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Sample records for ck2 phosphorylation-dependent interaction

  1. 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; Brunstein, Elena; Olsen, Birgitte B; Vilk, Greg; Litchfield, David W; Issinger, Olaf-Georg; Niefind, Karsten

    2011-01-01

    tetramer. To this end, we used recombinant, C-terminal truncated forms of human CK2 subunits that are able to form the holoenzyme. We analyzed the interaction thermodynamics between the binding of CK2α and CK2β as well as the impact of changes in temperature, pH, and the ionization enthalpy of the buffer...... Leu41 or Phe54 single mutations were most disruptive to binding of CK2β. Additionally, these CK2α mutants retained their kinase activity. Furthermore, the substitution of Leu41 in combination with Phe54 showed that the individual mutations were not additive, suggesting that the cooperative action of...

  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

    Protein kinase CK2 predominantly exists as a heterotetrameric holoenyzme consisting of two catalytic subunits (CK2alpha) and two non-catalytic subunits (CK2beta). Early investigations which we review here had revealed the presence of two types of contacts between CK2alpha and CK2beta: a primary...... interaction responsible for the stability of the CK2 holoenzyme and stimulatory for the catalytic activity, and a secondary interaction which is inhibitory and in which the acidic loop of CK2beta associates with the basic stretch and the (p+1)-loop of CK2alpha. At the end of the last decade both types of...... 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 in the...

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

    DEFF Research Database (Denmark)

    Bischoff, Nils; Olsen, Birgitte; Raaf, Jennifer; Bretner, Maria; Issinger, Olaf-Georg; Niefind, Karsten

    2011-01-01

    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 ...

  4. The interaction of CK2alpha and CK2beta, the subunits of protein kinase CK2, requires CK2beta in a preformed conformation and is enthalpically driven

    DEFF Research Database (Denmark)

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

    2008-01-01

    The protein kinase CK2 (former name: "casein kinase 2") predominantly occurs as a heterotetrameric holoenzyme composed of two catalytic chains (CK2alpha) and two noncatalytic subunits (CK2beta). The CK2beta subunits form a stable dimer to which the CK2alpha monomers are attached independently. In...... contrast to the cyclins in the case of the cyclin-dependent kinases CK2beta is no on-switch of CK2alpha; rather the formation of the CK2 holoenzyme is accompanied with an overall change of the enzyme's profile including a modulation of the substrate specificity, an increase of the thermostability, and an...... allocation of docking sites for membranes and other proteins. In this study we used C-terminal deletion variants of human CK2alpha and CK2beta that were enzymologically fully competent and in particular able to form a heterotetrameric holoenzyme. With differential scanning calorimetry (DSC) we confirmed the...

  5. 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 deposited...... in the EMBL database under the accession numbers R08806 and Z17360, for the ribosomal protein L5 and for A-Raf kinase. All isolated clones except the one for CK2 beta showed no interaction with the catalytic alpha subunit of CK2. A-Raf kinase is a new interesting partner of CK2 beta. The isolated A...

  6. p21WAF1/CIP1 interacts with protein kinase CK2

    DEFF Research Database (Denmark)

    Götz, C; Wagner, P; Issinger, O G;

    1996-01-01

    p21WAF1/CIP1 which belongs to a class of regulatory proteins that interact with cyclin dependent kinases is a potent inhibitor of these kinases. The inhibition of the cyclin dependent kinases induces an arrest of cells in the G phase of the cell cycle. In addition p21WAF1/CIP1 associates with PCNA...... and inhibits DNA replication. Here, we show that p21WAF1/CIP1 binds to the regulatory beta-subunit of protein kinase CK2 but not to the catalytic alpha-subunit. Binding of p21WAF1/CIP1 down regulates the kinase activity of CK2 with respect to the phosphorylation of the beta-subunit of CK2, casein and...... the C-terminus of p53. This study demonstrates a new binding partner for the regulatory beta-subunit of protein kinase CK2 which regulates the activity of the holoenzyme....

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

    DEFF Research Database (Denmark)

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

    1999-01-01

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

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

    Science.gov (United States)

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

    2016-08-19

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

  9. 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; Yoo, Eungyoung; Ulucan, Oezlem; Herzig, Stefan; Issinger, Olaf-Georg; Helms, Volkhard; Goetz, Claudia; Neundorf, Ines; Niefind, Karsten; Pietsch, Markus

    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...

  10. 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...... view that protein kinase CK2 plays an important role in certain steps of apoptosis....

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    -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...

  12. Protein kinase CK2 interacts with Chk2 and phosphorylates Mre11 on serine 649

    International Nuclear Information System (INIS)

    The Mre11-Rad50-Nbs1 protein complex has been known to be involved in a variety of DNA metabolic events that involve DNA double-strand breaks (DSBs). The phosphorylation of Mre11 is increased in response to ionizing radiation, which suggests that phosphorylation of Mre11 may be an important regulatory mechanism of this complex. Mre11-phosphorylating kinase activities were observed in Chk2 immunoprecipitates and HeLa nuclear extracts. Through the tandem affinity tagging system and conventional chromatography, this kinase was purified and identified as protein kinase CK2. CK2 phosphorylates Mre11 in vitro. In vitro kinase assay with a series of truncated Mre11 proteins as substrates for CK2 and site-directed mutagenesis showed that serine 649 of Mre11 is mainly phosphorylated by CK2 in vitro. In vivo labeling and phosphopeptide mapping analysis revealed that this phosphorylation occurs in vivo. These data implicate CK2 as a potential upstream regulator of Mre11 function

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

    DEFF Research Database (Denmark)

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

    1997-01-01

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

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

    Science.gov (United States)

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

    2016-06-01

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

  15. Analysis of transient phosphorylation-dependent protein-protein interactions in living mammalian cells using split-TEV

    Directory of Open Access Journals (Sweden)

    Botvinnik Anna

    2008-07-01

    Full Text Available Abstract Background Regulated protein-protein interactions (PPIs are pivotal molecular switches that are important for the regulation of signaling processes within eukaryotic cells. Cellular signaling is altered in various disease conditions and offers interesting options for pharmacological interventions. Constitutive PPIs are usually mediated by large interaction domains. In contrast, stimulus-regulated PPIs often depend on small post-translational modifications and are thus better suited targets for drug development. However, the detection of modification-dependent PPIs with biochemical methods still remains a labour- and material-intensive task, and many pivotal PPIs that are potentially suited for pharmacological intervention most likely remain to be identified. The availability of methods to easily identify and quantify stimulus-dependent, potentially also transient interaction events, is therefore essential. The assays should be applicable to intact mammalian cells, optimally also to primary cells in culture. Results In this study, we adapted the split-TEV system to quantify phosphorylation-dependent and transient PPIs that occur at the membrane and in the cytosol of living mammalian cells. Split-TEV is based on a PPI-induced functional complementation of two inactive TEV protease fragments fused to interaction partners of choice. Genetically encoded transcription-coupled and proteolysis-only TEV reporter systems were used to convert the TEV activity into an easily quantifiable readout. We measured the phosphorylation-dependent interaction between the pro-apoptotic protein Bad and the adapter proteins 14-3-3ε and ζ in NIH-3T3 fibroblasts and in primary cultured neurons. Using split-TEV assays, we show that Bad specifically interacts with 14-3-3 isoforms when phosphorylated by protein kinase Akt-1/PKB at Ser136. We also measured the phosphorylation-dependent Bad/14-3-3 interactions mediated by endogenous and transient Akt-1 activity. We

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

    DEFF Research Database (Denmark)

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

    2000-01-01

    Protein kinase CK2 has been implicated in the regulation of a wide range of proteins that are important in cell proliferation and differentiation. Here we demonstrate that the stress signaling agents anisomycin, arsenite, and tumor necrosis factor-alpha stimulate the specific enzyme activity of CK2...

  17. CK2-mediated stimulation of Pol I transcription by stabilization of UBF–SL1 interaction

    OpenAIRE

    Lin, Chih-Yin; Navarro, Sonia; Reddy, Sita; Comai, Lucio

    2006-01-01

    High levels of rRNA synthesis by RNA polymerase I are important for cell growth and proliferation. In vitro studies have indicated that the formation of a stable complex between the HMG box factor [Upstream binding factor (UBF)] and SL1 at the rRNA gene promoter is necessary to direct multiple rounds of Pol I transcription initiation. The recruitment of SL1 to the promoter occurs through protein interactions with UBF and is regulated by phosphorylation of UBF. Here we show that the protein ki...

  18. Analysis of phosphorylation-dependent protein-protein interactions of histone h3.

    Science.gov (United States)

    Klingberg, Rebecca; Jost, Jan Oliver; Schümann, Michael; Gelato, Kathy Ann; Fischle, Wolfgang; Krause, Eberhard; Schwarzer, Dirk

    2015-01-16

    Multiple posttranslational modifications (PTMs) of histone proteins including site-specific phosphorylation of serine and threonine residues govern the accessibility of chromatin. According to the histone code theory, PTMs recruit regulatory proteins or block their access to chromatin. Here, we report a general strategy for simultaneous analysis of both of these effects based on a SILAC MS scheme. We applied this approach for studying the biochemical role of phosphorylated S10 of histone H3. Differential pull-down experiments with H3-tails synthesized from l- and d-amino acids uncovered that histone acetyltransferase 1 (HAT1) and retinoblastoma-binding protein 7 (RBBP7) are part of the protein network, which interacts with the unmodified H3-tail. An additional H3-derived bait containing the nonhydrolyzable phospho-serine mimic phosphonomethylen-alanine (Pma) at S10 recruited several isoforms of the 14-3-3 family and blocked the recruitment of HAT1 and RBBP7 to the unmodified H3-tail. Our observations provide new insights into the many functions of H3S10 phosphorylation. In addition, the outlined methodology is generally applicable for studying specific binding partners of unmodified histone tails. PMID:25330109

  19. 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; Issinger, Olaf-Georg; Guerra, Barbara

    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......1. In this study, we show that Chk1 specifically phosphorylates in vitro the regulatory beta-subunit of CK2. Chymotryptic peptides and mutational analyses have revealed that CK2beta is phosphorylated at Thr213. Formation of a stable complex between CK2beta and Chk1 is not affected by the...

  20. Phosphorylation-Dependent PIH1D1 Interactions Define Substrate Specificity of the R2TP Cochaperone Complex

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    Zuzana Hořejší

    2014-04-01

    Full Text Available The R2TP cochaperone complex plays a critical role in the assembly of multisubunit machines, including small nucleolar ribonucleoproteins (snoRNPs, RNA polymerase II, and the mTORC1 and SMG1 kinase complexes, but the molecular basis of substrate recognition remains unclear. Here, we describe a phosphopeptide binding domain (PIH-N in the PIH1D1 subunit of the R2TP complex that preferentially binds to highly acidic phosphorylated proteins. A cocrystal structure of a PIH-N domain/TEL2 phosphopeptide complex reveals a highly specific phosphopeptide recognition mechanism in which Lys57 and 64 in PIH1D1, along with a conserved DpSDD phosphopeptide motif within TEL2, are essential and sufficient for binding. Proteomic analysis of PIH1D1 interactors identified R2TP complex substrates that are recruited by the PIH-N domain in a sequence-specific and phosphorylation-dependent manner suggestive of a common mechanism of substrate recognition. We propose that protein complexes assembled by the R2TP complex are defined by phosphorylation of a specific motif and recognition by the PIH1D1 subunit.

  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

    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...

  2. Phosphorylation of CRN2 by CK2 regulates F-actin and Arp2/3 interaction and inhibits cell migration

    OpenAIRE

    Xavier, Charles Peter; Rastetter, Raphael H.; Bloemacher, Margit; Morgan Beesly, Reginald Owen; Fernández Fernández, María Pilar; Wang, Conan; Osman, Asiah; Miyata, Yoshihiko; (et al.)

    2012-01-01

    CRN2 (synonyms: coronin 1C, coronin 3) functions in the re-organization of the actin network and is implicated in cellular processes like protrusion formation, secretion, migration and invasion. We demonstrate that CRN2 is a binding partner and substrate of protein kinase CK2, which phosphorylates CRN2 at S463 in its C-terminal coiled coil domain. Phosphomimetic S463D CRN2 loses the wild-type CRN2 ability to inhibit actin polymerization, to bundle F-actin, and to bind to the Arp2/3 complex. A...

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

  4. Protein kinase CK2 in human diseases

    DEFF Research Database (Denmark)

    Guerra, Barbara; Issinger, Olaf-Georg

    2008-01-01

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

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

    Science.gov (United States)

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

    2009-08-01

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

  6. 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; Niefind, Karsten

    2008-01-01

    The Ser/Thr kinase CK2 (previously called casein kinase 2) is composed of two catalytic chains (CK2 alpha) attached to a dimer of noncatalytic subunits (CK2 beta). CK2 is involved in suppression of apoptosis, cell survival, and tumorigenesis. To investigate these activities and possibly affect them......, 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 to...

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

    Science.gov (United States)

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

    2010-01-01

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

  8. Modulation of human checkpoint kinase Chk1 by the regulatory beta-subunit of protein kinase CK2

    DEFF Research Database (Denmark)

    Guerra, Barbara; Issinger, Olaf-Georg; Wang, Jean Y J

    2003-01-01

    Protein kinase CK2 is a serine/threonine protein kinase involved in various aspects of cellular regulation. The regulatory beta-subunit of CK2 exerts a central role not only in mediating formation of tetrameric CK2 complexes but also as a docking partner for several protein kinases. In this study......, CK2beta is found to interact with the human cell cycle checkpoint kinase Chk1. The Chk1-interacting region of CK2beta is localized at the C-terminus and the complex between CK2beta and Chk1 is devoid of the catalytic CK2alpha-subunit. The interaction between CK2beta and Chk1 leads to an increase in...... the Cdc25C phosphorylation activity of Chk1. The screening of several cell lines has revealed that the association between CK2beta and Chk1 also occurs in vivo at a different degree. Collectively, these studies confirm the implication of the regulatory beta-subunit of protein kinase CK2 in cell cycle...

  9. Structural basis of regulation and substrate specificity of protein kinase CK2 deduced from the modeling of protein-protein interactions

    Directory of Open Access Journals (Sweden)

    Srinivasan N

    2003-05-01

    Full Text Available Abstract Background Protein Kinase Casein Kinase 2 (PKCK2 is an ubiquitous Ser/Thr kinase expressed in all eukaryotes. It phosphorylates a number of proteins involved in various cellular processes. PKCK2 holoenzyme is catalytically active tetramer, composed of two homologous or identical and constitutively active catalytic (α and two identical regulatory (β subunits. The tetramer cannot phosphorylate some substrates that can be phosphorylated by PKCK2α in isolation. The present work explores the structural basis of this feature using computational analysis and modeling. Results We have initially built a model of PKCK2α bound to a substrate peptide with a conformation identical to that of the substrates in the available crystal structures of other kinases complexed with the substrates/ pseudosubstrates. In this model however, the fourth acidic residue in the consensus pattern of the substrate, S/T-X-X-D/E where S/T is the phosphorylation site, did not result in interaction with the active form of PKCK2α and is highly solvent exposed. Interaction of the acidic residue is observed if the substrate peptide adopts conformations as seen in β turn, α helix, or 310 helices. This type of conformation is observed and accommodated well by PKCK2α in calmodulin where the phosphorylation site is at the central helix. PP2A carries sequence patterns for PKCK2α phosphorylation. While the possibility of PP2A being phosphorylated by PKCK2 has been raised in the literature we use the model of PP2A to generate a model of PP2A-PKCK2α complex. PKCK2β undergoes phosphorylation by holoenzyme at the N-terminal region, and is accommodated very well in the limited space available at the substrate-binding site of the holoenzyme while the space is insufficient to accommodate the binding of PP2A or calmodulin in the holoenzyme. Conclusion Charge and shape complimentarity seems to play a role in substrate recognition and binding to PKCK2α, along with the consensus

  10. 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 in...... 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...

  11. Peptides derived from human galectin-3 N-terminal tail interact with its carbohydrate recognition domain in a phosphorylation-dependent manner

    Energy Technology Data Exchange (ETDEWEB)

    Berbís, M. Álvaro [Chemical and Physical Biology Department, Centro de Investigaciones Biológicas, CSIC, 28040 Madrid (Spain); André, Sabine [Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians University, 80539 Munich (Germany); Cañada, F. Javier [Chemical and Physical Biology Department, Centro de Investigaciones Biológicas, CSIC, 28040 Madrid (Spain); Pipkorn, Rüdiger [Central Peptide Synthesis Unit, German Cancer Research Center, 69120 Heidelberg (Germany); Ippel, Hans [Department of Biochemistry, CARIM, University of Maastricht, Maastricht (Netherlands); Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455 (United States); Mayo, Kevin H. [Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455 (United States); Kübler, Dieter [Biomolecular Interactions, German Cancer Research Center, 69120 Heidelberg (Germany); Gabius, Hans-Joachim [Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians University, 80539 Munich (Germany); Jiménez-Barbero, Jesús, E-mail: jjbarbero@cib.csic.es [Chemical and Physical Biology Department, Centro de Investigaciones Biológicas, CSIC, 28040 Madrid (Spain)

    2014-01-03

    Highlights: •Galectin-3 is composed of a carbohydrate recognition domain and an N-terminal tail. •Synthetic peptides derived from the tail are shown to interact with the CRD. •This interaction is modulated by Ser- and Tyr-phosphorylation of the peptides. -- Abstract: Galectin-3 (Gal-3) is a multi-functional effector protein that functions in the cytoplasm and the nucleus, as well as extracellularly following non-classical secretion. Structurally, Gal-3 is unique among galectins with its carbohydrate recognition domain (CRD) attached to a rather long N-terminal tail composed mostly of collagen-like repeats (nine in the human protein) and terminating in a short non-collagenous terminal peptide sequence unique in this lectin family and not yet fully explored. Although several Ser and Tyr sites within the N-terminal tail can be phosphorylated, the physiological significance of this post-translational modification remains unclear. Here, we used a series of synthetic (phospho)peptides derived from the tail to assess phosphorylation-mediated interactions with {sup 15}N-labeled Gal-3 CRD. HSQC-derived chemical shift perturbations revealed selective interactions at the backface of the CRD that were attenuated by phosphorylation of Tyr 107 and Tyr 118, while phosphorylation of Ser 6 and Ser 12 was essential. Controls with sequence scrambling underscored inherent specificity. Our studies shed light on how phosphorylation of the N-terminal tail may impact on Gal-3 function and prompt further studies using phosphorylated full-length protein.

  12. Peptides derived from human galectin-3 N-terminal tail interact with its carbohydrate recognition domain in a phosphorylation-dependent manner

    International Nuclear Information System (INIS)

    Highlights: •Galectin-3 is composed of a carbohydrate recognition domain and an N-terminal tail. •Synthetic peptides derived from the tail are shown to interact with the CRD. •This interaction is modulated by Ser- and Tyr-phosphorylation of the peptides. -- Abstract: Galectin-3 (Gal-3) is a multi-functional effector protein that functions in the cytoplasm and the nucleus, as well as extracellularly following non-classical secretion. Structurally, Gal-3 is unique among galectins with its carbohydrate recognition domain (CRD) attached to a rather long N-terminal tail composed mostly of collagen-like repeats (nine in the human protein) and terminating in a short non-collagenous terminal peptide sequence unique in this lectin family and not yet fully explored. Although several Ser and Tyr sites within the N-terminal tail can be phosphorylated, the physiological significance of this post-translational modification remains unclear. Here, we used a series of synthetic (phospho)peptides derived from the tail to assess phosphorylation-mediated interactions with 15N-labeled Gal-3 CRD. HSQC-derived chemical shift perturbations revealed selective interactions at the backface of the CRD that were attenuated by phosphorylation of Tyr 107 and Tyr 118, while phosphorylation of Ser 6 and Ser 12 was essential. Controls with sequence scrambling underscored inherent specificity. Our studies shed light on how phosphorylation of the N-terminal tail may impact on Gal-3 function and prompt further studies using phosphorylated full-length protein

  13. Association of CK2 with Polycomb complexes and its functional implications

    OpenAIRE

    Chandler, H.

    2013-01-01

    Polycomb group (PcG) proteins are important for establishing the patterns of gene expression in different cell types and are critical for the maintenance of pluripotency. They participate in multi-component complexes, such as Polycomb repressive complex 1 (PRC1), which modify, and bind to, histone tails. A number of auxiliary proteins consistently associate with PRC1, including the three subunits of protein kinase CK2 (CK2). The work described in this thesis investigates the interaction of CK...

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

    Science.gov (United States)

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

    2015-11-01

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

  16. 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.

  17. The Role of Protein Kinase CK2 in Glioblastoma Development

    OpenAIRE

    Ji, Haitao; Lu, Zhimin

    2013-01-01

    Glioblastoma (GBM) is the most prevalent and malignant primary brain tumor in adults, and its response to current therapies is limited. Protein kinase CK2 is overexpressed in GBM and regulates GBM cell survival, proliferation, and migration and brain tumorigenesis. Targeting CK2 for GBM treatment may benefit GBM patients.

  18. 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 as...

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

    Science.gov (United States)

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

    2015-01-01

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

  20. 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.

  1. 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; Issinger, O G

    2001-01-01

    The crystal structure of a fully active form of human protein kinase CK2 (casein kinase 2) consisting of two C-terminally truncated catalytic and two regulatory subunits has been determined at 3.1 A resolution. In the CK2 complex the regulatory subunits form a stable dimer linking the two catalyt...

  2. 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.

  3. 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; Larsen, Martin Røssel; Højrup, P; Boldyreff, 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...

  4. CK2 Phosphorylates and Inhibits TAp73 Tumor Suppressor Function to Promote Expression of Cancer Stem Cell Genes and Phenotype in Head and Neck Cancer

    Directory of Open Access Journals (Sweden)

    Hai Lu

    2014-10-01

    Full Text Available Cancer stem cells (CSC and genes have been linked to cancer development and therapeutic resistance, but the signaling mechanisms regulating CSC genes and phenotype are incompletely understood. CK2 has emerged as a key signal serine/threonine kinase that modulates diverse signal cascades regulating cell fate and growth. We previously showed that CK2 is often aberrantly expressed and activated in head and neck squamous cell carcinomas (HNSCC, concomitantly with mutant (mt tumor suppressor TP53, and inactivation of its family member, TAp73. Unexpectedly, we observed that classical stem cell genes Nanog, Sox2, and Oct4, are overexpressed in HNSCC with inactivated TAp73 and mtTP53. However, the potential relationship between CK2, TAp73 inactivation, and CSC phenotype is unknown. We reveal that inhibition of CK2 by pharmacologic inhibitors or siRNA inhibits the expression of CSC genes and side population (SP, while enhancing TAp73 mRNA and protein expression. Conversely, CK2 inhibitor attenuation of CSC protein expression and the SP by was abrogated by TAp73 siRNA. Bioinformatic analysis uncovered a single predicted CK2 threonine phosphorylation site (T27 within the N-terminal transactivation domain of TAp73. Nuclear CK2 and TAp73 interaction, confirmed by co-immunoprecipitation, was attenuated by CK2 inhibitor, or a T27A point-mutation of this predicted CK2 threonine phospho-acceptor site of TAp73. Further, T27A mutation attenuated phosphorylation, while enhancing TAp73 function in repressing CSC gene expression and SP cells. A new CK2 inhibitor, CX-4945, inhibited CSC related SP cells, clonogenic survival, and spheroid formation. Our study unveils a novel regulatory mechanism whereby aberrant CK2 signaling inhibits TAp73 to promote the expression of CSC genes and phenotype.

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

    International Nuclear Information System (INIS)

    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 (IC50) 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 (Hbind) is driven by intermolecular electrostatic interactions involving the triazole/imidazole ring, as indicated by a strong correlation between Hbind and ligand pKa. 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

  6. The Rice CK2 Kinase Regulates Trafficking of Phosphate Transporters in Response to Phosphate Levels[OPEN

    Science.gov (United States)

    Chen, Jieyu; Wang, Yifeng; Wang, Fei; Yang, Jian; Gao, Mingxing; Li, Changying; Liu, Yingyao; Liu, Yu; Yamaji, Naoki; Ma, Jian Feng; Paz-Ares, Javier; Nussaume, Laurent; Zhang, Shuqun; Yi, Keke; Wu, Zhongchang; Wu, Ping

    2015-01-01

    Phosphate transporters (PTs) mediate phosphorus uptake and are regulated at the transcriptional and posttranslational levels. In one key mechanism of posttranslational regulation, phosphorylation of PTs affects their trafficking from the endoplasmic reticulum (ER) to the plasma membrane. However, the kinase(s) mediating PT phosphorylation and the mechanism leading to ER retention of phosphorylated PTs remain unclear. In this study, we identified a rice (Oryza sativa) kinase subunit, CK2β3, which interacts with PT2 and PT8 in a yeast two-hybrid screen. Also, the CK2α3/β3 holoenzyme phosphorylates PT8 under phosphate-sufficient conditions. This phosphorylation inhibited the interaction of PT8 with PHOSPHATE TRANSPORTER TRAFFIC FACILITATOR1, a key cofactor regulating the exit of PTs from the ER to the plasma membrane. Additionally, phosphorus starvation promoted CK2β3 degradation, relieving the negative regulation of PT phosphorus-insufficient conditions. In accordance, transgenic expression of a nonphosphorylatable version of OsPT8 resulted in elevated levels of that protein at the plasma membrane and enhanced phosphorus accumulation and plant growth under various phosphorus regimes. Taken together, these results indicate that CK2α3/β3 negatively regulates PTs and phosphorus status regulates CK2α3/β3. PMID:25724641

  7. 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

    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 product p53 (amino acids 264-393 which also harbors the CK2beta interaction site at amino acids 287-340) mimicked the polylysine effect in all respects, ie. stimulation of phosphate incorporation by CK2 holoenzyme and inhibition in the presence of the catalytic CK2 alpha-subunit. Stimulation...... by p53(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...

  8. 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.

  9. 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...... target CK2 or other kinases with this property....

  10. Involvement of Plasmodium falciparum protein kinase CK2 in the chromatin assembly pathway

    Directory of Open Access Journals (Sweden)

    Dastidar Eeshita G

    2012-01-01

    Full Text Available Abstract Background Protein kinase CK2 is a pleiotropic serine/threonine protein kinase with hundreds of reported substrates, and plays an important role in a number of cellular processes. The cellular functions of Plasmodium falciparum CK2 (PfCK2 are unknown. The parasite's genome encodes one catalytic subunit, PfCK2α, which we have previously shown to be essential for completion of the asexual erythrocytic cycle, and two putative regulatory subunits, PfCK2β1 and PfCK2β2. Results We now show that the genes encoding both regulatory PfCK2 subunits (PfCK2β1 and PfCK2β2 cannot be disrupted. Using immunofluorescence and electron microscopy, we examined the intra-erythrocytic stages of transgenic parasite lines expressing hemagglutinin (HA-tagged catalytic and regulatory subunits (HA-CK2α, HA-PfCK2β1 or HA-PfCK2β2, and localized all three subunits to both cytoplasmic and nuclear compartments of the parasite. The same transgenic parasite lines were used to purify PfCK2β1- and PfCK2β2-containing complexes, which were analyzed by mass spectrometry. The recovered proteins were unevenly distributed between various pathways, with a large proportion of components of the chromatin assembly pathway being present in both PfCK2β1 and PfCK2β2 precipitates, implicating PfCK2 in chromatin dynamics. We also found that chromatin-related substrates such as nucleosome assembly proteins (Naps, histones, and two members of the Alba family are phosphorylated by PfCK2α in vitro. Conclusions Our reverse-genetics data show that each of the two regulatory PfCK2 subunits is required for completion of the asexual erythrocytic cycle. Our interactome study points to an implication of PfCK2 in many cellular pathways, with chromatin dynamics being identified as a major process regulated by PfCK2. This study paves the way for a kinome-wide interactomics-based approach to elucidate protein kinase function in malaria parasites.

  11. 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.

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

    Science.gov (United States)

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

    2008-02-28

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

  13. 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.

  14. Crystal structure of a C-terminal deletion mutant of human protein kinase CK2 catalytic subunit

    DEFF Research Database (Denmark)

    Ermakova, Inessa; Boldyreff, Brigitte; Issinger, Olaf-Georg; Niefind, Karsten

    2003-01-01

    Protein kinase CK2 (formerly called: casein kinase 2) is a heterotetrameric enzyme composed of two separate catalytic chains (CK2alpha) and a stable dimer of two non-catalytic subunits (CK2beta). CK2alpha is a highly conserved member of the superfamily of eukaryotic protein kinases. The crystal s...

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

    DEFF Research Database (Denmark)

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

    1998-01-01

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

  16. CK2 activity is modulated by growth rate in Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Research highlights: → CK2 subunits are nuclear both in glucose and in ethanol growing yeast cells. → CK2 activity is modulated in S. cerevisiae. → CK2 activity is higher in conditions supporting higher growth rates. → Vmax is higher in faster growing cells, while Km is not affected. -- Abstract: CK2 is a highly conserved protein kinase controlling different cellular processes. It shows a higher activity in proliferating mammalian cells, in various types of cancer cell lines and tumors. The findings presented herein provide the first evidence of an in vivo modulation of CK2 activity, dependent on growth rate, in Saccharomyces cerevisiae. In fact, CK2 activity, assayed on nuclear extracts, is shown to increase in exponential growing batch cultures at faster growth rate, while localization of catalytic and regulatory subunits is not nutritionally modulated. Differences in intracellular CK2 activity of glucose- and ethanol-grown cells appear to depend on both increase in molecule number and kcat. Also in chemostat cultures nuclear CK2 activity is higher in faster growing cells providing the first unequivocal demonstration that growth rate itself can affect CK2 activity in a eukaryotic organism.

  17. Protein kinase CK2 inhibition induces cell death via early impact on mitochondrial function*

    Science.gov (United States)

    Qaiser, Fatima; Trembley, Janeen H.; Kren, Betsy T.; Wu, Jing-Jiang; Naveed, A. Khaliq; Ahmed, Khalil

    2014-01-01

    CK2 (official acronym for casein kinase 2 or II) is a potent suppressor of apoptosis in response to diverse apoptotic stimuli —thus its molecular downregulation or activity inhibition results in potent induction of cell death. CK2 downregulation is known to impact mitochondrial apoptotic circuitry but the underlying mechanism(s) remain unclear. Utilizing prostate cancer cell lines subjected to CK2-specific inhibitors which cause loss of cell viability, we have found that CK2 inhibition in cells causes rapid early decrease in mitochondrial membrane potential (Δψm). Cells treated with the CK2 inhibitors TBB (4,5,6,7-tetrabromobenzotriazole) or TBCA (tetrabromocinnamic acid) demonstrate changes in Δψm which become apparent within 2 h, i.e., significantly prior to evidence of activation of other mitochondrial apoptotic signals whose temporal expression ensues subsequent to loss of Δψm. Further, we have demonstrated the presence of CK2 in purified mitochondria and it appears that the effect on Δψm evoked by inhibition of CK2 may involve mitochondrial localized CK2. Results also suggest that alterations in Ca2+ signaling may be involved in the CK2 mediated regulation of Δψm and mitochondrial permeability. Thus, we propose that a key mechanism of CK2 impact on mitochondrial apoptotic circuitry and cell death involves early loss of Δψm which may be a primary trigger for apoptotic signaling and cell death resulting from CK2 inhibition. PMID:25043911

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

    Science.gov (United States)

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

    2014-05-01

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

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

    DEFF Research Database (Denmark)

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

    1998-01-01

    The catalytic (alpha) subunit of protein kinase CK2 (CK2alpha) was originally cloned and overexpressed in the Escherichia coli strain pT7-7/BL21(DE3). The protein has been purified to homogeneity and crystallized. The crystals belong to the monoclinic space group C2, they have unit-cell parameters...

  20. 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...

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

    DEFF Research Database (Denmark)

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

    1993-01-01

    CKIIB, one of the CK-2 like enzymes which have been isolated from maize, has been shown to be a monomeric enzyme that cross-reacts with anti CK-2 alpha specific antibodies suggesting a possible relationship between the two proteins (Dobrowolska et al. (1992) Eur. J. Biochem. 204, 299-303). In ord...

  2. 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...

  3. Isoform-specific phosphorylation-dependent regulation of connexin hemichannels

    DEFF Research Database (Denmark)

    Alstrøm, Jette Skov; Hansen, Daniel Bloch; Nielsen, Morten Schak;

    2015-01-01

    Connexins form gap junction channels made up of two connexons (hemichannels) from adjacent cells. Unopposed hemichannels may open toward the extracellular space upon stimulation by, e.g., removal of divalent cations from the extracellular solution and allow isoform-specific transmembrane flux of...... fluorescent dyes and physiologically relevant molecules, such as ATP and ions. Connexin (Cx)43 and Cx30 are the major astrocytic connexins. Protein kinase C (PKC) regulates Cx43 in its cell-cell gap junction configuration and may also act to keep Cx43 hemichannels closed. In contrast, the regulation of Cx30...... hemichannels by PKC is unexplored. To determine phosphorylation-dependent regulation of Cx30 and Cx43 hemichannels, these were heterologously expressed in Xenopus laevis oocytes and opened with divalent cation-free solution. Inhibition of PKC activity did not affect hemichannel opening of either connexin. PKC...

  4. 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...... beta gene. Both genes contain a first untranslated exon. Also, the promoter regions from the human and murine CK2 beta gene share some common features, e.g., they contain neither a TATA nor a CAAT box, exon 1 is flanked by a cluster of CpG dinucleotides and recognition sequences for the Hpa...... has no counterpart in the murine gene. Hence, regulation of transcription of the CK2 beta gene by the catalytic CK2 alpha subunit as was described by Robitzki et al. (J. Biol. Chem. 268: 5694-5703, 1993) for the human gene cannot be considered a general regulatory mechanism....

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

    Directory of Open Access Journals (Sweden)

    Elaine M Smith

    2008-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Aron Szabó

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

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

    Science.gov (United States)

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

    2013-07-01

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

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

    OpenAIRE

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

    2009-01-01

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

  9. Asymmetric expression of protein kinase CK2 subunits in human kidney tumors

    DEFF Research Database (Denmark)

    Stalter, G; Siemer, S; Becht, E; Ziegler, M; Remberger, K; Issinger, O G

    1994-01-01

    of protein kinase CK2 alpha in tumors/normal tissue (T/N) was 1.58 and that of the protein kinase CK2 beta (T/N) was 2.65. The data suggest that the generally described increase in protein kinase CK2 activity in tumor cells may to some extent result from a deregulation in subunit biosynthesis or...... degradation. This at least partly owing to the presence of excess enzymatically active protein kinase alpha-subunit but also to a significantly higher presence of the non-catalytic beta-subunit....

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  11. 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

    Screening a natural compound library led to the identification of resorufin as a highly selective and potent inhibitor of protein kinase CK2. Out of 52 kinases tested, only CK2 was inhibited, in contrast to emodin, a structurally related, known CK2 inhibitor that, in addition to CK2, inhibited ten...... 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...... 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...

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

    Science.gov (United States)

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

    2012-02-01

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

  13. 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.

  14. 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.

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

    Science.gov (United States)

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

    2011-10-01

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

  16. 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....

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

    Science.gov (United States)

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

    2006-04-20

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

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

    OpenAIRE

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

    2009-01-01

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

  19. 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...

  20. 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, signa...

  1. 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...

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

    DEFF Research Database (Denmark)

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

    1996-01-01

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

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

    DEFF Research Database (Denmark)

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

    1995-01-01

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

  4. Regulation of DNA Methylation Patterns by CK2-Mediated Phosphorylation of Dnmt3a

    Directory of Open Access Journals (Sweden)

    Rachel Deplus

    2014-08-01

    Full Text Available DNA methylation is a central epigenetic modification that is established by de novo DNA methyltransferases. The mechanisms underlying the generation of genomic methylation patterns are still poorly understood. Using mass spectrometry and a phosphospecific Dnmt3a antibody, we demonstrate that CK2 phosphorylates endogenous Dnmt3a at two key residues located near its PWWP domain, thereby downregulating the ability of Dnmt3a to methylate DNA. Genome-wide DNA methylation analysis shows that CK2 primarily modulates CpG methylation of several repeats, most notably of Alu SINEs. This modulation can be directly attributed to CK2-mediated phosphorylation of Dnmt3a. We also find that CK2-mediated phosphorylation is required for localization of Dnmt3a to heterochromatin. By revealing phosphorylation as a mode of regulation of de novo DNA methyltransferase function and by uncovering a mechanism for the regulation of methylation at repetitive elements, our results shed light on the origin of DNA methylation patterns.

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Sung Won Lee

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

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

    DEFF Research Database (Denmark)

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

    1995-01-01

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

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

    OpenAIRE

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

    2015-01-01

    Intracellular circadian clocks, composed of clock genes that act in transcription-translation feedback loops, drive global rhythmic expression of the mammalian transcriptome and allow an organism to anticipate to the momentum of the day. Using a novel clock-perturbing peptide, we established a pivotal role for casein kinase (CK)-2-mediated circadian BMAL1-Ser90 phosphorylation (BMAL1-P) in regulating central and peripheral core clocks. Subsequent analysis of the underlying mechanism showed a ...

  9. Phosphorylation by CK2 and MAPK enhances calnexin association with ribosomes.

    Science.gov (United States)

    Chevet, E; Wong, H N; Gerber, D; Cochet, C; Fazel, A; Cameron, P H; Gushue, J N; Thomas, D Y; Bergeron, J J

    1999-07-01

    Calnexin was initially identified as an endoplasmic reticulum (ER) type I integral membrane protein, phosphorylated on its cytosolic domain by ER-associated protein kinases. Although the role of the ER luminal domain of calnexin has been established as a constituent of the molecular chaperone machinery of the ER, less is known about the role of the cytosolic phosphorylation of calnexin. Analysis by two-dimensional phosphopeptide maps revealed that calnexin was in vitro phosphorylated in isolated microsomes by casein kinase 2 (CK2) and extracellular-signal regulated kinase-1 (ERK-1) at sites corresponding to those for in vivo phosphorylation. In canine pancreatic microsomes, synergistic phosphorylation by CK2 and ERK-1 led to increased association of calnexin with membrane-bound ribosomes. In vivo, calnexin-associated ERK-1 activity was identified by co-immunoprecipitation. This activity was abolished in cells expressing a dominant-negative MEK-1. Activation of ERK-1 in cells by addition of serum led to a 4-fold increase in ribosome-associated calnexin over unstimulated cells. Taken together with studies revealing calnexin association with CK2 and ERK-1, a model is proposed whereby phosphorylation of calnexin leads to a potential increase in glycoprotein folding close to the translocon. PMID:10393181

  10. Potent and Selective CK2 Kinase Inhibitors with Effects on Wnt Pathway Signaling in Vivo.

    Science.gov (United States)

    Dowling, James E; Alimzhanov, Marat; Bao, Larry; Chuaqui, Claudio; Denz, Christopher R; Jenkins, Emma; Larsen, Nicholas A; Lyne, Paul D; Pontz, Timothy; Ye, Qing; Holdgate, Geoff A; Snow, Lindsay; O'Connell, Nichole; Ferguson, Andrew D

    2016-03-10

    The Wnt pathway is an evolutionarily conserved and tightly regulated signaling network with important roles in embryonic development and adult tissue regeneration. Impaired Wnt pathway regulation, arising from mutations in Wnt signaling components, such as Axin, APC, and β-catenin, results in uncontrolled cell growth and triggers oncogenesis. To explore the reported link between CK2 kinase activity and Wnt pathway signaling, we sought to identify a potent, selective inhibitor of CK2 suitable for proof of concept studies in vivo. Starting from a pyrazolo[1,5-a]pyrimidine lead (2), we identified compound 7h, a potent CK2 inhibitor with picomolar affinity that is highly selectivity against other kinase family enzymes and inhibits Wnt pathway signaling (IC50 = 50 nM) in DLD-1 cells. In addition, compound 7h has physicochemical properties that are suitable for formulation as an intravenous solution, has demonstrated good pharmacokinetics in preclinical species, and exhibits a high level of activity as a monotherapy in HCT-116 and SW-620 xenografts. PMID:26985319

  11. 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; Dobritsa, Anna A; Evstafieva, Alexandra G; Boldyreff, Brigitte; Issinger, Olaf-Georg; Gvozdev, Vladimir A

    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)tes-beta......-galactosidase fusion protein driven by the CK2(beta)tes promoter was found in transgenic flies at postmitotic stages of spermatogenesis. Examination of biochemical characteristics of a recombinant CK2(beta)tes protein expressed in Escherichia coli revealed properties similar to those of CK2beta: (a) CK2(beta......)tes protein stimulates CK2alpha catalytic activity toward synthetic peptide; (b) it inhibits phosphorylation of calmodulin and mediates stimulation of CK2alpha by polylysine; (c) it is able to form (CK2(beta)tes)2 dimers, as well as (CK2alpha)2(CK2(beta)tes)2 tetramers. Using the yeast two-hybrid system and...

  12. 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.

  13. Quantitative analysis of a phosphoproteome readily altered by the protein kinase CK2 inhibitor quinalizarin in HEK-293T cells.

    Science.gov (United States)

    Franchin, Cinzia; Cesaro, Luca; Salvi, Mauro; Millioni, Renato; Iori, Elisabetta; Cifani, Paolo; James, Peter; Arrigoni, Giorgio; Pinna, Lorenzo

    2015-06-01

    CK2 is an extremely pleiotropic Ser/Thr protein kinase, responsible for the generation of a large proportion of the human phosphoproteome and implicated in a wide variety of biological functions. CK2 plays a global role as an anti-apoptotic agent, a property which is believed to partially account for the addiction of many cancer cells to high CK2 levels. To gain information about the CK2 targets whose phosphorylation is primarily implicated in its pro-survival signaling advantage has been taken of quinalizarin (QZ) a cell permeable fairly specific CK2 inhibitor, previously shown to be able to block endogenous CK2 triggering an apoptotic response. HEK-293T cells either treated or not for 3h with 50μM QZ were exploited to perform a quantitative SILAC phosphoproteomic analysis of phosphosites readily responsive to QZ treatment. Our analysis led to the identification of 4883 phosphosites, belonging to 1693 phosphoproteins. 71 phosphosites (belonging to 47 proteins) underwent a 50% or more decreased occupancy upon QZ treatment. Almost 50% of these fulfilled the typical consensus sequence recognized by CK2 (S/T-x-x-E/D/pS) and in several cases were validated as bona fide substrates of CK2 either based on data in the literature or by performing in vitro phosphorylation experiments with purified proteins. The majority of the remaining phosphosites drastically decreased upon QZ treatment display the pS/T-P motif typical of proline directed protein kinases and a web logo extracted from them differentiates from the web logo extracted from all the proline directed phosphosites quantified during our analysis (1151 altogether). A paradoxical outcome of our study was the detection of 116 phosphosites (belonging to 92 proteins altogether) whose occupancy is substantially increased (50% or more), rather than decreased by QZ treatment: 40% of these display the typical motif recognized by proline directed kinases, while about 25% fulfill the CK2 consensus. Collectively taken our

  14. Proteomic Analysis of Calcium- and Phosphorylation-dependentCalmodulin Complexes in Mammalian Cells

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Deok-Jin; Wang, Daojing

    2006-05-26

    Protein conformational changes due to cofactor binding (e.g. metal ions, heme) and/or posttranslational modifications (e.g. phosphorylation) modulate dynamic protein complexes. Calmodulin (CaM) plays an essential role in regulating calcium (Ca{sup 2+}) signaling and homeostasis. No systematic approach on the identification of phosphorylation-dependent Ca{sup 2+}/CaM binding proteins has been published. Herein, we report a proteome-wide study of phosphorylation-dependent CaM binding proteins from mammalian cells. This method, termed 'Dynamic Phosphoprotein Complex Trapping', 'DPPC Trapping' for short, utilizes a combination of in vivo and in vitro assays. The basic strategy is to drastically shift the equilibrium towards endogenous phosphorylation of Ser, Thr, and Tyr at the global scale by inhibiting corresponding phosphatases in vivo. The phosphorylation-dependent calmodulin-binding proteins are then trapped in vitro in a Ca{sup 2+}-dependent manner by CaM-Sepharose chromatography. Finally, the isolated calmodulin-binding proteins are separated by SDS-PAGE and identified by LC/MS/MS. In parallel, the phosphorylation-dependent binding is visualized by silver staining and/or Western blotting. Using this method, we selectively identified over 120 CaM-associated proteins including many previously uncharacterized. We verified ubiquitin-protein ligase EDD1, inositol 1, 4, 5-triphosphate receptor type 1 (IP{sub 3}R1), and ATP-dependent RNA helicase DEAD box protein 3 (DDX3), as phosphorylation-dependent CaM binding proteins. To demonstrate the utilities of our method in understanding biological pathways, we showed that pSer/Thr of IP{sub 3}R1 in vivo by staurosporine-sensitive kinase(s), but not by PKA/PKG/PKC, significantly reduced the affinity of its Ca{sup 2+}-dependent CaM binding. However, pSer/Thr of IP{sub 3}R1 did not substantially affect its Ca{sup 2+}-independent CaM binding. We further showed that phosphatase PP1, but not PP2A or PP2B

  15. 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

    The Ser/Thr kinase CK2 (former name: casein kinase 2) is a heterotetrameric enzyme composed of two catalytic chains (CK2alpha) attached to a dimer of noncatalytic subunits. Together with the cyclin-dependent kinases and the mitogen-activated protein kinases, CK2alpha belongs to the CMGC family of...

  16. 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.

  17. 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.

  18. 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.

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

    Science.gov (United States)

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

    2004-10-12

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

  20. 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.

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

    Science.gov (United States)

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

    2007-01-01

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

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

    Science.gov (United States)

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

    2011-12-01

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

  3. Ability of CK2beta to selectively regulate cellular protein kinases

    DEFF Research Database (Denmark)

    Olsen, Birgitte; Guerra, Barbara

    2008-01-01

    The Wee1 protein kinase plays a prominent role in keeping cyclin dependent kinase 1 (CDK1) inactive during the G2 phase of the cell cycle. At the onset of mitosis, Wee1 is ubiquitinated by the E3 ubiquitin ligase SCF(beta-TrCP) and subsequently degraded by the proteasome machinery. Previously, it...... 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...

  4. 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; Jensen, Hans H; Pointu, Hervé; Olsen, Birgitte B; Cochet, Claude; Issinger, Olaf-Georg; Boldyreff, Brigitte

    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...... mice leads to postimplantation lethality. Mutant embryos were reduced in size at embryonic day 6.5 (E6.5). They did not exhibit signs of apoptosis but did show reduced cell proliferation. Mutant embryos were resorbed at E7.5. In vitro, CK2beta(-/-) morula development stopped after the blastocyst stage....... Attempts to generate homozygous embryonic stem (ES) cells failed. By using a conditional knockout approach, we show that lack of CK2beta is deleterious for mouse ES cells and primary embryonic fibroblasts. This is in contrast to what occurs with yeast cells, which can survive without functional CK2beta...

  5. The Phosphorylation-Dependent Regulation of Mitochondrial Proteins in Stress Responses

    Directory of Open Access Journals (Sweden)

    Yusuke Kanamaru

    2012-01-01

    Full Text Available To maintain cellular homeostasis, cells are equipped with precise systems that trigger the appropriate stress responses. Mitochondria not only provide cellular energy but also integrate stress response signaling pathways, including those regulating cell death. Several lines of evidence suggest that the mitochondrial proteins that function in this process, such as Bcl-2 family proteins in apoptosis and phosphoglycerate mutase family member 5 (PGAM5 in necroptosis, are regulated by several kinases. It has also been suggested that the phosphorylation-dependent regulation of mitochondrial fission machinery, dynamin-related protein 1 (Drp1, facilitates appropriate cellular stress responses. However, mitochondria themselves are also damaged by various stresses. To avoid the deleterious effects exerted by damaged mitochondria, cells remove these mitochondria in a selective autophagic degradation process called mitophagy. Interestingly, several kinases, such as PTEN-induced putative kinase 1 (PINK1 in mammals and stress-responsive mitogen-activated protein (MAP kinases in yeast, have recently been shown to be involved in mitophagy. In this paper, we focus on the phosphorylation-dependent regulation of mitochondrial proteins and discuss the roles of this regulation in the mitochondrial and cellular stress responses.

  6. 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.

  7. An in vitro ES cell-based clock recapitulation assay model identifies CK2α as an endogenous clock regulator.

    Science.gov (United States)

    Umemura, Yasuhiro; Yoshida, Junko; Wada, Masashi; Tsuchiya, Yoshiki; Minami, Yoichi; Watanabe, Hitomi; Kondoh, Gen; Takeda, Junji; Inokawa, Hitoshi; Horie, Kyoji; Yagita, Kazuhiro

    2013-01-01

    We previously reported emergence and disappearance of circadian molecular oscillations during differentiation of mouse embryonic stem (ES) cells and reprogramming of differentiated cells, respectively. Here we present a robust and stringent in vitro circadian clock formation assay that recapitulates in vivo circadian phenotypes. This assay system first confirmed that a mutant ES cell line lacking Casein Kinase I delta (CKIδ) induced ∼3 hours longer period-length of circadian rhythm than the wild type, which was compatible with recently reported results using CKIδ null mice. In addition, this assay system also revealed that a Casein Kinase 2 alpha subunit (CK2α) homozygous mutant ES cell line developed significantly longer (about 2.5 hours) periods of circadian clock oscillations after in vitro or in vivo differentiation. Moreover, revertant ES cell lines in which mutagenic vector sequences were deleted showed nearly wild type periods after differentiation, indicating that the abnormal circadian period of the mutant ES cell line originated from the mutation in the CK2α gene. Since CK2α deficient mice are embryonic lethal, this in vitro assay system represents the genetic evidence showing an essential role of CK2α in the mammalian circadian clock. This assay was successfully applied for the phenotype analysis of homozygous mutant ES cells, demonstrating that an ES cell-based in vitro assay is available for circadian genetic screening. PMID:23840637

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

    DEFF Research Database (Denmark)

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

    1992-01-01

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

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

    Science.gov (United States)

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

    2003-01-17

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

  10. Casein kinase Ⅱ interacts with prion protein in vitro and forms complex with na-tive prion protein in vivo

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The most essential and crucial step during the pathogenesis of transmissible spongiform encephalopathy is the conformational change of cellular prion protein to pathologic isoform. Casein kinase Ⅱ (CK2) is a ubiquitously expressed and evolutiouarily conserved pleiotropic protein kinase that is essential for viability. To explore the possible molecular interaction between CK2 and prion protein (PrP), the full-length sequences of human CK2α and CK2β complementary DNA were amplified with reverse transcription-polymerase chain reaction using the total messenger RNA from cell line SH-SY5Y as the template; then, the fusion proteins histidine-CK2α and glutathione S-transferase-histidine-CK2β were expressed in Escherichia coll. The interaction between CK2 and PrP was evaluated with co-immunoprecipi-tation and pull-down assays. The results demonstrated that recombinant PrP bound specifically with CK2α, but not with CK2β. The native CK2 and PrP in hamster brains interacted with each other, forming protein complexes. Three different glycosylated forms of PrP (diglycosylated, monoglycosylated and unglycosylated PrP) from normal brains interacted with the CK2α subunit, though the unglycosylated PrP seemed to have a stronger binding ability with CK2α subunit. The domain responsible for interacting with CK2α was located at the C-terminal segment of PrP (residues 91-231). This study proposed reliable experimental data for the molecular interaction between PrP and CK2α (both in recombinant and native categories), scientific clues for further assessing the potential biological significance of the PrP-CK2 interaction, and the possible role of CK2 in the pathogenesis of prion diseases.

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

    KAUST Repository

    Bigeard, Jean

    2014-07-10

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

  12. 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

    ) after separation by anionic exchange chromatography (MA7Q, BioRad) of the crude cellular extracts from cisplatin-treated cells, lower CK2 activity was found in the peak fractions confirming the results obtained with crude cellular extracts; (c) besides the detection of CK2 alpha subunit by...

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Laia Armengot

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

  15. Analysis of phosphorylation-dependent protein-protein interactions of histone H3.

    OpenAIRE

    Klingberg, R.; Jost, J.; Schümann, M; Gelato, K.; Fischle, W; Krause, E.; Schwarzer, D

    2015-01-01

    Multiple posttranslational modifications (PTMs) of histone proteins including site-specific phosphorylation of serine and threonine residues govern the accessibility of chromatin. According to the histone code theory, PTMs recruit regulatory proteins or block their access to chromatin. Here, we report a general strategy for simultaneous analysis of both of these effects based on a SILAC MS scheme. We applied this approach for studying the biochemical role of phosphorylated S10 of histone H3. ...

  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

    DMAT, TBB and resorufin differ in their selectivity against PI3K family members, since PI3K and DNA-PK are subject to inhibition by DMAT and TBB, however, not by resorufin. TBB and DMAT treatment together with cisplatin lead to an inhibition of cisplatin-induced stress signaling (as detected...... by phosphorylation of JNK and H2AX). In the case of resorufin no interference with the stress-signaling pathway is observed, supporting the notion that TBB and DMAT interfere with upstream molecules involved in genotoxic stress signaling. We have also tested the protein kinase CK2 inhibitors with respect to cell...

  17. CX-4945, an orally bioavailable selective inhibitor of protein kinase CK2, inhibits prosurvival and angiogenic signaling and exhibits antitumor efficacy.

    Science.gov (United States)

    Siddiqui-Jain, Adam; Drygin, Denis; Streiner, Nicole; Chua, Peter; Pierre, Fabrice; O'Brien, Sean E; Bliesath, Josh; Omori, Mayuko; Huser, Nanni; Ho, Caroline; Proffitt, Chris; Schwaebe, Michael K; Ryckman, David M; Rice, William G; Anderes, Kenna

    2010-12-15

    Malignant transformation and maintenance of the malignant phenotype depends on oncogenic and non-oncogenic proteins that are essential to mediate oncogene signaling and to support the altered physiologic demands induced by transformation. Protein kinase CK2 supports key prosurvival signaling pathways and represents a prototypical non-oncogene. In this study, we describe CX-4945, a potent and selective orally bioavailable small molecule inhibitor of CK2. The antiproliferative activity of CX-4945 against cancer cells correlated with expression levels of the CK2α catalytic subunit. Attenuation of PI3K/Akt signaling by CX-4945 was evidenced by dephosphorylation of Akt on the CK2-specific S129 site and the canonical S473 and T308 regulatory sites. CX-4945 caused cell-cycle arrest and selectively induced apoptosis in cancer cells relative to normal cells. In models of angiogenesis, CX-4945 inhibited human umbilical vein endothelial cell migration, tube formation, and blocked CK2-dependent hypoxia-induced factor 1 alpha (HIF-1α) transcription in cancer cells. When administered orally in murine xenograft models, CX-4945 was well tolerated and demonstrated robust antitumor activity with concomitant reductions of the mechanism-based biomarker phospho-p21 (T145). The observed antiproliferative and anti-angiogenic responses to CX-4945 in tumor cells and endothelial cells collectively illustrate that this compound exerts its antitumor effects through inhibition of CK2-dependent signaling in multiple pathways. Finally, CX-4945 is the first orally bioavailable small molecule inhibitor of CK2 to advance into human clinical trials, thereby paving the way for an entirely new class of targeted treatment for cancer. PMID:21159648

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2013-08-01

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

  1. Ck2-Dependent Phosphorylation Is Required to Maintain Pax7 Protein Levels in Proliferating Muscle Progenitors.

    Directory of Open Access Journals (Sweden)

    Natalia González

    Full Text Available Skeletal muscle regeneration and long term maintenance is directly link to the balance between self-renewal and differentiation of resident adult stem cells known as satellite cells. In turn, satellite cell fate is influenced by a functional interaction between the transcription factor Pax7 and members of the MyoD family of muscle regulatory factors. Thus, changes in the Pax7-to-MyoD protein ratio may act as a molecular rheostat fine-tuning acquisition of lineage identity while preventing precocious terminal differentiation. Pax7 is expressed in quiescent and proliferating satellite cells, while its levels decrease sharply in differentiating progenitors Pax7 is maintained in cells (reacquiring quiescence. While the mechanisms regulating Pax7 levels based on differentiation status are not well understood, we have recently described that Pax7 levels are directly regulated by the ubiquitin-ligase Nedd4, thus promoting proteasome-dependent Pax7 degradation in differentiating satellite cells. Here we show that Pax7 levels are maintained in proliferating muscle progenitors by a mechanism involving casein kinase 2-dependent Pax7 phosphorylation at S201. Point mutations preventing S201 phosphorylation or casein kinase 2 inhibition result in decreased Pax7 protein in proliferating muscle progenitors. Accordingly, this correlates directly with increased Pax7 ubiquitination. Finally, Pax7 down regulation induced by casein kinase 2 inhibition results in precocious myogenic induction, indicating early commitment to terminal differentiation. These observations highlight the critical role of post translational regulation of Pax7 as a molecular switch controlling muscle progenitor fate.

  2. Ck2-Dependent Phosphorylation Is Required to Maintain Pax7 Protein Levels in Proliferating Muscle Progenitors

    Science.gov (United States)

    González, Natalia; Moresco, James J.; Bustos, Francisco; Yates, John R.; Olguín, Hugo C.

    2016-01-01

    Skeletal muscle regeneration and long term maintenance is directly link to the balance between self-renewal and differentiation of resident adult stem cells known as satellite cells. In turn, satellite cell fate is influenced by a functional interaction between the transcription factor Pax7 and members of the MyoD family of muscle regulatory factors. Thus, changes in the Pax7-to-MyoD protein ratio may act as a molecular rheostat fine-tuning acquisition of lineage identity while preventing precocious terminal differentiation. Pax7 is expressed in quiescent and proliferating satellite cells, while its levels decrease sharply in differentiating progenitors Pax7 is maintained in cells (re)acquiring quiescence. While the mechanisms regulating Pax7 levels based on differentiation status are not well understood, we have recently described that Pax7 levels are directly regulated by the ubiquitin-ligase Nedd4, thus promoting proteasome-dependent Pax7 degradation in differentiating satellite cells. Here we show that Pax7 levels are maintained in proliferating muscle progenitors by a mechanism involving casein kinase 2-dependent Pax7 phosphorylation at S201. Point mutations preventing S201 phosphorylation or casein kinase 2 inhibition result in decreased Pax7 protein in proliferating muscle progenitors. Accordingly, this correlates directly with increased Pax7 ubiquitination. Finally, Pax7 down regulation induced by casein kinase 2 inhibition results in precocious myogenic induction, indicating early commitment to terminal differentiation. These observations highlight the critical role of post translational regulation of Pax7 as a molecular switch controlling muscle progenitor fate. PMID:27144531

  3. Identification of a Dual Inhibitor of SRPK1 and CK2 That Attenuates Pathological Angiogenesis of Macular Degeneration in Mice.

    Science.gov (United States)

    Morooka, Satoshi; Hoshina, Mitsuteru; Kii, Isao; Okabe, Takayoshi; Kojima, Hirotatsu; Inoue, Naoko; Okuno, Yukiko; Denawa, Masatsugu; Yoshida, Suguru; Fukuhara, Junichi; Ninomiya, Kensuke; Ikura, Teikichi; Furuya, Toshio; Nagano, Tetsuo; Noda, Kousuke; Ishida, Susumu; Hosoya, Takamitsu; Ito, Nobutoshi; Yoshimura, Nagahisa; Hagiwara, Masatoshi

    2015-08-01

    Excessive angiogenesis contributes to numerous diseases, including cancer and blinding retinopathy. Antibodies against vascular endothelial growth factor (VEGF) have been approved and are widely used in clinical treatment. Our previous studies using SRPIN340, a small molecule inhibitor of SRPK1 (serine-arginine protein kinase 1), demonstrated that SRPK1 is a potential target for the development of antiangiogenic drugs. In this study, we solved the structure of SRPK1 bound to SRPIN340 by X-ray crystallography. Using pharmacophore docking models followed by in vitro kinase assays, we screened a large-scale chemical library, and thus identified a new inhibitor of SRPK1. This inhibitor, SRPIN803, prevented VEGF production more effectively than SRPIN340 owing to the dual inhibition of SRPK1 and CK2 (casein kinase 2). In a mouse model of age-related macular degeneration, topical administration of eye ointment containing SRPIN803 significantly inhibited choroidal neovascularization, suggesting a clinical potential of SRPIN803 as a topical ointment for ocular neovascularization. Thus SRPIN803 merits further investigation as a novel inhibitor of VEGF. PMID:25993998

  4. 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...

  5. 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

    evidence by immunoprecipitation for an association of protein kinase CK2 holoenzyme (alpha2beta2), p53, and the ribosomal protein L5. The results suggest complexes between the CK2 holoenzyme and p53 but also p53/CKbeta complexes. Furthermore we provide evidence for the existence of high molecular mass...

  6. Phosphorylation-Dependent Regulation of the DNA Damage Response of Adaptor Protein KIBRA in Cancer Cells.

    Science.gov (United States)

    Mavuluri, Jayadev; Beesetti, Swarnalatha; Surabhi, Rohan; Kremerskothen, Joachim; Venkatraman, Ganesh; Rayala, Suresh K

    2016-05-01

    Multifunctional adaptor proteins encompassing various protein-protein interaction domains play a central role in the DNA damage response pathway. In this report, we show that KIBRA is a physiologically interacting reversible substrate of ataxia telangiectasia mutated (ATM) kinase. We identified the site of phosphorylation in KIBRA as threonine 1006, which is embedded within the serine/threonine (S/T) Q consensus motif, by site-directed mutagenesis, and we further confirmed the same with a phospho-(S/T) Q motif-specific antibody. Results from DNA repair functional assays such as the γ-H2AX assay, pulsed-field gel electrophoresis (PFGE), Comet assay, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) assay, and clonogenic cell survival assay using stable overexpression clones of wild-type (wt.) KIBRA and active (T1006E) and inactive (T1006A) KIBRA phosphorylation mutants showed that T1006 phosphorylation on KIBRA is essential for optimal DNA double-strand break repair in cancer cells. Further, results from stable retroviral short hairpin RNA-mediated knockdown (KD) clones of KIBRA and KIBRA knockout (KO) model cells generated by a clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 system showed that depleting KIBRA levels compromised the DNA repair functions in cancer cells upon inducing DNA damage. All these phenotypic events were reversed upon reconstitution of KIBRA into cells lacking KIBRA knock-in (KI) model cells. All these results point to the fact that phosphorylated KIBRA might be functioning as a scaffolding protein/adaptor protein facilitating the platform for further recruitment of other DNA damage response factors. In summary, these data demonstrate the imperative functional role of KIBRAper se(KIBRA phosphorylation at T1006 site as a molecular switch that regulates the DNA damage response, possibly via the nonhomologous end joining [NHEJ] pathway), suggesting that KIBRA could be a potential

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

    Directory of Open Access Journals (Sweden)

    Sabrina Manni

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

  8. Phosphorylation-Dependent PIH1D1 Interactions Define Substrate Specificity of the R2TP Cochaperone Complex

    OpenAIRE

    Zuzana Hořejší; Lasse Stach; Thomas G. Flower; Dhira Joshi; Helen Flynn; J. Mark Skehel; Nicola J. O’Reilly; Roksana W. Ogrodowicz; Stephen J. Smerdon; Simon J. Boulton

    2014-01-01

    Summary The R2TP cochaperone complex plays a critical role in the assembly of multisubunit machines, including small nucleolar ribonucleoproteins (snoRNPs), RNA polymerase II, and the mTORC1 and SMG1 kinase complexes, but the molecular basis of substrate recognition remains unclear. Here, we describe a phosphopeptide binding domain (PIH-N) in the PIH1D1 subunit of the R2TP complex that preferentially binds to highly acidic phosphorylated proteins. A cocrystal structure of a PIH-N domain/TEL2 ...

  9. Phosphorylation-Dependent Protein Interaction with Trypanosoma brucei 14-3-3 Proteins that Display Atypical Target Recognition

    OpenAIRE

    Inoue, Masahiro; Yasuda, Kouichi; Uemura, Haruki; Yasaka, Natsumi; Inoue, Hiroshi; Sei, Yoshitatsu; Horikoshi, Nobuo; Fukuma, Toshihide

    2010-01-01

    Background The 14-3-3 proteins are structurally conserved throughout eukaryotes and participate in protein kinase signaling. All 14-3-3 proteins are known to bind to evolutionally conserved phosphoserine-containing motifs (modes 1 and/or 2) with high affinity. In Trypanosoma brucei, 14-3-3I and II play pivotal roles in motility, cytokinesis and the cell cycle. However, none of the T. brucei 14-3-3 binding proteins have previously been documented. Methodology/Principal Findings Initially we sh...

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

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

    OpenAIRE

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

    2007-01-01

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

  12. 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

  13. Identification and characterization of a novel gene, c1orf109, encoding a CK2 substrate that is involved in cancer cell proliferation

    Directory of Open Access Journals (Sweden)

    Liu Shan-shan

    2012-05-01

    Full Text Available Abstract Background In the present study we identified a novel gene, Homo Sapiens Chromosome 1 ORF109 (c1orf109, GenBank ID: NM_017850.1, which encodes a substrate of CK2. We analyzed the regulation mode of the gene, the expression pattern and subcellular localization of the predicted protein in the cell, and its role involving in cell proliferation and cell cycle control. Methods Dual-luciferase reporter assay, chromatin immunoprecipitation and EMSA were used to analysis the basal transcriptional requirements of the predicted promoter regions. C1ORF109 expression was assessed by western blot analysis. The subcellular localization of C1ORF109 was detected by immunofluorescence and immune colloidal gold technique. Cell proliferation was evaluated using MTT assay and colony-forming assay. Results We found that two cis-acting elements within the crucial region of the c1orf109 promoter, one TATA box and one CAAT box, are required for maximal transcription of the c1orf109 gene. The 5′ flanking region of the c1orf109 gene could bind specific transcription factors and Sp1 may be one of them. Employing western blot analysis, we detected upregulated expression of c1orf109 in multiple cancer cell lines. The protein C1ORF109 was mainly located in the nucleus and cytoplasm. Moreover, we also found that C1ORF109 was a phosphoprotein in vivo and could be phosphorylated by the protein kinase CK2 in vitro. Exogenous expression of C1ORF109 in breast cancer Hs578T cells induced an increase in colony number and cell proliferation. A concomitant rise in levels of PCNA (proliferating cell nuclear antigen and cyclinD1 expression was observed. Meanwhile, knockdown of c1orf109 by siRNA in breast cancer MDA-MB-231 cells confirmed the role of c1orf109 in proliferation. Conclusions Taken together, our findings suggest that C1ORF109 may be the downstream target of protein kinase CK2 and involved in the regulation of cancer cell proliferation.

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

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Jiyeon Kim

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

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

    OpenAIRE

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

    2013-01-01

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

  17. Phosphorylation-dependent and -independent functions of p130 cooperate to evoke a sustained G1 block

    DEFF Research Database (Denmark)

    Hansen, Klaus; Farkas, T; Lukas, J;

    2001-01-01

    The retinoblastoma (pRb)-related p130 pocket protein is a regulator of cell growth and differentiation, and a candidate tumour suppressor. Both pRb and p130 operate through interactions with cellular proteins, including the E2F transcription factors. While such interactions are controlled by...

  18. 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...... cisplatin and carboplatin treatment, the RNA level of p53 dropped by 59% +/- 9% and 86% +/- 8% respectively, whereas the observed level of p53 protein rose to 7 and 10 times over the untreated control, respectively. Treatment with 33 microM cisplatin prompted apoptosis as early as 4 h after drug treatment...

  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; Meggio, F; Issinger, O G; Pinna, L A

    1997-01-01

    Protein kinase CK2 is a ubiquitous pleiotropic serine/threonine protein kinase whose holoenzyme is comprised of two catalytic (alpha and/or alpha') and two non-catalytic, beta-subunits. The beta-subunit possesses antagonist functions that can be physically dissected by generating synthetic...... fragments encompassing its N-terminal and C-terminal domains. Here we show that by mutating basic residues in the 74-77 and in the 191-198 regions of the alpha-subunit, the negative regulation by the beta-subunit and by its N-terminal synthetic fragment CK2beta-(1-77), which is observable using calmodulin...... as a substrate for phosphorylation, is drastically reduced. In contrast, the positive regulation by a C-terminal, CK2beta-(155-215)-peptide is unaffected or even increased. Moreover, the basal activity of alpha mutants K74-77A, K79R80K83A, and R191R195K198A toward specific peptide substrates is...

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

    Science.gov (United States)

    Park, Seong-Yeol; Bae, Young-Seuk

    2016-09-01

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

  1. Interaction of ribosomal protein L22 with casein kinase 2α: a novel mechanism for understanding the biology of non-small cell lung cancer.

    Science.gov (United States)

    Yang, Mingxia; Sun, Haibo; He, Ji; Wang, Hong; Yu, Xiaowei; Ma, Lei; Zhu, Changliang

    2014-07-01

    Dysfunction of ribosomal proteins (RPs) may play an important role in molecular tumorigenesis, such as lung cancer, acting in extraribosomal functions. Many protein-protein interaction studies and genetic screens have confirmed the extraribosomal capacity of RPs. As reported, ribosomal protein L22 (RPL22) dysfunction could increase cancer risk. In the present study, we examined RPL22-protein complexes in lung cancer cells. Tandem affinity purification (TAP) was used to screen the RPL22-protein complexes, and GST pull-down experiments and confocal microscopy were used to assess the protein-protein interaction. The experiment of kinase assay was used to study the function of the RPL22-protein complexes. The results showed that several differentially expressed proteins were isolated and identified by LC-MS/MS, which revealed that one of the protein complexes included casein kinase 2α (CK2α). RPL22 and CK2α interact in vitro. RPL22 also inhibited CK2α substrate phosphorylation in vitro. This is the first report of the RPL22-CK2α relationship in lung cancer. Dysregulated CK2 may impact cell proliferation and apoptosis, key features of cancer cell biology. Our results indicate that RPL22 may be a candidate anticancer agent due to its CK2α-binding and -inhibitory functions in human lung cancer. PMID:24840952

  2. Synergistic cytotoxic effects of bortezomib and CK2 inhibitor CX-4945 in acute lymphoblastic leukemia: turning off the prosurvival ER chaperone BIP/Grp78 and turning on the pro-apoptotic NF-κB

    Science.gov (United States)

    Buontempo, Francesca; Orsini, Ester; Lonetti, Annalisa; Cappellini, Alessandra; Chiarini, Francesca; Evangelisti, Camilla; Evangelisti, Cecilia; Melchionda, Fraia; Pession, Andrea; Bertaina, Alice; Locatelli, Franco; Bertacchini, Jessika; Neri, Luca Maria; McCubrey, James A.; Martelli, Alberto Maria

    2016-01-01

    The proteasome inhibitor bortezomib is a new targeted treatment option for refractory or relapsed acute lymphoblastic leukemia (ALL) patients. However, a limited efficacy of bortezomib alone has been reported. A terminal pro-apoptotic endoplasmic reticulum (ER) stress/unfolded protein response (UPR) is one of the several mechanisms of bortezomib-induced apoptosis. Recently, it has been documented that UPR disruption could be considered a selective anti-leukemia therapy. CX-4945, a potent casein kinase (CK) 2 inhibitor, has been found to induce apoptotic cell death in T-ALL preclinical models, via perturbation of ER/UPR pathway. In this study, we analyzed in T- and B-ALL preclinical settings, the molecular mechanisms of synergistic apoptotic effects observed after bortezomib/CX-4945 combined treatment. We demonstrated that, adding CX-4945 after bortezomib treatment, prevented leukemic cells from engaging a functional UPR in order to buffer the bortezomib-mediated proteotoxic stress in ER lumen. We documented that the combined treatment decreased pro-survival ER chaperon BIP/Grp78 expression, via reduction of chaperoning activity of Hsp90. Bortezomib/CX-4945 treatment inhibited NF-κB signaling in T-ALL cell lines and primary cells from T-ALL patients, but, intriguingly, in B-ALL cells the drug combination activated NF-κB p65 pro-apoptotic functions. In fact in B-cells, the combined treatment induced p65-HDAC1 association with consequent repression of the anti-apoptotic target genes, Bcl-xL and XIAP. Exposure to NEMO (IKKγ)-binding domain inhibitor peptide reduced the cytotoxic effects of bortezomib/CX-4945 treatment. Overall, our findings demonstrated that CK2 inhibition could be useful in combination with bortezomib as a novel therapeutic strategy in both T- and B-ALL. PMID:26593250

  3. Metastasis-associated protein Mts1 (S100A4) inhibits CK2-mediated phosphorylation and self-assembly of the heavy chain of nonmuscle myosin

    DEFF Research Database (Denmark)

    Kriajevska, M; Bronstein, I B; Scott, D J; Tarabykina, S; Fischer-Larsen, M; Issinger, O; Lukanidin, E

    A role for EF-hand calcium-binding protein Mts1 (S100A4) in the phosphorylation and the assembly of myosin filaments was studied. The nonmuscle myosin molecules form bipolar filaments, which interact with actin filaments to produce a contractile force. Phosphorylation of the myosin plays a regula...

  4. Phosphorylation-dependent changes in nucleotide binding, conformation, and dynamics of the first nucleotide binding domain (NBD1) of the sulfonylurea receptor 2B (SUR2B).

    Science.gov (United States)

    de Araujo, Elvin D; Alvarez, Claudia P; López-Alonso, Jorge P; Sooklal, Clarissa R; Stagljar, Marijana; Kanelis, Voula

    2015-09-11

    The sulfonylurea receptor 2B (SUR2B) forms the regulatory subunit of ATP-sensitive potassium (KATP) channels in vascular smooth muscle. Phosphorylation of the SUR2B nucleotide binding domains (NBD1 and NBD2) by protein kinase A results in increased channel open probability. Here, we investigate the effects of phosphorylation on the structure and nucleotide binding properties of NBD1. Phosphorylation sites in SUR2B NBD1 are located in an N-terminal tail that is disordered. Nuclear magnetic resonance (NMR) data indicate that phosphorylation of the N-terminal tail affects multiple residues in NBD1, including residues in the NBD2-binding site, and results in altered conformation and dynamics of NBD1. NMR spectra of NBD1 lacking the N-terminal tail, NBD1-ΔN, suggest that phosphorylation disrupts interactions of the N-terminal tail with the core of NBD1, a model supported by dynamic light scattering. Increased nucleotide binding of phosphorylated NBD1 and NBD1-ΔN, compared with non-phosphorylated NBD1, suggests that by disrupting the interaction of the NBD core with the N-terminal tail, phosphorylation also exposes the MgATP-binding site on NBD1. These data provide insights into the molecular basis by which phosphorylation of SUR2B NBD1 activates KATP channels. PMID:26198630

  5. INTERACT

    DEFF Research Database (Denmark)

    Jochum, Elizabeth; Borggreen, Gunhild; Murphey, TD

    , and demonstrated in public settings. We then describe INTERACT, a proposed research project that stages the robotic marionettes in a live performance. The interdisciplinary project brings humanities research to bear on scientific and technological inquiry, and culminates in the development a live......This paper considers the impact of visual art and performance on robotics and human-computer interaction and outlines a research project that combines puppetry and live performance with robotics. Kinesics—communication through movement—is the foundation of many theatre and performance traditions...... interaction between a human operator and an artificial actor or agent. We can apply insights from puppetry to develop culturally-aware robots. Here we describe the development of a robotic marionette theatre wherein robotic controllers assume the role of human puppeteers. The system has been built, tested...

  6. Characterization of CK2 holoenzyme variants with regard to crystallization

    DEFF Research Database (Denmark)

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

    2001-01-01

    efforts 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...

  7. Interactions

    DEFF Research Database (Denmark)

    The main theme of this anthology is the unique interaction between mathematics, physics and philosophy during the beginning of the 20th century. Seminal theories of modern physics and new fundamental mathematical structures were discovered or formed in this period. Significant physicists such as...

  8. 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; Llorens, F; Plana, M; Issinger, O G; Itarte, E

    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...

  9. Phosphorylation by CK2 and MAPK enhances calnexin association with ribosomes.

    OpenAIRE

    Chevet, E.; Wong, H N; Gerber, D.; Cochet, C; A Fazel; Cameron, P H; Gushue, J N; Thomas, D. Y.; Bergeron, J J

    1999-01-01

    Calnexin was initially identified as an endoplasmic reticulum (ER) type I integral membrane protein, phosphorylated on its cytosolic domain by ER-associated protein kinases. Although the role of the ER luminal domain of calnexin has been established as a constituent of the molecular chaperone machinery of the ER, less is known about the role of the cytosolic phosphorylation of calnexin. Analysis by two-dimensional phosphopeptide maps revealed that calnexin was in vitro phosphorylated in isola...

  10. A CK2-dependent mechanism for activation of the JAK-STAT signaling pathway

    OpenAIRE

    Zheng, Ying; Qin, Hongwei; Frank, Stuart J.; Deng, Luqin; Litchfield, David W.; Tefferi, Ayalew; Pardanani, Animesh; Lin, Fang-Tsyr; Li, Jingzhi; Sha, Bingdong; Benveniste, Etty N.

    2011-01-01

    JAK-STAT signaling is involved in the regulation of cell survival, proliferation, and differentiation. JAK tyrosine kinases can be transiently activated by cytokines or growth factors in normal cells, whereas they become constitutively activated as a result of mutations that affect their function in tumors. Specifically, the JAK2V617F mutation is present in the majority of patients with myeloproliferative disorders (MPDs) and is implicated in the pathogenesis of these diseases. In the present...

  11. Die Trinkwasser-Verhältnisse der Stadt Osnabrück : 2. Teil

    OpenAIRE

    Thörner, Wilhelm (Dr.)

    2013-01-01

    Im fünften Jahresbericht für die Jahre 1880-1882 des naturwissenschaftlichen Vereins zu Osnabrück machten wir, an der Hand einer größeren Reihe einschlägiger Untersuchungen, Mitteilungen über die Trinkwasser- Verhältnisse der Stadt Osnabrück. Diese aufklärenden Untersuchungen sind inzwischen stetig fortgesetzt worden und es haben sich, wie aus der umstehenden tabellarischen Zusammenstellung der Resultate der Analysen hervorgeht, die Trinkwasserverhältnisse unserer Stadt eher verschlechtert al...

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

    NARCIS (Netherlands)

    T. Tamaru (Teruya); M. Hattori (Mitsuru); K. Honda (Kousuke); Y. Nakahata (Yasukazu); P. Sassone-Corsi (Paolo); G.T.J. van der Horst (Gijsbertus); T. Ozawa (Takeaki); K. Takamatsu (Ken)

    2015-01-01

    textabstractIntracellular circadian clocks, composed of clock genes that act in transcription-translation feedback loops, drive global rhythmic expression of the mammalian transcriptome and allow an organism to anticipate to the momentum of the day. Using a novel clock-perturbing peptide, we establi

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

    DEFF Research Database (Denmark)

    Sarno, S; Vaglio, P; Meggio, F; Issinger, O G; Pinna, L A

    1996-01-01

    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...

  14. Phosphorylation Dependence of Hsp27 Multimeric Size and Molecular Chaperone Function*

    OpenAIRE

    Hayes, David; Napoli, Vanessa; Mazurkie, Andrew; Stafford, Walter F.; Graceffa, Philip

    2009-01-01

    The molecular chaperone Hsp27 exists as a distribution of large oligomers that are disassembled by phosphorylation at Ser-15, -78, and -82. It is controversial whether the unphosphorylated Hsp27 or the widely used triple Ser-to-Asp phospho-mimic mutant is the more active molecular chaperone in vitro. This question was investigated here by correlating chaperone activity, as measured by the aggregation of reduced insulin or α-lactalbumin, with Hsp27 self-association as monitored by analytical u...

  15. Perilipin Promotes HSL-Mediated Adipocyte Lipolysis via Phosphorylation-dependent and Independent Mechanisms

    Science.gov (United States)

    Hormone-sensitive lipase (HSL) is the predominant lipase effector of catecholamine-stimulated lipolysis in adipocytes. HSL-dependent lipolysis, in response to catecholamines, is mediated by protein kinase A (PKA)-dependent phosphorylation of perilipin A (Peri A), an essential lipid droplet (LD)-ass...

  16. Phosphorylation-dependent Trafficking of Plasma Membrane Proteins in Animal and Plant Cells

    Institute of Scientific and Technical Information of China (English)

    Remko Offringa; and Fang Huang

    2013-01-01

    In both unicellular and multicellular organisms, transmembrane (TM) proteins are sorted to and retained at specific membrane domains by endomembrane trafficking mechanisms that recognize sorting signals in the these proteins. The trafficking and distribution of plasma membrane (PM)-localized TM proteins (PM proteins), especially of those PM proteins that show an asymmetric distribution over the PM, has received much attention, as their proper PM localization is crucial for elementary signaling and transport processes, and defects in their localization often lead to severe disease symptoms or developmental defects. The subcellular localization of PM proteins is dynamically regulated by post-translational modifications, such as phosphorylation and ubiquitination. These modificaitons mostly occur on sorting signals that are located in the larger cytosolic domains of the cargo proteins. Here we review the effects of phosphorylation of PM proteins on their trafficking, and present the key examples from the animal field that have been subject to studies for already several decades, such as that of aquaporin 2 and the epidermal growth factor receptor. Our knowledge on cargo trafficking in plants is largely based on studies of the family of PIN FORMED (PIN) carriers that mediate the efflux of the plant hormone auxin. We will review what is known on the subcellular distribution and trafficking of PIN proteins, with a focus on how this is modulated by phosphorylation, and identify and discuss analogies and differences in trafficking with the well-studied animal examples.

  17. Inflammation-induced loss of Pdcd4 is mediated by phosphorylation-dependent degradation

    OpenAIRE

    Schmid, Tobias; Magdalena M Bajer; Blees, Johanna S.; Eifler, Lisa K.; Milke, Larissa; Rübsamen, Daniela; Schulz, Kathrin; Weigert, Andreas; Baker, Alyson R.; Nancy H. Colburn; Brüne, Bernhard

    2011-01-01

    The tumor suppressor programmed cell death 4 (Pdcd4) is lost in various tumor tissues. Loss of Pdcd4 has been associated with increased tumorigenic potential and tumor progression. While various mechanisms of Pdcd4 regulation have been described, the effect of an inflammatory tumor microenvironment on Pdcd4 protein expression has not been characterized so far. In the present study, we aimed to elucidate the molecular mechanisms of Pdcd4 protein regulation in tumor cells under inflammatory con...

  18. Phosphorylation-dependent down-regulation of apolipoprotein A5 by insulin

    Energy Technology Data Exchange (ETDEWEB)

    Nowak, Maxine; Helleboid-Chapman, Audrey; Jakel, Heidelinde; Rommens, Corinne; Martin, Genevieve; Duran-Sandoval, Daniel; Staels, Bart; Rubin, Edward M.; Pennacchio, Len A.; Taskinen, Marja-Riitta; Fruchart-Najib, Jamila; Fruchart, Jean-Charles

    2004-02-15

    The apolipoprotein A5 (APOA5) gene has been shown to be important in lowering plasma triglyceride levels. Since several studies have shown that hyperinsulinemia is associated with hypertriglyceridemia, we sought to determine whether APOA5 gene is regulated by insulin. We show here that cell and mouse treatments with insulin down-regulated APOA5 expression in a dose-dependent manner. Furthermore, we determined that insulin decreases APOA5 promoter activity and subsequent deletion analyses revealed an E-box-containing fragment. We showed that Upstream Stimulatory Factors, USF1/USF2, bind to the identified E-box in the APOA5 promoter. Moreover, in cotransfection studies, USF1 stimulates APOA5 promoter activity. The treatment with insulin reduces the binding of USF1/USF2 to APOA5 promoter. The inhibition of PI3K pathway with wortmannin abolished the insulin s effect on APOA5 gene transcription. Using oligoprecipitation method of USF from nuclear extracts, we demonstrated that phosphorylated USF1 failed to bind to APOA5 promoter. This indicates that the APOA5 gene transrepression by insulin involves a phosphorylation of USF through PI3K, that modulate their binding to APOA5 promoter and results in APOA5 down-regulation. The effect of exogenous hyperinsulinemia in healthy men shows a decrease of the plasma ApoAV level. These data suggest a potential mechanism involving APOA5 gene in hypertriglyceridemia associated with hyperinsulinemia.

  19. Phosphorylation-Dependent Targeting of Tetrahymena HP1 to Condensed Chromatin.

    Science.gov (United States)

    Yale, Katerina; Tackett, Alan J; Neuman, Monica; Bulley, Emily; Chait, Brian T; Wiley, Emily

    2016-01-01

    The evolutionarily conserved proteins related to heterochromatin protein 1 (HP1), originally described in Drosophila, are well known for their roles in heterochromatin assembly and gene silencing. Targeting of HP1 proteins to specific chromatin locales is mediated, at least in part, by the HP1 chromodomain, which binds to histone H3 methylated at lysine 9 that marks condensed regions of the genome. Mechanisms that regulate HP1 targeting are emerging from studies with yeast and metazoans and point to roles for posttranslational modifications. Here, we report that modifications of an HP1 homolog (Hhp1) in the ciliate model Tetrahymena thermophila correlated with the physiological state and with nuclear differentiation events involving the restructuring of chromatin. Results support the model in which Hhp1 chromodomain binds lysine 27-methylated histone H3, and we show that colocalization with this histone mark depends on phosphorylation at a single Cdc2/Cdk1 kinase site in the "hinge region" adjacent to the chromodomain. These findings help elucidate important functional roles of reversible posttranslational modifications of proteins in the HP1 family, in this case, regulating the targeting of a ciliate HP1 to chromatin regions marked with methylated H3 lysine 27. IMPORTANCE Compacting the genome to various degrees influences processes that use DNA as a template, such as gene transcription and replication. This project was aimed at learning more about the cellular mechanisms that control genome compaction. Posttranslational modifications of proteins involved in genome condensation are emerging as potentially important points of regulation. To help elucidate protein modifications and how they affect the function of condensation proteins, we investigated the phosphorylation of the chromatin protein called Hhp1 in the ciliated protozoan Tetrahymena thermophila. This is one of the first functional investigations of these modifications of a nonhistone chromatin condensation protein that acts on the ciliate genome, and discoveries will aid in identifying common, evolutionarily conserved strategies that control the dynamic compaction of genomes. PMID:27579368

  20. Site-specific Interaction Mapping of Phosphorylated Ubiquitin to Uncover Parkin Activation.

    Science.gov (United States)

    Yamano, Koji; Queliconi, Bruno B; Koyano, Fumika; Saeki, Yasushi; Hirokawa, Takatsugu; Tanaka, Keiji; Matsuda, Noriyuki

    2015-10-16

    Damaged mitochondria are eliminated through autophagy machinery. A cytosolic E3 ubiquitin ligase Parkin, a gene product mutated in familial Parkinsonism, is essential for this pathway. Recent progress has revealed that phosphorylation of both Parkin and ubiquitin at Ser(65) by PINK1 are crucial for activation and recruitment of Parkin to the damaged mitochondria. However, the mechanism by which phosphorylated ubiquitin associates with and activates phosphorylated Parkin E3 ligase activity remains largely unknown. Here, we analyze interactions between phosphorylated forms of both Parkin and ubiquitin at a spatial resolution of the amino acid residue by site-specific photo-crosslinking. We reveal that the in-between-RING (IBR) domain along with RING1 domain of Parkin preferentially binds to ubiquitin in a phosphorylation-dependent manner. Furthermore, another approach, the Fluoppi (fluorescent-based technology detecting protein-protein interaction) assay, also showed that pathogenic mutations in these domains blocked interactions with phosphomimetic ubiquitin in mammalian cells. Molecular modeling based on the site-specific photo-crosslinking interaction map combined with mass spectrometry strongly suggests that a novel binding mechanism between Parkin and ubiquitin leads to a Parkin conformational change with subsequent activation of Parkin E3 ligase activity. PMID:26260794

  1. An In Vitro ES Cell-Based Clock Recapitulation Assay Model Identifies CK2α as an Endogenous Clock Regulator

    OpenAIRE

    Umemura, Yasuhiro; Yoshida, Junko; Wada, Masashi; Tsuchiya, Yoshiki; Minami, Yoichi; Watanabe, Hitomi; Kondoh, Gen; Takeda, Junji; Inokawa, Hitoshi; Horie, Kyoji; Yagita, Kazuhiro

    2013-01-01

    We previously reported emergence and disappearance of circadian molecular oscillations during differentiation of mouse embryonic stem (ES) cells and reprogramming of differentiated cells, respectively. Here we present a robust and stringent in vitro circadian clock formation assay that recapitulates in vivo circadian phenotypes. This assay system first confirmed that a mutant ES cell line lacking Casein Kinase I delta (CKIδ) induced ∼3 hours longer period-length of circadian rhythm than the w...

  2. Funktionelle Charakterisierung der Protein-Kinase CK2 in der Suppression Th2-vermittelter Immunantworten durch regulatorische T-Zellen

    OpenAIRE

    Ulges, Alexander

    2013-01-01

    Regulatorische T-Zellen (Tregs) leisten durch ihre suppressiven Eigenschaften einen essenziellen Beitrag zur Aufrechterhaltung der immunologischen Toleranz. Sie verhindern schädliche Immunreaktionen gegen Autoantigene, kommensale Bakterien, sowie harmlose Nahrungsmittel-bestandteile. Gleichzeitig gewährleisten sie die Entwicklung effektiver Immunantworten gegen eindringende Pathogene, wie z.B. Parasiten, Bakterien und Viren. Damit haben Tregs direkten Einfluss auf das Gleichgewicht zwischen I...

  3. FBXL5 interacts with p150Glued and regulates its ubiquitination.

    Science.gov (United States)

    Zhang, Ning; Liu, Jing; Ding, Xia; Aikhionbare, Felix; Jin, Changjiang; Yao, Xuebiao

    2007-07-20

    The microtubule motor cytoplasmic dynein and its activator dynactin drive vesicular transport and mitotic spindle organization. p150(Glued) is the dynactin subunit responsible for binding to dynein and microtubules. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which governs phosphorylation-dependent ubiquitination and subsequent proteolysis. Our recent study showed that the proteolysis of mitotic kinesin CENP-E is mediated by SCF via a direct Skp1 link [D. Liu, N. Zhang, J. Du, X. Cai, M. Zhu, C. Jin, Z. Dou, C. Feng, Y. Yang, L. Liu, K. Takeyasu, W. Xie, X. Yao, Interaction of Skp1 with CENP-E at the midbody is essential for cytokinesis, Biochem. Biophys. Res. Commun. 345 (2006) 394-402]. Here we show that F-box protein FBXL5 interacts with p150(Glued) and orchestrates its turnover via ubiquitination. FBXL5 binds to p150(Glued)in vitro and in vivo. FBXL5 and p150(Glued) co-localize primarily in the cytoplasm with peri-nuclear enrichment in HeLa cells. Overexpression of FBXL5 promotes poly-ubiquitination of p150(Glued) and protein turnover of p150(Glued). Our findings provide a potential mechanism by which p150(Glued) protein function is regulated by SCFs. PMID:17532294

  4. FBXL5 interacts with p150 Glued and regulates its ubiquitination

    International Nuclear Information System (INIS)

    The microtubule motor cytoplasmic dynein and its activator dynactin drive vesicular transport and mitotic spindle organization. p150 Glued is the dynactin subunit responsible for binding to dynein and microtubules. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which governs phosphorylation-dependent ubiquitination and subsequent proteolysis. Our recent study showed that the proteolysis of mitotic kinesin CENP-E is mediated by SCF via a direct Skp1 link [D. Liu, N. Zhang, J. Du, X. Cai, M. Zhu, C. Jin, Z. Dou, C. Feng, Y. Yang, L. Liu, K. Takeyasu, W. Xie, X. Yao, Interaction of Skp1 with CENP-E at the midbody is essential for cytokinesis, Biochem. Biophys. Res. Commun. 345 (2006) 394-402]. Here we show that F-box protein FBXL5 interacts with p150 Glued and orchestrates its turnover via ubiquitination. FBXL5 binds to p150 Glued in vitro and in vivo. FBXL5 and p150 Glued co-localize primarily in the cytoplasm with peri-nuclear enrichment in HeLa cells. Overexpression of FBXL5 promotes poly-ubiquitination of p150 Glued and protein turnover of p150 Glued . Our findings provide a potential mechanism by which p150 Glued protein function is regulated by SCFs

  5. Evidence for Intermolecular Interactions between the Intracellular Domains of the Arabidopsis Receptor-Like Kinase ACR4, Its Homologs and the Wox5 Transcription Factor

    Science.gov (United States)

    Meyer, Matthew R.; Shah, Shweta; Zhang, J.; Rohrs, Henry; Rao, A. Gururaj

    2015-01-01

    Arabidopsis CRINKLY4 (ACR4) is a receptor-like kinase (RLK) involved in the global development of the plant. The Arabidopsis genome encodes four homologs of ACR4 that contain sequence similarity and analogous architectural elements to ACR4, termed Arabidopsis CRINKLY4 Related (AtCRRs) proteins. Additionally, a signaling module has been previously proposed including a postulated peptide ligand, CLE40, the ACR4 RLK, and the WOX5 transcription factor that engage in a possible feedback mechanism controlling stem cell differentiation. However, little biochemical evidence is available to ascertain the molecular aspects of receptor heterodimerization and the role of phosphorylation in these interactions. Therefore, we have undertaken an investigation of the in vitro interactions between the intracellular domains (ICD) of ACR4, the CRRs and WOX5. We demonstrate that interaction can occur between ACR4 and all four CRRs in the unphosphorylated state. However, phosphorylation dependency is observed for the interaction between ACR4 and CRR3. Furthermore, sequence analysis of the ACR4 gene family has revealed a conserved ‘KDSAF’ motif that may be involved in protein-protein interactions among the receptor family. We demonstrate that peptides harboring this conserved motif in CRR3 and CRK1are able to bind to the ACR4 kinase domain. Our investigations also indicate that the ACR4 ICD can interact with and phosphorylate the transcription factor WOX5. PMID:25756623

  6. Receptor-Like Kinase RUPO Interacts with Potassium Transporters to Regulate Pollen Tube Growth and Integrity in Rice

    Science.gov (United States)

    Liu, Lingtong; Zheng, Canhui; Kuang, Baijan; Wei, Liqin; Yan, Longfeng; Wang, Tai

    2016-01-01

    During sexual reproduction of flowering plants, the pollen tube grows fast and over a long distance within the pistil to deliver two sperms for double fertilization. Growing plant cells need to communicate constantly with external stimuli as well as monitor changes in surface tension of the cell wall and plasma membrane to coordinate these signals and internal growth machinery; however, the underlying mechanisms remain largely unknown. Here we show that the rice member of plant-specific receptor-like kinase CrRLK1Ls subfamily, Ruptured Pollen tube (RUPO), is specifically expressed in rice pollen. RUPO localizes to the apical plasma membrane and vesicle of pollen tubes and is required for male gamete transmission. K+ levels were greater in pollen of homozygous CRISPR-knockout lines than wild-type plants, and pollen tubes burst shortly after germination. We reveal the interaction of RUPO with high-affinity potassium transporters. Phosphorylation of RUPO established and dephosphorylation abolished the interaction. These results have revealed the receptor-like kinase as a regulator of high-affinity potassium transporters via phosphorylation-dependent interaction, and demonstrated a novel receptor-like kinase signaling pathway that mediates K+ homeostasis required for pollen tube growth and integrity. PMID:27447945

  7. α-Synuclein Aggregation and Ser-129 Phosphorylation-dependent Cell Death in Oligodendroglial Cells*S⃞

    OpenAIRE

    Kragh, Christine L.; Lund, Louise B.; Febbraro, Fabia; Hansen, Hanne D.; Gai, Wei-Ping; El-Agnaf, Omar; Richter-Landsberg, Christiane; Jensen, Poul Henning

    2009-01-01

    Multiple system atrophy is a neurodegenerative disorder characterized by accumulation of aggregated Ser-129-phosphorylated α-synuclein in oligodendrocytes. p25α is an oligodendroglial protein that potently stimulates α-synuclein aggregation in vitro. To model multiple system atrophy, we coexpressed human p25α and α-synuclein in the rat oligodendroglial cell line OLN-93 and observed a cellular response characterized by a fast retraction of microtubules from the cellular...

  8. Repression of virulence genes by phosphorylation-dependent oligomerization of CsrR at target promoters in S. pyogenes.

    Science.gov (United States)

    Miller, A A; Engleberg, N C; DiRita, V J

    2001-05-01

    csrRS encodes a two-component regulatory system that represses the transcription of a number of virulence factors in Streptococcus pyogenes, including the hyaluronic acid capsule and pyrogenic exotoxin B. CsrRS-regulated virulence factors have diverse functions during pathogenesis and are differentially expressed throughout growth. This suggests that multiple signals induce CsrRS-mediated gene regulation, or that regulated genes respond differently to CsrR, or both. As a first step in dissecting the csrRS signal transduction pathway, we determined the mechanism by which CsrR mediates the repression of its target promoters. We found that phosphorylated CsrR binds directly to all but one of the promoters of its regulated genes, with different affinities. Phosphorylation of CsrR enhances both oligomerization and DNA binding. We defined the binding site of CsrR at each of the regulated promoters using DNase I and hydroxyl radical footprinting. Based on these results, we propose a model for differential regulation by CsrRS. PMID:11401704

  9. Interleukin 2 regulates Raf-1 kinase activity through a tyrosine phosphorylation-dependent mechanism in a T-cell line.

    OpenAIRE

    Turner, B C; Tonks, N K; Rapp, U R; Reed, J. C.

    1993-01-01

    Previously we found that interleukin 2 (IL-2) induces tyrosine phosphorylation and activation of the serine/threonine-specific kinase encoded by the raf-1 protooncogene in a T-cell line, CTLL-2. Here we extended these findings by exploring the effects of selective removal of phosphate from tyrosines in p72-74-Raf-1 kinase that had been immunoprecipitated from IL-2-stimulated CTLL-2 cells. Treatment in vitro of IL-2-activated Raf-1 with the tyrosine-specific phosphatases CD45 and TCPTP (former...

  10. Identification of isoform-specific dynamics in phosphorylation-dependent STAT5 dimerization by quantitative mass spectrometry and mathematical modeling.

    Science.gov (United States)

    Boehm, Martin E; Adlung, Lorenz; Schilling, Marcel; Roth, Susanne; Klingmüller, Ursula; Lehmann, Wolf D

    2014-12-01

    STAT5A and STAT5B are important transcription factors that dimerize and transduce activation signals of cytokine receptors directly to the nucleus. A typical cytokine that mediates STAT5 activation is erythropoietin (Epo). Differential functions of STAT5A and STAT5B have been reported. However, the extent to which phosphorylated STAT5A and STAT5B (pSTAT5A, pSTAT5B) form homo- or heterodimers is not understood, nor is how this might influence the signal transmission to the nucleus. To study this, we designed a concept to investigate the isoform-specific dimerization behavior of pSTAT5A and pSTAT5B that comprises isoform-specific immunoprecipitation (IP), measurement of the degree of phosphorylation, and isoform ratio determination between STAT5A and STAT5B. For the main analytical method, we employed quantitative label-free and -based mass spectrometry. For the cellular model system, we used Epo receptor (EpoR)-expressing BaF3 cells (BaF3-EpoR) stimulated with Epo. Three hypotheses of dimer formation between pSTAT5A and pSTAT5B were used to explain the analytical results by a static mathematical model: formation of (i) homodimers only, (ii) heterodimers only, and (iii) random formation of homo- and heterodimers. The best agreement between experimental data and model simulations was found for the last case. Dynamics of cytoplasmic STAT5 dimerization could be explained by distinct nuclear import rates and individual nuclear retention for homo- and heterodimers of phosphorylated STAT5. PMID:25333863

  11. Quantitative analysis of some mechanisms affecting the yield of oxidative phosphorylation: dependence upon both fluxes and forces.

    Science.gov (United States)

    Rigoulet, M; Leverve, X; Fontaine, E; Ouhabi, R; Guérin, B

    1998-07-01

    The purpose of this work was to show how the quantitative definition of the different parameters involved in mitochondrial oxidative phosphorylation makes it possible to characterize the mechanisms by which the yield of ATP synthesis is affected. Three different factors have to be considered: (i) the size of the different forces involved (free energy of redox reactions and ATP synthesis, proton electrochemical difference); (ii) the physical properties of the inner mitochondrial membrane in terms of leaks (H+ and cations); and finally (iii) the properties of the different proton pumps involved in this system (kinetic properties, regulation, modification of intrinsic stoichiometry). The data presented different situations where one or more of these parameters are affected, leading to a different yield of oxidative phosphorylation. (1) By manipulating the actual flux through each of the respiratory chain units at constant protonmotive force in yeast mitochondria, we show that the ATP/O ratio decreases when the flux increases. Moreover, the highest efficiency was obtained when the respiratory rate was low and almost entirely controlled by the electron supply. (2) By using almitrine in different kinds of mitochondria, we show that this drug leads to a decrease in ATP synthesis efficiency by increasing the H+/ATP stoichiometry ofATP synthase (Rigoulet M et al. Biochim Biophys Acta 1018: 91-97, 1990). Since this enzyme is reversible, it was possible to test the effect of this drug on the reverse reaction of the enzyme i.e. extrusion of protons catalyzed by ATP hydrolysis. Hence, we are able to prove that, in this case, the decrease in efficiency of oxidative phosphorylation is due to a change in the mechanistic stoichiometry of this proton pump. To our knowledge, this is the first example of a modification in oxidative phosphorylation yield by a change in mechanistic stoichiometry of one of the proton pumps involved. (3) In a model of polyunsaturated fatty acid deficiency in rat, it was found that non-ohmic proton leak was increased, while ohmic leak was unchanged. Moreover, an increase in redox slipping was also involved, leading to a complex picture. However, the respective role of these two mechanisms may be deduced from their intrinsic properties. For each steady state condition, the quantitative effect of these two mechanisms in the decrease of oxidative phosphorylation efficiency depends on the values of different fluxes or forces involved. (4) Finally the comparison of the thermokinetic data in view of the three dimensional-structure of some pumps (X-ray diffraction) also gives some information concerning the putative mechanism of coupling (i.e. redox loop or proton pump) and their kinetic control versus regulation of mitochondrial oxidative phosphorylation. PMID:9746311

  12. Embarrassing Interactions

    DEFF Research Database (Denmark)

    Deterding, Sebastian; Lucero, Andrés; Holopainen, Jussi; Min, Chulhong; Cheok, Adrian; Waern, Annika; Walz, Steffen

    Wherever the rapid evolution of interactive technologies disrupts standing situational norms, creates new, often unclear situational audiences, or crosses cultural boundaries, embarrassment is likely. This makes embarrassment a fundamental adoption and engagement hurdle, but also a creative design...... space for human-computer interaction. However, research on embarrassment in HCI has remained scattered and unsystematic so far. This workshop therefore convenes researchers and practitioners to assemble and advance the current state of research on embarrassing interactions....

  13. Explicit Interaction

    DEFF Research Database (Denmark)

    Löwgren, Jonas; Eriksen, Mette Agger; Linde, Per; Olofsson, Stefan; Sokoler, Tomas; Grønfeldt, Peter; Rasmussen, Jørgen; Kramp, Gunnar; Käfer, Gerald; Schmid, Reiner; Wuchner, Egon

    2006-01-01

    We report an ongoing study of palpable computing to support surgical rehabilitation, in the general field of interaction design for ubiquitous computing. Through explorative design, fieldwork and participatory design techniques, we explore the design principle of explicit interaction as an...... interpretation of palpability, comprising usability as well as patient empowerment and socially performative issues. We present a prototype environment for video recording during physiotherapeutical consultation which illustrates our current thoughts on explicit interaction and serves as material for further...

  14. Floor interaction

    DEFF Research Database (Denmark)

    Petersen, Marianne Graves; Krogh, Peter; Ludvigsen, Martin; Lykke-Olesen, Andreas

    Within architecture, there is a long tradition of careful design of floors. The design has been concerned with both decorating floors and designing floors to carry information. Ubiquitous computing technology offers new opportunities for designing interactive floors. This paper presents three...... different interactive floor concepts. Through an urban perspective it draws upon the experiences of floors in architecture, and provides a set of design issues for designing interactive floors....

  15. Playful Interaction

    DEFF Research Database (Denmark)

    2003-01-01

    The video Playful Interaction describes a future architectural office, and envisions ideas and concepts for playful interactions between people, materials and appliances in a pervasive and augmented working environment. The video both describes existing developments, technologies and designs as...... well as ideas not yet implemented such as playful modes of interaction with an augmented ball. Playful Interaction has been used as a hybrid of a vision video and a video prototype (1). Externally the video has been used to visualising our new ideas, and internally the video has also worked to inspire...

  16. Thermodynamics of the interaction between Alzheimer's disease related tau protein and DNA.

    Directory of Open Access Journals (Sweden)

    Sergio Camero

    Full Text Available Tau hyperphosphorylation can be considered as one of the hallmarks of Alzheimer's disease and other tauophaties. Besides its well-known role as a microtubule associated protein, Tau displays a key function as a protector of genomic integrity in stress situations. Phosphorylation has been proven to regulate multiple processes including nuclear translocation of Tau. In this contribution, we are addressing the physicochemical nature of DNA-Tau interaction including the plausible influence of phosphorylation. By means of surface plasmon resonance (SPR we measured the equilibrium constant and the free energy, enthalpy and entropy changes associated to the Tau-DNA complex formation. Our results show that unphosphorylated Tau binding to DNA is reversible. This fact is in agreement with the protective role attributed to nuclear Tau, which stops binding to DNA once the insult is over. According to our thermodynamic data, oscillations in the concentration of dephosphorylated Tau available to DNA must be the variable determining the extent of Tau binding and DNA protection. In addition, thermodynamics of the interaction suggest that hydrophobicity must represent an important contribution to the stability of the Tau-DNA complex. SPR results together with those from Tau expression in HEK cells show that phosphorylation induces changes in Tau protein which prevent it from binding to DNA. The phosphorylation-dependent regulation of DNA binding is analogous to the Tau-microtubules binding inhibition induced by phosphorylation. Our results suggest that hydrophobicity may control Tau location and DNA interaction and that impairment of this Tau-DNA interaction, due to Tau hyperphosphorylation, could contribute to Alzheimer's pathogenesis.

  17. Interactive benchmarking

    DEFF Research Database (Denmark)

    Lawson, Lartey; Nielsen, Kurt

    2005-01-01

    We discuss individual learning by interactive benchmarking using stochastic frontier models. The interactions allow the user to tailor the performance evaluation to preferences and explore alternative improvement strategies by selecting and searching the different frontiers using directional...... suggested benchmarking tool. The study investigates how different characteristics on dairy farms influences the technical efficiency....

  18. Simple Interactions

    DEFF Research Database (Denmark)

    a Danish and international public. The exhibition Simple Interactions. Sound Art from Japan presents works by 9 Japanese artists at the Museum of Contemporary Art Roskilde. The exhibition mixes installations, performances and documentations, all of which examine how simple interactions can create...

  19. Kinesthetic Interaction

    DEFF Research Database (Denmark)

    Fogtmann, Maiken Hillerup; Fritsch, Jonas; Kortbek, Karen Johanne

    2008-01-01

    Within the Human-Computer Interaction community there is a growing interest in designing for the whole body in interaction design. The attempts aimed at addressing the body have very different outcomes spanning from theoretical arguments for understanding the body in the design process, to more...... practical examples of designing for bodily potential. This paper presents Kinesthetic Interaction as a unifying concept for describing the body in motion as a foundation for designing interactive systems. Based on the theoretical foundation for Kinesthetic Interaction, a conceptual framework is introduced...... to reveal bodily potential in relation to three design themes – kinesthetic development, kinesthetic means and kinesthetic disorder; and seven design parameters – engagement, sociality, movability, explicit motivation, implicit motivation, expressive meaning and kinesthetic empathy. The framework is...

  20. Aesthetic interaction

    DEFF Research Database (Denmark)

    Petersen, Marianne Graves; Iversen, Ole Sejer; Krogh, Peter; Ludvigsen, Martin

    There is a growing interest in considering aesthetic aspects in the design of interactive systems. A set of approaches are emerging each representing different applications of the terminology as well as different inherent assumptions on the role of the user, designer and interaction ideals. In this...... paper, we use the concept of Pragmatist Aesthetics to provide a framework for distinguishing between different approaches to aesthetics. Moreover, we use our own design cases to illustrate how pragmatist aesthetics is a promising path to follow in the context of designing interactive systems, as it...... promotes aesthetics of use, rather than aesthetics of appearance. We coin this approach in the perspective of aesthetic interaction. Finally we make the point that aesthetics is not re-defining everything known about interactive systems. We provide a framework placing this perspective among other...

  1. Interacting parasites

    Science.gov (United States)

    Lafferty, Kevin D.

    2010-01-01

    Parasitism is the most popular life-style on Earth, and many vertebrates host more than one kind of parasite at a time. A common assumption is that parasite species rarely interact, because they often exploit different tissues in a host, and this use of discrete resources limits competition (1). On page 243 of this issue, however, Telfer et al. (2) provide a convincing case of a highly interactive parasite community in voles, and show how infection with one parasite can affect susceptibility to others. If some human parasites are equally interactive, our current, disease-by-disease approach to modeling and treating infectious diseases is inadequate (3).

  2. Programming Interactivity

    CERN Document Server

    Noble, Joshua

    2012-01-01

    Ready to create rich interactive experiences with your artwork, designs, or prototypes? This is the ideal place to start. With this hands-on guide, you'll explore several themes in interactive art and design-including 3D graphics, sound, physical interaction, computer vision, and geolocation-and learn the basic programming and electronics concepts you need to implement them. No previous experience is necessary. You'll get a complete introduction to three free tools created specifically for artists and designers: the Processing programming language, the Arduino microcontroller, and the openFr

  3. Interaction Widget

    DEFF Research Database (Denmark)

    Ingstrup, Mads

    2003-01-01

    This pattern describes the idea of making a user interface of discrete, reusable entities---here called interaction widgets. The idea behind widgets is described using two perspectives, that of the user and that of the developer. It is the forces from these two perspectives that are balanced in the...... pattern. The intended audience of the pattern is developers and researchers within the field of human computer interaction....

  4. Interactive governance

    DEFF Research Database (Denmark)

    Sørensen, Eva; Torfing, Jacob; Peters, B. Guy;

    Governance has become one of the most commonly used concepts in contemporary political science. It is, however, often used to mean a variety of different things. This book helps to clarify this conceptual muddle by concentrating on one variety of governance-interactive governance. The authors argue...... that although the state may remain important for many aspects of governing, interactions between state and society represent an important, and perhaps increasingly important, dimension of governance. These interactions may be with social actors such as networks, with market actors or with other...... governments, but all these forms represent means of governing involving mixtures of state action with the actions of other entities.This book explores thoroughly this meaning of governance, and links it to broader questions of governance. In the process of explicating this dimension of governance the authors...

  5. Adhesion and degranulation promoting adapter protein (ADAP is a central hub for phosphotyrosine-mediated interactions in T cells.

    Directory of Open Access Journals (Sweden)

    Marc Sylvester

    Full Text Available TCR stimulation leads to an increase in cellular adhesion among other outcomes. The adhesion and degranulation promoting adapter protein (ADAP is known to be rapidly phosphorylated after T cell stimulation and relays the TCR signal to adhesion molecules of the integrin family. While three tyrosine phosphorylation sites have been characterized biochemically, the binding capabilities and associated functions of several other potential phosphotyrosine motifs remain unclear. Here, we utilize in vitro phosphorylation and mass spectrometry to map novel phosphotyrosine sites in the C-terminal part of human ADAP (486-783. Individual tyrosines were then mutated to phenylalanine and their relevance for cellular adhesion and migration was tested experimentally. Functionally important tyrosine residues include two sites within the folded hSH3 domains of ADAP and two at the C-terminus. Furthermore, using a peptide pulldown approach in combination with stable isotope labeling in cell culture (SILAC we identified SLP-76, PLCgamma, PIK3R1, Nck, CRK, Gads, and RasGAP as phospho-dependent binding partners of a central YDDV motif of ADAP. The phosphorylation-dependent interaction between ADAP and Nck was confirmed by yeast two-hybrid analysis, immunoprecipitation and binary pulldown experiments, indicating that ADAP directly links integrins to modulators of the cytoskeleton independent of SLP-76.

  6. Programming Interactivity

    CERN Document Server

    Noble, Joshua

    2009-01-01

    Make cool stuff. If you're a designer or artist without a lot of programming experience, this book will teach you to work with 2D and 3D graphics, sound, physical interaction, and electronic circuitry to create all sorts of interesting and compelling experiences -- online and off. Programming Interactivity explains programming and electrical engineering basics, and introduces three freely available tools created specifically for artists and designers: Processing, a Java-based programming language and environment for building projects on the desktop, Web, or mobile phonesArduino, a system t

  7. Weak Interactions

    Science.gov (United States)

    Lee, T. D.

    1957-06-01

    Experimental results on the non-conservation of parity and charge conservation in weak interactions are reviewed. The two-component theory of the neutrino is discussed. Lepton reactions are examined under the assumption of the law of conservation of leptons and that the neutrino is described by a two- component theory. From the results of this examination, the universal Fermi interactions are analyzed. Although reactions involving the neutrino can be described, the same is not true of reactions which do not involve the lepton, as the discussion of the decay of K mesons and hyperons shows. The question of the invariance of time reversal is next examined. (J.S.R.)

  8. Hadron interactions

    International Nuclear Information System (INIS)

    The proceedings contain invited lectures and papers presente at the symposium. Attention was devoted to hadron interactions a high energy in QCD, to the structure and decay of hadrons, the production of hadrons and supersymmetric particles in e+e- and ep collisions, to perturbation theory in quantum field theory, and new supersymmetric extensions of relativistic algebra. (Z.J

  9. Audiovisual Interaction

    DEFF Research Database (Denmark)

    Karandreas, Theodoros-Alexandros

    importance of each modality with respect to the overall quality evaluation. The results show that this was not due to specific interactions between stimuli but rather because the auditory modality dominated over the visual modality. Furthermore, for all experiments where less than optimal stimuli...

  10. Interactive Storytelling

    DEFF Research Database (Denmark)

    2015-01-01

    This book constitutes the refereed proceedings of the 8th International Conference on Interactive Digital Storytelling, ICIDS 2015, held in Copenhagen, Denmark, in November/December 2015. The 18 revised full papers and 13 short papers presented together with 9 posters, 9 workshop descriptions, and...

  11. Electroweak interactions

    International Nuclear Information System (INIS)

    The central part of the book consists of a comprehensive discussion of many scattering and decay processes involving electromagnetic, weak and strong interactions. A list of topics includes electron-proton scattering, Compton scattering, muon decay, electron-positron annihilation, photon and hadron structure functions, neutrino-nucleus scattering, Cabibbo theory, tau-lepton decays, W and Z boson decays, mixing phenomena and many others. For most processes, the author presents the appropriate Feynman diagrams, first-order matrix elements and the resulting cross sections or decay rates. The last section of Electroweak Interactions discusses some of the open or unanswered questions in the standard model, including the undiscovered top quark, the Higgs mechanism of electroweak symmetry breaking and detailed tests involving radiative effects. The book concludes with a brief account of ideas that extend beyond the standard model, such as left-right symmetric models, grand unified theories, compositeness, supersymmetry and string theory

  12. Interactive Storytelling

    DEFF Research Database (Denmark)

    Schoenau-Fog, Henrik; Reng, Lars

    2015-01-01

    This book constitutes the refereed proceedings of the 8th International Conference on Interactive Digital Storytelling, ICIDS 2015, held in Copenhagen, Denmark, in November/December 2015. The 18 revised full papers and 13 short papers presented together with 9 posters, 9 workshop descriptions, an...... 3 demonstration papers were carefully reviewed and selected from 80 submissions. The papers are organized in topical sections on theoretical and design foundations, technical advances, analyses and evaluation systems, and current and future usage scenarios and applications....

  13. Constructive Interactions

    OpenAIRE

    Lemoisson, Philippe; Cerri, Stefano A.; Mahe, Serge-André; Sallantin, Jean

    2003-01-01

    The new paradigm of "knowledge construction using experiential based and collaborative learning approaches" is an outstanding opportunity for interdisciplinary research. This document is an attempt to introduce and exemplify as much as possible using the lexicon of "social sciences", considerations and tools belonging to "artificial intelligence" (eg.:the machine learning tradition). In the paper we first draw a conceptual framework for rational agents in conversational interaction; then we u...

  14. Weak interactions

    International Nuclear Information System (INIS)

    These lectures are an introduction to the standard weak-electromagnetic gauge model and its experimental tests, followed by six-quark phenomenology and some Grand Unification schemes dealt with under the headings; charged-current fermi interaction, gauge theories, tests of the Salam-Weinberg model, natural flavour-conservation neutral current, triangle anomalies, more gauge fields, more quarks and leptons, grand unification, economy of parameters. 54 reference. (UK)

  15. Toward the rational design of protein kinase casein kinase-2 inhibitors.

    Science.gov (United States)

    Sarno, Stefania; Moro, Stefano; Meggio, Flavio; Zagotto, Giuseppe; Dal Ben, Diego; Ghisellini, Paola; Battistutta, Roberto; Zanotti, Giuseppe; Pinna, Lorenzo A

    2002-01-01

    Casein kinase-2 (CK2) probably is the most pleiotropic member of the protein kinase family, with more than 200 substrates known to date. Unlike the great majority of protein kinases, which are tightly regulated enzymes, CK2 is endowed with high constitutive activity, a feature that is suspected to underlie its oncogenic potential and possible implication in viral infections. This makes CK2 an attractive target for anti-neoplastic and antiviral drugs. Here, we present an overview of our present knowledge about CK2 inhibitors, with special reference to the information drawn from two recently solved crystal structures of CK2alpha in complex with emodin and with 4,5,6,7-tetrabromo-2-azabenzimidazole (TBB), this latter being the most specific CK2 inhibitor known to date. A comparison with a series of anthraquinone and xanthenone derivatives highlights the crucial relevance of the hydroxyl group at position 3 for inhibition by emodin, and discloses the possibility of increasing the inhibitory potency by placing an electron withdrawing group at position 5. We also present mutational data corroborating the relevance of two hydrophobic residues unique to CK2, Val66 and Ile174, for the interactions with emodin and TBB, but not with the flavonoid inhibitors quercetin and fisetin. In particular, the CK2alpha mutant V66A displays 27- and 11-fold higher IC(50) values with emodin and TBB, respectively, as compared with the wild-type, while the IC(50) value with quercetin is unchanged. The data presented pave the road toward the rational design of more potent and selective inhibitors of CK2 and the generation of CK2 mutants refractory to inhibition, useful to probe the implication of CK2 in specific cellular functions. PMID:12191608

  16. Casein kinase 2 inhibits HomolD-directed transcription by Rrn7 in Schizosaccharomyces pombe.

    Science.gov (United States)

    Moreira-Ramos, Sandra; Rojas, Diego A; Montes, Matías; Urbina, Fabiola; Miralles, Vicente J; Maldonado, Edio

    2015-02-01

    In Schizosaccharomyces pombe, ribosomal protein gene (RPG) promoters contain a TATA analogue element called the HomolD box. The HomolD-binding protein Rrn7 forms a complex with the RNA polymerase II machinery. Despite the importance of ribosome biogenesis to cell survival, the mechanisms involved in the regulation of transcription of eukaryotic RPGs are unknown. In this study, we identified Rrn7 as a new substrate of the pleiotropic casein kinase 2 (CK2), which is a regulator of basal transcription. Recombinant Rrn7 from S. pombe, which is often used as a model organism for studying eukaryotic transcription, interacted with CK2 in vitro and in vivo. Furthermore, CK2-mediated phosphorylation of Rrn7 inhibited its HomolD-directed transcriptional activity and ability to bind to an oligonucleotide containing a HomolD box in vitro. Mutation of Rrn7 at Thr67 abolished these effects, indicating that this residue is a critical CK2 phosphorylation site. Finally, Rrn7 interacted with the regulatory subunit of CK2 in vivo, inhibition of CK2 in vivo potentiated ribosomal protein gene transcription, and chromatin immunoprecipitation analyses identified that the catalytic subunit of CK2 was associated with the rpk5 gene promoter in S. pombe. Taken together, these data suggest that CK2 inhibits ribosomal protein gene transcription in S. pombe via phosphorylation of Rrn7 at Thr67. PMID:25410910

  17. Interactive Workspaces

    DEFF Research Database (Denmark)

    Mogensen, Preben Holst

    augmented reality, interactive building elements, and mobile devices to support new ways of working in a diversity of application domains with work situations ranging from individual work, through local collaboration, to distributed collaboration. The work situations may take place in offices/project rooms......Many application domains such as architecture, engineering, industrial design, city planning, environmental supervision, health care etc. share the properties of users working collaboratively with complex mixtures of physical and digital materials. Studies in such domains show that it is hard...

  18. Electroweak interactions

    CERN Document Server

    Maiani, Luciano

    2016-01-01

    Written by one of the world's leading experts on particle physics and the standard model―an award-winning former director general of CERN―this book provides an up-to-date account of electroweak interactions. Part of a series describing the formal, physical, and phenomenological aspects of the standard model of particle physics, the text introduces the mathematical concepts and applications of symmetry principles to particle physics, from the isotopic spin symmetry to the Eightfold Way and the Yang-Mills theories.

  19. Electromagnetic interactions

    CERN Document Server

    Bosanac, Slobodan Danko

    2016-01-01

    This book is devoted to theoretical methods used in the extreme circumstances of very strong electromagnetic fields. The development of high power lasers, ultrafast processes, manipulation of electromagnetic fields and the use of very fast charged particles interacting with other charges requires an adequate theoretical description. Because of the very strong electromagnetic field, traditional theoretical approaches, which have primarily a perturbative character, have to be replaced by descriptions going beyond them. In the book an extension of the semi-classical radiation theory and classical dynamics for particles is performed to analyze single charged atoms and dipoles submitted to electromagnetic pulses. Special attention is given to the important problem of field reaction and controlling dynamics of charges by an electromagnetic field.

  20. Unification of Electromagnetic Interactions and Gravitational Interactions

    Institute of Scientific and Technical Information of China (English)

    WU Ning

    2002-01-01

    Unified theory of gravitational interactions and electromagnetic interactions is discussed in this paper.Based on gauge principle, electromagnetic interactions and gravitational interactions are formulated in the same mannerand are unified in a semi-direct product group of U(1) Abelian gauge group and gravitational gauge group.

  1. Unification of Electromagnetic Interactions and Gravitational Interactions

    Institute of Scientific and Technical Information of China (English)

    WUNing

    2002-01-01

    Unified theory of gravitational interactions and electromagnetic interactions is discussed in this paper.Based on gauge principle,electromagnetic interactions and gravitational interactions are formulated in the same manner and are unified in a semi-direct product group of U(1) Abelian gauge group and gravitational gauge group.

  2. Unification of Electromagnetic Interactions and Gravitational Interactions

    OpenAIRE

    Wu, Ning

    2002-01-01

    Unified theory of gravitational interactions and electromagnetic interactions is discussed in this paper. Based on gauge principle, electromagnetic interactions and gravitational interactions are formulated in the same manner and are unified in a semi-direct product group of U(1) Abel gauge group and gravitational gauge group.

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

    DEFF Research Database (Denmark)

    Hjerrild, M; Milne, D; Dumaz, N; Hay, T; Issinger, O G; Meek, D

    ,6-dichlororibofuranosylbenzimidazole. Radiolabelling of cells expressing tagged recombinant wild-type MDM2 or a S267A (Ser(267)-->Ala) mutant, followed by phosphopeptide analysis, confirmed that Ser(267) is a cellular target for phosphorylation. Ser(267) mutants are still able to direct the degradation of p53, but in a slightly...

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

    OpenAIRE

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

    2008-01-01

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

  5. The regulatory beta-subunit of protein kinase CK2 accelerates the degradation of CDC25A phosphatase through the checkpoint kinase Chk1

    DEFF Research Database (Denmark)

    Kreutzer, Jan Nicolas; Guerra, Barbara

    2007-01-01

    Human CDC25 phosphatases play an important role in cell cycle regulation by removing inhibitory phosphate groups on cyclin-CDKs. Chk1 has been shown to phosphorylate CDC25 family members down-regulating their phosphatase activity through distinct mechanisms. The kinase activity of Chk1 is evident...... cell cycle progression is shown to enhance CDC25A degradation, and this occurs in a manner similar to that by which CDC25A is down-regulated upon activation of cellular checkpoint responses. By using RNA interference to specifically deplete cells of Chk1, we demonstrate that Chk1 mediates the down-regulation...... cell cycle regulation and indicate the mechanism by which CDC25A turnover might be regulated by Chk1 in the absence of DNA damage....

  6. 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

    Although a number of nucleoside diphosphate kinases (NDPKs) have been reported to act as inhibitors of metastasis or as a transcription factor in mammals, it is not known whether these functions are linked to their enzymatic activity or how this protein is regulated. In this report, we show that ...... on histidine residues, however, only the B isoform appeared to be serine phosphorylated....

  7. Drug Interaction API

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Interaction API is a web service for accessing drug-drug interactions. No license is needed to use the Interaction API. Currently, the API uses DrugBank for its...

  8. Phosphorylation-dependent differential regulation of plant growth, cell death, and innate immunity by the regulatory receptor-like kinase BAK1

    DEFF Research Database (Denmark)

    Schwessinger, Benjamin; Roux, Milena; Kadota, Yasuhiro;

    2011-01-01

    Plants rely heavily on receptor-like kinases (RLKs) for perception and integration of external and internal stimuli. The Arabidopsis regulatory leucine-rich repeat RLK (LRR-RLK) BAK1 is involved in steroid hormone responses, innate immunity, and cell death control. Here, we describe the different...

  9. The response of Arabidopsis root water transport to a challenging environment implicates reactive oxygen species- and phosphorylation-dependent internalization of aquaporins

    OpenAIRE

    Boursiac, Yann; Prak, Sodana; Boudet, Julie; Postaire, Olivier; Luu, Doan-Trung; Tournaire-Roux, Colette; Santoni, Véronique; Maurel, Christophe

    2008-01-01

    Aquaporins, which facilitate the diffusion of water across biological membranes, are key molecules for the regulation of water transport at the cell and organ levels. We recently reported that hydrogen peroxide (H2O2) acts as an intermediate in the regulation of Arabidopsis root water transport and aquaporins in response to NaCl and salicylic acid (SA).1 Its action involves signaling pathways and an internalization of aquaporins from the cell surface. The present addendum connects these findi...

  10. Strong interactions, Zweig's rule, and weaker interactions

    International Nuclear Information System (INIS)

    An attempt is made to connect five notions: Strong interaction scattering amplitudes do not involve the action of a Hamiltonian and are only Clebsch-Gordan coefficients. The four momentum vector P is an SU(something) operator. The four momentum of a quark does not change in a strong interaction scattering. Zweig's rule. Gluons should not be drawn in strong interaction scattering diagrams. Finally, a simple explanation will be offered for the weak interaction of leptons amongst themselves and with hadrons. (U.S.)

  11. Designing for mobile interaction

    DEFF Research Database (Denmark)

    Nazzi, Elena

    2009-01-01

    The theme of this PhD project is designing for mobile interaction with devices and services, for the accessing, making, and sharing of information, taking into account the dynamic physical and social settings that embrace this interaction. To narrow down this theme, the whole project focuses on the...... exploitation of social interaction --- in particular among senior citizens --- to enhance and support mobile interaction....

  12. Interaction for visualization

    CERN Document Server

    Tominski, Christian

    2015-01-01

    Visualization has become a valuable means for data exploration and analysis. Interactive visualization combines expressive graphical representations and effective user interaction. Although interaction is an important component of visualization approaches, much of the visualization literature tends to pay more attention to the graphical representation than to interaction.The goal of this work is to strengthen the interaction side of visualization. Based on a brief review of general aspects of interaction, we develop an interaction-oriented view on visualization. This view comprises five key as

  13. Bile acid interactions with cholangiocytes

    Institute of Scientific and Technical Information of China (English)

    Xuefeng Xia; Heather Francis; Shannon Glaser; Gianfranco Alpini; Gene LeSage

    2006-01-01

    Cholangiocytes are exposed to high concentrations of bile acids at their apical membrane. A selective transporter for bile acids, the Apical Sodium Bile Acid Cotransporter (ASBT) (also referred to as Ibat; gene name Slc10a2)is localized on the cholangiocyte apical membrane. On the basolateral membrane, four transport systems have been identified (t-ASBT, multidrug resistance (MDR)3,an unidentified anion exchanger system and organic solute transporter (Ost) heteromeric transporter, OstαOstβ. Together, these transporters unidirectionally move bile acids from ductal bile to the circulation. Bile acids absorbed by cholangiocytes recycle via the peribiliaryplexus back to hepatocytes for re-secretion into bile.This recycling of bile acids between hepatocytes and cholangiocytes is referred to as the cholehepatic shunt pathway. Recent studies suggest that the cholehepatic shunt pathway may contribute in overall hepatobiliary transport of bile acids and to the adaptation to chronic cholestasis due to extrahepatic obstruction. ASBT is acutely regulated by an adenosine 3', 5'-monophosphate (cAMP)-dependent translocation to the apical membrane and by phosphorylation-dependent ubiquitination and proteasome degradation. ASBT is chronically regulated by changes in gene expression in response to biliary bile acid concentration and inflammatory cytokines.Another potential function of cholangiocyte ASBT is to allow cholangiocytes to sample biliary bile acids in order to activate intracellular signaling pathways. Bile acids trigger changes in intracellular calcium, protein kinase C (PKC), phosphoinositide 3-kinase (PI3K), mitogenactivated protein (MAP) kinase and extracellular signalregulated protein kinase (ERK) intracellular signals.Bile acids significantly alter cholangiocyte secretion,proliferation and survival. Different bile acids have differential effects on cholangiocyte intracellular signals,and in some instances trigger opposing effects on cholangiocyte secretion

  14. Interaction Design: Foundations, Experiments

    OpenAIRE

    Hallnäs, Lars; Redström, Johan

    2006-01-01

    Interaction Design: Foundations, Experiments is the result of a series of projects, experiments and curricula aimed at investigating the foundations of interaction design in particular and design research in general. The first part of the book - Foundations - deals with foundational theoretical issues in interaction design. An analysis of two categorical mistakes -the empirical and interactive fallacies- forms a background to a discussion of interaction design as act design and of computa...

  15. PIC: Protein Interactions Calculator

    OpenAIRE

    Tina, KG; Bhadra, R.; Srinivasan, N.

    2007-01-01

    Interactions within a protein structure and interactions between proteins in an assembly are essential considerations in understanding molecular basis of stability and functions of proteins and their complexes. There are several weak and strong interactions that render stability to a protein structure or an assembly. Protein Interactions Calculator (PIC) is a server which, given the coordinate set of 3D structure of a protein or an assembly, computes various interactions such as disulphide bo...

  16. Interactive Pinball Business

    DEFF Research Database (Denmark)

    Buur, Jacob; Gudiksen, Sune

    2012-01-01

    Interaction design expands into new fields. Interaction design and business model innovation is a promising meeting of disciplines: Many businesses see the need to rethink their ways of doing business, and, as business models pose highly dynamic and interactive problems, interaction design has much...... to offer. This paper compares ‘tangible business models’ in the form of pinball-like contraptions, designed by interaction design students with those developed by groups of professionals around concrete business issues. We will show how the interactive models encourage business people to play with...... hypotheses and experiment with scenarios as a way of innovating their business models, and why this is so....

  17. Interactive pinball business

    DEFF Research Database (Denmark)

    Buur, Jacob; Gudiksen, Sune Klok

    2012-01-01

    Interaction design expands into new fields. Interaction design and business model innovation is a promising meeting of disciplines: Many businesses see the need to rethink their ways of doing business, and, as business models pose highly dynamic and interactive problems, interaction design has much...... to offer. This paper compares 'tangible business models' in the form of pinball-like contraptions, designed by interaction design students with those developed by groups of professionals around concrete business issues. We will show how the interactive models encourage business people to play with...... hypotheses and experiment with scenarios as a way of innovating their business models, and why this is so...

  18. Interacting dark sector with transversal interaction

    Energy Technology Data Exchange (ETDEWEB)

    Chimento, Luis P.; Richarte, Martín G. [Departamento de Física, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires and IFIBA, CONICET, Ciudad Universitaria, Pabellón I, Buenos Aires 1428 (Argentina)

    2015-03-26

    We investigate the interacting dark sector composed of dark matter, dark energy, and dark radiation for a spatially flat Friedmann-Robertson-Walker (FRW) background by introducing a three-dimensional internal space spanned by the interaction vector Q and solve the source equation for a linear transversal interaction. Then, we explore a realistic model with dark matter coupled to a scalar field plus a decoupled radiation term, analyze the amount of dark energy in the radiation era and find that our model is consistent with the recent measurements of cosmic microwave background anisotropy coming from Planck along with the future constraints achievable by CMBPol experiment.

  19. Sea Turtle Interaction Report

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Sea Turtle Interaction Report is a report sent out in pdf format to authorized individuals that summarizes sea turtle interactions in the longline fishery. The...

  20. Health Data Interactive (HDI)

    Data.gov (United States)

    U.S. Department of Health & Human Services — Health Data Interactive (HDI) presents a broad range of important public health indicators through an interactive web-based application that provides access to...

  1. Compton effect: interacting particles or interacting waves

    CERN Document Server

    Hernández, O F

    2005-01-01

    Traditional textbook explanations of the Compton effect treat the photon electron interaction as a particle collision. This explanation is a pedagogical disaster, implying that sometimes interactions are particle-like whereas quantum mechanics always demands that they be wave-like; a photon wavefunction evolves according to a wave equation until its collapse at measurement. If this is so why then does the classical radiation wave equation fail to predict the Compton effect? We address these issues and propose a clearer explanation.

  2. Plasma-wall interaction; Interaction plasma paroi

    Energy Technology Data Exchange (ETDEWEB)

    Reichle, R

    2004-07-01

    This document gathers the 43 slides presented in the framework of the week long lecture 'hot plasmas 2004' and dedicated to plasma-wall interaction in a tokamak. This document is divided into 4 parts: 1) thermal load on the wall, power extraction and particle recovery, 2) basic edge plasma physics, 3) processes that drive the plasma-solid interaction, and 4) material conditioning (surface treatment...) for ITER.

  3. Predictability of social interactions

    OpenAIRE

    Xu, Kevin S.

    2013-01-01

    The ability to predict social interactions between people has profound applications including targeted marketing and prediction of information diffusion and disease propagation. Previous work has shown that the location of an individual at any given time is highly predictable. This study examines the predictability of social interactions between people to determine whether interaction patterns are similarly predictable. I find that the locations and times of interactions for an individual are...

  4. Gaze Interactive Building Instructions

    DEFF Research Database (Denmark)

    Hansen, John Paulin; Ahmed, Zaheer; Mardanbeigi, Diako

    We combine eye tracking technology and mobile tablets to support hands-free interaction with digital building instructions. As a proof-of-concept we have developed a small interactive 3D environment where one can interact with digital blocks by gaze, keystroke and head gestures. Blocks may be moved...

  5. Food-Drug Interactions

    OpenAIRE

    Arshad Yar Khan; Nousheen Aslam; Rabia Bushra

    2011-01-01

    The effect of drug on a person may be different than expected because that drug interacts with another drug the person is taking (drug-drug interaction), food, beverages, dietary supplements the person is consuming (drug-nutrient/food interaction) or another disease the person has (drug-disease interaction). A drug interaction is a situation in which a substance affects the activity of a drug, i.e. the effects are increased or decreased, or they produce a new effect that neither produces on i...

  6. Grasp interaction with tablets

    CERN Document Server

    Wolf, Katrin

    2015-01-01

    This book presents guidelines for a future device type: a tablet that allows ergonomic front- and back-of-device interaction. These guidelines help designers and developers of user interfaces to build ergonomic applications for tablet devices, in particular for devices that enable back-of-device interaction. In addition, manufacturers of tablet devices obtain arguments that back-of-device interaction is a promising extension of the interaction design space and results in increased input capabilities, enriched design possibilities, and proven usability. The guidelines are derived from empirical studies and developed to fit the users’ skills to the way the novel device type is held. Three particular research areas that are relevant to develop design guidelines for tablet interaction are investigated: ergonomic gestures, interaction areas, and pointing techniques.

  7. Patient - patient interaction

    DEFF Research Database (Denmark)

    Birkelund, Regner; Søndergaard Larsen, Lene

    2013-01-01

    occasionally, the opposite was experienced too. Less typically, the patients experienced interaction with fellow patients as a burden and referred to it in negative terms. Conclusions:  Patients’ interaction resembled care as well as self-care. Patient–patient interaction was an important part of the social...... subcategories representing significance of patients’ interaction with fellow patients. Results:  The qualitative analysis resulted in two main categories: (i) Caring for fellow patients and (ii) Sharing illness information with fellow patients. Each of the main categories was elucidated through several...... subcategories. Our findings clearly showed that interpersonal interaction with fellow patients was of utmost importance when it came to care and support and when they needed information about their illness. Typically, the interpersonal interaction was experienced as giving and referred to in positive terms, but...

  8. Quantum interaction. Proceedings

    Energy Technology Data Exchange (ETDEWEB)

    Bruza, Peter [Queensland Univ. of Technology, Brisbane (Australia). Faculty of Science and Technology; Sofge, Donald [Navy Center for Applied Research in Artificial Intelligence, Washington, DC (United States). Naval Research Lab.; Lawless, William [Paine Coll., Augusta, GA (United States); Rijsbergen, Keith van [Glasgow Univ. (United Kingdom). Dept. of Computing Science; Klusch, Matthias (eds.) [German Research Center for Artificial Intelligence, Saarbruecken (Germany)

    2009-07-01

    This book constitutes the refereed proceedings of the Third International Symposium on Quantum Interaction, QI 2009, held in Saarbruecken, Germany, in March 2009. The 21 revised full papers presented together with the 3 position papers were carefully reviewed and selected from numerous submissions. The papers show the cross-disciplinary nature of quantum interaction covering topics such as computation, cognition, decision theory, information retrieval, information systems, social interaction, computational linguistics and finance. (orig.)

  9. Interactions in multispecies biofilms

    DEFF Research Database (Denmark)

    Burmølle, Mette; Ren, Dawei; Bjarnsholt, Thomas;

    2014-01-01

    The recent focus on complex bacterial communities has led to the recognition of interactions across species boundaries. This is particularly pronounced in multispecies biofilms, where synergistic interactions impact the bacterial distribution and overall biomass produced. Importantly, in a number...... of settings, the interactions in a multispecies biofilm affect its overall function, physiology, or surroundings, by resulting in enhanced resistance, virulence, or degradation of pollutants, which is of significant importance to human health and activities. The underlying mechanisms causing these...

  10. Interaction Before Agriculture

    DEFF Research Database (Denmark)

    Richter, Tobias; Garrard, Andrew; Allcock, Samantha;

    2011-01-01

    This article discusses social interaction in the Epipalaeolithic of southwest Asia. Discussions of contact, social relationships and social organization have primarily focused on the Pre-Pottery Neolithic and are often considered to represent typical hallmarks of emergent farming societies. The h...... for interaction. We argue that interaction between differently-constituted groups can be traced within the Early Epipalaeolithic of the southern Levant, suggesting that it is of far greater antiquity than previously considered....

  11. Electroweak interactions in nuclei

    Science.gov (United States)

    Henley, E. M.

    1984-06-01

    Nuclear and subnuclear degrees of freedom and lepton nucleus scattering were discussed. Electroweak interactions in nuclei were examined. Topics discussed include: introduction to electroweak theory; the Weinberg-Salam theory for leptons; the Weinberg-Salam theory for hadrons-the GIM mechanism; electron scattering as a probe of the electroweak interaction (observation of PV, the weak interaction for nucleons, and parity violation in atoms); and time reversed invariance and electric dipole moments of nucleons, nuclei, and atoms.

  12. ENTREPRENEURSHIP AS SOCIAL INTERACTION

    DEFF Research Database (Denmark)

    Larsen, Henry; Lima, Patricia; Olsen, Bente;

    2013-01-01

    This paper aims to explore how entrepreneurs work with innovation; to explore and develop attention points in understanding entrepreneurship as social processes of interaction between people. Through interviews and engagement with entrepreneurs and key stakeholders, their actual social practices...... entrepreneurship as socially constructed through local interactions between players and identify key themes in these interactions within the organisation, such as leadership, becoming part of the initiative and trust/mistrust. By doing so, this paper contributes to an understanding of entrepreneurship as social...

  13. Framing interactive methods

    DEFF Research Database (Denmark)

    Rasmussen, Lauge Baungaard

    2011-01-01

    Two paradigms of organization and leadership is outlined and compared. A theoretical model of interactive leadership is developed, combining learning, knowledge flow, leadership and organizational principles....

  14. Vision-based interaction

    CERN Document Server

    Turk, Matthew

    2013-01-01

    In its early years, the field of computer vision was largely motivated by researchers seeking computational models of biological vision and solutions to practical problems in manufacturing, defense, and medicine. For the past two decades or so, there has been an increasing interest in computer vision as an input modality in the context of human-computer interaction. Such vision-based interaction can endow interactive systems with visual capabilities similar to those important to human-human interaction, in order to perceive non-verbal cues and incorporate this information in applications such

  15. Philosophy of Interaction

    DEFF Research Database (Denmark)

    Svanæs, Dag

    2011-01-01

    This is an encyclopedia entry for the Interaction-Design.org free IxD encyclopedia. The topic of the entry is the application of the philosophy of Heidegger and Merleau-Ponty to a theory of interactivity. Comments by Don Norman and Eva Hornecker.......This is an encyclopedia entry for the Interaction-Design.org free IxD encyclopedia. The topic of the entry is the application of the philosophy of Heidegger and Merleau-Ponty to a theory of interactivity. Comments by Don Norman and Eva Hornecker....

  16. The Science of Interaction

    Energy Technology Data Exchange (ETDEWEB)

    Pike, William A.; Stasko, John T.; Chang, Remco; O' Connell, Theresa

    2009-09-23

    There is a growing recognition with the visual analytics community that interaction and inquiry are inextricable. It is through the interactive manipulation of a visual interface – the analytic discourse – that knowledge is constructed, tested, refined, and shared. This paper reflects on the interaction challenges raised in the original visual analytics research and development agenda and further explores the relationship between interaction and cognition. It identifies recent exemplars of visual analytics research that have made substantive progress toward the goals of a true science of interaction, which must include theories and testable premises about the most appropriate mechanisms for human-information interaction. Six areas for further work are highlighted as those among the highest priorities for the next five years of visual analytics research: ubiquitous, embodied interaction; capturing user intentionality; knowledge-based interfaces; principles of design and perception; collaboration; and interoperability. Ultimately, the goal of a science of interaction is to support the visual analytics community through the recognition and implementation of best practices in the representation of and interaction with visual displays.

  17. KinomeXplorer: an integrated platform for kinome biology studies

    DEFF Research Database (Denmark)

    Horn, Heiko; Schoof, Erwin; Kim, Jinho; Robin, Xavier; Miller, Martin Lee; Diella, Francesca; Palma, Anita; Cesareni, Gianni; Jensen, Lars Juhl; Linding, Rune

    2014-01-01

    A letter to the editor is presented related to the KinomeXplorer, an integrated platform providing workflows to efficiently analyze phosphorylation dependent interaction networks or kinase signaling networks....

  18. Interaction Analysis and Supervision.

    Science.gov (United States)

    Amidon, Edmund

    This paper describes a model that uses interaction analysis as a tool to provide feedback to a teacher in a microteaching situation. The author explains how interaction analysis can be used for teacher improvement, describes the category system used in the model, the data collection methods used, and the feedback techniques found in the model. (JF)

  19. Child Computer Interaction SIG

    DEFF Research Database (Denmark)

    Read, Janet; Hourcade, Juan Pablo; Markopoulos, Panos;

    The discipline of Child Computer Interaction (CCI) has been steadily growing and it is now firmly established as a community in its own right, having the annual IDC (Interaction and Design for Children) conference and its own journal and also enjoying its role as a highly recognisable and vibrant...

  20. Electroweak interactions in nuclei

    International Nuclear Information System (INIS)

    Topics include: introduction to electroweak theory; the Weinberg-Salam theory for leptons; the Weinberg-Salam theory for hadrons-the GIM mechanism; electron scattering as a probe of the electroweak interaction (observation of PV, the weak interaction for nucleons, and parity violation in atoms); and time reversed invariance and electric dipole moments of nucleons, nuclei, and atoms. 52 references

  1. Moving into an interaction

    DEFF Research Database (Denmark)

    Mortensen, Kristian; Hazel, Spencer

    2014-01-01

    Opening an interaction is a crucial step in establishing and maintaining social relationships. In this paper we describe how participants in an institutional setting, a help desk counter for exchange students at an international university, literally move into interaction. This is accomplished th...

  2. Future Interaction Design II

    CERN Document Server

    Isomaki, Heikki M

    2009-01-01

    Argues that it is the human character rather than the technology that should determine the nature of interaction, and that the term 'interaction design' covers a range of issues relevant to enabling quality design. This book discusses a number of topics, such as psychological design processes, gerotechnology, modeling, and e-learning

  3. Let Social Interaction Flourish

    Science.gov (United States)

    Case, Anny Fritzen

    2016-01-01

    The author describes lessons learned--through a high school project that grouped English language learners with native speakers to create a video--about ways to foster respectful, productive interaction among English learners and peers who are native speakers. The potential benefits of students who are just learning English interacting socially…

  4. INTERACT Station Catalogue - 2015

    DEFF Research Database (Denmark)

    INTERACT stations are located in all major environmental envelopes of the Arctic providing an ideal platform for studying climate change and its impact on the environment and local communities. Since alpine environments face similar changes and challenges as the Arctic, the INTERACT network also...

  5. Visualizing Dispersion Interactions

    Science.gov (United States)

    Gottschalk, Elinor; Venkataraman, Bhawani

    2014-01-01

    An animation and accompanying activity has been developed to help students visualize how dispersion interactions arise. The animation uses the gecko's ability to walk on vertical surfaces to illustrate how dispersion interactions play a role in macroscale outcomes. Assessment of student learning reveals that students were able to develop…

  6. Human Work Interaction Design

    DEFF Research Database (Denmark)

    Lopes, Arminda; Ørngreen, Rikke

    This book constitutes the thoroughly refereed post-conference proceedings of the Third IFIP WG 13.6 Working Conference on Human Work Interaction Design, HWID 2012, held in Copenhagen, Denmark, in December 2012. The 16 revised papers presented were carefully selected for inclusion in this volume. ......, and mobile probing. They have been organized in the following topical sections: work analysis: dimensions and methods; interactions, models and approaches; and evaluations, interactions and applications.......This book constitutes the thoroughly refereed post-conference proceedings of the Third IFIP WG 13.6 Working Conference on Human Work Interaction Design, HWID 2012, held in Copenhagen, Denmark, in December 2012. The 16 revised papers presented were carefully selected for inclusion in this volume....... The papers reflect many different areas and address many complex and diverse work domains, ranging from medical user interfaces, work and speech interactions at elderly care facilities, greenhouse climate control, navigating through large oil industry engineering models, crisis management, library usability...

  7. Laser-surface interactions

    CERN Document Server

    Ganeev, Rashid A

    2014-01-01

    This book is about the interaction of laser radiation with various surfaces at variable parameters of radiation. As a basic principle of classification we chose the energetic or intensity level of interaction of laser radiation with the surfaces. These two characteristics of laser radiation are the most important parameters defining entire spectrum of the processes occurring on the surfaces during interaction with electromagnetic waves. This is a first book containing a whole spectrum of the laser-surface interactions distinguished by the ranges of used laser intensity. It combines the surface response starting from extremely weak laser intensities (~1 W cm-2) up to the relativistic intensities (~1020 W cm-2 and higher). The book provides the basic information about lasers and acquaints the reader with both common applications of laser-surface interactions (laser-related printers, scanners, barcode readers, discs, material processing, military, holography, medicine, etc) and unusual uses of the processes on t...

  8. Fibronectin-cell interactions

    DEFF Research Database (Denmark)

    Couchman, J R; Austria, M R; Woods, A

    1990-01-01

    in vivo. Much data suggests that fibronectins may promote extracellular matrix assembly, and cell adhesion to those matrices. However, one outstanding enigma is that fibronectins may, under different circumstances, promote both cell migration and anchorage. An analysis of the interaction of fibroblasts...... with proteolytically derived and purified domains of plasma fibronectin revealed that the type of adhesion and the correlated cytoskeletal organization depended on multiple interactions of fibronectin domains with the cell surface. Human dermal fibroblasts were capable of interacting with the integrin-binding domain...... and both heparin-binding domains of the plasma fibronectin molecule and their interactions determined the type of adhesion. The same principle was seen in a study of the ability of plasma fibronectin to promote basement membrane assembly in an endodermal cell line, PF-HR9. There also, interactions of both...

  9. Magnetic interactions between nanoparticles

    Directory of Open Access Journals (Sweden)

    Steen Mørup

    2010-12-01

    Full Text Available We present a short overview of the influence of inter-particle interactions on the properties of magnetic nanoparticles. Strong magnetic dipole interactions between ferromagnetic or ferrimagnetic particles, that would be superparamagnetic if isolated, can result in a collective state of nanoparticles. This collective state has many similarities to spin-glasses. In samples of aggregated magnetic nanoparticles, exchange interactions are often important and this can also lead to a strong suppression of superparamagnetic relaxation. The temperature dependence of the order parameter in samples of strongly interacting hematite nanoparticles or goethite grains is well described by a simple mean field model. Exchange interactions between nanoparticles with different orientations of the easy axes can also result in a rotation of the sub-lattice magnetization directions.

  10. User interaction widgets for interactive theorem proving

    OpenAIRE

    Zacchiroli, Stefano

    2007-01-01

    Matita (that means pencil in Italian) is a new interactive theorem prover under development at the University of Bologna. When compared with state-of-the-art proof assistants, Matita presents both traditional and innovative aspects. The underlying calculus of the system, namely the Calculus of (Co)Inductive Constructions (CIC for short), is well-known and is used as the basis of another mainstream proof assistant—Coq—with which Matita is to some extent compatible. In the sam...

  11. Interaction English Teaching Model

    Institute of Scientific and Technical Information of China (English)

    穆宇娜

    2013-01-01

      Malash—Thomas pointed out“Interaction is a process in which people and things act upon each other through their ac⁃tions.”According to different subjects, interaction can be divided into human-computer interaction, people-people interaction and learner-content interaction. According to different forms, interactions can be divided into one-one interaction, one-more interac⁃tion and more-more interaction.“Interaction Education”means that teachers are leading parts and students are the center of class. During teaching process, teachers must lead students to discover. Demands from students can encourage teachers to inspire con⁃versely.Thus it can form a close communication between teachers and students. Teaching and learning are realized in a happy and harmonious atmosphere. Successful English teaching must take new bilateral teaching as the first part, which should let the func⁃tion of the two most important elements develop fully. Teachers should grasp opportunities to guide. Teaching methods need to be flexible, and contents of teaching need to be vivid;students should be keen to think, to participate actively, and can break the tradi⁃tion to produce fresh ideas, and in that situation the capability of students can develop fully. The educational model refers to the simplified description of detailed teaching activities. Possessing dual functions of theory and practice, the educational model is the manifestation of theoretical teaching method. The combination of interaction and educational model which are mentioned above form the“interactive teaching”model. With the coming of economic globalization and integration of science and technology, now communications are increasing with each passing day. If you want to take part in or to get in touch with others, you must use lan⁃guage. English has been learnt for 10 years in Middle school and in college, but it can’t be spoken very fluently. That is a realistic picture as the result of an

  12. Magnetic interactions between nanoparticles

    DEFF Research Database (Denmark)

    Mørup, Steen; Hansen, Mikkel Fougt; Frandsen, Cathrine

    2010-01-01

    We present a short overview of the influence of inter-particle interactions on the properties of magnetic nanoparticles. Strong magnetic dipole interactions between ferromagnetic or ferrimagnetic particles, that would be superparamagnetic if isolated, can result in a collective state of nanoparti......We present a short overview of the influence of inter-particle interactions on the properties of magnetic nanoparticles. Strong magnetic dipole interactions between ferromagnetic or ferrimagnetic particles, that would be superparamagnetic if isolated, can result in a collective state...... of nanoparticles. This collective state has many similarities to spin-glasses. In samples of aggregated magnetic nanoparticles, exchange interactions are often important and this can also lead to a strong suppression of superparamagnetic relaxation. The temperature dependence of the order parameter in samples...... of strongly interacting hematite nanoparticles or goethite grains is well described by a simple mean field model. Exchange interactions between nanoparticles with different orientations of the easy axes can also result in a rotation of the sub-lattice magnetization directions....

  13. Plasma-wall interactions

    International Nuclear Information System (INIS)

    The plasma wall interactions for two extreme cases, the 'vacuum model' and the 'cold gas blanket' are outlined. As a first step for understanding the plasma wall interactions the elementary interaction processes at the first wall are identified. These are energetic ion and neutral particle trapping and release, ion and neutral backscattering, ion sputtering, desorption by ions, photons and electrons and evaporation. These processes have only recently been started to be investigated in the parameter range of interest for fusion research. The few measured data and their extrapolation into regions not yet investigated are reviewed

  14. Interacting with virtual worlds

    Science.gov (United States)

    Zeltzer, David

    1991-01-01

    What tools should we provide the user for defining and interacting with objects and agents in virtual environments at varying levels of complexity? Understanding the appropriate simplifications to make is critical for modeling nontrivial environments and agents with varying levels of autonomy. I describe a set of abstraction mechanisms appropriate for constructing and interacting with virtual worlds, and I discuss how programming, and direct manipulation of guiding techniques, can be used to afford users interactive access to graphical simulations at appropriate levels of abstraction.

  15. Media Facades beyond Interaction

    DEFF Research Database (Denmark)

    Fritsch, Jonas

    2008-01-01

    As part of a the research project Digital Urban Living [www.digitalurbanliving.dk], we have taken part in the design of two large-scale installations that employ interactive technologies to facilitate participation and foster social interactions in public, urban settings. We present the two cases......, Aarhus by Light and Projected Poetry, and discuss the future trajectory of our work in this field, as well as some of our findings regarding the challenges of designing large-scale public interactive installations. In doing so, we specifically highlight the possibilities in relation to designing for...

  16. Interactive Strategy-Making

    DEFF Research Database (Denmark)

    Andersen, Torben Juul

    2015-01-01

    This article outlines an interactive strategy-making model that combines central reasoning with ongoing learning from decentralised responses. The management literature often presents strategy as implementing an optimal plan identified through rational analysis and ascribes potential shortcomings...... to failed communication and execution of the planned actions. However, effective strategy-making comprises both central reasoning from forward-looking planning considerations and decentralised responses to emerging events as interacting elements in a dynamic adaptive system. The interaction between...... these central and decentralised processes explains how strategic adaptation can thrive under turbulent conditions in the interface between central reasoning and decentralised responses....

  17. Semi-leptonic interactions

    International Nuclear Information System (INIS)

    In spite of the presence of poorly understood strong interaction effects, the theory of hadronic currents leads to a considerable predictive power. This is shown in the discussion of the semi-leptonic decays

  18. Atomic and Molecular Interactions

    International Nuclear Information System (INIS)

    The Gordon Research Conference (GRC) on Atomic and Molecular Interactions was held at Roger Williams University, Bristol, RI. Emphasis was placed on current unpublished research and discussion of the future target areas in this field

  19. Space for Interaction

    DEFF Research Database (Denmark)

    Jørgensen, Mariane Ellen; Folmer, Mette Blicher; Mullins, Michael;

    SPACE FOR INTERACTION QUALIFYING GROUP TREATMENT FOR PATIENTS WITH CHRONIC PAIN THROUGH OPTIMIZATION(?) OF SPACE. A RANDOMIZED PILOT STUDY. In a Ph-D. Mariane Ellen Jørgensen / Nurse + psykoterapist / maej@rn.dk / Pain Center / Aalborg University Hospital / Denmark / Mette Blicher Folmer...... Building Research Institute / Aalborg University / Denmark AIM Research shows the hospital space has significance for human healing processes and the physical environment can have both positive and negative impact on the interaction between patients and staff. In order to qualify treatment for patients...... with chronic pain, the effect and experience of two different rooms for group therapy were compared. Three hypotheses were tested: 1) Room decor affects the interaction and thus the psychotherapeutic group therapy 2) The meaning of space for the interaction could be measured on the effect of treatment 3...

  20. Theory of gravitational interactions

    CERN Document Server

    Gasperini, Maurizio

    2013-01-01

    This reference textbook is an up-to-date and self-contained introduction to the theory of gravitational interactions. The first part of the book follows the traditional presentation of general relativity as a geometric theory of the macroscopic gravitational field. A second, advanced part then discusses the deep analogies (and differences) between a geometric theory of gravity and the gauge theories of the other fundamental interactions. This fills a gap which is present in the context of the traditional approach to general relativity, and which usually makes students puzzled about the role of gravity. The necessary notions of differential geometry are reduced to the minimum, leaving more room for those aspects of gravitational physics of current phenomenological and theoretical interest, such as the properties of gravitational waves, the gravitational interactions of spinors, and the supersymmetric and higher-dimensional generalization of the Einstein equations. Theory of Gravitational Interactions will be o...

  1. Neutrino self-interactions

    Science.gov (United States)

    Hasenkamp, Jasper

    2016-03-01

    We propose a theory that equips the active neutrinos with interactions among themselves that are at least 3 orders of magnitude stronger than the weak interaction. We introduce an Abelian gauge group U (1 )X with vacuum expectation value vx≲O (100 MeV ) . An asymmetric mass matrix implements the active neutrinos as massless mass eigenstates carrying "effective" charges. To stabilize vx, supersymmetry breaking is mediated via loops to the additional sector with the only exception of xHiggs terms. No Standard Model interaction eigenstate carries U (1 )X charge. Thus, the dark photon's kinetic mixing is two-loop suppressed. With only simple and generic values of dimensionless parameters, our theory might explain the high-energy neutrino spectrum observed by IceCube including the PeV neutrinos. We comment on the imposing opportunity to incorporate a self-interacting dark matter candidate.

  2. Elementary particle interactions

    International Nuclear Information System (INIS)

    Work continues on strange particle production in weak interactions using data from a high-energy neutrino exposure in a freon bubble chamber. Meson photoproduction has also consumed considerable effort. Detector research and development activities have been carried out

  3. Neutrino Self-Interactions

    CERN Document Server

    Hasenkamp, Jasper

    2016-01-01

    We propose a theory that equips the active neutrinos with interactions among themselves that are at least three orders of magnitude stronger than the weak interaction. We introduce an Abelian gauge group $U(1)_x$ with vacuum expectation value $v_x \\lesssim \\mathcal{O}(100 \\textrm{ MeV})$. An asymmetric mass matrix implements the active neutrinos as massless mass eigenstates carrying "effective" charges. To stabilize $v_x$, supersymmetry breaking is mediated via loops to the additional sector with the only exception of xHiggs terms. No Standard Model interaction eigenstate carries $U(1)_x$ charge. Thus the dark photon's kinetic mixing is two-loop suppressed.With only simple and generic values of dimensionless parameters, our theory might explain the high-energy neutrino spectrum observed by IceCube including the PeV neutrinos. We comment on the imposing opportunity to incorporate a self-interacting dark matter candidate.

  4. Multiactivity in Social Interaction

    DEFF Research Database (Denmark)

    Doing more than one thing at the same time – a phenomenon that is often called ‘multitasking’ – is characteristic to many situations in everyday and professional life. Although we all experience it, its real time features remain understudied. Multiactivity in Social Interaction: Beyond multitasking...... offers a fresh view to the phenomenon by presenting studies that explore how two or more activities can be related and made co-relevant as people interact with one another. The studies build on the basis that multiactivity is a social, verbal and embodied phenomenon. They investigate multiactivity by...... using video recordings of real-life interactions from a range of different contexts, such as medical settings, office workplaces and car driving. With the companion collection Interacting with Objects: Language, materiality, and social activity, the book advances understanding of the complex...

  5. Nucleon-nucleon interactions

    International Nuclear Information System (INIS)

    Nucleon-nucleon interactions are at the heart of nuclear physics, bridging the gap between QCD and the effective interactions appropriate for the shell model. We discuss the current status of NN data sets, partial-wave analyses, and some of the issues that go into the construction of potential models. Our remarks are illustrated by reference to the Argonne v18 potential, one of a number of new potentials that fit elastic nucleon-nucleon data up to 350 MeV with a Χ2 per datum near 1. We also discuss the related issues of three-nucleon potentials, two-nucleon charge and current operators, and relativistic effects. We give some examples of calculations that can be made using these realistic descriptions of NN interactions. We conclude with some remarks on how our empirical knowledge of NN interactions may help constrain models at the quark level, and hence models of nucleon structure

  6. Human-machine interactions

    Science.gov (United States)

    Forsythe, J. Chris; Xavier, Patrick G.; Abbott, Robert G.; Brannon, Nathan G.; Bernard, Michael L.; Speed, Ann E.

    2009-04-28

    Digital technology utilizing a cognitive model based on human naturalistic decision-making processes, including pattern recognition and episodic memory, can reduce the dependency of human-machine interactions on the abilities of a human user and can enable a machine to more closely emulate human-like responses. Such a cognitive model can enable digital technology to use cognitive capacities fundamental to human-like communication and cooperation to interact with humans.

  7. Modelling interactions in fungi

    OpenAIRE

    Falconer, Ruth E; Bown, James L; White, Nia A.; Crawford, John W.

    2007-01-01

    Indeterminate organisms have received comparatively little attention in theoretical ecology and still there is much to be understood about the origins and consequences of community structure. The fungi comprise an entire kingdom of life and epitomize the indeterminate growth form. While interactions play a significant role in shaping the community structure of indeterminate organisms, to date most of our knowledge relating to fungi comes from observing interaction outcomes between two species...

  8. Neutrino Self-Interactions

    OpenAIRE

    Hasenkamp, Jasper(Center for Cosmology and Particle Physics, New York University, 70 Washington Square S, New York, NY, 10003 U.S.A.)

    2016-01-01

    We propose a theory that equips the active neutrinos with interactions among themselves that are at least three orders of magnitude stronger than the weak interaction. We introduce an Abelian gauge group $U(1)_x$ with vacuum expectation value $v_x \\lesssim \\mathcal{O}(100 \\textrm{ MeV})$. An asymmetric mass matrix implements the active neutrinos as massless mass eigenstates carrying "effective" charges. To stabilize $v_x$, supersymmetry breaking is mediated via loops to the additional sector ...

  9. Interaction with geospatial data

    OpenAIRE

    SCHOENING, Johannes

    2015-01-01

    My research interest lies at the interaction between human-computer interaction (HCI) and geoinformatics. I am interested in developing new methods and novel user interfaces to navigate through spatial information. This article will give a brief overview on my past and current research topics and streams. Generally speaking, geography is playing an increasingly important role in computer science and also in the field of HCI ranging from social computing to natural user interfaces (NUIs). At t...

  10. Beam-Material Interaction

    CERN Document Server

    Mokhov, N V

    2016-01-01

    Th is paper is motivated by the growing importance of better understanding of the phenomena and consequences of high- intensity energetic particle beam interactions with accelerator, generic target , and detector components. It reviews the principal physical processes of fast-particle interactions with matter, effects in materials under irradiation, materials response, related to component lifetime and performance, simulation techniques, and methods of mitigating the impact of radiation on the components and envir onment in challenging current and future application

  11. Interacting Holographic Phantom

    OpenAIRE

    Setare, M. R.

    2007-01-01

    In this paper we consider the holographic model of interacting dark energy in non-flat universe. With the choice of $c\\leq 0.84$, the interacting holographic dark energy can be described by a phantom scalar field. Then we show this phantomic description of the holographic dark energy with $c\\leq 0.84$ and reconstruct the potential of the phantom scalar field.

  12. Plasma-wall interaction

    International Nuclear Information System (INIS)

    This document gathers the 43 slides presented in the framework of the week long lecture 'hot plasmas 2004' and dedicated to plasma-wall interaction in a tokamak. This document is divided into 4 parts: 1) thermal load on the wall, power extraction and particle recovery, 2) basic edge plasma physics, 3) processes that drive the plasma-solid interaction, and 4) material conditioning (surface treatment...) for ITER

  13. CONCEPT OF DRUG INTERACTION

    OpenAIRE

    Singh Nidhi

    2012-01-01

    Drug interaction is an increasingly important cause of adverse reactions (ADR), and is the modification of the effect of one drug (object) by the prior or concomitant administration of another drug (precipitant drug). Drug interaction may either enhance or diminish the intended effect of one or both drugs. For example severe haemorrhage may occur if warfarin and salicylates (asprin) are combined. Precipitant drugs modify the object drug's absorption, distribution, metabolism, excretion or act...

  14. Strongly interacting new physics

    International Nuclear Information System (INIS)

    In this talk. I will describe two aspects of the breaking of electroweak symmetry by new, strong interactions. First I will review the model independent approach to the low energy form of such new interactions emdash the electroweak chiral Lagrangian. Next I will summarize some of the phenomenological challenges facing technicolor theories, in particular those associated with the generation of the top and bottom masses. copyright 1997 American Institute of Physics

  15. Interacting Agegraphic Dark Energy

    OpenAIRE

    Wei, Hao; Cai, Rong-Gen

    2007-01-01

    A new dark energy model, named "agegraphic dark energy", has been proposed recently, based on the so-called K\\'{a}rolyh\\'{a}zy uncertainty relation, which arises from quantum mechanics together with general relativity. In this note, we extend the original agegraphic dark energy model by including the interaction between agegraphic dark energy and pressureless (dark) matter. In the interacting agegraphic dark energy model, there are many interesting features different from the original agegrap...

  16. Quantum interaction. Selected papers

    International Nuclear Information System (INIS)

    This book constitutes the refereed proceedings of the 7th International Conference on Quantum Interaction, QI 2013, held in Leicester, UK, in July 2013. The 31 papers presented in this book were carefully selected from numerous submissions. The papers cover various topics on quantum interaction and revolve around four themes: information processing/retrieval/semantic representation and logic; cognition and decision making; finance/economics and social structures and biological systems.

  17. Smoking and Social Interaction

    OpenAIRE

    Poutvaara, Panu; Siemens, Lars-H. R.

    2007-01-01

    We study the social interaction of non-smokers and smokers as a sequential game, incorporating insights from social psychology and experimental economics into an economic model. Social norms a®ect human behavior such that non-smokers do not ask smokers to stop smoking and stay with them, even though disutility from smoking exceeds utility from social interaction. Overall, smoking is unduly often accepted when accommodating smoking is the social norm. The introduction of smoking and non-smokin...

  18. Soft interactions in Herwig++

    CERN Document Server

    Bahr, Manuel; Gieseke, Stefan; Seymour, Michael H

    2009-01-01

    We describe the recent developments to extend the multi-parton interaction model of underlying events in Herwig++ into the soft, non-perturbative, regime. This allows the program to describe also minimum bias collisions in which there is no hard interaction, for the first time. It is publicly available from versions 2.3 onwards and describes the Tevatron underlying event and minimum bias data. The extrapolations to the LHC nevertheless suffer considerable ambiguity, as we discuss.

  19. Quantum interaction. Selected papers

    Energy Technology Data Exchange (ETDEWEB)

    Atmanspacher, Harald [Eidgenoessische Technische Hochschule, Zurich (Switzerland); Haven, Emmanuel [Leicester Univ. (United Kingdom). School of Management; Kitto, Kirsty [Queensland Univ. of Technology, Brisbane, QLD (Australia); Raine, Derek (ed.) [Leicester Univ. (United Kingdom). Centre for Interdisciplinary Science

    2014-07-01

    This book constitutes the refereed proceedings of the 7th International Conference on Quantum Interaction, QI 2013, held in Leicester, UK, in July 2013. The 31 papers presented in this book were carefully selected from numerous submissions. The papers cover various topics on quantum interaction and revolve around four themes: information processing/retrieval/semantic representation and logic; cognition and decision making; finance/economics and social structures and biological systems.

  20. Grapefruit and drug interactions.

    Science.gov (United States)

    2012-12-01

    Since the late 1980s, grapefruit juice has been known to affect the metabolism of certain drugs. Several serious adverse effects involving drug interactions with grapefruit juice have been published in detail. The components of grapefruit juice vary considerably depending on the variety, maturity and origin of the fruit, local climatic conditions, and the manufacturing process. No single component accounts for all observed interactions. Other grapefruit products are also occasionally implicated, including preserves, lyophylised grapefruit juice, powdered whole grapefruit, grapefruit seed extract, and zest. Clinical reports of drug interactions with grapefruit juice are supported by pharmacokinetic studies, each usually involving about 10 healthy volunteers, in which the probable clinical consequences were extrapolated from the observed plasma concentrations. Grapefruit juice inhibits CYP3A4, the cytochrome P450 isoenzyme most often involved in drug metabolism. This increases plasma concentrations of the drugs concerned, creating a risk of overdose and dose-dependent adverse effects. Grapefruit juice also inhibits several other cytochrome P450 isoenzymes, but they are less frequently implicated in interactions with clinical consequences. Drugs interacting with grapefruit and inducing serious clinical consequences (confirmed or very probable) include: immunosuppressants, some statins, benzodiazepines, most calcium channel blockers, indinavir and carbamazepine. There are large inter-individual differences in enzyme efficiency. Along with the variable composition of grapefruit juice, this makes it difficult to predict the magnitude and clinical consequences of drug interactions with grapefruit juice in a given patient. There is increasing evidence that transporter proteins such as organic anion transporters and P-glycoprotein are involved in interactions between drugs and grapefruit juice. In practice, numerous drugs interact with grapefruit juice. Although only a few

  1. Drug interactions with grapefruit

    OpenAIRE

    Bojanić Vladmila V.; Bojanić Novica Z.; Bojanić Zoran Ž.

    2010-01-01

    Introduction. The concentration of many orally given medications may be affected by grapefruit or grapefruit juice consumption. It may result in numerous harmful effects. Interaction of grapefruit with drugs. Taking only one cup of juice may induce interactions with different drugs even during the period of a few days. The effect is induced by suppression of cytochrome P450 isoenzyme CYP3A4 in the intestinal wall. The Latin name of grapefruit, Citrus paradisi, is quite opposite to the e...

  2. Studies of Embodied Interaction

    OpenAIRE

    Stycke, Simon; Castillo Hansen, Frederikke; Debel, Niels; Heebøll, Lauge; Mohr, Markus

    2013-01-01

    The purpose of this project was to perform general studies on the phenomenon Embodied Interaction. Our motivation for doing this was the increasing interest, both creatively and commercially, in new ways to use our computer technologies in the tangible world, as well as in affecting the human perception. Embodied Interaction allows a person to use his body as an instrument in the world, and utilize his bodily presence and motions, to control software and hardware alike. By delv...

  3. Nonadditivity of nanoparticle interactions.

    Science.gov (United States)

    Batista, Carlos A Silvera; Larson, Ronald G; Kotov, Nicholas A

    2015-10-01

    Understanding interactions between inorganic nanoparticles (NPs) is central to comprehension of self-organization processes and a wide spectrum of physical, chemical, and biological phenomena. However, quantitative description of the interparticle forces is complicated by many obstacles that are not present, or not as severe, for microsize particles (μPs). Here we analyze the sources of these difficulties and chart a course for future research. Such difficulties can be traced to the increased importance of discreteness and fluctuations around NPs (relative to μPs) and to multiscale collective effects. Although these problems can be partially overcome by modifying classical theories for colloidal interactions, such an approach fails to manage the nonadditivity of electrostatic, van der Waals, hydrophobic, and other interactions at the nanoscale. Several heuristic rules identified here can be helpful for discriminating between additive and nonadditive nanoscale systems. Further work on NP interactions would benefit from embracing NPs as strongly correlated reconfigurable systems with diverse physical elements and multiscale coupling processes, which will require new experimental and theoretical tools. Meanwhile, the similarity between the size of medium constituents and NPs makes atomic simulations of their interactions increasingly practical. Evolving experimental tools can stimulate improvement of existing force fields. New scientific opportunities for a better understanding of the electronic origin of classical interactions are converging at the scale of NPs. PMID:26450215

  4. Strongly interacting Fermi gases

    Directory of Open Access Journals (Sweden)

    Bakr W.

    2013-08-01

    Full Text Available Strongly interacting gases of ultracold fermions have become an amazingly rich test-bed for many-body theories of fermionic matter. Here we present our recent experiments on these systems. Firstly, we discuss high-precision measurements on the thermodynamics of a strongly interacting Fermi gas across the superfluid transition. The onset of superfluidity is directly observed in the compressibility, the chemical potential, the entropy, and the heat capacity. Our measurements provide benchmarks for current many-body theories on strongly interacting fermions. Secondly, we have studied the evolution of fermion pairing from three to two dimensions in these gases, relating to the physics of layered superconductors. In the presence of p-wave interactions, Fermi gases are predicted to display toplogical superfluidity carrying Majorana edge states. Two possible avenues in this direction are discussed, our creation and direct observation of spin-orbit coupling in Fermi gases and the creation of fermionic molecules of 23Na 40K that will feature strong dipolar interactions in their absolute ground state.

  5. Interactions between photodegradation components

    Directory of Open Access Journals (Sweden)

    Abdollahi Yadollah

    2012-09-01

    Full Text Available Abstract Background The interactions of p-cresol photocatalytic degradation components were studied by response surface methodology. The study was designed by central composite design using the irradiation time, pH, the amount of photocatalyst and the p-cresol concentration as variables. The design was performed to obtain photodegradation % as actual responses. The actual responses were fitted with linear, two factor interactions, cubic and quadratic model to select an appropriate model. The selected model was validated by analysis of variance which provided evidences such as high F-value (845.09, very low P-value (2 = 0.999, adjusted R-squared (Radj2 = 0.998, predicted R-squared (Rpred2 = 0.994 and the adequate precision (95.94. Results From the validated model demonstrated that the component had interaction with irradiation time under 180 min of the time while the interaction with pH was above pH 9. Moreover, photocatalyst and p-cresol had interaction at minimal amount of photocatalyst (p-cresol. Conclusion These variables are interdependent and should be simultaneously considered during the photodegradation process, which is one of the advantages of the response surface methodology over the traditional laboratory method.

  6. The Demand for Social Interaction

    OpenAIRE

    Henry Saffer

    2005-01-01

    In this paper social interaction is modeled as a consumer good. Social interaction may provide an externality in the form of social capital, but the primary reason that individuals engage in social interaction is that these activities directly yield utility. It is important to note that some measures of social interaction show declines while many do not. A model of household production is employed to derive the demand for social interaction. The model shows that the demand for social interact...

  7. Dark Matter Gravitational Interactions

    CERN Document Server

    Tucker, R W

    1998-01-01

    We argue that the conjectured dark mater in the Universe may be endowed with a new kind of gravitational charge that couples to a short range gravitational interaction mediated by a massive vector field. A model is constructed that assimilates this concept into ideas of current inflationary cosmology. The model is also consistent with the observed behaviour of galactic rotation curves according to Newtonian dynamics. The essential idea is that stars composed of ordinary (as opposed to dark matter) experience Newtonian forces due to the presence of an all pervading background of massive gravitationally charged cold dark matter. The novel gravitational interactions are predicted to have a significant influence on pre-inflationary cosmology. The precise details depend on the nature of a gravitational Proca interaction and the description of matter. A gravitational Proca field configuration that gives rise to attractive forces between dark matter charges of like polarity exhibits homogeneous isotropic eternal cos...

  8. Electrocatalyst-support interactions

    Energy Technology Data Exchange (ETDEWEB)

    Kinoshita, K.

    1978-01-01

    The maximum utilization of noble metals as heterogeneous catalysts is achieved by dispersing the noble metals as small particles supported on a porous, high surface area powder. In some studies with supported noble metal catalysts, it has been reported that the metal particle interacts with the support material and that the interaction affects the catalytic properties of the metal. Experimental studies on metal-support interactions that are pertinent to electrocatalysis will be discussed. Platinum supported on carbon black is one of the most active electrocatalysts for oxygen reduction in phosphoric acid fuel cells. In the acid environment at 100 to 200/sup 0/C, the Pt surface area decreases with time due to the growth of the supported Pt particles. The effects of a liquid-phase environment on the particle growth mechanism of supported Pt catalysts is discussed. 60 references.

  9. History of Weak Interactions

    Science.gov (United States)

    Lee, T. D.

    1970-07-01

    While the phenomenon of beta-decay was discovered near the end of the last century, the notion that the weak interaction forms a separate field of physical forces evolved rather gradually. This became clear only after the experimental discoveries of other weak reactions such as muon-decay, muon-capture, etc., and the theoretical observation that all these reactions can be described by approximately the same coupling constant, thus giving rise to the notion of a universal weak interaction. Only then did one slowly recognize that the weak interaction force forms an independent field, perhaps on the same footing as the gravitational force, the electromagnetic force, and the strong nuclear and sub-nuclear forces.

  10. Dike/Drift Interactions

    International Nuclear Information System (INIS)

    This report presents and documents the model components and analyses that represent potential processes associated with propagation of a magma-filled crack (dike) migrating upward toward the surface, intersection of the dike with repository drifts, flow of magma in the drifts, and post-magma emplacement effects on repository performance. The processes that describe upward migration of a dike and magma flow down the drift are referred to as the dike intrusion submodel. The post-magma emplacement processes are referred to as the post-intrusion submodel. Collectively, these submodels are referred to as a conceptual model for dike/drift interaction. The model components and analyses of the dike/drift interaction conceptual model provide the technical basis for assessing the potential impacts of an igneous intrusion on repository performance, including those features, events, and processes (FEPs) related to dike/drift interaction (Section 6.1)

  11. "Interaction-Free" Imaging

    CERN Document Server

    White, A G; Nairz, O; Kwiat, P G; White, Andrew G.; Mitchell, Jay R.; Nairz, Olaf; Kwiat, Paul G.

    1998-01-01

    Using the complementary wave- and particle-like natures of photons, it is possible to make ``interaction-free'' measurements where the presence of an object can be determined with no photons being absorbed. We investigated several ``interaction-free'' imaging systems, i.e. systems that allow optical imaging of photosensitive objects with less than the classically expected amount of light being absorbed or scattered by the object. With the most promising system, we obtained high-resolution (10 \\mu m), one-dimensional profiles of a variety of objects (human hair, glass and metal wires, cloth fibers), by raster scanning each object through the system. We discuss possible applications and the present and future limits for interaction-free imaging.

  12. Dike/Drift Interactions

    Energy Technology Data Exchange (ETDEWEB)

    E. Gaffiney

    2004-11-23

    This report presents and documents the model components and analyses that represent potential processes associated with propagation of a magma-filled crack (dike) migrating upward toward the surface, intersection of the dike with repository drifts, flow of magma in the drifts, and post-magma emplacement effects on repository performance. The processes that describe upward migration of a dike and magma flow down the drift are referred to as the dike intrusion submodel. The post-magma emplacement processes are referred to as the post-intrusion submodel. Collectively, these submodels are referred to as a conceptual model for dike/drift interaction. The model components and analyses of the dike/drift interaction conceptual model provide the technical basis for assessing the potential impacts of an igneous intrusion on repository performance, including those features, events, and processes (FEPs) related to dike/drift interaction (Section 6.1).

  13. Star-Planet Interactions

    CERN Document Server

    Shkolnik, Evgenya; Cranmer, Steven; Fares, Rim; Fridlund, Malcolm; Pont, Frederic; Schmitt, Juergen; Smith, Alexis; Suzuki, Takeru

    2008-01-01

    Much effort has been invested in recent years, both observationally and theoretically, to understand the interacting processes taking place in planetary systems consisting of a hot Jupiter orbiting its star within 10 stellar radii. Several independent studies have converged on the same scenario: that a short-period planet can induce activity on the photosphere and upper atmosphere of its host star. The growing body of evidence for such magnetic star-planet interactions includes a diverse array of photometric, spectroscopic and spectropolarimetric studies. The nature of which is modeled to be strongly affected by both the stellar and planetary magnetic fields, possibly influencing the magnetic activity of both bodies, as well as affecting irradiation and non-thermal and dynamical processes. Tidal interactions are responsible for the circularization of the planet orbit, for the synchronization of the planet rotation with the orbital period, and may also synchronize the outer convective envelope of the star with...

  14. Sonic Interaction Design

    DEFF Research Database (Denmark)

    created for such contexts as mobile music, sensorimotor learning, rehabilitation, and gaming. The goal is not only to extend the existing research and pedagogical approaches to SID but also to foster domains of practice for sound designers, architects, interaction designers, media artists, product......) challenges these prevalent approaches by considering sound as an active medium that can enable novel sensory and social experiences through interactive technologies. This book offers an overview of the emerging SID research, discussing theories, methods, and practices, with a focus on the multisensory...... aspects of sonic experience. Sonic Interaction Design gathers contributions from scholars, artists, and designers working at the intersections of fields ranging from electronic music to cognitive science. They offer both theoretical considerations of key themes and case studies of products and systems...

  15. Interactive Topology Optimization

    DEFF Research Database (Denmark)

    Nobel-Jørgensen, Morten

    Interactivity is the continuous interaction between the user and the application to solve a task. Topology optimization is the optimization of structures in order to improve stiffness or other objectives. The goal of the thesis is to explore how topology optimization can be used in applications in...... an interactive and intuitive way. By creating such applications with an intuitive and simple user interface we allow non-engineers like designers and architects to easily experiment with boundary conditions, design domains and other optimization settings. This is in contrast to commercial topology...... optimization software where the users are assumed to be well-educated both in the finite element method and topology optimization. This dissertation describes how various topology optimization methods have been used for creating cross-platform applications with high performance. The user interface design is...

  16. Interactive Karyotyping Training

    Directory of Open Access Journals (Sweden)

    Ashwin Kotwaliwale

    2013-01-01

    Full Text Available Despite the wide use of newer techniques in genetic diagnostics, there remains a need for technologists to learn human chromosome morphology, identify abnormal metaphases and report clinical abnormalities. Global short age of cytogenetic trainers and a time consuming training process makes Karyotyping training difficult. We have developed a web based interactive Karyotyping training tool, KaryoTutor©, that allows technologists to learn karyotyping in an interactive environment and aids the trainer in the training process. KaryoTutor©provides visual clues for identifying abnormal chromosomes, provides instant test scores and includes a reference library of ideograms,sample chromosome images and reference materials. Trainees are able to recursively work on a case till a satisfactory result is achieved,with KaryoTutor providing interactive inputs.Additionally, trainers can assign cases and monitor trainee progress using audit trail management and other administrative features.

  17. Electron-positron interactions

    International Nuclear Information System (INIS)

    The experimental information available on e+e- interactions at the time of the Tbilisi Conference (Juli 1976) is reviewed. The topics of these lectures are: electron-positron storage rings, purely electromagnetic ee-interactions, phenomenology of hadron production, e+e- annihilation at low energies, nonresonant hadron production, the new particles psi-3105 and psi-3695, research for other vector states, radiative decays of psi-3105 and psi-3695, anti Q-Q model and predictions, the bound states of heavy quarks, data on new states with even charge conjugation, mesons with open charm, experimental evidence for charmed mesons and for a new lepton. (BJ)

  18. Thoughts on Interaction Design

    CERN Document Server

    Kolko, Jon

    2009-01-01

    Interaction Designers-whether practicing as Usability Engineers, Visual Interface Designers, or Information Architects-attempt to understand and shape human behavior in order to design products that are at once usable, useful, and desirable. Although the value of design is now recognized as essential to product development, the field is often misunderstood by managers and other team members, who don't understand a designer's role in a team. This can cause inefficient and ineffective products. Thoughts on Interaction Design gives individuals engaged in this profession the dialogue to justify t

  19. Gaze interaction from bed

    DEFF Research Database (Denmark)

    Hansen, John Paulin; San Agustin, Javier; Jensen, Henrik Tomra Skovsgaard Hegner

    2011-01-01

    This paper presents a low-cost gaze tracking solution for bedbound people composed of free-ware tracking software and commodity hardware. Gaze interaction is done on a large wall-projected image, visible to all people present in the room. The hardware equipment leaves physical space free to assist...... the person. Accuracy and precision of the tracking system was tested in an experiment with 12 subjects. We obtained a tracking quality that is sufficiently good to control applications designed for gaze interaction. The best tracking condition were achieved when people were sitting up compared to...

  20. Interacting binary stars

    CERN Document Server

    Sahade, Jorge; Ter Haar, D

    1978-01-01

    Interacting Binary Stars deals with the development, ideas, and problems in the study of interacting binary stars. The book consolidates the information that is scattered over many publications and papers and gives an account of important discoveries with relevant historical background. Chapters are devoted to the presentation and discussion of the different facets of the field, such as historical account of the development in the field of study of binary stars; the Roche equipotential surfaces; methods and techniques in space astronomy; and enumeration of binary star systems that are studied

  1. Multiactivity in Social Interaction

    DEFF Research Database (Denmark)

    Haddington, Pentti; Keisanen, Tiina; Mondada, Lorenza;

    2014-01-01

    Doing more than one thing at the same time – a phenomenon that is often called ‘multitasking’ – is characteristic to many situations in everyday and professional life. Although we all experience it, its real time features remain understudied. Multiactivity in Social Interaction: Beyond multitaski......, communication studies and discourse analysis, but will be very valuable for scholars in cognitive sciences, psychology and sociology.......Doing more than one thing at the same time – a phenomenon that is often called ‘multitasking’ – is characteristic to many situations in everyday and professional life. Although we all experience it, its real time features remain understudied. Multiactivity in Social Interaction: Beyond multitasking...

  2. Cultivating objects in interaction

    DEFF Research Database (Denmark)

    Hazel, Spencer

    2014-01-01

    This paper demonstrates how an initial indexing of objects through gesture and talk provides a residual basis for later indexical development across a stretch of discourse. I show how participants are able to perform an initial mobilization of affordances (Hutchby, 2001) of objects in the immediate...... the interactional resources which mundane everyday objects provide interactants in the multimodal design of their turns-at-talk. Although the objects which feature in the data – for example notepads, tables, computer monitors – have practical functions within the social ecology of these institutional settings...

  3. Interactive Shape Design

    CERN Document Server

    Cani, Marie-Paule; Wyvill, Geoff

    2008-01-01

    Providing an intuitive modeling system, which would enable us to communicate about any free-form shape we have in mind at least as quickly as with real-world tools, is one of the main challenges of digital shape design. The user should ideally be able to create, deform, and progressively add details to a shape, without being aware of the underlying mathematical representation nor being tied by any constraint on the geometrical or topological nature of the model. This book presents the field of interactive shape design from this perspective. Since interactively creating a shape builds on the hu

  4. Interactive Collaborative Books

    OpenAIRE

    Al-Mutawa, Abdullah M.

    2007-01-01

    Books are one of the most important tools to convey knowledge, they survived to be a convenient and portable source of information. On the other side, Electronic books (e-books) are playing a big role in attracting a huge number of readers, but still paper books are preferable by many people due to some drawbacks in e-books. Yet, Interactive books combines all positive features in ordinary books as well as e-books, the author is introducing a new Interactive Collaborative book that might chan...

  5. Acting, interacting, enacting

    DEFF Research Database (Denmark)

    Hazel, Spencer

    2015-01-01

    notes – which forms a framework within which members reflect on their performances, and discuss possible modifications to be taken up on later occasions. This is argued to be a useful practice that may prove beneficial to other professional settings, such as in heathcare provision...... from professional medical treatment of the body, rather than of the person. I adopt an interaction analytic approach to investigate how theatre practitioners develop representations of interaction in clinical environments. The article introduces one practice from the theatre rehearsal setting – doing...

  6. Honesty through repeated interactions.

    Science.gov (United States)

    Rich, Patricia; Zollman, Kevin J S

    2016-04-21

    In the study of signaling, it is well known that the cost of deception is an essential element for stable honest signaling in nature. In this paper, we show how costs for deception can arise endogenously from repeated interactions between individuals. Utilizing the Sir Philip Sidney game as an illustrative case, we show that repeated interactions can sustain honesty with no observable signal costs, even when deception cannot be directly observed. We provide a number of potential experimental tests for this theory which distinguish it from the available alternatives. PMID:26869213

  7. Diachronic Perspective and Interaction

    DEFF Research Database (Denmark)

    Marchetti, Emanuela; Valente, Andrea

    . Although this interaction style may appeal to teachers, as it reminds of school teaching, it has several disadvantages: a dialogue never occurs between adults and children, who listen in silence, hence it becomes hard to evaluate what has being learnt and how deeply, and finally it is not very engaging. An...... ongoing participatory inquiry is being conducted, to explore deeper forms of learning and communication for historical museums. Our hypothesis is that the diachronic perspective on historical processes, defined as social interaction within the environment through time, is a key missing element...

  8. Interactive shape metamorphosis

    Science.gov (United States)

    Chen, David T.; State, Andrei; Banks, David

    1994-01-01

    A technique for controlled metamorphosis between surfaces in 3-space is described. Well-understood techniques to produce shape metamorphosis between models in a 2D parametric space is applied. The user selects morphable features interactively, and the morphing process executes in real time on a high-performance graphics multicomputer.

  9. Alkane dimers interaction

    DEFF Research Database (Denmark)

    Ferrighi, Lara; Madsen, Georg Kent Hellerup; Hammer, Bjørk

    The interaction energies of a series of n-alkane dimers, from methane to decane, have been investigated with Density Functional Theory (DFT), using the MGGA-M06-L density functional. The results are compared both to the available wavefunction-based values as well as to dispersion corrected DFT...

  10. Phonon-dislocation interaction

    International Nuclear Information System (INIS)

    Thermal conductivity measurements on LiF crystals in the temperature range 0.04 to 30 K have demonstrated that, throughout this range, thermal phonons interact with dislocations via a dynamic or resonant process which is highly frequency- and phonon-mode dependent. The results of earlier work are consistent with this interpretation

  11. Experiencing affective interactive art

    NARCIS (Netherlands)

    Bialoskorski, Leticia S.S.; Westerink, Joyce H.D.M.; Broek, van den Egon L.

    2010-01-01

    The progress in the field of affective computing enables the realization of affective art. This paper describes the affective interactive art system Mood Swings, which interprets and visualizes affect expressed by a person. Mood Swings is founded on the integration of a framework for affective move

  12. Connectionist Interaction Information Retrieval.

    Science.gov (United States)

    Dominich, Sandor

    2003-01-01

    Discussion of connectionist views for adaptive clustering in information retrieval focuses on a connectionist clustering technique and activation spreading-based information retrieval model using the interaction information retrieval method. Presents theoretical as well as simulation results as regards computational complexity and includes…

  13. Interactions within wastewater systems

    NARCIS (Netherlands)

    Langeveld, J.G.

    2004-01-01

    Wastewater systems consist of sewer systems and wastewater treatment works. As the performance of a wastewater treatment plant is affected by the characteristics, i.e. operation and design, of the contributing sewer systems, knowledge of the interactions between sewers and wastewater treatment works

  14. Urban Interaction Design

    DEFF Research Database (Denmark)

    Brynskov, Martin; Bermúdez, Juan Carlos Carvajal; Fernández, Manu;

    table? What are the key concepts they are addressing in their work? In the second part of the book named 'Trends', we go into current developments in the networked city and how urban interaction design as a field addresses these. Taken together, these sections will not give the definite definition or...

  15. Dust-Plasma Interactions

    International Nuclear Information System (INIS)

    Our theoretical research on dust-plasma interactions has concentrated on three main areas: (a)studies of grain charging and applications; (b) waves and instabilities in weakly correlated dusty plasma with applications to space and laboratory plasmas; (c) waves in strongly coupled dusty plasmas.

  16. Virtual Interactive Space (VIS)

    DEFF Research Database (Denmark)

    Brooks, Anthony Lewis

    2015-01-01

    This paper shares code that enables the making of a Virtual Interactive Space (VIS) where the skin of the invisible active sensor area is dynamically responsive to the velocity of a limb e.g. hand. Used in proprioception training of movement the patch is at the core of the author’s Reafferentation...

  17. Proxemic Mobile Collocated Interactions

    DEFF Research Database (Denmark)

    Porcheron, Martin; Lucero, Andrés; Quigley, Aaron;

    2016-01-01

    Recent research on mobile collocated interactions has been looking at situations in which collocated users engage in collaborative activities using their mobile devices. However, existing practices fail to fully account for the culturally-dependent spatial relationships between people and their d...

  18. Empowered interaction through creativity

    DEFF Research Database (Denmark)

    Hasselblad, Stefan; Petersson, Eva; Brooks, Tony

    2007-01-01

    This paper reflects upon a case study where exploration, play and empowerment in interactive therapy sessions with audio and visual stimuli resulted in achievement, self-esteem and a shared pride between a young adult with profound and multiple learning disabilities (PMLD), his mother...... and family of similarly severe disabled users....

  19. Interaction and mindreading

    DEFF Research Database (Denmark)

    Michael, John

    2011-01-01

    In recent years, a number of theorists have developed approaches to social cognition that highlight the centrality of social interaction as opposed to mindreading (e.g. Gallagher and Zahavi 2008; Gallagher 2001, 2007, 2008; Hobson 2002; Reddy 2008; Hutto 2004; De Jaegher 2009; De Jaegher and Di...

  20. Tritium-surface interactions

    International Nuclear Information System (INIS)

    The report deals broadly with tritium-surface interactions as they relate to a fusion power reactor enterprise, viz., the vacuum chamber, first wall, peripherals, pumping, fuel recycling, isotope separation, repair and maintenance, decontamination and safety. The main emphasis is on plasma-surface interactions and the selection of materials for fusion chamber duty. A comprehensive review of the international (particularly U.S.) research and development is presented based upon a literature review (about 1 000 reports and papers) and upon visits to key laboratories, Sandia, Albuquerque, Sandia, Livermore and EGβG Idaho. An inventory of Canadian expertise and facilities for RβD on tritium-surface interactions is also presented. A number of proposals are made for the direction of an optimal Canadian RβD program, emphasizing the importance of building on strength in both the technological and fundamental areas. A compendium of specific projects and project areas is presented dealing primarily with plasma-wall interactions and permeation, anti-permeation materials and surfaces and health, safety and environmental considerations. Potential areas of industrial spinoff are identified

  1. Interactive Foresight Simulation

    DEFF Research Database (Denmark)

    Hansen, Mette Sanne; Rasmussen, Lauge Baungaard; Jacobsen, Peter

    2016-01-01

    The Combined Simulation Approach (CSA) is a way to evaluate risks and address potential unforeseen problems in a more interactive way than what is often observed in practice in companies or sectors. The approach is based on a combination of scenario analysis and discrete-event computer simulation...

  2. Critical ionization velocity interaction

    International Nuclear Information System (INIS)

    Different problems of current interest regarding the critical ionization velocity (CIV) phenomenon are discussed. The article is divided into five sections corresponding to different aspects of the interaction: velocity, magnetic field strength, geometry, neutral gas density, and time duration. In each section, experiments and theories - microscopic and macroscopic - are discussed

  3. Mobile Collocated Interactions

    DEFF Research Database (Denmark)

    Lucero, Andrés; Clawson, James; Lyons, Kent;

    2015-01-01

    Mobile devices such as smartphones and tablets were originally conceived and have traditionally been utilized for individual use. Research on mobile collocated interactions has been looking at situations in which collocated users engage in collaborative activities using their mobile devices, thus...

  4. Towards Directional Colloidal Interactions

    NARCIS (Netherlands)

    Kamp, M.

    2015-01-01

    Colloids are particles with a size on the scale of microns in at least one dimension. The central theme of this thesis is the synthesis of model colloids with anisotropic interactions - often called `patchy' colloids, as well as the search for new ways to assemble such colloids. Methods to build non

  5. Protein–DNA Interactions

    NARCIS (Netherlands)

    Kovacic, L.; Boelens, R.

    2012-01-01

    The recognition of specific DNA sequences by proteins and the coupling to signaling events are fundamental occurrences that lie at the root of many cellular processes. Many examples of tight control by protein–DNA interactions can be found in such dynamic processes as transcription, replication and

  6. Protein-protein interactions

    DEFF Research Database (Denmark)

    Byron, Olwyn; Vestergaard, Bente

    2015-01-01

    Responsive formation of protein:protein interaction (PPI) upon diverse stimuli is a fundament of cellular function. As a consequence, PPIs are complex, adaptive entities, and exist in structurally heterogeneous interplays defined by the energetic states of the free and complexed protomers. The...

  7. CONCEPT OF DRUG INTERACTION

    Directory of Open Access Journals (Sweden)

    Singh Nidhi

    2012-07-01

    Full Text Available Drug interaction is an increasingly important cause of adverse reactions (ADR, and is the modification of the effect of one drug (object by the prior or concomitant administration of another drug (precipitant drug. Drug interaction may either enhance or diminish the intended effect of one or both drugs. For example severe haemorrhage may occur if warfarin and salicylates (asprin are combined. Precipitant drugs modify the object drug's absorption, distribution, metabolism, excretion or actual clinical effect. Nonsteroidal anti-inflammatory drugs, antibiotics and, in particular, rifampin are common precipitant drugs prescribed in primary care practice. Drugs with a narrow therapeutic range or low therapeutic index are more likely to be the objects for serious drug interactions. Object drugs in common use include warfarin, fluoroquinolones, antiepileptic drugs, oral contraceptives, cisapride and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Many other drugs, act as precipitants or objects, and a number of drugs act as both. The aim of present review is to throw light on the concept of drug interaction.

  8. Protein–protein interactions

    NARCIS (Netherlands)

    Janin, J.; Bonvin, A.M.J.J.

    2013-01-01

    We are proud to present the first edition of the Protein–protein interactions Section of Current Opinion in Structural Biology. The Section is new, but the topic has been present in the journal from the very start. Volume 1, Issue 1, dated February 1991, had a review by Janin entitled Protein–protei

  9. TIDE-TSUNAMI INTERACTIONS

    Directory of Open Access Journals (Sweden)

    Zygmunt Kowalik

    2006-01-01

    Full Text Available In this paper we investigate important dynamics defining tsunami enhancement in the coastal regions and related to interaction with tides. Observations and computations of the Indian Ocean Tsunami usually show amplifications of the tsunami in the near-shore regions due to water shoaling. Additionally, numerous observations depicted quite long ringing of tsunami oscillations in the coastal regions, suggesting either local resonance or the local trapping of the tsunami energy. In the real ocean, the short-period tsunami wave rides on the longer-period tides. The question is whether these two waves can be superposed linearly for the purpose of determining the resulting sea surface height (SSH or rather in the shallow water they interact nonlinearly, enhancing/reducing the total sea level and currents. Since the near–shore bathymetry is important for the run-up computation, Weisz and Winter (2005 demonstrated that the changes of depth caused by tides should not be neglected in tsunami run-up considerations. On the other hand, we hypothesize that much more significant effect of the tsunami-tide interaction should be observed through the tidal and tsunami currents. In order to test this hypothesis we apply a simple set of 1-D equations of motion and continuity to demonstrate the dynamics of tsunami and tide interaction in the vicinity of the shelf break for two coastal domains: shallow waters of an elongated inlet and narrow shelf typical for deep waters of the Gulf of Alaska.

  10. A specific A/T polymorphism in Western tyrosine phosphorylation B-motifs regulates Helicobacter pylori CagA epithelial cell interactions.

    Directory of Open Access Journals (Sweden)

    Xue-Song Zhang

    2015-02-01

    Full Text Available Helicobacter pylori persistently colonizes the human stomach, with mixed roles in human health. The CagA protein, a key host-interaction factor, is translocated by a type IV secretion system into host epithelial cells, where its EPIYA tyrosine phosphorylation motifs (TPMs are recognized by host cell kinases, leading to multiple host cell signaling cascades. The CagA TPMs have been described as type A, B, C or D, each with a specific conserved amino acid sequence surrounding EPIYA. Database searching revealed strong non-random distribution of the B-motifs (including EPIYA and EPIYT in Western H. pylori isolates. In silico analysis of Western H. pylori CagA sequences provided evidence that the EPIYT B-TPMs are significantly less associated with gastric cancer than the EPIYA B-TPMs. By generating and using a phosphorylated CagA B-TPM-specific antibody, we demonstrated the phosphorylated state of the CagA B-TPM EPIYT during H. pylori co-culture with host cells. We also showed that within host cells, CagA interaction with phosphoinositol 3-kinase (PI3-kinase was B-TPM tyrosine-phosphorylation-dependent, and the recombinant CagA with EPIYT B-TPM had higher affinity to PI3-kinase and enhanced induction of AKT than the isogenic CagA with EPIYA B-TPM. Structural modeling of the CagA B-TPM motif bound to PI3-kinase indicated that the threonine residue at the pY+1 position forms a side-chain hydrogen bond to N-417 of PI3-kinase, which cannot be formed by alanine. During co-culture with AGS cells, an H. pylori strain with a CagA EPIYT B-TPM had significantly attenuated induction of interleukin-8 and hummingbird phenotype, compared to the isogenic strain with B-TPM EPIYA. These results suggest that the A/T polymorphisms could regulate CagA activity through interfering with host signaling pathways related to carcinogenesis, thus influencing cancer risk.

  11. Relativistic Geometry and Weak Interactions

    CERN Document Server

    González-Martin, G R

    2000-01-01

    Geometric interactions in a new relativistic geometric unified theory include interactions other than gravitation and electromagnetism. In a low energy limit one of these interactions leads essentially to a Fermi type theory of weak interactions including the Hamiltonian and coupling constant.

  12. Interactions of tritium and materials

    Energy Technology Data Exchange (ETDEWEB)

    Yamawaki, Michio; Yamaguchi, Kenji; Tanaka, Satoru; Ono, Futaba (Tokyo Univ., Tokai, Ibaraki (Japan). Nuclear Engineering Research Lab.); Yamamoto, Takuya

    1993-11-01

    In D-T burning fusion reactors, problems related to tritium-material interactions are vitally important. From this point of view, plasma-material interactions, blanket breeder material-tritium interactions, safety aspects of tritium-material interactions and tritium storage materials are reviewed with emphasis on the works going on in the authors' laboratories. (author) 83 refs.

  13. Interaction Design for Public Spaces

    DEFF Research Database (Denmark)

    Kortbek, Karen Johanne

    2008-01-01

    In this abstract I describe the doctorial research project "Interaction Design for Public Spaces". The objective of the project is to explore and design interaction contexts in culture related public spaces such as museums, experience centres and festivals. As a perspective on this domain, I will...... will help interaction designers when designing for bodily movement, and communicating and staging interactive content in public spaces....

  14. Serious drug interactions.

    Science.gov (United States)

    Aronson, J

    1993-10-01

    Of the many varieties of drug interactions, which occur when the disposition or actions of one drug are changed by another, only a few are serious or potentially fatal. A representative outline of some of these illustrates the problem. Precipitant drugs are those which produce the interaction, and object drugs are those whose effects are changed. The interactions which are usually significant are those which alter the metabolism, involve renal excretion, or change the effects of the object drug, especially when the object drug has a low therapeutic index (cardiovascular drugs, anticoagulants, drugs acting on the brain, hypoglycemic drugs, hormones, and cytotoxic drugs). Warfarin toxicity, for example, is produced by aspirin, phenylbutazone, and azapropazone. The dosage requirements of warfarin are reduced by chloramphenicol, ciprofloxacin and other quinolones, erythromycin and some of the other macrolides, metronidazole and other imidazoles, tetracyclines, amiodarone, cimetidine (but not ranitidine), and fibrates. Potassium-depleting drugs can potentiate the action of digoxin, and the elimination of digoxin can be reduced by amiodarone, propafenone, quinidine, and verapamil. Combined oral contraceptives can lose effectiveness through the interaction of carbamazepine, griseofulvin, phenytoin, or rifampicin, which increase estrogen metabolism. In addition, broad-spectrum antibiotics such as ampicillin or tetracyclines also reduce contraceptive effectiveness by altering gut absorption. Even a single drink of an alcoholic beverage may be dangerous to people taking antidepressants, antihistamines, antipsychotic drugs, benzodiazepines, or lithium. Antihistamines suffer inhibited metabolism in the liver if taken in conjunction with the antifungal imidazoles and some of the macrolide antibiotics. Cardiotoxicity of antihistamines is also enhanced by drugs with similar cardiotoxic effects. Lithium potentiation is enhanced by the new serotonin-reuptake inhibitors, and lithium

  15. Sustainable Buildings in Interaction

    DEFF Research Database (Denmark)

    Elle, Morten

    developments are going to consist of passive houses. The first sustainable buildings were built by their users, and the user – building interaction still play a decisive role for the performance of the present sustainable buildings. The users have to understand how the building functions. Urban design is...... essential for the possibilities of a sustainable building design: orientation and access to infrastructure are important factor. And the building design is decisive in making the city truly compact: dense in activities. In future, the interaction between the technical infrastructure, the buildings and their......The first attempts to build sustainable buildings in Denmark were typically located on the countryside. The basic idea was to create buildings that were independent of the technical infrastructure. District heating has, however, been the dominating solution to heating in buildings in Denmark, and...

  16. Dynamics of interacting diseases

    CERN Document Server

    Sanz, Joaquín; Meloni, Sandro; Moreno, Yamir

    2014-01-01

    Current modeling of infectious diseases allows for the study of complex and realistic scenarios that go from the population to the individual level of description. Most epidemic models however assume that the spreading process takes place on a single level (be it a single population, a meta-population system or a network of contacts). The latter is in part a consequence of our still limited knowledge about the interdependency of the many mechanisms and factors involved in disease spreading. In particular, interdependent contagion phenomena can only be addressed if we go beyond the scheme one pathogen-one network. In this paper, we study a model that allows describing the spreading dynamics of two concurrent diseases and apply it to a paradigmatic case of disease-disease interaction: the interaction between AIDS and Tuberculosis. Specifically, we characterize analytically the epidemic thresholds of the two diseases for different scenarios and also compute the temporal evolution characterizing the unfolding dyn...

  17. Ligand-Receptor Interactions

    CERN Document Server

    Bongrand, Pierre

    2008-01-01

    The formation and dissociation of specific noncovalent interactions between a variety of macromolecules play a crucial role in the function of biological systems. During the last few years, three main lines of research led to a dramatic improvement of our understanding of these important phenomena. First, combination of genetic engineering and X ray cristallography made available a simultaneous knowledg of the precise structure and affinity of series or related ligand-receptor systems differing by a few well-defined atoms. Second, improvement of computer power and simulation techniques allowed extended exploration of the interaction of realistic macromolecules. Third, simultaneous development of a variety of techniques based on atomic force microscopy, hydrodynamic flow, biomembrane probes, optical tweezers, magnetic fields or flexible transducers yielded direct experimental information of the behavior of single ligand receptor bonds. At the same time, investigation of well defined cellular models raised the ...

  18. Interactive Virtual Cinematography

    DEFF Research Database (Denmark)

    Burelli, Paolo

    A virtual camera represents the point-of-view of the player through which she perceives the game world and gets feedback on her actions. Thus, the virtual camera plays a vital role in 3D computer games and aects player experience and enjoyability in games. Interactive virtual cinematography is the...... process of visualising the content of a virtual environment by positioning and animating the virtual camera in the context of interactive applications such as a computer game. Camera placement and animation in games are usually directly controlled by the player or statically predened by designers. Direct....... The camera controller should dynamically and eciently translate these rules into camera positions and movements before (or while) the player plays the game. Automatically controlling the camera in virtual 3D dynamic environments is an open research problem and a challenging task. From an optimisation...

  19. Interactive White Board

    Directory of Open Access Journals (Sweden)

    Asadullah Khan Praveen Kumar Arun Nair Rishi R Hegde

    2012-02-01

    Full Text Available Visual Screen uses an inexpensive technique to transform an ordinary screen into a touch screen[1] using an ordinary camera[2]. The system can fullfill many tasks such as controlling a remote large display, and simulating a physical keyboard[4]. Users can naturally use their fingers or other tip pointers to issue commands and type texts. In many intelligent environments, instead of using conventional mice[3], keyboards[4] and joysticks[5], people are looking for an intuitive, immersive and cost-efficient interaction device. We describe two vision-based interface systems[10]. The first, Visual Screen, uses an inexpensive technique to transform an ordinary screen into a touch screen[1] using an ordinary camera[2], and a user can use his/her finger to interact with the computer. Touch screens[1] are very convenient because one can directly point to where it is interesting. No conventional mice[3] are needed.

  20. Interactive Energy Planning

    DEFF Research Database (Denmark)

    Blarke, Morten Boje

    2006-01-01

    anchoring along the shores of the land of communications and collaboration. Whether or not a particular typology is applicable, theory and praxis are establishing standpoints, which strengthens our understanding of the planning complex, and which should inspire improved energy planning methodologies and......Though it is being questioned whether planning theory should be fitted into neat typologies, some have described evolving planning theory as a journey away from ethnocentrism, through the lands of rationalism, pragmatism, socio-ecological idealism, political-economic mobilization, currently...... tools. This paper presents an “Interactive Energy Planning” framework, which is intended to support interactivity in planning, building on important theoretical and experimental advances in planning. In particular, the paper explores the potential significance of allowing a critical perspective on...

  1. Theory of fundamental interactions

    International Nuclear Information System (INIS)

    In the present article the theory of fundamental interactions is derived in a systematic way from the first principles. In the developed theory there is no separation between space-time and internal gauge space. Main equations for basic fields are derived. In is shown that the theory satisfies the correspondence principle and gives rise to new notions in the considered region. In particular, the conclusion is made about the existence of particles which are characterized not only by the mass, spin, charge but also by the moment of inertia. These are rotating particles, the particles which represent the notion of the rigid body on the microscopical level and give the key for understanding strong interactions. The main concepts and dynamical laws for these particles are formulated. The basic principles of the theory may be examined experimentally not in the distant future. 29 refs

  2. Interactive protein manipulation

    Energy Technology Data Exchange (ETDEWEB)

    SNCrivelli@lbl.gov

    2003-07-01

    We describe an interactive visualization and modeling program for the creation of protein structures ''from scratch''. The input to our program is an amino acid sequence -decoded from a gene- and a sequence of predicted secondary structure types for each amino acid-provided by external structure prediction programs. Our program can be used in the set-up phase of a protein structure prediction process; the structures created with it serve as input for a subsequent global internal energy minimization, or another method of protein structure prediction. Our program supports basic visualization methods for protein structures, interactive manipulation based on inverse kinematics, and visualization guides to aid a user in creating ''good'' initial structures.

  3. Plasmonic interaction between nanospheres

    CERN Document Server

    Yu, Sanghyeon

    2016-01-01

    When metallic nanospheres are nearly touching, strong nanofocusing of light can occur due to highly localized surface plasmons. It has potential applications in the design of nanophotonic devices, biosensing, and spectroscopy. Due to the singular behavior of electromagnetic fields in the narrow gap regions, its theoretical investigation is quite challenging in both analytical and numerical aspects. There are two approaches for studying the interaction between metallic spheres: transformation optics and the method of image charges. Here we clarify the connection between them. Based on the connection formula, we reveal the singular nature of plasmonic interaction between nanospheres in a completely analytical way. We also develop a hybrid numerical scheme for accurately and efficiently computing the field distribution produced by an arbitrary number of nearly touching plasmonic spheres.

  4. Interactive design center.

    Energy Technology Data Exchange (ETDEWEB)

    Pomplun, Alan R. (Sandia National Laboratories, Livermore, CA)

    2005-07-01

    Sandia's advanced computing resources provide researchers, engineers and analysts with the ability to develop and render highly detailed large-scale models and simulations. To take full advantage of these multi-million data point visualizations, display systems with comparable pixel counts are needed. The Interactive Design Center (IDC) is a second generation visualization theater designed to meet this need. The main display integrates twenty-seven projectors in a 9-wide by 3-high array with a total display resolution of more than 35 million pixels. Six individual SmartBoard displays offer interactive capabilities that include on-screen annotation and touch panel control of the facility's display systems. This report details the design, implementation and operation of this innovative facility.

  5. Intelligent Interactive Multimedia

    CERN Document Server

    Watanabe, Toyohide; Takahashi, Naohisa; 5th International Conference on Intelligent Interactive Multimedia Systems and Services

    2012-01-01

    This volume contains the Proceedings of the 5th International Conference on Intelligent Interactive Multimedia Systems and Services (KES-IIMSS-12).  The Conference was jointly organised by Nagoya University in Japan and the KES International organisation, and held in the attractive city of Gifu.   The KES-IIMSS conference series, (series chairs Prof. Maria Virvou and Prof. George Tsihrintzis), presents novel research in various areas of intelligent multimedia system relevant to the development of a new generation of interactive, user-centric devices and systems.  The aim of the conference is to provide an internationally respected forum for scientific research in the technologies and applications of this new and dynamic research area.

  6. Interactional Expertise and Embodiment

    CERN Document Server

    Collins, Harry

    2016-01-01

    In Part 1 of this paper, I introduce the idea of interactional expertise while in Part 2, I focus on its implications for philosophical theories of the importance of the body in forming our conceptual world. I argue that the way philosophers have dealt with the body turns attention away from the most important questions and that we cannot answer these questions without making the notion of socialisation, and therefore interactional expertise, a central concept in our thinking. This makes language at least as important, and often more important than bodily practice in our understanding of the world. The notion of a disembodied socialised agent leads in the direction of interesting questions while the notion of an embodied but unsocialised human actor is unimaginable.

  7. Interactive protein manipulation

    International Nuclear Information System (INIS)

    We describe an interactive visualization and modeling program for the creation of protein structures ''from scratch''. The input to our program is an amino acid sequence -decoded from a gene- and a sequence of predicted secondary structure types for each amino acid-provided by external structure prediction programs. Our program can be used in the set-up phase of a protein structure prediction process; the structures created with it serve as input for a subsequent global internal energy minimization, or another method of protein structure prediction. Our program supports basic visualization methods for protein structures, interactive manipulation based on inverse kinematics, and visualization guides to aid a user in creating ''good'' initial structures

  8. Embodying multilingual interaction

    DEFF Research Database (Denmark)

    Hazel, Spencer; Mortensen, Janus

    this linguistic diversity is managed in situ by participants engaged in dialogue with one another, and what it is used for in these transient multilingual communities. This paper presents CA-based micro-ethnographic analyses of language choice in an informal social setting – a kitchen – of an international study...... literature on language choice in interaction, our findings emphasize that analyses of language choice in multilingual settings need to take into account social actions beyond the words that are spoken. We show that facial, spatial and postural configurations, gaze orientation and gestures as well as prosodic...... in the particular community of practice that we are investigating. Reference Hazel, Spencer, and Janus Mortensen. forthcoming. Kitchen talk: Exploring linguistic practices in liminal institutional interactions in a multilingual university setting. in Language Alternation, Language Choice, and Language Encounter...

  9. Interactive Information Retrieval:

    DEFF Research Database (Denmark)

    Borlund, Pia

    This presentation addresses methodological issues of interactive information retrieval (IIR) evaluation in terms of what it entails to study users' use and interaction with IR systems, as well as their satisfaction with retrieved information. In particular, the presentation focuses on test design...... the habitat of the users to ensure a complete and realistic picture to enhance our understanding of IIR. The presentation also reflects on whether a re-thinking of the concept on an information need is necessary. One may ask whether it still makes sense to talk about types of information needs. Or...... should we rather study IIR from the perspective of search dedication and task load in order to also include everyday life information seeking? With this presentation, the IIR community is invited to an exchange of ideas and is encouraged to engage in collaborations with the solving of these (and other...

  10. Interactive Information Retrieval

    DEFF Research Database (Denmark)

    Borlund, Pia

    2013-01-01

    The paper introduces the research area of interactive information retrieval (IIR) from a historical point of view. Further, the focus here is on evaluation, because much research in IR deals with IR evaluation methodology due to the core research interest in IR performance, system interaction and...... satisfaction with retrieved information. In order to position IIR evaluation, the Cranfield model and the series of tests that led to the Cranfield model are outlined. Three iconic user-oriented studies and projects that all have contributed to how IIR is perceived and understood today are presented: The....... As a response to this call the ‘IIR evaluation model’ by Borlund (e.g., 2003a) is introduced. The objective of the IIR evaluation model is to facilitate IIR evaluation as close as possible to actual information searching and IR processes, though still in a relatively controlled evaluation environment...

  11. Interactive Chemical Reactivity Exploration

    CERN Document Server

    Haag, Moritz P; Bosson, Mael; Redon, Stephane; Reiher, Markus

    2014-01-01

    Elucidating chemical reactivity in complex molecular assemblies of a few hundred atoms is, despite the remarkable progress in quantum chemistry, still a major challenge. Black-box search methods to find intermediates and transition-state structures might fail in such situations because of the high-dimensionality of the potential energy surface. Here, we propose the concept of interactive chemical reactivity exploration to effectively introduce the chemist's intuition into the search process. We employ a haptic pointer device with force-feedback to allow the operator the direct manipulation of structures in three dimensions along with simultaneous perception of the quantum mechanical response upon structure modification as forces. We elaborate on the details of how such an interactive exploration should proceed and which technical difficulties need to be overcome. All reactivity-exploration concepts developed for this purpose have been implemented in the Samson programming environment.

  12. Wood–water interactions

    DEFF Research Database (Denmark)

    Engelund, Emil Tang

    2011-01-01

    Predicting the performance of wood for decades ahead is important when using the material for structural purposes. The performance is closely related to the hierarchical material structure of wood and the dependent interaction with water in the structure. Accurately predicting wood performance...... therefore requires an understanding of material structure from molecular to macroscopic level as well as of the impact of water molecules. The objective of this work is to investigate the performance of wood in terms of mechanical response of the material and effect of water. To understand the latter, one...... must first know in which parts of the wood structure, water is located. If parts of the water in wood are held in capillaries in the wood structure, these water molecules interact with the material differently than those held within wood cell walls. In this study, the occurrence of capillary water in...

  13. Identification of social interactions

    OpenAIRE

    Blume, Lawrence E.; William A Brock; Durlauf, Steven N.; Ioannides, Yannis M.

    2010-01-01

    Abstract: While interest in social determinants of individual behavior has led to a rich theoretical literature and many efforts to measure these influences, a mature "social econometrics" has yet to emerge. This chapter provides a critical overviewof the identification of social interactions. We consider linear and discrete choice models as well as social networks structures. We also consider experimental and quasi-experimental methods. In addition to describing the state of the identificati...

  14. Interactive Submodular Set Cover

    OpenAIRE

    Guillory, Andrew; Bilmes, Jeff

    2010-01-01

    We introduce a natural generalization of submodular set cover and exact active learning with a finite hypothesis class (query learning). We call this new problem interactive submodular set cover. Applications include advertising in social networks with hidden information. We give an approximation guarantee for a novel greedy algorithm and give a hardness of approximation result which matches up to constant factors. We also discuss negative results for simpler approaches and present encouragin...

  15. Interactive Submodular Set Cover

    CERN Document Server

    Guillory, Andrew

    2010-01-01

    We introduce a natural generalization of submodular set cover and exact active learning with a finite hypothesis class (query learning). We call this new problem interactive submodular set cover. Applications include advertising in social networks with hidden information. We give an approximation guarantee for a greedy algorithm and give a hardness of approximation result which matches up to constant factors. We also discuss the adaptivity gap for the problem and present encouraging early experimental results.

  16. Moxifloxacin-warfarin interaction

    Directory of Open Access Journals (Sweden)

    Yan Ji

    2012-01-01

    Full Text Available Two case reports presented here show elevated prothrombin time/international normalized ratios (PT/INR following coadministration of warfarin and moxifloxacin. Although the underlying mechanism of this interaction still remains unclear, health care providers should be careful when prescribing moxifloxacin to patients on warfarin therapy, especially to patients with low albumin levels. More frequent monitoring of INR in these patients may be warranted.

  17. Moxifloxacin-warfarin interaction

    OpenAIRE

    Ji, Yan; Hokayem, Youssef

    2012-01-01

    Two case reports presented here show elevated prothrombin time/international normalized ratios (PT/INR) following coadministration of warfarin and moxifloxacin. Although the underlying mechanism of this interaction still remains unclear, health care providers should be careful when prescribing moxifloxacin to patients on warfarin therapy, especially to patients with low albumin levels. More frequent monitoring of INR in these patients may be warranted.Keywords: warfarin; moxifloxacin; PT/INR;...

  18. Structural control interaction

    Science.gov (United States)

    Ryan, R. S.; Mowery, D. K.; Winder, S. W.; Worley, H. E.

    1973-01-01

    The basic guidance and control concepts that lead to structural control interaction and structural dynamic loads are identified. Space vehicle ascent flight load sources and the load relieving mechanism are discussed, along with the the characteristics and special problems of both present and future space vehicles including launch vehicles, orbiting vehicles, and the Space Shuttle flyback vehicle. The special dynamics and control analyses and test problems apparent at this time are summarized.

  19. Interactions faibles en harmonie

    CERN Multimedia

    1978-01-01

    Des résultats de haute précision obtenus à Stanford ouvrent la voie vers une unification des interactions faible et électromagnétique ; Présentation à la Conférence neutrino d'Oxford de nouveaux résultats en accord avec la théorie de la synthèse des forces faible et électro- magnétique

  20. Electric hydraulic interaction

    OpenAIRE

    Helle, Ola Høydal

    2011-01-01

    The hydraulic models representing hydro turbines and conduit system found instandard model libraries of power system analysis tools are often simplied mod-els. Subsequently, important information about the dynamics of the hydraulicsystem may not be properly represented by such models, putatively resultingin insucient representation of the interaction between the electric system andhydraulic system.In this master thesis three dierent hydraulic models for hydro power plantsequipped with Francis...

  1. Question answering and interactions

    OpenAIRE

    Séjourné, Kévin

    2009-01-01

    The question answering systems monolingual or multilingual allow to look in a large collection of documents (of journalistic type for example), or on Web an answer specified to a question. However, there is no possible interaction after the answer: we cannot ask for a precision, modify the question. Now often the answer cannot be directly brought ( too indistinct question), or is not completely satisfactory for the user. The subject of the thesis consists in spreading these works so as to all...

  2. Wave-Ice interaction

    Institute of Scientific and Technical Information of China (English)

    沈奚海莉

    2001-01-01

    The growth and movement of sea ice cover are influenced by the presence of wave field. Inturn, the wave field is influenced by the presence of ice cover. Their interaction is not fully understood.In this paper, we discuss some current understanding on wave attenuation when it propagates through frag-mented ice cover, ice drift due to the wave motion, and the growth characteristics of ice cover in wave field.

  3. [Unexpected drug-interaction].

    Science.gov (United States)

    Tajima, Yutaka

    2002-02-01

    The case of a male patient suffering from chronic normal pressure hydrocephalus is outlined. Antidepressant and pravastatin were administered because of the patient's abulia and hypercholesterolemia, but neuroleptic malignant syndrome-like conditions developed. All physicians should suppose the occurrence of such an "unexpected drug-interaction" in any case. The author considered that a good sense of careful discernment and rapid reference system of medical information are "essential tools" for clinical management. PMID:11925849

  4. Antinucleon-nucleus interactions

    Energy Technology Data Exchange (ETDEWEB)

    Dover, C.B.

    1987-01-01

    Recent experimental and theoretical results on anti p-nucleus interactions are reviewed. We focus on determinations of the anti p optical potential from elastic scattering, the use of (anti p, anti p') inelastic scattering to reveal aspects of the spin-isospin dependence of N anti N amplitudes, and some puzzling features of (anti p, anti n) charge exchange reactions on nuclei. 47 refs., 7 figs.

  5. SEEPAGE/INVERT INTERACTIONS

    International Nuclear Information System (INIS)

    As directed by a written development plan (CRWMS M andO 1999a), a conceptual model for water entering the drift and reacting with the invert materials is to be developed. The purpose of this conceptual model is to assist Performance Assessment Operations (PAO) and its Engineered Barrier Performance Department in modeling the geochemical environment within a repository drift, thus allowing PAO to provide a more detailed and complete in-drift geochemical model abstraction, and to answer the key technical issues (KTI) raised in the NRC Issue Resolution Status Report (IRSR) for the Evolution of the Near-Field Environment (NFE), Revision 2 (NRC 1999). This AMR also seeks to: (1) Develop a logical conceptual model for physical/chemical interactions between seepage and the invert materials; (2) screen potential processes and reactions that may occur between seepage and invert to evaluate the potential consequences of the interactions; and (3) outline how seepage/invert processes may be quantified. This document provides the conceptual framework for screening out insignificant processes and for identifying and evaluating those seepage/invert interactions that have the potential to be important to subsequent PAO analyses including the Engineered Barrier System (EBS) physical and chemical model abstraction effort. This model has been developed to serve as a basis for the in-drift geochemical analyses performed by PAO. Additionally, the concepts discussed within this report may also apply to certain near and far-field geochemical processes and may have conceptual application within the unsaturated zone (UZ) and saturated zone (SZ) transport modeling efforts. The seepage/invert interactions will not directly affect any principal factors

  6. Interactive Video Search

    OpenAIRE

    Schoeffmann, Klaus; Hopfgartner, Frank

    2015-01-01

    With an increasing amount of video data in our daily life, the need for content-based search in videos increases as well. Though a lot of research has been spent on video retrieval tools and methods which allow for automatic search in videos through content-based queries, still the performance of automatic video retrieval is far from optimal. In this tutorial we discussed (i) proposed solutions for improved video content navigation, (ii) typical interaction of content-based querying features,...

  7. Protein-surfactant interactions

    OpenAIRE

    Valstar, Ank

    2000-01-01

    Protein-surfactant interactions in aqueous media have been investigated. The globular proteins lysozyme and bovine serum albumin (BSA) served as model proteins. Several ionic and non-ionic surfactants were used. Fluorescence probe measurements showed that at low sodium dodecyl sulfate (SDS) concentration (< 0.1 M) one micelle-like SDS cluster is bound to lysozyme. From dynamic light scattering (DLS) results it was observed that lysozyme in the complex does not correspond to the fully unfol...

  8. Hydrophobic interaction chromatography

    OpenAIRE

    O'Connor, Brendan; Cummins, Phil

    2011-01-01

    Most proteins and large polypeptides have hydrophobic regions at their surface. These hydrophobic ‘patches’ are due to the presence of the side chains of hydrophobic or non-polar amino acids such as phenylalanine, tryptophan, alanine and methionine. These surface hydrophobic regions are interspersed between more hydrophilic or polar regions and the number, size and distribution of them is a specific characteristic of each protein. Hydrophobic Interaction Chromatography (HIC) is a commonly use...

  9. Interactions within wastewater systems

    OpenAIRE

    Langeveld, J.G.

    2004-01-01

    Wastewater systems consist of sewer systems and wastewater treatment works. As the performance of a wastewater treatment plant is affected by the characteristics, i.e. operation and design, of the contributing sewer systems, knowledge of the interactions between sewers and wastewater treatment works is very important when trying to understand and improve wastewater systems. The thesis comprises three main topics: Firstly, the sensitivity of wastewater treatment plant performance to influent f...

  10. Interactive tabletops in education

    OpenAIRE

    Dillenbourg, Pierre; Evans, Michael

    2011-01-01

    Interactive tabletops are gaining increased attention from CSCL researchers. This paper analyses the relation between this technology and teaching and learning processes. At a global level, one could argue that tabletops convey a socio-constructivist flavor: they support small teams that solve problems by exploring multiple solutions. The development of tabletop applications also witnesses the growing importance of face-to-face collaboration in CSCL and acknowledges the physicality of learnin...

  11. Interaction, Relationships And Networks

    OpenAIRE

    Benson-Rea, M

    1999-01-01

    This paper presents four case studies which have been selected to represent different insights into the strategic evaluation of relationships within one industry. From an analysis of how each of the case study firms has formed its networks of relationships, within its overall approach to industry strategy, we discuss how the interactions are evaluated, with a particular emergent focus on social or actor bonds. The strategy literature models strategy formation processes and content. The networ...

  12. Interaction Graphs: Exponentials

    OpenAIRE

    Seiller, Thomas

    2013-01-01

    This paper is the fourth of a series exposing a systematic combinatorial approach to Girard's Geometry of Interaction program. This program aims at obtaining particular realizability models for linear logic that accounts for the dynamics of cut-elimination. This fourth paper tackles the complex issue of defining exponential connectives in this framework. In order to succeed in this, we use the notion of graphings, a generalization of graphs which was defined in earlier work. We explain how we...

  13. ELEMENTARY PARTICLE INTERACTIONS

    Energy Technology Data Exchange (ETDEWEB)

    EFREMENKO, YURI; HANDLER, THOMAS; KAMYSHKOV, YURI; SIOPSIS, GEORGE; SPANIER, STEFAN

    2013-07-30

    The High-Energy Elementary Particle Interactions group at UT during the last three years worked on the following directions and projects: Collider-based Particle Physics; Neutrino Physics, particularly participation in “NOνA”, “Double Chooz”, and “KamLAND” neutrino experiments; and Theory, including Scattering amplitudes, Quark-gluon plasma; Holographic cosmology; Holographic superconductors; Charge density waves; Striped superconductors; and Holographic FFLO states.

  14. Model of dynamic interactions

    OpenAIRE

    Klimchik, Alexandr; Pashkevich, Anatol; Caro, Stéphane

    2013-01-01

    In robotic-based machining, an interaction between the workpiece and technological tool causes essential deflections that significantly decrease the manufacturing accuracy. Relevant compliance errors highly depend on the manipulator configuration and essentially differ throughout the workspace. Their influence is especially important for heavy serial robots. To overcome this difficulty this report presents a new technique for compensation of the compliance errors caused by technological proce...

  15. Interactive Mediated Reality

    OpenAIRE

    Grasset, Raphaël; Boissieux, Laurence; Gascuel, Jean-Dominique; Schmalstieg, Dieter

    2005-01-01

    International audience Mediated reality describes the concept of filtering our vision of reality, typically using a head-mounted video mixing display. We can redefine this idea in a more constructive context, applying dynamic changes to the appearance and geometry of objects in a real scene using computer graphics. In this paper, we propose new tools for interactively mediated reality. After describing a new generic framework for achieving this goal, we present a prototype system for paint...

  16. Matrix string interactions

    OpenAIRE

    Periwal, Vipul; Tafjord, Oyvind

    1998-01-01

    String configurations have been identified in compactified Matrix theory at vanishing string coupling. We show how the interactions of these strings are determined by the Yang-Mills gauge field on the worldsheet. At finite string coupling, this suggests the underlying dynamics is not well-approximated as a theory of strings. This may explain why string perturbation theory diverges badly, while Matrix string perturbation theory presumably has a perturbative expansion with properties similar to...

  17. Between autonomy and interaction

    DEFF Research Database (Denmark)

    Verwohlt, Betina

    In 2007, a smoking law was implemented in Denmark, banning indoor tobacco smoke in public places such as pubs, restaurants, workplaces, public offices, hospitals and shopping malls. The law marks a paradigm shift in Danish tobacco policy manifesting a stronger structural focus than has been the c...... attitudes towards structural initiatives before and after the implementation and discusses what causes changes in the population’s attitudes and whether the attitudes are best described as autonomous or as interactive with societal changes....

  18. Interactive Mathematics Textbooks

    DEFF Research Database (Denmark)

    Sinclair, Robert

    1999-01-01

    We claim that important considerations have been overlooked in designinginteractive mathematics educational software in the past.In particular,most previous work has concentrated on how to make use ofpre-existing software in mathematics education, rather than firstasking the more...... fundamentalquestion of which requirements mathematics education puts on software, and thendesigning software to fulfil these requirements.We present a working prototype system which takes a script defining an interactivemathematicaldocument and then provides a reader with an interactive realization of thatdocument....

  19. Dynamics of interacting quintessence

    International Nuclear Information System (INIS)

    In this paper,we investigate coupled quintessence with scaling potential assuming specific forms of the coupling as A namely, αρm, βρφ and σ(ρm + ρφ), and present phase space analysis for three different interacting models. We focus on the attractor solutions that can give rise to late time acceleration with ΩDE/ΩDM of order unity in order to alleviate the coincidence problem. (orig.)

  20. Interactive Chemical Reactivity Exploration

    OpenAIRE

    Haag, Moritz P.; Vaucher, Alain C.; Bosson, Mael; Redon, Stephane; Reiher, Markus

    2014-01-01

    Elucidating chemical reactivity in complex molecular assemblies of a few hundred atoms is, despite the remarkable progress in quantum chemistry, still a major challenge. Black-box search methods to find intermediates and transition-state structures might fail in such situations because of the high-dimensionality of the potential energy surface. Here, we propose the concept of interactive chemical reactivity exploration to effectively introduce the chemist's intuition into the search process. ...

  1. Orbital interactions in chemistry

    CERN Document Server

    Albright, Thomas A; Whangbo, Myung-Hwan

    2013-01-01

    Explains the underlying structure that unites all disciplines in chemistry Now in its second edition, this book explores organic, organometallic, inorganic, solid state, and materials chemistry, demonstrating how common molecular orbital situations arise throughout the whole chemical spectrum. The authors explore the relationships that enable readers to grasp the theory that underlies and connects traditional fields of study within chemistry, thereby providing a conceptual framework with which to think about chemical structure and reactivity problems. Orbital Interactions

  2. Interacting Dark Energy

    OpenAIRE

    Zhang, Xinmin

    2004-01-01

    In this paper I discuss some of the phenomenologies of models of the dark energy interacting with the ordinary matter. After a very brief review about the current constraint on the equation of the state of the dark energy from the SN and a new scenario of dark energy {\\it the Quintom}, I present models of Quintessential Baryo(Lepto)genesis, Quintessino dark matter and mass varying neutrinos in details.

  3. Interacting Multiview Tracker.

    Science.gov (United States)

    Yoon, Ju Hong; Yang, Ming-Hsuan; Yoon, Kuk-Jin

    2016-05-01

    A robust algorithm is proposed for tracking a target object in dynamic conditions including motion blurs, illumination changes, pose variations, and occlusions. To cope with these challenging factors, multiple trackers based on different feature representations are integrated within a probabilistic framework. Each view of the proposed multiview (multi-channel) feature learning algorithm is concerned with one particular feature representation of a target object from which a tracker is developed with different levels of reliability. With the multiple trackers, the proposed algorithm exploits tracker interaction and selection for robust tracking performance. In the tracker interaction, a transition probability matrix is used to estimate dependencies between trackers. Multiple trackers communicate with each other by sharing information of sample distributions. The tracker selection process determines the most reliable tracker with the highest probability. To account for object appearance changes, the transition probability matrix and tracker probability are updated in a recursive Bayesian framework by reflecting the tracker reliability measured by a robust tracker likelihood function that learns to account for both transient and stable appearance changes. Experimental results on benchmark datasets demonstrate that the proposed interacting multiview algorithm performs robustly and favorably against state-of-the-art methods in terms of several quantitative metrics. PMID:26336117

  4. AGNs and galaxy interactions

    CERN Document Server

    Alonso, M S; Tissera, P; Coldwell, G; Lambas, Diego G.; Tissera, Patricia; Coldwell, Georgina

    2007-01-01

    We perform a statistical analysis of AGN host characteristics and nuclear activity for AGNs in pairs and without companions. Our study concerns a sample of AGNs derived from the SDSS-DR4 data by Kauffmann et al (2003) and pair galaxies obtained from the same data set by Alonso et al. (2006). An eye-ball classification of images of 1607 close pairs ($r_p<25$ kpc $h^{-1}$, $\\Delta V<350$ km $s^{-1}$) according to the evidence of interaction through distorted morphologies and tidal features provides us with a more confident assessment of galaxy interactions from this sample. We notice that, at a given luminosity or stellar mass content, the fraction of AGNs is larger for pair galaxies exhibiting evidence for strong interaction and tidal features which also show sings of strong star formation activity. Nevertheless, this process accounts only for a $\\sim 10%$ increase of the fraction of AGNs. As in previous works, we find AGN hosts to be redder and with a larger concentration morphological index than non-AG...

  5. Drug interactions with grapefruit

    Directory of Open Access Journals (Sweden)

    Bojanić Vladmila V.

    2010-01-01

    Full Text Available Introduction. The concentration of many orally given medications may be affected by grapefruit or grapefruit juice consumption. It may result in numerous harmful effects. Interaction of grapefruit with drugs. Taking only one cup of juice may induce interactions with different drugs even during the period of a few days. The effect is induced by suppression of cytochrome P450 isoenzyme CYP3A4 in the intestinal wall. The Latin name of grapefruit, Citrus paradisi, is quite opposite to the effects which could be induced by taking grapefruit and some medications at the same time. It is necessary to avoid taking grapefruit with the drugs whose pharmacokinetics could be altered by the active principles found in that fruit. Discussion. The coloured grapefruit contains less furanocoumarins, but there is no difference in induction and intensity of pharmacokinetic interaction with drugs related to its colour. Other citrus fruits (orange, lemon do not have such effects, but some other fruits (pomegranate, stella fruit, banpeiyu, hassaku, takaoka-buntan and kinkan exert inhibitory effects on the activity of cytochrome P450 isoenzyme.

  6. Web Interactive Campus Map

    Directory of Open Access Journals (Sweden)

    Marylene S. Eder

    2015-03-01

    Full Text Available Abstract Interactive campus map is a web based application that can be accessed through a web browser. With the Google Map Application Programming Interface availability of the overlay function has been taken advantage to create custom map functionalities. Collection of building points were gathered for routing and to create polygons which serves as a representation of each building. The previous campus map provides a static visual representation of the campus. It uses legends building name and its corresponding building number in providing information. Due to its limited capabilities it became a realization to the researchers to create an interactive campus map.Storing data about the building room and staff information and university events and campus guide are among the primary features that this study has to offer. Interactive Web-based Campus Information System is intended in providing a Campus Information System.It is open to constant updates user-friendly for both trained and untrained users and capable of responding to all needs of users and carrying out analyses. Based on the data gathered through questionnaires researchers analyzed the results of the test survey and proved that the system is user friendly deliver information to users and the important features that the students expect.

  7. Transactional interactive multimedia banner

    Science.gov (United States)

    Shae, Zon-Yin; Wang, Xiping; von Kaenel, Juerg

    2000-05-01

    Advertising in TV broadcasting has shown that multimedia is a very effective means to present merchandise and attract shoppers. This has been applied to the Web by including animated multimedia banner ads on web pages. However, the issues of coupling interactive browsing, shopping, and secure transactions e.g. from inside a multimedia banner, have only recently started to being explored. Currently there is an explosively growing amount of back-end services available (e.g., business to business commerce (B2B), business to consumer (B2C) commerce, and infomercial services) in the Internet. These services are mostly accessible through static HTML web pages at a few specific web portals. In this paper, we will investigate the feasibility of using interactive multimedia banners as pervasive access point for the B2C, B2B, and infomercial services. We present a system architecture that involves a layer of middleware agents functioning as the bridge between the interactive multimedia banners and back-end services.

  8. Intercultural Interaction and Handicrafts

    Directory of Open Access Journals (Sweden)

    Mine CAN

    2015-07-01

    Full Text Available Technological developments in the world since the mid - 20th century, has increased intercultural communication and the whole world today has been informed of the existence of societies even in the most remote corners of the world. With increase in globaliza tion in cultural context, the importance of local differences has emerged more today. As a result, a process has initiated in which the similarities with differences, localization with the universalization and modernization with the tradition experienced s imutaneously and intercultural interaction has become inevitable and a natural phenomenon. However, handicrafts has been affected by cultural interactions negatively and the mistakes done caused the national culture and identities to weaken. For this reaso n, the necessity of experience of changing and developing in the frame of development with identity, transformation and cultural heritage today is emphasized. To be protected from the negative effects of the global interaction, many government produce prot ection and sustenance contracts, laws and projects by engaging in various initiatives. In the study, subjects is discussed with the examples of successful countries that aim to promote their local cultures globally and provide income.

  9. Asynchronous interactive control systems

    Science.gov (United States)

    Vuskovic, M. I.; Heer, E.

    1980-01-01

    A class of interactive control systems is derived by generalizing interactive manipulator control systems. The general structural properties of such systems are discussed and an appropriate general software implementation is proposed. This is based on the fact that tasks of interactive control systems can be represented as a network of a finite set of actions which have specific operational characteristics and specific resource requirements, and which are of limited duration. This has enabled the decomposition of the overall control algorithm into a set of subalgorithms, called subcontrollers, which can operate simultaneously and asynchronously. Coordinate transformations of sensor feedback data and actuator set-points have enabled the further simplification of the subcontrollers and have reduced their conflicting resource requirements. The modules of the decomposed control system are implemented as parallel processes with disjoint memory space communicating only by I/O. The synchronization mechanisms for dynamic resource allocation among subcontrollers and other synchronization mechanisms are also discussed in this paper. Such a software organization is suitable for the general form of multiprocessing using computer networks with distributed storage.

  10. Designing an interactive multimedia instructional environment: The Civil War Interactive

    OpenAIRE

    Ward M. Cates; Fontana, Lynn A.; Charles S. White

    1993-01-01

    This article describes the rationales behind the design decisions made in creating The Civil War Interactive, an interactive multimedia instructional product based on Ken Burns''s film series The Civil War.DOI:10.1080/0968776930010202

  11. Michigan molecular interactions r2: from interacting proteins to pathways

    OpenAIRE

    Tarcea, V. Glenn; Weymouth, Terry; Ade, Alex; Bookvich, Aaron; Gao, Jing; Mahavisno, Vasudeva; Wright, Zach; Chapman, Adriane; Jayapandian, Magesh; Özgür, Arzucan; Tian, Yuanyuan; Cavalcoli, Jim; Mirel, Barbara; Patel, Jignesh; Radev, Dragomir

    2008-01-01

    Molecular interaction data exists in a number of repositories, each with its own data format, molecule identifier and information coverage. Michigan molecular interactions (MiMI) assists scientists searching through this profusion of molecular interaction data. The original release of MiMI gathered data from well-known protein interaction databases, and deep merged this information while keeping track of provenance. Based on the feedback received from users, MiMI has been completely redesigne...

  12. Scattering with absorptive interaction

    Science.gov (United States)

    Cassing, W.; Stingl, M.; Weiguny, A.

    1982-07-01

    The S matrix for a wide class of complex and nonlocal potentials is studied, with special attention given to the motion of singularities in the complex k plane as a function of the imaginary coupling strength. Modifications of Levinson's theorem are obtained and discussed. Analytic approximations to the S matrix in the vicinity of narrow resonances are exhibited and compared to numerical results of resonating-group calculations. The problem of defining resonances in the case of complex interactions is discussed, making contact with the usual analysis of scattering in terms of Argand diagrams. NUCLEAR REACTIONS Scattering theory, S matrix for absorptive potentials.

  13. Laser-matter interaction

    International Nuclear Information System (INIS)

    A brief summary is given of the physics of the problem of laser-mater interaction. In the limit of very low intensities, the absorption is dominated by inverse bremsstrahlung. At higher intensities and in a homogeneous medium, there are several parametric processes that may become significant. The threshold intensities for the onset of several parametric instabilities are listed. Results for threshold intensities and growth rates just above threshold are briefly discussed for an inhomogeneous plasma. A brief description of resonance absorption in an inhomogeneous plasma is included. (author)

  14. Dust-Plasma Interactions

    International Nuclear Information System (INIS)

    The objective of our theoretical research under this grant over the past 3 years was to develop new understanding in a range of topics in the physics of dust-plasma interactions, with application to space and the laboratory. We conducted studies related to the physical properties of dust, waves and instabilities in both weakly coupled and strongly coupled dusty plasmas, and innovative possible applications. A major consideration in our choice of topics was to compare theory with experiments or observations, and to motivate new experiments, which we believe is important for developing this relatively new field. Our research is summarized, with reference to our list of journal publications.

  15. Flavivirus-Mosquito Interactions

    Directory of Open Access Journals (Sweden)

    Yan-Jang S. Huang

    2014-11-01

    Full Text Available The Flavivirus genus is in the family Flaviviridae and is comprised of more than 70 viruses. These viruses have a broad geographic range, circulating on every continent except Antarctica. Mosquito-borne flaviviruses, such as yellow fever virus, dengue virus serotypes 1–4, Japanese encephalitis virus, and West Nile virus are responsible for significant human morbidity and mortality in affected regions. This review focuses on what is known about flavivirus-mosquito interactions and presents key data collected from the field and laboratory-based molecular and ultrastructural evaluations.

  16. Anomalous gauge boson interactions

    International Nuclear Information System (INIS)

    We discuss the direct measurement of the trilinear vector boson couplings in present and future collider experiments. The major goals of such experiments will be the confirmation of the Standard Model (SM) predictions and the search for signals of new physics. We review our current theoretical understanding of anomalous trilinear gauge-boson self interactions. If the energy scale of the new physics is ∼ 1 TeV, these low energy anomalous couplings are expected to be no larger than Ο(10-2). Constraints from high precision measurements at LEP and low energy charged and neutral current processes are critically reviewed

  17. Interaction, transference, and subjectivity

    DEFF Research Database (Denmark)

    Lundgaard Andersen, Linda

    2012-01-01

    is also subjected to psychodynamic processes. In this article, I draw upon a number of research inquiries to illustrate how psychodynamic processes influence research processes: data production, research questions and methodology, relations to informants, as well as interpretation and analysis. I further...... are important filters for fieldwork. In general, fieldwork can be understood as processes where field reports and field analysis are determined by how the researcher interacts with and experiences the field, the events and informants in it, and how she subsequently develops an ethnography. However, fieldwork...

  18. Student interaction in workshops

    DEFF Research Database (Denmark)

    Evers, Winie

    2014-01-01

    A kind of teaching for active learning has been experimented with at SDU Sønderborg as part of the course Supply Chain Dynamics. In this course the students learn about complex systems, system dynamics as well as supply chain instability and oscillation, the course lecturer invited the author to...... experiment with novel workshop methods and techniques, where objects are used to illustrate and model business issues (Heinemann et al, 2011, Buur et al, 2013). The idea was to see how students could be engaged in a different and more interactive way to learn about these topics, by assigning the students a...

  19. Human Work Interaction Design

    DEFF Research Database (Denmark)

    Gonçalves, Frederica; Campos, Pedro; Clemmensen, Torkil

    2015-01-01

    In this paper, we review research in the emerging practice and research field of Human Work Interaction Design (HWID). We present a HWID framework, and a sample of 54 HWID related papers from workshops, conferences and journals from the period 2009–2014. We group the papers into six topical groups......, and then attempt to map these groups to the framework to find research gaps for future research. We find that the groups of papers cover all areas of the framework well for a variety of work and leisure domains. The area in strongest need for more research papers is the development of the holistic...... for research in prototyping and early organizational implementation...

  20. Alignment in hadronic interactions

    CERN Document Server

    Wibig, T

    2000-01-01

    The alignment of the products of very high energy interactions seen in mountain altitude experiments is one of the most puzzling phenomena in cosmic ray physics for quite a long time. The observations of the Pamir and Chacaltaya emulsion chamber groups and by the Tien-Shan extensive air shower experiment, together with a very clear event seen in the Concorde French-Japanese experiment in the stratosphere, makes the experimental basis very substantial. In the present paper a novel possible explanation is put forward.

  1. Drugging Membrane Protein Interactions.

    Science.gov (United States)

    Yin, Hang; Flynn, Aaron D

    2016-07-11

    The majority of therapeutics target membrane proteins, accessible on the surface of cells, to alter cellular signaling. Cells use membrane proteins to transduce signals into cells, transport ions and molecules, bind cells to a surface or substrate, and catalyze reactions. Newly devised technologies allow us to drug conventionally "undruggable" regions of membrane proteins, enabling modulation of protein-protein, protein-lipid, and protein-nucleic acid interactions. In this review, we survey the state of the art of high-throughput screening and rational design in drug discovery, and we evaluate the advances in biological understanding and technological capacity that will drive pharmacotherapy forward against unorthodox membrane protein targets. PMID:26863923

  2. Interacting Galaxies with MOND

    OpenAIRE

    Tiret, O; Combes, F

    2007-01-01

    We compare N-body simulations performed in MOND with analogs in Newtonian gravity with dark matter (DM). We have developed a code which solves the Poisson equation in both gravity models. It is a grid solver using adaptive mesh refinement techniques, allowing us to study isolated galaxies as well as interacting galaxies. Galaxies in MOND are found to form bars faster and stronger than in the DM model. In Newton dynamics, it is difficult to reproduce the observed high frequency of strong bars,...

  3. Human Computer Interaction

    Science.gov (United States)

    Bhagwani, Akhilesh; Sengar, Chitransh; Talwaniper, Jyotsna; Sharma, Shaan

    2012-08-01

    The paper basically deals with the study of HCI (Human computer interaction) or BCI(Brain-Computer-Interfaces) Technology that can be used for capturing brain signals and translating them into commands that allow humans to control (just by thinking) devices such as computers, robots, rehabilitation technology and virtual reality environments. The HCI is based as a direct communication pathway between the brain and an external device. BCIs are often aimed at assisting, augmenting, or repairing human cognitive or sensory-motor functions.The paper also deals with many advantages of BCI Technology along with some of its applications and some major drawbacks.

  4. Interactive Architecture #1

    OpenAIRE

    Oosterhuis, K.; X. Xia

    2007-01-01

    The iA bookzine series will consist of twelve issues, bi-annually published over a period of six years under the supervision of Prof. ir. Kas Oosterhuis, director of the Hperbody at the Delft University of Technology. Interactive Architecture - from here on abbreviated as iA - is NOT simply architecture that is responsive or adaptive to changing circumstances. On the contrary, iA is based on the concept of bi-directional communication, which requires two active parties. Naturally, communicati...

  5. Detection of molecular interactions

    Science.gov (United States)

    Groves, John T.; Baksh, Michael M.; Jaros, Michal

    2012-02-14

    A method and assay are described for measuring the interaction between a ligand and an analyte. The assay can include a suspension of colloidal particles that are associated with a ligand of interest. The colloidal particles are maintained in the suspension at or near a phase transition state from a condensed phase to a dispersed phase. An analyte to be tested is then added to the suspension. If the analyte binds to the ligand, a phase change occurs to indicate that the binding was successful.

  6. Interaction of open graphic dynamics

    OpenAIRE

    Dugowson, Stéphane

    2015-01-01

    The aim of this paper is to define what we shall call open graphic dynamics, their interactions and the dynamics produced by those interactions. It prepares the study of "open sub-categorical dynamics" and "open categorical dynamics".

  7. Hydrophobic interactions and chemical reactivity

    OpenAIRE

    Otto, Sijbren; Engberts, Jan B.F.N.

    2003-01-01

    This perspective describes how kinetic studies of organic reactions can be used to increase our understanding of hydrophobic interactions. In turn, our understanding of hydrophobic interactions can be used as a tool to influence chemical reactions.

  8. User producer interaction in context

    NARCIS (Netherlands)

    Nahuis, R.; Moors, E.H.M.; Smits, R.E.H.M.

    2012-01-01

    User producer interaction (UPI) increases chances for successful innovations. It is not always clear, however, what type of interaction is necessary in a particular context. This article identifies seven different types of UPI: constructing linkages, broadening, characterizing users, upstream involv

  9. Hadronic Interactions with Lattice QCD

    OpenAIRE

    Savage, Martin J.

    2008-01-01

    I discuss recent results of the NPLQCD Collaboration regarding the calculation of hadronic interactions with lattice QCD. A particular emphasis will be spent on pi-pi scattering and other meson interactions.

  10. Interaction in English Classroom Teaching

    Institute of Scientific and Technical Information of China (English)

    金晶

    2009-01-01

    This essay mainly elaborates on the interaction in English classroom teaching.It highlights the indispensable role interaction should play in teaching process.and give out a series of methods on how to promote the application of this strategy.

  11. Interactions in Dark Energy Models

    OpenAIRE

    Zhang, Yi; Hui LI; Gong, Yungui; Zhu, Zong-Hong

    2011-01-01

    We perform a full dynamical analysis by considering the interactions between dark energy and radiation, and dark energy and dark matter. We find that the interaction helps alleviate the coincidence problem for the quintessence model.

  12. Charged Dust Aggregate Interactions

    Science.gov (United States)

    Matthews, Lorin; Hyde, Truell

    2015-11-01

    A proper understanding of the behavior of dust particle aggregates immersed in a complex plasma first requires a knowledge of the basic properties of the system. Among the most important of these are the net electrostatic charge and higher multipole moments on the dust aggregate as well as the manner in which the aggregate interacts with the local electrostatic fields. The formation of elongated, fractal-like aggregates levitating in the sheath electric field of a weakly ionized RF generated plasma discharge has recently been observed experimentally. The resulting data has shown that as aggregates approach one another, they can both accelerate and rotate. At equilibrium, aggregates are observed to levitate with regular spacing, rotating about their long axis aligned parallel to the sheath electric field. Since gas drag tends to slow any such rotation, energy must be constantly fed into the system in order to sustain it. A numerical model designed to analyze this motion provides both the electrostatic charge and higher multipole moments of the aggregate while including the forces due to thermophoresis, neutral gas drag, and the ion wakefield. This model will be used to investigate the ambient conditions leading to the observed interactions. This research is funded by NSF Grant 1414523.

  13. XEphem: Interactive Astronomical Ephemeris

    Science.gov (United States)

    Downey, Elwood Charles

    2011-12-01

    XEphem is a scientific-grade interactive astronomical ephemeris package for UNIX-like systems. Written in C, X11 and Motif, it is easily ported to systems. Among other things, XEphem: computes heliocentric, geocentric and topocentric information for all objects; has built-in support for all planets; the moons of Mars, Jupiter, Saturn, Uranus and Earth; central meridian longitude of Mars and Jupiter; Saturn's rings; and Jupiter's Great Red Spot; allows user-defined objects including stars, deepsky objects, asteroids, comets and Earth satellites; provides special efficient handling of large catalogs including Tycho, Hipparcos, GSC; displays data in configurable tabular formats in conjunction with several interactive graphical views; displays a night-at-a-glance 24 hour graphic showing when any selected objects are up; displays 3-D stereo Solar System views that are particularly well suited for visualizing comet trajectories; quickly finds all close pairs of objects in the sky; and sorts and prints all catalogs with very flexible criteria for creating custom observing lists. Its capabilities are listed more fully in the user manual introduction.

  14. Electromagnetic Interactions of Muons

    CERN Multimedia

    2002-01-01

    This experiment was the first in a programme of physics experiments with high-energy muons using a large spectrometer facility. The aim of this experiment is to study the inelastic scattering of muons various targets to try to understand better the physics of virtual photon interactions over a wide of four-momentum transfer (q|2).\\\\ \\\\ The spectrometer includes a large aperture dipole magnet (2m x 1m) of bending power @C 5 T.m and a magnetized iron filter to distinguish the scattered muons from hadrons. Drift chambers and MWPC are used before and after the magnet to detect charged products of the interaction and to allow a momentum determination of the scattered muon to an accuracy of @C 1\\% at 100 GeV/c, and an angular definition of @+ 0.1 mrad. The triggering on scattered muons relies on three planes of scintillation counter hodoscopes before and after the magnetized iron, whose magnetic field serves to eliminate triggers from low momentum muons which are produced copiously by pion decay. \\\\ \\\\ The experime...

  15. Interactive fundamental physics

    International Nuclear Information System (INIS)

    THE REAL STUFF is an Expanded Media Physics Course aimed at students still in the formative early years of secondary school. Its consists of a working script for an interactive multimedia study unit in basic concepts of physics. The unit begins with a prologue on the Big Bang that sets the stage, and concludes with a lesson on Newton's first law of motion. The format is interactive, placing the individual student in control of a layered ''hypermedia'' structure that enables him or her to find a level of detail and difficulty that is comfortable and meaningful. The intent is to make physics relevant, intellectually accessible and fun. On-screen presenters and demonstrators will be females and males of various ages, ethnicities and backgrounds, and will include celebrities and physicists of note. A lean, layered design encourages repeated, cumulative study and makes the material useful for self-directed Teaming even by college students. THE REAL STUFF introduces a new science teaching paradigm, a way to teach science that will engage even students who have ''declined'' to be interested in science in the past. Increased participation in science by women, African-Americans and Spanish-speaking students is a particular goal

  16. JSPAM: Interacting galaxies modeller

    Science.gov (United States)

    Wallin, John F.; Holincheck, Anthony; Harvey, Allen

    2015-11-01

    JSPAM models galaxy collisions using a restricted n-body approach to speed up computation. Instead of using a softened point-mass potential, the software supports a modified version of the three component potential created by Hernquist (1994, ApJS 86, 389). Although spherically symmetric gravitationally potentials and a Gaussian model for the bulge are used to increase computational efficiency, the potential mimics that of a fully consistent n-body model of a galaxy. Dynamical friction has been implemented in the code to improve the accuracy of close approaches between galaxies. Simulations using this code using thousands of particles over the typical interaction times of a galaxy interaction take a few seconds on modern desktop workstations, making it ideal for rapidly prototyping the dynamics of colliding galaxies. Extensive testing of the code has shown that it produces nearly identical tidal features to those from hierarchical tree codes such as Gadget but using a fraction of the computational resources. This code was used in the Galaxy Zoo: Mergers project and is very well suited for automated fitting of galaxy mergers with automated pattern fitting approaches such as genetic algorithms. Java and Fortran versions of the code are available.

  17. Microbiome and immunological interactions.

    Science.gov (United States)

    Kelly, Denise; Mulder, Imke E

    2012-08-01

    The healthy human gut supports a complex and diverse microbiota, dominated by bacterial phylotypes belonging to Bacteroidetes and Firmicutes. In the inflamed gut, overall diversity decreases, coincident with a greater representation of Proteobacteria. There is growing evidence supporting an important role for human gut bacteria in mucosal immunity; interactions at the level of both intestinal and colonic epithelial cells, dendritic cells, and T and B immune cells have been documented. These interactions influence gut barrier and defense mechanisms that include antimicrobial peptide and secretory IgA synthesis. The functional effects of commensal bacteria on T helper cell differentiation have led to the emerging concept that microbiota composition determines T effector- and T regulatory-cell balance, immune responsiveness, and homeostasis. The importance of this biology in relation to immune homeostasis, inflammatory bowel disease, and the rising incidence of autoimmune diseases will be discussed. The detailed description of the human gut microbiota, integrated with evidence-based mechanisms of immune modulation, provides an exciting platform for the identification of next-generation probiotics and related pharmaceutical products. PMID:22861803

  18. Crack interaction with microstructure

    Directory of Open Access Journals (Sweden)

    Sharvan Kumar

    2007-09-01

    Full Text Available Designing microstructure for damage tolerance requires a detailed understanding of how an advancing crack interacts with the microstructure (and sometimes modifies it locally at multiple length scales. Advances in experimental techniques, such as the availability of well-controlled straining stages for optical and electron microscopes, the focused ion beam, electron backscattered diffraction, and nanoindentation, enable probing at these length scales in real time and through interrupted tests. Simultaneously, increasing computational power coupled with new computational methods, such as finite element analysis (FEA incorporating cohesive elements at the continuum level, discrete dislocation methodology at the mesoscopic level, and coupled atomistic/continuum methods that transitions atomic level information to the mesoscopic level, have made it possible to begin addressing these complex problems. By reviewing crack growth in a variety of multiphase alloys including steels, titanium aluminides, Mo alloys, and nanocrystalline metals, we demonstrate various aspects of crack interaction with microstructure, and how these problems are being addressed through experiments and computations.

  19. Nucleon-antinucleon interaction

    International Nuclear Information System (INIS)

    The current status of our understanding of the low energy nucleon-antinucleon (N anti N) interaction is reviewed. We compare several phenomenological models which fit the available N anti N cross section data. The more realistic of these models employ an annihilation potential W(r) which is spin, isospin and energy dependent. The microscopic origins for these dependences are discussed in terms of quark rearrangement and annihilation processes. It is argued that the study of N anti N annihilation offers a powerful means of studying quark dynamics at short distances. We also discuss how one may try to isolate coherent meson exchange contributions to the medium and long range part of the N anti N potential. These pieces of the N anti N interaction are calculable via the G-parity transformation from a model for the NN potential; their effects are predicted to be seen in N anti N spin observables, to be measured at LEAR. The possible existence of quasi-stable bound states or resonances of the anti N plus one or more nucleons is discussed, with emphasis on few-body systems. 42 references

  20. The Interactive Zoooz Guide

    Directory of Open Access Journals (Sweden)

    Thang Nguyen

    2010-12-01

    Full Text Available GPS (Global Positioning System technology is widely known for its ability to track down devices in real time. Combined with mobile phones, it has become a very powerful tool with a great potential for future development of mobile GPS applications. The Interactive ZooOz Guide was a final year industry project carried out by seven students from three separate courses to tackle a project that involves upgrading the Melbourne Zoo’s mapping system through the use of GPS technology. The aim of the project is to explorethe potential capability of using GPS in the Zoo environment. The proposed system uses a PDA device with a GPS receiver that tracks users’ location in real time as they are touring around the Zoo. In this paper, an insight into GPS technology is briefly reviewed and the design and implementation of “Interactive ZooOZ Guide” is described. Then GUI (Graphical User Interface is presented in detail. Finally conclusion is drawn from the “proof of concept” prototype.

  1. Induced expression of nucleolin phosphorylation-deficient mutant confers dominant-negative effect on cell proliferation.

    Directory of Open Access Journals (Sweden)

    Shu Xiao

    Full Text Available Nucleolin (NCL is a major nucleolar phosphoprotein that has pleiotropic effects on cell proliferation and is elevated in a variety of tumors. NCL is highly phosphorylated at the N-terminus by two major kinases: interphase casein kinase 2 (CK2 and mitotic cyclin-dependent kinase 1 (CDK1. Earlier we demonstrated that a NCL-mutant that is partly defective in undergoing phosphorylation by CK2 inhibits chromosomal replication through its interactions with Replication Protein A, mimicking the cellular response to DNA damage. We further delineated that the N-terminus of NCL associates with Hdm2, the most common E3 ubiquitin ligase of p53. We reported that NCL antagonizes Hdm2 to stabilize p53 and stimulates p53 transcriptional activity. Although NCL-phosphorylation by CK2 and ribosomal DNA transcription are closely coordinated during interphase, the role of NCL phosphorylation in regulating cell proliferation remains unexplored. We have therefore engineered unique human cells that specifically induce expression of NCL-wild type (WT or a phosphorylation-deficient NCL-mutant, 6/S*A where all the six CK2 consensus serine sites residing in the N-terminus NCL were mutated to alanine. Here we show that this NCL-mutant is defective in undergoing phosphorylation by CK2. We also demonstrate that NCL-phosphorylation by CK2 is required through the S-phase progression in cell cycle and hence proliferation. Induced expression of NCL with mutated CK2 phosphorylation sites stabilizes p53, results in higher expression of Bcl2 (B-cell lymphoma 2 homology 3 (BH3-only apoptotic markers and causes a dominant-negative effect on cell viability. Our unique cellular system thus provides the first evidential support to delineate phospho-specific functions of NCL on cell proliferation.

  2. Fuel-coolant interactions

    International Nuclear Information System (INIS)

    An important aspect of nuclear fuel behaviour that impacts on the fuel cycle is the interaction of the cladding with the coolant. In particular, the accumulation of deposited crud (corrosion products transported in the reactor coolant) on fuel element surfaces can severely hamper fuel performance by impeding heat transfer and promoting cladding corrosion, both of which may lead to fuel defects and the release of fission products and actinides to the primary coolant systems. Crud deposition is therefore an important consideration in reactor operation; it not only leads to poor performance and radiation field growth by exacerbating fuel defects but also serves as the source of radionuclides such as Co-60 which are major contaminants of out-reactor components. Furthermore, the sequestering of boron from the coolant by fuel deposits in PWRs can give rise to control problems as reactor flux characteristics are modified. As utilities apply the ALARA principle (As Low As Reasonably) to the management of occupational radiation doses and at the same time endeavour to optimise the fuel cycle, it becomes clear that an understanding of the mechanisms involved in coolant-cladding interactions is vital. There are several mechanisms of interest here. The source of crud is the fundamental corrosion process accruing on surfaces of the coolant system and the interaction of that process with local regimes of coolant flow. Accordingly, differences in the chemical and physical condition of the coolant across the reactor core and the steam generators are important factors in CANDUs and PWRs determining release of corrosion products from surfaces, while similar processes along the feedtrain influence crud levels in the reactor coolant in BWRs. The nature of suspended crud, which is determined by the materials of construction of the various components of the coolant system and the chemistry control of the coolant itself, determines the interaction with fuel cladding. Thus, crud in CANDUs

  3. MINT: the Molecular INTeraction database

    OpenAIRE

    Chatr-aryamontri, Andrew; Ceol, Arnaud; Palazzi, Luisa Montecchi; Nardelli, Giuliano; Schneider, Maria Victoria; Castagnoli, Luisa; Cesareni, Gianni

    2006-01-01

    The Molecular INTeraction database (MINT, ) aims at storing, in a structured format, information about molecular interactions (MIs) by extracting experimental details from work published in peer-reviewed journals. At present the MINT team focuses the curation work on physical interactions between proteins. Genetic or computationally inferred interactions are not included in the database. Over the past four years MINT has undergone extensive revision. The new version of MINT is based on a comp...

  4. The Discipline of Interactive Sonification

    OpenAIRE

    Hermann, Thomas; Hunt, Andy

    2004-01-01

    This paper argues for a special focus on the use of dynamic human interaction to explore datasets while they are being transformed into sound. We describe why this is a special case of both human computer interaction (HCI) techniques and sonification methods. Humans are adapted for interacting with their physical environment and making continuous use of all their senses. When this exploratory interaction is applied to a dataset (by continuously controlling its transformation into sound) new i...

  5. Phosphate Stabilization of Intermolecular Interactions

    OpenAIRE

    Jackson, Shelley N.; Wang, Hay-Yan J.; Yergey, Alfred; Woods, Amina S.

    2006-01-01

    Receptor heteromerization is an important phenomenon that results from the interaction of epitopes on two receptors. Previous studies have suggested the possibility of Dopamine D2- NMDA receptors’ interaction. We believe that the interaction is through an acidic epitope of the NMDA NR1 subunit (KVNSEEEEEDA) and a basic epitope of the D2 third intracellular loop (VLRRRRRKRVN), which was shown to also interact with the Adenosine A2A receptor. In previous work we highlighted the role of certain ...

  6. HUMAN INTERACTION WITH MOBILE APPLICATIONS

    OpenAIRE

    Alin Zamfiroiu; Emanuel Herteliu; Bogdan Vintila

    2012-01-01

    Computing - human interaction is a very important paradigm because informatics applications are created to be used by people via human interaction. Nowadays mobile applications are more used so is necessarily to talk about mobile - human interaction. In this paper types of mobile devices are presented. Citizen oriented character of mobile application and his utility are described. Different means of interactions with mobile devices are analyzed and in the end of the paper direction of mobile ...

  7. Design Principles for Interactive Software

    DEFF Research Database (Denmark)

    The book addresses the crucial intersection of human-computer interaction (HCI) and software engineering by asking both what users require from interactive systems and what developers need to produce well-engineered software. Needs are expressed as......The book addresses the crucial intersection of human-computer interaction (HCI) and software engineering by asking both what users require from interactive systems and what developers need to produce well-engineered software. Needs are expressed as...

  8. Household finances and social interaction

    OpenAIRE

    Brown, S; Taylor, K.

    2012-01-01

    In this paper, we investigate the relationship between social interaction and household finances using data from the British Household Panel Survey. We explore how social interaction influences the probability of holding different types of unsecured debt and assets, as well as how social interaction influences the levels of unsecured debt, financial assets and net worth held. Our findings suggest that social interaction has a positive influence upon the types of financial assets held, which i...

  9. Species interactions and plant polyploidy.

    Science.gov (United States)

    Segraves, Kari A; Anneberg, Thomas J

    2016-07-01

    Polyploidy is a common mode of speciation that can have far-reaching consequences for plant ecology and evolution. Because polyploidy can induce an array of phenotypic changes, there can be cascading effects on interactions with other species. These interactions, in turn, can have reciprocal effects on polyploid plants, potentially impacting their establishment and persistence. Although there is a wealth of information on the genetic and phenotypic effects of polyploidy, the study of species interactions in polyploid plants remains a comparatively young field. Here we reviewed the available evidence for how polyploidy may impact many types of species interactions that range from mutualism to antagonism. Specifically, we focused on three main questions: (1) Does polyploidy directly cause the formation of novel interactions not experienced by diploids, or does it create an opportunity for natural selection to then form novel interactions? (2) Does polyploidy cause consistent, predictable changes in species interactions vs. the evolution of idiosyncratic differences? (3) Does polyploidy lead to greater evolvability in species interactions? From the scarce evidence available, we found that novel interactions are rare but that polyploidy can induce changes in pollinator, herbivore, and pathogen interactions. Although further tests are needed, it is likely that selection following whole-genome duplication is important in all types of species interaction and that there are circumstances in which polyploidy can enhance the evolvability of interactions with other species. PMID:27370313

  10. Galaxy interactions : The HI signature

    NARCIS (Netherlands)

    Sancisi, R; Barnes, JE; Sanders, DB

    1999-01-01

    HI observations are an excellent tool for investigating tidal interactions. Ongoing major and minor interactions which can lead to traumatic mergers or to accretion and the triggering of star formation, show distinct HI signatures. Interactions and mergers in the recent past can also be recognized i

  11. Local Interaction on Random Graphs

    Directory of Open Access Journals (Sweden)

    Hans Haller

    2010-08-01

    Full Text Available We analyze dynamic local interaction in population games where the local interaction structure (modeled as a graph can change over time: A stochastic process generates a random sequence of graphs. This contrasts with models where the initial interaction structure (represented by a deterministic graph or the realization of a random graph cannot change over time.

  12. Quadratic spatial soliton interactions

    Science.gov (United States)

    Jankovic, Ladislav

    Quadratic spatial soliton interactions were investigated in this Dissertation. The first part deals with characterizing the principal features of multi-soliton generation and soliton self-reflection. The second deals with two beam processes leading to soliton interactions and collisions. These subjects were investigated both theoretically and experimentally. The experiments were performed by using potassium niobate (KNBO 3) and periodically poled potassium titanyl phosphate (KTP) crystals. These particular crystals were desirable for these experiments because of their large nonlinear coefficients and, more importantly, because the experiments could be performed under non-critical-phase-matching (NCPM) conditions. The single soliton generation measurements, performed on KNBO3 by launching the fundamental component only, showed a broad angular acceptance bandwidth which was important for the soliton collisions performed later. Furthermore, at high input intensities multi-soliton generation was observed for the first time. The influence on the multi-soliton patterns generated of the input intensity and beam symmetry was investigated. The combined experimental and theoretical efforts indicated that spatial and temporal noise on the input laser beam induced multi-soliton patterns. Another research direction pursued was intensity dependent soliton routing by using of a specially engineered quadratically nonlinear interface within a periodically poled KTP sample. This was the first time demonstration of the self-reflection phenomenon in a system with a quadratic nonlinearity. The feature investigated is believed to have a great potential for soliton routing and manipulation by engineered structures. A detailed investigation was conducted on two soliton interaction and collision processes. Birth of an additional soliton resulting from a two soliton collision was observed and characterized for the special case of a non-planar geometry. A small amount of spiraling, up to 30

  13. Human-Robot Interaction

    Science.gov (United States)

    Sandor, Aniko; Cross, E. Vincent, II; Chang, Mai Lee

    2015-01-01

    Human-robot interaction (HRI) is a discipline investigating the factors affecting the interactions between humans and robots. It is important to evaluate how the design of interfaces affect the human's ability to perform tasks effectively and efficiently when working with a robot. By understanding the effects of interface design on human performance, workload, and situation awareness, interfaces can be developed to appropriately support the human in performing tasks with minimal errors and with appropriate interaction time and effort. Thus, the results of research on human-robot interfaces have direct implications for the design of robotic systems. For efficient and effective remote navigation of a rover, a human operator needs to be aware of the robot's environment. However, during teleoperation, operators may get information about the environment only through a robot's front-mounted camera causing a keyhole effect. The keyhole effect reduces situation awareness which may manifest in navigation issues such as higher number of collisions, missing critical aspects of the environment, or reduced speed. One way to compensate for the keyhole effect and the ambiguities operators experience when they teleoperate a robot is adding multiple cameras and including the robot chassis in the camera view. Augmented reality, such as overlays, can also enhance the way a person sees objects in the environment or in camera views by making them more visible. Scenes can be augmented with integrated telemetry, procedures, or map information. Furthermore, the addition of an exocentric (i.e., third-person) field of view from a camera placed in the robot's environment may provide operators with the additional information needed to gain spatial awareness of the robot. Two research studies investigated possible mitigation approaches to address the keyhole effect: 1) combining the inclusion of the robot chassis in the camera view with augmented reality overlays, and 2) modifying the camera

  14. Cultivating objects in interaction

    DEFF Research Database (Denmark)

    Hazel, Spencer

    2014-01-01

    is chapter explores patterns of repeated orientations to physical objects in interactants’ visuo-spatial and haptic surround. A number of examples are presented from advice-giving activities in various institutional settings, where participants-in-interaction initially draw on material objects at...... hand while pursuing a particular line of explanation, and then return to these objects at later intervals. e analysis suggests that the objects are afforded representational properties through their being anchored to some referent in the talk, and that participants subsequently draw on these...... associations for describing, disambiguating or clarifying aspects of the relatively complex procedural frameworks discussed in the settings. is suggests that the temporal stability of material objects available to participants makes them an ideal resource to be developed as visual motifs....

  15. Interacting neural networks.

    Science.gov (United States)

    Metzler, R; Kinzel, W; Kanter, I

    2000-08-01

    Several scenarios of interacting neural networks which are trained either in an identical or in a competitive way are solved analytically. In the case of identical training each perceptron receives the output of its neighbor. The symmetry of the stationary state as well as the sensitivity to the used training algorithm are investigated. Two competitive perceptrons trained on mutually exclusive learning aims and a perceptron which is trained on the opposite of its own output are examined analytically. An ensemble of competitive perceptrons is used as decision-making algorithms in a model of a closed market (El Farol Bar problem or the Minority Game. In this game, a set of agents who have to make a binary decision is considered.); each network is trained on the history of minority decisions. This ensemble of perceptrons relaxes to a stationary state whose performance can be better than random. PMID:11088736

  16. Antigen antibody interactions

    CERN Document Server

    DeLisi, Charles

    1976-01-01

    1. 1 Organization of the Immune System One of the most important survival mechanisms of vertebrates is their ability to recognize and respond to the onslaught of pathogenic microbes to which they are conti- ously exposed. The collection of host cells and molecules involved in this recognition­ 12 response function constitutes its immune system. In man, it comprises about 10 cells 20 (lymphocytes) and 10 molecules (immunoglobulins). Its ontogenic development is c- strained by the requirement that it be capable of responding to an almost limitless variety of molecular configurations on foreign substances, while simultaneously remaining inert to those on self components. It has thus evolved to discriminate, with exquisite precision, between molecular patterns. The foreign substances which induce a response, called antigens, are typically large molecules such as proteins and polysaccharides. The portions of these with which immunoglobulins interact are called epitopes or determinants. A typical protein epitope m...

  17. Interactive molecular dynamics

    CERN Document Server

    Schroeder, Daniel V

    2015-01-01

    Physics students now have access to interactive molecular dynamics simulations that can model and animate the motions of hundreds of particles, such as noble gas atoms, that attract each other weakly at short distances but repel strongly when pressed together. Using these simulations, students can develop an understanding of forces and motions at the molecular scale, nonideal fluids, phases of matter, thermal equilibrium, nonequilibrium states, the Boltzmann distribution, the arrow of time, and much more. This article summarizes the basic features and capabilities of such a simulation, presents a variety of student exercises using it at the introductory and intermediate levels, and describes some enhancements that can further extend its uses. A working simulation code, in HTML5 and JavaScript for running within any modern Web browser, is provided as an online supplement.

  18. Interactive molecular dynamics

    Science.gov (United States)

    Schroeder, Daniel V.

    2015-03-01

    Physics students now have access to interactive molecular dynamics simulations that can model and animate the motions of hundreds of particles, such as noble gas atoms, that attract each other weakly at short distances but repel strongly when pressed together. Using these simulations, students can develop an understanding of forces and motions at the molecular scale, nonideal fluids, phases of matter, thermal equilibrium, nonequilibrium states, the Boltzmann distribution, the arrow of time, and much more. This article summarizes the basic features and capabilities of such a simulation, presents a variety of student exercises using it at the introductory and intermediate levels, and describes some enhancements that can further extend its uses. A working simulation code, in html5 and javascript for running within any modern Web browser, is provided as an online supplement.

  19. Human Work Interaction Design

    DEFF Research Database (Denmark)

    Gonçalves, Frederica; Campos, Pedro; Clemmensen, Torkil

    2015-01-01

    In this paper, we review research in the emerging practice and research field of Human Work Interaction Design (HWID). We present a HWID frame-work, and a sample of 54 papers from workshops, conferences and journals from the period 2009-2014. We group the papers into six topical groups, and then at......-tempt to map these groups to the framework to find research gaps for future re-search. We find that the groups of papers cover all areas of the framework well for a variety of work and leisure domains. The area in strongest need for more research papers is the development of the holistic framework itself....... Furthermore, much focus has been on studying design sketching or implemented systems-in-use, while little attention has been paid to mature design (prototypes) or early implementation (content templates). In conclusion, we recommend an update to the framework so that it can be also useful for research in...

  20. Interactive TV Narrativity

    Science.gov (United States)

    Ursu, Marian F.

    Looking back over the past 25 years, the impressive developments in information and communication technologies generated a booming popularity of the new forms of media consumption that allow for interactivity and mobility, such as Web information and entertainment and games. This was and still is particularly evident within the younger generation, who are the most avid adopters of both new technologies and new forms of media consumption (Schadler 2006; KPMG 2007). When asked, in 2006, which device they could not live without, 37% mentioned their PC, 26% their mobile phone, whereas only 17% mentioned their TVs (Schadler 2006); and all these were before the launch of products such as the iPhone, which offer increasing flexibility and mobility of the media experiences.

  1. Study of electroweak interactions

    International Nuclear Information System (INIS)

    The experimental study of electroweak interactions at Virginia Tech is multifaceted and consists of three parts. The first consists of analysis of the final states of matter produced in electron-positron annihilations at center-of-mass energies √s = 60 GeV at the TRISTAN collider in Japan (AMY). The second is a sensitive search for rare electroweak processes through a study of μ+ → e+γ at the LAMPF facility at Los Alamos (MEGA). It also includes a precise measurement of the Michel ρ parameter (RHO). The third activity is a R ampersand D detector development and is a precursor to anticipated experiments at proposed Bo meson factories in this country and/or abroad. The physics goals are the study of CP violation in the Bo system and the determination of the values for Kobayashi-Maskawa matrix

  2. Sustainable Buildings in Interaction

    DEFF Research Database (Denmark)

    Elle, Morten

    The first attempts to build sustainable buildings in Denmark were typically located on the countryside. The basic idea was to create buildings that were independent of the technical infrastructure. District heating has, however, been the dominating solution to heating in buildings in Denmark, and...... the focus on sustainable building have gradually turned from special houses on the countryside to normally looking houses in the urban fabric, integrated in the technical infrastructure. Some new built urban areas in Denmark will, however, not have to be supplied with district heating – these...... developments are going to consist of passive houses. The first sustainable buildings were built by their users, and the user – building interaction still play a decisive role for the performance of the present sustainable buildings. The users have to understand how the building functions. Urban design is...

  3. Universality in string interactions

    CERN Document Server

    Huang, Yu-tin; Wen, Congkao

    2016-01-01

    In this letter, we provide evidence for universality in the low-energy expansion of tree-level string interactions. More precisely, in the alpha'-expansion of tree-level scattering amplitudes, we conjecture that the leading transcendental coefficient at each order in alpha' is universal for all perturbative string theories. We have checked this universality up to seven points and trace its origin to the ability to restructure the disk integrals of open bosonic string into those of the superstring. The accompanying kinematic functions have the same low-energy limit and do not introduce any transcendental numbers in their alpha'-corrections. Universality in the closed-string sector then follows from the KLT-relations.

  4. Electroweak interactions at LEP

    International Nuclear Information System (INIS)

    Electroweak interaction at LEP are a subject based on a wealth of data, given the success of the CERN e+e- storage ring. The author will report on the results from the four experiments, ALEPH, DELPHI, L3 and OPAL after the analysis of about 1/2 of the data collected in 1989 and 1990. The review will cover the electroweak aspects of the process e+e- → Z* → f bar f where the fermions can be either quarks or leptons. The analysis of experimental data is based on the determination of the cross section integrated on the solid angle and on the asymmetry of forward-backward leptons in the final state. In this game the knowledge of the center mass energy is fundamental as the determination of the luminosity by which the event rate is normalized to compute the absolute cross section. Therefore a specific attention is given to these subjects

  5. The Interaction Programming Problem

    Institute of Scientific and Technical Information of China (English)

    LI Rong-sheng; CHENG Ying

    2001-01-01

    Based upon the research to the economic equilibrium problems, we present a kind of new mathematical programming problem-interaction programming problem (abbreviated by IPP). The IPP is composed of two or multiple parametric programming problems which is interrelated with each other. The IPP reflects the equality and mutual benefit relationship between two (or among multiple) economic planners in an economic system. In essence, the IPP is similar to the generalized Nash equilibria (GNE) game which has been given several names in the literature: social equilibria games, pseudo-Nash equilibria games, and equilibrium programming problems. In this paper, we establish the mathematical model and some basic concepts to the IPP. We investigate the structure and the properties of the IPP. We also give a necessary and sufficient conditions for the existence of the equilibrium points to a kind of linear IPP.

  6. Dark patterns in proxemic interactions

    DEFF Research Database (Denmark)

    Greenberg, Saul; Boring, Sebastian; Vermeulen, Jo; Dostal, Jakub

    2014-01-01

    easily exploited to the detriment of the user. In this paper, we offer a critical perspective on proxemic interactions in the form of dark patterns: ways proxemic interactions can be misused. We discuss a series of these patterns and describe how they apply to these types of interactions. In addition, we......Proxemics theory explains peoples' use of interpersonal distances to mediate their social interactions with others. Within Ubicomp, proxemic interaction researchers argue that people have a similar social understanding of their spatial relations with nearby digital devices, which can be exploited...

  7. Hadron nucleus interactions

    International Nuclear Information System (INIS)

    The elastic and inelastic scattering of intermediate energy (less than or equal to 1 GeV) protons by nuclei is considered first. The discussion focuses on the determination of the proton-nucleus optical potential in terms of the elementary nucleon-nucleon scattering amplitudes and the properties of the target and residual nucleus. The result is a series of terms for the optical potential. Then the interaction of pions with nuclei for energies in the neighborhood of the Δ-resonance is discussed. In this energy domain an incident pion will with high probability be absorbed by a nucleon to produce the Δ-resonance and thus form a Δ-particle hole state in the nucleus. Next, the subject of hypernuclei is taken up. The Λ hypernuclei and a recently observed Σ hypernuclei comprise situations in which the core nucleus can be probed by a baryon of roughly the same mass as a nucleon, with similar albeit not identical interactions with nucleons. But the Λ (or Σ) does not need to satisfy the Pauli exclusion principle with respect to the nucleons, and therefore can be in orbits forbidden to it if it were a nucleon. As the energy of the projectile increases, it becomes correspondingly more important to take relativistic effects into account. The importance of these effects is strikingly revealed by experiments involving the collision of ultrarelativistic hadrons, protons, pions, kaons (up to Fermilab energies) with nuclei. This phenomenon forms part of the final topic, which includes as well as the collision of relativistic heavy ion projectiles with nuclei. A nuclear Weiszaecker-Williams method developed for dealing with peripheral collisions is described. 32 figures, 10 tables

  8. HYDRODYNAMIC INTERACTIONS BETWEEN TWO BODIES

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    On the basis of model tests, potential flow theory, and viscous Computational Fluid Dynamics (CFD) method, the hydrodynamic interactions between two underwater bodies were investigated to determine the influencing factors, changing rule, interaction mechanism, and appropriate methods describing them. Some special phenomena were discovered in two series of near-wall interaction experiments. The mathematical model and predicting methods were presented for interacting forces near wall, and the calculation results agreed well with the experimental ones. From the comparisons among numerical results with respect to nonviscosity, numerical results with respect to viscosity, and measured results, data on the influence of viscosity on hydrodynamic interactions were obtained. For hydrodynamic interaction related to multi-body unsteady motions with six degrees of freedom that is difficult to simulate in tests, numerical predictions of unsteady interacting forces were given.

  9. Antiproton-nucleus interaction

    Science.gov (United States)

    Cugnon, J.; Vandermeulen, J.

    The antiproton-nucleus physics is reviewed. On the experimental side, the recent results obtained at the LEAR, BNL and KEK facilities are analyzed. A brief summary of the main pp and pn experimental data is also given. The antiproton-nucleus interaction can lead to elasic, inelastic and charge exchange scattering and to annihilation. The latter is very dominant. The scattering cross-sections are usually analyzed in terms of complex potential models. The relationship between potentials, charge conjugation and Dirac phenomenology is discussed. Much emphasis is put on the dynamics of the antiproton annihilation on nuclei. The energy transfer, pion absorption and target response are analyzed within the intranuclear cascade model. Special interest is devoted to strangeness production, hypernucleus formation and possible annihilation on two nucleons. Signatures for this new process are searched in experimental data. Finally, the highly debated question of quark-gluon formation is analyzed. Cet article constitue une revue de la physique antiproton-noyau. Du point de vue expérimental, cette revue porte particulièrement sur les récents résultats obtenus à LEAR, BNL et KEK. On y a aussi inclus une mise à jour des faits expérimentaux principaux pour pp et pn. L'interaction antiproton-noyau conduit à la diffusion élastique, inélastique et d'xA9change de charge et à des processus d'annihilation. Habituellement, les expériences de diffusion sont analysées en termes de potentiels complexes. La relation entre ces potentiels, la conjugaison de charge et la phénoménologie de Dirac est discutée. On s'est particulièrement intéressé à la dynamique de l'annihilation d'antiprotons sur des noyaux. Le transfert d'énergie, l'absorption de pions et la réponse de la cible sont analysés dans le cadre du modèle de cascade intranucléaire. Certains autres points sont discutés plus en détail: la production d'étrangeté, la formation d'hypernoyaux et l'annihilation sur

  10. Interactive Data Eyeslasses

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The data eyeglasses can read from the engineer’s eyes which details he needs to see on the building plans.A CMOS chip with an eyetracker in the microdisplay makes this possible.The eyeglasses are connected to a PDA,display information and respond to commands.For car designers,secret agents in the movies and jet fighter pilots,data eyeglasses-also called head-mounted displays,orHMDs for short-are everyday objects.They transport the wearer into virtual worlds or provide the user with data from the real environment.At present these devices can only display information."We want to make the eyeglasses bidirectional and interactive so thatnew areas of application can be opened up,"says Dr.Michael Scholles,business unit manager at the Fraunhofer Institute for PhotonicMicrosystems IPMS in Dresden.A group of scientists at IPMS is working on a device which incorporates eye tracking-users can influence the content presented by moving their eyes or fixing on certain points in the image.Without having to use any other devices to

  11. Wolbachia filarial interactions.

    Science.gov (United States)

    Taylor, Mark J; Voronin, Denis; Johnston, Kelly L; Ford, Louise

    2013-04-01

    Wolbachia pipientis is a widespread intracellular bacterial symbiont of arthropods and is common in insects. One of their more exotic and unexpected hosts is the filarial nematodes, notable for the parasites responsible for onchocerciasis (river blindness), lymphatic filariasis (elephantiasis) and dirofilariasis (heartworm). Wolbachia are only present in a subgroup of the filarial nematodes and do not extend to other groups of nematodes either parasitic or free-living. In the medically and veterinary important species that host Wolbachia, the symbiont has become an essential partner to key biological processes in the life of the nematode to the point where antibiotic elimination of the bacteria leads to a potent and effective anti-filarial drug treatment. We review the cellular and molecular basis of Wolbachia filarial interactions and highlight the key processes provided by the endosymbiont upon which the nematodes have become entirely dependent. This dependency is primarily restricted to periods of the lifecycle with heavy metabolic demands including growth and development of larval stages and embryogenesis in the adult female. Also, the longevity of filarial parasites is compromised following depletion of the symbiont, which for the first time has delivered a safe and effective treatment to kill adult parasites with antibiotics. PMID:23210448

  12. Dike/Drift Interactions

    International Nuclear Information System (INIS)

    This report documents the model of events associated with a potential intrusion of magma from a volcanic dike into a drift or drifts in the Yucca Mountain Nuclear Waste Repository. The following topics are included in this report: (1) A discussion of dike propagation, which provides the basis for describing the path that a representative dike, or swarm of dikes, would follow during an event. (2) A discussion of magma flow, which evaluates the interaction at the junction of the propagating dike with the drift and the movement of magmatic products into and down drifts and, potentially, through a drift to the surface by way of access drift or a secondary dike opened up along the drift. (3) A discussion of gas flow and conductive cooling of a magma-filled drift, describing how an adjacent drift that has not been intersected by a dike could be affected by post-intrusion phenomena. Note that a gas flow analysis is also addressed in ''Igneous Intrusion Impacts on Waste Form and Waste Packages'' (BSC 2003 [DIRS 161810]), and those results are consistent with the results presented in this report

  13. Copper/bentonite interaction

    International Nuclear Information System (INIS)

    The prediction of the processes and rate of corrosion of the KBS 2 copper canisters must be based on a proper scenario, which involves the physical state of the bentonite surrounding the canisters, and the chemical interaction between copper and bentonite. Literature data suggest slow Cu migration and Cu exchanging originally adsorbed cations. Two tests involving copper/bentonite contacts for 3 - 6 months in boreholes have yielded certain valuable information. Thus, Cu ion migration is indeed very slow and where it yields a sufficiently high concentration, it is associated with replacement of originally adsorbed Na ions, which should result in an increased permeability. In one of the tests the copper was separated from the bentonite by a partly air-filled slot. These conditions caused the formation of copper oxides and hydroxides which intermingled with the bentonite that expanded to fill the slot. Due to the low solubility of these copper compounds, the Cu ion concentration was too low to produce ion exchange during the time of observation. (Author)

  14. Influenza-Sediment Interactions

    Science.gov (United States)

    Trusiak, A.; Block, K. A.; Katz, A.; Gottlieb, P.; Alimova, A.; Galarza, J.; Wei, H.; Steiner, J. C.

    2013-12-01

    A typical water fowl can secrete 1012 influenza virions per day. Therefore it is not unexpected that influenza virions interact with sediments in the water column. The influence of sediments on avian influenza virions is not known. With the threat of avian influenza emerging into the human population, it is crucial to understand virus survivability and residence time in a body of water. Influenza and clay sediments are colloidal particles and thus aggregate as explained by DLVO (Derjaguin & Landau, Verwey & Overbeek) theory. Of great importance is an understanding of the types of particulate or macromolecular components that bind the virus particles, and whether the virus remains biologically active. We present results of hetero-aggregation and transmission electron microscopy experiments performed with influenza A/PR8/38. Influenza particles are suspended with sediment and minimal nutrients for several days, after which the components are evaluated to determine influenza concentration and survivability. Transmission electron microscopy results are reported on the influenza-sediment aggregates to elucidate structure and morphology of the components.

  15. Interacting boson approximation

    International Nuclear Information System (INIS)

    Lectures notes on the Interacting Boson Approximation are given. Topics include: angular momentum tensors; properties of T/sub i//sup (n)/ matrices; T/sub i//sup (n)/ matrices as Clebsch-Gordan coefficients; construction of higher rank tensors; normalization: trace of products of two s-rank tensors; completeness relation; algebra of U(N); eigenvalue of the quadratic Casimir operator for U(3); general result for U(N); angular momentum content of U(3) representation; p-Boson model; Hamiltonian; quadrupole transitions; S,P Boson model; expectation value of dipole operator; S-D model: U(6); quadratic Casimir operator; an O(5) subgroup; an O(6) subgroup; properties of O(5) representations; quadratic Casimir operator; quadratic Casimir operator for U(6); decomposition via SU(5) chain; a special O(3) decomposition of SU(3); useful identities; a useful property of D/sub αβγ/(α,β,γ = 4-8) as coupling coefficients; explicit construction of T/sub x//sup (2)/ and d/sub αβγ/; D-coefficients; eigenstates of T3; and summary of T = 2 states

  16. Strongly interacting ultracold polar molecules

    Science.gov (United States)

    Gadway, Bryce; Yan, Bo

    2016-08-01

    This paper reviews recent advances in the study of strongly interacting systems of dipolar molecules. Heteronuclear molecules feature large and tunable electric dipole moments, which give rise to long-range and anisotropic dipole–dipole interactions. Ultracold samples of dipolar molecules with long-range interactions offer a unique platform for quantum simulations and the study of correlated many-body physics. We provide an introduction to the physics of dipolar quantum gases, both electric and magnetic, and summarize the multipronged efforts to bring dipolar molecules into the quantum regime. We discuss in detail the recent experimental progress in realizing and studying strongly interacting systems of polar molecules trapped in optical lattices, with particular emphasis on the study of interacting spin systems and non-equilibrium quantum magnetism. Finally, we conclude with a brief discussion of the future prospects for studies of strongly interacting dipolar molecules.

  17. Strongly interacting ultracold polar molecules

    CERN Document Server

    Gadway, Bryce

    2016-01-01

    This paper reviews recent advances in the study of strongly interacting systems of dipolar molecules. Heteronuclear molecules feature large and tunable electric dipole moments, which give rise to long-range and anisotropic dipole-dipole interactions. Ultracold samples of dipolar molecules with long-range interactions offer a unique platform for quantum simulations and the study of correlated many-body physics. We provide an introduction to the physics of dipolar quantum gases, both electric and magnetic, and summarize the multipronged efforts to bring dipolar molecules into the quantum regime. We discuss in detail the recent experimental progress in realizing and studying strongly interacting systems of polar molecules trapped in optical lattices, with particular emphasis on the study of interacting spin systems and non-equilibrium quantum magnetism. Finally, we conclude with a brief discussion of the future prospects for studies of strongly interacting dipolar molecules.

  18. Animal-computer interaction SIG

    OpenAIRE

    Mancini, Clara; Lawson, Shaun; Van Der Linden, Janet; Häkkilä, Jonna; Noz, Frank; Juhlin, Oskar

    2012-01-01

    User-computer interaction research is demonstrating growing interest in the relation between animals and technology (e.g., computer-mediated interspecies interactions and animal-computer interfaces). However, as a research area, this topic is still underexplored and fragmented, and researchers lack opportunities to exchange ideas, identify resources, form collaborations and co-operatively develop a coherent research agenda. The Animal-Computer Interaction (ACI) SIG meeting aims to provide ...

  19. Interacting atoms in optical lattices

    OpenAIRE

    Mentink, Johan; Kokkelmans, Servaas

    2008-01-01

    We propose an easy to use model to solve for interacting atoms in an optical lattice. This model allows for the whole range of weakly to strongly interacting atoms, and it includes the coupling between relative and center-of-mass motion via anharmonic lattice terms. We apply this model to a high-precision spin dynamics experiment, and we discuss the corrections due to atomic interactions and the anharmonic coupling. Under suitable experimental conditions, energy can be transferred between the...

  20. Interaction themes in music therapy

    DEFF Research Database (Denmark)

    Holck, Ulla

    2004-01-01

    Based on a doctoral study, the author presents a type of music therapyinteraction called ?Interaction Themes.? These are developed fromsession to session and often appear in music therapy interventions withchildren with severe functional limitations, especially children withautism. Although...... whoseexpressions are often difficult to understand. The article describes thecharacteristics and functions of Interaction Themes, compares thephenomenon with music therapy case literature and delimits it in regardto other types of music therapy interaction with this client group. Theresults are described through...

  1. Pseudospin Conserving Shell Model Interactions

    OpenAIRE

    Ginocchio, Joseph N.

    2010-01-01

    Pseudospin symmetry is approximately conserved in nuclei. Normally shell model interactions are written in terms of spin an orbital angular momentum operators, not in terms of pseudospin and pseudo-orbital angular momentum operators. We determine the shell model interactions which conserve pseudospin symmetry and pseudo-orbital angular momentum symmetry and write them in terms of spin and orbital angular momentum operators including the tensor interaction. We show that, although the tensor in...

  2. Source Code Interaction on Touchscreens

    OpenAIRE

    Raab, Felix

    2016-01-01

    Direct interaction with touchscreens has become a primary way of using a device. This work seeks to devise interaction methods for editing textual source code on touch-enabled devices. With the advent of the “Post-PC Era”, touch-centric interaction has received considerable attention in both research and development. However, various limitations have impeded widespread adoption of programming environments on modern platforms. Previous attempts have mainly been successful by simplifying or con...

  3. Interaction between voriconazole and glimepiride

    OpenAIRE

    Shobha J; Muppidi M

    2010-01-01

    Voriconazole, a triazole antifungal, is gaining popularity in the treatment of invasive fungal infections, mostly in the immuno-compromised patients. Voriconazole, a CYP2C9 inhibitor, has many potential drug interactions. Its interactions are both due to its pharmacokinetic properties and the genetic polymorphism of CYP2C9 enzymes. Here is a case report of one such drug-drug interaction between voriconazole and glimepiride, an oral hypoglycemic agent, which led to prolonged and persistent hyp...

  4. Efficient Interaction in English Classroom

    Institute of Scientific and Technical Information of China (English)

    董红叶

    2013-01-01

    Lack of communicative competence will result in failure to efficiently interact with others and also weaken linguistic competence. This paper shows the importance of interaction through analyzing Klashen’s input hypothesis,emotional factors,lat⁃er Wittgenstein’s linguistic philosophy,selectivity and dynamics of languages. Different interaction activities are used in different teaching methods. A teacher needs to face all the challenges so as to find the most efficient way to teach in a language classroom.

  5. Weak interactions of elementary particles

    CERN Document Server

    Okun, Lev Borisovich

    1965-01-01

    International Series of Monographs in Natural Philosophy, Volume 5: Weak Interaction of Elementary Particles focuses on the composition, properties, and reactions of elementary particles and high energies. The book first discusses elementary particles. Concerns include isotopic invariance in the Sakata model; conservation of fundamental particles; scheme of isomultiplets in the Sakata model; universal, unitary-symmetric strong interaction; and universal weak interaction. The text also focuses on spinors, amplitudes, and currents. Wave function, calculation of traces, five bilinear covariants,

  6. Chemical interaction between undamaged plants

    OpenAIRE

    Glinwood, Robert; Ninkovic, Velemir; Pettersson, Jan

    2011-01-01

    Most research on plant–plant chemical interactions has focussed on events following herbivore or pathogen attack. However, undamaged plants also interact chemically as a natural facet of their behaviour, and this may have consequences for insects that use the plants as hosts. In this review, the links between allelopathy and insect behaviour are outlined. Findings on how chemical interactions between different plant species and genotypes affect aphid herbivores and their natural e...

  7. Nuclear interactions of heavy ions

    International Nuclear Information System (INIS)

    A possible source of preheat for heavy ion driven inertial fusion targets is the production of fast precursors by nuclear interactions between the incident heavy ions and the outer parts of the target. A model has been developed which roughly describes these interactions for all beam-target combinations for all incident energies. This interaction model has been applied to a specific capsule design. The resultant preheat is an order of magnitude below the level which could impair target performance

  8. Thermal imaging for interactive surfaces

    OpenAIRE

    Abdelrahman, Yomna

    2013-01-01

    Thermal camera operating in Far Infrared (FIR) is considered to be un- derexplored in elds other than security and law enforcement. Nevertheless, recently it drawn the attention of Human Computer Interaction (HCI) re- searchers as a new sensory system enabling novel interactive systems. They are robust to illumination changes and using it with well-known computer vi- sion techniques, the complexity of the interaction detection is highly reduced as compared to RGB and depth cameras. FIR radiat...

  9. Intergenerational Analysis of Social Interaction

    OpenAIRE

    Brown, Sarah; McHardy, Jolian; Taylor, Karl

    2011-01-01

    We explore the relationship between the social interaction of parents and their offspring from a theoretical and an empirical perspective. Our theoretical framework establishes possible explanations for the intergenerational transfer of social interaction whereby the social interaction of the parent may influence that of their offspring and vice versa. The empirical evidence, based on four data sets covering Great Britain and the U.S., is supportive of our theoretical priors. We find robust e...

  10. Social Interaction and Urban Sprawl

    OpenAIRE

    Brueckner, Jan Keith; Ann G. Largey

    2006-01-01

    Various authors, most notably Putnam (2000), have argued that low-density living reduces social capital and thus social interaction, and this argument has been used to buttress criticisms of urban sprawl. If low densities in fact reduce social interaction, then an externality arises, validating Putnam’s critique. In choosing their own lot sizes, consumers would fail to consider the loss of interaction benefits for their neighbors when lot size is increased. Lot sizes would then be inefficient...

  11. Structural interaction with control systems

    Science.gov (United States)

    Noll, R. B.; Zvara, J.

    1971-01-01

    A monograph which assesses the state of the art of space vehicle design and development is presented. The monograph presents criteria and recommended practices for determining the structural data and a mathematical structural model of the vehicle needed for accurate prediction of structure and control-system interaction; for design to minimize undesirable interactions between the structure and the control system; and for determining techniques to achieve the maximum desirable interactions and associated structural design benefits. All space vehicles are treated, including launch vehicles, spacecraft, and entry vehicles. Important structural characteristics which affect the structural model used for structural and control-system interaction analysis are given.

  12. Interaction Themes in Music Therapy

    DEFF Research Database (Denmark)

    Holck, Ulla

    2006-01-01

    Based on a doctoral study, the author presents a type of music therapy interaction called ‘Interaction Themes.’ These are developed from session to session and often appear in music therapy interventions with children with severe functional limitations, especially children with autism. Although...... whose expressions are often difficult to understand. The presented article describes the characteristics and functions of Interaction Themes, compares the phenomenon with music therapy case literature and delimits it in regard to other types of music therapy interaction with this client group....

  13. Interaction Themes in Music Therapy

    DEFF Research Database (Denmark)

    Holck, Ulla

    2006-01-01

    Based on a doctoral study, the author presents a type of music therapy interaction called ‘Interaction Themes.’ These are developed from session to session and often appear in music therapy interventions with children with severe functional limitations, especially children with autism. Although...... whose expressions are often difficult to understand. This presentation describes the characteristics and functions of Interaction Themes, compares the phenomenon with music therapy case literature and delimits it in regard to other types of music therapy interaction with this client group....

  14. RKKY interaction in bilayer graphene

    Science.gov (United States)

    Mohammadi, Yawar; Moradian, Rostam

    2015-12-01

    We study the RKKY interaction between two magnetic impurities located on the same layer (intralayer case) or on different layers (interlayer case) in undoped bilayer graphene (BLG) in the four-bands model, by directly calculating the Green functions in the eigenvalues and eigenvectors representation. Our results show that both intra- and interlayer RKKY interactions between two magnetic impurities located on the same (opposite) sublattice are always ferromagnetic (antiferromagnetic). Furthermore we find unusual long-distance decay of the RKKY interaction in BLG. The intralyer RKKY interactions between two magnetic impurities located on the same sublattice, J AnAn(R) and J BnBn(R), decay closely as 1 /R6 and 1 /R2 at large impurity distances respectively, but when they are located on opposite sublattices the RKKY interactions exhibit 1 /R4 decays approximately. In the interlayer case, the RKKY interactions between two magnetic impurities located on the same sublattice show a decay close to 1 /R4 at large impurity distances, but if two magnetic impurities be on opposite sublattices the RKKY interactions, J A1B2(R) and J B1A2(R), decay closely as 1 /R6 and 1 /R2 respectively. Both intra- and interlayer RKKY interactions have anisotropic oscillatory factors which for intralayer case is equal to that for single layer graphene (SLG). Our results at weak and strong interlayer coupling limits reduce to the RKKY interaction of SLG and that of BLG in the two-bands approximation respectively.

  15. The Ontogenesis of Telephone Interaction.

    Science.gov (United States)

    Mininni, Giuseppe

    1985-01-01

    A longitudinal study of the acquisition of telephone skills among five preschool children analyzed play telephone interactions and real telephone conversations for similarities and changes in performance. (MSE)

  16. Water-Mediated Hydrophobic Interactions.

    Science.gov (United States)

    Ben-Amotz, Dor

    2016-05-27

    Hydrophobic interactions are driven by the combined influence of the direct attraction between oily solutes and an additional water-mediated interaction whose magnitude (and sign) depends sensitively on both solute size and attraction. The resulting delicate balance can lead to a slightly repulsive water-mediated interaction that drives oily molecules apart rather than pushing them together and thus opposes their direct (van der Waals) attraction for each other. As a consequence, competing solute size-dependent crossovers weaken hydrophobic interactions sufficiently that they are only expected to significantly exceed random thermal energy fluctuations for processes that bury more than ∼1 nm(2) of water-exposed area. PMID:27215821

  17. Novicidin interactions with phospholipid membranes

    DEFF Research Database (Denmark)

    Balakrishnan, Vijay Shankar

    Antimicrobial peptides target bacterial cell membranes and are considered as potential antibiotics. Their interactions with cell membranes are studied using different approaches. This thesis comprises of the biophysical investigations on the antimicrobial peptide Novicidin, interacting with...... liposomes. The lipid-induced changes in the peptide due to membrane binding, and the peptide-induced changes in the membrane properties were investigated using various spectroscopic and calorimetric methods, and the structural and thermodynamic aspects of peptide-lipid interactions are discussed. This helps...... in understanding not only the antimicrobial nature of Novicidin, but also sheds light on the membrane-peptide interactions....

  18. Theoretical studies of molecular interactions

    Energy Technology Data Exchange (ETDEWEB)

    Lester, W.A. Jr. [Univ. of California, Berkeley (United States)

    1993-12-01

    This research program is directed at extending fundamental knowledge of atoms and molecules including their electronic structure, mutual interaction, collision dynamics, and interaction with radiation. The approach combines the use of ab initio methods--Hartree-Fock (HF) multiconfiguration HF, configuration interaction, and the recently developed quantum Monte Carlo (MC)--to describe electronic structure, intermolecular interactions, and other properties, with various methods of characterizing inelastic and reaction collision processes, and photodissociation dynamics. Present activity is focused on the development and application of the QMC method, surface catalyzed reactions, and reorientation cross sections.

  19. Functions of Interactive Visual Representations in Interactive Mathematical Textbooks

    Science.gov (United States)

    Yerushalmy, Michal

    2005-01-01

    The paper explores changes in technology that have implications for the teaching and learning of school mathematics. To this end, it examines aspects of interactive mathematical textbooks; specifically it analyzes functions authors may intend to be carried out by embedded interactive diagrams. The paper analyzes theoretical as well as practical…

  20. Seepage/Cement Interactions

    International Nuclear Information System (INIS)

    The Development Plan (CRWMS M andO 1999a) pertaining to this task defines the work scopes and objectives for development of various submodels for the Physical and Chemical Environment Abstraction Model for TSPA-LA. The Development Plan (CRWMS M andO 1999a) for this specific task establishes that an evaluation be performed of the chemical reactions between seepage that has entered the drift and concrete which might be used in the repository emplacement drifts. The Development Plan (CRWMS M andO 1999a) then states that the potential effects of these water/grout reactions on chemical conditions in the drift be assessed factoring in the influence of carbonation and the relatively small amount of grout. This task is also directed at: (1) developing a conceptualization of important cement/seepage interactions and potential impacts on EBS performance, (2) performing a screening analysis to assess the importance of cement/seepage interactions. As the work progresses and evolves on other studies, specifically the Engineered Barrier System: Physical and Chemical Environment (P andCE) Model (in progress), many of the issues associated with items 1 and 2, above, will be assessed. Such issues include: (1) Describing the mineralogy of the specified cementitious grout and its evolution over time. (2) Describing the composition of the water before contacting the grout. (3) Developing reasonable upper-bound estimates for the composition of water contacting grout, emphasizing pH and concentrations for anions such as sulfate. (4) Evaluating the equilibration of cement-influenced water with backfill and gas-phase CO2. (5) Developing reasonable-bound estimates for flow rate of affected water into the drift. The concept of estimating an ''upper-bound'' range for reaction between the grout and the seepage, particularly in terms of pH is based on equilibrium being established between the seepage and the grout. For example, this analysis can be based on equilibrium being established as

  1. INCA- INTERACTIVE CONTROLS ANALYSIS

    Science.gov (United States)

    Bauer, F. H.

    1994-01-01

    The Interactive Controls Analysis (INCA) program was developed to provide a user friendly environment for the design and analysis of linear control systems, primarily feedback control systems. INCA is designed for use with both small and large order systems. Using the interactive graphics capability, the INCA user can quickly plot a root locus, frequency response, or time response of either a continuous time system or a sampled data system. The system configuration and parameters can be easily changed, allowing the INCA user to design compensation networks and perform sensitivity analysis in a very convenient manner. A journal file capability is included. This stores an entire sequence of commands, generated during an INCA session into a file which can be accessed later. Also included in INCA are a context-sensitive help library, a screen editor, and plot windows. INCA is robust to VAX-specific overflow problems. The transfer function is the basic unit of INCA. Transfer functions are automatically saved and are available to the INCA user at any time. A powerful, user friendly transfer function manipulation and editing capability is built into the INCA program. The user can do all transfer function manipulations and plotting without leaving INCA, although provisions are made to input transfer functions from data files. By using a small set of commands, the user may compute and edit transfer functions, and then examine these functions by using the ROOT_LOCUS, FREQUENCY_RESPONSE, and TIME_RESPONSE capabilities. Basic input data, including gains, are handled as single-input single-output transfer functions. These functions can be developed using the function editor or by using FORTRAN- like arithmetic expressions. In addition to the arithmetic functions, special functions are available to 1) compute step, ramp, and sinusoid functions, 2) compute closed loop transfer functions, 3) convert from S plane to Z plane with optional advanced Z transform, and 4) convert from Z

  2. Interact - Access to the Arctic

    Science.gov (United States)

    Johansson, M.; Callaghan, T. V.

    2013-12-01

    INTERACT is currently a network of 50 terrestrial research stations from all Arctic countries, but is still growing. The network was inaugurated in January 2011 when it received an EU 7th Framework award. INTERACT's main objective is to build capacity for identifying, understanding, predicting and responding to diverse environmental changes throughout the wide environmental and land-use envelopes of the Arctic. Implicit in this objective is the task to build capacity for monitoring, research, education and outreach. INTERACT is increasing access to the Arctic: 20 INTERACT research stations in Europe and Russia are offering Transnational Access and so far, 5600 person-days of access have been granted from the total of 10,000 offered. An INTERACT Station Managers' Forum facilitates a dialogue among station managers on subjects such as best practice in station management and standardised monitoring. The Station Managers' Forum has produced a unique 'one-stop-shop' for information from 45 research stations in an informative and attractive Station Catalogue that is available in hard copy and on the INTERACT web site (www.eu-interact.org). INTERACT also includes three joint research activities that are improving monitoring in remote, harsh environments and are making data capture and dissemination more efficient. Already, new equipment for measuring feedbacks from the land surface to the climate system has been installed at several locations, while best practices for sensor networking have been established. INTERACT networks with most of the high-level Arctic organisations: it includes AMAP and WWF as partners, is endorsed by IASC and CBMP, has signed MoUs with ISAC and the University of the Arctic, is a task within SAON, and contributes to the Cold Region community within GEO/GEOSS. INTERACT welcomes other interactions.

  3. Strategic interaction and conventions

    Directory of Open Access Journals (Sweden)

    Espinosa, María Paz

    2012-03-01

    Full Text Available The scope of the paper is to review the literature that employs coordination games to study social norms and conventions from the viewpoint of game theory and cognitive psychology. We claim that those two alternative approaches are in fact complementary, as they provide different insights to explain how people converge to a unique system of self-fulfilling expectations in presence of multiple, equally viable, conventions. While game theory explains the emergence of conventions relying on efficiency and risk considerations, the psychological view is more concerned with frame and labeling effects. The interaction between these alternative (and, sometimes, competing effects leads to the result that coordination failures may well occur and, even when coordination takes place, there is no guarantee that the convention eventually established will be the most efficient.

    El objetivo de este artículo es presentar la literatura que emplea los juegos de coordinación para el estudio de normas y convenciones sociales, que se han analizado tanto desde el punto de vista de la teoría de juegos como de la psicología cognitiva. Argumentamos en este trabajo que estos dos enfoques alternativos son en realidad complementarios, dado que ambos contribuyen al entendimiento de los procesos mediante los cuales las personas llegan a coordinarse en un único sistema de expectativas autorrealizadas, en presencia de múltiples convenciones todas ellas igualmente viables. Mientras que la teoría de juegos explica la aparición de convenciones basándose en argumentos de eficiencia y comportamientos frente al riesgo, el enfoque de la psicología cognitiva utiliza en mayor medida consideraciones referidas al entorno y naturaleza de las decisiones. La interacción entre estos efectos diferentes (y en ocasiones, rivales desemboca con frecuencia en fallos de coordinación y, aun cuando la coordinación se produce, no hay garantía de que la convención en vigor sea la m

  4. Educational interactive multimedia software: The impact of interactivity on learning

    Science.gov (United States)

    Reamon, Derek Trent

    This dissertation discusses the design, development, deployment and testing of two versions of educational interactive multimedia software. Both versions of the software are focused on teaching mechanical engineering undergraduates about the fundamentals of direct-current (DC) motor physics and selection. The two versions of Motor Workshop software cover the same basic materials on motors, but differ in the level of interactivity between the students and the software. Here, the level of interactivity refers to the particular role of the computer in the interaction between the user and the software. In one version, the students navigate through information that is organized by topic, reading text, and viewing embedded video clips; this is referred to as "low-level interactivity" software because the computer simply presents the content. In the other version, the students are given a task to accomplish---they must design a small motor-driven 'virtual' vehicle that competes against computer-generated opponents. The interaction is guided by the software which offers advice from 'experts' and provides contextual information; we refer to this as "high-level interactivity" software because the computer is actively participating in the interaction. The software was used in two sets of experiments, where students using the low-level interactivity software served as the 'control group,' and students using the highly interactive software were the 'treatment group.' Data, including pre- and post-performance tests, questionnaire responses, learning style characterizations, activity tracking logs and videotapes were collected for analysis. Statistical and observational research methods were applied to the various data to test the hypothesis that the level of interactivity effects the learning situation, with higher levels of interactivity being more effective for learning. The results show that both the low-level and high-level interactive versions of the software were effective

  5. Results-Based Interaction Design

    Science.gov (United States)

    Weiss, Meredith

    2008-01-01

    Interaction design is a user-centered approach to development in which users and their goals are the driving force behind a project's design. Interaction design principles are fundamental to the design and implementation of effective websites, but they are not sufficient. This article argues that, to reach its full potential, a website should also…

  6. Temporal form in interaction design

    DEFF Research Database (Denmark)

    Vallgårda, Anna; Winther, Morten Trøstrup; Mørch, Nina;

    2015-01-01

    a nuanced account of what temporal form is in interaction design, and we look at related work synthesizing what we already know of the temporal concerns in interaction design and HCI. In the second part we present a design experiment through which we explore the experiential qualities of a set of 11...

  7. Protein-Protein Interaction Databases

    DEFF Research Database (Denmark)

    Szklarczyk, Damian; Jensen, Lars Juhl

    2015-01-01

    of research are explored. Here we present an overview of the most widely used protein-protein interaction databases and the methods they employ to gather, combine, and predict interactions. We also point out the trade-off between comprehensiveness and accuracy and the main pitfall scientists have to be aware...

  8. Interactive Information Visualization in Neuroimaging

    DEFF Research Database (Denmark)

    Nielsen, Finn Årup; Hansen, Lars Kai

    1998-01-01

    We describe a virtual environment for interactive visualization of 3D neuroimages. The environment is implemented in VRML and we will discuss the viability and limitation of this platform......We describe a virtual environment for interactive visualization of 3D neuroimages. The environment is implemented in VRML and we will discuss the viability and limitation of this platform...

  9. Perceived Attractiveness and Classroom Interactions

    Science.gov (United States)

    Algozzine, Bob

    1977-01-01

    Adams and Cohen (1974) demonstrated that facial attractiveness was a salient factor in differential student-teacher interactions. This research investigates further the interaction between teachers and children perceived to be attractive or unattractive by those teachers. It was hypothesized that attractive children would exhibit more "positive,"…

  10. Interactive Information Visualization in Neuroimaging

    DEFF Research Database (Denmark)

    Nielsen, Finn Årup; Hansen, Lars Kai

    We describe a virtual environment for interactive visualization of 3D neuroimages. The environment is implemented in VRML and we will discuss the viability and limitation of this platform......We describe a virtual environment for interactive visualization of 3D neuroimages. The environment is implemented in VRML and we will discuss the viability and limitation of this platform...

  11. Mobile Collocated Interactions With Wearables

    DEFF Research Database (Denmark)

    Lucero, Andrés; Wilde, Danielle; Robinson, Simon;

    2015-01-01

    powerful, and closer to our bodies. Therefore, mobile collocated interactions research, which originally looked at smartphones and tablets, will inevitably move towards fully integrated wearable technologies. The focus of this workshop is to bring together a community of researchers, designers and...... practitioners to explore the potential of extending mobile collocated interactions from, through and around the body using wearable technologies....

  12. Nitrogen interactions at metal surfaces

    NARCIS (Netherlands)

    Gleeson, M. A.; Kleyn, A. W.

    2013-01-01

    Molecular beam experiments with specially prepared beams allow the study of the interaction of very reactive species with surfaces. In the present case the interaction of N-atoms with Ag(1 1 1) is studied. The energy of the atoms is around 5 eV, precisely between the classical energy regimes of seed

  13. Designing Interactive Online Nursing Courses

    Science.gov (United States)

    Jain, Smita; Jain, Pawan

    2015-01-01

    This study empirically tests the relation between the instructional design elements and the overall meaningful interactions among online students. Eighteen online graduate nursing courses are analyzed using bivariate and multivariate analysis techniques. Findings suggest that the quantity of meaningful interaction among learners can be improved by…

  14. Interacting with a Virtual Conductor

    NARCIS (Netherlands)

    Bos, P.

    2007-01-01

    The task of conducting human musicians in a live performance by a computer has not yet been addressed extensively before. A few attempts exist at letting a computer perform this task, but there is no interactive virtual conductor who can conduct human musicians and can interact with these musicians.

  15. Stable interactions via proper deformations

    International Nuclear Information System (INIS)

    A new method is proposed for switching on interactions that are compatible with global symmetries and conservation laws of the original free theory. The method is applied to the control of stability in Lagrangian and non-Lagrangian theories with higher derivatives. By way of illustration, a wide class of stable interactions is constructed for the Pais–Uhlenbeck oscillator. (paper)

  16. Assessing Preference for Social Interactions

    Science.gov (United States)

    Clay, Casey J.; Samaha, Andrew L.; Bloom, Sarah E.; Bogoev, Bistra K.; Boyle, Megan A.

    2013-01-01

    We examined a procedure to assess preference for social interactions in individuals with intellectual and developmental disabilities. Preferences were identified in five individuals using a paired-choice procedure in which participants approached therapists who provided different forms of social interactions. A subsequent tracking test showed that…

  17. Eye Movements in Gaze Interaction

    DEFF Research Database (Denmark)

    Møllenbach, Emilie; Hansen, John Paulin; Lillholm, Martin

    2013-01-01

    Gaze as a sole input modality must support complex navigation and selection tasks. Gaze interaction combines specific eye movements and graphic display objects (GDOs). This paper suggests a unifying taxonomy of gaze interaction principles. The taxonomy deals with three types of eye movements...

  18. Interactive Flow in Exercise Pedagogy

    Science.gov (United States)

    Lloyd, Rebecca; Smith, Stephen

    2006-01-01

    A phenomenology of the bodily experience of interactive flow adds to Csikszentmihalyi's flow theory. Whereas Csikszentmihalyi attended to teachers' and students' experiences of flow separately, this inquiry explores flow through three water-inspired layers of physical interaction between fitness professionals and their clients. Teaching fitness is…

  19. Transient interactions between photosynthetic proteins

    NARCIS (Netherlands)

    Hulsker, Rinske

    2008-01-01

    The biological processes that are the basis of all life forms are mediated largely by protein-protein interactions. The protein complexes involved in these interactions can be categorised by their affinity, which results in a range from static to transient complexes. Electron transfer complexes, whi

  20. Family Interactions and Child Psychopathology.

    Science.gov (United States)

    Donenberg, Geri R.; Nelson, Dana

    Previous research has not correlated parent-child interaction patterns with different forms of child psychopathology. This study examined whether parent-child interaction corresponded with childhood depression/anxiety and childhood aggression. Forty-two clinically-referred children and adolescents, 8 to 16 years old, were classified into four…