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Sample records for ck2 structurally deviates

  1. 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...... features of the enzyme, such as its constitutive activity, acidophilic substrate specificity, dual-cosubstrate specificity and its heterotetrameric quarternary structure. Comprehensive sets of structural superimpositions reveal that both CK2alpha and CK2beta are relatively rigid molecules. In CK2beta...... the 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...

  2. Primary and secondary interactions between CK2alpha and CK2beta lead to ring-like structures in the crystals of the CK2 holoenzyme

    DEFF Research Database (Denmark)

    Niefind, Karsten; Issinger, Olaf-Georg

    2005-01-01

    a distinct aggregation propensity of CK2. We demonstrate here that in the CK2 holoenzyme crystals contacts between different CK2 tetramers exists which provide structural details of the secondary CK2alpha/CK2beta interactions. These mainly ionic interactions lead to trimeric rings of CK2 holoenzymes...

  3. 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

    in the ATP-binding loop, whereas human CK2alpha shows its largest adaptations in the hinge region connecting the two main domains of the protein kinase core. These observations emphasize the importance of local plasticity for ligand binding and demonstrate that two orthologues of an enzyme can behave quite...

  4. 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......Protein kinase CK2 (formerly "casein kinase 2") is composed of a central dimer of noncatalytic subunits (CK2β) binding two catalytic subunits. In humans, there are two isoforms of the catalytic subunit (and an additional splicing variant), one of which (CK2α) is well characterized. To supplement...

  5. Crystal structures of catalytic and regulatory subunits of rat protein kinase CK2

    Institute of Scientific and Technical Information of China (English)

    ZHOU WeiHong; SHEN YueQuan; QIN XiaoHong; YAN XiaoJie; XIE XingQiao; LI Liang; FANG ShaSha; LONG JiaFu; ADELMAN John; TANG Wei-Jen

    2009-01-01

    Protein kinase CK2 consists of two catalytic subunits (CK2α) and two regulatory subunits (CK2β). Here,we report the crystal structures of rat CK2α mutant (rCK2α-△C, 1-335) and CK2β(rCK2β). The overall topology of rCK2α-△C and rCK2βare very similar to the human enzyme, although large structural dif-ferences could be observed in the N-terminal domain of rCK2α-△C. Our reported structure of rCK2α-△C is in the close conformation state while the counterpart hCK2α is in the open conformation state, indi-cating the conformation of CK2α molecule has high plasticity. The structure of rCK2β represents the conformation of free CK2β. Upon CK2α binding, the C-terminal region undergoes a drastic conforma-tional change. The major region of interaction within the interface of CK2αCK2β may serve as a bridge to transmit the conformational change and thus regulate the activity of CK2α.

  6. 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

    subunits, which make no direct contact with one another. Each catalytic subunit interacts with both regulatory chains, predominantly via an extended C-terminal tail of the regulatory subunit. The CK2 structure is consistent with its constitutive activity and with a flexible role of the regulatory subunit......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....

  7. 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...... inactivated through urea, protease, and heat treatment. In contrast, the holoenzyme, either reconstituted or native, is much more stable when similar negative insults prevail. The beta subunit has at least three functions: (a) it is necessary for maximum activity of the enzyme under physiological salt...... 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...

  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

    2017-01-01

    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 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...

  10. 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...

  11. Structural and functional insights into the regulation mechanism of CK2 by IP6 and the intrinsically disordered protein Nopp140.

    Science.gov (United States)

    Lee, Won-Kyu; Son, Sang Hyeon; Jin, Bong-Suk; Na, Jung-Hyun; Kim, Soo-Youl; Kim, Kook-Han; Kim, Eunice Eunkyeong; Yu, Yeon Gyu; Lee, Hyung Ho

    2013-11-26

    Protein kinase CK2 is a ubiquitous kinase that can phosphorylate hundreds of cellular proteins and plays important roles in cell growth and development. Deregulation of CK2 is related to a variety of human cancers, and CK2 is regarded as a suppressor of apoptosis; therefore, it is a target of anticancer therapy. Nucleolar phosphoprotein 140 (Nopp140), which is an intrinsically disordered protein, interacts with CK2 and inhibits the latter's catalytic activity in vitro. Interestingly, the catalytic activity of CK2 is recovered in the presence of d-myo-inositol 1,2,3,4,5,6-hexakisphosphate (IP6). IP6 is widely distributed in animal cells, but the molecular mechanisms that govern its cellular functions in animal cells have not been completely elucidated. In this study, the crystal structure of CK2 in complex with IP6 showed that the lysine-rich cluster of CK2 plays an important role in binding to IP6. The biochemical experiments revealed that a Nopp140 fragment (residues 568-596) and IP6 competitively bind to the catalytic subunit of CK2 (CK2α), and phospho-Ser574 of Nopp140 significantly enhances its interaction with CK2α. Substitutions of K74E, K76E, and K77E in CK2α significantly reduced the interactions of CK2α with both IP6 and the Nopp140-derived peptide. Our study gives an insight into the regulation of CK2. In particular, our work suggests that CK2 activity is inhibited by Nopp140 and reactivated by IP6 by competitive binding at the substrate recognition site of CK2.

  12. 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

    and probably contributes to the constitutively active nature of CK2. The active centre is occupied by a partially disordered ATP molecule with the adenine base attached to a novel binding site of low specificity. This finding explains the observation that CK2, unlike other protein kinases, can use both ATP...

  13. 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...

  14. 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....

  15. 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

    using isothermal titration calorimetry (ITC). With structure-guided alanine scanning mutagenesis we truncated individual side chains in the hydrophobic amino acid cluster located within the CK2α interface to identify experimentally the amino acids that dominate affinity. The ITC results indicate...

  16. 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......Increased activity of protein kinase CK2 is associated with various types of cancer, neurodegenerative diseases, and chronic inflammation. In the search for CK2 inhibitors, attention has expanded toward compounds disturbing the interaction between CK2alpha and CK2beta in addition to established...... crystal structure of the Pc/CK2alpha1-335 complex. The dissociation constants obtained in the fluorescence anisotropy assay for binding of all compounds to human CK2alpha1-335 were validated by isothermal titration calorimetry. I-Pc was identified as the tightest binding ligand with a KD value of 240n...

  17. Gene targeting of CK2 catalytic subunits

    Science.gov (United States)

    Lou, David Y.; Toselli, Paul; Landesman-Bollag, Esther; Dominguez, Isabel

    2013-01-01

    Protein kinase CK2 is a highly conserved and ubiquitous serine–threonine kinase. It is a tetrameric enzyme that is made up of two regulatory CK2β subunits and two catalytic subunits, either CK2α/CK2α, CK2α/ CK2α′, or CK2α′/CK2α′. Although the two catalytic subunits diverge in their C termini, their enzymatic activities are similar. To identify the specific function of the two catalytic subunits in development, we have deleted them individually from the mouse genome by homologous recombination. We have previously reported that CK2α′is essential for male germ cell development, and we now demonstrate that CK2α has an essential role in embryogenesis, as mice lacking CK2α die in mid-embryogenesis, with cardiac and neural tube defects. PMID:18594950

  18. Gene targeting of CK2 catalytic subunits.

    Science.gov (United States)

    Seldin, David C; Lou, David Y; Toselli, Paul; Landesman-Bollag, Esther; Dominguez, Isabel

    2008-09-01

    Protein kinase CK2 is a highly conserved and ubiquitous serine-threonine kinase. It is a tetrameric enzyme that is made up of two regulatory CK2beta subunits and two catalytic subunits, either CK2alpha/CK2alpha, CK2alpha/CK2alpha', or CK2alpha'/CK2alpha'. Although the two catalytic subunits diverge in their C termini, their enzymatic activities are similar. To identify the specific function of the two catalytic subunits in development, we have deleted them individually from the mouse genome by homologous recombination. We have previously reported that CK2alpha' is essential for male germ cell development, and we now demonstrate that CK2alpha has an essential role in embryogenesis, as mice lacking CK2alpha die in mid-embryogenesis, with cardiac and neural tube defects.

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

    Science.gov (United States)

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

    2008-09-01

    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-rays (wavelength around 2 A) since they match the absorption edges of sulfur and chlorine. A particularly useful application of this phenomenon is the experimental detection of the sub-structures of the anomalous scatterers in protein crystals. We demonstrate this here with a crystal of a C-terminally truncated variant of human CK2alpha to which two molecules of the inhibitor 5,6-dichloro-1-beta-D-ribo-furanosyl-benzimidazole (DRB) are bound. The structure of this co-crystal has been solved recently. For this study we measured an additional diffraction data set at a wavelength of 2 A which showed strong anomalous dispersion effects. On the basis of these effects we detected all sulfur atoms of the protein, the two liganded DRB molecules and a total of 16 additional chloride ions some of them emerging at positions filled with water molecules in previous structure determinations. A number of chloride ions are bound to structural and functional important locations fitting to the constitutive activity and the acidophilic substrate specificity of the enzyme.

  20. 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

    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......, 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...... 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...

  1. 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

    (EPKs). To function as regulatory key components, EPKs normally exist in inactive ground states and are activated only upon specific signals. Typically, this activation is accompanied by large conformational changes in helix alpha C and in the activation segment, leading to a characteristic arrangement......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...... of catalytic key elements. For CK2alpha, however, no strict physiological control of activity is known. Accordingly, CK2alpha was found so far exclusively in the characteristic conformation of active EPKs, which is, in this case, additionally stabilized by a unique intramolecular contact between the N...

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

    DEFF Research Database (Denmark)

    Enkvist, Erki; Viht, Kaido; Bischoff, Nils

    2012-01-01

    Up-regulation of an acidophilic protein kinase, CK2, has been established in several types of cancer. This cognition has made CK2 an important target for drug development for cancer chemotherapy. The characterization of potential drug candidates, determination of the structure and clarification...

  3. The Development of CK2 Inhibitors: From Traditional Pharmacology to in Silico Rational Drug Design.

    Science.gov (United States)

    Cozza, Giorgio

    2017-02-20

    Casein kinase II (CK2) is an ubiquitous and pleiotropic serine/threonine protein kinase able to phosphorylate hundreds of substrates. Being implicated in several human diseases, from neurodegeneration to cancer, the biological roles of CK2 have been intensively studied. Upregulation of CK2 has been shown to be critical to tumor progression, making this kinase an attractive target for cancer therapy. Several CK2 inhibitors have been developed so far, the first being discovered by "trial and error testing". In the last decade, the development of in silico rational drug design has prompted the discovery, de novo design and optimization of several CK2 inhibitors, active in the low nanomolar range. The screening of big chemical libraries and the optimization of hit compounds by Structure Based Drug Design (SBDD) provide telling examples of a fruitful application of rational drug design to the development of CK2 inhibitors. Ligand Based Drug Design (LBDD) models have been also applied to CK2 drug discovery, however they were mainly focused on methodology improvements rather than being critical for de novo design and optimization. This manuscript provides detailed description of in silico methodologies whose applications to the design and development of CK2 inhibitors proved successful and promising.

  4. 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...... use either ATP or GTP as a cosubstrate. The structures of these complexes demonstrate that water molecules are critical to switch the active site of CK2 from an ATP- to a GTP-compatible state. An understanding of the structural basis of dual-cosubstrate specificity may help in the design of drugs...

  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

    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...... molecule seems to favour the partially and fully inactive states. This observation may be exploited to design effective and selective CK2 inhibitors....

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

    Science.gov (United States)

    Enkvist, Erki; Viht, Kaido; Bischoff, Nils; Vahter, Jürgen; Saaver, Siiri; Raidaru, Gerda; Issinger, Olaf-Georg; Niefind, Karsten; Uri, Asko

    2012-11-21

    Up-regulation of an acidophilic protein kinase, CK2, has been established in several types of cancer. This cognition has made CK2 an important target for drug development for cancer chemotherapy. The characterization of potential drug candidates, determination of the structure and clarification of the functions of CK2 could be facilitated by the application of small-molecule fluorescent probes that bind to the active site of the enzyme with high affinity and selectivity. We have used a bisubstrate approach for the development of a highly potent inhibitor of CK2. 4,5,6,7-Tetrabromo-1H-benzimidazole was conjugated with peptides containing multiple aspartate residues via different linkers. The design of the inhibitors was by crystallographic analysis of the complex of an inhibitor with the catalytic subunit of the enzyme (CK2α). The inhibitory potency of the synthesized compounds was established in a kinetic 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-647 gave the fluorescent probe ARC-1504 that possessed subnanomolar affinity towards both CK2α and the holoenzyme. The probe was used in a fluorescence anisotropy-based binding assay to measure the concentration of CK2α and characterize non-labelled ligands binding to the active site of CK2α.

  8. Exploring the CK2 Paradox: Restless, Dangerous, Dispensable

    Science.gov (United States)

    Franchin, Cinzia; Borgo, Christian; Zaramella, Silvia; Cesaro, Luca; Arrigoni, Giorgio; Salvi, Mauro; Pinna, Lorenzo A.

    2017-01-01

    The history of protein kinase CK2 is crowded with paradoxes and unanticipated findings. Named after a protein (casein) that is not among its physiological substrates, CK2 remained in search of its targets for more than two decades after its discovery in 1954, but it later came to be one of the most pleiotropic protein kinases. Being active in the absence of phosphorylation and/or specific stimuli, it looks unsuitable to participate in signaling cascades, but its “lateral” implication in a variety of signaling pathways is now soundly documented. At variance with many “onco-kinases”, CK2 is constitutively active, and no oncogenic CK2 mutant is known; still high CK2 activity correlates to neoplasia. Its pleiotropy and essential role may cast doubts on the actual “druggability” of CK2; however, a CK2 inhibitor is now in Phase II clinical trials for the treatment of cancer, and cell clones viable in the absence of CK2 are providing information about the mechanism by which cancer becomes addicted to high CK2 levels. A phosphoproteomics analysis of these CK2 null cells suggests that CK2 pleiotropy may be less pronounced than expected and supports the idea that the phosphoproteome generated by this kinase is flexible and not rigidly pre-determined. PMID:28117670

  9. Exploring the CK2 Paradox: Restless, Dangerous, Dispensable

    Directory of Open Access Journals (Sweden)

    Cinzia Franchin

    2017-01-01

    Full Text Available The history of protein kinase CK2 is crowded with paradoxes and unanticipated findings. Named after a protein (casein that is not among its physiological substrates, CK2 remained in search of its targets for more than two decades after its discovery in 1954, but it later came to be one of the most pleiotropic protein kinases. Being active in the absence of phosphorylation and/or specific stimuli, it looks unsuitable to participate in signaling cascades, but its “lateral” implication in a variety of signaling pathways is now soundly documented. At variance with many “onco-kinases”, CK2 is constitutively active, and no oncogenic CK2 mutant is known; still high CK2 activity correlates to neoplasia. Its pleiotropy and essential role may cast doubts on the actual “druggability” of CK2; however, a CK2 inhibitor is now in Phase II clinical trials for the treatment of cancer, and cell clones viable in the absence of CK2 are providing information about the mechanism by which cancer becomes addicted to high CK2 levels. A phosphoproteomics analysis of these CK2 null cells suggests that CK2 pleiotropy may be less pronounced than expected and supports the idea that the phosphoproteome generated by this kinase is flexible and not rigidly pre-determined.

  10. CK2α is essential for embryonic morphogenesis.

    Science.gov (United States)

    Dominguez, Isabel; Degano, Irene R; Chea, Kathleen; Cha, Julie; Toselli, Paul; Seldin, David C

    2011-10-01

    CK2 is a highly conserved serine-threonine kinase involved in biological processes such as embryonic development, circadian rhythms, inflammation, and cancer. Biochemical experiments have implicated CK2 in the control of several cellular processes and in the regulation of signal transduction pathways. Our laboratory is interested in characterizing the cellular, signaling, and molecular mechanisms regulated by CK2 during early embryonic development. For this purpose, animal models, including mice deficient in CK2 genes, are indispensable tools. Using CK2α gene-deficient mice, we have recently shown that CK2α is a critical regulator of mid-gestational morphogenetic processes, as CK2α deficiency results in defects in heart, brain, pharyngeal arch, tail bud, limb bud, and somite formation. Morphogenetic processes depend upon the precise coordination of essential cellular processes in which CK2 has been implicated, such as proliferation and survival. Here, we summarize the overall phenotype found in CK2α (-/- ) mice and describe our initial analysis aimed to identify the cellular processes affected in CK2α mutants.

  11. Structure of deviations from optimality in biological systems.

    Science.gov (United States)

    Pérez-Escudero, Alfonso; Rivera-Alba, Marta; de Polavieja, Gonzalo G

    2009-12-01

    Optimization theory has been used to analyze evolutionary adaptation. This theory has explained many features of biological systems, from the genetic code to animal behavior. However, these systems show important deviations from optimality. Typically, these deviations are large in some particular components of the system, whereas others seem to be almost optimal. Deviations from optimality may be due to many factors in evolution, including stochastic effects and finite time, that may not allow the system to reach the ideal optimum. However, we still expect the system to have a higher probability of reaching a state with a higher value of the proposed indirect measure of fitness. In systems of many components, this implies that the largest deviations are expected in those components with less impact on the indirect measure of fitness. Here, we show that this simple probabilistic rule explains deviations from optimality in two very different biological systems. In Caenorhabditis elegans, this rule successfully explains the experimental deviations of the position of neurons from the configuration of minimal wiring cost. In Escherichia coli, the probabilistic rule correctly obtains the structure of the experimental deviations of metabolic fluxes from the configuration that maximizes biomass production. This approach is proposed to explain or predict more data than optimization theory while using no extra parameters. Thus, it can also be used to find and refine hypotheses about which constraints have shaped biological structures in evolution.

  12. Protein kinase CK2: a newcomer in the 'druggable kinome'.

    Science.gov (United States)

    Pagano, M A; Cesaro, L; Meggio, F; Pinna, L A

    2006-12-01

    The acronym CK2 (derived from the misnomer 'casein kinase' 2) denotes one of the most pleiotropic members of the eukaryotic protein kinase superfamily, characterized by an acidic consensus sequence in which a carboxylic acid (or pre-phosphorylated) side chain at position n+3 relative to the target serine/threonine residue plays a crucial role. The latest repertoire of CK2 substrates includes approx. 300 proteins, but the analysis of available phosphopeptide databases from different sources suggests that CK2 alone may be responsible for the generation of a much larger proportion (10-20%) of the eukaryotic phosphoproteome. Although for the time being CK2 is not included among protein kinases whose inhibitors are in clinical practice or in advanced clinical trials, evidence is accumulating that elevated CK2 constitutive activity co-operates to induce a number of pathological conditions, including cancer, infectious diseases, neurodegeneration and cardiovascular pathologies. The development and usage of cell-permeant, selective inhibitors discloses a scenario whereby CK2 plays a global anti-apoptotic role, which under special circumstances may lead to untimely and pathogenic cell survival.

  13. 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.

  14. Protein kinase CK2 in human diseases

    DEFF Research Database (Denmark)

    Guerra, Barbara; Issinger, Olaf-Georg

    2008-01-01

    in various disease processes including cancer has been gained in recent years, and the present review may help to further elucidate its aberrant role in many disease states. Its peculiar structural features [3-9] may be advantageous in designing tailor-made compounds with the possibility to specifically...

  15. Oligo-aspartic acid conjugates with benzo[c][2,6]naphthyridine-8-carboxylic acid scaffold as picomolar inhibitors of CK2.

    Science.gov (United States)

    Vahter, Jürgen; Viht, Kaido; Uri, Asko; Enkvist, Erki

    2017-02-28

    Structurally diverse inhibitors of the protein kinase CK2 are required for regulation of this ubiquitous protein to establish biological roles of the enzyme which catalyzes the phosphorylation of a vast number of substrate proteins. In this article we disclose a series of new bisubstrate inhibitors of CK2 that are structurally represented by the oligo(l-Asp) peptide conjugates of benzo[c][2,6]naphthyridine-8-carboxylic acid. This fragment originated from CX-4945, the first in class inhibitor taken to clinical trials. The most potent conjugates possessed two-digit picomolar affinity and clear selectivity for CK2α in a panel of 140 protein kinases. Labeling of the inhibitors with a fluorescent dye yielded probes for a fluorescence anisotropy-based binding/displacement assay which can be used for analysis of CK2 and precise determination of affinity of the highly potent (tight-binding) CK2-targeting inhibitors.

  16. 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....

  17. 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

  18. 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

    2011-12-09

    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.

  19. 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

    Screening for protein kinase CK2 inhibitors of the structural diversity compound library (DTP NCI/NIH) led to the discovery of 4-[(E)-(fluoren-9-ylidenehydrazinylidene)-methyl]benzoic acid (E9). E9 induces apoptotic cell death in various cancer cell lines and upon hypoxia, the compound suppresses...... 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...

  20. The Alpha Catalytic Subunit of Protein Kinase CK2 Is Required for Mouse Embryonic Development▿

    Science.gov (United States)

    Lou, David Y.; Dominguez, Isabel; Toselli, Paul; Landesman-Bollag, Esther; O'Brien, Conor; Seldin, David C.

    2008-01-01

    Protein kinase CK2 (formerly casein kinase II) is a highly conserved and ubiquitous serine/threonine kinase that is composed of two catalytic subunits (CK2α and/or CK2α′) and two CK2β regulatory subunits. CK2 has many substrates in cells, and key roles in yeast cell physiology have been uncovered by introducing subunit mutations. Gene-targeting experiments have demonstrated that in mice, the CK2β gene is required for early embryonic development, while the CK2α′ subunit appears to be essential only for normal spermatogenesis. We have used homologous recombination to disrupt the CK2α gene in the mouse germ line. Embryos lacking CK2α have a marked reduction in CK2 activity in spite of the presence of the CK2α′ subunit. CK2α−/− embryos die in mid-gestation, with abnormalities including open neural tubes and reductions in the branchial arches. Defects in the formation of the heart lead to hydrops fetalis and are likely the cause of embryonic lethality. Thus, CK2α appears to play an essential and uncompensated role in mammalian development. PMID:17954558

  1. 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

    adopts a closed conformation correlating to a canonically established catalytic spine as is typical for eukaryotic protein kinases. In the corresponding crystal packing the hinge/helix αD region is nearly unaffected by crystal contacts, so that largely unbiased conformational adaptions are possible....... This is documented by published human CK2α structures with the same crystal packing but with an open hinge/helix αD region, one of which has been redetermined here with a higher symmetry. An overview of all published human CK2α crystal packings serves as the basis for a discussion of the factors that determine...

  2. Developmental and growth defects in mice with combined deficiency of CK2 catalytic genes.

    Science.gov (United States)

    Landesman-Bollag, Esther; Belkina, Anna; Hovey, Beth; Connors, Edward; Cox, Charles; Seldin, David C

    2011-10-01

    The CK2 α and α' catalytic gene products have overlapping biochemical activity, but in vivo, their functions are very different. Deletion of both alleles of CK2α leads to mid-gestational embryonic lethality, while deletion of both alleles of CK2α' does not interfere with viability or development of embryos; however, adult CK2α'-/-males are infertile. To further elucidate developmental roles of CK2, and analyze functional overlap between the two catalytic genes, mice with combined knockouts were bred. Mice bearing any two CK2 catalytic alleles were phenotypically normal. However, inheritance of a single CK2α allele, without either CK2α' allele, resulted in partial embryonic lethality. Such mice that survived through embryogenesis were smaller at birth than littermate controls, and weighed less throughout life. However, their cardiac function and lifespan were normal. Fibroblasts derived from CK2α+/-CK2α'-/- embryos grew poorly in culture. These experiments demonstrate that combined loss of one CK2α allele and both CK2α' alleles leads to unique abnormalities of growth and development.

  3. Overexpression of nuclear protein kinase CK2 α catalytic subunit (CK2α as a poor prognosticator in human colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Kai-Yuan Lin

    Full Text Available BACKGROUND: Colorectal cancer (CRC is one of the most common malignancies but the current therapeutic approaches for advanced CRC are less efficient. Thus, novel therapeutic approaches are badly needed. The purpose of this study is to investigate the involvement of nuclear protein kinase CK2 α subunit (CK2α in tumor progression, and in the prognosis of human CRC. METHODOLOGY/PRINCIPAL FINDINGS: Expression levels of nuclear CK2α were analyzed in 245 colorectal tissues from patients with CRC by immunohistochemistry, quantitative real-time PCR and Western blot. We correlated the expression levels with clinicopathologic parameters and prognosis in human CRC patients. Overexpression of nuclear CK2α was significantly correlated with depth of invasion, nodal status, American Joint Committee on Cancer (AJCC staging, degree of differentiation, and perineural invasion. Patients with high expression levels of nuclear CK2α had a significantly poorer overall survival rate compared with patients with low expression levels of nuclear CK2α. In multi-variate Cox regression analysis, overexpression of nuclear CK2α was proven to be an independent prognostic marker for CRC. In addition, DLD-1 human colon cancer cells were employed as a cellular model to study the role of CK2α on cell growth, and the expression of CK2α in DLD-1 cells was inhibited by using siRNA technology. The data indicated that CK2α-specific siRNA treatment resulted in growth inhibition. CONCLUSIONS/SIGNIFICANCE: Taken together, overexpression of nuclear CK2α can be a useful marker for predicting the outcome of patients with CRC.

  4. 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.

  5. In Search of Small Molecule Inhibitors Targeting the Flexible CK2 Subunit Interface

    Directory of Open Access Journals (Sweden)

    Benoît Bestgen

    2017-02-01

    Full Text Available Protein kinase CK2 is a tetrameric holoenzyme composed of two catalytic (α and/or α’ subunits and two regulatory (β subunits. Crystallographic data paired with fluorescence imaging techniques have suggested that the formation of the CK2 holoenzyme complex within cells is a dynamic process. Although the monomeric CK2α subunit is endowed with a constitutive catalytic activity, many of the plethora of CK2 substrates are exclusively phosphorylated by the CK2 holoenzyme. This means that the spatial and high affinity interaction between CK2α and CK2β subunits is critically important and that its disruption may provide a powerful and selective way to block the phosphorylation of substrates requiring the presence of CK2β. In search of compounds inhibiting this critical protein–protein interaction, we previously designed an active cyclic peptide (Pc derived from the CK2β carboxy-terminal domain that can efficiently antagonize the CK2 subunit interaction. To understand the functional significance of this interaction, we generated cell-permeable versions of Pc, exploring its molecular mechanisms of action and the perturbations of the signaling pathways that it induces in intact cells. The identification of small molecules inhibitors of this critical interaction may represent the first-choice approach to manipulate CK2 in an unconventional way.

  6. 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

    cells, all others in Escherichia coli. IC(50) studies involving the established CK2 inhibitors DMAT, TBBt, TBBz, apigenin and emodin were carried out and the K(i) values calculated. Although the differences in the K(i) values found were modest, there was a general tendency showing that the CK2...

  7. Development of Pharmacophore Model for Indeno[1,2-b]indoles as Human Protein Kinase CK2 Inhibitors and Database Mining

    Directory of Open Access Journals (Sweden)

    Samer Haidar

    2017-01-01

    Full Text Available Protein kinase CK2, initially designated as casein kinase 2, is an ubiquitously expressed serine/threonine kinase. This enzyme, implicated in many cellular processes, is highly expressed and active in many tumor cells. A large number of compounds has been developed as inhibitors comprising different backbones. Beside others, structures with an indeno[1,2-b]indole scaffold turned out to be potent new leads. With the aim of developing new inhibitors of human protein kinase CK2, we report here on the generation of common feature pharmacophore model to further explain the binding requirements for human CK2 inhibitors. Nine common chemical features of indeno[1,2-b]indole-type CK2 inhibitors were determined using MOE software (Chemical Computing Group, Montreal, Canada. This pharmacophore model was used for database mining with the aim to identify novel scaffolds for developing new potent and selective CK2 inhibitors. Using this strategy several structures were selected by searching inside the ZINC compound database. One of the selected compounds was bikaverin (6,11-dihydroxy-3,8-dimethoxy-1-methylbenzo[b]xanthene-7,10,12-trione, a natural compound which is produced by several kinds of fungi. This compound was tested on human recombinant CK2 and turned out to be an active inhibitor with an IC50 value of 1.24 µM.

  8. Ablation of Protein Kinase CK2β in Skeletal Muscle Fibers Interferes with Their Oxidative Capacity

    Directory of Open Access Journals (Sweden)

    Nane Eiber

    2017-01-01

    Full Text Available The tetrameric protein kinase CK2 was identified playing a role at neuromuscular junctions by studying CK2β-deficient muscle fibers in mice, and in cultured immortalized C2C12 muscle cells after individual knockdown of CK2α and CK2β subunits. In muscle cells, CK2 activity appeared to be at least required for regular aggregation of nicotinic acetylcholine receptors, which serves as a hallmark for the presence of a postsynaptic apparatus. Here, we set out to determine whether any other feature accompanies CK2β-deficient muscle fibers. Hind limb muscles gastrocnemius, plantaris, and soleus of adult wildtype and CK2β-deficient mice were dissected, cross-sectioned, and stained histochemically by Gomori trichrome and for nicotinamide adenine dinucleotide (NADH dehydrogenase and succinate dehydrogenase (SDH enzymatic activities. A reduction of oxidative enzymatic activity was determined for CK2β-deficient muscle fibers in comparison with wildtype controls. Importantly, the CK2β-deficient fibers, muscle fibers that typically exhibit high NADH dehydrogenase and SDH activities, like slow-type fibers, showed a marked reduction in these activities. Altogether, our data indicate additional impairments in the absence of CK2β in skeletal muscle fibers, pointing to an eventual mitochondrial myopathy.

  9. The C-terminal domain of human grp94 protects the catalytic subunit of protein kinase CK2 (CK2alpha) against thermal aggregation. Role of disulfide bonds

    DEFF Research Database (Denmark)

    Roher, N; Miró, F; Boldyreff, B

    2001-01-01

    The C-terminal domain (residues 518-803) of the 94 kDa glucose regulated protein (grp94) was expressed in Escherichia coli as a fusion protein with a His6-N-terminal tag (grp94-CT). This truncated form of grp94 formed dimers and oligomers that could be dissociated into monomers by treatment...... with dithiothreitol. Grp94-CT conferred protection against aggregation on the catalytic subunit of protein kinase CK2 (CK2alpha), although it did not protect against thermal inactivation. This anti-aggregation effect of grp94-CT was concentration dependent, with full protection achieved at grp94-CT/CK2alpha molar...

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

    DEFF Research Database (Denmark)

    Boldyreff, B; Meggio, F; Dobrowolska, G

    1993-01-01

    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...

  11. 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....

  12. Ability of CK2beta to selectively regulate cellular protein kinases

    DEFF Research Database (Denmark)

    Olsen, Birgitte; Guerra, Barbara

    2008-01-01

    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......-subunit of protein kinase CK2 can interact with Wee1 in high molecular mass complexes. Indirect immunofluorescence microscopy revealled subcellular co-localisation of CK2beta and Wee1 in the nucleus. Moreover, in vitro phosphorylation assays showed that CK2beta indirectly up-regulates the activity of CDK1...

  13. 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...

  14. INTERACCIONES INTRA E INTERMOLECULARES DE LA PROTEINAQUINASA CK2: ESTUDIO ESTRUCTURAL Y FUNCIONAL DE DOMINIOS ESPECIFICOS.

    OpenAIRE

    TAPIA PINEDA, JULIO CESAR

    2003-01-01

    La proteinaquinasa CK2 es una enzima ubicua en el mundo eucariótico, formada por la asociación de subunidades catalíticas a o a' y regulatorias l en las combinaciones a22, a'22 o aa' 2 . La diferencia estructural fundamental entre las subunidades CK2a de 190p.

  15. 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...

  16. 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.

  17. 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....

  18. 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.

  19. 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.

  20. Constitutive Phosphorylation of STAT3 by the CK2-BLNK-CD5 Complex.

    Science.gov (United States)

    Rozovski, Uri; Harris, David M; Li, Ping; Liu, Zhiming; Jain, Preetesh; Veletic, Ivo; Ferrajoli, Alessandra; Burger, Jan; O'Brien, Susan; Bose, Prithviraj; Thompson, Philip; Jain, Nitin; Wierda, William; Keating, Michael J; Estrov, Zeev

    2017-01-27

    In chronic lymphocytic leukemia (CLL), STAT3 is constitutively phosphorylated on serine 727 and plays a role in the pathobiology of CLL. However, what induces constitutive phosphorylation of STAT3 is currently unknown. Mass spectrometry was used to identify casein kinase 2 (CK2), a serine/threonine kinase that co-immunoprecipitated with serine phosphorylated STAT3 (pSTAT3). Furthermore, activated CK2 incubated with recombinant STAT3 induced phosphorylation of STAT3 on serine 727. Although STAT3 and CK2 are present in normal B- and T-cells, STAT3 is not constitutively phosphorylated in these cells. Further study found that CD5 and BLNK co-expressed in CLL, but not in normal B- or T-cells, are required for STAT3 phosphorylation. To elucidate the relationship of CD5 and BLNK to CK2 and STAT3, STAT3 was immunoprecipitated from CLL cells and CK2, CD5, and BLNK were detected in the immunoprecipitate. Conversely, STAT3, CD5, and BLNK were in the immunoprecipitate of CLL cells immunoprecipitated with CK2 antibodies. Furthermore, siRNA knockdown of CD5 or BLNK, or treatment with CD5-neutralizing antibodies significantly reduced the levels of serine pSTAT3 in CLL cells. Finally, confocal microscopy determined that CD5 is cell membrane bound and fractionation studies revealed that the CK2/CD5/BLNK/STAT3 complex remains in the cytoplasm, whereas serine pSTAT3 is shuttled to the nucleus.

  1. 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.

  2. 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...

  3. 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 valuescancer 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).

  4. CK2 blockade causes MPNST cell apoptosis and promotes degradation of β-catenin.

    Science.gov (United States)

    Kendall, Jed J; Chaney, Katherine E; Patel, Ami V; Rizvi, Tilat A; Largaespada, David A; Ratner, Nancy

    2016-08-16

    Malignant peripheral nerve sheath tumors (MPNSTs) are soft tissue sarcomas that are a major cause of mortality of Neurofibromatosis type 1 (NF1) patients. MPNST patients have few therapeutic options available and only complete surgical resection can be curative. MPNST formation and survival are dependent on activated β-catenin signaling. The goal of this study was to determine if inhibition of the CK2 enzyme can be therapeutically exploited in MPNSTs, given CK2's role in mainta ining oncogenic phenotypes including stabilization of β-catenin. We found that CK2α is over-expressed in MPNSTs and is critical for maintaining cell survival, as the CK2 inhibitor, CX-4945 (Silmitasertib), and shRNA targeting CK2α each significantly reduce MPNST cell viability. These effects were preceded by loss of critical signaling pathways in MPNSTs, including destabilization of β-catenin and TCF8. CX-4945 administration in vivo slowed tumor growth and extends survival time. We conclude that CK2 inhibition is a promising approach to blocking β-catenin in MPNST cells, although combinatorial therapies may be required for maximal efficacy.

  5. 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.

  6. RP1 Is a Phosphorylation Target of CK2 and Is Involved in Cell Adhesion

    Science.gov (United States)

    Göttig, Stephan; Henschler, Reinhard; Markuly, Norbert; Kleber, Sascha; Faust, Michael; Mischo, Axel; Bauer, Stefan; Zweifel, Martin; Knuth, Alexander; Renner, Christoph; Wadle, Andreas

    2013-01-01

    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 Ser236 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-ASP236 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 Ser236 by CK2 seems to play a significant role in cell adhesion and might initiate new insights in the CK2 and EB1 family protein association. PMID:23844040

  7. Identification of a Potent Allosteric Inhibitor of Human Protein Kinase CK2 by Bacterial Surface Display Library Screening.

    Science.gov (United States)

    Nienberg, Christian; Garmann, Claudia; Gratz, Andreas; Bollacke, Andre; Götz, Claudia; Jose, Joachim

    2017-01-05

    Human protein kinase CK2 has emerged as promising target for the treatment of neoplastic diseases. The vast majority of kinase inhibitors known today target the ATP binding site, which is highly conserved among kinases and hence leads to limited selectivity. In order to identify non-ATP competitive inhibitors, a 12-mer peptide library of 6 × 10⁵ variants was displayed on the surface of E. coli by autodisplay. Screening of this peptide library on variants with affinity to CK2 was performed by fluorophore-conjugated CK2 and subsequent flow cytometry. Single cell sorting of CK2-bound E. coli yielded new peptide variants, which were tested on inhibition of CK2 by a CE-based assay. Peptide B2 (DCRGLIVMIKLH) was the most potent inhibitor of both, CK2 holoenzyme and the catalytic CK2α subunit (IC50 = 0.8 µM). Using different ATP concentrations and different substrate concentrations for IC50 determination, B2 was shown to be neither ATP- nor substrate competitive. By microscale thermophoresis (MST) the KD value of B2 with CK2α was determined to be 2.16 µM, whereas no binding of B2 to CK2β-subunit was detectable. To our surprise, besides inhibition of enzymatic activity, B2 also disturbed the interaction of CK2α with CK2β at higher concentrations (≥25 µM).

  8. Identification of a Potent Allosteric Inhibitor of Human Protein Kinase CK2 by Bacterial Surface Display Library Screening

    Directory of Open Access Journals (Sweden)

    Christian Nienberg

    2017-01-01

    Full Text Available Human protein kinase CK2 has emerged as promising target for the treatment of neoplastic diseases. The vast majority of kinase inhibitors known today target the ATP binding site, which is highly conserved among kinases and hence leads to limited selectivity. In order to identify non-ATP competitive inhibitors, a 12-mer peptide library of 6 × 105 variants was displayed on the surface of E. coli by autodisplay. Screening of this peptide library on variants with affinity to CK2 was performed by fluorophore-conjugated CK2 and subsequent flow cytometry. Single cell sorting of CK2-bound E. coli yielded new peptide variants, which were tested on inhibition of CK2 by a CE-based assay. Peptide B2 (DCRGLIVMIKLH was the most potent inhibitor of both, CK2 holoenzyme and the catalytic CK2α subunit (IC50 = 0.8 µM. Using different ATP concentrations and different substrate concentrations for IC50 determination, B2 was shown to be neither ATP- nor substrate competitive. By microscale thermophoresis (MST the KD value of B2 with CK2α was determined to be 2.16 µM, whereas no binding of B2 to CK2β-subunit was detectable. To our surprise, besides inhibition of enzymatic activity, B2 also disturbed the interaction of CK2α with CK2β at higher concentrations (≥25 µM.

  9. 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

  10. 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.

  11. 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.

  12. Protein kinase CK2α catalytic subunit ameliorates diabetic renal inflammatory fibrosis via NF-κB signaling pathway.

    Science.gov (United States)

    Huang, Junying; Chen, Zhiquan; Li, Jie; Chen, Qiuhong; Li, Jingyan; Gong, Wenyan; Huang, Jiani; Liu, Peiqing; Huang, Heqing

    2017-02-23

    Activation of casein kinase 2 (CK2) is closely linked to the body disturbance of carbohydrate metabolism and inflammatory reaction. The renal chronic inflammatory reaction in the setting of diabetes is one of the important hallmarks of diabetic renal fibrosis. However, it remains unknown whether CK2 influences the process of diabetic renal fibrosis. The current study is aimed to investigate if CK2α ameliorates renal inflammatory fibrosis in diabetes via NF-κB pathway. To explore potential regulatory mechanism of CK2α, the expression and activity of CK2α, which were studied by plasmid transfection, selective inhibitor, small-interfering RNA (siRNA) and adenovirus infection in vitro or in vivo, were analyzed by means of western blotting (WB), dual luciferase reporter assay and electrophoretic mobility shift assay (EMSA). The following findings were observed: (1) Expression of CK2α was upregulated in kidneys of db/db and KKAy diabetic mice; (2) Inhibition of CK2α kinase activity or knockdown of CK2α protein expression suppressed high glucose-induced expressions of FN and ICAM-1 in glomerular mesangial cells (GMCs); (3) Inhibition of CK2α kinase activity or knockdown of CK2α protein expression not only restrained IκB degradation, but also suppressed HG-induced nuclear accumulation, transcriptional activity and DNA binding activity of NF-κB in GMCs; (4) Treatment of TBB or CK2α RNAi adenovirus infection ameliorated renal fibrosis in diabetic animals; (5) Treatment of TBB or CK2α RNAi adenovirus infection suppressed IκB degradation and NF-κB nuclear accumulation in glomeruli of diabetic animals. This study indicates the essential role of CK2α in regulating the diabetic renal pathological process of inflammatory fibrosis via NF-κB pathway, and inhibition of CK2α may serve as a promising therapeutic strategy for diabetic nephropathy.

  13. 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

    2015-01-08

    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.

  14. 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.

  15. 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.

  16. Phosphoproteomics Identifies CK2 as a Negative Regulator of Beige Adipocyte Thermogenesis and Energy Expenditure.

    Science.gov (United States)

    Shinoda, Kosaku; Ohyama, Kana; Hasegawa, Yutaka; Chang, Hsin-Yi; Ogura, Mayu; Sato, Ayaka; Hong, Haemin; Hosono, Takashi; Sharp, Louis Z; Scheel, David W; Graham, Mark; Ishihama, Yasushi; Kajimura, Shingo

    2015-12-01

    Catecholamines promote lipolysis both in brown and white adipocytes, whereas the same stimuli preferentially activate thermogenesis in brown adipocytes. Molecular mechanisms for the adipose-selective activation of thermogenesis remain poorly understood. Here, we employed quantitative phosphoproteomics to map global and temporal phosphorylation profiles in brown, beige, and white adipocytes under β3-adrenenoceptor activation and identified kinases responsible for the adipose-selective phosphorylation profiles. We found that casein kinase2 (CK2) activity is preferentially higher in white adipocytes than brown/beige adipocytes. Genetic or pharmacological blockade of CK2 in white adipocytes activates the thermogenic program in response to cAMP stimuli. Such activation is largely through reduced CK2-mediated phosphorylation of class I HDACs. Notably, inhibition of CK2 promotes beige adipocyte biogenesis and leads to an increase in whole-body energy expenditure and ameliorates diet-induced obesity and insulin resistance. These results indicate that CK2 is a plausible target to rewire the β3-adrenenoceptor signaling cascade that promotes thermogenesis in adipocytes.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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

    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%.......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...

  2. 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.

  3. Protein Kinase CK2α Maintains Extracellular Signal-regulated Kinase (ERK) Activity in a CK2α Kinase-independent Manner to Promote Resistance to Inhibitors of RAF and MEK but Not ERK in BRAF Mutant Melanoma.

    Science.gov (United States)

    Zhou, Bingying; Ritt, Daniel A; Morrison, Deborah K; Der, Channing J; Cox, Adrienne D

    2016-08-19

    The protein kinase casein kinase 2 (CK2) is a pleiotropic and constitutively active kinase that plays crucial roles in cellular proliferation and survival. Overexpression of CK2, particularly the α catalytic subunit (CK2α, CSNK2A1), has been implicated in a wide variety of cancers and is associated with poorer survival and resistance to both conventional and targeted anticancer therapies. Here, we found that CK2α protein is elevated in melanoma cell lines compared with normal human melanocytes. We then tested the involvement of CK2α in drug resistance to Food and Drug Administration-approved single agent targeted therapies for melanoma. In BRAF mutant melanoma cells, ectopic CK2α decreased sensitivity to vemurafenib (BRAF inhibitor), dabrafenib (BRAF inhibitor), and trametinib (MEK inhibitor) by a mechanism distinct from that of mutant NRAS. Conversely, knockdown of CK2α sensitized cells to inhibitor treatment. CK2α-mediated RAF-MEK kinase inhibitor resistance was tightly linked to its maintenance of ERK phosphorylation. We found that CK2α post-translationally regulates the ERK-specific phosphatase dual specificity phosphatase 6 (DUSP6) in a kinase dependent-manner, decreasing its abundance. However, we unexpectedly showed, by using a kinase-inactive mutant of CK2α, that RAF-MEK inhibitor resistance did not rely on CK2α kinase catalytic function, and both wild-type and kinase-inactive CK2α maintained ERK phosphorylation upon inhibition of BRAF or MEK. That both wild-type and kinase-inactive CK2α bound equally well to the RAF-MEK-ERK scaffold kinase suppressor of Ras 1 (KSR1) suggested that CK2α increases KSR facilitation of ERK phosphorylation. Accordingly, CK2α did not cause resistance to direct inhibition of ERK by the ERK1/2-selective inhibitor SCH772984. Our findings support a kinase-independent scaffolding function of CK2α that promotes resistance to RAF- and MEK-targeted therapies.

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

    OpenAIRE

    2015-01-01

    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. Patie...

  5. Cloning and purification of protein kinase CK2 recombinant alpha and beta subunits from the Mediterranean fly Ceratitis capitata.

    Science.gov (United States)

    Kouyanou-Koutsoukou, Sophia; Baier, Andrea; Kolaitis, Regina-Maria; Maniatopoulou, Evanthia; Thanopoulou, Konstantina; Szyszka, Ryszard

    2011-10-01

    The Mediterranean fruit fly Ceratitis capitata is an insect capable of wreaking extensive damage to a wide range of fruit crops. Protein kinase CK2 is a ubiquitous Ser/Thr kinase that is highly conserved among eukaryotes; it is a heterotetramer composed of two catalytic (α) and a dimer of regulatory (β) subunits. We present here the construction of the cDNA molecules of the CK2α and CK2β subunits from the medfly C. capitata by the 5'/3' RACE and RT-PCR methods, respectively. CcCK2α catalytic subunit presents the characteristic and conserved features of a typical protein kinase, similar to the regulatory CcCK2β subunit, that also possess the conserved features of regulatory CK2β subunits, as revealed by comparison of their predicted amino acid sequences with other eukaryotic species. The recombinant CcCK2α and CcCK2β proteins were purified by affinity chromatography to homogeneity, after overexpression in Escherichia coli. CcCK2α is capable to utilize GTP and its activity and is inhibited by polyanions and stimulated by polycations in phosphorylation assays, using purified acidic ribosomal protein P1 as a substrate.

  6. Synthesis of novel polybrominated benzimidazole derivatives-potential CK2 inhibitors with anticancer and proapoptotic activity.

    Science.gov (United States)

    Łukowska-Chojnacka, Edyta; Wińska, Patrycja; Wielechowska, Monika; Poprzeczko, Martyna; Bretner, Maria

    2016-02-15

    The efficient method for the synthesis of novel cell permeable inhibitors of protein kinase CK2 with anticancer and proapoptotic activity has been developed. A series of polybrominated benzimiadazole derivatives substituted by various cyanoalkyl groups have been synthesized. Cyanoethyl derivatives were obtained by Michael type addition of 4,5,6,7-tetrabromo-1H-benzimidazole (TBBi) and 4,5,6,7-tetrabromo-2-methyl-1H-benzimidazole to acrylonitrile, whilst cyanomethyl, cyanopropyl and cyanobutyl analogs by N-alkylation of 4,5,6,7-tetrabromo-1H-benzimidazole and 4,5,6,7-tetrabromo-2-methyl-1H-benzimidazole with appropriate cyanoalkyl halides. The inhibitory activity against protein kinase rhCK2α catalytic subunit and cytotoxicity against two human cancer cell lines: acute lymphocytic leukemia (CCRF-CEM) and breast (MCF-7) were evaluated for all newly synthesized compounds. Additionally, the proapoptotic activity toward leukemia cells and intracellular inhibition of CK2 for the most cytotoxic derivatives have been performed, demonstrating 4,5,6,7-tetrabromo-2-methyl-1H-benzimidazole as a new selective inhibitor of rhCK2 with twenty-fold better proapoptotic activity than parental compound (TBBi).

  7. Stimulation of Leishmania tropica protein kinase CK2 activities by platelet-activating factor (PAF).

    Science.gov (United States)

    Dutra, Patricia M L; Vieira, Danielle P; Meyer-Fernandes, Jose R; Silva-Neto, Mario A C; Lopes, Angela H

    2009-09-01

    Leishmania tropica is one of the causative agents of cutaneous leishmaniasis. Platelet-activating factor (PAF) is a phospholipid mediator in diverse biological and pathophysiological processes. Here we show that PAF promoted a three-fold increase on ecto-protein kinase and a three-fold increase on the secreted kinase activity of L. tropica live promastigotes. When casein was added to the reaction medium, along with PAF, there was a four-fold increase on the ecto-kinase activity. When live L. tropica promastigotes were pre-incubated for 30 min in the presence of PAF-plus casein, a six-fold increase on the secreted kinase activity was observed. Also, a protein released from L. tropica promastigotes reacted with polyclonal antibodies for the mammalian CK2 alpha catalytic subunit. Furthermore, in vitro mouse macrophage infection by L. tropica was doubled when promastigotes were pre-treated for 2 h with PAF. Similar results were obtained when the interaction was performed in the presence of purified CK2 or casein. TBB and DRB, CK2 inhibitors, reversed PAF enhancement of macrophage infection by L. tropica. WEB 2086, a competitive PAF antagonist, reversed all PAF effects here described. This study shows for the first time that PAF promotes the activation of two isoforms of CK2, secreted and membrane-bound, correlating these activities to infection of mouse macrophages.

  8. 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...

  9. 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 ...

  10. 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

    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...

  11. Targeting CK2-driven non-oncogene addiction in B-cell tumors.

    Science.gov (United States)

    Mandato, E; Manni, S; Zaffino, F; Semenzato, G; Piazza, F

    2016-11-24

    Genetic mutations of oncogenes often underlie deranged cell growth and altered differentiation pathways leading to malignant transformation of B-lymphocytes. However, addiction to oncogenes is not the only drive to lymphoid tumor pathogenesis. Dependence on non-oncogenes, which act by propelling basic mechanisms of cell proliferation and survival, has also been recognized in the pathobiology of lymphoid leukemias, lymphomas and multiple myeloma. Among the growing number of molecules that may uphold non-oncogene addiction, a key place is increasingly being recognized to the serine-threonine kinase CK2. This enzyme is overexpressed and overactive in B-acute lymphoblastic leukemia, multiple myeloma, chronic lymphocytic leukemia and non-Hodgkin lymphomas, such as mantle cell, follicular, Burkitt's and diffuse large B-cell lymphomas. In these tumors, CK2 may serve the activity of oncogenes, similar to BCR-ABL and c-MYC, control the activation of critical signaling cascades, such as NF-κB (nuclear factor-κB), STAT3 (signal transducer and activator of transcription 3) and PTEN/PI3K/AKT (phosphatase and tensin homolog protein/phosphoinositide 3-kinase/AKR thymoma), and sustain multiple cellular stress-elicited pathways, such as the proteotoxic stress, unfolded protein and DNA-damage responses. CK2 has also been shown to have an essential role in tuning signals derived from the stromal tumor microenvironment. Not surprisingly, targeting CK2 in lymphoid tumor cell lines or mouse xenograft models can boost the cytotoxic effects of both conventional chemotherapeutics and novel agents, similar to heat-shock protein 90, proteasome and tyrosine kinases inhibitors. In this review, we summarize the evidence indicating how CK2 embodies most of the features of a cancer growth-promoting non-oncogene, focusing on lymphoid tumors. We further discuss the preclinical data of the use of small ATP-competitive CK2 inhibitors, which hold the promise to be additional options in novel drug

  12. 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...

  13. CK2(beta)tes gene encodes a testis-specific isoform of the regulatory subunit of casein kinase 2 in Drosophila melanogaster

    DEFF Research Database (Denmark)

    Kalmykova, Alla I; Shevelyov, Yuri Y; Polesskaya, Oksana O

    2002-01-01

    An earlier described CK2(beta)tes gene of Drosophila melanogaster is shown to encode a male germline specific isoform of regulatory beta subunit of casein kinase 2. Western-analysis using anti-CK2(beta)tes Ig revealed CK2(beta)tes protein in Drosophila testes extract. Expression of a CK2(beta...... and coimmunoprecipitation analysis of protein extract from Drosophila testes, we demonstrated an association between CK2(beta)tes and CK2alpha. Northern-analysis has shown that another regulatory (beta') subunit found recently in D. melanogaster genome is also testis-specific. Thus, we describe the first example of two...

  14. CK2 phosphorylation inactivates DNA binding by the papillomavirus E1 and E2 proteins.

    Science.gov (United States)

    Schuck, Stephen; Ruse, Cristian; Stenlund, Arne

    2013-07-01

    Papillomaviruses have complex life cycles that are understood only superficially. Although it is well established that the viral E1 and E2 proteins play key roles in controlling viral transcription and DNA replication, how these factors are regulated is not well understood. Here, we demonstrate that phosphorylation by the protein kinase CK2 controls the biochemical activities of the bovine papillomavirus E1 and E2 proteins by modifying their DNA binding activity. Phosphorylation at multiple sites in the N-terminal domain in E1 results in the loss of sequence-specific DNA binding activity, a feature that is also conserved in human papillomavirus (HPV) E1 proteins. The bovine papillomavirus (BPV) E2 protein, when phosphorylated by CK2 on two specific sites in the hinge, also loses its site-specific DNA binding activity. Mutation of these sites in E2 results in greatly increased levels of latent viral DNA replication, indicating that CK2 phosphorylation of E2 is a negative regulator of viral DNA replication during latent viral replication. In contrast, mutation of the N-terminal phosphorylation sites in E1 has no effect on latent viral DNA replication. We propose that the phosphorylation of the N terminus of E1 plays a role only in vegetative viral DNA replication, and consistent with such a role, caspase 3 cleavage of E1, which has been shown to be necessary for vegetative viral DNA replication, restores the DNA binding activity to phosphorylated E1.

  15. 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.

  16. 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...... viability and inhibition of endogenous CK2 activity in the absence and presence of the anti-cancer drug cisplatin. The strongest effect on viability was observed with resorufin. In contrast to resorufin, TBB protected cells from cisplatin-induced cell killing. Furthermore, the inhibition of endogenous CK2...

  17. Nanoencapsulated anti-CK2 small molecule drug or siRNA specifically targets malignant cancer but not benign cells.

    Science.gov (United States)

    Trembley, Janeen H; Unger, Gretchen M; Korman, Vicci L; Tobolt, Diane K; Kazimierczuk, Zygmunt; Pinna, Lorenzo A; Kren, Betsy T; Ahmed, Khalil

    2012-02-01

    CK2, a pleiotropic Ser/Thr kinase, is an important target for cancer therapy. We tested our novel tenfibgen-based nanocapsule for delivery of the inhibitor 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole (DMAT) and an siRNA directed against both CK2α and α' catalytic subunits to prostate cancer cells. We present data on the TBG nanocapsule itself and on CK2 inhibition or downregulation in treated cells, including effects on Nuclear Factor-kappa B (NF-κB) p65. By direct comparison of two CK2-directed cargos, our data provide proof that the TBG encapsulation design for delivery of drugs specifically to cancer cells has strong potential for small molecule- and nucleic acid-based cancer therapy.

  18. 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.

  19. 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.

  20. 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.

  1. Design, synthesis and evaluation of 3-quinoline carboxylic acids as new inhibitors of protein kinase CK2.

    Science.gov (United States)

    Syniugin, Anatolii R; Ostrynska, Olga V; Chekanov, Maksym O; Volynets, Galyna P; Starosyla, Sergiy A; Bdzhola, Volodymyr G; Yarmoluk, Sergiy M

    2016-01-01

    In this article, the derivatives of 3-quinoline carboxylic acid were studied as inhibitors of protein kinase CK2. Forty-three new compounds were synthesized. Among them 22 compounds inhibiting CK2 with IC50 in the range from 0.65 to 18.2 μM were identified. The most active inhibitors were found among tetrazolo-quinoline-4-carboxylic acid and 2-aminoquinoline-3-carboxylic acid derivatives.

  2. 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...

  3. 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

    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 in m....... Thus, our study demonstrates that in mammals, CK2beta is essential for viability at the cellular level, possibly because it acquired new functions during evolution.......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...

  4. Targeting Protein Kinase CK2: Evaluating CX-4945 Potential for GL261 Glioblastoma Therapy in Immunocompetent Mice

    Science.gov (United States)

    Ferrer-Font, Laura; Villamañan, Lucia; Arias-Ramos, Nuria; Vilardell, Jordi; Plana, Maria; Ruzzene, Maria; Pinna, Lorenzo A.; Itarte, Emilio; Arús, Carles; Candiota, Ana Paula

    2017-01-01

    Glioblastoma (GBM) causes poor survival in patients even with aggressive treatment. Temozolomide (TMZ) is the standard chemotherapeutic choice for GBM treatment but resistance always ensues. Protein kinase CK2 (CK2) contributes to tumour development and proliferation in cancer, and it is overexpressed in human GBM. Accordingly, targeting CK2 in GBM may benefit patients. Our goal has been to evaluate whether CK2 inhibitors (iCK2s) could increase survival in an immunocompetent preclinical GBM model. Cultured GL261 cells were treated with different iCK2s including CX-4945, and target effects evaluated in vitro. CX-4945 was found to decrease CK2 activity and Akt(S129) phosphorylation in GL261 cells. Longitudinal in vivo studies with CX-4945 alone or in combination with TMZ were performed in tumour-bearing mice. Increase in survival (p < 0.05) was found with combined CX-4945 and TMZ metronomic treatment (54.7 ± 11.9 days, n = 6) when compared to individual metronomic treatments (CX-4945: 24.5 ± 2.0 and TMZ: 38.7 ± 2.7, n = 6) and controls (22.5 ± 1.2, n = 6). Despite this, CX-4945 did not improve mice outcome when administered on every/alternate days, either alone or in combination with 3-cycle TMZ. The highest survival rate was obtained with the metronomic combined TMZ+CX-4945 every 6 days, pointing to the participation of the immune system or other ancillary mechanism in therapy response. PMID:28208677

  5. 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.

  6. Targeting Protein Kinase CK2: Evaluating CX-4945 Potential for GL261 Glioblastoma Therapy in Immunocompetent Mice

    Directory of Open Access Journals (Sweden)

    Laura Ferrer-Font

    2017-02-01

    Full Text Available Glioblastoma (GBM causes poor survival in patients even with aggressive treatment. Temozolomide (TMZ is the standard chemotherapeutic choice for GBM treatment but resistance always ensues. Protein kinase CK2 (CK2 contributes to tumour development and proliferation in cancer, and it is overexpressed in human GBM. Accordingly, targeting CK2 in GBM may benefit patients. Our goal has been to evaluate whether CK2 inhibitors (iCK2s could increase survival in an immunocompetent preclinical GBM model. Cultured GL261 cells were treated with different iCK2s including CX-4945, and target effects evaluated in vitro. CX-4945 was found to decrease CK2 activity and Akt(S129 phosphorylation in GL261 cells. Longitudinal in vivo studies with CX-4945 alone or in combination with TMZ were performed in tumour-bearing mice. Increase in survival (p < 0.05 was found with combined CX-4945 and TMZ metronomic treatment (54.7 ± 11.9 days, n = 6 when compared to individual metronomic treatments (CX-4945: 24.5 ± 2.0 and TMZ: 38.7 ± 2.7, n = 6 and controls (22.5 ± 1.2, n = 6. Despite this, CX-4945 did not improve mice outcome when administered on every/alternate days, either alone or in combination with 3-cycle TMZ. The highest survival rate was obtained with the metronomic combined TMZ+CX-4945 every 6 days, pointing to the participation of the immune system or other ancillary mechanism in therapy response.

  7. 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

  8. 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.

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

    Science.gov (United States)

    Girardi, Cristina; Ottaviani, Daniele; Pinna, Lorenzo A.; Ruzzene, Maria

    2015-01-01

    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 (dis)regulation. 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. PMID:26558259

  10. On the Hamiltonian structure of large deviations in stochastic hybrid systems

    Science.gov (United States)

    Bressloff, Paul C.; Faugeras, Olivier

    2017-03-01

    We present a new derivation of the classical action underlying a large deviation principle (LDP) for a stochastic hybrid system, which couples a piecewise deterministic dynamical system in {{{R}}d} with a time-homogeneous Markov chain on some discrete space Γ . We assume that the Markov chain on Γ is ergodic, and that the discrete dynamics is much faster than the piecewise deterministic dynamics (separation of time-scales). Using the Perron–Frobenius theorem and the calculus-of-variations, we show that the resulting action Hamiltonian is given by the Perron eigenvalue of a | Γ | -dimensional linear equation. The corresponding linear operator depends on the transition rates of the Markov chain and the nonlinear functions of the piecewise deterministic system. We compare the Hamiltonian to one derived using WKB methods, and show that the latter is a reduction of the former. We also indicate how the analysis can be extended to a multi-scale stochastic process, in which the continuous dynamics is described by a piecewise stochastic differential equations (SDE). Finally, we illustrate the theory by considering applications to conductance-based models of membrane voltage fluctuations in the presence of stochastic ion channels.

  11. Decreased Degradation of Internalized Follicle-Stimulating Hormone Caused by Mutation of Aspartic Acid 6.30550 in a Protein Kinase-CK2 Consensus Sequence in the Third Intracellular Loop of Human Follicle-Stimulating Hormone Receptor1

    Science.gov (United States)

    Kluetzman, Kerri S.; Thomas, Richard M.; Nechamen, Cheryl A.; Dias, James A.

    2011-01-01

    A naturally occurring mutation in follicle-stimulating hormone receptor (FSHR) gene has been reported: an amino acid change to glycine occurs at a conserved aspartic acid 550 (D550, D567, D6.30567). This residue is contained in a protein kinase-CK2 consensus site present in human FSHR (hFSHR) intracellular loop 3 (iL3). Because CK2 has been reported to play a role in trafficking of some receptors, the potential roles for CK2 and D550 in FSHR function were evaluated by generating a D550A mutation in the hFSHR. The hFSHR-D550A binds hormone similarly to WT-hFSHR when expressed in HEK293T cells. Western blot analyses showed lower levels of mature hFSHR-D550A. Maximal cAMP production of both hFSHR-D550A as well as the naturally occurring mutation hFSHR-D550G was diminished, but constitutive activity was not observed. Unexpectedly, when 125I-hFSH bound to hFSHR-D550A or hFSHR-D550G, intracellular accumulation of radiolabeled FSH was observed. Both sucrose and dominant-negative dynamin blocked internalization of radiolabeled FSH and its commensurate intracellular accumulation. Accumulation of radiolabeled FSH in cells transfected with hFSHR-D550A is due to a defect in degradation of hFSH as measured in pulse chase studies, and confocal microscopy imaging revealed that FSH accumulated in large intracellular structures. CK2 kinase activity is not required for proper degradation of internalized FSH because inhibition of CK2 kinase activity in cells expressing hFSHR did not uncouple degradation of internalized radiolabeled FSH. Additionally, the CK2 consensus site in FSHR iL3 is not required for binding because CK2alpha coimmunoprecipitated with hFSHR-D550A. Thus, mutation of D550 uncouples the link between internalization and degradation of hFSH. PMID:21270425

  12. 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

  13. 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。

  14. Annexin-1 Mediates Microglial Activation and Migration via the CK2 Pathway during Oxygen–Glucose Deprivation/Reperfusion

    Directory of Open Access Journals (Sweden)

    Shuangxi Liu

    2016-10-01

    Full Text Available Annexin-1 (ANXA1 has shown neuroprotective effects and microglia play significant roles during central nervous system injury, yet the underlying mechanisms remain unclear. This study sought to determine whether ANXA1 regulates microglial response to oxygen–glucose deprivation/reperfusion (OGD/R treatment and to clarify the downstream molecular mechanism. In rat hippocampal slices, OGD/R treatment enhanced the ANXA1 expression in neuron, the formyl peptide receptor (FPRs expression in microglia, and the microglial activation in the CA1 region (cornu ammonis 1. These effects were reversed by the FPRs antagonist Boc1. The cell membrane currents amplitude of BV-2 microglia (the microglial like cell-line was increased when treated with Ac2-26, the N-terminal peptide of ANXA1. Ac2-26 treatment enhanced BV-2 microglial migration whereas Boc1 treatment inhibited the migration. In BV-2 microglia, both the expression of the CK2 target phosphorylated α-E-catenin and the binding of casein kinase II (CK2 with α-E-catenin were elevated by Ac2-26, these effects were counteracted by the CK2 inhibitor TBB and small interfering (si RNA directed against transcripts of CK2 and FPRs. Moreover, both TBB and siRNA-mediated inhibition of CK2 blocked Ac2-26-mediated BV-2 microglia migration. Our findings indicate that ANXA1 promotes microglial activation and migration during OGD/R via FPRs, and CK2 target α-E-catenin phosphorylation is involved in this process.

  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. 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 ...

  17. 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.

  18. Assessment of the effect of deviated nasal septum on the structure of nasal cavity.

    Science.gov (United States)

    Wang, Junguo; Dou, Xin; Liu, Dingding; Song, Panpan; Qian, Xiaoyun; Wang, Shoulin; Gao, Xia

    2016-06-01

    The present study was aimed to investigate the effects of DNS on the structure of nasal cavity. The paranasal sinus coronal view CT of 108 patients with DNS and 129 hospitalized patients without DNS was retrospectively analyzed. The transverse diameter of nasal cavity (a), transverse diameter of nasal cavity and paranasal sinus (b), angle between maxillary and palatal bone, interalveolar distance, and maxillary rotation distance were measured. The ratio of a/b in experimental group was 0.367 ± 0.006 which was significantly (P = 0.0023) less than that in control group (0.391 ± 0.005). For the angle between maxillary and palatal bone, there was no significant difference found between DNS and control group for both right and left sides. The interalveolar distance was 40.75 mm in experimental group, and 38.8 mm in control (P = 0.0002). For the maxillary rotation distance, findings were considered as significant (P DNS affects the development of nasal cavity and paranasal sinus, as well as increases the interalveolar distance and maxillary rotation distance. These influences may be caused by the alteration of airflow inside the nasal cavities.

  19. 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...... with the holoenzyme. Polylysine stimulated MDM2 phosphorylation by CK2 holoenzyme threefold in contrast to the alpha-subunit-catalyzed MDM2 phosphorylation which was reduced by about 66% when polylysine was added. Full length p53, but also a peptide representing a C-terminal fragment of the tumor suppressor gene......(264-393) was on the average close to twofold and inhibition in the case of the alpha-subunit-catalyzed MDM2 phosphorylation was about 40%. Phosphorylation of MDM2 by CK2 holoenzyme in the presence of the p21(WAF1/CIP1), known to be a potent inhibitor of cyclin-dependent protein kinases, also led to a significant reduction...

  20. 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

    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...

  1. 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...... of the recombinant beta subunit. By this latter procedure five mutated tetrameric holoenzymes were obtained as judged from their subunit composition, sedimentation coefficient on sucrose gradient ultracentrifugation, and increased activity toward a specific peptide substrate as compared with the isolated alpha...... subunits. The kinetic constants and the phosphorylation efficiencies (V(max)/Km) of all the mutants with the parent peptide RRRADDSDDDDD and a series of derivatives, in which individual aspartic acids were replaced by alanines, have been determined. Three mutants, namely K74A,K75A,K76A,K77A; K79A, R80A,K83...

  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. Examination of CK2α and NF-κB p65 expression in human benign prostatic hyperplasia and prostate cancer tissues.

    Science.gov (United States)

    Qaiser, Fatima; Trembley, Janeen H; Sadiq, Sarah; Muhammad, Iqbal; Younis, Rubina; Hashmi, Shoaib Naiyar; Murtaza, Badar; Rector, Thomas S; Naveed, Abdul Khaliq; Ahmed, Khalil

    2016-09-01

    Protein kinase CK2 plays a critical role in cell growth, proliferation, and suppression of cell death. CK2 is overexpressed, especially in the nuclear compartment, in the majority of cancers, including prostate cancer (PCa). CK2-mediated activation of transcription factor nuclear factor kappa B (NF-κB) p65 is a key step in cellular proliferation, resulting in translocation of NF-κB p65 from the cytoplasm to the nucleus. As CK2 expression and activity are also elevated in benign prostatic hyperplasia (BPH), we sought to increase the knowledge of CK2 function in benign and malignant prostate by examination of the relationships between nuclear CK2 and nuclear NF-κB p65 protein expression. The expression level and localization of CK2α and NF-κB p65 proteins in PCa and BPH tissue specimens was determined. Nuclear CK2α and NF-κB p65 protein levels are significantly higher in PCa compared with BPH, and these proteins are positively correlated with each other in both diseases. Nuclear NF-κB p65 levels correlated with Ki-67 or with cytoplasmic NF-κB p65 expression in BPH, but not in PCa. The findings provide information that combined analysis of CK2α and NF-κB p65 expression in prostate specimens relates to the disease status. Increased nuclear NF-κB p65 expression levels in PCa specifically related to nuclear CK2α levels, indicating a possible CK2-dependent relationship in malignancy. In contrast, nuclear NF-κB p65 protein levels related to both Ki-67 and cytoplasmic NF-κB p65 levels exclusively in BPH, suggesting a potential separate impact for NF-κB p65 function in proliferation for benign disease as opposed to malignant disease.

  4. Phosphorylation of the Fas associated factor FAF1 by protein kinase CK2 and identification of serines 289 and 291 as the in vitro phosphorylation sites

    DEFF Research Database (Denmark)

    Jensen, H H; Hjerrild, M; Guerra, B;

    2001-01-01

    We previously identified the human Fas associated factor (FAF1) as one of the interacting partners of protein kinase CK2 beta subunit. Since FAF1 is a phosphoprotein we investigated whether it is a substrate for CK2. Here, we report the full length human FAF1 cDNA sequence, expression of FAF1 in ...

  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. 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.

  7. 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.

  8. 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.

  9. Cystic fibrosis transmembrane regulator fragments with the Phe508 deletion exert a dual allosteric control over the master kinase CK2

    Science.gov (United States)

    Pagano, Mario A.; Marin, Oriano; Cozza, Giorgio; Sarno, Stefania; Meggio, Flavio; Treharne, Kate J.; Mehta, Anil; Pinna, Lorenzo A.

    2011-01-01

    Cystic fibrosis mostly follows a single Phe508 deletion in CFTR (cystic fibrosis transmembrane regulator) (CFTRΔF508), thereby causing premature fragmentation of the nascent protein with concomitant alterations of diverse cellular functions. We show that CK2, the most pleiotropic protein kinase, undergoes allosteric control of its different cellular forms in the presence of short CFTR peptides encompassing the Phe508 deletion: these CFTRΔF508 peptides drastically inhibit the isolated catalytic subunit (α) of the kinase and yet up-regulate the holoenzyme, composed of two catalytic and two non-catalytic (β) subunits. Remarkable agreement between in silico docking and our biochemical data point to different sites for the CFTRΔF508 peptide binding on isolated CK2α and on CK2β assembled into the holoenzyme, suggesting that CK2 targeting may be perturbed in cells expressing CFTRΔF508; this could shed light on some pleiotropic aspects of cystic fibrosis disease. PMID:19925455

  10. Apigenin: Selective CK2 inhibitor increases Ikaros expression and improves T cell homeostasis and function in murine pancreatic cancer

    Science.gov (United States)

    Nelson, Nadine; Szekeres, Karoly; Iclozan, Cristina; Rivera, Ivannie Ortiz; McGill, Andrew; Johnson, Gbemisola; Nwogu, Onyekachi

    2017-01-01

    Pancreatic cancer (PC) evades immune destruction by favoring the development of regulatory T cells (Tregs) that inhibit effector T cells. The transcription factor Ikaros is critical for lymphocyte development, especially T cells. We have previously shown that downregulation of Ikaros occurs as a result of its protein degradation by the ubiquitin-proteasome system in our Panc02 tumor-bearing (TB) mouse model. Mechanistically, we observed a deregulation in the balance between Casein Kinase II (CK2) and protein phosphatase 1 (PP1), which suggested that increased CK2 activity is responsible for regulating Ikaros’ stability in our model. We also showed that this loss of Ikaros expression is associated with a significant decrease in CD4+ and CD8+ T cell percentages but increased CD4+CD25+ Tregs in TB mice. In this study, we evaluated the effects of the dietary flavonoid apigenin (API), on Ikaros expression and T cell immune responses. Treatment of splenocytes from naïve mice with (API) stabilized Ikaros expression and prevented Ikaros downregulation in the presence of murine Panc02 cells in vitro, similar to the proteasome inhibitor MG132. In vivo treatment of TB mice with apigenin (TB-API) improved survival, reduced tumor weights and prevented splenomegaly. API treatment also restored protein expression of some Ikaros isoforms, which may be attributed to its moderate inhibition of CK2 activity from splenocytes of TB-API mice. This partial restoration of Ikaros expression was accompanied by a significant increase in CD4+ and CD8+ T cell percentages and a reduction in Treg percentages in TB-API mice. In addition, CD8+ T cells from TB-API mice produced more IFN-γ and their splenocytes were better able to prime allogeneic CD8+ T cell responses compared to TB mice. These results provide further evidence that Ikaros is regulated by CK2 in our pancreatic cancer model. More importantly, our findings suggest that API may be a possible therapeutic agent for stabilizing Ikaros

  11. 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.

  12. 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.

  13. 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.

  14. Large-deviation principles, stochastic effective actions, path entropies, and the structure and meaning of thermodynamic descriptions

    Science.gov (United States)

    Smith, Eric

    2011-04-01

    The meaning of thermodynamic descriptions is found in large-deviations scaling (Ellis 1985 Entropy, Large Deviations, and Statistical Mechanics (New York: Springer); Touchette 2009 Phys. Rep. 478 1-69) of the probabilities for fluctuations of averaged quantities. The central function expressing large-deviations scaling is the entropy, which is the basis both for fluctuation theorems and for characterizing the thermodynamic interactions of systems. Freidlin-Wentzell theory (Freidlin and Wentzell 1998 Random Perturbations in Dynamical Systems 2nd edn (New York: Springer)) provides a quite general formulation of large-deviations scaling for non-equilibrium stochastic processes, through a remarkable representation in terms of a Hamiltonian dynamical system. A number of related methods now exist to construct the Freidlin-Wentzell Hamiltonian for many kinds of stochastic processes; one method due to Doi (1976 J. Phys. A: Math. Gen. 9 1465-78 1976 J. Phys. A: Math. Gen. 9 1479) and Peliti (1985 J. Physique 46 1469; 1986 J. Phys. A: Math. Gen. 19 L365, appropriate to integer counting statistics, is widely used in reaction-diffusion theory. Using these tools together with a path-entropy method due to Jaynes (1980 Annu. Rev. Phys. Chem. 31 579-601), this review shows how to construct entropy functions that both express large-deviations scaling of fluctuations, and describe system-environment interactions, for discrete stochastic processes either at or away from equilibrium. A collection of variational methods familiar within quantum field theory, but less commonly applied to the Doi-Peliti construction, is used to define a 'stochastic effective action', which is the large-deviations rate function for arbitrary non-equilibrium paths. We show how common principles of entropy maximization, applied to different ensembles of states or of histories, lead to different entropy functions and different sets of thermodynamic state variables. Yet the relations among all these levels of

  15. Large-deviation principles, stochastic effective actions, path entropies, and the structure and meaning of thermodynamic descriptions

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Eric [Santa Fe Institute, 1399 Hyde Park Road, Santa Fe, NM 87501 (United States)

    2011-04-15

    The meaning of thermodynamic descriptions is found in large-deviations scaling (Ellis 1985 Entropy, Large Deviations, and Statistical Mechanics (New York: Springer); Touchette 2009 Phys. Rep. 478 1-69) of the probabilities for fluctuations of averaged quantities. The central function expressing large-deviations scaling is the entropy, which is the basis both for fluctuation theorems and for characterizing the thermodynamic interactions of systems. Freidlin-Wentzell theory (Freidlin and Wentzell 1998 Random Perturbations in Dynamical Systems 2nd edn (New York: Springer)) provides a quite general formulation of large-deviations scaling for non-equilibrium stochastic processes, through a remarkable representation in terms of a Hamiltonian dynamical system. A number of related methods now exist to construct the Freidlin-Wentzell Hamiltonian for many kinds of stochastic processes; one method due to Doi (1976 J. Phys. A: Math. Gen. 9 1465-78; 1976 J. Phys. A: Math. Gen. 9 1479) and Peliti (1985 J. Physique 46 1469; 1986 J. Phys. A: Math. Gen. 19 L365, appropriate to integer counting statistics, is widely used in reaction-diffusion theory. Using these tools together with a path-entropy method due to Jaynes (1980 Annu. Rev. Phys. Chem. 31 579-601), this review shows how to construct entropy functions that both express large-deviations scaling of fluctuations, and describe system-environment interactions, for discrete stochastic processes either at or away from equilibrium. A collection of variational methods familiar within quantum field theory, but less commonly applied to the Doi-Peliti construction, is used to define a 'stochastic effective action', which is the large-deviations rate function for arbitrary non-equilibrium paths. We show how common principles of entropy maximization, applied to different ensembles of states or of histories, lead to different entropy functions and different sets of thermodynamic state variables. Yet the relations among all these

  16. Phosphoproteomics Reveals HMGA1, a CK2 Substrate, as a Drug-Resistant Target in Non-Small Cell Lung Cancer

    Science.gov (United States)

    Wang, Yi-Ting; Pan, Szu-Hua; Tsai, Chia-Feng; Kuo, Ting-Chun; Hsu, Yuan-Ling; Yen, Hsin-Yung; Choong, Wai-Kok; Wu, Hsin-Yi; Liao, Yen-Chen; Hong, Tse-Ming; Sung, Ting-Yi; Yang, Pan-Chyr; Chen, Yu-Ju

    2017-01-01

    Although EGFR tyrosine kinase inhibitors (TKIs) have demonstrated good efficacy in non-small-cell lung cancer (NSCLC) patients harboring EGFR mutations, most patients develop intrinsic and acquired resistance. We quantitatively profiled the phosphoproteome and proteome of drug-sensitive and drug-resistant NSCLC cells under gefitinib treatment. The construction of a dose-dependent responsive kinase-substrate network of 1548 phosphoproteins and 3834 proteins revealed CK2-centric modules as the dominant core network for the potential gefitinib resistance-associated proteins. CK2 knockdown decreased cell survival in gefitinib-resistant NSCLCs. Using motif analysis to identify the CK2 core sub-network, we verified that elevated phosphorylation level of a CK2 substrate, HMGA1 was a critical node contributing to EGFR-TKI resistance in NSCLC cell. Both HMGA1 knockdown or mutation of the CK2 phosphorylation site, S102, of HMGA1 reinforced the efficacy of gefitinib in resistant NSCLC cells through reactivation of the downstream signaling of EGFR. Our results delineate the TKI resistance-associated kinase-substrate network, suggesting a potential therapeutic strategy for overcoming TKI-induced resistance in NSCLC. PMID:28290473

  17. 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

  18. 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.

  19. 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...... interference results in delayed cell-cycle progression at the onset of mitosis. Knockdown of CK2beta causes stabilization of Wee1 and increased phosphorylation of CDK1 at the inhibitory Tyr15. PLK1-Wee1 association is an essential event in the degradation of Wee1 in unperturbed cell cycle. We have found...... regulatory subunit, identifying it as a new component of signaling pathways that regulate cell-cycle progression at the entry of mitosis.Oncogene advance online publication, 12 May 2008; doi:10.1038/onc.2008.146....

  20. Propagation of structural deviations of poly(amidoamine) fan-shape dendrimers (generations 0-3) characterized by MALDI and electrospray mass spectrometry

    Science.gov (United States)

    Giordanengo, Rémi; Mazarin, Michaël; Wu, Jiangyu; Peng, Ling; Charles, Laurence

    2007-10-01

    Fan-shape PAMAM dendrimers, from generations 0 to 3, were analyzed by mass spectrometry, using both MALDI and electrospray ionization techniques, to identify any structural deviations present in each sample. First, it could be concluded that all detected molecules were present in the samples as they were detected in MALDI as well as in electrospray mass spectra. Apart from commonly reported dendrimer defects ("missing arm" and "molecular loop"), new impurities were found to arise from propagation of these defects during the synthesis of upper generations. These assignments were based on both compound molecular weight and, when ions were detected with sufficient abundance, deviations from perfect structure behaviour during MS/MS experiments. Since new impurities could be created, either from perfect or defective molecules, during each new generation dendrimer synthesis, models were built to predict the molecular weight of a compound as a function of its synthesis history and efficiently guide mass spectral interpretation.

  1. 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.

  2. 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

    -subunit or in the CK2 holoenzyme (alpha 2 beta 2). Here, concentrations of the first antibody of 1 ng/ml still allowed the detection of the subunit. Immunoblotting of crude cellular extracts from various tissue cultures (man, mouse, and hamster), from human tumors, and the nonneoplastic tissue allowed the detection...... of the CK2 beta-subunit. The detected epitope of this antibody was, as determined by the epitope analysis technique, 123GLSDI127....

  3. Phase-resolved functional optical coherence tomography: simultaneous imaging of in situ tissue structure, blood flow velocity, standard deviation, birefringence, and Stokes vectors in human skin

    Science.gov (United States)

    Ren, Hongwu; Ding, Zhihua; Zhao, Yonghua; Miao, Jianjun; Nelson, J. Stuart; Chen, Zhongping

    2002-10-01

    We describe a phase-resolved functional optical coherence tomography system that can simultaneously yield in situ images of tissue structure, blood flow velocity, standard deviation, birefringence, and the Stokes vectors in human skin. Multifunctional images were obtained by processing of analytical interference fringe signals derived from two perpendicular polarization-detection channels. The blood flow velocity and standard deviation images were obtained by comparison of the phases from pairs of analytical signals in neighboring A-lines in the same polarization state. The analytical signals from two polarization-diversity detection channels were used to determine the four Stokes vectors for four reference polarization states. From the four Stokes vectors, the birefringence image, which is not sensitive to the orientation of the optical axis in the sample, was obtained. Multifunctional in situ images of a port wine stain birthmark in human skin are presented.

  4. 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...... cisplatin and carboplatin on the mRNA and protein levels of p53, MDM2 and CK2 in a murine teratocarcinoma cell line F9. Northern and Western blot analyses were performed and the CK2 activity was determined. The degree of apoptosis after drug treatment was assessed using the TUNEL test. Six hours after...

  5. 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.

  6. 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.

  7. CK2 abrogates the inhibitory effects of PRH/HHEX on prostate cancer cell migration and invasion and acts through PRH to control cell proliferation

    Science.gov (United States)

    Siddiqui, Y H; Kershaw, R M; Humphreys, E H; Assis Junior, E M; Chaudhri, S; Jayaraman, P-S; Gaston, K

    2017-01-01

    PRH/HHEX (proline-rich homeodomain protein/haematopoietically expressed homeobox protein) is a transcription factor that controls cell proliferation, cell differentiation and cell migration. Our previous work has shown that in haematopoietic cells, Protein Kinase CK2-dependent phosphorylation of PRH results in the inhibition of PRH DNA-binding activity, increased cleavage of PRH by the proteasome and the misregulation of PRH target genes. Here we show that PRH and hyper-phosphorylated PRH are present in normal prostate epithelial cells, and that hyper-phosphorylated PRH levels are elevated in benign prostatic hyperplasia, prostatic adenocarcinoma, and prostate cancer cell lines. A reduction in PRH protein levels increases the motility of normal prostate epithelial cells and conversely, PRH over-expression inhibits prostate cancer cell migration and blocks the ability of these cells to invade an extracellular matrix. We show that CK2 over-expression blocks the repression of prostate cancer cell migration and invasion by PRH. In addition, we show that PRH knockdown in normal immortalised prostate cells results in an increase in the population of cells capable of colony formation in Matrigel, as well as increased cell invasion and decreased E-cadherin expression. Inhibition of CK2 reduces PRH phosphorylation and reduces prostate cell proliferation but the effects of CK2 inhibition on cell proliferation are abrogated in PRH knockdown cells. These data suggest that the increased phosphorylation of PRH in prostate cancer cells increases both cell proliferation and tumour cell migration/invasion. PMID:28134934

  8. 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...

  9. 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

    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 ...

  10. 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).

  11. 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.

  12. 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.

    Science.gov (United States)

    Manni, Sabrina; Brancalion, Alessandra; Mandato, Elisa; Tubi, Laura Quotti; Colpo, Anna; Pizzi, Marco; Cappellesso, Rocco; Zaffino, Fortunato; Di Maggio, Speranza Antonia; Cabrelle, Anna; Marino, Filippo; Zambello, Renato; Trentin, Livio; Adami, Fausto; Gurrieri, Carmela; Semenzato, Gianpietro; Piazza, Francesco

    2013-01-01

    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.

  13. 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.

  14. 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.

  15. 左卡尼汀对特发性弱精子症精子质量及蛋白激酶CK2活性的影响%Effects of Levocarnitine on sperm quality and activity of protein kinase CK2 in patients with idiopathic asthenozoospermia

    Institute of Scientific and Technical Information of China (English)

    黄雪坤; 尚慧玲; 黄娟华; 刘建霞; 张四友

    2011-01-01

    目的 研究左卡尼汀对特发性弱精子症精子质量及蛋白激酶CK2活性的影响,从而探讨其可能的作用机制.方法 利用计算机辅助精子分析(CASA)系统对35例特发性弱精子症患者接受左卡尼汀(1 g/次,tid)治疗前、治疗3个月后和15例健康男性的精液进行分析;提取精子总蛋白,利用同位素掺入法检测精子蛋白激酶CK2活性.结果 左卡尼汀能显著提高特发性弱精子症患者精子的活动率、前向性运动精子百分率(a+b级)、曲线运动速度(VCL)、直线运动速度(VSL)和平均路径运动速度(VAP).左卡尼汀治疗前CK2活性每分钟计算值为1445±431,治疗后为2209±502,治疗后精液CK2活性明显升高(P<0.05).治疗前后CK2活性变化与治疗前后精子活动率(r=0.45,P<0.05)、a+b级(r=0.58,P<0.01)、VCL(r=0.43,P<0.05)、VSL(r=0.40,P<0.05)、VAP(r=0.41,P<0.05)变化均呈正相关性.结论 左卡尼汀能显著提高特发性弱精子症精子质量,其作用机制可能是增加了蛋白激酶CK2活性.%Objective To study the effects of Levocarnitine on sperm quality and activity of protein kinase CK2 in patients with idiopathic asthenozoospermia , and further explore the possible molecular mechanisms. Methods Sperms, obtained from 35 idiopathic asthenozoospermia patients before and after treated with Levocarnitine ( 1 g/time, tid) for 3 months and 15 healthy fertile men, were analyzed by computer-aid semen analysis ( CASA ) system. In addition, protein was extracted from those sperm samples and the CK2 activity was assayed by detecting incorporation of 32P of [ 7- P] ATP into the substrate. Results The sperm in idiopathic asthenozoospermia patients treated with Levocarnitine showed a significant increase in sperm progressive motility , grade a + b sperm percent, curvilinear velocity ( VCL) , straight-line velocity (VSL) and average path velocity (VAP). CK2 activity in idiopathic asthenozoospermia patients after treated with Levocarnitine

  16. Large Deviations and Metastability

    Science.gov (United States)

    Olivieri, Enzo; Eulália Vares, Maria

    2005-02-01

    This self-contained account of the main results in large deviation theory includes recent developments and emphasizes the Freidlin-Wentzell results on small random perturbations. Metastability is described on physical grounds, followed by the development of more exacting approaches to its description. The first part of the book then develops such pertinent tools as the theory of large deviations which is used to provide a physically relevant dynamical description of metastability. Written for graduate students, this book affords an excellent route into contemporary research as well.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  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. 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...

  3. Apigenin inhibits proliferation and induces apoptosis in human multiple myeloma cells through targeting the trinity of CK2, Cdc37 and Hsp90

    Directory of Open Access Journals (Sweden)

    Xu Yuan-Ji

    2011-08-01

    Full Text Available Abstract Background Multiple myeloma (MM is a B-cell malignancy that is largely incurable and is characterized by the accumulation of malignant plasma cells in the bone marrow. Apigenin, a common flavonoid, has been reported to suppress proliferation in a wide variety of solid tumors and hematological cancers; however its mechanism is not well understood and its effect on MM cells has not been determined. Results In this study, we investigated the effects of apigenin on MM cell lines and on primary MM cells. Cell viability assays demonstrated that apigenin exhibited cytotoxicity against both MM cell lines and primary MM cells but not against normal peripheral blood mononuclear cells. Together, kinase assays, immunoprecipitation and western blot analysis showed that apigenin inhibited CK2 kinase activity, decreased phosphorylation of Cdc37, disassociated the Hsp90/Cdc37/client complex and induced the degradation of multiple kinase clients, including RIP1, Src, Raf-1, Cdk4 and AKT. By depleting these kinases, apigenin suppressed both constitutive and inducible activation of STAT3, ERK, AKT and NF-κB. The treatment also downregulated the expression of the antiapoptotic proteins Mcl-1, Bcl-2, Bcl-xL, XIAP and Survivin, which ultimately induced apoptosis in MM cells. In addition, apigenin had a greater effects in depleting Hsp90 clients when used in combination with the Hsp90 inhibitor geldanamycin and the histone deacetylase inhibitor vorinostat. Conclusions Our results suggest that the primary mechanisms by which apigenin kill MM cells is by targeting the trinity of CK2-Cdc37-Hsp90, and this observation reveals the therapeutic potential of apigenin in treating multiple myeloma.

  4. Deviating From the Benchmarks

    DEFF Research Database (Denmark)

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

    survival? The analysis is based on a matched employer-employee dataset and covers about 17,500 startups in manufacturing and services. We adopt a new procedure to estimate individual benchmarks for the quantity and quality of initial human resources, acknowledging correlations between hiring decisions...... 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...

  5. 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...

  6. [Participation of proteinkinase CK2 in regulation of human erythrocytes plasma membrane redox system activity: relative contribution of ca(2+)-dependent and ca(2+)-independent mechanisms of its activation].

    Science.gov (United States)

    Iakovenko, I N; Zhirnov, V V; Kozachenko, O P; Shablykin, O V; Brovarets', V S

    2012-01-01

    Involvement of protein kinase CK2 (2.7.11.1) in modulation of live cells trans-plasma membrane electron transport was first discovered. Using human erythrocytes a decrease of plasma membrane redox system (PMRS) activity is shown under the action of specific protein kinase CK2 inhibitors. Using inhibitory analysis the activity regulation of human erythrocytes PMRS by Ca(2+)-dependent and Ca(2+)-independent mechanisms were investigated. It was shown that functional Ca(2+)-antagonists (nitrendipine and calmidazolium) significantly increased, and functional Ca(2+)-agonists to some extent reduced or did not affect the trans-plasma membrane electron transport in these cells.

  7. Safety and preliminary efficacy data of a novel Casein Kinase 2 (CK2 peptide inhibitor administered intralesionally at four dose levels in patients with cervical malignancies

    Directory of Open Access Journals (Sweden)

    Alonso Daniel F

    2009-05-01

    Full Text Available Abstract Background Cervical cancer is now considered the second leading cause of death among women worldwide, and its incidence has reached alarming levels, especially in developing countries. Similarly, high grade squamous intraepithelial lesion (HSIL, the precursor stage for cervical cancer, represents a growing health problem among younger women as the HSIL management regimes that have been developed are not fully effective. From the etiological point of view, the presence of Human Papillomavirus (HPV has been demonstrated to play a crucial role for developing cervical malignancies, and viral DNA has been detected in 99.7% of cervical tumors at the later stages. CIGB-300 is a novel cyclic synthetic peptide that induces apoptosis in malignant cells and elicits antitumor activity in cancer animal models. CIGB-300 impairs the Casein Kinase (CK2 phosphorylation, by targeting the substrate's phosphoaceptor domain. Based on the perspectives of CIGB-300 to treat cancer, this "first-in-human" study investigated its safety and tolerability in patients with cervical malignancies. Methods Thirty-one women with colposcopically and histologically diagnosed microinvasive or pre-invasive cervical cancer were enrolled in a dose escalating study. CIGB-300 was administered sequentially at 14, 70, 245 and 490 mg by intralesional injections during 5 consecutive days to groups of 7 – 10 patients. Toxicity was monitored daily until fifteen days after the end of treatment, when patients underwent conization. Digital colposcopy, histology, and HPV status were also evaluated. Results No maximum-tolerated dose or dose-limiting toxicity was achieved. The most frequent local events were pain, bleeding, hematoma and erythema at the injection site. The systemic adverse events were rash, facial edema, itching, hot flashes, and localized cramps. 75% of the patients experienced a significant lesion reduction at colposcopy and 19% exhibited full histological regression

  8. p53 and the ribosomal protein L5 participate in high molecular mass complex formation with protein kinase CK2 in murine teratocarcinoma cell line F9 after serum stimulation and cisplatin treatment

    DEFF Research Database (Denmark)

    Guerra, B; Issinger, O G

    1998-01-01

    Using the murine teratocarcinoma cell line F9 we investigated the influence of serum stimulation and cisplatin treatment on the p53, CK2, MDM2 levels. Both treatments led to an increase of p53, though with different kinetics; the other proteins investigated were not affected. We present direct...

  9. 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.)

  10. Paroxysmal upgaze deviation: case report

    OpenAIRE

    Echeverría-Palacio CM; Benavidez-Fierro MA

    2012-01-01

    The paroxysmal upgaze deviation is a syndrome that described in infants for first time in 1988; there are just about 50 case reports worldwide ever since. Its etiology is unclear and though it prognosis is variable; most case reports indicate that during growth the episodes tend to decrease in frequency and duration until they disappear. It describes a 16-months old male child who since 11-months old presented many episodes of variable conjugate upward deviation of the eyes, compensatory neck...

  11. 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.

  12. 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.

  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: 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

  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

    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.

  15. 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.

  16. 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。

  17. Large deviations in Taylor dispersion

    Science.gov (United States)

    Kahlen, Marcel; Engel, Andreas; Van den Broeck, Christian

    2017-01-01

    We establish a link between the phenomenon of Taylor dispersion and the theory of empirical distributions. Using this connection, we derive, upon applying the theory of large deviations, an alternative and much more precise description of the long-time regime for Taylor dispersion.

  18. 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…

  19. Basic residues in the 74-83 and 191-198 segments of protein kinase CK2 catalytic subunit are implicated in negative but not in positive regulation by the beta-subunit

    DEFF Research Database (Denmark)

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

    1997-01-01

    by the beta-subunit many fold more than that of alpha wild type, while extrastimulation by beta mutant D55L56E57A, observable with alpha wild type, is abolished with these mutants. These data support the conclusion that down regulation by the acidic residues clustered in the N-terminal moiety of beta...... sensitive to inhibition by either beta-subunit or its N-terminal, CK2beta-(1-77)-peptide, while its stimulation by the C-terminal peptide, CK2beta-(155-215), is comparable to that of alpha wild type. These observations suggest an indirect role of Val66 in conferring to the alpha-subunit a conformation less...

  20. 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...

  1. 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...

  2. Paroxysmal upgaze deviation: case report

    Directory of Open Access Journals (Sweden)

    Echeverría-Palacio CM

    2012-05-01

    Full Text Available The paroxysmal upgaze deviation is a syndrome that described in infants for first time in 1988; there are just about 50 case reports worldwide ever since. Its etiology is unclear and though it prognosis is variable; most case reports indicate that during growth the episodes tend to decrease in frequency and duration until they disappear. It describes a 16-months old male child who since 11-months old presented many episodes of variable conjugate upward deviation of the eyes, compensatory neck flexion and down-beat saccades in attempted downgaze. These events are predominantly diurnal, and are exacerbated by stressful situations such as fasting or insomnia, however and improve with sleep. They have normal neurologic and ophthalmologic examination, and neuroimaging and EEG findings are not relevant.

  3. 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.

  4. Prolonged insulin stimulation down-regulates GLUT4 through oxidative stress-mediated retromer inhibition by a protein kinase CK2-dependent mechanism in 3T3-L1 adipocytes.

    Science.gov (United States)

    Ma, Jinhui; Nakagawa, Yuko; Kojima, Itaru; Shibata, Hiroshi

    2014-01-03

    Although insulin acutely stimulates glucose uptake by promotion of GLUT4 translocation from intracellular compartments to the plasma membrane in adipocytes and muscles, long term insulin stimulation causes GLUT4 depletion that is particularly prominent in the insulin-responsive GLUT4 storage compartment. This effect is caused mainly by accelerated lysosomal degradation of GLUT4, although the mechanism is not fully defined. Here we show that insulin acutely induced dissociation of retromer components from the low density microsomal membranes of 3T3-L1 adipocytes that was accompanied by disruption of the interaction of Vps35 with sortilin. This insulin effect was dependent on the activity of protein kinase CK2 but not phosphatidylinositol 3-kinase or extracellular signal-regulated kinase 1/2. Knockdown of Vps26 decreased GLUT4 to a level comparable with that with insulin stimulation for 4 h. Vps35 with a mutation in the CK2 phosphorylation motif (Vps35-S7A) was resistant to insulin-induced dissociation from the low density microsomal membrane, and its overexpression attenuated GLUT4 down-regulation with insulin. Furthermore, insulin-generated hydrogen peroxide was an upstream mediator of the insulin action on retromer and GLUT4. These results suggested that insulin-generated oxidative stress switches the GLUT4 sorting direction to lysosomes through inhibition of the retromer function in a CK2-dependent manner.

  5. RESEARCH ON THICKNESS DEVIATION CRITERIA OF STEEL PLATE IN STEEL STRUCTURE CODE%钢结构规范中钢板厚度偏差问题的研究

    Institute of Scientific and Technical Information of China (English)

    陈会荣

    2012-01-01

    Thickness is a main factor affecting the bearing capacity of steel plate. If the thickness deviation of steel plate is not clear, potential safety hazard may exist or unnecessary waste may be caused. Due to the fact that allowable thickness deviation of steel plate is not unified in national standards, supervision and construction units may choose different criteria during comprehension and implementation of these standards, causing relatively obvious errors. Rational proposals are put forward after comparison of steel plate thicknesses between Code for design of steel structures (GB 50017-2003) and Code for acceptance of construction quality of steel structures(GB 50205-2001).%钢板的厚度尺寸是影响承载力的主要因素,如果板厚尺寸偏差不明确,不是造成安全隐患,就是造成不必要的浪费.在钢板厚度允许偏差上,由于国家标准的不统一,使得在工程监理及施工单位的理解和执行中,选择规范不同而造成误差.通过对比《钢结构设计规范》(GB 50017-2003)、《钢结构工程施工质量验收规范》(GB 50205-2001)等规范中钢板厚度允许偏差,提出合理化建议.

  6. 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.

  7. 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....

  8. 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...

  9. 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...

  10. 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....

  11. 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...

  12. 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...

  13. 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...

  14. Structural Safety Analysis on Tube Sheet With Deviated Holes in Steam Generator%蒸汽发生器管板孔桥超差情况下的结构安全性分析

    Institute of Scientific and Technical Information of China (English)

    李海龙; 王庆; 徐宇; 熊冬庆; 王臣; 张跃

    2014-01-01

    蒸汽发生器制造过程中对管板进行深孔钻时,发生管板孔桥超差。管板二次侧的3个管孔C165‐R59、C167‐R59、C168‐R58不能满足设计要求,管板一次侧的这些管孔满足设计要求。针对该不符合项,核审评单位联合蒸汽发生器制造单位和设计单位,从管板的强度、管板孔桥超差不符合项对流致振动的影响、堵管后的传热管应力分析、传热管堵管的压差对孔桥强度的影响、孔桥超差导致的传热管接触磨损等角度进行了结构安全性分析。分析结果表明,目前的堵管方案合理可行,但需加强在役阶段的跟踪检查,以保证修复的可靠性和质量。%During the manufacturing process of the steam generator ,deviated holes were detected w hen drilling the tube sheet . T he sizes of three holes including C165‐R59 , C167‐R59 and C168‐R58 on the secondary side of the tube sheet don’t meet the design requirements ,while the sizes and positions of those holes on the primary side are within design requirements . The structural safety analyses ,including tube sheet strength , influence of tube sheet with deviated holes on flow induced vibration (FIV ) , stress analysis of plugged tubes ,influence of the differential pressure between the plugged tubes and the unplugged tubes on the strength ,and fretting wear between tubes caused by deviated holes ,were done by the nuclear safety reviewer combined with the manufac‐turer and the designer .T he results show that the repair plan is reasonable and feasibili‐ty .Meanwhile ,in‐service follow‐up inspections must be strengthened to insure the quality and reliability of plugged tubes .

  15. [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.

  16. 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...

  17. 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....

  18. 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...

  19. 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)...

  20. 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....

  1. 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....

  2. Vertical deviations of the midplane of the Galaxy.

    Science.gov (United States)

    Malhotra, S.; Rhoads, J. E.

    Besides the integral sign warp in the outer Galaxy, the gas in the Milky Way shows small, but systematic deviations from a flat z = 0 plane both in the inner and the outer Galaxy. In the inner Galaxy, the tangent points have no distance ambiguity, so their distances, and hence midplane deviations, can be measured. From the tangent point analysis the authors find that the molecular and atomic gas layers deviate from the z = 0 plane with an amplitude of ≅50 pc. Whether these deviations are due to a small, smooth inner warp or are similar to the m = 10 mode corrugations found in the outer Galaxy (Kulkarni, Blitz & Heiles, 1982) can be checked by looking at the two-dimensional (in Galactic radius and azimuthal angle) structure of the z deviations. For the inner Galaxy, distance ambiguity at points other than the tangent points makes the interpretation difficult, but these hypotheses can be checked in a limited way. Magnetic instabilities can cause vertical deviations of the gas, but if stars share the same deviations the origin has to be gravitational.

  3. Perception of midline deviations in smile esthetics by laypersons

    Science.gov (United States)

    Ferreira, Jamille Barros; da Silva, Licínio Esmeraldo; Caetano, Márcia Tereza de Oliveira; da Motta, Andrea Fonseca Jardim; Cury-Saramago, Adriana de Alcantara; Mucha, José Nelson

    2016-01-01

    ABSTRACT Objective: To evaluate the esthetic perception of upper dental midline deviation by laypersons and if adjacent structures influence their judgment. Methods: An album with 12 randomly distributed frontal view photographs of the smile of a woman with the midline digitally deviated was evaluated by 95 laypersons. The frontal view smiling photograph was modified to create from 1 mm to 5 mm deviations in the upper midline to the left side. The photographs were cropped in two different manners and divided into two groups of six photographs each: group LCN included the lips, chin, and two-thirds of the nose, and group L included the lips only. The laypersons performed the rate of each smile using a visual analog scale (VAS). Wilcoxon test, Student’s t-test and Mann-Whitney test were applied, adopting a 5% level of significance. Results: Laypersons were able to perceive midline deviations starting at 1 mm. Statistically significant results (p< 0.05) were found for all multiple comparisons of the values in photographs of group LCN and for almost all comparisons in photographs of group L. Comparisons between the photographs of groups LCN and L showed statistically significant values (p< 0.05) when the deviation was 1 mm. Conclusions: Laypersons were able to perceive the upper dental midline deviations of 1 mm, and above when the adjacent structures of the smiles were included. Deviations of 2 mm and above when the lips only were included. The visualization of structures adjacent to the smile demonstrated influence on the perception of midline deviation. PMID:28125140

  4. Perception of midline deviations in smile esthetics by laypersons

    Directory of Open Access Journals (Sweden)

    Jamille Barros Ferreira

    Full Text Available ABSTRACT Objective: To evaluate the esthetic perception of upper dental midline deviation by laypersons and if adjacent structures influence their judgment. Methods: An album with 12 randomly distributed frontal view photographs of the smile of a woman with the midline digitally deviated was evaluated by 95 laypersons. The frontal view smiling photograph was modified to create from 1 mm to 5 mm deviations in the upper midline to the left side. The photographs were cropped in two different manners and divided into two groups of six photographs each: group LCN included the lips, chin, and two-thirds of the nose, and group L included the lips only. The laypersons performed the rate of each smile using a visual analog scale (VAS. Wilcoxon test, Student’s t-test and Mann-Whitney test were applied, adopting a 5% level of significance. Results: Laypersons were able to perceive midline deviations starting at 1 mm. Statistically significant results (p< 0.05 were found for all multiple comparisons of the values in photographs of group LCN and for almost all comparisons in photographs of group L. Comparisons between the photographs of groups LCN and L showed statistically significant values (p< 0.05 when the deviation was 1 mm. Conclusions: Laypersons were able to perceive the upper dental midline deviations of 1 mm, and above when the adjacent structures of the smiles were included. Deviations of 2 mm and above when the lips only were included. The visualization of structures adjacent to the smile demonstrated influence on the perception of midline deviation.

  5. 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.

  6. 20 CFR 435.4 - Deviations.

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Deviations. 435.4 Section 435.4 Employees' Benefits SOCIAL SECURITY ADMINISTRATION UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND AGREEMENTS WITH... General § 435.4 Deviations. The Office of Management and Budget (OMB) may grant exceptions for classes...

  7. 48 CFR 3001.403 - Individual deviations.

    Science.gov (United States)

    2010-10-01

    .... 3001.403 Section 3001.403 Federal Acquisition Regulations System DEPARTMENT OF HOMELAND SECURITY... from the FAR and HSAR 3001.403 Individual deviations. Unless precluded by law, executive order, or..., including complete documentation of the justification for the deviation (See HSAM 3001.403)....

  8. 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...

  9. 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...

  10. 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.

  11. Large deviations for a random speed particle

    CERN Document Server

    Lefevere, Raphael; Zambotti, Lorenzo

    2011-01-01

    We investigate large deviations for the empirical measure of the position and momentum of a particle traveling in a box with hot walls. The particle travels with uniform speed from left to right, until it hits the right boundary. Then it is absorbed and re-emitted from the left boundary with a new random speed, taken from an i.i.d. sequence. It turns out that this simple model, often used to simulate a heat bath, displays unusually complex large deviations features, that we explain in detail. In particular, if the tail of the update distribution of the speed is sufficiently oscillating, then the empirical measure does not satisfy a large deviations principle, and we exhibit optimal lower and upper large deviations functionals.

  12. 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.

  13. 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.

  14. The large deviations theorem and ergodicity

    Energy Technology Data Exchange (ETDEWEB)

    Gu Rongbao [School of Finance, Nanjing University of Finance and Economics, Nanjing 210046 (China)

    2007-12-15

    In this paper, some relationships between stochastic and topological properties of dynamical systems are studied. For a continuous map f from a compact metric space X into itself, we show that if f satisfies the large deviations theorem then it is topologically ergodic. Moreover, we introduce the topologically strong ergodicity, and prove that if f is a topologically strongly ergodic map satisfying the large deviations theorem then it is sensitively dependent on initial conditions.

  15. 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.

  16. Large deviation theory for coin tossing and turbulence.

    Science.gov (United States)

    Chakraborty, Sagar; Saha, Arnab; Bhattacharjee, Jayanta K

    2009-11-01

    Large deviations play a significant role in many branches of nonequilibrium statistical physics. They are difficult to handle because their effects, though small, are not amenable to perturbation theory. Even the Gaussian model, which is the usual initial step for most perturbation theories, fails to be a starting point while discussing intermittency in fluid turbulence, where large deviations dominate. Our contention is: in the large deviation theory, the central role is played by the distribution associated with the tossing of a coin and the simple coin toss is the "Gaussian model" of problems where rare events play significant role. We illustrate this by applying it to calculate the multifractal exponents of the order structure factors in fully developed turbulence.

  17. Cosolvency and deviations from log-linear solubilization.

    Science.gov (United States)

    Rubino, J T; Yalkowsky, S H

    1987-06-01

    The solubilities of three nonpolar drugs, phenytoin, diazepam, and benzocaine, have been measured in 14 cosolvent-water binary mixtures. The observed solubilities were examined for deviations from solubilities calculated by the equation log Sm = f log Sc + (1 - f) log Sw, where Sm is the solubility of the drug in the cosolvent-water mixture, Sc is the solubility of the drug in neat cosolvent, f is the volume fraction of cosolvent, and Sw is the solubility of the drug in water. When presented graphically, the patterns of the deviations were similar for all three drugs in mixtures of amphiprotic cosolvents (glycols, polyols, and alcohols) and water as well as nonpolar, aprotic cosolvents (dioxane, triglyme, dimethyl isosorbide) and water. The deviations were positive for phenytoin and benzocaine but negative for diazepam in mixtures of dipolar, aprotic cosolvents (dimethylsulfoxide, dimethylformamide, and dimethylacetamide) and water. The source of the deviations could not consistently be attributed to physical properties of the cosolvent-water mixtures or to alterations in the solute crystal. Similarities between the results of this study and those of previous investigations suggest that changes in the structure of the solvent play a role in the deviations from the expected solubilities.

  18. On large deviations for ensembles of distributions

    Science.gov (United States)

    Khrychev, D. A.

    2013-11-01

    The paper is concerned with the large deviations problem in the Freidlin-Wentzell formulation without the assumption of the uniqueness of the solution to the equation involving white noise. In other words, it is assumed that for each \\varepsilon>0 the nonempty set \\mathscr P_\\varepsilon of weak solutions is not necessarily a singleton. Analogues of a number of concepts in the theory of large deviations are introduced for the set \\{\\mathscr P_\\varepsilon,\\,\\varepsilon>0\\}, hereafter referred to as an ensemble of distributions. The ensembles of weak solutions of an n-dimensional stochastic Navier-Stokes system and stochastic wave equation with power-law nonlinearity are shown to be uniformly exponentially tight. An idempotent Wiener process in a Hilbert space and idempotent partial differential equations are defined. The accumulation points in the sense of large deviations of the ensembles in question are shown to be weak solutions of the corresponding idempotent equations. Bibliography: 14 titles.

  19. 41 CFR 109-1.5304 - Deviations.

    Science.gov (United States)

    2010-07-01

    ... Secretary for Procurement and Assistance Management. A HFO's decision not to provide life-cycle control... through the cognizant HFO to the Deputy Assistant Secretary for Procurement and Assistance Management. ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Deviations....

  20. Voice Deviations and Coexisting Communication Disorders.

    Science.gov (United States)

    St. Louis, Kenneth O.; And Others

    1992-01-01

    This study examined the coexistence of other communicative disorders with voice disorders in about 3,400 children in grades 1-12 at 100 sites throughout the United States. The majority of voice-disordered children had coexisting articulation deviations and also differed from controls on two language measures and mean pure-tone hearing thresholds.…

  1. 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…

  2. 43 CFR 12.904 - Deviations.

    Science.gov (United States)

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Deviations. 12.904 Section 12.904 Public Lands: Interior Office of the Secretary of the Interior ADMINISTRATIVE AND AUDIT REQUIREMENTS AND COST PRINCIPLES FOR ASSISTANCE PROGRAMS Uniform Administrative Requirements for Grants and Agreements...

  3. Vertex deviation maps to bracked the Milky Way resonant radius

    Science.gov (United States)

    Roca-Fàbrega, S.; Antoja, T.; Figueras, F.; Valenzuela, O.; Romero-Gómez, M.; Pichardo, B.

    2015-05-01

    We map the kinematics of stars in simulated galaxy disks with spiral arms using the velocity ellipsoid vertex deviation (l_v). We use test particle simulations, and for the first time, fully self-consistent high resolution N-body models. We compare our maps with the Tight Winding Approximation model analytical predictions. We see that for all barred models spiral arms rotate closely to a rigid body manner and the vertex deviation values correlate with the density peaks position bounded by overdense and underdense regions. In such cases, vertex deviation sign changes from negative to positive when crossing the spiral arms in the direction of disk rotation, in regions where the spiral arms are in between corotation (CR) and the Outer Lindblad Resonance (OLR). By contrast, when the arm sections are inside the CR and outside the OLR, l_v changes from negative to positive.We propose that measurements of the vertex deviations pattern can be used to trace the position of the main resonances of the spiral arms. We propose that this technique might exploit future data from Gaia and APOGEE surveys. For unbarred N-body simulations with spiral arms corotating with disk material at all radii, our analysis suggests that no clear correlation exists between l_v and density structures.

  4. 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.

  5. Investigating deviations from norms in court interpreting

    DEFF Research Database (Denmark)

    Dubslaff, Friedel; Martinsen, Bodil

    , in some cases, all - professional users involved (judges, lawyers, prosecutors). As far as the non-Danish speaking users are concerned, it has, with one notable exception, unfortunately not been possible to obtain data from this group via questionnaires. As this type of data, however, is important...... 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...... deviations and sanctions in every case. By way of example: Several judges, who had given their consent to recordings of authentic data in connection with the research project, reported that they had experienced problems with insufficient language proficiency on the part of untrained interpreters speaking...

  6. 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 ...

  7. Large deviations for tandem queueing systems

    Directory of Open Access Journals (Sweden)

    Roland L. Dobrushin

    1994-01-01

    Full Text Available The crude asymptotics of the large delay probability in a tandem queueing system is considered. The main result states that one of the two channels in the tandem system defines the crude asymptotics. The constant that determines the crude asymptotics is given. The results obtained are based on the large deviation principle for random processes with independent increments on an infinite interval recently established by the authors.

  8. On large deviations for ensembles of distributions

    Energy Technology Data Exchange (ETDEWEB)

    Khrychev, D A [Moscow State Institute of Radio-Engineering, Electronics and Automation (Technical University), Moscow (Russian Federation)

    2013-11-30

    The paper is concerned with the large deviations problem in the Freidlin-Wentzell formulation without the assumption of the uniqueness of the solution to the equation involving white noise. In other words, it is assumed that for each ε>0 the nonempty set P{sub ε} of weak solutions is not necessarily a singleton. Analogues of a number of concepts in the theory of large deviations are introduced for the set (P{sub ε}, ε>0), hereafter referred to as an ensemble of distributions. The ensembles of weak solutions of an n-dimensional stochastic Navier-Stokes system and stochastic wave equation with power-law nonlinearity are shown to be uniformly exponentially tight. An idempotent Wiener process in a Hilbert space and idempotent partial differential equations are defined. The accumulation points in the sense of large deviations of the ensembles in question are shown to be weak solutions of the corresponding idempotent equations. Bibliography: 14 titles.

  9. Contiguous Uniform Deviation for Multiple Linear Regression in Pattern Recognition

    Science.gov (United States)

    Andriana, A. S.; Prihatmanto, D.; Hidaya, E. M. I.; Supriana, I.; Machbub, C.

    2017-01-01

    Understanding images by recognizing its objects is still a challenging task. Face elements detection has been developed by researchers but not yet shows enough information (low resolution in information) needed for recognizing objects. Available face recognition methods still have error in classification and need a huge amount of examples which may still be incomplete. Another approach which is still rare in understanding images uses pattern structures or syntactic grammars describing shape detail features. Image pixel values are also processed as signal patterns which are approximated by mathematical function curve fitting. This paper attempts to add contiguous uniform deviation method to curve fitting algorithm to increase applicability in image recognition system related to object movement. The combination of multiple linear regression and contiguous uniform deviation method are applied to the function of image pixel values, and show results in higher resolution (more information) of visual object detail description in object movement.

  10. 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.

  11. 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.

  12. Guessing Revisited: A Large Deviations Approach

    CERN Document Server

    Hanawal, Manjesh Kumar

    2010-01-01

    The problem of guessing a random string is revisited. A close relation between guessing and compression is first established. Then it is shown that if the sequence of distributions of the information spectrum satisfies the large deviation property with a certain rate function, then the limiting guessing exponent exists and is a scalar multiple of the Legendre-Fenchel dual of the rate function. Other sufficient conditions related to certain continuity properties of the information spectrum are briefly discussed. This approach highlights the importance of the information spectrum in determining the limiting guessing exponent. All known prior results are then re-derived as example applications of our unifying approach.

  13. Meiosis and its deviations in polyploid plants.

    Science.gov (United States)

    Grandont, L; Jenczewski, E; Lloyd, A

    2013-01-01

    Meiosis is a fundamental process in all sexual organisms that ensures fertility and genome stability and creates genetic diversity. For each of these outcomes, the exclusive formation of crossovers between homologous chromosomes is needed. This is more difficult to achieve in polyploid species which have more than 2 sets of chromosomes able to recombine. In this review, we describe how meiosis and meiotic recombination 'deviate' in polyploid plants compared to diploids, and give an overview of current knowledge on how they are regulated. See also the sister article focusing on animals by Stenberg and Saura in this themed issue.

  14. 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.

  15. 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.

  16. 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.

  17. 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...

  18. 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.

  19. 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.

  20. Large Deviations for Random Matricial Moment Problems

    CERN Document Server

    Nagel, Jan; Gamboa, Fabrice; Rouault, Alain

    2010-01-01

    We consider the moment space $\\mathcal{M}_n^{K}$ corresponding to $p \\times p$ complex matrix measures defined on $K$ ($K=[0,1]$ or $K=\\D$). We endow this set with the uniform law. We are mainly interested in large deviations principles (LDP) when $n \\rightarrow \\infty$. First we fix an integer $k$ and study the vector of the first $k$ components of a random element of $\\mathcal{M}_n^{K}$. We obtain a LDP in the set of $k$-arrays of $p\\times p$ matrices. Then we lift a random element of $\\mathcal{M}_n^{K}$ into a random measure and prove a LDP at the level of random measures. We end with a LDP on Carth\\'eodory and Schur random functions. These last functions are well connected to the above random measure. In all these problems, we take advantage of the so-called canonical moments technique by introducing new (matricial) random variables that are independent and have explicit distributions.

  1. Meiosis and its deviations in polyploid animals.

    Science.gov (United States)

    Stenberg, P; Saura, A

    2013-01-01

    We review the different modes of meiosis and its deviations encountered in polyploid animals. Bisexual reproduction involving normal meiosis occurs in some allopolyploid frogs with variable degrees of polyploidy. Aberrant modes of bisexual reproduction include gynogenesis, where a sperm stimulates the egg to develop. The sperm may enter the egg but there is no fertilization and syngamy. In hybridogenesis, a genome is eliminated to produce haploid or diploid eggs or sperm. Ploidy can be elevated by fertilization with a haploid sperm in meiotic hybridogenesis, which elevates the ploidy of hybrid offspring such that they produce diploid gametes. Polyploids are then produced in the next generation. In kleptogenesis, females acquire full or partial genomes from their partners. In pre-equalizing hybrid meiosis, one genome is transmitted in the Mendelian fashion, while the other is transmitted clonally. Parthenogenetic animals have a very wide range of mechanisms for restoring or maintaining the mother's ploidy level, including gamete duplication, terminal fusion, central fusion, fusion of the first polar nucleus with the product of the first division, and premeiotic duplication followed by a normal meiosis. In apomictic parthenogenesis, meiosis is replaced by what is effectively mitotic cell division. The above modes have different evolutionary consequences, which are discussed. See also the sister article by Grandont et al. in this themed issue.

  2. 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.

  3. 21 CFR 330.11 - NDA deviations from applicable monograph.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false NDA deviations from applicable monograph. 330.11... EFFECTIVE AND NOT MISBRANDED Administrative Procedures § 330.11 NDA deviations from applicable monograph. A new drug application requesting approval of an OTC drug deviating in any respect from a monograph...

  4. 9 CFR 318.308 - Deviations in processing.

    Science.gov (United States)

    2010-01-01

    ... AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY...) Deviations in processing (or process deviations) must be handled according to: (1)(i) A HACCP plan for canned...) of this section. (c) (d) Procedures for handling process deviations where the HACCP plan...

  5. 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

  6. Deviations from Fick's law in Lorentz gases

    NARCIS (Netherlands)

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

    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

  7. Probabilistic Deviation Detection and Optimal Thresholds

    Science.gov (United States)

    2014-01-01

    JAGUAR , CDAP/ICAP, etc.) and (2) substituting the blackboard-based DEEP dependency with a common global world state structure. We would be happy to...Markov Model ICAP Interactive Collaboration Environment for COA Assessment Planning ICD Interface Control Document JAGUAR Joint Air Ground Unified

  8. 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.

  9. Mod-ϕ convergence normality zones and precise deviations

    CERN Document Server

    Féray, Valentin; Nikeghbali, Ashkan

    2016-01-01

    The canonical way to establish the central limit theorem for i.i.d. random variables is to use characteristic functions and Lévy’s continuity theorem. This monograph focuses on this characteristic function approach and presents a renormalization theory called mod-ϕ convergence. This type of convergence is a relatively new concept with many deep ramifications, and has not previously been published in a single accessible volume. The authors construct an extremely flexible framework using this concept in order to study limit theorems and large deviations for a number of probabilistic models related to classical probability, combinatorics, non-commutative random variables, as well as geometric and number-theoretical objects. Intended for researchers in probability theory, the text is carefully well-written and well-structured, containing a great amount of detail and interesting examples. .

  10. Classroom Note: Computational and Conceptual Understanding of the Connections among Standard Deviations, Z-Scores, and Normal Distributions

    Science.gov (United States)

    Reyes, Melissa Lopez

    2003-01-01

    A structure for learning the connections among standard deviations, z-scores, and normal distributions is presented. The components of this structure are classified into intuitive or previously learned conceptual knowledge, computational knowledge, and formalized conceptual knowledge. (Contains 1 figure.)

  11. Study on image processing of panoramic X-ray using deviation improvement software.

    Science.gov (United States)

    Kim, Tae-Gon; Lee, Yang-Sun; Kim, Young-Pyo; Park, Yong-Pil; Cheon, Min-Woo

    2014-01-01

    Utilization of panoramic X-ray device is getting wider. Panoramic X-ray has low resolution than general X-ray device and it occurs to distortion by deviation of image synthesis. Due to structural problems, it has been used restrictively to identify of tooth structure, not for whole head. Therefore, it designed and produced panoramic X-ray device which is possible to diagnostic coverage can be extended and had to be adjusted interval control between X-ray generator and image processing for whole of Maxillofacia's diagnosis. Produced panoramic X-ray device is composed basically of short image synthesis. In addition, it was confirmed the results by used the device which was applied deviation of the brightness of the image, filter to improve the location of the deviation and interpolation method. In this study, it was used 13 images including the front. It occurs to brightness deviation, position deviation, and geometric correction when synthesis of image, but it had been solved by deviation improvement software and a change of CCD camera's scan line which is used for image acquisition. Therefore, it confirmed expansion possibility of utilization range to commonly used panoramic X-ray device.

  12. Mechanism Modeling and Simulation Based on Dimensional Deviation

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    To analyze the effects on motion characteristics of mechanisms of dimensional variations, a study on random dimensional deviation generation techniques for 3D models on the basis of the present mechanical modeling software was carried out, which utilized the redeveloped interfaces provided by the modeling software to develop a random dimensional deviation generation system with certain probability distribution characteristics. This system has been used to perform modeling and simulation of the specific mechanical time delayed mechanism under multiple deviation varieties, simulation results indicate the dynamic characteristics of the mechanism are influenced significantly by the dimensional deviation in the tolerance distribution range, which should be emphasized in the design.

  13. 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.

  14. 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...

  15. 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...

  16. Large Deviations without Principle: Join the Shortest Queue

    NARCIS (Netherlands)

    Ridder, Ad; Shwartz, Adam

    2004-01-01

    We develop a methodology for studying "large deviations type" questions. Our approach does not require that the large deviations principle holds, and is thus applicable to a larg class of systems. We study a system of queues with exponential servers, which share an arrival stream. Arrivals are route

  17. Large deviations for stochastic flows and their applications

    Institute of Scientific and Technical Information of China (English)

    高付清; 任佳刚

    2001-01-01

    Large deviations for stochastic flow solutions to SDEs containing a small parameter are studied. The obtained results are applied to establish a Cp, r-large deviation principle for stochastic flows and for solutions to anticipating SDEs. The recent results of Millet-Nualart-Sans and Yoshida are improved and refined.

  18. 7 CFR 3015.3 - Conflicting policies and deviations.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Conflicting policies and deviations. 3015.3 Section... Conflicting policies and deviations. (a) Statutory provisions. Federal statutes that apply to some USDA grant..., when permissible under existing laws. In those instances where a program receives an exception to...

  19. Downhole control of deviation with steerable straight-hole turbodrills

    Energy Technology Data Exchange (ETDEWEB)

    Gaynor, T.M.

    1988-03-01

    Advances in directional drilling have until recently been confined to issues that are peripheral to the central problem of controlling assembly behavior downhole. Examples of these advances are measurement while drilling (MWD) and the increasing use of computer assistance in well planning. These were significant steps forward, but the major problem remained. Changes in formation deviation tendencies led to trips to change bottomhole assemblies (BHA's) to cope with the new conditions. There is almost no direct control of deviation behavior. The steerable straight-hole turbodrill (SST) addresses this problem directly, allowing alteration of the well course without the need to trip. The availability of such a system radically changes the way in which directional well planning may be approached. This paper describes the equipment used and the equipment's construction and operational requirements. It discusses the capabilities and current limitation of the systems. Field results are presented for some 300,000 ft (91 500 m) of deviated drilling carried out over 2 years in Alaska and the North Sea. A series of four highly deviated wells totaling 35,000 ft (10 700m) with only three deviation trips is included. The SST is the first deviation drilling system to achieve deviation control over long sections without tripping to change BHA's. Bits and downhole equipment are now more reliable and long-lived than ever, therefore, deviation trips are becoming a major target for well cost saving.

  20. Large Deviations and a Fluctuation Symmetry for Chaotic Homeomorphisms

    NARCIS (Netherlands)

    Maes, Christian; Verbitskiy, Evgeny

    2003-01-01

    We consider expansive homeomorphisms with the specification property. We give a new simple proof of a large deviation principle for Gibbs measures corresponding to a regular potential and we establish a general symmetry of the rate function for the large deviations of the antisymmetric part, under t

  1. Characterizing pathological deviations from normality using constrained manifold-learning.

    Science.gov (United States)

    Duchateau, Nicolas; De Craene, Mathieu; Piella, Gemma; Frangi, Alejandro F

    2011-01-01

    We propose a technique to represent a pathological pattern as a deviation from normality along a manifold structure. Each subject is represented by a map of local motion abnormalities, obtained from a statistical atlas of motion built from a healthy population. The algorithm learns a manifold from a set of patients with varying degrees of the same pathology. The approach extends recent manifold-learning techniques by constraining the manifold to pass by a physiologically meaningful origin representing a normal motion pattern. Individuals are compared to the manifold population through a distance that combines a mapping to the manifold and the path along the manifold to reach its origin. The method is applied in the context of cardiac resynchronization therapy (CRT), focusing on a specific motion pattern of intra-ventricular dyssynchrony called septal flash (SF). We estimate the manifold from 50 CRT candidates with SF and test it on 38 CRT candidates and 21 healthy volunteers. Experiments highlight the need of nonlinear techniques to learn the studied data, and the relevance of the computed distance for comparing individuals to a specific pathological pattern.

  2. 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.

  3. 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.

  4. 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.

  5. 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).

  6. 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.

  7. 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.

  8. 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.

  9. Large Deviations for Multi-valued Stochastic Differential Equations

    CERN Document Server

    Ren, Jiagang; Zhang, Xicheng

    2009-01-01

    We prove a large deviation principle of Freidlin-Wentzell's type for the multivalued stochastic differential equations with monotone drifts, which in particular contains a class of SDEs with reflection in a convex domain.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Comparison of estimators of standard deviation for hydrologic time series.

    Science.gov (United States)

    Tasker, Gary D.; Gilroy, E.J.

    1982-01-01

    Unbiasing factors as a function of serial correlation, rho, and sample size, n for the sample standard deviation of a lag one autoregressive model were generated by random number simulation. Monte Carlo experiments were used to compare the performance of several alternative methods for estimating the standard deviation sigma of a lag one autoregressive model in terms of bias, root mean square error, probability of underestimation, and expected opportunity design loss. -from Authors

  16. General Freidlin-Wentzell large deviations and positive diffusions

    OpenAIRE

    P. Baldi; Caramellino, L.

    2011-01-01

    Abstract We prove Freidlin-Wentzell Large Deviation estimates under rather minimal assumptions. This allows to derive Wentzell-Freidlin Large Deviation estimates for diffusions on the positive half line with coefficients that are neither bounded nor Lipschitz continuous. This applies to models of interest in Finance, i.e. the CIR and the CEV models, which are positive diffusion processes whose diffusion coefficient is only Holder continuous. correspondence: C...

  17. Large Deviations and a Fluctuation Symmetry for Chaotic Homeomorphisms

    Science.gov (United States)

    Maes, Christian; Verbitskiy, Evgeny

    We consider expansive homeomorphisms with the specification property. We give a new simple proof of a large deviation principle for Gibbs measures corresponding to a regular potential and we establish a general symmetry of the rate function for the large deviations of the antisymmetric part, under time-reversal, of the potential. This generalizes the Gallavotti-Cohen fluctuation theorem to a larger class of chaotic systems.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. Minimizing Hexapod Robot Foot Deviations Using Multilayer Perceptron

    Directory of Open Access Journals (Sweden)

    Vytautas Valaitis

    2015-12-01

    Full Text Available Rough-terrain traversability is one of the most valuable characteristics of walking robots. Even despite their slower speeds and more complex control algorithms, walking robots have far wider usability than wheeled or tracked robots. However, efficient movement over irregular surfaces can only be achieved by eliminating all possible difficulties, which in many cases are caused by a high number of degrees of freedom, feet slippage, frictions and inertias between different robot parts or even badly developed inverse kinematics (IK. In this paper we address the hexapod robot-foot deviation problem. We compare the foot-positioning accuracy of unconfigured inverse kinematics and Multilayer Perceptron-based (MLP methods via theory, computer modelling and experiments on a physical robot. Using MLP-based methods, we were able to significantly decrease deviations while reaching desired positions with the hexapod’s foot. Furthermore, this method is able to compensate for deviations of the robot arising from any possible reason.

  4. 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.

  5. 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.

  6. 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 ...

  7. 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...

  8. Heterodyne Angle Deviation Interferometry in Vibration and Bubble Measurements

    Directory of Open Access Journals (Sweden)

    Ming-Hung Chiu

    2016-07-01

    Full Text Available We proposed heterodyne angle deviation interferometry (HADI for angle deviation measurements. The phase shift of an angular sensor (which can be a metal film or a surface plasmon resonance (SPR prism is proportional to the deviation angle of the test beam. The method has been demonstrated in bubble and speaker’s vibration measurements in this paper. In the speaker’s vibration measurement, the voltage from the phase channel of a lock-in amplifier includes the vibration level and frequency. In bubble measurement, we can count the number of bubbles passing through the cross section of the laser beam and measure the bubble size from the phase pulse signal.

  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. Moderate Deviation Principles for Stochastic Differential Equations with Jumps

    Science.gov (United States)

    2014-01-15

    random measure and an in�nite dimensional Brownian motion) was derived. As in the Brownian motion case, the representation is motivated in part by...deviations of a smaller order than in large deviation theory . Consider for example an independent and identically distributed (iid) sequence fYigi1 of...8217") " E " 1 2 Z X[0;T ] ( ")21fj "jB"gdT + F G "("N " 1’") # " 1 2 3M 2(1); (3.6) where the last inequality follows from (3.5) on

  11. 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.

  12. UNUSUAL SEXUAL DEVIATIONS IN A YOUNG MAN: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    John Dinesh

    2014-08-01

    Full Text Available Sexual deviance in human refers to abnormal sexual expression. Though it is very difficult to exactly say what is normal or abnormal in sexual relationships, some sexual behaviors are clearly documented as abnormal in our society. Paraphilias or perversions are sexual stimuli or acts that are deviations from normal sexual behaviors, but are necessary for some individual’s to experience arousal and orgasm. Here we discuss abnormal sexual deviations in a young married male who presented with just feelings of guilt and without any psychosocial dysfunctions because of his uncommon sexual perversions.

  13. Influence of Deviation on Optical Transmission through Aperiodic Superlattices

    Institute of Scientific and Technical Information of China (English)

    YIN Hai-Long; YANG Xiang-Bo; LAN Sheng; HU Wei

    2007-01-01

    We propose a deviation model and study the influences of the relative error and sensitivity of a machine on the transmission coefficients (TCs) of Fibonacci superlattices. It is found that for a system with fewer layers, the influence of deviation can be ignored. When superlattices become more complicated, they may be fabricated by a machine with suitable relative error and possess the designed value of TC. However, when the number of system layers exceeds some critical value, superlattices should be manufactured only by precise machines. The influence of the sensitivity is also discussed.

  14. 48 CFR 2901.403 - Individual deviations from the FAR.

    Science.gov (United States)

    2010-10-01

    ... the FAR. 2901.403 Section 2901.403 Federal Acquisition Regulations System DEPARTMENT OF LABOR GENERAL DEPARTMENT OF LABOR ACQUISITION REGULATION SYSTEM Deviations From the FAR and DOLAR 2901.403 Individual... provisions (see FAR 1.403) or DOLAR provisions, which affect only one contracting action, unless FAR...

  15. Large Deviation for Supercritical Branching Processes with Immigration

    Institute of Scientific and Technical Information of China (English)

    Jing Ning LIU; Mei ZHANG

    2016-01-01

    In this paper, we study the large deviation for a supercritical branching process with immigration controlled by a sequence of non-negative integer-valued independently identical distributed random variables, improving the previous results for non immigration processes. We rely heavily on the detail description and limit property of the generating function of immigration processes.

  16. 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.

  17. Dynamic deviation Volterra predistorter designed for linearizing power amplifiers

    OpenAIRE

    2011-01-01

    Polynomial models of predistorter combined by the "black box" principle have been considered. A Volterra model using one-dimensional dynamic deviation was proposed. An adaptive predistorter was synthesized for linearizing the Wiener–Hammerstein model of power amplifiers. Estimates of the linearization accuracy and a comparative analysis of predistorter models were also presented.

  18. 9 CFR 381.308 - Deviations in processing.

    Science.gov (United States)

    2010-01-01

    ... AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY PRODUCTS INSPECTION AND VOLUNTARY...) must be handled according to: (1)(i) A HACCP plan for canned product that addresses hazards associated... (d) of this section. (c) (d) Procedures for handling process deviations where the HACCP plan...

  19. Freidlin-Wentzell's Large Deviations for Stochastic Evolution Equations

    OpenAIRE

    Ren, Jiagang; Zhang, Xicheng

    2008-01-01

    We prove a Freidlin-Wentzell large deviation principle for general stochastic evolution equations with small perturbation multiplicative noises. In particular, our general result can be used to deal with a large class of quasi linear stochastic partial differential equations, such as stochastic porous medium equations and stochastic reaction diffusion equations with polynomial growth zero order term and $p$-Laplacian second order term.

  20. Optical vibration and deviation measurement of rotating machine parts

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    It is of interest to get appropriate information about the dynamic behaviour of rotating machinery parts in service. This paper presents an approach of optical vibration and deviation measurement of such parts. Essential of this method is an image derotator combined with a high speed camera or a laser doppler vibrometer (LDV).

  1. An experimental study of credible deviations and ACDC

    NARCIS (Netherlands)

    de Groot Ruiz, A.; Offerman, T.; Onderstal, S.

    2011-01-01

    We test the Average Credible Deviation Criterion (ACDC), a stability measure and refinement for cheap talk equilibria introduced in De Groot Ruiz, Offerman & Onderstal (2011b). ACDC has been shown to be predictive under general conditions and to organize data well in previous experiments meant to te

  2. A novel method to bracket the corotation radius in galaxy discs: vertex deviation maps

    Science.gov (United States)

    Roca-Fàbrega, Santi; Antoja, Teresa; Figueras, Francesca; Valenzuela, Octavio; Romero-Gómez, Mercè; Pichardo, Bárbara

    2014-05-01

    We map the kinematics of stars in simulated galaxy discs with spiral arms using the velocity ellipsoid vertex deviation (l_v). We use test particle simulations, and for the first time, fully self-consistent high-resolution N-body models. We compare our maps with the tight winding approximation model analytical predictions. We see that for all barred models, spiral arms rotate closely to a rigid body manner and the vertex deviation values correlate with the density peak's position bounded by overdense and underdense regions. In such cases, vertex deviation sign changes from negative to positive when crossing the spiral arms in the direction of disc rotation, in regions where the spiral arms are in between corotation radius (CR) and the Outer Lindblad Resonance (OLR). By contrast, when the arm sections are inside the CR and outside the OLR, l_v changes from negative to positive. We propose that measurements of the vertex deviation's pattern can be used to trace the position of the main resonances of the spiral arms. We propose that this technique might exploit future data from Gaia and APO Galactic Evolution Experiment (APOGEE) surveys. For unbarred N-body simulations with spiral arms corotating with disc material at all radii, our analysis suggests that no clear correlation exists between l_v and density structures.

  3. Vertical deviation and A pattern of type Ⅲ Duane retraction syndrome

    Institute of Scientific and Technical Information of China (English)

    SHE Hai-cheng; MAN Feng-yuan; WANG Zhen-chang; WANG Jing-hui; JIAO Yong-hong; ZHAO Kan-xing

    2012-01-01

    Background Researches in ocular electromyography (EMG) and Magnetic resonance imaging (MRI) of patients with Duane retraction syndrome (DRS) suggest that there may be additional abnormalities such as paradoxical innervation between horizontal rectus muscles and vertical rectus muscles,hypoplasia of vertical rectus muscle and that oblique muscles may also contribute to the heterogeneity of the clinical manifestation of DRS.This paper reports the results of superior rectus recession for vertical deviation and A pattern in DRS Type Ⅲ and discusses the pathogenesis of the disease.Methods Superior and lateral rectus recession were performed in 5 cases of Huber type Ⅲ DRS to treat vertical deviation and A pattern strabismus.Before operation,MRI of the brain,brainstem,cavernous sinus,and orbits were performed.Results All subjects had unilateral limitation of both abduction and adduction,with palpebral fissure narrowing and globe retraction in adduction.Three cases had A pattern of strabismus,three cases had hypertropia.The abducens nerves (CN6) were either absent or hypoplasitic in the brainstem in all patients.Two eyes had larger oculomotor foramen.Two eyes had hypoplasia of the superior rectus and the inferior rectus.There was presumably a branch of the third cranial nerve (CN3) innervating the lateral rectus (LR) in one eye.While in another eye,two branches of CN3 sent into medial rectus were revealed.After surgery,vertical deviation in the primary position was reduced in all patients and A pattern was eliminated in 3 patients.One patient developed 10Δ consecutive esotropia postoperatively,Conclusion The results suggest that structural abnormalities of vertical muscle and abnormal orbital innervation may be related to vertical deviation and the presence of A pattern in DRS type Ⅲ.Recession of the superior rectus muscle seems to be a safe and effective treatment for vertical deviation and A pattern strabismus in DRS Type Ⅲ.

  4. 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.

  5. 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

  6. Magnetic Elements at Finite Temperature and Large Deviation Theory

    Science.gov (United States)

    Kohn, R. V.; Reznikoff, M. G.; vanden-Eijnden, E.

    2005-08-01

    We investigate thermally activated phenomena in micromagnetics using large deviation theory and concepts from stochastic resonance. We give a natural mathematical definition of finite-temperature astroids, finite-temperature hysteresis loops, etc. Generically, these objects emerge when the (generalized) Arrhenius timescale governing the thermally activated barrier crossing event of magnetic switching matches the timescale at which the magnetic element is pulsed or ramped by an external field; in the special and physically relevant case of multiple-pulse experiments, on the other hand, short-time switching can lead to non-Arrhenius behavior. We show how large deviation theory can be used to explain some properties of the astroids, like their shrinking and sharpening as the number of applied pulses is increased. We also investigate the influence of the dynamics, in particular the relative importance of the gyromagnetic and the damping terms. Finally, we discuss some issues and open questions regarding spatially nonuniform magnetization.

  7. 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...

  8. Moderate Deviation Principle for dynamical systems with small random perturbation

    CERN Document Server

    ma, Yutao; Wu, Liming

    2011-01-01

    Consider the stochastic differential equation in $\\rr^d$ dX^{\\e}_t&=b(X^{\\e}_t)dt+\\sqrt{\\e}\\sigma(X^\\e_t)dB_t X^{\\e}_0&=x_0,\\quad x_0\\in\\rr^d where $b:\\rr^d\\rightarrow\\rr^d$ is $C^1$ such that $ \\leq C(1+|x|^2)$, $\\sigma:\\rr^d\\rightarrow \\MM(d\\times n)$ is locally Lipschitzian with linear growth, and $B_t$ is a standard Brownian motion taking values in $\\rr^n$. Freidlin-Wentzell's theorem gives the large deviation principle for $X^\\e$ for small $\\e$. In this paper we establish its moderate deviation principle.

  9. 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...

  10. Exact Moderate and Large Deviations for Linear Processes

    CERN Document Server

    Peligrada, Magda; Zhong, Yunda; Wu, Wei Biao

    2011-01-01

    Large and moderate deviation probabilities play an important role in many applied areas, such as insurance and risk analysis. This paper studies the exact moderate and large deviation asymptotics in non-logarithmic form for linear processes with independent innovations. The linear processes we analyze are general and therefore they include the long memory case. We give an asymptotic representation for probability of the tail of the normalized sums and specify the zones in which it can be approximated either by a standard normal distribution or by the marginal distribution of the innovation process. The results are then applied to regression estimates, moving averages, fractionally integrated processes, linear processes with regularly varying exponents and functions of linear processes. We also consider the computation of value at risk and expected shortfall, fundamental quantities in risk theory and finance.

  11. OSMOSIS: A CAUSE OF APPARENT DEVIATIONS FROM DARCY'S LAW.

    Science.gov (United States)

    Olsen, Harold W.

    1985-01-01

    This review of the existing evidence shows that osmosis causes intercepts in flow rate versus hydraulic gradient relationships that are consistent with the observed deviations from Darcy's law at very low gradients. Moreover, it is suggested that a natural cause of osmosis in laboratory samples could be chemical reactions such as those involved in aging effects. This hypothesis is analogous to the previously proposed occurrence of electroosmosis in nature generated by geochemical weathering reactions. Refs.

  12. Probing the deviation from maximal mixing of atmospheric neutrinos

    CERN Document Server

    Choubey, S; Choubey, Sandhya; Roy, Probir

    2006-01-01

    Pioneering atmospheric muon neutrino experiments have demonstrated the near-maximal magnitude of the flavor mixing angle $\\theta_{23}$. But the precise value of the deviation $D \\equiv 1/2 - \\sin^2 \\theta_{23}$ from maximality (if nonzero) needs to be known, being of great interest -- especially to builders of neutrino mass and mixing models. We quantitatively investigate in a three generation framework the feasibility of determining $D$ in a statistically significant manner from studies of the atmospheric $\

  13. Moderate deviations for the eigenvalue counting function of Wigner matrices

    CERN Document Server

    Doering, Hanna

    2011-01-01

    We establish a moderate deviation principle (MDP) for the number of eigenvalues of a Wigner matrix in an interval. The proof relies on fine asymptotics of the variance of the eigenvalue counting function of GUE matrices due to Gustavsson. The extension to large families of Wigner matrices is based on the Tao and Vu Four Moment Theorem and applies localization results by Erd\\"os, Yau and Yin. Moreover we investigate families of covariance matrices as well.

  14. 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.

  15. Detecting deviations from pure EOF during CE separations.

    Science.gov (United States)

    O'Grady, John F; Noonan, Kathryn Y; McDonnell, Patrick; Mancuso, Aaron J; Frederick, Kimberley A

    2007-07-01

    CE separations are known for their high separation efficiencies. In systems with EOF, the high efficiencies benefit from the flat, plug profile that is characteristic of EOF. When a velocity gradient is present, such as in separations which have nonuniform buffer ionic strength, surface adsorption or differences in the height of the ends of the capillary, a parabolic flow component is introduced. This deviation from purely EOF yields increased peak dispersion and a subsequent decrease in separation performance. This work details a rapid method for detecting deviations from ideal plug flow during the course of a separation using the radially averaged flow profile of a photobleached fluorophore added to the BGE. By comparing the ratio of two different data analysis procedures, deviations from ideal plug flow can be detected. This method allows rapid measurement of flow character and does not interfere with the concurrent separation. We demonstrate easy detection of the onset of hydrodynamic flow induced by both gravity siphoning and an ionic strength buffer discontinuity. A brief analysis of the radially averaged peak shapes is also presented.

  16. Geometric deviation modeling by kinematic matrix based on Lagrangian coordinate

    Science.gov (United States)

    Liu, Weidong; Hu, Yueming; Liu, Yu; Dai, Wanyi

    2015-09-01

    Typical representation of dimension and geometric accuracy is limited to the self-representation of dimension and geometric deviation based on geometry variation thinking, yet the interactivity affection of geometric variation and gesture variation of multi-rigid body is not included. In this paper, a kinematic matrix model based on Lagrangian coordinate is introduced, with the purpose of unified model for geometric variation and gesture variation and their interactive and integrated analysis. Kinematic model with joint, local base and movable base is built. The ideal feature of functional geometry is treated as the base body; the fitting feature of functional geometry is treated as the adjacent movable body; the local base of the kinematic model is fixed onto the ideal geometry, and the movable base of the kinematic model is fixed onto the fitting geometry. Furthermore, the geometric deviation is treated as relative location or rotation variation between the movable base and the local base, and it's expressed by the Lagrangian coordinate. Moreover, kinematic matrix based on Lagrangian coordinate for different types of geometry tolerance zones is constructed, and total freedom for each kinematic model is discussed. Finally, the Lagrangian coordinate library, kinematic matrix library for geometric deviation modeling is illustrated, and an example of block and piston fits is introduced. Dimension and geometric tolerances of the shaft and hole fitting feature are constructed by kinematic matrix and Lagrangian coordinate, and the results indicate that the proposed kinematic matrix is capable and robust in dimension and geometric tolerances modeling.

  17. 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

  18. 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.

  19. Characterization of CK2 holoenzyme variants with regard to crystallization

    DEFF Research Database (Denmark)

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

    2001-01-01

    severely. One of the approaches chosen was the production of a chimeric holoenzyme made up from a human regulatory subunit and a catalytic subunit from Z. mays. The plant catalytic subunit, in contrast to the human counterpart is very stable and does not undergo this kind of degradation. The second...

  20. Large deviations for Markov chains in the positive quadrant

    Science.gov (United States)

    Borovkov, A. A.; Mogul'skii, A. A.

    2001-10-01

    The paper deals with so-called N-partially space-homogeneous time-homogeneous Markov chains X(y,n), n=0,1,2,\\dots, X(y,0)=y, in the positive quadrant \\mathbb R^{2+}=\\{x=(x_2,x_2):x_1\\geqslant0,\\ x_2\\geqslant0\\}. These Markov chains are characterized by the following property of the transition probabilities P(y,A)=\\mathsf P(X(y,1)\\in A): for some N\\geqslant 0 the measure P(y,dx) depends only on x_2, y_2, and x_1-y_1 in the domain x_1>N, y_1>N, and only on x_1, y_1, and x_2-y_2 in the domain x_2>N, y_2>N. For such chains the asymptotic behaviour of \\displaystyle \\ln\\mathsf P\\Bigl(\\frac 1sX(y,n)\\in B\\Bigr), \\qquad \\ln\\mathsf P\\bigl(X(y,n)\\in x+B\\bigr) is found for a fixed set B as s\\to\\infty, \\vert x\\vert\\to\\infty, and n\\to\\infty. Some other conditions on the growth of parameters are also considered, for example, \\vert x-y\\vert\\to\\infty, \\vert y\\vert\\to\\infty. A study is made of the structure of the most probable trajectories, which give the main contribution to this asymptotics, and a number of other results pertaining to the topic are established. Similar results are obtained for the narrower class of 0-partially homogeneous ergodic chains under less restrictive moment conditions on the transition probabilities P(y,dx). Moreover, exact asymptotic expressions for the probabilities \\mathsf P(X(0,n)\\in x+B) are found for 0-partially homogeneous ergodic chains under some additional conditions. The interest in partially homogeneous Markov chains in positive octants is due to the mathematical aspects (new and interesting problems arise in the framework of general large deviation theory) as well as applied issues, for such chains prove to be quite accurate mathematical models for numerous basic types of queueing and communication networks such as the widely known Jackson networks, polling systems, or communication networks associated with the ALOHA algorithm. There is a vast literature dealing with the analysis of these objects. The

  1. 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

  2. Quenched Large Deviations for Interacting Diffusions in Random Media

    Science.gov (United States)

    Luçon, Eric

    2017-03-01

    The aim of the paper is to establish a large deviation principle (LDP) for the empirical measure of mean-field interacting diffusions in a random environment. The point is to derive such a result once the environment has been frozen (quenched model). The main theorem states that a LDP holds for every sequence of environment satisfying appropriate convergence condition, with a rate function that does not depend on the disorder and is different from the rate function in the averaged model. Similar results concerning the empirical flow and local empirical measures are provided.

  3. 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.

  4. Elimination of Nonlinear Deviations in Thermal Lattice BGK Models

    CERN Document Server

    Chen, Y; Hongo, T; Chen, Yu; Ohashi, Hirotada; Akiyam, Mamoru

    1993-01-01

    Abstracet: We present a new thermal lattice BGK model in D-dimensional space for the numerical calculation of fluid dynamics. This model uses a higher order expansion of equilibrium distribution in Maxwellian type. In the mean time the lattice symmetry is upgraded to ensure the isotropy of 6th order tensor. These manipulations lead to macroscopic equations free from nonlinear deviations. We demonstrate the improvements by conducting classical Chapman-Enskog analysis and by numerical simulation of shear wave flow. The transport coefficients are measured numerically, too.

  5. 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...

  6. Large deviations estimates for the multiscale analysis of heart rate variability

    Science.gov (United States)

    Loiseau, Patrick; Médigue, Claire; Gonçalves, Paulo; Attia, Najmeddine; Seuret, Stéphane; Cottin, François; Chemla, Denis; Sorine, Michel; Barral, Julien

    2012-11-01

    In the realm of multiscale signal analysis, multifractal analysis provides a natural and rich framework to measure the roughness of a time series. As such, it has drawn special attention of both mathematicians and practitioners, and led them to characterize relevant physiological factors impacting the heart rate variability. Notwithstanding these considerable progresses, multifractal analysis almost exclusively developed around the concept of Legendre singularity spectrum, for which efficient and elaborate estimators exist, but which are structurally blind to subtle features like non-concavity or, to a certain extent, non scaling of the distributions. Large deviations theory allows bypassing these limitations but it is only very recently that performing estimators were proposed to reliably compute the corresponding large deviations singularity spectrum. In this article, we illustrate the relevance of this approach, on both theoretical objects and on human heart rate signals from the Physionet public database. As conjectured, we verify that large deviations principles reveal significant information that otherwise remains hidden with classical approaches, and which can be reminiscent of some physiological characteristics. In particular we quantify the presence/absence of scale invariance of RR signals.

  7. Simulation of extension, radial and ulnar deviation of the wrist with a rigid body spring model.

    Science.gov (United States)

    Fischli, S; Sellens, R W; Beek, M; Pichora, D R

    2009-06-19

    A novel computational model of the wrist that predicts carpal bone motion was developed in order to investigate the complex kinematics of the human wrist. This rigid body spring model (RBSM) of the wrist was built using surface models of the eight carpal bones, the bases of the five metacarpal bones, and the distal parts of the ulna and radius, all obtained from computed tomography (CT) scans of a cadaver upper limb. Elastic contact conditions between the rigid bodies modeled the influence of the cartilage layers, and ligamentous structures were constructed using nonlinear, tension-only spring elements. Motion of the wrist was simulated by applying forces to the tendons of the five main wrist muscles modeled. Three wrist motions were simulated: extension, ulnar deviation and radial deviation. The model was tested and tuned by comparing the simulated displacement and orientation of the carpal bones with previously obtained CT-scans of the same cadaver arm in deviated (45 degrees ulnar and 15 degrees radial), and extended (57 degrees ) wrist positions. Simulation results for the scaphoid, lunate, capitate, hamate and triquetrum are presented here and provide credible prediction of carpal bone movement. These are the first reported results of such a model. They indicate promise that this model will assist in future wrist kinematics investigations. However, further optimization and validation are required to define and guarantee the validity of results.

  8. 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.

  9. 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.

  10. 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...

  11. 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.

  12. Deviation Optimal Learning using Greedy Q-aggregation

    CERN Document Server

    Dai, Dong; Zhang, Tong

    2012-01-01

    Given a finite family of functions, the goal of model selection is to construct a procedure that mimics the function from this family that is the closest to an unknown regression function. More precisely, we consider a general regression model with fixed design and measure the distance between functions by the mean squared error at the design points. While procedures based on exponential weights are known to solve the problem of model selection in expectation, they are, surprisingly, sub-optimal in deviation. We propose a new formulation called Q-aggregation that addresses this limitation; namely, its solution leads to sharp oracle inequalities that are optimal in a minimax sense. Moreover, based on the new formulation, we design greedy Q-aggregation procedures that produce sparse aggregation models achieving the optimal rate. The convergence and performance of these greedy procedures are illustrated and compared with other standard methods on simulated examples.

  13. 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.

  14. Kalman Filtering with Intermittent Observations: Weak Convergence and Moderate Deviations

    CERN Document Server

    Kar, Soummya

    2009-01-01

    The paper considers the problem of Kalman filtering with intermittent observations, where the observation packet arrival process is modeled as a Bernoulli process. We start by extending the results of \\cite{Riccati-weakconv} to show that the sequence of random conditional error covariance matrices converges in distribution to a unique invariant distribution $\\mathbb{\\mu}^{\\bar{\\gamma}}$, as long as the packet arrival probability $\\bar{\\gamma}>0$. We completely characterize the sequence ${\\mathbb{\\mu}^{\\bar{\\gamma}}}$ of invariant distributions as $\\bar{\\gamma}\\uparrow 1$, by showing that the sequence ${\\mathbb{\\mu}^{\\bar{\\gamma}}}$ satisfies a moderate deviations principle (MDP) with a good rate function $I$, which is explicitly characterized. We then study the sequence of invariant distributions ${\\mathbb{\\mu}^{\\bar{\\gamma}}}$ as $\\bar{\\gamma}\\uparrow 1$. We show that, as $\\bar{\\gamma}\\uparrow 1$, ...

  15. A Historical Study of Contemporary Human Rights: Deviation or Extinction?

    Directory of Open Access Journals (Sweden)

    Tanel Kerikmäe

    2016-10-01

    Full Text Available Human rights is a core issue of continuing political, legal and economic relevance. The current article discusses the historical perceptions of the very essence of human rights standards and poses the question whether the Realpolitik of the changed world and Europe can justify the deviation from the “purist” approach to human rights. The EU Charter, as the most eminent and contemporary “bill of rights”, is chosen as an example of the divergence from “traditional values”. The article does not offer solutions but rather focuses on the expansive development in the doctrinal approach of interpreting human rights that has not been conceptually agreed upon by historians, philosophers and legal scholars.

  16. 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.

  17. A sella turcica bridge in subjects with severe craniofacial deviations.

    Science.gov (United States)

    Becktor, J P; Einersen, S; Kjaer, I

    2000-02-01

    In earlier studies, a sella turcica bridge was stated to occur in 1.75 to 6 per cent of the population. The occurrence of a sella turcica bridge has not previously been studied in a group of patients with craniofacial deviations treated by surgery. Profile radiographs from 177 individuals who had undergone combined orthodontic and surgical treatment at the Copenhagen School of Dentistry were studied. A sella turcica bridge was registered in those subjects where the radiograph revealed a continuous band of bony tissue from the anterior cranial fossa to the posterior cranial fossa across the sella turcica. Two types of sella turcica bridge were identified. A sella turcica bridge occurred in 18.6 per cent of the subjects.

  18. Spine deviations and orthodontic treatment of asymmetric malocclusions in children

    Directory of Open Access Journals (Sweden)

    Lippold Carsten

    2012-08-01

    Full Text Available Abstract Background The aim of this randomized clinical trial was to assess the effect of early orthodontic treatment for unilateral posterior cross bite in the late deciduous and early mixed dentition using orthopedic parameters. Methods Early orthodontic treatment was performed by initial maxillary expansion and subsequent activator therapy (Münster treatment concept. The patient sample was initially comprised of 80 patients with unilateral posterior cross bite (mean age 7.3 years, SD 2.1 years. After randomization, 77 children attended the initial examination appointment (therapy = 37, control = 40; 31 children in the therapy group and 35 children in the control group were monitored at the follow-up examination (T2. The mean interval between T1 and T2 was 1.1 years (SD 0.2 years. Rasterstereography was used for back shape analysis at T1 and T2. Using the profile, the kyphotic and lordotic angle, the surface rotation, the lateral deviation, pelvic tilt and pelvic torsion, statistical differences at T1 and T2 between the therapy and control groups were calculated (t-test. Our working hypothesis was, that early orthodontic treatment can induce negative therapeutic changes in body posture through thoracic and lumbar position changes in preadolescents with uniltaral cross bite. Results No clinically relevant differences between the control and the therapy groups at T1 and T2 were found for the parameters of kyphotic and lordotic angle, the surface rotation, lateral deviation, pelvic tilt, and pelvic torsion. Conclusions Our working hypothesis was tested to be not correct (within the limitations of this study. This randomized clinical trial demonstrates that in a juvenile population with unilateral posterior cross bite the selected early orthodontic treatment protocol does not affect negatively the postural parameters. Trial registration DRKS00003497 on DRKS

  19. Regulation on radial position deviation for vertical AMB systems

    Science.gov (United States)

    Tsai, Nan-Chyuan; Kuo, Chien-Hsien; Lee, Rong-Mao

    2007-10-01

    As a source of model uncertainty, gyroscopic effect, depending on rotor speed, is studied for the vertical active magnetic bearing (VAMB) systems which are increasingly used in various industries such as clean rooms, compressors and satellites. This research applies H∞ controller to regulate the rotor position deviations of the VAMB systems in four degrees of freedom. The performance of H∞ controller is examined by experimental simulations to inspect its closed-loop stiffness, rise time and capability to suppress the high frequency disturbances. Although the H∞ is inferior to the LQR in position deviation regulation, the required control current in the electromagnetic bearings is much less than that for LQR or PID and the performance robustness is well retained. In order to ensure the stability robustness of H∞ controller, two approaches, by Kharitonov polynomials and TITO (two inputs & two outputs) Nyquist Stability Criterion, are employed to synthesize the control feedback loop. A test rig is built to further verify the efficacy of the proposed H∞ controller experimentally. Two Eddy-current types of gap sensors, perpendicular to each other, are included to the realistic rotor-bearing system. A four-pole magnetic bearing is used as the actuator for generation of control force. The commercial I/O module unit with A/D and D/A converters, dSPACE DS1104, is integrated to the VAMB, gap sensors, power amplifiers and signal processing circuits. The H∞ is designed on the basis of rotor speed 10 K rpm but in fact it is significantly robust with respect to the rotor speed, varying from 6.5 to 13.5 K rpm.

  20. Deviation from Power Law Behavior in Landslide Phenomenon

    Science.gov (United States)

    Li, L.; Lan, H.; Wu, Y.

    2013-12-01

    Power law distribution of magnitude is widely observed in many natural hazards (e.g., earthquake, floods, tornadoes, and forest fires). Landslide is unique as the size distribution of landslide is characterized by a power law decrease with a rollover in the small size end. Yet, the emergence of the rollover, i.e., the deviation from power law behavior for small size landslides, remains a mystery. In this contribution, we grouped the forces applied on landslide bodies into two categories: 1) the forces proportional to the volume of failure mass (gravity and friction), and 2) the forces proportional to the area of failure surface (cohesion). Failure occurs when the forces proportional to volume exceed the forces proportional to surface area. As such, given a certain mechanical configuration, the failure volume to failure surface area ratio must exceed a corresponding threshold to guarantee a failure. Assuming all landslides share a uniform shape, which means the volume to surface area ratio of landslide regularly increase with the landslide volume, a cutoff of landslide volume distribution in the small size end can be defined. However, in realistic landslide phenomena, where heterogeneities of landslide shape and mechanical configuration are existent, a simple cutoff of landslide volume distribution does not exist. The stochasticity of landslide shape introduce a probability distribution of the volume to surface area ratio with regard to landslide volume, with which the probability that the volume to surface ratio exceed the threshold can be estimated regarding values of landslide volume. An experiment based on empirical data showed that this probability can induce the power law distribution of landslide volume roll down in the small size end. We therefore proposed that the constraints on the failure volume to failure surface area ratio together with the heterogeneity of landslide geometry and mechanical configuration attribute for the deviation from power law

  1. Amplification biases: possible differences among deviating gene expressions

    Directory of Open Access Journals (Sweden)

    Piumi Francois

    2008-01-01

    Full Text Available Abstract Background Gene expression profiling has become a tool of choice to study pathological or developmental questions but in most cases the material is scarce and requires sample amplification. Two main procedures have been used: in vitro transcription (IVT and polymerase chain reaction (PCR, the former known as linear and the latter as exponential. Previous reports identified enzymatic pitfalls in PCR and IVT protocols; however the possible differences between the sequences affected by these amplification defaults were only rarely explored. Results Screening a bovine cDNA array dedicated to embryonic stages with embryonic (n = 3 and somatic tissues (n = 2, we proceeded to moderate amplifications starting from 1 μg of total RNA (global PCR or IVT one round. Whatever the tissue, 16% of the probes were involved in deviating gene expressions due to amplification defaults. These distortions were likely due to the molecular features of the affected sequences (position within a gene, GC content, hairpin number but also to the relative abundance of these transcripts within the tissues. These deviating genes mainly encoded housekeeping genes from physiological or cellular processes (70% and constituted 2 subsets which did not overlap (molecular features, signal intensities, gene ID. However, the differential expressions identified between embryonic stages were both reliable (minor intersect with biased expressions and relevant (biologically validated. In addition, the relative expression levels of those genes were biologically similar between amplified and unamplified samples. Conclusion Conversely to the most recent reports which challenged the use of intense amplification procedures on minute amounts of RNA, we chose moderate PCR and IVT amplifications for our gene profiling study. Conclusively, it appeared that systematic biases arose even with moderate amplification procedures, independently of (i the sample used: brain, ovary or embryos, (ii

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

    Science.gov (United States)

    Budini, Adrián A

    2011-07-01

    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 nonstationary statistical properties of its fluctuations. Here we study this formalism through a statistical mechanics approach, that is, with an auxiliary counting process that maximizes an entropy function associated with the thermodynamic potential. We show that the realizations of this auxiliary process can be obtained after applying a conditional measurement scheme to the original ones, providing is this way an alternative measurement interpretation of the thermodynamic approach. General results are obtained for renewal counting processes, that is, those where the time intervals between consecutive events are independent and defined by a unique waiting time distribution. The underlying statistical mechanics is controlled by the same waiting time distribution, rescaled by an exponential decay measured by the free energy function. A scale invariance, shift closure, and intermittence phenomena are obtained and interpreted in this context. Similar conclusions apply for nonrenewal processes when the memory between successive events is induced by a stochastic waiting time distribution.

  3. 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 ...

  4. 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.

  5. Optimal aggregation of noisy observations: A large deviations approach

    Energy Technology Data Exchange (ETDEWEB)

    Murayama, Tatsuto; Davis, Peter, E-mail: murayama@cslab.kecl.ntt.co.j, E-mail: davis@cslab.kecl.ntt.co.j [NTT Communication Science Laboratories, NTT Corporation, 2-4, Hikaridai, Seika-cho, Keihanna, Kyoto 619-0237 (Japan)

    2010-06-01

    Sensing and data aggregation tasks in distributed systems should not be considered as separate issues. The quality of collective estimation involves a fundamental tradeoff between sensing quality, which can be increased by increasing the number of sensors, and aggregation quality under a given capacity of the network, which decreases if the number of sensors is too large. In this paper, we examine a system level strategy for optimal aggregation of data from an ensemble of independent sensors. In particular, we consider large scale aggregation from very many sensors, in which case the network capacity diverges to infinity. Then, by applying the large deviations techniques, we conclude the following significant result: larger scale aggregation always outperforms smaller scale aggregation at higher noise levels, while below a critical value of noise, there exist moderate scale aggregation levels at which optimal estimation is realized. At a critical value of noise, there is an abrupt change in the behavior of a parameter characterizing the aggregation strategy, similar to a phase transition in statistical physics.

  6. 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.

  7. 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.

  8. 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).

  9. 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.

  10. Remarks on the consistency of minimal deviations from General Relativity

    CERN Document Server

    Pons, Josep M

    2010-01-01

    We study the consequences of the modification of the phase space structure of General Relativity imposed by breaking the full diffeomorphism invariance but retaining the time foliation preserving diffeomorphisms. We examine the different sectors in phase space that satisfy the new structure of constraints. For some sectors we find an infinite tower of constraints. In spite of that, we also show that these sectors allow for solutions, among them some well known families of black hole and cosmologies which fulfill all the constraints. We raise some physical concerns on the consequences of an absolute Galilean time, on the thermodynamical pathologies of such models and on their unusual vacuum structure.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. On the applicability of the geodesic deviation equation in General Relativity

    CERN Document Server

    Philipp, Dennis; Laemmerzahl, Claus

    2016-01-01

    Within the theory of General Relativity we study the solution and range of applicability of the standard geodesic deviation equation in highly symmetric spacetimes. The deviation equation is used to model satellite orbit constellations around the earth. In particular, we reconsider the deviation equation in Newtonian gravity and then determine relativistic effects within the theory of General Relativity. The deviation of nearby orbits, as constructed from exact solutions of the underlying geodesic equation, is compared to the solution of the geodesic deviation equation to assess the accuracy of the latter. Furthermore, we comment on the so-called Shirokov effect in Schwarzschild spacetime.

  16. Vibrational investigation on FT-IR and FT-Raman spectra, IR intensity, Raman activity, peak resemblance, ideal estimation, standard deviation of computed frequencies analyses and electronic structure on 3-methyl-1,2-butadiene using HF and DFT (LSDA/B3LYP/B3PW91) calculations.

    Science.gov (United States)

    Ramalingam, S; Jayaprakash, A; Mohan, S; Karabacak, M

    2011-11-01

    FT-IR and FT-Raman (4000-100 cm(-1)) spectral measurements of 3-methyl-1,2-butadiene (3M12B) have been attempted in the present work. Ab-initio HF and DFT (LSDA/B3LYP/B3PW91) calculations have been performed giving energies, optimized structures, harmonic vibrational frequencies, IR intensities and Raman activities. Complete vibrational assignments on the observed spectra are made with vibrational frequencies obtained by HF and DFT (LSDA/B3LYP/B3PW91) at 6-31G(d,p) and 6-311G(d,p) basis sets. The results of the calculations have been used to simulate IR and Raman spectra for the molecule that showed good agreement with the observed spectra. The potential energy distribution (PED) corresponding to each of the observed frequencies are calculated which confirms the reliability and precision of the assignment and analysis of the vibrational fundamentals modes. The oscillation of vibrational frequencies of butadiene due to the couple of methyl group is also discussed. A study on the electronic properties such as HOMO and LUMO energies, were performed by time-dependent DFT (TD-DFT) approach. The calculated HOMO and LUMO energies show that charge transfer occurs within the molecule. The thermodynamic properties of the title compound at different temperatures reveal the correlations between standard heat capacities (C) standard entropies (S), and standard enthalpy changes (H).

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. Deviation from van't Hoff dependence in RP-LC induced by tautomeric interconversion observed for four compounds.

    Science.gov (United States)

    Galaon, Toma; David, Victor

    2011-06-01

    The most encountered situations in reversed-phase liquid chromatography for temperature dependence of retention are those obeying the linear equation known as the van't Hoff plot. When studying compounds that are involved in structural modifications, it is likely that the temperature dependences of their retention factors do not follow this rule. It is the aim of this paper to report some particular cases when compounds involved in tautomeric interconversion have a different retention behavior with temperature: a deviation from the linearity of ln k on 1/T, or, in certain temperature ranges, temperature increase leading to a retention increase. Examples of compounds exhibiting deviation from the van't Hoff temperature dependence are piroxicam, drotaverine, vincamine, and epivincamine. A simple thermodynamic model relying on tautomeric equilibria in mobile phase is proposed for these compounds, which gives a polynomial dependence between ln k and 1/T.

  4. The Manifestation of Stopping Sets and Absorbing Sets as Deviations on the Computation Trees of LDPC Codes

    Directory of Open Access Journals (Sweden)

    Eric Psota

    2010-01-01

    Full Text Available The error mechanisms of iterative message-passing decoders for low-density parity-check codes are studied. A tutorial review is given of the various graphical structures, including trapping sets, stopping sets, and absorbing sets that are frequently used to characterize the errors observed in simulations of iterative decoding of low-density parity-check codes. The connections between trapping sets and deviations on computation trees are explored in depth using the notion of problematic trapping sets in order to bridge the experimental and analytic approaches to these error mechanisms. A new iterative algorithm for finding low-weight problematic trapping sets is presented and shown to be capable of identifying many trapping sets that are frequently observed during iterative decoding of low-density parity-check codes on the additive white Gaussian noise channel. Finally, a new method is given for characterizing the weight of deviations that result from problematic trapping sets.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 21 CFR 600.14 - Reporting of biological product deviations by licensed manufacturers.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Reporting of biological product deviations by... HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS BIOLOGICAL PRODUCTS: GENERAL Establishment Standards § 600.14 Reporting of biological product deviations by licensed manufacturers. (a) Who must report...

  10. 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.

  11. Large Deviations Methods and the Join-the-Shortest-Queue Model

    NARCIS (Netherlands)

    Ridder, Ad; Shwartz, Adam

    2005-01-01

    We develop a methodology for studying ''large deviations type'' questions. Our approach does not require that the large deviations principle holds, and is thus applicable to a larg class of systems. We study a system of queues with exponential servers, which share an arrival stream. Arrivals are rou

  12. Dynamical Gibbs-non-Gibbs transitions : a study via coupling and large deviations

    NARCIS (Netherlands)

    Wang, Feijia

    2012-01-01

    In this thesis we use both the two-layer and the large-deviation approach to study the conservation and loss of the Gibbs property for both lattice and mean-field spin systems. Chapter 1 gives general backgrounds on Gibbs and non-Gibbs measures and outlines the the two-layer and the large-deviation

  13. Rate Function of Large Deviation for a Class of Nonhomogeneous Markov Chains on Supercritical Percolation Network

    Institute of Scientific and Technical Information of China (English)

    Zhong Hao XU; Dong HAN

    2011-01-01

    We model an epidemic with a class of nonhomogeneous Markov chains on the supercritical percolation network on Zd.The large deviations law for the Markov chain is given.Explicit expression of the rate function for large deviation is obtained.

  14. 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.

  15. 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.

  16. 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.

  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-deviation joint statistics of the finite-time Lyapunov spectrum in isotropic turbulence

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Perry L., E-mail: pjohns86@jhu.edu; Meneveau, Charles [Department of Mechanical Engineering and Center for Environmental and Applied Fluid Mechanics, The Johns Hopkins University, 3400 N. Charles Street, Baltimore, Maryland 21218 (United States)

    2015-08-15

    One of the hallmarks of turbulent flows is the chaotic behavior of fluid particle paths with exponentially growing separation among them while their distance does not exceed the viscous range. The maximal (positive) Lyapunov exponent represents the average strength of the exponential growth rate, while fluctuations in the rate of growth are characterized by the finite-time Lyapunov exponents (FTLEs). In the last decade or so, the notion of Lagrangian coherent structures (which are often computed using FTLEs) has gained attention as a tool for visualizing coherent trajectory patterns in a flow and distinguishing regions of the flow with different mixing properties. A quantitative statistical characterization of FTLEs can be accomplished using the statistical theory of large deviations, based on the so-called Cramér function. To obtain the Cramér function from data, we use both the method based on measuring moments and measuring histograms and introduce a finite-size correction to the histogram-based method. We generalize the existing univariate formalism to the joint distributions of the two FTLEs needed to fully specify the Lyapunov spectrum in 3D flows. The joint Cramér function of turbulence is measured from two direct numerical simulation datasets of isotropic turbulence. Results are compared with joint statistics of FTLEs computed using only the symmetric part of the velocity gradient tensor, as well as with joint statistics of instantaneous strain-rate eigenvalues. When using only the strain contribution of the velocity gradient, the maximal FTLE nearly doubles in magnitude, highlighting the role of rotation in de-correlating the fluid deformations along particle paths. We also extend the large-deviation theory to study the statistics of the ratio of FTLEs. The most likely ratio of the FTLEs λ{sub 1} : λ{sub 2} : λ{sub 3} is shown to be about 4:1:−5, compared to about 8:3:−11 when using only the strain-rate tensor for calculating fluid volume

  19. 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.

  20. On the relation between uncertainties of weighted frequency averages and the various types of Allan deviations

    CERN Document Server

    Benkler, Erik; Sterr, Uwe

    2015-01-01

    The power spectral density in Fourier frequency domain, and the different variants of the Allan deviation (ADEV) in dependence on the averaging time are well established tools to analyse the fluctuation properties and frequency instability of an oscillatory signal. It is often supposed that the statistical uncertainty of a measured average frequency is given by the ADEV at a well considered averaging time. However, this approach requires further mathematical justification and refinement, which has already been done regarding the original ADEV for certain noise types. Here we provide the necessary background to use the modified Allan deviation (modADEV) and other two-sample deviations to determine the uncertainty of weighted frequency averages. The type of two-sample deviation used to determine the uncertainty depends on the method used for determination of the average. We find that the modADEV, which is connected with $\\Lambda$-weighted averaging, and the two sample deviation associated to a linear phase regr...

  1. 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...

  2. Assessment of gait deviation on the Babinski-Weill test in healthy Brazilians

    Directory of Open Access Journals (Sweden)

    Camila Souza Miranda

    2013-09-01

    Full Text Available Objective The aim of this study was to validate a simple and reproducible method for assessing gait deviation on the Babinski-Weill test in a representative sample of healthy Brazilians. Methods Gait deviations were measured in 75 individuals (median=30 years, 41 women for forward, backwards, and Babinski-Weill steps. The test entailed blindfolded individuals walking 10 paces at a frequency of 1 Hz with deviations subsequently measured by a protractor. Results Mean gait deviation forward was 0.53° with standard deviation (SD=4.22 and backwards was 2.14° with SD=4.29. No significant difference in deviation was detected between genders (t test p=0.40 forward and p=0.77 backwards or for age (ANOVA, p=0.33 forward and p=0.63 backwards. On the Babinski-Weill test, mean gait deviation was 5.26°; SD=16.32 in women and -3.11°; SD=12.41 in men, with no significant difference between genders (t test, p=0.056. Discussion Defining normative gait patterns helps distinguish pathological states.

  3. 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.

  4. 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.

  5. Large deviation functions in a system of diffusing particles with creation and annihilation.

    Science.gov (United States)

    Popkov, V; Schütz, G M

    2011-08-01

    Large deviation functions for an exactly solvable lattice gas model of diffusing particles on a ring, subject to pair annihilation and creation, are obtained analytically using exact free-fermion techniques. Our findings for the large deviation function for the current are compared to recent results of Appert-Rolland et al. [Phys. Rev. E 78, 021122 (2008)] for diffusive systems with conserved particle number. Unlike conservative dynamics, our nonconservative model has no universal finite-size corrections for the cumulants. However, the leading Gaussian part has the same variance as in the conservative case. We also elucidate some properties of the large deviation functions associated with particle creation and annihilation.

  6. 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.

  7. Precise Large Deviations for Sums of Negatively Associated Random Variables with Common Dominatedly Varying Tails

    Institute of Scientific and Technical Information of China (English)

    Yue Bao WANG; Kai Yong WANG; Dong Ya CHENG

    2006-01-01

    In this paper, we obtain results on precise large deviations for non-random and random sums of negatively associated nonnegative random variables with common dominatedly varying tail distribution function. We discover that, under certain conditions, three precise large-deviation probabilities with different centering numbers are equivalent to each other. Furthermore, we investigate precise large deviations for sums of negatively associated nonnegative random variables with certain negatively dependent occurrences. The obtained results extend and improve the corresponding results of Ng, Tang, Yan and Yang (J. Appl. Prob., 41, 93-107, 2004).

  8. 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.

  9. 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...

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. Effect of stress on energy flux deviation of ultrasonic waves in GR/EP composites

    Science.gov (United States)

    Prosser, William H.; Kriz, R. D.; Fitting, Dale W.

    1990-01-01

    Ultrasonic waves suffer energy flux deviation in graphite/epoxy because of the large anisotropy. The angle of deviation is a function of the elastic coefficients. For nonlinear solids, these coefficients and thus the angle of deviation is a function of stress. Acoustoelastic theory was used to model the effect of stress on flux deviation for unidirectional T300/5208 using previously measured elastic coefficients. Computations were made for uniaxial stress along the x3 axis (fiber axis) and the x1 for waves propagating in the x1x3 plane. These results predict a shift as large as three degrees for the quasi-transverse wave. The shift in energy flux offers a new nondestructive technique of evaluating stress in composites.

  15. 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...

  16. PERIODIC SOLUTIONS TO p-LAPLACIAN GENERALIZED LINARD EQUATION WITH DEVIATING ARGUMENTS

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Using the theory of coincidence degree,we study a kind of periodic solutions to p-Laplacian generalized Liénard equation with deviating arguments. A result on the existence of periodic solutions is obtained.

  17. General Large Deviations and Functional Iterated Logarithm Law for Multivalued Stochastic Differential Equations

    OpenAIRE

    Ren, Jiagang; Wu, Jing; Zhang, Hua

    2015-01-01

    In this paper, we prove a large deviation principle of Freidlin-Wentzell's type for the multivalued stochastic differential equations. As an application, we derive a functional iterated logarithm law for the solutions of multivalued stochastic differential equations.

  18. THE INFLUENCE OF TECHNICAL DEVIATIONS OVER EFFORTS FROM A 4R SPHERICAL QUADRILATERAL MECHANISM

    Directory of Open Access Journals (Sweden)

    Nicolae PANDREA

    2013-05-01

    Full Text Available In the present paper is mechanically defined the notion of technical deviation (geometrical through a matrix of pluckerian coordinates and those influence over the efforts from the 4R spherical quadrilateral mechanism elements.

  19. Hemingway’s Internal Deviation from His Primary Norm in The Old Man and the Sea

    Directory of Open Access Journals (Sweden)

    Trisnowati Tanto

    2009-01-01

    Full Text Available Ernest Hemingway is well known for the use of short and simple sentences when writing his novels since he aims at ‘[getting] the most out of the least’. This sentence-simplicity style is Hemingway’s primary norm. The Old Man and the Sea is the perfect example of this. However, in this novel, he sometimes uses long, complex sentences to describe certain points, and this sentence-complexity style can be said to be Hemingway’s secondary norm. In this case, there is a deviation within Hemingway’s own style of writing – an internal deviation. The deviation is obviously done on purpose as a kind of distraction so as to make the readers aware of the special and important ‘message’ that Hemingway wants to convey. In this novel, the deviation is used to build the elements of suspense and foreshadowing in much detail.

  20. Ensemble standar deviation of wind speed and direction of the FDDA input to WRF

    Data.gov (United States)

    U.S. Environmental Protection Agency — NetCDF file of the SREF standard deviation of wind speed and direction that was used to inject variability in the FDDA input. variable U_NDG_OLD contains standard...

  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. Monotone Regression and Correction for Order Relation Deviations in Indicator Kriging

    Institute of Scientific and Technical Information of China (English)

    Han Yan; Yang Yiheng

    2008-01-01

    The indicator kriging (IK) is one of the most efficient nonparametric methods in geo-statistics. The order relation problem in the conditional cumulative distribution values obtained by IK is the most severe drawback of it. The correction of order relation deviations is an essential and important part of IK approach. A monotone regression was proposed as a new correction method which could minimize the deviation from original quintiles value, although, ensuring all order relations.

  3. Gear transmission dynamic: Effects of tooth profile deviations and support flexibility

    OpenAIRE

    Fernández del Rincón, Alfonso; Iglesias Santamaría, Miguel; Juan de Luna, Ana Magdalena de; García Fernández, Pablo; Sancibrián Herrera, Ramón; Viadero Rueda, Fernando

    2014-01-01

    In this work a non-linear dynamic model of spur gear transmissions previously developed by the authors is extended to include both desired (relief) and undesired (manufacture errors) deviations in the tooth profile. The model uses a hybrid method for the calculation of meshing forces, which combines FE analysis and analytical formulation, so that it enables a very straightforward implementation of the tooth profile deviations. The model approach handles well non-linearity due to the variable ...

  4. 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.

  5. Analyzing Vegetation Change in an Elephant-Impacted Landscape Using the Moving Standard Deviation Index

    OpenAIRE

    Timothy J. Fullman; Erin L. Bunting

    2014-01-01

    Northern Botswana is influenced by various socio-ecological drivers of landscape change. The African elephant ( Loxodonta africana ) is one of the leading sources of landscape shifts in this region. Developing the ability to assess elephant impacts on savanna vegetation is important to promote effective management strategies. The Moving Standard Deviation Index (MSDI) applies a standard deviation calculation to remote sensing imagery to assess degradation of vegetation. Used previously for as...

  6. 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.

  7. 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.

  8. 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.

  9. Non-classical large deviations for a noisy system with non-isolated attractors

    Science.gov (United States)

    Bouchet, Freddy; Touchette, Hugo

    2012-05-01

    We study the large deviations of a simple noise-perturbed dynamical system having continuous sets of steady states, which mimic those found in some partial differential equations related, for example, to turbulence problems. The system is a two-dimensional nonlinear Langevin equation involving a dissipative, non-potential force, which has the essential effect of creating a line of stable fixed points (attracting line) touching a line of unstable fixed points (repelling line). Using different analytical and numerical techniques, we show that the stationary distribution of this system satisfies, in the low-noise limit, a large deviation principle containing two competing terms: (i) a 'classical' but sub-dominant large deviation term, which can be derived from the Freidlin-Wentzell theory of large deviations by studying the fluctuation paths or instantons of the system near the attracting line, and (ii) a dominant large deviation term, which does not follow from the Freidlin-Wentzell theory, as it is related to fluctuation paths of zero action, referred to as sub-instantons, emanating from the repelling line. We discuss the nature of these sub-instantons, and show how they arise from the connection between the attracting and repelling lines. We also discuss in a more general way how we expect these to arise in more general stochastic systems having connected sets of stable and unstable fixed points, and how they should determine the large deviation properties of these systems.

  10. Deviations between Contract Sums and Final Accounts: The Case of Capital Projects in Ghana

    Directory of Open Access Journals (Sweden)

    Kofi Offei-Nyako

    2016-01-01

    Full Text Available Cost estimation is particularly difficult, often leading to considerable deviations. For capital projects, especially transport infrastructure projects, deviations hover around an average of 28% of the estimated cost. There are several factors that cause these deviations between the final accounts and the contract sum. How these factors combine to cause deviations between the contract sum and the final account in recent times has been of great concern to construction managers and researchers alike. This study sought to identify the significant factors that result in deviations between contract sums and the final accounts of capital projects. Using a sample size of 45, comprising contractors, consultants, and clients, the factors identified using Relative Important Indices were “price fluctuations,” “late material delivery,” “changes in the scope of work,” “fluctuations in the market demand,” and “changes in design.” Using Kendall’s coefficient of concordance, a coefficient p value of 0.068 was obtained. As such, the null hypothesis was rejected as there was a level of agreement among the respondents. Again, based on a significance test run, 26 out of the 40 identified factors used for the analysis were seen to be significant in influencing the deviations between contract sums and final accounts figures.

  11. 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.

  12. Using the Newcomb-Benford Law as a Deviation Identification Method in Continuous Auditing Environments: A Proposal for Detecting Deviations over Time

    Directory of Open Access Journals (Sweden)

    Wilton Bernardino da Silva

    Full Text Available ABSTRACT This paper used the Newcomb-Benford Law (NB Law to analyze 210,899 contracts issued by sixty management units in two states in the Brazilian Northeast in 2010. In this article we seek to address the following question: What proposal emerges from the need to identify financial deviations over time in terms of NB Law compliance in continuous auditing scenarios? To this end, the goal of the paper is to analyze this compliance with the aim of identifying deviations over time. The analysis focuses on first significant digit distribution. Graphical analysis of observed frequencies and time series of relative discrepancies reveals the formation of typical patterns of divergences from Public Tenders Law (Federal Law n. 8.666/93. From the results obtained, we conclude that time series analysis of NB Law compliance can improve the accuracy of sampling procedures in continuous auditing.

  13. 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

  14. 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

  15. 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.

  16. Avoiding moving obstacles by deviation from a mobile robot`s nominal path

    Energy Technology Data Exchange (ETDEWEB)

    Tsoularis, A.; Kambhampati, C. [Univ. of Reading, Whiteknights (United Kingdom). Dept. of Cybernetics

    1999-05-01

    This paper deals with the problem of obstacle avoidance by deviation from the nominal path. Deviation is the only option available to the robot when the acceleration or deceleration plan on the nominal path fails to produce a viable avoidance strategy. The obstacle avoidance on the nominal path was dealt with in the authors` previous development, where the robot`s motion was only subject to an upper bound on its speed. When the robot has to deviate, its motion is subject to a maximum steering constraint and a maximum deviation constraint in addition to the maximum speed constraint. The problem is solved geometrically by identifying final states for the robot that are reachable, satisfy all the constraints, and guarantee collision avoidance. The final state-reachability conditions that the authors obtain in the process ensure that no unnecessary deviation plan is initiated. These conditions, along with the simplicity of the geometric arguments they employ, make the scheme an attractive option for on-line implementation. The only significant complexity arises when minimizing the performance index. They have suggested dynamic programming as an optimization took, but any other nonlinear optimization technique can be adopted.

  17. Measurement of z-axis deviation angle of electro-optic crystal by conoscopic interference

    Science.gov (United States)

    Li, Dong; Liu, Yong; Liu, Xu; Jiang, Hongzhen; Zheng, Fanglan

    2016-09-01

    Properties of plasma electrode pockels cell is directly affected by the Z-axis deviation angle of the electro-optic crystal. Therefore, high precision measurement of the Z-axis deviation angle is indispensable. By using conoscopic interference technique, a measurement system for Z-axis deviation angle of electro-optic crystal is introduced. The principle of conoscopic interference method is described in detail, and a series of techniques are implied in this measurement system to improve the accuracy. High-precision positioning method of the crystal based on Michelson interference is proposed to determine the normal consistency of crystal, which can ensure the high positioning repeatability of crystal in the measurement process. The positioning comparison experiment of the crystal shows that the standard deviation of our method is less than 1pixel, which is much better than the traditional method (nearly 4pixels). Moreover, melatope extraction algorithm of optical axis based on image matching technique is proposed to ensure the melatope can be extracted in high precision. Calibration method of the normal of transmission surface of crystal is also proposed. The experiment results show that the PV and rms of Z-axis deviation angle is less than 0.05mrad and 0.02mrad, respectively. The repeatability accuracy is less than 0.01mrad.

  18. Intermittent changing axis deviation with intermittent left anterior hemiblock during atrial flutter with subclinical hyperthyroidism.

    Science.gov (United States)

    Patanè, Salvatore; Marte, Filippo

    2009-06-26

    Subclinical hyperthyroidism is an increasingly recognized entity that is defined as a normal serum free thyroxine and free triiodothyronine levels with a thyroid-stimulating hormone level suppressed below the normal range and usually undetectable. It has been reported that subclinical hyperthyroidism is not associated with CHD or mortality from cardiovascular causes but it is usually associated with a higher heart rate and a higher risk of supraventricular arrhythmias including atrial fibrillation and atrial flutter. Intermittent changing axis deviation during atrial fibrillation has also rarely been reported. We present a case of intermittent changing axis deviation with intermittent left anterior hemiblock in a 59-year-old Italian man with atrial flutter and subclinical hyperthyroidism. To our knowledge, this is the first report of intermittent changing axis deviation with intermittent left anterior hemiblock in a patient with atrial flutter.

  19. Standard Practice for Optical Distortion and Deviation of Transparent Parts Using the Double-Exposure Method

    CERN Document Server

    American Society for Testing and Materials. Philadelphia

    2009-01-01

    1.1 This photographic practice determines the optical distortion and deviation of a line of sight through a simple transparent part, such as a commercial aircraft windshield or a cabin window. This practice applies to essentially flat or nearly flat parts and may not be suitable for highly curved materials. 1.2 Test Method F 801 addresses optical deviation (angluar deviation) and Test Method F 2156 addresses optical distortion using grid line slope. These test methods should be used instead of Practice F 733 whenever practical. 1.3 This standard does not purport to address the safety concerns associated with its use. It is the responsibility of the user of this standard to establish appropriate safety and health practices and determine the applicability of regulatory limitations prior to use.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 9 CFR 317.7 - Products for foreign commerce; printing labels in foreign language permissible; other deviations.

    Science.gov (United States)

    2010-01-01

    ...; printing labels in foreign language permissible; other deviations. 317.7 Section 317.7 Animals and Animal... permissible; other deviations. Labels to be affixed to packages of products for foreign commerce may be... the usage of the country to which exported and other deviations from the form of labeling...

  5. Kardar-Parisi-Zhang Equation and Large Deviations for Random Walks in Weak Random Environments

    Science.gov (United States)

    Corwin, Ivan; Gu, Yu

    2017-01-01

    We consider the transition probabilities for random walks in 1+1 dimensional space-time random environments (RWRE). For critically tuned weak disorder we prove a sharp large deviation result: after appropriate rescaling, the transition probabilities for the RWRE evaluated in the large deviation regime, converge to the solution to the stochastic heat equation (SHE) with multiplicative noise (the logarithm of which is the KPZ equation). We apply this to the exactly solvable Beta RWRE and additionally present a formal derivation of the convergence of certain moment formulas for that model to those for the SHE.

  6. Large deviations for a stochastic Landau-Lifshitz equation, extended version

    CERN Document Server

    Brzeźniak, Z; Jegaraj, T

    2012-01-01

    We study a stochastic Landau-Lifshitz equation on a bounded interval and with finite dimensional noise; this could be a simple model of magnetization in a needle-shaped domain in magnetic media. After showing that a unique, regular solution exists, we obtain a large deviation principle for small noise asymptotics of solutions using the weak convergence method. We then apply the large deviation principle to show that small noise in the field can cause magnetization reversal and also to show the importance of the shape anisotropy parameter for reducing the disturbance of the magnetization caused by small noise in the field.

  7. 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.

  8. 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.

  9. Large deviations and occupation times for spin particle systems with long range interactions

    Institute of Scientific and Technical Information of China (English)

    陈金文

    2000-01-01

    The large deviation principle for spin particle systems with long range interactions has been studied. It is shown that most of the results in Chen J.W. and Dai Pra P. ’s previous papers can be extended to the present situation. A particularly interesting result is the variational principle which characterizes the stationary Markov measures of such systems as the zeros of the governing LD rate functions. Uniqueness of such measure is studied from this as well as other point of view. We then apply the results to the occupation times of the systems. New large deviation and convergence results are obtained.

  10. Large deviations and occupation times for spin particle systems with long range interactions

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The large deviation principle for spin particle systems with long range interactions has been studied. It is shown that most of the results in Chen J.W. and Dai Pra P.'s previous papers can be extended to the present situation. A particularly interesting result is the variational principle which characterizes the stationary Markov measures of such systems as the zeros of the governing LD rate functions. Uniqueness of such measure is studied from this as well as other point of view. We then apply the results to the occupation times of the systems. New large deviation and convergence results are obtained.

  11. On Translation Errors and Culture Deviations in China English from An-gle of Language Inclusivity

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hai-bo

    2014-01-01

    Any language must have the inclusivity of its own,otherwise it can hardly get developed. The English language has got the most powerful inclusivity, which makes itself the lingua franca of the world. However, as one of language varieties, China English develops with a lot of translation errors and culture deviations, which makes itself doubtful. As a result, a view comes into being that none errors can be permitted in China English, otherwise China English couldn’t exist. But finally, it turns out that translation errors and culture deviations in China English are acceptable due to the language inclusivity.

  12. The effect of deconfinement phase transition on rotochemical deviations in stars containing mixed phase matter

    CERN Document Server

    Wei, Wei

    2011-01-01

    As a neutron star spins down, its core density increase, changing the relative equilibrium concentration, and causing deconfinement phase transition as well. hadron matter are converted into quark matter in the interior, which enhances the deviation of chemical equilibrium state. We study such deviations and its chemical energy release.Applying to the simulation of cooling neutron stars, we find the surface effective temperature of neutron stars is promoted obviously. This implies that the deconfinement phase transition is able to raise the chemical heating efficiency.

  13. Molecular dynamics investigation on the deviation from stoichiometry in martensitic transformation

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, Tetsuro, E-mail: tetsuro.suzuki@nifty.com [National Institute for Materials Science (Japan); Shimno, Masato; Otsuka, Kazuhiro; Ren, Xiaobing [National Institute for Materials Science (Japan); Saxena, Avadh [National Institute for Materials Science (Japan); Los Alamos National Laboratory (United States)

    2013-11-15

    Highlights: ► We have studied the martensitic transformation in Ti–Ni alloy near 50:50 stoichiometry. ► The atomistic process of the martensitic transformation is simulated by use of the molecular dynamics based on the 8-4 Lennard–Jones potential. ► The molecular dynamics provide atomistic picture when the formation of the martensite is suppressed for the deviation from 50:50 stoichiometry. -- Abstract: How the martensitic transformation in Ti–Ni alloy depends on the deviation from the stoichiometry is investigated by use of the molecular dynamics based on a simple model potential.

  14. 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…

  15. 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.

  16. 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.

  17. 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

  18. Process-level quenched large deviations for random walk in random environment

    CERN Document Server

    Rassoul-Agha, Firas

    2009-01-01

    We consider a bounded step size random walk in an ergodic random environment with some ellipticity, on an integer lattice of arbitrary dimension. We prove a level 3 large deviation principle, under almost every environment, with rate function related to a relative entropy.

  19. 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...

  20. 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.

  1. VOICE RELATED QUALITY OF LIFE IN INDIVIDUALS WITH DEVIATED NASAL SEPTUM

    Directory of Open Access Journals (Sweden)

    Prakash

    2014-08-01

    Full Text Available Deviated nasal septum (DNS is a common disorder which alters the nasal cavity anatomically and physiologically and results in nasal obstruction for breathing, nasal blockage, allergies, allergic rhinitis, and dryness of throat, thus influencing the person’s quality of life. Literature indicates that acoustic and resonatory characteristics of voice are negatively influenced in individuals with DNS due to the compensation by laryngeal system to the blockage in the resonatory chamber. In this context, the present study was aimed to investigate the voice related quality of life in individuals with deviated nasal septum. Forty individuals with severely deviated nasal septum confirmed by an Otorhinolaryngologist through anterior rhinoscopy, computerized tomography and twenty five age and gender matched controls filled the Kannada version of Voice Handicap Index-10 (VHI questionnaire. Results indicated significant impact of deviated nasal septum on voice related quality of life in 55% of the participants with DNS. Results of Mann-Whitney U test indicated significant effect of DNS on VHI scores in individuals with DNS compared to controls (p<0.001. With respect to response to the individual questions under VHI, although response was negative to most of the questions, two questions that received highest score belong to physical domain of VHI and are related to breathing difficulty and variations in voice throughout the day, indicating that they have more difficulty due to nasal blockage to airflow per se than their day-to-day functionality or communication.

  2. 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

  3. Deviations from Ideal Sublimation Vapor Pressure Behavior in Mixtures of Polycyclic Aromatic Compounds with Interacting Heteroatoms.

    Science.gov (United States)

    Goldfarb, Jillian L; Suuberg, Eric M

    2010-08-01

    Despite the relatively small atomic fraction of a given heteroatom in a binary mixture of polycyclic aromatic compounds (PAC), the inclusion of heteroatomic substituted compounds can significantly impact mixture vapor pressure behavior over a wide range of temperatures. The vapor pressures of several binary PAC mixtures containing various heteroatoms show varying behavior, from practically ideal behavior following Raoult's law to significant deviations from ideality depending on the heteroatom(s) present in the mixture. Mixtures were synthesized using the quench-cool technique with equimolar amounts of two PAC, both containing heteroatoms such as aldehyde, carboxyl, nitrogen, and sulfur substituent groups. For some mixtures, deviation from ideality is inversely related to temperature, though in other cases we see deviations from ideality increasing with temperature, whereas some appear independent of temperature. Most commonly we see lower vapor pressures than predicted by Raoult's law, which indicates that the interacting heteroatoms prefer the solid mixture phase as opposed to the vapor phase. Although negative deviations predominate from Raoult's Law, the varying mixtures investigated show both higher and lower enthalpies and entropies of sublimation than predicted. In each mixture, a higher enthalpy of sublimation leads to higher entropy of sublimation than predicted, and vice versa.

  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. A clinical study of deviated nasal septum with special reference to conventional and endoscopic septoplasty

    Directory of Open Access Journals (Sweden)

    Mohammad Nizamuddin Khan

    2016-12-01

    Conclusions: Our study showed that functional outcome was better and post-operative complications were less in endoscopic septoplasty. Endoscopic septoplasty provides better illumination which helps to identify septal deviation accurately while reducing the postoperative complications due to limited dissection and lesser trauma to septal cartilage. [Int J Res Med Sci 2016; 4(12.000: 5165-5171

  6. Postnatal hematopoiesis and gut microbiota in NOD mice deviate from C57BL/6 mice

    DEFF Research Database (Denmark)

    Damlund, Dina Silke Malling; Metzdorff, Stine Broeng; Hasselby, Jane Preuss

    2016-01-01

    Neonatal studies in different mouse strains reveal that early life colonization affects the development of adaptive immunity in mice. The nonobese diabetic (NOD) mouse spontaneously develops autoimmune diabetes, but neonatal studies of NOD mice are lacking. We hypothesized that NOD mice deviate f...

  7. 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.

  8. 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.

  9. On the influence of airfoil deviations on the aerodynamic performance of wind turbine rotors

    Science.gov (United States)

    Winstroth, J.; Seume, J. R.

    2016-09-01

    The manufacture of large wind turbine rotor blades is a difficult task that still involves a certain degree of manual labor. Due to the complexity, airfoil deviations between the design airfoils and the manufactured blade are certain to arise. Presently, the understanding of the impact of manufacturing uncertainties on the aerodynamic performance is still incomplete. The present work analyzes the influence of a series of airfoil deviations likely to occur during manufacturing by means of Computational Fluid Dynamics and the aeroelastic code FAST. The average power production of the NREL 5MW wind turbine is used to evaluate the different airfoil deviations. Analyzed deviations include: Mold tilt towards the leading and trailing edge, thick bond lines, thick bond lines with cantilever correction, backward facing steps and airfoil waviness. The most severe influences are observed for mold tilt towards the leading and thick bond lines. By applying the cantilever correction, the influence of thick bond lines is almost compensated. Airfoil waviness is very dependent on amplitude height and the location along the surface of the airfoil. Increased influence is observed for backward facing steps, once they are high enough to trigger boundary layer transition close to the leading edge.

  10. 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.

  11. Moderate Deviation for the Single Point Catalytic Super-Brownian Motion

    Institute of Scientific and Technical Information of China (English)

    Xu YANG; Mei ZHANG

    2012-01-01

    We establish the moderate deviation for the density process of the single point catalytic super-Brownian motion.The main tools are the abstract G(a)rtner-Ellis theorem,Dawson-G(a)rtner theorem and the contraction principle.The rate function is expressed by the Fenchel-Legendre transform of log-exponential moment generation function.

  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. 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.

  14. On the Large Deviation Rate Function for the Empirical Measures of Reversible Jump Markov Processes

    Science.gov (United States)

    2013-09-12

    function. Ann. Probab., 13:342�362, 1985. [10] Walter Rudin . Functional Analysis. McGraw-Hill, New York, 1991. [11] D.W. Stroock. An Introduction to the Theory of Large Deviations. Springer- Verlag, New York, 1984. 36 39

  15. Deviation Among Technology Reviews: An Informative Enrichment of Technology Evolution Theory for Marketing

    NARCIS (Netherlands)

    A. Sood (Ashish); S. Stremersch (Stefan)

    2010-01-01

    textabstractUnderstanding technological change is of critical importance to marketers, as it bears new markets, new brands, new customers, and new market leaders. This paper examines the deviation among reviews of a technology’s performance and its consequences for inferences on technology evolution

  16. Modular Multilevel Converter Modelling, Control and Analysis under Grid Frequency Deviations

    DEFF Research Database (Denmark)

    Sztykiel, Michal; da Silva, Rodrigo; Teodorescu, Remus;

    2012-01-01

    A tool for component sizing for MMCs has been developed and tested through simulations in PLECS. The steady-state behaviour under grid frequency deviations - interesting for offshore wind farm connections - has been analysed, providing insights in MMC characteristics and further testing the propo...

  17. Modular multilevel converter modelling, control and analysis under grid frequency deviations

    DEFF Research Database (Denmark)

    Sztykiel, Michal; da Silva, Rodrigo; Teodorescu, Remus;

    2013-01-01

    A tool for component sizing for MMCs has been developed and tested through simulations in PLECS. The steady-state behaviour under grid frequency deviations — interesting for offshore wind farm connections — has been analysed, providing insights in MMC characteristics and further testing the propo...

  18. A novel method to bracket the corotation radius in galaxy discs: vertex deviation maps

    NARCIS (Netherlands)

    Roca-Fàbrega, Santi; Antoja, Teresa; Figueras, Francesca; Valenzuela, Octavio; Romero-Gómez, Mercè; Pichardo, Bárbara

    2014-01-01

    We map the kinematics of stars in simulated galaxy discs with spiral arms using the velocity ellipsoid vertex deviation (l_v). We use test particle simulations, and for the first time, fully self-consistent high-resolution N-body models. We compare our maps with the tight winding approximation model

  19. An improved device for bioimpedance deviation measurements based on 4-electrode half bridge

    Science.gov (United States)

    Liu, Yang; Qiao, Xiaoyan; Li, Gang; Lin, Ling

    2016-10-01

    Researches on monitoring the body fluid changes have attracted much attention during recent years. Real-time bioimpedance deviation detection has good potential for evaluating body fluid changes. In this paper, an improved device based on the self-balancing half bridge and the 4-electrode technique is proposed, which is able to detect minor bioimpedance deviations. The 4-electrode technique is used to remove the interference from contact impedance. Furthermore, the automatic balancing half bridge is utilized to deduct the high-level static impedance baseline, and thus, the dynamic range is enlarged. Moreover, a digital lock-in algorithm based on oversampling improved the effective resolution of the system. Validation experiments show that the minimum bioimpedance deviation measured in the experiment can reach 1 Ω even when the bioimpedance baseline is 10 kΩ and the noise level is low. The system has advantages of high resolution, high magnification, large dynamic range, and good self-adaptability for bioimpedance deviation detection.

  20. Large Deviations Theorems for Empirical Measures in Freidlin-Wentzell Exit Problems

    OpenAIRE

    Mikami, Toshio

    1991-01-01

    We consider the jump-type Markov processes which are small random perturbations of dynamical systems and their empirical processes. We prove large deviations theorems for empirical measures which are marginal measures of empirical processes at the exit time of Markov processes from a bounded domain in a $d$-dimensional Euclidean space $\\mathscr{R}^d$.

  1. 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.

  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. Current fluctuations and statistics during a large deviation event in an exactly solvable transport model

    Science.gov (United States)

    Hurtado, Pablo I.; Garrido, Pedro L.

    2009-02-01

    We study the distribution of the time-integrated current in an exactly solvable toy model of heat conduction, both analytically and numerically. The simplicity of the model allows us to derive the full current large deviation function and the system statistics during a large deviation event. In this way we unveil a relation between system statistics at the end of a large deviation event and for intermediate times. The mid-time statistics is independent of the sign of the current, a reflection of the time-reversal symmetry of microscopic dynamics, while the end-time statistics does depend on the current sign, and also on its microscopic definition. We compare our exact results with simulations based on the direct evaluation of large deviation functions, analyzing the finite-size corrections of this simulation method and deriving detailed bounds for its applicability. We also show how the Gallavotti-Cohen fluctuation theorem can be used to determine the range of validity of simulation results.

  4. DYSFUNCTION OF THE MODERN RUSSIAN FAMILY AND PROBLEM OF THE DEVIATING SOCIALIZATION OF TEENAGERS

    Directory of Open Access Journals (Sweden)

    Tatyana I. BARSUKOVA

    2015-01-01

    Full Text Available In article influence of dysfunction of the family interpreted by authors as a negative consequence of its transformation, on deviations in socialization of teenagers, in their sotsializatsionnykh trajectories, on a gabitualization of "trouble" is analysed. Locates that violation of functioning of a family (its dysfunction in the attitude towards the teenager can be referred to determinants of deviations of socialization. Negative influence of a disfunktsionalnost of a family on formation of the identity of the modern teenager is shown in his deviant acts of a negative orientation now; forms of deviant behavior in which these deviations, and also consequences of refusal of a number of families of performance of economic and economic and protective functions prove are described. Author's definition of the normal and deviating socialization is presented. Attempt to define border between the normal and deviating socialization, between normal sotsializatsionny process and anomiyny, deformable becomes. By authors of article it is proved that the deviating socialization the deviation from sotsializatsionny norm as multidimensional a standard is the cornerstone, of fiksiruyushchy a sotsializirovannost of the person. Definition of sotsializatsionny norm as interval, as admissible in behavior of people and as its regulator is given. The emphasis is placed on a role of trajectory model of socialization which changes depending on influence of a family on socialization of teenagers. The choice locates in article as object of research of the teenager that at such age some "binarity" of the personality, a combination in it of lines, both the adult, and the child is observed. It, according to authors, complicates a choice the teenager of ethical standards and vital values. Besides, variety of alternatives at a choice of norms and behavior models it is complicated by a polinormativnost of social space of the teenager. The

  5. 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 ...

  6. 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.

  7. Changing axis deviation and paroxysmal atrial flutter associated with subclinical hyperthyroidism.

    Science.gov (United States)

    Patanè, Salvatore; Marte, Filippo

    2010-10-08

    Subclinical hyperthyroidism is an increasingly recognized entity that is defined as a normal serum free thyroxine and free triiodothyronine levels with a thyroid-stimulating hormone level suppressed below the normal range and usually undetectable. It has been reported that subclinical hyperthyroidism is not associated with coronary heart disease or mortality from cardiovascular causes but it is sufficient to induce arrhythmias including atrial fibrillation and atrial flutter. It has also been reported that increased factor X activity in patients with subclinical hyperthyroidism represents a potential hypercoagulable state. Rarely, it has also been reported intermittent changing axis deviation during atrial fibrillation and during atrial flutter. We present a case of paroxysmal atrial flutter and changing axis deviation associated with subclinical hyperthyroidism, in a 76-year-old Italian man. Also this case focuses attention on the importance of a correct evaluation of subclinical hyperthyroidism.

  8. Apparent Deviations from Keplerian Acceleration for Stars Around the Supermassive Black Hole at the Galactic Center

    CERN Document Server

    Loeb, A

    2003-01-01

    We show that the time-dependent Doppler effect should induce measureable deviations of the time history of the projected orbit of a star around the supermassive black hole in the Galactic center (SgrA*) from the expected Keplerian history. In particular, the line-of-sight acceleration of the star generates apparent acceleration of its image along its velocity vector on the sky, even if its actual Keplerian acceleration in this direction vanishes. The excess apparent acceleration simply results from the transformation of time between the reference frames of the observer and the star. Although the excess acceleration averages to zero over a full closed orbit, it could lead to systematic offsets of a few percent in estimates of the dynamical mass or position of the black hole that rely on partially sampled orbits with pericentric distances of ~100AU. Deviations of this magnitude from apparent Keplerian dynamics of known stars should be detectable by future observations.

  9. MUSiC A General Search for Deviations from Monte Carlo Predictions in CMS

    CERN Document Server

    Biallass, Philipp

    2009-01-01

    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.

  10. 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...

  11. MUSiC - A general search for deviations from monte carlo predictions in CMS

    Science.gov (United States)

    Biallass, Philipp A.; CMS Collaboration

    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.

  12. MUSiC - A Generic Search for Deviations from Monte Carlo Predictions in CMS

    Science.gov (United States)

    Hof, Carsten

    2009-05-01

    We present a model independent analysis approach, 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 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. 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.

  13. Differential Deposition to Correct Surface Figure Deviations in Astronomical Grazing-Incidence X-Ray Optics

    Science.gov (United States)

    Kilaru, Kiranmayee; Ramsey, Brian D.; Gubarev, Mikhail V.

    2011-01-01

    A coating technique is being developed to correct the surface figure deviations in reflective-grazing-incidence X-ray optics. These optics are typically designed to have precise conic profiles, and any deviation in this profile, as a result of fabrication, results in a degradation of the imaging performance. To correct the mirror profiles, physical vapor deposition has been utilized to selectively deposit a filler material inside the mirror shell. The technique, termed differential deposition, has been implemented as a proof of concept on miniature X-ray optics developed at MSFC for medical-imaging applications. The technique is now being transferred to larger grazing-incidence optics suitable for astronomy and progress to date is reported.

  14. Reaction Wheel Installation Deviation Compensation for Overactuated Spacecraft with Finite-Time Attitude Control

    Directory of Open Access Journals (Sweden)

    Aihua Zhang

    2013-01-01

    Full Text Available A novel attitude tracking control scheme is presented for overactuated spacecraft to address the attitude stabilization problem in presence of reaction wheel installation deviation, external disturbance and uncertain mass of moment inertia. An adaptive sliding mode control technique is proposed to track the uncertainty. A Lyapunov-based analysis shows that the compensation control law can guarantee that the desired attitude trajectories are followed in finite-time. The key feature of the proposed control strategy is that it globally asymptotically stabilizes the system, even in the presence of reaction wheel installation deviation, external disturbances, and uncertain mass of moment inertia. The attitude track performance using the proposed finite-time compensation control is evaluated through a numerical example.

  15. Lower Current Large Deviations for Zero-Range Processes on a Ring

    Science.gov (United States)

    Chleboun, Paul; Grosskinsky, Stefan; Pizzoferrato, Andrea

    2017-04-01

    We study lower large deviations for the current of totally asymmetric zero-range processes on a ring with concave current-density relation. We use an approach by Jensen and Varadhan which has previously been applied to exclusion processes, to realize current fluctuations by travelling wave density profiles corresponding to non-entropic weak solutions of the hyperbolic scaling limit of the process. We further establish a dynamic transition, where large deviations of the current below a certain value are no longer typically attained by non-entropic weak solutions, but by condensed profiles, where a non-zero fraction of all the particles accumulates on a single fixed lattice site. This leads to a general characterization of the rate function, which is illustrated by providing detailed results for four generic examples of jump rates, including constant rates, decreasing rates, unbounded sublinear rates and asymptotically linear rates. Our results on the dynamic transition are supported by numerical simulations using a cloning algorithm.

  16. 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.

  17. 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)

  18. 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.

  19. Investigation of Cu(In,Ga)Se2 Solar Cell Performance Deviations in Nominally Equal Absorbers

    Science.gov (United States)

    Knecht, Robin; Parisi, Jürgen; Riedel, Ingo; Schäffler, Raymund; Dimmler, Bernhard

    2012-10-01

    Cu(In,Ga)Se2 (CIGSe) solar cells were fabricated independently by industrial scale co-evaporation in two separate production lines with the same nominal composition and thickness of the absorber film. Although the device properties were believed to be the same we observed substantial deviations of the respective values of the open circuit voltage (ΔVOC = 40 mV) and of the fill factor (ΔFF= 4%), whereas the short circuit current was essentially the same. We performed fundamental device analysis, space charge and defect spectroscopy, transient photoluminescence as well as in-depth profiling of the chemical gradients of the absorber films. Using the results from the experiments we set up a simulation baseline which allowed us to conclude that the apparent deviations can be related to the presence of deep recombination centers with different concentration within the CIGSe absorber as well as to variations of the band gap grading.

  20. Confusing Sterile Neutrinos with Deviation from Tribimaximal Mixing at Neutrino Telescopes

    CERN Document Server

    Awasthi, Ram Lal

    2007-01-01

    We expound the impact of extra sterile species on the ultra high energy neutrino fluxes in neutrino telescopes. We use three types of well-known flux ratios and compare the values of these flux ratios in presence of sterile neutrinos, with those predicted by deviation from the tribimaximal mixing scheme. We show that in neutrino telescopes, its easy to confuse between the signature of sterile neutrinos with that of the deviation from tribimaximal mixing. We also show that if the measured flux ratios acquire a value well outside the range predicted by the standard scenario with three active neutrinos only, it might be possible to tell the presence of extra sterile neutrinos by observing ultra high energy neutrinos in the upcoming neutrino telescopes.

  1. Local Group Dwarf Spheroidals: Correlated Deviations from the Baryonic Tully-Fisher Relation

    CERN Document Server

    McGaugh, Stacy S

    2010-01-01

    Local Group dwarf spheroidal satellite galaxies are the faintest extragalactic stellar systems known. We examine recent data for these objects in the plane of the Baryonic Tully-Fisher Relation (BTFR). While some dwarf spheroidals adhere to the BTFR, others deviate substantially. We examine the residuals from the BTFR and find that they are not random. The residuals correlate with luminosity, size, metallicity, ellipticity, and susceptibility of the dwarfs to tidal disruption. Fainter, more elliptical, and tidally more susceptible dwarfs deviate further from the BTFR. We consider a variety of mechanisms that might lead to this behavior. Reionization does not, by itself, suffice to explain all aspects of the data. Further mechanisms such as supernova feedback or ram pressure stripping may remove gas that would otherwise be present to satisfy the baryonic mass budget. The correlation with ellipticity and tidal susceptibility implies that the usual assumption of spherical systems in stable equilibria may not hol...

  2. The large deviation function for entropy production: the optimal trajectory and the role of fluctuations

    Science.gov (United States)

    Speck, Thomas; Engel, Andreas; Seifert, Udo

    2012-12-01

    We study the large deviation function for the entropy production rate in two driven one-dimensional systems: the asymmetric random walk on a discrete lattice and Brownian motion in a continuous periodic potential. We compare two approaches: using the Donsker-Varadhan theory and using the Freidlin-Wentzell theory. We show that the wings of the large deviation function are dominated by a single optimal trajectory: either in the forward direction (positive rate) or in the backward direction (negative rate). The joining of the two branches at zero entropy production implies a non-differentiability and thus the appearance of a ‘kink’. However, around zero entropy production, many trajectories contribute and thus the ‘kink’ is smeared out.

  3. 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.

  4. 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)

  5. Postnatal Hematopoiesis and Gut Microbiota in NOD Mice Deviate from C57BL/6 Mice

    Directory of Open Access Journals (Sweden)

    Dina Silke Malling Damlund

    2016-01-01

    Full Text Available Neonatal studies in different mouse strains reveal that early life colonization affects the development of adaptive immunity in mice. The nonobese diabetic (NOD mouse spontaneously develops autoimmune diabetes, but neonatal studies of NOD mice are lacking. We hypothesized that NOD mice deviate from another much used mouse strain, C57BL/6, with respect to postnatal microbiota and/or hematopoiesis and compared this in newborn mice of dams housed under the same conditions. A distinct bacteria profile rich in staphylococci was found at postnatal days (PND 1–4 in NOD mice. Furthermore, a distinct splenic cell profile high in a granulocytic phenotype was evident in the neonatal NOD mice whereas neonatal C57BL/6 mice showed a profile rich in monocytes. Neonatal expression of Reg3g and Muc2 in the gut was deviating in NOD mice and coincided with fewer bacteria attaching to the Mucosal surface in NOD compared to C57BL/6 mice.

  6. 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.

  7. 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.

  8. MARSHALLIAN DEVIATION: NEW OBSERVABLE CRITERION TO MEASURE TRANSACTION PATHS IN DOUBLE AUCTION MARKETS

    Institute of Scientific and Technical Information of China (English)

    ZHAN Wenjie; WANG Shouyang; ZHANG Jinlong; YANG Jie; K.K. Lai

    2002-01-01

    In measuring the trade process in a double auction (DA) market, there is not any observable criterion that is able to describe the matching pairs and their transaction order dynamically. In this paper, we propose a new observable criterion called Marshalliandeviation. It can be used to measure the distance of a transaction path deviating from theMarshallian path mathematically, and to answer the question why buyers with high valueswill trade with sellers with low costs in advance in some types of DA but not in others.Furthermore, three factors influencing the Marshallian deviations both in the CDA and inthe PDA are also studied. They are respectively the strategic algorithm, the transactionduration and the number of traders. A few interesting findings are presented.

  9. Application of Allan Deviation to Assessing Uncertainties of Continuous-measurement Instruments, and Optimizing Calibration Schemes

    Science.gov (United States)

    Jacobson, Gloria; Rella, Chris; Farinas, Alejandro

    2014-05-01

    Technological advancement of instrumentation in atmospheric and other geoscience disciplines over the past decade has lead to a shift from discrete sample analysis to continuous, in-situ monitoring. Standard error analysis used for discrete measurements is not sufficient to assess and compare the error contribution of noise and drift from continuous-measurement instruments, and a different statistical analysis approach should be applied. The Allan standard deviation analysis technique developed for atomic clock stability assessment by David W. Allan [1] can be effectively and gainfully applied to continuous measurement instruments. As an example, P. Werle et al has applied these techniques to look at signal averaging for atmospheric monitoring by Tunable Diode-Laser Absorption Spectroscopy (TDLAS) [2]. This presentation will build on, and translate prior foundational publications to provide contextual definitions and guidelines for the practical application of this analysis technique to continuous scientific measurements. The specific example of a Picarro G2401 Cavity Ringdown Spectroscopy (CRDS) analyzer used for continuous, atmospheric monitoring of CO2, CH4 and CO will be used to define the basics features the Allan deviation, assess factors affecting the analysis, and explore the time-series to Allan deviation plot translation for different types of instrument noise (white noise, linear drift, and interpolated data). In addition, the useful application of using an Allan deviation to optimize and predict the performance of different calibration schemes will be presented. Even though this presentation will use the specific example of the Picarro G2401 CRDS Analyzer for atmospheric monitoring, the objective is to present the information such that it can be successfully applied to other instrument sets and disciplines. [1] D.W. Allan, "Statistics of Atomic Frequency Standards," Proc, IEEE, vol. 54, pp 221-230, Feb 1966 [2] P. Werle, R. Miicke, F. Slemr, "The Limits

  10. Probability of ventricular fibrillation: allometric model based on the ST deviation

    Directory of Open Access Journals (Sweden)

    Arini Pedro D

    2011-01-01

    Full Text Available Abstract Background Allometry, in general biology, measures the relative growth of a part in relation to the whole living organism. Using reported clinical data, we apply this concept for evaluating the probability of ventricular fibrillation based on the electrocardiographic ST-segment deviation values. Methods Data collected by previous reports were used to fit an allometric model in order to estimate ventricular fibrillation probability. Patients presenting either with death, myocardial infarction or unstable angina were included to calculate such probability as, VFp = δ + β (ST, for three different ST deviations. The coefficients δ and β were obtained as the best fit to the clinical data extended over observational periods of 1, 6, 12 and 48 months from occurrence of the first reported chest pain accompanied by ST deviation. Results By application of the above equation in log-log representation, the fitting procedure produced the following overall coefficients: Average β = 0.46, with a maximum = 0.62 and a minimum = 0.42; Average δ = 1.28, with a maximum = 1.79 and a minimum = 0.92. For a 2 mm ST-deviation, the full range of predicted ventricular fibrillation probability extended from about 13% at 1 month up to 86% at 4 years after the original cardiac event. Conclusions These results, at least preliminarily, appear acceptable and still call for full clinical test. The model seems promising, especially if other parameters were taken into account, such as blood cardiac enzyme concentrations, ischemic or infarcted epicardial areas or ejection fraction. It is concluded, considering these results and a few references found in the literature, that the allometric model shows good predictive practical value to aid medical decisions.

  11. Bilateral dissociated vertical deviation in a case of congenital hereditary endothelial dystrophy

    Directory of Open Access Journals (Sweden)

    Bhola Rahul

    2006-01-01

    Full Text Available Dissociated vertical deviation (DVD is an intermittent anomaly of the non-fixing eye. Although association of DVD with sensory visual deprivation owing to congenital or acquired opacities of the ocular media has been reported, its association with congenital hereditary endothelial dystrophy (CHED has not been reported hitherto. We report a case having a bilateral asymmetric DVD, in a know case of bilateral CHED.

  12. Perio dic Solutions for p-Laplacian Neutral Functional Differential Equation with a Deviating Argument

    Institute of Scientific and Technical Information of China (English)

    CHEN Wen-bin; GAO Fang; LU Shi-ping

    2013-01-01

    In this paper, by using the continuation theorem of coincidence degree theory and some analysis methods, we study a kind of periodic solutions to p-Laplacian neutral functional differential equation with a deviating argument (ϕp(x(t)-cx(t-σ))0)0+f(t, x0(t))+g(t, x(t-τ(t)))=e(t), some new results on the existence of periodic solutions is obtained.

  13. Vertical Vergence Adaptation Produces an Objective Vertical Deviation That Changes With Head Tilt

    Science.gov (United States)

    Irsch, Kristina; Guyton, David L.; Ramey, Nicholas A.; Adyanthaya, Rohit S.; Ying, Howard S.

    2013-01-01

    Purpose. To document the cyclovertical ocular motor mechanism used for vertical fusion in healthy subjects, and to explore whether vertical vergence training in healthy individuals can produce objectively confirmed vertical deviations that change with head tilt, revealing a basic mechanism that can produce a pattern of misalignment in an otherwise normal ocular motor system that is similar to superior oblique muscle paresis (SOP). Methods. Seven subjects with normal orthoptic examinations were adapted to vertical image disparities using our tilting haploscopic eye-tracking apparatus presenting concentric circle targets without torsional cues. Static eye positions were recorded with head straight and when tilted 45 degrees to the left and right, during both binocular and monocular viewing. Results. Vertical fusional vergence was accompanied by a cycloversion, with the downward-moving eye intorting and the upward-moving eye extorting, implicating primary involvement of the oblique extraocular muscles. After adaptation to the slowly increasing vertical target separation, all subjects developed a temporary vertical deviation in the straight ahead position that increased with head tilt to one side and decreased with head tilt to the other side. Conclusions. These results not only show that head-tilt–dependent changes in vertical deviation are not necessarily pathognomonic for SOP, but also, and more importantly, suggest mechanisms that can mimic SOP and suggest a possible role for vertical vergence training in reducing deviations and thus the amount of head tilt required for fusion. Ultimately, vertical vergence training may provide an adjunct or alternative to extraocular muscle surgery in selected cases. PMID:23572100

  14. Historical Reflection on Deviation in Transfer Policy of Agricultural Surplus Labor at Early Stage of China

    Institute of Scientific and Technical Information of China (English)

    Chengjun; ZHANG

    2015-01-01

    This paper firstly made an analysis on transfer of agricultural surplus labor in the end of the 20 th century. On this basis,it made reflection on policy of agricultural surplus labor. Then,it stated that there is a great deviation of transfer of agricultural surplus labor from practical requirement and pointed out basic internationally recognized ideas of agricultural surplus labor transfer. Finally,it came up with recommendations for formulating agricultural surplus labor transfer.

  15. 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.

  16. Large deviation principle of Freidlin-Wentzell type for pinned diffusion processes

    OpenAIRE

    Inahama, Yuzuru

    2012-01-01

    Since T. Lyons invented rough path theory, one of its most successful applications is a new proof of Freidlin-Wentzell's large deviation principle for diffusion processes. In this paper we extend this method to the case of pinned diffusion processes under a mild ellipticity assumption. Besides rough path theory, our main tool is quasi-sure analysis, which is a kind of potential theory in Malliavin calculus.

  17. Large deviation principle of Freidlin-Wentzell type for pinned diffusion processes

    CERN Document Server

    Inahama, Yuzuru

    2012-01-01

    Since T. Lyons invented rough path theory, one of its most successful applications is a new proof of Freidlin-Wentzell's large deviation principle for diffusion processes. In this paper we extend this method to the case of pinned diffusion processes under a mild ellipticity assumption. Besides rough path theory, our main tool is quasi-sure analysis, which is one of the deepest parts of Malliavin calculus.

  18. Effect of Wrist Deviation on Median Nerve Cross-Sectional Area at Proximal Carpal Tunnel Level

    Directory of Open Access Journals (Sweden)

    Ping Yeap LOH

    2015-10-01

    Full Text Available Background: Carpal tunnel syndrome (CTS is one of the most common musculoskeletal disorders among computer users. Computer users exhibit various wrist angles while typing. Dynamic changes of wrist angle may cause different degrees of median nerve compression. The objective of this study was thus to investigate the effects of the combination of wrist flexion-extension with wrist deviation on median nerve cross-sectional area (MNCSA.Methods:  Eight right-handed participants were recruited in this study. Both wrists were examined by sonographic ultrasound (US at the proximal carpal tunnel level in the transverse plane. A total of nine wrist positions were examined, including wrist neutral (WN, wrist flexion (WF30°, and wrist extension (WE30°, together with three wrist deviation conditions, namely, without radial deviation (RD and ulnar deviation (UD, with maximal RD and with maximal UD. MNCSA was measured by tracing method with ImageJ.Results: Paired t-test showed a significant difference of WN MNCSA between the dominant hand (7.93 ± 0.63 mm2 and the non-dominant hand (6.98 ± 0.42 mm2 (P<0.001. Two-way repeated-measures ANOVA (handedness as an independent factor showed that WF30° and WE30° caused significant differences of MNCSA when compared with WN (P<0.001. However, wrist RD/UD did not have a significant interaction with the changes of MNCSA in WN, WF and WE positions.Conclusion: The results indicate a significant reduction of MNCSA when WN changed to WF and WE. Wrist RD and UD did not cause significant changes of MNCSA at different wrist positions. Keywords: Median nerve, Ultrasound, Wrist active holding, Nerve deformation

  19. A unified approach to the large deviations for small perturbations of random evolution equations

    Institute of Scientific and Technical Information of China (English)

    胡亦钧

    1997-01-01

    Let be the processes governed by the following stochastic differential equations:where v (t) is a random process independent of the Brownian motion B(·).Some large deviation (LD) properties of are proved.For a particular case,an explicit representation of the rate function is also given,which solves a problem posed by Eizenberg and Freidlin.In the meantime,an abstract LD theorem is obtained.

  20. A framework for the direct evaluation of large deviations in non-Markovian processes

    Science.gov (United States)

    Cavallaro, Massimo; Harris, Rosemary J.

    2016-11-01

    We propose a general framework to simulate stochastic trajectories with arbitrarily long memory dependence and efficiently evaluate large deviation functions associated to time-extensive observables. This extends the ‘cloning’ procedure of Giardiná et al (2006 Phys. Rev. Lett. 96 120603) to non-Markovian systems. We demonstrate the validity of this method by testing non-Markovian variants of an ion-channel model and the totally asymmetric exclusion process, recovering results obtainable by other means.