC

    CERN Document Server

    Vanbavinckhove, G; Bartolini, R; Calaga, R; Giovannozzi, M; Maclean, E H; Miyamoto, R; Schmidt, F; Tomas, R

    2011-01-01

    Higher order effects can play an important role in the performance of the LHC. Lack of knowledge of these pa- rameters can increase the tune footprint and compromise the beam lifetime. First measurements of these parameters at injection and flattop have been conducted. Detailed sim- ulations are compared to the measurements together with discussions on the measurement limitations.

  6. Time-Discrete Higher-Order ALE Formulations: Stability

    KAUST Repository

    Bonito, Andrea; Kyza, Irene; Nochetto, Ricardo H.

    2013-01-01

    on the stability of the PDE but may influence that of a discrete scheme. We examine this critical issue for higher-order time stepping without space discretization. We propose time-discrete discontinuous Galerkin (dG) numerical schemes of any order for a time

  7. Meta-Logical Reasoning in Higher-Order Logic

    DEFF Research Database (Denmark)

    Villadsen, Jørgen; Schlichtkrull, Anders; Hess, Andreas Viktor

    The semantics of first-order logic (FOL) can be described in the meta-language of higher-order logic (HOL). Using HOL one can prove key properties of FOL such as soundness and completeness. Furthermore, one can prove sentences in FOL valid using the formalized FOL semantics. To aid...

  8. Decidable Fragments of a Higher Order Calculus with Locations

    DEFF Research Database (Denmark)

    Bundgaard, Mikkel; Godskesen, Jens Christian; Huttel, Hans

    2009-01-01

    Homer is a higher order process calculus with locations. In this paper we study Homer in the setting of the semantic finite control property, which is a finite reachability criterion that implies decidability of barbed bisimilarity. We show that strong and weak barbed bisimilarity are undecidable...

  9. Computer-Mediated Assessment of Higher-Order Thinking Development

    Science.gov (United States)

    Tilchin, Oleg; Raiyn, Jamal

    2015-01-01

    Solving complicated problems in a contemporary knowledge-based society requires higher-order thinking (HOT). The most productive way to encourage development of HOT in students is through use of the Problem-based Learning (PBL) model. This model organizes learning by solving corresponding problems relative to study courses. Students are directed…

  10. Higher-order chaotic oscillator using active bessel filter

    DEFF Research Database (Denmark)

    Lindberg, Erik; Mykolaitis, Gytis; Bumelien, Skaidra

    2010-01-01

    A higher-order oscillator, including a nonlinear unit and an 8th-order low-pass active Bessel filter is described. The Bessel unit plays the role of "three-in-one": a delay line, an amplifier and a filter. Results of hardware experiments and numerical simulation are presented. Depending...

  11. Constrained variational calculus for higher order classical field theories

    Energy Technology Data Exchange (ETDEWEB)

    Campos, Cedric M; De Leon, Manuel; De Diego, David MartIn, E-mail: cedricmc@icmat.e, E-mail: mdeleon@icmat.e, E-mail: david.martin@icmat.e [Instituto de Ciencias Matematicas, CSIC-UAM-UC3M-UCM, Serrano 123, 28006 Madrid (Spain)

    2010-11-12

    We develop an intrinsic geometrical setting for higher order constrained field theories. As a main tool we use an appropriate generalization of the classical Skinner-Rusk formalism. Some examples of applications are studied, in particular to the geometrical description of optimal control theory for partial differential equations.

  12. Constrained variational calculus for higher order classical field theories

    International Nuclear Information System (INIS)

    Campos, Cedric M; De Leon, Manuel; De Diego, David MartIn

    2010-01-01

    We develop an intrinsic geometrical setting for higher order constrained field theories. As a main tool we use an appropriate generalization of the classical Skinner-Rusk formalism. Some examples of applications are studied, in particular to the geometrical description of optimal control theory for partial differential equations.

  13. Higher-Order Integral Equation Methods in Computational Electromagnetics

    DEFF Research Database (Denmark)

    Jørgensen, Erik; Meincke, Peter

    Higher-order integral equation methods have been investigated. The study has focused on improving the accuracy and efficiency of the Method of Moments (MoM) applied to electromagnetic problems. A new set of hierarchical Legendre basis functions of arbitrary order is developed. The new basis...

  14. Higher-Order Separation Logic in Isabelle/HOLCF

    DEFF Research Database (Denmark)

    Varming, Carsten; Birkedal, Lars

    2008-01-01

    We formalize higher-order separation logic for a first-order imperative language with procedures and local variables in Isabelle/HOLCF. The assertion language is modeled in such a way that one may use any theory defined in Isabelle/HOLCF to construct assertions, e.g., primitive recursion, least o...

  15. Order-sorted Algebraic Specifications with Higher-order Functions

    DEFF Research Database (Denmark)

    Haxthausen, Anne Elisabeth

    1995-01-01

    This paper gives a proposal for how order-sorted algebraic specification languages can be extended with higher-order functions. The approach taken is a generalisation to the order-sorted case of an approach given by Mller, Tarlecki and Wirsing for the many-sorted case. The main idea in the proposal...

  16. Enhancing Higher Order Thinking Skills through Clinical Simulation

    Science.gov (United States)

    Varutharaju, Elengovan; Ratnavadivel, Nagendralingan

    2014-01-01

    Purpose: The study aimed to explore, describe and analyse the design and implementation of clinical simulation as a pedagogical tool in bridging the deficiency of higher order thinking skills among para-medical students, and to make recommendations on incorporating clinical simulation as a pedagogical tool to enhance thinking skills and align the…

  17. Improved Multilevel Fast Multipole Method for Higher-Order discretizations

    DEFF Research Database (Denmark)

    Borries, Oscar Peter; Meincke, Peter; Jorgensen, Erik

    2014-01-01

    The Multilevel Fast Multipole Method (MLFMM) allows for a reduced computational complexity when solving electromagnetic scattering problems. Combining this with the reduced number of unknowns provided by Higher-Order discretizations has proven to be a difficult task, with the general conclusion b...

  18. Higher-Order Hierarchical Legendre Basis Functions in Applications

    DEFF Research Database (Denmark)

    Kim, Oleksiy S.; Jørgensen, Erik; Meincke, Peter

    2007-01-01

    The higher-order hierarchical Legendre basis functions have been developed for effective solution of integral equations with the method of moments. They are derived from orthogonal Legendre polynomials modified to enforce normal continuity between neighboring mesh elements, while preserving a high...

  19. Chromatin Hydrodynamics

    Science.gov (United States)

    Bruinsma, Robijn; Grosberg, Alexander Y.; Rabin, Yitzhak; Zidovska, Alexandra

    2014-01-01

    Following recent observations of large scale correlated motion of chromatin inside the nuclei of live differentiated cells, we present a hydrodynamic theory—the two-fluid model—in which the content of a nucleus is described as a chromatin solution with the nucleoplasm playing the role of the solvent and the chromatin fiber that of a solute. This system is subject to both passive thermal fluctuations and active scalar and vector events that are associated with free energy consumption, such as ATP hydrolysis. Scalar events drive the longitudinal viscoelastic modes (where the chromatin fiber moves relative to the solvent) while vector events generate the transverse modes (where the chromatin fiber moves together with the solvent). Using linear response methods, we derive explicit expressions for the response functions that connect the chromatin density and velocity correlation functions to the corresponding correlation functions of the active sources and the complex viscoelastic moduli of the chromatin solution. We then derive general expressions for the flow spectral density of the chromatin velocity field. We use the theory to analyze experimental results recently obtained by one of the present authors and her co-workers. We find that the time dependence of the experimental data for both native and ATP-depleted chromatin can be well-fitted using a simple model—the Maxwell fluid—for the complex modulus, although there is some discrepancy in terms of the wavevector dependence. Thermal fluctuations of ATP-depleted cells are predominantly longitudinal. ATP-active cells exhibit intense transverse long wavelength velocity fluctuations driven by force dipoles. Fluctuations with wavenumbers larger than a few inverse microns are dominated by concentration fluctuations with the same spectrum as thermal fluctuations but with increased intensity. PMID:24806919

  20. Higher order QCD corrections in small x physics

    International Nuclear Information System (INIS)

    Chachamis, G.

    2006-11-01

    We study higher order QCD corrections in small x Physics. The numerical implementation of the full NLO photon impact factor is the remaining necessary piece for the testing of the NLO BFKL resummation against data from physical processes, such as γ * γ * collisions. We perform the numerical integration over phase space for the virtual corrections to the NLO photon impact factor. This, along with the previously calculated real corrections, makes feasible in the near future first estimates for the γ*γ* total cross section, since the convolution of the full impact factor with the NLO BFKL gluon Green's function is now straightforward. The NLO corrections for the photon impact factor are sizeable and negative. In the second part of this thesis, we estimate higher order correction to the BK equation. We are mainly interested in whether partonic saturation delays or not in rapidity when going beyond the leading order. In our investigation, we use the so called 'rapidity veto' which forbid two emissions to be very close in rapidity, to 'switch on' higher order corrections to the BK equation. From analytic and numerical analysis, we conclude that indeed saturation does delay in rapidity when higher order corrections are taken into account. In the last part, we investigate higher order QCD corrections as additional corrections to the Electroweak (EW) sector. The question of whether BFKL corrections are of any importance in the Regge limit for the EW sector seems natural; although they arise in higher loop level, the accumulation of logarithms in energy s at high energies, cannot be dismissed without an investigation. We focus on the process γγ→ZZ. We calculate the pQCD corrections in the forward region at leading logarithmic (LL) BFKL accuracy, which are of the order of few percent at the TeV energy scale. (orig.)

  1. Higher order QCD corrections in small x physics

    Energy Technology Data Exchange (ETDEWEB)

    Chachamis, G.

    2006-11-15

    We study higher order QCD corrections in small x Physics. The numerical implementation of the full NLO photon impact factor is the remaining necessary piece for the testing of the NLO BFKL resummation against data from physical processes, such as {gamma}{sup *}{gamma}{sup *} collisions. We perform the numerical integration over phase space for the virtual corrections to the NLO photon impact factor. This, along with the previously calculated real corrections, makes feasible in the near future first estimates for the {gamma}*{gamma}* total cross section, since the convolution of the full impact factor with the NLO BFKL gluon Green's function is now straightforward. The NLO corrections for the photon impact factor are sizeable and negative. In the second part of this thesis, we estimate higher order correction to the BK equation. We are mainly interested in whether partonic saturation delays or not in rapidity when going beyond the leading order. In our investigation, we use the so called 'rapidity veto' which forbid two emissions to be very close in rapidity, to 'switch on' higher order corrections to the BK equation. From analytic and numerical analysis, we conclude that indeed saturation does delay in rapidity when higher order corrections are taken into account. In the last part, we investigate higher order QCD corrections as additional corrections to the Electroweak (EW) sector. The question of whether BFKL corrections are of any importance in the Regge limit for the EW sector seems natural; although they arise in higher loop level, the accumulation of logarithms in energy s at high energies, cannot be dismissed without an investigation. We focus on the process {gamma}{gamma}{yields}ZZ. We calculate the pQCD corrections in the forward region at leading logarithmic (LL) BFKL accuracy, which are of the order of few percent at the TeV energy scale. (orig.)

  2. Complex mutual regulation of facilitates chromatin transcription (FACT) subunits on both mRNA and protein levels in human cells.

    Science.gov (United States)

    Safina, Alfiya; Garcia, Henry; Commane, Mairead; Guryanova, Olga; Degan, Seamus; Kolesnikova, Kateryna; Gurova, Katerina V

    2013-08-01

    Facilitates chromatin transcription (FACT) is a chromatin remodeling complex with two subunits: SSRP1 and SPT16. Mechanisms controlling FACT levels are of interest, since the complex is not expressed in most differentiated cells, but is frequently upregulated in cancer, particularly in poorly differentiated, aggressive tumors. Moreover, inhibition of FACT expression or function in tumor cells interferes with their survival. Here we demonstrate that SSRP1 and SPT16 protein levels decline upon induction of cellular differentiation or senescence in vitro and that similar declines in protein levels for both SSRP1 and SPT16 occur upon RNAi-mediated knockdown of either SSRP1 or SPT16. The interdependence of SSRP1 and SPT16 protein levels was found to be due to their association with SSRP1 and SPT16 mRNAs, which stabilizes the proteins. In particular, presence of SSRP1 mRNA is critical for SPT16 protein stability. In addition, binding of SSRP1 and SPT16 mRNAs to the FACT complex increases the stability and efficiency of translation of the mRNAs. These data support a model in which the FACT complex is stable when SSRP1 mRNA is present, but quickly degrades when SSRP1 mRNA levels drop. In the absence of FACT complex, SSRP1 and SPT16 mRNAs are unstable and inefficiently translated, making reactivation of FACT function unlikely in normal cells. Thus, we have described a complex and unusual mode of regulation controlling cellular FACT levels that results in amplified and stringent control of FACT activity. The FACT dependence of tumor cells suggests that mechanisms controlling FACT levels could be targeted for anticancer therapy.

  3. Self-similarity of higher-order moving averages

    Science.gov (United States)

    Arianos, Sergio; Carbone, Anna; Türk, Christian

    2011-10-01

    In this work, higher-order moving average polynomials are defined by straightforward generalization of the standard moving average. The self-similarity of the polynomials is analyzed for fractional Brownian series and quantified in terms of the Hurst exponent H by using the detrending moving average method. We prove that the exponent H of the fractional Brownian series and of the detrending moving average variance asymptotically agree for the first-order polynomial. Such asymptotic values are compared with the results obtained by the simulations. The higher-order polynomials correspond to trend estimates at shorter time scales as the degree of the polynomial increases. Importantly, the increase of polynomial degree does not require to change the moving average window. Thus trends at different time scales can be obtained on data sets with the same size. These polynomials could be interesting for those applications relying on trend estimates over different time horizons (financial markets) or on filtering at different frequencies (image analysis).

  4. Comparison Criteria for Nonlinear Functional Dynamic Equations of Higher Order

    Directory of Open Access Journals (Sweden)

    Taher S. Hassan

    2016-01-01

    Full Text Available We will consider the higher order functional dynamic equations with mixed nonlinearities of the form xnt+∑j=0Npjtϕγjxφjt=0, on an above-unbounded time scale T, where n≥2, xi(t≔ri(tϕαixi-1Δ(t,  i=1,…,n-1,   with  x0=x,  ϕβ(u≔uβsgn⁡u, and α[i,j]≔αi⋯αj. The function φi:T→T is a rd-continuous function such that limt→∞φi(t=∞ for j=0,1,…,N. The results extend and improve some known results in the literature on higher order nonlinear dynamic equations.

  5. Higher order mode damping in Kaon factory RF cavities

    International Nuclear Information System (INIS)

    Enegren, T.; Poirier, R.; Griffin, J.; Walling, L.; Thiessen, H.A.; Smythe, W.R.

    1989-05-01

    Proposed designs for Kaon factory accelerators require that the rf cavities support beam currents on the order of several amperes. The beam current has Fourier components at all multiples of the rf frequency. Empty rf buckets produce additional components at all multiples of the revolution frequency. If a Fourier component of the beam coincides with the resonant frequency of a higher order mode of the cavity, which is inevitable if the cavity has a large frequency swing, significant excitation of this mode can occur. The induced voltage may then excite coupled bunch mode instabilities. Effective means are required to damp higher order modes without significantly affecting the fundamental mode. A mode damping scheme based on coupled transmission lines has been investigated and is report

  6. Higher Order Differential Attack on 6-Round MISTY1

    Science.gov (United States)

    Tsunoo, Yukiyasu; Saito, Teruo; Nakashima, Hiroki; Shigeri, Maki

    MISTY1 is a 64-bit block cipher that has provable security against differential and linear cryptanalysis. MISTY1 is one of the algorithms selected in the European NESSIE project, and it has been recommended for Japanese e-Government ciphers by the CRYPTREC project. This paper reports a previously unknown higher order differential characteristic of 4-round MISTY1 with the FL functions. It also shows that a higher order differential attack that utilizes this newly discovered characteristic is successful against 6-round MISTY1 with the FL functions. This attack can recover a partial subkey with a data complexity of 253.7 and a computational complexity of 264.4, which is better than any previous cryptanalysis of MISTY1.

  7. Higher-order risk preferences in social settings.

    Science.gov (United States)

    Heinrich, Timo; Mayrhofer, Thomas

    2018-01-01

    We study prudence and temperance (next to risk aversion) in social settings. Previous experimental studies have shown that these higher-order risk preferences affect the choices of individuals deciding privately on lotteries that only affect their own payoff. Yet, many risky and financially relevant decisions are made in the social settings of households or organizations. We elicit higher-order risk preferences of individuals and systematically vary how an individual's decision is made (alone or while communicating with a partner) and who is affected by the decision (only the individual or the partner as well). In doing so, we can isolate the effects of other-regarding concerns and communication on choices. Our results reveal that the majority of choices are risk averse, prudent, and temperate across social settings. We also observe that individuals are influenced significantly by the preferences of a partner when they are able to communicate and choices are payoff-relevant for both of them.

  8. Higher-order geodesic deviations applied to the Kerr metric

    CERN Document Server

    Colistete, R J; Kerner, R

    2002-01-01

    Starting with an exact and simple geodesic, we generate approximate geodesics by summing up higher-order geodesic deviations within a general relativistic setting, without using Newtonian and post-Newtonian approximations. We apply this method to the problem of closed orbital motion of test particles in the Kerr metric spacetime. With a simple circular orbit in the equatorial plane taken as the initial geodesic, we obtain finite eccentricity orbits in the form of Taylor series with the eccentricity playing the role of a small parameter. The explicit expressions of these higher-order geodesic deviations are derived using successive systems of linear equations with constant coefficients, whose solutions are of harmonic oscillator type. This scheme gives best results when applied to orbits with low eccentricities, but with arbitrary possible values of (GM/Rc sup 2).

  9. An Algorithm for Higher Order Hopf Normal Forms

    Directory of Open Access Journals (Sweden)

    A.Y.T. Leung

    1995-01-01

    Full Text Available Normal form theory is important for studying the qualitative behavior of nonlinear oscillators. In some cases, higher order normal forms are required to understand the dynamic behavior near an equilibrium or a periodic orbit. However, the computation of high-order normal forms is usually quite complicated. This article provides an explicit formula for the normalization of nonlinear differential equations. The higher order normal form is given explicitly. Illustrative examples include a cubic system, a quadratic system and a Duffing–Van der Pol system. We use exact arithmetic and find that the undamped Duffing equation can be represented by an exact polynomial differential amplitude equation in a finite number of terms.

  10. The higher order flux mapping method in large size PHWRs

    International Nuclear Information System (INIS)

    Kulkarni, A.K.; Balaraman, V.; Purandare, H.D.

    1997-01-01

    A new higher order method is proposed for obtaining flux map using single set of expansion mode. In this procedure, one can make use of the difference between predicted value of detector reading and their actual values for determining the strength of local fluxes around detector site. The local fluxes are arising due to constant perturbation changes (both extrinsic and intrinsic) taking place in the reactor. (author)

  11. Practical Programming with Higher-Order Encodings and Dependent Types

    DEFF Research Database (Denmark)

    Poswolsky, Adam; Schürmann, Carsten

    2008-01-01

    , tedious, and error-prone. In this paper, we describe the underlying calculus of Delphin. Delphin is a fully implemented functional-programming language supporting reasoning over higher-order encodings and dependent types, while maintaining the benefits of HOAS. More specifically, just as representations...... for instantiation from those that will remain uninstantiated, utilizing a variation of Miller and Tiu’s ∇-quantifier [1]....

  12. Modeling Human Behaviour with Higher Order Logic: Insider Threats

    DEFF Research Database (Denmark)

    Boender, Jaap; Ivanova, Marieta Georgieva; Kammuller, Florian

    2014-01-01

    it to the sociological process of logical explanation. As a case study on modeling human behaviour, we present the modeling and analysis of insider threats as a Higher Order Logic theory in Isabelle/HOL. We show how each of the three step process of sociological explanation can be seen in our modeling of insider’s state......, its context within an organisation and the effects on security as outcomes of a theorem proving analysis....

  13. Higher order Bose-Einstein correlations in identical particle production

    International Nuclear Information System (INIS)

    Biyajima, M.

    1990-01-01

    A diagram technique to calculate the higher order Bose-Einstein correlations is formulated. This technique is applied to derive explicit expressions for the n-pion correlation functions for n = 2, 3, 4, and 5, and numerical predictions are given. In a comparison with the AFS and NA23 data on two-pion and three-pion Bose-Einstein correlations good agreement is obtained. 21 refs., 5 figs. (Authors)

  14. UV-induced structural changes in chromatin

    International Nuclear Information System (INIS)

    Lang, H.; Zimmer, C.; Vengerov, Yu.Yu.

    1985-01-01

    UV-induced structural alterations of chromatin were studied by means of CD, electron microscopic, and gel electrophoretic measurements. The results indicate that chromatin undergoes serious structural changes after irradiation even at very low fluences. In the low fluence range the structural transitions from the higher ordered chromatin structure to the unfolded state occur without detectable changes in the content of histone H1 and of the core histones. Histone H1 disappears only at fluences above 10 kJ/m 2 . Furthermore, DNA in chromatin is much more sensitive against UV-irradiation and shows a higher degree of strand scission relative to free DNA. While fragmentation in free DNA occurs at fluences above 15 kJ/m 2 , it occurs even at 5.5 kJ/m 2 in the case of chromatin. The biological meaning of the observed UV-induced structural alterations of chromatin is discussed. (author)

  15. Higher-Order Finite Element Solutions of Option Prices

    DEFF Research Database (Denmark)

    Raahauge, Peter

    2004-01-01

    Kinks and jumps in the payoff function of option contracts prevent an effectiveimplementation of higher-order numerical approximation methods. Moreover, thederivatives (the greeks) are not easily determined around such singularities, even withstandard lower-order methods. This paper suggests...... for prices as well as for first and second order derivatives(delta and gamma). Unlike similar studies, numerical approximation errors aremeasured both as weighted averages and in the supnorm over a state space includingtime-to-maturities down to a split second.KEYWORDS: Numerical option pricing, Transformed...

  16. Higher-order Brunnian structures and possible physical realizations

    DEFF Research Database (Denmark)

    A. Baas, Nils; V. Fedorov, D.; S. Jensen, A.

    2014-01-01

    We consider few-body bound state systems and provide precise definitions of Borromean and Brunnian systems. The initial concepts are more than a hundred years old and originated in mathematical knot-theory as purely geometric considerations. About thirty years ago they were generalized and applied...... to the binding of systems in nature. It now appears that recent generalization to higher order Brunnian structures may potentially be realized as laboratory made or naturally occurring systems. With the binding energy as measure, we discuss possibilities of physical realization in nuclei, cold atoms...

  17. Development of higher order mode couplers at Cornell

    International Nuclear Information System (INIS)

    Amato, J.C.

    1988-01-01

    Higher order mode (HOM) couplers are integral parts of a superconducting accelerator cavity. The damping which the couplers must provide is dictated by the frequency and shunt impedance of the cavity modes as well as by the stability requirements of the accelerator incorporating the cavities. Cornell's 5-cell 1500 MHz elliptical cavity was designed for use in a 50 x 50 GeV electron-positron storage ring with a total beam current of 3.5 mA (CESR-II). HOM couplers for the Cornell cavity were designed and evaluated with this machine in mind. The development of these couplers is described in this paper. 8 references, 8 figures

  18. Theory of a higher-order Sturm-Liouville equation

    CERN Document Server

    Kozlov, Vladimir

    1997-01-01

    This book develops a detailed theory of a generalized Sturm-Liouville Equation, which includes conditions of solvability, classes of uniqueness, positivity properties of solutions and Green's functions, asymptotic properties of solutions at infinity. Of independent interest, the higher-order Sturm-Liouville equation also proved to have important applications to differential equations with operator coefficients and elliptic boundary value problems for domains with non-smooth boundaries. The book addresses graduate students and researchers in ordinary and partial differential equations, and is accessible with a standard undergraduate course in real analysis.

  19. Integrable higher order deformations of Heisenberg supermagnetic model

    International Nuclear Information System (INIS)

    Guo Jiafeng; Yan Zhaowen; Wang Shikun; Wu Ke; Zhao Weizhong

    2009-01-01

    The Heisenberg supermagnet model is an integrable supersymmetric system and has a close relationship with the strong electron correlated Hubbard model. In this paper, we investigate the integrable higher order deformations of Heisenberg supermagnet models with two different constraints: (i) S 2 =3S-2I for S is an element of USPL(2/1)/S(U(2)xU(1)) and (ii) S 2 =S for S is an element of USPL(2/1)/S(L(1/1)xU(1)). In terms of the gauge transformation, their corresponding gauge equivalent counterparts are derived.

  20. Oscillation of solutions of some higher order linear differential equations

    Directory of Open Access Journals (Sweden)

    Hong-Yan Xu

    2009-11-01

    Full Text Available In this paper, we deal with the order of growth and the hyper order of solutions of higher order linear differential equations $$f^{(k}+B_{k-1}f^{(k-1}+\\cdots+B_1f'+B_0f=F$$ where $B_j(z (j=0,1,\\ldots,k-1$ and $F$ are entire functions or polynomials. Some results are obtained which improve and extend previous results given by Z.-X. Chen, J. Wang, T.-B. Cao and C.-H. Li.

  1. Higher order temporal finite element methods through mixed formalisms.

    Science.gov (United States)

    Kim, Jinkyu

    2014-01-01

    The extended framework of Hamilton's principle and the mixed convolved action principle provide new rigorous weak variational formalism for a broad range of initial boundary value problems in mathematical physics and mechanics. In this paper, their potential when adopting temporally higher order approximations is investigated. The classical single-degree-of-freedom dynamical systems are primarily considered to validate and to investigate the performance of the numerical algorithms developed from both formulations. For the undamped system, all the algorithms are symplectic and unconditionally stable with respect to the time step. For the damped system, they are shown to be accurate with good convergence characteristics.

  2. Programming real-time executives in higher order language

    Science.gov (United States)

    Foudriat, E. C.

    1982-01-01

    Methods by which real-time executive programs can be implemented in a higher order language are discussed, using HAL/S and Path Pascal languages as program examples. Techniques are presented by which noncyclic tasks can readily be incorporated into the executive system. Situations are shown where the executive system can fail to meet its task scheduling and yet be able to recover either by rephasing the clock or stacking the information for later processing. The concept of deadline processing is shown to enable more effective mixing of time and information synchronized systems.

  3. Squeezing of higher order Hermite-Gauss modes

    DEFF Research Database (Denmark)

    Lassen, Mikael Østergaard

    2008-01-01

    The present paper gives an overview of the experimental generation of squeezing in higher order Hermite-Gaussian modes with an optical parametric ampli¯er (OPA). This work was awarded with The European Optical Society (EOS) price 2007. The purpose of the prize is to encourage a European dimension...... in research in pure and applied optics. The EOS prize is awarded based on the selection criteria of high professionalism, academic and technical quality. Following the EOS Prize rules, the conditions for eligibility are that the work was performed in Europe and that it is published under the auspices...

  4. Higher-order dynamical effects in Coulomb dissociation

    International Nuclear Information System (INIS)

    Esbensen, H.

    1994-06-01

    We study the effect of higher-order processes in Coulomb dissociation of 11 Li by numerically solving the three-dimensional time-dependent Schroedinger equation for the relative motion of a di-neutron and the 9 Li core. Comparisons are made to first-order perturbation theory and to measurements. The calculated Coulomb reacceleration effects improve the agreement with experiment, but some discrepancy remains. The effects are much smaller in the dissociation of 11 Be, and they decrease with increasing beam energy. (orig.)

  5. Inseparability inequalities for higher order moments for bipartite systems

    International Nuclear Information System (INIS)

    Agarwal, G S; Biswas, Asoka

    2005-01-01

    There are several examples of bipartite entangled states of continuous variables for which the existing criteria for entanglement using the inequalities involving the second-order moments are insufficient. We derive new inequalities involving higher order correlation, for testing entanglement in non-Gaussian states. In this context, we study an example of a non-Gaussian state, which is a bipartite entangled state of the form Ψ(x a , x b ) ∝ (αx a + βx b ) e -(x a 2 +x b 2 )/2 . Our results open up an avenue to search for new inequalities to test entanglement in non-Gaussian states

  6. Higher-order thinking in foreign language learning

    OpenAIRE

    Bastos, Ascensão; Ramos, Altina

    2017-01-01

    A project is being conducted in English as a foreign language (EFL), involving eleventh graders in formal and non-formal learning contexts, in a Portuguese high school. The goal of this study is to examine the impact of cognitive tools and higher-order thinking processes on the learning of EFL and achievement of larger processes oriented to action, involving problem solving, decision-making and creation of new products. YouTube videos emerge as cognitive tools in the process. Final results sh...

  7. PRR11 regulates late-S to G2/M phase progression and induces premature chromatin condensation (PCC)

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Chundong; Zhang, Ying; Li, Yi; Zhu, Huifang; Wang, Yitao; Cai, Wei [Department of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016 (China); Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016 (China); Zhu, Jiang [Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016 (China); Ozaki, Toshinori [Laboratory of DNA Damage Signaling, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuohku, Chiba 260-8717 (Japan); Bu, Youquan, E-mail: buyqcn@aliyun.com [Department of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing 400016 (China); Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016 (China)

    2015-03-13

    Recently, we have demonstrated that proline-rich protein 11 (PRR11) is a novel tumor-related gene product likely implicated in the regulation of cell cycle progression as well as lung cancer development. However, its precise role in cell cycle progression remains unclear. In the present study, we have further investigated the expression pattern and functional implication of PRR11 during cell cycle in detail in human lung carcinoma-derived H1299 cells. According to our immunofluorescence study, PRR11 was expressed largely in cytoplasm, the amount of PRR11 started to increase in the late S phase, and was retained until just before mitotic telophase. Consistent with those observations, siRNA-mediated knockdown of PRR11 caused a significant cell cycle arrest in the late S phase. Intriguingly, the treatment with dNTPs further augmented PRR11 silencing-mediated S phase arrest. Moreover, knockdown of PRR11 also resulted in a remarkable retardation of G2/M progression, and PRR11-knockdown cells subsequently underwent G2 phase cell cycle arrest accompanied by obvious mitotic defects such as multipolar spindles and multiple nuclei. In addition, forced expression of PRR11 promoted the premature Chromatin condensation (PCC), and then proliferation of PRR11-expressing cells was massively attenuated and induced apoptosis. Taken together, our current observations strongly suggest that PRR11, which is strictly regulated during cell cycle progression, plays a pivotal role in the regulation of accurate cell cycle progression through the late S phase to mitosis. - Highlights: • PRR11 started to increase in the late S phase and was retained until just before mitotic telophase. • PRR11-knockdown caused a significant cell cycle arrest in the late S phase and G2 phase. • The treatment with dNTPs further augmented PRR11 silencing-mediated S phase arrest. • PRR11-knockdown led to multipolar spindles and multiple nuclei. • Forced expression of PRR11 promoted the PCC and inhibited

  8. PRR11 regulates late-S to G2/M phase progression and induces premature chromatin condensation (PCC)

    International Nuclear Information System (INIS)

    Zhang, Chundong; Zhang, Ying; Li, Yi; Zhu, Huifang; Wang, Yitao; Cai, Wei; Zhu, Jiang; Ozaki, Toshinori; Bu, Youquan

    2015-01-01

    Recently, we have demonstrated that proline-rich protein 11 (PRR11) is a novel tumor-related gene product likely implicated in the regulation of cell cycle progression as well as lung cancer development. However, its precise role in cell cycle progression remains unclear. In the present study, we have further investigated the expression pattern and functional implication of PRR11 during cell cycle in detail in human lung carcinoma-derived H1299 cells. According to our immunofluorescence study, PRR11 was expressed largely in cytoplasm, the amount of PRR11 started to increase in the late S phase, and was retained until just before mitotic telophase. Consistent with those observations, siRNA-mediated knockdown of PRR11 caused a significant cell cycle arrest in the late S phase. Intriguingly, the treatment with dNTPs further augmented PRR11 silencing-mediated S phase arrest. Moreover, knockdown of PRR11 also resulted in a remarkable retardation of G2/M progression, and PRR11-knockdown cells subsequently underwent G2 phase cell cycle arrest accompanied by obvious mitotic defects such as multipolar spindles and multiple nuclei. In addition, forced expression of PRR11 promoted the premature Chromatin condensation (PCC), and then proliferation of PRR11-expressing cells was massively attenuated and induced apoptosis. Taken together, our current observations strongly suggest that PRR11, which is strictly regulated during cell cycle progression, plays a pivotal role in the regulation of accurate cell cycle progression through the late S phase to mitosis. - Highlights: • PRR11 started to increase in the late S phase and was retained until just before mitotic telophase. • PRR11-knockdown caused a significant cell cycle arrest in the late S phase and G2 phase. • The treatment with dNTPs further augmented PRR11 silencing-mediated S phase arrest. • PRR11-knockdown led to multipolar spindles and multiple nuclei. • Forced expression of PRR11 promoted the PCC and inhibited

  9. Compiler-Directed Transformation for Higher-Order Stencils

    Energy Technology Data Exchange (ETDEWEB)

    Basu, Protonu [Univ. of Utah, Salt Lake City, UT (United States); Hall, Mary [Univ. of Utah, Salt Lake City, UT (United States); Williams, Samuel [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Straalen, Brian Van [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Oliker, Leonid [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Colella, Phillip [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2015-07-20

    As the cost of data movement increasingly dominates performance, developers of finite-volume and finite-difference solutions for partial differential equations (PDEs) are exploring novel higher-order stencils that increase numerical accuracy and computational intensity. This paper describes a new compiler reordering transformation applied to stencil operators that performs partial sums in buffers, and reuses the partial sums in computing multiple results. This optimization has multiple effect son improving stencil performance that are particularly important to higher-order stencils: exploits data reuse, reduces floating-point operations, and exposes efficient SIMD parallelism to backend compilers. We study the benefit of this optimization in the context of Geometric Multigrid (GMG), a widely used method to solvePDEs, using four different Jacobi smoothers built from 7-, 13-, 27-and 125-point stencils. We quantify performance, speedup, andnumerical accuracy, and use the Roofline model to qualify our results. Ultimately, we obtain over 4× speedup on the smoothers themselves and up to a 3× speedup on the multigrid solver. Finally, we demonstrate that high-order multigrid solvers have the potential of reducing total data movement and energy by several orders of magnitude.

  10. Time-Discrete Higher-Order ALE Formulations: Stability

    KAUST Repository

    Bonito, Andrea

    2013-01-01

    Arbitrary Lagrangian Eulerian (ALE) formulations deal with PDEs on deformable domains upon extending the domain velocity from the boundary into the bulk with the purpose of keeping mesh regularity. This arbitrary extension has no effect on the stability of the PDE but may influence that of a discrete scheme. We examine this critical issue for higher-order time stepping without space discretization. We propose time-discrete discontinuous Galerkin (dG) numerical schemes of any order for a time-dependent advection-diffusion-model problem in moving domains, and study their stability properties. The analysis hinges on the validity of the Reynold\\'s identity for dG. Exploiting the variational structure and assuming exact integration, we prove that our conservative and nonconservative dG schemes are equivalent and unconditionally stable. The same results remain true for piecewise polynomial ALE maps of any degree and suitable quadrature that guarantees the validity of the Reynold\\'s identity. This approach generalizes the so-called geometric conservation law to higher-order methods. We also prove that simpler Runge-Kutta-Radau methods of any order are conditionally stable, that is, subject to a mild ALE constraint on the time steps. Numerical experiments corroborate and complement our theoretical results. © 2013 Society for Industrial and Applied Mathematics.

  11. Higher-Order Cyclostationarity Detection for Spectrum Sensing

    Directory of Open Access Journals (Sweden)

    Julien Renard

    2010-01-01

    Full Text Available Recent years have shown a growing interest in the concept of Cognitive Radios (CRs, able to access portions of the electromagnetic spectrum in an opportunistic operating way. Such systems require efficient detectors able to work in low Signal-to-Noise Ratio (SNR environments, with little or no information about the signals they are trying to detect. Energy detectors are widely used to perform such blind detection tasks, but quickly reach the so-called SNR wall below which detection becomes impossible Tandra (2005. Cyclostationarity detectors are an interesting alternative to energy detectors, as they exploit hidden periodicities present in man-made signals, but absent in noise. Such detectors use quadratic transformations of the signals to extract the hidden sine-waves. While most of the literature focuses on the second-order transformations of the signals, we investigate the potential of higher-order transformations of the signals. Using the theory of Higher-Order Cyclostationarity (HOCS, we derive a fourth-order detector that performs similarly to the second-order ones to detect linearly modulated signals, at SNR around 0 dB, which may be used if the signals of interest do not exhibit second-order cyclostationarity. More generally this paper reviews the relevant aspects of the cyclostationary and HOCS theory, and shows their potential for spectrum sensing.

  12. Higher-Order Spectrum in Understanding Nonlinearity in EEG Rhythms

    Directory of Open Access Journals (Sweden)

    Cauchy Pradhan

    2012-01-01

    Full Text Available The fundamental nature of the brain's electrical activities recorded as electroencephalogram (EEG remains unknown. Linear stochastic models and spectral estimates are the most common methods for the analysis of EEG because of their robustness, simplicity of interpretation, and apparent association with rhythmic behavioral patterns in nature. In this paper, we extend the use of higher-order spectrum in order to indicate the hidden characteristics of EEG signals that simply do not arise from random processes. The higher-order spectrum is an extension Fourier spectrum that uses higher moments for spectral estimates. This essentially nullifies all Gaussian random effects, therefore, can reveal non-Gaussian and nonlinear characteristics in the complex patterns of EEG time series. The paper demonstrates the distinguishing features of bispectral analysis for chaotic systems, filtered noises, and normal background EEG activity. The bispectrum analysis detects nonlinear interactions; however, it does not quantify the coupling strength. The squared bicoherence in the nonredundant region has been estimated to demonstrate nonlinear coupling. The bicoherence values are minimal for white Gaussian noises (WGNs and filtered noises. Higher bicoherence values in chaotic time series and normal background EEG activities are indicative of nonlinear coupling in these systems. The paper shows utility of bispectral methods as an analytical tool in understanding neural process underlying human EEG patterns.

  13. Interplay of ribosomal DNA loci in nucleolar dominance: dominant NORs are up-regulated by chromatin dynamics in the wheat-rye system.

    Directory of Open Access Journals (Sweden)

    Manuela Silva

    Full Text Available BACKGROUND: Chromatin organizational and topological plasticity, and its functions in gene expression regulation, have been strongly revealed by the analysis of nucleolar dominance in hybrids and polyploids where one parental set of ribosomal RNA (rDNA genes that are clustered in nucleolar organizing regions (NORs, is rendered silent by epigenetic pathways and heterochromatization. However, information on the behaviour of dominant NORs is very sparse and needed for an integrative knowledge of differential gene transcription levels and chromatin specific domain interactions. METHODOLOGY/PRINCIPAL FINDINGS: Using molecular and cytological approaches in a wheat-rye addition line (wheat genome plus the rye nucleolar chromosome pair 1R, we investigated transcriptional activity and chromatin topology of the wheat dominant NORs in a nucleolar dominance situation. Herein we report dominant NORs up-regulation in the addition line through quantitative real-time PCR and silver-staining technique. Accompanying this modification in wheat rDNA trascription level, we also disclose that perinucleolar knobs of ribosomal chromatin are almost transcriptionally silent due to the residual detection of BrUTP incorporation in these domains, contrary to the marked labelling of intranucleolar condensed rDNA. Further, by comparative confocal analysis of nuclei probed to wheat and rye NORs, we found that in the wheat-rye addition line there is a significant decrease in the number of wheat-origin perinucleolar rDNA knobs, corresponding to a diminution of the rDNA heterochromatic fraction of the dominant (wheat NORs. CONCLUSIONS/SIGNIFICANCE: We demonstrate that inter-specific interactions leading to wheat-origin NOR dominance results not only on the silencing of rye origin NOR loci, but dominant NORs are also modified in their transcriptional activity and interphase organization. The results show a cross-talk between wheat and rye NORs, mediated by ribosomal chromatin

  14. CHD8, A Novel Beta-Catenin Associated Chromatin Remodeling Enzyme, Regulates Androgen Receptor Mediated Gene Transcription

    National Research Council Canada - National Science Library

    Bochar, Daniel A

    2008-01-01

    .... To better understand the function of beta-catenin in AR mediated transcription, we have identified a novel chromatin remodeling enzyme, CHD8, that can associate with beta-catenin and functions in AR...

  15. Higher order perturbation theory - An example for discussion

    International Nuclear Information System (INIS)

    Lewins, J.D.; Parks, G.; Babb, A.L.

    1986-01-01

    Higher order perturbation theory is developed in the form of a Taylor series expansion to third order to calculate the thermal utilization of a nonuniform cell. The development takes advantage of the self-adjoint property of the diffusion operator to provide a simple development of this illustration of generalized perturbation theory employing scalar perturbation parameters. The results show how a designer might employ a second-order theory to quantify proposed design improvements, together with the limitations of second- and third-order theory. The chosen example has an exact optimization solution and thus provides a clear understanding of the role of perturbation theory at its various orders. Convergence and the computational advantages and disadvantages of the method are discussed

  16. Higher-order force moments of active particles

    Science.gov (United States)

    Nasouri, Babak; Elfring, Gwynn J.

    2018-04-01

    Active particles moving through fluids generate disturbance flows due to their activity. For simplicity, the induced flow field is often modeled by the leading terms in a far-field approximation of the Stokes equations, whose coefficients are the force, torque, and stresslet (zeroth- and first-order force moments) of the active particle. This level of approximation is quite useful, but may also fail to predict more complex behaviors that are observed experimentally. In this study, to provide a better approximation, we evaluate the contribution of the second-order force moments to the flow field and, by reciprocal theorem, present explicit formulas for the stresslet dipole, rotlet dipole, and potential dipole for an arbitrarily shaped active particle. As examples of this method, we derive modified Faxén laws for active spherical particles and resolve higher-order moments for active rod-like particles.

  17. Higher-order automatic differentiation of mathematical functions

    Science.gov (United States)

    Charpentier, Isabelle; Dal Cappello, Claude

    2015-04-01

    Functions of mathematical physics such as the Bessel functions, the Chebyshev polynomials, the Gauss hypergeometric function and so forth, have practical applications in many scientific domains. On the one hand, differentiation formulas provided in reference books apply to real or complex variables. These do not account for the chain rule. On the other hand, based on the chain rule, the automatic differentiation has become a natural tool in numerical modeling. Nevertheless automatic differentiation tools do not deal with the numerous mathematical functions. This paper describes formulas and provides codes for the higher-order automatic differentiation of mathematical functions. The first method is based on Faà di Bruno's formula that generalizes the chain rule. The second one makes use of the second order differential equation they satisfy. Both methods are exemplified with the aforementioned functions.

  18. Influence of higher order modes on angled-facet amplifiers

    DEFF Research Database (Denmark)

    Wang, Z.; Mikkelsen, B.; Stubkjær, Kristian

    1991-01-01

    The influence of the first-order mode on the residual reflectivity of angled-facet amplifiers is analyzed. For a 7 degrees angled-facet ridge waveguide amplifier with a single-layer antireflective (AR) coating, a gain ripple lower than 1-dB at 25-dB gain can be obtained independent...... of the polarization, even in the presence of a first-order mode with a 15-dB gain. The tolerances for the thickness and refractive index of the AR coating are reduced by a factor of three compared to operation in the fundamental mode only. The influence of the higher order mode can virtually be suppressed...

  19. Higher order branching of periodic orbits from polynomial isochrones

    Directory of Open Access Journals (Sweden)

    B. Toni

    1999-09-01

    Full Text Available We discuss the higher order local bifurcations of limit cycles from polynomial isochrones (linearizable centers when the linearizing transformation is explicitly known and yields a polynomial perturbation one-form. Using a method based on the relative cohomology decomposition of polynomial one-forms complemented with a step reduction process, we give an explicit formula for the overall upper bound of branch points of limit cycles in an arbitrary $n$ degree polynomial perturbation of the linear isochrone, and provide an algorithmic procedure to compute the upper bound at successive orders. We derive a complete analysis of the nonlinear cubic Hamiltonian isochrone and show that at most nine branch points of limit cycles can bifurcate in a cubic polynomial perturbation. Moreover, perturbations with exactly two, three, four, six, and nine local families of limit cycles may be constructed.

  20. Minimization of heat slab nodes with higher order boundary conditions

    International Nuclear Information System (INIS)

    Solbrig, C.W.

    1992-01-01

    The accuracy of a numerical solution can be limited by the numerical approximation to the boundary conditions rather than the accuracy of the equations which describe the interior. The study presented in this paper compares the results from two different numerical formulations of the convective boundary condition on the face of a heat transfer slab. The standard representation of the boundary condition in a test problem yielded an unacceptable error even when the heat transfer slab was partitioned into over 300 nodes. A higher order boundary condition representation was obtained by using a second order approximation for the first derivative at the boundary and combining it with the general equation used for inner nodes. This latter formulation produced reasonable results when as few as ten nodes were used

  1. Mixed Higher Order Variational Model for Image Recovery

    Directory of Open Access Journals (Sweden)

    Pengfei Liu

    2014-01-01

    Full Text Available A novel mixed higher order regularizer involving the first and second degree image derivatives is proposed in this paper. Using spectral decomposition, we reformulate the new regularizer as a weighted L1-L2 mixed norm of image derivatives. Due to the equivalent formulation of the proposed regularizer, an efficient fast projected gradient algorithm combined with monotone fast iterative shrinkage thresholding, called, FPG-MFISTA, is designed to solve the resulting variational image recovery problems under majorization-minimization framework. Finally, we demonstrate the effectiveness of the proposed regularization scheme by the experimental comparisons with total variation (TV scheme, nonlocal TV scheme, and current second degree methods. Specifically, the proposed approach achieves better results than related state-of-the-art methods in terms of peak signal to ratio (PSNR and restoration quality.

  2. MHD stability analysis using higher order spline functions

    Energy Technology Data Exchange (ETDEWEB)

    Ida, Akihiro [Department of Energy Engineering and Science, Graduate School of Engineering, Nagoya University, Nagoya, Aichi (Japan); Todoroki, Jiro; Sanuki, Heiji

    1999-04-01

    The eigenvalue problem of the linearized magnetohydrodynamic (MHD) equation is formulated by using higher order spline functions as the base functions of Ritz-Galerkin approximation. When the displacement vector normal to the magnetic surface (in the magnetic surface) is interpolated by B-spline functions of degree p{sub 1} (degree p{sub 2}), which is continuously c{sub 1}-th (c{sub 2}-th) differentiable on neighboring finite elements, the sufficient conditions for the good approximation is given by p{sub 1}{>=}p{sub 2}+1, c{sub 1}{<=}c{sub 2}+1, (c{sub 1}{>=}1, p{sub 2}{>=}c{sub 2}{>=}0). The influence of the numerical integration upon the convergence of calculated eigenvalues is discussed. (author)

  3. Higher-order momentum distributions and locally affine LDDMM registration

    DEFF Research Database (Denmark)

    Sommer, Stefan Horst; Nielsen, Mads; Darkner, Sune

    2013-01-01

    description of affine transformations and subsequent compact description of non-translational movement in a globally nonrigid deformation. The resulting representation contains directly interpretable information from both mathematical and modeling perspectives. We develop the mathematical construction......To achieve sparse parametrizations that allow intuitive analysis, we aim to represent deformation with a basis containing interpretable elements, and we wish to use elements that have the description capacity to represent the deformation compactly. To accomplish this, we introduce in this paper...... higher-order momentum distributions in the large deformation diffeomorphic metric mapping (LDDMM) registration framework. While the zeroth-order moments previously used in LDDMM only describe local displacement, the first-order momenta that are proposed here represent a basis that allows local...

  4. Higher order corrections to asymptotic-de Sitter inflation

    Science.gov (United States)

    Mohsenzadeh, M.; Yusofi, E.

    2017-08-01

    Since trans-Planckian considerations can be associated with the re-definition of the initial vacuum, we investigate further the influence of trans-Planckian physics on the spectra produced by the initial quasi-de Sitter (dS) state during inflation. We use the asymptotic-dS mode to study the trans-Planckian correction of the power spectrum to the quasi-dS inflation. The obtained spectra consist of higher order corrections associated with the type of geometry and harmonic terms sensitive to the fluctuations of space-time (or gravitational waves) during inflation. As an important result, the amplitude of the power spectrum is dependent on the choice of c, i.e. the type of space-time in the period of inflation. Also, the results are always valid for any asymptotic dS space-time and particularly coincide with the conventional results for dS and flat space-time.

  5. Higher-order techniques for some problems of nonlinear control

    Directory of Open Access Journals (Sweden)

    Sarychev Andrey V.

    2002-01-01

    Full Text Available A natural first step when dealing with a nonlinear problem is an application of some version of linearization principle. This includes the well known linearization principles for controllability, observability and stability and also first-order optimality conditions such as Lagrange multipliers rule or Pontryagin's maximum principle. In many interesting and important problems of nonlinear control the linearization principle fails to provide a solution. In the present paper we provide some examples of how higher-order methods of differential geometric control theory can be used for the study nonlinear control systems in such cases. The presentation includes: nonlinear systems with impulsive and distribution-like inputs; second-order optimality conditions for bang–bang extremals of optimal control problems; methods of high-order averaging for studying stability and stabilization of time-variant control systems.

  6. Higher order statistical moment application for solar PV potential analysis

    Science.gov (United States)

    Basri, Mohd Juhari Mat; Abdullah, Samizee; Azrulhisham, Engku Ahmad; Harun, Khairulezuan

    2016-10-01

    Solar photovoltaic energy could be as alternative energy to fossil fuel, which is depleting and posing a global warming problem. However, this renewable energy is so variable and intermittent to be relied on. Therefore the knowledge of energy potential is very important for any site to build this solar photovoltaic power generation system. Here, the application of higher order statistical moment model is being analyzed using data collected from 5MW grid-connected photovoltaic system. Due to the dynamic changes of skewness and kurtosis of AC power and solar irradiance distributions of the solar farm, Pearson system where the probability distribution is calculated by matching their theoretical moments with that of the empirical moments of a distribution could be suitable for this purpose. On the advantage of the Pearson system in MATLAB, a software programming has been developed to help in data processing for distribution fitting and potential analysis for future projection of amount of AC power and solar irradiance availability.

  7. Recognition of higher order patterns in proteins: immunologic kernels.

    Directory of Open Access Journals (Sweden)

    Robert D Bremel

    Full Text Available By applying analysis of the principal components of amino acid physical properties we predicted cathepsin cleavage sites, MHC binding affinity, and probability of B-cell epitope binding of peptides in tetanus toxin and in ten diverse additional proteins. Cross-correlation of these metrics, for peptides of all possible amino acid index positions, each evaluated in the context of a ±25 amino acid flanking region, indicated that there is a strongly repetitive pattern of short peptides of approximately thirty amino acids each bounded by cathepsin cleavage sites and each comprising B-cell linear epitopes, MHC-I and MHC-II binding peptides. Such "immunologic kernel" peptides comprise all signals necessary for adaptive immunologic cognition, response and recall. The patterns described indicate a higher order spatial integration that forms a symbolic logic coordinating the adaptive immune system.

  8. Higher-order phase transitions on financial markets

    Science.gov (United States)

    Kasprzak, A.; Kutner, R.; Perelló, J.; Masoliver, J.

    2010-08-01

    Statistical and thermodynamic properties of the anomalous multifractal structure of random interevent (or intertransaction) times were thoroughly studied by using the extended continuous-time random walk (CTRW) formalism of Montroll, Weiss, Scher, and Lax. Although this formalism is quite general (and can be applied to any interhuman communication with nontrivial priority), we consider it in the context of a financial market where heterogeneous agent activities can occur within a wide spectrum of time scales. As the main general consequence, we found (by additionally using the Saddle-Point Approximation) the scaling or power-dependent form of the partition function, Z(q'). It diverges for any negative scaling powers q' (which justifies the name anomalous) while for positive ones it shows the scaling with the general exponent τ(q'). This exponent is the nonanalytic (singular) or noninteger power of q', which is one of the pilar of higher-order phase transitions. In definition of the partition function we used the pausing-time distribution (PTD) as the central one, which takes the form of convolution (or superstatistics used, e.g. for describing turbulence as well as the financial market). Its integral kernel is given by the stretched exponential distribution (often used in disordered systems). This kernel extends both the exponential distribution assumed in the original version of the CTRW formalism (for description of the transient photocurrent measured in amorphous glassy material) as well as the Gaussian one sometimes used in this context (e.g. for diffusion of hydrogen in amorphous metals or for aging effects in glasses). Our most important finding is the third- and higher-order phase transitions, which can be roughly interpreted as transitions between the phase where high frequency trading is most visible and the phase defined by low frequency trading. The specific order of the phase transition directly depends upon the shape exponent α defining the stretched

  9. Predictors of third and Higher order births in India

    Directory of Open Access Journals (Sweden)

    Payal Singh

    2015-12-01

    Full Text Available Background: Total fertility rate (TFR reflecting population growth is closely related to higher order parity progression. Many Indian states reached replacement level of TFR, but still states constituting nearly 40% population are with TFR ≥ 3. The predictors are the desire of son’s, poor contraceptives practices, younger age at marriage, child loss and shorter birth spacing. Objective: This analysis assessed the degree of relation of 3rd and higher order parity progression with the above mentioned predictors. Material and Methods: State/Union Territories wise proportions of women: progressing to ≥3 births, more sons desire, birth spacing <24 months, adopting modern contraception and median marriage age <18 years along with infant mortality rate (IMR were taken from NFHS-III report. Correlation matrix and stepwise forward multiple regression carried. Significance was seen at 5%. Results: Hindi speaking states constituting 38.92% nation population recorded TFR ≥3. Positive correlation of mothers progressing ≥ 3 births was highest (0.746 with those desiring more sons followed by IMR (0.445; while maximum negative correlation with those practicing modern contraceptives (-0.565 followed by median age at marriage (-0.391. Multiple regression analysis in order identified desire of more sons, practicing modern contraception and shorter birth spacing as the significant predictors and jointly explained 77.9% of the total variation with gain of 15.5% by adding modern contraceptive practice and 8.3% by adding shorter birth spacing. Conclusions: Desire of more sons appeared the most important predictor to progress ≥3 births that is governed by society culture and educational attainment, require attitudinal change. Further, mothers need motivation to practice both spacing and terminal methods once family is complete.

  10. Higher-order conditioning is impaired by hippocampal lesions.

    Science.gov (United States)

    Gilboa, Asaf; Sekeres, Melanie; Moscovitch, Morris; Winocur, Gordon

    2014-09-22

    Behavior in the real world is rarely motivated by primary conditioned stimuli that have been directly associated with potent unconditioned reinforcers. Instead, motivation and choice behavior are driven by complex chains of higher-order associations that are only indirectly linked to intrinsic reward and often exert their influence outside awareness. Second-order conditioning (SOC) [1] is a basic associative-learning mechanism whereby stimuli acquire motivational salience by proxy, in the absence of primary incentives [2, 3]. Memory-systems theories consider first-order conditioning (FOC) and SOC to be prime examples of hippocampal-independent nondeclarative memory [4, 5]. Accordingly, neurobiological models of SOC focus almost exclusively on nondeclarative neural systems that support motivational salience and reward value. Transfer of value from a conditioned stimulus to a neutral stimulus is thought to require the basolateral amygdala [6, 7] and the ventral striatum [2, 3], but not the hippocampus. We developed a new paradigm to measure appetitive SOC of tones in rats. Hippocampal lesions severely impaired both acquisition and expression of SOC despite normal FOC. Unlike controls, rats with hippocampal lesions could not discriminate between positive and negative secondary conditioned tones, although they exhibited general familiarity with previously presented tones compared with new tones. Importantly, normal rats' behavior, in contrast to that of hippocampal groups, also revealed different confidence levels as indexed by effort, a central characteristic of hippocampal relational memory. The results indicate, contrary to current systems models, that representations of intrinsic relationships between reward value, stimulus identity, and motivation require hippocampal mediation when these relationships are of a higher order. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Global functional analysis of nucleophosmin in Taxol response, cancer, chromatin regulation, and ribosomal DNA transcription

    International Nuclear Information System (INIS)

    Bergstralh, Daniel T.; Conti, Brian J.; Moore, Chris B.; Brickey, W. June; Taxman, Debra J.; Ting, Jenny P.-Y.

    2007-01-01

    Analysis of lung cancer response to chemotherapeutic agents showed the accumulation of a Taxol-induced protein that reacted with an anti-phospho-MEK1/2 antibody. Mass spectroscopy identified the protein as nucleophosmin/B23 (NPM), a multifunctional protein with diverse roles: ribosome biosynthesis, p53 regulation, nuclear-cytoplasmic shuttling, and centrosome duplication. Our work demonstrates that following cellular exposure to mitosis-arresting agents, NPM is phosphorylated and its chromatographic property is altered, suggesting changes in function during mitosis. To determine the functional relevance of NPM, its expression in tumor cells was reduced by siRNA. Cells with reduced NPM were treated with Taxol followed by microarray profiling accompanied by gene/protein pathway analyses. These studies demonstrate several expected and unexpected consequences of NPM depletion. The predominant downstream effectors of NPM are genes involved in cell proliferation, cancer, and the cell cycle. In congruence with its role in cancer, NPM is over-expressed in primary malignant lung cancer tissues. We also demonstrate a role for NPM in the expression of genes encoding SET (TAF1β) and the histone methylase SET8. Additionally, we show that NPM is required for a previously unobserved G2/M upregulation of TAF1A, which encodes the rDNA transcription factor TAF I 48. These results demonstrate multi-faceted functions of NPM that can affect cancer cells

  12. Replicating chromatin: a tale of histones

    DEFF Research Database (Denmark)

    Groth, Anja

    2009-01-01

    Chromatin serves structural and functional roles crucial for genome stability and correct gene expression. This organization must be reproduced on daughter strands during replication to maintain proper overlay of epigenetic fabric onto genetic sequence. Nucleosomes constitute the structural...... framework of chromatin and carry information to specify higher-order organization and gene expression. When replication forks traverse the chromosomes, nucleosomes are transiently disrupted, allowing the replication machinery to gain access to DNA. Histone recycling, together with new deposition, ensures...

  13. Enrichment of HP1a on Drosophila chromosome 4 genes creates an alternate chromatin structure critical for regulation in this heterochromatic domain.

    Directory of Open Access Journals (Sweden)

    Nicole C Riddle

    2012-09-01

    Full Text Available Chromatin environments differ greatly within a eukaryotic genome, depending on expression state, chromosomal location, and nuclear position. In genomic regions characterized by high repeat content and high gene density, chromatin structure must silence transposable elements but permit expression of embedded genes. We have investigated one such region, chromosome 4 of Drosophila melanogaster. Using chromatin-immunoprecipitation followed by microarray (ChIP-chip analysis, we examined enrichment patterns of 20 histone modifications and 25 chromosomal proteins in S2 and BG3 cells, as well as the changes in several marks resulting from mutations in key proteins. Active genes on chromosome 4 are distinct from those in euchromatin or pericentric heterochromatin: while there is a depletion of silencing marks at the transcription start sites (TSSs, HP1a and H3K9me3, but not H3K9me2, are enriched strongly over gene bodies. Intriguingly, genes on chromosome 4 are less frequently associated with paused polymerase. However, when the chromatin is altered by depleting HP1a or POF, the RNA pol II enrichment patterns of many chromosome 4 genes shift, showing a significant decrease over gene bodies but not at TSSs, accompanied by lower expression of those genes. Chromosome 4 genes have a low incidence of TRL/GAGA factor binding sites and a low T(m downstream of the TSS, characteristics that could contribute to a low incidence of RNA polymerase pausing. Our data also indicate that EGG and POF jointly regulate H3K9 methylation and promote HP1a binding over gene bodies, while HP1a targeting and H3K9 methylation are maintained at the repeats by an independent mechanism. The HP1a-enriched, POF-associated chromatin structure over the gene bodies may represent one type of adaptation for genes embedded in repetitive DNA.

  14. Higher order effects in electroweak theory 1981-12 (KEK)

    International Nuclear Information System (INIS)

    Aoki, Ken-ichi

    1982-01-01

    This is a brief report on the higher order or loop effects in electroweak theory. The discussion is based on the Weinberg Salam model and QCD. The loop correction to weak interaction is described. The renormalization conditions were applied to physical parameters, α(QED), M(W) and M(Z). It is expected to obtain experimentally the values of M(W) and M(Z) with the accuracy of 0.1 percent. In this scheme, the parameters were fixed loop by loop. The correction was evaluated along the present on-shell scheme. The general estimation of the order of correction was performed. The evaluation of the size of terms in one-loop correction was made. The examples of one loop analysis are presented. The leading logarithmic correction such as α ln(m 2 q 2 /M 2 ) is discussed. The system was described by H(eff) with the local operator O(i), in which the propagator of heavy particles was contracted. The effective interaction was obtained as C(i) (q 2 ) O(i), where C(i)(q 2 ) satisfies a proper equation of a renormalization group. As the practical examples, μ-decay, charged current and neutral current were studied. The correction to electron neutral current and the shift of M(W) and M(Z) were numerically obtained. Comments on quark mass and the uncertainty of sin 2 (theta) from the νN reaction are presented. (Kato, T.)

  15. Higher-order scalar interactions and SM vacuum stability

    Energy Technology Data Exchange (ETDEWEB)

    Lalak, Zygmunt; Lewicki, Marek; Olszewski, Paweł [Institute of Theoretical Physics, Faculty of Physics, University of Warsawul. Hoża 69, Warsaw (Poland)

    2014-05-26

    Investigation of the structure of the Standard Model effective potential at very large field strengths opens a window towards new phenomena and can reveal properties of the UV completion of the SM. The map of the lifetimes of the vacua of the SM enhanced by nonrenormalizable scalar couplings has been compiled to show how new interactions modify stability of the electroweak vacuum. Whereas it is possible to stabilize the SM by adding Planck scale suppressed interactions and taking into account running of the new couplings, the generic effect is shortening the lifetime and hence further destabilisation of the SM electroweak vacuum. These findings have been illustrated with phase diagrams of modified SM-like models. It has been demonstrated that stabilisation can be achieved by lowering the suppression scale of higher order operators while picking up such combinations of new couplings, which do not deepen the new minima of the potential. Our results show the dependence of the lifetime of the electroweak minimum on the magnitude of the new couplings, including cases with very small couplings (which means very large effective suppression scale) and couplings vastly different in magnitude (which corresponds to two different suppression scales)

  16. General relativity and gauge gravity theories of higher order

    International Nuclear Information System (INIS)

    Konopleva, N.P.

    1998-01-01

    It is a short review of today's gauge gravity theories and their relations with Einstein General Relativity. The conceptions of construction of the gauge gravity theories with higher derivatives are analyzed. GR is regarded as the gauge gravity theory corresponding to the choice of G ∞4 as the local gauge symmetry group and the symmetrical tensor of rank two g μν as the field variable. Using the mathematical technique, single for all fundamental interactions (namely variational formalism for infinite Lie groups), we can obtain Einstein's theory as the gauge theory without any changes. All other gauge approaches lead to non-Einstein theories of gravity. But above-mentioned mathematical technique permits us to construct the gauge gravity theory of higher order (for instance SO (3,1)-gravity) so that all vacuum solutions of Einstein equations are the solutions of the SO (3,1)-gravity theory. The structure of equations of SO(3,1)-gravity becomes analogous to Weeler-Misner geometrodynamics one

  17. Predicting perceptual learning from higher-order cortical processing.

    Science.gov (United States)

    Wang, Fang; Huang, Jing; Lv, Yaping; Ma, Xiaoli; Yang, Bin; Wang, Encong; Du, Boqi; Li, Wu; Song, Yan

    2016-01-01

    Visual perceptual learning has been shown to be highly specific to the retinotopic location and attributes of the trained stimulus. Recent psychophysical studies suggest that these specificities, which have been associated with early retinotopic visual cortex, may in fact not be inherent in perceptual learning and could be related to higher-order brain functions. Here we provide direct electrophysiological evidence in support of this proposition. In a series of event-related potential (ERP) experiments, we recorded high-density electroencephalography (EEG) from human adults over the course of learning in a texture discrimination task (TDT). The results consistently showed that the earliest C1 component (68-84ms), known to reflect V1 activity driven by feedforward inputs, was not modulated by learning regardless of whether the behavioral improvement is location specific or not. In contrast, two later posterior ERP components (posterior P1 and P160-350) over the occipital cortex and one anterior ERP component (anterior P160-350) over the prefrontal cortex were progressively modified day by day. Moreover, the change of the anterior component was closely correlated with improved behavioral performance on a daily basis. Consistent with recent psychophysical and imaging observations, our results indicate that perceptual learning can mainly involve changes in higher-level visual cortex as well as in the neural networks responsible for cognitive functions such as attention and decision making. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Estimation of uncertainties from missing higher orders in perturbative calculations

    International Nuclear Information System (INIS)

    Bagnaschi, E.

    2015-05-01

    In this proceeding we present the results of our recent study (hep-ph/1409.5036) of the statistical performances of two different approaches, Scale Variation (SV) and the Bayesian model of Cacciari and Houdeau (CH)(hep-ph/1105.5152) (which we also extend to observables with initial state hadrons), to the estimation of Missing Higher-Order Uncertainties (MHOUs)(hep-ph/1307.1843) in perturbation theory. The behavior of the models is determined by analyzing, on a wide set of observables, how the MHOU intervals they produce are successful in predicting the next orders. We observe that the Bayesian model behaves consistently, producing intervals at 68% Degree of Belief (DoB) comparable with the scale variation intervals with a rescaling factor r larger than 2 and closer to 4. Concerning SV, our analysis allows the derivation of a heuristic Confidence Level (CL) for the intervals. We find that assigning a CL of 68% to the intervals obtained with the conventional choice of varying the scales within a factor of two with respect to the central scale could potentially lead to an underestimation of the uncertainties in the case of observables with initial state hadrons.

  19. Higher-Order Synaptic Interactions Coordinate Dynamics in Recurrent Networks.

    Directory of Open Access Journals (Sweden)

    Brendan Chambers

    2016-08-01

    Full Text Available Linking synaptic connectivity to dynamics is key to understanding information processing in neocortex. Circuit dynamics emerge from complex interactions of interconnected neurons, necessitating that links between connectivity and dynamics be evaluated at the network level. Here we map propagating activity in large neuronal ensembles from mouse neocortex and compare it to a recurrent network model, where connectivity can be precisely measured and manipulated. We find that a dynamical feature dominates statistical descriptions of propagating activity for both neocortex and the model: convergent clusters comprised of fan-in triangle motifs, where two input neurons are themselves connected. Fan-in triangles coordinate the timing of presynaptic inputs during ongoing activity to effectively generate postsynaptic spiking. As a result, paradoxically, fan-in triangles dominate the statistics of spike propagation even in randomly connected recurrent networks. Interplay between higher-order synaptic connectivity and the integrative properties of neurons constrains the structure of network dynamics and shapes the routing of information in neocortex.

  20. Effective description of higher-order scalar-tensor theories

    Energy Technology Data Exchange (ETDEWEB)

    Langlois, David [APC—Astroparticule et Cosmologie, Université Paris Diderot Paris 7, 75013 Paris (France); Mancarella, Michele; Vernizzi, Filippo [Institut de physique théorique, Université Paris Saclay, CEA, CNRS, 91191 Gif-sur-Yvette (France); Noui, Karim, E-mail: langlois@apc.univ-paris7.fr, E-mail: michele.mancarella@cea.fr, E-mail: karim.noui@lmpt.univ-tours.fr, E-mail: filippo.vernizzi@cea.fr [Laboratoire de Mathématiques et Physique Théorique, Université François Rabelais, Parc de Grandmont, 37200 Tours (France)

    2017-05-01

    Most existing theories of dark energy and/or modified gravity, involving a scalar degree of freedom, can be conveniently described within the framework of the Effective Theory of Dark Energy, based on the unitary gauge where the scalar field is uniform. We extend this effective approach by allowing the Lagrangian in unitary gauge to depend on the time derivative of the lapse function. Although this dependence generically signals the presence of an extra scalar degree of freedom, theories that contain only one propagating scalar degree of freedom, in addition to the usual tensor modes, can be constructed by requiring the initial Lagrangian to be degenerate. Starting from a general quadratic action, we derive the dispersion relations for the linear perturbations around Minkowski and a cosmological background. Our analysis directly applies to the recently introduced Degenerate Higher-Order Scalar-Tensor (DHOST) theories. For these theories, we find that one cannot recover a Poisson-like equation in the static linear regime except for the subclass that includes the Horndeski and so-called 'beyond Horndeski' theories. We also discuss Lorentz-breaking models inspired by Horava gravity.

  1. Higher order mode analysis of the SNS superconducting linac

    CERN Document Server

    Sang Ho Kim; Dong Jeon; Sundelin, R

    2001-01-01

    Higher order modes (HOM's) of monopoles, dipoles, quadrupoles and sextupoles in beta =0.61 and beta =0.81 6-cell superconducting (SC) cavities for the Spallation Neutron Source (SNS) project, have been found up to about 3 GHz and their properties such as R/Q, trapping possibility, etc have been figured out concerning manufacturing imperfection. The main issues of HOM's are beam instabilities (published separately) and HOM induced power especially from TM monopoles. The time structure of SNS beam has three different time scales of pulses, which are micro-pulse, midi-pulse and macropulse. Each time structure will generate resonances. When a mode is near these resonance frequencies, the induced voltage could be large and accordingly the resulting HOM power. In order to understand the effects from such a complex beam time structure on the mode excitation and resulting HOM power, analytic expressions are developed. With these analytic expressions, the induced HOM voltage and HOM power were calculated by assuming e...

  2. Scalar brane backgrounds in higher order curvature gravity

    International Nuclear Information System (INIS)

    Charmousis, Christos; Davis, Stephen C.; Dufaux, Jean-Francois

    2003-01-01

    We investigate maximally symmetric brane world solutions with a scalar field. Five-dimensional bulk gravity is described by a general lagrangian which yields field equations containing no higher than second order derivatives. This includes the Gauss-Bonnet combination for the graviton. Stability and gravitational properties of such solutions are considered, and we particularly emphasise the modifications induced by the higher order terms. In particular it is shown that higher curvature corrections to Einstein theory can give rise to instabilities in brane world solutions. A method for analytically obtaining the general solution for such actions is outlined. Generically, the requirement of a finite volume element together with the absence of a naked singularity in the bulk imposes fine-tuning of the brane tension. A model with a moduli scalar field is analysed in detail and we address questions of instability and non-singular self-tuning solutions. In particular, we discuss a case with a normalisable zero mode but infinite volume element. (author)

  3. Analysis of higher order harmonics with holographic reflection gratings

    Science.gov (United States)

    Mas-Abellan, P.; Madrigal, R.; Fimia, A.

    2017-05-01

    Silver halide emulsions have been considered one of the most energetic sensitive materials for holographic applications. Nonlinear recording effects on holographic reflection gratings recorded on silver halide emulsions have been studied by different authors obtaining excellent experimental results. In this communication specifically we focused our investigation on the effects of refractive index modulation, trying to get high levels of overmodulation that will produce high order harmonics. We studied the influence of the overmodulation and its effects on the transmission spectra for a wide exposure range by use of 9 μm thickness films of ultrafine grain emulsion BB640, exposed to single collimated beams using a red He-Ne laser (wavelength 632.8 nm) with Denisyuk configuration obtaining a spatial frequency of 4990 l/mm recorded on the emulsion. The experimental results show that high overmodulation levels of refractive index produce second order harmonics with high diffraction efficiency (higher than 75%) and a narrow grating bandwidth (12.5 nm). Results also show that overmodulation produce diffraction spectra deformation of the second order harmonic, transforming the spectrum from sinusoidal to approximation of square shape due to very high overmodulation. Increasing the levels of overmodulation of refractive index, we have obtained higher order harmonics, obtaining third order harmonic with diffraction efficiency (up to 23%) and narrowing grating bandwidth (5 nm). This study is the first step to develop a new easy technique to obtain narrow spectral filters based on the use of high index modulation reflection gratings.

  4. Correlated stopping, proton clusters and higher order proton cumulants

    Energy Technology Data Exchange (ETDEWEB)

    Bzdak, Adam [AGH University of Science and Technology, Faculty of Physics and Applied Computer Science, Krakow (Poland); Koch, Volker [Lawrence Berkeley National Laboratory, Nuclear Science Division, Berkeley, CA (United States); Skokov, Vladimir [RIKEN/BNL, Brookhaven National Laboratory, Upton, NY (United States)

    2017-05-15

    We investigate possible effects of correlations between stopped nucleons on higher order proton cumulants at low energy heavy-ion collisions. We find that fluctuations of the number of wounded nucleons N{sub part} lead to rather nontrivial dependence of the correlations on the centrality; however, this effect is too small to explain the large and positive four-proton correlations found in the preliminary data collected by the STAR collaboration at √(s) = 7.7 GeV. We further demonstrate that, by taking into account additional proton clustering, we are able to qualitatively reproduce the preliminary experimental data. We speculate that this clustering may originate either from collective/multi-collision stopping which is expected to be effective at lower energies or from a possible first-order phase transition, or from (attractive) final state interactions. To test these ideas we propose to measure a mixed multi-particle correlation between stopped protons and a produced particle (e.g. pion, antiproton). (orig.)

  5. Near integrability of kink lattice with higher order interactions

    Science.gov (United States)

    Jiang, Yun-Guo; Liu, Jia-Zhen; He, Song

    2017-11-01

    We make use of Manton’s analytical method to investigate the force between kinks and anti-kinks at large distances in 1+1 dimensional field theory. The related potential has infinite order corrections of exponential pattern, and the coefficients for each order are determined. These coefficients can also be obtained by solving the equation of the fluctuations around the vacuum. At the lowest order, the kink lattice represents the Toda lattice. With higher order correction terms, the kink lattice can represent one kind of generic Toda lattice. With only two sites, the kink lattice is classically integrable. If the number of sites of the lattice is larger than two, the kink lattice is not integrable but is a near integrable system. We make use of Flaschka’s variables to study the Lax pair of the kink lattice. These Flaschka’s variables have interesting algebraic relations and non-integrability can be manifested. We also discuss the higher Hamiltonians for the deformed open Toda lattice, which has a similar result to the ordinary deformed Toda. Supported by Shandong Provincial Natural Science Foundation (ZR2014AQ007), National Natural Science Foundation of China (11403015, U1531105), S. He is supported by Max-Planck fellowship in Germany and National Natural Science Foundation of China (11305235)

  6. Higher order corrections to energy levels of muonic atoms

    International Nuclear Information System (INIS)

    Rinker, G.A. Jr.; Steffen, R.M.

    1975-08-01

    In order to facilitate the analysis of muonic x-ray spectra, the results of numerical computations of all higher order quantum electrodynamical corrections to the energy levels of muonic atoms are presented in tabular and graphical form. These corrections include the vacuum polarization corrections caused by emission and reabsorption of virtual electron pairs to all orders, including ''double-bubble'' and ''cracked-egg'' diagrams. An estimate of the Delbruecke scattering-type correction is presented. The Lamb-shift (second- and fourth-order vertex) corrections have been calculated including the correction for the anomalous magnetic moment of the muon. The relativistic nuclear motion (or recoil) correction as well as the correction caused by the screening of the atomic electrons is presented in graphs. For the sake of completeness a graph of the nuclear polarization as computed on the basis of Chen's approach has been included. All calculations were made with a two-parameter Fermi distribution of the nuclear charge density. 7 figures, 23 references

  7. Higher-order relativistic periastron advances and binary pulsars

    International Nuclear Information System (INIS)

    Damour, T.; Schafer, G.

    1988-01-01

    The contributions to the periastron advance of a system of two condensed bodies coming from relativistic dynamical effects of order higher than the usual first post-Newtonian (1PN) equations of motion are investigated. The structure of the solution of the orbital second post-Newtonian (2PN) equations of motion is given in a simple parametrized form. The contributions to the secular pariastron advance, and the period, of orbital 2PN effects are then explicitly worked out by using the Hamilton-Jacobi method. The spin-orbit contribution to the secular precession of the orbit in space is rederived in a streamlined way by making full use of Hamiltonian methods. These results are then applied to the theoretical interpretation of the observational data of pulsars in close eccentric binary systems. It is shown that the higher-order relativistic contributions are already of theoretical and astophysical significance for interpreting the high-precision measurement of the secular periastron advance of PSR 1913+16 achived by Taylor and coworkers. The case of extremely fast spinning (millisecond) binary pulsars is also discussed, and shown to offer an easier ground for getting new tests of general relativity, and/or, a direct measurement of the moment of inertia of a neutron star

  8. Higher Order Modes Excitation of Micro Cantilever Beams

    KAUST Repository

    Jaber, Nizar

    2014-05-01

    In this study, we present analytical and experimental investigation of electrically actuated micro cantilever based resonators. These devices are fabricated using polyimide and coated with chrome and gold layers from both sides. The cantilevers are highly curled up due to stress gradient, which is a common imperfection in surface micro machining. Using a laser Doppler vibrometer, we applied a noise signal to experimentally find the first four resonance frequencies. Then, using a data acquisition card, we swept the excitation frequency around the first four natural modes of vibrations. Theoretically, we derived a reduced order model using the Galerkin method to simulate the dynamics of the system. Extensive numerical analysis and computations were performed. The numerical analysis was able to provide good matching with experimental values of the resonance frequencies. Also, we proved the ability to excite higher order modes using partial electrodes with shapes that resemble the shape of the mode of interest. Such micro-resonators are shown to be promising for applications in mass and gas sensing.

  9. Holographic conductivity of holographic superconductors with higher-order corrections

    Energy Technology Data Exchange (ETDEWEB)

    Sheykhi, Ahmad [Shiraz University, Physics Department and Biruni Observatory, College of Sciences, Shiraz (Iran, Islamic Republic of); Research Institute for Astronomy and Astrophysics of Maragha (RIAAM), Maragha (Iran, Islamic Republic of); Ghazanfari, Afsoon; Dehyadegari, Amin [Shiraz University, Physics Department and Biruni Observatory, College of Sciences, Shiraz (Iran, Islamic Republic of)

    2018-02-15

    We analytically and numerically disclose the effects of the higher-order correction terms in the gravity and in the gauge field on the properties of s-wave holographic superconductors. On the gravity side, we consider the higher curvature Gauss-Bonnet corrections and on the gauge field side, we add a quadratic correction term to the Maxwell Lagrangian. We show that, for this system, one can still obtain an analytical relation between the critical temperature and the charge density. We also calculate the critical exponent and the condensation value both analytically and numerically. We use a variational method, based on the Sturm-Liouville eigenvalue problem for our analytical study, as well as a numerical shooting method in order to compare with our analytical results. For a fixed value of the Gauss-Bonnet parameter, we observe that the critical temperature decreases with increasing the nonlinearity of the gauge field. This implies that the nonlinear correction term to the Maxwell electrodynamics makes the condensation harder. We also study the holographic conductivity of the system and disclose the effects of the Gauss-Bonnet and nonlinear parameters α and b on the superconducting gap. We observe that, for various values of α and b, the real part of the conductivity is proportional to the frequency per temperature, ω/T, as the frequency is large enough. Besides, the conductivity has a minimum in the imaginary part which is shifted toward greater frequency with decreasing temperature. (orig.)

  10. Higher-order scene statistics of breast images

    Science.gov (United States)

    Abbey, Craig K.; Sohl-Dickstein, Jascha N.; Olshausen, Bruno A.; Eckstein, Miguel P.; Boone, John M.

    2009-02-01

    Researchers studying human and computer vision have found description and construction of these systems greatly aided by analysis of the statistical properties of naturally occurring scenes. More specifically, it has been found that receptive fields with directional selectivity and bandwidth properties similar to mammalian visual systems are more closely matched to the statistics of natural scenes. It is argued that this allows for sparse representation of the independent components of natural images [Olshausen and Field, Nature, 1996]. These theories have important implications for medical image perception. For example, will a system that is designed to represent the independent components of natural scenes, where objects occlude one another and illumination is typically reflected, be appropriate for X-ray imaging, where features superimpose on one another and illumination is transmissive? In this research we begin to examine these issues by evaluating higher-order statistical properties of breast images from X-ray projection mammography (PM) and dedicated breast computed tomography (bCT). We evaluate kurtosis in responses of octave bandwidth Gabor filters applied to PM and to coronal slices of bCT scans. We find that kurtosis in PM rises and quickly saturates for filter center frequencies with an average value above 0.95. By contrast, kurtosis in bCT peaks near 0.20 cyc/mm with kurtosis of approximately 2. Our findings suggest that the human visual system may be tuned to represent breast tissue more effectively in bCT over a specific range of spatial frequencies.

  11. Higher-order Skyrme hair of black holes

    Science.gov (United States)

    Gudnason, Sven Bjarke; Nitta, Muneto

    2018-05-01

    Higher-order derivative terms are considered as replacement for the Skyrme term in an Einstein-Skyrme-like model in order to pinpoint which properties are necessary for a black hole to possess stable static scalar hair. We find two new models able to support stable black hole hair in the limit of the Skyrme term being turned off. They contain 8 and 12 derivatives, respectively, and are roughly the Skyrme-term squared and the so-called BPS-Skyrme-term squared. In the twelfth-order model we find that the lower branches, which are normally unstable, become stable in the limit where the Skyrme term is turned off. We check this claim with a linear stability analysis. Finally, we find for a certain range of the gravitational coupling and horizon radius, that the twelfth-order model contains 4 solutions as opposed to 2. More surprisingly, the lowest part of the would-be unstable branch turns out to be the stable one of the 4 solutions.

  12. Higher order total variation regularization for EIT reconstruction.

    Science.gov (United States)

    Gong, Bo; Schullcke, Benjamin; Krueger-Ziolek, Sabine; Zhang, Fan; Mueller-Lisse, Ullrich; Moeller, Knut

    2018-01-08

    Electrical impedance tomography (EIT) attempts to reveal the conductivity distribution of a domain based on the electrical boundary condition. This is an ill-posed inverse problem; its solution is very unstable. Total variation (TV) regularization is one of the techniques commonly employed to stabilize reconstructions. However, it is well known that TV regularization induces staircase effects, which are not realistic in clinical applications. To reduce such artifacts, modified TV regularization terms considering a higher order differential operator were developed in several previous studies. One of them is called total generalized variation (TGV) regularization. TGV regularization has been successively applied in image processing in a regular grid context. In this study, we adapted TGV regularization to the finite element model (FEM) framework for EIT reconstruction. Reconstructions using simulation and clinical data were performed. First results indicate that, in comparison to TV regularization, TGV regularization promotes more realistic images. Graphical abstract Reconstructed conductivity changes located on selected vertical lines. For each of the reconstructed images as well as the ground truth image, conductivity changes located along the selected left and right vertical lines are plotted. In these plots, the notation GT in the legend stands for ground truth, TV stands for total variation method, and TGV stands for total generalized variation method. Reconstructed conductivity distributions from the GREIT algorithm are also demonstrated.

  13. Higher-order gravity and the classical equivalence principle

    Science.gov (United States)

    Accioly, Antonio; Herdy, Wallace

    2017-11-01

    As is well known, the deflection of any particle by a gravitational field within the context of Einstein’s general relativity — which is a geometrical theory — is, of course, nondispersive. Nevertheless, as we shall show in this paper, the mentioned result will change totally if the bending is analyzed — at the tree level — in the framework of higher-order gravity. Indeed, to first order, the deflection angle corresponding to the scattering of different quantum particles by the gravitational field mentioned above is not only spin dependent, it is also dispersive (energy-dependent). Consequently, it violates the classical equivalence principle (universality of free fall, or equality of inertial and gravitational masses) which is a nonlocal principle. However, contrary to popular belief, it is in agreement with the weak equivalence principle which is nothing but a statement about purely local effects. It is worthy of note that the weak equivalence principle encompasses the classical equivalence principle locally. We also show that the claim that there exists an incompatibility between quantum mechanics and the weak equivalence principle, is incorrect.

  14. On higher-order corrections in M theory

    International Nuclear Information System (INIS)

    Howe, P.S.; Tsimpis, D.

    2003-01-01

    A theoretical analysis of higher-order corrections to D=11 supergravity is given in a superspace framework. It is shown that any deformation of D=11 supergravity for which the lowest-dimensional component of the four-form G 4 vanishes is trivial. This implies that the equations of motion of D=11 supergravity are specified by an element of a certain spinorial cohomology group and generalises previous results obtained using spinorial or pure spinor cohomology to the fully non-linear theory. The first deformation of the theory is given by an element of a different spinorial cohomology group with coefficients which are local tensorial functions of the massless supergravity fields. The four-form Bianchi Identities are solved, to first order and at dimension -{1/2}, in the case that the lowest-dimensional component of G 4 is non-zero. Moreover, it is shown how one can calculate the first-order correction to the dimension-zero torsion and thus to the supergravity equations of motion given an explicit expression for this object in terms of the supergravity fields. The version of the theory with both a four-form and a seven-form is discussed in the presence of the five-brane anomaly-cancelling term. It is shown that the supersymmetric completion of this term exists and it is argued that it is the unique anomaly-cancelling invariant at this dimension which is at least quartic in the fields. This implies that the first deformation of the theory is completely determined by the anomaly term from which one can, in principle, read off the corrections to all of the superspace field strength tensors. (author)

  15. Threshold resummation and higher order effects in QCD

    International Nuclear Information System (INIS)

    Ringer, Felix Maximilian

    2015-01-01

    Quantum chromodynamics (QCD) is a quantum field theory that describes the strong interactions between quarks and gluons, the building blocks of all hadrons. Thanks to the experimental progress over the past decades, there has been an ever-growing need for QCD precision calculations for scattering processes involving hadrons. For processes at large momentum transfer, perturbative QCD offers a systematic approach for obtaining precise predictions. This approach relies on two key concepts: the asymptotic freedom of QCD and factorization. In a perturbative calculation at higher orders, the infrared cancellation between virtual and real emission diagrams generally leaves behind logarithmic contributions. In many observables relevant for hadronic scattering these logarithms are associated with a kinematic threshold and are hence known as ''threshold logarithms''. They become large when the available phase space for real gluon emission shrinks. In order to obtain a reliable prediction from QCD, the threshold logarithms need to be taken into account to all orders in the strong coupling constant, a procedure known as ''threshold resummation''. The main focus of my PhD thesis is on studies of QCD threshold resummation effects beyond the next-to-leading logarithmic order. Here we primarily consider the production of hadron pairs in hadronic collisions as an example. In addition, we also consider hadronic jet production, which is particularly interesting for the phenomenology at the LHC. For both processes, we fully take into account the non-trivial QCD color structure of the underlying partonic hard- scattering cross sections. We find that threshold resummation leads to sizable numerical effects in the kinematic regimes relevant for comparisons to experimental data.

  16. 1957-2007: 50 Years of Higher Order Programming Languages

    Directory of Open Access Journals (Sweden)

    Alen Lovrenčić

    2009-06-01

    Full Text Available Fifty years ago one of the greatest breakthroughs in computer programming and in the history of computers happened -- the appearance of FORTRAN, the first higher-order programming language. From that time until now hundreds of programming languages were invented, different programming paradigms were defined, all with the main goal to make computer programming easier and closer to as many people as possible. Many battles were fought among scientists as well as among developers around concepts of programming, programming languages and paradigms. It can be said that programming paradigms and programming languages were very often a trigger for many changes and improvements in computer science as well as in computer industry. Definitely, computer programming is one of the cornerstones of computer science.Today there are many tools that give a help in the process of programming, but there is still a programming tasks that can be solved only manually. Therefore, programming is still one of the most creative parts of interaction with computers.Programmers should chose programming language in accordance to task they have to solve, but very often, they chose it in accordance to their personal preferences, their beliefs and many other subjective reasons.Nevertheless, the market of programming languages can be merciless to languages as history was merciless to some people, even whole nations. Programming languages and developers get born, live and die leaving more or less tracks and successors, and not always the best survives. The history of programming languages is closely connected to the history of computers and computer science itself. Every single thing from one of them has its reflexions onto the other. This paper gives a short overview of last fifty years of computer programming and computer programming languages, but also gives many ideas that influenced other aspects of computer science. Particularly, programming paradigms are described, their

  17. Higher order energy transfer. Quantum electrodynamical calculations and graphical representation

    International Nuclear Information System (INIS)

    Jenkins, R.D.

    2000-01-01

    In Chapter 1, a novel method of calculating quantum electrodynamic amplitudes is formulated using combinatorial theory. This technique is used throughout instead of conventional time-ordered methods. A variety of hyperspaces are discussed to highlight isomorphism between a number of A generalisation of Pascal's triangle is shown to be beneficial in determining the form of hyperspace graphs. Chapter 2 describes laser assisted resonance energy transfer (LARET), a higher order perturbative contribution to the well-known process resonance energy transfer, accommodating an off resonance auxiliary laser field to stimulate the migration. Interest focuses on energy exchanges between two uncorrelated molecular species, as in a system where molecules are randomly oriented. Both phase-weighted and standard isotropic averaging are required for the calculations. Results are discussed in terms of a laser intensity-dependent mechanism. Identifying the applied field regime where LARET should prove experimentally significant, transfer rate increases of up to 30% are predicted. General results for three-center energy transfer are elucidated in chapter 3. Cooperative and accretive mechanistic pathways are identified with theory formulated to elicit their role in a variety of energy transfer phenomena and their relative dominance. In multichromophoric the interplay of such factors is analysed with regard to molecular architectures. The alignments and magnitudes of donor and acceptor transition moments and polarisabilities prove to have profound effects on achievable pooling efficiency for linear configurations. Also optimum configurations are offered. In ionic lattices, although both mechanisms play significant roles in pooling and cutting processes, only the accretive is responsible for sensitisation. The local, microscopic level results are used to gauge the lattice response, encompassing concentration and structural effects. (author)

  18. Preparation and characterization of stable aqueous higher-order fullerenes

    International Nuclear Information System (INIS)

    Aich, Nirupam; Flora, Joseph R V; Saleh, Navid B

    2012-01-01

    Stable aqueous suspensions of nC 60 and individual higher fullerenes, i.e. C 70 , C 76 and C 84 , are prepared by a calorimetric modification of a commonly used liquid–liquid extraction technique. The energy requirement for synthesis of higher fullerenes has been guided by molecular-scale interaction energy calculations. Solubilized fullerenes show crystalline behavior by exhibiting lattice fringes in high resolution transmission electron microscopy images. The fullerene colloidal suspensions thus prepared are stable with a narrow distribution of cluster radii (42.7 ± 0.8 nm, 46.0 ± 14.0 nm, 60 ± 3.2 nm and 56.3 ± 1.1 nm for nC 60 , nC 70 , nC 76 and nC 84 , respectively) as measured by time-resolved dynamic light scattering. The ζ-potential values for all fullerene samples showed negative surface potentials with similar magnitude ( − 38.6 ± 5.8 mV, − 39.1 ± 4.2 mV, − 38.9 ± 5.8 mV and − 41.7 ± 5.1 mV for nC 60 , nC 70 , nC 76 and nC 84 , respectively), which provide electrostatic stability to the colloidal clusters. This energy-based modified solubilization technique to produce stable aqueous fullerenes will likely aid in future studies focusing on better applicability, determination of colloidal properties, and understanding of environmental fate, transport and toxicity of higher-order fullerenes. (paper)

  19. Chromatin-mediated transcriptional regulation by the yeast architectural factors NHP6A and NHP6B

    DEFF Research Database (Denmark)

    Moreira, José Manuel Alfonso; Holmberg, S

    2000-01-01

    The Saccharomyces cerevisiae NHP6A and NHP6B proteins are chromatin architectural factors, functionally and structurally related to the mammalian high mobility group (HMG)-1 and -2 proteins, a family of non-sequence-specific DNA binding proteins. nhp6a nhp6b mutants have various morphological...

  20. Analysis of wheezes using wavelet higher order spectral features.

    Science.gov (United States)

    Taplidou, Styliani A; Hadjileontiadis, Leontios J

    2010-07-01

    . This paves the way for the use of the wavelet higher order spectral features as an input vector to an efficient classifier. Apparently, this would integrate the intrinsic characteristics of wheezes within computerized diagnostic tools toward their more efficient evaluation.

  1. Higher-order aberrations and visual acuity after LASEK.

    Science.gov (United States)

    Urgancioglu, Berrak; Bilgihan, Kamil; Ozturk, Sertac

    2008-08-01

    To determine ocular higher-order aberrations (HOAs) in eyes with supernormal vision after myopic astigmatic laser subepithelial keratomileusis (LASEK) and to compare the findings with those in eyes with natural supernormal vision. Ocular HOAs were measured after LASEK in 20 eyes of 12 myopic astigmatic patients with postoperative uncorrected visual acuity (UCVA) of >20/16 (group 1). Patients who were included in the study had no visual symptoms like glare, halo or double vision. The measurements were taken 8.3 +/- 3 months after LASEK surgery. In group 2 ocular HOAs were examined in 20 eyes of 10 subjects with natural UCVA of >20/16 as a control. Measurements were taken across a pupil with a diameter of 4.0 mm and 6.0 mm. Root-mean-square (RMS) values of HOAs, Z(3)-1, Z(3)1, Z(4)0, Z(5)-1, Z(5)1 and Z(6)0 were analyzed. The mean RMS values for each order were higher in group 1 when compared with group 2 at 4.0 mm and 6.0 mm pupil diameters. There was no statistically significant difference between groups in spherical and coma aberrations (P > 0.05). Mean RMS values for total HOAs were 0.187 +/- 0.09 microm at 4.0 mm and 0.438 +/- 0.178 microm at 6.0 mm pupil in group 1 and 0.120 +/- 0.049 microm at 4.0 mm and 0.344 +/- 0.083 microm at 6.0 mm pupil in group 2. The difference between groups in total HOAs was statistically significant at 4.0 mm and 6.0 mm pupil diameters (P < 0.05). Ocular HOAs exist in eyes with supernormal vision. After LASEK, the amount of HOAs of the eye increases under both mesopic and photopic conditions. However the amount of HOA increase does not seem to be consistent with visual symptoms.

  2. Dynamics and phenomenology of higher order gravity cosmological models

    Science.gov (United States)

    Moldenhauer, Jacob Andrew

    2010-10-01

    I present here some new results about a systematic approach to higher-order gravity (HOG) cosmological models. The HOG models are derived from curvature invariants that are more general than the Einstein-Hilbert action. Some of the models exhibit late-time cosmic acceleration without the need for dark energy and fit some current observations. The open question is that there are an infinite number of invariants that one could select, and many of the published papers have stressed the need to find a systematic approach that will allow one to study methodically the various possibilities. We explore a new connection that we made between theorems from the theory of invariants in general relativity and these cosmological models. In summary, the theorems demonstrate that curvature invariants are not all independent from each other and that for a given Ricci Segre type and Petrov type (symmetry classification) of the space-time, there exists a complete minimal set of independent invariants (a basis) in terms of which all the other invariants can be expressed. As an immediate consequence of the proposed approach, the number of invariants to consider is dramatically reduced from infinity to four invariants in the worst case and to only two invariants in the cases of interest, including all Friedmann-Lemaitre-Robertson-Walker metrics. We derive models that pass stability and physical acceptability conditions. We derive dynamical equations and phase portrait analyses that show the promise of the systematic approach. We consider observational constraints from magnitude-redshift Supernovae Type Ia data, distance to the last scattering surface of the Cosmic Microwave Background radiation, and Baryon Acoustic Oscillations. We put observational constraints on general HOG models. We constrain different forms of the Gauss-Bonnet, f(G), modified gravity models with these observations. We show some of these models pass solar system tests. We seek to find models that pass physical and

  3. Chromatin in embryonic stem cell neuronal differentiation.

    Science.gov (United States)

    Meshorer, E

    2007-03-01

    Chromatin, the basic regulatory unit of the eukaryotic genetic material, is controlled by epigenetic mechanisms including histone modifications, histone variants, DNA methylation and chromatin remodeling. Cellular differentiation involves large changes in gene expression concomitant with alterations in genome organization and chromatin structure. Such changes are particularly evident in self-renewing pluripotent embryonic stem cells, which begin, in terms of cell fate, as a tabula rasa, and through the process of differentiation, acquire distinct identities. Here I describe the changes in chromatin that accompany neuronal differentiation, particularly of embryonic stem cells, and discuss how chromatin serves as the master regulator of cellular destiny.

  4. Fanconi anemia proteins localize to chromatin and the nuclear matrix in a DNA damage- and cell cycle-regulated manner.

    Science.gov (United States)

    Qiao, F; Moss, A; Kupfer, G M

    2001-06-29

    Fanconi anemia (FA) is a genetic disease characterized by congenital defects, bone marrow failure, and cancer susceptibility. Cells from patients with FA exhibit genomic instability and hypersensitivity to DNA cross linking agents such as mitomycin C. Despite the identification of seven complementation groups and the cloning of six genes, the function of the encoded gene products remains elusive. The FancA (Fanconi anemia complementation group A), FancC, and FancG proteins have been detected within a nuclear complex, but no change in level, binding, or localization has been reported as a result of drug treatment or cell cycle. We show that in immunofluorescence studies, FancA appears as a non-nucleolar nuclear protein that is excluded from condensed, mitotic chromosomes. Biochemical fractionation reveals that the FA proteins are found in nuclear matrix and chromatin and that treatment with mitomycin C results in increase of the FA proteins in nuclear matrix and chromatin fractions. This induction occurs in wild-type cells and mutant FA-D (Fanconi complementation group D) cells but not in mutant FA-A cells. Immunoprecipitation of FancA protein in chromatin demonstrates the coprecipitation of FancA, FancC, and FancG, showing that the FA proteins move together as a complex. Also, fractionation of mitotic cells confirms the lack of FA proteins in chromatin or the nuclear matrix. Furthermore, phosphorylation of FancG was found to be temporally correlated with exit of the FA complex from chromosomes at mitosis. Taken together, these findings suggest a role for FA proteins in chromatin and nuclear matrix.

  5. Genome-wide specificity of DNA binding, gene regulation, and chromatin remodeling by TALE- and CRISPR/Cas9-based transcriptional activators.

    Science.gov (United States)

    Polstein, Lauren R; Perez-Pinera, Pablo; Kocak, D Dewran; Vockley, Christopher M; Bledsoe, Peggy; Song, Lingyun; Safi, Alexias; Crawford, Gregory E; Reddy, Timothy E; Gersbach, Charles A

    2015-08-01

    Genome engineering technologies based on the CRISPR/Cas9 and TALE systems are enabling new approaches in science and biotechnology. However, the specificity of these tools in complex genomes and the role of chromatin structure in determining DNA binding are not well understood. We analyzed the genome-wide effects of TALE- and CRISPR-based transcriptional activators in human cells using ChIP-seq to assess DNA-binding specificity and RNA-seq to measure the specificity of perturbing the transcriptome. Additionally, DNase-seq was used to assess genome-wide chromatin remodeling that occurs as a result of their action. Our results show that these transcription factors are highly specific in both DNA binding and gene regulation and are able to open targeted regions of closed chromatin independent of gene activation. Collectively, these results underscore the potential for these technologies to make precise changes to gene expression for gene and cell therapies or fundamental studies of gene function. © 2015 Polstein et al.; Published by Cold Spring Harbor Laboratory Press.

  6. Encouraging Student Autonomy through Higher Order Thinking Skills

    Science.gov (United States)

    Smith, Victoria D.; Darvas, Janet W.

    2017-01-01

    This article discusses how to empower students to work, think, and act independently in the higher education setting. Inspiring students to progress through the stages of Bloom's Taxonomy emboldens them to discover intrinsic motivation and self-regulated learning. This article defines and focuses on the importance of teaching intrinsic motivation…

  7. Higher-Order Structure in Bacterial VapBC Toxin-Antitoxin Complexes

    DEFF Research Database (Denmark)

    Bendtsen, Kirstine L; Brodersen, Ditlev E

    2017-01-01

    Toxin-antitoxin systems are widespread in the bacterial kingdom, including in pathogenic species, where they allow rapid adaptation to changing environmental conditions through selective inhibition of key cellular processes, such as DNA replication or protein translation. Under normal growth...... that allow auto-regulation of transcription by direct binding to promoter DNA. In this chapter, we review our current understanding of the structural characteristics of type II toxin-antitoxin complexes in bacterial cells, with a special emphasis on the staggering variety of higher-order architecture...... conditions, type II toxins are inhibited through tight protein-protein interaction with a cognate antitoxin protein. This toxin-antitoxin complex associates into a higher-order macromolecular structure, typically heterotetrameric or heterooctameric, exposing two DNA binding domains on the antitoxin...

  8. The MAP kinase ERK and its scaffold protein MP1 interact with the chromatin regulator Corto during Drosophila wing tissue development

    Science.gov (United States)

    2011-01-01

    Background Mitogen-activated protein kinase (MAPK) cascades (p38, JNK, ERK pathways) are involved in cell fate acquisition during development. These kinase modules are associated with scaffold proteins that control their activity. In Drosophila, dMP1, that encodes an ERK scaffold protein, regulates ERK signaling during wing development and contributes to intervein and vein cell differentiation. Functional relationships during wing development between a chromatin regulator, the Enhancer of Trithorax and Polycomb Corto, ERK and its scaffold protein dMP1, are examined here. Results Genetic interactions show that corto and dMP1 act together to antagonize rolled (which encodes ERK) in the future intervein cells, thus promoting intervein fate. Although Corto, ERK and dMP1 are present in both cytoplasmic and nucleus compartments, they interact exclusively in nucleus extracts. Furthermore, Corto, ERK and dMP1 co-localize on several sites on polytene chromosomes, suggesting that they regulate gene expression directly on chromatin. Finally, Corto is phosphorylated. Interestingly, its phosphorylation pattern differs between cytoplasm and nucleus and changes upon ERK activation. Conclusions Our data therefore suggest that the Enhancer of Trithorax and Polycomb Corto could participate in regulating vein and intervein genes during wing tissue development in response to ERK signaling. PMID:21401930

  9. The MAP kinase ERK and its scaffold protein MP1 interact with the chromatin regulator Corto during Drosophila wing tissue development.

    Science.gov (United States)

    Mouchel-Vielh, Emmanuèle; Rougeot, Julien; Decoville, Martine; Peronnet, Frédérique

    2011-03-14

    Mitogen-activated protein kinase (MAPK) cascades (p38, JNK, ERK pathways) are involved in cell fate acquisition during development. These kinase modules are associated with scaffold proteins that control their activity. In Drosophila, dMP1, that encodes an ERK scaffold protein, regulates ERK signaling during wing development and contributes to intervein and vein cell differentiation. Functional relationships during wing development between a chromatin regulator, the Enhancer of Trithorax and Polycomb Corto, ERK and its scaffold protein dMP1, are examined here. Genetic interactions show that corto and dMP1 act together to antagonize rolled (which encodes ERK) in the future intervein cells, thus promoting intervein fate. Although Corto, ERK and dMP1 are present in both cytoplasmic and nucleus compartments, they interact exclusively in nucleus extracts. Furthermore, Corto, ERK and dMP1 co-localize on several sites on polytene chromosomes, suggesting that they regulate gene expression directly on chromatin. Finally, Corto is phosphorylated. Interestingly, its phosphorylation pattern differs between cytoplasm and nucleus and changes upon ERK activation. Our data therefore suggest that the Enhancer of Trithorax and Polycomb Corto could participate in regulating vein and intervein genes during wing tissue development in response to ERK signaling.

  10. The MAP kinase ERK and its scaffold protein MP1 interact with the chromatin regulator Corto during Drosophila wing tissue development

    Directory of Open Access Journals (Sweden)

    Peronnet Frédérique

    2011-03-01

    Full Text Available Abstract Background Mitogen-activated protein kinase (MAPK cascades (p38, JNK, ERK pathways are involved in cell fate acquisition during development. These kinase modules are associated with scaffold proteins that control their activity. In Drosophila, dMP1, that encodes an ERK scaffold protein, regulates ERK signaling during wing development and contributes to intervein and vein cell differentiation. Functional relationships during wing development between a chromatin regulator, the Enhancer of Trithorax and Polycomb Corto, ERK and its scaffold protein dMP1, are examined here. Results Genetic interactions show that corto and dMP1 act together to antagonize rolled (which encodes ERK in the future intervein cells, thus promoting intervein fate. Although Corto, ERK and dMP1 are present in both cytoplasmic and nucleus compartments, they interact exclusively in nucleus extracts. Furthermore, Corto, ERK and dMP1 co-localize on several sites on polytene chromosomes, suggesting that they regulate gene expression directly on chromatin. Finally, Corto is phosphorylated. Interestingly, its phosphorylation pattern differs between cytoplasm and nucleus and changes upon ERK activation. Conclusions Our data therefore suggest that the Enhancer of Trithorax and Polycomb Corto could participate in regulating vein and intervein genes during wing tissue development in response to ERK signaling.

  11. Distribution of u.v.-induced repair events in higher-order chromatin loops in human and hamster fibroblasts

    International Nuclear Information System (INIS)

    Mullenders, L.H.F.; Zeeland, A.A. van; Natarajan, A.T.; Kesteren, A.C. van; Bussmann, C.J.M.

    1986-01-01

    The repair of u.v.-induced damage in human and rodent cells was investigated at the level of DNA loops attached to the nuclear matrix. After 2 h post-u.v. incubation, DNase I digestion studies revealed a 3- to 4-fold enrichment of repair-labeled DNA at the nuclear matrix in four xeroderma pigmentosum cell strains belonging to complementation group C. Two xeroderma pigmentosum cell strains of complementation group D and Syrian hamster embryonic cells, as well as in HeLa cells and normal human fibroblasts, no enrichment of repair-labeled DNA at the nuclear matrix was observed. Visualization of repair events in DNA loops by autoradiography of DNA halo - matrix structures confirmed the biochemical observations. The presence or absence of preferential repair of nuclear matrix-associated DNA paralleled the presence or absence of inhomogeneity in the distribution of T4 endonuclease-V-sensitive sites. In xeroderma pigmentosum cells of complementation group C showed that after 2 h post-u.v. incubation, repair events were found at both attachment sites in a limited number of loops and that large domains of loops were not subjected to repair. (author)

  12. Chromatin organisation during Arabidopsis root development

    NARCIS (Netherlands)

    Lorvellec, M.

    2007-01-01

    The genetic information is stored in a highly compact manner in every nucleus. About 150 bp of DNA is packed around a histone octamer constituting a nucleosome. Nucleosomes are linked together by histone H1 and further compaction of this "beads on a string" form higher-order chromatin structures.

  13. Tet2 and Tet3 cooperate with B-lineage transcription factors to regulate DNA modification and chromatin accessibility.

    Science.gov (United States)

    Lio, Chan-Wang; Zhang, Jiayuan; González-Avalos, Edahí; Hogan, Patrick G; Chang, Xing; Rao, Anjana

    2016-11-21

    Ten-eleven translocation (TET) enzymes oxidize 5-methylcytosine, facilitating DNA demethylation and generating new epigenetic marks. Here we show that concomitant loss of Tet2 and Tet3 in mice at early B cell stage blocked the pro- to pre-B cell transition in the bone marrow, decreased Irf4 expression and impaired the germline transcription and rearrangement of the Igκ locus. Tet2/3-deficient pro-B cells showed increased CpG methylation at the Igκ 3' and distal enhancers that was mimicked by depletion of E2A or PU.1, as well as a global decrease in chromatin accessibility at enhancers. Importantly, re-expression of the Tet2 catalytic domain in Tet2/3-deficient B cells resulted in demethylation of the Igκ enhancers and restored their chromatin accessibility. Our data suggest that TET proteins and lineage-specific transcription factors cooperate to influence chromatin accessibility and Igκ enhancer function by modulating the modification status of DNA.

  14. RegulatING chromatin regulators

    DEFF Research Database (Denmark)

    Satpathy, Shankha; Nabbi, Arash; Riabowol, Karl

    2013-01-01

    The five human ING genes encode at least 15 splicing isoforms, most of which affect cell growth, differentiation and apoptosis through their ability to alter gene expression by epigenetic mechanisms. Since their discovery in 1996, ING proteins have been classified as type II tumour suppressors on...

  15. Cardiac-enriched BAF chromatin-remodeling complex subunit Baf60c regulates gene expression programs essential for heart development and function

    Directory of Open Access Journals (Sweden)

    Xin Sun

    2018-01-01

    Full Text Available How chromatin-remodeling complexes modulate gene networks to control organ-specific properties is not well understood. For example, Baf60c (Smarcd3 encodes a cardiac-enriched subunit of the SWI/SNF-like BAF chromatin complex, but its role in heart development is not fully understood. We found that constitutive loss of Baf60c leads to embryonic cardiac hypoplasia and pronounced cardiac dysfunction. Conditional deletion of Baf60c in cardiomyocytes resulted in postnatal dilated cardiomyopathy with impaired contractile function. Baf60c regulates a gene expression program that includes genes encoding contractile proteins, modulators of sarcomere function, and cardiac metabolic genes. Many of the genes deregulated in Baf60c null embryos are targets of the MEF2/SRF co-factor Myocardin (MYOCD. In a yeast two-hybrid screen, we identified MYOCD as a BAF60c interacting factor; we showed that BAF60c and MYOCD directly and functionally interact. We conclude that Baf60c is essential for coordinating a program of gene expression that regulates the fundamental functional properties of cardiomyocytes.

  16. Wigner higher-order spectra: definition, properties, computation and application to transient signal analysis

    OpenAIRE

    Rodríguez Fonollosa, Javier; Nikias, Chrysostomos L.

    1993-01-01

    The Wigner higher order moment spectra (WHOS) are defined as extensions of the Wigner-Ville distribution (WD) to higher order moment spectra domains. A general class of time-frequency higher order moment spectra is also defined in terms of arbitrary higher order moments of the signal as generalizations of the Cohen’s general class of time-frequency representations. The properties of the general class of time-frequency higher order moment spectra can be related to the properties...

  17. The C-terminal domain of Brd2 is important for chromatin interaction and regulation of transcription and alternative splicing

    Czech Academy of Sciences Publication Activity Database

    Hnilicová, Jarmila; Hozeifi, Samira; Stejskalová, Eva; Dušková, Eva; Poser, I.; Humpolíčková, Jana; Hof, Martin; Staněk, David

    2013-01-01

    Roč. 24, č. 22 (2013), s. 3557-3568 ISSN 1059-1524 R&D Projects: GA AV ČR KAN200520801; GA ČR GAP305/10/0424; GA ČR GBP208/12/G016; GA ČR(CZ) GBP305/12/G034 Institutional support: RVO:68378050 ; RVO:61388955 Keywords : Brd2 * alternative splicing * chromatin Subject RIV: EB - Genetics ; Molecular Biology; CF - Physical ; Theoretical Chemistry (UFCH-W) Impact factor: 4.548, year: 2013

  18. Classical and Nonclassical Estrogen Receptor Action on Chromatin Templates

    National Research Council Canada - National Science Library

    Nordeen, Steven

    2000-01-01

    .... Using newly-developed approaches, I investigated mechanisms of estrogen/estrogen receptor action on chromatin templates in vitro in order to better understand the role of chromatin in steroid-regulated gene expression...

  19. Classical and Nonclassical Estrogen Receptor Action on Chromatin Templaces

    National Research Council Canada - National Science Library

    Nordeen, Steve

    2001-01-01

    .... Using newly-developed approaches, I investigated mechanisms of estrogen/estrogen receptor action on chromatin templates in vitro in order to better understand the role of chromatin in steroid-regulated gene expression...

  20. Chromatin Repressive Complexes in Stem Cells, Development, and Cancer

    DEFF Research Database (Denmark)

    Laugesen, Anne; Helin, Kristian

    2014-01-01

    The chromatin environment is essential for the correct specification and preservation of cell identity through modulation and maintenance of transcription patterns. Many chromatin regulators are required for development, stem cell maintenance, and differentiation. Here, we review the roles...

  1. Radiation response and chromatin dynamics

    International Nuclear Information System (INIS)

    Ikura, Tsuyoshi

    2009-01-01

    Described is a recent progress in studies of chromatin structural alterations induced by DNA damage by radiation. DNA in eukaryotes exists in the chromatin structure and different mechanisms of response to damage and repair of DNA from those in prokaryotes have been recognized. Chromatin is composed from its unit structure of mono-nucleosome, which is formed from DNA and an octamer of core histones of H2A, H2B, H3 and H4. When DNA is damaged, histone structural alterations are required for repair factors and checkpoint proteins to access the damaged site. At the actual genome damage, chemical modification of histone to work as a code occurs dependently on the damage where chromatin remodeling factors and histone chaperone participate for structural alteration and remodeling. As well, the exchange of histone variants and fluidization of histones are recently reported. Known chemical modification involves phosphorylation, acetylation and ubiquitination of H2AX (a variant of H2A), and acetylation and methylation of H3. Each complex of TIP60, NuA4 and INO80 is known to be included in the regulation of chromatin with damaged/repaired DNA for remodeling, but little is known about recruitment of the factors concerned at the damage site. Regulatory mechanisms in above chromatin dynamics with consideration of quality and timing of radiation should be further elucidated for understanding the precise response to DNA damage. (K.T.)

  2. Chromatin-bound IκBα regulates a subset of polycomb target genes in differentiation and cancer.

    Science.gov (United States)

    Mulero, María Carmen; Ferres-Marco, Dolors; Islam, Abul; Margalef, Pol; Pecoraro, Matteo; Toll, Agustí; Drechsel, Nils; Charneco, Cristina; Davis, Shelly; Bellora, Nicolás; Gallardo, Fernando; López-Arribillaga, Erika; Asensio-Juan, Elena; Rodilla, Verónica; González, Jessica; Iglesias, Mar; Shih, Vincent; Mar Albà, M; Di Croce, Luciano; Hoffmann, Alexander; Miyamoto, Shigeki; Villà-Freixa, Jordi; López-Bigas, Nuria; Keyes, William M; Domínguez, María; Bigas, Anna; Espinosa, Lluís

    2013-08-12

    IκB proteins are the primary inhibitors of NF-κB. Here, we demonstrate that sumoylated and phosphorylated IκBα accumulates in the nucleus of keratinocytes and interacts with histones H2A and H4 at the regulatory region of HOX and IRX genes. Chromatin-bound IκBα modulates Polycomb recruitment and imparts their competence to be activated by TNFα. Mutations in the Drosophila IκBα gene cactus enhance the homeotic phenotype of Polycomb mutants, which is not counteracted by mutations in dorsal/NF-κB. Oncogenic transformation of keratinocytes results in cytoplasmic IκBα translocation associated with a massive activation of Hox. Accumulation of cytoplasmic IκBα was found in squamous cell carcinoma (SCC) associated with IKK activation and HOX upregulation. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. From higher order thinking to higher order behavior: exploring the relationship between early cognitive skills and social competence in black boys.

    Science.gov (United States)

    Scott, Kristin M; Barbarin, Oscar A; Brown, Jeffrey M

    2013-01-01

    This study examines the relations of higher order (i.e., abstract) thinking (HOT) skills to specific domains of social competence in Black boys (n = 108) attending publicly sponsored prekindergarten (pre-K) programs. Data for the study were collected as part of the National Center for Early Development and Learning (NCEDL) Multi-State Study, a national, longitudinal study examining the quality and outcomes in a representative sample of publicly sponsored pre-K programs in six states (N = 240). Pre-K and kindergarten teachers rated randomly selected children on measures of abstract thinking, self-regulation, and social functioning at the beginning and end of each school year. Applying structural equation modeling, compared with earlier time points, HOT measured in the fall of kindergarten significantly predicted each of the domains of social competence in the spring of kindergarten, with the exception of peer social skills, while controlling for general cognitive ability. Results suggest that early intervention to improve HOT may be an effective and more focused approach to address concerns about Black boys' early social competencies in specific domains and potentially reduce the risk of later social difficulties. © 2013 American Orthopsychiatric Association.

  4. Transcription Through Chromatin - Dynamic Organization of Genes

    Indian Academy of Sciences (India)

    different proteins involved in the synthesis of mRNA from the. DNA template. ... CBP - CREB Binding Protein. CHRAC. Chromatin .... nucleosomal interactions, and thereby change the chromatin structure, as per the ..... methyltransferases in gene regulation is yet to be elucidated. .... Molecular Biology and. Genetics Unit.

  5. The Meaning of Higher-Order Factors in Reflective-Measurement Models

    Science.gov (United States)

    Eid, Michael; Koch, Tobias

    2014-01-01

    Higher-order factor analysis is a widely used approach for analyzing the structure of a multidimensional test. Whenever first-order factors are correlated researchers are tempted to apply a higher-order factor model. But is this reasonable? What do the higher-order factors measure? What is their meaning? Willoughby, Holochwost, Blanton, and Blair…

  6. On the expressiveness and decidability of higher-order process calculi

    NARCIS (Netherlands)

    Lanese, Ivan; Perez, Jorge A.; Sangiorgi, Davide; Schmitt, Alan

    In higher-order process calculi, the values exchanged in communications may contain processes. A core calculus of higher-order concurrency is studied; it has only the operators necessary to express higher-order communications: input prefix, process output, and parallel composition. By exhibiting a

  7. Analysis of Buried Dielectric Objects Using Higher-Order MoM for Volume Integral Equations

    DEFF Research Database (Denmark)

    Kim, Oleksiy S.; Meincke, Peter; Breinbjerg, Olav

    2004-01-01

    A higher-order method of moments (MoM) is applied to solve a volume integral equation for dielectric objects in layered media. In comparison to low-order methods, the higher-order MoM, which is based on higher-order hierarchical Legendre vector basis functions and curvilinear hexahedral elements,...

  8. AP-1-mediated chromatin looping regulates ZEB2 transcription: new insights into TNFα-induced epithelial–mesenchymal transition in triple-negative breast cancer

    Science.gov (United States)

    Qiao, Yichun; Shiue, Chiou-Nan; Zhu, Jian; Zhuang, Ting; Jonsson, Philip; Wright, Anthony P.H.; Zhao, Chunyan; Dahlman-Wright, Karin

    2015-01-01

    The molecular determinants of malignant cell behaviour in triple-negative breast cancer (TNBC) are poorly understood. Recent studies have shown that regulators of epithelial-mesenchymal transition (EMT) are potential therapeutic targets for TNBC. In this study, we demonstrate that the inflammatory cytokine TNFα induces EMT in TNBC cells via activation of AP-1 signaling and subsequently induces expression of the EMT regulator ZEB2. We also show that TNFα activates both the PI3K/Akt and MAPK/ERK pathways, which act upstream of AP-1. We further investigated in detail AP-1 regulation of ZEB2 expression. We show that two ZEB2 transcripts derived from distinct promoters are both expressed in breast cancer cell lines and breast tumor samples. Using the chromosome conformation capture assay, we demonstrate that AP-1, when activated by TNFα, binds to a site in promoter 1b of the ZEB2 gene where it regulates the expression of both promoter 1b and 1a, the latter via mediating long range chromatin interactions. Overall, this work provides a plausible mechanism for inflammation-induced metastatic potential in TNBC, involving a novel regulatory mechanism governing ZEB2 isoform expression. PMID:25762639

  9. Chromatin Remodelers: From Function to Dysfunction

    Directory of Open Access Journals (Sweden)

    Gernot Längst

    2015-06-01

    Full Text Available Chromatin remodelers are key players in the regulation of chromatin accessibility and nucleosome positioning on the eukaryotic DNA, thereby essential for all DNA dependent biological processes. Thus, it is not surprising that upon of deregulation of those molecular machines healthy cells can turn into cancerous cells. Even though the remodeling enzymes are very abundant and a multitude of different enzymes and chromatin remodeling complexes exist in the cell, the particular remodeling complex with its specific nucleosome positioning features must be at the right place at the right time in order to ensure the proper regulation of the DNA dependent processes. To achieve this, chromatin remodeling complexes harbor protein domains that specifically read chromatin targeting signals, such as histone modifications, DNA sequence/structure, non-coding RNAs, histone variants or DNA bound interacting proteins. Recent studies reveal the interaction between non-coding RNAs and chromatin remodeling complexes showing importance of RNA in remodeling enzyme targeting, scaffolding and regulation. In this review, we summarize current understanding of chromatin remodeling enzyme targeting to chromatin and their role in cancer development.

  10. A hierarchical generalization of the acoustic reciprocity theorem involving higher-order derivatives and interaction quantities.

    Science.gov (United States)

    Lin, Ju; Li, Jie; Li, Xiaolei; Wang, Ning

    2016-10-01

    An acoustic reciprocity theorem is generalized, for a smoothly varying perturbed medium, to a hierarchy of reciprocity theorems including higher-order derivatives of acoustic fields. The standard reciprocity theorem is the first member of the hierarchy. It is shown that the conservation of higher-order interaction quantities is related closely to higher-order derivative distributions of perturbed media. Then integral reciprocity theorems are obtained by applying Gauss's divergence theorem, which give explicit integral representations connecting higher-order interactions and higher-order derivative distributions of perturbed media. Some possible applications to an inverse problem are also discussed.

  11. Method of moments solution of volume integral equations using higher-order hierarchical Legendre basis functions

    DEFF Research Database (Denmark)

    Kim, Oleksiy S.; Jørgensen, Erik; Meincke, Peter

    2004-01-01

    An efficient higher-order method of moments (MoM) solution of volume integral equations is presented. The higher-order MoM solution is based on higher-order hierarchical Legendre basis functions and higher-order geometry modeling. An unstructured mesh composed of 8-node trilinear and/or curved 27...... of magnitude in comparison to existing higher-order hierarchical basis functions. Consequently, an iterative solver can be applied even for high expansion orders. Numerical results demonstrate excellent agreement with the analytical Mie series solution for a dielectric sphere as well as with results obtained...

  12. Chromatin Remodeling and Plant Immunity.

    Science.gov (United States)

    Chen, W; Zhu, Q; Liu, Y; Zhang, Q

    Chromatin remodeling, an important facet of the regulation of gene expression in eukaryotes, is performed by two major types of multisubunit complexes, covalent histone- or DNA-modifying complexes, and ATP-dependent chromosome remodeling complexes. Snf2 family DNA-dependent ATPases constitute the catalytic subunits of ATP-dependent chromosome remodeling complexes, which accounts for energy supply during chromatin remodeling. Increasing evidence indicates a critical role of chromatin remodeling in the establishment of long-lasting, even transgenerational immune memory in plants, which is supported by the findings that DNA methylation, histone deacetylation, and histone methylation can prime the promoters of immune-related genes required for disease defense. So what are the links between Snf2-mediated ATP-dependent chromosome remodeling and plant immunity, and what mechanisms might support its involvement in disease resistance? © 2017 Elsevier Inc. All rights reserved.

  13. Map of open and closed chromatin domains in Drosophila genome.

    Science.gov (United States)

    Milon, Beatrice; Sun, Yezhou; Chang, Weizhong; Creasy, Todd; Mahurkar, Anup; Shetty, Amol; Nurminsky, Dmitry; Nurminskaya, Maria

    2014-11-18

    Chromatin compactness has been considered a major determinant of gene activity and has been associated with specific chromatin modifications in studies on a few individual genetic loci. At the same time, genome-wide patterns of open and closed chromatin have been understudied, and are at present largely predicted from chromatin modification and gene expression data. However the universal applicability of such predictions is not self-evident, and requires experimental verification. We developed and implemented a high-throughput analysis for general chromatin sensitivity to DNase I which provides a comprehensive epigenomic assessment in a single assay. Contiguous domains of open and closed chromatin were identified by computational analysis of the data, and correlated to other genome annotations including predicted chromatin "states", individual chromatin modifications, nuclear lamina interactions, and gene expression. While showing that the widely trusted predictions of chromatin structure are correct in the majority of cases, we detected diverse "exceptions" from the conventional rules. We found a profound paucity of chromatin modifications in a major fraction of closed chromatin, and identified a number of loci where chromatin configuration is opposite to that expected from modification and gene expression patterns. Further, we observed that chromatin of large introns tends to be closed even when the genes are expressed, and that a significant proportion of active genes including their promoters are located in closed chromatin. These findings reveal limitations of the existing predictive models, indicate novel mechanisms of epigenetic regulation, and provide important insights into genome organization and function.

  14. Gene expression profiling of prostate tissue identifies chromatin regulation as a potential link between obesity and lethal prostate cancer.

    Science.gov (United States)

    Ebot, Ericka M; Gerke, Travis; Labbé, David P; Sinnott, Jennifer A; Zadra, Giorgia; Rider, Jennifer R; Tyekucheva, Svitlana; Wilson, Kathryn M; Kelly, Rachel S; Shui, Irene M; Loda, Massimo; Kantoff, Philip W; Finn, Stephen; Vander Heiden, Matthew G; Brown, Myles; Giovannucci, Edward L; Mucci, Lorelei A

    2017-11-01

    Obese men are at higher risk of advanced prostate cancer and cancer-specific mortality; however, the biology underlying this association remains unclear. This study examined gene expression profiles of prostate tissue to identify biological processes differentially expressed by obesity status and lethal prostate cancer. Gene expression profiling was performed on tumor (n = 402) and adjacent normal (n = 200) prostate tissue from participants in 2 prospective cohorts who had been diagnosed with prostate cancer from 1982 to 2005. Body mass index (BMI) was calculated from the questionnaire immediately preceding cancer diagnosis. Men were followed for metastases or prostate cancer-specific death (lethal disease) through 2011. Gene Ontology biological processes differentially expressed by BMI were identified using gene set enrichment analysis. Pathway scores were computed by averaging the signal intensities of member genes. Odds ratios (ORs) for lethal prostate cancer were estimated with logistic regression. Among 402 men, 48% were healthy weight, 31% were overweight, and 21% were very overweight/obese. Fifteen gene sets were enriched in tumor tissue, but not normal tissue, of very overweight/obese men versus healthy-weight men; 5 of these were related to chromatin modification and remodeling (false-discovery rate 7, 41% vs 17%; P = 2 × 10 -4 ) and an increased risk of lethal disease that was independent of grade and stage (OR, 5.26; 95% confidence interval, 2.37-12.25). This study improves our understanding of the biology of aggressive prostate cancer and identifies a potential mechanistic link between obesity and prostate cancer death that warrants further study. Cancer 2017;123:4130-4138. © 2017 American Cancer Society. © 2017 American Cancer Society.

  15. Chromatin is wonderful stuff.

    NARCIS (Netherlands)

    van Driel, R.

    2007-01-01

    Chromatin molecules have properties that set them aside from all other biomacromolecules in the cell. (i) Chromosomes, which are single chromatin molecules, are the largest macromolecules in eukaryotic cells. (ii) Chromatin molecules carry the cell's genetic and epigenetic information and all

  16. Global chromatin fibre compaction in response to DNA damage

    International Nuclear Information System (INIS)

    Hamilton, Charlotte; Hayward, Richard L.; Gilbert, Nick

    2011-01-01

    Highlights: ► Robust KAP1 phosphorylation in response to DNA damage in HCT116 cells. ► DNA repair foci are found in soluble chromatin. ► Biophysical analysis reveals global chromatin fibre compaction after DNA damage. ► DNA damage is accompanied by rapid linker histone dephosphorylation. -- Abstract: DNA is protected by packaging it into higher order chromatin fibres, but this can impede nuclear processes like DNA repair. Despite considerable research into the factors required for signalling and repairing DNA damage, it is unclear if there are concomitant changes in global chromatin fibre structure. In human cells DNA double strand break (DSB) formation triggers a signalling cascade resulting in H2AX phosphorylation (γH2AX), the rapid recruitment of chromatin associated proteins and the subsequent repair of damaged sites. KAP1 is a transcriptional corepressor and in HCT116 cells we found that after DSB formation by chemicals or ionising radiation there was a wave of, predominantly ATM dependent, KAP1 phosphorylation. Both KAP1 and phosphorylated KAP1 were readily extracted from cells indicating they do not have a structural role and γH2AX was extracted in soluble chromatin indicating that sites of damage are not attached to an underlying structural matrix. After DSB formation we did not find a concomitant change in the sensitivity of chromatin fibres to micrococcal nuclease digestion. Therefore to directly investigate higher order chromatin fibre structures we used a biophysical sedimentation technique based on sucrose gradient centrifugation to compare the conformation of chromatin fibres isolated from cells before and after DNA DSB formation. After damage we found global chromatin fibre compaction, accompanied by rapid linker histone dephosphorylation, consistent with fibres being more regularly folded or fibre deformation being stabilized by linker histones. We suggest that following DSB formation, although there is localised chromatin unfolding to

  17. A higher-order numerical framework for stochastic simulation of chemical reaction systems.

    KAUST Repository

    Székely, Tamás

    2012-07-15

    BACKGROUND: In this paper, we present a framework for improving the accuracy of fixed-step methods for Monte Carlo simulation of discrete stochastic chemical kinetics. Stochasticity is ubiquitous in many areas of cell biology, for example in gene regulation, biochemical cascades and cell-cell interaction. However most discrete stochastic simulation techniques are slow. We apply Richardson extrapolation to the moments of three fixed-step methods, the Euler, midpoint and θ-trapezoidal τ-leap methods, to demonstrate the power of stochastic extrapolation. The extrapolation framework can increase the order of convergence of any fixed-step discrete stochastic solver and is very easy to implement; the only condition for its use is knowledge of the appropriate terms of the global error expansion of the solver in terms of its stepsize. In practical terms, a higher-order method with a larger stepsize can achieve the same level of accuracy as a lower-order method with a smaller one, potentially reducing the computational time of the system. RESULTS: By obtaining a global error expansion for a general weak first-order method, we prove that extrapolation can increase the weak order of convergence for the moments of the Euler and the midpoint τ-leap methods, from one to two. This is supported by numerical simulations of several chemical systems of biological importance using the Euler, midpoint and θ-trapezoidal τ-leap methods. In almost all cases, extrapolation results in an improvement of accuracy. As in the case of ordinary and stochastic differential equations, extrapolation can be repeated to obtain even higher-order approximations. CONCLUSIONS: Extrapolation is a general framework for increasing the order of accuracy of any fixed-step stochastic solver. This enables the simulation of complicated systems in less time, allowing for more realistic biochemical problems to be solved.

  18. Mathematics Teachers’ Interpretation of Higher-Order Thinking in Bloom’s Taxonomy

    OpenAIRE

    Tony Thompson

    2008-01-01

    This study investigated mathematics teachers’ interpretation of higher-order thinking in Bloom’s Taxonomy. Thirty-two high school mathematics teachers from the southeast U.S. were asked to (a) define lower- and higher-order thinking, (b) identify which thinking skills in Bloom’s Taxonomy represented lower- and higher-order thinking, and (c) create an Algebra I final exam item representative of each thinking skill. Results indicate that mathematics teachers have difficulty interpreting the thi...

  19. Chromatin Structure and Function

    CERN Document Server

    Wolffe, Alan P

    1999-01-01

    The Third Edition of Chromatin: Structure and Function brings the reader up-to-date with the remarkable progress in chromatin research over the past three years. It has been extensively rewritten to cover new material on chromatin remodeling, histone modification, nuclear compartmentalization, DNA methylation, and transcriptional co-activators and co-repressors. The book is written in a clear and concise fashion, with 60 new illustrations. Chromatin: Structure and Function provides the reader with a concise and coherent account of the nature, structure, and assembly of chromatin and its active

  20. PRE-SERVICE MATHEMATICS TEACHERS’ CONCEPTION OF HIGHER-ORDER THINKING LEVEL IN BLOOM'S TAXONOMY

    OpenAIRE

    Damianus D Samo

    2017-01-01

    The purpose of this study is to explore pre-service mathematics teachers' conception of higher-order thinking in Bloom's Taxonomy, to explore pre-service mathematics teachers' ability in categorizing six cognitive levels of Bloom's Taxonomy as lower-order thinking and higher-order thinking, and pre-service mathematics teachers' ability in identifying some questionable items as lower-order and higher-order thinking. The higher-order thinking is the type of non-algorithm thinking which include ...

  1. Analysis and Improvement of the Generic Higher-Order Masking Scheme of FSE 2012

    OpenAIRE

    Roy, Arnab; Venkatesh, Srinivas Vivek

    2013-01-01

    Masking is a well-known technique used to prevent block cipher implementations from side-channel attacks. Higher-order side channel attacks (e.g. higher-order DPA attack) on widely used block cipher like AES have motivated the design of efficient higher-order masking schemes. Indeed, it is known that as the masking order increases, the difficulty of side-channel attack increases exponentially. However, the main problem in higher-order masking is to design an efficient and secure technique for...

  2. Neuronal migration is regulated by endogenous RNAi and chromatin-binding factor ZFP-1/AF10 in Caenorhabditis elegans.

    Science.gov (United States)

    Kennedy, Lisa M; Grishok, Alla

    2014-05-01

    Endogenous short RNAs and the conserved plant homeodomain (PHD) zinc-finger protein ZFP-1/AF10 regulate overlapping sets of genes in Caenorhabditis elegans, which suggests that they control common biological pathways. We have shown recently that the RNAi factor RDE-4 and ZFP-1 negatively modulate transcription of the insulin/PI3 signaling-dependent kinase PDK-1 to promote C. elegans fitness. Moreover, we have demonstrated that the insulin/IGF-1-PI3K-signaling pathway regulates the activity of the DAF-16/FOXO transcription factor in the hypodermis to nonautonomously promote the anterior migrations of the hermaphrodite-specific neurons (HSNs) during embryogenesis of C. elegans. In this study, we implicate the PHD-containing isoform of ZFP-1 and endogenous RNAi in the regulation of HSN migration. ZFP-1 affects HSN migration in part through its negative effect on pdk-1 transcription and modulation of downstream DAF-16 activity. We also identify a novel role for ZFP-1 and RNAi pathway components, including RDE-4, in the regulation of HSN migration in parallel with DAF-16. Therefore, the coordinated activities of DAF-16, ZFP-1, and endogenous RNAi contribute to gene regulation during development to ensure proper neuronal positioning.

  3. Mediator binds to boundaries of chromosomal interaction domains and to proteins involved in DNA looping, RNA metabolism, chromatin remodeling, and actin assembly.

    Science.gov (United States)

    Chereji, Razvan V; Bharatula, Vasudha; Elfving, Nils; Blomberg, Jeanette; Larsson, Miriam; Morozov, Alexandre V; Broach, James R; Björklund, Stefan

    2017-09-06

    Mediator is a multi-unit molecular complex that plays a key role in transferring signals from transcriptional regulators to RNA polymerase II in eukaryotes. We have combined biochemical purification of the Saccharomyces cerevisiae Mediator from chromatin with chromatin immunoprecipitation in order to reveal Mediator occupancy on DNA genome-wide, and to identify proteins interacting specifically with Mediator on the chromatin template. Tandem mass spectrometry of proteins in immunoprecipitates of mediator complexes revealed specific interactions between Mediator and the RSC, Arp2/Arp3, CPF, CF 1A and Lsm complexes in chromatin. These factors are primarily involved in chromatin remodeling, actin assembly, mRNA 3'-end processing, gene looping and mRNA decay, but they have also been shown to enter the nucleus and participate in Pol II transcription. Moreover, we have found that Mediator, in addition to binding Pol II promoters, occupies chromosomal interacting domain (CID) boundaries and that Mediator in chromatin associates with proteins that have been shown to interact with CID boundaries, such as Sth1, Ssu72 and histone H4. This suggests that Mediator plays a significant role in higher-order genome organization. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  4. Authentic Instruction for 21st Century Learning: Higher Order Thinking in an Inclusive School

    Science.gov (United States)

    Preus, Betty

    2012-01-01

    The author studied a public junior high school identified as successfully implementing authentic instruction. Such instruction emphasizes higher order thinking, deep knowledge, substantive conversation, and value beyond school. To determine in what ways higher order thinking was fostered both for students with and without disabilities, the author…

  5. An Investigation of Higher-Order Thinking Skills in Smaller Learning Community Social Studies Classrooms

    Science.gov (United States)

    Fischer, Christopher; Bol, Linda; Pribesh, Shana

    2011-01-01

    This study investigated the extent to which higher-order thinking skills are promoted in social studies classes in high schools that are implementing smaller learning communities (SLCs). Data collection in this mixed-methods study included classroom observations and in-depth interviews. Findings indicated that higher-order thinking was rarely…

  6. From "Hello" to Higher-Order Thinking: The Effect of Coaching and Feedback on Online Chats

    Science.gov (United States)

    Stein, David S.; Wanstreet, Constance E.; Slagle, Paula; Trinko, Lynn A.; Lutz, Michelle

    2013-01-01

    This exploratory study examined the effect of a coaching and feedback intervention in teaching presence and social presence on higher-order thinking in an online community of inquiry. Coaching occurred before each chat, and feedback was provided immediately afterwards. The findings suggest that over time, the frequency of higher-order thinking…

  7. Comparing higher order models for the EORTC QLQ-C30

    DEFF Research Database (Denmark)

    Gundy, Chad M; Fayers, Peter M; Grønvold, Mogens

    2012-01-01

    To investigate the statistical fit of alternative higher order models for summarizing the health-related quality of life profile generated by the EORTC QLQ-C30 questionnaire.......To investigate the statistical fit of alternative higher order models for summarizing the health-related quality of life profile generated by the EORTC QLQ-C30 questionnaire....

  8. Teaching Higher Order Thinking in the Introductory MIS Course: A Model-Directed Approach

    Science.gov (United States)

    Wang, Shouhong; Wang, Hai

    2011-01-01

    One vision of education evolution is to change the modes of thinking of students. Critical thinking, design thinking, and system thinking are higher order thinking paradigms that are specifically pertinent to business education. A model-directed approach to teaching and learning higher order thinking is proposed. An example of application of the…

  9. Exact Solutions to Nonlinear Schroedinger Equation and Higher-Order Nonlinear Schroedinger Equation

    International Nuclear Information System (INIS)

    Ren Ji; Ruan Hangyu

    2008-01-01

    We study solutions of the nonlinear Schroedinger equation (NLSE) and higher-order nonlinear Schroedinger equation (HONLSE) with variable coefficients. By considering all the higher-order effect of HONLSE as a new dependent variable, the NLSE and HONLSE can be changed into one equation. Using the generalized Lie group reduction method (GLGRM), the abundant solutions of NLSE and HONLSE are obtained

  10. Higher Order Thinking Skills among Secondary School Students in Science Learning

    Science.gov (United States)

    Saido, Gulistan Mohammed; Siraj, Saedah; Bin Nordin, Abu Bakar; Al Amedy, Omed Saadallah

    2015-01-01

    A central goal of science education is to help students to develop their higher order thinking skills to enable them to face the challenges of daily life. Enhancing students' higher order thinking skills is the main goal of the Kurdish Science Curriculum in the Iraqi-Kurdistan region. This study aimed at assessing 7th grade students' higher order…

  11. The Relationship between Higher Order Thinking Skills and Academic Performance of Student in Mathematics Instruction

    Science.gov (United States)

    Tanujaya, Benidiktus; Mumu, Jeinne; Margono, Gaguk

    2017-01-01

    Higher order thinking skills (HOTS) is one of important aspects in education. Students with high level of higher order thinking skills tend to be more successful. However, do this phenomenon also happen in the learning of Mathematics? To answer this question, this research aims to study the relationship between HOTS and students' academic…

  12. Multi-domain, higher order level set scheme for 3D image segmentation on the GPU

    DEFF Research Database (Denmark)

    Sharma, Ojaswa; Zhang, Qin; Anton, François

    2010-01-01

    to evaluate level set surfaces that are $C^2$ continuous, but are slow due to high computational burden. In this paper, we provide a higher order GPU based solver for fast and efficient segmentation of large volumetric images. We also extend the higher order method to multi-domain segmentation. Our streaming...

  13. Higher-order blackhole solutions in N=2 supergravity and Calabi-Yau string backgrounds

    NARCIS (Netherlands)

    Behrndt, K.; Cardoso, G.L.; de Wit, B.Q.P.J.; Lüst, D.; Mohaupt, T.; Sabra, W.A.

    1998-01-01

    Based on special geometry, we consider corrections to N=2 extremal black-hole solutions and their entropies originating from higher-order derivative terms in N=2 supergravity. These corrections are described by a holomorphic function, and the higher-order black-hole solutions can be expressed in

  14. Construction of special eye models for investigation of chromatic and higher-order aberrations of eyes.

    Science.gov (United States)

    Zhai, Yi; Wang, Yan; Wang, Zhaoqi; Liu, Yongji; Zhang, Lin; He, Yuanqing; Chang, Shengjiang

    2014-01-01

    An achromatic element eliminating only longitudinal chromatic aberration (LCA) while maintaining transverse chromatic aberration (TCA) is established for the eye model, which involves the angle formed by the visual and optical axis. To investigate the impacts of higher-order aberrations on vision, the actual data of higher-order aberrations of human eyes with three typical levels are introduced into the eye model along visual axis. Moreover, three kinds of individual eye models are established to investigate the impacts of higher-order aberrations, chromatic aberration (LCA+TCA), LCA and TCA on vision under the photopic condition, respectively. Results show that for most human eyes, the impact of chromatic aberration on vision is much stronger than that of higher-order aberrations, and the impact of LCA in chromatic aberration dominates. The impact of TCA is approximately equal to that of normal level higher-order aberrations and it can be ignored when LCA exists.

  15. The Higher Order Structure of Environmental Attitudes: A Cross-Cultural Examination

    Directory of Open Access Journals (Sweden)

    Taciano L. Milfont

    2010-01-01

    Full Text Available Past research has suggested that Preservation and Utilization are the two higher order dimensions forming the hierarchical structure of environmental attitudes. This means that these two higher order dimensions could group all kinds of perceptions or beliefs regarding the natural environment people have. A crosscultural study was conducted in Brazil, New Zealand, and South Africa to test this hierarchical structure of environmental attitudes. Results from single- and multi-group confirmatory factor analyses demonstrated that environmental attitudes are a multidimensional construct, and that their first-order factors associate to each other to form a vertical structure. However, the question whether the vertical structure comprise a single higher order factor or two higher order factors still remains unanswered. These results are discussed and directions for future research trying to demonstrate that Preservation and Utilization, taken as distinct second-order environmental attitudes factors, are more empirically meaningful than a single and generalised environmental attitudes higher order factor are presented.

  16. Autism-Associated Chromatin Regulator Brg1/SmarcA4 Is Required for Synapse Development and Myocyte Enhancer Factor 2-Mediated Synapse Remodeling.

    Science.gov (United States)

    Zhang, Zilai; Cao, Mou; Chang, Chia-Wei; Wang, Cindy; Shi, Xuanming; Zhan, Xiaoming; Birnbaum, Shari G; Bezprozvanny, Ilya; Huber, Kimberly M; Wu, Jiang I

    2016-01-01

    Synapse development requires normal neuronal activities and the precise expression of synapse-related genes. Dysregulation of synaptic genes results in neurological diseases such as autism spectrum disorders (ASD). Mutations in genes encoding chromatin-remodeling factor Brg1/SmarcA4 and its associated proteins are the genetic causes of several developmental diseases with neurological defects and autistic symptoms. Recent large-scale genomic studies predicted Brg1/SmarcA4 as one of the key nodes of the ASD gene network. We report that Brg1 deletion in early postnatal hippocampal neurons led to reduced dendritic spine density and maturation and impaired synapse activities. In developing mice, neuronal Brg1 deletion caused severe neurological defects. Gene expression analyses indicated that Brg1 regulates a significant number of genes known to be involved in synapse function and implicated in ASD. We found that Brg1 is required for dendritic spine/synapse elimination mediated by the ASD-associated transcription factor myocyte enhancer factor 2 (MEF2) and that Brg1 regulates the activity-induced expression of a specific subset of genes that overlap significantly with the targets of MEF2. Our analyses showed that Brg1 interacts with MEF2 and that MEF2 is required for Brg1 recruitment to target genes in response to neuron activation. Thus, Brg1 plays important roles in both synapse development/maturation and MEF2-mediated synapse remodeling. Our study reveals specific functions of the epigenetic regulator Brg1 in synapse development and provides insights into its role in neurological diseases such as ASD. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  17. 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...

  18. Verifying object-oriented programs with higher-order separation logic in Coq

    DEFF Research Database (Denmark)

    Bengtson, Jesper; Jensen, Jonas Braband; Sieczkowski, Filip

    2011-01-01

    We present a shallow Coq embedding of a higher-order separation logic with nested triples for an object-oriented programming language. Moreover, we develop novel specification and proof patterns for reasoning in higher-order separation logic with nested triples about programs that use interfaces...... and interface inheritance. In particular, we show how to use the higher-order features of the Coq formalisation to specify and reason modularly about programs that (1) depend on some unknown code satisfying a specification or that (2) return objects conforming to a certain specification. All of our results have...

  19. Lagrangian-Hamiltonian unified formalism for autonomous higher order dynamical systems

    International Nuclear Information System (INIS)

    Prieto-Martinez, Pedro Daniel; Roman-Roy, Narciso

    2011-01-01

    The Lagrangian-Hamiltonian unified formalism of Skinner and Rusk was originally stated for autonomous dynamical systems in classical mechanics. It has been generalized for non-autonomous first-order mechanical systems, as well as for first-order and higher order field theories. However, a complete generalization to higher order mechanical systems is yet to be described. In this work, after reviewing the natural geometrical setting and the Lagrangian and Hamiltonian formalisms for higher order autonomous mechanical systems, we develop a complete generalization of the Lagrangian-Hamiltonian unified formalism for these kinds of systems, and we use it to analyze some physical models from this new point of view. (paper)

  20. Higher order capacity statistics of multi-hop transmission systems over Rayleigh fading channels

    KAUST Repository

    Yilmaz, Ferkan

    2012-03-01

    In this paper, we present an exact analytical expression to evaluate the higher order statistics of the channel capacity for amplify and forward (AF) multihop transmission systems operating over Rayleigh fading channels. Furthermore, we present simple and efficient closed-form expression to the higher order moments of the channel capacity of dual hop transmission system with Rayleigh fading channels. In order to analyze the behavior of the higher order capacity statistics and investigate the usefulness of the mathematical analysis, some selected numerical and simulation results are presented. Our results are found to be in perfect agreement. © 2012 IEEE.

  1. Modular specification and verification for higher-order languages with state

    DEFF Research Database (Denmark)

    Svendsen, Kasper

    The overall topic of this thesis is modular reasoning for higher-order languages with state. The thesis consists of four mostly independent chapters that each deal with a different aspect of reasoning about higher-order languages with state. The unifying theme throughout all four chapters is higher....... The third chapter of the thesis is a case study of the C# joins library. What makes this library interesting as a case study is that it combines a lot of advanced features (higher-order code with effects, concurrency, recursion through the store, shared mutable state, and fine-grained synchronization...

  2. Analysis of Scattering by Inhomogeneous Dielectric Objects Using Higher-Order Hierarchical MoM

    DEFF Research Database (Denmark)

    Kim, Oleksiy S.; Jørgensen, Erik; Meincke, Peter

    2003-01-01

    An efficient technique for the analysis of electromagnetic scattering by arbitrary shaped inhomogeneous dielectric objects is presented. The technique is based on a higher-order method of moments (MoM) solution of the volume integral equation. This higher-order MoM solution comprises recently...... that the condition number of the resulting MoM matrix is reduced by several orders of magnitude in comparison to existing higher-order hierarchical basis functions and, consequently, an iterative solver can be applied even for high expansion orders. Numerical results demonstrate excellent agreement...

  3. Generating higher-order Lie algebras by expanding Maurer-Cartan forms

    International Nuclear Information System (INIS)

    Caroca, R.; Merino, N.; Salgado, P.; Perez, A.

    2009-01-01

    By means of a generalization of the Maurer-Cartan expansion method, we construct a procedure to obtain expanded higher-order Lie algebras. The expanded higher-order Maurer-Cartan equations for the case G=V 0 +V 1 are found. A dual formulation for the S-expansion multialgebra procedure is also considered. The expanded higher-order Maurer-Cartan equations are recovered from S-expansion formalism by choosing a special semigroup. This dual method could be useful in finding a generalization to the case of a generalized free differential algebra, which may be relevant for physical applications in, e.g., higher-spin gauge theories.

  4. Modeling 3D PCMI using the Extended Finite Element Method with higher order elements

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, W. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Spencer, Benjamin W. [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2017-03-31

    This report documents the recent development to enable XFEM to work with higher order elements. It also demonstrates the application of higher order (quadratic) elements to both 2D and 3D models of PCMI problems, where discrete fractures in the fuel are represented using XFEM. The modeling results demonstrate the ability of the higher order XFEM to accurately capture the effects of a crack on the response in the vicinity of the intersecting surfaces of cracked fuel and cladding, as well as represent smooth responses in the regions away from the crack.

  5. High motivation for exercise is associated with altered chromatin regulators of monoamine receptor gene expression in the striatum of selectively bred mice.

    Science.gov (United States)

    Saul, M C; Majdak, P; Perez, S; Reilly, M; Garland, T; Rhodes, J S

    2017-03-01

    Although exercise is critical for health, many lack the motivation to exercise, and it is unclear how motivation might be increased. To uncover the molecular underpinnings of increased motivation for exercise, we analyzed the transcriptome of the striatum in four mouse lines selectively bred for high voluntary wheel running and four non-selected control lines. The striatum was dissected and RNA was extracted and sequenced from four individuals of each line. We found multiple genes and gene systems with strong relationships to both selection and running history over the previous 6 days. Among these genes were Htr1b, a serotonin receptor subunit and Slc38a2, a marker for both glutamatergic and γ-aminobutyric acid (GABA)-ergic signaling. System analysis of the raw results found enrichment of transcriptional regulation and kinase genes. Further, we identified a splice variant affecting the Wnt-related Golgi signaling gene Tmed5. Using coexpression network analysis, we found a cluster of interrelated coexpression modules with relationships to running behavior. From these modules, we built a network correlated with running that predicts a mechanistic relationship between transcriptional regulation by nucleosome structure and Htr1b expression. The Library of Integrated Network-Based Cellular Signatures identified the protein kinase C δ inhibitor, rottlerin, the tyrosine kinase inhibitor, Linifanib and the delta-opioid receptor antagonist 7-benzylidenenaltrexone as potential compounds for increasing the motivation to run. Taken together, our findings support a neurobiological framework of exercise motivation where chromatin state leads to differences in dopamine signaling through modulation of both the primary neurotransmitters glutamate and GABA, and by neuromodulators such as serotonin. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  6. Higher-Order Blind Signal Feature Separation: An Enabling Technology for Battlefield Awareness

    National Research Council Canada - National Science Library

    Su, Wei; Kosinski, John A

    2006-01-01

    Higher-order transform blind signal feature classification is discussed for separating bar-shaped, circular, squared, circular-squared, and offset-diamonded constellation patterns of digital linear signals...

  7. Higher-Order Wavefront Aberrations for Populations of Young Emmetropes and Myopes

    Directory of Open Access Journals (Sweden)

    Jinhua Bao

    2009-01-01

    Conclusions: Human eyes have systematical higher order aberrations in population, and factors that cause bilateral symmetry of wavefront aberrations between the right and left eyes made important contribution to the systematical aberrations.

  8. A Content Analysis of General Chemistry Laboratory Manuals for Evidence of Higher-Order Cognitive Tasks

    Science.gov (United States)

    Domin, Daniel S.

    1999-01-01

    The science laboratory instructional environment is ideal for fostering the development of problem-solving, manipulative, and higher-order thinking skills: the skills needed by today's learner to compete in an ever increasing technology-based society. This paper reports the results of a content analysis of ten general chemistry laboratory manuals. Three experiments from each manual were examined for evidence of higher-order cognitive activities. Analysis was based upon the six major cognitive categories of Bloom's Taxonomy of Educational Objectives: knowledge, comprehension, application, analysis, synthesis, and evaluation. The results of this study show that the overwhelming majority of general chemistry laboratory manuals provide tasks that require the use of only the lower-order cognitive skills: knowledge, comprehension, and application. Two of the laboratory manuals were disparate in having activities that utilized higher-order cognition. I describe the instructional strategies used within these manuals to foster higher-order cognitive development.

  9. The Need to Deliver Higher-Order Skills in the Context of Marketing in SMEs

    Science.gov (United States)

    Copley, Paul

    2013-01-01

    It is argued that the delivery of learning and the development of skills and competences are central to SME success; and there appears to be a requirement for higher-order education and training that can deliver a

  10. Covariant quantization of infinite spin particle models, and higher order gauge theories

    International Nuclear Information System (INIS)

    Edgren, Ludde; Marnelius, Robert

    2006-01-01

    Further properties of a recently proposed higher order infinite spin particle model are derived. Infinitely many classically equivalent but different Hamiltonian formulations are shown to exist. This leads to a condition of uniqueness in the quantization process. A consistent covariant quantization is shown to exist. Also a recently proposed supersymmetric version for half-odd integer spins is quantized. A general algorithm to derive gauge invariances of higher order Lagrangians is given and applied to the infinite spin particle model, and to a new higher order model for a spinning particle which is proposed here, as well as to a previously given higher order rigid particle model. The latter two models are also covariantly quantized

  11. Higher-order asymptotic homogenization of periodic materials with low scale separation

    NARCIS (Netherlands)

    Ameen, M.M.; Peerlings, R.H.J.; Geers, M.G.D

    2016-01-01

    In this work, we investigate the limits of classical homogenization theories pertaining to homogenization of periodic linear elastic composite materials at low scale separations and demonstrate the effectiveness of higher-order periodic homogenization in alleviating this limitation. Classical

  12. Higher Order Thinking in the Australian Army Suite of Logistic Officer Courses

    National Research Council Canada - National Science Library

    Bradford, Scott R

    2006-01-01

    .... The current Suite of Logistic Officer Courses (SOLOC) has been recently criticized for failing to meet this requirement, with the general perception that there is a distinct lack of higher-order thinking competencies within this continuum...

  13. Non-Poisson Dichotomous Noise: Higher-Order Correlation Functions and Aging

    National Research Council Canada - National Science Library

    Allegrini, Paolo; Grigolini, Paolo; Palatella, Luigi; West, Bruce J

    2004-01-01

    .... The transition of psi(tau) from the exponential to the nonexponential condition yields the breakdown of the usual factorization condition of higher-order correlation functions, as well as the birth of aging effects...

  14. Higher order modes excitation of electrostatically actuated clamped–clamped microbeams: experimental and analytical investigation

    KAUST Repository

    Jaber, Nizar; Ramini, Abdallah; Carreno, Armando Arpys Arevalo; Younis, Mohammad I.

    2016-01-01

    © 2016 IOP Publishing Ltd. In this study, we demonstrate analytically and experimentally the excitations of the higher order modes of vibrations in electrostatically actuated clamped-clamped microbeam resonators. The concept is based on using

  15. A stable higher order space time Galerkin marching-on-in-time scheme

    KAUST Repository

    Pray, Andrew J.; Shanker, Balasubramaniam; Bagci, Hakan

    2013-01-01

    We present a method for the stable solution of time-domain integral equations. The method uses a technique developed in [1] to accurately evaluate matrix elements. As opposed to existing stabilization schemes, the method presented uses higher order

  16. Connection between weighted LPC and higher-order statistics for AR model estimation

    NARCIS (Netherlands)

    Kamp, Y.; Ma, C.

    1993-01-01

    This paper establishes the relationship between a weighted linear prediction method used for robust analysis of voiced speech and the autoregressive modelling based on higher-order statistics, known as cumulants

  17. Deformation from symmetry for Schrodinger equations of higher order on unbounded domains

    Directory of Open Access Journals (Sweden)

    Addolorata Salvatore

    2003-06-01

    Full Text Available By means of a perturbation method recently introduced by Bolle, we discuss the existence of infinitely many solutions for a class of perturbed symmetric higher order Schrodinger equations with non-homogeneous boundary data on unbounded domains.

  18. Exact solutions for the higher-order nonlinear Schoerdinger equation in nonlinear optical fibres

    International Nuclear Information System (INIS)

    Liu Chunping

    2005-01-01

    First, by using the generally projective Riccati equation method, many kinds of exact solutions for the higher-order nonlinear Schoerdinger equation in nonlinear optical fibres are obtained in a unified way. Then, some relations among these solutions are revealed

  19. Visualization and processing of higher order descriptors for multi-valued data

    CERN Document Server

    Schultz, Thomas

    2015-01-01

    Modern imaging techniques and computational simulations yield complex multi-valued data that require higher-order mathematical descriptors. This book addresses topics of importance when dealing with such data, including frameworks for image processing, visualization, and statistical analysis of higher-order descriptors. It also provides examples of the successful use of higher-order descriptors in specific applications and a glimpse of the next generation of diffusion MRI. To do so, it combines contributions on new developments, current challenges in this area, and state-of-the-art surveys.   Compared to the increasing importance of higher-order descriptors in a range of applications, tools for analysis and processing are still relatively hard to come by. Even though application areas such as medical imaging, fluid dynamics, and structural mechanics are very different in nature they face many shared challenges. This book provides an interdisciplinary perspective on this topic with contributions from key rese...

  20. The geometry of higher-order Lagrange spaces applications to mechanics and physics

    CERN Document Server

    Miron, Radu

    1997-01-01

    This monograph is devoted to the problem of the geometrizing of Lagrangians which depend on higher-order accelerations It presents a construction of the geometry of the total space of the bundle of the accelerations of order k>=1 A geometrical study of the notion of the higher-order Lagrange space is conducted, and the old problem of prolongation of Riemannian spaces to k-osculator manifolds is solved Also, the geometrical ground for variational calculus on the integral of actions involving higher-order Lagrangians is dealt with Applications to higher-order analytical mechanics and theoretical physics are included as well Audience This volume will be of interest to scientists whose work involves differential geometry, mechanics of particles and systems, calculus of variation and optimal control, optimization, optics, electromagnetic theory, and biology

  1. Higher order capacity statistics of multi-hop transmission systems over Rayleigh fading channels

    KAUST Repository

    Yilmaz, Ferkan; Tabassum, Hina; Alouini, Mohamed-Slim

    2012-01-01

    In this paper, we present an exact analytical expression to evaluate the higher order statistics of the channel capacity for amplify and forward (AF) multihop transmission systems operating over Rayleigh fading channels. Furthermore, we present

  2. Low Dose Radiation-Induced Genome and Epigenome Instability Symposium and Epigenetic Mechanisms, DNA Repair, and Chromatin Symposium at the EMS 2008 Annual Meeting - October 2008

    Energy Technology Data Exchange (ETDEWEB)

    Morgan, William F; Kovalchuk, Olga; Dolinoy, Dana C; Dubrova, Yuri E; Coleman, Matthew A; Schär, Primo; Pogribny, Igor; Hendzel, Michael

    2010-02-19

    The Low Dose Radiation Symposium thoughtfully addressed ionizing radiation non-mutational but transmissable alterations in surviving cells. Deregulation of epigenetic processes has been strongly implicated in carcinogenesis, and there is increasing realization that a significant fraction of non-targeted and adaptive mechanisms in response to ionizing radiation are likely to be epigenetic in nature. Much remains to be learned about how chromatin and epigenetic regulators affect responses to low doses of radiation, and how low dose radiation impacts other epigenetic processes. The Epigenetic Mechanisms Symposium focused on on epigenetic mechanisms and their interplay with DNA repair and chromatin changes. Addressing the fact that the most well understood mediators of epigenetic regulation are histone modifications and DNA methylation. Low levels of radiation can lead to changes in the methylation status of certain gene promoters and the expression of DNA methyltransferases, However, epigenetic regulation can also involve changes in higher order chromosome structure.

  3. Solution of volume-surface integral equations using higher-order hierarchical Legendre basis functions

    DEFF Research Database (Denmark)

    Kim, Oleksiy S.; Meincke, Peter; Breinbjerg, Olav

    2007-01-01

    The problem of electromagnetic scattering by composite metallic and dielectric objects is solved using the coupled volume-surface integral equation (VSIE). The method of moments (MoM) based on higher-order hierarchical Legendre basis functions and higher-order curvilinear geometrical elements...... with the analytical Mie series solution. Scattering by more complex metal-dielectric objects are also considered to compare the presented technique with other numerical methods....

  4. Ultra-compact Higher-Order-Mode Pass Filter in a Silicon Waveguide

    DEFF Research Database (Denmark)

    Guan, Xiaowei; Frandsen, Lars Hagedorn; Ding, Yunhong

    2015-01-01

    An 3.7 μm long higher-order-mode pass filter with an extinction ratio larger than 20 dB is demonstrated in a 1D corrugated silicon multimode waveguide......An 3.7 μm long higher-order-mode pass filter with an extinction ratio larger than 20 dB is demonstrated in a 1D corrugated silicon multimode waveguide...

  5. Higher order mode of a microstripline fed cylindrical dielectric resonator antenna

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, A. V. Praveen, E-mail: praveen.kumar@pilani.bits-pilani.ac.in [Department of Electrical and Electronics Engineering, BITS Pilani, Pilani, Rajasthan-333 031 (India)

    2016-03-09

    A microstrip transmission line can be used to excite the broadside radiating mode of a cylindrical dielectric resonator antenna (CDRA). The same is found to excite considerably well a higher order mode (HOM) as well. However unlike the broadside mode, the higher order mode gives distorted radiation pattern which makes this mode less useful for practical applications. The cause of distortion in the HOM radiation and the dependence of HOM coupling on the microstrip feed line are explored using HFSS simulations.

  6. Capturing Structural Heterogeneity in Chromatin Fibers.

    Science.gov (United States)

    Ekundayo, Babatunde; Richmond, Timothy J; Schalch, Thomas

    2017-10-13

    Chromatin fiber organization is implicated in processes such as transcription, DNA repair and chromosome segregation, but how nucleosomes interact to form higher-order structure remains poorly understood. We solved two crystal structures of tetranucleosomes with approximately 11-bp DNA linker length at 5.8 and 6.7 Å resolution. Minimal intramolecular nucleosome-nucleosome interactions result in a fiber model resembling a flat ribbon that is compatible with a two-start helical architecture, and that exposes histone and DNA surfaces to the environment. The differences in the two structures combined with electron microscopy reveal heterogeneous structural states, and we used site-specific chemical crosslinking to assess the diversity of nucleosome-nucleosome interactions through identification of structure-sensitive crosslink sites that provide a means to characterize fibers in solution. The chromatin fiber architectures observed here provide a basis for understanding heterogeneous chromatin higher-order structures as they occur in a genomic context. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Defining Higher-Order Turbulent Moment Closures with an Artificial Neural Network and Random Forest

    Science.gov (United States)

    McGibbon, J.; Bretherton, C. S.

    2017-12-01

    Unresolved turbulent advection and clouds must be parameterized in atmospheric models. Modern higher-order closure schemes depend on analytic moment closure assumptions that diagnose higher-order moments in terms of lower-order ones. These are then tested against Large-Eddy Simulation (LES) higher-order moment relations. However, these relations may not be neatly analytic in nature. Rather than rely on an analytic higher-order moment closure, can we use machine learning on LES data itself to define a higher-order moment closure?We assess the ability of a deep artificial neural network (NN) and random forest (RF) to perform this task using a set of observationally-based LES runs from the MAGIC field campaign. By training on a subset of 12 simulations and testing on remaining simulations, we avoid over-fitting the training data.Performance of the NN and RF will be assessed and compared to the Analytic Double Gaussian 1 (ADG1) closure assumed by Cloudy Layers Unified By Binormals (CLUBB), a higher-order turbulence closure currently used in the Community Atmosphere Model (CAM). We will show that the RF outperforms the NN and the ADG1 closure for the MAGIC cases within this diagnostic framework. Progress and challenges in using a diagnostic machine learning closure within a prognostic cloud and turbulence parameterization will also be discussed.

  8. Structured illumination to spatially map chromatin motions.

    Science.gov (United States)

    Bonin, Keith; Smelser, Amanda; Moreno, Naike Salvador; Holzwarth, George; Wang, Kevin; Levy, Preston; Vidi, Pierre-Alexandre

    2018-05-01

    We describe a simple optical method that creates structured illumination of a photoactivatable probe and apply this method to characterize chromatin motions in nuclei of live cells. A laser beam coupled to a diffractive optical element at the back focal plane of an excitation objective generates an array of near diffraction-limited beamlets with FWHM of 340  ±  30  nm, which simultaneously photoactivate a 7  ×  7 matrix pattern of GFP-labeled histones, with spots 1.70  μm apart. From the movements of the photoactivated spots, we map chromatin diffusion coefficients at multiple microdomains of the cell nucleus. The results show correlated motions of nearest chromatin microdomain neighbors, whereas chromatin movements are uncorrelated at the global scale of the nucleus. The method also reveals a DNA damage-dependent decrease in chromatin diffusion. The diffractive optical element instrumentation can be easily and cheaply implemented on commercial inverted fluorescence microscopes to analyze adherent cell culture models. A protocol to measure chromatin motions in nonadherent human hematopoietic stem and progenitor cells is also described. We anticipate that the method will contribute to the identification of the mechanisms regulating chromatin mobility, which influences most genomic processes and may underlie the biogenesis of genomic translocations associated with hematologic malignancies. (2018) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

  9. Chromatin meets its organizers.

    Science.gov (United States)

    Bodnar, Megan S; Spector, David L

    2013-06-06

    Chromatin organization and gene-gene interactions are critical components of carrying out developmental programs. Phillips-Cremins et al. identify a series of unexpected architectural proteins that work in a combinatorial manner to functionally organize chromatin in a cell-type-specific manner at the submegabase-length scale. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Chromatin Immunoprecipitation (ChIP) using Drosophila tissue

    OpenAIRE

    Tran, Vuong; Gan, Qiang; Chen, Xin

    2012-01-01

    Epigenetics remains a rapidly developing field that studies how the chromatin state contributes to differential gene expression in distinct cell types at different developmental stages. Epigenetic regulation contributes to a broad spectrum of biological processes, including cellular differentiation during embryonic development and homeostasis in adulthood. A critical strategy in epigenetic studies is to examine how various histone modifications and chromatin factors regulate gene expression. ...

  11. Chromatin architecture and gene expression in Escherichia coli

    DEFF Research Database (Denmark)

    Willenbrock, Hanni; Ussery, David

    2004-01-01

    Two recent genome-scale analyses underscore the importance of DNA topology and chromatin structure in regulating transcription in Escherichia coli.......Two recent genome-scale analyses underscore the importance of DNA topology and chromatin structure in regulating transcription in Escherichia coli....

  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. Impaired chromatin remodelling at STAT1-regulated promoters leads to global unresponsiveness of Toxoplasma gondii-infected macrophages to IFN-γ.

    Directory of Open Access Journals (Sweden)

    Christine Lang

    2012-01-01

    Full Text Available Intracellular pathogens including the apicomplexan and opportunistic parasite Toxoplasma gondii profoundly modify their host cells in order to establish infection. We have shown previously that intracellular T. gondii inhibit up-regulation of regulatory and effector functions in murine macrophages (MΦ stimulated with interferon (IFN-γ, which is the cytokine crucial for controlling the parasites' replication. Using genome-wide transcriptome analysis we show herein that infection with T. gondii leads to global unresponsiveness of murine macrophages to IFN-γ. More than 61% and 89% of the transcripts, which were induced or repressed by IFN-γ in non-infected MΦ, respectively, were not altered after stimulation of T. gondii-infected cells with IFN-γ. These genes are involved in a variety of biological processes, which are mostly but not exclusively related to immune responses. Analyses of the underlying mechanisms revealed that IFN-γ-triggered nuclear translocation of STAT1 still occurred in Toxoplasma-infected MΦ. However, STAT1 bound aberrantly to oligonucleotides containing the IFN-γ-responsive gamma-activated site (GAS consensus sequence. Conversely, IFN-γ did not induce formation of active GAS-STAT1 complexes in nuclear extracts from infected MΦ. Mass spectrometry of protein complexes bound to GAS oligonucleotides showed that T. gondii-infected MΦ are unable to recruit non-muscle actin to IFN-γ-responsive DNA sequences, which appeared to be independent of stimulation with IFN-γ and of STAT1 binding. IFN-γ-induced recruitment of BRG-1 and acetylation of core histones at the IFN-γ-regulated CIITA promoter IV, but not β-actin was diminished by >90% in Toxoplasma-infected MΦ as compared to non-infected control cells. Remarkably, treatment with histone deacetylase inhibitors restored the ability of infected macrophages to express the IFN-γ regulated genes H2-A/E and CIITA. Taken together, these results indicate that Toxoplasma

  14. Simulation of Radiation-Induced Damage Distribution to evaluate Models for Higher-Order Chromosome Organisation

    NARCIS (Netherlands)

    T.A. Knoch (Tobias); P. Quicken (Peter); G. Kreth (Gregor); W. Friedland (Werner); A.A. Friedl (Anna)

    2003-01-01

    textabstractThe structure of chromatin at the level of the 30 nm fibre has been studied in considerable detail, but little is known about how this fibre is arranged within the interphase chromosome territory. Over the years, various polymer models were developed to simulate chromosome structure,

  15. The Cellular DNA Helicase ChlR1 Regulates Chromatin and Nuclear Matrix Attachment of the Human Papillomavirus 16 E2 Protein and High-Copy-Number Viral Genome Establishment.

    Science.gov (United States)

    Harris, Leanne; McFarlane-Majeed, Laura; Campos-León, Karen; Roberts, Sally; Parish, Joanna L

    2017-01-01

    In papillomavirus infections, the viral genome is established as a double-stranded DNA episome. To segregate the episomes into daughter cells during mitosis, they are tethered to cellular chromatin by the viral E2 protein. We previously demonstrated that the E2 proteins of diverse papillomavirus types, including bovine papillomavirus (BPV) and human papillomavirus 16 (HPV16), associate with the cellular DNA helicase ChlR1. This virus-host interaction is important for the tethering of BPV E2 to mitotic chromatin and the stable maintenance of BPV episomes. The role of the association between E2 and ChlR1 in the HPV16 life cycle is unresolved. Here we show that an HPV16 E2 Y131A mutant (E2 Y131A ) had significantly reduced binding to ChlR1 but retained transcriptional activation and viral origin-dependent replication functions. Subcellular fractionation of keratinocytes expressing E2 Y131A showed a marked change in the localization of the protein. Compared to that of wild-type E2 (E2 WT ), the chromatin-bound pool of E2 Y131A was decreased, concomitant with an increase in nuclear matrix-associated protein. Cell cycle synchronization indicated that the shift in subcellular localization of E2 Y131A occurred in mid-S phase. A similar alteration between the subcellular pools of the E2 WT protein occurred upon ChlR1 silencing. Notably, in an HPV16 life cycle model in primary human keratinocytes, mutant E2 Y131A genomes were established as episomes, but at a markedly lower copy number than that of wild-type HPV16 genomes, and they were not maintained upon cell passage. Our studies indicate that ChlR1 is an important regulator of the chromatin association of E2 and of the establishment and maintenance of HPV16 episomes. Infections with high-risk human papillomaviruses (HPVs) are a major cause of anogenital and oropharyngeal cancers. During infection, the circular DNA genome of HPV persists within the nucleus, independently of the host cell chromatin. Persistence of infection

  16. Higher order aberrations in amblyopic children and their role in refractory amblyopia

    Directory of Open Access Journals (Sweden)

    Arnaldo Dias-Santos

    2014-12-01

    Full Text Available Objective: Some studies have hypothesized that an unfavourable higher order aberrometric profile could act as an amblyogenic mechanism and may be responsible for some amblyopic cases that are refractory to conventional treatment or cases of “idiopathic” amblyopia. This study compared the aberrometric profile in amblyopic children to that of children with normal visual development and compared the aberrometric profile in corrected amblyopic eyes and refractory amblyopic eyes with that of healthy eyes. Methods: Cross-sectional study with three groups of children – the CA group (22 eyes of 11 children with unilateral corrected amblyopia, the RA group (24 eyes of 13 children with unilateral refractory amblyopia and the C group (28 eyes of 14 children with normal visual development. Higher order aberrations were evaluated using an OPD-Scan III (NIDEK. Comparisons of the aberrometric profile were made between these groups as well as between the amblyopic and healthy eyes within the CA and RA groups. Results: Higher order aberrations with greater impact in visual quality were not significantly higher in the CA and RA groups when compared with the C group. Moreover, there were no statistically significant differences in the higher order aberrometric profile between the amblyopic and healthy eyes within the CA and RA groups. Conclusions: Contrary to lower order aberrations (e.g., myopia, hyperopia, primary astigmatism, higher order aberrations do not seem to be involved in the etiopathogenesis of amblyopia. Therefore, these are likely not the cause of most cases of refractory amblyopia.

  17. MIMO processing based on higher-order Poincaré spheres

    Science.gov (United States)

    Fernandes, Gil M.; Muga, Nelson J.; Pinto, Armando N.

    2017-08-01

    A multi-input multi-output (MIMO) algorithm based on higher-order Poincaré spheres is demonstrated for space-division multiplexing (SDM) systems. The MIMO algorithm is modulation format agnostic, robust to frequency offset and does not require training sequences. In this approach, the space-multiplexed signal is decomposed in sets of two tributary signals, with each set represented in a higher-order Poincaré sphere. For any arbitrary complex modulation format, the samples of two tributaries can be represented in a given higher-order Poincaré sphere with a symmetry plane. The crosstalk along propagation changes the spatial orientation of this plane and, therefore, it can be compensated by computing and realigning the best fit plane. We show how the transmitted signal can be successfully recovered using this procedure for all possible combinations of tributaries. Moreover, we analyze the convergence speed for the MIMO technique considering several optical-to-noise ratios.

  18. Recurrent activity in higher order, modality non-specific brain regions

    DEFF Research Database (Denmark)

    Lou, Hans Olav Christensen; Joensson, Morten; Biermann-Ruben, Katja

    2011-01-01

    It has been proposed that the workings of the brain are mainly intrinsically generated recurrent neuronal activity, with sensory inputs as modifiers of such activity in both sensory and higher order modality non-specific regions. This is supported by the demonstration of recurrent neuronal activity...... in the visual system as a response to visual stimulation. In contrast recurrent activity has never been demonstrated before in higher order modality non-specific regions. Using magneto-encephalography and Granger causality analysis, we tested in a paralimbic network the hypothesis that stimulation may enhance...... causal recurrent interaction between higher-order, modality non-specific regions. The network includes anterior cingulate/medial prefrontal and posterior cingulate/medial parietal cortices together with pulvinar thalami, a network known to be effective in autobiographic memory retrieval and self...

  19. Higher order polynomial expansion nodal method for hexagonal core neutronics analysis

    International Nuclear Information System (INIS)

    Jin, Young Cho; Chang, Hyo Kim

    1998-01-01

    A higher-order polynomial expansion nodal(PEN) method is newly formulated as a means to improve the accuracy of the conventional PEN method solutions to multi-group diffusion equations in hexagonal core geometry. The new method is applied to solving various hexagonal core neutronics benchmark problems. The computational accuracy of the higher order PEN method is then compared with that of the conventional PEN method, the analytic function expansion nodal (AFEN) method, and the ANC-H method. It is demonstrated that the higher order PEN method improves the accuracy of the conventional PEN method and that it compares very well with the other nodal methods like the AFEN and ANC-H methods in accuracy

  20. Alignment of learning objectives and assessments in therapeutics courses to foster higher-order thinking.

    Science.gov (United States)

    FitzPatrick, Beverly; Hawboldt, John; Doyle, Daniel; Genge, Terri

    2015-02-17

    To determine whether national educational outcomes, course objectives, and classroom assessments for 2 therapeutics courses were aligned for curricular content and cognitive processes, and if they included higher-order thinking. Document analysis and student focus groups were used. Outcomes, objectives, and assessment tasks were matched for specific therapeutics content and cognitive processes. Anderson and Krathwohl's Taxonomy was used to define higher-order thinking. Students discussed whether assessments tested objectives and described their thinking when responding to assessments. There were 7 outcomes, 31 objectives, and 412 assessment tasks. The alignment for content and cognitive processes was not satisfactory. Twelve students participated in the focus groups. Students thought more short-answer questions than multiple choice questions matched the objectives for content and required higher-order thinking. The alignment analysis provided data that could be used to reveal and strengthen the enacted curriculum and improve student learning.

  1. A Linear-Elasticity Solver for Higher-Order Space-Time Mesh Deformation

    Science.gov (United States)

    Diosady, Laslo T.; Murman, Scott M.

    2018-01-01

    A linear-elasticity approach is presented for the generation of meshes appropriate for a higher-order space-time discontinuous finite-element method. The equations of linear-elasticity are discretized using a higher-order, spatially-continuous, finite-element method. Given an initial finite-element mesh, and a specified boundary displacement, we solve for the mesh displacements to obtain a higher-order curvilinear mesh. Alternatively, for moving-domain problems we use the linear-elasticity approach to solve for a temporally discontinuous mesh velocity on each time-slab and recover a continuous mesh deformation by integrating the velocity. The applicability of this methodology is presented for several benchmark test cases.

  2. Collocated electrodynamic FDTD schemes using overlapping Yee grids and higher-order Hodge duals

    Science.gov (United States)

    Deimert, C.; Potter, M. E.; Okoniewski, M.

    2016-12-01

    The collocated Lebedev grid has previously been proposed as an alternative to the Yee grid for electromagnetic finite-difference time-domain (FDTD) simulations. While it performs better in anisotropic media, it performs poorly in isotropic media because it is equivalent to four overlapping, uncoupled Yee grids. We propose to couple the four Yee grids and fix the Lebedev method using discrete exterior calculus (DEC) with higher-order Hodge duals. We find that higher-order Hodge duals do improve the performance of the Lebedev grid, but they also improve the Yee grid by a similar amount. The effectiveness of coupling overlapping Yee grids with a higher-order Hodge dual is thus questionable. However, the theoretical foundations developed to derive these methods may be of interest in other problems.

  3. Higher order magnetic modulation structures in rare earth metal, alloys and compounds under extreme conditions

    International Nuclear Information System (INIS)

    Kawano, S.

    2003-01-01

    Magnetic materials consisting of rare earth ions form modulation structures such as a helical or sinusoidal structure caused by the oscillating magnetic interaction between rare earth ions due to RKKY magnetic interaction. These modulation structures, in some cases, develop further to higher order modulation structures by additional modulations caused by higher order crystalline electric field, magnetic interactions such as spin-lattice interaction, external magnetic field and pressure. The higher order modulation structures are observed in a spin-slip structure or a helifan structure in Ho, and a tilt helix structure in a TbEr alloy. Paramagnetic ions originated from frustration generate many magnetic phases under applied external magnetic field. KUR neutron diffraction groups have performed the development and adjustment of high-pressure instruments and external magnetic fields for neutron diffraction spectrometers. The studies of 'neutron diffraction under extreme conditions' by the seven groups are described in this report. (Y. Kazumata)

  4. Development of a Higher Order Laminate Theory for Modeling Composites with Induced Strain Actuators

    Science.gov (United States)

    Chattopadhyay, Aditi; Seeley, Charles E.

    1996-01-01

    A refined higher order plate theory is developed to investigate the actuation mechanism of piezoelectric materials surface bonded or embedded in composite laminates. The current analysis uses a displacement field which accurately accounts for transverse shear stresses. Some higher order terms are identified by using the conditions that shear stresses vanish at all free surfaces. Therefore, all boundary conditions for displacements and stresses are satisfied in the present theory. The analysis is implemented using the finite element method which provides a convenient means to construct a numerical solution due to the discrete nature of the actuators. The higher order theory is computationally less expensive than a full three dimensional analysis. The theory is also shown to agree well with published experimental results. Numerical examples are presented for composite plates with thicknesses ranging from thin to very thick.

  5. Application of Higher-Order Cumulant in Fault Diagnosis of Rolling Bearing

    International Nuclear Information System (INIS)

    Shen, Yongjun; Yang, Shaopu; Wang, Junfeng

    2013-01-01

    In this paper a new method of pattern recognition based on higher-order cumulant and envelope analysis is presented. The core of this new method is to construct analytical signals from the given signals and obtain the envelope signals firstly, then compute and compare the higher-order cumulants of the envelope signals. The higher-order cumulants could be used as a characteristic quantity to distinguish these given signals. As an example, this method is applied in fault diagnosis for 197726 rolling bearing of freight locomotive. The comparisons of the second-order, third-order and fourth-order cumulants of the envelope signals from different vibration signals of rolling bearing show this new method could discriminate the normal and two fault signals distinctly

  6. Equivalence of two Fixed-Point Semantics for Definitional Higher-Order Logic Programs

    Directory of Open Access Journals (Sweden)

    Angelos Charalambidis

    2015-09-01

    Full Text Available Two distinct research approaches have been proposed for assigning a purely extensional semantics to higher-order logic programming. The former approach uses classical domain theoretic tools while the latter builds on a fixed-point construction defined on a syntactic instantiation of the source program. The relationships between these two approaches had not been investigated until now. In this paper we demonstrate that for a very broad class of programs, namely the class of definitional programs introduced by W. W. Wadge, the two approaches coincide (with respect to ground atoms that involve symbols of the program. On the other hand, we argue that if existential higher-order variables are allowed to appear in the bodies of program rules, the two approaches are in general different. The results of the paper contribute to a better understanding of the semantics of higher-order logic programming.

  7. Neurodevelopmental outcomes of triplets or higher-order extremely low birth weight infants.

    Science.gov (United States)

    Wadhawan, Rajan; Oh, William; Vohr, Betty R; Wrage, Lisa; Das, Abhik; Bell, Edward F; Laptook, Abbot R; Shankaran, Seetha; Stoll, Barbara J; Walsh, Michele C; Higgins, Rosemary D

    2011-03-01

    Extremely low birth weight twins have a higher rate of death or neurodevelopmental impairment than singletons. Higher-order extremely low birth weight multiple births may have an even higher rate of death or neurodevelopmental impairment. Extremely low birth weight (birth weight 401-1000 g) multiple births born in participating centers of the Neonatal Research Network between 1996 and 2005 were assessed for death or neurodevelopmental impairment at 18 to 22 months' corrected age. Neurodevelopmental impairment was defined by the presence of 1 or more of the following: moderate to severe cerebral palsy; mental developmental index score or psychomotor developmental index score less than 70; severe bilateral deafness; or blindness. Infants who died within 12 hours of birth were excluded. Maternal and infant demographic and clinical variables were compared among singleton, twin, and triplet or higher-order infants. Logistic regression analysis was performed to establish the association between singletons, twins, and triplet or higher-order multiples and death or neurodevelopmental impairment, controlling for confounding variables that may affect death or neurodevelopmental impairment. Our cohort consisted of 8296 singleton, 2164 twin, and 521 triplet or higher-order infants. The risk of death or neurodevelopmental impairment was increased in triplets or higher-order multiples when compared with singletons (adjusted odds ratio: 1.7 [95% confidence interval: 1.29-2.24]), and there was a trend toward an increased risk when compared with twins (adjusted odds ratio: 1.27 [95% confidence: 0.95-1.71]). Triplet or higher-order births are associated with an increased risk of death or neurodevelopmental impairment at 18 to 22 months' corrected age when compared with extremely low birth weight singleton infants, and there was a trend toward an increased risk when compared with twins.

  8. A finite deformation theory of higher-order gradient crystal plasticity

    DEFF Research Database (Denmark)

    Kuroda, Mitsutoshi; Tvergaard, Viggo

    2008-01-01

    crystal plasticity that is based on an assumption of the existence of higher-order stresses. Furthermore, a boundary-value problem for simple shear of a constrained thin strip is studied numerically, and some characteristic features of finite deformation are demonstrated through a comparison to a solution......For higher-order gradient crystal plasticity, a finite deformation formulation is presented. The theory does not deviate much from the conventional crystal plasticity theory. Only a back stress effect and additional differential equations for evolution of the geometrically necessary dislocation...

  9. Higher-order geodesic deviation for charged particles and resonance induced by gravitational waves

    Science.gov (United States)

    Heydari-Fard, M.; Hasani, S. N.

    We generalize the higher-order geodesic deviation for the structure-less test particles to the higher-order geodesic deviation equations of the charged particles [R. Kerner, J. W. van Holten and R. Colistete Jr., Class. Quantum Grav. 18 (2001) 4725]. By solving these equations for charged particles moving in a constant magnetic field in the spacetime of a gravitational wave, we show for both cases when the gravitational wave is parallel and perpendicular to the constant magnetic field, a magnetic resonance appears at wg = Ω. This feature might be useful to detect the gravitational wave with high frequencies.

  10. Higher-order resonant electronic recombination as a manifestation of configuration interaction

    International Nuclear Information System (INIS)

    Beilmann, C; Amaro, P; Tashenov, S; Bekker, H; Harman, Z; Crespo López-Urrutia, J R

    2013-01-01

    Theoretical and experimental investigations of higher-order electron–ion recombination resonances including inter-shell excitations are presented for L-shell ions of Kr with the aim of examining details of atomic structure calculations. The particular importance of electron–electron interaction and configuration mixing effects for these recombination processes enables their use for detailed tests of electron correlation effects. A test of the required level of considered mixing configurations is presented and further experiments involving higher-order recombination channels are motivated. (paper)

  11. Higher order BLG supersymmetry transformations from 10-dimensional super Yang Mills

    Energy Technology Data Exchange (ETDEWEB)

    Hall, John [Alumnus of Physics Department, Imperial College,South Kensington, London, SW7 2AZ (United Kingdom); Low, Andrew [Physics Department, Wimbledon High School,Mansel Road, London, SW19 4AB (United Kingdom)

    2014-06-26

    We study a Simple Route for constructing the higher order Bagger-Lambert-Gustavsson theory - both supersymmetry transformations and Lagrangian - starting from knowledge of only the 10-dimensional Super Yang Mills Fermion Supersymmetry transformation. We are able to uniquely determine the four-derivative order corrected supersymmetry transformations, to lowest non-trivial order in Fermions, for the most general three-algebra theory. For the special case of Euclidean three-algbera, we reproduce the result presented in arXiv:1207.1208, with significantly less labour. In addition, we apply our method to calculate the quadratic fermion terms in the higher order BLG fermion supersymmetry transformation.

  12. Dietary polyphenols and chromatin remodeling.

    Science.gov (United States)

    Russo, Gian Luigi; Vastolo, Viviana; Ciccarelli, Marco; Albano, Luigi; Macchia, Paolo Emidio; Ungaro, Paola

    2017-08-13

    Polyphenols are the most abundant phytochemicals in fruits, vegetables, and plant-derived beverages. Recent findings suggest that polyphenols display the ability to reverse adverse epigenetic regulation involved in pathological conditions, such as obesity, metabolic disorder, cardiovascular and neurodegenerative diseases, and various forms of cancer. Epigenetics, defined as heritable changes to the transcriptome, independent from those occurring in the genome, includes DNA methylation, histone modifications, and posttranscriptional gene regulation by noncoding RNAs. Sinergistically and cooperatively, these processes regulate gene expression by changing chromatin organization and DNA accessibility. Such induced epigenetic changes can be inherited during cell division, resulting in permanent maintenance of the acquired phenotype, but they may also occur throughout an individual life-course and may ultimately influence phenotypic outcomes (health and disease risk). In the last decade, a number of studies have shown that nutrients can affect metabolic traits by altering the structure of chromatin and directly regulate both transcription and translational processes. In this context, dietary polyphenol-targeted epigenetics becomes an attractive approach for disease prevention and intervention. Here, we will review how polyphenols, including flavonoids, curcuminoids, and stilbenes, modulate the establishment and maintenance of key epigenetic marks, thereby influencing gene expression and, hence, disease risk and health.

  13. The nonlocal boundary value problems for strongly singular higher-order nonlinear functional-differential equations

    Czech Academy of Sciences Publication Activity Database

    Mukhigulashvili, Sulkhan

    -, č. 35 (2015), s. 23-50 ISSN 1126-8042 Institutional support: RVO:67985840 Keywords : higher order functional differential equations * Dirichlet boundary value problem * strong singularity Subject RIV: BA - General Mathematics http://ijpam.uniud.it/online_issue/201535/03-Mukhigulashvili.pdf

  14. Toward an Understanding of Higher-Order Thinking among Minority Students.

    Science.gov (United States)

    Armour-Thomas, Eleanor; And Others

    1992-01-01

    Used principal-factors extraction with varimax rotation analysis to clarify nature and function of higher-order thinking among minority high school students (n=107) from economically disadvantaged backgrounds. Results allowed for specification of mental processes associated with the construct and the extent to which students reported awareness and…

  15. Developing Learning Model Based on Local Culture and Instrument for Mathematical Higher Order Thinking Ability

    Science.gov (United States)

    Saragih, Sahat; Napitupulu, E. Elvis; Fauzi, Amin

    2017-01-01

    This research aims to develop a student-centered learning model based on local culture and instrument of mathematical higher order thinking of junior high school students in the frame of the 2013-Curriculum in North Sumatra, Indonesia. The subjects of the research are seventh graders which are taken proportionally random consisted of three public…

  16. In-Service Teacher Education: Asking Questions for Higher Order Thinking in Visual Literacy

    Science.gov (United States)

    Moodley, Visvaganthie

    2013-01-01

    The kinds of questions teachers ask may thwart or promote learner high-order thinking; teachers themselves must have expertise in questioning skills to promote higher order cognition among learners. Drawing on experiential knowledge of assessment, and as an English-teaching professional development programme (PDP) facilitator, I demonstrate that…

  17. Development of an Instrument to Measure Higher Order Thinking Skills in Senior High School Mathematics Instruction

    Science.gov (United States)

    Tanujaya, Benidiktus

    2016-01-01

    The purpose of this research was to develop an instrument that can be used to measure higher-order thinking skills (HOTS) in mathematics instruction of high school students. This research was conducted using a standard procedure of instrument development, from the development of conceptual definitions, development of operational definitions,…

  18. The Higher Order Factor Structure and Gender Invariance of the Pathological Narcissism Inventory

    Science.gov (United States)

    Wright, Aidan G. C.; Lukowitsky, Mark R.; Pincus, Aaron L.; Conroy, David E.

    2010-01-01

    The Pathological Narcissism Inventory (PNI) is a recently developed multidimensional inventory for the assessment of pathological narcissism. The authors describe and report the results of two studies that investigate the higher order factor structure and gender invariance of the PNI. The results of the first study indicate that the PNI has a…

  19. The advantage of higher-order theory of mind in the game of limited bidding

    NARCIS (Netherlands)

    De Weerd, H.; Verheij, B.; van Eijck, J.; Verbrugge, L. C.

    2011-01-01

    Higher-order theory of mind is the ability to recursively model mental states of other agents. It is known that adults in general can reason adequately at the second order (covering attributions like "Alice knows that Bob knows that she wrote a novel under pseudonym"), but there are cognitive limits

  20. Massive, massless and ghost modes of gravitational waves from higher-order gravity

    DEFF Research Database (Denmark)

    Bogdanos, Charalampos; Capozziello, Salvatore; De Laurentis, Mariafelicia

    We linearize the field equations for higher order theories that contain scalar invariants other than the Ricci scalar. We find that besides a massless spin-2 field (the standard graviton), the theory contains also spin-0 and spin-2 massive modes with the latter being, in general, ghost modes. Then...

  1. Method of applying single higher order polynomial basis function over multiple domains

    CSIR Research Space (South Africa)

    Lysko, AA

    2010-03-01

    Full Text Available A novel method has been devised where one set of higher order polynomial-based basis functions can be applied over several wire segments, thus permitting to decouple the number of unknowns from the number of segments, and so from the geometrical...

  2. Impedance Eduction in Large Ducts Containing Higher-Order Modes and Grazing Flow

    Science.gov (United States)

    Watson, Willie R.; Jones, Michael G.

    2017-01-01

    Impedance eduction test data are acquired in ducts with small and large cross-sectional areas at the NASA Langley Research Center. An improved data acquisition system in the large duct has resulted in increased control of the acoustic energy in source modes and more accurate resolution of higher-order duct modes compared to previous tests. Two impedance eduction methods that take advantage of the improved data acquisition to educe the liner impedance in grazing flow are presented. One method measures the axial propagation constant of a dominant mode in the liner test section (by implementing the Kumarsean and Tufts algorithm) and educes the impedance from an exact analytical expression. The second method solves numerically the convected Helmholtz equation and minimizes an objective function to obtain the liner impedance. The two methods are tested first on data synthesized from an exact mode solution and then on measured data. Results show that when the methods are applied to data acquired in the larger duct with a dominant higher-order mode, the same impedance spectra are educed as that obtained in the small duct where only the plane wave mode propagates. This result holds for each higher-order mode in the large duct provided that the higher-order mode is sufficiently attenuated by the liner.

  3. Controlled generation of higher-order Poincaré sphere beams from a laser

    CSIR Research Space (South Africa)

    Naidoo, Darryl

    2016-03-01

    Full Text Available . 10: 327-332 Controlled generation of higher-order Poincaré sphere beams from a laser Naidoo D Roux FS Dudley A Litvin I Piccirillo B Marrucci L Forbes A ABSTRACT: The angular momentum of light can be described by positions on a...

  4. On the origin of higher braces and higher-order derivations

    Czech Academy of Sciences Publication Activity Database

    Markl, Martin

    2015-01-01

    Roč. 10, č. 3 (2015), s. 637-667 ISSN 2193-8407 Institutional support: RVO:67985840 Keywords : Koszul braces * Börjeseon braces * higher-order derivation Subject RIV: BA - General Mathematics Impact factor: 0.600, year: 2015 http://link.springer.com/article/10.1007/s40062-014-0079-2

  5. Superpositions of higher-order bessel beams and nondiffracting speckle fields

    CSIR Research Space (South Africa)

    Dudley, Angela L

    2009-08-01

    Full Text Available speckle fields. The paper reports on illuminating a ring slit aperture with light which has an azimuthal phase dependence, such that the field produced is a superposition of two higher-order Bessel beams. In the case that the phase dependence of the light...

  6. EXISTENCE OF PERIODIC SOLUTION TO HIGHER ORDER DIFFERENTIAL EQUATIONS WITH DEVIATING ARGUMENT

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    In this paper,using the coincidence degree theory of Mawhin,we investigate the existence of periodic solutions to higher order differential equations with deviating argument. Some new results on the existence of periodic solutions to the equations are obtained. In addition,we give an example to illustrate the main results.

  7. Teaching Biotechnology through Case Studies--Can We Improve Higher Order Thinking Skills of Nonscience Majors?

    Science.gov (United States)

    Dori, Yehudit J.; Tal, Revital T.; Tsaushu, Masha

    2003-01-01

    Teaching nonscience majors topics in biotechnology through case studies is the focus of this research. Our "Biotechnology, Environment, and Related Issues" module, developed within the "Science for All" framework, is aimed at elevating the level of students' scientific and technological literacy and their higher order thinking…

  8. Compound waves in a higher order nonlinear model of thermoviscous fluids

    DEFF Research Database (Denmark)

    Rønne Rasmussen, Anders; Sørensen, Mads Peter; Gaididei, Yuri B.

    2016-01-01

    A generalized traveling wave ansatz is used to investigate compound shock waves in a higher order nonlinear model of a thermoviscous fluid. The fluid velocity potential is written as a traveling wave plus a linear function of space and time. The latter offers the possibility of predicting...

  9. Oscillation of certain higher-order neutral partial functional differential equations.

    Science.gov (United States)

    Li, Wei Nian; Sheng, Weihong

    2016-01-01

    In this paper, we study the oscillation of certain higher-order neutral partial functional differential equations with the Robin boundary conditions. Some oscillation criteria are established. Two examples are given to illustrate the main results in the end of this paper.

  10. Orthogonal Higher Order Structure of the WISC-IV Spanish Using Hierarchical Exploratory Factor Analytic Procedures

    Science.gov (United States)

    McGill, Ryan J.; Canivez, Gary L.

    2016-01-01

    As recommended by Carroll, the present study examined the factor structure of the Wechsler Intelligence Scale for Children-Fourth Edition Spanish (WISC-IV Spanish) normative sample using higher order exploratory factor analytic techniques not included in the WISC-IV Spanish Technical Manual. Results indicated that the WISC-IV Spanish subtests were…

  11. A review of higher order strain gradient theories of plasticity: Origins ...

    Indian Academy of Sciences (India)

    require higher order boundary conditions that enable us to model effects of disloca- ..... where ǫ0 is a reference strain, σ0 the yield stress and n the strain hardening exponent. The ...... Petch N J 1953 J. Iron Steel Inst. London 173: 25. Pantleon ...

  12. Foundational (co)datatypes and (co)recursion for higher-order logic

    NARCIS (Netherlands)

    Biendarra, Julian; Blanchette, Jasmin Christian; Bouzy, Aymeric; Desharnais, Martin; Fleury, Mathias; Hölzl, Johannes; Kunčar, Ondřej; Lochbihler, Andreas; Meier, Fabian; Panny, Lorenz; Popescu, Andrei; Sternagel, Christian; Thiemann, René; Traytel, Dmitriy; Dixon, C.; Finger, M.

    2017-01-01

    We describe a line of work that started in 2011 towards enriching Isabelle/HOL’s language with coinductive datatypes, which allow infinite values, and with a more expressive notion of inductive datatype than previously supported by any system based on higher-order logic. These (co)datatypes are

  13. Higher-order QCD corrections to inclusive particle production in panti p collisions

    International Nuclear Information System (INIS)

    Borzumati, F.M.; Kniehl, B.A.; Kramer, G.

    1992-10-01

    Inclusive single-particle production cross sections have been calculated including higher-order QCD corrections. Transverse-momentum and rapidity distributions are presented and the scale dependence is studied. The results are compared with experimental data from the CERN Spanti pS Collider and the Fermilab Tevatron. (orig.)

  14. On realization of nonlinear systems described by higher-order differential equations

    NARCIS (Netherlands)

    van der Schaft, Arjan

    1987-01-01

    We consider systems of smooth nonlinear differential and algebraic equations in which some of the variables are distinguished as “external variables.” The realization problem is to replace the higher-order implicit differential equations by first-order explicit differential equations and the

  15. Stabilization of solutions to higher-order nonlinear Schrodinger equation with localized damping

    Directory of Open Access Journals (Sweden)

    Eleni Bisognin

    2007-01-01

    Full Text Available We study the stabilization of solutions to higher-order nonlinear Schrodinger equations in a bounded interval under the effect of a localized damping mechanism. We use multiplier techniques to obtain exponential decay in time of the solutions of the linear and nonlinear equations.

  16. A simplified parsimonious higher order multivariate Markov chain model with new convergence condition

    Science.gov (United States)

    Wang, Chao; Yang, Chuan-sheng

    2017-09-01

    In this paper, we present a simplified parsimonious higher-order multivariate Markov chain model with new convergence condition. (TPHOMMCM-NCC). Moreover, estimation method of the parameters in TPHOMMCM-NCC is give. Numerical experiments illustrate the effectiveness of TPHOMMCM-NCC.

  17. A Probabilistic Model of Visual Working Memory: Incorporating Higher Order Regularities into Working Memory Capacity Estimates

    Science.gov (United States)

    Brady, Timothy F.; Tenenbaum, Joshua B.

    2013-01-01

    When remembering a real-world scene, people encode both detailed information about specific objects and higher order information like the overall gist of the scene. However, formal models of change detection, like those used to estimate visual working memory capacity, assume observers encode only a simple memory representation that includes no…

  18. Higher order hierarchical discretization scheme for surface integral equations for layered media

    DEFF Research Database (Denmark)

    Jørgensen, Erik; Kim, Oleksiy S.; Meincke, Peter

    2004-01-01

    This paper presents an efficient technique for the analysis of electromagnetic scattering by arbitrarily shaped perfectly conducting objects in layered media. The technique is based on a higher order method of moments (MoM) solution of the electric field, magnetic field, or combined-field integra...

  19. Shape invariant higher-order Bessel-like beams carrying orbital angular momentum

    CSIR Research Space (South Africa)

    Ismail, Y

    2012-09-01

    Full Text Available -1 Journal of Optics September 2012/ Vol. 14 Shape invariant higher-order Bessel-like beams carrying orbital angular momentum Y Ismail1,2, N Khilo3, V Belyi3 and A Forbes1,2 1 School of Physics, University of KwaZulu-Natal, Private Bag X54001...

  20. Perturbative theory of higher-order collision-enhanced wave mixing

    International Nuclear Information System (INIS)

    Trebino, R.; Rahn, L.A.

    1989-01-01

    This paper reports on collision-enhanced resonances which represent an interesting class of nonlinear- optical processes. They occur because collisional dephasing can rephase quantum-mechanical amplitudes that ordinarily cancel out exactly, thereby allowing otherwise unobservable wave-mixing resonances to be seen. This is an especially interesting phenomenon because these resonances are coherent effects that are induced by an incoherent process (collisional dephasing). First predicted in the late 1970s and eventually observed in 1981, these novel effects have now been seen in a wide variety of four-wave-mixing experiments, ranging from self-focusing to coherent anti-Stokes Raman spectroscopy. Recently, the authors have extended these observations to higher order, where the authors have shown both experimentally and theoretically the higher-order, collision-enhanced effects exist in nonlinear optics, appearing as subharmonics of two-photon resonances. Indeed, the authors have found that collision-enhanced processes are ideal systems for studying higher-order, nonlinear-optical effects because very high orders can be made to contribute with little or no saturation braodening. Experiments on sodium in a flame using six- and eight-wave-mixing geometries have revealed still higher-order effects (at least as high- order as χ (13) )

  1. Information and Communication Technologies (ICT) in an Elementary School: Students' Engagement in Higher Order Thinking

    Science.gov (United States)

    Lim, Cher Ping; Tay, Lee Yong

    2003-01-01

    Based on a case study of an elementary school in Singapore, this article describes and analyzes how different types of ICT tools (informative, situating, constructive, and communicative tools) are used to engage students in higher-order thinking. The discussion emphasizes that the objective of the lesson and the orienting activities, rather than…

  2. Higher-Order Statistical Correlations and Mutual Information Among Particles in a Quantum Well

    International Nuclear Information System (INIS)

    Yépez, V. S.; Sagar, R. P.; Laguna, H. G.

    2017-01-01

    The influence of wave function symmetry on statistical correlation is studied for the case of three non-interacting spin-free quantum particles in a unidimensional box, in position and in momentum space. Higher-order statistical correlations occurring among the three particles in this quantum system is quantified via higher-order mutual information and compared to the correlation between pairs of variables in this model, and to the correlation in the two-particle system. The results for the higher-order mutual information show that there are states where the symmetric wave functions are more correlated than the antisymmetric ones with same quantum numbers. This holds in position as well as in momentum space. This behavior is opposite to that observed for the correlation between pairs of variables in this model, and the two-particle system, where the antisymmetric wave functions are in general more correlated. These results are also consistent with those observed in a system of three uncoupled oscillators. The use of higher-order mutual information as a correlation measure, is monitored and examined by considering a superposition of states or systems with two Slater determinants. (author)

  3. Strategic Learning in Youth with Traumatic Brain Injury: Evidence for Stall in Higher-Order Cognition

    Science.gov (United States)

    Gamino, Jacquelyn F.; Chapman, Sandra B.; Cook, Lori G.

    2009-01-01

    Little is known about strategic learning ability in preteens and adolescents with traumatic brain injury (TBI). Strategic learning is the ability to combine and synthesize details to form abstracted gist-based meanings, a higher-order cognitive skill associated with frontal lobe functions and higher classroom performance. Summarization tasks were…

  4. Second- and Higher-Order Virial Coefficients Derived from Equations of State for Real Gases

    Science.gov (United States)

    Parkinson, William A.

    2009-01-01

    Derivation of the second- and higher-order virial coefficients for models of the gaseous state is demonstrated by employing a direct differential method and subsequent term-by-term comparison to power series expansions. This communication demonstrates the application of this technique to van der Waals representations of virial coefficients.…

  5. Quantum Noether identities for non-local transformations in higher-order derivatives theories

    International Nuclear Information System (INIS)

    Li, Z.P.; Long, Z.W.

    2003-01-01

    Based on the phase-space generating functional of the Green function for a system with a regular/singular higher-order Lagrangian, the quantum canonical Noether identities (NIs) under a local and non-local transformation in phase space have been deduced, respectively. For a singular higher-order Lagrangian, one must use an effective canonical action I eff P in quantum canonical NIs instead of the classical I P in classical canonical NIs. The quantum NIs under a local and non-local transformation in configuration space for a gauge-invariant system with a higher-order Lagrangian have also been derived. The above results hold true whether or not the Jacobian of the transformation is equal to unity or not. It has been pointed out that in certain cases the quantum NIs may be converted to conservation laws at the quantum level. This algorithm to derive the quantum conservation laws is significantly different from the quantum first Noether theorem. The applications of our formulation to the Yang-Mills fields and non-Abelian Chern-Simons (CS) theories with higher-order derivatives are given, and the conserved quantities at the quantum level for local and non-local transformations are found, respectively. (orig.)

  6. Higher-Order Statistical Correlations and Mutual Information Among Particles in a Quantum Well

    Science.gov (United States)

    Yépez, V. S.; Sagar, R. P.; Laguna, H. G.

    2017-12-01

    The influence of wave function symmetry on statistical correlation is studied for the case of three non-interacting spin-free quantum particles in a unidimensional box, in position and in momentum space. Higher-order statistical correlations occurring among the three particles in this quantum system is quantified via higher-order mutual information and compared to the correlation between pairs of variables in this model, and to the correlation in the two-particle system. The results for the higher-order mutual information show that there are states where the symmetric wave functions are more correlated than the antisymmetric ones with same quantum numbers. This holds in position as well as in momentum space. This behavior is opposite to that observed for the correlation between pairs of variables in this model, and the two-particle system, where the antisymmetric wave functions are in general more correlated. These results are also consistent with those observed in a system of three uncoupled oscillators. The use of higher-order mutual information as a correlation measure, is monitored and examined by considering a superposition of states or systems with two Slater determinants.

  7. Higher order multi-term time-fractional partial differential equations involving Caputo-Fabrizio derivative

    Directory of Open Access Journals (Sweden)

    Erkinjon Karimov

    2017-10-01

    Full Text Available In this work we discuss higher order multi-term partial differential equation (PDE with the Caputo-Fabrizio fractional derivative in time. Using method of separation of variables, we reduce fractional order partial differential equation to the integer order. We represent explicit solution of formulated problem in particular case by Fourier series.

  8. Higher order multi-term time-fractional partial differential equations involving Caputo-Fabrizio derivative

    OpenAIRE

    Erkinjon Karimov; Sardor Pirnafasov

    2017-01-01

    In this work we discuss higher order multi-term partial differential equation (PDE) with the Caputo-Fabrizio fractional derivative in time. Using method of separation of variables, we reduce fractional order partial differential equation to the integer order. We represent explicit solution of formulated problem in particular case by Fourier series.

  9. Mathematics in Finance and Economics: Importance of Teaching Higher Order Mathematical Thinking Skills in Finance

    Science.gov (United States)

    Tularam, Gurudeo Anand

    2013-01-01

    This paper addresses the importance of teaching mathematics in business and finance schools of tertiary institutions of Australia. The paper explores the nature of thinking and reasoning required for advancement financial or economic studies involves the use of higher order thinking and creativity skills (HOTS) for teaching in mathematics classes.…

  10. Performance-Based Task Assessment of Higher-Order Proficiencies in Redesigned STEM High Schools

    Science.gov (United States)

    Ernst, Jeremy V.; Glennie, Elizabeth; Li, Songze

    2017-01-01

    This study explored student abilities in applying conceptual knowledge when presented with structured performance tasks. Specifically, the study gauged proficiency in higher-order applications of students enrolled in earth and environmental science or biology. The student sample was drawn from a Redesigned STEM high school model where a tested…

  11. Higher order equivalent edge currents for fringe wave radar scattering by perfectly conducting polygonal plates

    DEFF Research Database (Denmark)

    Breinbjerg, Olav

    1992-01-01

    An approach for including higher order edge diffraction in the equivalent edge current (EEC) method is proposed. This approach, which applies to monostatic as well as bistatic radar configurations with perfectly conducting polygonal plates, involves three distinct sets of EECs. All of these sets...

  12. Geometrical optics in general relativity: A study of the higher order corrections

    International Nuclear Information System (INIS)

    Anile, A.M.

    1976-01-01

    The higher order corrections to geometrical optics are studied in general relativity for an electromagnetic test wave. An explicit expression is found for the average energy--momentum tensor which takes into account the first-order corrections. Finally the first-order corrections to the well-known area-intensity law of geometrical optics are derived

  13. The focal boundary value problem for strongly singular higher-order nonlinear functional-differential equations

    Czech Academy of Sciences Publication Activity Database

    Mukhigulashvili, Sulkhan; Půža, B.

    2015-01-01

    Roč. 2015, January (2015), s. 17 ISSN 1687-2770 Institutional support: RVO:67985840 Keywords : higher order nonlinear functional-differential equations * two-point right-focal boundary value problem * strong singularity Subject RIV: BA - General Mathematics Impact factor: 0.642, year: 2015 http://link.springer.com/article/10.1186%2Fs13661-014-0277-1

  14. Superpositions of higher-order bessel beams and nondiffracting speckle fields - (SAIP 2009)

    CSIR Research Space (South Africa)

    Dudley, Angela L

    2009-07-01

    Full Text Available speckle fields. The paper reports on illuminating a ring slit aperture with light which has an azimuthal phase dependence, such that the field produced is a superposition of two higher-order Bessel beams. In the case that the phase dependence of the light...

  15. A Hybrid PO - Higher-Order Hierarchical MoM Formulation using Curvilinear Geometry Modeling

    DEFF Research Database (Denmark)

    Jørgensen, E.; Meincke, Peter; Breinbjerg, Olav

    2003-01-01

    which implies a very modest memory requirement. Nevertheless, the hierarchical feature of the basis functions maintains the ability to treat small geometrical details efficiently. In addition, the scatterer is modelled with higher-order curved patches which allows accurate modelling of curved surfaces...

  16. Encouraging Higher-Order Thinking in General Chemistry by Scaffolding Student Learning Using Marzano's Taxonomy

    Science.gov (United States)

    Toledo, Santiago; Dubas, Justin M.

    2016-01-01

    An emphasis on higher-order thinking within the curriculum has been a subject of interest in the chemical and STEM literature due to its ability to promote meaningful, transferable learning in students. The systematic use of learning taxonomies could be a practical way to scaffold student learning in order to achieve this goal. This work proposes…

  17. Higher-order multipole amplitude measurement in psi ' -> gamma chi(c2)

    NARCIS (Netherlands)

    Ablikim, M.; Achasov, M. N.; Alberto, D.; An, F. F.; An, Q.; An, Z. H.; Bai, J. Z.; Baldini, R.; Ban, Y.; Becker, J.; Berger, N.; Bertani, M.; Bian, J. M.; Boger, E.; Bondarenko, O.; Boyko, I.; Briere, R. A.; Bytev, V.; Cai, X.; Calcaterra, A. C.; Cao, G. F.; Chang, J. F.; Chelkov, G.; Chen, G.; Chen, H. S.; Chen, J. C.; Chen, M. L.; Chen, S. J.; Chen, Y.; Chen, Y. B.; Cheng, H. P.; Chu, Y. P.; Cronin-Hennessy, D.; Dai, H. L.; Dai, J. P.; Dedovich, D.; Deng, Z. Y.; Denysenko, I.; Destefanis, M.; Ding, Y.; Dong, L. Y.; Dong, M. Y.; Du, S. X.; Fang, J.; Fang, S. S.; Feng, C. Q.; Fu, C. D.; Fu, J. L.; Gao, Y.; Geng, C.; Goetzen, K.; Gong, W. X.; Greco, M.; Gu, M. H.; Gu, Y. T.; Guan, Y. H.; Guo, A. Q.; Guo, L. B.; Guo, Y. P.; Han, Y. L.; Hao, X. Q.; Harris, F. A.; He, K. L.; He, M.; He, Z. Y.; Heng, Y. K.; Hou, Z. L.; Hu, H. M.; Hu, J. F.; Hu, T.; Huang, B.; Huang, G. M.; Huang, J. S.; Huang, X. T.; Huang, Y. P.; Hussain, T.; Ji, C. S.; Ji, Q.; Ji, X. B.; Ji, X. L.; Jia, L. K.; Jiang, L. L.; Jiang, X. S.; Jiao, J. B.; Jiao, Z.; Jin, D. P.; Jin, S.; Jing, F. F.; Kalantar-Nayestanaki, N.; Kavatsyuk, M.; Kuehn, W.; Lai, W.; Lange, J. S.; Leung, J. K. C.; Li, C. H.; Li, Cheng; Li, Cui; Li, D. M.; Li, F.; Li, G.; Li, H. B.; Li, J. C.; Li, K.; Li, Lei; Li, N. B.; Li, Q. J.; Li, S. L.; Li, W. D.; Li, W. G.; Li, X. L.; Li, X. N.; Li, X. Q.; Li, X. R.; Li, Z. B.; Liang, H.; Liang, Y. F.; Liang, Y. T.; Liao, X. T.; Liu, B. J.; Liu, C. L.; Liu, C. X.; Liu, C. Y.; Liu, F. H.; Liu, Fang; Liu, Feng; Liu, H.; Liu, H. B.; Liu, H. H.; Liu, H. M.; Liu, H. W.; Liu, J. P.; Liu, K.; Liu, K.; Liu, K. Y.; Liu, Q.; Liu, S. B.; Liu, X.; Liu, X. H.; Liu, Y. B.; Liu, Y. W.; Liu, Yong; Liu, Z. A.; Liu, Zhiqiang; Liu, Zhiqing; Loehner, H.; Lu, G. R.; Lu, H. J.; Lu, J. G.; Lu, Q. W.; Lu, X. R.; Lu, Y. P.; Luo, C. L.; Luo, M. X.; Luo, T.; Luo, X. L.; Lv, M.; Ma, C. L.; Ma, F. C.; Ma, H. L.; Ma, Q. M.; Ma, S.; Ma, T.; Ma, X.; Ma, X. Y.; Maggiora, M.; Malik, Q. A.; Mao, H.; Mao, Y. J.; Mao, Z. P.; Messchendorp, J. G.; Min, J.; Min, T. J.; Mitchell, R. E.; Mo, X. H.; Muchnoi, N. Yu; Nefedov, Y.; Nikolaev, I. B.; Ning, Z.; Olsen, S. L.; Ouyang, Q.; Pacetti, S.; Park, J. W.; Pelizaeus, M.; Peters, K.; Ping, J. L.; Ping, R. G.; Poling, R.; Pun, C. S. J.; Qi, M.; Qian, S.; Qiao, C. F.; Qin, X. S.; Qiu, J. F.; Rashid, K. H.; Rong, G.; Ruan, X. D.; Sarantsev, A.; Schulze, J.; Shao, M.; Shen, C. P.; Shen, X. Y.; Sheng, H. Y.; Shepherd, M. R.; Song, X. Y.; Spataro, S.; Spruck, B.; Sun, D. H.; Sun, G. X.; Sun, J. F.; Sun, S. S.; Sun, X. D.; Sun, Y. J.; Sun, Y. Z.; Sun, Z. J.; Sun, Z. T.; Tang, C. J.; Tang, X.; Tian, H. L.; Toth, D.; Varner, G. S.; Wang, B.; Wang, B. Q.; Wang, K.; Wang, L. L.; Wang, L. S.; Wang, M.; Wang, P.; Wang, P. L.; Wang, Q.; Wang, Q. J.; Wang, S. G.; Wang, X. L.; Wang, Y. D.; Wang, Y. F.; Wang, Y. Q.; Wang, Z.; Wang, Z. G.; Wang, Z. Y.; Wei, D. H.; Wen, Q. G.; Wen, S. P.; Wiedner, U.; Wu, L. H.; Wu, N.; Wu, W.; Wu, Z.; Xiao, Z. J.; Xie, Y. G.; Xiu, Q. L.; Xu, G. F.; Xu, G. M.; Xu, H.; Xu, Q. J.; Xu, X. P.; Xu, Y.; Xu, Z. R.; Xu, Z. Z.; Xue, Z.; Yan, L.; Yan, W. B.; Yan, Y. H.; Yang, H. X.; Yang, T.; Yang, Y.; Yang, Y. X.; Ye, H.; Ye, M.; Ye, M. H.; Yu, B. X.; Yu, C. X.; Yu, S. P.; Yuan, C. Z.; Yuan, W. L.; Yuan, Y.; Zafar, A. A.; Zallo, A.; Zeng, Y.; Zhang, B. X.; Zhang, B. Y.; Zhang, C.; Zhang, C. C.; Zhang, D. H.; Zhang, H. H.; Zhang, H. Y.; Zhang, J.; Zhang, J. Q.; Zhang, J. W.; Zhang, J. Y.; Zhang, J. Z.; Zhang, L.; Zhang, S. H.; Zhang, T. R.; Zhang, X. J.; Zhang, X. Y.; Zhang, Y.; Zhang, Y. H.; Zhang, Y. S.; Zhang, Z. P.; Zhang, Z. Y.; Zhao, G.; Zhao, H. S.; Zhao, Jiawei; Zhao, Jingwei; Zhao, Lei; Zhao, Ling; Zhao, M. G.; Zhao, Q.; Zhao, S. J.; Zhao, T. C.; Zhao, X. H.; Zhao, Y. B.; Zhao, Z. G.; Zhao, Z. L.; Zhemchugov, A.; Zheng, B.; Zheng, J. P.; Zheng, Y. H.; Zheng, Z. P.; Zhong, B.; Zhong, J.; Zhong, L.; Zhou, L.; Zhou, X. K.; Zhou, X. R.; Zhu, C.; Zhu, K.; Zhu, K. J.; Zhu, S. H.; Zhu, X. L.; Zhu, X. W.; Zhu, Y. S.; Zhu, Z. A.; Zhuang, J.; Zou, B. S.; Zou, J. H.; Zuo, J. X.

    2011-01-01

    Using 106 x 10(6) psi' events collected with the BESIII detector at the BEPCII storage ring, the higher-order multipole amplitudes in the radiative transition psi' -> gamma chi(c2) -> gamma pi(+)pi(-)/gamma K+K- are measured. A fit to the chi(c2) production and decay angular distributions yields M2

  18. Unifying refinement and hoare-style reasoning in a logic for higher-order concurrency

    DEFF Research Database (Denmark)

    Turon, Aaron; Dreyer, Derek; Birkedal, Lars

    2013-01-01

    Modular programming and modular verification go hand in hand, but most existing logics for concurrency ignore two crucial forms of modularity: *higher-order functions*, which are essential for building reusable components, and *granularity abstraction*, a key technique for hiding the intricacies ...

  19. Analysis of warping deformation modes using higher order ANCF beam element

    Science.gov (United States)

    Orzechowski, Grzegorz; Shabana, Ahmed A.

    2016-02-01

    Most classical beam theories assume that the beam cross section remains a rigid surface under an arbitrary loading condition. However, in the absolute nodal coordinate formulation (ANCF) continuum-based beams, this assumption can be relaxed allowing for capturing deformation modes that couple the cross-section deformation and beam bending, torsion, and/or elongation. The deformation modes captured by ANCF finite elements depend on the interpolating polynomials used. The most widely used spatial ANCF beam element employs linear approximation in the transverse direction, thereby restricting the cross section deformation and leading to locking problems. The objective of this investigation is to examine the behavior of a higher order ANCF beam element that includes quadratic interpolation in the transverse directions. This higher order element allows capturing warping and non-uniform stretching distribution. Furthermore, this higher order element allows for increasing the degree of continuity at the element interface. It is shown in this paper that the higher order ANCF beam element can be used effectively to capture warping and eliminate Poisson locking that characterizes lower order ANCF finite elements. It is also shown that increasing the degree of continuity requires a special attention in order to have acceptable results. Because higher order elements can be more computationally expensive than the lower order elements, the use of reduced integration for evaluating the stress forces and the use of explicit and implicit numerical integrations to solve the nonlinear dynamic equations of motion are investigated in this paper. It is shown that the use of some of these integration methods can be very effective in reducing the CPU time without adversely affecting the solution accuracy.

  20. The Role of Chromatin-Associated Proteins in Cancer

    DEFF Research Database (Denmark)

    Helin, Kristian; Minucci, Saverio

    2017-01-01

    The organization of the chromatin structure is essential for maintaining cell-type-specific gene expression and therefore for cell identity. This structure is highly dynamic and is regulated by a large number of chromatin-associated proteins that are required for normal development...... and differentiation. Recurrent somatic mutations have been found with high frequency in genes coding for chromatin-associated proteins in cancer, and several of these are required for cancer maintenance. In this review, we discuss recent advances in understanding the role of chromatin-associated proteins...

  1. Quantifying the impact of scholarly papers based on higher-order weighted citations.

    Science.gov (United States)

    Bai, Xiaomei; Zhang, Fuli; Hou, Jie; Lee, Ivan; Kong, Xiangjie; Tolba, Amr; Xia, Feng

    2018-01-01

    Quantifying the impact of a scholarly paper is of great significance, yet the effect of geographical distance of cited papers has not been explored. In this paper, we examine 30,596 papers published in Physical Review C, and identify the relationship between citations and geographical distances between author affiliations. Subsequently, a relative citation weight is applied to assess the impact of a scholarly paper. A higher-order weighted quantum PageRank algorithm is also developed to address the behavior of multiple step citation flow. Capturing the citation dynamics with higher-order dependencies reveals the actual impact of papers, including necessary self-citations that are sometimes excluded in prior studies. Quantum PageRank is utilized in this paper to help differentiating nodes whose PageRank values are identical.

  2. Engaging adolescents with LD in higher order thinking about history concepts using integrated content enhancement routines.

    Science.gov (United States)

    Bulgren, Janis; Deshler, Donald D; Lenz, B Keith

    2007-01-01

    The understanding and use of historical concepts specified in national history standards pose many challenges to students. These challenges include both the acquisition of content knowledge and the use of that knowledge in ways that require higher order thinking. All students, including adolescents with learning disabilities (LD), are expected to understand and use concepts of history to pass high-stakes assessments and to participate meaningfully in a democratic society. This article describes Content Enhancement Routines (CERs) to illustrate instructional planning, teaching, and assessing for higher order thinking with examples from an American history unit. Research on the individual components of Content Enhancement Routines will be illustrated with data from 1 of the routines. The potential use of integrated sets of materials and procedures across grade levels and content areas will be discussed.

  3. A Study of Enhanced, Higher Order Boussinesq-Type Equations and Their Numerical Modelling

    DEFF Research Database (Denmark)

    Banijamali, Babak

    model is designated for the solution of higher-order Boussinesq-type equations, formulated in terms of the horizontal velocity at an arbitrary depth vector. Various discretisation techniques and grid definitions have been considered in this endeavour, undertaking a detailed analysis of the selected......This project has encompassed efforts in two separate veins: on the one hand, the acquiring of highly accurate model equations of the Boussinesq-type, and on the other hand, the theoretical and practical work in implementing such equations in the form of conventional numerical models, with obvious...... potential for applications to the realm of numerical modelling in coastal engineering. The derivation and analysis of several forms of higher-order in dispersion and non-linearity Boussinesq-type equations have been undertaken, obtaining and investigating the properties of a new and generalised class...

  4. Optimizing students’ scientific communication skills through higher order thinking virtual laboratory (HOTVL)

    Science.gov (United States)

    Sapriadil, S.; Setiawan, A.; Suhandi, A.; Malik, A.; Safitri, D.; Lisdiani, S. A. S.; Hermita, N.

    2018-05-01

    Communication skill is one skill that is very needed in this 21st century. Preparing and teaching this skill in teaching physics is relatively important. The focus of this research is to optimizing of students’ scientific communication skills after the applied higher order thinking virtual laboratory (HOTVL) on topic electric circuit. This research then employed experimental study particularly posttest-only control group design. The subject in this research involved thirty senior high school students which were taken using purposive sampling. A sample of seventy (70) students participated in the research. An equivalent number of thirty five (35) students were assigned to the control and experimental group. The results of this study found that students using higher order thinking virtual laboratory (HOTVL) in laboratory activities had higher scientific communication skills than students who used the verification virtual lab.

  5. An initial framework for the language of higher-order thinking mathematics practices

    Science.gov (United States)

    Staples, Megan E.; Truxaw, Mary P.

    2012-09-01

    This article presents an examination of the language demands of cognitively demanding tasks and proposes an initial framework for the language demands of higher-order mathematics thinking practices. We articulate four categories for this framework: language of generalisation, language of comparison, language of proportional reasoning, and language of analysing impact. These categories were developed out of our collaborative work to design and implement higher-order thinking tasks with a group of Grade 9 (14- and 15-year-olds) teachers teaching in a linguistically diverse setting; analyses of student work samples on these tasks; and our knowledge of the literature. We describe each type of language demand and then analyse student work in each category to reveal linguistic challenges facing students as they engage these mathematical tasks. Implications for teaching and professional development are discussed.

  6. An Efficient Higher-Order Quasilinearization Method for Solving Nonlinear BVPs

    Directory of Open Access Journals (Sweden)

    Eman S. Alaidarous

    2013-01-01

    Full Text Available In this research paper, we present higher-order quasilinearization methods for the boundary value problems as well as coupled boundary value problems. The construction of higher-order convergent methods depends on a decomposition method which is different from Adomain decomposition method (Motsa and Sibanda, 2013. The reported method is very general and can be extended to desired order of convergence for highly nonlinear differential equations and also computationally superior to proposed iterative method based on Adomain decomposition because our proposed iterative scheme avoids the calculations of Adomain polynomials and achieves the same computational order of convergence as authors have claimed in Motsa and Sibanda, 2013. In order to check the validity and computational performance, the constructed iterative schemes are also successfully applied to bifurcation problems to calculate the values of critical parameters. The numerical performance is also tested for one-dimension Bratu and Frank-Kamenetzkii equations.

  7. Evidence for higher-order effects in L-shell ionization by proton impact

    International Nuclear Information System (INIS)

    Sarkadi, L.; Mukoyama, T.

    1988-01-01

    It is widely believed that higher order processes of ion-atom collisions are negligible in cases of light projectiles like proton. Recent refined experiments tried to prove that the existence of such effects were comperable with the experimental errors, and they showed the unexpected relative importance of the higher order processes. Thus a new coupled channel calculation was performed for proton-gold atom collision in the energy range of 0.15-3.0 MeV, including dynamical subshell coupling effects. The results show that the deviations from the first order cross sections reach 40% at low collision energy. This result made necessary to correct the calculations of L-shell X-ray production cross sections. (D.G.) 6 refs

  8. Higher-order meshing of implicit geometries, Part II: Approximations on manifolds

    Science.gov (United States)

    Fries, T. P.; Schöllhammer, D.

    2017-11-01

    A new concept for the higher-order accurate approximation of partial differential equations on manifolds is proposed where a surface mesh composed by higher-order elements is automatically generated based on level-set data. Thereby, it enables a completely automatic workflow from the geometric description to the numerical analysis without any user-intervention. A master level-set function defines the shape of the manifold through its zero-isosurface which is then restricted to a finite domain by additional level-set functions. It is ensured that the surface elements are sufficiently continuous and shape regular which is achieved by manipulating the background mesh. The numerical results show that optimal convergence rates are obtained with a moderate increase in the condition number compared to handcrafted surface meshes.

  9. Higher-order predictions for splitting functions and coefficient functions from physical evolution kernels

    International Nuclear Information System (INIS)

    Vogt, A; Soar, G.; Vermaseren, J.A.M.

    2010-01-01

    We have studied the physical evolution kernels for nine non-singlet observables in deep-inelastic scattering (DIS), semi-inclusive e + e - annihilation and the Drell-Yan (DY) process, and for the flavour-singlet case of the photon- and heavy-top Higgs-exchange structure functions (F 2 , F φ ) in DIS. All known contributions to these kernels show an only single-logarithmic large-x enhancement at all powers of (1-x). Conjecturing that this behaviour persists to (all) higher orders, we have predicted the highest three (DY: two) double logarithms of the higher-order non-singlet coefficient functions and of the four-loop singlet splitting functions. The coefficient-function predictions can be written as exponentiations of 1/N-suppressed contributions in Mellin-N space which, however, are less predictive than the well-known exponentiation of the ln k N terms. (orig.)

  10. Quantifying the impact of scholarly papers based on higher-order weighted citations

    Science.gov (United States)

    Bai, Xiaomei; Zhang, Fuli; Hou, Jie; Kong, Xiangjie; Tolba, Amr; Xia, Feng

    2018-01-01

    Quantifying the impact of a scholarly paper is of great significance, yet the effect of geographical distance of cited papers has not been explored. In this paper, we examine 30,596 papers published in Physical Review C, and identify the relationship between citations and geographical distances between author affiliations. Subsequently, a relative citation weight is applied to assess the impact of a scholarly paper. A higher-order weighted quantum PageRank algorithm is also developed to address the behavior of multiple step citation flow. Capturing the citation dynamics with higher-order dependencies reveals the actual impact of papers, including necessary self-citations that are sometimes excluded in prior studies. Quantum PageRank is utilized in this paper to help differentiating nodes whose PageRank values are identical. PMID:29596426

  11. ANOVA-HDMR structure of the higher order nodal diffusion solution

    International Nuclear Information System (INIS)

    Bokov, P. M.; Prinsloo, R. H.; Tomasevic, D. I.

    2013-01-01

    Nodal diffusion methods still represent a standard in global reactor calculations, but employ some ad-hoc approximations (such as the quadratic leakage approximation) which limit their accuracy in cases where reference quality solutions are sought. In this work we solve the nodal diffusion equations utilizing the so-called higher-order nodal methods to generate reference quality solutions and to decompose the obtained solutions via a technique known as High Dimensional Model Representation (HDMR). This representation and associated decomposition of the solution provides a new formulation of the transverse leakage term. The HDMR structure is investigated via the technique of Analysis of Variance (ANOVA), which indicates why the existing class of transversely-integrated nodal methods prove to be so successful. Furthermore, the analysis leads to a potential solution method for generating reference quality solutions at a much reduced calculational cost, by applying the ANOVA technique to the full higher order solution. (authors)

  12. Coaxial higher-order mode damper employing a high-pass filter

    International Nuclear Information System (INIS)

    Kang, Y.W.; Jiang, X.

    1997-01-01

    Two different types of coaxial higher-order mode (HOM) dampers have been investigated for the Advanced Photon Source (APS) storage ring cavities: e-probe dampers and h-loop dampers. Realization of the h-loop dampers has been difficult because the loop antenna couples not only to the HOMs but also to the accelerating mode and results in loss of Q at the fundamental frequency. Previously, a first-order fundamental rejection filter was tested with unsatisfactory rejection characteristics. This problem can be overcome by using a higher-order high-pass filter between the loop and the matched load. Prototype dampers have been fabricated and tested in a storage ring single-cell cavity and the damping characteristic was analyzed

  13. Propagation of high power electromagnetic beam in relativistic magnetoplasma: Higher order paraxial ray theory

    Science.gov (United States)

    Gill, Tarsem Singh; Kaur, Ravinder; Mahajan, Ranju

    2010-09-01

    This paper presents an analysis of self-consistent, steady-state, theoretical model, which explains the ring formation in a Gaussian electromagnetic beam propagating in a magnetoplasma, characterized by relativistic nonlinearity. Higher order terms (up to r4) in the expansion of the dielectric function and the eikonal have been taken into account. The condition for the formation of a dark and bright ring derived earlier by Misra and Mishra [J. Plasma Phys. 75, 769 (2009)] has been used to study focusing/defocusing of the beam. It is seen that inclusion of higher order terms does significantly affect the dependence of the beam width on the distance of propagation. Further, the effect of the magnetic field and the nature of nonlinearity on the ring formation and self-focusing of the beam have been explored.

  14. Propagation of high power electromagnetic beam in relativistic magnetoplasma: Higher order paraxial ray theory

    International Nuclear Information System (INIS)

    Gill, Tarsem Singh; Kaur, Ravinder; Mahajan, Ranju

    2010-01-01

    This paper presents an analysis of self-consistent, steady-state, theoretical model, which explains the ring formation in a Gaussian electromagnetic beam propagating in a magnetoplasma, characterized by relativistic nonlinearity. Higher order terms (up to r 4 ) in the expansion of the dielectric function and the eikonal have been taken into account. The condition for the formation of a dark and bright ring derived earlier by Misra and Mishra [J. Plasma Phys. 75, 769 (2009)] has been used to study focusing/defocusing of the beam. It is seen that inclusion of higher order terms does significantly affect the dependence of the beam width on the distance of propagation. Further, the effect of the magnetic field and the nature of nonlinearity on the ring formation and self-focusing of the beam have been explored.

  15. Robust rooftop extraction from visible band images using higher order CRF

    KAUST Repository

    Li, Er

    2015-08-01

    In this paper, we propose a robust framework for building extraction in visible band images. We first get an initial classification of the pixels based on an unsupervised presegmentation. Then, we develop a novel conditional random field (CRF) formulation to achieve accurate rooftops extraction, which incorporates pixel-level information and segment-level information for the identification of rooftops. Comparing with the commonly used CRF model, a higher order potential defined on segment is added in our model, by exploiting region consistency and shape feature at segment level. Our experiments show that the proposed higher order CRF model outperforms the state-of-the-art methods both at pixel and object levels on rooftops with complex structures and sizes in challenging environments. © 1980-2012 IEEE.

  16. John Carroll’s Views on Intelligence: Bi-Factor vs. Higher-Order Models

    Directory of Open Access Journals (Sweden)

    A. Alexander Beaujean

    2015-10-01

    Full Text Available The development of factor models is inextricably tied to the history of intelligence research. One of the most commonly-cited scholars in the field is John Carroll, whose three-stratum theory of cognitive ability has been one of the most influential models of cognitive ability in the past 20 years. Nonetheless, there is disagreement about how Carroll conceptualized the factors in his model. Some argue that his model is best represented through a higher-order model, while others argue that a bi-factor model is a better representation. Carroll was explicit about what he perceived the best way to represent his model, but his writings are not always easy to understand. In this article, I clarify his position by first describing the details and implications of bi-factor and higher-order models then show that Carroll’s published views are better represented by a bi-factor model.

  17. A higher order space-time Galerkin scheme for time domain integral equations

    KAUST Repository

    Pray, Andrew J.; Beghein, Yves; Nair, Naveen V.; Cools, Kristof; Bagci, Hakan; Shanker, Balasubramaniam

    2014-01-01

    Stability of time domain integral equation (TDIE) solvers has remained an elusive goal formany years. Advancement of this research has largely progressed on four fronts: 1) Exact integration, 2) Lubich quadrature, 3) smooth temporal basis functions, and 4) space-time separation of convolutions with the retarded potential. The latter method's efficacy in stabilizing solutions to the time domain electric field integral equation (TD-EFIE) was previously reported for first-order surface descriptions (flat elements) and zeroth-order functions as the temporal basis. In this work, we develop the methodology necessary to extend the scheme to higher order surface descriptions as well as to enable its use with higher order basis functions in both space and time. These basis functions are then used in a space-time Galerkin framework. A number of results are presented that demonstrate convergence in time. The viability of the space-time separation method in producing stable results is demonstrated experimentally for these examples.

  18. Discrete Maximum Principle for Higher-Order Finite Elements in 1D

    Czech Academy of Sciences Publication Activity Database

    Vejchodský, Tomáš; Šolín, Pavel

    2007-01-01

    Roč. 76, č. 260 (2007), s. 1833-1846 ISSN 0025-5718 R&D Projects: GA ČR GP201/04/P021 Institutional research plan: CEZ:AV0Z10190503; CEZ:AV0Z20760514 Keywords : discrete maximum principle * discrete Grren´s function * higher-order elements Subject RIV: BA - General Mathematics Impact factor: 1.230, year: 2007

  19. Tunnelling effects of solitons in optical fibers with higher-order effects

    Energy Technology Data Exchange (ETDEWEB)

    Dai, Chao-Qing [Zhejiang A and F Univ., Lin' an (China). School of Sciences; Suzhou Univ., Jiangsu (China). School of Physical Science and Technology; Zhu, Hai-Ping [Zhejiang Lishui Univ., Zhejiang (China). School of Science; Zheng, Chun-Long [Shaoguan Univ., Guangdong (China). College of Physics and Electromechanical Engineering

    2012-06-15

    We construct four types of analytical soliton solutions for the higher-order nonlinear Schroedinger equation with distributed coefficients. These solutions include bright solitons, dark solitons, combined solitons, and M-shaped solitons. Moreover, the explicit functions which describe the evolution of the width, peak, and phase are discussed exactly. We finally discuss the nonlinear soliton tunnelling effect for four types of femtosecond solitons. (orig.)

  20. Temperature dependent investigation on optically active process of higher-order bands in irradiated silicon

    International Nuclear Information System (INIS)

    Shi Yi; Nanjing Univ., JS; Wu Fengmei; Nanjing Univ., JS; Zheng Youdou; Nanjing Univ., JS; Suezawa, M.; Imai, M.; Sumino, K.

    1996-01-01

    Optically active processes of the higher-order bands (HOB) are investigated at different temperatures in fast neutron irradiated silicon using Fourier transform infrared absorption measurement. It is shown that the optically active process is nearly temperature independent below 80 K, the slow decay process remains up to a heating temperature of 180 K. The observations are analyzed in terms of the relaxation behavior of photoexcited carriers governed by fast neutron radiation induced defect clusters. (orig.)

  1. Dynamic Correction of Higher-Order Deflection Aberrations in the Environmental SEM

    Czech Academy of Sciences Publication Activity Database

    Oral, Martin; Neděla, Vilém

    2015-01-01

    Roč. 21, S4 (2015), s. 194-199 ISSN 1431-9276 R&D Projects: GA ČR(CZ) GA14-22777S; GA MŠk(CZ) LO1212 Institutional support: RVO:68081731 Keywords : environmental SEM * ESEM * shifted deflection pivot point * Higher order deflection aberrations * vignetting * dynamic focusing * dynamic stigmator * dynamic correction Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering Impact factor: 1.730, year: 2015

  2. Asymptotic estimates and exponential stability for higher-order monotone difference equations

    Directory of Open Access Journals (Sweden)

    Pituk Mihály

    2005-01-01

    Full Text Available Asymptotic estimates are established for higher-order scalar difference equations and inequalities the right-hand sides of which generate a monotone system with respect to the discrete exponential ordering. It is shown that in some cases the exponential estimates can be replaced with a more precise limit relation. As corollaries, a generalization of discrete Halanay-type inequalities and explicit sufficient conditions for the global exponential stability of the zero solution are given.

  3. Asymptotic estimates and exponential stability for higher-order monotone difference equations

    Directory of Open Access Journals (Sweden)

    Mihály Pituk

    2005-03-01

    Full Text Available Asymptotic estimates are established for higher-order scalar difference equations and inequalities the right-hand sides of which generate a monotone system with respect to the discrete exponential ordering. It is shown that in some cases the exponential estimates can be replaced with a more precise limit relation. As corollaries, a generalization of discrete Halanay-type inequalities and explicit sufficient conditions for the global exponential stability of the zero solution are given.

  4. A single dose of oxytocin nasal spray improves higher-order social cognition in schizophrenia.

    Science.gov (United States)

    Guastella, Adam J; Ward, Philip B; Hickie, Ian B; Shahrestani, Sara; Hodge, Marie Antoinette Redoblado; Scott, Elizabeth M; Langdon, Robyn

    2015-11-01

    Schizophrenia is associated with significant impairments in both higher and lower order social cognitive performance and these impairments contribute to poor social functioning. People with schizophrenia report poor social functioning to be one of their greatest unmet treatment needs. Recent studies have suggested the potential of oxytocin as such a treatment, but mixed results render it uncertain what aspects of social cognition are improved by oxytocin and, subsequently, how oxytocin might best be applied as a therapeutic. The aim of this study was to determine whether a single dose of oxytocin improved higher-order and lower-order social cognition performance for patients with schizophrenia across a well-established battery of social cognition tests. Twenty-one male patients received both a single dose of oxytocin nasal spray (24IU) and a placebo, two weeks apart in a randomized within-subjects placebo controlled design. Following each administration, participants completed the social cognition tasks, as well as a test of general neurocognition. Results revealed that oxytocin particularly enhanced performance on higher order social cognition tasks, with no effects on general neurocognition. Results for individual tasks showed most improvement on tests measuring appreciation of indirect hints and recognition of social faux pas. These results suggest that oxytocin, if combined to enhance social cognition learning, may be beneficial when targeted at higher order social cognition domains. This study also suggests that these higher order tasks, which assess social cognitive processing in a social communication context, may provide useful markers of response to oxytocin in schizophrenia. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Combined solitary-wave solution for coupled higher-order nonlinear Schroedinger equations

    International Nuclear Information System (INIS)

    Tian Jinping; Tian Huiping; Li Zhonghao; Zhou Guosheng

    2004-01-01

    Coupled nonlinear Schroedinger equations model several interesting physical phenomena. We used a trigonometric function transform method based on a homogeneous balance to solve the coupled higher-order nonlinear Schroedinger equations. We obtained four pairs of exact solitary-wave solutions including a dark and a bright-soliton pair, a bright- and a dark-soliton pair, a bright- and a bright-soliton pair, and the last pair, a combined bright-dark-soliton pair

  6. On the mild solutions of higher-order differential equations in Banach spaces

    Directory of Open Access Journals (Sweden)

    Nguyen Thanh Lan

    2003-01-01

    Full Text Available For the higher-order abstract differential equation u(n(t=Au(t+f(t, t∈ℝ, we give a new definition of mild solutions. We then characterize the regular admissibility of a translation-invariant subspace ℳ of BUC(ℝ,E with respect to the above-mentioned equation in terms of solvability of the operator equation AX−Xn=C. As applications, periodicity and almost periodicity of mild solutions are also proved.

  7. Higher Order Aitken Extrapolation with Application to Converging and Diverging Gauss-Seidel Iterations

    OpenAIRE

    Tiruneh, Ababu Teklemariam

    2013-01-01

    Aitken extrapolation normally applied to convergent fixed point iteration is extended to extrapolate the solution of a divergent iteration. In addition, higher order Aitken extrapolation is introduced that enables successive decomposition of high Eigen values of the iteration matrix to enable convergence. While extrapolation of a convergent fixed point iteration using a geometric series sum is a known form of Aitken acceleration, it is shown in this paper that the same formula can be used to ...

  8. Exotic quantum holonomy and higher-order exceptional points in quantum kicked tops

    OpenAIRE

    Tanaka, Atushi; Kim, Sang Wook; Cheon, Taksu

    2014-01-01

    The correspondence between exotic quantum holonomy that occurs in families of Hermitian cycles, and exceptional points (EPs) for non-Hermitian quantum theory is examined in quantum kicked tops. Under a suitable condition, an explicit expressions of the adiabatic parameter dependencies of quasienergies and stationary states, which exhibit anholonomies, are obtained. It is also shown that the quantum kicked tops with the complexified adiabatic parameter have a higher order EP, which is broken i...

  9. Growth of meromorphic solutions of higher-order linear differential equations

    Directory of Open Access Journals (Sweden)

    Wenjuan Chen

    2009-01-01

    Full Text Available In this paper, we investigate the higher-order linear differential equations with meromorphic coefficients. We improve and extend a result of M.S. Liu and C.L. Yuan, by using the estimates for the logarithmic derivative of a transcendental meromorphic function due to Gundersen, and the extended Winman-Valiron theory which proved by J. Wang and H.X. Yi. In addition, we also consider the nonhomogeneous linear differential equations.

  10. Higher order multiple pregnancy outcomes in the Maltese islands 2000-2004

    OpenAIRE

    Savona-Ventura, Charles; Gatt, Miriam; Vella, Katya; Grima, Stephen

    2008-01-01

    Higher order multiple births have increased significantly in the last decades throughout the developed world. In spite of advances in obstetric care seen throughout the second half of the twentieth century, the perinatal outcomes associated with a multiple pregnancy remain associated with increased morbidity and mortality for the mother and the infants. This study attempts to assess the characteristics and outcomes of these maternities in the Maltese population. The National maternity data fo...

  11. Soliton and periodic solutions for higher order wave equations of KdV type (I)

    International Nuclear Information System (INIS)

    Khuri, S.A.

    2005-01-01

    The aim of the paper is twofold. First, a new ansaetze is introduced for the construction of exact solutions for higher order wave equations of KdV type (I). We show the existence of a class of discontinuous soliton solutions with infinite spikes. Second, the projective Riccati technique is implemented as an alternate approach for obtaining new exact solutions, solitary solutions, and periodic wave solutions

  12. Contribution of higher order terms in the reductive perturbation theory, 2

    International Nuclear Information System (INIS)

    Ichikawa, Y.H.; Mitsuhashi, Teruo; Konno, Kimiaki.

    1977-01-01

    Contribution of higher order terms in the reductive perturbation theory has been investigated for nonlinear propagation of strongly dispersive ion plasma wave. The basic set of fluid equation is reduced to a coupled set of the nonlinear Schroedinger equation for the first order perturbed potential and a linear inhomogeneous equation for the second order perturbed potential. A steady state solution of the coupled set of equations has been solved analytically in the asymptotic limit of small wave number. (auth.)

  13. Transition, coexistence, and interaction of vector localized waves arising from higher-order effects

    International Nuclear Information System (INIS)

    Liu, Chong; Yang, Zhan-Ying; Zhao, Li-Chen; Yang, Wen-Li

    2015-01-01

    We study vector localized waves on continuous wave background with higher-order effects in a two-mode optical fiber. The striking properties of transition, coexistence, and interaction of these localized waves arising from higher-order effects are revealed in combination with corresponding modulation instability (MI) characteristics. It shows that these vector localized wave properties have no analogues in the case without higher-order effects. Specifically, compared to the scalar case, an intriguing transition between bright–dark rogue waves and w-shaped–anti-w-shaped solitons, which occurs as a result of the attenuation of MI growth rate to vanishing in the zero-frequency perturbation region, is exhibited with the relative background frequency. In particular, our results show that the w-shaped–anti-w-shaped solitons can coexist with breathers, coinciding with the MI analysis where the coexistence condition is a mixture of a modulation stability and MI region. It is interesting that their interaction is inelastic and describes a fusion process. In addition, we demonstrate an annihilation phenomenon for the interaction of two w-shaped solitons which is identified essentially as an inelastic collision in this system. -- Highlights: •Vector rogue wave properties induced by higher-order effects are studied. •A transition between vector rogue waves and solitons is obtained. •The link between the transition and modulation instability (MI) is demonstrated. •The coexistence of vector solitons and breathers coincides with the MI features. •An annihilation phenomenon for the vector two w-shaped solitons is presented.

  14. Transition, coexistence, and interaction of vector localized waves arising from higher-order effects

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Chong [School of Physics, Northwest University, Xi’an 710069 (China); Yang, Zhan-Ying, E-mail: zyyang@nwu.edu.cn [School of Physics, Northwest University, Xi’an 710069 (China); Zhao, Li-Chen, E-mail: zhaolichen3@163.com [School of Physics, Northwest University, Xi’an 710069 (China); Yang, Wen-Li [Institute of Modern Physics, Northwest University, Xi’an 710069 (China)

    2015-11-15

    We study vector localized waves on continuous wave background with higher-order effects in a two-mode optical fiber. The striking properties of transition, coexistence, and interaction of these localized waves arising from higher-order effects are revealed in combination with corresponding modulation instability (MI) characteristics. It shows that these vector localized wave properties have no analogues in the case without higher-order effects. Specifically, compared to the scalar case, an intriguing transition between bright–dark rogue waves and w-shaped–anti-w-shaped solitons, which occurs as a result of the attenuation of MI growth rate to vanishing in the zero-frequency perturbation region, is exhibited with the relative background frequency. In particular, our results show that the w-shaped–anti-w-shaped solitons can coexist with breathers, coinciding with the MI analysis where the coexistence condition is a mixture of a modulation stability and MI region. It is interesting that their interaction is inelastic and describes a fusion process. In addition, we demonstrate an annihilation phenomenon for the interaction of two w-shaped solitons which is identified essentially as an inelastic collision in this system. -- Highlights: •Vector rogue wave properties induced by higher-order effects are studied. •A transition between vector rogue waves and solitons is obtained. •The link between the transition and modulation instability (MI) is demonstrated. •The coexistence of vector solitons and breathers coincides with the MI features. •An annihilation phenomenon for the vector two w-shaped solitons is presented.

  15. Sleep inertia, sleep homeostatic and circadian influences on higher-order cognitive functions.

    Science.gov (United States)

    Burke, Tina M; Scheer, Frank A J L; Ronda, Joseph M; Czeisler, Charles A; Wright, Kenneth P

    2015-08-01

    Sleep inertia, sleep homeostatic and circadian processes modulate cognition, including reaction time, memory, mood and alertness. How these processes influence higher-order cognitive functions is not well known. Six participants completed a 73-day-long study that included two 14-day-long 28-h forced desynchrony protocols to examine separate and interacting influences of sleep inertia, sleep homeostasis and circadian phase on higher-order cognitive functions of inhibitory control and selective visual attention. Cognitive performance for most measures was impaired immediately after scheduled awakening and improved during the first ~2-4 h of wakefulness (decreasing sleep inertia); worsened thereafter until scheduled bedtime (increasing sleep homeostasis); and was worst at ~60° and best at ~240° (circadian modulation, with worst and best phases corresponding to ~09:00 and ~21:00 hours, respectively, in individuals with a habitual wake time of 07:00 hours). The relative influences of sleep inertia, sleep homeostasis and circadian phase depended on the specific higher-order cognitive function task examined. Inhibitory control appeared to be modulated most strongly by circadian phase, whereas selective visual attention for a spatial-configuration search task was modulated most strongly by sleep inertia. These findings demonstrate that some higher-order cognitive processes are differentially sensitive to different sleep-wake regulatory processes. Differential modulation of cognitive functions by different sleep-wake regulatory processes has important implications for understanding mechanisms contributing to performance impairments during adverse circadian phases, sleep deprivation and/or upon awakening from sleep. © 2015 European Sleep Research Society.

  16. On the formulations of higher-order strain gradient crystal plasticity models

    DEFF Research Database (Denmark)

    Kuroda, M.; Tvergaard, Viggo

    2008-01-01

    Recently, several higher-order extensions to the crystal plasticity theory have been proposed to incorporate effects of material length scales that were missing links in the conventional continuum mechanics. The extended theories are classified into work-conjugate and non-work-conjugate types. A ...... deformation. In this paper, the discussion is extended to a more general situation, i.e. the context of multiple and three-dimensional slip deformations....

  17. Wilson's theory of critical phenomena. Higher order corrections to critical exponents

    International Nuclear Information System (INIS)

    Zinn-Justin, J.

    1973-01-01

    The Wilson's theory of critical phenomena is presented, in the context of renormalized field theory in d dimension and of the Callan-Symanzik equations. This theory allows in particular to compute critical exponents that govern the behavior of some correlation functions near the critical temperature, as power series in epsilon=4-d, using the standard perturbation theory. Owing to the large value of the expansion parameter epsilon, whose physical value is one, it is very important to perform higher order calculations [fr

  18. A stable higher order space time Galerkin marching-on-in-time scheme

    KAUST Repository

    Pray, Andrew J.

    2013-07-01

    We present a method for the stable solution of time-domain integral equations. The method uses a technique developed in [1] to accurately evaluate matrix elements. As opposed to existing stabilization schemes, the method presented uses higher order basis functions in time to improve the accuracy of the solver. The method is validated by showing convergence in temporal basis function order, time step size, and geometric discretization order. © 2013 IEEE.

  19. Integrated Software Development System/Higher Order Software Conceptual Description (ISDS/HOS)

    Science.gov (United States)

    1976-11-01

    Structured Flowchart Conventions 270 6.3.5.3 Design Diagram Notation 273 xii HIGHER ORDER SOFTWARE, INC. 843 MASSACHUSETTS AVENUE. CAMBRIDGE, MASSACHUSETTS...associated with the process steps. They also reference other HIPO diagrams as well an non-HIPO documentation such as flowcharts or decision tables of...syntax that is easy to learn and must provide the novice with some prompting to help him avoid classic beginner errors. Desirable editing capabilities

  20. Higher order Stark effect and transition probabilities on hyperfine structure components of hydrogen like atoms

    Energy Technology Data Exchange (ETDEWEB)

    Pal' chikov, V.G. [National Research Institute for Physical-Technical and Radiotechnical Measurements - VNIIFTRI (Russian Federation)], E-mail: vitpal@mail.ru

    2000-08-15

    A quantum-electrodynamical (QED) perturbation theory is developed for hydrogen and hydrogen-like atomic systems with interaction between bound electrons and radiative field being treated as the perturbation. The dependence of the perturbed energy of levels on hyperfine structure (hfs) effects and on the higher-order Stark effect is investigated. Numerical results have been obtained for the transition probability between the hfs components of hydrogen-like bismuth.

  1. Optimizing of the higher order mode dampers in the 56MHz SRF cavity

    International Nuclear Information System (INIS)

    Wu, Q.; Ben-Zvi, I.

    2010-01-01

    Earlier, we reported that a 56 MHz cavity was designed for a luminosity upgrade of the RHIC, and presented the requirements for Higher Order Mode (HOM) damping, the design of the HOM dampers, along with measurements and simulations of the HOM dampers. In this report, we describe our optimization of the dampers performance, and the modifications we made to their original design. We also optimized the number of the HOM dampers, and tested different configurations of locations for them.

  2. A Frank mixture copula family for modeling higher-order correlations of neural spike counts

    International Nuclear Information System (INIS)

    Onken, Arno; Obermayer, Klaus

    2009-01-01

    In order to evaluate the importance of higher-order correlations in neural spike count codes, flexible statistical models of dependent multivariate spike counts are required. Copula families, parametric multivariate distributions that represent dependencies, can be applied to construct such models. We introduce the Frank mixture family as a new copula family that has separate parameters for all pairwise and higher-order correlations. In contrast to the Farlie-Gumbel-Morgenstern copula family that shares this property, the Frank mixture copula can model strong correlations. We apply spike count models based on the Frank mixture copula to data generated by a network of leaky integrate-and-fire neurons and compare the goodness of fit to distributions based on the Farlie-Gumbel-Morgenstern family. Finally, we evaluate the importance of using proper single neuron spike count distributions on the Shannon information. We find notable deviations in the entropy that increase with decreasing firing rates. Moreover, we find that the Frank mixture family increases the log likelihood of the fit significantly compared to the Farlie-Gumbel-Morgenstern family. This shows that the Frank mixture copula is a useful tool to assess the importance of higher-order correlations in spike count codes.

  3. Symmetries, invariants and generating functions: higher-order statistics of biased tracers

    Science.gov (United States)

    Munshi, Dipak

    2018-01-01

    Gravitationally collapsed objects are known to be biased tracers of an underlying density contrast. Using symmetry arguments, generalised biasing schemes have recently been developed to relate the halo density contrast δh with the underlying density contrast δ, divergence of velocity θ and their higher-order derivatives. This is done by constructing invariants such as s, t, ψ,η. We show how the generating function formalism in Eulerian standard perturbation theory (SPT) can be used to show that many of the additional terms based on extended Galilean and Lifshitz symmetry actually do not make any contribution to the higher-order statistics of biased tracers. Other terms can also be drastically simplified allowing us to write the vertices associated with δh in terms of the vertices of δ and θ, the higher-order derivatives and the bias coefficients. We also compute the cumulant correlators (CCs) for two different tracer populations. These perturbative results are valid for tree-level contributions but at an arbitrary order. We also take into account the stochastic nature bias in our analysis. Extending previous results of a local polynomial model of bias, we express the one-point cumulants Script SN and their two-point counterparts, the CCs i.e. Script Cpq, of biased tracers in terms of that of their underlying density contrast counterparts. As a by-product of our calculation we also discuss the results using approximations based on Lagrangian perturbation theory (LPT).

  4. Higher-order neural network software for distortion invariant object recognition

    Science.gov (United States)

    Reid, Max B.; Spirkovska, Lilly

    1991-01-01

    The state-of-the-art in pattern recognition for such applications as automatic target recognition and industrial robotic vision relies on digital image processing. We present a higher-order neural network model and software which performs the complete feature extraction-pattern classification paradigm required for automatic pattern recognition. Using a third-order neural network, we demonstrate complete, 100 percent accurate invariance to distortions of scale, position, and in-plate rotation. In a higher-order neural network, feature extraction is built into the network, and does not have to be learned. Only the relatively simple classification step must be learned. This is key to achieving very rapid training. The training set is much smaller than with standard neural network software because the higher-order network only has to be shown one view of each object to be learned, not every possible view. The software and graphical user interface run on any Sun workstation. Results of the use of the neural software in autonomous robotic vision systems are presented. Such a system could have extensive application in robotic manufacturing.

  5. Higher-order stochastic differential equations and the positive Wigner function

    Science.gov (United States)

    Drummond, P. D.

    2017-12-01

    General higher-order stochastic processes that correspond to any diffusion-type tensor of higher than second order are obtained. The relationship of multivariate higher-order stochastic differential equations with tensor decomposition theory and tensor rank is explained. Techniques for generating the requisite complex higher-order noise are proved to exist either using polar coordinates and γ distributions, or from products of Gaussian variates. This method is shown to allow the calculation of the dynamics of the Wigner function, after it is extended to a complex phase space. The results are illustrated physically through dynamical calculations of the positive Wigner distribution for three-mode parametric downconversion, widely used in quantum optics. The approach eliminates paradoxes arising from truncation of the higher derivative terms in Wigner function time evolution. Anomalous results of negative populations and vacuum scattering found in truncated Wigner quantum simulations in quantum optics and Bose-Einstein condensate dynamics are shown not to occur with this type of stochastic theory.

  6. Security Analysis of 7-Round MISTY1 against Higher Order Differential Attacks

    Science.gov (United States)

    Tsunoo, Yukiyasu; Saito, Teruo; Shigeri, Maki; Kawabata, Takeshi

    MISTY1 is a 64-bit block cipher that has provable security against differential and linear cryptanalysis. MISTY1 is one of the algorithms selected in the European NESSIE project, and it has been recommended for Japanese e-Government ciphers by the CRYPTREC project. This paper shows that higher order differential attacks can be successful against 7-round versions of MISTY1 with FL functions. The attack on 7-round MISTY1 can recover a partial subkey with a data complexity of 254.1 and a computational complexity of 2120.8, which signifies the first successful attack on 7-round MISTY1 with no limitation such as a weak key. This paper also evaluates the complexity of this higher order differential attack on MISTY1 in which the key schedule is replaced by a pseudorandom function. It is shown that resistance to the higher order differential attack is not substantially improved even in 7-round MISTY1 in which the key schedule is replaced by a pseudorandom function.

  7. Educating Grade 6 students for higher-order thinking and its influence on creativity

    Directory of Open Access Journals (Sweden)

    Wajeeh Daher

    2017-08-01

    Full Text Available Educating students for higher-order thinking provides them with tools that turn them into more critical thinkers. This supports them in overcoming life problems that they encounter, as well as becoming an integral part of the society. This students’ education is attended to by educational organisations that emphasise the positive consequences of educating students for higher-order thinking, including creative thinking. One way to do that is through educational programmes that educate for higher-order thinking. One such programme is the Cognitive Research Trust (CoRT thinking programme. The present research intended to examine the effect of the participation of Grade 6 students in a CoRT programme on their creative thinking. Fifty-three students participated in the research; 27 participated in a CoRT programme, while 26 did not participate in such programme. The ANCOVA test showed that the students who participated in the CoRT programme outperformed significantly, in creative thinking, the students who did not. Moreover, the students in the CoRT programme whose achievement scores were between 86 and 100 outperformed significantly the other achievement groups of students. Furthermore, students with reported high ability outperformed significantly the other ability groups of students. The results did not show statistically significant differences in students’ creativity attributed to gender.

  8. A Higher-Order Neural Network Design for Improving Segmentation Performance in Medical Image Series

    International Nuclear Information System (INIS)

    Selvi, Eşref; Selver, M Alper; Güzeliş, Cüneyt; Dicle, Oǧuz

    2014-01-01

    Segmentation of anatomical structures from medical image series is an ongoing field of research. Although, organs of interest are three-dimensional in nature, slice-by-slice approaches are widely used in clinical applications because of their ease of integration with the current manual segmentation scheme. To be able to use slice-by-slice techniques effectively, adjacent slice information, which represents likelihood of a region to be the structure of interest, plays critical role. Recent studies focus on using distance transform directly as a feature or to increase the feature values at the vicinity of the search area. This study presents a novel approach by constructing a higher order neural network, the input layer of which receives features together with their multiplications with the distance transform. This allows higher-order interactions between features through the non-linearity introduced by the multiplication. The application of the proposed method to 9 CT datasets for segmentation of the liver shows higher performance than well-known higher order classification neural networks

  9. Transverse vibrations of shear-deformable beams using a general higher order theory

    Science.gov (United States)

    Kosmatka, J. B.

    1993-01-01

    A general higher order theory is developed to study the static and vibrational behavior of beam structures having an arbitrary cross section that utilizes both out-of-plane shear-dependent warping and in-plane (anticlastic) deformations. The equations of motion are derived via Hamilton's principle, where the full 3D constitutive relations are used. A simplified version of the general higher-order theory is also presented for beams having an arbitrary cross section that includes out-of-plane shear deformation but assumes that stresses within the cross section and in-plane deformations are negligible. This simplified model, which is accurate for long to moderately short wavelengths, offers substantial improvements over existing higher order theories that are limited to beams with thin rectangular cross sections. The current approach will be very useful in the study of thin-wall closed-cell beams such as airfoil-type sections where the magnitude of shear-related cross-sectional warping is significant.

  10. Compositional modeling of three-phase flow with gravity using higher-order finite element methods

    KAUST Repository

    Moortgat, Joachim

    2011-05-11

    A wide range of applications in subsurface flow involve water, a nonaqueous phase liquid (NAPL) or oil, and a gas phase, such as air or CO2. The numerical simulation of such processes is computationally challenging and requires accurate compositional modeling of three-phase flow in porous media. In this work, we simulate for the first time three-phase compositional flow using higher-order finite element methods. Gravity poses complications in modeling multiphase processes because it drives countercurrent flow among phases. To resolve this issue, we propose a new method for the upwinding of three-phase mobilities. Numerical examples, related to enhanced oil recovery and carbon sequestration, are presented to illustrate the capabilities of the proposed algorithm. We pay special attention to challenges associated with gravitational instabilities and take into account compressibility and various phase behavior effects, including swelling, viscosity changes, and vaporization. We find that the proposed higher-order method can capture sharp solution discontinuities, yielding accurate predictions of phase boundaries arising in computational three-phase flow. This work sets the stage for a broad extension of the higher-order methods for numerical simulation of three-phase flow for complex geometries and processes.

  11. Higher Order, Hybrid BEM/FEM Methods Applied to Antenna Modeling

    Science.gov (United States)

    Fink, P. W.; Wilton, D. R.; Dobbins, J. A.

    2002-01-01

    In this presentation, the authors address topics relevant to higher order modeling using hybrid BEM/FEM formulations. The first of these is the limitation on convergence rates imposed by geometric modeling errors in the analysis of scattering by a dielectric sphere. The second topic is the application of an Incomplete LU Threshold (ILUT) preconditioner to solve the linear system resulting from the BEM/FEM formulation. The final tOpic is the application of the higher order BEM/FEM formulation to antenna modeling problems. The authors have previously presented work on the benefits of higher order modeling. To achieve these benefits, special attention is required in the integration of singular and near-singular terms arising in the surface integral equation. Several methods for handling these terms have been presented. It is also well known that achieving he high rates of convergence afforded by higher order bases may als'o require the employment of higher order geometry models. A number of publications have described the use of quadratic elements to model curved surfaces. The authors have shown in an EFIE formulation, applied to scattering by a PEC .sphere, that quadratic order elements may be insufficient to prevent the domination of modeling errors. In fact, on a PEC sphere with radius r = 0.58 Lambda(sub 0), a quartic order geometry representation was required to obtain a convergence benefi.t from quadratic bases when compared to the convergence rate achieved with linear bases. Initial trials indicate that, for a dielectric sphere of the same radius, - requirements on the geometry model are not as severe as for the PEC sphere. The authors will present convergence results for higher order bases as a function of the geometry model order in the hybrid BEM/FEM formulation applied to dielectric spheres. It is well known that the system matrix resulting from the hybrid BEM/FEM formulation is ill -conditioned. For many real applications, a good preconditioner is required

  12. Engineering the path to higher-order thinking in elementary education: A problem-based learning approach for STEM integration

    Science.gov (United States)

    Rehmat, Abeera Parvaiz

    As we progress into the 21st century, higher-order thinking skills and achievement in science and math are essential to meet the educational requirement of STEM careers. Educators need to think of innovative ways to engage and prepare students for current and future challenges while cultivating an interest among students in STEM disciplines. An instructional pedagogy that can capture students' attention, support interdisciplinary STEM practices, and foster higher-order thinking skills is problem-based learning. Problem-based learning embedded in the social constructivist view of teaching and learning (Savery & Duffy, 1995) promotes self-regulated learning that is enhanced through exploration, cooperative social activity, and discourse (Fosnot, 1996). This quasi-experimental mixed methods study was conducted with 98 fourth grade students. The study utilized STEM content assessments, a standardized critical thinking test, STEM attitude survey, PBL questionnaire, and field notes from classroom observations to investigate the impact of problem-based learning on students' content knowledge, critical thinking, and their attitude towards STEM. Subsequently, it explored students' experiences of STEM integration in a PBL environment. The quantitative results revealed a significant difference between groups in regards to their content knowledge, critical thinking skills, and STEM attitude. From the qualitative results, three themes emerged: learning approaches, increased interaction, and design and engineering implementation. From the overall data set, students described the PBL environment to be highly interactive that prompted them to employ multiple approaches, including design and engineering to solve the problem.

  13. Student's Perceived Level and Teachers' Teaching Strategies of Higher Order Thinking Skills: A Study on Higher Educational Institutions in Thailand

    Science.gov (United States)

    Shukla, Divya; Dungsungnoen, Aj Pattaradanai

    2016-01-01

    Higher order thinking skills (HOTS) has portrayed immense industry demand and the major goal of educational institution in imparting education is to inculcate higher order thinking skills. This compiles and mandate the institutions and instructor to develop the higher order thinking skills among students in order to prepare them for effective…

  14. Reprogramming the chromatin landscape

    DEFF Research Database (Denmark)

    Miranda, Tina B; Voss, Ty C; Sung, Myong-Hee

    2013-01-01

    , mechanistic details defining the cellular interactions between ER and GR are poorly understood. We investigated genome-wide binding profiles for ER and GR upon coactivation and characterized the status of the chromatin landscape. We describe a novel mechanism dictating the molecular interplay between ER...... and GR. Upon induction, GR modulates access of ER to specific sites in the genome by reorganization of the chromatin configuration for these elements. Binding to these newly accessible sites occurs either by direct recognition of ER response elements or indirectly through interactions with other factors...

  15. Chromatin proteins and modifications as drug targets

    DEFF Research Database (Denmark)

    Helin, Kristian; Dhanak, Dashyant

    2013-01-01

    A plethora of groundbreaking studies have demonstrated the importance of chromatin-associated proteins and post-translational modifications of histones, proteins and DNA (so-called epigenetic modifications) for transcriptional control and normal development. Disruption of epigenetic control...... is a frequent event in disease, and the first epigenetic-based therapies for cancer treatment have been approved. A generation of new classes of potent and specific inhibitors for several chromatin-associated proteins have shown promise in preclinical trials. Although the biology of epigenetic regulation...

  16. Dynamics of Histone Tails within Chromatin

    Science.gov (United States)

    Bernier, Morgan; North, Justin; Page, Michael; Jaroniec, Christopher; Hammel, Christopher; Poirier, Michael

    2012-02-01

    Genetic information in humans is encoded within DNA molecules that is wrapped around histone octamer proteins and compacted into a highly conserved structural polymer, chromatin. The physical and material properties of chromatin appear to influence gene expression by altering the accessibility of proteins to the DNA. The tails of the histones are flexible domains that are thought to play a role in regulating DNA accessibility and compaction; however the molecular mechanisms for these phenomena are not understood. I will present CW-EPR studies on site directed spin labeled nucleosomes that probe the structure and dynamics of these histone tails within nucleosomes.

  17. Heterochromatinization associated with cell differentiation as a model to study DNA double strand break induction and repair in the context of higher-order chromatin structure

    Czech Academy of Sciences Publication Activity Database

    Falk, Martin; Lukášová, Emilie; Štefančíková, Lenka; Baranová, E.; Falková, Iva; Ježková, L.; Davídková, Marie; Bačíková, Alena; Vachelová, Jana; Michaelidesová, Anna; Kozubek, Stanislav

    2014-01-01

    Roč. 83, Jan (2014), s. 177-185 ISSN 0969-8043 R&D Projects: GA MŠk(CZ) LD12039 Institutional support: RVO:68081707 ; RVO:61389005 Keywords : DNA double strand break (DSB) repair * Immature and terminally differentiated granulocytes * gamma H2AX/53BP1 repair foci Subject RIV: BO - Biophysics; BO - Biophysics (UJF-V) Impact factor: 1.231, year: 2014

  18. SHARP: A Spatially Higher-order, Relativistic Particle-in-cell Code

    Energy Technology Data Exchange (ETDEWEB)

    Shalaby, Mohamad; Broderick, Avery E. [Department of Physics and Astronomy, University of Waterloo, 200 University Avenue West, Waterloo, ON, N2L 3G1 (Canada); Chang, Philip [Department of Physics, University of Wisconsin-Milwaukee, 1900 E. Kenwood Boulevard, Milwaukee, WI 53211 (United States); Pfrommer, Christoph [Leibniz-Institut für Astrophysik Potsdam (AIP), An der Sternwarte 16, D-14482 Potsdam (Germany); Lamberts, Astrid [Theoretical Astrophysics, California Institute of Technology, Pasadena, CA 91125 (United States); Puchwein, Ewald, E-mail: mshalaby@live.ca [Institute of Astronomy and Kavli Institute for Cosmology, University of Cambridge, Madingley Road, Cambridge, CB3 0HA (United Kingdom)

    2017-05-20

    Numerical heating in particle-in-cell (PIC) codes currently precludes the accurate simulation of cold, relativistic plasma over long periods, severely limiting their applications in astrophysical environments. We present a spatially higher-order accurate relativistic PIC algorithm in one spatial dimension, which conserves charge and momentum exactly. We utilize the smoothness implied by the usage of higher-order interpolation functions to achieve a spatially higher-order accurate algorithm (up to the fifth order). We validate our algorithm against several test problems—thermal stability of stationary plasma, stability of linear plasma waves, and two-stream instability in the relativistic and non-relativistic regimes. Comparing our simulations to exact solutions of the dispersion relations, we demonstrate that SHARP can quantitatively reproduce important kinetic features of the linear regime. Our simulations have a superior ability to control energy non-conservation and avoid numerical heating in comparison to common second-order schemes. We provide a natural definition for convergence of a general PIC algorithm: the complement of physical modes captured by the simulation, i.e., those that lie above the Poisson noise, must grow commensurately with the resolution. This implies that it is necessary to simultaneously increase the number of particles per cell and decrease the cell size. We demonstrate that traditional ways for testing for convergence fail, leading to plateauing of the energy error. This new PIC code enables us to faithfully study the long-term evolution of plasma problems that require absolute control of the energy and momentum conservation.

  19. The detection of higher-order acoustic transitions is reflected in the N1 ERP.

    Science.gov (United States)

    Weise, Annekathrin; Schröger, Erich; Horváth, János

    2018-01-30

    The auditory system features various types of dedicated change detectors enabling the rapid parsing of auditory stimulation into distinct events. The activity of such detectors is reflected by the N1 ERP. Interestingly, certain acoustic transitions show an asymmetric N1 elicitation pattern: whereas first-order transitions (e.g., a change from a segment of constant frequency to a frequency glide [c-to-g change]) elicit N1, higher-order transitions (e.g., glide-to-constant [g-to-c] changes) do not. Consensus attributes this asymmetry to the absence of any available sensory mechanism that is able to rapidly detect higher-order changes. In contrast, our study provides compelling evidence for such a mechanism. We collected electrophysiological and behavioral data in a transient-detection paradigm. In each condition, a random (50%-50%) sequence of two types of tones occurred, which did or did not contain a transition (e.g., c-to-g and constant stimuli or g-to-c and glide tones). Additionally, the rate of pitch change of the glide varied (i.e., 10 vs. 40 semitones per second) in order to increase the number of responding neural assemblies. The rate manipulation modulated transient ERPs and behavioral detection performance for g-to-c transitions much stronger than for c-to-g transitions. The topographic and tomographic analyses suggest that the N1 response to c-to-g and also to g-to-c transitions emerged from the superior temporal gyrus. This strongly supports a sensory mechanism that allows the fast detection of higher-order changes. © 2018 Society for Psychophysiological Research.

  20. Simulated and Virtual Science Laboratory Experiments: Improving Critical Thinking and Higher-Order Learning Skills

    Science.gov (United States)

    Simon, Nicole A.

    Virtual laboratory experiments using interactive computer simulations are not being employed as viable alternatives to laboratory science curriculum at extensive enough rates within higher education. Rote traditional lab experiments are currently the norm and are not addressing inquiry, Critical Thinking, and cognition throughout the laboratory experience, linking with educational technologies (Pyatt & Sims, 2007; 2011; Trundle & Bell, 2010). A causal-comparative quantitative study was conducted with 150 learners enrolled at a two-year community college, to determine the effects of simulation laboratory experiments on Higher-Order Learning, Critical Thinking Skills, and Cognitive Load. The treatment population used simulated experiments, while the non-treatment sections performed traditional expository experiments. A comparison was made using the Revised Two-Factor Study Process survey, Motivated Strategies for Learning Questionnaire, and the Scientific Attitude Inventory survey, using a Repeated Measures ANOVA test for treatment or non-treatment. A main effect of simulated laboratory experiments was found for both Higher-Order Learning, [F (1, 148) = 30.32,p = 0.00, eta2 = 0.12] and Critical Thinking Skills, [F (1, 148) = 14.64,p = 0.00, eta 2 = 0.17] such that simulations showed greater increases than traditional experiments. Post-lab treatment group self-reports indicated increased marginal means (+4.86) in Higher-Order Learning and Critical Thinking Skills, compared to the non-treatment group (+4.71). Simulations also improved the scientific skills and mastery of basic scientific subject matter. It is recommended that additional research recognize that learners' Critical Thinking Skills change due to different instructional methodologies that occur throughout a semester.