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Sample records for ck2 structurally deviates

  1. The catalytic subunit of human protein kinase CK2 structurally deviates from its maize homologue in complex with the nucleotide competitive inhibitor emodin

    DEFF Research Database (Denmark)

    Raaf, Jennifer; Klopffleisch, Karsten; Issinger, Olaf-Georg;

    2008-01-01

    biological research, and small organic inhibitors addressing CK2 are of considerable interest. We describe here the complex structure between a C-terminal deletion mutant of human CK2alpha and the ATP-competitive inhibitor emodin (1,3,8-trihydroxy-6-methylanthraquinone, International Union of Pure...

  2. Protein kinase CK2 in health and disease: Protein kinase CK2: from structures to insights

    DEFF Research Database (Denmark)

    Niefind, K; Raaf, J; Issinger, Olaf-Georg

    2009-01-01

    Within the last decade, 40 crystal structures corresponding to protein kinase CK2 (former name 'casein kinase 2'), to its catalytic subunit CK2alpha and to its regulatory subunit CK2beta were published. Together they provide a valuable, yet by far not complete basis to rationalize the biochemical...... critical region of CK2alpha recruitment is pre-formed in the unbound state. In CK2alpha the activation segment - a key element of protein kinase regulation - adapts invariably the typical conformation of the active enzymes. Recent structures of human CK2alpha revealed a surprising plasticity in the ATP...

  3. Structure of the human protein kinase CK2 catalytic subunit CK2α' and interaction thermodynamics with the regulatory subunit CK2β

    DEFF Research Database (Denmark)

    Bischoff, Nils; Olsen, Birgitte; Raaf, Jennifer;

    2011-01-01

    the limited biochemical knowledge about the second paralog (CK2α'), we developed a well-soluble catalytically active full-length mutant of human CK2α', characterized it by Michaelis-Menten kinetics and isothermal titration calorimetry, and determined its crystal structure to a resolution of 2 Å. The affinity...... in CK2α' is stabilized by two elements that are absent in CK2α: (1) the extension of the N-terminal β-sheet by an additional β-strand, and (2) the filling of a conserved hydrophobic cavity between the β4/β5 loop and helix αC by a tryptophan residue. Moreover, the interdomain hinge region of CK2α' adopts...... a fully functional conformation, while unbound CK2α is often found with a nonproductive hinge conformation that is overcome only by CK2β binding. Taken together, CK2α' exhibits a significantly lower affinity for CK2β than CK2α; moreover, in functionally critical regions, it is less dependent on CK2β...

  4. Crystal structure of human protein kinase CK2: insights into basic properties of the CK2 holoenzyme

    DEFF Research Database (Denmark)

    Niefind, K; Guerra, B; Ermakowa, I;

    2001-01-01

    The crystal structure of a fully active form of human protein kinase CK2 (casein kinase 2) consisting of two C-terminally truncated catalytic and two regulatory subunits has been determined at 3.1 A resolution. In the CK2 complex the regulatory subunits form a stable dimer linking the two catalytic...... as a docking partner for various protein kinases. Furthermore it shows an inter-domain mobility in the catalytic subunit known to be functionally important in protein kinases and detected here for the first time directly within one crystal structure....

  5. Protein kinase CK2 structure-function relationship

    DEFF Research Database (Denmark)

    Boldyreff, B; Meggio, F; Pinna, L A;

    1994-01-01

    Protein kinase CK2 subunits alpha and beta were expressed either separately or together in a bacterial expression system (pT7-7/BL21(DE3)) and purified to homogeneity. After mixing the subunits, a CK2 holoenzyme (alpha 2 beta 2) was spontaneously reconstituted, which displays identical features...... conditions, (b) it protects the alpha subunit against denaturing agents or conditions, and (c) it alters the substrate specificity of the alpha subunit. By site-directed mutagenesis, certain functions of the beta subunit could be assigned to specific amino acids or domains. Twenty one mutants of the beta...

  6. Crystal structure of the catalytic subunit of protein kinase CK2 from Zea mays at 2.1 A resolution

    DEFF Research Database (Denmark)

    Niefind, K; Guerra, B; Pinna, L A;

    1998-01-01

    CK2alpha is the catalytic subunit of protein kinase CK2, an acidophilic and constitutively active eukaryotic Ser/Thr kinase involved in cell proliferation. A crystal structure, at 2.1 A resolution, of recombinant maize CK2alpha (rmCK2alpha) in the presence of ATP and Mg2+, shows the enzyme in an ...

  7. Structure-function analysis of the beta regulatory subunit of protein kinase CK2 by targeting embryonic stem cell.

    Science.gov (United States)

    Ziercher, Léa; Filhol, Odile; Laudet, Béatrice; Prudent, Renaud; Cochet, Claude; Buchou, Thierry

    2011-10-01

    Programs that govern stem cell maintenance and pluripotency are dependent on extracellular factors and of intrinsic cell modulators. Embryonic stem (ES) cells with a specific depletion of the gene encoding the regulatory subunit of protein kinase CK2 (CK2β) revealed a viability defect. However, analysis of CK2β functions along the neural lineage established CK2β as a positive regulator for neural stem/progenitor cell (NSC) proliferation and multipotency. By using an in vitro genetic conditional approach, we demonstrate in this work that specific domains of CK2β involved in the regulatory function towards CK2 catalytic subunits are crucial structural determinants for ES cell homeostasis. PMID:21861102

  8. Biophysical characterization of the structural change of Nopp140, an intrinsically disordered protein, in the interaction with CK2α.

    Science.gov (United States)

    Na, Jung-Hyun; Lee, Won-Kyu; Kim, Yuyoung; Jeong, Cherlhyun; Song, Seung Soo; Cha, Sun-Shin; Han, Kyou-Hoon; Shin, Yeon-Kyun; Yu, Yeon Gyu

    2016-08-19

    Nucleolar phosphoprotein 140 (Nopp140) is a nucleolar protein, more than 80% of which is disordered. Previous studies have shown that the C-terminal region of Nopp140 (residues 568-596) interacts with protein kinase CK2α, and inhibits the catalytic activity of CK2. Although the region of Nopp140 responsible for the interaction with CK2α was identified, the structural features and the effect of this interaction on the structure of Nopp140 have not been defined due to the difficulty of structural characterization of disordered protein. In this study, the disordered feature of Nopp140 and the effect of CK2α on the structure of Nopp140 were examined using single-molecule fluorescence resonance energy transfer (smFRET) and electron paramagnetic resonance (EPR). The interaction with CK2α was increased conformational rigidity of the CK2α-interacting region of Nopp140 (Nopp140C), suggesting that the disordered and flexible conformation of Nopp140C became more rigid conformation as it binds to CK2α. In addition, site specific spin labeling and EPR analysis confirmed that the residues 574-589 of Nopp140 are critical for binding to CK2α. Similar technical approaches can be applied to analyze the conformational changes in other IDPs during their interactions with binding partners. PMID:27297113

  9. Structure of the gene encoding the murine protein kinase CK2 beta subunit

    DEFF Research Database (Denmark)

    Boldyreff, B; Issinger, O G

    1995-01-01

    The mouse protein kinase CK2 beta subunit gene (Csnk2b) is composed of seven exons contained within 7874 bp. The exon and intron lengths extend from 76 to 321 and 111 to 1272 bp, respectively. The lengths of the murine coding exons correspond exactly to the lengths of the exons in the human CK2...

  10. Structure of protein kinase CK2: dimerization of the human beta-subunit

    DEFF Research Database (Denmark)

    Boldyreff, B; Mietens, U; Issinger, O G

    1996-01-01

    Protein kinase CK2 has been shown to be elevated in all so far investigated solid tumors and its catalytic subunit has been shown to serve as an oncogene product. CK2 is a heterotetrameric serine-threonine kinase composed of two catalytic (alpha and/or alpha') and two regulatory beta...

  11. Inhibition of protein kinase CK2 by anthraquinone-related compounds. A structural insight.

    Science.gov (United States)

    De Moliner, Erika; Moro, Stefano; Sarno, Stefania; Zagotto, Giuseppe; Zanotti, Giuseppe; Pinna, Lorenzo A; Battistutta, Roberto

    2003-01-17

    Protein kinases play key roles in signal transduction and therefore are among the most attractive targets for drug design. The pharmacological aptitude of protein kinase inhibitors is highlighted by the observation that various diseases with special reference to cancer are because of the abnormal expression/activity of individual kinases. The resolution of the three-dimensional structure of the target kinase in complex with inhibitors is often the starting point for the rational design of this kind of drugs, some of which are already in advanced clinical trial or even in clinical practice. Here we present and discuss three new crystal structures of ATP site-directed inhibitors in complex with "casein kinase-2" (CK2), a constitutively active protein kinase implicated in a variety of cellular functions and misfunctions. With the help of theoretical calculations, we disclose some key features underlying the inhibitory efficiency of anthraquinone derivatives, outlining three different binding modes into the active site. In particular, we show that a nitro group in a hydroxyanthraquinone scaffold decreases the inhibitory constants K(i) because of electron-withdrawing and resonance effects that enhance the polarization of hydroxylic substituents in paraposition. PMID:12419810

  12. The protein kinase CK2(Andante) holoenzyme structure supports proposed models of autoregulation and trans-autophosphorylation

    DEFF Research Database (Denmark)

    Schnitzler, Alexander; Olsen, Birgitte Brinkmann; Issinger, Olaf-Georg;

    2014-01-01

    (Andante) that contains a CK2β variant mutated in a CK2α-contact helix and described to be responsible for a prolonged circadian rhythm in Drosophila. The increased propensity of CK2(Andante) to form aggregates with completely blocked active sites may contribute to this phenotype....

  13. Coumarin as attractive casein kinase 2 (CK2) inhibitor scaffold: an integrate approach to elucidate the putative binding motif and explain structure-activity relationships.

    Science.gov (United States)

    Chilin, Adriana; Battistutta, Roberto; Bortolato, Andrea; Cozza, Giorgio; Zanatta, Samuele; Poletto, Giorgia; Mazzorana, Marco; Zagotto, Giuseppe; Uriarte, Eugenio; Guiotto, Adriano; Pinna, Lorenzo A; Meggio, Flavio; Moro, Stefano

    2008-02-28

    Casein kinase 2 (CK2) is an ubiquitous, essential, and highly pleiotropic protein kinase whose abnormally high constitutive activity is suspected to underlie its pathogenic potential in neoplasia and other diseases. Recently, using different virtual screening approaches, we have identified several novel CK2 inhibitors. In particular, we have discovered that coumarin moiety can be considered an attractive CK2 inhibitor scaffold. In the present work, we have synthetized and tested a small library of coumarins (more than 60), rationalizing the observed structure-activity relationship. Moreover, the most promising inhibitor, 3,8-dibromo-7-hydroxy-4-methylchromen-2-one (DBC), has been also crystallized in complex with CK2, and the experimental binding mode has been used to derive a linear interaction energy (LIE) model. PMID:18251491

  14. Structure and Property Based Design of Pyrazolo[1,5-a]pyrimidine Inhibitors of CK2 Kinase with Activity in Vivo.

    Science.gov (United States)

    Dowling, James E; Alimzhanov, Marat; Bao, Larry; Block, Michael H; Chuaqui, Claudio; Cooke, Emma L; Denz, Christopher R; Hird, Alex; Huang, Shan; Larsen, Nicholas A; Peng, Bo; Pontz, Timothy W; Rivard-Costa, Caroline; Saeh, Jamal Carlos; Thakur, Kumar; Ye, Qing; Zhang, Tao; Lyne, Paul D

    2013-08-01

    In this letter, we describe the design, synthesis, and structure-activity relationship of 5-anilinopyrazolo[1,5-a]pyrimidine inhibitors of CK2 kinase. Property-based optimization of early leads using the 7-oxetan-3-yl amino group led to a series of matched molecular pairs with lower lipophilicity, decreased affinity for human plasma proteins, and reduced binding to the hERG ion channel. Agents in this study were shown to modulate pAKT(S129), a direct substrate of CK2, in vitro and in vivo, and exhibited tumor growth inhibition when administered orally in a murine DLD-1 xenograft. PMID:24900749

  15. Protein kinase CK2 in human diseases

    DEFF Research Database (Denmark)

    Guerra, Barbara; Issinger, Olaf-Georg

    2008-01-01

    Protein kinase CK2 (formerly referred to as casein kinase II) is an evolutionary conserved, ubiquitous protein kinase. There are two paralog catalytic subunits, i.e. alpha (A1) and alpha' (A2). The alpha and alpha' subunits are linked to two beta subunits to produce a heterotetrameric structure....... The catalytic alpha subunits are distantly related to the CMGC subfamily of kinases, such as the Cdk kinases. There are some peculiarities associated with protein kinase CK2, which are not found with most other protein kinases: (i) the enzyme is constitutively active, (ii) it can use ATP and GTP and...... specifically target this protein kinase [10]. Since not all the aspects of what has been published on CK2 can be covered in this review, we would like to recommend the following reviews; (i) for general information on CK2 [11-18] and (ii) with a focus on aberrant CK2 [19-22]....

  16. The CK2 alpha/CK2 beta interface of human protein kinase CK2 harbors a binding pocket for small molecules

    DEFF Research Database (Denmark)

    Raaf, Jennifer; Brunstein, Elena; Issinger, Olaf-Georg;

    2008-01-01

    , selective CK2 inhibitors are required. An often-used CK2 inhibitor is 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB). In a complex structure with human CK2 alpha, DRB binds to the canonical ATP cleft, but additionally it occupies an allosteric site that can be alternatively filled by glycerol....... Inhibition kinetic studies corroborate the dual binding mode of the inhibitor. Structural comparisons reveal a surprising conformational plasticity of human CK2 alpha around both DRB binding sites. After local rearrangement, the allosteric site serves as a CK2 beta interface. This opens the potential...

  17. Structural features underlying the selectivity of the kinase inhibitors NBC and dNBC: role of a nitro group that discriminates between CK2 and DYRK1A.

    Science.gov (United States)

    Sarno, Stefania; Mazzorana, Marco; Traynor, Ryan; Ruzzene, Maria; Cozza, Giorgio; Pagano, Mario A; Meggio, Flavio; Zagotto, Giuseppe; Battistutta, Roberto; Pinna, Lorenzo A

    2012-02-01

    8-hydroxy-4-methyl-9-nitrobenzo(g)chromen-2-one (NBC) has been found to be a fairly potent ATP site-directed inhibitor of protein kinase CK2 (Ki = 0.22 μM). Here, we show that NBC also inhibits PIM kinases, especially PIM1 and PIM3, the latter as potently as CK2. Upon removal of the nitro group, to give 8-hydroxy-4-methyl-benzo(g)chromen-2-one (here referred to as "denitro NBC", dNBC), the inhibitory power toward CK2 is almost entirely lost (IC(50) > 30 μM) whereas that toward PIM1 and PIM3 is maintained; in addition, dNBC is a potent inhibitor of a number of other kinases that are weakly inhibited or unaffected by NBC, with special reference to DYRK1A whose IC(50) values with NBC and dNBC are 15 and 0.60 μM, respectively. Therefore, the observation that NBC, unlike dNBC, is a potent inducer of apoptosis is consistent with the notion that this effect is mediated by inhibition of endogenous CK2. The structural features underlying NBC selectivity have been revealed by inspecting its 3D structure in complex with the catalytic subunit of Z. mays CK2. The crucial role of the nitro group is exerted both through a direct electrostatic interaction with the side chain of Lys68 and, indirectly, by enhancing the acidic dissociation constant of the adjacent hydroxyl group which interacts with a conserved water molecule in the deepest part of the cavity. By contrast, the very same nitro group is deleterious for the binding to the active site of DYRK1A, as disclosed by molecular docking. This provides the rationale for preferential inhibition of DYRK1A by dNBC. PMID:21720886

  18. CK2: a protein kinase in need of control

    DEFF Research Database (Denmark)

    Guerra, B; Boldyreff, B; Sarno, S;

    1999-01-01

    Protein kinase CK2 is a heterotetrameric alpha2beta2 Ser/Thr protein kinase with some features unusual among the eukaryotic protein kinases: (1) CK2 recognizes phosphoacceptor sites specified by several acidic determinants; (2) CK2 can use both ATP and GTP as phosphoryl donors; and (3...... response to nucleotide analogs. The increasing knowledge of CK2 structure-function relationships will allow the design of highly selective inhibitors of this pleiotropic kinase with oncogenic potential....

  19. First inactive conformation of CK2 alpha, the catalytic subunit of protein kinase CK2

    DEFF Research Database (Denmark)

    Raaf, Jennifer; Issinger, Olaf-Georg; Niefind, Karsten

    2009-01-01

    The Ser/Thr kinase casein kinase 2 (CK2) is a heterotetrameric enzyme composed of two catalytic chains (CK2alpha, catalytic subunit of CK2) attached to a dimer of two noncatalytic subunits (CK2beta, noncatalytic subunit of CK2). CK2alpha belongs to the superfamily of eukaryotic protein kinases...

  20. Interaction between CK2α and CK2β, the subunits of protein kinase CK2: thermodynamic contributions of key residues on the CK2α surface

    DEFF Research Database (Denmark)

    Raaf, Jennifer; Bischoff, Nils; Klopffleisch, Karsten;

    2011-01-01

    The protein Ser/Thr kinase CK2 (former name: casein kinase II) exists predominantly as a heterotetrameric holoenzyme composed of two catalytic subunits (CK2α) bound to a dimer of noncatalytic subunits (CK2β). We undertook a study to further understand how these subunits interact to form the tetra...

  1. GTP plus water mimic ATP in the active site of protein kinase CK2

    DEFF Research Database (Denmark)

    Niefind, K; Pütter, M; Guerra, B;

    1999-01-01

    The structures of the catalytic subunit of protein kinase CK2 from Zea mays complexed with Mg2+ and with analogs of ATP or GTP were determined to 2.2 A resolution. Unlike most other protein kinases, CK2 from various sources shows 'dual-cosubstrate specificity', that is, the ability to efficiently...... that target CK2 or other kinases with this property....

  2. The crystal structure of the complex of Zea mays alpha subunit with a fragment of human beta subunit provides the clue to the architecture of protein kinase CK2 holoenzyme

    DEFF Research Database (Denmark)

    Battistutta, R; Sarno, S; De Moliner, E;

    2000-01-01

    , presents a molecular twofold axis, with each peptide interacting with both alpha chains. In the derived model of the holoenzyme, the regulatory subunits are positioned on the opposite side with respect to the opening of the catalytic sites, that remain accessible to substrates and cosubstrates. The beta......The crystal structure of a complex between the catalytic alpha subunit of Zea mays CK2 and a 23-mer peptide corresponding the C-terminal sequence 181-203 of the human CK2 regulatory beta subunit has been determined at 3.16-A resolution. The complex, composed of two alpha chains and two peptides...... subunit can influence the catalytic activity both directly and by promoting the formation of the alpha2 dimer, in which each alpha chain interacts with the active site of the other. Furthermore, the two active sites are so close in space that they can simultaneously bind and phosphorylate two...

  3. Low-density crystal packing of human protein kinase CK2 catalytic subunit in complex with resorufin or other ligands

    DEFF Research Database (Denmark)

    Klopffleisch, Karsten; Issinger, Olaf Georg; Niefind, Karsten;

    2012-01-01

    A low-resolution structure of the catalytic subunit CK2α of human protein kinase CK2 (formerly known as casein kinase 2) in complex with the ATP-competitive inhibitor resorufin is presented. The structure supplements previous human CK2α structures in which the interdomain hinge/helix αD region...

  4. Quinalizarin as a potent, selective and cell-permeable inhibitor of protein kinase CK2.

    Science.gov (United States)

    Cozza, Giorgio; Mazzorana, Marco; Papinutto, Elena; Bain, Jenny; Elliott, Matthew; di Maira, Giovanni; Gianoncelli, Alessandra; Pagano, Mario A; Sarno, Stefania; Ruzzene, Maria; Battistutta, Roberto; Meggio, Flavio; Moro, Stefano; Zagotto, Giuseppe; Pinna, Lorenzo A

    2009-08-01

    Emodin (1,3,8-trihydroxy-6-methyl-anthraquinone) is a moderately potent and poorly selective inhibitor of protein kinase CK2, one of the most pleiotropic serine/threonine protein kinases, implicated in neoplasia and in other global diseases. By virtual screening of the MMS (Molecular Modeling Section) database, we have now identified quinalizarin (1,2,5,8-tetrahydroxyanthraquinone) as an inhibitor of CK2 that is more potent and selective than emodin. CK2 inhibition by quinalizarin is competitive with respect to ATP, with a Ki value of approx. 50 nM. Tested at 1 microM concentration on a panel of 75 protein kinases, quinalizarin drastically inhibits only CK2, with a promiscuity score (11.1), which is the lowest ever reported so far for a CK2 inhibitor. Especially remarkable is the ability of quinalizarin to discriminate between CK2 and a number of kinases, notably DYRK1a (dual-specificity tyrosine-phosphorylated and -regulated kinase), PIM (provirus integration site for Moloney murine leukaemia virus) 1, 2 and 3, HIPK2 (homeodomain-interacting protein kinase-2), MNK1 [MAPK (mitogen-activated protein kinase)-interacting kinase 1], ERK8 (extracellular-signal-regulated kinase 8) and PKD1 (protein kinase D 1), which conversely tend to be inhibited as drastically as CK2 by commercially available CK2 inhibitors. The determination of the crystal structure of a complex between quinalizarin and CK2alpha subunit highlights the relevance of polar interactions in stabilizing the binding, an unusual characteristic for a CK2 inhibitor, and disclose other structural features which may account for the narrow selectivity of this compound. Tested on Jurkat cells, quinalizarin proved able to inhibit endogenous CK2 and to induce apoptosis more efficiently than the commonly used CK2 inhibitors TBB (4,5,6,7-tetrabromo-1H-benzotriazole) and DMAT (2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole). PMID:19432557

  5. Protein kinase CK2: evidence for a protein kinase CK2beta subunit fraction, devoid of the catalytic CK2alpha subunit, in mouse brain and testicles

    DEFF Research Database (Denmark)

    Guerra, B; Siemer, S; Boldyreff, B;

    1999-01-01

    The highest CK2 activity was found in mouse testicles and brain, followed by spleen, liver, lung, kidney and heart. The activity values were directly correlated with the protein expression level of the CK2 subunits alpha (catalytic) and beta (regulatory). The alpha' subunit was only detected...... found for testicles and brain. The amount of CK2beta protein in brain in comparison to the other organs (except testicles) was estimated to be ca. 2-3-fold higher whereas the ratio of CK2beta between testicles and brain was estimated to be 3-4-fold. Results from the immunoprecipitation experiments...... support the notion for the existence of free CK2beta population and/or CK2beta in complex with other protein(s) present in brain and testicles. In all other mouse organs investigated, i.e. heart, lung, liver, kidney and spleen, no comparable amount of free CK2beta was observed. This is the first...

  6. Conformational plasticity of the catalytic subunit of protein kinase CK2 and its consequences for regulation and drug design

    DEFF Research Database (Denmark)

    Niefind, Karsten; Issinger, Olaf-Georg

    2010-01-01

    plasticity of important ATP-binding elements - the interdomain hinge region and the glycine-rich loop - was discovered. In fully active CK2alpha the hinge region is open and does not anchor the ATP ribose, but alternatively it can adopt a closed conformation, form hydrogen bonds to the ribose moiety and thus......At the first glance CK2alpha, the catalytic subunit of protein kinase CK2, is a rigid molecule: in contrast to many eukaryotic protein kinases in CK2alpha the canonical regulatory key elements like the activation segment occur exclusively in their typical active conformations. This observation fits...... well to the constitutive activity of the enzyme, meaning, its independence from phosphorylation or other characteristic control factors. Most CK2alpha structures are based on the enzyme from Zea mays, supplemented by an increasing number of human CK2alpha structures. In the latter a surprising...

  7. The Selectivity of CK2 Inhibitor Quinalizarin: A Reevaluation

    Directory of Open Access Journals (Sweden)

    Giorgio Cozza

    2015-01-01

    Full Text Available Many polyphenolic compounds have been reported to inhibit protein kinases, with special reference to CK2, a pleiotropic serine/threonine kinase, implicated in neoplasia, neurodegenerative disease, and viral infections. In general however these compounds are not endowed with stringent selectivity. Among them quinalizarin (1,2,5,8-tetrahydroxyanthraquinone turned out to be particularly potent (Ki = 0.058 μM and quite selective as judged by profiling it on a small panel of 70 protein kinases. Here, by profiling quinalizarin on a larger panel of 140 kinases we reach the conclusion that quinalizarin is one of the most selective inhibitors of CK2, superior to the first-in-class CK2 inhibitor, CX-4945, now in clinical trials for the treatment of cancer. Moreover here we show that quinalizarin is able to discriminate between the isolated CK2 catalytic subunit (CK2α and CK2 holoenzyme (CK2α2β2, consistent with in silico and in vitro analyses.

  8. Interactions of protein kinase CK2beta subunit within the holoenzyme and with other proteins

    DEFF Research Database (Denmark)

    Kusk, M; Ahmed, R; Thomsen, B;

    1999-01-01

    Protein kinase CK2 is a ubiquitous, highly conserved protein kinase with a tetrameric alpha2beta2 structure. For the formation of this tetrameric complex a beta-alpha dimer seems to be a prerequisite. Using the two-hybrid system and a series of CK2beta deletion mutants, we mapped domains involved...... in alpha-beta and beta-beta interactions. We also detected an intramolecular beta interaction within the amino acid stretch 132-165. Using CK2beta as a bait in a two-hybrid library screening several new putative cellular partners have been identified, among them the S6 kinase p90rsk, the putative tumor...... suppressor protein Doc-1, the Fas-associated protein FAF1, the mitochondrial translational initiation factor 2 and propionyl CoA carboxylase beta subunit....

  9. Biochemical characterization of CK2alpha and alpha' paralogues and their derived holoenzymes: evidence for the existence of a heterotrimeric CK2alpha'-holoenzyme forming trimeric complexes

    DEFF Research Database (Denmark)

    Olsen, Birgitte; Rasmussen, Tine; Niefind, Karsten;

    2008-01-01

    Altogether 2 holoenzymes and 4 catalytic CK2 constructs were expressed and characterized i.e. CK2alpha (2) (1-335) beta(2); CK2alpha'-derived holoenzyme; CK2alpha(1-335); MBP-CK2alpha'; His-tagged CK2alpha and His-tagged CK2alpha'. The two His-tagged catalytic subunits were expressed in insect......2alpha'-derived holoenzyme eluted at a position corresponding to a molecular mass of 105 kDa which is significantly below the elution of the CK2alpha (2) (1-335) beta(2) holoenzyme (145 kDa). Calmodulin was not phosphorylated by either CK2alpha (2) (1-335) beta(2) or the CK2alpha'-derived holoenzyme...

  10. Inhibition of CK2 Activity by TCDD via Binding to ATP-competitive Binding Site of Catalytic Subunit:Insight from Computational Studies

    Institute of Scientific and Technical Information of China (English)

    XU Xian-jin; CANNISTRARO Salvatore; BIZZARRI Anna-rita; ZENG Yi; CHEN Wei-zu; WANG Cun-xin

    2013-01-01

    Alternative mechanisms of toxic effects induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD),instead of the binding to aryl hydrocarbon receptor(AhR),have been taken into consideration.It has been recently shown that TCDD reduces rapidly the activity of CK2(casein kinase Ⅱ) both in vivo and in vitro.It is found that TCDD has high molecular similarities to the known inhibitors of CK2 catalytic subunit(CK2α).This suggests that TCDD could also be an ATP-competitive inhibitor of CK2α.In this work,docking TCDD to CK2 was carried out based on the two structures of CK2α from maize and human,respectively.The binding free energies of the predicted CK2α-TCDD complexes estimated by the molecular mechanics/Poisson-Boltzmann surface area(MM/PBSA) method are from -85.1 kJ/mol to-114.3 kJ/mol for maize and are from-96.1 kJ/mol to-118.2 kJ/mol for human,which are comparable to those estimated for the known inhibitor and also ATP with CK2α.The energetic analysis also reveals that the van der Waals interaction is the dominant contribution to the binding free energy.These results are also useful for designing new drugs for a target of overexpressing CK2 in cancers.

  11. Characterization of CK2 holoenzyme variants with regard to crystallization

    DEFF Research Database (Denmark)

    Guerra, B; Niefind, K; Ermakowa, I;

    2001-01-01

    that the catalytic subunit moiety of the human CK2 holoenzyme is not stable neither as a free subunit nor in the tetrameric complex. All attempts to prevent degradation failed. Hence, alternative approaches were designed in order to avoid this degradation, which was expected to hamper any crystallization efforts...... strategy to tackle the problem of instability was to produce the homologous recombinant human CK2 holoenzyme and then, instead of trying to avoid degradation, attempt to accelerate degradation until all catalytic subunit material was converted to the degraded form, i.e. a 40 kDa polypeptide....

  12. Crystallographic evidence for deviating C3b structure?

    OpenAIRE

    Janssen, B.J.C.; Read, R.J.; Brunger, A. T.; Gros, P

    2007-01-01

    Activation of C3 into C3b is a critical step in the complement immune response against pathogenic, immunogenic and apoptotic particles. Ajees et al.1 report a crystal structure of C3b, which deviates from the one reported by Janssen et al.2 and Wiesmann et al.3. Analysis of the data deposited by Ajees et al.1 reveals features that are inconsistent with known physical properties of macromolecular structures and their diffraction data. Therefore, Ajees et al. do not provide substantial evidence...

  13. Phosphorylation of the regulatory beta-subunit of protein kinase CK2 by checkpoint kinase Chk1: identification of the in vitro CK2beta phosphorylation site

    DEFF Research Database (Denmark)

    Kristensen, Lars P; Larsen, Martin Røssel; Højrup, Peter;

    2004-01-01

    The regulatory beta-subunit of protein kinase CK2 mediates the formation of the CK2 tetrameric form and it has functions independent of CK2 catalytic subunit through interaction with several intracellular proteins. Recently, we have shown that CK2beta associates with the human checkpoint kinase Chk...... by the modification of Thr213 but it does require the presence of an active Chk1 kinase....

  14. Development of a high-throughput screening-compatible assay to identify inhibitors of the CK2alpha/CK2beta interaction

    DEFF Research Database (Denmark)

    Hochscherf, Jennifer; Lindenblatt, Dirk; Steinkrueger, Michaela;

    2015-01-01

    active site-directed approaches. The current article describes the development of a fluorescence anisotropy-based assay that mimics the principle of CK2 subunit interaction by using CK2alpha1-335 and the fluorescent probe CF-Ahx-Pc as a CK2beta analog. In addition, we identified new inhibitors able...

  15. Urolithin as a converging scaffold linking ellagic acid and coumarin analogues: design of potent protein kinase CK2 inhibitors.

    Science.gov (United States)

    Cozza, Giorgio; Gianoncelli, Alessandra; Bonvini, Paolo; Zorzi, Elisa; Pasquale, Riccardo; Rosolen, Angelo; Pinna, Lorenzo A; Meggio, Flavio; Zagotto, Giuseppe; Moro, Stefano

    2011-12-01

    Casein kinase 2 (CK2) is a ubiquitous, essential, and highly pleiotropic protein kinase; its abnormally high constitutive activity is suspected to underlie its pathogenic potential in neoplasia and other relevant diseases. Previously, using different in silico screening approaches, two potent and selective CK2 inhibitors were identified by our group: ellagic acid, a naturally occurring tannic acid derivative (K(i)=20 nM) and 3,8-dibromo-7-hydroxy-4-methylchromen-2-one (DBC, K(i)=60 nM). Comparing the crystallographic binding modes of both ellagic acid and DBC, an X-ray structure-driven merging approach was taken to design novel CK2 inhibitors with improved target affinity. A urolithin moiety is proposed as a possible bridging scaffold between the two known CK2 inhibitors, ellagic acid and DBC. Optimization of urolithin A as the bridging moiety led to the identification of 4-bromo-3,8-dihydroxy-benzo[c]chromen-6-one as a novel, potent and selective CK2 inhibitor, which shows a K(i) value of 7 nM against the protein kinase, representing a significant improvement in affinity for the target compared with the two parent fragments. PMID:21972104

  16. Velocity Structure Determination Through Seismic Waveform Modeling and Time Deviations

    Science.gov (United States)

    Savage, B.; Zhu, L.; Tan, Y.; Helmberger, D. V.

    2001-12-01

    Through the use of seismic waveforms recorded by TriNet, a dataset of earthquake focal mechanisms and deviations (time shifts) relative to a standard model facilitates the investigation of the crust and uppermost mantle of southern California. The CAP method of focal mechanism determination, in use by TriNet on a routine basis, provides time shifts for surface waves and Pnl arrivals independently relative to the reference model. These shifts serve as initial data for calibration of local and regional seismic paths. Time shifts from the CAP method are derived by splitting the Pnl section of the waveform, the first arriving Pn to just before the arrival of the S wave, from the much slower surface waves then cross-correlating the data with synthetic waveforms computed from a standard model. Surface waves interact with the entire crust, but the upper crust causes the greatest effect. Whereas, Pnl arrivals sample the deeper crust, upper mantle, and source region. This natural division separates the upper from lower crust for regional calibration and structural modeling and allows 3-D velocity maps to be created using the resulting time shifts. Further examination of Pnl and other arrivals which interact with the Moho illuminate the complex nature of this boundary. Initial attempts at using the first 10 seconds of the Pnl section to determine upper most mantle structure have proven insightful. Two large earthquakes north of southern California in Nevada and Mammoth Lakes, CA allow the creation of record sections from 200 to 600 km. As the paths swing from east to west across southern California, simple 1-D models turn into complex structure, dramatically changing the waveform character. Using finite difference models to explain the structure, we determine that a low velocity zone is present at the base of the crust and extends to 100 km in depth. Velocity variations of 5 percent of the mantle in combination with steeply sloping edges produces complex waveform variations

  17. Protein kinase CK2 inhibition is associated with the destabilization of HIF-1α in human cancer cells

    DEFF Research Database (Denmark)

    Guerra, Barbara; Rasmussen, Tine D. L.; Schnitzler, Alexander;

    2015-01-01

    CK2-catalyzed HSP90/Cdc37 phosphorylation and induces HIF-1alpha degradation. Furthermore, E9 exerts a strong anti-tumour activity by inducing necrosis in murine xenograft models underlining its potential to be used for cancer treatment in future clinical studies. Crystal structure analysis of human...

  18. Isomeric mono-, di-, and tri-bromobenzo-1H-triazoles as inhibitors of human protein kinase CK2α.

    Directory of Open Access Journals (Sweden)

    Romualda Wąsik

    Full Text Available To further clarify the role of the individual bromine atoms of 4,5,6,7-tetrabromotriazole (TBBt, a relatively selective inhibitor of protein kinase CK2, we have examined the inhibition (IC(50 of human CK2α by the two mono-, the four di-, and the two tri- bromobenzotriazoles relative to that of TBBt. Halogenation of the central vicinal C(5/C(6 atoms proved to be a key factor in enhancing inhibitory activity, in that 5,6-di-Br(2Bt and 4,5,6-Br(3Bt were almost as effective inhibitors as TBBt, notwithstanding their marked differences in pK(a for dissociation of the triazole proton. The decrease in pK(a on halogenation of the peripheral C(4/C(7 atoms virtually nullifies the gain due to hydrophobic interactions, and does not lead to a decrease in IC(50. Molecular modeling of structures of complexes of the ligands with the enzyme, as well as QSAR analysis, pointed to a balance of hydrophobic and electrostatic interactions as a discriminator of inhibitory activity. The role of halogen bonding remains debatable, as originally noted for the crystal structure of TBBt with CK2α (pdb1j91. Finally we direct attention to the promising applicability of our series of well-defined halogenated benzotriazoles to studies on inhibition of kinases other than CK2.

  19. Fas-associated factor 1 interacts with protein kinase CK2 in vivo upon apoptosis induction

    DEFF Research Database (Denmark)

    Guerra, B; Boldyreff, B; Issinger, O G

    2001-01-01

    We show here that in several different cell lines protein kinase CK2 and Fas-associated factor 1 (FAF1) exist together in a complex which is stable to high monovalent salt concentration. The CK2/FAF1 complex formation is significantly increased after induction of apoptosis with various DNA damaging...... the view that protein kinase CK2 plays an important role in certain steps of apoptosis....

  20. Expression and characterization of a recombinant maize CK-2 alpha subunit

    DEFF Research Database (Denmark)

    Boldyreff, B; Meggio, F; Dobrowolska, G;

    1993-01-01

    CKIIB, one of the CK-2 like enzymes which have been isolated from maize, has been shown to be a monomeric enzyme that cross-reacts with anti CK-2 alpha specific antibodies suggesting a possible relationship between the two proteins (Dobrowolska et al. (1992) Eur. J. Biochem. 204, 299-303). In order...... to support the immunological data also by biochemical and biophysical experiments the availability of a recombinant CK-2 alpha from maize was a prerequisite. A maize cDNA clone of maize CK-2 alpha was expressed in the bacterial strain BL21 (DE3). The recombinant protein was purified to homogeneity; its...... molecular mass on one-dimensional SDS PAGE was estimated to be 36.5 kDa. The calculated molecular mass according to the amino acid composition is 39,228 Da (332 amino acids). The recombinant maize CK-2 alpha (rmCK-2 alpha) exhibited mostly the same properties as the recombinant human CK-2 alpha (rhCK-2...

  1. A-Raf kinase is a new interacting partner of protein kinase CK2 beta subunit

    DEFF Research Database (Denmark)

    Boldyreff, B; Issinger, O G

    1997-01-01

    In a search for protein kinase CK2 beta subunit binding proteins using the two-hybrid system, more than 1000 positive clones were isolated. Beside clones for the alpha' and beta subunit of CK2, there were clones coding for a so far unknown protein, whose partial cDNA sequence was already deposite...

  2. Emerging roles of protein kinase CK2 in abscisic acid (ABA signaling

    Directory of Open Access Journals (Sweden)

    Belmiro eVilela

    2015-11-01

    Full Text Available The phytohormone abscisic acid (ABA regulates many aspects of plant growth and development as well as responses to multiple stresses. Post-translational modifications such as phosphorylation or ubiquitination have pivotal roles in the regulation of ABA signaling. In addition to the positive regulator sucrose non-fermenting-1 related protein kinase 2 (SnRK2, the relevance of the role of other protein kinases, such as CK2, has been recently highlighted. We have recently established that CK2 phosphorylates the maize ortholog of open stomata 1 OST1, ZmOST1, suggesting a role of CK2 phosphorylation in the control of ZmOST1 protein degradation (Vilela et al., 2015. CK2 is a pleiotropic enzyme involved in multiple developmental and stress-responsive pathways. This review summarizes recent advances that taken together suggest a prominent role of protein kinase CK2 in ABA signaling and related processes.

  3. Protein kinase CK2 and its role in cellular proliferation, development and pathology

    DEFF Research Database (Denmark)

    Guerra, B; Issinger, O G

    1999-01-01

    Protein kinase CK2 is a pleiotropic, ubiquitous and constitutively active protein kinase that can use both ATP and GTP as phosphoryl donors with specificity for serine/threonine residues in the vicinity of acidic amino acids. Recent results show that the enzyme is involved in transcription...... conserved throughout evolution. Furthermore the existence of different CK2beta-related proteins together with the observation of deregulated CK2beta levels in tumor cells and the reported association of CK2beta protein with key proteins in signal transduction, e.g. A-Raf, Mos, pg90rsk etc. are suggestive...... for an additional physiological role of CK2beta protein beside being the regulatory compound in the tetrameric holoenzyme....

  4. In vitro and in vivo assays of protein kinase CK2 activity.

    Science.gov (United States)

    Prudent, Renaud; Sautel, Céline F; Moucadel, Virginie; Laudet, Béatrice; Filhol, Odile; Cochet, Claude

    2010-01-01

    Protein kinase CK2 (formerly casein kinase 2) is recognized as a central component in the control of the cellular homeostasis; however, much remains unknown regarding its regulation and its implication in cellular transformation and carcinogenesis. Moreover, study of CK2 function and regulation in a cellular context is complicated by the dynamic multisubunit architecture of this protein kinase. Although a number of robust techniques are available to assay CK2 activity in vitro, there is a demand for sensitive and specific assays to evaluate its activity in living cells. We hereby provide a detailed description of several assays for monitoring the CK2 activity and its subunit interaction in living cells. The guidelines presented herein should enable researchers in the field to establish strategies for cellular screenings of CK2 inhibitors. PMID:21050938

  5. Dominant-negative CK2alpha induces potent effects on circadian rhythmicity.

    Directory of Open Access Journals (Sweden)

    Elaine M Smith

    2008-01-01

    Full Text Available Circadian clocks organize the precise timing of cellular and behavioral events. In Drosophila, circadian clocks consist of negative feedback loops in which the clock component PERIOD (PER represses its own transcription. PER phosphorylation is a critical step in timing the onset and termination of this feedback. The protein kinase CK2 has been linked to circadian timing, but the importance of this contribution is unclear; it is not certain where and when CK2 acts to regulate circadian rhythms. To determine its temporal and spatial functions, a dominant negative mutant of the catalytic alpha subunit, CK2alpha(Tik, was targeted to circadian neurons. Behaviorally, CK2alpha(Tik induces severe period lengthening (approximately 33 h, greater than nearly all known circadian mutant alleles, and abolishes detectable free-running behavioral rhythmicity at high levels of expression. CK2alpha(Tik, when targeted to a subset of pacemaker neurons, generates period splitting, resulting in flies exhibiting both long and near 24-h periods. These behavioral effects are evident even when CK2alpha(Tik expression is induced only during adulthood, implicating an acute role for CK2alpha function in circadian rhythms. CK2alpha(Tik expression results in reduced PER phosphorylation, delayed nuclear entry, and dampened cycling with elevated trough levels of PER. Heightened trough levels of per transcript accompany increased protein levels, suggesting that CK2alpha(Tik disturbs negative feedback of PER on its own transcription. Taken together, these in vivo data implicate a central role of CK2alpha function in timing PER negative feedback in adult circadian neurons.

  6. CK2 Secreted by Leishmania braziliensis Mediates Macrophage Association Invasion: A Comparative Study between Virulent and Avirulent Promastigotes

    Directory of Open Access Journals (Sweden)

    Ana Madeira Brito Zylbersztejn

    2015-01-01

    Full Text Available CK2 is a protein kinase distributed in different compartments of Leishmania braziliensis: an externally oriented ecto-CK2, an intracellular CK2, and a secreted CK2. This latter form is constitutively secreted from the parasite (CsCK2, but such secretion may be highly enhanced by the association of specific molecules, including enzyme substrates, which lead to a higher enzymatic activity, called inductively secreted CK2 (IsCK2. Here, we examined the influence of secreted CK2 (sCK2 activity on the infectivity of a virulent L. braziliensis strain. The virulent strain presented 121-fold higher total CK2 activity than those found in an avirulent strain. The use of specific CK2 inhibitors (TBB, DRB, or heparin inhibited virulent parasite growth, whereas no effect was observed in the avirulent parasites. When these inhibitors were added to the interaction assays between the virulent L. braziliensis strain and macrophages, association index was drastically inhibited. Polyamines enhanced sCK2 activity and increased the association index between parasites and macrophages. Finally, sCK2 and the supernatant of the virulent strain increased the association index between the avirulent strain and macrophages, which was inhibited by TBB. Thus, the kinase enzyme CK2 seems to be important to invasion mechanisms of L. braziliensis.

  7. CK2 Secreted by Leishmania braziliensis Mediates Macrophage Association Invasion: A Comparative Study between Virulent and Avirulent Promastigotes

    Science.gov (United States)

    Zylbersztejn, Ana Madeira Brito; de Morais, Carlos Gustavo Vieira; Lima, Ana Karina Castro; Souza, Joyce Eliza de Oliveira; Lopes, Angela Hampshire; Da-Silva, Sílvia Amaral Gonçalves; Silva-Neto, Mário Alberto Cardoso; Dutra, Patrícia Maria Lourenço

    2015-01-01

    CK2 is a protein kinase distributed in different compartments of Leishmania braziliensis: an externally oriented ecto-CK2, an intracellular CK2, and a secreted CK2. This latter form is constitutively secreted from the parasite (CsCK2), but such secretion may be highly enhanced by the association of specific molecules, including enzyme substrates, which lead to a higher enzymatic activity, called inductively secreted CK2 (IsCK2). Here, we examined the influence of secreted CK2 (sCK2) activity on the infectivity of a virulent L. braziliensis strain. The virulent strain presented 121-fold higher total CK2 activity than those found in an avirulent strain. The use of specific CK2 inhibitors (TBB, DRB, or heparin) inhibited virulent parasite growth, whereas no effect was observed in the avirulent parasites. When these inhibitors were added to the interaction assays between the virulent L. braziliensis strain and macrophages, association index was drastically inhibited. Polyamines enhanced sCK2 activity and increased the association index between parasites and macrophages. Finally, sCK2 and the supernatant of the virulent strain increased the association index between the avirulent strain and macrophages, which was inhibited by TBB. Thus, the kinase enzyme CK2 seems to be important to invasion mechanisms of L. braziliensis. PMID:26120579

  8. The CK2 kinase stabilizes CLOCK and represses its activity in the Drosophila circadian oscillator.

    Directory of Open Access Journals (Sweden)

    Aron Szabó

    Full Text Available Phosphorylation is a pivotal regulatory mechanism for protein stability and activity in circadian clocks regardless of their evolutionary origin. It determines the speed and strength of molecular oscillations by acting on transcriptional activators and their repressors, which form negative feedback loops. In Drosophila, the CK2 kinase phosphorylates and destabilizes the PERIOD (PER and TIMELESS (TIM proteins, which inhibit CLOCK (CLK transcriptional activity. Here we show that CK2 also targets the CLK activator directly. Downregulating the activity of the catalytic α subunit of CK2 induces CLK degradation, even in the absence of PER and TIM. Unexpectedly, the regulatory β subunit of the CK2 holoenzyme is not required for the regulation of CLK stability. In addition, downregulation of CK2α activity decreases CLK phosphorylation and increases per and tim transcription. These results indicate that CK2 inhibits CLK degradation while reducing its activity. Since the CK1 kinase promotes CLK degradation, we suggest that CLK stability and transcriptional activity result from counteracting effects of CK1 and CK2.

  9. Exploiting the repertoire of CK2 inhibitors to target DYRK and PIM kinases.

    Science.gov (United States)

    Cozza, Giorgio; Sarno, Stefania; Ruzzene, Maria; Girardi, Cristina; Orzeszko, Andrzej; Kazimierczuk, Zygmunt; Zagotto, Giuseppe; Bonaiuto, Emanuela; Di Paolo, Maria Luisa; Pinna, Lorenzo A

    2013-07-01

    Advantage has been taken of the relative promiscuity of commonly used inhibitors of protein kinase CK2 to develop compounds that can be exploited for the selective inhibition of druggable kinases other than CK2 itself. Here we summarize data obtained by altering the scaffold of CK2 inhibitors to give rise to novel selective inhibitors of DYRK1A and to a powerful cell permeable dual inhibitor of PIM1 and CK2. In the former case one of the new compounds, C624 (naphto [1,2-b]benzofuran-5,9-diol) displays a potency comparable to that of the first-in-class DYRK1A inhibitor, harmine, lacking however the drawback of drastically inhibiting monoamine oxidase-A (MAO-A) as harmine does. On the other hand the promiscuous CK2 inhibitor 4,5,6,7-tetrabromo-1H-benzimidazole (TBI,TBBz) has been derivatized with a sugar moiety to generate a 1-(β-D-2'-deoxyribofuranosyl)-4,5,6,7-tetrabromo-1H-benzimidazole (TDB) compound which inhibits PIM1 and CK2 with comparably high efficacy (IC50 values<100nM) and remarkable selectivity. TDB, unlike other dual PIM1/CK2 inhibitors described in the literature is readily cell permeable and displays a cytotoxic effect on cancer cells consistent with concomitant inhibition of both its onco-kinase targets. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases (2012). PMID:23360763

  10. CK2 phosphorylation of eukaryotic translation initiation factor 5 potentiates cell cycle progression

    OpenAIRE

    Homma, Miwako Kato; Wada, Ikuo; Suzuki, Toshiyuki; Yamaki, Junko; Krebs, Edwin G.; Homma, Yoshimi

    2005-01-01

    Casein kinase 2 (CK2) is a ubiquitous eukaryotic Ser/Thr protein kinase that plays an important role in cell cycle progression. Although its function in this process remains unclear, it is known to be required for the G1 and G2/M phase transitions in yeast. Here, we show that CK2 activity changes notably during cell cycle progression and is increased within 3 h of serum stimulation of quiescent cells. During the time period in which it exhibits high enzymatic activity, CK2 associates with and...

  11. Quinalizarin as a potent, selective and cell permeable inhibitor of protein kinase CK2

    OpenAIRE

    Cozza, Giorgio; Mazzorana, Marco; Papinutto, Elena; Bain, Jenny; Elliott, Matthew; Di Maira, Giovanni; Gianoncelli, Alessandra; Pagano, Mario A.; Sarno, Stefania; Ruzzene, Maria; Battistutta, Roberto; Meggio, Flavio; Moro, Stefano; Zagotto, Giuseppe; Pinna, Lorenzo A.

    2009-01-01

    Abstract Emodin (1,3,8-trihydroxy-6-methyl-anthraquinone) is a moderately potent and poorly selective inhibitor of CK2, one of the most pleiotropic Ser/Thr protein kinases, implicated in neoplasia and in other global diseases. By virtual screening of the MMS database we have now identified quinalizarin (1,2,5,8-tetrahydroxy-anthraquinone) as an inhibitor of CK2 more potent and selective than emodin. CK2 inhibition by quinalizarin is competitive with respect to ATP, with a Ki value ...

  12. Purification and characterization of recombinant protein kinase CK2 from Zea mays expressed in Escherichia coli

    DEFF Research Database (Denmark)

    Riera, Marta; Pages, Montserrat; Issinger, Olaf Georg;

    2003-01-01

    Recombinant protein kinase subunits rmCK2alpha-1 and rmCK2beta-1 from Zea mays were expressed separately in Escherichia coli and assembled to a fully active tetrameric holoenzyme complex in vitro. The obtained maize holoenzyme was purified to homogeneity, biochemically characterized, and compared...... to CK2 from human. Kinetic measurements of the recombinant maize holoenzyme (rmCK2) revealed k(cat) values for ATP and GTP of 4 and 2s(-1), respectively; whereas the recombinant maize catalytic subunit showed almost equal values for ATP and GTP, i.e., ca. 0.8s(-1). A comparison of the k(cat)/K(m) ratio...

  13. Two putative protein kinase CK2 phosphorylation sites are important for Myf-5 activity

    DEFF Research Database (Denmark)

    Winter, B; Kautzner, I; Issinger, O G;

    1997-01-01

    Myf-5, a member of a family of muscle-specific transcription factors, is important for myogenic cell determination and differentiation. Here, we report that Myf-5 protein constitutes a substrate for phosphorylation in vitro by protein kinase CK2. We identified two potential phosphorylation sites...... localization and/or protein stability. Our data suggest that CK2-mediated phosphorylation of Myf-5 is required for Myf-5 activity....

  14. Design, validation and efficacy of bisubstrate inhibitors specifically affecting ecto-CK2 kinase activity.

    Science.gov (United States)

    Cozza, Giorgio; Zanin, Sofia; Sarno, Stefania; Costa, Elena; Girardi, Cristina; Ribaudo, Giovanni; Salvi, Mauro; Zagotto, Giuseppe; Ruzzene, Maria; Pinna, Lorenzo A

    2015-11-01

    By derivatizing the purely competitive CK2 inhibitor N1-(4,5,6,7-tetrabromo-1H-benzimidazol-2-yl)-propane-1,3-diamine (K137) at its 3-amino position with a peptidic fragment composed of three or four glutamic or aspartic acid residues, a new family of bisubstrate inhibitors has been generated whose ability to simultaneously interact with both the ATP and the phosphoacceptor substrate-binding sites has been probed by running mixed competition kinetics and by mutational mapping of the kinase residues implicated in substrate recognition. The most effective bisubstrate inhibitor, K137-E4, interacts with three functional regions of the kinase: the hydrophobic pocket close to the ATP-binding site, the basic residues of the p+1 loop that recognizes the acidic determinant at position n+1 and the basic residues of α-helixC that recognize the acidic determinant at position n+3. Compared with the parent inhibitor (K137), K137-E4 is severalfold more potent (IC50 25 compared with 130 nM) and more selective, failing to inhibit any other kinase as drastically as CK2 out of 140 enzymes, whereas 35 kinases are inhibited more potently than CK2 by K137. K137-E4 is unable to penetrate the cell and to inhibit endogenous CK2, its pro-apoptotic efficacy being negligible compared with cell-permeant inhibitors; however, it readily inhibits ecto-CK2 on the outer cell surface, reducing the phosphorylation of several external phosphoproteins. Inhibition of ecto-CK2 by K137-E4 is accompanied by a slower migration of cancer cells as judged by wound healing assays. On the basis of the cellular responses to K137-E4, we conclude that ecto-CK2 is implicated in cell motility, whereas its contribution to the pro-survival role of CK2 is negligible. PMID:26349539

  15. RP1 is a phosphorylation target of CK2 and is involved in cell adhesion.

    Directory of Open Access Journals (Sweden)

    Frank Stenner

    Full Text Available RP1 (synonym: MAPRE2, EB2 is a member of the microtubule binding EB1 protein family, which interacts with APC, a key regulatory molecule in the Wnt signalling pathway. While the other EB1 proteins are well characterized the cellular function and regulation of RP1 remain speculative to date. However, recently RP1 has been implicated in pancreatic cancerogenesis. CK2 is a pleiotropic kinase involved in adhesion, proliferation and anti-apoptosis. Overexpression of protein kinase CK2 is a hallmark of many cancers and supports the malignant phenotype of tumor cells. In this study we investigate the interaction of protein kinase CK2 with RP1 and demonstrate that CK2 phosphorylates RP1 at Ser(236 in vitro. Stable RP1 expression in cell lines leads to a significant cleavage and down-regulation of N-cadherin and impaired adhesion. Cells expressing a Phospho-mimicking point mutant RP1-ASP(236 show a marked decrease of adhesion to endothelial cells under shear stress. Inversely, we found that the cells under shear stress downregulate endogenous RP1, most likely to improve cellular adhesion. Accordingly, when RP1 expression is suppressed by shRNA, cells lacking RP1 display significantly increased cell adherence to surfaces. In summary, RP1 phosphorylation at Ser(236 by CK2 seems to play a significant role in cell adhesion and might initiate new insights in the CK2 and EB1 family protein association.

  16. Thermodynamics parameters for binding of halogenated benzotriazole inhibitors of human protein kinase CK2α.

    Science.gov (United States)

    Winiewska, Maria; Kucińska, Katarzyna; Makowska, Małgorzata; Poznański, Jarosław; Shugar, David

    2015-10-01

    The interaction of human CK2α (hCK2α) with nine halogenated benzotriazoles, TBBt and its analogues representing all possible patterns of halogenation on the benzene ring of benzotriazole, was studied by biophysical methods. Thermal stability of protein-ligand complexes, monitored by calorimetric (DSC) and optical (DSF) methods, showed that the increase in the mid-point temperature for unfolding of protein-ligand complexes (i.e. potency of ligand binding to hCK2α) follow the inhibitory activities determined by biochemical assays. The dissociation constant for the ATP-hCK2α complex was estimated with the aid of microscale thermophoresis (MST) as 4.3±1.8 μM, and MST-derived dissociation constants determined for halogenated benzotriazoles, when converted according to known ATP concentrations, perfectly reconstruct IC50 values determined by the biochemical assays. Ligand-dependent quenching of tyrosine fluorescence, together with molecular modeling and DSC-derived heats of unfolding, support the hypothesis that halogenated benzotriazoles bind in at least two alternative orientations, and those that are efficient hCK2α inhibitors bind in the orientation which TBBt adopts in its complex with maize CK2α. DSC-derived apparent heat for ligand binding (ΔΔHbind) is driven by intermolecular electrostatic interactions between Lys68 and the triazole ring of the ligand, as indicated by a good correlation between ΔΔHbind and ligand pKa. Overall results, additionally supported by molecular modeling, confirm that a balance of hydrophobic and electrostatic interactions contribute predominantly (~40 kJ/mol), relative to possible intermolecular halogen/hydrogen bonding (less than 10 kJ/mol), in binding of halogenated benzotriazoles to the ATP-binding site of hCK2α. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases.

  17. Protein kinase CK2 modulates IL-6 expression in inflammatory breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Drygin, Denis, E-mail: ddrygin@cylenepharma.com; Ho, Caroline B.; Omori, Mayuko; Bliesath, Joshua; Proffitt, Chris; Rice, Rachel; Siddiqui-Jain, Adam; O' Brien, Sean; Padgett, Claire; Lim, John K.C.; Anderes, Kenna; Rice, William G.; Ryckman, David

    2011-11-11

    Highlights: Black-Right-Pointing-Pointer We examine the potential cross-talk between CK2 and IL-6. Black-Right-Pointing-Pointer Inhibition of CK2 by siRNA or CX-4945 inhibits expression of IL-6 in models of IBC. Black-Right-Pointing-Pointer Treatment of IBC patient in the clinic with CX-4945 reduces her IL-6 plasma levels. Black-Right-Pointing-Pointer We demonstrate that CK2 is a potential therapeutic target for IL-6 driven diseases. -- Abstract: Inflammatory breast cancer is driven by pro-angiogenic and pro-inflammatory cytokines. One of them Interleukin-6 (IL-6) is implicated in cancer cell proliferation and survival, and promotes angiogenesis, inflammation and metastasis. While IL-6 has been shown to be upregulated by several oncogenes, the mechanism behind this phenomenon is not well characterized. Here we demonstrate that the pleotropic Serine/Threonine kinase CK2 is implicated in the regulation of IL-6 expression in a model of inflammatory breast cancer. We used siRNAs targeted toward CK2 and a selective small molecule inhibitor of CK2, CX-4945, to inhibit the expression and thus suppress the secretion of IL-6 in in vitro as well as in vivo models. Moreover, we report that in a clinical trial, CX-4945 was able to dramatically reduce IL-6 levels in plasma of an inflammatory breast cancer patient. Our data shed a new light on the regulation of IL-6 expression and position CX-4945 and potentially other inhibitors of CK2, for the treatment of IL-6-driven cancers and possibly other diseases where IL-6 is instrumental, including rheumatoid arthritis.

  18. CK2 phosphorylation of eukaryotic translation initiation factor 5 potentiates cell cycle progression

    Science.gov (United States)

    Homma, Miwako Kato; Wada, Ikuo; Suzuki, Toshiyuki; Yamaki, Junko; Krebs, Edwin G.; Homma, Yoshimi

    2005-01-01

    Casein kinase 2 (CK2) is a ubiquitous eukaryotic Ser/Thr protein kinase that plays an important role in cell cycle progression. Although its function in this process remains unclear, it is known to be required for the G1 and G2/M phase transitions in yeast. Here, we show that CK2 activity changes notably during cell cycle progression and is increased within 3 h of serum stimulation of quiescent cells. During the time period in which it exhibits high enzymatic activity, CK2 associates with and phosphorylates a key molecule for translation initiation, eukaryotic translation initiation factor (eIF) 5. Using MS, we show that Ser-389 and -390 of eIF5 are major sites of phosphorylation by CK2. This is confirmed using eIF5 mutants that lack CK2 sites; the phosphorylation levels of mutant eIF5 proteins are significantly reduced, relative to WT eIF5, both in vitro and in vivo. Expression of these mutants reveals that they have a dominant-negative effect on phosphorylation of endogenous eIF5, and that they perturb synchronous progression of cells through S to M phase, resulting in a significant reduction in growth rate. Furthermore, the formation of mature eIF5/eIF2/eIF3 complex is reduced in these cells, and, in fact, restricted diffusional motion of WT eIF5 was almost abolished in a GFP-tagged eIF5 mutant lacking CK2 phosphorylation sites, as measured by fluorescence correlation spectroscopy. These results suggest that CK2 may be involved in the regulation of cell cycle progression by associating with and phosphorylating a key molecule for translation initiation. PMID:16227438

  19. Converting potent indeno[1,2-b]indole inhibitors of protein kinase CK2 into selective inhibitors of the breast cancer resistance protein ABCG2.

    Science.gov (United States)

    Jabor Gozzi, Gustavo; Bouaziz, Zouhair; Winter, Evelyn; Daflon-Yunes, Nathalia; Aichele, Dagmar; Nacereddine, Abdelhamid; Marminon, Christelle; Valdameri, Glaucio; Zeinyeh, Waël; Bollacke, Andre; Guillon, Jean; Lacoudre, Aline; Pinaud, Noël; Cadena, Silvia M; Jose, Joachim; Le Borgne, Marc; Di Pietro, Attilio

    2015-01-01

    A series of indeno[1,2-b]indole-9,10-dione derivatives were synthesized as human casein kinase II (CK2) inhibitors. The most potent inhibitors contained a N(5)-isopropyl substituent on the C-ring. The same series of compounds was found to also inhibit the breast cancer resistance protein ABCG2 but with totally different structure-activity relationships: a N(5)-phenethyl substituent was critical, and additional hydrophobic substituents at position 7 or 8 of the D-ring or a methoxy at phenethyl position ortho or meta also contributed to inhibition. The best ABCG2 inhibitors, such as 4c, 4h, 4i, 4j, and 4k, behaved as very weak inhibitors of CK2, whereas the most potent CK2 inhibitors, such as 4a, 4p, and 4e, displayed limited interaction with ABCG2. It was therefore possible to convert, through suitable substitutions of the indeno[1,2-b]indole-9,10-dione scaffold, potent CK2 inhibitors into selective ABCG2 inhibitors and vice versa. In addition, some of the best ABCG2 inhibitors, which displayed a very low cytotoxicity, thus giving a high therapeutic ratio, and appeared not to be transported, constitute promising candidates for further investigations.

  20. CRY Drives Cyclic CK2-Mediated BMAL1 Phosphorylation to Control the Mammalian Circadian Clock

    Science.gov (United States)

    Tamaru, Teruya; Hattori, Mitsuru; Honda, Kousuke; Nakahata, Yasukazu; Sassone-Corsi, Paolo; van der Horst, Gijsbertus T. J.; Ozawa, Takeaki; Takamatsu, Ken

    2015-01-01

    Intracellular circadian clocks, composed of clock genes that act in transcription-translation feedback loops, drive global rhythmic expression of the mammalian transcriptome and allow an organism to anticipate to the momentum of the day. Using a novel clock-perturbing peptide, we established a pivotal role for casein kinase (CK)-2-mediated circadian BMAL1-Ser90 phosphorylation (BMAL1-P) in regulating central and peripheral core clocks. Subsequent analysis of the underlying mechanism showed a novel role of CRY as a repressor for protein kinase. Co-immunoprecipitation experiments and real-time monitoring of protein–protein interactions revealed that CRY-mediated periodic binding of CK2β to BMAL1 inhibits BMAL1-Ser90 phosphorylation by CK2α. The FAD binding domain of CRY1, two C-terminal BMAL1 domains, and particularly BMAL1-Lys537 acetylation/deacetylation by CLOCK/SIRT1, were shown to be critical for CRY-mediated BMAL1–CK2β binding. Reciprocally, BMAL1-Ser90 phosphorylation is prerequisite for BMAL1-Lys537 acetylation. We propose a dual negative-feedback model in which a CRY-dependent CK2-driven posttranslational BMAL1–P-BMAL1 loop is an integral part of the core clock oscillator. PMID:26562092

  1. CRY Drives Cyclic CK2-Mediated BMAL1 Phosphorylation to Control the Mammalian Circadian Clock.

    Directory of Open Access Journals (Sweden)

    Teruya Tamaru

    Full Text Available Intracellular circadian clocks, composed of clock genes that act in transcription-translation feedback loops, drive global rhythmic expression of the mammalian transcriptome and allow an organism to anticipate to the momentum of the day. Using a novel clock-perturbing peptide, we established a pivotal role for casein kinase (CK-2-mediated circadian BMAL1-Ser90 phosphorylation (BMAL1-P in regulating central and peripheral core clocks. Subsequent analysis of the underlying mechanism showed a novel role of CRY as a repressor for protein kinase. Co-immunoprecipitation experiments and real-time monitoring of protein-protein interactions revealed that CRY-mediated periodic binding of CK2β to BMAL1 inhibits BMAL1-Ser90 phosphorylation by CK2α. The FAD binding domain of CRY1, two C-terminal BMAL1 domains, and particularly BMAL1-Lys537 acetylation/deacetylation by CLOCK/SIRT1, were shown to be critical for CRY-mediated BMAL1-CK2β binding. Reciprocally, BMAL1-Ser90 phosphorylation is prerequisite for BMAL1-Lys537 acetylation. We propose a dual negative-feedback model in which a CRY-dependent CK2-driven posttranslational BMAL1-P-BMAL1 loop is an integral part of the core clock oscillator.

  2. CK2 phosphorylates Sec31 and regulates ER-To-Golgi trafficking.

    Directory of Open Access Journals (Sweden)

    Mayuko Koreishi

    Full Text Available Protein export from the endoplasmic reticulum (ER is an initial and rate-limiting step of molecular trafficking and secretion. This is mediated by coat protein II (COPII-coated vesicles, whose formation requires small GTPase Sar1 and 6 Sec proteins including Sec23 and Sec31. Sec31 is a component of the outer layer of COPII coat and has been identified as a phosphoprotein. The initiation and promotion of COPII vesicle formation is regulated by Sar1; however, the mechanism regulating the completion of COPII vesicle formation followed by vesicle release is largely unknown. Hypothesizing that the Sec31 phosphorylation may be such a mechanism, we identified phosphorylation sites in the middle linker region of Sec31. Sec31 phosphorylation appeared to decrease its association with ER membranes and Sec23. Non-phosphorylatable mutant of Sec31 stayed longer at ER exit sites and bound more strongly to Sec23. We also found that CK2 is one of the kinases responsible for Sec31 phosphorylation because CK2 knockdown decreased Sec31 phosphorylation, whereas CK2 overexpression increased Sec31 phosphorylation. Furthermore, CK2 knockdown increased affinity of Sec31 for Sec23 and inhibited ER-to-Golgi trafficking. These results suggest that Sec31 phosphorylation by CK2 controls the duration of COPII vesicle formation, which regulates ER-to-Golgi trafficking.

  3. THE STRUCTURE AND PRECISE MODERATE DEVIATIONS OF RANDOM VARIABLES WITH DOMINATEDLY VARYING TAILS

    Institute of Scientific and Technical Information of China (English)

    WANG Yuebao; YANG Yang

    2005-01-01

    This paper shows the structure of the random variables with dominatedly varying tails and that of the associated random variables,and obtains some results on these r.v.s' precise moderate deviations with random centralizing constants,which extend the boundary γλ(t) of large deviations to γ(λ(t))1/s,where γ>0,1<s<2,λ(t) is the expectation of the random index N(t),t>O.

  4. Site-Specific Labeling of Protein Kinase CK2: Combining Surface Display and Click Chemistry for Drug Discovery Applications.

    Science.gov (United States)

    Nienberg, Christian; Retterath, Anika; Becher, Kira-Sophie; Saenger, Thorsten; Mootz, Henning D; Jose, Joachim

    2016-06-27

    Human CK2 is a heterotetrameric constitutively active serine/threonine protein kinase and is an emerging target in current anti-cancer drug discovery. The kinase is composed of two catalytic CK2α subunits and two regulatory CK2β subunits. In order to establish an assay to identify protein-protein-interaction inhibitors (PPI) of the CK2α/CK2β interface, a bioorthogonal click reaction was used to modify the protein kinase α-subunit with a fluorophore. By expanding the genetic code, the unnatural amino acid para azidophenylalanine (pAzF) could be incorporated into CK2α. Performing the SPAAC click reaction (Strain-Promoted Azide-Alkyne Cycloaddition) by the use of a dibenzylcyclooctyne-fluorophore (DBCO-fluorophore) led to a specifically labeled human protein kinase CK2α. This site-specific labeling does not impair the phosphorylation activity of CK2, which was evaluated by capillary electrophoresis. Furthermore a dissociation constant (KD) of 631 ± 86.2 nM was determined for the substrate αS1-casein towards CK2α. This labeling strategy was also applied to CK2β subunit on Escherichia coli, indicating the site-specific modifications of proteins on the bacterial cell surface when displayed by Autodisplay.

  5. Site-Specific Labeling of Protein Kinase CK2: Combining Surface Display and Click Chemistry for Drug Discovery Applications

    Directory of Open Access Journals (Sweden)

    Christian Nienberg

    2016-06-01

    Full Text Available Human CK2 is a heterotetrameric constitutively active serine/threonine protein kinase and is an emerging target in current anti-cancer drug discovery. The kinase is composed of two catalytic CK2α subunits and two regulatory CK2β subunits. In order to establish an assay to identify protein-protein-interaction inhibitors (PPI of the CK2α/CK2β interface, a bioorthogonal click reaction was used to modify the protein kinase α-subunit with a fluorophore. By expanding the genetic code, the unnatural amino acid para azidophenylalanine (pAzF could be incorporated into CK2α. Performing the SPAAC click reaction (Strain-Promoted Azide-Alkyne Cycloaddition by the use of a dibenzylcyclooctyne-fluorophore (DBCO-fluorophore led to a specifically labeled human protein kinase CK2α. This site-specific labeling does not impair the phosphorylation activity of CK2, which was evaluated by capillary electrophoresis. Furthermore a dissociation constant (KD of 631 ± 86.2 nM was determined for the substrate αS1-casein towards CK2α. This labeling strategy was also applied to CK2β subunit on Escherichia coli, indicating the site-specific modifications of proteins on the bacterial cell surface when displayed by Autodisplay.

  6. Site-Specific Labeling of Protein Kinase CK2: Combining Surface Display and Click Chemistry for Drug Discovery Applications †

    Science.gov (United States)

    Nienberg, Christian; Retterath, Anika; Becher, Kira-Sophie; Saenger, Thorsten; Mootz, Henning D.; Jose, Joachim

    2016-01-01

    Human CK2 is a heterotetrameric constitutively active serine/threonine protein kinase and is an emerging target in current anti-cancer drug discovery. The kinase is composed of two catalytic CK2α subunits and two regulatory CK2β subunits. In order to establish an assay to identify protein-protein-interaction inhibitors (PPI) of the CK2α/CK2β interface, a bioorthogonal click reaction was used to modify the protein kinase α-subunit with a fluorophore. By expanding the genetic code, the unnatural amino acid para azidophenylalanine (pAzF) could be incorporated into CK2α. Performing the SPAAC click reaction (Strain-Promoted Azide-Alkyne Cycloaddition) by the use of a dibenzylcyclooctyne-fluorophore (DBCO-fluorophore) led to a specifically labeled human protein kinase CK2α. This site-specific labeling does not impair the phosphorylation activity of CK2, which was evaluated by capillary electrophoresis. Furthermore a dissociation constant (KD) of 631 ± 86.2 nM was determined for the substrate αS1-casein towards CK2α. This labeling strategy was also applied to CK2β subunit on Escherichia coli, indicating the site-specific modifications of proteins on the bacterial cell surface when displayed by Autodisplay. PMID:27355959

  7. Expression, purification and crystallization of the catalytic subunit of protein kinase CK2 from Zea mays

    DEFF Research Database (Denmark)

    Guerra, B; Niefind, K; Pinna, L A;

    1998-01-01

    The catalytic (alpha) subunit of protein kinase CK2 (CK2alpha) was originally cloned and overexpressed in the Escherichia coli strain pT7-7/BL21(DE3). The protein has been purified to homogeneity and crystallized. The crystals belong to the monoclinic space group C2, they have unit-cell parameters...... a = 142.6, b = 61.3, c = 45.6 A, beta = 103.3 degrees and diffract X-rays to at least 2.0 A resolution. The calculated crystal packing parameter is Vm = 2.47 A3 Da-1 suggesting that one CK2alpha molecule is contained in the asymmetric unit and that the solvent content of the unit cell is 50%....

  8. Mutational analysis of residues implicated in the interaction between protein kinase CK2 and peptide substrates

    DEFF Research Database (Denmark)

    Sarno, S; Vaglio, P; Marin, O;

    1997-01-01

    Sixteen derivatives of the optimal peptide substrate RRRA-DDSDDDDD in which aspartic acids were singly or multiply substituted by alanine have been assayed for their phosphorylation efficiency by either wild type protein kinase CK2 or CK2 alpha mutants defective in substrate recognition. With wild...... substitutions tend to have a more than additive effect even if they affect individually dispensable aspartic acids; thus, double, triple, and quintuple substitutions at positions n - 2 and -1, and n + 2, +4, and +5 had detrimental consequences comparable to those observed with substitutions at n + 1 and n + 3....... However, if the suboptimal substrate RRRA-AASDDDDD was used, the single mutants K49A, K71A, K77A, R80A, and H160A also exhibited Km values significantly higher than those of wild type CK2. Kinetic analysis with singly substituted derivatives of peptide RRRA-DDSDDDDD revealed that K49 is implicated in the...

  9. Identification of ellagic acid as potent inhibitor of protein kinase CK2: a successful example of a virtual screening application.

    Science.gov (United States)

    Cozza, Giorgio; Bonvini, Paolo; Zorzi, Elisa; Poletto, Giorgia; Pagano, Mario A; Sarno, Stefania; Donella-Deana, Arianna; Zagotto, Giuseppe; Rosolen, Angelo; Pinna, Lorenzo A; Meggio, Flavio; Moro, Stefano

    2006-04-20

    Casein kinase 2 (CK2) is a ubiquitous, essential, and highly pleiotropic protein kinase whose abnormally high constitutive activity is suspected to underlie its pathogenic potential in neoplasia and other diseases. Using a virtual screening approach, we have identified the ellagic acid, a naturally occurring tannic acid derivative, as a novel potent CK2 inhibitor. At present, ellagic acid represents the most potent known CK2 inhibitor (K(i) = 20 nM). PMID:16610779

  10. A subnanomolar fluorescent probe for protein kinase CK2 interaction studies

    DEFF Research Database (Denmark)

    Enkvist, Erki; Viht, Kaido; Bischoff, Nils;

    2012-01-01

    assay that used thin layer chromatography for the measurement of the rate of phosphorylation of fluorescently labelled peptide 5-TAMRA-RADDSDDDDD. The most potent inhibitor, ARC-1502 (K(i) = 0.5 nM), revealed high selectivity for CK2α in a panel of 140 protein kinases. Labelling of ARC-1502 with PromoFluor...

  11. Regulation of taurine transport systems by protein kinase CK2 in mammalian cells

    DEFF Research Database (Denmark)

    Lambert, Ian Henry; Hansen, Daniel Bloch

    2011-01-01

    Maintaining cell volume is critical for cellular function yet shift in cell volume is a prerequisite for mitosis and apoptosis. The ubiquitously and evolutionary conserved serine/threonine kinase CK2 promotes cell survival and suppresses apoptosis. The present review describes how mammalian cells...

  12. Mapping the residues of protein kinase CK2 implicated in substrate recognition

    DEFF Research Database (Denmark)

    Sarno, S; Boldyreff, B; Marin, O;

    1995-01-01

    Six mutants of protein kinase CK2 alpha subunit in which basic residues have been mutated into alanines were assayed for their capability to phosphorylate the peptide RRRADDSDDDDD. Two mutants (R228A and R278K279R280A) behaved more or less as alpha wild type and one (H160,166A) was nearly inactive...

  13. Mapping the residues of protein kinase CK2 alpha subunit responsible for responsiveness to polyanionic inhibitors

    DEFF Research Database (Denmark)

    Vaglio, P; Sarno, S; Marin, O;

    1996-01-01

    The quadruple mutation of the whole basic cluster, K74KKK77 conserved in the catalytic subunits of protein kinase CK2 and implicated in substrate recognition, not only abolishes inhibition by heparin but even induces with some peptide substrates an up to 5-fold stimulation by heparin in the 0...

  14. Identification of hematein as a novel inhibitor of protein kinase CK2 from a natural product library

    International Nuclear Information System (INIS)

    Casein kinase 2 (CK2) is dysregulated in various human cancers and is a promising target for cancer therapy. To date, there is no small molecular CK2 inhibitor in clinical trial yet. With the aim to identify novel CK2 inhibitors, we screened a natural product library. We adopted cell-based proliferation and CK2 kinase assays to screen CK2 inhibitors from a natural compound library. Dose-dependent response of CK2 inhibitors in vitro was determined by a radioisotope kinase assay. Western blot analysis was used to evaluate down stream Akt phosphorylation and apoptosis. Apoptosis was also evaluated by annexin-V/propidium iodide (PI) labeling method using flow cytometry. Inhibition effects of CK2 inhibitors on the growth of cancer and normal cells were evaluated by cell proliferation and viability assays. Hematein was identified as a novel CK2 inhibitor that is highly selective among a panel of kinases. It appears to be an ATP non-competitive and partially reversible CK2 inhibitor with an IC50 value of 0.55 μM. In addition, hematein inhibited cancer cell growth partially through down-regulation of Akt phosphorylation and induced apoptosis in these cells. Furthermore, hematein exerted stronger inhibition effects on the growth of cancer cells than in normal cells. In this study, we showed that hematein is a novel selective and cell permeable small molecule CK2 inhibitor. Hematein showed stronger growth inhibition effects to cancer cells when compared to normal cells. This compound may represent a promising class of CK2 inhibitors

  15. Downregulation of protein kinase CK2 activity facilitates tumor necrosis factor-α-mediated chondrocyte death through apoptosis and autophagy.

    Directory of Open Access Journals (Sweden)

    Sung Won Lee

    Full Text Available Despite the numerous studies of protein kinase CK2, little progress has been made in understanding its function in chondrocyte death. Our previous study first demonstrated that CK2 is involved in apoptosis of rat articular chondrocytes. Recent studies have suggested that CK2 downregulation is associated with aging. Thus examining the involvement of CK2 downregulation in chondrocyte death is an urgently required task. We undertook this study to examine whether CK2 downregulation modulates chondrocyte death. We first measured CK2 activity in articular chondrocytes of 6-, 21- and 30-month-old rats. Noticeably, CK2 activity was downregulated in chondrocytes with advancing age. To build an in vitro experimental system for simulating tumor necrosis factor (TNF-α-induced cell death in aged chondrocytes with decreased CK2 activity, chondrocytes were co-treated with CK2 inhibitors and TNF-α. Viability assay demonstrated that CK2 inhibitors facilitated TNF-α-mediated chondrocyte death. Pulsed-field gel electrophoresis, nuclear staining, flow cytometry, TUNEL staining, confocal microscopy, western blot and transmission electron microscopy were conducted to assess cell death modes. The results of multiple assays showed that this cell death was mediated by apoptosis. Importantly, autophagy was also involved in this process, as supported by the appearance of a punctuate LC3 pattern and autophagic vacuoles. The inhibition of autophagy by silencing of autophage-related genes 5 and 7 as well as by 3-methyladenine treatment protected chondrocytes against cell death and caspase activation, indicating that autophagy led to the induction of apoptosis. Autophagic cells were observed in cartilage obtained from osteoarthritis (OA model rats and human OA patients. Our findings indicate that CK2 down regulation facilitates TNF-α-mediated chondrocyte death through apoptosis and autophagy. It should be clarified in the future if autophagy observed is a consequence

  16. The carboxy terminus of p53 mimics the polylysine effect of protein kinase CK2-catalyzed MDM2 phosphorylation

    DEFF Research Database (Denmark)

    Guerra, B; Götz, C; Wagner, P;

    1997-01-01

    The oncogene product MDM2 can be phosphorylated by protein kinase CK2 in vitro 0.5-1 mol of phosphate were incorporated per mol MDM2 protein. The catalytic subunit of protein kinase CK2 (alpha-subunit) catalyzed the incorporation of twice as much phosphate into the MDM2 protein as it was obtained...

  17. Text localization using standard deviation analysis of structure elements and support vector machines

    Directory of Open Access Journals (Sweden)

    Zagoris Konstantinos

    2011-01-01

    Full Text Available Abstract A text localization technique is required to successfully exploit document images such as technical articles and letters. The proposed method detects and extracts text areas from document images. Initially a connected components analysis technique detects blocks of foreground objects. Then, a descriptor that consists of a set of suitable document structure elements is extracted from the blocks. This is achieved by incorporating an algorithm called Standard Deviation Analysis of Structure Elements (SDASE which maximizes the separability between the blocks. Another feature of the SDASE is that its length adapts according to the requirements of the application. Finally, the descriptor of each block is used as input to a trained support vector machines that classify the block as text or not. The proposed technique is also capable of adjusting to the text structure of the documents. Experimental results on benchmarking databases demonstrate the effectiveness of the proposed method.

  18. Protein structure validation by generalized linear model root-mean-square deviation prediction.

    Science.gov (United States)

    Bagaria, Anurag; Jaravine, Victor; Huang, Yuanpeng J; Montelione, Gaetano T; Güntert, Peter

    2012-02-01

    Large-scale initiatives for obtaining spatial protein structures by experimental or computational means have accentuated the need for the critical assessment of protein structure determination and prediction methods. These include blind test projects such as the critical assessment of protein structure prediction (CASP) and the critical assessment of protein structure determination by nuclear magnetic resonance (CASD-NMR). An important aim is to establish structure validation criteria that can reliably assess the accuracy of a new protein structure. Various quality measures derived from the coordinates have been proposed. A universal structural quality assessment method should combine multiple individual scores in a meaningful way, which is challenging because of their different measurement units. Here, we present a method based on a generalized linear model (GLM) that combines diverse protein structure quality scores into a single quantity with intuitive meaning, namely the predicted coordinate root-mean-square deviation (RMSD) value between the present structure and the (unavailable) "true" structure (GLM-RMSD). For two sets of structural models from the CASD-NMR and CASP projects, this GLM-RMSD value was compared with the actual accuracy given by the RMSD value to the corresponding, experimentally determined reference structure from the Protein Data Bank (PDB). The correlation coefficients between actual (model vs. reference from PDB) and predicted (model vs. "true") heavy-atom RMSDs were 0.69 and 0.76, for the two datasets from CASD-NMR and CASP, respectively, which is considerably higher than those for the individual scores (-0.24 to 0.68). The GLM-RMSD can thus predict the accuracy of protein structures more reliably than individual coordinate-based quality scores.

  19. Crystallization and preliminary characterization of crystals of human protein kinase CK2

    DEFF Research Database (Denmark)

    Niefind, K; Guerra, B; Ermakowa, I;

    2000-01-01

    The heterotetrameric recombinant holoenzyme of human protein kinase CK2 was purified to homogeneity. It degraded spontaneously to a stable and fully active state in which the catalytic subunit was about 5 kDa smaller than the wild type. The degraded enzyme was crystallized using polyethylene glycol...... 3350 as precipitant. The crystals belong to the hexagonal space group P6(3). They have unit-cell parameters a = b = 176.0, c = 93.6 A and diffract X-rays to at least 3.5 A resolution. The calculated crystal packing parameter is V(M) = 3.22 A(3) Da(-1), suggesting that one CK2 tetramer is contained...

  20. Isolation and characterization of a monoclonal anti-protein kinase CK2 beta-subunit antibody of the IgG class for the direct detection of CK2 beta-subunit in tissue cultures of various mammalian species and human tumors

    DEFF Research Database (Denmark)

    Nastainczyk, W; Schmidt-Spaniol, I; Boldyreff, B;

    1995-01-01

    A murine monoclonal anti-protein kinase CK2 beta antibody was isolated and characterized. The antibody detects 1 pmol of purified recombinant CK2 beta-subunit after analysis on SDS-PAGE. Alternatively undenatured CK2 beta-subunit was detected by an ELISA assay either as recombinant CK2 beta-subun...

  1. Protein Kinase CK2 Expression Predicts Relapse Survival in ERα Dependent Breast Cancer, and Modulates ERα Expression in Vitro

    Directory of Open Access Journals (Sweden)

    Marlon D. Williams

    2015-12-01

    Full Text Available The heterotetrameric protein kinase CK2 has been associated with oncogenic transformation, and our previous studies have shown that it may affect estrogenic signaling. Here, we investigate the role of the protein kinase CK2 in regulating ERα (estrogen receptor α signaling in breast cancer. We determined the correlation of CK2α expression with relapse free breast cancer patient survival utilizing Kaplan Meier Plotter (kmplot.com/analysis/ to mine breast cancer microarrays repositories. Patients were stratified according to ERα status, histological grade, and hormonal therapy. Luciferase reporter assays and flow cytometry were implemented to determine the impact of CK2 inhibition on ERE-mediated gene expression and expression of ERα protein. CK2α expression is associated with shorter relapse free survival among ERα (+ patients with grade 1 or 2 tumors, as well as among those patients receiving hormonal therapy. Biochemical inhibition of CK2 activity results in increased ER-transactivation as well as increased expression among ERα (+ and ERα (− breast cancer cell lines. These findings suggest that CK2 may contribute to estrogen-independent cell proliferation and breast tumor progression, and may potentially serve as a biomarker and pharmacological target in breast cancer.

  2. Stress-induced activation of protein kinase CK2 by direct interaction with p38 mitogen-activated protein kinase

    DEFF Research Database (Denmark)

    Sayed, M; Kim, S O; Salh, B S;

    2000-01-01

    Protein kinase CK2 has been implicated in the regulation of a wide range of proteins that are important in cell proliferation and differentiation. Here we demonstrate that the stress signaling agents anisomycin, arsenite, and tumor necrosis factor-alpha stimulate the specific enzyme activity of CK2...... to be an allosteric mechanism. Furthermore, we demonstrate that anisomycin- and tumor necrosis factor-alpha-induced phosphorylation of p53 at Ser-392, which is important for the transcriptional activity of this growth suppressor protein, requires p38 MAP kinase and CK2 activities....... in the human cervical carcinoma HeLa cells by up to 8-fold, and this could be blocked by the p38 MAP kinase inhibitor SB203580. We show that p38alpha MAP kinase, in a phosphorylation-dependent manner, can directly interact with the alpha and beta subunits of CK2 to activate the holoenzyme through what appears...

  3. Thermodynamic parameters for binding of some halogenated inhibitors of human protein kinase CK2

    Energy Technology Data Exchange (ETDEWEB)

    Winiewska, Maria; Makowska, Małgorzata [Institute of Biochemistry and Biophysics PAS, Warszawa (Poland); Maj, Piotr [Institute of Biochemistry and Biophysics PAS, Warszawa (Poland); Nencki Institute of Experimental Biology PAS, Warszawa (Poland); Wielechowska, Monika; Bretner, Maria [Warsaw University of Technology, Faculty of Chemistry, Warszawa (Poland); Poznański, Jarosław, E-mail: jarek@ibb.waw.pl [Institute of Biochemistry and Biophysics PAS, Warszawa (Poland); Shugar, David [Institute of Biochemistry and Biophysics PAS, Warszawa (Poland)

    2015-01-02

    Highlights: • Two new compounds being potential human CK2a inhibitors are studied. • Their IC50 values were determined in vitro. • The heats of binding and kbind were estimated using DSC. • The increased stability of protein–ligand complexes was followed by fluorescence. • Methylated TBBt derivative (MeBr3Br) is almost as active as TBBt. - Abstract: The interaction of human CK2α with a series of tetrabromobenzotriazole (TBBt) and tetrabromobenzimidazole (TBBz) analogs, in which one of the bromine atoms proximal to the triazole/imidazole ring is replaced by a methyl group, was studied by biochemical (IC{sub 50}) and biophysical methods (thermal stability of protein–ligand complex monitored by DSC and fluorescence). Two newly synthesized tri-bromo derivatives display inhibitory activity comparable to that of the reference compounds, TBBt and TBBz, respectively. DSC analysis of the stability of protein–ligand complexes shows that the heat of ligand binding (H{sub bind}) is driven by intermolecular electrostatic interactions involving the triazole/imidazole ring, as indicated by a strong correlation between H{sub bind} and ligand pK{sub a}. Screening, based on fluorescence-monitored thermal unfolding of protein–ligand complexes, gave comparable results, clearly identifying ligands that most strongly bind to the protein. Overall results, additionally supported by molecular modeling, confirm that a balance of hydrophobic and electrostatic interactions contribute predominantly, relative to possible intermolecular halogen bonding, in binding of the ligands to the CK2α ATP-binding site.

  4. Effects of the CK2 inhibitors CX-4945 and CX-5011 on drug-resistant cells.

    Directory of Open Access Journals (Sweden)

    Sofia Zanin

    Full Text Available CK2 is a pleiotropic protein kinase, which regulates many survival pathways and plays a global anti-apoptotic function. It is highly expressed in tumor cells, and is presently considered a promising therapeutic target. Among the many inhibitors available for this kinase, the recently developed CX-4945 and CX-5011 have proved to be very potent, selective and effective in inducing cell death in tumor cells; CX-4945 has recently entered clinical trials. However, no data are available on the efficacy of these compounds to overcome drug resistance, a major reasons of cancer therapy failure. Here we address this point, by studying their effects in several tumor cell lines, each available as variant R resistant to drug-induced apoptosis, and normal-sensitive variant S. We found that the inhibition of endogenous CK2 was very similar in S and R treated cells, with more than 50% CK2 activity reduction at sub-micromolar concentrations of CX-4945 and CX-5011. A consequent apoptotic response was induced both in S and R variants of each pairs. Moreover, the combined treatment of CX-4945 plus vinblastine was able to sensitize to vinblastine R cells that are otherwise almost insensitive to this conventional antitumor drug. Consistently, doxorubicin accumulation in multidrug resistant (MDR cells was greatly increased by CX-4945.In summary, we demonstrated that all the R variants are sensitive to CX-4945 and CX-5011; since some of the treated R lines express the extrusion pump Pgp, often responsible of the MDR phenotype, we can also conclude that the two inhibitors can successfully overcome the MDR phenomenon.

  5. Ability of CK2beta to selectively regulate cellular protein kinases

    DEFF Research Database (Denmark)

    Olsen, Birgitte; Guerra, Barbara

    2008-01-01

    The Wee1 protein kinase plays a prominent role in keeping cyclin dependent kinase 1 (CDK1) inactive during the G2 phase of the cell cycle. At the onset of mitosis, Wee1 is ubiquitinated by the E3 ubiquitin ligase SCF(beta-TrCP) and subsequently degraded by the proteasome machinery. Previously...... additional phosphodegrons recognised by beta-TrCP. These events contribute to destabilise Wee1 at the onset of mitosis (Watanabe et al. Proc Natl Acad Sci USA 101:4419-4424, 2004). We show here that in addition to the ability of CK2 to phosphorylate Wee1 as reported earlier, the regulatory beta...

  6. Protein kinase CK2 mutants defective in substrate recognition. Purification and kinetic analysis

    DEFF Research Database (Denmark)

    Sarno, S; Vaglio, P; Meggio, F;

    1996-01-01

    Five mutants of protein kinase CK2 alpha subunit in which altogether 14 basic residues were singly to quadruply replaced by alanines (K74A,K75A,K76A,K77A; K79A, R80A,K83A; R191A,R195A,K198A; R228A; and R278A, K279A,R280A) have been purified to near homogeneity either as such or after addition...... downstream from serine, the other basic residues seem to play a more elusive and/or indirect role in catalysis....

  7. Protein Kinase CK2 Regulates Cytoskeletal Reorganization during Ionizing Radiation-Induced Senescence of Human Mesenchymal Stem Cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Daojing; Jang, Deok-Jin

    2009-08-21

    Human mesenchymal stem cells (hMSC) are critical for tissue regeneration. How hMSC respond to genotoxic stresses and potentially contribute to aging and cancer remain underexplored. We demonstrated that ionizing radiation induced cellular senescence of hMSC over a period of 10 days, showing a critical transition between day 3 and day 6. This was confirmed by senescence-associated beta-galactosidase (SA-{beta}-gal) staining, protein expression profiles of key cell cycle regulators (retinoblastoma (Rb) protein, p53, p21{sup waf1/Cip1}, and p16{sup INK4A}), and senescence-associated secretory phenotypes (SASPs) (IL-8, IL-12, GRO, and MDC). We observed dramatic cytoskeletal reorganization of hMSC through reduction of myosin-10, redistribution of myosin-9, and secretion of profilin-1. Using a SILAC-based phosphoproteomics method, we detected significant reduction of myosin-9 phosphorylation at Ser1943, coinciding with its redistribution. Importantly, through treatment with cell permeable inhibitors (4,5,6,7-tetrabromo-1H-benzotriazole (TBB) and 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole (DMAT)), and gene knockdown using RNA interference, we identified CK2, a kinase responsible for myosin-9 phosphorylation at Ser1943, as a key factor contributing to the radiation-induced senescence of hMSC. We showed that individual knockdown of CK2 catalytic subunits CK2{alpha} and CK2{alpha}{prime} induced hMSC senescence. However, only knockdown of CK2{alpha} resulted in morphological phenotypes resembling those of radiation-induced senescence. These results suggest that CK2{alpha} and CK2{alpha}{prime} play differential roles in hMSC senescence progression, and their relative expression might represent a novel regulatory mechanism for CK2 activity.

  8. Resorufin: a lead for a new protein kinase CK2 inhibitor

    DEFF Research Database (Denmark)

    Sandholt, Iben Skjøth; Olsen, Birgitte Brinkmann; Guerra, Barbara;

    2009-01-01

    treatment with 40 mol/l resorufin led to 15-20% dead cells; however, no caspase-mediated apoptosis was observed. In the case of the colorectal carcinoma HCT116 cell line, a similar picture was obtained, yet, when resorufin was administered to cells treated with doxorubicin, apoptosis was strongly induced...... other kinases by 90%. The IC50 values determined for the CK2 holoenzymes were 1.5 mol/l and for the free catalytic subunits ca. 4 mol/l. Altogether four cell lines were subjected to resorufin and emodin treatment. In the case of the three prostate carcinoma cell lines (PC-3, DU-145, LNCaP), 24 h...... within 24 h. Endogenous protein kinase CK2 was inhibited by resorufin by ca. 80% in the three prostate cell lines. In the case of the HCT116 cells, the inhibition was only 40% supporting the notion of cell line-specific selectivity. Moreover, we analysed the effect of resorufin and emodin on selected...

  9. Detection of phospho-sites generated by protein kinase CK2 in CFTR: mechanistic aspects of Thr1471 phosphorylation.

    Directory of Open Access Journals (Sweden)

    Andrea Venerando

    Full Text Available By mass spectrometry analysis of mouse Cystic Fibrosis Transmembrane-conductance Regulator (mCFTR expressed in yeast we have detected 21 phosphopeptides accounting for 22 potential phospho-residues, 12 of which could be unambiguously assigned. Most are conserved in human CFTR (hCFTR and the majority cluster in the Regulatory Domain, lying within consensus sequences for PKA, as identified in previous mammalian studies. This validates our yeast expression model. A number of phospho-residues were novel and human conserved, notably mouse Ser670, Ser723, Ser737, and Thr1467, that all lie in acidic sequences, compatible with their phosphorylation by protein kinase CK2. Thr1467 is localized in the C-terminal tail, embedded in a functionally important and very acidic sequence (EETEEE which displays an optimal consensus for protein kinase CK2. Herein, we show that Thr1467, homologous to human Thr1471 is readily phosphorylated by CK2. Indeed a 42 amino acid peptide encompassing the C-terminal segment of human CFTR is readily phosphorylated at Thr1471 with favorable kinetics (Km 1.7 µM by CK2 holoenzyme, but neither by its isolated catalytic subunit nor by other acidophilic Ser/Thr kinases (CK1, PLK2/3, GCK/FAM20C. Our finding that by treating CFTR expressing BHK cells with the very specific CK2 inhibitor CX4945, newly synthesized wild type CFTR (and even more its Phe508del mutant accumulates more abundantly than in the absence of CK2 inhibitor, supports the conclusion that phosphorylation of CFTR by CK2 correlates with decreased stability of the protein.

  10. Inhibition of protein kinase CK2 by condensed polyphenolic derivatives. An in vitro and in vivo study.

    Science.gov (United States)

    Meggio, Flavio; Pagano, Mario A; Moro, Stefano; Zagotto, Giuseppe; Ruzzene, Maria; Sarno, Stefania; Cozza, Giorgio; Bain, Jenny; Elliott, Matthew; Deana, Arianna Donella; Brunati, Anna Maria; Pinna, Lorenzo A

    2004-10-12

    ATP site-directed inhibitors that can target individual kinases are powerful tools for use in signal transduction research, all the more so in the case of a pleiotropic, constitutively active protein kinase such as CK2, which is not turned on in response to specific stimuli. By screening a library of more than 200 derivatives of natural polyphenolic compounds, we have identified 16 molecules which inhibit CK2 with IC(50) values of CK2 within a panel of 33 protein kinases tested. Treatment of Jurkat cells with these compounds promotes inhibition of endogenous CK2 and induction of apoptosis. A correlation is observed between their efficacy as CK2 inhibitors (as judged from IC(50) values) and their capacity to induce cell death (DC(50) values). Mutations of the unique CK2alpha residues Val66 and/or Ile174 to alanine have a detrimental effect on inhibition by these compounds with 16-67-fold increases in IC(50) values. The combined usage of these reagents can be exploited to gain information about cellular functions mediated by CK2. PMID:15461466

  11. Different Persistence of the Cellular Effects Promoted by Protein Kinase CK2 Inhibitors CX-4945 and TDB

    Directory of Open Access Journals (Sweden)

    Cristina Girardi

    2015-01-01

    Full Text Available We compare the cellular efficacy of two selective and cell permeable inhibitors of the antiapoptotic kinase CK2. One inhibitor, CX-4945, is already in clinical trials as antitumor drug, while the other, TDB, has been recently successfully employed to demonstrate the implication of CK2 in cellular (disregulation. We found that, upon treatment of cancer cells with these compounds, the extent of inhibition of endocellular CK2 is initially comparable but becomes significantly different after the inhibitors are removed from the cellular medium: while in CX-4945 treated cells CK2 activity is restored to control level after 24 h, in the case of TDB it is still strongly reduced after 4 days from removal. The biological effects of the two inhibitors have been analyzed by performing clonogenic, spheroid formation, and wound-healing assays: we observed a permanent inhibition of cell survival and migration in TDB-treated cells even after the inhibitor removal, while in the case of CX-4945 only its maintenance for the whole duration of the assay insured a persisting effect. We suggest that the superiority of TDB in maintaining kinase activity inhibited and perpetuating the consequent effects is an added value to be considered when planning new therapies based on CK2 targeting.

  12. Tetrabromocinnamic acid (TBCA) and related compounds represent a new class of specific protein kinase CK2 inhibitors.

    Science.gov (United States)

    Pagano, Mario A; Poletto, Giorgia; Di Maira, Giovanni; Cozza, Giorgio; Ruzzene, Maria; Sarno, Stefania; Bain, Jenny; Elliott, Matthew; Moro, Stefano; Zagotto, Giuseppe; Meggio, Flavio; Pinna, Lorenzo A

    2007-01-01

    Abnormally high constitutive activity of protein kinase CK2, levels of which are elevated in a variety of tumours, is suspected to underlie its pathogenic potential. The most widely employed CK2 inhibitor is 4,5,6,7-tetrabromobenzotriazole (TBB), which exhibits a comparable efficacy toward another kinase, DYRK1 a. Here we describe the development of a new class of CK2 inhibitors, conceptually derived from TBB, which have lost their potency toward DYRK1 a. In particular, tetrabromocinnamic acid (TBCA) inhibits CK2 five times more efficiently than TBB (IC50 values 0.11 and 0.56 microM, respectively), without having any comparable effect on DYRK1 a (IC50 24.5 microM) or on a panel of 28 protein kinases. The usefulness of TBCA for cellular studies has been validated by showing that it reduces the viability of Jurkat cells more efficiently than TBB through enhancement of apoptosis. Collectively taken, the reported data support the view that suitably derivatized tetrabromobenzene molecules may provide powerful reagents for dissecting the cellular functions of CK2 and counteracting its pathogenic potentials. PMID:17133643

  13. Effects of siRNA specific to the protein kinase CK2α on apoptosis of laryngeal carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    WANG Jian-ting; GONG Shu-sheng

    2012-01-01

    Background The relationship between apoptosis and tumors is a major focus in cancer research.RNA interference (RNAi) technology has emerged as a very potent tool to generate cellular knockdown phenotypes of a desired gene.The aim of this study was to explore the effect of siRNA specific to the protein casein kinase 2a (CK2α) on apoptosis of laryngeal carcinoma cells and to explore possible mechanisms.Methods An siRNA expression plasmid specific to CK2α,psiRNA-hH1neo-CK2a,and a non-specific siRNA expression plasmid,psiRNA-hH1neo-cont,were constructed and transfected into Hep-2 cells by a lipofectamine method.The mRNA and protein levels of CK2a in transfected cells were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting analysis.Apoptosis was measured by Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) double-staining methods.The morphological changes to Hep-2 cells were observed under transmission electron microscopy (TEM).The levels of Bcl-2 and Bax proteins were measured by Western blotting analysis.Results Levels of CK2a mRNA and protein were significantly decreased in the psiRNA-hHlneo-CK2α group compared to the other groups (P <0.05).The apoptotic rate of the psiRNA-hHlneo-CK2a transfected group was significantly higher compared to that in the untransfected group and the siRNA-hH1neo-cont transfected group (25.66%±0.83%,3.66%±0.43%,and 5.18%±0.22%) (P <0.05).Compared with the untransfected group and the siRNA-hH1neo-cont transfected group,the psiRNA-hH1neo-CK2a transfected group presented with classical ultrastructural features of apoptosis,such as karyopyknosis,chromatic agglutination adjacent to the nuclear membrane,and apoptotic bodies.Compared with the other two groups,the level of Bcl-2 protein in the psiRNA-hH1neo-CK2α transfected group was decreased (0.20±0.09 vs.0.72±0.16,0.56±0.11,P <0.01),while the Bax protein level was increased (0.81±0.17 vs.0.26±0.12,0.33±0

  14. 抑制CK2增加Sorbitol引起的肺癌细胞凋亡

    Institute of Scientific and Technical Information of China (English)

    齐昕; 徐晓光; 蒋颖超

    2014-01-01

    目的:探讨抑制CK2对雷帕霉素引起的肺癌细胞凋亡的影响。方法选用人肺癌A549细胞,MTT方法检测单独利用山梨醇( Sor-bitol)或者联合CK2抑制剂TBB对A549细胞活性的影响,Western印迹检测单独利用 Sorbitol或者联合 CK2抑制剂TBB凋亡相关蛋白 caspase-3和PARP,以及线粒体凋亡相关蛋白细胞色素C表达水平的影响。结果 MTT结果显示,Sorbitol可以显著引起A549细胞活性下降,并呈现时间依赖性和剂量依赖性。 Western印迹结果显示,Sorbitol可以引起凋亡相关蛋白Cleaved PARP、Cleaved caspase-3以及细胞色素C表达水平明显上升。 MTT结果显示,联合应用CK2抑制剂可以明显增加Sorbitol,引起细胞活性降低。 Western印迹显示,与单独给予Sorbitol比较,联合应用CK2抑制剂 TBB,凋亡相关蛋白Cleaved PARP、Cleaved caspase-3进一步增加。结论 CK2抑制剂TBB可提高人肺癌A549细胞对Sorbitol的敏感性。

  15. Protein kinase CK2 localizes to sites of DNA double-strand break regulating the cellular response to DNA damage

    Directory of Open Access Journals (Sweden)

    Olsen Birgitte B

    2012-03-01

    Full Text Available Abstract Background The DNA-dependent protein kinase (DNA-PK is a nuclear complex composed of a large catalytic subunit (DNA-PKcs and a heterodimeric DNA-targeting subunit Ku. DNA-PK is a major component of the non-homologous end-joining (NHEJ repair mechanism, which is activated in the presence of DNA double-strand breaks induced by ionizing radiation, reactive oxygen species and radiomimetic drugs. We have recently reported that down-regulation of protein kinase CK2 by siRNA interference results in enhanced cell death specifically in DNA-PKcs-proficient human glioblastoma cells, and this event is accompanied by decreased autophosphorylation of DNA-PKcs at S2056 and delayed repair of DNA double-strand breaks. Results In the present study, we show that CK2 co-localizes with phosphorylated histone H2AX to sites of DNA damage and while CK2 gene knockdown is associated with delayed DNA damage repair, its overexpression accelerates this process. We report for the first time evidence that lack of CK2 destabilizes the interaction of DNA-PKcs with DNA and with Ku80 at sites of genetic lesions. Furthermore, we show that CK2 regulates the phosphorylation levels of DNA-PKcs only in response to direct induction of DNA double-strand breaks. Conclusions Taken together, these results strongly indicate that CK2 plays a prominent role in NHEJ by facilitating and/or stabilizing the binding of DNA-PKcs and, possibly other repair proteins, to the DNA ends contributing to efficient DNA damage repair in mammalian cells.

  16. Disruption of the regulatory beta subunit of protein kinase CK2 in mice leads to a cell-autonomous defect and early embryonic lethality

    DEFF Research Database (Denmark)

    Buchou, Thierry; Vernet, Muriel; Blond, Olivier;

    2003-01-01

    . Attempts to generate homozygous embryonic stem (ES) cells failed. By using a conditional knockout approach, we show that lack of CK2beta is deleterious for mouse ES cells and primary embryonic fibroblasts. This is in contrast to what occurs with yeast cells, which can survive without functional CK2beta...... in mice leads to postimplantation lethality. Mutant embryos were reduced in size at embryonic day 6.5 (E6.5). They did not exhibit signs of apoptosis but did show reduced cell proliferation. Mutant embryos were resorbed at E7.5. In vitro, CK2beta(-/-) morula development stopped after the blastocyst stage......Protein kinase CK2 is a ubiquitous protein kinase implicated in proliferation and cell survival. Its regulatory beta subunit, CK2beta, which is encoded by a single gene in mammals, has been suspected of regulating other protein kinases. In this work, we show that knockout of the CK2beta gene...

  17. A surface-plasmon-resonance analysis of polylysine interactions with a peptide substrate of protein kinase CK2 and with the enzyme

    OpenAIRE

    Benítez, María J.; Mier, Gerardo; Briones Fernández-Pola, Fernando; Moreno, Francisco J.; Juan S Jiménez

    1997-01-01

    The mechanism of protein kinase CK2 (CK2) activity stimulation by polylysine has been studied by surface plasmon resonance (SPR). The kinetics of the polylysine interaction with a peptide substrate of the enzyme, and with the enzyme itself, have been investigated. A peptide containing a threonine (T) residue surrounded by a cluster of negatively charged acidic [arginine (R) and glutamic acid (E)] residues, RRREEETEEE, and specifically phosphorylated by CK2, was selected. Polylysine interacts ...

  18. The functional interplay between protein kinase CK2 and CCA1 transcriptional activity is essential for clock temperature compensation in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Sergi Portolés

    2010-11-01

    Full Text Available Circadian rhythms are daily biological oscillations driven by an endogenous mechanism known as circadian clock. The protein kinase CK2 is one of the few clock components that is evolutionary conserved among different taxonomic groups. CK2 regulates the stability and nuclear localization of essential clock proteins in mammals, fungi, and insects. Two CK2 regulatory subunits, CKB3 and CKB4, have been also linked with the Arabidopsis thaliana circadian system. However, the biological relevance and the precise mechanisms of CK2 function within the plant clockwork are not known. By using ChIP and Double-ChIP experiments together with in vivo luminescence assays at different temperatures, we were able to identify a temperature-dependent function for CK2 modulating circadian period length. Our study uncovers a previously unpredicted mechanism for CK2 antagonizing the key clock regulator CIRCADIAN CLOCK-ASSOCIATED 1 (CCA1. CK2 activity does not alter protein accumulation or subcellular localization but interferes with CCA1 binding affinity to the promoters of the oscillator genes. High temperatures enhance the CCA1 binding activity, which is precisely counterbalanced by the CK2 opposing function. Altering this balance by over-expression, mutation, or pharmacological inhibition affects the temperature compensation profile, providing a mechanism by which plants regulate circadian period at changing temperatures. Therefore, our study establishes a new model demonstrating that two opposing and temperature-dependent activities (CCA1-CK2 are essential for clock temperature compensation in Arabidopsis.

  19. Inhibition of CK2α down-regulates Hedgehog/Gli signaling leading to a reduction of a stem-like side population in human lung cancer cells.

    Directory of Open Access Journals (Sweden)

    Shulin Zhang

    Full Text Available Protein kinase CK2 is frequently elevated in a variety of human cancers. The Hedgehog (Hh signaling pathway has been implicated in stem cell maintenance, and its aberrant activation has been indicated in several types of cancer, including lung cancer. In this study, we show that CK2 is positively involved in Hh/Gli signaling in lung cancer cell lines A549 and H1299. First, we found a correlation between CK2α and Gli1 mRNA levels in 100 primary lung cancer tissues. Down-regulation of Gli1 expression and transcriptional activity were demonstrated after the silencing of CK2α in lung cancer cells. In addition, CK2α siRNA down-regulated the expression of Hh target genes. Furthermore, two small-molecule CK2α inhibitors led to a dose-dependent inhibition of Gli1 expression and transcriptional activity in lung cancer cells. Reversely, forced over-expression of CK2α resulted in an increase both in Gli1 expression and transcriptional activity in A549 cells. Finally, the inhibition of Hh/Gli by CK2α siRNA led to a reduction of a cancer stem cell-like side population that shows higher ABCG2 expression level. Thus, we report that the inhibition of CK2α down-regulates Hh/Gli signaling and subsequently reduces stem-like side population in human lung cancer cells.

  20. Isolation and characterization of a monoclonal anti CK-2 alpha subunit antibody of the IgG1 subclass

    DEFF Research Database (Denmark)

    Schmidt-Spaniol, I; Boldyreff, B; Issinger, O G

    1992-01-01

    A monoclonal antibody was produced against the recombinant human alpha subunit of CK-2. The antibody was of the IgG1 subclass and it was isolated from serum-free cell culture media and purified by affinity chromatography on Protein G Sepharose. The antibody can be used to detect specifically the ...

  1. Casein kinase 2 (CK2) phosphorylates the deubiquitylase OTUB1 at Ser16 to trigger its nuclear localization.

    Science.gov (United States)

    Herhaus, Lina; Perez-Oliva, Ana B; Cozza, Giorgio; Gourlay, Robert; Weidlich, Simone; Campbell, David G; Pinna, Lorenzo A; Sapkota, Gopal P

    2015-01-01

    The deubiquitylating enzyme OTUB1 is present in all tissues and targets many substrates, in both the cytosol and nucleus. We found that casein kinase 2 (CK2) phosphorylated OTUB1 at Ser(16) to promote its nuclear accumulation in cells. Pharmacological inhibition or genetic ablation of CK2 blocked the phosphorylation of OTUB1 at Ser(16), causing its nuclear exclusion in various cell types. Whereas we detected unphosphorylated OTUB1 mainly in the cytosol, we detected Ser(16)-phosphorylated OTUB1 only in the nucleus. In vitro, Ser(16)-phosphorylated OTUB1 and nonphosphorylated OTUB1 exhibited similar catalytic activity, bound K63-linked ubiquitin chains, and interacted with the E2 enzyme UBE2N. CK2-mediated phosphorylation and subsequent nuclear localization of OTUB1 promoted the formation of 53BP1 (p53-binding protein 1) DNA repair foci in the nucleus of osteosarcoma cells exposed to ionizing radiation. Our findings indicate that the activity of CK2 is necessary for the nuclear translocation and subsequent function of OTUB1 in DNA damage repair. PMID:25872870

  2. GSK-3 and CK2 Kinases Converge on Timeless to Regulate the Master Clock

    Directory of Open Access Journals (Sweden)

    Deniz Top

    2016-07-01

    Full Text Available The molecular clock relies on a delayed negative feedback loop of transcriptional regulation to generate oscillating gene expression. Although the principal components of the clock are present in all circadian neurons, different neuronal clusters have varying effects on rhythmic behavior, suggesting that the clocks they house are differently regulated. Combining biochemical and genetic techniques in Drosophila, we identify a phosphorylation program native to the master pacemaker neurons that regulates the timing of nuclear accumulation of the Period/Timeless repressor complex. GSK-3/SGG binds and phosphorylates Period-bound Timeless, triggering a CK2-mediated phosphorylation cascade. Mutations that block the hierarchical phosphorylation of Timeless in vitro also delay nuclear accumulation in both tissue culture and in vivo and predictably change rhythmic behavior. This two-kinase phosphorylation cascade is anatomically restricted to the eight master pacemaker neurons, distinguishing the regulatory mechanism of the molecular clock within these neurons from the other clocks that cooperate to govern behavioral rhythmicity.

  3. Standard deviations

    CERN Document Server

    Smith, Gary

    2015-01-01

    Did you know that having a messy room will make you racist? Or that human beings possess the ability to postpone death until after important ceremonial occasions? Or that people live three to five years longer if they have positive initials, like ACE? All of these ‘facts' have been argued with a straight face by researchers and backed up with reams of data and convincing statistics.As Nobel Prize-winning economist Ronald Coase once cynically observed, ‘If you torture data long enough, it will confess.' Lying with statistics is a time-honoured con. In Standard Deviations, ec

  4. A Process Deviation Analysis Framework

    OpenAIRE

    Depaire, Benoit; Swinnen, Jo; Jans, Mieke; Vanhoof, Koen

    2013-01-01

    Process deviation analysis is becoming increasingly important for companies. This paper presents a framework which structures the field of process deviation analysis and identies new research opportunities. Application of the framework starts from managerial questions which relate to specific deviation categories and methodological steps. Finally a general outline to detect high-level process deviations is formulated.

  5. Protein kinase CK2 is widely expressed in follicular, Burkitt and diffuse large B-cell lymphomas and propels malignant B-cell growth.

    Science.gov (United States)

    Pizzi, Marco; Piazza, Francesco; Agostinelli, Claudio; Fuligni, Fabio; Benvenuti, Pietro; Mandato, Elisa; Casellato, Alessandro; Rugge, Massimo; Semenzato, Gianpietro; Pileri, Stefano A

    2015-03-30

    Serine-threonine kinase CK2 is highly expressed and pivotal for survival and proliferation in multiple myeloma, chronic lymphocytic leukemia and mantle cell lymphoma. Here, we investigated the expression of α catalytic and β regulatory CK2 subunits by immunohistochemistry in 57 follicular (FL), 18 Burkitt (BL), 52 diffuse large B-cell (DLBCL) non-Hodgkin lymphomas (NHL) and in normal reactive follicles. In silico evaluation of available Gene Expression Profile (GEP) data sets from patients and Western blot (WB) analysis in NHL cell-lines were also performed. Moreover, the novel, clinical-grade, ATP-competitive CK2-inhibitor CX-4945 (Silmitasertib) was assayed on lymphoma cells. CK2 was detected in 98.4% of cases with a trend towards a stronger CK2α immunostain in BL compared to FL and DLBCL. No significant differences were observed between Germinal Center B (GCB) and non-GCB DLBCL types. GEP data and WB confirmed elevated CK2 mRNA and protein levels as well as active phosphorylation of specific targets in NHL cells. CX-4945 caused a dose-dependent growth-arresting effect on GCB, non-GCB DLBCL and BL cell-lines and it efficiently shut off phosphorylation of NF-κB RelA and CDC37 on CK2 target sites. Thus, CK2 is highly expressed and could represent a suitable therapeutic target in BL, FL and DLBCL NHL.

  6. The Protein Kinase CK2 Mediates Cross-Talk between Auxin- and Salicylic Acid-Signaling Pathways in the Regulation of PINOID Transcription.

    Science.gov (United States)

    Armengot, Laia; Caldarella, Eleonora; Marquès-Bueno, Maria Mar; Martínez, M Carmen

    2016-01-01

    The protein kinase CK2 is a ubiquitous and highly conserved enzyme, the activity of which is vital for eukaryotic cells. We recently demonstrated that CK2 modulates salicylic acid (SA) homeostasis in Arabidopsis thaliana, and that functional interplay between CK2 and SA sustains transcriptional expression of PIN-FORMED (PIN) genes. In this work, we show that CK2 also plays a key role in the transcriptional regulation of PINOID (PID), an AGC protein kinase that modulates the apical/basal localization of auxin-efflux transporters. We show that PID transcription is up-regulated by auxin and by SA and that CK2 is involved in both pathways. On the one hand, CK2 activity is required for proteosome-dependent degradation of AXR3, a member of the AUX/IAA family of auxin transcriptional repressors that must be degraded to activate auxin-responsive gene expression. On the other hand, the role of CK2 in SA homeostasis and, indirectly, in SA-driven PID transcription, was confirmed by using Arabidopsis NahG transgenic plants, which cannot accumulate SA. In conclusion, our results evidence a role for CK2 as a functional link in the negative cross-talk between auxin- and SA-signaling. PMID:27275924

  7. The Protein Kinase CK2 Mediates Cross-Talk between Auxin- and Salicylic Acid-Signaling Pathways in the Regulation of PINOID Transcription.

    Directory of Open Access Journals (Sweden)

    Laia Armengot

    Full Text Available The protein kinase CK2 is a ubiquitous and highly conserved enzyme, the activity of which is vital for eukaryotic cells. We recently demonstrated that CK2 modulates salicylic acid (SA homeostasis in Arabidopsis thaliana, and that functional interplay between CK2 and SA sustains transcriptional expression of PIN-FORMED (PIN genes. In this work, we show that CK2 also plays a key role in the transcriptional regulation of PINOID (PID, an AGC protein kinase that modulates the apical/basal localization of auxin-efflux transporters. We show that PID transcription is up-regulated by auxin and by SA and that CK2 is involved in both pathways. On the one hand, CK2 activity is required for proteosome-dependent degradation of AXR3, a member of the AUX/IAA family of auxin transcriptional repressors that must be degraded to activate auxin-responsive gene expression. On the other hand, the role of CK2 in SA homeostasis and, indirectly, in SA-driven PID transcription, was confirmed by using Arabidopsis NahG transgenic plants, which cannot accumulate SA. In conclusion, our results evidence a role for CK2 as a functional link in the negative cross-talk between auxin- and SA-signaling.

  8. Oncogenic potential of CK2α and its regulatory role in EGF-induced HDAC2 expression in human liver cancer.

    Science.gov (United States)

    Kim, Hyung S; Chang, Young G; Bae, Hyun J; Eun, Jung W; Shen, Qingyu; Park, Se J; Shin, Woo C; Lee, Eun K; Park, Soha; Ahn, Young M; Park, Won S; Lee, Jung Y; Nam, Suk W

    2014-02-01

    Histone deacetylase 2 (HDAC2) is aberrantly regulated and plays a pivotal role in the development of hepatocellular carcinoma (HCC) through regulation of cell-cycle components at the transcriptional level, but the underlying mechanism leading to oncogenic HDAC2 remains unknown. In this study, we show that expression of CK2α (casein kinase II α subunit) was up-regulated in a large cohort of human HCC patients, and that high expression of CK2α was significantly associated with poor prognosis of HCC patients in terms of five-year overall survival. It was also found that CK2α over-expression positively correlated with HDAC2 over-expression in a subset of HCCs. We observed that treatment with epidermal growth factor (EGF) elicited an increase in CK2α expression and Akt phosphorylation, causing induction of HDAC2 expression in liver cancer cells. It was also observed that ectopic expression of dominant-negative CK2α blocked EGF-induced HDAC2 expression, and that ectopic CK2α expression attenuated the suppressive effect of Akt knockdown on HDAC2 expression in liver cancer cells. Targeted disruption of CK2α influenced the cell cycle, causing a significant increase in the number of liver cancer cells remaining in G₂/M phase, and suppressed growth via repression of Cdc25c and cyclin B in liver cancer cells. Taken together, our findings suggest the oncogenic potential of CK2α in liver tumorigenesis. Furthermore, a regulatory mechanism for HDAC2 expression is proposed whereby EGF induces transcriptional activation of HDAC2 by CK2α/Akt activation in liver cancer cells. Therefore, this makes CK2α a promising target in cancer therapy.

  9. Selectivity analysis of protein kinase CK2 inhibitors DMAT, TBB and resorufin in cisplatin-induced stress responses

    DEFF Research Database (Denmark)

    Fritz, Gerhard; Issinger, Olaf-Georg; Olsen, Birgitte Brinkmann

    2009-01-01

    Targeting protein kinases as a therapeutic approach to treat various diseases, especially cancer is currently a fast growing business. Although many inhibitors are available, exhibiting remarkable potency, the major challenge is their selectivity. Here we show that the protein kinase CK2 inhibitors...... DMAT, TBB and resorufin differ in their selectivity against PI3K family members, since PI3K and DNA-PK are subject to inhibition by DMAT and TBB, however, not by resorufin. TBB and DMAT treatment together with cisplatin lead to an inhibition of cisplatin-induced stress signaling (as detected...... by phosphorylation of JNK and H2AX). In the case of resorufin no interference with the stress-signaling pathway is observed, supporting the notion that TBB and DMAT interfere with upstream molecules involved in genotoxic stress signaling. We have also tested the protein kinase CK2 inhibitors with respect to cell...

  10. Exploring the prominent performance of CX-4945 derivatives as protein kinase CK2 inhibitors by a combined computational study.

    Science.gov (United States)

    Wang, Xuwen; Pan, Peichen; Li, Youyong; Li, Dan; Hou, Tingjun

    2014-05-01

    Protein kinase CK2, also known as casein kinase II, is related to various cellular events and is a potential target for numerous cancers. In this study, we attempted to gain more insight into the inhibition process of CK2 by a series of CX-4945 derivatives through an integrated computational study that combines molecular docking, molecular dynamics (MD) simulations, and binding free energy calculations. Based on the binding poses predicted by molecular docking, the MD simulations were performed to explore the dynamic binding processes for ten selected inhibitors. Then, both Molecular Mechanics/Poisson Boltzmann Surface Area (MM/PBSA) and Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) techniques were employed to predict the binding affinities of the studied systems. The predicted binding energies of the selected inhibitors correlate well with their experimental activities (r(2) = 0.78). The van der Waals term is the most favorable component for the total energies. The free energy decomposition on a per residue basis reveals that the residue K68 is essential for the electrostatic interactions between CK2 and the studied inhibitors and numerous residues, including L45, V53, V66, F113, M163 and I174, play critical roles in forming van der Waals interactions with the inhibitors. Finally, a number of new derivatives were designed and the binding affinity and the predicted binding free energies of each designed molecule were obtained on the basis of molecular docking and MM/PBSA. It is expected that our research will benefit the future rational design of novel and potent inhibitors of CK2. PMID:24647611

  11. CK2 activity is required for the interaction of FGF14 with voltage-gated sodium channels and neuronal excitability.

    Science.gov (United States)

    Hsu, Wei-Chun J; Scala, Federico; Nenov, Miroslav N; Wildburger, Norelle C; Elferink, Hannah; Singh, Aditya K; Chesson, Charles B; Buzhdygan, Tetyana; Sohail, Maveen; Shavkunov, Alexander S; Panova, Neli I; Nilsson, Carol L; Rudra, Jai S; Lichti, Cheryl F; Laezza, Fernanda

    2016-06-01

    Recent data shows that fibroblast growth factor 14 (FGF14) binds to and controls the function of the voltage-gated sodium (Nav) channel with phenotypic outcomes on neuronal excitability. Mutations in the FGF14 gene in humans have been associated with brain disorders that are partially recapitulated in Fgf14(-/-) mice. Thus, signaling pathways that modulate the FGF14:Nav channel interaction may be important therapeutic targets. Bioluminescence-based screening of small molecule modulators of the FGF14:Nav1.6 complex identified 4,5,6,7 -: tetrabromobenzotriazole (TBB), a potent casein kinase 2 (CK2) inhibitor, as a strong suppressor of FGF14:Nav1.6 interaction. Inhibition of CK2 through TBB reduces the interaction of FGF14 with Nav1.6 and Nav1.2 channels. Mass spectrometry confirmed direct phosphorylation of FGF14 by CK2 at S228 and S230, and mutation to alanine at these sites modified FGF14 modulation of Nav1.6-mediated currents. In 1 d in vitro hippocampal neurons, TBB induced a reduction in FGF14 expression, a decrease in transient Na(+) current amplitude, and a hyperpolarizing shift in the voltage dependence of Nav channel steady-state inactivation. In mature neurons, TBB reduces the axodendritic polarity of FGF14. In cornu ammonis area 1 hippocampal slices from wild-type mice, TBB impairs neuronal excitability by increasing action potential threshold and lowering firing frequency. Importantly, these changes in excitability are recapitulated in Fgf14(-/-) mice, and deletion of Fgf14 occludes TBB-dependent phenotypes observed in wild-type mice. These results suggest that a CK2-FGF14 axis may regulate Nav channels and neuronal excitability.-Hsu, W.-C. J., Scala, F., Nenov, M. N., Wildburger, N. C., Elferink, H., Singh, A. K., Chesson, C. B., Buzhdygan, T., Sohail, M., Shavkunov, A. S., Panova, N. I., Nilsson, C. L., Rudra, J. S., Lichti, C. F., Laezza, F. CK2 activity is required for the interaction of FGF14 with voltage-gated sodium channels and neuronal

  12. Protein kinase CK2 interacts at the neuromuscular synapse with Rapsyn, Rac1, 14-3-3γ, and Dok-7 proteins and phosphorylates the latter two.

    Science.gov (United States)

    Herrmann, Dustin; Straubinger, Marion; Hashemolhosseini, Said

    2015-09-11

    Previously, we demonstrated that the protein kinase CK2 associates with and phosphorylates the receptor tyrosine kinase MuSK (muscle specific receptor tyrosine kinase) at the neuromuscular junction (NMJ), thereby preventing fragmentation of the NMJs (Cheusova, T., Khan, M. A., Schubert, S. W., Gavin, A. C., Buchou, T., Jacob, G., Sticht, H., Allende, J., Boldyreff, B., Brenner, H. R., and Hashemolhosseini, S. (2006) Genes Dev. 20, 1800-1816). Here, we asked whether CK2 interacts with other proteins involved in processes at the NMJ, which would be consistent with the previous observation that CK2 appears enriched at the NMJ. We identified the following proteins to interact with protein kinase CK2: (a) the α and β subunits of the nicotinic acetylcholine receptors with weak interaction, (b) dishevelled (Dsh), and (c) another four proteins, Rapsyn, Rac1, 14-3-3γ, and Dok-7, with strong interaction. CK2 phosphorylated 14-3-3γ at serine residue 235 and Dok-7 at several serine residues but does not phosphorylate Rapsyn or Rac1. Furthermore, phosphomimetic Dok-7 mutants aggregated nicotinic acetylcholine receptors in C2C12 myotubes with significantly higher frequency than wild type Dok-7. Additionally, we mapped the interacting epitopes of all four binding partners to CK2 and thereby gained insights into the potential role of the CK2/Rapsyn interaction.

  13. Synthesis and biological evaluation of novel substituted pyrrolo[1,2-a]quinoxaline derivatives as inhibitors of the human protein kinase CK2.

    Science.gov (United States)

    Guillon, Jean; Le Borgne, Marc; Rimbault, Charlotte; Moreau, Stéphane; Savrimoutou, Solène; Pinaud, Noël; Baratin, Sophie; Marchivie, Mathieu; Roche, Séverine; Bollacke, Andre; Pecci, Adali; Alvarez, Lautaro; Desplat, Vanessa; Jose, Joachim

    2013-07-01

    Herein we describe the synthesis and properties of substituted phenylaminopyrrolo[1,2-a]quinoxaline-carboxylic acid derivatives as a novel class of potent inhibitors of the human protein kinase CK2. A set of 15 compounds was designed and synthesized using convenient and straightforward synthesis protocols. The compounds were tested for inhibition of human protein kinase CK2, which is a potential drug target for many diseases including inflammatory disorders and cancer. New inhibitors with IC50 in the micro- and sub-micromolar range were identified. The most promising compound, the 4-[(3-chlorophenyl)amino]pyrrolo[1,2-a]quinoxaline-3-carboxylic acid 1c inhibited human CK2 with an IC50 of 49 nM. Our findings indicate that pyrrolo[1,2-a]quinoxalines are a promising starting scaffold for further development and optimization of human protein kinase CK2 inhibitors.

  14. Deviating From the Benchmarks

    DEFF Research Database (Denmark)

    Rocha, Vera; Van Praag, Mirjam; Carneiro, Anabela

    This paper studies three related questions: To what extent otherwise similar startups employ different quantities and qualities of human capital at the moment of entry? How persistent are initial human capital choices over time? And how does deviating from human capital benchmarks influence firm......, founders human capital, and the ownership structure of startups (solo entrepreneurs versus entrepreneurial teams). We then study the survival implications of exogenous deviations from these benchmarks, based on spline models for survival data. Our results indicate that (especially negative) deviations from...... the benchmark can be substantial, are persistent over time, and hinder the survival of firms. The implications may, however, vary according to the sector and the ownership structure at entry. Given the stickiness of initial choices, wrong human capital decisions at entry turn out to be a close to irreversible...

  15. The regulatory beta-subunit of protein kinase CK2 regulates cell-cycle progression at the onset of mitosis

    DEFF Research Database (Denmark)

    Yde, C W; Olsen, B B; Meek, D;

    2008-01-01

    Cell-cycle transition from the G(2) phase into mitosis is regulated by the cyclin-dependent protein kinase 1 (CDK1) in complex with cyclin B. CDK1 activity is controlled by both inhibitory phosphorylation, catalysed by the Myt1 and Wee1 kinases, and activating dephosphorylation, mediated by the CDC......25 dual-specificity phosphatase family members. In somatic cells, Wee1 is downregulated by phosphorylation and ubiquitin-mediated degradation to ensure rapid activation of CDK1 at the beginning of M phase. Here, we show that downregulation of the regulatory beta-subunit of protein kinase CK2 by RNA...

  16. Tenfibgen ligand nanoencapsulation delivers bi-functional anti-CK2 RNAi oligomer to key sites for prostate cancer targeting using human xenograft tumors in mice.

    Directory of Open Access Journals (Sweden)

    Janeen H Trembley

    Full Text Available Protected and specific delivery of nucleic acids to malignant cells remains a highly desirable approach for cancer therapy. Here we present data on the physical and chemical characteristics, mechanism of action, and pilot therapeutic efficacy of a tenfibgen (TBG-shell nanocapsule technology for tumor-directed delivery of single stranded DNA/RNA chimeric oligomers targeting CK2αα' to xenograft tumors in mice. The sub-50 nm size TBG nanocapsule (s50-TBG is a slightly negatively charged, uniform particle of 15 - 20 nm size which confers protection to the nucleic acid cargo. The DNA/RNA chimeric oligomer (RNAi-CK2 functions to decrease CK2αα' expression levels via both siRNA and antisense mechanisms. Systemic delivery of s50-TBG-RNAi-CK2 specifically targets malignant cells, including tumor cells in bone, and at low doses reduces size and CK2-related signals in orthotopic primary and metastatic xenograft prostate cancer tumors. In conclusion, the s50-TBG nanoencapsulation technology together with the chimeric oligomer targeting CK2αα' offer significant promise for systemic treatment of prostate malignancy.

  17. INHIBITORY EFFECT AND KINETIC ANALYSIS OF SODIUM QUERCETIN-7,4′-DISULPHATE ON RECOMBINANT HUMAN PROTEIN KINASE CK2 HOLOENZYME%槲皮素-7,4′-二硫酸酯钠对重组人CK2全酶的抑制作用及动力学分析

    Institute of Scientific and Technical Information of China (English)

    刘新光; 梁念慈; 刘文; 佘戟; 莫丽儿

    2002-01-01

    目的观察槲皮素-7,4′-二硫酸酯钠(sodium quercetin-7,4′-disulphate,SQDS)对重组人CK2全酶的直接作用及酶动力学机制.方法通过测定转移到CK2底物上的[γ-32P]ATP的32P放射活度检测不同条件下的重组人CK2全酶的活性.结果重组人CK2是一种Ca2+,cAMP和cGMP等第二信使非依赖性蛋白激酶,与天然CK2的性质一致.SQDS对重组人CK2全酶有很强的抑制作用,IC50为4.4 μmol·L-1,抑制作用大于已知CK2抑制剂DRB和A3.CK2的动力学研究表明:SQDS与ATP和酪蛋白分别呈竞争性和非竞争性抑制作用.结论 SQDS是有效的CK2抑制剂,对于开发更有效的CK2抑制剂及将SQDS用于临床提供了一定的实验依据.

  18. Systematic diversification of benzylidene heterocycles yields novel inhibitor scaffolds selective for Dyrk1A, Clk1 and CK2.

    Science.gov (United States)

    Mariano, Marica; Hartmann, Rolf W; Engel, Matthias

    2016-04-13

    The dual-specificity tyrosine-regulated kinase 1A (Dyrk1A) has gathered much interest as a pharmacological target in Alzheimer's disease (AD), but it plays a role in malignant brain tumors as well. As both diseases are multi-factorial, further protein kinases, such as Clk1 and CK2, were proposed to contribute to the pathogenesis. We designed a new class of α-benzylidene-γ-butyrolactone inhibitors that showed low micromolar potencies against Dyrk1A and/or Clk1 and a good selectivity profile among the most frequently reported off-target kinases. A systematic replacement of the heterocyclic moiety gave access to further inhibitor classes with interesting selectivity profiles, demonstrating that the benzylidene heterocycles provide a versatile tool box for developing inhibitors of the CMGC kinase family members Dyr1A/1B, Clk1/4 and CK2. Efficacy for the inhibition of Dyrk1A-mediated tau phosphorylation was demonstrated in a cell-based assay. Multi-targeted but not non-specific kinase inhibitors were also obtained, that co-inhibited the lipid kinases PI3Kα/γ. These compounds were shown to inhibit the proliferation of U87MG cells in the low micromolar range. Based on the molecular properties, the inhibitors described here hold promise for CNS activity. PMID:26896709

  19. Geometry drives the "deviated-bending" of the bi-tubular structures of the 9 + 2 axoneme in the flagellum.

    Science.gov (United States)

    Cibert, Christian; Heck, Jean-Vivien

    2004-11-01

    The axoneme "9 + 2" is basically a system constituted of a cylinder of 9 microtubule doublets surrounding a central pair of microtubules. These bi-tubular structures are considered as the support system of the active molecular complexes that generate and regulate the axonemal movement. Schoutens has calculated their moments of inertia [Schoutens, 1994: Journal of Theoretical Biology 171:163-177]. The results obtained allowed us to assume that these bi-tubular systems are endowed with dynamic properties that could be involved in the regulation of the axonemal machinery. For the first time, using the finite elements methods and the resistance of material principles, we have now calculated that the curvature of the axoneme induces the deviated-bending of the bi-tubular structures of the axoneme, because of their geometry only; they behave as beams in a framework. This approach is similar to the one used to measure the deflection of a single microtubule [Kasas et al., 2004: Chem Phys Chem 5:252-257]. These behaviors induce internal movement or constraints of either couples or triplets of doublets within the axonemal cylinder that could be directly involved in a constrained or a spontaneous "convergence/divergence" equilibrium of the cylindrical generatrices that they draw along the axonemal cylinder, which could apparently regulate the activity of the axonemal motors (the dynein arms). These results are discussed here, taking into consideration the dynamic propagation of the wave train along the flagellar axoneme, and the regulated balance between the activities of the two opposite sides of the axoneme during the beat. This study raises a few questions about the architecture-activity duo of the axonemal doublets. PMID:15368611

  20. Characterization of protein kinase CK2 protein subunits and p53 in F9 teratocarcinoma cells in the absence and presence of cisplatin

    DEFF Research Database (Denmark)

    Küpper, M; Köster, M; Schmidt-Spaniol, I;

    1994-01-01

    cell extracts treated with and without cisplatin were analyzed by ion exchange chromatography for protein kinase CK2 alpha/beta subunits and p53 distribution. The following results were obtained: (a) in crude extracts of cisplatin-treated cells, CK2 activity was sometimes reduced by as much as 50%; (b......The effect of cis-diaminedichloroplatinum(II) (cisplatin) on the induction of p53 and protein kinase CK2 activity was studied in the mouse teratocarcinoma cell line F9. Treatment of the cells with the chemotherapeutic agent cisplatin led to the detection of p53 3 h after addition of the drug. F9...... by immunostaining, we have detected, at a concentration of approximately 200 mM NaCl, a protein of approximately 46 kDa which reacted with the CK2 alpha-specific antibody. This fraction was devoid of CK2 activity; and (d) cisplatin-treated cells exhibited p53 protein, which was mostly eluting ahead but also partly...

  1. Casein Kinase 2 (CK2)-mediated Phosphorylation of Hsp90β as a Novel Mechanism of Rifampin-induced MDR1 Expression.

    Science.gov (United States)

    Kim, So Won; Hasanuzzaman, Md; Cho, Munju; Heo, Ye Rang; Ryu, Min-Jung; Ha, Na-Young; Park, Hyun June; Park, Hyung-Yeon; Shin, Jae-Gook

    2015-07-01

    The P-glycoprotein (P-gp) encoded by the MDR1 gene is a drug-exporting transporter located in the cellular membrane. P-gp induction is regarded as one of the main mechanisms underlying drug-induced resistance. Although there is great interest in the regulation of P-gp expression, little is known about its underlying regulatory mechanisms. In this study, we demonstrate that casein kinase 2 (CK2)-mediated phosphorylation of heat shock protein 90β (Hsp90β) and subsequent stabilization of PXR is a key mechanism in the regulation of MDR1 expression. Furthermore, we show that CK2 is directly activated by rifampin. Upon exposure to rifampin, CK2 catalyzes the phosphorylation of Hsp90β at the Ser-225/254 residues. Phosphorylated Hsp90β then interacts with PXR, causing a subsequent increase in its stability, leading to the induction of P-gp expression. In addition, inhibition of CK2 and Hsp90β enhances the down-regulation of PXR and P-gp expression. The results of this study may facilitate the development of new strategies to prevent multidrug resistance and provide a plausible mechanism for acquired drug resistance by CK2-mediated regulation of P-gp expression. PMID:25995454

  2. Integrated transcriptomic and proteomic analysis identifies protein kinase CK2 as a key signaling node in an inflammatory cytokine network in ovarian cancer cells

    Science.gov (United States)

    Kulbe, Hagen; Iorio, Francesco; Chakravarty, Probir; Milagre, Carla S.; Moore, Robert; Thompson, Richard G.; Everitt, Gemma; Canosa, Monica; Montoya, Alexander; Drygin, Denis; Braicu, Ioana; Sehouli, Jalid; Saez-Rodriguez, Julio; Cutillas, Pedro R.; Balkwill, Frances R.

    2016-01-01

    We previously showed how key pathways in cancer-related inflammation and Notch signaling are part of an autocrine malignant cell network in ovarian cancer. This network, which we named the “TNF network”, has paracrine actions within the tumor microenvironment, influencing angiogenesis and the immune cell infiltrate. The aim of this study was to identify critical regulators in the signaling pathways of the TNF network in ovarian cancer cells that might be therapeutic targets. To achieve our aim, we used a systems biology approach, combining data from phospho-proteomic mass spectrometry and gene expression array analysis. Among the potential therapeutic kinase targets identified was the protein kinase Casein kinase II (CK2). Knockdown of CK2 expression in malignant cells by siRNA or treatment with the specific CK2 inhibitor CX-4945 significantly decreased Notch signaling and reduced constitutive cytokine release in ovarian cancer cell lines that expressed the TNF network as well as malignant cells isolated from high grade serous ovarian cancer ascites. The expression of the same cytokines was also inhibited after treatment with CX-4945 in a 3D organotypic model. CK2 inhibition was associated with concomitant inhibition of proliferative activity, reduced angiogenesis and experimental peritoneal ovarian tumor growth. In conclusion, we have identified kinases, particularly CK2, associated with the TNF network that may play a central role in sustaining the cytokine network and/or mediating its effects in ovarian cancer. PMID:26871292

  3. Rational Design of Coumarin Derivatives as CK2 Inhibitors by Improving the Interaction with the Hinge Region.

    Science.gov (United States)

    Zhang, Na; Chen, Wen-Juan; Zhou, Yue; Zhao, Hongtao; Zhong, Ru-Gang

    2016-01-01

    Design of novel coumarin derivatives as CK2 inhibitors were attempted by targeting the interaction with the hinge region. A set of substituents capable of forming a hydrogen bond or halogen bond with the hinge region were screened in silico, and trifluoromethyl emerges as a promising motif by forming favorable electrostatic interaction and a presumable halogen bond with the hinge region. As proof of concept, three trifluoromethyl derivatives of coumarin were synthesized and tested in vitro. The results indicated that replacement of methyl by trifluoromethyl leads to a modest 5-fold improvement in potency, with the most active compound being 0.4 µM. The newly designed compounds were further screened on one lung cancer cell line A549, showing low micromolar anti-proliferative activity.

  4. Inhibitory effect and its kinetic analysis of tyrphostin AG1478 on recombinant human protein kinase CK2 holoenzyme%Tyrphostin AG1478对重组人蛋白激酶CK2全酶的抑制作用及其动力学分析

    Institute of Scientific and Technical Information of China (English)

    刘新光; 梁念慈

    2002-01-01

    目的:观察Tyrphostin AG1478[4-(3-氯苯胺基)-6,7-二甲氧喹唑啉]对重组人蛋白激酶CK2全酶的直接作用及其酶动力学机制.方法:在体外等摩尔数混合重组蛋白激酶CK2 α和β亚基构成CK2全酶,在不同条件下测定CK2的活性.CK2活性通过测定转移到CK2底物上的[γ-32P]ATP或[γ-32P]GTP的32P放射活度来检测.结果:重组人CK2是一种Ca2+、[KG*2]cAMP和cGMP等第二信使非依赖性蛋白激酶,与天然CK2的性质一致.AG1478对重组人CK2全酶具有很强的抑制作用,IC50为25.9 μmol/L,抑制作用接近于已知的CK2抑制剂N-(2-氨乙基)-5-氯萘-1-硫胺(A3),稍小于5,6-二氯-1-β-呋喃糖苯并咪唑(DRB).AG1478对重组人CK2的动力学研究表明:它与GTP和酪蛋白均呈竞争性抑制作用,是一种双底物抑制剂.结论:AG1478不仅是高效特异的表皮生长因子受体酪氨酸蛋白激酶的抑制剂,而且也是一种新型有效的蛋白激酶CK2抑制剂.重组人蛋白激酶CK2可作为一种较为简便的筛选和开发有效CK2抑制剂的分子靶点.%AIM: To study the direct effect of tyrphostin AG1478[4-( 3-chloroanilino )-6, 7-dimethoxyquinazoline ] on re-combinant human protein kinase CK2 holoenzyme and itskinetics. METHODS: Recombinant human proteinkinase CK2 α and β subunits were mixed at equal molar ratio and CK2 holoenzyme were reconstituted. The CK2activity was assayed by detecting incorporation of [γ-32P]ATP or [γ-32P]GTP into substrates in various conditions. RESULTS: These results demonstrated that the recombinant human CK2 was a second messengers (Ca2+ , cAMP, and cGMP)-independent protein kinase,the characterization and function of the reconstituted holoenzyme were consistent with those of native CK2. AG1478 strongly inhibited the holoenzyme activity of recombinant human protein kinase CK2 with IC50 of 25.9μmol/L, the inhibition is very close to that of N-(2-aminoethyl )-5-chloronaphthalene-l-sulfonamide ( A3 ),but less potent than that of 5

  5. Phosphorylation of murine double minute clone 2 (MDM2) protein at serine-267 by protein kinase CK2 in vitro and in cultured cells

    DEFF Research Database (Denmark)

    Hjerrild, M; Milne, D; Dumaz, N;

    2001-01-01

    activation, promote disruption of the p53-MDM2 complex, as in the case of ionizing radiation, or block MDM2 synthesis and thereby reduce cellular MDM2 levels, as in the case of UV radiation. It is therefore likely that MDM2, which is known to be modified by ubiquitination, SUMOylation and multi...... the central acidic domain of MDM2. Fractionation of cellular extracts revealed the presence of a single Ser(267) protein kinase which co-purified with CK2 on ion-exchange chromatography and, like CK2, was subject to inhibition by micromolar concentrations of the CK2-specific inhibitor 5......,6-dichlororibofuranosylbenzimidazole. Radiolabelling of cells expressing tagged recombinant wild-type MDM2 or a S267A (Ser(267)-->Ala) mutant, followed by phosphopeptide analysis, confirmed that Ser(267) is a cellular target for phosphorylation. Ser(267) mutants are still able to direct the degradation of p53, but in a slightly...

  6. A specific inhibitor of protein kinase CK2 delays gamma-H2Ax foci removal and reduces clonogenic survival of irradiated mammalian cells

    Directory of Open Access Journals (Sweden)

    Huber Peter E

    2011-02-01

    Full Text Available Abstract Background The protein kinase CK2 sustains multiple pro-survival functions in cellular DNA damage response and its level is tightly regulated in normal cells but elevated in cancers. Because CK2 is thus considered as potential therapeutic target, DNA double-strand break (DSB formation and rejoining, apoptosis induction and clonogenic survival was assessed in irradiated mammalian cells upon chemical inhibition of CK2. Methods MRC5 human fibroblasts and WIDR human colon carcinoma cells were incubated with highly specific CK2 inhibitor 4,5,6,7-tetrabromobenzotriazole (TBB, or mock-treated, 2 hours prior to irradiation. DSB was measured by pulsed-field electrophoresis (PFGE as well as gamma-H2AX foci formation and removal. Apoptosis induction was tested by DAPI staining and sub-G1 flow cytometry, survival was quantified by clonogenic assay. Results TBB treatment did not affect initial DNA fragmention (PFGE; up to 80 Gy or foci formation (1 Gy. While DNA fragment rejoining (PFGE was not inhibited by the drug, TBB clearly delayed gamma-H2AX foci disappearence during postirradiation incubation. No apoptosis induction could be detected for up to 38 hours for both cell lines and exposure conditions (monotherapies or combination, but TBB treatment at this moderately toxic concentration of 20 μM (about 40% survival enhanced radiation-induced cell killing in the clonogenic assay. Conclusions The data imply a role of CK2 in gamma-H2AX dephosporylation, most likely through its known ability to stimulate PP2A phosphatase, rather than DSB rejoining. The slight but definite clonogenic radiosensitization by TBB does apparently not result from interference with an apoptosis suppression function of CK2 in these cells but could reflect inhibitor-induced uncoupling of DNA damage response decay from break ligation.

  7. Phosphorylation of cystic fibrosis transmembrane conductance regulator (CFTR) serine-511 by the combined action of tyrosine kinases and CK2: the implication of tyrosine-512 and phenylalanine-508.

    Science.gov (United States)

    Cesaro, Luca; Marin, Oriano; Venerando, Andrea; Donella-Deana, Arianna; Pinna, Lorenzo A

    2013-12-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) harbors, close to Phe-508, whose deletion is the commonest cause of cystic fibrosis, a conserved potential CK2 phospho-acceptor site (Ser511), which however is not susceptible to phosphorylation by CK2. To shed light on this apparent paradox, a series of systematically substituted peptides encompassing Ser511 were assayed for their ability to be phosphorylated. The main outcomes of our study are the following: (a) Tyr512 plays a prominent role as a negative determinant as its replacement by Ala restores Ser511 phosphorylation by CK2; (b) an even more pronounced phosphorylation of Ser511 is promoted if Tyr512 is replaced by phospho-tyrosine instead of alanine; (c) Tyr512 and, to a lesser extent, Tyr515 are readily phosphorylated by Lyn, a protein tyrosine kinase of the Src family, in a manner which is enhanced by the concomitant Phe508 deletion. Collectively taken, our data, in conjunction with the notion that Tyr515 is phosphorylated in vivo, disclose the possibility that CFTR Ser511 can be phosphorylated by the combined action of tyrosine kinases and CK2 and disclose a new mechanism of hierarchical phosphorylation where the role of the priming kinase is that of removing negative determinant(s).

  8. 甜菜BvCK2基因全长cDNA的克隆和序列分析%Molecular Cloning and Sequence Analysis of the Full-length cDNA of Gene BvCK2 from Beta vulgaris

    Institute of Scientific and Technical Information of China (English)

    鲁振强; 潘彦遥; 陈连江; 朱延明; 李春宇

    2009-01-01

    甜菜M14品系在细胞胚胎学和遗传学特征上具有鲜明的无融合生殖现象.为了寻找在这一特殊的生殖过程中的相关基因及其调控作用,实验通过同源克隆及cDNA末端快速扩增(RACE)的方法,首次从甜菜M14品系中克隆了与生殖相关的基因ByCK2(Beta vulgaris casein kinase 2)的全长cDNA序列,长度为1 501 bp,开放阅读框为1002 bp,编码333个氨基酸.根据氨基酸序列计算蛋白分子量为39.28kDa,pI=8.16.同源比对表明,ByCK2与烟草CK2(GenBank No.A1437635)的相似度为64.22%,与百合CK2(GenBank No.AF517838)的相似度为65.18%.通过细胞内定位分析,BvCK2所编码的蛋白主要存在于细胞核中.

  9. X-radiographic study of rare-earth compounds with special regardment of modulated structures. The response of the crystal structure to stoichiometry deviations

    International Nuclear Information System (INIS)

    Even shortly after World War II, as large amounts of ultrapure rare earths (RE) became available for scientific research, a large reservoir of peculiar phenomena was uncovered. These had not been investigated before or were completely unknown. Examples of these phenomena are, magnetic ordering, the KONDO effect, quantum critical points, heavy fermion behaviour, as well as superconductivity. A strong influence of small variations of the chemical composition on the physical properties had been observed. The main focus of the present thesis is the detailed elucidation of the crystal structure of fundamental representatives of this class of substances, as well as the influence of dedicated variations of the chemical composition on their structure and properties. In particular, the characterisation of modulated crystals is an important facet. A large spectrum of physical methods, especially X-ray diffraction, is employed in the investigations. Results on oriented intergrowth in the Y-Ni-B-C system, incommensurately ordered vacancies in the Ce-Si system, incorporation of stacking faults as well as commensurately ordered transition metal atoms (TM) in the RE-TM-Si system and site specific occupancy in the Y-Mn-Fe-O system are presented. Their elucidation is reported for the first time. It is shown which consequences the structural peculiarities will have on the physical properties. An objective of this thesis is to give an overview of the possible ''answers'' that can be obtained with regard to the influence of the crystal structure of rare earth transition metal compounds on deviations of the chemical composition. (orig.)

  10. Protein kinase CK2 inhibition down modulates the NF-κB and STAT3 survival pathways, enhances the cellular proteotoxic stress and synergistically boosts the cytotoxic effect of bortezomib on multiple myeloma and mantle cell lymphoma cells.

    Directory of Open Access Journals (Sweden)

    Sabrina Manni

    Full Text Available CK2 is a pivotal pro-survival protein kinase in multiple myeloma that may likely impinge on bortezomib-regulated cellular pathways. In the present study, we investigated CK2 expression in multiple myeloma and mantle cell lymphoma, two bortezomib-responsive B cell tumors, as well as its involvement in bortezomib-induced cytotoxicity and signaling cascades potentially mediating bortezomib resistance. In both tumors, CK2 expression correlated with that of its activated targets NF-κB and STAT3 transcription factors. Bortezomib-induced proliferation arrest and apoptosis were significantly amplified by the simultaneous inhibition of CK2 with two inhibitors (CX-4945 and K27 in multiple myeloma and mantle cell lymphoma cell lines, in a model of multiple myeloma bone marrow microenvironment and in cells isolated from patients. CK2 inhibition empowered bortezomib-triggered mitochondrial-dependent cell death. Phosphorylation of NF-κB p65 on Ser529 (a CK2 target site and rise of the levels of the endoplasmic reticulum stress kinase/endoribonuclease Ire1α were markedly reduced upon CK2 inhibition, as were STAT3 phospho Ser727 levels. On the contrary, CK2 inhibition increased phospho Ser51 eIF2α levels and enhanced the bortezomib-dependent accumulation of poly-ubiquitylated proteins and of the proteotoxic stress-associated chaperone Hsp70. Our data suggest that CK2 over expression in multiple myeloma and mantle cell lymphoma cells might sustain survival signaling cascades and can antagonize bortezomib-induced apoptosis at different levels. CK2 inhibitors could be useful in bortezomib-based combination therapies.

  11. Enhancing the Apoptotic Potential of Insulin-Like Growth Factor-Binding Protein-3 in Prostate Cancer by Modulation of CK2 Phosphorylation

    OpenAIRE

    Cobb, Laura J.; Mehta, Hemal; Cohen, Pinchas

    2009-01-01

    IGF-binding protein 3 (IGFBP-3) promotes apoptosis by both IGF-dependent and -independent mechanisms. We have previously reported that phosphorylation of IGFBP-3 (S156) by DNA-dependent protein kinase enhances its nuclear accumulation and is essential for its ability to interact with retinoid X receptor-α and induce apoptosis in cultured prostate cancer cells. Using specific chemical inhibitors and small interfering RNA, we demonstrate that preventing casein kinase 2 (CK2) activation enhanced...

  12. Mitotic Activation of a Novel Histone Deacetylase 3-Linker Histone H1.3 Protein Complex by Protein Kinase CK2.

    Science.gov (United States)

    Patil, Hemangi; Wilks, Carrie; Gonzalez, Rhiannon W; Dhanireddy, Sudheer; Conrad-Webb, Heather; Bergel, Michael

    2016-02-12

    Histone deacetylase 3 (HDAC3) and linker histone H1 are involved in both chromatin compaction and the regulation of mitotic progression. However, the mechanisms by which HDAC3 and H1 regulate mitosis and the factors controlling HDAC3 and H1 activity during mitosis are unclear. Furthermore, as of now, no association between class I, II, or IV (non-sirtuin) HDACs and linker histones has been reported. Here we describe a novel HDAC3-H1.3 complex containing silencing mediator of retinoic acid and thyroid hormone receptor (SMRT) and nuclear receptor corepressor 1 (N-CoR) that accumulated in synchronized HeLa cells in late G2 phase and mitosis. Nonetheless, the deacetylation activity by HDAC3 in the complex was evident only in mitotic complexes. HDAC3 associated with H1.3 was highly phosphorylated on Ser-424 only during mitosis. Isolation of inactive HDAC3-H1.3 complexes from late G2 phase cells, and phosphorylation of HDAC3 in the complexes at serine 424 by protein kinase CK2 (also known as casein kinase 2) activated the HDAC3 in vitro. In vivo, CK2α and CK2α' double knockdown cells demonstrated a significant decrease in HDAC3 Ser-424 phosphorylation during mitosis. HDAC3 and H1.3 co-localized in between the chromosomes, with polar microtubules and spindle poles during metaphase through telophase, and partially co-localized with chromatin during prophase and interphase. H1 has been reported previously to associate with microtubules and, therefore, could potentially function in targeting HDAC3 to the microtubules. We suggest that phosphorylation of HDAC3 in the complex by CK2 during mitosis activates the complex for a dual role: compaction of the mitotic chromatin and regulation of polar microtubules dynamic instability.

  13. Human herpesvirus 6B induces phosphorylation of p53 in its regulatory domain by a CK2- and p38-independent pathway

    DEFF Research Database (Denmark)

    Øster, Bodil; Bundgaard, Bettina; Hupp, TR;

    2008-01-01

    Here, we demonstrate that human herpesvirus 6B (HHV-6B) infection upregulates the tumour suppressor p53 and induces phosphorylation of p53 at Ser392. Interestingly, phosphorylation at the equivalent site has previously been shown to correlate with p53 tumour suppression in murine models. Although...... or Cdk9, eluted in column fractions that phosphorylated p53 at Ser392. However, treatment of cells with neither the CK2 and Cdk9 inhibitor 5,6-dichloro-1-beta-d-ribofuranosylbenzimidazole (DRB) nor p38 kinase inhibitors reduced HHV-6B-induced Ser392 phosphorylation significantly. Knockdown of the CK2......beta subunit or p38alpha by small interfering RNA had no effect on HHV-6B-induced phosphorylation of p53 at Ser392. Thus, HHV-6B induces p53 Ser392 phosphorylation by an atypical pathway independent of CK2 and p38 kinases, whereas mitogen-activated protein (MAP) kinase signalling pathways are involved...

  14. LARGE DEVIATIONS AND MODERATE DEVIATIONS FOR SUMS OF NEGATIVELY DEPENDENT RANDOM VARIABLES

    Institute of Scientific and Technical Information of China (English)

    Liu Li; Wan Chenggao; Feng Yanqin

    2011-01-01

    In this article, we obtain the large deviations and moderate deviations for negatively dependent (ND) and non-identically distributed random variables defined on (-∞, +∞). The results show that for some non-identical random variables, precise large deviations and moderate deviations remain insensitive to negative dependence structure.

  15. Ice-binding site of snow mold fungus antifreeze protein deviates from structural regularity and high conservation.

    Science.gov (United States)

    Kondo, Hidemasa; Hanada, Yuichi; Sugimoto, Hiroshi; Hoshino, Tamotsu; Garnham, Christopher P; Davies, Peter L; Tsuda, Sakae

    2012-06-12

    Antifreeze proteins (AFPs) are found in organisms ranging from fish to bacteria, where they serve different functions to facilitate survival of their host. AFPs that protect freeze-intolerant fish and insects from internal ice growth bind to ice using a regular array of well-conserved residues/motifs. Less is known about the role of AFPs in freeze-tolerant species, which might be to beneficially alter the structure of ice in or around the host. Here we report the 0.95-Å high-resolution crystal structure of a 223-residue secreted AFP from the snow mold fungus Typhula ishikariensis. Its main structural element is an irregular β-helix with six loops of 18 or more residues that lies alongside an α-helix. β-Helices have independently evolved as AFPs on several occasions and seem ideally structured to bind to several planes of ice, including the basal plane. A novelty of the β-helical fold is the nonsequential arrangement of loops that places the N- and C termini inside the solenoid of β-helical coils. The ice-binding site (IBS), which could not be predicted from sequence or structure, was located by site-directed mutagenesis to the flattest surface of the protein. It is remarkable for its lack of regularity and its poor conservation in homologs from psychrophilic diatoms and bacteria and other fungi.

  16. Generation of deviation parameters for amino acid singlets, doublets and triplets from three-dimensional structures of proteins and its implications for secondary structure prediction from amino acid sequences

    Indian Academy of Sciences (India)

    S A Mugilan; K Veluraja

    2000-03-01

    We present a new method, secondary structure prediction by deviation parameter (SSPDP) for predicting the secondary structure of proteins from amino acid sequence. Deviation parameters (DP) for amino acid singlets, doublets and triplets were computed with respect to secondary structural elements of proteins based on the dictionary of secondary structure prediction (DSSP)-generated secondary structure for 408 selected non-homologous proteins. To the amino acid triplets which are not found in the selected dataset, a DP value of zero is assigned with respect to the secondary structural elements of proteins. The total number of parameters generated is 15,432, in the possible parameters of 25,260. Deviation parameter is complete with respect to amino acid singlets, doublets, and partially complete with respect to amino acid triplets. These generated parameters were used to predict secondary structural elements from amino acid sequence. The secondary structure predicted by our method (SSPDP) was compared with that of single sequence (NNPREDICT) and multiple sequence (PHD) methods. The average value of the percentage of prediction accuracy for α-helix by SSPDP, NNPREDICT and PHD methods was found to be 57%, 44% and 69% respectively for the proteins in the selected dataset. For -strand the prediction accuracy is found to be 69%, 21% and 53% respectively by SSPDP, NNPREDICT and PHD methods. This clearly indicates that the secondary structure prediction by our method is as good as PHD method but much better than NNPREDICT method.

  17. pVHL acts as an Adapter to Promote the Inhibitory Phosphorylation of the NF-κB Agonist Card9 by CK2

    OpenAIRE

    Yang, Haifeng; Minamishima, Yoji Andrew; Yan, Qin; Schlisio, Susanne; Benjamin L Ebert; Zhang, Xiaoping; Zhang, Liang; Kim, William Y.; Olumi, Aria F.; William G Kaelin

    2007-01-01

    The VHL tumor suppressor protein (pVHL) is part of an E3 ubiquitin ligase that targets HIF for destruction. pVHL-defective renal carcinoma cells exhibit increased NF-κB activity but the mechanism is unclear. NF-κB affects tumorigenesis and therapeutic resistance in some settings. We found that pVHL associates with the NF-κB agonist Card9 but does not target Card9 for destruction. Instead, pVHL serves as an adaptor that promotes the phosphorylation of the Card9 C-terminus by CK2. Elimination o...

  18. Many-electron effects in photoelectron spectroscopy. [Deviations from Koopman's one-electron model, satellite structure, configuration interaction, mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Martin, R.L.

    1976-06-01

    The deviations from Koopmans' one-electron model of photoionization which lead to satellite structure in the photoelectron spectrum are examined within the formalism of configuration interaction (CI). The mechanisms which contribute to satellite intensity may be classified as continuum state configuration interaction, final ionic state configuration interaction, and initial state configuration interaction. The discussion centers around the last two mechanisms, these being the prime contributors to the satellite intensity well above threshold. Specific examples of theoretical ''spectra'' are presented for the F(1s) region of HF and the 1s region of neon. The agreement between theory and experiment is found to be excellent. In these two instances, initial state configuration interaction contributions increase the satellite intensity and are of nearly equal importance to the final ionic state mixing.

  19. Pharmacologic inhibition of the CK2-mediated phosphorylation of B23/NPM in cancer cells selectively modulates genes related to protein synthesis, energetic metabolism, and ribosomal biogenesis.

    Science.gov (United States)

    Perera, Yasser; Pedroso, Seidy; Borras-Hidalgo, Orlando; Vázquez, Dania M; Miranda, Jamilet; Villareal, Adelaida; Falcón, Viviana; Cruz, Luis D; Farinas, Hernán G; Perea, Silvio E

    2015-06-01

    B23/NPM is a multifunctional nucleolar protein frequently overexpressed, mutated, or rearranged in neoplastic tissues. B23/NPM is involved in diverse biological processes and is mainly regulated by heteroligomer association and posttranslational modification, phosphorylation being a major posttranslational event. While the role of B23/NPM in supporting and/or driving malignant transformation is widely recognized, the particular relevance of its CK2-mediated phosphorylation remains unsolved. Interestingly, the pharmacologic inhibition of such phosphorylation event by CIGB-300, a clinical-grade peptide drug, was previously associated to apoptosis induction in tumor cell lines. In this work, we sought to identify the biological processes modulated by CIGB-300 in a lung cancer cell line using subtractive suppression hybridization and subsequent functional annotation clustering. Our results indicate that CIGB-300 modulates a subset of genes involved in protein synthesis (ES = 8.4, p NPM in cancer cells, revealing at the same time the potentialities of its pharmacological manipulation for cancer therapy. Finally, this work also suggests several candidate gene biomarkers to be evaluated during the clinical development of the anti-CK2 peptide CIGB-300.

  20. Sexual "Variation" without "Deviation"

    Science.gov (United States)

    Turnage, John R.; Logan, Daniel L.

    1975-01-01

    Non-heterosexual behavior continues to be labeled "deviant" or "maladaptive" by those propounding a learning formulation of sexual behavior. It is suggested that the term "variation" replace, in part, the term "deviation" when describing non-heterosexual behavior, especially homosexuality. (Author)

  1. Inhibition of protein kinase CK2 reduces CYP24A1 expression and enhances 1,25-dihydroxyvitamin D3 anti-tumor activity in human prostate cancer cells

    Science.gov (United States)

    Luo, Wei; Yu, Wei-Dong; Ma, Yingyu; Chernov, Mikhail; Trump, Donald L.; Johnson, Candace S.

    2013-01-01

    Vitamin D has broad range of physiological functions and anti-tumor effects. 24-hydroxylase, encoded by the CYP24A1 gene, is the key enzyme for degrading many forms of vitamin D including the most active form, 1,25D3. Inhibition of CYP24A1 enhances 1,25D3 anti-tumor activity. In order to isolate regulators of CYP24A1 expression in prostate cancer cells, we established a stable prostate cancer cell line PC3 with CYP24A1 promoter driving luciferase expression to screen a small molecular library for compounds that inhibit CYP24A1 promoter activity. From this screening, we identified, 4,5,6,7-tetrabromobenzimidazole (TBBz), a protein kinase CK2 selective inhibitor as a disruptor of CYP24A1 promoter activity. We show that TBBz inhibits CYP24A1 promoter activity induced by 1,25D3 in prostate cancer cells. In addition, TBBz downregulates endogenous CYP24A1 mRNA level in TBBz treated PC3 cells. Furthermore, siRNA-mediated CK2 knockdown reduces 1,25D3 induced CYP24A1 mRNA expression in PC3 cells. These results suggest that CK2 contributes to 1,25D3 mediated target gene expression. Lastly, inhibition of CK2 by TBBz or CK2 siRNA significantly enhanced 1,25D3 mediated anti-proliferative effect in vitro and in vivo in a xenograft model. In summary, our findings reveal that protein kinase CK2 is involved in the regulation of CYP24A1 expression by 1,25D3 and CK2 inhibitor enhances 1,25D3 mediated anti-tumor effect. PMID:23358686

  2. Inhibition of nucleoside diphosphate kinase activity by in vitro phosphorylation by protein kinase CK2. Differential phosphorylation of NDP kinases in HeLa cells in culture

    DEFF Research Database (Denmark)

    Biondi, R M; Engel, M; Sauane, M;

    1996-01-01

    that in vitro protein kinase CK2 catalyzed phosphorylation of human NDPK A inhibits its enzymatic activity by inhibiting the first step of its ping-pong mechanism of catalysis: its autophosphorylation. Upon in vivo 32P labeling of HeLa cells, we observed that both human NDPKs, A and B, were autophosphorylated......Although a number of nucleoside diphosphate kinases (NDPKs) have been reported to act as inhibitors of metastasis or as a transcription factor in mammals, it is not known whether these functions are linked to their enzymatic activity or how this protein is regulated. In this report, we show...... on histidine residues, however, only the B isoform appeared to be serine phosphorylated....

  3. LIMSUP DEVIATIONS ON TREES

    Institute of Scientific and Technical Information of China (English)

    Fan Aihua

    2004-01-01

    The vertices of an infinite locally finite tree T are labelled by a collection of i.i.d. real random variables {Xσ}σ∈T which defines a tree indexed walk Sσ = ∑θ<r≤σXr. We introduce and study the oscillations of the walk:Exact Hausdorff dimension of the set of such ξ 's is calculated. An application is given to study the local variation of Brownian motion. A general limsup deviation problem on trees is also studied.

  4. Effect of an inhibitor of protein kinase CK2 on radiosensitivity of human lung cancer cells%蛋白激酶CK2抑制剂对肺癌细胞系放射敏感性的影响

    Institute of Scientific and Technical Information of China (English)

    李倩雯; 刘莉; 伍钢; 孟睿; 李珂; 张盛; 杨天洋; 周瑜; 李振宇; 周方正; 马虹; 董晓荣

    2015-01-01

    Objective To evaluate the effect of an inhibitor of protein kinase CK2 on the radiosensitivity of human lung cancer cells. Methods The protein levels of CK2 α and β subunits in different lung cancer cell lines were measured by Western blot. Clonogenic assays were performed to assess the effect of a CK2 inhibitor, quinalizarin, on the radiosensitivity of lung adenocarcinoma A549 cells and large cell lung cancer H460 cells. The effects of the combination of quinalizarin and X⁃ray irradiation on the apoptosis and cell cycle of A549 and H460 cells were measured by flow cytometry. The differences between two groups were analyzed by analysis of variance and t⁃test. Results Western blot revealed that theαandβsubunits of CK2 were overexpressed in non⁃small cell lung cancer cells (A549,H460, and H1650 cells), which were considered insensitive to X⁃ray irradiation, whereas a lower expression of these two subunits were found in small cell lung cancer cells ( H446 cells) , which were sensitive to X⁃ray irradiation. The clonogenic assays showed that A549 and H460 cells pre⁃exposed to quinalizarin had a significantly lower survival fraction compared with the control group and had a sensitization enhancement ratio greater than 1. 0( D0 were 2. 771 and 2. 463 respectively) . The combination of quinalizarin and X⁃ray irradiation did not increase the apoptosis of A549 and H460 cells ( X⁃ray+Quinalizarin vs. Quinalizarin, A549, P=0. 487 and H460, P=0. 254) , but caused significant G2/M arrest compared with under X⁃ray irradiation only ( X⁃ray +Quinalizarin:X⁃ray, A549, P=0. 000;H460, P=0. 002 and X⁃ray+Quinalizarin:Quinalizarin, A549, P=0. 000;H460,P=0. 000) . Conclusions Quinalizarin, as a CK2 inhibitor, can increase the radiosensitivity of non⁃small cell lung cancer cells.%目的:探讨蛋白激酶CK2抑制剂对肺癌细胞系放射敏感性的影响。方法通过蛋白印迹法检测蛋白激酶CK2α、β亚基在不同肺癌细胞系中的表达

  5. CK2 inhibitor CX-4945 blocks TGF-β1-induced epithelial-to-mesenchymal transition in A549 human lung adenocarcinoma cells.

    Directory of Open Access Journals (Sweden)

    Jiyeon Kim

    Full Text Available BACKGROUND: The epithelial-to-mesenchymal transition (EMT is a major phenotype of cancer metastasis and invasion. As a druggable cancer target, the inhibition of protein kinase CK2 (formally named to casein kinase 2 has been suggested as a promising therapeutic strategy to treat EMT-controlled cancer metastasis. This study aimed to evaluate the effect of the CK2 inhibitor CX-4945 on the processes of cancer migration and invasion during the EMT in A549 human lung adenocarcinoma cells. MATERIALS AND METHODS: The effect of CX-4945 on TGF-β1-induced EMT was evaluated in A549 cells treated with TGF-β1 (5 ng/ml and CX-4945. The effect of CX-4945 on TGF-β1-induced cadherin switch and activation of key signaling molecules involved in Smad, non-Smad, Wnt and focal adhesion signaling pathways were investigated by Western blot analysis, immunocytochemistry and reporter assay. Additionally, the effect of CX-4945 on TGF-β1-induced migration and invasion was investigated by wound healing assay, Boyden chamber assay, gelatin zymography, and the quantitative real-time PCR. RESULTS: CX-4945 inhibits the TGF-β1-induced cadherin switch and the activation of key signaling molecules involved in Smad (Smad2/3, Twist and Snail, non-Smad (Akt and Erk, Wnt (β-catenin and focal adhesion signaling pathways (FAK, Src and paxillin that cooperatively regulate the overall process of EMT. As a result, CX-4945 inhibits the migration and invasion of A549 cells accompanied with the downregulation of MMP-2 and 9. CONCLUSIONS: Clinical evaluation of CX-4945 in humans as a single agent in solid tumors and multiple myeloma has established its promising pharmacokinetic, pharmacodynamic, and safety profiles. Beyond regression of tumor mass, CX-4945 may be advanced as a new therapy for cancer metastasis and EMT-related disorders.

  6. 新疆产业结构对就业结构偏离效应实证研究∗%A Study of the Deviation Effect between the Industrial Structure and the Employment Structure in Xinjiang

    Institute of Scientific and Technical Information of China (English)

    赵军; 时乐乐

    2013-01-01

      运用改革开放以来新疆的数据,实证分析产业结构对就业结构的偏离效应。结果显示:新疆各地州的产业结构对就业结构偏离效应有很大差异;第一产业存在大量剩余劳动力;第二产业的产业结构和就业结构的偏离效应正在扩大,存在很大的就业缺口;第三产业的就业空间已经饱和。最后根据实证研究结论指出新疆目前产业就业发展面临的问题。%Using the data of Xinjiang since the implementation of the Reform and Opening-up Policy, this paper makes an empirical analysis of the deviation effect of Xinjiang regional industry on the employment structure. It concludes that: there exists a big difference in the deviation effects between Xinjiang regional industrial structure and the employment structure; there is a big surplus labor in the primary industry and the deviation effect of the industrial structure and the employment structure is expanding in the secondary industry — a big employment demand. The employment in the tertiary industry is nearly saturated. Finally, it points out the problems currently facing the industry and employment development in Xinjiang.

  7. Diversity-oriented synthesis of pyrazolo[4,3-b]indoles by gold-catalysed three-component annulation: application to the development of a new class of CK2 inhibitors.

    OpenAIRE

    Hou, Zengye; Oishi, Shinya; Suzuki, Yamato; Kure, Tatsuhide; Nakanishi, Isao; Hirasawa, Akira; Tsujimoto, Gozoh; Ohno, Hiroaki; Fujii, Nobutaka

    2013-01-01

    Pyrazolo[4,3-b]indole derivatives have been designed as novel CK2 inhibitor compounds based on the binding mode analysis of a previously reported phenylpyrazole-type CK2 inhibitor. A series of pyrazolo[4,3-b]indoles and related dihydropyrazolo[4,3-b]indoles were efficiently prepared from simple starting materials using a gold-catalysed three-component annulation reaction as a key step. Several of the newly synthesized compounds displayed high levels of inhibitory activity, indicating that the...

  8. Determination of mRNA, and protein levels of p53, MDM2 and protein kinase CK2 subunits in F9 cells after treatment with the apoptosis-inducing drugs cisplatin and carboplatin

    DEFF Research Database (Denmark)

    Siemer, S; Ornskov, D; Guerra, B;

    1999-01-01

    Protein kinase CK2 is a pleiotropic serine/threonine kinase which has been shown to phosphorylate numerous substrates. Evidence is accumulating that CK2 may exist complexed to a variety of cellular proteins, e.g. p53, MDM2, and A-Raf. Here, we explored the effects of the chemotherapeutic drugs....... More than 50% apoptotic cells were seen after 6 h. We conclude that cisplatin and its second generation drug carboplatin act similarly i.e. both drugs cause a concomitant decrease in p53 mRNA and an increase in p53 protein level. After 4 h treatment with either of the two drugs, p53 levels reach...

  9. Remark on Structure of Expectation Values of Flavor-Lepton Numbers with respect to Neutrino-Source Hadron States: Deviation from Fermi's Golden Relatio

    CERN Document Server

    Fujii, Kanji

    2016-01-01

    In our preceeding reports, we have pointed out that a unified description of weak decays accompanying neutrinos and the oscillation process is obtained on the basis of the expectation values of flavor-neutrino numbers with respect to the neutrino-source hadron state. In the present report, we investigate the effect on the expectation values due to the deviation from Fermi's golden relation, and give concrete features of these deviations in the case of $\\pi^+$ and $K^+$-decays under the simple situation with the $3$-momentum $\\vec{p_A}=0$ for $A=\\pi^+$, $K^+$. %numerical results under simple situations.

  10. Large deviations from freeness

    CERN Document Server

    Kargin, Vladislav

    2010-01-01

    Let H=A+UBU* where A and B are two N-by-N Hermitian matrices and U is a Haar-distributed random unitary matrix, and let \\mu_H, \\mu_A, and \\mu_B be empirical measures of eigenvalues of matrices H, A, and B, respectively. Then, it is known (see, for example, Pastur-Vasilchuk, CMP, 2000, v.214, pp.249-286) that for large N, measure \\mu_H is close to the free convolution of measures \\mu_A and \\mu_B, where the free convolution is a non-linear operation on probability measures. The large deviations of the cumulative distribution function of \\mu_H from its expectation have been studied by Chatterjee in JFA, 2007, v. 245, pp.379-389. In this paper we improve Chatterjee's estimate and show that P {\\sup_x |F_H (x) -F_+ (x)| > \\delta} < exp [-f(\\delta) N^2], where F_H (x) and F_+ (x) denote the cumulative distribution functions of \\mu_H and the free convolution of \\mu_A and \\mu_B, respectively, and where f(\\delta) is a specific function.

  11. Segmentation Using Symmetry Deviation

    DEFF Research Database (Denmark)

    Hollensen, Christian; Højgaard, L.; Specht, L.;

    2011-01-01

    hypopharyngeal cancer patients to find anatomical symmetry and evaluate it against the standard deviation of the normal patients to locate pathologic volumes. Combining the information with an absolute PET threshold of 3 Standard uptake value (SUV) a volume was automatically delineated. The overlap of automated...... segmentations on manual contours was evaluated using concordance index and sensitivity for the hypopharyngeal patients. The resulting concordance index and sensitivity was compared with the result of using a threshold of 3 SUV using a paired t-test. Results: The anatomical and symmetrical atlas was constructed...... and sensitivity of respectively 0.43±0.15 and 0.56±0.18 was acquired. It was compared to the concordance index of segmentation using absolute threshold of 3 SUV giving respectively 0.41±0.16 and 0.51±0.19 for concordance index and sensitivity yielding p-values of 0.33 and 0.01 for a paired t-test respectively....

  12. Large deviations and idempotent probability

    CERN Document Server

    Puhalskii, Anatolii

    2001-01-01

    In the view of many probabilists, author Anatolii Puhalskii''s research results stand among the most significant achievements in the modern theory of large deviations. In fact, his work marked a turning point in the depth of our understanding of the connections between the large deviation principle (LDP) and well-known methods for establishing weak convergence results.Large Deviations and Idempotent Probability expounds upon the recent methodology of building large deviation theory along the lines of weak convergence theory. The author develops an idempotent (or maxitive) probability theory, introduces idempotent analogues of martingales (maxingales), Wiener and Poisson processes, and Ito differential equations, and studies their properties. The large deviation principle for stochastic processes is formulated as a certain type of convergence of stochastic processes to idempotent processes. The author calls this large deviation convergence.The approach to establishing large deviation convergence uses novel com...

  13. CK2 phosphorylation of human centrins 1 and 2 regulates their binding to the DNA repair protein XPC, the centrosomal protein Sfi1 and the phototransduction protein transducin β.

    Science.gov (United States)

    Grecu, Dora; Assairi, Liliane

    2014-01-01

    Centrins are calcium-binding proteins that can interact with several cellular targets (Sfi1, XPC, Sac3 and transducin β) through the same hydrophobic triad. However, two different orientations of the centrin-binding motif have been observed: W(1)xxL(4)xxxL(8) for XPC (xeroderma pigmentosum group C protein) and the opposite orientation L(8)xxxL(4)xxW(1) for Sfi1 (suppressor of fermentation-induced loss of stress resistance protein 1), Sac3 and transducin β. Centrins are also phosphorylated by several protein kinases, among which is CK2. The purpose of this study was to determine the binding mechanism of human centrins to three targets (transducin β, Sfi1 and XPC), and the effects of in vitro phosphorylation by CK2 of centrins 1 and 2 with regard to this binding mechanism. We identified the centrin-binding motif at the COOH extremity of transducin β. Human centrin 1 binds to transducin β only in the presence of calcium with a binding constant lower than the binding constant observed for Sfi1 and for XPC. The affinity constants of centrin 1 were 0.10 10(6) M(-1), 249 10(6) M(-1) and 52.5 10(6) M(-1) for Trd, R17-Sfi1 and P17-XPC respectively. CK2 phosphorylates human centrin 1 at residue T138 and human centrin 2 at residues T138 and S158. Consequently CK2 phosphorylation abolished the binding of centrin 1 to transducin β and reduced the binding to Sfi1 and XPC. CK2 phosphorylation of centrin 2 at T138 and S158 abolished the binding to Sfi1 as assessed using a C-HsCen2 T138D-S158D phosphomimetic form of centrin 2.

  14. CK2 phosphorylation of human centrins 1 and 2 regulates their binding to the DNA repair protein XPC, the centrosomal protein Sfi1 and the phototransduction protein transducin β

    Science.gov (United States)

    Grecu, Dora; Assairi, Liliane

    2014-01-01

    Centrins are calcium-binding proteins that can interact with several cellular targets (Sfi1, XPC, Sac3 and transducin β) through the same hydrophobic triad. However, two different orientations of the centrin-binding motif have been observed: W1xxL4xxxL8 for XPC (xeroderma pigmentosum group C protein) and the opposite orientation L8xxxL4xxW1 for Sfi1 (suppressor of fermentation-induced loss of stress resistance protein 1), Sac3 and transducin β. Centrins are also phosphorylated by several protein kinases, among which is CK2. The purpose of this study was to determine the binding mechanism of human centrins to three targets (transducin β, Sfi1 and XPC), and the effects of in vitro phosphorylation by CK2 of centrins 1 and 2 with regard to this binding mechanism. We identified the centrin-binding motif at the COOH extremity of transducin β. Human centrin 1 binds to transducin β only in the presence of calcium with a binding constant lower than the binding constant observed for Sfi1 and for XPC. The affinity constants of centrin 1 were 0.10 106 M−1, 249 106 M−1 and 52.5 106 M−1 for Trd, R17-Sfi1 and P17-XPC respectively. CK2 phosphorylates human centrin 1 at residue T138 and human centrin 2 at residues T138 and S158. Consequently CK2 phosphorylation abolished the binding of centrin 1 to transducin β and reduced the binding to Sfi1 and XPC. CK2 phosphorylation of centrin 2 at T138 and S158 abolished the binding to Sfi1 as assessed using a C-HsCen2 T138D-S158D phosphomimetic form of centrin 2. PMID:24918055

  15. CK2 phosphorylation of human centrins 1 and 2 regulates their binding to the DNA repair protein XPC, the centrosomal protein Sfi1 and the phototransduction protein transducin β

    Directory of Open Access Journals (Sweden)

    Dora Grecu

    2014-01-01

    Full Text Available Centrins are calcium-binding proteins that can interact with several cellular targets (Sfi1, XPC, Sac3 and transducin β through the same hydrophobic triad. However, two different orientations of the centrin-binding motif have been observed: W1xxL4xxxL8 for XPC (xeroderma pigmentosum group C protein and the opposite orientation L8xxxL4xxW1 for Sfi1 (suppressor of fermentation-induced loss of stress resistance protein 1, Sac3 and transducin β. Centrins are also phosphorylated by several protein kinases, among which is CK2. The purpose of this study was to determine the binding mechanism of human centrins to three targets (transducin β, Sfi1 and XPC, and the effects of in vitro phosphorylation by CK2 of centrins 1 and 2 with regard to this binding mechanism. We identified the centrin-binding motif at the COOH extremity of transducin β. Human centrin 1 binds to transducin β only in the presence of calcium with a binding constant lower than the binding constant observed for Sfi1 and for XPC. The affinity constants of centrin 1 were 0.10 106 M−1, 249 106 M−1 and 52.5 106 M−1 for Trd, R17-Sfi1 and P17-XPC respectively. CK2 phosphorylates human centrin 1 at residue T138 and human centrin 2 at residues T138 and S158. Consequently CK2 phosphorylation abolished the binding of centrin 1 to transducin β and reduced the binding to Sfi1 and XPC. CK2 phosphorylation of centrin 2 at T138 and S158 abolished the binding to Sfi1 as assessed using a C-HsCen2 T138D-S158D phosphomimetic form of centrin 2.

  16. On geodesic deviation in Schwarzschild spacetime

    CERN Document Server

    Philipp, Dennis; Laemmerzahl, Claus; Deshpande, Kaustubh

    2015-01-01

    For metrology, geodesy and gravimetry in space, satellite based instruments and measurement techniques are used and the orbits of the satellites as well as possible deviations between nearby ones are of central interest. The measurement of this deviation itself gives insight into the underlying structure of the spacetime geometry, which is curved and therefore described by the theory of general relativity (GR). In the context of GR, the deviation of nearby geodesics can be described by the Jacobi equation that is a result of linearizing the geodesic equation around a known reference geodesic with respect to the deviation vector and the relative velocity. We review the derivation of this Jacobi equation and restrict ourselves to the simple case of the spacetime outside a spherically symmetric mass distribution and circular reference geodesics to find solutions by projecting the Jacobi equation on a parallel propagated tetrad as done by Fuchs. Using his results, we construct solutions of the Jacobi equation for...

  17. X-radiographic study of rare-earth compounds with special regardment of modulated structures. The response of the crystal structure to stoichiometry deviations; Roentgengraphische Untersuchung von Seltenerdverbindungen mit besonderer Beruecksichtigung modulierter Strukturen. Die Antwort der Kristallstruktur auf Stoechiometrieabweichungen

    Energy Technology Data Exchange (ETDEWEB)

    Leisegang, Tilmann

    2010-04-09

    Even shortly after World War II, as large amounts of ultrapure rare earths (RE) became available for scientific research, a large reservoir of peculiar phenomena was uncovered. These had not been investigated before or were completely unknown. Examples of these phenomena are, magnetic ordering, the KONDO effect, quantum critical points, heavy fermion behaviour, as well as superconductivity. A strong influence of small variations of the chemical composition on the physical properties had been observed. The main focus of the present thesis is the detailed elucidation of the crystal structure of fundamental representatives of this class of substances, as well as the influence of dedicated variations of the chemical composition on their structure and properties. In particular, the characterisation of modulated crystals is an important facet. A large spectrum of physical methods, especially X-ray diffraction, is employed in the investigations. Results on oriented intergrowth in the Y-Ni-B-C system, incommensurately ordered vacancies in the Ce-Si system, incorporation of stacking faults as well as commensurately ordered transition metal atoms (TM) in the RE-TM-Si system and site specific occupancy in the Y-Mn-Fe-O system are presented. Their elucidation is reported for the first time. It is shown which consequences the structural peculiarities will have on the physical properties. An objective of this thesis is to give an overview of the possible ''answers'' that can be obtained with regard to the influence of the crystal structure of rare earth transition metal compounds on deviations of the chemical composition. (orig.)

  18. Jianshu province economy growth and employment structure deviation research%江苏省经济增长与就业结构偏离研究

    Institute of Scientific and Technical Information of China (English)

    邵夫林; 潘志昂; 杨道建; 杨宪超

    2012-01-01

    In this paper,through the establishmentof mathematical model,using the methods of mathematical statistics analyzes the relationship among the industry practitioners in Jiangsu Province,GDP and total fixed asset investment.The results reflect the situation of Jiangsu Province's employment growth in recent years,the basic contour and the divergence between economic growth rate and the employment rate recent years.Based on adjusted linear regression model,we suggest he reasons for deviation between economic growth rate and employment growth rate,additionally,providing several measures to maintain fast economic growth,those measures were vigorously developing the tertiary industry,pushing the development of human resources,improving the forms of employment in order to promote employment growth.%本文通过建立统计模型,运用数理统计的方法分析了江苏省各产业从业人员、地区生产总值和全社会固定资产投资之间的关系,反映了近年来江苏省就业增长状况的基本轮廊和江苏省近几年的经济发展与就业率相背离的现状,基于调整线性回归模型对经济增长率与就业增长率偏离的原因进行了分析,得出了保持经济适度快速增长,大力发展第三产业,开发人力资源,完善就业形式以促进就业增长等观点。

  19. Semantic Deviation in Oliver Twist

    Institute of Scientific and Technical Information of China (English)

    康艺凡

    2016-01-01

    Dickens, with his adeptness with language, applies semantic deviation skillfully in his realistic novel Oliver Twist. However, most studies and comments home and abroad on it mainly focus on such aspects as humanity, society, and characters. Therefore, this thesis will take a stylistic approach to Oliver Twist from the perspective of semantic deviation, which is achieved by the use of irony, hyperbole, and pun and analyze how the application of the technique makes the novel attractive.

  20. Angle-deviation optical profilometer

    Institute of Scientific and Technical Information of China (English)

    Chen-Tai Tan; Yuan-Sheng Chan; Zhen-Chin Lin; Ming-Hung Chiu

    2011-01-01

    @@ We propose a new optical profilometer for three-dimensional (3D) surface profile measurement in real time.The deviation angle is based on geometrical optics and is proportional to the apex angle of a test plate.Measuring the reflectivity of a parallelogram prism allows detection of the deviation angle when the beam is incident at the nearby critical angle. The reflectivity is inversely proportional to the deviation angle and proportional to the apex angle and surface height. We use a charge-coupled device (CCD) camera at the image plane to capture the reflectivity profile and obtain the 3D surface profile directly.%We propose a new optical profilometer for three-dimensional (3D) surface profile measurement in real time.The deviation angle is based on geometrical optics and is proportional to the apex angle of a test plate.Measuring the refiectivity of a parallelogram prism allows detection of the deviation angle when the beam is incident at the nearby critical angle. The refiectivity is inversely proportional to the deviation angle and proportional to the apex angle and surface height. We use a charge-coupled device (CCD) camera at the image plane to capture the refiectivity profile and obtain the 3D surface profile directly.

  1. Insights from soft X-rays: the chlorine and sulfur sub-structures of a CK2alpha/DRB complex

    OpenAIRE

    Raaf, J.; Issinger, O.-G.; Niefind, K.

    2008-01-01

    The diffraction pattern of a protein crystal is normally a product of the interference of electromagnetic waves scattered by electrons of the crystalline sample. The diffraction pattern undergoes systematic changes in case additionally X-ray absorption occurs, meaning if the wavelength of the primary X-ray beam is relatively close to the absorption edge of selected elements of the sample. The resulting effects are summarized as "anomalous dispersion" and can be always observed with "soft" X-r...

  2. Large deviations and rain showers

    OpenAIRE

    Wilkinson, Michael

    2015-01-01

    Rainfall from ice-free cumulus clouds requires collisions of large numbers of microscopic droplets to create every raindrop. The onset of rain showers can be surprisingly rapid, much faster than the mean time required for a single collision. Large-deviation theory is used to explain this observation.

  3. Standard Deviation for Small Samples

    Science.gov (United States)

    Joarder, Anwar H.; Latif, Raja M.

    2006-01-01

    Neater representations for variance are given for small sample sizes, especially for 3 and 4. With these representations, variance can be calculated without a calculator if sample sizes are small and observations are integers, and an upper bound for the standard deviation is immediate. Accessible proofs of lower and upper bounds are presented for…

  4. 48 CFR 2001.403 - Individual deviations.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Individual deviations. 2001... Individual deviations. In individual cases, deviations from either the FAR or the NRCAR will be authorized... deviations clearly in the best interest of the Government. Individual deviations must be authorized...

  5. 48 CFR 801.403 - Individual deviations.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Individual deviations. 801... Individual deviations. (a) Authority to authorize individual deviations from the FAR and VAAR is delegated to... nature of the deviation. (d) The DSPE may authorize individual deviations from the FAR and VAAR when...

  6. Perception of aircraft Deviation Cues

    Science.gov (United States)

    Martin, Lynne; Azuma, Ronald; Fox, Jason; Verma, Savita; Lozito, Sandra

    2005-01-01

    To begin to address the need for new displays, required by a future airspace concept to support new roles that will be assigned to flight crews, a study of potentially informative display cues was undertaken. Two cues were tested on a simple plan display - aircraft trajectory and flight corridor. Of particular interest was the speed and accuracy with which participants could detect an aircraft deviating outside its flight corridor. Presence of the trajectory cue significantly reduced participant reaction time to a deviation while the flight corridor cue did not. Although non-significant, the flight corridor cue seemed to have a relationship with the accuracy of participants judgments rather than their speed. As this is the second of a series of studies, these issues will be addressed further in future studies.

  7. Inactivation of the FoxO3a transcription factor is associated with the production of reactive oxygen species during protein kinase CK2 downregulation-mediated senescence in human colon cancer and breast cancer cells.

    Science.gov (United States)

    Park, Seong-Yeol; Bae, Young-Seuk

    2016-09-01

    We previously showed that protein kinase CK2 downregulation mediates senescence through the reactive oxygen species (ROS)-p53-p21(Cip1/WAF1) pathway in various human cells. In the present study, we investigated whether the FoxO3a transcription factor is associated with ROS production during CK2 downregulation-induced senescence in human colon cancer HCT116 and breast cancer MCF-7 cells. FoxO3a overexpression suppressed ROS production and p53 stabilization induced by a CK2α knockdown. CK2α downregulation induced nuclear export of FoxO3a through stimulation of AKT-mediated phosphorylation of FoxO3a and decreased transcription of its target genes (Cu/ZnSOD, MnSOD, and catalase). In contrast, CK2α overexpression inhibited AKT-mediated FoxO3a phosphorylation. This resulted in nuclear accumulation of FoxO3a, and elevated expression of its target genes. Therefore, these data indicate for the first time that CK2 downregulation stimulates ROS generation by inhibiting FoxO3a during premature senescence in human colon and breast cancer cells. PMID:27470586

  8. Worldline deviations of charged spinning particles

    Energy Technology Data Exchange (ETDEWEB)

    Heydari-Fard, M. [Department of Physics, Shahid Beheshti University, Evin, 19839 Tehran (Iran, Islamic Republic of); Mohseni, M. [Physics Department, Payame Noor University, 19395-4697 Tehran (Iran, Islamic Republic of)]. E-mail: m-mohseni@pnu.ac.ir; Sepangi, H.R. [Department of Physics, Shahid Beheshti University, Evin, 19839 Tehran (Iran, Islamic Republic of); Institute for Studies in Theoretical Physics and Mathematics, Tehran (Iran, Islamic Republic of)

    2005-10-20

    The geodesic deviation equation is generalized to worldline deviation equations describing the relative accelerations of charged spinning particles in the framework of Dixon-Souriau equations of motion.

  9. Worldline deviations of charged spinning particles

    CERN Document Server

    Heydari-Fard, M; Sepangi, H R

    2005-01-01

    The geodesic deviation equation is generalized to worldline deviation equations describing the relative accelerations of charged spinning particles in the framework of Dixon-Souriau equations of motion.

  10. The Analysis of a Deviation of Investment and Corporate Governance.

    OpenAIRE

    HISA Shoichi

    2008-01-01

    Investment of firms is affected by not only fundamentals factors, but liquidity constraint, ownership or corporate structure. Information structure between manager and owner is a significant factor to decide the level of investment, and deviation of investment from optimal condition. The reputation model between manager and owner suggest that the separate of ownership and management may induce the deviation of investment, and indicate that governance structure is important to reduce it. In th...

  11. The Analysis of a Deviation of Investment and Corporate Governance

    OpenAIRE

    Shoichi Hisa

    2008-01-01

    Investment of firms is affected by not only fundamentals factors, but liquidity constraint, ownership or corporate structure. Information structure between manager and owner is a significant factor to decide the level of investment, and deviation of investment from optimal condition. The reputation model between manager and owner suggest that the separate of ownership and management may induce the deviation of investment, and indicate that governance structure is important to reduce it. In th...

  12. Large deviations and portfolio optimization

    Science.gov (United States)

    Sornette, Didier

    Risk control and optimal diversification constitute a major focus in the finance and insurance industries as well as, more or less consciously, in our everyday life. We present a discussion of the characterization of risks and of the optimization of portfolios that starts from a simple illustrative model and ends by a general functional integral formulation. A major item is that risk, usually thought of as one-dimensional in the conventional mean-variance approach, has to be addressed by the full distribution of losses. Furthermore, the time-horizon of the investment is shown to play a major role. We show the importance of accounting for large fluctuations and use the theory of Cramér for large deviations in this context. We first treat a simple model with a single risky asset that exemplifies the distinction between the average return and the typical return and the role of large deviations in multiplicative processes, and the different optimal strategies for the investors depending on their size. We then analyze the case of assets whose price variations are distributed according to exponential laws, a situation that is found to describe daily price variations reasonably well. Several portfolio optimization strategies are presented that aim at controlling large risks. We end by extending the standard mean-variance portfolio optimization theory, first within the quasi-Gaussian approximation and then using a general formulation for non-Gaussian correlated assets in terms of the formalism of functional integrals developed in the field theory of critical phenomena.

  13. 48 CFR 1301.403 - Individual deviations.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Individual deviations... DEPARTMENT OF COMMERCE ACQUISITION REGULATIONS SYSTEM Deviations From the FAR 1301.403 Individual deviations. The designee authorized to approve individual deviations from the FAR is set forth in CAM 1301.70....

  14. 48 CFR 401.403 - Individual deviations.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Individual deviations. 401... AGRICULTURE ACQUISITION REGULATION SYSTEM Deviations From the FAR and AGAR 401.403 Individual deviations. In individual cases, deviations from either the FAR or the AGAR will be authorized only when essential to...

  15. 48 CFR 2801.403 - Individual deviations.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Individual deviations. 2801... OF JUSTICE ACQUISITION REGULATIONS SYSTEM Deviations From the FAR and JAR 2801.403 Individual deviations. Individual deviations from the FAR or the JAR shall be approved by the head of the...

  16. 48 CFR 301.403 - Individual deviations.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Individual deviations. 301... ACQUISITION REGULATION SYSTEM Deviations From the FAR 301.403 Individual deviations. Contracting activities shall prepare requests for individual deviations to either the FAR or HHSAR in accordance with 301.470....

  17. 48 CFR 1501.403 - Individual deviations.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Individual deviations. 1501.403 Section 1501.403 Federal Acquisition Regulations System ENVIRONMENTAL PROTECTION AGENCY GENERAL GENERAL Deviations 1501.403 Individual deviations. Requests for individual deviations from the FAR and...

  18. 48 CFR 501.403 - Individual deviations.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Individual deviations. 501... Individual deviations. (a) An individual deviation affects only one contract action. (1) The Head of the Contracting Activity (HCA) must approve an individual deviation to the FAR. The authority to grant...

  19. 48 CFR 2401.403 - Individual deviations.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Individual deviations. 2401... DEVELOPMENT GENERAL FEDERAL ACQUISITION REGULATION SYSTEM Deviations 2401.403 Individual deviations. In individual cases, proposed deviations from the FAR or HUDAR shall be submitted to the Senior...

  20. Deviations in human gut microbiota

    DEFF Research Database (Denmark)

    Casén, C; Vebø, H C; Sekelja, M;

    2015-01-01

    BACKGROUND: Dysbiosis is associated with many diseases, including irritable bowel syndrome (IBS), inflammatory bowel diseases (IBD), obesity and diabetes. Potential clinical impact of imbalance in the intestinal microbiota suggests need for new standardised diagnostic methods to facilitate...... microbiome profiling. AIM: To develop and validate a novel diagnostic test using faecal samples to profile the intestinal microbiota and identify and characterise dysbiosis. METHODS: Fifty-four DNA probes targeting ≥300 bacteria on different taxonomic levels were selected based on ability to distinguish......, and potential clinically relevant deviation in the microbiome from normobiosis. This model was tested in different samples from healthy volunteers and IBS and IBD patients (n = 330) to determine the ability to detect dysbiosis. RESULTS: Validation confirms dysbiosis was detected in 73% of IBS patients, 70...

  1. [The crooked nose: correction of dorsal and caudal septal deviations].

    Science.gov (United States)

    Foda, H M T

    2010-09-01

    The deviated nose represents a complex cosmetic and functional problem. Septal surgery plays a central role in the successful management of the externally deviated nose. This study included 800 patients seeking rhinoplasty to correct external nasal deviations; 71% of these suffered from variable degrees of nasal obstruction. Septal surgery was necessary in 736 (92%) patients, not only to improve breathing, but also to achieve a straight, symmetric external nose. A graduated surgical approach was adopted to allow correction of the dorsal and caudal deviations of the nasal septum without weakening its structural support to the nasal dorsum or nasal tip. The approach depended on full mobilization of deviated cartilage, followed by straightening of the cartilage and its fixation in the corrected position by using bony splinting grafts through an external rhinoplasty approach. PMID:20809379

  2. 48 CFR 2501.403 - Individual deviations.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Individual deviations. 2501.403 Section 2501.403 Federal Acquisition Regulations System NATIONAL SCIENCE FOUNDATION GENERAL FEDERAL ACQUISITION REGULATIONS SYSTEM Deviations From the FAR 2501.403 Individual deviations....

  3. 48 CFR 1901.403 - Individual deviations.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Individual deviations. 1901.403 Section 1901.403 Federal Acquisition Regulations System BROADCASTING BOARD OF GOVERNORS GENERAL... Individual deviations. Deviations from the IAAR or the FAR in individual cases shall be authorized by...

  4. 48 CFR 3401.403 - Individual deviations.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Individual deviations. 3401.403 Section 3401.403 Federal Acquisition Regulations System DEPARTMENT OF EDUCATION ACQUISITION REGULATION GENERAL ED ACQUISITION REGULATION SYSTEM Deviations 3401.403 Individual deviations. An...

  5. 48 CFR 201.403 - Individual deviations.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Individual deviations. 201.403 Section 201.403 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM... Individual deviations. (1) Individual deviations, except those described in 201.402(1) and paragraph (2)...

  6. 48 CFR 1.403 - Individual deviations.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Individual deviations. 1.403 Section 1.403 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION GENERAL FEDERAL ACQUISITION REGULATIONS SYSTEM Deviations from the FAR 1.403 Individual deviations....

  7. 48 CFR 601.403 - Individual deviations.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Individual deviations. 601.403 Section 601.403 Federal Acquisition Regulations System DEPARTMENT OF STATE GENERAL DEPARTMENT OF STATE ACQUISITION REGULATIONS SYSTEM Deviations from the FAR 601.403 Individual deviations....

  8. The Standard Deviation of Launch Vehicle Environments

    Science.gov (United States)

    Yunis, Isam

    2005-01-01

    Statistical analysis is used in the development of the launch vehicle environments of acoustics, vibrations, and shock. The standard deviation of these environments is critical to accurate statistical extrema. However, often very little data exists to define the standard deviation and it is better to use a typical standard deviation than one derived from a few measurements. This paper uses Space Shuttle and expendable launch vehicle flight data to define a typical standard deviation for acoustics and vibrations. The results suggest that 3dB is a conservative and reasonable standard deviation for the source environment and the payload environment.

  9. Nasal Septal Deviation and Facial Skeletal Asymmetries.

    Science.gov (United States)

    Hartman, Christopher; Holton, Nathan; Miller, Steven; Yokley, Todd; Marshall, Steven; Srinivasan, Sreedevi; Southard, Thomas

    2016-03-01

    During ontogeny, the nasal septum exerts a morphogenetic influence on the surrounding facial skeleton. While the influence of the septum is well established in long snouted animal models, its role in human facial growth is less clear. If the septum is a facial growth center in humans, we would predict that deviated septal growth would be associated with facial skeletal asymmetries. Using computed tomographic (CT) scans of n = 55 adult subjects, the purpose of this study was to test whether there is a correlation between septal deviation and facial asymmetries using three-dimensional (3D) geometric morphometric techniques. We calculated deviation as a percentage of septal volume relative to the volume of a modeled non-deviated septum. We then recorded skeletal landmarks representing the nasal, palatal, and lateral facial regions. Landmark data were superimposed using Procrustes analysis. First, we examined the correlation between nasal septal deviation and the overall magnitude of asymmetry. Next, we assessed whether there was a relationship between nasal septal deviation and more localized aspects of asymmetry using multivariate regression analysis. Our results indicate that while there was no correlation between septal deviation and the overall magnitude of asymmetry, septal deviation was associated with asymmetry primarily in the nasal floor and the palatal region. Septal deviation was unassociated with asymmetries in the lateral facial skeleton. Though we did not test the causal relationship between nasal septal deviation and facial asymmetry, our results suggest that the nasal septum may have an influence on patterns of adult facial form. PMID:26677010

  10. Deviations from Born-Oppenheimer theory in structural chemistry: Jahn-Teller, pseudo Jahn-Teller, and hidden pseudo Jahn-Teller effects in C3H3 and C3H3(-).

    Science.gov (United States)

    Kayi, H; Garcia-Fernandez, P; Bersuker, I B; Boggs, J E

    2013-09-12

    The electronic structure and vibronic coupling in two similar molecular systems, radical C3H3 and anion C3H3(-), in ground and excited states, are investigated in detail to show how their equilibrium structures, in deviation from the Born-Oppenheimer approximation, originate from the vibronic mixing of at least two electronic states, producing the Jahn-Teller (JT), pseudo JT (PJT), and hidden PJT effects. Starting with the high-symmetry geometry D3h of C3H3, we evaluated its 2-fold degenerate ground electronic state (2)E″ and two lowest excited states (2)A1' and (2)E' and found that all of them contribute to the distortion of the ground state via the JT vibronic coupling problem E″ ⊗ e' and two PJT problems (E″ + A1') ⊗ e″ and (E″ + E') ⊗ (a2″ + e″); all the three active normal modes e'(1335 cm(-1)), e″(1030 cm(-1)), and a2″(778 cm(-1)) are imaginary, meaning that all the three vibronic couplings are sufficiently strong to cause instability, albeit in different directions. The first of them, the ground state JT effect, enhances one of the C-C bonds (toward an ethylenic form with C2v symmetry), while the two PJT effects produce, respectively, cis (a2″ toward C3v symmetry) and trans (e″) puckering of the hydrogen atoms. As a result, C3H3 has two coexisting equilibrium configurations with different geometry. In the C3H3(-) anion, the ground electronic state in D3h symmetry is an orbitally nondegenerate spin triplet (3)A2' with a group of close in energy singlet and triplet excited states in the order of (1)A1', (3)A1″, (1)E″, (3)E″, and (1)E'. This shows that two PJT couplings, ((3)A2' + (3)A1″) ⊗ a2″ and ((3)A2' + (3)E″) ⊗ e″, may influence the geometry of the equilibrium structure in the (3)A2' state. Indeed, both vibrational modes, a2″(1034 cm(-1)) and e″(1284 cm(-1)), are imaginary in this state. Similar to the radical case, they produce, respectively, cis (a2″) and trans (e″) puckering of the hydrogen atoms

  11. Moderate Deviations for Mean Field Particle Models

    CERN Document Server

    Del Moral, Pierre; Wu, Liming

    2012-01-01

    This article is concerned with moderate deviation principles of a general class of mean eld type interacting particle models. We discuss functional moderate deviations of the occupation measures for both the strong -topology on the space of fi nite and bounded measures as well as for the corresponding stochastic processes on some class of functions equipped with the uniform topology. Our approach is based on an original semigroup analysis combined with stochastic perturbation techniques and projective limit large deviation methods.

  12. Small shape deviations causes complex dynamics in large electric generators

    Science.gov (United States)

    Lundström, Niklas L. P.; Grafström, Anton; Aidanpää, Jan-Olov

    2014-05-01

    We prove that combinations of small eccentricity, ovality and/or triangularity in the rotor and stator can produce complex whirling motions of an unbalanced rotor in large synchronous generators. It is concluded which structures of shape deviations that are more harmful, in the sense of producing complex whirling motions, than others. For each such structure, we derive simplified equations of motions from which we conclude analytically the relation between shape deviations and mass unbalance that yield non-smooth whirling motions. Finally we discuss validity of our results in the sense of modeling of the unbalanced magnetic pull force.

  13. 41 CFR 105-1.110 - Deviation.

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Deviation. 105-1.110 Section 105-1.110 Public Contracts and Property Management Federal Property Management Regulations System (Continued) GENERAL SERVICES ADMINISTRATION 1-INTRODUCTION 1.1-Regulations System § 105-1.110 Deviation....

  14. Deviation of Register in English Talk Shows

    Institute of Scientific and Technical Information of China (English)

    贺静

    2016-01-01

    Halliday's register theory and G. Leech's deviation of register are the general knowledge of the topic in the academic field. This paper focuses on connection between deviation of register and humorous effects in English talk shows. The significance of this paper is to put this theory in broader use and to help English learners better understand western humor and talk shows.

  15. 48 CFR 1201.403 - Individual deviations.

    Science.gov (United States)

    2010-10-01

    ...) 48 CFR 1.405(e) applies). However, see TAM 1201.403. ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Individual deviations... FEDERAL ACQUISITION REGULATIONS SYSTEM 70-Deviations From the FAR and TAR 1201.403 Individual...

  16. 48 CFR 1401.403 - Individual deviations.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Individual deviations. 1401.403 Section 1401.403 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR GENERAL DEPARTMENT OF THE INTERIOR ACQUISITION REGULATION SYSTEM Deviations from the FAR and DIAR 1401.403...

  17. Exploring Students' Conceptions of the Standard Deviation

    Science.gov (United States)

    delMas, Robert; Liu, Yan

    2005-01-01

    This study investigated introductory statistics students' conceptual understanding of the standard deviation. A computer environment was designed to promote students' ability to coordinate characteristics of variation of values about the mean with the size of the standard deviation as a measure of that variation. Twelve students participated in an…

  18. The causes and prevention measures of column deviation nearby expansion joint in reinforced concrete frame structure%框架结构伸缩缝柱偏位成因及防治措施

    Institute of Scientific and Technical Information of China (English)

    张树华

    2015-01-01

    分析了钢筋混凝土框架结构伸缩缝柱在混凝土浇筑过程中产生偏位的原因,从设计方面、施工方法以及质量管理方面提出了伸缩缝柱钢筋混凝土偏位防治措施及处理方案,供工程技术人员参考。%The paper analyzes the reasons for the deviation of the expansion joints in the concrete grouting process at the reinforced concrete framework,and points out the prevention measures and treatment for the reinforced concrete deviation of the expansion joint column from design, construction method,and quality management,so as to provide some reference for technicians.

  19. 控制变换尾下END序列随机和的广义精致大偏差%Extended Precise Large Deviations of Random Sums in the Presence of Dominated Variation END Structure

    Institute of Scientific and Technical Information of China (English)

    胡怡玉; 何基娇; 周之寒

    2014-01-01

    重尾场合下随机变量随机和的精致大偏差是现代金融保险学中一项重要研究课题。假定理赔序列为一列END同分布随机变量序列,带控制变换尾,理赔到来过程为一般计数过程,且与理赔序列相互独立,在更弱的条件下,将文献[5]等中所做的一致变换尾上的广义精致大偏差推广到控制变换尾上,得到相应的偏离均值的大偏差结果。%The precise large deviations of random sums in heavy-tailed random variables is an important research topic in modern insur-ance and finance.Let the claims be a sequence of END real-valued identically distributed random variables with dominated variation, the claims is common counting process and independent from its sequence.Under the weaker condition,the extended precise large deviations of random sums which had been done in the document[5 ]was promoted to dominated variation,the largest deviation of con-sequential deflection mean is acquired.

  20. Path Deviation Equations in AP-Geometry

    CERN Document Server

    Wanas, M I

    2005-01-01

    Recently, it has been shown that Absolute Parallelism (AP) geometry admits paths that are naturally quantized. These paths have been used to describe the motion of spinning particles in a background gravitational field. In case of a weak static gravitational field limits, the paths are applied successfully to interpret the discrepancy in the motion of thermal neutrons in the Earth's gravitational field (COW-experiment). The aim of the present work is to explore the properties of the deviation equations corresponding to these paths. In the present work the deviation equations are derived and compared to the geodesic deviation equation of the Riemannian geometry.

  1. Sport and Social Deviations - a Prognostic Attitude

    Directory of Open Access Journals (Sweden)

    Kosiewicz Jerzy

    2014-06-01

    Full Text Available The author focuses his attention first of all on social deviations which play a negative role in highly competitive sport. He tries to define - from the viewpoint of philosophy - how they will influence its future form.

  2. Large Deviations in Quantum Spin Chain

    CERN Document Server

    Ogata, Yoshiko

    2008-01-01

    We show the full large deviation principle for KMS-states and $C^*$-finitely correlated states on a quantum spin chain. We cover general local observables. Our main tool is Ruelle's transfer operator method.

  3. Kinematic Deviations In Children With Cerebral Palsy

    OpenAIRE

    Sangeux, Morgan; ARMAND, Stéphane

    2015-01-01

    In gait analysis, a large portion of the work consists in finding the underlying causes of the abnormal movement observed during walking. The patient’s kinematics of walking is compared to that of typically developed children and the deviations are further analysed. Over the years, clinicians have observed multiple-joints kinematics deviations that were frequent in children with cerebral palsy and devised gait patterns in order to group patients and support management algorithms. However, the...

  4. Large deviations for fractional Poisson processes

    CERN Document Server

    Beghin, Luisa

    2012-01-01

    We present large deviation results for two versions of fractional Poisson processes: the main version which is a renewal process, and the alternative version where all the random variables are weighted Poisson distributed. We also present a sample path large deviation result for suitably normalized counting processes; finally we show how this result can be applied to the two versions of fractional Poisson processes considered in this paper.

  5. Scaling Deviations for Neutrino Reactions in Aysmptotically Free Field Theories

    Science.gov (United States)

    Wilczek, F. A.; Zee, A.; Treiman, S. B.

    1974-11-01

    Several aspects of deep inelastic neutrino scattering are discussed in the framework of asymptotically free field theories. We first consider the growth behavior of the total cross sections at large energies. Because of the deviations from strict scaling which are characteristic of such theories the growth need not be linear. However, upper and lower bounds are established which rather closely bracket a linear growth. We next consider in more detail the expected pattern of scaling deviation for the structure functions and, correspondingly, for the differential cross sections. The analysis here is based on certain speculative assumptions. The focus is on qualitative effects of scaling breakdown as they may show up in the X and y distributions. The last section of the paper deals with deviations from the Callan-Gross relation.

  6. The large deviation approach to statistical mechanics

    Energy Technology Data Exchange (ETDEWEB)

    Touchette, Hugo [School of Mathematical Sciences, Queen Mary University of London, London E1 4NS (United Kingdom)], E-mail: h.touchette@qmul.ac.uk

    2009-07-15

    The theory of large deviations is concerned with the exponential decay of probabilities of large fluctuations in random systems. These probabilities are important in many fields of study, including statistics, finance, and engineering, as they often yield valuable information about the large fluctuations of a random system around its most probable state or trajectory. In the context of equilibrium statistical mechanics, the theory of large deviations provides exponential-order estimates of probabilities that refine and generalize Einstein's theory of fluctuations. This review explores this and other connections between large deviation theory and statistical mechanics, in an effort to show that the mathematical language of statistical mechanics is the language of large deviation theory. The first part of the review presents the basics of large deviation theory, and works out many of its classical applications related to sums of random variables and Markov processes. The second part goes through many problems and results of statistical mechanics, and shows how these can be formulated and derived within the context of large deviation theory. The problems and results treated cover a wide range of physical systems, including equilibrium many-particle systems, noise-perturbed dynamics, nonequilibrium systems, as well as multifractals, disordered systems, and chaotic systems. This review also covers many fundamental aspects of statistical mechanics, such as the derivation of variational principles characterizing equilibrium and nonequilibrium states, the breaking of the Legendre transform for nonconcave entropies, and the characterization of nonequilibrium fluctuations through fluctuation relations.

  7. Spectral deviations for the damped wave equation

    OpenAIRE

    Anantharaman, Nalini

    2009-01-01

    We prove a Weyl-type fractal upper bound for the spectrum of the damped wave equation, on a negatively curved compact manifold. It is known that most of the eigenvalues have an imaginary part close to the average of the damping function. We count the number of eigenvalues in a given horizontal strip deviating from this typical behaviour; the exponent that appears naturally is the `entropy' that gives the deviation rate from the Birkhoff ergodic theorem for the geodesic flow. A Weyl-type lower...

  8. Measuring the deviation from the Rutherford formula

    OpenAIRE

    Kuraev, E. A.; Shatnev, M.; Tomasi-Gustafsson, E.

    2009-01-01

    Modern experiments with heavy ion-leptons collisions open the possibility to measure the deviation of cross section of small angles electron(positron)-ion elastic scattering from the Rutherford formula due to multiple virtual photons exchange. The charge asymmetry and the polarization of the scattered leptons are calculated and numerical predictions are given. A generalization to elastic proton-nucleus scattering is discussed.

  9. 41 CFR 115-1.110 - Deviations.

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Deviations. 115-1.110 Section 115-1.110 Public Contracts and Property Management Federal Property Management Regulations System (Continued) ENVIRONMENTAL PROTECTION AGENCY 1-INTRODUCTION 1.1-Regulation System § 115-1.110...

  10. Bodily Deviations and Body Image in Adolescence

    Science.gov (United States)

    Vilhjalmsson, Runar; Kristjansdottir, Gudrun; Ward, Dianne S.

    2012-01-01

    Adolescents with unusually sized or shaped bodies may experience ridicule, rejection, or exclusion based on their negatively valued bodily characteristics. Such experiences can have negative consequences for a person's image and evaluation of self. This study focuses on the relationship between bodily deviations and body image and is based on a…

  11. 41 CFR 101-1.110 - Deviation.

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 2 2010-07-01 2010-07-01 true Deviation. 101-1.110 Section 101-1.110 Public Contracts and Property Management Federal Property Management Regulations System FEDERAL PROPERTY MANAGEMENT REGULATIONS GENERAL 1-INTRODUCTION 1.1-Regulation System § 101-1.110...

  12. From Stein Identities to Moderate Deviations

    CERN Document Server

    Chen, Louis H Y; Shao, Qi-Man

    2009-01-01

    Stein's method is applied to obtain a Cram\\'er type moderate deviation result for dependent random variables whose dependence is defined in terms of a Stein identity. The result is optimal when applied to the combinatorial central limit theorem, the binary expansion of a random integer, the anti-voter model on a complete graph, and the Curie-Weiss model.

  13. 24 CFR 84.4 - Deviations.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Deviations. 84.4 Section 84.4 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER EDUCATION, HOSPITALS, AND...

  14. A robust standard deviation control chart

    NARCIS (Netherlands)

    M. Schoonhoven; R.J.M.M. Does

    2012-01-01

    This article studies the robustness of Phase I estimators for the standard deviation control chart. A Phase I estimator should be efficient in the absence of contaminations and resistant to disturbances. Most of the robust estimators proposed in the literature are robust against either diffuse distu

  15. MODERATE DEVIATIONS AND LARGE DEVIATIONS FOR A TEST OF SYMMETRY BASED ON KERNEL DENSITY ESTIMATOR

    Institute of Scientific and Technical Information of China (English)

    He Xiaoxia; Gao Fuqing

    2008-01-01

    Let fn be a non-parametric kernel density estimator based on a kernel function K. And a sequence of independent and identically distributed random variables taking values in R. The goal of this article is to prove moderate deviations and large deviations for the statistic sup x∈R|fn(x) - fn(-X)|.

  16. The Deviation of China’s Government Procurement Remedy System Structure Design Concept and Its Adjustment%我国政府采购救济制度构设理念之偏差及其调整

    Institute of Scientific and Technical Information of China (English)

    刘铠

    2015-01-01

    我国政府采购救济制度实践中所反映的问题在制度层面表现为质疑投诉程序冗长、救济范围较窄、救济对象欠全面等,其深层次的根源在于构设理念的偏差。行政控制理念主导下的政府采购救济制度存在内在缺失,与欧盟和GPA协定的理念模式相距甚远。由是,根本解决政府采购救济制度现实问题之策略应为:转变传统的行政权力主导的救济体系,在救济制度构设中充分考虑公益与私益、公平与效率、自由与秩序等价值目标的平衡。%The current problems reflected in the practice of China’s government procurement remedy system in institutional level include manifest as long challenge and complaint procedure, narrow scope of relief, incomprehensive recipients, and so on. Its deep cause is the deviation of the construction idea. There is an internal absence for government procurement remedy system dominated by administration controlling principle, and this is far from the conceptual model of European Union and GPA Agreement. Thus, the fundamental strategy to solve the real problem of government procurement remedy system is: transform the traditional executive power-dominated remedy system, in the construction of remedy system, as well as take full account of the balance of value goal, such as public and private interests, fairness and efficiency, liberty and order.

  17. Deviations from LTE in a stellar atmosphere

    Science.gov (United States)

    Kalkofen, W.; Klein, R. I.; Stein, R. F.

    1979-01-01

    Deviations for LTE are investigated in an atmosphere of hydrogen atoms with one bound level, satisfying the equations of radiative, hydrostatic, and statistical equilibrium. The departure coefficient and the kinetic temperature as functions of the frequency dependence of the radiative cross section are studied analytically and numerically. Near the outer boundary of the atmosphere, the departure coefficient is smaller than unity when the radiative cross section grows with frequency faster than with the square of frequency; it exceeds unity otherwise. Far from the boundary the departure coefficient tends to exceed unity for any frequency dependence of the radiative cross section. Overpopulation always implies that the kinetic temperature in the statistical-equilibrium atmosphere is higher than the temperature in the corresponding LTE atmosphere. Upper and lower bounds on the kinetic temperature are given for an atmosphere with deviations from LTE only in the optically shallow layers when the emergent intensity can be described by a radiation temperature.

  18. Large Deviation Strategy for Inverse Problem

    CERN Document Server

    Ojima, Izumi

    2011-01-01

    Taken traditionally as a no-go theorem against the theorization of inductive processes, Duheme-Quine thesis may interfere with the essence of statistical inference. This difficulty can be resolved by \\textquotedblleft Micro-Macro duality\\textquotedblright\\ \\cite{Oj03, Oj05} which clarifies the importance of specifying the pertinent aspects and accuracy relevant to concrete contexts of scientific discussions and which ensures the matching between what to be described and what to describe in the form of the validity of duality relations. This consolidates the foundations of the inverse problem, induction method, and statistical inference crucial for the sound relations between theory and experiments. To achieve the purpose, we propose here Large Deviation Strategy (LDS for short) on the basis of Micro-Macro duality, quadrality scheme, and large deviation principle. According to the quadrality scheme emphasizing the basic roles played by the dynamics, algebra of observables together with its representations and ...

  19. Note onset deviations as musical piece signatures.

    Directory of Open Access Journals (Sweden)

    Joan Serrà

    Full Text Available A competent interpretation of a musical composition presents several non-explicit departures from the written score. Timing variations are perhaps the most important ones: they are fundamental for expressive performance and a key ingredient for conferring a human-like quality to machine-based music renditions. However, the nature of such variations is still an open research question, with diverse theories that indicate a multi-dimensional phenomenon. In the present study, we consider event-shift timing variations and show that sequences of note onset deviations are robust and reliable predictors of the musical piece being played, irrespective of the performer. In fact, our results suggest that only a few consecutive onset deviations are already enough to identify a musical composition with statistically significant accuracy. We consider a mid-size collection of commercial recordings of classical guitar pieces and follow a quantitative approach based on the combination of standard statistical tools and machine learning techniques with the semi-automatic estimation of onset deviations. Besides the reported results, we believe that the considered materials and the methodology followed widen the testing ground for studying musical timing and could open new perspectives in related research fields.

  20. Note onset deviations as musical piece signatures.

    Science.gov (United States)

    Serrà, Joan; Özaslan, Tan Hakan; Arcos, Josep Lluis

    2013-01-01

    A competent interpretation of a musical composition presents several non-explicit departures from the written score. Timing variations are perhaps the most important ones: they are fundamental for expressive performance and a key ingredient for conferring a human-like quality to machine-based music renditions. However, the nature of such variations is still an open research question, with diverse theories that indicate a multi-dimensional phenomenon. In the present study, we consider event-shift timing variations and show that sequences of note onset deviations are robust and reliable predictors of the musical piece being played, irrespective of the performer. In fact, our results suggest that only a few consecutive onset deviations are already enough to identify a musical composition with statistically significant accuracy. We consider a mid-size collection of commercial recordings of classical guitar pieces and follow a quantitative approach based on the combination of standard statistical tools and machine learning techniques with the semi-automatic estimation of onset deviations. Besides the reported results, we believe that the considered materials and the methodology followed widen the testing ground for studying musical timing and could open new perspectives in related research fields. PMID:23935971

  1. Observable Deviations from Homogeneity in an Inhomogeneous Universe

    CERN Document Server

    Giblin, John T; Starkman, Glenn D

    2016-01-01

    How does inhomogeneity affect our interpretation of cosmological observations? It has long been wondered to what extent the observable properties of an inhomogeneous universe differ from those of a corresponding Friedman-Lemaitre-Robertson-Walker (FLRW) model, and how the inhomogeneities affect that correspondence. Here, we use numerical relativity to study the behavior of light beams traversing an inhomogeneous universe and construct the resulting Hubble diagrams. The universe that emerges exhibits an average FLRW behavior, but inhomogeneous structures contribute to deviations in observables across the observer's sky. We also investigate the relationship between angular diameter distance and the angular extent of a source, finding deviations that grow with source redshift. These departures from FLRW are important path-dependent effects with implications for using real observables in an inhomogeneous universe such as our own.

  2. LARGE DEVIATIONS AND MODERATE DEVIATIONS FOR m-NEGATIVELY ASSOCIATED RANDOM VARIABLES

    Institute of Scientific and Technical Information of China (English)

    Hu Yijun; Ming Ruixing; Yang Wenquan

    2007-01-01

    M-negatively associated random variables, which generalizes the classical one of negatively associated random variables and includes m-dependent sequences as its particular case, are introduced and studied. Large deviation principles and moderate deviation upper bounds for stationary m-negatively associated random variables are proved.Kolmogorov-type and Marcinkiewicz-type strong laws of large numbers as well as the three series theorem for m-negatively associated random variables are also given.

  3. Investigating deviations from norms in court interpreting

    DEFF Research Database (Denmark)

    Dubslaff, Friedel; Martinsen, Bodil

    of the interpreted events and by drawing on responses to the questionnaires and comments provided by these two groups. The explicit instructions issued by the Danish Court Administration (Guidelines for court interpreting) will serve as point of departure for the investigation of deviations from the prevailing norms...... to the flexibility of the concept of norms, it lends itself excellently to inquiries into interpreting, i.e. to an object of study which may be said to be characterized by an even higher degree of variability than translation. The present study forms part of a comprehensive research project on court interpreting...

  4. Standard deviation of scatterometer measurements from space.

    Science.gov (United States)

    Fischer, R. E.

    1972-01-01

    The standard deviation of scatterometer measurements has been derived under assumptions applicable to spaceborne scatterometers. Numerical results are presented which show that, with sufficiently long integration times, input signal-to-noise ratios below unity do not cause excessive degradation of measurement accuracy. The effects on measurement accuracy due to varying integration times and changing the ratio of signal bandwidth to IF filter-noise bandwidth are also plotted. The results of the analysis may resolve a controversy by showing that in fact statistically useful scatterometer measurements can be made from space using a 20-W transmitter, such as will be used on the S-193 experiment for Skylab-A.

  5. Deviation from Alday-Maldacena duality for wavy circle

    International Nuclear Information System (INIS)

    Alday-Maldacena conjecture is stated in this paper that the area AΠ of the minimal surface in AdS5 space with a boundary Π, located in Euclidean space at infinity of AdS5, coincides with a double integral DΠ along Π, the Abelian Wilson average in an auxiliary dual model. This comes from Alday and Maldacena's original proposal and the BDS conjecture on the extrapolation of the MHV amplitudes. The boundary Π is a polygon formed by momenta of n external light-like particles in N=4 SYM theory, and in a certain n=∞ limit it can be substituted by an arbitrary smooth curve (wavy circle). The Alday-Maldacena conjecture is known to be violated for n>5, when it fails to be supported by the peculiar global dual conformal invariance, however, the structure of deviations remains obscure. The case of wavy lines can appear more convenient for analysis of these deviations due to the systematic method developed in [H. Itoyama, A. Mironov, A. Morozov, Anomaly in n=∞ Alday-Maldacena duality for wavy circle, JHEP 0807 (2008) 024, (arXiv:0803.1547)] for (perturbative) evaluation of minimal areas, which is not yet available in the presence of angles at finite n. We correct a mistake in that paper and explicitly evaluate the h2h-bar2 terms, where the first deviation from the Alday-Maldacena duality arises for the wavy circle.

  6. Allan deviation analysis of financial return series

    Science.gov (United States)

    Hernández-Pérez, R.

    2012-05-01

    We perform a scaling analysis for the return series of different financial assets applying the Allan deviation (ADEV), which is used in the time and frequency metrology to characterize quantitatively the stability of frequency standards since it has demonstrated to be a robust quantity to analyze fluctuations of non-stationary time series for different observation intervals. The data used are opening price daily series for assets from different markets during a time span of around ten years. We found that the ADEV results for the return series at short scales resemble those expected for an uncorrelated series, consistent with the efficient market hypothesis. On the other hand, the ADEV results for absolute return series for short scales (first one or two decades) decrease following approximately a scaling relation up to a point that is different for almost each asset, after which the ADEV deviates from scaling, which suggests that the presence of clustering, long-range dependence and non-stationarity signatures in the series drive the results for large observation intervals.

  7. Theory of Deviation and Its Application in College English Teaching

    Institute of Scientific and Technical Information of China (English)

    Xu Yanqiu

    2008-01-01

    Deviation is an important concept in stylistics.Besides Shklovskij and Mukarovsky,who made a theoreti cal generalization of deviational phenomena,Leech is the one who studies deviation systematically and catego rizes it into groups.To apply the theory of deviation to College English teaching is an effective way to culti rate students' interest in and aesthetic ability of English texts.

  8. Surgical Success Rates for Horizontal Concomitant Deviations According to the Type and Degree of Deviation

    Directory of Open Access Journals (Sweden)

    İhsan Çaça

    2004-01-01

    Full Text Available We evaluated the correlation with success rates and deviation type and degree inhorizontal concomitant deviations. 104 horizontal concomitan strabismus cases whowere operated in our clinic between January 1994 – December 2000 were included in thestudy. 56 cases undergone recession-resection procedure in the same eye 19 cases twomuscle recession and one muscle resection, 20 cases two muscle recession, 9 cases onlyone muscle recession. 10 ± prism diopter deviation in postoperative sixth monthexamination was accepted as surgical success.Surgical success rate was 90% and 89.3% in the cases with deviation angle of 15-30and 31-50 prism diopter respectively. Success rate was 78.9% if the angle was more than50 prism diopter. According to strabismus type when surgical success rate examined; inalternan esotropia 88.33%, in alternan exotropia 84.6%, in monocular esotropia 88%and in monocular exotropia 83.3% success was fixed. Statistically significant differencewas not found between strabismus type and surgical success rate. The binocular visiongaining rate was found as 51.8% after the treatment of cases.In strabismus surgery, preoperative deviation angle was found to be an effectivefactor on the success rate.

  9. An discussion on Graphological Deviation in Oliver Twist

    Institute of Scientific and Technical Information of China (English)

    肖潇

    2016-01-01

    In stylistic analysis,when we identifying the stylistic features in literary works,deviation serves as an important sign.According to Leech,there are eight types of deviation in poetry:lexical deviation,grammatical deviation,phonological deviation,graphological deviation,semantic deviation,dialectal deviation,deviation of register,deviation of historical period. Realism marks as an significant development in the history of fiction,for its success in achieving an exposure of the truth of people’s real life and fierce social problems.And foregrounded feature is inevitable part that constitute his language style.We will focus on Oliver Twist,for it is presented with unique writing style,which worthy our investigation.

  10. Large deviation approach to the generalized random energy model

    Energy Technology Data Exchange (ETDEWEB)

    Dorlas, T.C.; Dukes, W.M.B. [School of Theoretical Physics, Dublin Institute for Advanced Studies, Dublin (Ireland)

    2002-05-24

    The generalized random energy model is a generalization of the random energy model introduced by Derrida to mimic the ultrametric structure of the Parisi solution of the Sherrington-Kirkpatrick model of a spin glass. It was solved exactly in two special cases by Derrida and Gardner. A complete solution for the thermodynamics in the general case was given by Capocaccia et al. Here we use large deviation theory to analyse the model in a very straightforward way. We also show that the variational expression for the free energy can be evaluated easily using the Cauchy-Schwarz inequality. (author)

  11. Deviating measurements in radiation protection. Legal assessment of deviations in radiation protection measurements

    International Nuclear Information System (INIS)

    This study investigates how, from a legal point of view, deviations in radiation protection measurements should be treated in comparisons between measured results and limits stipulated by nuclear legislation or goods transport regulations. A case-by-case distinction is proposed which is based on the legal concequences of the respective measurement. Commentaries on nuclear law contain no references to the legal assessment of deviating measurements in radiation protection. The examples quoted in legal commentaries on civil and criminal proceedings of the way in which errors made in measurements for speed control and determinations of the alcohol content in the blood are to be taken into account, and a commentary on ozone legislation, are examined for analogies with radiation protection measurements. Leading cases in the nuclear field are evaluated in the light of the requirements applying in case of deviations in measurements. The final section summarizes the most important findings and conclusions. (orig.)

  12. Hypotropic Dissociated Vertical Deviation; a Case Report

    Directory of Open Access Journals (Sweden)

    Zhale Rajavi

    2013-01-01

    Full Text Available Purpose: To report the clinical features of a rare case of hypotropic dissociated vertical deviation (DVD. Case report: A 25-year-old female was referred with unilateral esotropia, hypotropia and slow variable downward drift in her left eye. She had history of esotropia since she had been 3-4 months of age. Best corrected visual acuity was 20/20 in her right eye and 20/40 in the left one when hyperopia was corrected. She underwent bimedial rectus muscle recession of 5.25mm for 45 prism diopters (PDs of esotropia. She was orthophoric 3 months after surgery and no further operation was planned for correction of the hypotropic DVD. Conclusion: This rare case of hypotropic DVD showed only mild amblyopia in her non-fixating eye. The etiology was most probably acquired considering hyperopia as a sign of early onset accommodative esotropia.

  13. Large Deviations and Asymptotic Methods in Finance

    CERN Document Server

    Gatheral, Jim; Gulisashvili, Archil; Jacquier, Antoine; Teichmann, Josef

    2015-01-01

    Topics covered in this volume (large deviations, differential geometry, asymptotic expansions, central limit theorems) give a full picture of the current advances in the application of asymptotic methods in mathematical finance, and thereby provide rigorous solutions to important mathematical and financial issues, such as implied volatility asymptotics, local volatility extrapolation, systemic risk and volatility estimation. This volume gathers together ground-breaking results in this field by some of its leading experts. Over the past decade, asymptotic methods have played an increasingly important role in the study of the behaviour of (financial) models. These methods provide a useful alternative to numerical methods in settings where the latter may lose accuracy (in extremes such as small and large strikes, and small maturities), and lead to a clearer understanding of the behaviour of models, and of the influence of parameters on this behaviour. Graduate students, researchers and practitioners will find th...

  14. Spotting deviations from R^2 inflation

    CERN Document Server

    de la Cruz-Dombriz, Alvaro; Odintsov, Sergei D; Saez-Gomez, Diego

    2016-01-01

    We discuss the soundness of inflationary scenarios in theories beyond the Starobinsky model, namely a class of theories described by arbitrary functions of the Ricci scalar and the K-essence field. We discuss the pathologies associated with higher-order equations of motion which will be shown to constrain the stability of this class of theories. We provide a general framework to calculate the slow-roll parameters and the corresponding mappings to the theory parameters. For paradigmatic gravitational models within the class of theories under consideration we illustrate the power of the Planck/Bicep2 latest results to constrain such gravitational Lagrangians. Finally, bounds for potential deviations from Starobinsky-like inflation are derived.

  15. LARGE DEVIATIONS FOR SOME DEPENDENT SEQUENCES

    Institute of Scientific and Technical Information of China (English)

    Hu Shuhe; Wang Xuejun

    2008-01-01

    Let (Xi) be a martingale difference sequence and Sn=n∑i=1 Xi. Suppose (Xi) is bounded in Lp. In the case p2, Lesigne and Volny (Stochastic Process. Appl. 96 (2001) 143) obtained the estimation μ(Sn n) < cn-p/2, Yulin Li (Statist. Probab.Lett. 62 (2003) 317) generalized the result to the case when p ∈(1, 2) and obtained μ(Sn n) < cn1-P, these are optimal in a certain sense. In this article, the authors study the large deviation of Sn for some dependent sequences and obtain the same order optimal upper bounds for μ(Sn n) as those for martingale difference sequence.

  16. The role of septal surgery in management of the deviated nose.

    Science.gov (United States)

    Foda, Hossam M T

    2005-02-01

    The deviated nose represents a complex cosmetic and functional problem. Septal surgery plays a central role in the successful management of the externally deviated nose. This study included 260 patients seeking rhinoplasty to correct external nasal deviations; 75 percent of them had various degrees of nasal obstruction. Septal surgery was necessary in 232 patients (89 percent), not only to improve breathing but also to achieve a straight, symmetrical, external nose as well. A graduated surgical approach was adopted to allow correction of the dorsal and caudal deviations of the nasal septum without weakening its structural support to the dorsum or nasal tip. The approach depended on full mobilization of deviated cartilage, followed by straightening of the cartilage and its fixation in the corrected position by using bony splinting grafts through an external rhinoplasty approach. PMID:15692343

  17. Large Deviations in Fast-Slow Systems

    Science.gov (United States)

    Bouchet, Freddy; Grafke, Tobias; Tangarife, Tomás; Vanden-Eijnden, Eric

    2016-02-01

    The incidence of rare events in fast-slow systems is investigated via analysis of the large deviation principle (LDP) that characterizes the likelihood and pathway of large fluctuations of the slow variables away from their mean behavior—such fluctuations are rare on short time-scales but become ubiquitous eventually. Classical results prove that this LDP involves an Hamilton-Jacobi equation whose Hamiltonian is related to the leading eigenvalue of the generator of the fast process, and is typically non-quadratic in the momenta—in other words, the LDP for the slow variables in fast-slow systems is different in general from that of any stochastic differential equation (SDE) one would write for the slow variables alone. It is shown here that the eigenvalue problem for the Hamiltonian can be reduced to a simpler algebraic equation for this Hamiltonian for a specific class of systems in which the fast variables satisfy a linear equation whose coefficients depend nonlinearly on the slow variables, and the fast variables enter quadratically the equation for the slow variables. These results are illustrated via examples, inspired by kinetic theories of turbulent flows and plasma, in which the quasipotential characterizing the long time behavior of the system is calculated and shown again to be different from that of an SDE.

  18. The Role of Burden and Deviation in Ostracizing Others.

    Science.gov (United States)

    Wesselmann, Eric D; Wirth, James H; Pryor, John B; Reeder, Glenn D; Williams, Kipling D

    2015-01-01

    Ostracism (being excluded and ignored) is a painful experience, so why do individuals ostracize others? Previous research suggests individuals often ostracize those who are deviate, but not always. We posit that there may be two types of deviation, burdensome and non-burdensome, and the former is most likely to be ostracized. Study 1 manipulated burdensome deviation by programming a group member to perform more slowly (8 or 16 sec.) than others (4 sec.) in a virtual ball-toss game. Participants perceived slower players as more burdensome and deviate than normal speed players. Additionally, participants ostracized (gave fewer ball tosses to) the slowest player. Study 2 examined participant responses to both burdensome deviation (8- and 16-sec. players) and non-burdensome deviation (goth appearance). Participants again perceived the slower players to be burdensome and deviate, and ostracized them. They perceived the goth player to be deviate but not burdensome and did not ostracize this player. PMID:26267129

  19. Large deviations for Glauber dynamics of continuous gas

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    This paper is devoted to the large deviation principles of the Glauber-type dynamics of finite or infinite volume continuous particle systems.We prove that the level-2 empirical process satisfies the large deviation principles in the weak convergence topology,while it does not satisfy the large deviation principles in the T-topology.

  20. 14 CFR 21.609 - Approval for deviation.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Approval for deviation. 21.609 Section 21.609 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT... deviation. (a) Each manufacturer who requests approval to deviate from any performance standard of a...

  1. A Visual Model for the Variance and Standard Deviation

    Science.gov (United States)

    Orris, J. B.

    2011-01-01

    This paper shows how the variance and standard deviation can be represented graphically by looking at each squared deviation as a graphical object--in particular, as a square. A series of displays show how the standard deviation is the size of the average square.

  2. 7 CFR 400.204 - Notification of deviation from standards.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Notification of deviation from standards. 400.204... Contract-Standards for Approval § 400.204 Notification of deviation from standards. A Contractor shall advise the Corporation immediately if the Contractor deviates from the requirements of these...

  3. Deviations from the local field approximation in negative streamer heads

    CERN Document Server

    Li, C; Ebert, U; van der Mullen, J J A M; Ebert, Ute; Li, Chao

    2007-01-01

    Negative streamer ionization fronts in nitrogen under normal conditions are investigated both in a particle model and in a fluid model in local field approximation. The parameter functions for the fluid model are derived from swarm experiments in the particle model. The front structure on the inner scale is investigated in a 1D setting, allowing reasonable run-time and memory consumption and high numerical accuracy without introducing super-particles. If the reduced electric field immediately before the front is >= 50kV/(cm bar), solutions of fluid and particle model agree very well. If the field increases up to 200kV/(cm bar), the solutions of particle and fluid model deviate, in particular, the ionization level behind the front becomes up to 60% higher in the particle model while the velocity is rather insensitive. Particle and fluid model deviate because electrons with high energies do not yet fully run away from the front, but are somewhat ahead. This leads to increasing ionization rates in the particle m...

  4. Heritability of strabismus: genetic influence is specific to eso-deviation and independent of refractive error.

    Science.gov (United States)

    Sanfilippo, Paul G; Hammond, Christopher J; Staffieri, Sandra E; Kearns, Lisa S; Melissa Liew, S H; Barbour, Julie M; Hewitt, Alex W; Ge, Dongliang; Snieder, Harold; Mackinnon, Jane R; Brown, Shayne A; Lorenz, Birgit; Spector, Tim D; Martin, Nicholas G; Wilmer, Jeremy B; Mackey, David A

    2012-10-01

    Strabismus represents a complex oculomotor disorder characterized by the deviation of one or both eyes and poor vision. A more sophisticated understanding of the genetic liability of strabismus is required to guide searches for associated molecular variants. In this classical twin study of 1,462 twin pairs, we examined the relative influence of genes and environment in comitant strabismus, and the degree to which these influences can be explained by factors in common with refractive error. Participants were examined for the presence of latent ('phoria') and manifest ('tropia') strabismus using cover-uncover and alternate cover tests. Two phenotypes were distinguished: eso-deviation (esophoria and esotropia) and exo-deviation (exophoria and exotropia). Structural equation modeling was subsequently employed to partition the observed phenotypic variation in the twin data into specific variance components. The prevalence of eso-deviation and exo-deviation was 8.6% and 20.7%, respectively. For eso-deviation, the polychoric correlation was significantly greater in monozygotic (MZ) (r = 0.65) compared to dizygotic (DZ) twin pairs (r = 0.33), suggesting a genetic role (p = .003). There was no significant difference in polychoric correlation between MZ (r = 0.55) and DZ twin pairs (r = 0.53) for exo-deviation (p = .86), implying that genetic factors do not play a significant role in the etiology of exo-deviation. The heritability of an eso-deviation was 0.64 (95% CI 0.50-0.75). The additive genetic correlation for eso-deviation and refractive error was 0.13 and the bivariate heritability (i.e., shared variance) was less than 1%, suggesting negligible shared genetic effect. This study documents a substantial heritability of 64% for eso-deviation, yet no corresponding heritability for exo-deviation, suggesting that the genetic contribution to strabismus may be specific to eso-deviation. Future studies are now needed to identify the genes associated with eso-deviation and

  5. Efficient computation of root mean square deviations under rigid transformations.

    Science.gov (United States)

    Hildebrandt, Anna K; Dietzen, Matthias; Lengauer, Thomas; Lenhof, Hans-Peter; Althaus, Ernst; Hildebrandt, Andreas

    2014-04-15

    The computation of root mean square deviations (RMSD) is an important step in many bioinformatics applications. If approached naively, each RMSD computation takes time linear in the number of atoms. In addition, a careful implementation is required to achieve numerical stability, which further increases runtimes. In practice, the structural variations under consideration are often induced by rigid transformations of the protein, or are at least dominated by a rigid component. In this work, we show how RMSD values resulting from rigid transformations can be computed in constant time from the protein's covariance matrix, which can be precomputed in linear time. As a typical application scenario is protein clustering, we will also show how the Ward-distance which is popular in this field can be reduced to RMSD evaluations, yielding a constant time approach for their computation.

  6. Deviations from Fick's law in Lorentz gases

    OpenAIRE

    Lowe, C.P.; Frenkel, D.; van der Hoef, M. A.

    1997-01-01

    We have calculated the self-dynamic structure factorF(k,t) for tagged particle motion in hopping Lorentz gases. We find evidence that, even at long times, the probability distribution function for the displacement of the particles is highly non-Gaussian. At very small values of the wave vector this manifests itself as the divergence of the Burnett coefficient (the fourth moment of the distribution never approaching a value characteristic of a Gaussian). At somewhat larger wave vectors we find...

  7. Some large deviations in Kingman's coalescent

    OpenAIRE

    Depperschmidt, Andrej; Pfaffelhuber, Peter; Scheuringer, Annika

    2013-01-01

    Kingman's coalescent is a random tree that arises from classical population genetic models such as the Moran model. The individuals alive in these models correspond to the leaves in the tree and the following two laws of large numbers concerning the structure of the tree-top are well-known: (i) The (shortest) distance, denoted by $T_n$, from the tree-top to the level when there are $n$ lines in the tree satisfies $nT_n \\xrightarrow{n\\to\\infty} 2$ almost surely; (ii) At time $T_n$, the populat...

  8. Optimal Penalties on Deviations from Budgetary Targets

    Directory of Open Access Journals (Sweden)

    Séverine Menguy

    2014-01-01

    Full Text Available Beyond traditional arguments justifying the introduction of fiscal rules, this paper analyses their potential contribution to an indirect budgetary coordination between the member countries of a monetary union. Indeed, thanks to appropriate fiscal penalties, the noncooperative and decentralized equilibrium could get closer to the optimal equilibrium where the budgetary authorities cooperate. Our macroeconomic model shows that whatever penalty on the structural budgetary deficit would be optimal in case of asymmetric shocks. A moderate penalty on the excessive indebtedness level would be optimal in “normal times,” or in case of asymmetric shocks if openness to trade and price flexibility are sufficiently high, whereas the share of public consumption in GDP, taxations rates, and indebtedness levels is sufficiently weak in the monetary union. Besides, in case of symmetric shocks, a fiscal penalty would be useful to decrease the excessive budgetary activism, even if it doesn’t allow reaching the optimal and first-best equilibrium. Furthermore, the fiscal penalty should always be an increasing function of the share of public consumption in GDP and of taxation rates but a decreasing function of the strength of automatic stabilizers, of openness to trade, and of price flexibility in the member countries of the monetary union.

  9. Geometry of River Networks; 1, Scaling, Fluctuations, and Deviations

    CERN Document Server

    Dodds, P S; Dodds, Peter Sheridan; Rothman, Daniel H.

    2000-01-01

    This article is the first in a series of three papers investigating the detailed geometry of river networks. Large-scale river networks mark an important class of two-dimensional branching networks, being not only of intrinsic interest but also a pervasive natural phenomenon. In the description of river network structure, scaling laws are uniformly observed. Reported values of scaling exponents vary suggesting that no unique set of scaling exponents exists. To improve this current understanding of scaling in river networks and to provide a fuller description of branching network structure, we report here a theoretical and empirical study of fluctuations about and deviations from scaling. We examine data for continent-scale river networks such as the Mississippi and the Amazon and draw inspiration from a simple model of directed, random networks. We center our investigations on the scaling of the length of sub-basin's dominant stream with its area, a characterization of basin shape known as Hack's law. We gene...

  10. Clinical study of the factors affecting radioulnar deviation of the wrist joint

    Directory of Open Access Journals (Sweden)

    Kanavaros Panagiotis

    2010-01-01

    Full Text Available Abstract Background The radioulnar carpal joint is critical for hand and wrist function. Radioulnar deviation indicates distal radioulnar joint flexibility and reflects the structure and function of the carpal bones, ulna, radius and ligaments. The present study examined whether radioulnar deviation is affected by gender, manual labor, playing a musical instrument, playing sport, handedness, previous fracture or prior inflammation. The study used clinical findings based on anatomical landmarks Methods The ulnar, radial and total deviations for both left and right hands were measured in 300 subjects (157 men and 143 women of mean age 21.7 years. Measurements were made with the forearm in a fixed pronated position using a novel specially designed goniometer. The gender of each subject was recorded, and information on playing of sport, playing a musical instrument, manual labor, handedness, and history of fracture or inflammation was sought. Data were analyzed using a multifactor ANOVA test. Results No statistically significant difference (p-value > 0.05 was found between those comparing groups except the total deviation of athletes' left hand versus the total deviation of non athletes' left hand (p-value 0.041 Conclusions This study was based on clinical findings using anatomical landmarks. We found that manual workers and athletes showed greater left hand flexibility. This suggests that activities that place chronic stress on the radiocarpal joint can independently affect radioulnar deviation.

  11. 38 CFR 36.4304 - Deviations; changes of identity.

    Science.gov (United States)

    2010-07-01

    ... identity. 36.4304 Section 36.4304 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS... Deviations; changes of identity. A deviation of more than 5 percent between the estimates upon which a... change in the identity of the property upon which the original appraisal was based, will invalidate...

  12. 基础教育评价机制的偏差及纠偏对策——兼谈高校招生录取“结构性成绩”模式%On Deviation of Evaluation System of Fundamental Education and the Coping Strategies: Reflections on the Mode of Structural Grade of University Admission

    Institute of Scientific and Technical Information of China (English)

    戴前伦

    2011-01-01

    The scientific evaluation system is of great significance of orientation for the fundamental education. However, there exist limitations like evaluating deviation and distorted achievement evaluation. The causes for these limitations lie in the mal-position of cognition of educational reality and lack of scientific evaluation. We should have the correct orientation of evaluation on educational administration management and on the entrance examination. On this basis, we can implement the mode of structural grade to strengthen the quality education and development of fundamental education.%科学的评价机制对基础教育具有重要的导向作用。但当下的基础教育存在着管理评价偏差和业绩评价扭曲的弊端。造成这些弊端的深层次原因是教育本体认知的错位和科学评价的缺位。建立科学的教育评价机制应端正教育行政管理的评价导向和升学考试的评价导向,实验、实施高校招生录取“结构性成绩”模式,以促进我国素质教育的有力推行和基础教育的蓬勃发展。

  13. Importance of Nasal Septal Deviation Type on Planning of Surgery

    Directory of Open Access Journals (Sweden)

    Imran Aydogdu

    2015-11-01

    Full Text Available Aim: Aim of study is to evaluate effectiveness of pre operative data and classification of septal deviation in planning of surgical intervention. Material and Method: 60 patients who were operated because of septal deviation were included to study. 30 patients were applied open technique and other 30 were applied closed technique septoplasty. Types of septal deviations in both groups were classified according to Baumann’s classification peri operatively. Data obtained from both groups were compared by Mann Whitney U test. Results: Type 4 and 3 were the most common deformities seen in open technique group, whereas type 1 and 5 were the most common deformities in closed technique group. We detected significant difference between deviation types clustered between 2 techniques. Discussion: Pre operative assesment of septal deviation type helps surgeon to choose surgical technique.

  14. A Maximum Likelihood Approach to Least Absolute Deviation Regression

    Directory of Open Access Journals (Sweden)

    Yinbo Li

    2004-09-01

    Full Text Available Least absolute deviation (LAD regression is an important tool used in numerous applications throughout science and engineering, mainly due to the intrinsic robust characteristics of LAD. In this paper, we show that the optimization needed to solve the LAD regression problem can be viewed as a sequence of maximum likelihood estimates (MLE of location. The derived algorithm reduces to an iterative procedure where a simple coordinate transformation is applied during each iteration to direct the optimization procedure along edge lines of the cost surface, followed by an MLE of location which is executed by a weighted median operation. Requiring weighted medians only, the new algorithm can be easily modularized for hardware implementation, as opposed to most of the other existing LAD methods which require complicated operations such as matrix entry manipulations. One exception is Wesolowsky's direct descent algorithm, which among the top algorithms is also based on weighted median operations. Simulation shows that the new algorithm is superior in speed to Wesolowsky's algorithm, which is simple in structure as well. The new algorithm provides a better tradeoff solution between convergence speed and implementation complexity.

  15. Fluctuations and large deviations in non-equilibrium systems

    Indian Academy of Sciences (India)

    B Derrida

    2005-05-01

    For systems in contact with two reservoirs at different densities or with two thermostats at different temperatures, the large deviation function of the density gives a possible way of extending the notion of free energy to non-equilibrium systems. This large deviation function of the density can be calculated explicitly for exclusion models in one dimension with open boundary conditions. For these models, one can also obtain the distribution of the current of particles flowing through the system and the results lead to a simple conjecture for the large deviation function of the current of more general diffusive systems.

  16. Large deviations for two scale chemical kinetic processes

    CERN Document Server

    Li, Tiejun

    2015-01-01

    We formulate the large deviations for a class of two scale chemical kinetic processes motivated from biological applications. The result is successfully applied to treat a genetic switching model with positive feedbacks. The corresponding Hamiltonian is convex with respect to the momentum variable as a by-product of the large deviation theory. This property ensures its superiority in the rare event simulations compared with the result obtained by formal WKB asymptotics. The result is of general interest to understand the large deviations for multiscale problems.

  17. Influence of form deviations on the tolerance analysis

    Directory of Open Access Journals (Sweden)

    Mouhssine Chahbouni

    2014-06-01

    Full Text Available The objective of this paper is to present the influence of form deviations on the tolerance analysis of an assembly. For this we will study initially the tolerance analysis using the deviations and clearances domains method, a second time we will integrate the influence of form tolerances on the allowable deviation domain. To illustrate this analysis we used a classical assembly with position and form tolerances (coaxiality and cylindricity. Finally a comparative study between the two cases was illustrated. Keywords:Tolerance Analysis, CAD/CAM, Assembly Systems, Engineering Drawings.

  18. Large Deviations: An Introduction to 2007 Abel Prize

    Indian Academy of Sciences (India)

    S Ramasubramanian

    2008-05-01

    2007 Abel prize has been awarded to S R S Varadhan for creating a unified theory of large deviations. We attempt to give a flavour of this branch of probability theory, highlighting the role of Varadhan.

  19. Bounds of Deviation for Branching Chains in Random Environments

    Institute of Scientific and Technical Information of China (English)

    Wei Gang WANG

    2011-01-01

    We consider non-extinct branching processes in general random environments. Under the condition of means and second moments of each generation being bounded, we give the upper bounds and lower bounds for some form deviations of the process.

  20. Deviation of the statistical fluctuation in heterogeneous anomalous diffusion

    CERN Document Server

    Itto, Yuichi

    2016-01-01

    The exponent of anomalous diffusion of virus in cytoplasm of a living cell is experimentally known to fluctuate depending on localized areas of the cytoplasm, indicating heterogeneity of diffusion. In a recent paper (Itto, 2012), a maximum-entropy-principle approach has been developed in order to propose an Ansatz for the statistical distribution of such exponent fluctuations. Based on this approach, here the deviation of the statistical distribution of the fluctuations from the proposed one is studied from the viewpoint of Einstein's theory of fluctuations (of the thermodynamic quantities). This may present a step toward understanding the statistical property of the deviation. It is shown in a certain class of small deviations that the deviation obeys the multivariate Gaussian distribution.

  1. A Note on a Normal Distribution with Varying Standard Deviation

    Directory of Open Access Journals (Sweden)

    Mahabaleshwara Holla

    1965-01-01

    Full Text Available A normal distribution with varying standard deviation has been considered in this note. Statistical properties of the distribution and the estimation of the parameters involved therein are also discussed.

  2. Spin-geodesic deviations in the Schwarzschild spacetime

    Science.gov (United States)

    Bini, Donato; Geralico, Andrea; Jantzen, Robert T.

    2011-04-01

    The deviation of the path of a spinning particle from a circular geodesic in the Schwarzschild spacetime is studied by an extension of the idea of geodesic deviation. Within the Mathisson-Papapetrou-Dixon model and assuming the spin parameter to be sufficiently small so that it makes sense to linearize the equations of motion in the spin variables as well as in the geodesic deviation, the spin-curvature force adds an additional driving term to the second order system of linear ordinary differential equations satisfied by nearby geodesics. Choosing initial conditions for geodesic motion leads to solutions for which the deviations are entirely due to the spin-curvature force, and one finds that the spinning particle position for a given fixed total spin oscillates roughly within an ellipse in the plane perpendicular to the motion, while the azimuthal motion undergoes similar oscillations plus an additional secular drift which varies with spin orientation.

  3. Spin-geodesic deviations in the Schwarzschild spacetime

    CERN Document Server

    Bini, Donato; Jantzen, Robert T

    2014-01-01

    The deviation of the path of a spinning particle from a circular geodesic in the Schwarzschild spacetime is studied by an extension of the idea of geodesic deviation. Within the Mathisson-Papapetrou-Dixon model and assuming the spin parameter to be sufficiently small so that it makes sense to linearize the equations of motion in the spin variables as well as in the geodesic deviation, the spin-curvature force adds an additional driving term to the second order system of linear ordinary differential equations satisfied by nearby geodesics. Choosing initial conditions for geodesic motion leads to solutions for which the deviations are entirely due to the spin-curvature force, and one finds that the spinning particle position for a given fixed total spin oscillates roughly within an ellipse in the plane perpendicular to the motion, while the azimuthal motion undergoes similar oscillations plus an additional secular drift which varies with spin orientation.

  4. Deviations from the critical state model observed in niobium

    OpenAIRE

    Gijsbertse, E.A.; Klundert, van de, L.J.M.

    1980-01-01

    The values of the critical current density of niobium slabs, measured with the help of trapezoidal ac magnetic fields are not in agreement with the critical state model. Extensions of this model are suggested to explain the observed deviation.

  5. RELATIVE ENTROPY AND LARGE DEVIATIONS UNDER SUBLINEAR EXPECTATIONS

    Institute of Scientific and Technical Information of China (English)

    Gao Fuqing; Xu Mingzhou

    2012-01-01

    We give a definition of relative entropy with respect to a sublinear expectation and establish large deviation principle for the empirical measures for independent random variables under the sublinear expectation.

  6. A Hybrid Method with Deviational Particles for Spatial Inhomogeneous Plasma

    CERN Document Server

    Yan, Bokai

    2015-01-01

    In this work we propose a Hybrid method with Deviational Particles (HDP) for a plasma modeled by the inhomogeneous Vlasov-Poisson-Landau system. We split the distribution into a Maxwellian part evolved by a grid based fluid solver and a deviation part simulated by numerical particles. These particles, named deviational particles, could be both positive and negative. We combine the Monte Carlo method proposed in \\cite{YC15}, a Particle in Cell method and a Macro-Micro decomposition method \\cite{BLM08} to design an efficient hybrid method. Furthermore, coarse particles are employed to accelerate the simulation. A particle resampling technique on both deviational particles and coarse particles is also investigated and improved. The efficiency is significantly improved compared to a PIC-MCC method, especially near the fluid regime.

  7. Static large deviations of boundary driven exclusion processes

    CERN Document Server

    Farfan, Jonathan

    2009-01-01

    We prove that the stationary measure associated to a boundary driven exclusion process in any dimension satisfies a large deviation principle with rate function given by the quasi potential of the Freidlin and Wentzell theory.

  8. A Note on Standard Deviation and Standard Error

    Science.gov (United States)

    Hassani, Hossein; Ghodsi, Mansoureh; Howell, Gareth

    2010-01-01

    Many students confuse the standard deviation and standard error of the mean and are unsure which, if either, to use in presenting data. In this article, we endeavour to address these questions and cover some related ambiguities about these quantities.

  9. New g-2 measurement deviates further from Standard Model

    CERN Multimedia

    2004-01-01

    "The latest result from an international collaboration of scientists investigating how the spin of a muon is affected as this type of subatomic particle moves through a magnetic field deviates further than previous measurements from theoretical predictions" (1 page).

  10. Analysis of principle deviation of subpixel Zernike moments operator

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    In original Zernike moments subpixel edge operator, ideal step edge model is chosen for calculating four parameters of a pixel point, and therefore principle deviation is caused by edge model. In order to discuss the effect of principle deviation on edge location, sampled edge model is chosen for calculating edge parameters, principle deviation of edge translation l is derived based on Zernike moments edge detection theory, and modified formula of l is given for Zernike moments operator with masks of 5×5 size. Both theory analysis and testing result demonstrate that principle deviation is zero when edge translation l is limited in central pixel of a sampled window. In another case, the modification of l should be considered, which results in edge location accuracy of non-subpixel level for this subpixel edge operator.

  11. Quenched moderate deviations principle for random walk in random environment

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    We derive a quenched moderate deviations principle for the one-dimensional nearest random walk in random environment,where the environment is assumed to be stationary and ergodic.The approach is based on hitting time decomposition.

  12. Large deviation theory to model systems under an external feedback

    OpenAIRE

    Gagliardi, Alessio; Pecchia, Alessandro; Di Carlo, Aldo

    2016-01-01

    In this paper we address the problem of systems under an external feedback. This is performed using a large deviation approach and rate distortion from information theory. In particular we define a lower boundary for the maximum entropy reduction that can be obtained using a feedback apparatus with a well defined accuracy in terms of measurement of the state of the system. The large deviation approach allows also to define a new set of potentials, including information, which similarly to mor...

  13. An Upper Bound of Large Deviations for Capacities

    OpenAIRE

    Xiaomin Cao

    2014-01-01

    Up to now, most of the academic researches about the large deviation and risk theory are under the framework of the classical linear expectations. But motivated by problems of model uncertainties in statistics, measures of risk, and superhedging in finance, sublinear expectations are extensively studied. In this paper, we obtain a type of large deviation principle under the sublinear expectation. This result is a new expression of the Gärtner-Ellis theorem under the sublinear expectations whi...

  14. Large Deviation Theory for a Homogenized and "Corrected" Elliptic ODE

    OpenAIRE

    Bal, Guillaume; Ghanem, Roger; Langmore, Ian

    2010-01-01

    We study a one-dimensional elliptic problem with highly oscillatory random diffusion coefficient. We derive a homogenized solution and a so-called Gaussian corrector. We also prove a "pointwise" large deviation principle (LDP) for the full solution and approximate this LDP with a more tractable form. These results allow one to access the limits of Gaussian correctors. In general, the corrector does not capture the large deviation behavior. Applications to uncertainty quantification are consid...

  15. Deviations from Vegard’s law in ternary III-V alloys

    KAUST Repository

    Murphy, S. T.

    2010-08-03

    Vegard’s law states that, at a constant temperature, the volume of an alloy can be determined from a linear interpolation of its constituent’s volumes. Deviations from this description occur such that volumes are both greater and smaller than the linear relationship would predict. Here we use special quasirandom structures and density functional theory to investigate such deviations for MxN1−xAs ternary alloys, where M and N are group III species (B, Al, Ga, and In). Our simulations predict a tendency, with the exception of AlxGa1−xAs, for the volume of the ternary alloys to be smaller than that determined from the linear interpolation of the volumes of the MAs and BAs binary alloys. Importantly, we establish a simple relationship linking the relative size of the group III atoms in the alloy and the predicted magnitude of the deviation from Vegard’s law.

  16. CALCULATION OF BASIC ENVIRONMENTAL GEOSTROPHIC FLOW AND STATISTICAL STUDY ON TC TRACK AND ITS DEVIATION

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Using the T63L16 analysis data with the resolution of 1.875╳1.875 degree of latitude and longitude obtained from National Meteorological Center (NMC) and the real central position information of tropical cyclone (referred to as TC hereafter) numbered by NMC, the basic environmental geostrophic flow at 126 time levels of 25 TCs in 1996 are calculated. The vertical distribution features of the flows are analyzed. Besides, the deviation of real TC tracks from the flows (referred as steering deviation hereafter, namely, the deviation between the real central position of TC and the position calculated according to the steering flow) is also investigated. The result shows that the steering deviation would be different if the domain used to calculate the steering flow is different. The present paper obtains the optimum domain size to calculate the steering flow. It is found that the steering deviation is related to the velocity of steering flow and the initial latitude and intensity of TC itself, and that TC motion has relationship with the vertical shear structure of environmental geostrophic flow. The result also shows that the optimum steering flow is the deep-layer averaged basic flow from 1000 hPa to 200 hPa. Having the knowledge of these principle and features would help make accurate forecast of TC motion.

  17. Nasal Septal Deviations: A Systematic Review of Classification Systems

    Science.gov (United States)

    Teixeira, Jeffrey; Certal, Victor; Chang, Edward T.; Camacho, Macario

    2016-01-01

    Objective. To systematically review the international literature for internal nasal septal deviation classification systems and summarize them for clinical and research purposes. Data Sources. Four databases (including PubMed/MEDLINE) were systematically searched through December 16, 2015. Methods. Systematic review, adhering to PRISMA. Results. After removal of duplicates, this study screened 952 articles for relevance. A final comprehensive review of 50 articles identified that 15 of these articles met the eligibility criteria. The classification systems defined in these articles included C-shaped, S-shaped, reverse C-shaped, and reverse S-shaped descriptions of the septal deviation in both the cephalocaudal and anteroposterior dimensions. Additional studies reported use of computed tomography and categorized deviation based on predefined locations. Three studies graded the severity of septal deviations based on the amount of deflection. The systems defined in the literature also included an evaluation of nasal septal spurs and perforations. Conclusion. This systematic review ascertained that the majority of the currently published classification systems for internal nasal septal deviations can be summarized by C-shaped or reverse C-shaped, as well as S-shaped or reverse S-shaped deviations in the anteroposterior and cephalocaudal dimensions. For imaging studies, predefined points have been defined along the septum. Common terminology can facilitate future research. PMID:26933510

  18. Nasal Septal Deviations: A Systematic Review of Classification Systems

    Directory of Open Access Journals (Sweden)

    Jeffrey Teixeira

    2016-01-01

    Full Text Available Objective. To systematically review the international literature for internal nasal septal deviation classification systems and summarize them for clinical and research purposes. Data Sources. Four databases (including PubMed/MEDLINE were systematically searched through December 16, 2015. Methods. Systematic review, adhering to PRISMA. Results. After removal of duplicates, this study screened 952 articles for relevance. A final comprehensive review of 50 articles identified that 15 of these articles met the eligibility criteria. The classification systems defined in these articles included C-shaped, S-shaped, reverse C-shaped, and reverse S-shaped descriptions of the septal deviation in both the cephalocaudal and anteroposterior dimensions. Additional studies reported use of computed tomography and categorized deviation based on predefined locations. Three studies graded the severity of septal deviations based on the amount of deflection. The systems defined in the literature also included an evaluation of nasal septal spurs and perforations. Conclusion. This systematic review ascertained that the majority of the currently published classification systems for internal nasal septal deviations can be summarized by C-shaped or reverse C-shaped, as well as S-shaped or reverse S-shaped deviations in the anteroposterior and cephalocaudal dimensions. For imaging studies, predefined points have been defined along the septum. Common terminology can facilitate future research.

  19. Setup deviations in wedged pair irradiation of parotid gland and tonsillar tumors, measured with an electronic portal imaging device

    International Nuclear Information System (INIS)

    The first aim of this study was to quantify estimated translational setup deviations of patients treated with a wedged pair of oblique beams for parotid gland and tonsillar tumors, using portal imaging. The second aim was to design an off-line setup verification procedure, to improve the setup accuracy, if necessary. Thirty-one patients were treated with two conformal fields (anterior-oblique and posterior-oblique). The patients were immobilized with a head cast. For the last 10 patients, the rigidity of the cast was improved while, in addition, wax molds with metal markers were placed into the outer ear for image correlation. Portal images were acquired about weekly. Setup deviations were analyzed, using anatomical structures and, when available, metal markers for image matching. The consistency of the deviations was determined by the correlation between deviations in the cranio-caudal direction, as measured from both beams. When the deviations were consistent, the translational setup deviation during a treatment session could be described by a three-dimensional (3D) vector. A setup verification procedure was designed using a computer simulation. The statistics of the 3D setup deviations were used as input. The output consisted of the resulting setup accuracy and workload (i.e., the number of setup corrections and portal images). Using the anatomical structures for image correlation, the deviations in the cranio-caudal direction were not correlated, either for the old or the improved cast. However, by using the metal markers, the deviations were correlated and a 3D analysis could be performed. The standard deviations, averaged over the three directions, were equal to 1.8 and 1.4 mm for the distribution of systematic and random deviations, respectively. Application of a setup verification procedure, with 0.7 corrections on the average per patient, could potentially reduce the percentage of 3D systematic deviations larger than 4 mm from 30 to 2%. It can be concluded

  20. Deviations from Newton's law in supersymmetric large extra dimensions

    Science.gov (United States)

    Callin, P.; Burgess, C. P.

    2006-09-01

    Deviations from Newton's inverse-squared law at the micron length scale are smoking-gun signals for models containing supersymmetric large extra dimensions (SLEDs), which have been proposed as approaches for resolving the cosmological constant problem. Just like their non-supersymmetric counterparts, SLED models predict gravity to deviate from the inverse-square law because of the advent of new dimensions at sub-millimeter scales. However SLED models differ from their non-supersymmetric counterparts in three important ways: (i) the size of the extra dimensions is fixed by the observed value of the dark energy density, making it impossible to shorten the range over which new deviations from Newton's law must be seen; (ii) supersymmetry predicts there to be more fields in the extra dimensions than just gravity, implying different types of couplings to matter and the possibility of repulsive as well as attractive interactions; and (iii) the same mechanism which is purported to keep the cosmological constant naturally small also keeps the extra-dimensional moduli effectively massless, leading to deviations from general relativity in the far infrared of the scalar-tensor form. We here explore the deviations from Newton's law which are predicted over micron distances, and show the ways in which they differ and resemble those in the non-supersymmetric case.

  1. Large Deviations for the Boundary Driven Symmetric Simple Exclusion Process

    Energy Technology Data Exchange (ETDEWEB)

    Bertini, L. [Universita di Roma La Sapienza, Dipartimento di Matematica (Italy)], E-mail: bertini@mat.uniroma1.it; De Sole, A. [MIT, Department of Mathematics (United States)], E-mail: desole@alum.mit.edu; Gabrielli, D. [Universita di Roma La Sapienza, Dipartimento di Matematica (Italy)], E-mail: gabriell@univaq.it; Jona-Lasinio, G. [Universita di Roma La Sapienza, Dipartimento di Fisica and INFN (Italy)], E-mail: jona@roma1.infn.it; Landim, C. [IMPA (Brazil)], E-mail: landim@impa.br

    2003-08-15

    The large deviation properties of equilibrium (reversible) lattice gases are mathematically reasonably well understood. Much less is known in nonequilibrium, namely for nonreversible systems. In this paper we consider a simple example of a nonequilibrium situation, the symmetric simple exclusion process in which we let the system exchange particles with the boundaries at two different rates. We prove a dynamical large deviation principle for the empirical density which describes the probability of fluctuations from the solutions of the hydrodynamic equation. The so-called quasi potential, which measures the cost of a fluctuation from the stationary state, is then defined by a variational problem for the dynamical large deviation rate function. By characterizing the optimal path, we prove that the quasi potential can also be obtained from a static variational problem introduced by Derrida, Lebowitz, and Speer.

  2. Deviations From Newton's Law in Supersymmetric Large Extra Dimensions

    CERN Document Server

    Callin, P

    2006-01-01

    Deviations from Newton's Inverse-Squared Law at the micron length scale are smoking-gun signals for models containing Supersymmetric Large Extra Dimensions (SLEDs), which have been proposed as approaches for resolving the Cosmological Constant Problem. Just like their non-supersymmetric counterparts, SLED models predict gravity to deviate from the inverse-square law because of the advent of new dimensions at sub-millimeter scales. However SLED models differ from their non-supersymmetric counterparts in three important ways: (i) the size of the extra dimensions is fixed by the observed value of the Dark Energy density, making it impossible to shorten the range over which new deviations from Newton's law must be seen; (ii) supersymmetry predicts there to be more fields in the extra dimensions than just gravity, implying different types of couplings to matter and the possibility of repulsive as well as attractive interactions; and (iii) the same mechanism which is purported to keep the cosmological constant natu...

  3. Why historical east deviation experiments are so difficult to perform?

    Science.gov (United States)

    Darbois Texier, Baptiste; Cohen, Caroline; Quere, David; Clanet, Christophe

    2012-11-01

    From the 17th to the 19th century, a big deal was to prove Earth rotation existence. For this purpose, numerous experimental physicists from Borelli in 1668 to Reich in 1832 tried to measure an eastward deviation of a falling sphere. Reich performed 106 falling experiments on a 158.5 m deep mine pit. The mean eastward deviation of its experiments is 2.8 cm. This value corresponds exactly with the theoretical one predicted by Laplace and Gauss expression at Freiberg latitude where experiments were conducted. While Reich took extreme precautions to perform its experiments, the dispersion on its results is very important. Actually aerodynamic lift forces on a smooth sphere made its free fall non perfectly straight. We understand Reich's results dispersion considering fluctuating lift forces intensity on a smooth sphere at those Reynolds numbers (Re ~104 -105). This study provides a criterion above which we can distinguish between lift force and Coriolis deviation during a free fall experiment.

  4. Mean-deviation analysis in the theory of choice.

    Science.gov (United States)

    Grechuk, Bogdan; Molyboha, Anton; Zabarankin, Michael

    2012-08-01

    Mean-deviation analysis, along with the existing theories of coherent risk measures and dual utility, is examined in the context of the theory of choice under uncertainty, which studies rational preference relations for random outcomes based on different sets of axioms such as transitivity, monotonicity, continuity, etc. An axiomatic foundation of the theory of coherent risk measures is obtained as a relaxation of the axioms of the dual utility theory, and a further relaxation of the axioms are shown to lead to the mean-deviation analysis. Paradoxes arising from the sets of axioms corresponding to these theories and their possible resolutions are discussed, and application of the mean-deviation analysis to optimal risk sharing and portfolio selection in the context of rational choice is considered.

  5. The missing ingredient in effective-medium theories: Standard deviations

    CERN Document Server

    Bohren, Craig F; Lakhtakia, Akhlesh

    2012-01-01

    Effective-medium theories for electromagnetic constitutive parameters of particulate composite materials are theories of averages. Standard deviations are absent because of the lack of rigorous theories. But ensemble averages and standard deviations can be calculated from a rigorous theory of reflection by planar multilayers. Average reflectivities at all angles of incidence and two orthogonal polarization states for a multilayer composed of two kinds of electrically thin layers agree well with reflectivities for a single layer with the same overall thickness and a volume-weighted average of the relative permittivities of these two components. But the relative standard deviation can be appreciable depending on the angle of incidence and the polarization state of the incident illumination, and increases with increasing difference between the constitutive parameters of the two layers. This suggests that average constitutive parameters obtained from effective-medium theories do not have uniform validity for all ...

  6. Spin-geodesic deviations in the Kerr spacetime

    Science.gov (United States)

    Bini, D.; Geralico, A.

    2011-11-01

    The dynamics of extended spinning bodies in the Kerr spacetime is investigated in the pole-dipole particle approximation and under the assumption that the spin-curvature force only slightly deviates the particle from a geodesic path. The spin parameter is thus assumed to be very small and the back reaction on the spacetime geometry neglected. This approach naturally leads to solve the Mathisson-Papapetrou-Dixon equations linearized in the spin variables as well as in the deviation vector, with the same initial conditions as for geodesic motion. General deviations from generic geodesic motion are studied, generalizing previous results limited to the very special case of an equatorial circular geodesic as the reference path.

  7. Spin-geodesic deviations in the Kerr spacetime

    CERN Document Server

    Bini, Donato

    2014-01-01

    The dynamics of extended spinning bodies in the Kerr spacetime is investigated in the pole-dipole particle approximation and under the assumption that the spin-curvature force only slightly deviates the particle from a geodesic path. The spin parameter is thus assumed to be very small and the back reaction on the spacetime geometry neglected. This approach naturally leads to solve the Mathisson-Papapetrou-Dixon equations linearized in the spin variables as well as in the deviation vector, with the same initial conditions as for geodesic motion. General deviations from generic geodesic motion are studied, generalizing previous results limited to the very special case of an equatorial circular geodesic as the reference path.

  8. Follicle and endocrine dynamics during experimental follicle deviation in mares.

    Science.gov (United States)

    Ginther, O J; Meira, C; Beg, M A; Bergfelt, D R

    2002-09-01

    Deviation during a follicular wave in mares begins when the largest follicle (F1) reaches a mean diameter of 22.5 mm and is characterized by continued growth of F1 to become the dominant follicle and regression of F2 to become the largest subordinate follicle. In the present study, F1 was ablated at the expected beginning of deviation (Hour 0) to provide a reference point for characterizing the intrafollicular changes preceding experimental deviation between F2 and F3. Diameters and concentrations of follicular fluid factors in F2 and F3 were determined in F1-ablated mares at Hours 0, 12, 24, 48, or 72 (n = 8 mares/group). Circulating FSH concentrations were greater (P 0.1) to the diameter of F1 and FSH concentration at Hour 0, respectively. A differential change between F2 and F3 was not detected in follicular fluid concentrations of estradiol, inhibin-A, and activin-A by the beginning of experimental deviation. However, estradiol was higher in F2 at Hours 0 and 12 and inhibin-A was higher in F2 throughout the experiment, and both factors could have been involved in experimental deviation. Free insulin-like growth factor-1 (IGF-1) increased (P < 0.05) in F2 beginning at Hour 12 and was higher (P < 0.05) in F2 than in F3 by the beginning of experimental deviation. Temporally, this result indicated that intrafollicular IGF-1 was involved in conversion of F2 from a destined subordinate follicle to a dominant follicle. PMID:12193395

  9. Deviation of eyes and head in acute cerebral stroke

    Directory of Open Access Journals (Sweden)

    Ilg UJ

    2006-06-01

    Full Text Available Abstract Background It is a well-known phenomenon that some patients with acute left or right hemisphere stroke show a deviation of the eyes (Prévost's sign and head to one side. Here we investigated whether both right- and left-sided brain lesions may cause this deviation. Moreover, we studied the relationship between this phenomenon and spatial neglect. In contrast to previous studies, we determined not only the discrete presence or absence of eye deviation with the naked eye through clinical inspection, but actually measured the extent of horizontal eye-in-head and head-on-trunk deviation. In further contrast, measurements were performed early after stroke onset (1.5 days on average. Methods Eye-in-head and head-on-trunk positions were measured at the bedside in 33 patients with acute unilateral left or right cerebral stroke consecutively admitted to our stroke unit. Results Each single patient with spatial neglect and right hemisphere lesion showed a marked deviation of the eyes and the head to the ipsilesional, right side. The average spontaneous gaze position in this group was 46° right, while it was close to the saggital body midline (0° in the groups with acute left- or right-sided stroke but no spatial neglect as well as in healthy subjects. Conclusion A marked horizontal eye and head deviation observed ~1.5 days post-stroke is not a symptom associated with acute cerebral lesions per se, nor is a general symptom of right hemisphere lesions, but rather is specific for stroke patients with spatial neglect. The evaluation of the patient's horizontal eye and head position thus could serve as a brief and easy way helping to diagnose spatial neglect, in addition to the traditional paper-and-pencil tests.

  10. Sample-path Large Deviations in Credit Risk

    CERN Document Server

    Leijdekker, Vincent; Spreij, Peter

    2009-01-01

    The event of large losses plays an important role in credit risk. As these large losses are typically rare, and portfolios usually consist of a large number of positions, large deviation theory is the natural tool to analyze the tail asymptotics of the probabilities involved. We first derive a sample-path large deviation principle (LDP) for the portfolio's loss process, which enables the computation of the logarithmic decay rate of the probabilities of interest. In addition, we derive exact asymptotic results for a number of specific rare-event probabilities, such as the probability of the loss process exceeding some given function.

  11. A large deviation principle for join the shortest queue

    OpenAIRE

    Puhalskii, Anatolii A.; Vladimirov, Alexander A.

    2005-01-01

    We consider a join-the-shortest-queue model which is as follows. There are $K$ single FIFO servers and $M$ arrival processes. The customers from a given arrival process can be served only by servers from a certain subset of all servers. The actual destination is the server with the smallest weighted queue length. The arrival processes are assumed to obey a large deviation principle while the service is exponential. A large deviation principle is established for the queue-length process. The a...

  12. Large Deviations for Multiscale Diffusions via Weak Convergence Methods

    CERN Document Server

    Dupuis, Paul

    2010-01-01

    We study the large deviations principle for locally periodic stochastic differential equations with small noise and fast oscillating coefficients. There are three possible regimes depending on how fast the intensity of the noise goes to zero relative to the homogenization parameter. We use weak convergence methods which provide convenient representations for the action functional for all three regimes. Along the way we study weak limits of related controlled SDEs with fast oscillating coefficients and derive, in some cases, a control that nearly achieves the large deviations lower bound at the prelimit level. This control is useful for designing efficient importance sampling schemes for multiscale diffusions driven by small noise.

  13. Understanding positive and negative deviations in polarity of ionic liquid mixtures by pseudo-solvent approach.

    Science.gov (United States)

    Beniwal, Vijay; Kumar, Anil

    2016-08-24

    Physico-chemical properties of liquid mixtures in general display large deviations from linear behaviour, arising out of complex specific and non-specific intermolecular interactions. The polarity of liquid mixtures displaying large positive and negative deviations can be minimized and linear mixing can be achieved in liquids using a pseudo-solvent methodology. The work described herein is designed to investigate the influence of different physical parameters on the linear pseudo-solvent composition in ionic liquid mixtures. For this purpose, we have determined the deviations from linearity, ΔE values (defined as given by ) for binary mixtures of a variety of ionic liquids, including two molecular solvents, DMSO and formamide. Firstly, the investigations were carried out in three 1-butyl-3-methylimidazolium cation based aprotic ionic liquids and the roles of anionic structure and hydrogen bond acceptor basicities (β values) of the ionic liquids were determined. The influence of the cationic structure, i.e., the hydrogen bond donor acidity (α values) and non-associative nature of the ionic liquids, was determined using C2-methylated analogs, 1-butyl-2,3-dimethylimidazolium cation based ionic liquids. The role of the protic nature of ionic liquids was studied in two protic ionic liquids, viz., 1-methylimidazolium formate and 1-methylimidazolium acetate. The effects of the temperature, pseudo-solvent structure and solvatochromic probe structure on the ΔE values were also explored. PMID:27523572

  14. Developmental aspects of the deviated nose -a verwoerd study-

    OpenAIRE

    Grewal, DS; Irani, Dinaz K

    1999-01-01

    In childhood functional, infectious, aesthetic and social problems can result from a deviated septum and nose, further research on the anatomic development, the mechanism of growth, and the process of wound healing is needed to develop surgical techniques that not only correct the present problem but also ensure the further normal growth of the septum and nose.

  15. Large Deviation Analysis of Rapid Onset of Rain Showers

    OpenAIRE

    Wilkinson, Michael

    2016-01-01

    Rainfall from ice-free cumulus clouds requires collisions of large numbers of microscopic droplets to create every raindrop. The onset of rain showers can be surprisingly rapid, much faster than the mean time required for a single collision. Large-deviation theory is used to explain this observation.

  16. 49 CFR 110.120 - Deviation from this part.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Deviation from this part. 110.120 Section 110.120 Transportation Other Regulations Relating to Transportation PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION HAZARDOUS MATERIALS AND OIL TRANSPORTATION HAZARDOUS MATERIALS PUBLIC SECTOR TRAINING AND PLANNING...

  17. A Positional Deviation Sensor for Training of Robots

    Directory of Open Access Journals (Sweden)

    Fredrik Dessen

    1988-04-01

    Full Text Available A device for physically guiding a robot manipulator through its task is described. It consists of inductive, contact-free positional deviation sensors. The sensor will be used in high performance sensory control systems. The paper describes problems concerning multi-dimensional, non-linear measurement functions and the design of the servo control system.

  18. The one-shot deviation principle for sequential rationality

    DEFF Research Database (Denmark)

    Hendon, Ebbe; Whitta-Jacobsen, Hans Jørgen; Sloth, Birgitte

    1996-01-01

    We present a decentralization result which is useful for practical and theoretical work with sequential equilibrium, perfect Bayesian equilibrium, and related equilibrium concepts for extensive form games. A weak consistency condition is sufficient to obtain an analogy to the well known One-Stage......-Stage-Deviation Principle for subgame perfect equilibrium...

  19. Generalized deviation equations and entanglement first law for Rotating BTZ

    CERN Document Server

    Ghosh, Avirup

    2016-01-01

    The change in Holographic entanglement entropy (HEE) for small fluctuations about pure AdS is given by a perturbative expansion of the area functional in terms of the change in the bulk metric and the embedded extremal surface. However it is known that change in the embedding appear at second order or higher. In this paper we show that these changes in the embedding can be systematically calculated in the 2+1 dimensional case by accounting for the deviation of the spacelike geodesics between a spacetime and perturbations over it. Here we consider rotating BTZ as perturbation over $AdS_3$ and study deviations of spacelike geodesics in them. We argue that these deviations arise naturally as solutions of a "generalized geodesic deviation equation". Using this we perturbatively calculate the changes in HEE upto second order, for rotating BTZ. This expression matches with the small system size expansion of the change in HEE obtained by HRT (Hubeny, Rangamani and Takayanagi) proposal for rotating BTZ. We also give ...

  20. Large Deviation Analysis of Rapid Onset of Rain Showers.

    Science.gov (United States)

    Wilkinson, Michael

    2016-01-01

    Rainfall from ice-free cumulus clouds requires collisions of large numbers of microscopic droplets to create every raindrop. The onset of rain showers can be surprisingly rapid, much faster than the mean time required for a single collision. Large-deviation theory is used to explain this observation. PMID:26799046

  1. The Effect of Type of Punishment on Resistance to Deviation.

    Science.gov (United States)

    LaVoie, Joseph C.

    The comparative effectiveness of an aversive stimulus, withholding of resources, withdrawal of love and reasoning, when used alone and combined with praise, was assessed in the standard laboratory punishment paradigm using 120 first and second graders as subjects. Resistance to deviation was used as the measure of punishment effectiveness. Sex of…

  2. Estimation of Transition Probabilities Using Median Absolute Deviations

    OpenAIRE

    Kim, C. S.; Schaible, Glenn D.

    1988-01-01

    The probability-constrained minimum absolute deviations (MAD) estimator appears to be superior to the probability-constrained quadratic programming estimator in estimating transition probabilities with limited aggregate time series data Futhermore, one can reduce the number of columns in the probability-constrained MAD simplex tableau by adopting the median property

  3. International asset pricing under segmentation and PPP deviations

    NARCIS (Netherlands)

    I. Chaieb; V. Errunza

    2007-01-01

    We analyze the impact of both purchasing power parity (PPP) deviations and market segmentation on asset pricing and investor's portfolio holdings. The freely traded securities command a world market risk premium and an inflation risk premium. The securities that can be held by only a subset of inves

  4. Semiparametric Bernstein-von Mises for the error standard deviation

    NARCIS (Netherlands)

    R. de Jonge; H. van Zanten

    2013-01-01

    We study Bayes procedures for nonparametric regression problems with Gaussian errors, giving conditions under which a Bernstein-von Mises result holds for the marginal posterior distribution of the error standard deviation. We apply our general results to show that a single Bayes procedure using a h

  5. Robust Confidence Interval for a Ratio of Standard Deviations

    Science.gov (United States)

    Bonett, Douglas G.

    2006-01-01

    Comparing variability of test scores across alternate forms, test conditions, or subpopulations is a fundamental problem in psychometrics. A confidence interval for a ratio of standard deviations is proposed that performs as well as the classic method with normal distributions and performs dramatically better with nonnormal distributions. A simple…

  6. Large systematic deviations in the haptic perception of parallelity

    NARCIS (Netherlands)

    Kappers, A.M.L.

    1999-01-01

    Recently, Kappers and Koenderink (1999 Perception 28 781-795) showed that what subjects haptically perceive as parallel often deviates greatly from what is actually physically parallel. In their experiment, subjects had to rotate a test bar in such a way that it felt as though it was parallel to a r

  7. Deviation from the superparamagnetic behaviour of fine-particle systems

    CERN Document Server

    Malaescu, I

    2000-01-01

    Studies concerning superparamagnetic behaviour of fine magnetic particle systems were performed using static and radiofrequency measurements, in the range 1-60 MHz. The samples were: a ferrofluid with magnetite particles dispersed in kerosene (sample A), magnetite powder (sample B) and the same magnetite powder dispersed in a polymer (sample C). Radiofrequency measurements indicated a maximum in the imaginary part of the complex magnetic susceptibility, for each of the samples, at frequencies with the magnitude order of tens of MHz, the origin of which was assigned to Neel-type relaxation processes. The static measurements showed a Langevin-type dependence of magnetisation M and of susceptibility chi, on the magnetic field for sample A. For samples B and C deviations from this type of dependence were found. These deviations were analysed qualitatively and explained in terms of the interparticle interactions, dispersion medium influence and surface effects.

  8. Geodesics and Geodesic Deviation for Impulsive Gravitational Waves

    CERN Document Server

    Steinbauer, R

    1998-01-01

    The geometry of impulsive pp-waves is explored via the analysis of the geodesic and geodesic deviation equation using the distributional form of the metric. The geodesic equation involves formally ill-defined products of distributions due to the nonlinearity of the equations and the presence of the Dirac delta distribution. Thus, strictly speaking, it cannot be treated within Schwartz's linear theory of distributions. To cope with this problem we proceed by first regularizing the delta singularity, then solving the regularized equation within classical smooth functions and, finally, obtaining a distributional, regularization-idependent limit as solution to the original problem. We also treat the Jacobi equation which, despite being linear in the deviation vector field, involves even more delicate singular expressions, like the ``square'' of the delta distribution. Again the same regularization procedure provides us with a perfectly well behaved smooth regularization and a regularization-independent distributi...

  9. Large deviations for stochastic flows and their applications

    Institute of Scientific and Technical Information of China (English)

    GAO; Fuqing(

    2001-01-01

    [1]Yoshida, N., A large deviation principle for (r,p)-capacities on the Wiener space, Proba. Th. Rel. Fields, 1993, 94:473-488.[2]Gao, F. Q., Large deviations of (r,p)-capacities for diffusion processes, Advances in Math. (in Chinese), 1996, 25:500-509.[3]Millet, A., Nualart, D., Sanz, M., Large deviations for a class of anticipating stochastic differential equations, Ann.Prob.. 1993, 20: 1902-1931.[4]Millet, A., Nualart, D., Sans, M., Composition of large deviation principles and applications, in Stochastic Analysis (ed.Mayer, E. ), San Diego: Academic Press, 1991, 383-395.[5]Ocone, D., Pardoux, E., A generalized Ito-Ventzell formula, Applications to a class of anticipating stochastic differentialequations, Ann. Inst. Poincaré, Sect. B, 1989, 25: 39-71.[6]Malliavin, P., Nualart, D., Quasi sure analysis of stochastic flows and Banach space valued smooth functionals on the Wiener space, J. Funct. Anal., 1993, 112: 287-317.[7]Huang, Z., Ren, J. , Quasi sure stochastic flows, Stoch. Stoch. Rep. , 1990, 33: 149-157.[8]Gao, E. Q., Large deviations for diffusion processes in Hslder norm, Advances in Math. (in Chinese), 1997, 26: 147-158.[9]Arous, B. G. , Ledoux, M., Grandes déviations sur la déviations de Freidlin-Wentzell en norme holderienne, 1994, Lecr.Notes in Math. , 1994, 987: 1583.[10]Baldi, P. , Sanz, M. , Une remarque sur la théorie des grandes deviations, Lect. Notes Math., 1991, 1485: 345-348.[11]Airault, H., Malliavin, P., Intégration géometrique sur l'espace de Wiener, Bull. Sci. Math., 1988, 112: 3-52.[12]Ikeda, N. , Watanabe, S., Stochastic Differential Equations and Diffusion Processes, 2nd ed., Amsterdam-Kodansha-Tokyo:North-Holland, 1988.[13]Malliavin, P., Stochastic Analysis, Grundlehren der Mathematischen Wissenschaften 313, Berlin: Springer-Verlag, 1997.[14]Brzezniak, Z., Elworthy, K. D., Stochastic flows of diffeomorphism. In Stochastic Analysis and Applications (eds. Davies,I. M.. Truman

  10. Deviations in delineated GTV caused by artefacts in 4DCT

    DEFF Research Database (Denmark)

    Persson, Gitte Fredberg; Nygaard, Ditte Eklund; Brink, Carsten;

    2010-01-01

    BACKGROUND AND PURPOSE: Four-dimensional computed tomography (4DCT) is used for breathing-adapted radiotherapy planning. Irregular breathing, large tumour motion or interpolation of images can cause artefacts in the 4DCT. This study evaluates the impact of artefacts on gross tumour volume (GTV......) size. MATERIAL AND METHODS: In 19 4DCT scans of patients with peripheral lung tumours, GTV was delineated in all bins. Variations in GTV size between bins in each 4DCT scan were analysed and correlated to tumour motion and variations in breathing signal amplitude and breathing signal period. End......-expiration GTV size (GTVexp) was considered as reference for GTV size. Intra-session delineation error was estimated by re-delineation of GTV in eight of the 4DCT scans. RESULTS: In 16 of the 4DCT scans the maximum deviations from GTVexp were larger than could be explained by delineation error. The deviations...

  11. Large deviation function of the partially asymmetric exclusion process.

    Science.gov (United States)

    Lee, D S; Kim, D

    1999-06-01

    The large deviation function obtained recently by Derrida and Lebowitz [Phys. Rev. Lett. 80, 209 (1998)] for the totally asymmetric exclusion process is generalized to the partially asymmetric case in the scaling limit. The asymmetry parameter rescales the scaling variable in a simple way. The finite-size corrections to the universal scaling function and the universal cumulant ratio are also obtained to the leading order. PMID:11969632

  12. Large deviations of inverse processes with nonlinear scalings

    OpenAIRE

    Duffield, N. G.; Whitt, W.

    1998-01-01

    We show, under regularity conditions, that a nonnegative nondecreasing real-valued stochastic process satisfies a large deviation principle (LDP) with nonlinear scaling if and only if its inverse process does. We also determine how the associated scaling and rate functions must be related. A key condition for the LDP equivalence is for the composition of two of the scaling functions to be regularly varying with nonnegative index. We apply the LDP equivalence to develop equiv...

  13. Trends and Deviations in Federal, State and Local Finance

    OpenAIRE

    Jeffrey S. Zax

    1986-01-01

    This paper contains a descriptive analysis o+ real per capita annual revenues, expenditures, deficits, debt levels and capital expenditures for federal, state and local government finance in the United States for the rears 1952-83. It summarizes each time series as a deterministic trend and an ARIM characterization of the deviations around trend. These summaries demonstrate that civilian capital outlays are falling at an accelerating pace in ail levels of government; federal government expend...

  14. Detection of Deviations in Mobile Applications Network Behavior

    OpenAIRE

    Chekina, L.; Mimran, D.; Rokach, L.; Elovici, Y.; Shapira, B.

    2012-01-01

    In this paper a novel system for detecting meaningful deviations in a mobile application's network behavior is proposed. The main goal of the proposed system is to protect mobile device users and cellular infrastructure companies from malicious applications. The new system is capable of: (1) identifying malicious attacks or masquerading applications installed on a mobile device, and (2) identifying republishing of popular applications injected with a malicious code. The detection is performed...

  15. Diagram of measurement series elements deviation from local linear approximations

    OpenAIRE

    Lande, D. V.; Snarskii, A. A.

    2009-01-01

    Method for detection and visualization of trends, periodicities, local peculiarities in measurement series (dL-method) based on DFA technology (Detrended fluctuation analysis) is proposed. The essence of the method lies in reflecting the values of absolute deviation of measurement accumulation series points from the respective values of linear approximation. It is shown that dL-method in some cases allows better determination of local peculiarities than wavelet-analysis. Easy-to-realize appro...

  16. Large deviations of ergodic counting processes: a statistical mechanics approach

    OpenAIRE

    Budini, Adrian A.

    2011-01-01

    The large-deviation method allows to characterize an ergodic counting process in terms of a thermodynamic frame where a free energy function determines the asymptotic non-stationary statistical properties of its fluctuations. Here, we study this formalism through a statistical mechanics approach, i.e., with an auxiliary counting process that maximizes an entropy function associated to the thermodynamic potential. We show that the realizations of this auxiliary process can be obtained after ap...

  17. Predictive visual tracking based on least absolute deviation estimation

    Institute of Scientific and Technical Information of China (English)

    Rongtai Cai; Yanjie Wang

    2008-01-01

    To cope with the occlusion and intersection between targets and the environment, location prediction is employed in the visual tracking system. Target trace is fitted by sliding subsection polynomials based on least absolute deviation (LAD) estimation, and the future location of target is predicted with the fitted trace. Experiment results show that the proposed location prediction algorithm based on LAD estimation has significant robustness advantages over least square (LS) estimation, and it is more effective than LS-based methods in visual tracking.

  18. Quantifying prosthetic gait deviation using simple outcome measures

    Science.gov (United States)

    Kark, Lauren; Odell, Ross; McIntosh, Andrew S; Simmons, Anne

    2016-01-01

    AIM: To develop a subset of simple outcome measures to quantify prosthetic gait deviation without needing three-dimensional gait analysis (3DGA). METHODS: Eight unilateral, transfemoral amputees and 12 unilateral, transtibial amputees were recruited. Twenty-eight able-bodied controls were recruited. All participants underwent 3DGA, the timed-up-and-go test and the six-minute walk test (6MWT). The lower-limb amputees also completed the Prosthesis Evaluation Questionnaire. Results from 3DGA were summarised using the gait deviation index (GDI), which was subsequently regressed, using stepwise regression, against the other measures. RESULTS: Step-length (SL), self-selected walking speed (SSWS) and the distance walked during the 6MWT (6MWD) were significantly correlated with GDI. The 6MWD was the strongest, single predictor of the GDI, followed by SL and SSWS. The predictive ability of the regression equations were improved following inclusion of self-report data related to mobility and prosthetic utility. CONCLUSION: This study offers a practicable alternative to quantifying kinematic deviation without the need to conduct complete 3DGA. PMID:27335814

  19. PROBABILISTIC MEASURES FOR INTERESTINGNESS OF DEVIATIONS – A SURVEY

    Directory of Open Access Journals (Sweden)

    Adnan Masood

    2013-03-01

    Full Text Available Association rule mining has long being plagued with the problem of finding meaningful, actionable knowledge from the large set of rules. In this age of data deluge with modern computing capabilities, we gather, distribute, and store information in vast amounts from diverse data sources. With such data profusion, the core knowledge discovery problem becomes efficient data retrieval rather than simply finding heaps of information. The most common approach is to employ measures of rule interestingness to filter the results of the association rule generation process. However, study of literature suggests that interestingness is difficult to define quantitatively and can be best summarized as, a record or pattern is interesting if it suggests a change in an established model. Almost twenty years ago, Gregory Piatetsky-Shapiro and Christopher J. Matheus, in their paper, “The Interestingness of Deviations,” argued that deviations should be grouped together in a finding and that the interestingness of a finding is the estimated benefit from a possible action connected to it. Since then, this field has progressed and new data mining techniques have been introduced to address the subjective, objective, and semantic interestingness measures. In this brief survey, we review the current state of literature around interestingness of deviations, i.e. outliers with specific interest around probabilistic measures using Bayesian belief networks.

  20. An analysis of anatomic landmark mobility and setup deviations in radiotherapy for lung cancer

    International Nuclear Information System (INIS)

    Purpose: To identify thoracic structures that exhibit little internal motion during irradiation and to determine setup variations in patients with lung cancer. Methods and Materials: Intrafractional images were generated with an electronic portal-imaging device from the AP fields of 10 patients, during several fractions. To determine the intrafractional mobility of thoracic structures, visible structures were contoured in every image and matched with a reference image by means of a cross-correlation algorithm. Setup variations were determined by comparing portal images with the digitized simulator films using the stable structures as landmarks. Results: Mobility was limited in the lateral direction for the trachea, thoracic wall, paraspinal line, and aortic notch, and in the craniocaudal direction for the clavicle, aortic notch, and thoracic wall. Analysis of patient setup revealed random deviations of 2.0 mm (1 SD) in the lateral direction and 2.8 mm in the craniocaudal direction, while the systematic deviations were 2.5 and 2.0 mm (1 SD) respectively. Conclusions: We have identified thoracic structures that exhibit little internal motion in the frontal plane, and recommend that these structures be used for verifying patient setup during radiotherapy. The daily variation in the setup of lung cancer patients at our center appears to be acceptable

  1. Estimation of random deviation effect of pipeline geometry on hydraulic nonuniformity at reactor inlet

    International Nuclear Information System (INIS)

    Approximate formula enabling to evaluate hydraulic nonuniformity at reactor core inlet is given. The mentioned nonuniformity depends on 13 structural parameters of reactor hydraulic pipeline - from branch pipes up to the header. Dispersion technique for evaluation of the effect of structural parameter deviation on the spread of resulting nonuniformity is applied to the dependence. Coefficients of the effect have been obtained. Calculation has been conducted for the example, the minimal flow rate in reactor channel has been evaluated as 0.65±0.14

  2. Determining Statistically Significant Deviations from a Model Crater Production Function for Estimating Resurfacing Events

    Science.gov (United States)

    Weaver, B. P.; Hilbe, J. M.; Robbins, S. J.; Plesko, C. S.; Riggs, J. D.

    2015-05-01

    Many crater analysts will search for deviations of observed crater population data from model crater populations and treat those deviations as a modification event - usually resurfacing. We will discuss how to assign confidences for these deviations.

  3. A study on the deviation aspects of the poem “The Eightieth Stage”

    Directory of Open Access Journals (Sweden)

    Soghra Salmaninejad Mehrabadi

    2016-02-01

    Full Text Available Abstract  One of the methods of literature review is addressing the literary forms that deeply attracted formalists’ attention. Formalists emphasizes certain shapes and forms and methods of literary language. In their view, the task of literature and art is not making known but representing the elements in the realm of art. So, for creating an outstanding work, novelty is not just important, but modes of expression can show a new dimension of the world to audience.   Shklovsky raised for the first time the term “de familiarization”. In his opinion, art renews sensory perception and transforms the familiar rules and seemingly enduring structures of reality. He believes defamiliarization is seeing things out of their natural context. According to Leach, the two usual methods to distinguish the general language from the language of arts are rule-increasing and rule-decreasing.   In deviation occurs a resurrection of words and the author creates a double pleasure through language games in contact with the audience. Imagery, music and syntax can produce a kind of defamiliarization.   Akhavan in the poem “The Eightieth Stag e ” has used a variety of deviations. The first is in the name of poetry. In this paper, the norms of lexical, semantic and stylistic in the poem “Eightieth Stage” is checked.   Lexical deviation Sartre says the poet does not use the words, but sometimes words would use the new syntax. Akhavan in the words sometimes making terms such as “mardestan (masculinity, faramoshzar (plains of oblivion, gandomand (Robust, golazin (inflorescence, parhib (deception and ...” and sometimes new compounds alters magically the effect of poetry. His compounds like talaei makhmal avayan (golden voices and velvet, pak ayin (clean rituals, malmalin dastar (silver turban, marde mardestan (men of masculinity, rakhshe rakhshande (the brilliant horse and…" makes illustration that in some of synergistic base has helped to the poet

  4. Deviations in Tribimaximal Mixing From Sterile Neutrino Sector

    CERN Document Server

    Dev, S; Gautam, Radha Raman

    2016-01-01

    We explore the possibility of generating a non-zero $U_{e3}$ element of the neutrino mixing matrix from tribimaximal neutrino mixing by adding a light sterile neutrino to the active neutrinos. Small active-sterile mixing can provide the necessary deviation from tribimaximal mixing to generate a non-zero $\\theta_{13}$ and atmospheric mixing $\\theta_{23}$ different from maximal. Assuming no CP-violation, we study the phenomenological impact of sterile neutrinos in the context of current neutrino oscillation data. The tribimaximal pattern is broken in such a manner that the second column of tribimaximal mixing remains intact in the neutrino mixing matrix.

  5. Frequency deviations and generation scheduling in the nordic system

    DEFF Research Database (Denmark)

    Li, Zhongwei; Samuelsson, Olaf; Garcia-Valle, Rodrigo

    2011-01-01

    High penetration of variable generation such as wind power increases the demands on frequency control. The same applies to island operation and in particular if this involves variable generation, which is planned at the Danish island Bornholm. While it is obvious that the frequency control need to...... the frequency deviations and hourly scheduled generation. A simple model is given to reproduce these deterministic frequency variations. Simulations indicate that smaller system size as is typical for island operation does not necessarily increase these frequency variations provided load, generation...

  6. Brief Analysis of the Semantic Deviation in Oliver Twist

    Institute of Scientific and Technical Information of China (English)

    黄二靓

    2016-01-01

    As one of the foremost critical realist writers of the Victorian era, Charles Dickens is adept at using language to create all kinds of characters in a humorous or ironic tone. Therefore he received massive popularity for his unique style in storytelling. Oliver Twist is one of Charles Dickens's masterpieces and also the most appropriate choice for the stylistic study on Charles Dickens. This thesis endeavors to explore the aesthetic effect of semantic deviation appearing in Oliver Twist so that we can have a better comprehension about the excellent writing skill of Charles Dickens.

  7. Distribution of standard deviation of an observable among superposed states

    Science.gov (United States)

    Yu, Chang-shui; Shao, Ting-ting; Li, Dong-mo

    2016-10-01

    The standard deviation (SD) quantifies the spread of the observed values on a measurement of an observable. In this paper, we study the distribution of SD among the different components of a superposition state. It is found that the SD of an observable on a superposition state can be well bounded by the SDs of the superposed states. We also show that the bounds also serve as good bounds on coherence of a superposition state. As a further generalization, we give an alternative definition of incompatibility of two observables subject to a given state and show how the incompatibility subject to a superposition state is distributed.

  8. Beat the Deviations in Estimating Maximum Power of Thermoelectric Modules

    DEFF Research Database (Denmark)

    Gao, Junling; Chen, Min

    2013-01-01

    Under a certain temperature difference, the maximum power of a thermoelectric module can be estimated by the open-circuit voltage and the short-circuit current. In practical measurement, there exist two switch modes, either from open to short or from short to open, but the two modes can give...... different estimations on the maximum power. Using TEG-127-2.8-3.5-250 and TEG-127-1.4-1.6-250 as two examples, the difference is about 10%, leading to some deviations with the temperature change. This paper analyzes such differences by means of a nonlinear numerical model of thermoelectricity, and finds out...

  9. Utilizing a vanadium redox flow battery to avoid wind power deviation penalties in an electricity market

    International Nuclear Information System (INIS)

    Highlights: • Vanadium redox flow battery utilized for wind power grid integration was studied. • Technical and financial analyses at single wind farm level were performed. • 2 MW/6 MW h VRFB is suitable for mitigating power deviations for a 10 MW wind farm. • Economic incentives might be required in the short-term until the VRFB prices drop. - Abstract: Utilizing a vanadium redox flow battery (VRFB) for better market integration of wind power at a single wind farm level was evaluated. A model which combines a VRFB unit and a medium sized (10 MW) wind farm was developed and the battery was utilized to compensate for the deviations resulting from the forecast errors in an electricity market bidding structure. VRFB software model which was introduced in our previous paper was integrated with real wind power data, power forecasts and market data based on the Spanish electricity market. Economy of the system was evaluated by financial assessments which were done by considering the VRFB costs and the amount of deviation penalty payments resulting from forecast inaccuracies

  10. The Time Deviation in Packet-Based Synchronization.

    Science.gov (United States)

    Weiss, M A; Shenoi, Kishan

    2016-04-01

    The telecommunications industry has used the time deviation (TDEV) very effectively for specifying network equipment clock performance as well as the performance of timing signals generated by Central Office equipment such as primary reference clocks and building integrated timing supplies (BITS) and synchronization supply units (SSUs). We discuss here the development of TDEV, and the variations of TDEV motivated by the advent of packet-switching and the steady transformation of the telecom network from circuit-switched-based to packet-switched-based. We illustrate these with simulation of the performance of the precise time protocol (PTP) across a packet-switched network. We then apply published methods to automatically determine noise types, and use these to predict time dispersion from a master clock for a slave clock using these PTP packets to stay synchronized. The result shows how TDEV and the other deviations provide an extensive array of tools for telecom networks, as well as for general time and frequency applications. PMID:26529756

  11. Some Deviations Associated With Vector Perturbation Diffraction Theory

    Science.gov (United States)

    Stover, John C.; Hourmand, Bahrarr

    1985-01-01

    Last year at this conference our lab presented some data which strongly supports the use of the vector perturbation relationship between light scattered from smooth surfaces and the surface power spectral density (PSD). Last year's data showed that a consistent answer was obtained for the PSD for measurements taken with S and P polarization, with incident angles up to 45', for positive and negative sweeps, and for one and two dimensional samples. If in fact the theoretical relationship is correct then this must be the case, as the PSD is determined by a combination of surface topography and the scattering situation (geometry, polarization, wavelength, etc.). It appears, however that for large scatter angles (>700) and for large angles of incidence (>60 °) there is some deviation in the calculated PSD. In addition, the high angle scatter region is an area where a scatterometer with a semicircular detector sweep loses the one-to-one relationship between detector position and surface spatial frequency. Or, in other words, light diffracted to high scatter angles from single spatial frequencies appears over a small band on the observation semicircle instead of a diffraction limited point. Fata supporting these two deviations is presented. Although they are not regarded as serious violations of the vector perturbation theory they do impose a limit on the useful range over which the PSD may be calculated.

  12. Large deviations for random walk in a random environment

    CERN Document Server

    Yilmaz, Atilla

    2008-01-01

    In this work, we study the large deviation properties of random walk in a random environment on $\\mathbb{Z}^d$ with $d\\geq1$. We start with the quenched case, take the point of view of the particle, and prove the large deviation principle (LDP) for the pair empirical measure of the environment Markov chain. By an appropriate contraction, we deduce the quenched LDP for the mean velocity of the particle and obtain a variational formula for the corresponding rate function $I_q$. We propose an Ansatz for the minimizer of this formula. This Ansatz is easily verified when $d=1$. In his 2003 paper, Varadhan proves the averaged LDP for the mean velocity and gives a variational formula for the corresponding rate function $I_a$. Under the non-nestling assumption (resp. Kalikow's condition), we show that $I_a$ is strictly convex and analytic on a non-empty open set $\\mathcal{A}$, and that the true velocity $\\xi_o$ is an element (resp. in the closure) of $\\mathcal{A}$. We then identify the minimizer of Varadhan's variati...

  13. Temperature deviation index and elderly mortality in Japan

    Science.gov (United States)

    Lim, Youn-Hee; Reid, Colleen E.; Honda, Yasushi; Kim, Ho

    2016-07-01

    Few studies have examined how the precedence of abnormal temperatures in previous neighboring years affects the population's health. In the present study, we attempted to quantify the health effects of abnormal weather patterns by creating a metric called the temperature deviation index (TDI) and estimated the effects of TDI on mortality in Japan. We used data from 47 prefectures in Japan to compute the TDI on days between May and September from 1966 to 2010. The TDI is a summed product of an indicator of absence of high temperatures in the neighboring years, and more weights were assigned to the years closest to the current year. To estimate the TDI effects on elderly mortality, we used generalized linear modeling with a Poisson distribution after adjusting for apparent temperature, barometric pressure, day of the week, and time trend. For each prefecture, we estimated the TDI effects and pooled the estimates to yield a national average for 1991-2010 in Japan. The estimated effects of TDI in middle- or high-latitude prefectures were greater than in low-latitude prefectures. The estimated national average of TDI effects was a 0.5 % (95 % confidence intervals [CI], 0.1, 1.0) increase in elderly mortality per 1-unit (around 1 standard deviation) increase in the TDI. The significant pooled estimation of TDI effects was mainly due to the TDI effects on summer days with moderate temperature (25th-49th percentile, mean temperature 22.9 °C): a 1.9 % (95 % CI, 1.1, 2.6) increase in elderly mortality per 1-unit increase in the TDI. However, TDI effects were insignificant in other temperature ranges. These findings suggest that elderly deaths increased on moderate temperature days in the summer that differed substantially from days during that time window in the neighboring years. Therefore, not only high temperature itself but also temperature deviation compared to previous years could be considered to be a risk factor for elderly mortality in the summer.

  14. Large deviations of the maximal eigenvalue of random matrices

    CERN Document Server

    Borot, Gaëtan; Majumdar, Satya; Nadal, Céline

    2011-01-01

    We present detailed computations of the 'at least finite' terms (three dominant orders) of the free energy in a one-cut matrix model with a hard edge a, in beta-ensembles, with any polynomial potential. beta is a positive number, so not restricted to the standard values beta = 1 (hermitian matrices), beta = 1/2 (symmetric matrices), beta = 2 (quaternionic self-dual matrices). This model allows to study the statistic of the maximum eigenvalue of random matrices. We compute the large deviation function to the left of the expected maximum. We specialize our results to the gaussian beta-ensembles and check them numerically. Our method is based on general results and procedures already developed in the literature to solve the Pastur equations (also called "loop equations"). It allows to compute the left tail of the analog of Tracy-Widom laws for any beta, including the constant term.

  15. Large Deviation Results for Generalized Compound Negative Binomial Risk Models

    Institute of Scientific and Technical Information of China (English)

    Fan-chao Kong; Chen Shen

    2009-01-01

    In this paper we extend and improve some results of the large deviation for random sums of random variables.Let {Xn;n≥1} be a sequence of non-negative,independent and identically distributed random variables with common heavy-tailed distribution function F and finite mean μ∈R+,{N(n);n≥0} be a sequence of negative binomial distributed random variables with a parameter p ∈(0,1),n≥0,let {M(n);n≥0} be a Poisson process with intensity λ0.Suppose {N(n);n≥0},{Xn;n≥1} and {M(n);n≥0} are mutually results.These results can be applied to certain problems in insurance and finance.

  16. Prevalence of voice quality deviations in the normal adult population.

    Science.gov (United States)

    Brindle, B R; Morris, H L

    1979-11-01

    The purpose of this study was to determine the prevalence of voice quality deviations in a normal adult population. One-hundred twelve subjects, aged 17 to 80, read a short paragraph aloud into a high-fidelity tape recorder and completed a case history questionnaire. A group of 11 pretrained judges rated overall performance of each taped sample on a seven-point equal-appearing intervals scale, then designated those quality components which contributed toward deviant ratings. Eighty-two percent of the group received a mean severity rating lower than 1.99; 16% had a rating between 2.00 and 2.99; and 2% was assigned a mean rating higher than 3.00.

  17. Large deviations from the thermodynamic limit in globally coupled maps

    CERN Document Server

    Hamm, A

    1999-01-01

    Systems of a large number N of globally coupled maps have become popular as a relatively simple prototype of high-dimensional dynamics, showing many interesting and typical phenomena like synchronisation, cluster formation and multistability, and having potential applications in systems like Josephson junction arrays or in biophysical models. There exists a wealth of numerical investigations of globally coupled maps. While much progress has been made in the explanation of the macroscopic behaviour of such systems in the limit of infinite N, there is still need for a sound theory about the asymptotic behaviour of finite-N systems as N approaches infinity. This article introduces a method by which it is possible to obtain asymptotic estimates for long-term deviations from the thermodynamic limit behaviour. This method is based upon the concept of quasipotentials, originally developed by Freidlin, Wentzell, and others for describing the influence of small random perturbations on the long-term behaviour of dynami...

  18. Distributed Detection over Noisy Networks: Large Deviations Analysis

    CERN Document Server

    Jakovetic, Dusan; Xavier, Joao

    2011-01-01

    We study the large deviations performance of consensus+innovations distributed detection over noisy networks, where sensors at a time step k cooperate with immediate neighbors (consensus) and assimilate their new observations (innovation.) We show that, even under noisy communication, \\emph{all sensors} can achieve exponential decay e^{-k C_{\\mathrm{dis}}} of the detection error probability, even when certain (or most) sensors cannot detect the event of interest in isolation. We achieve this by designing a single time scale stochastic approximation type distributed detector with the optimal weight sequence {\\alpha_k}, by which sensors weigh their neighbors' messages. The optimal design of {\\alpha_k} balances the opposing effects of communication noise and information flow from neighbors: larger, slowly decaying \\alpha_k improves information flow but injects more communication noise. Further, we quantify the best achievable C_{\\mathrm{dis}} as a function of the sensing signal and noise, communication noise, an...

  19. Lyapunov exponents of linear cocycles continuity via large deviations

    CERN Document Server

    Duarte, Pedro

    2016-01-01

    The aim of this monograph is to present a general method of proving continuity of Lyapunov exponents of linear cocycles. The method uses an inductive procedure based on a general, geometric version of the Avalanche Principle. The main assumption required by this method is the availability of appropriate large deviation type estimates for quantities related to the iterates of the base and fiber dynamics associated with the linear cocycle. We establish such estimates for various models of random and quasi-periodic cocycles. Our method has its origins in a paper of M. Goldstein and W. Schlag. Our present work expands upon their approach in both depth and breadth. We conclude this monograph with a list of related open problems, some of which may be treated using a similar approach.

  20. Large deviations of heat flow in harmonic chains

    International Nuclear Information System (INIS)

    We consider heat transport across a harmonic chain connected at its two ends to white-noise Langevin reservoirs at different temperatures. In the steady state of this system the heat Q flowing from one reservoir into the system in a finite time τ has a distribution P(Q, τ). We study the large time form of the corresponding moment generating function (e−λQ) ∼ g(λ)eτμ(λ). Exact formal expressions, in terms of phonon Green's functions, are obtained for both μ(λ) and also the lowest order correction g(λ). We point out that, in general, a knowledge of both μ(λ) and g(λ) is required for finding the large deviation function associated with P(Q, τ). The function μ(λ) is known to be the largest eigenvector of an appropriate Fokker–Planck type operator and our method also gives the corresponding eigenvector exactly

  1. Deviations from uniform power law scaling in nonstationary time series

    Science.gov (United States)

    Viswanathan, G. M.; Peng, C. K.; Stanley, H. E.; Goldberger, A. L.

    1997-01-01

    A classic problem in physics is the analysis of highly nonstationary time series that typically exhibit long-range correlations. Here we test the hypothesis that the scaling properties of the dynamics of healthy physiological systems are more stable than those of pathological systems by studying beat-to-beat fluctuations in the human heart rate. We develop techniques based on the Fano factor and Allan factor functions, as well as on detrended fluctuation analysis, for quantifying deviations from uniform power-law scaling in nonstationary time series. By analyzing extremely long data sets of up to N = 10(5) beats for 11 healthy subjects, we find that the fluctuations in the heart rate scale approximately uniformly over several temporal orders of magnitude. By contrast, we find that in data sets of comparable length for 14 subjects with heart disease, the fluctuations grow erratically, indicating a loss of scaling stability.

  2. Does Nasal Septal Deviation Affect the Success of Tympanoplasty Surgery?

    Science.gov (United States)

    Tan, M; Kalcioglu, MT; Akarcay, M; Toplu, Y; Karaca, S

    2015-01-01

    ABSTRACT Objective: This paper deals with the investigation of the effects of nasal septal deviation evaluated by acoustic rhinometry (ARM) in the success of tympanoplasty surgery. Subject and Methods: All patients who underwent tympanoplasty surgery by the same surgeon were reviewed. The patients with nasopharyngeal or nasal masses, polyps, symptoms of allergic rhinitis or rhinosinusitis, or concha bullosa were excluded from the study. Forty patients who underwent tympanoplasty at least one year ago were included in the study. The patients were divided into two groups according to the graft success results. Acoustic rhinometry evaluations of the patients were performed. Results: There were 25 and 15 cases in the intact graft (group A) and re-perforated group (group B), respectively. For the same side of the operated ear, ARM values of group A were 0.47 cm 2 at the first narrowest cross-sectional area (MCA 1), 0.43 cm2 at the second narrowest cross-sectional area (MCA 2), 1.51 cm3 volume at the first 2 cm of the nasal cavity (Vol 1) and 3.33 cm3 volume between the second and fifth cm of the nasal cavity (Vol 2). Acoustic rhinometry values of group B were 0.50 cm2, 0.47 cm2, 1.60 cm3 and 3.19 cm3 for MCA 1, MCA 2, Vol 1, and Vol 2, respectively. Conclusion: The results of this study showed that nasal septal deviation may not affect the success of tympanoplasty surgery, and septoplasty may not be necessary before ear surgery. PMID:26624593

  3. Constraints on deviations from ΛCDM within Horndeski gravity

    Science.gov (United States)

    Bellini, Emilio; Cuesta, Antonio J.; Jimenez, Raul; Verde, Licia

    2016-02-01

    Recent anomalies found in cosmological datasets such as the low multipoles of the Cosmic Microwave Background or the low redshift amplitude and growth of clustering measured by e.g., abundance of galaxy clusters and redshift space distortions in galaxy surveys, have motivated explorations of models beyond standard ΛCDM. Of particular interest are models where general relativity (GR) is modified on large cosmological scales. Here we consider deviations from ΛCDM+GR within the context of Horndeski gravity, which is the most general theory of gravity with second derivatives in the equations of motion. We adopt a parametrization in which the four additional Horndeski functions of time αi(t) are proportional to the cosmological density of dark energy ΩDE(t). Constraints on this extended parameter space using a suite of state-of-the art cosmological observations are presented for the first time. Although the theory is able to accommodate the low multipoles of the Cosmic Microwave Background and the low amplitude of fluctuations from redshift space distortions, we find no significant tension with ΛCDM+GR when performing a global fit to recent cosmological data and thus there is no evidence against ΛCDM+GR from an analysis of the value of the Bayesian evidence ratio of the modified gravity models with respect to ΛCDM, despite introducing extra parameters. The posterior distribution of these extra parameters that we derive return strong constraints on any possible deviations from ΛCDM+GR in the context of Horndeski gravity. We illustrate how our results can be applied to a more general frameworks of modified gravity models.

  4. Quantum Properties of a General Path Deviation Equation in the Pap-Geometry

    CERN Document Server

    Wanas, M I

    2004-01-01

    A path deviation equation in the Parameterized Absolute Parallelism (PAP) geometry is derived. This equation includes curvature and torsion terms. These terms are found to be naturally quantized. The equation represents the deviation from a general path equation, in the PAP-geometry, derived by the author in a previous work. It is shown that, as the effect of the torsion, on the deviation, increases, the effect of the curvature decreases. It is also shown that the general path deviation equation can be reduced to the geodesic deviation equation if PAP-geometry becomes Riemannian. The equation can be used to study the deviation from the trajectories of spinning elementary particles.

  5. Gait Deviations in Children with Autism Spectrum Disorders: A Review

    Directory of Open Access Journals (Sweden)

    Deirdre Kindregan

    2015-01-01

    Full Text Available In recent years, it has become clear that children with autism spectrum disorders (ASDs have difficulty with gross motor function and coordination, factors which influence gait. Knowledge of gait abnormalities may be useful for assessment and treatment planning. This paper reviews the literature assessing gait deviations in children with ASD. Five online databases were searched using keywords “gait” and “autism,” and 11 studies were found which examined gait in childhood ASD. Children with ASD tend to augment their walking stability with a reduced stride length, increased step width and therefore wider base of support, and increased time in the stance phase. Children with ASD have reduced range of motion at the ankle and knee during gait, with increased hip flexion. Decreased peak hip flexor and ankle plantar flexor moments in children with ASD may imply weakness around these joints, which is further exhibited by a reduction in ground reaction forces at toe-off in children with ASD. Children with ASD have altered gait patterns to healthy controls, widened base of support, and reduced range of motion. Several studies refer to cerebellar and basal ganglia involvement as the patterns described suggest alterations in those areas of the brain. Further research should compare children with ASD to other clinical groups to improve assessment and treatment planning.

  6. Drastic deviations from stoichiometry transfer during pulsed laser deposition

    Science.gov (United States)

    Dittrich, Arne; Eberl, Christian; Schlenkrich, Susanne; Schlenkrich, Felix; Döring, Florian; Krebs, Hans-Ulrich

    2016-04-01

    In common, one of the most characteristic properties of pulsed laser deposition is the stoichiometry transfer between target and substrate, which has been used heavily for many complex systems. In this paper we show that it is yet possible to obtain drastic deviations from stoichiometry transfer in a binary system by just varying the fluence during laser deposition. In the W-Cu system, the W concentration of films grown from a composite W60Cu40 target (60 wt% W) was indeed continuously changed over an unprecedented large range of 0-70 wt% W. Close to the deposition threshold, pure Cu films are formed due to the much higher vapor pressure of Cu. At higher laser fluences, more and more W-rich W-Cu alloy samples are obtained, since ion implantation and intermixing processes occur. These alloys can reach W contents even higher than that of the target because of enhanced resputtering and reflection of the lighter Cu atoms at the film surface. Stoichiometric films with 60 wt% of W are only obtained at laser fluences around 2.7 J/cm2, when the strong Cu evaporation from the target and reflection and resputtering effects of Cu at the film surface are in balance.

  7. Testing large-angle deviation from Gaussianity in CMB maps

    CERN Document Server

    Bernui, A; Teixeira, A F F

    2010-01-01

    A detection of the level of non-Gaussianity in the CMB data is essential to discriminate among inflationary models and also to test alternative primordial scenarios. However, the extraction of primordial non-Gaussianity is a difficult endeavor since several effects of non-primordial nature can produce non-Gaussianity. On the other hand, different statistical tools can in principle provide information about distinct forms of non-Gaussianity. Thus, any single statistical estimator cannot be sensitive to all possible forms of non-Gaussianity. In this context, to shed some light in the potential sources of deviation from Gaussianity in CMB data it is important to use different statistical indicators. In a recent paper we proposed two new large-angle non-Gaussianity indicators which provide measures of the departure from Gaussianity on large angular scales. We used these indicators to carry out analyses of non-Gaussianity of the bands and of the foreground-reduced WMAP maps with and without the KQ75 mask. Here we ...

  8. Constraints on deviations from {\\Lambda}CDM within Horndeski gravity

    CERN Document Server

    Bellini, Emilio; Jimenez, Raul; Verde, Licia

    2015-01-01

    Recent anomalies found in cosmological datasets such as the low multipoles of the Cosmic Microwave Background or the low redshift amplitude and growth of clustering measured by e.g., abundance of galaxy clusters and redshift space distortions in galaxy surveys, have motivated explorations of models beyond standard {\\Lambda}CDM. Of particular interest are models where general relativity (GR) is modified on large cosmological scales. Here we consider deviations from {\\Lambda}CDM+GR within the context of Horndeski gravity, which is the most general theory of gravity with second derivatives in the equations of motion. We adopt a parametrization in which the four additional Horndeski functions of time {\\alpha}_i(t) are proportional to the cosmological density of dark energy {\\Omega}_DE(t). Constraints on this extended parameter space using a suite of state-of-the art cosmological observations are presented for the first time. Although the theory is able to accommodate the low multipoles of the Cosmic Microwave Bac...

  9. Determination of ensemble-average pairwise root mean-square deviation from experimental B-factors.

    Science.gov (United States)

    Kuzmanic, Antonija; Zagrovic, Bojan

    2010-03-01

    Root mean-square deviation (RMSD) after roto-translational least-squares fitting is a measure of global structural similarity of macromolecules used commonly. On the other hand, experimental x-ray B-factors are used frequently to study local structural heterogeneity and dynamics in macromolecules by providing direct information about root mean-square fluctuations (RMSF) that can also be calculated from molecular dynamics simulations. We provide a mathematical derivation showing that, given a set of conservative assumptions, a root mean-square ensemble-average of an all-against-all distribution of pairwise RMSD for a single molecular species, (1/2), is directly related to average B-factors () and (1/2). We show this relationship and explore its limits of validity on a heterogeneous ensemble of structures taken from molecular dynamics simulations of villin headpiece generated using distributed-computing techniques and the Folding@Home cluster. Our results provide a basis for quantifying global structural diversity of macromolecules in crystals directly from x-ray experiments, and we show this on a large set of structures taken from the Protein Data Bank. In particular, we show that the ensemble-average pairwise backbone RMSD for a microscopic ensemble underlying a typical protein x-ray structure is approximately 1.1 A, under the assumption that the principal contribution to experimental B-factors is conformational variability.

  10. Sea Surface Height Deviation, Aviso, 0.25 degrees, Global, Science Quality

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Aviso Sea Surface Height Deviation is the deviation from the mean geoid as measured from 1993 - 1995. This is Science Quality data.

  11. MODERATE DEVIATIONS FROM HYDRODYNAMIC LIMIT OF A GINZBURG-LANDAU MODEL

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The authors consider the moderate deviations of hydrodynamic limit for Ginzburg-Landau models. The moderate deviation principle of hydrodynamic limit for a specific Ginzburg-Landau model is obtained and an explicit formula of the rate function is derived.

  12. Moderate deviations for the quenched mean of the super-Brownian motion with random immigration

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Moderate deviations for the quenched mean of the super-Brownian motion with random immigration are proved for 3≤d≤6, which fills in the gap between central limit theorem(CLT)and large deviation principle(LDP).

  13. Large-deviation statistics of vorticity stretching in isotropic turbulence.

    Science.gov (United States)

    Johnson, Perry L; Meneveau, Charles

    2016-03-01

    A key feature of three-dimensional fluid turbulence is the stretching and realignment of vorticity by the action of the strain rate. It is shown in this paper, using the cumulant-generating function, that the cumulative vorticity stretching along a Lagrangian path in isotropic turbulence obeys a large deviation principle. As a result, the relevant statistics can be described by the vorticity stretching Cramér function. This function is computed from a direct numerical simulation data set at a Taylor-scale Reynolds number of Re(λ)=433 and compared to those of the finite-time Lyapunov exponents (FTLE) for material deformation. As expected, the mean cumulative vorticity stretching is slightly less than that of the most-stretched material line (largest FTLE), due to the vorticity's preferential alignment with the second-largest eigenvalue of strain rate and the material line's preferential alignment with the largest eigenvalue. However, the vorticity stretching tends to be significantly larger than the second-largest FTLE, and the Cramér functions reveal that the statistics of vorticity stretching fluctuations are more similar to those of the largest FTLE. In an attempt to relate the vorticity stretching statistics to the vorticity magnitude probability density function in statistically stationary conditions, a model Kramers-Moyal equation is constructed using the statistics encoded in the Cramér function. The model predicts a stretched-exponential tail for the vorticity magnitude probability density function, with good agreement for the exponent but significant difference (35%) in the prefactor.

  14. 7 CFR 400.174 - Notification of deviation from financial standards.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 6 2010-01-01 2010-01-01 false Notification of deviation from financial standards... Agreement-Standards for Approval; Regulations for the 1997 and Subsequent Reinsurance Years § 400.174 Notification of deviation from financial standards. An insurer must immediately advise FCIC if it deviates...

  15. 1 CFR 21.14 - Deviations from standard organization of the Code of Federal Regulations.

    Science.gov (United States)

    2010-01-01

    ... 1 General Provisions 1 2010-01-01 2010-01-01 false Deviations from standard organization of the... CODIFICATION General Numbering § 21.14 Deviations from standard organization of the Code of Federal Regulations. (a) Any deviation from standard Code of Federal Regulations designations must be approved in...

  16. Necessary and sufficient conditions for moderate deviations of dependent random variables with heavy tails

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    This paper studies the moderate deviations of real-valued extended negatively dependent(END) random variables with consistently varying tails.The moderate deviations of partial sums are first given.The results are then used to establish the necessary and sufficient conditions for the moderate deviations of random sums under certain circumstances.

  17. System for the measurement of the deviation of a laser beam from the vertical direction.

    Science.gov (United States)

    Zeng, Tao; Lu, Yunfeng; Yang, Hongxin; Hu, Pengcheng; Liu, Yongmeng; Li, Zhengkun; Zhang, Zhonghua

    2016-04-01

    If a used "vertical beam" is not perfectly vertical in a measurement, a cosine error will be introduced into it. To decrease and compensate for this cosine error, a measurement system is proposed to measure the deviation of the laser beam from the vertical direction. The structure of our measurement system is illustrated, and a model for solving for the deviation angle is established. As the distance of the beam spots on the charge-coupled device is the essential parameter for the measurement results, the acquisition process for this distance is explained. Moreover, the accuracy of the algorithm used in the acquisition process is also tested by experiments. Further, a self-correction module is designed and applied to reduce the error caused by the corner cube reflector in the system. The characteristics of the measurement system such as the resolution, stability, temperature drift, and direction accuracy are analyzed through experiments. The combined uncertainty of the measurement system is calculated to be 11×10-6  rad.

  18. ON FATIGUE CRACK PATH DEVIATION AT ELEVATED TEMPERATURE IN ELECTRON BEAM REPAIRED WELDMENTS OF TURBINE DISK

    Institute of Scientific and Technical Information of China (English)

    H.Q. Zhang; H.Y. Zhao; Y.H. Zhang; L.H. Li; X.A. Zhang

    2004-01-01

    Fatigue crack growth behaviors in electron beam weldments of a nickel-base superalloy are studied. The objective of this paper is to discuss effects of the inhomogeneity of mechanical performance on fatigue crack growth (FCG) rate and crack path deviation (CPD). The base metal served in a turbine disk of aerospace engine was selected to fabricate bead-on-plate weldments by using electron beam welding. Some wedge-type opening loading specimens, notched in three different zone of weld metal, HAZ and base metal, were employed and performed fatigue crack growth tests at 650℃. The results show that the fatigue crack growth of electron beam welded joints is instable due to the influence of mechanical heterogeneities. Owing to the crack deviation at the weld metal and hcat-affected-zone (HAZ), the effective growth driving force at the tip of fatigue crack was reduced with the reduction of the effective stress intensity factor (SIF) which finally causes fatigue crack rate decrease. Fatigue crack was strongly affected by size and the symmetrical characteristics of the plastic zone at the crack tip, which means that the integrity of the welded structure containing the fatigue crack mainly depended on the toughness of the low strength zone.

  19. The CK2 inhibitor quninalizarin enhances the anti-proliferative effect of icotinib on EGFR-TKIs-resistant cell lines and its underlying mechanisms%蛋白激酶2抑制剂增强盐酸埃克替尼对表皮生长因子受体-酪氨酸激酶抑制剂耐药细胞的增殖抑制作用及机制

    Institute of Scientific and Technical Information of China (English)

    周瑜; 伍钢; 孟睿; 张盛; 李珂; 李倩雯; 周方正; 李振宇; 马虹; 董晓荣; 刘莉

    2016-01-01

    [Abstr act] Objective To explore whether quninalizarin, an specific inhibitor of protein kinase CK2, could sensitize icotinib in EGFR-TKIs (epithelial growth factor receptor-tyrosine kinase inhibitor)-resistant cell lines and uncover the underlying mechanisms.Methods MTT assay was performed to evaluate the inhibitory effect of quninalizarin, icotinib or the combination of both on cell proliferation in several lung adenocarcinoma cell lines.Western blot assay was used to assess if combined inhibition of EGFR and protein kinase CK2 by icotinib and quninalizarin, exerts effect on the expression and phosphorylation of major proteins of EGFR signaling pathways.Results The IC50 of HCC827, H1650 , H1975 and A549 cells for icotinib were (8.07±2.00) μmol/L, (66.01±6.64) μmol/L, (265.60±9.47) μmol/L and( 87.88±6.8)μmol/L, respectively, indicating that HCC827 cells are sensitive to icotinib, and the H1650, H1975 and A549 cells are relatively resistant to icotinib.When treated with both quninalizarin and icotinib in the concentration of 50 μmol/L, the viability of H1650, H1975 and A549 cells was (40.64±3.73)%, (65.74± 3.27)% and (44.96±0.48)%, respectively, significantly lower than that of H1650 , H1975 and A549 cells treated with 50 μmol/L icotinib alone (55.05±1.22)%, (71.98±1.60)% and (61.74±6.18)%, respectively (P<0.01 for all).When treated with both 100 μmol/L quninalizarin and 100 μmol/L icotinib, the viability of H1650, H1975and A 549 ells were (23.35±0.81)%, (55.70±1.03)%, (33.42±1.33)%,respectively, significantly lower than the viability of H1650, H1975 and A549 cells treated with 100 μmol/L icotinib alone (40.57±2.65)%, (62.40±2.05)% and (44.97±8.20)%, respectively, (P<0.01 for all).The two-way ANOVA analysis showed that compared with the viability of EGFR-TKIs-resistant cells ( H1650, H1975, A549) treated with 50 μmol/L and 100 μmol/L icotinib alone, the viability of cells treated with icotinib and quinalizarin were significantly

  20. Outcomes of Surgical Treatment in Cases of Dissociated Vertical Deviation

    Directory of Open Access Journals (Sweden)

    Serpil Akar

    2014-03-01

    Full Text Available Objectives: To investigate the results of different surgical techniques for treating cases of dissociated vertical deviation (DVD. Materials and Methods: A retrospective review of medical records was performed, including 94 eyes of 47 patients who had undergone bilateral superior rectus (SR recessions (Group 1, bilateral SR recession with posterior fixation sutures (Group 2, or bilateral inferior oblique (IO anterior transposition surgery (Group 3 for treatment of DVD. Nineteen patients underwent secondary procedures (SR weakening or IO anterior transposition because of unsatisfactory results. The amount of the DVD in primary position before and after surgery, postoperative success ratios, and probable complications were evaluated. The Wilcoxon signed ranks test and chi-squared test were used for statistical evaluations. Results: In 69% of the 32 eyes in group 1, 65% of the 20 eyes in group 2, and 79% of the 42 eyes in group 3, satisfactory control of the DVD in primary position was achieved. All eyes undergoing both SR weakening and IO anterior transposition had a residual DVD of less than 5 prism diopters (pd. Of the total of 94 eyes, in 26 (89.6% of 29 eyes that had a preoperative DVD angle of more than 15 pd [ten eyes from group 1, seven eyes from group 2, and nine eyes from group 3], the residual DVD angle after surgery was more than 5 pd. However, in the 65 eyes with preoperative DVD of 15 pd or less (21from Group 1, 12 from Group 2, and 32 from Group 3, the residual DVD angle after the operation was less than 5 pd. Two eyes of 2 patients had -1 limitation to elevation after surgery. Conclusion: Only IO anterior transposition or SR weakening surgery appear to be a successful surgical approaches in the management of patients with mild- and moderate-angle (≤15 pd DVD. Weakening both the SR and IO muscles yield a greater success in the management of patients with large-angle (>15 pd DVD. (Turk J Ophthalmol 2014; 44: 132-7

  1. A study of decision-making behavior of aircraft pilots deviating from a planned flight

    Science.gov (United States)

    Flather, G. W., II; Giffin, W. C.; Rockwell, T. H.

    1981-01-01

    This paper outlines an investigation into the worth structures of pilots facing a deviation from a planned flight. A 'paper and pencil' simulation was used to frame the situation into which pilots interjected their own decision making skills in a simple ranking of candidate diversion airports with varying locational, navigational aid, radar and weather attributes. Using the conjoint measurement technique, attribute worth functions of 30 pilots were constructed. It was discovered that systematic differences in the worth functions of the pilots did not occur as a result of dividing the pilot sample according to any measure of flight hour experience. However, differences were found when the pilot sample was grouped according to grade of pilot certificate, type of pilot training, and type of flying most commonly done.

  2. Expected distributions of root-mean-square positional deviations in proteins.

    Science.gov (United States)

    Pitera, Jed W

    2014-06-19

    The atom positional root-mean-square deviation (RMSD) is a standard tool for comparing the similarity of two molecular structures. It is used to characterize the quality of biomolecular simulations, to cluster conformations, and as a reaction coordinate for conformational changes. This work presents an approximate analytic form for the expected distribution of RMSD values for a protein or polymer fluctuating about a stable native structure. The mean and maximum of the expected distribution are independent of chain length for long chains and linearly proportional to the average atom positional root-mean-square fluctuations (RMSF). To approximate the RMSD distribution for random-coil or unfolded ensembles, numerical distributions of RMSD were generated for ensembles of self-avoiding and non-self-avoiding random walks. In both cases, for all reference structures tested for chains more than three monomers long, the distributions have a maximum distant from the origin with a power-law dependence on chain length. The purely entropic nature of this result implies that care must be taken when interpreting stable high-RMSD regions of the free-energy landscape as "intermediates" or well-defined stable states.

  3. Speaker adapted dynamic lexicons containing phonetic deviations of words

    Institute of Scientific and Technical Information of China (English)

    Bahram VAZIRNEZHAD; Farshad ALMASGANJ; Seyed Mohammad AHADI; Ari CHANEN

    2009-01-01

    Speaker variability is an important source of speech variations which makes continuous speech recognition a difficult task. Adapting automatic speech recognition (ASR) models to the speaker variations is a well-known strategy to cope with the challenge. Almost all such techniques focus on developing adaptation solutions within the acoustic models of the ASR systems. Although variations of the acoustic features constitute an important portion of the inter-speaker variations, they do not cover variations at the phonetic level. Phonetic variations are known to form an important part of variations which are influenced by both micro-segmental and suprasegmental factors. Inter-speaker phonetic variations are influenced by the structure and anatomy of a speaker's articulatory system and also his/her speaking style which is driven by many speaker background characteristics such as accent, gender, age, socioeconomic and educational class. The effect of inter-speaker variations in the feature space may cause explicit phone recognition errors. These errors can be compensated later by having appropriate pronunciation variants for the lexicon entries which consider likely phone misclassifications besides pronunciation. In this paper, we introduce speaker adaptive dynamic pronunciation models, which generate different lexicons for various speaker clusters and different ranges of speech rate. The models are hybrids of speaker adapted contextual rules and dynamic generalized decision trees, which take into account word phonological structures, rate of speech, unigram probabilities and stress to generate pronunciation variants of words. Employing the set of speaker adapted dynamic lexicons in a Farsi (Persian) continuous speech recognition task results in word error rate reductions of as much as 10.1% in a speaker-dependent scenario and 7.4% in a speaker-independent scenario.

  4. Statistical properties of the deviations of f 0 F 2 from monthly medians

    Directory of Open Access Journals (Sweden)

    Y. Tulunay

    2002-06-01

    Full Text Available The deviations of hourly f 0 F 2 from monthly medians for 20 stations in Europe during the period 1958-1998 are studied. Spectral analysis is used to show that, both for original data (for each hour and for the deviations from monthly medians, the deterministic components are the harmonics of 11 years (solar cycle, 1 year and its harmonics, 27 days and 12 h 50.49 m (2nd harmonic of lunar rotation period L 2 periodicities. Using histograms for one year samples, it is shown that the deviations from monthly medians are nearly zero mean (mean < 0.5 and approximately Gaussian (relative difference range between %10 to %20 and their standard deviations are larger for daylight hours (in the range 5-7. It is shown that the amplitude distribution of the positive and negative deviations is nearly symmetrical at night hours, but asymmetrical for day hours. The positive and negative deviations are then studied separately and it is observed that the positive deviations are nearly independent of R12 except for high latitudes, but negative deviations are modulated by R12 . The 90% confidence interval for negative deviations for each station and each hour is computed as a linear model in terms of R12. After correction for local time, it is shown that for all hours the confidence intervals increase with latitude but decrease above 60N. Long-term trend analysis showed that there is an increase in the amplitude of positive deviations from monthly means irrespective of the solar conditions. Using spectral analysis it is also shown that the seasonal dependency of negative deviations is more accentuated than the seasonal dependency of positive deviations especially at low latitudes. In certain stations, it is also observed that the 4th harmonic of 1 year corresponding to a periodicity of 3 months, which is missing in f 0 F 2 data, appears in the spectra of negative variations.

  5. Century-Scale of Standard Deviation in Europe Historical Temperature Records

    Science.gov (United States)

    Xie, F.

    2015-12-01

    The standard deviation (STD) variability in long historical temperature records in Europe is analyzed. It is found that STD is changeable with time, and a century-scale variation is revealed, which further indicates a century-scale intensity modulation of the large-scale temperature variability. The Atlantic multidecadal oscillation (AMO) can cause significant impacts in standard deviation. During the periods of 1870-1910 and 1950-80, increasing standard deviation corresponds to increasing AMO index, while the periods of 1920-50 and 1980-2000 decreasing standard deviation corresponds to decreasing AMO index. The findings herein suggest a new perspective on the understanding of climatic change

  6. An Analysis of the Linguistic Deviation in Chapter X of Oliver Twist

    Institute of Scientific and Technical Information of China (English)

    刘聪

    2013-01-01

    Charles Dickens is one of the greatest critical realist writers of the Victorian Age. In language, he is often compared with William Shakespeare for his adeptness with the vernacular and large vocabulary. Charles Dickens achieved a recognizable place among English writers through the use of the stylistic features in his fictional language. Oliver Twist is the best representative of Charles Dickens’style, which makes it the most appropriate choice for the present stylistic study on Charles Dickens. No one who has ever read the dehumanizing workhouse scenes of Oliver Twist and the dark, criminal underworld life can forget them. This thesis attempts to investigate Oliver Twist through the approach of modern stylistics, particularly the theory of linguistic devia-tion. This thesis consists of an introduction, the main body and a conclusion. The introduction offers a brief summary of the com-ments on Charles Dickens and Chapter X of Oliver Twist, introduces the newly rising linguistic deviation theories, and brings about the theories on which this thesis settles. The main body explores the deviation effects produced from four aspects: lexical deviation, grammatical deviation, graphological deviation, and semantic deviation. It endeavors to show Dickens ’manipulating language and the effects achieved through this manipulation. The conclusion mainly sums up the previous analysis, and reveals the theme of the novel, positive effect of linguistic deviation and significance of deviation application.

  7. Bilateral symmetry of the mastoid processes in jaw deformity cases with mandibular deviation

    International Nuclear Information System (INIS)

    We used three-dimensional computed tomography (3D-CT) to investigate differences in the amount of mandibular deviation and the position of the mastoid processes at the insertion of the sternocleidomastoid muscle in subjects who had jaw deformities with mandibular deviation. We measured the distance from the Frankfort horizontal (FH), frontal and sagittal median planes to the mastoid processes. We also measured mandibular deviation as the distance from the sagittal median plane to Me (Me deviation distance), the angle of the FH plane to Ag line (vertical mandibular deviation angle), as well as the angle of the sagittal median plane to Ag line (axial mandibular deviation angle). We calculated the ratios of the vertical, anteroposterior and lateral distances from each plane to the bilateral mastoid processes. Significant correlation was found between the Me deviation distance and the ratio of the vertical distance to the bilateral mastoid processes. Significant correlation was also found between the axial mandibular deviation angle and the ratio of the vertical distance to the bilateral mastoid processes. Our results suggest that in patients with jaw deformities there is a correlation between deviation of the mandible from the body axis and the position of the mastoid processes. (author)

  8. Effects of Thickness Deviation of Elastic Plates in Multi-Layered Resonance Systems on Frequency Spectra

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hui; ZHANG Shu-Yi; FAN Li

    2009-01-01

    A model of high-overtone bulk acoustic resonators is used to study the effects of thickness deviation of elastic plates on resonance frequency spectra in planar multi-layered systems. The resonance frequency shifts induced by the thickness deviations of the elastic plates periodically vary with the resonance order, which depends on the acoustic impedance ratios of the elastic plates to piezoelectric patches. Additionally, the center lines of the frequency shift oscillations Hnearly change with the orders of the resonance modes, and their slopes are sensitive to the thickness deviations of the plates, which can be used to quantitatively evaluate the thickness deviations.

  9. Deviation of congruent composition in Fe-Pd system

    Institute of Scientific and Technical Information of China (English)

    Tetsuo Mohri; Daisuke Hamajima; Ying Chen

    2006-01-01

    The first-principles calculation of the disordered L10 phase boundary for the Fe-Pd system is attempted by com bining the FLAPW electronic structure total energy calculations and the cluster variation method via the cluster expansion method. The lattice vibration effects are taken into account based on the Debye-Gruneisen model within quasi-harmonic approximation. The transition temperature is reproduced with very high accuracy. However, the experimental congruent tions are attempted based on the phenomenological Lennard-Jones type pair potential, which is capable of introducing both tetragonality of the L10 ordered phase and additional configurational freedom because of the magnetic spins. The preliminary calculations indicate that the tetragonality enhances the stability of the L10 ordered phase and the magnetic contributions also change the transition temperature. Despite these findings, the shift of the congruent composition still remains as a subject that needs further research. The electronic origin of the shifting of the congruent composition is briefly discussed.

  10. A correlational study of scoliosis and trunk balance in adult patients with mandibular deviation.

    Directory of Open Access Journals (Sweden)

    Shuncheng Zhou

    Full Text Available Previous studies have confirmed that patients with mandibular deviation often have abnormal morphology of their cervical vertebrae. However, the relationship between mandibular deviation, scoliosis, and trunk balance has not been studied. Currently, mandibular deviation is usually treated as a single pathology, which leads to poor clinical efficiency. We investigated the relationship of spine coronal morphology and trunk balance in adult patients with mandibular deviation, and compared the finding to those in healthy volunteers. 35 adult patients with skeletal mandibular deviation and 10 healthy volunteers underwent anterior X-ray films of the head and posteroanterior X-ray films of the spine. Landmarks and lines were drawn and measured on these films. The axis distance method was used to measure the degree of scoliosis and the balance angle method was used to measure trunk balance. The relationship of mandibular deviation, spine coronal morphology and trunk balance was evaluated with the Pearson correlation method. The spine coronal morphology of patients with mandibular deviation demonstrated an "S" type curve, while a straight line parallel with the gravity line was found in the control group (significant difference, p1°, while the control group had a normal trunk balance (imbalance angle <1°. There was a significant difference between the two groups (p<0.01. The degree of scoliosis and shoulder imbalance correlated with the degree of mandibular deviation, and presented a linear trend. The direction of mandibular deviation was the same as that of the lateral bending of thoracolumbar vertebrae, which was opposite to the direction of lateral bending of cervical vertebrae. Our study shows the degree of mandibular deviation has a high correlation with the degree of scoliosis and trunk imbalance, all the three deformities should be clinically evaluated in the management of mandibular deviation.

  11. Deviations from the Gutenberg–Richter law on account of a random distribution of block sizes

    International Nuclear Information System (INIS)

    This paper studies properties of a continuum with structure. The characteristic size of the structure governs the fact that difference relations are nonautomatically transformed into differential ones. It is impossible to consider an infinitesimal volume of a body, to which the major conservation laws could be applied, because the minimum representative volume of the body must contain at least a few elementary microstructures. The corresponding equations of motion are equations of infinite order, solutions of which include, along with usual sound waves, unusual waves with abnormally low velocities without a lower limit. It is shown that in such media weak perturbations can increase or decrease outside the limits. The number of complex roots of the corresponding dispersion equation, which can be interpreted as the number of unstable solutions, depends on the specific surface of cracks and is an almost linear dependence on a logarithmic scale, as in the seismological Gutenberg–Richter law. If the distance between one pore (crack) to another one is a random value with some distribution, we must write another dispersion equation and examine different scenarios depending on the statistical characteristics of the random distribution. In this case, there are sufficient deviations from the Gutenberg–Richter law and this theoretical result corresponds to some field and laboratory observations

  12. Deviations from the Gutenberg–Richter law on account of a random distribution of block sizes

    Energy Technology Data Exchange (ETDEWEB)

    Sibiryakov, B. P., E-mail: sibiryakovbp@ipgg.sbras.ru [Trofimuk Institute of Oil and Gas Geology and Geophysics SB RAS, Novosibirsk, 630090 (Russian Federation); Novosibirsk State University, Novosibirsk, 630090 (Russian Federation)

    2015-10-27

    This paper studies properties of a continuum with structure. The characteristic size of the structure governs the fact that difference relations are nonautomatically transformed into differential ones. It is impossible to consider an infinitesimal volume of a body, to which the major conservation laws could be applied, because the minimum representative volume of the body must contain at least a few elementary microstructures. The corresponding equations of motion are equations of infinite order, solutions of which include, along with usual sound waves, unusual waves with abnormally low velocities without a lower limit. It is shown that in such media weak perturbations can increase or decrease outside the limits. The number of complex roots of the corresponding dispersion equation, which can be interpreted as the number of unstable solutions, depends on the specific surface of cracks and is an almost linear dependence on a logarithmic scale, as in the seismological Gutenberg–Richter law. If the distance between one pore (crack) to another one is a random value with some distribution, we must write another dispersion equation and examine different scenarios depending on the statistical characteristics of the random distribution. In this case, there are sufficient deviations from the Gutenberg–Richter law and this theoretical result corresponds to some field and laboratory observations.

  13. Urban scaling and its deviations: revealing the structure of wealth, innovation and crime across cities.

    Directory of Open Access Journals (Sweden)

    Luís M A Bettencourt

    Full Text Available With urban population increasing dramatically worldwide, cities are playing an increasingly critical role in human societies and the sustainability of the planet. An obstacle to effective policy is the lack of meaningful urban metrics based on a quantitative understanding of cities. Typically, linear per capita indicators are used to characterize and rank cities. However, these implicitly ignore the fundamental role of nonlinear agglomeration integral to the life history of cities. As such, per capita indicators conflate general nonlinear effects, common to all cities, with local dynamics, specific to each city, failing to provide direct measures of the impact of local events and policy. Agglomeration nonlinearities are explicitly manifested by the superlinear power law scaling of most urban socioeconomic indicators with population size, all with similar exponents (1.15. As a result larger cities are disproportionally the centers of innovation, wealth and crime, all to approximately the same degree. We use these general urban laws to develop new urban metrics that disentangle dynamics at different scales and provide true measures of local urban performance. New rankings of cities and a novel and simpler perspective on urban systems emerge. We find that local urban dynamics display long-term memory, so cities under or outperforming their size expectation maintain such (disadvantage for decades. Spatiotemporal correlation analyses reveal a novel functional taxonomy of U.S. metropolitan areas that is generally not organized geographically but based instead on common local economic models, innovation strategies and patterns of crime.

  14. Urban scaling and its deviations: revealing the structure of wealth, innovation and crime across cities.

    Science.gov (United States)

    Bettencourt, Luís M A; Lobo, José; Strumsky, Deborah; West, Geoffrey B

    2010-11-10

    With urban population increasing dramatically worldwide, cities are playing an increasingly critical role in human societies and the sustainability of the planet. An obstacle to effective policy is the lack of meaningful urban metrics based on a quantitative understanding of cities. Typically, linear per capita indicators are used to characterize and rank cities. However, these implicitly ignore the fundamental role of nonlinear agglomeration integral to the life history of cities. As such, per capita indicators conflate general nonlinear effects, common to all cities, with local dynamics, specific to each city, failing to provide direct measures of the impact of local events and policy. Agglomeration nonlinearities are explicitly manifested by the superlinear power law scaling of most urban socioeconomic indicators with population size, all with similar exponents (1.15). As a result larger cities are disproportionally the centers of innovation, wealth and crime, all to approximately the same degree. We use these general urban laws to develop new urban metrics that disentangle dynamics at different scales and provide true measures of local urban performance. New rankings of cities and a novel and simpler perspective on urban systems emerge. We find that local urban dynamics display long-term memory, so cities under or outperforming their size expectation maintain such (dis)advantage for decades. Spatiotemporal correlation analyses reveal a novel functional taxonomy of U.S. metropolitan areas that is generally not organized geographically but based instead on common local economic models, innovation strategies and patterns of crime.

  15. On Translation of Language Deviation from the Perspective of Peter Newmark’s Translation Dichotomy

    Institute of Scientific and Technical Information of China (English)

    胡娜; 延宏

    2016-01-01

    Language deviation can bring fresh vitality to literary creation. In literary works translation,through adoption of proper translation strategies, the effects created by language deviation in the original text can be efficiently reproduced. Here, the writer attempts to make a narration and relevant analyses on it.

  16. On the concentration of large deviations for fat tailed distributions, with application to financial data

    Science.gov (United States)

    Filiasi, Mario; Livan, Giacomo; Marsili, Matteo; Peressi, Maria; Vesselli, Erik; Zarinelli, Elia

    2014-09-01

    Large deviations for fat tailed distributions, i.e. those that decay slower than exponential, are not only relatively likely, but they also occur in a rather peculiar way where a finite fraction of the whole sample deviation is concentrated on a single variable. The regime of large deviations is separated from the regime of typical fluctuations by a phase transition where the symmetry between the points in the sample is spontaneously broken. For stochastic processes with a fat tailed microscopic noise, this implies that, while typical realizations are well described by a diffusion process with continuous sample paths, large deviation paths are typically discontinuous. For eigenvalues of random matrices with fat tailed distributed elements, a large deviation where the trace of the matrix is anomalously large concentrates on just a single eigenvalue, whereas in the thin tailed world the large deviation affects the whole distribution. These results find a natural application to finance. Since the price dynamics of financial stocks are characterized by fat tailed increments, large fluctuations in stock prices are expected to be realized by discrete jumps. Interestingly, we find that large excursions of prices are more likely realized by continuous drifts rather than by discontinuous jumps. Indeed, auto correlations suppress the concentration of large deviations. Financial covariance matrices also exhibit an anomalously large eigenvalue, the market mode, as compared to the prediction of random matrix theory. We show that this is explained by a large deviation with excess covariance rather than by one with excess volatility.

  17. Large Deviations for Parameter Estimators of Some Time Inhomogeneous Diffusion Process

    Institute of Scientific and Technical Information of China (English)

    Shou Jiang ZHAO; Fu Qing GAO

    2011-01-01

    The goal of this paper is to study large deviations for estimator and score function of some time inhomogeneous diffusion process.Large deviation in the non-steepness case with explicit rate functions is obtained by using parameter-dependent change of measure.

  18. Large Deviations for Empirical Measures of Not Necessarily Irreducible Countable Markov Chains with Arbitrary Initial Measures

    Institute of Scientific and Technical Information of China (English)

    Yi Wen JIANG; Li Ming WU

    2005-01-01

    All known results on large deviations of occupation measures of Markov processes are based on the assumption of (essential) irreducibility. In this paper we establish the weak* large deviation principle of occupation measures for any countable Markov chain with arbitrary initial measures. The new rate function that we obtain is not convex and depends on the initial measure, contrary to the (essentially) irreducible case.

  19. 75 FR 67093 - Iceberg Water Deviating From Identity Standard; Temporary Permit for Market Testing

    Science.gov (United States)

    2010-11-01

    ... Corp., to market test a product designated as ``GLACE Rare Iceberg Water'' that deviates from the U.S... HUMAN SERVICES Food and Drug Administration Iceberg Water Deviating From Identity Standard; Temporary Permit for Market Testing AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The...

  20. Determination of real machine-tool settings and minimization of real surface deviation by computerized inspection

    Science.gov (United States)

    Litvin, Faydor L.; Kuan, Chihping; Zhang, YI

    1991-01-01

    A numerical method is developed for the minimization of deviations of real tooth surfaces from the theoretical ones. The deviations are caused by errors of manufacturing, errors of installment of machine-tool settings and distortion of surfaces by heat-treatment. The deviations are determined by coordinate measurements of gear tooth surfaces. The minimization of deviations is based on the proper correction of initially applied machine-tool settings. The contents of accomplished research project cover the following topics: (1) Descriptions of the principle of coordinate measurements of gear tooth surfaces; (2) Deviation of theoretical tooth surfaces (with examples of surfaces of hypoid gears and references for spiral bevel gears); (3) Determination of the reference point and the grid; (4) Determination of the deviations of real tooth surfaces at the points of the grid; and (5) Determination of required corrections of machine-tool settings for minimization of deviations. The procedure for minimization of deviations is based on numerical solution of an overdetermined system of n linear equations in m unknowns (m much less than n ), where n is the number of points of measurements and m is the number of parameters of applied machine-tool settings to be corrected. The developed approach is illustrated with numerical examples.

  1. Moderate Deviations for M-estimators in Linear Models with φ-mixing Errors

    Institute of Scientific and Technical Information of China (English)

    Jun FAN

    2012-01-01

    In this paper,the moderate deviations for the M-estimators of regression parameter in a linear model are obtained when the errors form a strictly stationary φ-mixing sequence.The results are applied to study many different types of M-estimators such as Huber's estimator,Lp-regression estimator,least squares estimator and least absolute deviation estimator.

  2. 7 CFR 1724.52 - Permitted deviations from RUS construction standards.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 11 2010-01-01 2010-01-01 false Permitted deviations from RUS construction standards... POLICIES AND PROCEDURES Electric System Design § 1724.52 Permitted deviations from RUS construction standards. The provisions of this section apply to all borrower electric system facilities regardless of...

  3. Design and analysis of control charts for standard deviation with estimated parameters

    NARCIS (Netherlands)

    M. Schoonhoven; M. Riaz; R.J.M.M. Does

    2011-01-01

    This paper concerns the design and analysis of the standard deviation control chart with estimated limits. We consider an extensive range of statistics to estimate the in-control standard deviation (Phase I) and design the control chart for real-time process monitoring (Phase II) by determining the

  4. An Upper Bound on Standard Deviation as a Function of Range

    Science.gov (United States)

    Petocz, Peter

    2005-01-01

    This article disproves a conjecture that the ratio of the maximum standard deviation to the range of a set of data decreases as the number of data points increases. It also provides an alternative and more general approach for examining the standard deviation as a function of the range.

  5. A method for detecting alignment deviation on a thread-measuring instrument

    International Nuclear Information System (INIS)

    Alignment deviation is an important factor affecting measurement accuracy in screw thread measurement. It needs to be detected and controlled to ensure the accuracy of relative thread parameters. The influence on pitch diameter caused by the alignment deviations of workpiece and probe is analyzed in this paper. In order to detect and control the alignment deviation, a vision detection method for the probe tip points is proposed, which integrates the detection of corners and edges and the prediction of motion. Then the X-axial rotation deviation is calculated by tracking the tip points both up and down. The result of tests demonstrates that the detection accuracy of the X-axial rotation deviation is 0.0654° with the background changing during the probe movement. The repeatability of the test procedure is ±0.16%, which proves the detection method is adequately qualified for application. (paper)

  6. Deformation behavior of A6063 tube with initial thickness deviation in free hydraulic bulging

    Institute of Scientific and Technical Information of China (English)

    YANG Lian-fa; GUO Cheng; DENG Yang

    2006-01-01

    Experiment on seamless tubes of aluminum alloy A6063 with initial thickness deviation of 0-20% was conducted through a free hydraulic bulging with tube ends free. The influence of initial thickness deviation on the cross-section profile, thickness distribution, maximum internal pressure and maximum radial expansion was investigated. FEM simulation was also performed in order to examine and help explaining the experimental results. The results indicate that the internal pressure and maximum internal pressure appear to be little influenced by the initial thickness deviation, and that the cross-section profile of the bulged tube changes diversely and can not be a perfect circle. The results also suggest that the increase in initial thickness deviation may lead to a remarkable decrease in maximum radial expansion, and a rapid increase in thickness deviation and the center eccentricity of the inner and outer profiles.

  7. Statistical characterization of deviations from planned flight trajectories in air traffic management

    CERN Document Server

    Bongiorno, C; Lillo, F; Mantegna, R N; Miccichè, S

    2016-01-01

    Understanding the relation between planned and realized flight trajectories and the determinants of flight deviations is of great importance in air traffic management. In this paper we perform an in depth investigation of the statistical properties of planned and realized air traffic on the German airspace during a 28 day periods, corresponding to an AIRAC cycle. We find that realized trajectories are on average shorter than planned ones and this effect is stronger during night-time than daytime. Flights are more frequently deviated close to the departure airport and at a relatively large angle to destination. Moreover, the probability of a deviation is higher in low traffic phases. All these evidences indicate that deviations are mostly used by controllers to give directs to flights when traffic conditions allow it. Finally we introduce a new metric, termed difork, which is able to characterize navigation points according to the likelihood that a deviation occurs there. Difork allows to identify in a statist...

  8. The Impact of Advanced Technologies on Treatment Deviations in Radiation Treatment Delivery

    International Nuclear Information System (INIS)

    Purpose: To assess the impact of new technologies on deviation rates in radiation therapy (RT). Methods and Materials: Treatment delivery deviations in RT were prospectively monitored during a time of technology upgrade. In January 2003, our department had three accelerators, none with 'modern' technologies (e.g., without multileaf collimators [MLC]). In 2003 to 2004, we upgraded to five new accelerators, four with MLC, and associated advanced capabilities. The deviation rates among patients treated on 'high-technology' versus 'low-technology' machines (defined as those with vs. without MLC) were compared over time using the two-tailed Fisher's exact test. Results: In 2003, there was no significant difference between the deviation rate in the 'high-technology' versus 'low-technology' groups (0.16% vs. 0.11%, p = 0.45). In 2005 to 2006, the deviation rate for the 'high-technology' groups was lower than the 'low-technology' (0.083% vs. 0.21%, p = 0.009). This difference was caused by a decline in deviations on the 'high-technology' machines over time (p = 0.053), as well as an unexpected trend toward an increase in deviations over time on the 'low-technology' machines (p = 0.15). Conclusions: Advances in RT delivery systems appear to reduce the rate of treatment deviations. Deviation rates on 'high-technology' machines with MLC decline over time, suggesting a learning curve after the introduction of new technologies. Associated with the adoption of 'high-technology' was an unexpected increase in the deviation rate with 'low-technology' approaches, which may reflect an over-reliance on tools inherent to 'high-technology' machines. With the introduction of new technologies, continued diligence is needed to ensure that staff remain proficient with 'low-technology' approaches

  9. Differential processing of melodic, rhythmic and simple tone deviations in musicians--an MEG study.

    Science.gov (United States)

    Lappe, Claudia; Lappe, Markus; Pantev, Christo

    2016-01-01

    Rhythm and melody are two basic characteristics of music. Performing musicians have to pay attention to both, and avoid errors in either aspect of their performance. To investigate the neural processes involved in detecting melodic and rhythmic errors from auditory input we tested musicians on both kinds of deviations in a mismatch negativity (MMN) design. We found that MMN responses to a rhythmic deviation occurred at shorter latencies than MMN responses to a melodic deviation. Beamformer source analysis showed that the melodic deviation activated superior temporal, inferior frontal and superior frontal areas whereas the activation pattern of the rhythmic deviation focused more strongly on inferior and superior parietal areas, in addition to superior temporal cortex. Activation in the supplementary motor area occurred for both types of deviations. We also recorded responses to similar pitch and tempo deviations in a simple, non-musical repetitive tone pattern. In this case, there was no latency difference between the MMNs and cortical activation was smaller and mostly limited to auditory cortex. The results suggest that prediction and error detection of musical stimuli in trained musicians involve a broad cortical network and that rhythmic and melodic errors are processed in partially different cortical streams. PMID:26436712

  10. Deviations from the Schmidt-Kennicutt relations during early galaxy evolution

    CERN Document Server

    Papadopoulos, Padelis P

    2010-01-01

    We utilize detailed time-varying models of the coupled evolution of stars and the HI, H_2, and CO-bright H_2 gas phases in galaxy-sized numerical simulations to explore the evolution of gas-rich and/or metal-poor systems, expected to be numerous in the Early Universe. The inclusion of the CO-bright H_2 gas phase, and the realistic rendering of star formation as an H_2-regulated process (and the new feedback processes that this entails) allows the most realistic tracking of strongly evolving galaxies, and much better comparison with observations. We find that while galaxies eventually settle into states conforming to Schmidt-Kennicutt (S-K) relations, significant and systematic deviations of their star formation rates (SFRs) from the latter occur, especially pronounced and prolonged for ... ...This indicates potentially serious limitations of (S-K)-type relations as reliable sub-grid elements of star formation physics in simulations of structure formation in the Early Universe. We anticipate that galaxies with...

  11. A negative deviation from Porod’s law in SAXS of organo—MSU—X

    Institute of Scientific and Technical Information of China (English)

    Z.H.Li; Y.J.Gong; D.Wu; Y.H.Sun; J.Wang; Y.Liu; B.Z.Dong; Z.H.Li; Y.J.

    2001-01-01

    Small-angle X-ray scattering(SAXS)using synchrotron radiation as X-ray source has been employed to charactcizc the microscopic structrure of organo-modified mesoporous molecular sieves(organo-MSU-X)prepared by a one-pot template-directed synthesis.It is shown that the SAXS profile is hardly constant with Porod’s law showing a negative slope,i.e.,negative deviation.This suggests that there is diffuse interfacial layer located between the pores and the matrix.This suggests that the organic groups remain covalently linked to the matrix,as indicated by 29SiCP MAS NMR and FT-IR.The average thickness of the interfacial layer was found to be about 1nm for each of the three samples with different kinds and the same amounts(20? of organic groups.This kind of material has also been proved to possess both surface and mass fractal structure of the amophous porous silica materials.2001 Elsevier Science B.V.All rights reserved.

  12. Effect of tool centreline deviation on the mechanical properties of friction stir welded DH36 steel

    International Nuclear Information System (INIS)

    Highlights: • FSW of DH36 was tolerant to a centreline defect induced by tool deviation. • High strength welds up to 2.5 mm centreline tool deviation with ductile PM fracture. • Critical tolerance to centreline tool deviation at 4 mm with ductile weld metal fracture. • Brittle fracture above 4 mm deviation led to significant reduction in yield strength. - Abstract: Friction stir welding of steel has gone through recent tool and optimisation developments allowing the process to be considered as a technically superior alternative to fusion welding. This study expanded the scientific foundation of friction stir welding of DH36 steel to analyse the effect on weld quality when the rotating tool increasingly deviates away from the weld centreline. A centreline defect was deliberately but gradually introduced along the length of the weld seam. The tolerance to tool deviation towards both the advancing side and the retreating side of the weld was measured in terms of the transverse yield strength. Three discrete fracture modes were observed in transverse tensile specimen. Up to a tool deviation of 2.5 mm, ductile fracture in the parent material was observed and there was not a significant reduction in the yield strength of the weldment. The critical tool deviation occurred at 4 mm, where transverse tensile specimens fractured in a high strength ductile mode in the weld metal. Brittle behaviour in specimens above the 4 mm tolerance level resulted in a significant decrease in the transverse yield strength. Fracture within the weld metal was directed along the boundary between the heat-affected zone and thermo-mechanically affected zone, attributable to an abrupt change in the grain size and complexity of the two weld zones at this boundary. Friction stir welding of DH36 was found to be a tolerant joining process to the centreline deviation of the rotating tool

  13. A contribution to large deviations for heavy-tailed random sums

    Institute of Scientific and Technical Information of China (English)

    SU; Chun

    2001-01-01

    [1] Nagaev, A. V., Integral limit theorems for large deviations when Cramer's condition is not fulfilled I, II, Theory Prob. Appl., 1969, 14: 51-64, 193-208.[2] Nagaev, A. V., Limit theorems for large deviations where Cramer's conditions are violated (In Russian), Izv. Akad. Nauk USSR Ser., Fiz-Mat Nauk., 1969, 7: 17.[3] Heyde, C. C., A contribution to the theory of large deviations for sums of independent random variables, Z. Wahrscheinlichkeitsth, 1967, 7: 303.[4] Heyde, C. C., On large deviation probabilities for sums of random variables which are not attracted to the normal law, Ann. Math. Statist., 1967, 38: 1575.[5] Heyde, C. C., On large deviation probabilities in the case of attraction to a nonnormal stable law, Sanky, 1968, 30: 253.[6] Nagaev, S. V., Large deviations for sums of independent random variables, in Sixth Prague Conf. on Information Theory, Random Processes and Statistical Decision Functions, Prague: Academic, 1973, 657674.[7] Nagaev, S. V., Large deviations of sums of independent random variables, Ann. Prob., 1979, 7: 745.[8] Embrechts, P., Klüppelberg, C., Mikosch, T., Modelling Extremal Events for Insurance and Finance, Berlin-Heidelberg: Springer-Verlag, 1997.[9] Cline, D. B. H., Hsing, T., Large deviation probabilities for sums and maxima of random variables with heavy or subexponential tails, Preprint, Texas A&M University, 1991.[10] Klüppelberg, C., Mikosch, T., Large deviations of heavy-tailed random sums with applications to insurance and finance, J. Appl. Prob., 1997, 34: 293.

  14. Deviations of the glass transition temperature in amorphous conjugated polymer thin films

    Science.gov (United States)

    Liu, Dan; Osuna Orozco, Rodrigo; Wang, Tao

    2013-08-01

    The deviations of the glass transition temperature (Tg) in thin films of an amorphous conjugated polymer poly(9,9-dioctylfluorene-co-N-(4-butylphenyl)diphenylamine) (TFB) are reported. Monotonic and nonmonotonic Tg deviations are observed in TFB thin films supported on Si-SiOx and poly(3,4-ethylenedioxythiophene) poly(styrenesulfonate) (PEDOT:PSS), respectively. A three-layer model is developed to fit both monotonic and nonmonotonic Tg deviations in these films. A 5-nm PEDOT:PSS capping layer was not found to be effective to remove the free-surface effect in Si-SiOx supported TFB films.

  15. Method for solving fully fuzzy linear programming problems using deviation degree measure

    Institute of Scientific and Technical Information of China (English)

    Haifang Cheng; Weilai Huang; Jianhu Cai

    2013-01-01

    A new ful y fuzzy linear programming (FFLP) prob-lem with fuzzy equality constraints is discussed. Using deviation degree measures, the FFLP problem is transformed into a crispδ-parametric linear programming (LP) problem. Giving the value of deviation degree in each constraint, the δ-fuzzy optimal so-lution of the FFLP problem can be obtained by solving this LP problem. An algorithm is also proposed to find a balance-fuzzy optimal solution between two goals in conflict: to improve the va-lues of the objective function and to decrease the values of the deviation degrees. A numerical example is solved to il ustrate the proposed method.

  16. Level 1 quenched large deviation principle for random walk in dynamic random environment

    CERN Document Server

    Drewitz, David Campos Alexander

    2011-01-01

    Consider a random walk on a continuous time-dependent random environment on the hiper-cubic lattice. Recently, Rassoul-Agha, Seppalainen and Yilmaz proved a general large deviation principle under mild ergodicity assumptions on the random environment for such a random walk, establishing first a level 2 and 3 large deviation principle. Here we present an alternative short proof of the level 1 large deviations under mild ergodicity assumptions on the environment, which provides the existence and convexity of the rate function, in the continuous time case. Our methods are based on the use of sub-additive ergodic theorem as presented by Varadhan in 2003.

  17. Analysis of Road Base Uniformity via the Deviation of Modulus of Asphalt Mixtures

    Institute of Scientific and Technical Information of China (English)

    ZHI Yufeng; ZHANG Xiaoning

    2007-01-01

    The modulus deviation of base material calculated from the data of falling weight deflectometer (FWD) was used to evaluate the uniformity of road base so as to reflect the construction quality. Four parameters,the repeatability standard deviation of the data in the same driveway, the reproducibility standard deviation of the data in the different driveway, the consistency statistics value of the data in the different driveway, and the consistency statistics value of the data in the same driveway, were introduced for the construction uniformity analysis. The experimental result shows that the materials modulus calculated from FWD has a highly correlative relationship with the uniformity of road base.

  18. A large deviations approach to limit theory for heavy-tailed time series

    DEFF Research Database (Denmark)

    Mikosch, Thomas Valentin; Wintenberger, Olivier

    2016-01-01

    In this paper we propagate a large deviations approach for proving limit theory for (generally) multivariate time series with heavy tails. We make this notion precise by introducing regularly varying time series. We provide general large deviation results for functionals acting on a sample path...... and vanishing in some neighborhood of the origin. We study a variety of such functionals, including large deviations of random walks, their suprema, the ruin functional, and further derive weak limit theory for maxima, point processes, cluster functionals and the tail empirical process. One of the main results...

  19. Advanced ground-based gravitational-wave detectors' potential to detect generic deviations from general relativity

    CERN Document Server

    Narikawa, Tatsuya

    2016-01-01

    We discuss the potential of the advanced ground-based gravitational-wave detectors, such as LIGO, Virgo, and KAGRA, to detect generic deviations of gravitational waveforms from the prediction of General Relativity. We use the parameterized post-Einsteinian formalism to characterize the deviations, and assess how much magnitude of the deviations are detectable by using an approximate decision scheme based on Bayesian statistics. We find that there exist detectable regions of the parameterized post-Einsteinian parameters by using a single gravitational wave event. The regions are not excluded by currently existing binary pulsar observations for the parameterized post-Einsteinian parameters at higher post-Newtonian order.

  20. Distance-based standard deviation analysis method for line width roughness data

    Science.gov (United States)

    Bzik, Thomas J.; Rao, Madhukar B.; Zhang, Peng

    2005-05-01

    Linewidth roughness (LWR) is a major challenge for 90nm node and below. As feature sizes decrease, the reliable measurement, statistical comparison and interpretation of LWR data become increasingly important. The reliability of all LWR statistical analysis methods are strongly impacted by the architecture of LWR data being analyzed. Some of the key structural aspects of the collected data include: measurement box size, distance between neighboring measurements and whether measurement boxes have been "stitched" together for analysis. Additionally, the true nature of underlying line width variation, including both cyclical and non-cyclical trends, impacts how reliable a given interpretation will be. Current statistical methodologies for linewidth data are oriented at estimation of the frequency and scale of cyclical variation in linewidth components. Fourier analysis is traditionally applied for this purpose. Such analyses assume both that there is a cyclical component (e.g., sinusoidal) or components in the data to be modeled, as well as implicitly assuming a Gaussian error distribution for the linewidth variation that remains after modeling. The assumption that Fourier analysis is appropriate for LWR data often not met in practice by the LWR data undergoing analysis. A more model-independent approach, distance-based standard deviations, is proposed for use as part of an LWR statistical analysis methodology. It is based on the calculation of local standard deviations of linewidth for all possible distances between measured points. This methodology permits the statistical comparison of linewidth roughness over any distance of interest and makes efficient use of all data for a given measurement box length. It can determine the minimum measurement box length required to capture all linewidth variation. In addition, the method can confirm the validity of line stitching to increase measurement box size, and locate the sources of variance in the overall LWR value (e

  1. Large deviation statistics of non-equilibrium fluctuations in a sheared model-fluid

    Science.gov (United States)

    Dolai, Pritha; Simha, Aditi

    2016-08-01

    We analyse the statistics of the shear stress in a one dimensional model fluid, that exhibits a rich phase behaviour akin to real complex fluids under shear. We show that the energy flux satisfies the Gallavotti-Cohen FT across all phases in the system. The theorem allows us to define an effective temperature which deviates considerably from the equilibrium temperature as the noise in the system increases. This deviation is negligible when the system size is small. The dependence of the effective temperature on the strain rate is phase-dependent. It doesn’t vary much at the phase boundaries. The effective temperature can also be determined from the large deviation function of the energy flux. The local strain rate statistics obeys the large deviation principle and satisfies a fluctuation relation. It does not exhibit a distinct kink near zero strain rate because of inertia of the rotors in our system.

  2. CALCULATION ALGORITHM FOR STUDYING EFFORTS IN THE 4R SPHERICAL QUADRILATERAL MECHANISMS BECAUSE OF TECHNICAL DEVIATIONS

    Directory of Open Access Journals (Sweden)

    Ion BULAC

    2013-05-01

    Full Text Available Due to technical deviations, in the elements of the 4R spatial spherical mechanism appear efforts thatadditionally loads the mechanism, efforts that can be determined with the calculation algorithm that will bepresented in this paper

  3. Large-Deviation Results for Discriminant Statistics of Gaussian Locally Stationary Processes

    Directory of Open Access Journals (Sweden)

    Junichi Hirukawa

    2012-01-01

    Full Text Available This paper discusses the large-deviation principle of discriminant statistics for Gaussian locally stationary processes. First, large-deviation theorems for quadratic forms and the log-likelihood ratio for a Gaussian locally stationary process with a mean function are proved. Their asymptotics are described by the large deviation rate functions. Second, we consider the situations where processes are misspecified to be stationary. In these misspecified cases, we formally make the log-likelihood ratio discriminant statistics and derive the large deviation theorems of them. Since they are complicated, they are evaluated and illustrated by numerical examples. We realize the misspecification of the process to be stationary seriously affecting our discrimination.

  4. Deviation Prevention Ability of Rollers in Continuous Annealing Furnace and Application

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yan; YANG Quan; HE An-rui; YAO Xi-jiang; GUO De-fu

    2012-01-01

    In order to reduce the strip deviation in the practical production procedure in the continuous annealing fur- nace, a dynamic simulation model was built through finite element method (FEM) to conduct the quantification cal- culation of the effect of regular roller contour types on strip deviation. The result reveals that comparing to the flat roller, forward roller contour can prevent the strip deviation to some degree. In terms of prevention ability, double- taper roller is the strongest, single-taper roller and crown roller are less stronger; and more roller contour values raise the prevention ability. Accordingly, optimization method was applied to continuous annealing furnace, and it largely reduced accidents such as strip break and limited speed that are caused by the deviation.

  5. Large deviations for Hilbert space valued Wiener processes: a sequence space approach

    OpenAIRE

    Andresen, Andreas; Imkeller, Peter; Perkowski, Nicolas

    2012-01-01

    Ciesielski's isomorphism between the space of alpha-H\\"older continuous functions and the space of bounded sequences is used to give an alternative proof of the large deviation principle for Wiener processes with values in Hilbert space.

  6. 40 CFR 60.2220 - What must I include in the deviation report?

    Science.gov (United States)

    2010-07-01

    ... Commercial and Industrial Solid Waste Incineration Units for Which Construction Is Commenced After November... § 60.2215, for any pollutant or parameter that deviated from the emission limitations or...

  7. 40 CFR 62.14740 - What must I include in the deviation report?

    Science.gov (United States)

    2010-07-01

    ... POLLUTANTS Federal Plan Requirements for Commercial and Industrial Solid Waste Incineration Units That... include in the deviation report? In each report required under § 62.14735, for any pollutant or...

  8. 40 CFR 60.2780 - What must I include in the deviation report?

    Science.gov (United States)

    2010-07-01

    ... Compliance Times for Commercial and Industrial Solid Waste Incineration Units that Commenced Construction On... the deviation report? In each report required under § 60.2775, for any pollutant or parameter...

  9. 41 CFR 102-33.10 - May we request approval to deviate from these rules?

    Science.gov (United States)

    2010-07-01

    ...,” revised May 22, 1992. You should consult with GSA's Aircraft Management Policy Division (MTA) before you request a deviation. Also, you should fax a copy of your letter of request to MTA at 202-501-6742 at...

  10. Moderate deviations and functional limits for random processes with stationary and independent increments

    Institute of Scientific and Technical Information of China (English)

    GAO; Fuqing

    2006-01-01

    We first give a functional moderate deviation principle for random processes with stationary and independent increments under the Ledoux's condition.Then we apply the result to laws of the iterated logarithm.

  11. Large Deviations for Stochastic Partial Differential Equations Driven by a Poisson Random Measure

    CERN Document Server

    Budhiraja, Amarjit; Dupuis, Paul

    2012-01-01

    Stochastic partial differential equations driven by Poisson random measures (PRM) have been proposed as models for many different physical systems, where they are viewed as a refinement of a corresponding noiseless partial differential equations (PDE). A systematic framework for the study of probabilities of deviations of the stochastic PDE from the deterministic PDE is through the theory of large deviations. The goal of this work is to develop the large deviation theory for small Poisson noise perturbations of a general class of deterministic infinite dimensional models. Although the analogous questions for finite dimensional systems have been well studied, there are currently no general results in the infinite dimensional setting. This is in part due to the fact that in this setting solutions may have little spatial regularity, and thus classical approximation methods for large deviation analysis become intractable. The approach taken here, which is based on a variational representation for nonnegative func...

  12. THE INCIDENCE OF BENDER-GESTALT FIGURE DEVIATIONS IN A GROUP OF MENTALLY RETARDED PSYCHIATRIC PATIENTS

    Directory of Open Access Journals (Sweden)

    Habibollah Ghassemzadeh

    1994-06-01

    Full Text Available The Bender-Gestalt Test was given to thirty mentally-retarded psychiatric patients. The mean, standard deviation, and standard error were 56.73, 26.25, and 4.80 respectively. Rotation was the most frequent major deviation which occurred in all the designs."nDesign # 7 was the most difficult one to be reproduced in the sample. This design by itself, was subject to 47% of distortion, 79% of omission, and 21% of rotation.

  13. Model for crystallization kinetics: Deviations from Kolmogorov-Johnson-Mehl-Avrami kinetics

    OpenAIRE

    Castro, Mario; Domínguez-Adame Acosta, Francisco; Sánchez, A; Rodriguez, T.

    1999-01-01

    We propose a simple and versatile model to understand the deviations from the well-known Kolmogorov-Johnson-Mehl-Avrami kinetics theory found in metal recrystallization and amorphous semiconductor crystallization. We analyze the kinetics of the transformation and the grain-size distribution of the product material, finding a good overall agreement between our model and available experimental data. The information so obtained could help to relate the mentioned experimental deviations due to pr...

  14. Large deviations for multidimensional state-dependent shot-noise processes

    OpenAIRE

    Budhiraja, Amarjit; Nyquist, Pierre

    2015-01-01

    Shot-noise processes are used in applied probability to model a variety of physical systems in, for example, teletraffic theory, insurance and risk theory, and in the engineering sciences. In this paper we prove a large deviation principle for the sample-paths of a general class of multidimensional state-dependent Poisson shot-noise processes. The result covers previously known large deviation results for one-dimensional state-independent shot-noise processes with light tail...

  15. Finite-time deviations from exponential decay in the Weisskopf-Wigner model of spontaneous emission

    International Nuclear Information System (INIS)

    For the first time to the authors' knowledge, a mathematically rigorous method is used for treating finite-time deviations from the exponential decay in the case of spontaneous Lyman-α transition in a two-level hydrogenic atom. In the so-called Weisskopf-Wigner model (where the rotating-wave approximation is implied), finite-time deviations with a rigorous validity range, based on accurate error estimations, are derived. (orig.)

  16. Left-Deviating Prism Adaptation in Left Neglect Patient: Reflexions on a Negative Result

    OpenAIRE

    Jacques Luauté; Sophie Jacquin-Courtois; Jacinta O'Shea; Laure Christophe; Gilles Rode; Dominique Boisson; Yves Rossetti

    2012-01-01

    Adaptation to right-deviating prisms is a promising intervention for the rehabilitation of patients with left spatial neglect. In order to test the lateral specificity of prism adaptation on left neglect, the present study evaluated the effect of left-deviating prism on straight-ahead pointing movements and on several classical neuropsychological tests in a group of five right brain-damaged patients with left spatial neglect. A group of healthy subjects was also included for comparison purpos...

  17. Cost Contingency as the Standard Deviation of the Cost Estimate for Cost Engineering

    OpenAIRE

    Geoffrey Rothwell

    2004-01-01

    Traditional cost contingency estimation relies heavily on expert judgment based on various cost-engineering standards. This paper compares project stages, accuracy ranges, and cost contingencies recommended by the Association for the Advancement of Cost Engineering International and the Electric Power Research Institute. It shows that current guidelines are consistent with contingencies equal to the standard deviation of the cost estimate. It suggests how this standard deviation can be derive...

  18. Research of the Problem of Vehicle Deviation%车辆跑偏问题研究

    Institute of Scientific and Technical Information of China (English)

    唐晓峰

    2009-01-01

    针对售后常见的车辆跑偏问题,提出两种通用的评判方法以及评判标准;同时着重分析了车辆跑偏产生原理以及解决的办法.%Two evaluation methods and standards are put forward aiming at the after - sales problem of vehicle deviation. The principle of vehiele deviation and its solution method are focused.

  19. Analysis of the neutron albedo’s influence on TIP deviations in Forsmark 1

    OpenAIRE

    Skan, Moa

    2016-01-01

    In the operation of a nuclear reactor, detailed calculations are performed to predict the power distribution in the core and to ensure the maintenance of a number of safety margins. Repeatedly during a power cycle, the predictions are verified in so-called TIP measurements, and the consequences of possible deviations are investigated. During the latest power cycles until today, the Forsmark 1 reactor has experienced large deviations in TIP measurements at the edge of the reactor core that ha...

  20. Deviations from early--time quasilinear behaviour for the quantum kicked rotor near the classical limit

    CERN Document Server

    Sadgrove, M; Parkins, S; Leonhardt, R; Sadgrove, Mark; Mullins, Terry; Parkins, Scott; Leonhardt, Rainer

    2004-01-01

    We present experimental measurements of the mean energy for the atom optics kicked rotor after just two kicks. The energy is found to deviate from the quasi--linear value for small kicking periods. The observed deviation is explained by recent theoretical results which include the effect of a non--uniform initial momentum distribution, previously applied only to systems using much colder atoms than ours.

  1. Model Evaluation the Effect of Size, Shape and Surface Condition of Apatite Nanocrystals on the Deviation of Ca / P ratio from stoichiometric

    Directory of Open Access Journals (Sweden)

    S.N. Danilchenko

    2014-04-01

    Full Text Available The causes of Са / Р ratio deviation in biological apatites from stoichiometric one were discussed. By the simple model evaluation Са / Р ratio was shown to deviate from stoichiometric one because of small sizes of crystals, and peculiarities in chemical composition of their facets. Also size effect is noted to be unsufficient for explanation of wide variations of Са / Р ratio in biological apatites. It proves the significant contribution of lattice isovalent and heterovalent substitution into variability of Са / Р ratio. The problem of revealing the predominant causes of Са / Р deviation from stoichiometric one and estimation of their relative contribution is related to determination of the functional role of the structural imperfections in biological apatites of different origin.

  2. Gait deviations and compensations in pediatric patients with increased femoral torsion.

    Science.gov (United States)

    Bruderer-Hofstetter, Marina; Fenner, Verena; Payne, Erika; Zdenek, Katja; Klima, Harry; Wegener, Regina

    2015-02-01

    Coxa antetorta describes an abnormal torsion of the femur. It is commonly considered a cosmetic problem and is treated surgically only in severe cases and the presence of physical complaints. The purpose of this study was to identify deviations in gait kinematics and kinetics in pediatric patients caused by coxa antetorta and to categorize these deviations into primary and secondary deviations. We conducted a retrospective, cross-sectional three-dimensional (3D) gait analysis study to detect gait deviations in adolescents (n = 18; age range 10.5-17.5 years) with coxa antetorta compared to age-matched healthy control subjects (n = 17). Principal component (PC) analysis was used for data reduction. Linear mixed models applied to PC-scores were used to estimate the main effects within retained PCs followed by a post-hoc subgroup analysis. Patients walked with smaller external foot progression angle, greater knee adduction, more internally rotated and flexed hips and greater anterior pelvic tilt. Subgroup analysis revealed that-depending on knee alignment-patients had higher knee and hip adduction moments. These deviations in joint kinematics and kinetics may be associated with physical complaints and accelerated development of osteoarthritis. Assessment of gait deviations related to coxa antetorta using 3D gait analysis may be an additional tool in individual clinical decision-making.

  3. Inferior Oblique Muscle Weakening: Is It Possible to Quantify Its Effects on Horizontal Deviations?

    Directory of Open Access Journals (Sweden)

    Hande Taylan Sekeroglu

    2012-01-01

    Full Text Available Objective. To evaluate and quantify the effect of inferior oblique muscle weakening on horizontal deviations. Methods. The medical files of patients who had undergone an inferior oblique weakening as a single procedure were all reviewed. The main measures were the type of inferior oblique overaction (IOOA, pre- and postoperative amount of IOOA, and horizontal deviations in primary position. Results. The study was conducted with 66 patients (30 males, 36 females. The median age was 11 years (1–49. Of the 66 patients, 30 (45.5% had primary and 36 (54.5% had secondary IOOA. The most common procedure was inferior oblique anteriorization in 32 patients (48.5%. The mean postoperative horizontal and vertical deviations and the amount of IOOA were decreased postoperatively ( for all. The median amount of correction of horizontal near and distance deviations was (0–20. The preoperative amount of IOOA, the presence of fourth nerve palsy, and the type of the weakening procedure had no significant effect on the amount of correction of horizontal deviations. Conclusion. The inferior oblique weakening procedures have secondary effects and warrant reduction of horizontal deviations in varying degrees. This should be borne in mind in planning a simultaneous horizontal muscle surgery and setting the surgical amount.

  4. A strategy to objectively evaluate the necessity of correcting detected target deviations in image guided radiotherapy

    International Nuclear Information System (INIS)

    Image guided radiotherapy technologies are being increasingly utilized in the treatment of various cancers. These technologies have enhanced the ability to detect temporal and spatial deviations of the target volume relative to planned radiation beams. Correcting these detected deviations may, in principle, improve the accuracy of dose delivery to the target. However, in many situations, a clinical decision has to be made as to whether it is necessary to correct some of the deviations since the relevant dosimetric impact may or may not be significant, and the corresponding corrective action may be either impractical or time consuming. Ideally this decision should be based on objective and reproducible criteria rather than subjective judgment. In this study, a strategy is proposed for the objective evaluation of the necessity of deviation correction during the treatment verification process. At the treatment stage, without any alteration from the planned beams, the treatment beams should provide the desired dose coverage to the geometric volume identical to the planning target volume (PTV). Given this fact, the planned dose distribution and PTV geometry were used to compute the dose coverage and PTV enclosure of the clinical target volume (CTV) that was detected from imaging during the treatment setup verification. The spatial differences between the detected CTV and the planning CTV are essentially the target deviations. The extent of the PTV enclosure of the detected CTV as well as its dose coverage were used as criteria to evaluate the necessity of correcting any of the target deviations. This strategy, in principle, should be applicable to any type of target deviations, including both target deformable and positional changes and should be independent of how the deviations are detected. The proposed strategy was used on two clinical prostate cancer cases. In both cases, gold markers were implanted inside the prostate for the purpose of treatment setup

  5. PSYCHOLOGICAL MECHANISMS OF FORMATION OF DEVIATIONS IN THE PERIOD OF PREPARATION FOR MOTHERHOOD

    Directory of Open Access Journals (Sweden)

    S. A. Moreva

    2015-01-01

    Full Text Available The article presents a social-psychological indicators of stress, coping mechanisms, rigidity and psychological component gestational dominant as risk factors predisposing to deviations in the context of preparedness for motherhood, marked psychological characteristics of pregnant women main group.Material and methods. The study was conducted on the basis of obstetric clinics SSMU, prenatal maternity hospital number 4 and the Centre for Medical Prevention (Cabinet crisis pregnancy. Total was attended by 52 women aged 18 to 44 years, at different stages of pregnancy – from 5 to 39 weeks. Methodological apparatus consisted of a structured interview questionnaire “Medical and social data of the pregnant woman” methodology for determining the stress and social adaptation of Holmes and Rage (1967, a questionnaire of coping R. Lazarus and S. Folkman (WCQ, 1988, Tomsk questionnaire rigidity G.V. Zalewski (TORZ, 1987, test on pregnant I.V. Dobryakova (1996. Data processing was carried out using statistical methods Spearman rank correlation coefficient, nonparametric Mann–Whitney U and Kruskal–Wallis H and φ * – Fisher's angular transformation.Results. Significant psychological factors that may influence the formation of readiness for motherhood among women of the main group can be considered an unplanned pregnancy (65%, and also its not gelendost (35%.Studies of stress resistance was detected in pregnant women from the main group low stress levels (88%, and only 12% have a high degree. Most of the women from the сomparison group reverse the situation 64% have a high degree of stress, this suggests that the presence of previously state miscarriage is for this group of stress.On the formation of readiness for motherhood affects not only the presence of stressful situations, butalso how the woman in their lives. Using U-test Mann–Whitney, were statistically significant differences were observed among the main group and сomparison group in

  6. Deviations outside the acceptance limits in the IAEA/WHO TLD audits for radiotherapy hospitals

    International Nuclear Information System (INIS)

    The main purpose of the IAEA/WHO TLD postal dose audit programme for dosimetry in radiotherapy is to provide an independent verification of the dose delivered by treatment machines in radiotherapy hospitals. The results of the TLD audit are considered acceptable if the relative deviation between the participant's stated dose and the TLD determined dose is within ±5%. The goal of this note is to draw the attention of participants of the TLD programme to some of the common reasons for deviations outside the acceptance limits. Armed with this knowledge, other participants may avoid similar problems in the future. The analysis of deviations presented here is based on the results of TLD audits of the calibration of approximately 1000 Co-60 beams and 600 high-energy X-ray beams performed in the period 1996-2001. A total of 259 deviations outside the ±5% limits have been detected, including 204 deviations for Co-60 beams (20% of all Co-60 beams checked) and 55 for high-energy X-ray beams (10% of all X-ray beams checked). It is worth mentioning that the percentage of large deviations (beyond 10%) is also higher for Co-60 beams than for high-energy X-ray beams. Some problems may be caused by obsolete dosimetry equipment or poor treatment machine conditions. Other problems may be due to insufficient training of staff working in radiotherapy. The clinical relevance of severe TLD deviations detected in the audit programme was confirmed in many cases, but, fortunately, not all-poor dosimetric results reflect deficiencies in the calibration of clinical beams or machine faults. Sometime it happens, that the TLDs are irradiated with an incorrect dose due to misunderstanding of the instructions on how to perform the TLD irradiation. Such dosimetry errors would have no direct impact on actual dose delivered to a patient

  7. Identification of characteristic model-observation deviations for coupled data assimilation

    Science.gov (United States)

    Geppert, Gernot; Ament, Felix

    2016-04-01

    Exchange fluxes of water and energy between the land surface and the atmosphere lead to the propagation of errors from one model component to the other. Data assimilation can correct such errors in two ways, either by correcting the observed state directly or by changing the state that caused the exchange fluxes. The land surface, for example, strongly determines the temperature in the atmospheric boundary layer. The assimilation of boundary layer temperature can then correct the model's temperature directly. Or the assimilation of boundary layer temperature can act on the model's land surface state. A coupled data assimilation system should exploit these links and enable the second type of correction across model components. Data assimilation relies on instantaneous deviations between model forecasts and observations. Such instantaneous deviations are often hard to relate to errors in specific model components. Therefore, model verification builds on more sophisticated statistics such as long-term biases, gradients, phase shifts, or conditional differences that yield characteristic differences between model forecasts and observations. Compared to the instantaneous deviations in data assimilation, the characteristic deviations in model verification are more closely linked to errors in specific model components. Consequently, such characteristic deviations can potentially be used for data assimilation across model components where instantaneous deviations are not sufficiently informative. As a first step towards data assimilation with characteristic deviations (here named fingerprints), we use ensembles of simulations with the Icosahedral Non-hydrostatic (ICON) model to identify applicable statistics of observable variables. We run ICON in a large eddy simulation configuration on a small, limited domain and systematically perturb soil and land-surface parameters and states to produce the ensembles. Subsequently, we test statistics of boundary layer observables to

  8. Deviations in the endocrine system and brain of patients with fibromyalgia: cause or consequence of pain and associated features?

    Science.gov (United States)

    Geenen, Rinie; Bijlsma, Johannes W J

    2010-04-01

    The brain and endocrine system are crucial interfaces responding to pathological and psychological processes. This review discusses whether endocrine deviations and structural and functional changes in the brain are a cause or consequence of fibromyalgia. Studies in patients with fibromyalgia virtually uniformly observed subtle alterations in hypothalamic pituitary adrenal functioning, hyporeactive autonomic nervous system responsiveness to stressors, and structural and functional changes in the brain. Our model proposes that predisposing factors, such as genetic vulnerability and trauma, have led to an alteration of the nociceptive system including several neuroendocrine changes. The resulting pain and associated symptoms, such as sleep disturbance, low fitness, fatigue, stress, and distress, are a cause of new neuroendocrine changes. The model predicts that favorable neuroendocrine changes are to be expected after successful pharmacological or non-pharmacological interventions that target pain and associated symptoms.

  9. Geodesic Deviation Equation in $\\Lambda$CDM $f(T,\\mathcal{T})$ gravity

    CERN Document Server

    Ganiou, M G; Houndjo, M J S; Tossa, J

    2016-01-01

    The geodesic deviation equation has been investigated in the framework of $f(T,\\mathcal{T})$ gravity, where $T$ denotes the torsion and $\\mathcal{T}$ is the trace of the energy-momentum tensor, respectively. The FRW metric is assumed and the geodesic deviation equation has been established following the General Relativity approach in the first hand and secondly, by a direct method using the modified Friedmann equations. Via fundamental observers and null vector fields with FRW background, we have generalized the Raychaudhuri equation and the Mattig relation in $f(T,\\mathcal{T})$ gravity. Furthermore, we have numerically solved the geodesic deviation equation for null vector fields by considering a particular form of $f(T,\\mathcal{T})$ which induces interesting results susceptible to be tested with observational data.

  10. Geodesic Deviation Equation in ΛCDM f(T,{T}) Gravity

    Science.gov (United States)

    Ganiou, M. G.; Salako, Ines G.; Houndjo, M. J. S.; Tossa, J.

    2016-09-01

    The geodesic deviation equation has been investigated in the framework of f(T,{T}) gravity, where T denotes the torsion and {T} is the trace of the energy-momentum tensor, respectively. The FRW metric is assumed and the geodesic deviation equation has been established following the General Relativity approach in the first hand and secondly, by a direct method using the modified Friedmann equations. Via fundamental observers and null vector fields with FRW background, we have generalized the Raychaudhuri equation and the Mattig relation in f(T,{T}) gravity. Furthermore, we have numerically solved the geodesic deviation equation for null vector fields by considering a particular form of f(T,{T}) which induces interesting results susceptible to be tested with observational data.

  11. Analysis of Deviations in an Agent and Ontology-Based Dialogue Management System

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Algorithms of detecting dialogue deviations from a dialogue topic in an agent and ontology-based dialogue management system(AODMS) are proposed. In AODMS, agents and ontologies are introduced to represent domain knowledge. And general algorithms that model dialogue phenomena in different domains can be realized in that complex relationships between knowledge in different domains can be described by ontologies. An evaluation of the dialogue management system with deviation-judging algorithms on 736 utterances shows that the AODMS is able to talk about the given topic consistently and answer 86.6% of the utterances, while only 72.1% of the utterances can be responded correctly without deviation-judging module.

  12. Large deviations of the shifted index number in the Gaussian ensemble

    Science.gov (United States)

    Pérez Castillo, Isaac

    2016-06-01

    We show that, using the Coulomb fluid approach, we are able to derive a rate function \\Psi(c,x) of two variables that captures: (i) the large deviations of bulk eigenvalues; (ii) the large deviations of extreme eigenvalues (both left and right large deviations); (iii) the statistics of the fraction c of eigenvalues to the left of a position x. Thus, \\Psi(c,x) explains the full order statistics of the eigenvalues of large random Gaussian matrices as well as the statistics of the shifted index number. All our analytical findings are thoroughly compared with Monte Carlo simulations, obtaining excellent agreement. A summary of preliminary results has already been presented in Pérez Castillo (2014 Phys. Rev. E 90 040102) in the context of one-dimensional trapped spinless fermions in a harmonic potential.

  13. Subfamily logos: visualization of sequence deviations at alignment positions with high information content

    Directory of Open Access Journals (Sweden)

    Beitz Eric

    2006-06-01

    Full Text Available Abstract Background Recognition of relevant sequence deviations can be valuable for elucidating functional differences between protein subfamilies. Interesting residues at highly conserved positions can then be mutated and experimentally analyzed. However, identification of such sites is tedious because automated approaches are scarce. Results Subfamily logos visualize subfamily-specific sequence deviations. The display is similar to classical sequence logos but extends into the negative range. Positive, upright characters correspond to residues which are characteristic for the subfamily, negative, upside-down characters to residues typical for the remaining sequences. The symbol height is adjusted to the information content of the alignment position. Residues which are conserved throughout do not appear. Conclusion Subfamily logos provide an intuitive display of relevant sequence deviations. The method has proven to be valid using a set of 135 aligned aquaporin sequences in which established subfamily-specific positions were readily identified by the algorithm.

  14. Deviating measurements in radiation protection. Legal assessment of deviations in radiation protection measurements; Messabweichungen im Strahlenschutz. Rechtliche Bewertung von Abweichungen bei Strahlenschutzmessungen

    Energy Technology Data Exchange (ETDEWEB)

    Hoegl, A.

    1996-07-01

    This study investigates how, from a legal point of view, deviations in radiation protection measurements should be treated in comparisons between measured results and limits stipulated by nuclear legislation or goods transport regulations. A case-by-case distinction is proposed which is based on the legal concequences of the respective measurement. Commentaries on nuclear law contain no references to the legal assessment of deviating measurements in radiation protection. The examples quoted in legal commentaries on civil and criminal proceedings of the way in which errors made in measurements for speed control and determinations of the alcohol content in the blood are to be taken into account, and a commentary on ozone legislation, are examined for analogies with radiation protection measurements. Leading cases in the nuclear field are evaluated in the light of the requirements applying in case of deviations in measurements. The final section summarizes the most important findings and conclusions. (orig.) [Deutsch] Es wird untersucht, wie aus rechtlicher Sicht Messabweichungen bei Strahlenschutzmessungen zu beruecksichtigen sind, wenn Messergebnisse mit Grenzwerten des Atomrechts oder Gueterverkehrsrechts verglichen werden. Hierzu wird eine Fallunterscheidung vorgeschlagen, die von den jeweiligen Rechtsfolgen eine Messung ausgeht. In Kommentaren zum Atomrecht konnten keine Hinweise fuer die rechtliche Bewertung von Messabweichungen bei Strahlenschutzmessungen gefunden werden. Die in Rechtskommentaren zur Zivil- und Strafprozessordnung enthaltenen Beispiele der Fehlerberuecksichtigung bei Messungen zur Geschwindigkeitsueberwachung und Blutalkoholbestimmung sowie ein Kommentar zum Ozongesetz wurden auf Analogien zu Strahlenschutzmessungen untersucht. Gerichtliche Grundsatzentscheidungen aus dem Bereich der Kerntechnik werden im Hinblick auf Anforderungen bei Messabweichungen ausgewertet. Im letzten Abschnitt sind die wichtigsten Ergebnisse und Schlussfolgerungen

  15. Will Septal Correction Surgery for Deviated Nasal Septum Improve the Sense of Smell? A Prospective Study

    Directory of Open Access Journals (Sweden)

    Neelima Gupta

    2015-01-01

    Full Text Available Background and Objectives. Nasal obstruction due to deviated nasal septum is a common problem bringing a patient to an otorhinolaryngologist. Occasionally, these patients may also complain of olfactory impairment. We proposed to study the effect of septal deviation on the lateralised olfactory function and the change in olfaction after surgery of the septum (septoplasty. Methods. Forty-one patients with deviated nasal septum were evaluated for nasal airflow, olfactory score, and nasal symptomatology. Septoplasty was done under local anesthesia. Pre- and postoperative olfactory scores, airflow and olfactory scores, and nasal symptomatology and olfactory scores were compared and correlated. Results. The range of preoperative composite olfactory score (COS on the side of septal deviation was 4–14 (mean 7.90±2.234 and on the nonobstructed side was 9–18 (mean 14.49±2.378. Severity of deviated nasal septum and preoperative COS of diseased side were correlated and the correlation was found to be significant (rho = −0.690, p=0.000 (<0.001. The preoperative mean COS (7.90±2.234 was compared with the postoperative mean COS (12.39±3.687 and the improvement was found to be statistically significant (p=0.000 (<0.001. Conclusion. We found improvement in olfactory function in 70.6% patients after surgery, no change in 20.1%, and reduced function in 7.6%. With the limitation of a small sample size and a potential repeat testing bias, we would conclude that correction of nasal septal deviation may lead to improvement in sense of smell.

  16. 41 CFR 102-38.30 - How does an executive agency request a deviation from the provisions of this part?

    Science.gov (United States)

    2010-07-01

    ... which are distinct from the standard deviation process and specific to the requirements of the Federal... agency request a deviation from the provisions of this part? 102-38.30 Section 102-38.30 Public Contracts... executive agency request a deviation from the provisions of this part? Refer to §§ 102-2.60 through...

  17. Deviation from zeitgeist and motivation in the intergenerational transmission of individualistic and collectivistic values in East Germany and Shanghai, China.

    Science.gov (United States)

    Schönpflug, Ute; Yan, Song

    2014-01-01

    Intergenerational intrafamilial transmission is a process by which acquired information passes from parent to offspring. The authors examined mechanisms of intergenerational transmission of individualistic and collectivistic values in 216 families with 1 adolescent child in 2 societies: East Germany and the Shanghai region in China. To clarify the impact of transmission from mother and father to son or daughter, this study analyzed the filter model by U. Schönpflug and L. Bilz (2009), including zeitgeist concerning value climate in the social context, each family member's deviation from the zeitgeist, and the familial motivation to transmit. The 2-dimensional structure (individualism and collectivism) of 10 values of the Portrait Value Questionnaire (Schwartz, Lehmann, & Rocca, 1999) differed somewhat in the 2 regions for adolescents and their fathers, but not for mothers. In East Germany, no significant direct transmission of value orientation was observed, whereas in Shanghai, fathers transmitted individualism and collectivism values. Family motivation impacted significantly on the child's value orientation in both regions. The zeitgeist measure had no significant influence on the transmission process whereas deviation from zeitgeist did. The gender of the child determined the level and transmission of collectivism, but not the transfer of individualism.

  18. Deviation from zeitgeist and motivation in the intergenerational transmission of individualistic and collectivistic values in East Germany and Shanghai, China.

    Science.gov (United States)

    Schönpflug, Ute; Yan, Song

    2014-01-01

    Intergenerational intrafamilial transmission is a process by which acquired information passes from parent to offspring. The authors examined mechanisms of intergenerational transmission of individualistic and collectivistic values in 216 families with 1 adolescent child in 2 societies: East Germany and the Shanghai region in China. To clarify the impact of transmission from mother and father to son or daughter, this study analyzed the filter model by U. Schönpflug and L. Bilz (2009), including zeitgeist concerning value climate in the social context, each family member's deviation from the zeitgeist, and the familial motivation to transmit. The 2-dimensional structure (individualism and collectivism) of 10 values of the Portrait Value Questionnaire (Schwartz, Lehmann, & Rocca, 1999) differed somewhat in the 2 regions for adolescents and their fathers, but not for mothers. In East Germany, no significant direct transmission of value orientation was observed, whereas in Shanghai, fathers transmitted individualism and collectivism values. Family motivation impacted significantly on the child's value orientation in both regions. The zeitgeist measure had no significant influence on the transmission process whereas deviation from zeitgeist did. The gender of the child determined the level and transmission of collectivism, but not the transfer of individualism. PMID:24796155

  19. From dynamic to static Large Deviations in boundary driven exclusion particle systems.

    CERN Document Server

    Bodineau, T

    2002-01-01

    We consider the large deviations for the stationary measures associated to a boundary driven symmetric simple exclusion process. Starting from the large deviations for the hydrodynamics and following the Freidlin and Wentzell's strategy, we prove that the rate function is given by the quasi--potential of the Freidlin and Wentzell theory. This result is motivated by the recent developments on the non-equilibrium stationary measures by Derrida, Lebowitz and Speer and the more closely related dynamical approach by Bertini, De Sole, Gabrielli, Jona Lasinio, Landim.

  20. Sensitivity analysis of the channel estimation deviation to the MAP decoding algorithm

    Institute of Scientific and Technical Information of China (English)

    WAN Ke; FAN Ping-zhi

    2006-01-01

    As a necessary input parameter for maximum a-posteriori(MAP) decoding algorithm,SNR is normally obtained from the channel estimation unit.Corresponding research indicated that SNR estimation deviation degraded the performance of Turbo decoding significantly.In this paper,MAP decoding algorithm with SNR estimation deviation was investigated in detail,and the degradation mechanism of Turbo decoding was explained analytically.The theoretical analysis and computer simulation disclosed the specific reasons for the performance degradation when SNR estimation was less than the actual value,and for the higher sensitivity of SNR estimation to long-frame Turbo codes.

  1. Control of the multiclass G/G/1 queue in the moderate deviation regime

    CERN Document Server

    Atar, Rami

    2012-01-01

    A multi-class single-server system with general service time distributions is studied in a moderate deviation heavy traffic regime. In the scaling limit, an optimal control problem associated with the model is shown to be governed by a differential game, that can be explicitly solved. While the characterization of the limit by a differential game is akin to results at the large deviation scale, the analysis of the problem is closely related to the much studied area of control in heavy traffic at the diffusion scale.

  2. Quenched large deviations for multidimensional random walk in random environment: a variational formula

    CERN Document Server

    Rosenbluth, Jeffrey M

    2008-01-01

    We take the point of view of the particle in a multidimensional nearest neighbor random walk in random environment (RWRE). We prove a quenched large deviation principle and derive a variational formula for the quenched rate function. Most of the previous results in this area rely on the subadditive ergodic theorem. We employ a different technique which is based on a minimax theorem. Large deviation principles for RWRE have been proven for i.i.d. nestling environments subject to a moment condition and for ergodic uniformly elliptic environments. We assume only that the environment is ergodic and the transition probabilities satisfy a moment condition.

  3. Definition of resulting angle of the deviation after the passage of neutrons through the crystal

    International Nuclear Information System (INIS)

    The present paper is dedicated to the consideration of passage of neutrons in the crystal. The expression for intensity distribution is obtained by the method of the multiple scattering theories. The received results are applied to calculation angle of the deviation of neutrons by nucleus of the crystal. Here is shown that at the large angle of deviation, the intensity of distribution decreases with reduction of angle much more slowly than till Gaussian law. The received expression for the angle of the dviation allows defining of the impulse of the neutron

  4. Fixed pattern deviations in Si pixel detectors measured using the Medipix 1 readout chip

    CERN Document Server

    Tlustos, L; Davidson, D; Heijne, Erik H M; Mikulec, B

    2003-01-01

    Dopant fluctuations and other defects in silicon wafers can lead to systematic errors in several parameters in particle or single-photon detection. In imaging applications non-uniformities in sensors or readout give rise to fixed pattern image noise and degradation of achievable spatial resolution for a given flux. High granularity pixel detectors offer the possibility to investigate local properties of the detector material on a microscopic scale. In this paper, we study fixed pattern detection fluctuations and detector inhomogeneities using the Medipix 1 readout chip. Low-frequency fixed pattern signal deviations due to dopant inhomogeneities can be separated from high-frequency deviations.

  5. Allan Deviation Plot as a Tool for Quartz-Enhanced Photoacoustic Sensors Noise Analysis.

    Science.gov (United States)

    Giglio, Marilena; Patimisco, Pietro; Sampaolo, Angelo; Scamarcio, Gaetano; Tittel, Frank K; Spagnolo, Vincenzo

    2016-04-01

    We report here on the use of the Allan deviation plot to analyze the long-term stability of a quartz-enhanced photoacoustic (QEPAS) gas sensor. The Allan plot provides information about the optimum averaging time for the QEPAS signal and allows the prediction of its ultimate detection limit. The Allan deviation can also be used to determine the main sources of noise coming from the individual components of the sensor. Quartz tuning fork thermal noise dominates for integration times up to 275 s, whereas at longer averaging times, the main contribution to the sensor noise originates from laser power instabilities.

  6. Maxillary palatal ramp prosthesis: A prosthodontic solution to manage mandibular deviation following surgery

    Directory of Open Access Journals (Sweden)

    Sampa Ray (Bhattacharya

    2015-01-01

    Full Text Available Mandibular resection following surgical treatment for neoplastic lesions of the oral cavity leads to numerous complications including altered mandibular movements, disfigurement, difficult in swallowing, impaired speech and articulation, and deviation of the mandible towards the resected site. Various prosthetic methods are employed to reduce or minimize mandibular deviation and improve and restore the lost functions and esthetic, like maxillomandibular fixation, implant supported prosthesis, removable mandibular guide flange prosthesis, and palatal based guidance restoration. This clinical report describes the rehabilitation of a patient following segmental mandibulectomy using palatal ramp prosthesis.

  7. Stylistic Analysis of Rossetti’s Song with the Technique of Deviation

    Institute of Scientific and Technical Information of China (English)

    胡争艳

    2013-01-01

    Song is one of Christina Georgina Rossetti’s most outstanding death poems, dealing with the main themes that she concerns:death, love and religion. This paper tries to use the technique of deviation that refers to violations to the standard lan⁃guage and readers’expectations to interpret this poem’s stylistic features from the aspects of grammar, phonology, image, theme and narrative point of view. Through the stylistic analysis with the method of deviation, its solemn theme is exposed clearly.

  8. Quantitative evaluation of standard deviations of group velocity dispersion in optical fibre using parametric amplification

    DEFF Research Database (Denmark)

    Rishøj, Lars Søgaard; Svane, Ask Sebastian; Lund-Hansen, Toke;

    2014-01-01

    A numerical model for parametric amplifiers, which include stochastic variations of the group velocity dispersion (GVD), is presented. The impact on the gain is investigated, both with respect to the magnitude of the variations and by the effect caused by changing the wavelength of the pump. It i....... It is demonstrated that the described model is able to predict the experimental results and thereby provide a quantitative evaluation of the standard deviation of the GVD. For the investigated fibre, a standard deviation of 0.01 ps/(nm km) was found....

  9. LARGE DEVIATION FOR THE EMPIRICAL CORRELATION COEFFICIENT OF TWO GAUSSIAN RANDOM VARIABLES

    Institute of Scientific and Technical Information of China (English)

    Shen Si

    2007-01-01

    In this article, the author obtains the large deviation principles for the empirical correlation coefficient of two Gaussian random variables X and Y. Especially, when considering two independent Gaussian random variables X, Y with the means EX, EY(both known), wherein the author gives two kinds of different proofs and gets the same results.

  10. Electrocardiographic precordial ST-segment deviations and the risk of cardiovascular death

    DEFF Research Database (Denmark)

    Rasmussen, Peter Vibe; Nielsen, Jonas Bille; Pietersen, Adrian;

    2014-01-01

    computerized analysis of ECGs from 285 194 persons, we evaluated the association between precordial ST-segment deviations and the risk of CVD. All data on medication, comorbidity, and outcomes were retrieved from Danish registries. After a median follow-up period of 5.8 years, there were 6679 cardiovascular...

  11. Existence of piecewise continuous mild solutions for impulsive functional differential equations with iterated deviating arguments

    Directory of Open Access Journals (Sweden)

    Pradeep Kumar

    2013-10-01

    Full Text Available The objective of this article is to prove the existence of piecewise continuous mild solutions to impulsive functional differential equation with iterated deviating arguments in a Banach space. The results are obtained by using the theory of analytic semigroups and fixed point theorems.

  12. A rare case of minimal deviation adenocarcinoma of the uterine cervix in a renal transplant recipient.

    LENUS (Irish Health Repository)

    Fanning, D M

    2009-02-03

    INTRODUCTION: We report the first described case of minimal deviation adenocarcinoma of the uterine cervix in the setting of a female renal cadaveric transplant recipient. MATERIALS AND METHODS: A retrospective review of this clinical case was performed. CONCLUSION: This rare cancer represents only about 1% of all cervical adenocarcinoma.

  13. Large deviations for the Fleming-Viot process with neutral mutation and selection

    OpenAIRE

    Dawson, Donald; Feng, Shui

    1998-01-01

    Large deviation principles are established for the Fleming-Viot processes with neutral mutation and selection, and the corresponding equilibrium measures as the sampling rate goes to 0. All results are first proved for the finite allele model, and then generalized, through the projective limit technique, to the infinite allele model. Explicit expressions are obtained for the rate functions.

  14. Large Deviations for Empirical Process of Mean-Field Interacting Particle System with Unbounded Jumps

    OpenAIRE

    Feng, Shui

    1994-01-01

    A large deviation system is established for the empirical processes of a mean-field interacting particle system with unbounded jump rates under assumptions that are satisfied by many interesting models including the first and the second Schlogl models. The action functional obtained has a form that is very useful for applications.

  15. 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.

  16. Gait Deviation Index, Gait Profile Score and Gait Variable Score in children with spastic cerebral palsy

    DEFF Research Database (Denmark)

    Rasmussen, Helle Mätzke; Nielsen, Dennis Brandborg; Pedersen, Niels Wisbech;

    2015-01-01

    Abstract The Gait Deviation Index (GDI) and Gait Profile Score (GPS) are the most used summary measures of gait in children with cerebral palsy (CP). However, the reliability and agreement of these indices have not been investigated, limiting their clinimetric quality for research and clinical...

  17. A rare case of minimal deviation adenocarcinoma of the uterine cervix in a renal transplant recipient.

    LENUS (Irish Health Repository)

    Fanning, D M

    2012-02-01

    INTRODUCTION: We report the first described case of minimal deviation adenocarcinoma of the uterine cervix in the setting of a female renal cadaveric transplant recipient. MATERIALS AND METHODS: A retrospective review of this clinical case was performed. CONCLUSION: This rare cancer represents only about 1% of all cervical adenocarcinoma.

  18. Analysis on the deviation of feeder pipe ultrasonic thickness-measuring data

    International Nuclear Information System (INIS)

    This paper is an analysis on the large deviation of feeder ultrasonic thickness-measuring data in Qinshan NPP III, through which the influence of the inner surface of thin wall carbon steel pipe on ultrasonic thickness measurement accuracy is verified and a principle for selection of a thickness measuring probe for thin wall carbon steel pipe with rough inner surface is introduced. (author)

  19. Analysis of apical deviation by type of system used to drive NRT® MANI rotary instruments

    Directory of Open Access Journals (Sweden)

    Elise Sasso Faccin

    2014-01-01

    Full Text Available Purpose: One of the major challenges encountered in treatment of curved canals is maintaining their original features. This study aimed to examine whether the type of system used with NRT® rotary instruments might in fl uence the occurrence of deviation in the apical region. Methods: Twenty simulated curved canals were divided into two experimental groups. In Group 1, canal preparation was performed with the pneumatic hand piece, using constant speed, but without torque control. In Group 2, an electric motor with constant speed and torque control was used. The simulated blocks were photographed before and after preparation using a platform to maintain the same position in both photographs. Images were manipulated in Adobe Photoshop® to evaluate deviation at 1 mm and 3 mm from the working length (WL. The t test was used for statistical analysis of data. The signi fi cance level was set at 1%. Results and Conclusion: Group 2 (electric motor had lower values for deviation at both locations analyzed (1 mm and 3 mm from the WL. In both groups, sites 3 mm from the WL had lower mean deviation than sites 1 mm from WL.

  20. Deviations of the lepton mapping matrix from the Harrison-Perkins-Scott form

    Institute of Scientific and Technical Information of China (English)

    R.Friedberg; T.D.Lee

    2010-01-01

    We propose a simple set of hypotheses governing the deviations of the leptonic mapping matrix from the Harrison-Perkins-Scott(HPS)form.These deviations are supposed to arise entirely from a perturbation of the mass matrix in the charged lepton sector.The perturbing matrix is assumed to be purely imaginary(thus maximally T-violating)and to have a strength in energy scale no greater(but perhaps smaller)than the muon mass.As we shall show,it then follows that the absolute value of the mapping matrix elements pertaining to the tan lepton deviate by no more than O((mμ/mτ)2)≈3.5 × 10-3 from their HPS values.Assuming that(mμ/mτ)2 can be neglected,we derive two simple constraints on the four parameters θ12,θ23,θ31,and δ of the mapping matrix.These constraints are independent of the details of the imaginary T-violating perturbation of the charged lepton mass matrix.We also show that the e and μ parts of the mapping matrix have a definite form governed by two parameters a and β; any deviation of order mμ/mτ can be accommodated by adjusting these two parameters.

  1. Possible deviations from (V-A) charged currents: precise measurement of muon decay parameters

    International Nuclear Information System (INIS)

    This short review examines the experimental limits on possible deviations from (V-A) charged weak currents, as would occur at some mass scale, for example, in manifestly left-right-symmetric electro-weak theories. Both present and anticipated limits are considered, emphasizing muon-decay experiments but including other experimental input where convenient

  2. OSCILLATION RESULTS RELATED TO INTEGRAL AVERAGING TECHNIQUE FOR EVEN ORDER NEUTRAL DIFFERENTIAL EQUATION WITH DEVIATING ARGUMENTS

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    In this paper, we study an even order neutral differential equation with deviating arguments, and obtain new oscillation results without the assumptions which were required for related results given before. Our results extend and improve many known oscillation criteria, based on the standard integral averaging technique.

  3. Deviating from the standard: effects on labor continuity and career patterns

    NARCIS (Netherlands)

    Roman, A.A.

    2006-01-01

    Deviating from a standard career path is increasingly becoming an option for individuals to combine paid labor with other important life domains. These career detours emerge in diverse labor forms such as part-time jobs, temporary working hour reductions, and labor force time-outs, used to alleviate

  4. AUTOMATED METERING SYSTEM FOR CONTROL OF THE SPATIAL-ANGULAR DEVIATIONS

    Directory of Open Access Journals (Sweden)

    G. A. Zvetkov

    2012-01-01

    Full Text Available Automatic metering system using devices and instruments for inertial navigation has been elaborated. The system allows more accurate measurement of angular deviation of installation sites for scientific equipment. Enhanced functionality is achieved by additional measuring of the azimuth angle error.

  5. J* INTEGRAL OF THE SPECIFIC DEVIATOR STRAIN ENERGY AND ITS APPLICATION

    Institute of Scientific and Technical Information of China (English)

    蒋玉川; 王启智

    2004-01-01

    First the deviator strain energy is introduced, then the problem of plane-crack critical growth was discussed, a path independent line integral J * was defined, furthermore its conservation was proved strictly. As application examples, Mode-I stress intensity factors of cracked beams were obtained with present approach. The results are shown to agree well with those available in the open literature.

  6. Solutions to quasi-linear differential equations with iterated deviating arguments

    Directory of Open Access Journals (Sweden)

    Rajib Haloi

    2014-12-01

    Full Text Available We establish sufficient conditions for the existence and uniqueness of solutions to quasi-linear differential equations with iterated deviating arguments, complex Banach space. The results are obtained by using the semigroup theory for parabolic equations and fixed point theorems. The main results are illustrated by an example.

  7. Dynamical large deviations for a boundary driven stochastic lattice gas model with many conserved quantities

    CERN Document Server

    Farfan, Jonathan; Valentim, Fabio J

    2009-01-01

    We prove the dynamical large deviations for a particle system in which particles may have different velocities. We assume that we have two infinite reservoirs of particles at the boundary: this is the so-called boundary driven process. The dynamics we considered consists of a weakly asymmetric simple exclusion process with collision among particles having different velocities.

  8. Deviations from Desired Age at Marriage: Mental Health Differences across Marital Status

    Science.gov (United States)

    Carlson, Daniel L.

    2012-01-01

    Although several factors condition mental health differences between married and never-married adults, given recent increases in marriage delay and permanent singlehood, one modifying factor--deviation from desired age at marriage--has yet to be examined. Using data from the National Longitudinal Survey of Youth 1979 (N = 7,277), the author tested…

  9. Deviations of the distributions of seismic energies from the Gutenberg-Richter law

    CERN Document Server

    Pisarenko, V; Rodkin, M

    2003-01-01

    A new non-parametric statistic is introduced for the characterization of deviations from power laws. It is tested on the distribution of seismic energies given by the Gutenberg-Richter law. Based on the two first statistical log-moments, it evaluates quantitatively the deviations of the distribution of scalar seismic moments from a power-like (Pareto) law. This statistic is close to zero for the Pareto law with arbitrary power index, and deviates from zero for any non-Pareto distribution. A version of this statistic for discrete distribution of quantified magnitudes is also given. A methodology based on this statistics consisting in scanning the lower threshold for earthquake energies provides an explicit visualization of deviations from the Pareto law, surpassing in sensitivity the standard Hill estimator or other known techniques. This new statistical technique has been applied to shallow earthquakes (h < 70 km) both in subduction zones and in mid-ocean ridge zones (using the Harvard catalog of seismic m...

  10. MUSiC - An Automated Scan for Deviations between Data and Monte Carlo Simulation

    International Nuclear Information System (INIS)

    A model independent analysis approach is presented, systematically scanning the data for deviations from the standard model Monte Carlo expectation. Such an analysis can contribute to the understanding of the CMS detector and the tuning of event generators. The approach is sensitive to a variety of models of new physics, including those not yet thought of.

  11. Determination of the relations governing the evolution of the standard deviations of the distribution of pollution

    International Nuclear Information System (INIS)

    An original concept on the difference of behaviour of the high frequency (small-scale) and low frequency (large-scale) atmospheric turbulence relatively to the mean wind speed has been introduced. Through a dimensional analysis based on TAYLOR's formulation, it has been shown that the parameter of the atmospheric dispersion standard-deviations was the travel distance near the source, and the travel time far from the source. Using hypotheses on the energy spectrum in the atmosphere, a numerical application has made it possible to quantify the evolution of the horizontal standard deviation for different mean wind speeds between 0,2 and 10m/s. The areas of validity of the parameter (travel distance or travel time) are clearly shown. The first one is confined in the near field and is all the smaller if the wind speed decreases. For t > 5000s, the dependence on the wind speed of the horizontal standard-deviation expressed in function of the travel time becomes insignificant. The horizontal standard-deviation is only function of the travel time. Results are compared with experimental data obtained in the atmosphere. The similar evolution of the calculated and experimental curves confirms the validity of the hypothesis and input data in calculation. This study can be applied to radioactive effluents transport in the atmosphere

  12. Sinonasal Headaches and Post-Operative Outcomes after Septoplasty in Patients with Nasal Septal Deviation

    Directory of Open Access Journals (Sweden)

    Ali Ghazipour

    2011-03-01

    Headache is one of the most common symptoms in patients with nasal anatomical abnormalities such as septal deviation and usually responds well to surgical treatment. More studies with long-term follow-ups seems to be inevitable to determine the relationship between headaches and nasal anatomical abnormalities, accurate surgical results in patients’ recovery and the recurrence rate of headaches.

  13. Estimating maize water stress by standard deviation of canopy temperature in thermal imagery

    Science.gov (United States)

    A new crop water stress index using standard deviation of canopy temperature as an input was developed to monitor crop water status. In this study, thermal imagery was taken from maize under various levels of deficit irrigation treatments in different crop growing stages. The Expectation-Maximizatio...

  14. On the Linear Relation between the Mean and the Standard Deviation of a Response Time Distribution

    Science.gov (United States)

    Wagenmakers, Eric-Jan; Brown, Scott

    2007-01-01

    Although it is generally accepted that the spread of a response time (RT) distribution increases with the mean, the precise nature of this relation remains relatively unexplored. The authors show that in several descriptive RT distributions, the standard deviation increases linearly with the mean. Results from a wide range of tasks from different…

  15. Unbiased Estimation Formula of Unit Weight Standard Deviation in Regularization Solution

    Institute of Scientific and Technical Information of China (English)

    SHEN Yunzhong; LIU Dajie

    2004-01-01

    Regularization method is an effective method for solving ill-posed equation. In this paper the unbiased estimation formula of unit weight standard deviation in the regularization solution is derived and the formula is verified with numerical case of 1 000 sample data by use of the typical ill-posed equation, i.e. the Fredholm integration equation of the first kind.

  16. What determines the informativeness of firms' explanations for deviations from the Dutch corporate governance code?

    NARCIS (Netherlands)

    Hooghiemstra, R.B.H.

    2012-01-01

    The comply-or-explain principle is a common feature of corporate governance codes. While prior studies investigated compliance with corporate governance codes as well as the effects of compliance on firm behaviour and performance, explanations for deviations from a corporate governance code remain l

  17. A CK2-dependent mechanism for activation of the JAK-STAT signaling pathway

    OpenAIRE

    Zheng, Ying; Qin, Hongwei; Frank, Stuart J.; Deng, Luqin; Litchfield, David W.; Tefferi, Ayalew; Pardanani, Animesh; Lin, Fang-Tsyr; Li, Jingzhi; Sha, Bingdong; Benveniste, Etty N.

    2011-01-01

    JAK-STAT signaling is involved in the regulation of cell survival, proliferation, and differentiation. JAK tyrosine kinases can be transiently activated by cytokines or growth factors in normal cells, whereas they become constitutively activated as a result of mutations that affect their function in tumors. Specifically, the JAK2V617F mutation is present in the majority of patients with myeloproliferative disorders (MPDs) and is implicated in the pathogenesis of these diseases. In the present...

  18. Die Trinkwasser-Verhältnisse der Stadt Osnabrück : 2. Teil

    OpenAIRE

    Thörner, Wilhelm (Dr.)

    2013-01-01

    Im fünften Jahresbericht für die Jahre 1880-1882 des naturwissenschaftlichen Vereins zu Osnabrück machten wir, an der Hand einer größeren Reihe einschlägiger Untersuchungen, Mitteilungen über die Trinkwasser- Verhältnisse der Stadt Osnabrück. Diese aufklärenden Untersuchungen sind inzwischen stetig fortgesetzt worden und es haben sich, wie aus der umstehenden tabellarischen Zusammenstellung der Resultate der Analysen hervorgeht, die Trinkwasserverhältnisse unserer Stadt eher verschlechtert al...

  19. Ck2-Dependent Phosphorylation Is Required to Maintain Pax7 Protein Levels in Proliferating Muscle Progenitors.

    Directory of Open Access Journals (Sweden)

    Natalia González

    Full Text Available Skeletal muscle regeneration and long term maintenance is directly link to the balance between self-renewal and differentiation of resident adult stem cells known as satellite cells. In turn, satellite cell fate is influenced by a functional interaction between the transcription factor Pax7 and members of the MyoD family of muscle regulatory factors. Thus, changes in the Pax7-to-MyoD protein ratio may act as a molecular rheostat fine-tuning acquisition of lineage identity while preventing precocious terminal differentiation. Pax7 is expressed in quiescent and proliferating satellite cells, while its levels decrease sharply in differentiating progenitors Pax7 is maintained in cells (reacquiring quiescence. While the mechanisms regulating Pax7 levels based on differentiation status are not well understood, we have recently described that Pax7 levels are directly regulated by the ubiquitin-ligase Nedd4, thus promoting proteasome-dependent Pax7 degradation in differentiating satellite cells. Here we show that Pax7 levels are maintained in proliferating muscle progenitors by a mechanism involving casein kinase 2-dependent Pax7 phosphorylation at S201. Point mutations preventing S201 phosphorylation or casein kinase 2 inhibition result in decreased Pax7 protein in proliferating muscle progenitors. Accordingly, this correlates directly with increased Pax7 ubiquitination. Finally, Pax7 down regulation induced by casein kinase 2 inhibition results in precocious myogenic induction, indicating early commitment to terminal differentiation. These observations highlight the critical role of post translational regulation of Pax7 as a molecular switch controlling muscle progenitor fate.

  20. CRY Drives Cyclic CK2-Mediated BMAL1 Phosphorylation to Control the Mammalian Circadian Clock

    NARCIS (Netherlands)

    T. Tamaru (Teruya); M. Hattori (Mitsuru); K. Honda (Kousuke); Y. Nakahata (Yasukazu); P. Sassone-Corsi (Paolo); G.T.J. van der Horst (Gijsbertus); T. Ozawa (Takeaki); K. Takamatsu (Ken)

    2015-01-01

    textabstractIntracellular circadian clocks, composed of clock genes that act in transcription-translation feedback loops, drive global rhythmic expression of the mammalian transcriptome and allow an organism to anticipate to the momentum of the day. Using a novel clock-perturbing peptide, we establi

  1. p21WAF1/CIP1 interacts with protein kinase CK2

    DEFF Research Database (Denmark)

    Götz, C; Wagner, P; Issinger, O G;

    1996-01-01

    p21WAF1/CIP1 which belongs to a class of regulatory proteins that interact with cyclin dependent kinases is a potent inhibitor of these kinases. The inhibition of the cyclin dependent kinases induces an arrest of cells in the G phase of the cell cycle. In addition p21WAF1/CIP1 associates with PCNA...

  2. Study Of The Effect Of Nasal- Septal Deviation On The Middle Ear Pressure

    Directory of Open Access Journals (Sweden)

    Motesaddi Zarandi M

    2003-10-01

    Full Text Available Eustachian tube connects middle ear space to the nasopharyngeal space. Upper airway obstruction, with any cause, can derange Eustachian tube function. Nasal septal deviation is one of the prevalent causes of upper airway obstruction which can affects the ventilation function of Eustachian tube."nMaterials and Methods: This study was conducted on the patients who underwent septoplasty due to severe septal deviation leading to unilateral nasal obstruction in Amiraalam hospital from summer of 1378 till the spring of 1379."nResults: There was 140 patients whose data were as: female patients 34 (24.3% male patients 106 (75.7%, mean age (22.7. Median age (20 years and mode of age (18 years of age. they were from 12 to 40 years of age."nConclusion: Comparison between preoperative and postoperative middle ear pressures shows no any significant statistical difference (p=0.798.

  3. MUSIC -- An Automated Scan for Deviations between Data and Monte Carlo Simulation

    CERN Document Server

    CMS Collaboration

    We present a model independent analysis approach, systematically scanning the data for deviations from the Monte Carlo expectation. Such an analysis can contribute to the understanding of the detector and the tuning of the event generators. Due to the minimal theoretical bias this approach is sensitive to a variety of models, including those not yet thought of. Events are classified into event classes according to their particle content (muons, electrons, photons, jets and missing transverse energy). A broad scan of various distributions is performed, identifying significant deviations from the Monte Carlo simulation. We outline the importance of systematic uncertainties, which are taken into account rigorously within the algorithm. Possible detector effects and generator issues, as well as models involving supersymmetry and new heavy gauge bosons have been used as an input to the search algorithm. %Several models involving supersymmetry, new heavy gauge bosons and leptoquarks, as well as possible detector ef...

  4. Interharmonics analysis of power signals with fundamental frequency deviation using Kalman filtering

    Energy Technology Data Exchange (ETDEWEB)

    Koese, Neslihan; Salor, Oezguel; Leblebicioglu, Kemal [TUBITAK UZAY, Power Electronics Group, TR 06531 Ankara (Turkey); METU, Electrical and Electronics Eng. Dept., TR 06531 Ankara (Turkey)

    2010-09-15

    In this paper a spectral decomposition-based method for interharmonic computation is proposed for power systems where the fundamental frequency fluctuates significantly. In the proposed method, the frequency domain components of the voltage waveform are obtained by Kalman filtering. Both the system fundamental frequency and the correct spectrum of the voltage waveform, and hence the exact interharmonics are obtained. The proposed method is tested with both simulated and field data obtained from different electric arc furnace (EAF) plants, where the system frequency deviates continuously due to the fluctuating load demands. Since the interharmonic frequencies are obtained by using Kalman filtering, no leakage effect of the DFT-based methods is involved in case of frequency deviations, which is an important advantage of the proposed method. (author)

  5. Evidence of fissiogenic Cs estimated from Ba isotopic deviations in an Oklo natural reactor zone

    Science.gov (United States)

    Hidaka, Hiroshi; Holliger, Philippe; Masuda, Akimasa

    1993-01-01

    Isotopic studies of many elements from the uranium ore natural nuclear reactors at Oklo provide useful information on the migration of radioactive nuclides. The fissiogenic isotopic composition of Ba is particularly interesting, as it is an important indication in the search for fissiogenic Cs. In this report we detail the detection of remarkable isotopic deviations of Ba in the Oklo samples and estimate the geochemical behaviour of fissiogenic Cs from excess Ba isotopes. Six samples systematically collected from borehole SF84 (zone 10) at the Oklo uranium mine have been analyzed. Isotopic deviations of Ba indicate the existence of fissiogenic Cs and Ba. A good correlation between the elemental abundance of Cs and isotopic abundances of excess 135Ba and 137Ba suggests that fissiogenic 135Ba and 137Ba behaved as Cs rather than Ba.

  6. Living at the Edge: A Large Deviations Approach to the Outage MIMO Capacity

    CERN Document Server

    Kazakopoulos, P; Moustakas, A L; Caire, G

    2009-01-01

    Using a large deviations approach we calculate the probability distribution of the mutual information of MIMO channels in the limit of large antenna numbers. In contrast to previous methods that only focused at the distribution close to its mean (thus obtaining an asymptotically Gaussian distribution), we calculate the full distribution, including its tails which strongly deviate from the Gaussian behavior near the mean. The resulting distribution interpolates seamlessly between the Gaussian approximation for rates $R$ close to the ergodic value of the mutual information and the approach of Zheng and Tse for large signal to noise ratios $\\rho$. This calculation provides us with a tool to obtain outage probabilities analytically at any point in the $(R, \\rho, N)$ parameter space, as long as the number of antennas $N$ is not too small. In addition, this method also yields the probability distribution of eigenvalues constrained in the subspace where the mutual information per antenna is fixed to $R$ for a given ...

  7. Dispersion in Rectangular Networks: Effective Diffusivity and Large-Deviation Rate Function

    Science.gov (United States)

    Tzella, Alexandra; Vanneste, Jacques

    2016-09-01

    The dispersion of a diffusive scalar in a fluid flowing through a network has many applications including to biological flows, porous media, water supply, and urban pollution. Motivated by this, we develop a large-deviation theory that predicts the evolution of the concentration of a scalar released in a rectangular network in the limit of large time t ≫1 . This theory provides an approximation for the concentration that remains valid for large distances from the center of mass, specifically for distances up to O (t ) and thus much beyond the O (t1 /2) range where a standard Gaussian approximation holds. A byproduct of the approach is a closed-form expression for the effective diffusivity tensor that governs this Gaussian approximation. Monte Carlo simulations of Brownian particles confirm the large-deviation results and demonstrate their effectiveness in describing the scalar distribution when t is only moderately large.

  8. Analysis of laser cutting speed influence on the surface quality and shape deviation of steel parts

    Science.gov (United States)

    Kowalczyk, R.; Zebala, W.

    2014-11-01

    The results of laser cutting speed influence on the quality of machined surface, defined by the Ra roughness parameter and the shape errors, in case of machining two types of steel: i) P265GH, ii) 1.4307 are presented in the paper. Two CO2 laser cutters with maximum power of the laser beam 4000W and 3200W were used for the investigation. The characteristics of the roughness parameter Ra depending on the laser cutting speed vc are presented. The diagrams of shape deviation of the machined specimens for the greatest and lowest values of the Ra for the both laser cutters are also presented. The deviation values from the theoretical profile of the particular samples, taking into account the type of the cut-out shape profiles (circular, linear) are calculated.

  9. A contribution to large deviations for heavy-tailed random sums

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    In this paper we consider the large deviations for random sums S(t)=∑N(t)i=1Xi, t≥0, where {Xn, n≥1} are independent, identically distributed and non-negative random variables with a common heavy-tailed distribution function F, and {N(t), t≥0} is a process of non-negative integer-valued random variables, independent of {Xn, n≥1}. Under the assumption that the tail of F is of Pareto's type (regularly or extended regularly varying), we investigate what reasonable condition can be given on {N(t), t≥0} under which precise large deviation for S(t) holds. In particular, the condition we obtain is satisfied for renewal counting processes.

  10. A technique to compensate the specified flow deviation among control areas

    Energy Technology Data Exchange (ETDEWEB)

    Ramirez, Juan M.; Cano E Mauricio; Ruiz Leon, Javier [Cinvestav - Unidad Guadalajara, Av. Patria No. 3200-39, Col. La Calma, 45080 Zapopan, Jal (Mexico)

    2007-05-15

    This paper is aimed to present a strategy to compensate the deviations of the tie line power flow among control areas after a load change in some of them. In an actual power system, the area control error (ACE) is not necessarily a measure able to correct both the deviations of frequency and the tie line flows. In this paper a hierarchical strategy to carry out this purpose is proposed. It is assumed that each area has at least one generator in charge of carrying out the automatic generation control (AGC). A detailed state space model is used without necessity of carrying out many of the assumptions that commonly are considered for this type of studies. Results of simulation are exhibited that show the applicability of the proposal. (author)

  11. MUSiC - A general search for deviations from Monte Carlo predictions in CMS

    International Nuclear Information System (INIS)

    A model independent analysis approach in CMS is presented, systematically scanning the data for deviations from the Monte Carlo expectation. Such an analysis can contribute to the understanding of the detector and the tuning of the event generators. Furthermore, due to the minimal theoretical bias this approach is sensitive to a variety of models of new physics, including those not yet thought of. Events are classified into event classes according to their particle content (muons, electrons, photons, jets and missing transverse energy). A broad scan of various distributions is performed, identifying significant deviations from the Monte Carlo simulation. The importance of systematic uncertainties is outlined, which are taken into account rigorously within the algorithm. Possible detector effects and generator issues, as well as models involving Supersymmetry and new heavy gauge bosons are used as an input to the search algorithm.

  12. Variograms of the Cosmic Microwave Background Temperature Fluctuations: Confirmation of Deviations from Statistical Isotropy

    CERN Document Server

    Cayon, Laura

    2010-01-01

    The Standard Inflationary model predicts an isotropic distribution of the Cosmic Microwave Background temperature fluctuations. Detection of deviations from statistical isotropy would call for a revision of the physics of the early universe. This paper introduces the variogram as a powerful tool to detect and characterize deviations from statistical isotropy in Cosmic Microwave Background maps. Application to the Wilkinson Microwave Anisotropy Probe data clearly shows differences between the northern and the southern hemispheres. The sill and range of the northern hemisphere's variogram are lower than those of the southern hemisphere. Moreover the variogram for the northern hemisphere lies outside the 99% c.l. for scales above ten degrees. Differences between the northern and southern hemispheres in the functional dependence of the variogram with the scale can be used as a validation bench mark for proposed anisotropic cosmological models.

  13. An alternative approach to the analysis of sucker-rod dynamics in vertical and deviated wells

    Energy Technology Data Exchange (ETDEWEB)

    Lollback, P.A.; Wang, G.Y.; Rahman, S.S. [The Centre for Petroleum Engineering, School of Applied Science, The University of New South Wales, Sydney (Australia)

    1997-05-01

    A set of partial differential equations which consider the combined effects of fluid column, sucker-rod string and tubing motion were developed to describe the motion of a sucker-rod pumping system. If the tubing is fixed, only the fluid column and rod motion need be considered; however, when the tubing is free to move, energy in the system is lost and, therefore, pump system efficiency declines, hence, the need to consider these effects in the design of the sucker-rod system. Using finite differences this model was used to evaluate performance of sucker-rod pumps (pumping rate as a function of number of strokes, stroke length, rod length, ratio of plunger to cylinder diameter, etc.) in both vertical and deviated wells. The results indicate that the developed model simply and accurately models the dynamic motion of the sucker-rod string. The examples presented illustrate its general applicability in both vertical and deviated wells

  14. A phase deviation based split-spectrum processing algorithm for ultrasonic flaw detection

    Institute of Scientific and Technical Information of China (English)

    LIU Zhenqing

    2002-01-01

    The Split Spectrum Processing (SSP) technique has proved its ability in reduction of interference noise in ultrasonic nondestructive testing for coarse grained materials. However,the results of SSP algorithms are not sufficiently stable since they are sensitive to the filter bank and filter parameters. And the mechanism of the technique to fully explore the signals is not clear. The statistical phase response characteristic of filter outputs for ultrasonic testing is discussed. Thus, a new SSP algorithm based on phase standard deviation is proposed. The performance is examined for both computer simulated and experimental data, and compared to commonly used minimum algorithm. The phase standard deviation algorithm is proved its superior effect and is less sensitive on the number of filters.

  15. Missing data in aftershock sequences: explaining the deviations from scaling laws.

    Science.gov (United States)

    Lennartz, Sabine; Bunde, Armin; Turcotte, Donald L

    2008-10-01

    In this paper we extend the branching aftershock sequence model to study the role of missing data at short times and small amplitudes after a mainshock. We apply this model, which contains three parameters characterizing the missing data, to the magnitude and temporal statistics of four aftershock sequences in California. We find that the observed time-dependent deviations of the frequency-magnitude scaling from the Gutenberg-Richter power law dependency can be described quantitatively by the model. We also show that, for the same set of parameters, the model is able to explain quantitatively the observed magnitude-dependent deviations of the temporal decay of aftershocks from Omori's law. In addition, we show that the same sets of data can also reproduce quite well the various functional forms of the probability density functions of the return times between consecutive events with magnitudes above a prescribed threshold, as well as the violation of scaling at short and intermediate time scales.

  16. MUSiC - A general search for deviations from Monte Carlo predictions in CMS

    Energy Technology Data Exchange (ETDEWEB)

    Biallass, Philipp A, E-mail: biallass@cern.c [Physics Institute IIIA, RWTH Aachen, Physikzentrum, 52056 Aachen (Germany)

    2009-06-01

    A model independent analysis approach in CMS is presented, systematically scanning the data for deviations from the Monte Carlo expectation. Such an analysis can contribute to the understanding of the detector and the tuning of the event generators. Furthermore, due to the minimal theoretical bias this approach is sensitive to a variety of models of new physics, including those not yet thought of. Events are classified into event classes according to their particle content (muons, electrons, photons, jets and missing transverse energy). A broad scan of various distributions is performed, identifying significant deviations from the Monte Carlo simulation. The importance of systematic uncertainties is outlined, which are taken into account rigorously within the algorithm. Possible detector effects and generator issues, as well as models involving Supersymmetry and new heavy gauge bosons are used as an input to the search algorithm.

  17. PSYCHOLOGICAL MECHANISMS OF FORMATION OF DEVIATIONS IN THE PERIOD OF PREPARATION FOR MOTHERHOOD

    OpenAIRE

    S. A. Moreva; A. V. Silaeva; A. N. Kornetov; Ye. N. Borodina; A. Ye. Yankovskaya; N. I. Pryadukhina; N. E. Golovakha; V. B. Obukhovskaya

    2015-01-01

    The article presents a social-psychological indicators of stress, coping mechanisms, rigidity and psychological component gestational dominant as risk factors predisposing to deviations in the context of preparedness for motherhood, marked psychological characteristics of pregnant women main group.Material and methods. The study was conducted on the basis of obstetric clinics SSMU, prenatal maternity hospital number 4 and the Centre for Medical Prevention (Cabinet crisis pregnancy). Total was...

  18. Stochastic Optimization for Portfolio Selection Problem with Mean Absolute Negative Deviation Measure

    OpenAIRE

    Kamil, Anton A.; Adli Mustafa; Khlipah Ibrahim

    2009-01-01

    Problem statement: The most important character within optimization problem is the uncertainty of the future returns. Approach: To handle such problems, we utilized probabilistic methods alongside with optimization techniques. We developed single stage and two stage stochastic programming with recourse. The models were developed for risk adverse investors and the objective of the stochastic programming models is to minimize the maximum downside semi deviation. We used the so-called Here-and-N...

  19. Estimation of horizontal stress magnitudes in a reservoir using sonic data from a deviated borehole

    Science.gov (United States)

    Sinha, Bikash K.; Wendt, Anke S.

    2013-04-01

    Geomechanical analysis of sonic data from a deviated wellbore requires rotation of the formation principal stresses to those referred to the wellbore measurement axes. Sonic data and wellbore stability are influenced by these rotated stresses. Inversion of sonic data for formation stress magnitudes has been performed on a deviated wellbore located in the North Sea. The well azimuth is about 36.5 degrees from the maximum horizontal stress direction and a deviation of 35.2 degrees from the vertical. The logged interval comprised gas/condensate in the upper part, and water in the lower part. Production of the reservoir caused a decrease of pore pressure of up to 13.4 MPa in the gas zone and almost no reduction in the pore pressure in the water zone. The new inversion algorithm estimates the maximum and minimum horizontal stresses using radial profiles of the three shear stiffness moduli in the two axial and cross-sectional planes of a deviated borehole. This algorithm inverts differences in the far-field shear moduli together with the two difference equations obtained from radial profiles of the dipole shear moduli in the two axial planes between near and far radial positions from the borehole surface. Results for estimated horizontal stress magnitudes obtained in the depleted areas of the well showed significant differences from the nearly isotropic stress state before production. Estimates of stress magnitudes after depletion showed a sharp increase in differences among the three principal stresses from 2% before production to a ratio of overburden to minimum horizontal stress in the order of 10% to 20% and maximum to minimum horizontal stresses from 5% to 10%. The redistribution of formation stresses in depleted reservoirs is important for maintaining geomechanical reservoir and wellbore stability and has a considerable impact on reservoir management and subsequent drilling and completion decisions. Acknowledgement Schlumberger gratefully acknowledges the

  20. Individuality That is Unheard of: Systematic Temporal Deviations in Scale Playing Leave an Inaudible Pianistic Fingerprint.

    Science.gov (United States)

    Van Vugt, Floris Tijmen; Jabusch, Hans-Christian; Altenmüller, Eckart

    2013-01-01

    Whatever we do, we do it in our own way, and we recognize master artists by small samples of their work. This study investigates individuality of temporal deviations in musical scales in pianists in the absence of deliberate expressive intention. Note-by-note timing deviations away from regularity form a remarkably consistent "pianistic fingerprint." First, eight professional pianists played C-major scales in two sessions, separated by 15 min. Euclidian distances between deviation traces originating from different pianists were reliably larger than traces originating from the same pianist. As a result, a simple classifier that matched deviation traces by minimizing their distance was able to recognize each pianist with 100% accuracy. Furthermore, within each pianist, fingerprints produced by the same movements were more similar than fingerprints resulting in the same scale sound. This allowed us to conclude that the fingerprints are mostly neuromuscular rather than intentional or expressive in nature. However, human listeners were not able to distinguish the temporal fingerprints by ear. Next, 18 pianists played C-major scales on a normal or muted piano. Recognition rates ranged from 83 to 100%, further supporting the view that auditory feedback is not implicated in the creation of the temporal signature. Finally, 20 pianists were recognized 20 months later at above chance level, showing signature effects to be long lasting. Our results indicate that even non-expressive playing of scales reveals consistent, partially effector-unspecific, but inaudible inter-individual differences. We suggest that machine learning studies into individuality in performance will need to take into account unintentional but consistent variability below the perceptual threshold.