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Sample records for bubr1 kinetochore interactions

  1. Two functionally distinct kinetochore pools of BubR1 ensure accurate chromosome segregation

    DEFF Research Database (Denmark)

    Zhang, Gang; Mendez, Blanca Lopez; Sedgwick, Garry G

    2016-01-01

    The BubR1/Bub3 complex is an important regulator of chromosome segregation as it facilitates proper kinetochore-microtubule interactions and is also an essential component of the spindle assembly checkpoint (SAC). Whether BubR1/Bub3 localization to kinetochores in human cells stimulates SAC signa...

  2. Structure of a Blinkin-BUBR1 complex reveals an interaction crucial for kinetochore-mitotic checkpoint regulation via an unanticipated binding Site

    DEFF Research Database (Denmark)

    Bolanos-Garcia, Victor M; Lischetti, Tiziana; Matak-Vinković, Dijana

    2011-01-01

    The maintenance of genomic stability relies on the spindle assembly checkpoint (SAC), which ensures accurate chromosome segregation by delaying the onset of anaphase until all chromosomes are properly bioriented and attached to the mitotic spindle. BUB1 and BUBR1 kinases are central for this proc...

  3. Distinct domains in Bub1 localize RZZ and BubR1 to kinetochores to regulate the checkpoint

    DEFF Research Database (Denmark)

    Zhang, Gang; Lischetti, Tiziana; Hayward, Daniel G

    2015-01-01

    The spindle assembly checkpoint (SAC) ensures proper chromosome segregation by delaying anaphase onset in response to unattached kinetochores. Checkpoint signalling requires the kinetochore localization of the Mad1-Mad2 complex that in more complex eukaryotes depends on the Rod-Zwilch-ZW10 (RZZ......) complex. The kinetochore protein Zwint has been proposed to be the kinetochore receptor for RZZ, but here we show that Bub1 and not Zwint is required for RZZ recruitment. We find that the middle region of Bub1 encompassing a domain essential for SAC signalling contributes to RZZ localization. In addition......, we show that a distinct region in Bub1 mediates kinetochore localization of BubR1 through direct binding, but surprisingly removal of this region increases checkpoint strength. Our work thus uncovers how Bub1 coordinates checkpoint signalling by distinct domains for RZZ and BubR1 recruitment...

  4. The architecture of the BubR1 tetratricopeptide tandem repeat defines a protein motif underlying mitotic checkpoint-kinetochore communication.

    Science.gov (United States)

    Bolanos-Garcia, Victor M; Nilsson, Jakob; Blundell, Tom L

    2012-01-01

    The accurate and timely transmission of the genetic material to progeny during successive rounds of cell division is sine qua non for the maintenance of genome stability. Eukaryotic cells have evolved a surveillance mechanism, the mitotic spindle assembly checkpoint (SAC), to prevent premature advance to anaphase before every chromosome is properly attached to microtubules of the mitotic spindle. The architecture of the KNL1-BubR1 complex reveals important features of the molecular recognition between SAC components and the kinetochore. The interaction is important for a functional SAC as substitution of BubR1 residues engaged in KNL1 binding impaired the SAC and BubR1 recruitment into checkpoint complexes in stable cell lines. Here we discuss the implications of the disorder-to-order transition of KNL1 upon BubR1 binding for SAC signaling and propose a mechanistic model of how BUBs binding may affect the recognition of KNL1 by its other interacting partners.

  5. Drosophila CENP-A mutations cause a BubR1-dependent early mitotic delay without normal localization of kinetochore components.

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    Michael D Blower

    2006-07-01

    Full Text Available The centromere/kinetochore complex plays an essential role in cell and organismal viability by ensuring chromosome movements during mitosis and meiosis. The kinetochore also mediates the spindle attachment checkpoint (SAC, which delays anaphase initiation until all chromosomes have achieved bipolar attachment of kinetochores to the mitotic spindle. CENP-A proteins are centromere-specific chromatin components that provide both a structural and a functional foundation for kinetochore formation. Here we show that cells in Drosophila embryos homozygous for null mutations in CENP-A (CID display an early mitotic delay. This mitotic delay is not suppressed by inactivation of the DNA damage checkpoint and is unlikely to be the result of DNA damage. Surprisingly, mutation of the SAC component BUBR1 partially suppresses this mitotic delay. Furthermore, cid mutants retain an intact SAC response to spindle disruption despite the inability of many kinetochore proteins, including SAC components, to target to kinetochores. We propose that SAC components are able to monitor spindle assembly and inhibit cell cycle progression in the absence of sustained kinetochore localization.

  6. Loss of Centromere Cohesion in Aneuploid Human Oocytes Correlates with Decreased Kinetochore Localization of the Sac Proteins Bub1 and Bubr1.

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    Lagirand-Cantaloube, Julie; Ciabrini, Cendrine; Charrasse, Sophie; Ferrieres, Alice; Castro, Anna; Anahory, Tal; Lorca, Thierry

    2017-03-13

    In human eggs, aneuploidy increases with age and can result in infertility and genetic diseases. Studies in mouse oocytes suggest that reduced centromere cohesion and spindle assembly checkpoint (SAC) activity could be at the origin of chromosome missegregation. Little is known about these two features in humans. Here, we show that in human eggs, inter-kinetochore distances of bivalent chromosomes strongly increase with age. This results in the formation of univalent chromosomes during metaphase I (MI) and of single chromatids in metaphase II (MII). We also investigated SAC activity by checking the localization of BUB1 and BUBR1. We found that they localize at the kinetochore with a similar temporal timing than in mitotic cells and in a MPS1-dependent manner, suggesting that the SAC signalling pathway is active in human oocytes. Moreover, our data also suggest that this checkpoint is inactivated when centromere cohesion is lost in MI and consequently cannot inhibit premature sister chromatid separation. Finally, we show that the kinetochore localization of BUB1 and BUBR1 decreases with the age of the oocyte donors. This could contribute to oocyte aneuploidy.

  7. The architecture of the BubR1 tetratricopeptide tandem repeat defines a protein motif underlying mitotic checkpoint-kinetochore communication

    DEFF Research Database (Denmark)

    Bolanos-Garcia, Victor M; Nilsson, Jakob; Blundell, Tom L

    2012-01-01

    as substitution of BubR1 residues engaged in KNL1 binding impaired the SAC and BubR1 recruitment into checkpoint complexes in stable cell lines. Here we discuss the implications of the disorder-to-order transition of KNL1 upon BubR1 binding for SAC signaling and propose a mechanistic model of how BUBs binding may...

  8. BUBR1 recruits PP2A via the B56 family of targeting subunits to promote chromosome congression

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    Peng Xu

    2013-03-01

    BUBR1 is a mitotic phosphoprotein essential for the maintenance of chromosome stability by promoting chromosome congression and proper kinetochore–microtubule (K-fiber attachment, but the underlying mechanism(s has remained elusive. Here we identify BUBR1 as a binding partner of the B56 family of Protein Phosphatase 2A regulatory subunits. The interaction between BUBR1 and the B56 family is required for chromosome congression, since point mutations in BUBR1 that block B56 binding abolish chromosome congression. The BUBR1:B56-PP2A complex opposes Aurora B kinase activity, since loss of the complex can be reverted by inhibiting Aurora B. Importantly, we show that the failure of BUBR1 to recruit B56-PP2A also contributes to the chromosome congression defects found in cells derived from patients with the Mosaic Variegated Aneuploidy (MVA syndrome. Together, we propose that B56-PP2A is a key mediator of BUBR1's role in chromosome congression and functions by antagonizing Aurora B activity at the kinetochore for establishing stable kinetochore–microtubule attachment at the metaphase plate.

  9. Crystal structure of a PP2A B56-BubR1 complex and its implications for PP2A substrate recruitment and localization

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    Jiao Wang

    2016-06-01

    Full Text Available ABSTRACT Protein phosphatase 2A (PP2A accounts for the majority of total Ser/Thr phosphatase activities in most cell types and regulates many biological processes. PP2A holoenzymes contain a scaffold A subunit, a catalytic C subunit, and one of the regulatory/targeting B subunits. How the B subunit controls PP2A localization and substrate specificity, which is a crucial aspect of PP2A regulation, remains poorly understood. The kinetochore is a critical site for PP2A functioning, where PP2A orchestrates chromosome segregation through its interactions with BubR1. The PP2A-BubR1 interaction plays important roles in both spindle checkpoint silencing and stable microtubule-kinetochore attachment. Here we present the crystal structure of a PP2A B56-BubR1 complex, which demonstrates that a conserved BubR1 LxxIxE motif binds to the concave side of the B56 pseudo-HEAT repeats. The BubR1 motif binds to a groove formed between B56 HEAT repeats 3 and 4, which is quite distant from the B56 binding surface for PP2A catalytic C subunit and thus is unlikely to affect PP2A activity. In addition, the BubR1 binding site on B56 is far from the B56 binding site of shugoshin, another kinetochore PP2A-binding protein, and thus BubR1 and shugoshin can potentially interact with PP2A-B56 simultaneously. Our structural and biochemical analysis indicates that other proteins with the LxxIxE motif may also bind to the same PP2A B56 surface. Thus, our structure of the PP2A B56-BubR1 complex provides important insights into how the B56 subunit directs the recruitment of PP2A to specific targets.

  10. The internal Cdc20 binding site in BubR1 facilitates both spindle assembly checkpoint signalling and silencing

    DEFF Research Database (Denmark)

    Lischetti, Tiziana; Zhang, Gang; Sedgwick, Garry G

    2014-01-01

    Improperly attached kinetochores activate the spindle assembly checkpoint (SAC) and by an unknown mechanism catalyse the binding of two checkpoint proteins, Mad2 and BubR1, to Cdc20 forming the mitotic checkpoint complex (MCC). Here, to address the functional role of Cdc20 kinetochore localization...... in the SAC, we delineate the molecular details of its interaction with kinetochores. We find that BubR1 recruits the bulk of Cdc20 to kinetochores through its internal Cdc20 binding domain (IC20BD). We show that preventing Cdc20 kinetochore localization by removal of the IC20BD has a limited effect...... on the SAC because the IC20BD is also required for efficient SAC silencing. Indeed, the IC20BD can disrupt the MCC providing a mechanism for its role in SAC silencing. We thus uncover an unexpected dual function of the second Cdc20 binding site in BubR1 in promoting both efficient SAC signalling and SAC...

  11. BubR1 Promotes Bub3-Dependent APC/C Inhibition during Spindle Assembly Checkpoint Signaling.

    Science.gov (United States)

    Overlack, Katharina; Bange, Tanja; Weissmann, Florian; Faesen, Alex C; Maffini, Stefano; Primorac, Ivana; Müller, Franziska; Peters, Jan-Michael; Musacchio, Andrea

    2017-10-09

    The spindle assembly checkpoint (SAC) prevents premature sister chromatid separation during mitosis. Phosphorylation of unattached kinetochores by the Mps1 kinase promotes recruitment of SAC machinery that catalyzes assembly of the SAC effector mitotic checkpoint complex (MCC). The SAC protein Bub3 is a phospho-amino acid adaptor that forms structurally related stable complexes with functionally distinct paralogs named Bub1 and BubR1. A short motif ("loop") of Bub1, but not the equivalent loop of BubR1, enhances binding of Bub3 to kinetochore phospho-targets. Here, we asked whether the BubR1 loop directs Bub3 to different phospho-targets. The BubR1 loop is essential for SAC function and cannot be removed or replaced with the Bub1 loop. BubR1 loop mutants bind Bub3 and are normally incorporated in MCC in vitro but have reduced ability to inhibit the MCC target anaphase-promoting complex (APC/C), suggesting that BubR1:Bub3 recognition and inhibition of APC/C requires phosphorylation. Thus, small sequence differences in Bub1 and BubR1 direct Bub3 to different phosphorylated targets in the SAC signaling cascade. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  12. The vertebrate mitotic checkpoint protein BUBR1 is an unusual pseudokinase.

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    Suijkerbuijk, Saskia J E; van Dam, Teunis J P; Karagöz, G Elif; von Castelmur, Eleonore; Hubner, Nina C; Duarte, Afonso M S; Vleugel, Mathijs; Perrakis, Anastassis; Rüdiger, Stefan G D; Snel, Berend; Kops, Geert J P L

    2012-06-12

    Chromosomal stability is safeguarded by a mitotic checkpoint, of which BUB1 and Mad3/BUBR1 are core components. These paralogs have similar, but not identical, domain organization. We show that Mad3/BUBR1 and BUB1 paralogous pairs arose by nine independent gene duplications throughout evolution, followed by parallel subfunctionalization in which preservation of the ancestral, amino-terminal KEN box or kinase domain was mutually exclusive. In one exception, vertebrate BUBR1-defined by the KEN box-preserved the kinase domain but allowed nonconserved degeneration of catalytic motifs. Although BUBR1 evolved to a typical pseudokinase in some vertebrates, it retained the catalytic triad in humans. However, we show that putative catalysis by human BUBR1 is dispensable for error-free chromosome segregation. Instead, residues that interact with ATP in conventional kinases are essential for conformational stability in BUBR1. We propose that parallel evolution of BUBR1 orthologs rendered its kinase function dispensable in vertebrates, producing an unusual, triad-containing pseudokinase. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. The kinetochore interaction network (KIN) of ascomycetes.

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    Freitag, Michael

    2016-01-01

    Chromosome segregation relies on coordinated activity of a large assembly of proteins, the kinetochore interaction network (KIN). How conserved the underlying mechanisms driving the epigenetic phenomenon of centromere and kinetochore assembly and maintenance are remains unclear, even though various eukaryotic models have been studied. More than 50 different proteins, many in multiple copies, comprise the KIN or are associated with fungal centromeres and kinetochores. Proteins isolated from immune sera recognized centromeric regions on chromosomes and thus were named centromere proteins (CENPs). CENP-A, sometimes called centromere-specific H3 (CenH3), is incorporated into nucleosomes within or near centromeres. The constitutive centromere-associated network (CCAN) assembles on this specialized chromatin, likely based on specific interactions with and requiring presence of CENP-C. The outer kinetochore comprises the Knl1-Mis12-Ndc80 (KMN) protein complexes that connect CCAN to spindles, accomplished by binding and stabilizing microtubules (MTs) and in the process generating load-bearing assemblies for chromatid segregation. In most fungi the Dam1/DASH complex connects the KMN complexes to MTs. Fungi present a rich resource to investigate mechanistic commonalities but also differences in kinetochore architecture. While ascomycetes have sets of CCAN and KMN proteins that are conserved with those of budding yeast or metazoans, searching other major branches of the fungal kingdom revealed that CCAN proteins are poorly conserved at the primary sequence level. Several conserved binding motifs or domains within KMN complexes have been described recently, and these features of ascomycete KIN proteins are shared with most metazoan proteins. In addition, several ascomycete-specific domains have been identified here. © 2016 by The Mycological Society of America.

  14. Direct binding between BubR1 and B56-PP2A phosphatase complexes regulate mitotic progression

    DEFF Research Database (Denmark)

    Kruse, Thomas; Zhang, Gang; Larsen, Marie Sofie Yoo

    2013-01-01

    but the mechanism behind this is not clear. Here we show that BubR1 directly binds to the B56 family of PP2A regulatory subunits through a conserved motif that is phosphorylated by Cdk1 and Plk1. Two highly conserved hydrophobic residues surrounding the S670 Cdk1 phosphorylation site are required for B56 binding...... Aurora B kinase activity at improperly attached kinetochores by recruiting B56-PP2A phosphatase complexes....

  15. Bub3-BubR1-dependent sequestration of Cdc20Fizzy at DNA breaks facilitates the correct segregation of broken chromosomes.

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    Derive, Nicolas; Landmann, Cedric; Montembault, Emilie; Claverie, Marie-Charlotte; Pierre-Elies, Priscillia; Goutte-Gattat, Damien; Founounou, Nabila; McCusker, Derek; Royou, Anne

    2015-11-09

    The presence of DNA double-strand breaks during mitosis is particularly challenging for the cell, as it produces broken chromosomes lacking a centromere. This situation can cause genomic instability resulting from improper segregation of the broken fragments into daughter cells. We recently uncovered a process by which broken chromosomes are faithfully transmitted via the BubR1-dependent tethering of the two broken chromosome ends. However, the mechanisms underlying BubR1 recruitment and function on broken chromosomes were largely unknown. We show that BubR1 requires interaction with Bub3 to localize on the broken chromosome fragments and to mediate their proper segregation. We also find that Cdc20, a cofactor of the E3 ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C), accumulates on DNA breaks in a BubR1 KEN box-dependent manner. A biosensor for APC/C activity demonstrates a BubR1-dependent local inhibition of APC/C around the segregating broken chromosome. We therefore propose that the Bub3-BubR1 complex on broken DNA inhibits the APC/C locally via the sequestration of Cdc20, thus promoting proper transmission of broken chromosomes. © 2015 Derive et al.

  16. The chromosomal passenger complex controls spindle checkpoint function independent from its role in correcting microtubule-kinetochore interactions

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    Vader, Gerben; Cruijsen, Carin W. A.; van Harn, Tanja; Vromans, Martijn J. M.; Medema, Rene H.; Lens, Susanne M. A.

    2007-01-01

    The chromosomal passenger complex (CPC) is a critical regulator of chromosome segregation during mitosis by correcting nonbipolar microtubule-kinetochore interactions. By severing these interactions, the CPC is thought to create unattached kinetochores that are subsequently sensed by the spindle

  17. Suppression of Genomic Instabilities Caused by Chromosome Mis-segregation: A Perspective From Studying BubR1 and Sgo1

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    Wei Dai

    2009-12-01

    Full Text Available Aneuploidy is a major manifestation of chromosomal instability, which is defined as a numerical abnormality of chromosomes in diploid cells. It is highly prevalent in a variety of human malignancies. Increased chromosomal instability is the major driving force for tumor development and progression. To suppress genomic stability during cell division, eukaryotic cells have evolved important molecular mechanisms, commonly referred to as checkpoints. The spindle checkpoint ensures that cells with defective mitotic spindles or a defective interaction between the spindles and kinetochores do not initiate chromosomal segregation during mitosis. Extensive studies have identified and characterized more than a dozen genes that play important roles in the regulation of the spindle checkpoint in mammalian cells. During the past decade, we have carried out extensive investigation of the role of BubR1 (Bub1-related kinase and Sgo1 (shugoshin 1, two important gene products that safeguard accurate chromosome segregation during mitosis. This mini-review summarizes our studies, as well as those by other researchers in the field, on the functions of these two checkpoint proteins and their molecular regulation during mitosis. Further elucidation of the molecular mechanisms of the spindle checkpoint regulation has the potential to identify important mitotic targets for rational anticancer drug design.

  18. BubR1 insufficiency impairs angiogenesis in aging and in experimental critical limb ischemic mice.

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    Okadome, Jun; Matsumoto, Takuya; Yoshiya, Keiji; Matsuda, Daisuke; Tamada, Kouji; Onimaru, Mitsuho; Nakano, Kaku; Egashira, Kensuke; Yonemitsu, Yoshikazu; Maehara, Yoshihiko

    2017-09-30

    Budding uninhibited by benzimidazole-related 1 (BubR1), a cell cycle-related protein, is an essential component of the spindle checkpoint that regulates cell division. Mice in which BubR1 expression is reduced to 10% of the normal level display the phenotypic features of progeria. However, the role of BubR1 in vascular diseases and angiogenesis remains unknown. To investigate the influence of BubR1 on angiogenesis, we generated a low-null-BubR1-expressing (BubR1L/-) mouse strain with reduced BubR1 expression as low as 15% of the normal level without any abnormalities in appearance. To elucidate the role of BubR1 in angiogenesis, we used a hind limb ischemia model induced in BubR1L/- mice and age-matched wild-type (WT) littermates. To evaluate the pathologic influence of BubR1 on angiogenesis, we measured the blood flow before and after hind limb ischemia surgery, and the expression of typical angiogenic factors in vivo and in vitro. In WT mice, blood flow in the ischemic left limb gradually recovered to approximately 80%, 14 days after surgery. Conversely, in the BubR1L/- group, blood flow in the left ischemic limb recovered to at most 30% (14 days after surgery, P calf muscles from BubR1L/- mice, regenerated muscle bundles, granulation tissue, and inflammatory cell invasion were more evident than in calf muscles from WT mice at 14 days after surgery. All WT mice at 14 days after surgery had complete limb salvage, but loss of limbs was observed in approximately 70% of BubR1L/- mice (P muscles was lower in BubR1L/- mice compared with WT mice (P muscle cells treated with BubR1 knockdown siRNA were lower compared with scramble siRNA under hypoxic conditions (P muscles after hind limb ischemia surgery were also significantly lower in BubR1L/- mice compared with WT mice (P < .05). BubR1 insufficiency impairs angiogenesis and results in limb loss in ischemic hind limbs. BubR1 may be a crucial angiogenic factor and might be beneficial for the treatment of limb ischemia. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

  19. Stranglehold on the spindle assembly checkpoint: the human papillomavirus E2 protein provokes BUBR1-dependent aneuploidy.

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    Tan, Chye Ling; Teissier, Sébastien; Gunaratne, Jayantha; Quek, Ling Shih; Bellanger, Sophie

    2015-01-01

    The Human Papillomavirus (HPV) E2 protein, which inhibits the E6 and E7 viral oncogenes, is believed to have anti-oncogenic properties. Here, we challenge this view and show that HPV-18 E2 over-activates the Spindle Assembly Checkpoint (SAC) and induces DNA breaks in mitosis followed by aneuploidy. This phenotype is associated with interaction of E2 with the Mitotic Checkpoint Complex (MCC) proteins Cdc20, MAD2 and BUBR1. While BUBR1 silencing rescues the mitotic phenotype induced by E2, p53 silencing or presence of E6/E7 (inactivating p53 and increasing BUBR1 levels respectively) both amplify it. This work pinpoints E2 as a key protein in the initiation of HPV-induced cervical cancer and identifies the SAC as a target for oncogenic pathogens. Moreover, our results suggest a role of p53 in regulating the mitotic process itself and highlight SAC over-activation in a p53-negative context as a highly pathogenic event.

  20. The vertebrate mitotic checkpoint protein BUBR1 is an unusual pseudokinase.

    NARCIS (Netherlands)

    Suijkerbuijk, S.J.; Dam, T.J.P. van; Karagoz, G.E.; Castelmur, E. von; Hubner, N.C.; Duarte, A.M.; Vleugel, M.; Perrakis, A.; Rudiger, S.G.; Snel, B.; Kops, G.J.

    2012-01-01

    Chromosomal stability is safeguarded by a mitotic checkpoint, of which BUB1 and Mad3/BUBR1 are core components. These paralogs have similar, but not identical, domain organization. We show that Mad3/BUBR1 and BUB1 paralogous pairs arose by nine independent gene duplications throughout evolution,

  1. The Vertebrate Mitotic Checkpoint Protein BUBR1 Is an Unusual Pseudokinase

    NARCIS (Netherlands)

    Suijkerbuijk, Saskia J.E.; van Dam, Teunis J.P.; Karagöz, G. Elif; von Castelmur, Eleonore; Hubner, Nina C.; Duarte, Afonso M.S.; Vleugel, Mathijs; Perrakis, Anastassis; Rüdiger, Stefan G.D.|info:eu-repo/dai/nl/314076662; Snel, Berend|info:eu-repo/dai/nl/241508215; Kops, Geert J.P.L.

    2012-01-01

    Chromosomal stability is safeguarded by a mitotic checkpoint, of which BUB1 and Mad3/BUBR1 are core components. These paralogs have similar, but not identical, domain organization. We show that Mad3/BUBR1 and BUB1 paralogous pairs arose by nine independent gene duplications throughout evolution,

  2. Meiosis I chromosome segregation is established through regulation of microtubule–kinetochore interactions

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    Miller, Matthew P; Ünal, Elçin; Brar, Gloria A; Amon, Angelika

    2012-01-01

    During meiosis, a single round of DNA replication is followed by two consecutive rounds of nuclear divisions called meiosis I and meiosis II. In meiosis I, homologous chromosomes segregate, while sister chromatids remain together. Determining how this unusual chromosome segregation behavior is established is central to understanding germ cell development. Here we show that preventing microtubule–kinetochore interactions during premeiotic S phase and prophase I is essential for establishing the meiosis I chromosome segregation pattern. Premature interactions of kinetochores with microtubules transform meiosis I into a mitosis-like division by disrupting two key meiosis I events: coorientation of sister kinetochores and protection of centromeric cohesin removal from chromosomes. Furthermore we find that restricting outer kinetochore assembly contributes to preventing premature engagement of microtubules with kinetochores. We propose that inhibition of microtubule–kinetochore interactions during premeiotic S phase and prophase I is central to establishing the unique meiosis I chromosome segregation pattern. DOI: http://dx.doi.org/10.7554/eLife.00117.001 PMID:23275833

  3. Synthetic Physical Interactions Map Kinetochore-Checkpoint Activation Regions

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    Guðjón Ólafsson

    2016-08-01

    Full Text Available The spindle assembly checkpoint (SAC is a key mechanism to regulate the timing of mitosis and ensure that chromosomes are correctly segregated to daughter cells. The recruitment of the Mad1 and Mad2 proteins to the kinetochore is normally necessary for SAC activation. This recruitment is coordinated by the SAC kinase Mps1, which phosphorylates residues at the kinetochore to facilitate binding of Bub1, Bub3, Mad1, and Mad2. There is evidence that the essential function of Mps1 is to direct recruitment of Mad1/2. To test this model, we have systematically recruited Mad1, Mad2, and Mps1 to most proteins in the yeast kinetochore, and find that, while Mps1 is sufficient for checkpoint activation, recruitment of either Mad1 or Mad2 is not. These data indicate an important role for Mps1 phosphorylation in SAC activation, beyond the direct recruitment of Mad1 and Mad2.

  4. The kinetochore

    National Research Council Canada - National Science Library

    Cheeseman, Iain M

    2014-01-01

    .... The central player in this process is the macromolecular kinetochore structure, which binds to both chromosomal DNA and spindle microtubule polymers to direct chromosome alignment and segregation...

  5. Localization and Function of Budding Yeast CENP-A Depends upon Kinetochore Protein Interactions and Is Independent of Canonical Centromere Sequence

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    Kung-Hsien Ho

    2014-12-01

    Full Text Available In many eukaryotes, the centromere is epigenetically specified and not strictly defined by sequence. In contrast, budding yeast has a specific 125 bp sequence required for kinetochore function. Despite the difference in centromere specification, budding yeast and multicellular eukaryotic centromeres contain a highly conserved histone H3 variant, CENP-A. The localization of budding yeast CENP-A, Cse4, requires the centromere DNA binding components, which are not conserved in multicellular eukaryotes. Here, we report that Cse4 localizes and functions at a synthetic kinetochore assembly site that lacks centromere sequence. The outer kinetochore Dam1-DASH and inner kinetochore CBF3 complexes are required for Cse4 localization to that site. Furthermore, the natural kinetochore also requires the outer kinetochore proteins for full Cse4 localization. Our results suggest that Cse4 localization at a functional kinetochore does not require the recognition of a specific DNA sequence by the CBF3 complex; rather, its localization depends on stable interactions among kinetochore proteins.

  6. BubR1 Acts as a Promoter in Cellular Motility of Human Oral Squamous Cancer Cells through Regulating MMP-2 and MMP-9

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    Chou-Kit Chou

    2015-07-01

    Full Text Available BubR1 is a critical component of spindle assembly checkpoint, ensuring proper chromatin segregation during mitosis. Recent studies showed that BubR1 was overexpressed in many cancer cells, including oral squamous cell carcinomas (OSCC. However, the effect of BubR1 on metastasis of OSCC remains unclear. This study aimed to unravel the role of BubR1 in the progression of OSCC and confirm the expression of BubR1 in a panel of malignant OSCC cell lines with different invasive abilities. The results of quantitative real-time PCR showed that the mRNA level of BubR1 was markedly increased in four OSCC cell lines, Ca9-22, HSC3, SCC9 and Cal-27 cells, compared to two normal cells, normal human oral keratinocytes (HOK and human gingival fibroblasts (HGF. Moreover, the expression of BubR1 in these four OSCC cell lines was positively correlated with their motility. Immunofluorescence revealed that BubR1 was mostly localized in the cytosol of human gingival carcinoma Ca9-22 cells. BubR1 knockdown significantly decreased cellular invasion but slightly affect cellular proliferation on both Ca9-22 and Cal-27 cells. Consistently, the activities of metastasis-associated metalloproteinases MMP-2 and MMP-9 were attenuated in BubR1 knockdown Ca9-22 cells, suggesting the role of BubR1 in promotion of OSCC migration. Our present study defines an alternative pathway in promoting metastasis of OSCC cells, and the expression of BubR1 could be a prognostic index in OSCC patients.

  7. Mechanics of kinetochore microtubules and their interactions with chromosomes during cell division

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    Nazockdast, Ehssan; Fürthauer, Sebastian; Redemann, Stephanie; Baumgart, Johannes; Lindow, Norbert; Kratz, Andrea; Prohaska, Steffen; Müller-Reichert, Thomas; Shelley, Michael

    2016-11-01

    The accurate segregation of chromosomes, and subsequent cell division, in Eukaryotic cells is achieved by the interactions of an assembly of microtubules (MTs) and motor-proteins, known as the mitotic spindle. We use a combination of our computational platform for simulating cytoskeletal assemblies and our structural data from high-resolution electron tomography of the mitotic spindle, to study the kinetics and mechanics of MTs in the spindle, and their interactions with chromosomes during chromosome segregation in the first cell division in C.elegans embryo. We focus on kinetochore MTs, or KMTs, which have one end attached to a chromosome. KMTs are thought to be a key mechanical component in chromosome segregation. Using exploratory simulations of MT growth, bending, hydrodynamic interactions, and attachment to chromosomes, we propose a mechanical model for KMT-chromosome interactions that reproduces observed KMT length and shape distributions from electron tomography. We find that including detailed hydrodynamic interactions between KMTs is essential for agreement with the experimental observations.

  8. Structure of the MIS12 Complex and Molecular Basis of Its Interaction with CENP-C at Human Kinetochores.

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    Petrovic, Arsen; Keller, Jenny; Liu, Yahui; Overlack, Katharina; John, Juliane; Dimitrova, Yoana N; Jenni, Simon; van Gerwen, Suzan; Stege, Patricia; Wohlgemuth, Sabine; Rombaut, Pascaline; Herzog, Franz; Harrison, Stephen C; Vetter, Ingrid R; Musacchio, Andrea

    2016-11-03

    Kinetochores, multisubunit protein assemblies, connect chromosomes to spindle microtubules to promote chromosome segregation. The 10-subunit KMN assembly (comprising KNL1, MIS12, and NDC80 complexes, designated KNL1C, MIS12C, and NDC80C) binds microtubules and regulates mitotic checkpoint function through NDC80C and KNL1C, respectively. MIS12C, on the other hand, connects the KMN to the chromosome-proximal domain of the kinetochore through a direct interaction with CENP-C. The structural basis for this crucial bridging function of MIS12C is unknown. Here, we report crystal structures of human MIS12C associated with a fragment of CENP-C and unveil the role of Aurora B kinase in the regulation of this interaction. The structure of MIS12:CENP-C complements previously determined high-resolution structures of functional regions of NDC80C and KNL1C and allows us to build a near-complete structural model of the KMN assembly. Our work illuminates the structural organization of essential chromosome segregation machinery that is conserved in most eukaryotes. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  9. Movement of chromosomes with severed kinetochore microtubules.

    Science.gov (United States)

    Forer, Arthur; Johansen, Kristen M; Johansen, Jørgen

    2015-05-01

    Experiments dating from 1966 and thereafter showed that anaphase chromosomes continued to move poleward after their kinetochore microtubules were severed by ultraviolet microbeam irradiation. These observations were initially met with scepticism as they contradicted the prevailing view that kinetochore fibre microtubules pulled chromosomes to the pole. However, recent experiments using visible light laser microbeam irradiations have corroborated these earlier experiments as anaphase chromosomes again were shown to move poleward after their kinetochore microtubules were severed. Thus, multiple independent studies using different techniques have shown that chromosomes can indeed move poleward without direct microtubule connections to the pole, with only a kinetochore 'stub' of microtubules. An issue not yet settled is: what propels the disconnected chromosome? There are two not necessarily mutually exclusive proposals in the literature: (1) chromosome movement is propelled by the kinetochore stub interacting with non-kinetochore microtubules and (2) chromosome movement is propelled by a spindle matrix acting on the stub. In this review, we summarise the data indicating that chromosomes can move with severed kinetochore microtubules and we discuss proposed mechanisms for chromosome movement with severed kinetochore microtubules.

  10. Mitotic spindle: kinetochore fibers hold on tight to interpolar bundles.

    Science.gov (United States)

    Tolić, Iva M

    2017-07-19

    When a cell starts to divide, it forms a spindle, a micro-machine made of microtubules, which separates the duplicated chromosomes. The attachment of microtubules to chromosomes is mediated by kinetochores, protein complexes on the chromosome. Spindle microtubules can be divided into three major classes: kinetochore microtubules, which form k-fibers ending at the kinetochore; interpolar microtubules, which extend from the opposite sides of the spindle and interact in the middle; and astral microtubules, which extend towards the cell cortex. Recent work in human cells has shown a close relationship between interpolar and kinetochore microtubules, where interpolar bundles are attached laterally to kinetochore fibers almost all along their length, acting as a bridge between sister k-fibers. Most of the interpolar bundles are attached to a pair of sister kinetochore fibers and vice versa. Thus, the spindle is made of modules consisting of a pair of sister kinetochore fibers and a bundle of interpolar microtubules that connects them. These interpolar bundles, termed bridging fibers, balance the forces acting at kinetochores and support the rounded shape of the spindle during metaphase. This review discusses the structure, function, and formation of kinetochore fibers and interpolar bundles, with an emphasis on how they interact. Their connections have an impact on the force balance in the spindle and on chromosome movement during mitosis because the forces in interpolar bundles are transmitted to kinetochore fibers and hence to kinetochores through these connections.

  11. Divergent polo box domains underpin the unique kinetoplastid kinetochore.

    Science.gov (United States)

    Nerusheva, Olga O; Akiyoshi, Bungo

    2016-03-01

    Kinetochores are macromolecular machines that drive eukaryotic chromosome segregation by interacting with centromeric DNA and spindle microtubules. While most eukaryotes possess conventional kinetochore proteins, evolutionarily distant kinetoplastid species have unconventional kinetochore proteins, composed of at least 19 proteins (KKT1-19). Polo-like kinase (PLK) is not a structural kinetochore component in either system. Here, we report the identification of an additional kinetochore protein, KKT20, in Trypanosoma brucei. KKT20 has sequence similarity with KKT2 and KKT3 in the Cys-rich region, and all three proteins have weak but significant similarity to the polo box domain (PBD) of PLK. These divergent PBDs of KKT2 and KKT20 are sufficient for kinetochore localization in vivo. We propose that the ancestral PLK acquired a Cys-rich region and then underwent gene duplication events to give rise to three structural kinetochore proteins in kinetoplastids. © 2016 The Authors.

  12. Studying Kinetochore Kinases

    NARCIS (Netherlands)

    Saurin, Adrian T; Kops, Geert J P L

    2016-01-01

    Mitotic kinetochores are signaling network hubs that regulate chromosome movements, attachment error-correction, and the spindle assembly checkpoint. Key switches in these networks are kinases and phosphatases that enable rapid responses to changing conditions. Describing the mechanisms and dynamics

  13. The Mub1/Ubr2 ubiquitin ligase complex regulates the conserved Dsn1 kinetochore protein.

    Directory of Open Access Journals (Sweden)

    Bungo Akiyoshi

    Full Text Available The kinetochore is the macromolecular complex that assembles onto centromeric DNA and orchestrates the segregation of duplicated chromosomes. More than 60 components make up the budding yeast kinetochore, including inner kinetochore proteins that bind to centromeric chromatin and outer proteins that directly interact with microtubules. However, little is known about how these components assemble into a functional kinetochore and whether there are quality control mechanisms that monitor kinetochore integrity. We previously developed a method to isolate kinetochore particles via purification of the conserved Dsn1 kinetochore protein. We find that the Mub1/Ubr2 ubiquitin ligase complex associates with kinetochore particles through the CENP-C(Mif2 protein. Although Mub1/Ubr2 are not stable kinetochore components in vivo, they regulate the levels of the conserved outer kinetochore protein Dsn1 via ubiquitylation. Strikingly, a deletion of Mub1/Ubr2 restores the levels and viability of a mutant Dsn1 protein, reminiscent of quality control systems that target aberrant proteins for degradation. Consistent with this, Mub1/Ubr2 help to maintain viability when kinetochores are defective. Together, our data identify a previously unknown regulatory mechanism for the conserved Dsn1 kinetochore protein. We propose that Mub1/Ubr2 are part of a quality control system that monitors kinetochore integrity, thus ensuring genomic stability.

  14. Complex regulation of sister kinetochore orientation in meiosis-I

    Indian Academy of Sciences (India)

    Kinetochores mediate chromosome movement during cell division by interacting with the spindle microtubules. Sexual reproduction necessitates the daunting task of reducing ploidy (number of chromosome sets) in the gametes, which depends upon the specialized properties of meiosis. Kinetochores have a central role in ...

  15. Studying Kinetochores In Vivo Using FLIM-FRET.

    Science.gov (United States)

    Yoo, Tae Yeon; Needleman, Daniel J

    2016-01-01

    Kinetochores play essential roles in coordinating mitosis, as a mechanical connector between chromosome and microtubule and as a source of numerous biochemical signals. These mechanical and biochemical behaviors of kinetochores change dynamically in cells during mitosis. Therefore, understanding kinetochore function requires an imaging tool that quantifies the protein-protein interactions or biochemical changes with high spatiotemporal resolution. FRET has previously been used in combination with biosensors to probe protein-protein interactions and biochemical activity. In this chapter, we introduce FLIM-FRET, a lifetime-based method that quantifies FRET, and describe the use of FLIM-FRET as a method for studying dynamic kinetochore behavior in cells with high spatiotemporal resolution.

  16. Kinetochore microtubules in PTK cells

    OpenAIRE

    1992-01-01

    We have analyzed the fine structure of 10 chromosomal fibers from mitotic spindles of PtK1 cells in metaphase and anaphase, using electron microscopy of serial thin sections and computer image processing to follow the trajectories of the component microtubules (MTs) in three dimensions. Most of the kinetochore MTs ran from their kinetochore to the vicinity of the pole, retaining a clustered arrangement over their entire length. This MT bundle was invaded by large numbers of other MTs that wer...

  17. Looping in on Ndc80 - how does a protein loop at the kinetochore control chromosome segregation?

    DEFF Research Database (Denmark)

    Nilsson, Jakob

    2012-01-01

    Segregation of chromosomes during mitosis requires the interaction of dynamic microtubules with the kinetochore, a large protein structure established on the centromere region of sister chromatids. The core microtubule-binding activity of the kinetochore resides in the KMN network, an outer...

  18. A TOGgle for Tension at Kinetochores

    OpenAIRE

    Cheerambathur, Dhanya K.; Prevo, Bram; Desai, Arshad

    2016-01-01

    Differential stability of kinetochore-microtubule attachments at low versus high tension is critical for accurate chromosome segregation. Miller et al. find that a TOG domain microtubule-binding protein imparts intrinsic tension selectivity to kinetochore-microtubule attachments.

  19. The pseudo GTPase CENP-M drives human kinetochore assembly.

    Science.gov (United States)

    Basilico, Federica; Maffini, Stefano; Weir, John R; Prumbaum, Daniel; Rojas, Ana M; Zimniak, Tomasz; De Antoni, Anna; Jeganathan, Sadasivam; Voss, Beate; van Gerwen, Suzan; Krenn, Veronica; Massimiliano, Lucia; Valencia, Alfonso; Vetter, Ingrid R; Herzog, Franz; Raunser, Stefan; Pasqualato, Sebastiano; Musacchio, Andrea

    2014-07-08

    Kinetochores, multi-subunit complexes that assemble at the interface with centromeres, bind spindle microtubules to ensure faithful delivery of chromosomes during cell division. The configuration and function of the kinetochore-centromere interface is poorly understood. We report that a protein at this interface, CENP-M, is structurally and evolutionarily related to small GTPases but is incapable of GTP-binding and conformational switching. We show that CENP-M is crucially required for the assembly and stability of a tetramer also comprising CENP-I, CENP-H, and CENP-K, the HIKM complex, which we extensively characterize through a combination of structural, biochemical, and cell biological approaches. A point mutant affecting the CENP-M/CENP-I interaction hampers kinetochore assembly and chromosome alignment and prevents kinetochore recruitment of the CENP-T/W complex, questioning a role of CENP-T/W as founder of an independent axis of kinetochore assembly. Our studies identify a single pathway having CENP-C as founder, and CENP-H/I/K/M and CENP-T/W as CENP-C-dependent followers.DOI: http://dx.doi.org/10.7554/eLife.02978.001. Copyright © 2014, Basilico et al.

  20. Ringing the changes: emerging roles for DASH at the kinetochore-microtubule Interface.

    Science.gov (United States)

    Buttrick, Graham J; Millar, Jonathan B A

    2011-04-01

    Regulated interaction between kinetochores and the mitotic spindle is essential for the fidelity of chromosome segregation. Potentially deleterious attachments are corrected during prometaphase and metaphase. Correct attachments must persist during anaphase, when spindle-generated forces separate chromosomes to opposite poles. In yeast, the heterodecameric DASH complex plays a vital pole in maintaining this link. In vitro DASH forms both oligomeric patches and rings that can form load-bearing attachments with the tips of polymerising and depolymerising microtubules. In vivo, DASH localises primarily at the kinetochore, and has a role maintaining correct attachment between spindles and chromosomes in both Saccharomyces cerevisiae and Schizosaccharomyces pombe. Recent work has begun to describe how DASH acts alongside other components of the outer kinetochore to create a dynamic, regulated kinetochore-microtubule interface. Here, we review some of the key experiments into DASH function and discuss their implications for the nature of kinetochore-microtubule attachments in yeast and other organisms.

  1. Complex regulation of sister kinetochore orientation in meiosis-I

    Indian Academy of Sciences (India)

    Prakash

    The single microtubule captured by a kinetochore rules out the possibility of merotelic attachment. Ultrastructural analysis of normal meiosis-I spindle in budding yeast further indicates that a single. Figure 3. Zip1p in meiotic chromosome interaction. (A) Schematic diagram of the ultrastructure of synaptonemal complex (see ...

  2. Kinetochore malfunction in human pathologies

    NARCIS (Netherlands)

    de Wolf, Bas; Kops, Geert J.P.L.

    2017-01-01

    The cell cycle culminates in mitosis with the purpose of dividing the cell’s DNA content equally over two daughter cells. Error-free segregation relies on correct connections between chromosomes and spindle microtubules. Kinetochores are complex multi-protein assemblies that mediate these

  3. Implications for kinetochore-microtubule attachment from the structure of an engineered Ndc80 complex.

    Science.gov (United States)

    Ciferri, Claudio; Pasqualato, Sebastiano; Screpanti, Emanuela; Varetti, Gianluca; Santaguida, Stefano; Dos Reis, Gabriel; Maiolica, Alessio; Polka, Jessica; De Luca, Jennifer G; De Wulf, Peter; Salek, Mogjiborahman; Rappsilber, Juri; Moores, Carolyn A; Salmon, Edward D; Musacchio, Andrea

    2008-05-02

    Kinetochores are proteinaceous assemblies that mediate the interaction of chromosomes with the mitotic spindle. The 180 kDa Ndc80 complex is a direct point of contact between kinetochores and microtubules. Its four subunits contain coiled coils and form an elongated rod structure with functional globular domains at either end. We crystallized an engineered "bonsai" Ndc80 complex containing a shortened rod domain but retaining the globular domains required for kinetochore localization and microtubule binding. The structure reveals a microtubule-binding interface containing a pair of tightly interacting calponin-homology (CH) domains with a previously unknown arrangement. The interaction with microtubules is cooperative and predominantly electrostatic. It involves positive charges in the CH domains and in the N-terminal tail of the Ndc80 subunit and negative charges in tubulin C-terminal tails and is regulated by the Aurora B kinase. We discuss our results with reference to current models of kinetochore-microtubule attachment and centromere organization.

  4. Regulation of outer kinetochore Ndc80 complex-based microtubule attachments by the central kinetochore Mis12/MIND complex

    Science.gov (United States)

    Kudalkar, Emily M.; Scarborough, Emily A.; Umbreit, Neil T.; Zelter, Alex; Gestaut, Daniel R.; Riffle, Michael; Johnson, Richard S.; MacCoss, Michael J.; Asbury, Charles L.; Davis, Trisha N.

    2015-01-01

    Multiple protein subcomplexes of the kinetochore cooperate as a cohesive molecular unit that forms load-bearing microtubule attachments that drive mitotic chromosome movements. There is intriguing evidence suggesting that central kinetochore components influence kinetochore–microtubule attachment, but the mechanism remains unclear. Here, we find that the conserved Mis12/MIND (Mtw1, Nsl1, Nnf1, Dsn1) and Ndc80 (Ndc80, Nuf2, Spc24, Spc25) complexes are connected by an extensive network of contacts, each essential for viability in cells, and collectively able to withstand substantial tensile load. Using a single-molecule approach, we demonstrate that an individual MIND complex enhances the microtubule-binding affinity of a single Ndc80 complex by fourfold. MIND itself does not bind microtubules. Instead, MIND binds Ndc80 complex far from the microtubule-binding domain and confers increased microtubule interaction of the complex. In addition, MIND activation is redundant with the effects of a mutation in Ndc80 that might alter its ability to adopt a folded conformation. Together, our results suggest a previously unidentified mechanism for regulating microtubule binding of an outer kinetochore component by a central kinetochore complex. PMID:26430240

  5. The role of the Saccharomyces cerevisiae Rdh54 DNA translocase at kinetochores

    DEFF Research Database (Denmark)

    Bacinskaja, Giedre

    ), which responds to unattached kinetochores or lack of tension between sister chromatids and arrests the cell cycle until all chromosomes are properly attached to the spindle. However, if the trigger activating either the DNA damage checkpoint or the SAC persists, then cell cycle arrest will not necessary...... be maintained indefinitely, because the cell can re-enter the cell cycle through a process termed adaptation. In this study, I investigated the role of the Saccharomyces cerevisiae Rdh54 DNA translocase at kinetochores. Rdh54 is involved in DNA repair by homologous recombination (HR) and is required...... for adaptation to the DNA damage checkpoint. At the cell biological level, fluorescently tagged Rdh54 localizes not only to DNA repair sites but also to kinetochores. To understand the functional importance of Rdh54 localization to kinetochores, I screened for potential interaction partners of Rdh54...

  6. A direct role of Mad1 in the spindle assembly checkpoint beyond Mad2 kinetochore recruitment

    DEFF Research Database (Denmark)

    Kruse, Thomas; Larsen, Marie Sofie Yoo; Sedgwick, Garry G

    2014-01-01

    . The conversion of O-Mad2 into C-Mad2 at unattached kinetochores is thought to be a key step in activating the SAC. The "template model" proposes that this is achieved by the recruitment of soluble O-Mad2 to C-Mad2 bound at kinetochores through its interaction with Mad1. Whether Mad1 has additional roles...... in the SAC beyond recruitment of C-Mad2 to kinetochores has not yet been addressed. Here, we show that Mad1 is required for mitotic arrest even when C-Mad2 is artificially recruited to kinetochores, indicating that it has indeed an additional function in promoting the checkpoint. The C-terminal globular...

  7. A TOGgle for Tension at Kinetochores.

    Science.gov (United States)

    Cheerambathur, Dhanya K; Prevo, Bram; Desai, Arshad

    2016-06-02

    Differential stability of kinetochore-microtubule attachments at low versus high tension is critical for accurate chromosome segregation. Miller et al. find that a TOG domain microtubule-binding protein imparts intrinsic tension selectivity to kinetochore-microtubule attachments. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Evolution of the Kinetochore Network in Eukaryotes

    NARCIS (Netherlands)

    Tromer, E.C.

    2017-01-01

    Kinetochores are highly specialized macromolecular machines built on top of centromeric chromatin to orchestrate the synchronous and equal distribution of chromosomes during mitosis and meiosis. Each kinetochore consists of up to hundreds of copies of a core complex of ~75 proteins that together

  9. Phosphatase-regulated recruitment of the spindle- and Kinetochore-Associated (Ska) Complex to kinetochores.

    Science.gov (United States)

    Sivakumar, Sushama; Gorbsky, Gary J

    2017-10-05

    Kinetochores move chromosomes on dynamic spindle microtubules and regulate signaling of the spindle checkpoint. The Spindle and Kinetochore-Associated (Ska) Complex, a hexamer composed of two copies of Ska1, Ska2 and Ska3, has been implicated in both roles. Phosphorylation of kinetochore components by the well-studied mitotic kinases, Cdk1, Aurora B, Plk1, Mps1, and Bub1 regulate chromosome movement and checkpoint signaling. Roles for the opposing phosphatases are more poorly defined. Recently, we showed that the C terminus of Ska1 recruits protein phosphatase 1 (PP1) to kinetochores. Here we show that PP1 and protein phosphatase 2A (PP2A) both promote accumulation of Ska at kinetochores. Depletion of PP1 or PP2A by siRNA reduces Ska binding at kinetochores, impairs alignment of chromosomes to the spindle midplane, and causes metaphase delay or arrest, phenotypes that are also seen after depletion of Ska. Artificial tethering of PP1 to the outer kinetochore protein Nuf2 promotes Ska recruitment to kinetochores, and it reduces but does not fully rescue chromosome alignment and metaphase arrest defects seen after Ska depletion. We propose that Ska has multiple functions in promoting mitotic progression and that kinetochore-associated phosphatases function in a positive feedback cycle to reinforce Ska complex accumulation at kinetochores. © 2017. Published by The Company of Biologists Ltd.

  10. Poleward force at the kinetochore in metaphase depends on the number of kinetochore microtubules

    Energy Technology Data Exchange (ETDEWEB)

    Hays, T.S.; Salmon, E.D. (Univ. of North Carolina, Chapel Hill (USA))

    1990-02-01

    To examine the dependence of poleward force at a kinetochore on the number of kinetochore microtubules (kMTs), we altered the normal balance in the number of microtubules at opposing homologous kinetochores in meiosis I grasshopper spermatocytes at metaphase with a focused laser microbeam. Observations were made with light and electron microscopy. Irradiations that partially damaged one homologous kinetochore caused the bivalent chromosome to shift to a new equilibrium position closer to the pole to which the unirradiated kinetochore was tethered; the greater the dose of irradiation, the farther the chromosome moved. The number of kMTs on the irradiated kinetochore decreased with severity of irradiation, while the number of kMTs on the unirradiated kinetochore remained constant and independent of chromosome-to-pole distance. Assuming a balance of forces on the chromosome at congression equilibrium, our results demonstrate that the net poleward force on a chromosome depends on the number of kMTs and the distance from the pole. In contrast, the velocity of chromosome movement showed little dependence on the number of kMTs. Possible mechanisms which explain the relationship between the poleward force at a kinetochore, the number of kinetochore microtubules, and the lengths of the kinetochore fibers at congression equilibrium include a traction fiber model in which poleward force producers are distributed along the length of the kinetochore fibers, or a kinetochore motor-polar ejection model in which force producers located at or near the kinetochore pull the chromosomes poleward along the kMTs and against an ejection force that is produced by the polar microtubule array and increases in strength toward the pole.

  11. CENP-T provides a structural platform for outer kinetochore assembly.

    Science.gov (United States)

    Nishino, Tatsuya; Rago, Florencia; Hori, Tetsuya; Tomii, Kentaro; Cheeseman, Iain M; Fukagawa, Tatsuo

    2013-02-06

    The kinetochore forms a dynamic interface with microtubules from the mitotic spindle during mitosis. The Ndc80 complex acts as the key microtubule-binding complex at kinetochores. However, it is unclear how the Ndc80 complex associates with the inner kinetochore proteins that assemble upon centromeric chromatin. Here, based on a high-resolution structural analysis, we demonstrate that the N-terminal region of vertebrate CENP-T interacts with the 'RWD' domain in the Spc24/25 portion of the Ndc80 complex. Phosphorylation of CENP-T strengthens a cryptic hydrophobic interaction between CENP-T and Spc25 resulting in a phospho-regulated interaction that occurs without direct recognition of the phosphorylated residue. The Ndc80 complex interacts with both CENP-T and the Mis12 complex, but we find that these interactions are mutually exclusive, supporting a model in which two distinct pathways target the Ndc80 complex to kinetochores. Our results provide a model for how the multiple protein complexes at kinetochores associate in a phospho-regulated manner.

  12. Dynein at kinetochores: Making the connection.

    Science.gov (United States)

    McHugh, Toni; Welburn, Julie P I

    2017-04-03

    Dynein removes the checkpoint proteins from kinetochores once chromosomes are bioriented. In this issue, Gama et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201610108) and Mosalaganti et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201611060) reveal the molecular basis for how dynein and its adaptor protein Spindly are recruited to the ROD-Zw10-Zwilch complex in the fibrous corona of unattached kinetochores. © 2017 McHugh and Welburn.

  13. The ultrastructure of the kinetochore and kinetochore fiber in Drosophila somatic cells

    Science.gov (United States)

    Hergert, Polla J.; Moutinho-Pereira, Sara; Dong, Yimin; Vandenbeldt, Kristin J.; Rieder, Conly L.; McEwen, Bruce F.

    2009-01-01

    Drosophila melanogaster is a widely used model organism for the molecular dissection of mitosis in animals. However, despite the popularity of this system, no studies have been published on the ultrastructure of Drosophila kinetochores and kinetochore fibers (K-fibers) in somatic cells. To amend this situation, we used correlative light (LM) and electron microscopy (EM) to study kinetochores in cultured Drosophila S2 cells during metaphase, and after colchicine treatment to depolymerize all microtubules (MTs). We find that the structure of attached kinetochores in S2 cells is indistinct, consisting of an amorphous inner zone associated with a more electron-dense peripheral surface layer that is approximately 40–50 nm thick. On average, each S2 kinetochore binds 11±2 MTs, in contrast to the 4–6 MTs per kinetochore reported for Drosophila spermatocytes. Importantly, nearly all of the kinetochore MT plus ends terminate in the peripheral surface layer, which we argue is analogous to the outer plate in vertebrate kinetochores. Our structural observations provide important data for assessing the results of RNAi studies of mitosis, as well as for the development of mathematical modelling and computer simulation studies in Drosophila and related organisms. PMID:16909258

  14. Budding yeast kinetochore proteins, Chl4 and Ctf19, are required to maintain SPB-centromere proximity during G1 and late anaphase.

    Directory of Open Access Journals (Sweden)

    Soumitra Sau

    Full Text Available In the budding yeast, centromeres stay clustered near the spindle pole bodies (SPBs through most of the cell cycle. This SPB-centromere proximity requires microtubules and functional kinetochores, which are protein complexes formed on the centromeres and capable of binding microtubules. The clustering is suggested by earlier studies to depend also on protein-protein interactions between SPB and kinetochore components. Previously it has been shown that the absence of non-essential kinetochore proteins of the Ctf19 complex weakens kinetochore-microtubule interaction, but whether this compromised interaction affects centromere/kinetochore positioning inside the nucleus is unknown. We found that in G1 and in late anaphase, SPB-centromere proximity was disturbed in mutant cells lacking Ctf19 complex members,Chl4p and/or Ctf19p, whose centromeres lay further away from their SPBs than those of the wild-type cells. We unequivocally show that the SPB-centromere proximity and distances are not dependent on physical interactions between SPB and kinetochore components, but involve microtubule-dependent forces only. Further insight on the positional difference between wild-type and mutant kinetochores was gained by generating computational models governed by (1 independently regulated, but constant kinetochore microtubule (kMT dynamics, (2 poleward tension on kinetochore and the antagonistic polar ejection force and (3 length and force dependent kMT dynamics. Numerical data obtained from the third model concurs with experimental results and suggests that the absence of Chl4p and/or Ctf19p increases the penetration depth of a growing kMT inside the kinetochore and increases the rescue frequency of a depolymerizing kMT. Both the processes result in increased distance between SPB and centromere.

  15. Budding Yeast Kinetochore Proteins, Chl4 and Ctf19, Are Required to Maintain SPB-Centromere Proximity during G1 and Late Anaphase

    Science.gov (United States)

    Sau, Soumitra; Sutradhar, Sabyasachi; Paul, Raja; Sinha, Pratima

    2014-01-01

    In the budding yeast, centromeres stay clustered near the spindle pole bodies (SPBs) through most of the cell cycle. This SPB-centromere proximity requires microtubules and functional kinetochores, which are protein complexes formed on the centromeres and capable of binding microtubules. The clustering is suggested by earlier studies to depend also on protein-protein interactions between SPB and kinetochore components. Previously it has been shown that the absence of non-essential kinetochore proteins of the Ctf19 complex weakens kinetochore-microtubule interaction, but whether this compromised interaction affects centromere/kinetochore positioning inside the nucleus is unknown. We found that in G1 and in late anaphase, SPB-centromere proximity was disturbed in mutant cells lacking Ctf19 complex members,Chl4p and/or Ctf19p, whose centromeres lay further away from their SPBs than those of the wild-type cells. We unequivocally show that the SPB-centromere proximity and distances are not dependent on physical interactions between SPB and kinetochore components, but involve microtubule-dependent forces only. Further insight on the positional difference between wild-type and mutant kinetochores was gained by generating computational models governed by (1) independently regulated, but constant kinetochore microtubule (kMT) dynamics, (2) poleward tension on kinetochore and the antagonistic polar ejection force and (3) length and force dependent kMT dynamics. Numerical data obtained from the third model concurs with experimental results and suggests that the absence of Chl4p and/or Ctf19p increases the penetration depth of a growing kMT inside the kinetochore and increases the rescue frequency of a depolymerizing kMT. Both the processes result in increased distance between SPB and centromere. PMID:25003500

  16. The Monopolin Complex Crosslinks Kinetochore Components to Regulate Chromosome-Microtubule Attachments

    Energy Technology Data Exchange (ETDEWEB)

    Corbett, Kevin D.; Yip, Calvin K.; Ee, Ly-Sha; Walz, Thomas; Amon, Angelika; Harrison, Stephen C. (Harvard-Med); (MIT)

    2010-09-27

    The monopolin complex regulates different types of kinetochore-microtubule attachments in fungi, ensuring sister chromatid co-orientation in Saccharomyces cerevisiae meiosis I and inhibiting merotelic attachment in Schizosaccharomyces pombe mitosis. In addition, the monopolin complex maintains the integrity and silencing of ribosomal DNA (rDNA) repeats in the nucleolus. We show here that the S. cerevisiae Csm1/Lrs4 monopolin subcomplex has a distinctive V-shaped structure, with two pairs of protein-protein interaction domains positioned {approx}10 nm apart. Csm1 presents a conserved hydrophobic surface patch that binds two kinetochore proteins: Dsn1, a subunit of the outer-kinetochore MIND/Mis12 complex, and Mif2/CENP-C. Csm1 point-mutations that disrupt kinetochore-subunit binding also disrupt sister chromatid co-orientation in S. cerevisiae meiosis I. We further show that the same Csm1 point-mutations affect rDNA silencing, probably by disrupting binding to the rDNA-associated protein Tof2. We propose that Csm1/Lrs4 functions as a molecular clamp, crosslinking kinetochore components to enforce sister chromatid co-orientation in S. cerevisiae meiosis I and to suppress merotelic attachment in S. pombe mitosis, and crosslinking rDNA repeats to aid rDNA silencing.

  17. The mitotic checkpoint kinase NEK2A regulates kinetochore microtubule attachment stability.

    Science.gov (United States)

    Du, J; Cai, X; Yao, J; Ding, X; Wu, Q; Pei, S; Jiang, K; Zhang, Y; Wang, W; Shi, Y; Lai, Y; Shen, J; Teng, M; Huang, H; Fei, Q; Reddy, E S; Zhu, J; Jin, C; Yao, X

    2008-07-03

    Loss or gain of whole chromosome, the form of chromosome instability commonly associated with cancers is thought to arise from aberrant chromosome segregation during cell division. Chromosome segregation in mitosis is orchestrated by the interaction of kinetochores with spindle microtubules. Our studies show that NEK2A is a kinetochore-associated protein kinase essential for faithful chromosome segregation. However, it was unclear how NEK2A ensures accurate chromosome segregation in mitosis. Here we show that NEK2A-mediated Hec1 (highly expressed in cancer) phosphorylation is essential for faithful kinetochore microtubule attachments in mitosis. Using phospho-specific antibody, our studies show that NEK2A phosphorylates Hec1 at Ser165 during mitosis. Although such phosphorylation is not required for assembly of Hec1 to the kinetochore, expression of non-phosphorylatable mutant Hec1(S165) perturbed chromosome congression and resulted in a dramatic increase in microtubule attachment errors, including syntelic and monotelic attachments. Our in vitro reconstitution experiment demonstrated that Hec1 binds to microtubule in low affinity and phosphorylation by NEK2A, which prevents aberrant kinetochore-microtubule connections in vivo, increases the affinity of the Ndc80 complex for microtubules in vitro. Thus, our studies illustrate a novel regulatory mechanism in which NEK2A kinase operates a faithful chromosome attachment to spindle microtubule, which prevents chromosome instability during cell division.

  18. Abnormal kinetochore-generated pulling forces from expressing a N-terminally modified Hec1.

    Directory of Open Access Journals (Sweden)

    Marta Mattiuzzo

    Full Text Available BACKGROUND: Highly Expressed in Cancer protein 1 (Hec1 is a constituent of the Ndc80 complex, a kinetochore component that has been shown to have a fundamental role in stable kinetochore-microtubule attachment, chromosome alignment and spindle checkpoint activation at mitosis. HEC1 RNA is found up-regulated in several cancer cells, suggesting a role for HEC1 deregulation in cancer. In light of this, we have investigated the consequences of experimentally-driven Hec1 expression on mitosis and chromosome segregation in an inducible expression system from human cells. METHODOLOGY/PRINCIPAL FINDINGS: Overexpression of Hec1 could never be obtained in HeLa clones inducibly expressing C-terminally tagged Hec1 or untagged Hec1, suggesting that Hec1 cellular levels are tightly controlled. On the contrary, a chimeric protein with an EGFP tag fused to the Hec1 N-terminus accumulated in cells and disrupted mitotic division. EGFP- Hec1 cells underwent altered chromosome segregation within multipolar spindles that originated from centriole splitting. We found that EGFP-Hec1 assembled a mutant Ndc80 complex that was unable to rescue the mitotic phenotypes of Hec1 depletion. Kinetochores harboring EGFP-Hec1 formed persisting lateral microtubule-kinetochore interactions that recruited the plus-end depolymerase MCAK and the microtubule stabilizing protein HURP on K-fibers. In these conditions the plus-end kinesin CENP-E was preferentially retained at kinetochores. RNAi-mediated CENP-E depletion further demonstrated that CENP-E function was required for multipolar spindle formation in EGFP-Hec1 expressing cells. CONCLUSIONS/SIGNIFICANCE: Our study suggests that modifications on Hec1 N-terminal tail can alter kinetochore-microtubule attachment stability and influence Ndc80 complex function independently from the intracellular levels of the protein. N-terminally modified Hec1 promotes spindle pole fragmentation by CENP-E-mediated plus-end directed kinetochore

  19. Kinetochore-microtubule attachment is sufficient to satisfy the human spindle assembly checkpoint

    NARCIS (Netherlands)

    Etemad, Banafsheh; Kuijt, Timo E F; Kops, Geert J P L

    2015-01-01

    The spindle assembly checkpoint (SAC) is a genome surveillance mechanism that protects against aneuploidization. Despite profound progress on understanding mechanisms of its activation, it remains unknown what aspect of chromosome-spindle interactions is monitored by the SAC: kinetochore-microtubule

  20. How the kinetochore couples microtubule force and centromere stretch to move chromosomes

    Science.gov (United States)

    Suzuki, Aussie; Badger, Benjamin L.; Haase, Julian; Ohashi, Tomoo; Erickson, Harold P.; Salmon, Edward D.; Bloom, Kerry

    2016-01-01

    Summary The Ndc80 complex (Ndc80, Nuf2, Spc24, Spc25) is a highly conserved kinetochore protein essential for end-on anchorage to spindle microtubule plus-ends and for force generation coupled to plus-end polymerization and depolymerization. Spc24/Spc25 at one end of the Ndc80 complex binds the kinetochore. The N-terminal tail and CH domains of Ndc80 bind microtubules, and an internal domain binds microtubule-associated proteins (MAPs) such as the Dam1 complex. To determine how the microtubule and MAP binding domains of Ndc80 contribute to force production at the kinetochore in budding yeast, we have inserted a FRET tension sensor into the Ndc80 protein about halfway between its microtubule binding and internal loop domains. The data support a mechanical model of force generation at metaphase where the position of the kinetochore relative to the microtubule plus-end reflects the relative strengths of microtubule depolymerization, centromere stretch and microtubule binding interactions with Ndc80 and Dam1 complexes. PMID:26974660

  1. Identification of novel mitosis regulators through data mining with human centromere/kinetochore proteins as group queries

    Directory of Open Access Journals (Sweden)

    Tipton Aaron R

    2012-06-01

    Full Text Available Abstract Background Proteins functioning in the same biological pathway tend to be transcriptionally co-regulated or form protein-protein interactions (PPI. Multiple spatially and temporally regulated events are coordinated during mitosis to achieve faithful chromosome segregation. The molecular players participating in mitosis regulation are still being unravelled experimentally or using in silico methods. Results An extensive literature review has led to a compilation of 196 human centromere/kinetochore proteins, all with experimental evidence supporting the subcellular localization. Sixty-four were designated as “core” centromere/kinetochore components based on peak expression and/or well-characterized functions during mitosis. By interrogating and integrating online resources, we have mined for genes/proteins that display transcriptional co-expression or PPI with the core centromere/kinetochore components. Top-ranked hubs in either co-expression or PPI network are not only enriched with known mitosis regulators, but also contain candidates whose mitotic functions are not yet established. Experimental validation found that KIAA1377 is a novel centrosomal protein that also associates with microtubules and midbody; while TRIP13 is a novel kinetochore protein and directly interacts with mitotic checkpoint silencing protein p31comet. Conclusions Transcriptional co-expression and PPI network analyses with known human centromere/kinetochore proteins as a query group help identify novel potential mitosis regulators.

  2. RWD domain: a recurring module in kinetochore architecture shown by a Ctf19-Mcm21 complex structure

    Energy Technology Data Exchange (ETDEWEB)

    Schmitzberger, Florian; Harrison, Stephen C [Harvard-Med

    2012-04-30

    The proteins Ctf19, Okp1, Mcm21 and Ame1 are the components of COMA, a subassembly of budding-yeast kinetochores. We have determined the crystal structure of a conserved COMA subcomplex - the Ctf19 - Mcm21 heterodimer - from Kluyveromyces lactis. Both proteins contain 'double-RWD' domains, which together form a Y-shaped framework with flexible N-terminal extensions. The kinetochore proteins Csm1, Spc24 and Spc25 have related single RWD domains, and Ctf19 and Mcm21 associate with pseudo-twofold symmetry analogous to that in the Csm1 homodimer and the Spc24-Spc25 heterodimer. The double-RWD domain core of the Ctf19-Mcm21 heterodimer is sufficient for association with Okp1-Ame1; the less conserved N-terminal regions may interact with components of a more extensive 'CTF19 complex'. Our structure shows the RWD domain to be a recurring module of kinetochore architecture that may be present in other kinetochore substructures. Like many eukaryotic molecular machines, kinetochores may have evolved from simpler assemblies by multiplication of a few ancestral modules.

  3. RWD domain: a recurring module in kinetochore architecture shown by a Ctf19-Mcm21 complex structure.

    Science.gov (United States)

    Schmitzberger, Florian; Harrison, Stephen C

    2012-03-01

    The proteins Ctf19, Okp1, Mcm21 and Ame1 are the components of COMA, a subassembly of budding-yeast kinetochores. We have determined the crystal structure of a conserved COMA subcomplex--the Ctf19-Mcm21 heterodimer--from Kluyveromyces lactis. Both proteins contain 'double-RWD' domains, which together form a Y-shaped framework with flexible N-terminal extensions. The kinetochore proteins Csm1, Spc24 and Spc25 have related single RWD domains, and Ctf19 and Mcm21 associate with pseudo-twofold symmetry analogous to that in the Csm1 homodimer and the Spc24-Spc25 heterodimer. The double-RWD domain core of the Ctf19-Mcm21 heterodimer is sufficient for association with Okp1-Ame1; the less conserved N-terminal regions may interact with components of a more extensive 'CTF19 complex'. Our structure shows the RWD domain to be a recurring module of kinetochore architecture that may be present in other kinetochore substructures. Like many eukaryotic molecular machines, kinetochores may have evolved from simpler assemblies by multiplication of a few ancestral modules.

  4. CLIP-170 facilitates the formation of kinetochore-microtubule attachments

    NARCIS (Netherlands)

    Tanenbaum, M.E.; Galjart, N.; Vugt, M.A.T.M. van; Medema, R.H.

    2006-01-01

    CLIP-170 is a microtubule 'plus end tracking' protein involved in several microtubule-dependent processes in interphase. At the onset of mitosis, CLIP-170 localizes to kinetochores, but at metaphase, it is no longer detectable at kinetochores. Although RNA interference (RNAi) experiments have

  5. Sister kinetochores are mechanically fused during meiosis I in yeast.

    Science.gov (United States)

    Sarangapani, Krishna K; Duro, Eris; Deng, Yi; Alves, Flavia de Lima; Ye, Qiaozhen; Opoku, Kwaku N; Ceto, Steven; Rappsilber, Juri; Corbett, Kevin D; Biggins, Sue; Marston, Adèle L; Asbury, Charles L

    2014-10-10

    Production of healthy gametes requires a reductional meiosis I division in which replicated sister chromatids comigrate, rather than separate as in mitosis or meiosis II. Fusion of sister kinetochores during meiosis I may underlie sister chromatid comigration in diverse organisms, but direct evidence for such fusion has been lacking. We used laser trapping and quantitative fluorescence microscopy to study native kinetochore particles isolated from yeast. Meiosis I kinetochores formed stronger attachments and carried more microtubule-binding elements than kinetochores isolated from cells in mitosis or meiosis II. The meiosis I-specific monopolin complex was both necessary and sufficient to drive these modifications. Thus, kinetochore fusion directs sister chromatid comigration, a conserved feature of meiosis that is fundamental to Mendelian inheritance. Copyright © 2014, American Association for the Advancement of Science.

  6. Development of kinetochores during early mitosis in HeLa cells and the stability of a trilaminar kinetochore structure

    Energy Technology Data Exchange (ETDEWEB)

    Schroeter, D.; Paweletz, N.; Finze, E.M.; Kiesewetter, U.L. [German Cancer Research Center, Heidelberg (Germany)

    1993-12-31

    The ultrastructure of the kinetochore varies during the course of mitosis. This variation is considered to be a progressive maturation process that may correlate with kinetochore function. We examined the development of kinetochore structures on condensing prophase chromosomes in HeLa cells. Usually, one accepts the three laminar structure of the kinetochore of a condensed metaphase chromosome to reflect the general state and to be a prerequisite for microtubule attachment. The study of developing kinetochores in mitotic cells revealed unquestionable exceptions from this dogma. At the onset of chromatin condensation, indicating the beginning of prophase, the nuclear envelope and the nucleoli are still intact. First indications for kinetochore formation, documented as clouds of a fibrous material or as the {open_quotes}kinetochore ball structure{close_quotes} can be identified along or close to distinct heterochromatic, condensed chromatin elements. These fibrils extend from or interdigitate with the folding chromatin. Enhanced density of the ball structure represents a condensation process. Concomitantly a segregation of a plate structure is detected, occuring at a distal zone but obviously not at the end of the fibrils. This differentiation into kinetochore plate and corona more or less coincides with two other important prophase processes: the first tangential contacts to single microtubules and the mitotic breakdown of the nuclear envelope. But evidence will be discussed that these early prophase features not necessarily depend on each other and that the formation of a characteristic, trilaminar kinetochore structure does not guarantee its function. Conversely, structurally incomplete kinetochores can establish microtubular contacts for the attachment of chromosomes into the spindle.

  7. Plc1p is required for proper chromatin structure and activity of the kinetochore in Saccharomyces cerevisiae by facilitating recruitment of the RSC complex.

    Science.gov (United States)

    Desai, Parima; Guha, Nilanjan; Galdieri, Luciano; Hadi, Sara; Vancura, Ales

    2009-05-01

    High-fidelity chromosome segregation during mitosis requires kinetochores, protein complexes that assemble on centromeric DNA and mediate chromosome attachment to spindle microtubules. In budding yeast, phosphoinositide-specific phospholipase C (Plc1p encoded by PLC1 gene) is important for function of kinetochores. Deletion of PLC1 results in alterations in chromatin structure of centromeres, reduced binding of microtubules to minichromosomes, and a higher frequency of chromosome loss. The mechanism of Plc1p's involvement in kinetochore activity was not initially obvious; however, a testable hypothesis emerged with the discovery of the role of inositol polyphosphates (InsPs), produced by a Plc1p-dependent pathway, in the regulation of chromatin-remodeling complexes. In addition, the remodels structure of chromatin (RSC) chromatin-remodeling complex was found to associate with kinetochores and to affect centromeric chromatin structure. We report here that Plc1p and InsPs are required for recruitment of the RSC complex to kinetochores, which is important for establishing proper chromatin structure of centromeres and centromere proximal regions. Mutations in PLC1 and components of the RSC complex exhibit strong genetic interactions and display synthetic growth defect, altered nuclear morphology, and higher frequency of minichromosome loss. The results thus provide a mechanistic explanation for the previously elusive role of Plc1p and InsPs in kinetochore function.

  8. The Drosophila orthologue of the INT6 onco-protein regulates mitotic microtubule growth and kinetochore structure.

    Directory of Open Access Journals (Sweden)

    Fioranna Renda

    2017-05-01

    Full Text Available INT6/eIF3e is a highly conserved component of the translation initiation complex that interacts with both the 26S proteasome and the COP9 signalosome, two complexes implicated in ubiquitin-mediated protein degradation. The INT6 gene was originally identified as the insertion site of the mouse mammary tumor virus (MMTV, and later shown to be involved in human tumorigenesis. Here we show that depletion of the Drosophila orthologue of INT6 (Int6 results in short mitotic spindles and deformed centromeres and kinetochores with low intra-kinetochore distance. Poleward flux of microtubule subunits during metaphase is reduced, although fluorescence recovery after photobleaching (FRAP demonstrates that microtubules remain dynamic both near the kinetochores and at spindle poles. Mitotic progression is delayed during metaphase due to the activity of the spindle assembly checkpoint (SAC. Interestingly, a deubiquitinated form of the kinesin Klp67A (a putative orthologue of human Kif18A accumulates near the kinetochores in Int6-depleted cells. Consistent with this finding, Klp67A overexpression mimics the Int6 RNAi phenotype. Furthermore, simultaneous depletion of Int6 and Klp67A results in a phenotype identical to RNAi of just Klp67A, which indicates that Klp67A deficiency is epistatic over Int6 deficiency. We propose that Int6-mediated ubiquitination is required to control the activity of Klp67A. In the absence of this control, excess of Klp67A at the kinetochore suppresses microtubule plus-end polymerization, which in turn results in reduced microtubule flux, spindle shortening, and centromere/kinetochore deformation.

  9. A new piece in the kinetochore jigsaw puzzle.

    Science.gov (United States)

    Corbett, Kevin D; Desai, Arshad

    2014-08-18

    In eukaryotic cell division, the kinetochore mediates chromosome attachment to spindle microtubules and acts as a scaffold for signaling pathways, ensuring the accuracy of chromosome segregation. The architecture of the kinetochore underlies its function in mitosis. In this issue, Hornung et al. (2014. J. Cell Biol. http://dx.doi.org/201403081) identify an unexpected linkage between the inner and outer regions of the kinetochore in budding yeast that suggests a new model for the construction of this interface. © 2014 Corbett and Desai.

  10. Micronuclei with kinetochores in human melanoma cells and rectal carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Weissenborn, U.; Streffer, C. (Essen Univ. (Gesamthochschule) (Germany, F.R.). Inst. fuer Medizinische Strahlenbiologie)

    1991-02-01

    Micronucleus frequencies were analysed in an X-irradiated human melanoma cell line and in untreated rectal carcinoma cells. As a special aspect of the micronucleus formation, micronuclei-containing kinetochores were analysed by the method of indirect immunofluorescence. The incidence of kinetochore-positive micronuclei was taken as a measure of chromosome loss. The authors have attempted to summarize the data by means of a numerical expression which takes into account the relation between lost chromosomes, visible as kinetochore-positive micronuclei, and the total sum of micronuclei. (author).

  11. Differences in the origins of kinetochore-positive and kinetochore-negative micronuclei: A live cell imaging study

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Erkang, E-mail: erkangj@ustc.edu.cn

    2016-05-15

    Highlights: • Most Kinetochore-negative micronuclei were derived from kinetochore-negative displaced chromosomes, kinetochore-negative lagging chromosomes and fragments of broken chromosome bridges in mitosis of MN-free cells. • Most Kinetochore-positive micronuclei were derived from kinetochore-positive displaced chromosomes, kinetochore-positive lagging chromosomes and fragments of broken chromosome bridges in mitosis of MN-free cells. • Kinetochore-positive lagging chromosomes developed into kinetochore-positive micronuclei at the higher frequency than kinetochore-positive displaced chromosomes, kinetochore-negative lagging chromosomes developed into kinetochore-negative micronuclei at the higher rate than kinetochore-negative displaced chromosomes and broken chromosome bridges produced K−MNi and/or K+MNi. - Abstract: Micronuclei (MNi) are extensively used to evaluate genotoxicity and chromosomal instability. Classification of kinetochore-negative (K−MNi) and kinetochore-positive micronuclei (K+MNi) improves the specificity and sensitivity of the micronucleus (MN) test; however, the fundamental differences in the origins of K−MNi and K+MNi have not been addressed due to the limitations of traditional methods. In the current study, HeLa CENP B-GFP H2B-mCherry cells were constructed in which histone 2B (H2B) and centromere protein B (CENP B) were expressed as fusion proteins to monomeric Cherry (mCherry) and EGFP, respectively. MNi were identified using H2B-mCherry; K+MN contained CENP B-GFP, while K−MN did not. Long-term live cell imaging was conducted to examine MN formation in the dual-color fluorescent HeLa cells. The results suggested that K−MNi were derived from kinetochore-negative displaced chromosomes (K−DCs), kinetochore-negative lagging chromosomes (K−LCs) and fragments of broken chromosome bridges (CBs) during late mitotic stages. The results also indicated that K+MNi are derived from kinetochore-positive displaced chromosomes (K

  12. Mechanisms to Avoid and Correct Erroneous Kinetochore-Microtubule Attachments

    Directory of Open Access Journals (Sweden)

    Michael A. Lampson

    2017-01-01

    Full Text Available In dividing vertebrate cells multiple microtubules must connect to mitotic kinetochores in a highly stereotypical manner, with each sister kinetochore forming microtubule attachments to only one spindle pole. The exact sequence of events by which this goal is achieved varies considerably from cell to cell because of the variable locations of kinetochores and spindle poles, and randomness of initial microtubule attachments. These chance encounters with the kinetochores nonetheless ultimately lead to the desired outcome with high fidelity and in a limited time frame, providing one of the most startling examples of biological self-organization. This chapter discusses mechanisms that contribute to accurate chromosome segregation by helping dividing cells to avoid and resolve improper microtubule attachments.

  13. The centromere: chromatin foundation for the kinetochore machinery

    National Research Council Canada - National Science Library

    Fukagawa, Tatsuo; Earnshaw, William C

    2014-01-01

    Since discovery of the centromere-specific histone H3 variant CENP-A, centromeres have come to be defined as chromatin structures that establish the assembly site for the complex kinetochore machinery...

  14. Ndc10 is a platform for inner kinetochore assembly in budding yeast

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Uhn-Soo; Harrison, Stephen C. (Harvard-Med)

    2012-01-10

    Kinetochores link centromeric DNA to spindle microtubules and ensure faithful chromosome segregation during mitosis. In point-centromere yeasts, the CBF3 complex Skp1-Ctf13-(Cep3){sub 2}-(Ndc10){sub 2} recognizes a conserved centromeric DNA element through contacts made by Cep3 and Ndc10. We describe here the five-domain organization of Kluyveromyces lactis Ndc10 and the structure at 2.8 {angstrom} resolution of domains I-II (residues 1-402) bound to DNA. The structure resembles tyrosine DNA recombinases, although it lacks both endonuclease and ligase activities. Structural and biochemical data demonstrate that each subunit of the Ndc10 dimer binds a separate fragment of DNA, suggesting that Ndc10 stabilizes a DNA loop at the centromere. We describe in vitro association experiments showing that specific domains of Ndc10 interact with each of the known inner-kinetochore proteins or protein complexes in budding yeast. We propose that Ndc10 provides a central platform for inner-kinetochore assembly.

  15. The CENP-A NAC/CAD kinetochore complex controls chromosome congression and spindle bipolarity.

    Science.gov (United States)

    McClelland, Sarah E; Borusu, Satyarebala; Amaro, Ana C; Winter, Jennifer R; Belwal, Mukta; McAinsh, Andrew D; Meraldi, Patrick

    2007-12-12

    Kinetochores are complex protein machines that link chromosomes to spindle microtubules and contain a structural core composed of two conserved protein-protein interaction networks: the well-characterized KMN (KNL1/MIND/NDC80) and the recently identified CENP-A NAC/CAD. Here we show that the CENP-A NAC/CAD subunits can be assigned to one of two different functional classes; depletion of Class I proteins (Mcm21R(CENP-O) and Fta1R(CENP-L)) causes a failure in bipolar spindle assembly. In contrast, depletion of Class II proteins (CENP-H, Chl4R(CENP-N), CENP-I and Sim4R(CENP-K)) prevents binding of Class I proteins and causes chromosome congression defects, but does not perturb spindle formation. Co-depletion of Class I and Class II proteins restores spindle bipolarity, suggesting that Class I proteins regulate or counteract the function of Class II proteins. We also demonstrate that CENP-A NAC/CAD and KMN regulate kinetochore-microtubule attachments independently, even though CENP-A NAC/CAD can modulate NDC80 levels at kinetochores. Based on our results, we propose that the cooperative action of CENP-A NAC/CAD subunits and the KMN network drives efficient chromosome segregation and bipolar spindle assembly during mitosis.

  16. Bub1 targeting to centromeres is sufficient for Sgo1 recruitment in the absence of kinetochores.

    Science.gov (United States)

    Williams, Samantha J; Abrieu, Ariane; Losada, Ana

    2017-03-01

    Centromeric chromatin containing the histone H3 variant centromere protein A (CENP-A) directs kinetochore assembly through a hierarchical binding of CENPs, starting with CENP-C and CENP-T. Centromeres are also the chromosomal regions where cohesion, mediated by cohesin, is most prominently maintained in mitosis. While most cohesin dissociates from chromosome arms in prophase, Shugoshin 1 (Sgo1) prevents this process at centromeres. Centromeric localization of Sgo1 depends on histone H2A phosphorylation by the kinase Bub1, but whether additional interactions with kinetochore components are required for Sgo1 recruitment is unclear. Using the Xenopus egg cell-free system, we here show that both CENP-C and CENP-T can independently drive centromeric accumulation of Sgo1 through recruitment of Bub1 to the KNL1, MIS12, NDC80 (KMN) network. The spindle assembly checkpoint (SAC) kinase Mps1 is also required for this pathway even in the absence of checkpoint signaling. Sgo1 recruitment is abolished in chromosomes lacking kinetochore components other than CENP-A. However, forced targeting of Bub1 to centromeres is sufficient to restore Sgo1 localization under this condition.

  17. RED, a Spindle Pole-associated Protein, Is Required for Kinetochore Localization of MAD1, Mitotic Progression, and Activation of the Spindle Assembly Checkpoint*

    Science.gov (United States)

    Yeh, Pei-Chi; Yeh, Chang-Ching; Chen, Yi-Cheng; Juang, Yue-Li

    2012-01-01

    The spindle assembly checkpoint (SAC) is essential for ensuring the proper attachment of kinetochores to the spindle and, thus, the precise separation of paired sister chromatids during mitosis. The SAC proteins are recruited to the unattached kinetochores for activation of the SAC in prometaphase. However, it has been less studied whether activation of the SAC also requires the proteins that do not localize to the kinetochores. Here, we show that the nuclear protein RED, also called IK, a down-regulator of human leukocyte antigen (HLA) II, interacts with the human SAC protein MAD1. Two RED-interacting regions identified in MAD1 are from amino acid residues 301–340 and 439–480, designated as MAD1(301–340) and MAD1(439–480), respectively. Our observations reveal that RED is a spindle pole-associated protein that colocalizes with MAD1 at the spindle poles in metaphase and anaphase. Depletion of RED can cause a shorter mitotic timing, a failure in the kinetochore localization of MAD1 in prometaphase, and a defect in the SAC. Furthermore, the RED-interacting peptides MAD1(301–340) and MAD1(439–480), fused to enhanced green fluorescence protein, can colocalize with RED at the spindle poles in prometaphase, and their expression can abrogate the SAC. Taken together, we conclude that RED is required for kinetochore localization of MAD1, mitotic progression, and activation of the SAC. PMID:22351768

  18. Microtubule Sliding within the Bridging Fiber Pushes Kinetochore Fibers Apart to Segregate Chromosomes.

    Science.gov (United States)

    Vukušić, Kruno; Buđa, Renata; Bosilj, Agneza; Milas, Ana; Pavin, Nenad; Tolić, Iva M

    2017-10-09

    During cell division, mitotic spindle microtubules segregate chromosomes by exerting forces on kinetochores. What forces drive chromosome segregation in anaphase remains a central question. The current model for anaphase in human cells includes shortening of kinetochore fibers and separation of spindle poles. Both processes require kinetochores to be linked with the poles. Here we show, by combining laser ablation, photoactivation, and theoretical modeling, that kinetochores can separate without any attachment to one spindle pole. This separation requires the bridging fiber, a microtubule bundle that connects sister kinetochore fibers. Bridging fiber microtubules in intact spindles slide apart with kinetochore fibers, indicating strong crosslinks between them. We conclude that sliding of microtubules within the bridging fibers drives pole separation and pushes kinetochore fibers poleward by the friction of passive crosslinks between these fibers. Thus, sliding within the bridging fiber works together with the shortening of kinetochore fibers to segregate chromosomes. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  19. Synergistic Control of Kinetochore Protein Levels by Psh1 and Ubr2.

    Directory of Open Access Journals (Sweden)

    Eva Herrero

    2016-02-01

    Full Text Available The accurate segregation of chromosomes during cell division is achieved by attachment of chromosomes to the mitotic spindle via the kinetochore, a large multi-protein complex that assembles on centromeres. The budding yeast kinetochore comprises more than 60 different proteins. Although the structure and function of many of these proteins has been investigated, we have little understanding of the steady state regulation of kinetochores. The primary model of kinetochore homeostasis suggests that kinetochores assemble hierarchically from the centromeric DNA via the inclusion of a centromere-specific histone into chromatin. We tested this model by trying to perturb kinetochore protein levels by overexpressing an outer kinetochore gene, MTW1. This increase in protein failed to change protein recruitment, consistent with the hierarchical assembly model. However, we find that deletion of Psh1, a key ubiquitin ligase that is known to restrict inner kinetochore protein loading, does not increase levels of outer kinetochore proteins, thus breaking the normal kinetochore stoichiometry. This perturbation leads to chromosome segregation defects, which can be partially suppressed by mutation of Ubr2, a second ubiquitin ligase that normally restricts protein levels at the outer kinetochore. Together these data show that Psh1 and Ubr2 synergistically control the amount of proteins at the kinetochore.

  20. Sequential multisite phospho-regulation of KNL1-BUB3 interfaces at mitotic kinetochores

    NARCIS (Netherlands)

    Vleugel, Mathijs; Omerzu, Manja; Groenewold, Vincent; Hadders, Michael A; Lens, Susanne M A; Kops, Geert J P L

    2015-01-01

    Regulated recruitment of the kinase-adaptor complex BUB1/BUB3 to kinetochores is crucial for correcting faulty chromosome-spindle attachments and for spindle assembly checkpoint (SAC) signaling. BUB1/BUB3 localizes to kinetochores by binding phosphorylated MELT motifs (MELpT) in the kinetochore

  1. The Ndc80 internal loop is required for recruitment of the Ska complex to establish end-on microtubule attachment to kinetochores

    DEFF Research Database (Denmark)

    Zhang, Gang; Kelstrup, Christian D; Hu, Xiao-Wen

    2012-01-01

    The Ndc80 complex establishes end-on attachment of kinetochores to microtubules essential for chromosome segregation. The Ndc80 subunit is characterized by an N-terminal region, that binds directly to microtubules, and a long coiled-coil region that interacts with Nuf2. A loop region in Ndc80...... that generates a kink in the structure disrupts the long coiled-coil region but the exact function of this loop is not clear.Here we show that this loop region is essential for end-on attachment of kinetochores to microtubules in human cells. Cells expressing loop mutants of Ndc80 are unable to align...... the chromosomes and stable kinetochore fibers are absent. Through quantitative mass spectrometry and immunofluorescence we find that the binding of the Ska complex depends on the loop region explaining why end-on attachment is defective. This underscores the importance of the Ndc80 loop region in coordinating...

  2. Dynein/Dynactin-mediated transport of kinetochore components off kinetochores and onto spindle poles induced by nordihydroguaiaretic acid.

    Directory of Open Access Journals (Sweden)

    Jakub K Famulski

    2011-01-01

    Full Text Available The mitotic checkpoint functions to ensure accurate chromosome segregation by regulating the progression from metaphase to anaphase. Once the checkpoint has been satisfied, it is inactivated in order to allow the cell to proceed into anaphase and complete the cell cycle. The minus end-directed microtubule motor dynein/dynactin has been implicated in the silencing of the mitotic checkpoint by "stripping" checkpoint proteins off kinetochores. A recent study suggested that Nordihydroguaiaretic acid (NDGA stimulates dynein/dynactin-mediated transport of its cargo including ZW10 (Zeste White 10. We analyzed the effects of NDGA on dynein/dynactin dependent transport of the RZZ (Zeste White 10, Roughdeal, Zwilch complex as well as other kinetochore components from kinetochores to spindle poles. Through this approach we have catalogued several kinetochore and centromere components as dynein/dynactin cargo. These include hZW10, hZwilch, hROD, hSpindly, hMad1, hMad2, hCENP-E, hCdc27, cyclin-B and hMps1. Furthermore, we found that treatment with NDGA induced a robust accumulation and complete stabilization of hZW10 at spindle poles. This finding suggests that NDGA may not induce dynein/dynactin transport but rather interfere with cargo release. Lastly, we determined that NDGA induced accumulation of checkpoint proteins at the poles requires dynein/dynactin-mediated transport, hZW10 kinetochore localization and kinetochore-microtubule attachments but not tension or Aurora B kinase activity.

  3. KiT: a MATLAB package for kinetochore tracking.

    Science.gov (United States)

    Armond, Jonathan W; Vladimirou, Elina; McAinsh, Andrew D; Burroughs, Nigel J

    2016-06-15

    During mitosis, chromosomes are attached to the mitotic spindle via large protein complexes called kinetochores. The motion of kinetochores throughout mitosis is intricate and automated quantitative tracking of their motion has already revealed many surprising facets of their behaviour. Here, we present 'KiT' (Kinetochore Tracking)-an easy-to-use, open-source software package for tracking kinetochores from live-cell fluorescent movies. KiT supports 2D, 3D and multi-colour movies, quantification of fluorescence, integrated deconvolution, parallel execution and multiple algorithms for particle localization. KiT is free, open-source software implemented in MATLAB and runs on all MATLAB supported platforms. KiT can be downloaded as a package from http://www.mechanochemistry.org/mcainsh/software.php The source repository is available at https://bitbucket.org/jarmond/kit and under continuing development. Supplementary data are available at Bioinformatics online. jonathan.armond@warwick.ac.uk. © The Author 2016. Published by Oxford University Press.

  4. The kinetochore is an enhancer of pericentric cohesin binding.

    Directory of Open Access Journals (Sweden)

    Stewart A Weber

    2004-09-01

    Full Text Available The recruitment of cohesins to pericentric chromatin in some organisms appears to require heterochromatin associated with repetitive DNA. However, neocentromeres and budding yeast centromeres lack flanking repetitive DNA, indicating that cohesin recruitment occurs through an alternative pathway. Here, we demonstrate that all budding yeast chromosomes assemble cohesin domains that extend over 20-50 kb of unique pericentric sequences flanking the conserved 120-bp centromeric DNA. The assembly of these cohesin domains requires the presence of a functional kinetochore in every cell cycle. A similar enhancement of cohesin binding was also observed in regions flanking an ectopic centromere. At both endogenous and ectopic locations, the centromeric enhancer amplified the inherent levels of cohesin binding that are unique to each region. Thus, kinetochores are enhancers of cohesin association that act over tens of kilobases to assemble pericentric cohesin domains. These domains are larger than the pericentric regions stretched by microtubule attachments, and thus are likely to counter microtubule-dependent forces. Kinetochores mediate two essential segregation functions: chromosome movement through microtubule attachment and biorientation of sister chromatids through the recruitment of high levels of cohesin to pericentric regions. We suggest that the coordination of chromosome movement and biorientation makes the kinetochore an autonomous segregation unit.

  5. EZH2 is required for mouse oocyte meiotic maturation by interacting with and stabilizing spindle assembly checkpoint protein BubRI

    Science.gov (United States)

    Qu, Yi; Lu, Danyu; Jiang, Hao; Chi, Xiaochun; Zhang, Hongquan

    2016-01-01

    Enhancer of zeste homolog 2 (EZH2) trimethylates histone H3 Lys 27 and plays key roles in a variety of biological processes. Stability of spindle assembly checkpoint protein BubR1 is essential for mitosis in somatic cells and for meiosis in oocytes. However, the role of EZH2 in oocyte meiotic maturation was unknown. Here, we presented a mechanism underlying EZH2 control of BubR1 stability in the meiosis of mouse oocytes. We identified a methyltransferase activity-independent function of EZH2 by demonstrating that EZH2 regulates spindle assembly and the polar body I extrusion. EZH2 was increased with the oocyte progression from GVBD to MII, while EZH2 was concentrated on the chromosomes. Interestingly, inhibition of EZH2 methyltranferase activity by DZNep or GSK343 did not affect oocyte meiotic maturation. However, depletion of EZH2 by morpholino led to chromosome misalignment and abnormal spindle assembly. Furthermore, ectopic expression of EZH2 led to oocyte meiotic maturation arrested at the MI stage followed by chromosome misalignment and aneuploidy. Mechanistically, EZH2 directly interacted with and stabilized BubR1, an effect driving EZH2 into the concert of meiosis regulation. Collectively, we provided a paradigm that EZH2 is required for mouse oocyte meiotic maturation. PMID:27226494

  6. Flow cytometry measurements of human chromosome kinetochore labeling

    Energy Technology Data Exchange (ETDEWEB)

    Fantes, J.A.; Green, D.K.; Malloy, P.; Sumner, A.T.

    1989-03-01

    A method for the preparation and measurement of immunofluorescent human chromosome centromeres in suspension is described using CREST antibodies, which bind to the centromeric region of chromosomes. Fluorescein isothiocyanate (FITC)-conjugated antihuman antibodies provide the fluorescent label. Labeled chromosomes are examined on microscope slides and by flow cytometry. In both cases a dye which binds to DNA is added to provide identification of the chromosome groups. Sera from different CREST patients vary in their ability to bind to chromosome arms in addition to the centromeric region. Flow cytometry and microfluorimetry measurements have shown that with a given CREST serum the differences in kinetochore fluorescence between chromosomes are only minor. Flow cytometry experiments to relate the number of dicentric chromosomes, induced by in vitro radiation of peripheral blood cells to the slightly increased number of chromosomes with above-average kinetochore fluorescence did not produce decisive radiation dosimetry results.

  7. A sequential multi-target Mps1 phosphorylation cascade promotes spindle checkpoint signaling

    OpenAIRE

    Ji, Zhejian; Gao, Haishan; Jia, Luying; Li, Bing; Yu, Hongtao

    2017-01-01

    The master spindle checkpoint kinase Mps1 senses kinetochore-microtubule attachment and promotes checkpoint signaling to ensure accurate chromosome segregation. The kinetochore scaffold Knl1, when phosphorylated by Mps1, recruits checkpoint complexes Bub1?Bub3 and BubR1?Bub3 to unattached kinetochores. Active checkpoint signaling ultimately enhances the assembly of the mitotic checkpoint complex (MCC) consisting of BubR1?Bub3, Mad2, and Cdc20, which inhibits the anaphase-promoting complex or ...

  8. Evolutionary dynamics of the kinetochore network in eukaryotes as revealed by comparative genomics

    NARCIS (Netherlands)

    van Hooff, Jolien Je; Tromer, Eelco; van Wijk, Leny; Snel, Berend; Kops, Geert Jpl

    2017-01-01

    During eukaryotic cell division, the sister chromatids of duplicated chromosomes are pulled apart by microtubules, which connect via kinetochores. The kinetochore is a multiprotein structure that links centromeres to microtubules, and that emits molecular signals in order to safeguard the equal

  9. Evolution and regulation of mitotic checkpoint protein recruitment by the kinetochore scaffold KNL1

    NARCIS (Netherlands)

    Vleugel, M.

    2014-01-01

    Faithful chromosome segregation in mitosis depends on a tight coordination between the formation of proper kinetochore-microtubule attachments and mitotic checkpoint (MC) activation and silencing. The outer kinetochore scaffold KNL1 plays an essential integrative role in these processes since it

  10. Fibrils connect microtubule tips with kinetochores: a mechanism to couple tubulin dynamics to chromosome motion.

    Science.gov (United States)

    McIntosh, J Richard; Grishchuk, Ekaterina L; Morphew, Mary K; Efremov, Artem K; Zhudenkov, Kirill; Volkov, Vladimir A; Cheeseman, Iain M; Desai, Arshad; Mastronarde, David N; Ataullakhanov, Fazly I

    2008-10-17

    Kinetochores of mitotic chromosomes are coupled to spindle microtubules in ways that allow the energy from tubulin dynamics to drive chromosome motion. Most kinetochore-associated microtubule ends display curving "protofilaments," strands of tubulin dimers that bend away from the microtubule axis. Both a kinetochore "plate" and an encircling, ring-shaped protein complex have been proposed to link protofilament bending to poleward chromosome motion. Here we show by electron tomography that slender fibrils connect curved protofilaments directly to the inner kinetochore. Fibril-protofilament associations correlate with a local straightening of the flared protofilaments. Theoretical analysis reveals that protofilament-fibril connections would be efficient couplers for chromosome motion, and experimental work on two very different kinetochore components suggests that filamentous proteins can couple shortening microtubules to cargo movements. These analyses define a ring-independent mechanism for harnessing microtubule dynamics directly to chromosome movement.

  11. Mechanism for G2 phase-specific nuclear export of the kinetochore protein CENP-F.

    Science.gov (United States)

    Loftus, Kyle M; Cui, Heying; Coutavas, Elias; King, David S; Ceravolo, Amanda; Pereiras, Dylan; Solmaz, Sozanne R

    2017-08-03

    Centromere protein F (CENP-F) is a component of the kinetochore and a regulator of cell cycle progression. CENP-F recruits the dynein transport machinery and orchestrates several cell cycle-specific transport events, including transport of the nucleus, mitochondria and chromosomes. A key regulatory step for several of these functions is likely the G2 phase-specific export of CENP-F from the nucleus to the cytosol, where the cytoplasmic dynein transport machinery resides; however, the molecular mechanism of this process is elusive. Here, we have identified 3 phosphorylation sites within the bipartite classical nuclear localization signal (cNLS) of CENP-F. These sites are specific for cyclin-dependent kinase 1 (Cdk1), which is active in G2 phase. Phosphomimetic mutations of these residues strongly diminish the interaction of the CENP-F cNLS with its nuclear transport receptor karyopherin α. These mutations also diminish nuclear localization of the CENP-F cNLS in cells. Notably, the cNLS is phosphorylated in the -1 position, which is important to orient the adjacent major motif for binding into its pocket on karyopherin α. We propose that localization of CENP-F is regulated by a cNLS, and a nuclear export pathway, resulting in nuclear localization during most of interphase. In G2 phase, the cNLS is weakened by phosphorylation through Cdk1, likely resulting in nuclear export of CENP-F via the still active nuclear export pathway. Once CENP-F resides in the cytosol, it can engage in pathways that are important for cell cycle progression, kinetochore assembly and the faithful segregation of chromosomes into daughter cells.

  12. Kinetochore-microtubule attachment throughout mitosis potentiated by the elongated stalk of the kinetochore kinesin CENP-E.

    Science.gov (United States)

    Vitre, Benjamin; Gudimchuk, Nikita; Borda, Ranier; Kim, Yumi; Heuser, John E; Cleveland, Don W; Grishchuk, Ekaterina L

    2014-08-01

    Centromere protein E (CENP-E) is a highly elongated kinesin that transports pole-proximal chromosomes during congression in prometaphase. During metaphase, it facilitates kinetochore-microtubule end-on attachment required to achieve and maintain chromosome alignment. In vitro CENP-E can walk processively along microtubule tracks and follow both growing and shrinking microtubule plus ends. Neither the CENP-E-dependent transport along microtubules nor its tip-tracking activity requires the unusually long coiled-coil stalk of CENP-E. The biological role for the CENP-E stalk has now been identified through creation of "Bonsai" CENP-E with significantly shortened stalk but wild-type motor and tail domains. We demonstrate that Bonsai CENP-E fails to bind microtubules in vitro unless a cargo is contemporaneously bound via its C-terminal tail. In contrast, both full-length and truncated CENP-E that has no stalk and tail exhibit robust motility with and without cargo binding, highlighting the importance of CENP-E stalk for its activity. Correspondingly, kinetochore attachment to microtubule ends is shown to be disrupted in cells whose CENP-E has a shortened stalk, thereby producing chromosome misalignment in metaphase and lagging chromosomes during anaphase. Together these findings establish an unexpected role of CENP-E elongated stalk in ensuring stability of kinetochore-microtubule attachments during chromosome congression and segregation. © 2014 Vitre, Gudimchuk, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  13. Sensing Chromosome Bi-Orientation by Spatial Separation of Aurora B Kinase from Kinetochore Substrates

    NARCIS (Netherlands)

    Liu, Dan; Vader, Gerben; Vromans, Martijn J. M.; Lampson, Michael A.; Lens, Susanne M. A.

    2009-01-01

    Successful cell division requires that chromosomes attach to opposite poles of the mitotic spindle (bi-orientation). Aurora B kinase regulates chromosome-spindle attachments by phosphorylating kinetochore substrates that bind microtubules. Centromere tension stabilizes bi-oriented attachments, but

  14. A sequential multi-target Mps1 phosphorylation cascade promotes spindle checkpoint signaling.

    Science.gov (United States)

    Ji, Zhejian; Gao, Haishan; Jia, Luying; Li, Bing; Yu, Hongtao

    2017-01-10

    The master spindle checkpoint kinase Mps1 senses kinetochore-microtubule attachment and promotes checkpoint signaling to ensure accurate chromosome segregation. The kinetochore scaffold Knl1, when phosphorylated by Mps1, recruits checkpoint complexes Bub1-Bub3 and BubR1-Bub3 to unattached kinetochores. Active checkpoint signaling ultimately enhances the assembly of the mitotic checkpoint complex (MCC) consisting of BubR1-Bub3, Mad2, and Cdc20, which inhibits the anaphase-promoting complex or cyclosome bound to Cdc20 (APC/C(Cdc20)) to delay anaphase onset. Using in vitro reconstitution, we show that Mps1 promotes APC/C inhibition by MCC components through phosphorylating Bub1 and Mad1. Phosphorylated Bub1 binds to Mad1-Mad2. Phosphorylated Mad1 directly interacts with Cdc20. Mutations of Mps1 phosphorylation sites in Bub1 or Mad1 abrogate the spindle checkpoint in human cells. Therefore, Mps1 promotes checkpoint activation through sequentially phosphorylating Knl1, Bub1, and Mad1. This sequential multi-target phosphorylation cascade makes the checkpoint highly responsive to Mps1 and to kinetochore-microtubule attachment.

  15. Protein purification technique that allows detection of sumoylation and ubiquitination of budding yeast kinetochore proteins Ndc10 and Ndc80.

    Science.gov (United States)

    Ohkuni, Kentaro; Takahashi, Yoshimitsu; Basrai, Munira A

    2015-05-03

    Post-translational Modifications (PTMs), such as phosphorylation, methylation, acetylation, ubiquitination, and sumoylation, regulate the cellular function of many proteins. PTMs of kinetochore proteins that associate with centromeric DNA mediate faithful chromosome segregation to maintain genome stability. Biochemical approaches such as mass spectrometry and western blot analysis are most commonly used for identification of PTMs. Here, a protein purification method is described that allows the detection of both sumoylation and ubiquitination of the kinetochore proteins, Ndc10 and Ndc80, in Saccharomyces cerevisiae. A strain that expresses polyhistidine-Flag-tagged Smt3 (HF-Smt3) and Myc-tagged Ndc10 or Ndc80 was constructed and used for our studies. For detection of sumoylation, we devised a protocol to affinity purify His-tagged sumoylated proteins by using nickel beads and used western blot analysis with anti-Myc antibody to detect sumoylated Ndc10 and Ndc80. For detection of ubiquitination, we devised a protocol for immunoprecipitation of Myc-tagged proteins and used western blot analysis with anti-Ub antibody to show that Ndc10 and Ndc80 are ubiquitinated. Our results show that epitope tagged-protein of interest in the His-Flag tagged Smt3 strain facilitates the detection of multiple PTMs. Future studies should allow exploitation of this technique to identify and characterize protein interactions that are dependent on a specific PTM.

  16. The chromosomal passenger complex and the spindle assembly checkpoint: kinetochore-microtubule error correction and beyond

    Directory of Open Access Journals (Sweden)

    Maia André F

    2008-05-01

    Full Text Available Abstract During mitosis, correct bipolar chromosome attachment to the mitotic spindle is an essential prerequisite for the equal segregation of chromosomes. The spindle assembly checkpoint can prevent chromosome segregation as long as not all chromosome pairs have obtained bipolar attachment to the spindle. The chromosomal passenger complex plays a crucial role during chromosome alignment by correcting faulty chromosome-spindle interactions (e.g. attachments that do not generate tension. In the process of doing so, the chromosomal passenger complex generates unattached chromosomes, a specific situation that is known to promote checkpoint activity. However, several studies have implicated an additional, more direct role for the chromosomal passenger complex in enforcing the mitotic arrest imposed by the spindle assembly checkpoint. In this review, we discuss the different roles played by the chromosomal passenger complex in ensuring proper mitotic checkpoint function. Additionally, we discuss the possibility that besides monitoring the presence of unattached kinetochores, the spindle assembly checkpoint may also be capable of responding to chromosome-microtubule interactions that do not generate tension and we propose experimental set-ups to study this.

  17. Spatial Rule-Based Modeling: A Method and Its Application to the Human Mitotic Kinetochore

    Directory of Open Access Journals (Sweden)

    Jan Huwald

    2013-07-01

    Full Text Available A common problem in the analysis of biological systems is the combinatorial explosion that emerges from the complexity of multi-protein assemblies. Conventional formalisms, like differential equations, Boolean networks and Bayesian networks, are unsuitable for dealing with the combinatorial explosion, because they are designed for a restricted state space with fixed dimensionality. To overcome this problem, the rule-based modeling language, BioNetGen, and the spatial extension, SRSim, have been developed. Here, we describe how to apply rule-based modeling to integrate experimental data from different sources into a single spatial simulation model and how to analyze the output of that model. The starting point for this approach can be a combination of molecular interaction data, reaction network data, proximities, binding and diffusion kinetics and molecular geometries at different levels of detail. We describe the technique and then use it to construct a model of the human mitotic inner and outer kinetochore, including the spindle assembly checkpoint signaling pathway. This allows us to demonstrate the utility of the procedure, show how a novel perspective for understanding such complex systems becomes accessible and elaborate on challenges that arise in the formulation, simulation and analysis of spatial rule-based models.

  18. Human condensin function is essential for centromeric chromatin assembly and proper sister kinetochore orientation.

    Directory of Open Access Journals (Sweden)

    Alexander Samoshkin

    Full Text Available Condensins I and II in vertebrates are essential ATP-dependent complexes necessary for chromosome condensation in mitosis. Condensins depletion is known to perturb structure and function of centromeres, however the mechanism of this functional link remains elusive. Depletion of condensin activity is now shown to result in a significant loss of loading of CENP-A, the histone H3 variant found at active centromeres and the proposed epigenetic mark of centromere identity. Absence of condensins and/or CENP-A insufficiency produced a specific kinetochore defect, such that a functional mitotic checkpoint cannot prevent chromosome missegregation resulting from improper attachment of sister kinetochores to spindle microtubules. Spindle microtubule-dependent deformation of both inner kinetochores and the HEC1/Ndc80 microtubule-capturing module, then results in kinetochore separation from the Aurora B pool and ensuing reduced kinase activity at centromeres. Moreover, recovery from mitosis-inhibition by monastrol revealed a high incidence of merotelic attachment that was nearly identical with condensin depletion, Aurora B inactivation, or both, indicating that the Aurora B dysfunction is the key defect leading to chromosome missegregation in condensin-depleted cells. Thus, beyond a requirement for global chromosome condensation, condensins play a pivotal role in centromere assembly, proper spatial positioning of microtubule-capturing modules and positioning complexes of the inner centromere versus kinetochore plates.

  19. Incomplete pole orientation of kinetochores in complex meiotic metaphase I configurations delays metaphase-anaphase transition in Secale.

    Science.gov (United States)

    Sybenga, J

    2014-04-01

    To prevent unbalanced chromosome segregation, meiotic metaphase I - anaphase I transition is carefully regulated by delaying anaphase until all kinetochores are well oriented (anaphase checkpoint) in mammals and insects. In plants this has not yet been established. In heterozygotes of two reciprocal translocations of Secale cereale, with one chromosome replaced by its two telocentric arms, anaphase delay was correlated with the orientation of the kinetochores of the complex of five chromosomes. The terminal kinetochores of the half chromosomes were readily elongated and pole oriented. Chains of five chromosomes with all five kinetochores orienting on alternate poles where the first to start anaphase. Kinetochores of two adjacent chromosomes when oriented on the same pole were partly shielded and less well pole directed. Anaphase was delayed. Cells with this configuration accumulated during anther development. Kinetochores in metacentric chromosomes lacking chiasmata in one arm (in trivalents and bivalents) were slightly better pole oriented and delayed anaphase less. Release of chromatid cohesion as triggered by kinetochore stretch is apparently delayed by inadequate exposition and pole orientation of the kinetochores. It is a mild form of an anaphase checkpoint, in normal material synchronizing bivalent segregation.

  20. Mislocalization of the Drosophila centromere-specific histone CIDpromotes formation of functional ectopic kinetochores

    Energy Technology Data Exchange (ETDEWEB)

    Heun, Patrick; Erhardt, Sylvia; Blower, Michael D.; Weiss,Samara; Skora, Andrew D.; Karpen, Gary H.

    2006-01-30

    The centromere-specific histone variant CENP-A (CID in Drosophila) is a structural and functional foundation for kinetochore formation and chromosome segregation. Here, we show that overexpressed CID is mislocalized into normally non-centromeric regions in Drosophila tissue culture cells and animals. Analysis of mitoses in living and fixed cells reveals that mitotic delays, anaphase bridges, chromosome fragmentation, and cell and organismal lethality are all direct consequences of CID mislocalization. In addition, proteins that are normally restricted to endogenous kinetochores assemble at a subset of ectopic CID incorporation regions. The presence of microtubule motors and binding proteins, spindle attachments, and aberrant chromosome morphologies demonstrate that these ectopic kinetochores are functional. We conclude that CID mislocalization promotes formation of ectopic centromeres and multicentric chromosomes, which causes chromosome missegregation, aneuploidy, and growth defects. Thus, CENP-A mislocalization is one possible mechanism for genome instability during cancer progression, as well as centromere plasticity during evolution.

  1. A Kinase-Phosphatase Network that Regulates Kinetochore-Microtubule Attachments and the SAC.

    Science.gov (United States)

    Vallardi, Giulia; Cordeiro, Marilia Henriques; Saurin, Adrian Thomas

    2017-01-01

    The KMN network (for KNL1, MIS12 and NDC80 complexes) is a hub for signalling at the outer kinetochore. It integrates the activities of two kinases (MPS1 and Aurora B) and two phosphatases (PP1 and PP2A-B56) to regulate kinetochore-microtubule attachments and the spindle assembly checkpoint (SAC). We will first discuss each of these enzymes separately, to describe how they are regulated at kinetochores and why this is important for their primary function in controlling either microtubule attachments or the SAC. We will then discuss why inhibiting any one of them individually produces secondary effects on all the others. This cross-talk may help to explain why all enzymes have been linked to both processes, even though the direct evidence suggests they each control only one. This chapter therefore describes how a network of kinases and phosphatases work together to regulate two key mitotic processes.

  2. The Microtubule-Stabilizing Protein CLASP1 Associates with the Theileria annulata Schizont Surface via Its Kinetochore-Binding Domain

    Science.gov (United States)

    Huber, Sandra; Theiler, Romina; de Quervain, Daniel; Wiens, Olga; Karangenc, Tulin; Heussler, Volker; Dobbelaere, Dirk

    2017-01-01

    ABSTRACT Theileria is an apicomplexan parasite whose presence within the cytoplasm of a leukocyte induces cellular transformation and causes uncontrolled proliferation and clonal expansion of the infected cell. The intracellular schizont utilizes the host cell’s own mitotic machinery to ensure its distribution to both daughter cells by associating closely with microtubules (MTs) and incorporating itself within the central spindle. We show that CLASP1, an MT-stabilizing protein that plays important roles in regulating kinetochore-MT attachment and central spindle positioning, is sequestered at the Theileria annulata schizont surface. We used live-cell imaging and immunofluorescence in combination with MT depolymerization assays to demonstrate that CLASP1 binds to the schizont surface in an MT-independent manner throughout the cell cycle and that the recruitment of the related CLASP2 protein to the schizont is MT dependent. By transfecting Theileria-infected cells with a panel of truncation mutants, we found that the kinetochore-binding domain of CLASP1 is necessary and sufficient for parasite localization, revealing that CLASP1 interaction with the parasite occurs independently of EB1. We overexpressed the MT-binding domain of CLASP1 in parasitized cells. This exhibited a dominant negative effect on host MT stability and led to altered parasite size and morphology, emphasizing the importance of proper MT dynamics for Theileria partitioning during host cell division. Using coimmunoprecipitation, we demonstrate that CLASP1 interacts, directly or indirectly, with the schizont membrane protein p104, and we describe for the first time TA03615, a Theileria protein which localizes to the parasite surface, where it has the potential to participate in parasite-host interactions. IMPORTANCE T. annulata, the only eukaryote known to be capable of transforming another eukaryote, is a widespread parasite of veterinary importance that puts 250 million cattle at risk worldwide

  3. Inactivation of a Human Kinetochore by Specific Targeting of Chromatin Modifiers

    Science.gov (United States)

    Nakano, Megumi; Cardinale, Stefano; Noskov, Vladimir N.; Gassmann, Reto; Vagnarelli, Paola; Kandels-Lewis, Stefanie; Larionov, Vladimir; Earnshaw, William C.; Masumoto, Hiroshi

    2008-01-01

    Summary We have used a human artificial chromosome (HAC) to manipulate the epigenetic state of chromatin within an active kinetochore. The HAC has a dimeric α-satellite repeat containing one natural monomer with a CENP-B binding site, and one completely artificial synthetic monomer with the CENP-B box replaced by a tetracycline operator (tetO). This HAC exhibits normal kinetochore protein composition and mitotic stability. Targeting of several tet-repressor (tetR) fusions into the centromere had no effect on kinetochore function. However, altering the chromatin state to a more open configuration with the tTA transcriptional activator or to a more closed state with the tTS transcription silencer caused missegregation and loss of the HAC. tTS binding caused the loss of CENP-A, CENP-B, CENP-C, and H3K4me2 from the centromere accompanied by an accumulation of histone H3K9me3. Our results reveal that a dynamic balance between centromeric chromatin and heterochromatin is essential for vertebrate kinetochore activity. PMID:18410728

  4. Correction of microtubule-kinetochore attachment errors: Mechanisms and role in tumor suppression

    NARCIS (Netherlands)

    Ricke, R.M.; Deursen, J.M.A. van

    2011-01-01

    During mitosis, cells segregate duplicated chromosomes with high fidelity in order to maintain genome stability. Proper attachment of sister kinetochores to spindle microtubules is critical for accurate chromosome segregation and is driven by complex mechanisms that promote the capture of unattached

  5. Small kinetochore associated protein (SKAP promotes UV-induced cell apoptosis through negatively regulating pre-mRNA processing factor 19 (Prp19.

    Directory of Open Access Journals (Sweden)

    Shan Lu

    Full Text Available Apoptosis is a regulated cellular suicide program that is critical for the development and maintenance of healthy tissues. Previous studies have shown that small kinetochore associated protein (SKAP cooperates with kinetochore and mitotic spindle proteins to regulate mitosis. However, the role of SKAP in apoptosis has not been investigated. We have identified a new interaction involving SKAP, and we propose a mechanism through which SKAP regulates cell apoptosis. Our experiments demonstrate that both overexpression and knockdown of SKAP sensitize cells to UV-induced apoptosis. Further study has revealed that SKAP interacts with Pre-mRNA processing Factor 19 (Prp19. We find that UV-induced apoptosis can be inhibited by ectopic expression of Prp19, whereas silencing Prp19 has the opposite effect. Additionally, SKAP negatively regulates the protein levels of Prp19, whereas Prp19 does not alter SKAP expression. Finally, rescue experiments demonstrate that the pro-apoptotic role of SKAP is executed through Prp19. Taken together, these findings suggest that SKAP promotes UV-induced cell apoptosis by negatively regulating the anti-apoptotic protein Prp19.

  6. Unique geometry of sister kinetochores in human oocytes during meiosis I may explain maternal age-associated increases in chromosomal abnormalities

    Directory of Open Access Journals (Sweden)

    Jessica Patel

    2016-02-01

    Full Text Available The first meiotic division in human oocytes is highly error-prone and contributes to the uniquely high incidence of aneuploidy observed in human pregnancies. A successful meiosis I (MI division entails separation of homologous chromosome pairs and co-segregation of sister chromatids. For this to happen, sister kinetochores must form attachments to spindle kinetochore-fibres emanating from the same pole. In mouse and budding yeast, sister kinetochores remain closely associated with each other during MI, enabling them to act as a single unified structure. However, whether this arrangement also applies in human meiosis I oocytes was unclear. In this study, we perform high-resolution imaging of over 1900 kinetochores in human oocytes, to examine the geometry and architecture of the human meiotic kinetochore. We reveal that sister kinetochores in MI are not physically fused, and instead individual kinetochores within a pair are capable of forming independent attachments to spindle k-fibres. Notably, with increasing female age, the separation between kinetochores increases, suggesting a degradation of centromeric cohesion and/or changes in kinetochore architecture. Our data suggest that the differential arrangement of sister kinetochores and dual k-fibre attachments may explain the high proportion of unstable attachments that form in MI and thus indicate why human oocytes are prone to aneuploidy, particularly with increasing maternal age.

  7. Predominant induction of kinetochore-containing micronuclei by extracts of diesel exhaust particulates in cultured human lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Odagiri, Youichi; Uchida, Hiroyuki; Kawamura, Ken; Adachi, Shuichi; Takemoto, Kazuo (Saitama Medical School (Japan)); Jian-Xin Zhang (West China Univ. of Medical Sciences, Sichuan (China))

    1994-01-01

    The aneuploidy-inducing activity of extracts of diesel exhaust particulates from light duty (LD) and heavy duty (HD) engines was investigated in cultured peripheral blood lymphocytes of 8 healthy donors using the cytokinesis-block micronucleus test with the kinetochore labelling modification. A majority of the subjects tested showed a significant kinetochore-positive micronucleus induction after treatment with the highest dose (150 [mu]g/ml) of LD extract, although some subjects also showed induction of kinetochore-negative micronuclei. Only one subject had significantly increased numbers of kinetochore-positive micronuclei at a dose of 400 [mu]g/ml of HD extract. These results suggest that diesel extract, at least LD extract, possesses the ability to induce whole chromosome loss (aneuploidy) preferentially, although there are also chromosome breaks. 21 refs., 2 figs., 3 tabs.

  8. Microinjection of biotin-tubulin into anaphase cells induces transient elongation of kinetochore microtubules and reversal of chromosome-to-pole motion.

    Science.gov (United States)

    Shelden, E; Wadsworth, P

    1992-03-01

    During prometaphase and metaphase of mitosis, tubulin subunit incorporation into kinetochore microtubules occurs proximal to the kinetochore, at the plus-ends of kinetochore microtubules. During anaphase, subunit loss from kinetochore fiber microtubules is also thought to occur mainly from microtubule plus-ends, proximal to the kinetochore. Thus, the kinetochore can mediate both subunit addition and loss while maintaining an attachment to kinetochore microtubules. To examine the relationship between chromosome motion and tubulin subunit assembly in anaphase, we have injected anaphase cells with biotin-labeled tubulin subunits. The pattern of biotin-tubulin incorporation was revealed using immunoelectron and confocal fluorescence microscopy of cells fixed after injection; chromosome motion was analyzed using video records of living injected cells. When anaphase cells are examined approximately 30 s after injection with biotin-tubulin, bright "tufts" of fluorescence are detected proximal to the kinetochores. Electron microscopic immunocytochemistry further reveals that these tufts of biotin-tubulin-containing microtubules are continuous with unlabeled kinetochore fiber microtubules. Biotin-tubulin incorporation proximal to the kinetochore in anaphase cells is detected after injection of 3-30 mg/ml biotin-tubulin, but not in cells injected with 0.3 mg/ml biotin-tubulin. At intermediate concentrations of biotin-tubulin (3-5 mg/ml), incorporation at the kinetochore can be detected within 15 s after injection; by approximately 1 min after injection discrete tufts of fluorescence are no longer detected, although some incorporation throughout the kinetochore fiber and into nonkinetochore microtubules is observed. At higher concentrations of injected biotin-tubulin (13 mg/ml), incorporation at the kinetochore is more extensive and occurs for longer periods of time than at intermediate concentrations. Incorporation of biotin-tubulin proximal to the kinetochore can be

  9. Chromosome Bridges Maintain Kinetochore-Microtubule Attachment throughout Mitosis and Rarely Break during Anaphase.

    Science.gov (United States)

    Pampalona, Judit; Roscioli, Emanuele; Silkworth, William T; Bowden, Brent; Genescà, Anna; Tusell, Laura; Cimini, Daniela

    2016-01-01

    Accurate chromosome segregation during cell division is essential to maintain genome stability, and chromosome segregation errors are causally linked to genetic disorders and cancer. An anaphase chromosome bridge is a particular chromosome segregation error observed in cells that enter mitosis with fused chromosomes/sister chromatids. The widely accepted Breakage/Fusion/Bridge cycle model proposes that anaphase chromosome bridges break during mitosis to generate chromosome ends that will fuse during the following cell cycle, thus forming new bridges that will break, and so on. However, various studies have also shown a link between chromosome bridges and aneuploidy and/or polyploidy. In this study, we investigated the behavior and properties of chromosome bridges during mitosis, with the idea to gain insight into the potential mechanism underlying chromosome bridge-induced aneuploidy. We find that only a small number of chromosome bridges break during anaphase, whereas the rest persist through mitosis into the subsequent cell cycle. We also find that the microtubule bundles (k-fibers) bound to bridge kinetochores are not prone to breakage/detachment, thus supporting the conclusion that k-fiber detachment is not the cause of chromosome bridge-induced aneuploidy. Instead, our data suggest that while the microtubules bound to the kinetochores of normally segregating chromosomes shorten substantially during anaphase, the k-fibers bound to bridge kinetochores shorten only slightly, and may even lengthen, during anaphase. This causes some of the bridge kinetochores/chromosomes to lag behind in a position that is proximal to the cell/spindle equator and may cause the bridged chromosomes to be segregated into the same daughter nucleus or to form a micronucleus.

  10. Age-associated micronuclei, kinetochores and sex chromosome loss in men

    Energy Technology Data Exchange (ETDEWEB)

    Nath, J.; Hando, J. [West Virginia Univ., Morgantown, WV (United States); Tucker, J.D. [Lawrence Livermore National Laboratory, CA (United States)

    1995-11-01

    Studies on aneuploidy have shown a significant increase in the loss of chromosomes in both males and females with age and also a significant increase in micronucleus formation in lymphocytes with age. This study attempted (1) to ascertain whether the age-associated increase in Y chromosome loss and micronucleus formation are related. (2) to determine whether there is a correlation between Y chromosome-negative metaphase cells and Y chromosome-positive micronuclei from the same donors, and (3) to determine the relationships among the kinetochore status of micronuclei, Y chromosome-positive micronuclei, and age. Blood samples were obtained from thirty-five healthy males ranging in age from 22 to 79 years, and from the umbilical cords of eighteen newborn males. Two thousand binucleated cells were scored per sample. The kinetochore status of each micronucleus was recorded. Slides were then hybridized with the Y chromosome specific probe pHY10, labeled with biotinylated dUTP, and visualized with fluorescein conjugated avidin. All micronucleated cells were relocated and scored as Y+ or Y- depending on their Y probe status. A total of 303 micronuclei were scored, of which 41 (13.5%) contained the Y chromosome. ANOVA shows a significant increase in the number of Y chromosome-positive micronuclei with age (p<0.001). Of the 41 Y+ micronuclei 36 (87.8%) were kinetochore negative, suggesting a relationship between the absence of kinetochore function and micronucleus formation. Also, 500 metaphase spreads per sample were scored for the Y chromosome, showing an increase in Y-cells with age (p<0.001). A correlation analysis between Y chromosome-positive micronuclei and Y chromosome-negative metaphase cells resulted in a correlation coefficient of 0.71 (p.005).

  11. Role of Intrinsic and Extrinsic Factors in the Regulation of the Mitotic Checkpoint Kinase Bub1.

    Directory of Open Access Journals (Sweden)

    Claudia Breit

    Full Text Available The spindle assembly checkpoint (SAC monitors microtubule attachment to kinetochores to ensure accurate sister chromatid segregation during mitosis. The SAC members Bub1 and BubR1 are paralogs that underwent significant functional specializations during evolution. We report an in-depth characterization of the kinase domains of Bub1 and BubR1. BubR1 kinase domain binds nucleotides but is unable to deliver catalytic activity in vitro. Conversely, Bub1 is an active kinase regulated by intra-molecular phosphorylation at the P+1 loop. The crystal structure of the phosphorylated Bub1 kinase domain illustrates a hitherto unknown conformation of the P+1 loop docked into the active site of the Bub1 kinase. Both Bub1 and BubR1 bind Bub3 constitutively. A hydrodynamic characterization of Bub1:Bub3 and BubR1:Bub3 demonstrates both complexes to have 1:1 stoichiometry, with no additional oligomerization. Conversely, Bub1:Bub3 and BubR1:Bub3 combine to form a heterotetramer. Neither BubR1:Bub3 nor Knl1, the kinetochore receptor of Bub1:Bub3, modulate the kinase activity of Bub1 in vitro, suggesting autonomous regulation of the Bub1 kinase domain. We complement our study with an analysis of the Bub1 substrates. Our results contribute to the mechanistic characterization of a crucial cell cycle checkpoint.

  12. Zwint-1 is required for spindle assembly checkpoint function and kinetochore-microtubule attachment during oocyte meiosis.

    Science.gov (United States)

    Woo Seo, Dong; Yeop You, Seung; Chung, Woo-Jae; Cho, Dong-Hyung; Kim, Jae-Sung; Su Oh, Jeong

    2015-10-21

    The key step for faithful chromosome segregation during meiosis is kinetochore assembly. Defects in this process result in aneuploidy, leading to miscarriages, infertility and various birth defects. However, the roles of kinetochores in homologous chromosome segregation during meiosis are ill-defined. Here we found that Zwint-1 is required for homologous chromosome segregation during meiosis. Knockdown of Zwint-1 accelerated the first meiosis by abrogating the kinetochore recruitment of Mad2, leading to chromosome misalignment and a high incidence of aneuploidy. Although Zwint-1 knockdown did not affect Aurora C kinase activity, the meiotic defects following Zwint-1 knockdown were similar to those observed with ZM447439 treatment. Importantly, the chromosome misalignment following Aurora C kinase inhibition was not restored after removing the inhibitor in Zwint-1-knockdown oocytes, whereas the defect was rescued after the inhibitor washout in the control oocytes. These results suggest that Aurora C kinase-mediated correction of erroneous kinetochore-microtubule attachment is primarily regulated by Zwint-1. Our results provide the first evidence that Zwint-1 is required to correct erroneous kinetochore-microtubule attachment and regulate spindle checkpoint function during meiosis.

  13. CDK-1 Inhibition in G2 Stabilizes Kinetochore-Microtubules in the following Mitosis.

    Directory of Open Access Journals (Sweden)

    A Sophia Gayek

    Full Text Available Cell proliferation is driven by cyclical activation of cyclin-dependent kinases (CDKs, which produce distinct biochemical cell cycle phases. Mitosis (M phase is orchestrated by CDK-1, complexed with mitotic cyclins. During M phase, chromosomes are segregated by a bipolar array of microtubules called the mitotic spindle. The essential bipolarity of the mitotic spindle is established by the kinesin-5 Eg5, but factors influencing the maintenance of spindle bipolarity are not fully understood. Here, we describe an unexpected link between inhibiting CDK-1 before mitosis and bipolar spindle maintenance. Spindles in human RPE-1 cells normally collapse to monopolar structures when Eg5 is inhibited at metaphase. However, we found that inhibition of CDK-1 in the G2 phase of the cell cycle improved the ability of RPE-1 cells to maintain spindle bipolarity without Eg5 activity in the mitosis immediately after release from CDK-1 inhibition. This improved bipolarity maintenance correlated with an increase in the stability of kinetochore-microtubules, the subset of microtubules that link chromosomes to the spindle. The improvement in bipolarity maintenance after CDK-1 inhibition in G2 required both the kinesin-12 Kif15 and increased stability of kinetochore-microtubules. Consistent with increased kinetochore-microtubule stability, we find that inhibition of CDK-1 in G2 impairs mitotic fidelity by increasing the incidence of lagging chromosomes in anaphase. These results suggest that inhibition of CDK-1 in G2 causes unpredicted effects in mitosis, even after CDK-1 inhibition is relieved.

  14. Theory of dynamic force spectroscopy for kinetochore-microtubule attachments: rupture force distribution

    CERN Document Server

    Ghanti, Dipanwita

    2016-01-01

    Application of pulling force, under force-clamp conditions, to kinetochore-microtubule attachments {\\it in-vitro} revealed a catch-bond-like behavior. In an earlier paper ({\\it Sharma et al. Phys. Biol. (2014)} the physical origin of this apparently counter-intuitive phenomenon was traced to the nature of the force-dependence of the (de-)polymerization kinetics of the microtubules. In this brief communication that work is extended to situations where the external forced is ramped up till the attachment gets ruptured. In spite of the fundamental differences in the underlying mechanisms, the trend of variation of the rupture force distribution observed in our model kinetochore-microtubule attachment with the increasing loading rate is qualitatively similar to that displayed by the catch bonds formed in some other ligand-receptor systems. Our theoretical predictions can be tested experimentally by a straightforward modification of the protocol for controlling the force in the optical trap set up that was used in...

  15. Mps1 Regulates Kinetochore-Microtubule Attachment Stability via the Ska Complex to Ensure Error-Free Chromosome Segregation.

    Science.gov (United States)

    Maciejowski, John; Drechsler, Hauke; Grundner-Culemann, Kathrin; Ballister, Edward R; Rodriguez-Rodriguez, Jose-Antonio; Rodriguez-Bravo, Veronica; Jones, Mathew J K; Foley, Emily; Lampson, Michael A; Daub, Henrik; McAinsh, Andrew D; Jallepalli, Prasad V

    2017-04-24

    The spindle assembly checkpoint kinase Mps1 not only inhibits anaphase but also corrects erroneous attachments that could lead to missegregation and aneuploidy. However, Mps1's error correction-relevant substrates are unknown. Using a chemically tuned kinetochore-targeting assay, we show that Mps1 destabilizes microtubule attachments (K fibers) epistatically to Aurora B, the other major error-correcting kinase. Through quantitative proteomics, we identify multiple sites of Mps1-regulated phosphorylation at the outer kinetochore. Substrate modification was microtubule sensitive and opposed by PP2A-B56 phosphatases that stabilize chromosome-spindle attachment. Consistently, Mps1 inhibition rescued K-fiber stability after depleting PP2A-B56. We also identify the Ska complex as a key effector of Mps1 at the kinetochore-microtubule interface, as mutations that mimic constitutive phosphorylation destabilized K fibers in vivo and reduced the efficiency of the Ska complex's conversion from lattice diffusion to end-coupled microtubule binding in vitro. Our results reveal how Mps1 dynamically modifies kinetochores to correct improper attachments and ensure faithful chromosome segregation. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. GTPase Ran strongly accumulates at the kinetochores of somatic chromosomes in the spermatogonial mitoses of Acricotopus lucidus (Diptera, Chironomidae).

    Science.gov (United States)

    Staiber, Wolfgang

    2014-07-01

    Unequal chromosome segregation and spindle formation occurs in the last gonial mitosis in the germ line of the chironomid Acricotopus lucidus. During this differential mitosis, all germ line-limited chromosomes (=Ks) migrate undivided to only one pole of the cell, while the somatic chromosomes (=Ss) first remain in the metaphase plane, and with the arrival of the Ks at the pole, they then separate equally. The evolutionarily conserved GTPase Ran plays a crucial role in many cellular processes. This includes the regulation of microtubule nucleation and stabilisation at kinetochores and of spindle assembly during mitosis, which is promoted by a RanGTP concentration gradient that forms around the mitotic chromosomes (Kalab et al. in Science 295:2452-2456, 2002, Nature 440:697-701, 2006). In the present study, a strong accumulation of Ran was detected by immunofluorescence at the kinetochores of the Ss in normal gonial and differential gonial mitoses of males of A. lucidus. In contrast, no Ran accumulation was observed at the kinetochores of the Ss in the metaphases of brain ganglia mitoses or of aberrant spermatocytes or in metaphases I and II of spermatocyte meiotic divisions. Likewise, there was no accumulation at the kinetochores of Drosophila melanogaster mitotic chromosomes from larval brains. The specific accumulation of Ran at the kinetochores of the Ss in differential gonial mitoses of A. lucidus strongly suggests that Ran is involved in a mechanism acting in this exceptional mitosis, which retains the Ss at the metaphase plane and prevents a premature separation and unequal segregation of the Ss during monopolar migration of the Ks.

  17. Characterisation of centromere (kinetochore) antigen reactive with sera of patients with a scleroderma variant (CREST syndrome).

    Science.gov (United States)

    Nishikai, M; Okano, Y; Yamashita, H; Watanabe, M

    1984-01-01

    Anticentromere (kinetochore) antibody is the marker antibody in CREST syndrome, but the precise molecular composition of the partner antigen has been poorly defined. This report describes for the first time a procedure for the successful extraction and biochemical characterisation of the centromere antigen molecule. The centromere antigen was extracted with 4M NaCl solution. The molecular weight of the partner antigen of the centromere antibody was determined to be 70 000 daltons by the SDS-PAGE and immunoblotting methods. A Sephacryl S-300 column experiment confirmed these results. Centromere antigenic activity was preserved at pHs between 3 and 11 and was resistant to three enzymes, trypsin, RNase, and DNase. Images PMID:6524984

  18. Sex-chromosome anaphase movements in crane-fly spermatocytes are coordinated: ultraviolet microbeam irradiation of one kinetochore of one sex chromosome blocks the movements of both sex chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Swedak, J.A.M.; Forer, A.

    1987-11-01

    Sex chromosomes in crane-fly spermatocytes move polewards at anaphase after the autosomes have reached the poles. We irradiated one kinetochore of one sex chromosome using an ultraviolet microbeam. When both sex chromosomes were normally oriented, irradiation of a single kinetochore permanently blocked movement of both sex chromosomes. Irradiation of non-kinetochore chromosomal regions or of spindle fibres did not block movement, or blocked movement only temporarily. We argue that ultraviolet irradiation of one kinetochore blocks movement of both sex chromosomes because of effects on a 'signal' system. Irradiation of one kinetochore of a maloriented sex chromosome did not block motion of either sex chromosome. However, irradiation of one kinetochore of a normally oriented sex chromosome permanently blocked motion of both that sex chromosome and the maloriented sex chromosome. Thus for the signal system to allow the sex chromosomes to move to the pole each sex chromosome must have one spindle fibre to each pole.

  19. Identification of a predominant co-regulation among kinetochore genes, prospective regulatory elements, and association with genomic instability.

    Directory of Open Access Journals (Sweden)

    William C Reinhold

    Full Text Available The NCI-60 cell line panel is the most extensively characterized set of cells in existence, and has been used extensively as a screening tool for drug discovery. Previously, the potential of this panel has not been applied to the fundamental cellular processes of chromosome segregation. In the current study, we used data from multiple microarray platforms accumulated for the NCI-60 to characterize an expression pattern of genes involved in kinetochore assembly. This analysis revealed that 17 genes encoding the constitutive centromere associated network of the kinetochore core (the CCAN complex plus four additional genes with established importance in kinetochore maintenance (CENPE, CENPF, INCENP, and MIS12 exhibit similar patterns of expression in the NCI-60, suggesting a mechanism for co-regulated transcription of these genes which is maintained despite the multiple genetic and epigenetic rearrangements accumulated in these cells (such as variations in DNA copy number and karyotypic complexity. A complex group of potential regulatory influences are identified for these genes, including the transcription factors CREB1, E2F1, FOXE1, and FOXM1, DNA copy number variation, and microRNAs has-miR-200a, 23a, 23b, 30a, 30c, 27b, 374b, 365. Thus, our results provide a template for experimental studies on the regulation of genes encoding kinetochore proteins, the process that, when aberrant, leads to the aneuploidy that is a hallmark of many cancers. We propose that the comparison of expression profiles in the NCI-60 cell line panel could be a tool for the identification of other gene groups whose products are involved in the assembly of organelle protein complexes.

  20. Identification of a predominant co-regulation among kinetochore genes, prospective regulatory elements, and association with genomic instability.

    Science.gov (United States)

    Reinhold, William C; Erliandri, Indri; Liu, Hongfang; Zoppoli, Gabriele; Pommier, Yves; Larionov, Vladimir

    2011-01-01

    The NCI-60 cell line panel is the most extensively characterized set of cells in existence, and has been used extensively as a screening tool for drug discovery. Previously, the potential of this panel has not been applied to the fundamental cellular processes of chromosome segregation. In the current study, we used data from multiple microarray platforms accumulated for the NCI-60 to characterize an expression pattern of genes involved in kinetochore assembly. This analysis revealed that 17 genes encoding the constitutive centromere associated network of the kinetochore core (the CCAN complex) plus four additional genes with established importance in kinetochore maintenance (CENPE, CENPF, INCENP, and MIS12) exhibit similar patterns of expression in the NCI-60, suggesting a mechanism for co-regulated transcription of these genes which is maintained despite the multiple genetic and epigenetic rearrangements accumulated in these cells (such as variations in DNA copy number and karyotypic complexity). A complex group of potential regulatory influences are identified for these genes, including the transcription factors CREB1, E2F1, FOXE1, and FOXM1, DNA copy number variation, and microRNAs has-miR-200a, 23a, 23b, 30a, 30c, 27b, 374b, 365. Thus, our results provide a template for experimental studies on the regulation of genes encoding kinetochore proteins, the process that, when aberrant, leads to the aneuploidy that is a hallmark of many cancers. We propose that the comparison of expression profiles in the NCI-60 cell line panel could be a tool for the identification of other gene groups whose products are involved in the assembly of organelle protein complexes.

  1. The progeroid gene BubR1 regulates axon myelination and motor function

    NARCIS (Netherlands)

    Choi, C.I.; Yoo, K.H.; Hussaini, S.M.; Jeon, B.T.; Welby, J.; Gan, H.; Scarisbrick, I.A.; Zhang, Z.; Baker, D.J.; Deursen, J.M.A. van; Rodriguez, M.; Jang, M.H.

    2016-01-01

    Myelination, the process by which oligodendrocytes form the myelin sheath around axons, is key to axonal signal transduction and related motor function in the central nervous system (CNS). Aging is characterized by degenerative changes in the myelin sheath, although the molecular underpinnings of

  2. A minimal number of MELT repeats supports all functions of KNL1 in chromosome segregation

    DEFF Research Database (Denmark)

    Zhang, Gang; Lischetti, Tiziana; Nilsson, Jakob

    2013-01-01

    The Bub1-Bub3 and BubR1-Bub3 checkpoint complexes, or the Bubs, contribute to the accurate segregation of chromosomes during mitosis by promoting chromosome bi-orientation and halting exit from mitosis if this fails. The complexes associate with kinetochores during mitosis, which is required...

  3. Epigenetic engineering reveals a balance between histone modifications and transcription in kinetochore maintenance.

    Science.gov (United States)

    Molina, Oscar; Vargiu, Giulia; Abad, Maria Alba; Zhiteneva, Alisa; Jeyaprakash, A Arockia; Masumoto, Hiroshi; Kouprina, Natalay; Larionov, Vladimir; Earnshaw, William C

    2016-11-14

    Centromeres consist of specialized centrochromatin containing CENP-A nucleosomes intermingled with H3 nucleosomes carrying transcription-associated modifications. We have designed a novel synthetic biology 'in situ epistasis' analysis in which H3 dimethylated on lysine 4 (H3K4me2) demethylase LSD2 plus synthetic modules with competing activities are simultaneously targeted to a synthetic alphoidtetO HAC centromere. This allows us to uncouple transcription from histone modifications at the centromere. Here, we report that H3K4me2 loss decreases centromeric transcription, CENP-A assembly and stability and causes spreading of H3K9me3 across the HAC, ultimately inactivating the centromere. Surprisingly, CENP-28/Eaf6-induced transcription of the alphoidtetO array associated with H4K12 acetylation does not rescue the phenotype, whereas p65-induced transcription associated with H3K9 acetylation does rescue. Thus mitotic transcription plus histone modifications including H3K9ac constitute the 'epigenetic landscape' allowing CENP-A assembly and centrochromatin maintenance. H3K4me2 is required for the transcription and H3K9ac may form a barrier to prevent heterochromatin spreading and kinetochore inactivation at human centromeres.

  4. Kinetochore-microtubule stability governs the metaphase requirement for Eg5

    Science.gov (United States)

    Gayek, A. Sophia; Ohi, Ryoma

    2014-01-01

    The mitotic spindle is a bipolar, microtubule (MT)-based cellular machine that segregates the duplicated genome into two daughter cells. The kinesin-5 Eg5 establishes the bipolar geometry of the mitotic spindle, but previous work in mammalian cells suggested that this motor is unimportant for the maintenance of spindle bipolarity. Although it is known that Kif15, a second mitotic kinesin, enforces spindle bipolarity in the absence of Eg5, how Kif15 functions in this capacity and/or whether other biochemical or physical properties of the spindle promote its bipolarity have been poorly studied. Here we report that not all human cell lines can efficiently maintain bipolarity without Eg5, despite their expressing Kif15. We show that the stability of chromosome-attached kinetochore-MTs (K-MTs) is important for bipolar spindle maintenance without Eg5. Cells that efficiently maintain bipolar spindles without Eg5 have more stable K-MTs than those that collapse without Eg5. Consistent with this observation, artificial destabilization of K-MTs promotes spindle collapse without Eg5, whereas stabilizing K-MTs improves bipolar spindle maintenance without Eg5. Our findings suggest that either rapid K-MT turnover pulls poles inward or slow K-MT turnover allows for greater resistance to inward-directed forces. PMID:24807901

  5. PP2A regulates kinetochore-microtubule attachment during meiosis I in oocyte.

    Science.gov (United States)

    Tang, An; Shi, Peiliang; Song, Anying; Zou, Dayuan; Zhou, Yue; Gu, Pengyu; Huang, Zan; Wang, Qinghua; Lin, Zhaoyu; Gao, Xiang

    2016-06-02

    Studies using in vitro cultured oocytes have indicated that the protein phosphatase 2A (PP2A), a major serine/threonine protein phosphatase, participates in multiple steps of meiosis. Details of oocyte maturation regulation by PP2A remain unclear and an in vivo model can provide more convincing information. Here, we inactivated PP2A by mutating genes encoding for its catalytic subunits (PP2Acs) in mouse oocytes. We found that eliminating both PP2Acs caused female infertility. Oocytes lacking PP2Acs failed to complete 1(st) meiotic division due to chromosome misalignment and abnormal spindle assembly. In mitosis, PP2A counteracts Aurora kinase B/C (AurkB/C) to facilitate correct kinetochore-microtubule (KT-MT) attachment. In meiosis I in oocyte, we found that PP2Ac deficiency destabilized KT-MT attachments. Chemical inhibition of AurkB/C in PP2Ac-null oocytes partly restored the formation of lateral/merotelic KT-MT attachments but not correct KT-MT attachments. Taken together, our findings demonstrate that PP2Acs are essential for chromosome alignments and regulate the formation of correct KT-MT attachments in meiosis I in oocytes.

  6. MAST/Orbit has a role in microtubule–kinetochore attachment and is essential for chromosome alignment and maintenance of spindle bipolarity

    Science.gov (United States)

    Maiato, Helder; Sampaio, Paula; Lemos, Catarina L.; Findlay, John; Carmena, Mar; Earnshaw, William C.; Sunkel, Claudio E.

    2002-01-01

    Multiple asters (MAST)/Orbit is a member of a new family of nonmotor microtubule-associated proteins that has been previously shown to be required for the organization of the mitotic spindle. Here we provide evidence that MAST/Orbit is required for functional kinetochore attachment, chromosome congression, and the maintenance of spindle bipolarity. In vivo analysis of Drosophila mast mutant embryos undergoing early mitotic divisions revealed that chromosomes are unable to reach a stable metaphase alignment and that bipolar spindles collapse as centrosomes move progressively closer toward the cell center and eventually organize into a monopolar configuration. Similarly, soon after depletion of MAST/Orbit in Drosophila S2 cells by double-stranded RNA interference, cells are unable to form a metaphase plate and instead assemble monopolar spindles with chromosomes localized close to the center of the aster. In these cells, kinetochores either fail to achieve end-on attachment or are associated with short microtubules. Remarkably, when microtubule dynamics is suppressed in MAST-depleted cells, chromosomes localize at the periphery of the monopolar aster associated with the plus ends of well-defined microtubule bundles. Furthermore, in these cells, dynein and ZW10 accumulate at kinetochores and fail to transfer to microtubules. However, loss of MAST/Orbit does not affect the kinetochore localization of D-CLIP-190. Together, these results strongly support the conclusion that MAST/Orbit is required for microtubules to form functional attachments to kinetochores and to maintain spindle bipolarity. PMID:12034769

  7. KI motifs of human Knl1 enhance assembly of comprehensive spindle checkpoint complexes around MELT repeats.

    Science.gov (United States)

    Krenn, Veronica; Overlack, Katharina; Primorac, Ivana; van Gerwen, Suzan; Musacchio, Andrea

    2014-01-06

    The KMN network, a ten-subunit protein complex, mediates the interaction of kinetochores with spindle microtubules and recruits spindle assembly checkpoint (SAC) constituents to halt cells in mitosis until attainment of sister chromatid biorientation. Two types of motifs in the KMN subunit Knl1 interact with SAC proteins. Lys-Ile (KI) motifs, found in vertebrates, interact with the TPR motifs of Bub1 and BubR1. Met-Glu-Leu-Thr (MELT) repeats, ubiquitous in evolution, recruit the Bub3/Bub1 complex in a phosphorylation-dependent manner. The exact contributions of KI and MELT motifs to SAC signaling and chromosome alignment are unclear. We report here that KI motifs cooperate strongly with the neighboring single MELT motif in the N-terminal 250 residues (Knl1(1-250)) of human Knl1 to seed a comprehensive assembly of SAC proteins. In cells depleted of endogenous Knl1, kinetochore-targeted Knl1(1-250) suffices to restore SAC and chromosome alignment. Individual MELT repeats outside of Knl1(1-250), which lack flanking KI motifs, establish qualitatively similar sets of interactions, but less efficiently. MELT sequences on Knl1 emerge from our analysis as the platforms on which SAC complexes become assembled. Our results show that KI motifs are enhancers of MELT function in assembling SAC signaling complexes, and that they might have evolved to limit the expansion of MELT motifs by providing a more robust mechanism of SAC signaling around a single MELT. We shed light on the mechanism of Bub1 and BubR1 recruitment and identify crucial questions for future studies. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Human papillomavirus type 16 E7 oncoprotein engages but does not abrogate the mitotic spindle assembly checkpoint

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Yueyang [Division of Infectious Diseases, Brigham and Women' s Hospital and Biological and Biomedical Sciences Program, Harvard Medical School, Boston, MA 02115 (United States); Munger, Karl, E-mail: kmunger@rics.bwh.harvard.edu [Division of Infectious Diseases, Brigham and Women' s Hospital and Biological and Biomedical Sciences Program, Harvard Medical School, Boston, MA 02115 (United States)

    2012-10-10

    The mitotic spindle assembly checkpoint (SAC) ensures faithful chromosome segregation during mitosis by censoring kinetochore-microtubule interactions. It is frequently rendered dysfunctional during carcinogenesis causing chromosome missegregation and genomic instability. There are conflicting reports whether the HPV16 E7 oncoprotein drives chromosomal instability by abolishing the SAC. Here we report that degradation of mitotic cyclins is impaired in cells with HPV16 E7 expression. RNAi-mediated depletion of Mad2 or BubR1 indicated the involvement of the SAC, suggesting that HPV16 E7 expression causes sustained SAC engagement. Mutational analyses revealed that HPV16 E7 sequences that are necessary for retinoblastoma tumor suppressor protein binding as well as sequences previously implicated in binding the nuclear and mitotic apparatus (NuMA) protein and in delocalizing dynein from the mitotic spindle contribute to SAC engagement. Importantly, however, HPV16 E7 does not markedly compromise the SAC response to microtubule poisons.

  9. MAPK-activated protein kinase 2 is required for mouse meiotic spindle assembly and kinetochore-microtubule attachment.

    Directory of Open Access Journals (Sweden)

    Ju Yuan

    Full Text Available MAPK-activated protein kinase 2 (MK2, a direct substrate of p38 MAPK, plays key roles in multiple physiological functions in mitosis. Here, we show for the first time the unique distribution pattern of MK2 in meiosis. Phospho-MK2 was localized on bipolar spindle minus ends and along the interstitial axes of homologous chromosomes extending over centromere regions and arm regions at metaphase of first meiosis (MI stage in mouse oocytes. At metaphase of second meiosis (MII stage, p-MK2 was localized on the bipolar spindle minus ends and at the inner centromere region of sister chromatids as dots. Knockdown or inhibition of MK2 resulted in spindle defects. Spindles were surrounded by irregular nondisjunction chromosomes, which were arranged in an amphitelic or syntelic/monotelic manner, or chromosomes detached from the spindles. Kinetochore-microtubule attachments were impaired in MK2-deficient oocytes because spindle microtubules became unstable in response to cold treatment. In addition, homologous chromosome segregation and meiosis progression were inhibited in these oocytes. Our data suggest that MK2 may be essential for functional meiotic bipolar spindle formation, chromosome segregation and proper kinetochore-microtubule attachments.

  10. CENP-C and CENP-I are key connecting factors for kinetochore and CENP-A assembly.

    Science.gov (United States)

    Shono, Nobuaki; Ohzeki, Jun-ichirou; Otake, Koichiro; Martins, Nuno M C; Nagase, Takahiro; Kimura, Hiroshi; Larionov, Vladimir; Earnshaw, William C; Masumoto, Hiroshi

    2015-12-15

    Although it is generally accepted that chromatin containing the histone H3 variant CENP-A is an epigenetic mark maintaining centromere identity, the pathways leading to the formation and maintenance of centromere chromatin remain unclear. We previously generated human artificial chromosomes (HACs) whose centromeres contain a synthetic alpha-satellite (alphoid) DNA array containing the tetracycline operator (alphoid(tetO)). We also obtained cell lines bearing the alphoid(tetO) array at ectopic integration sites on chromosomal arms. Here, we have examined the regulation of CENP-A assembly at centromeres as well as de novo assembly on the ectopic arrays by tethering tetracycline repressor (tetR) fusions of substantial centromeric factors and chromatin modifiers. This analysis revealed four classes of factors that influence CENP-A assembly. Interestingly, many kinetochore structural components induced de novo CENP-A assembly at the ectopic site. We showed that these components work by recruiting CENP-C and subsequently recruiting M18BP1. Furthermore, we found that CENP-I can also recruit M18BP1 and, as a consequence, enhances M18BP1 assembly on centromeres in the downstream of CENP-C. Thus, we suggest that CENP-C and CENP-I are key factors connecting kinetochore to CENP-A assembly. © 2015. Published by The Company of Biologists Ltd.

  11. The Smc5-Smc6 complex regulates recombination at centromeric regions and affects kinetochore protein sumoylation during normal growth.

    Directory of Open Access Journals (Sweden)

    Vladimir Yong-Gonzales

    Full Text Available The Smc5-Smc6 complex in Saccharomyces cerevisiae is both essential for growth and important for coping with genotoxic stress. While it facilitates damage tolerance throughout the genome under genotoxin treatment, its function during unperturbed growth is mainly documented for repetitive DNA sequence maintenance. Here we provide physical and genetic evidence showing that the Smc5-Smc6 complex regulates recombination at non-repetitive loci such as centromeres in the absence of DNA damaging agents. Mutating Smc6 results in the accumulation of recombination intermediates at centromeres and other unique sequences as assayed by 2D gel analysis. In addition, smc6 mutant cells exhibit increased levels of Rad52 foci that co-localize with centromere markers. A rad52 mutation that decreases centromeric, but not overall, levels of Rad52 foci in smc6 mutants suppresses the nocodazole sensitivity of these cells, suggesting that the Smc6-mediated regulation of recombination at centromeric regions impacts centromere-related functions. In addition to influencing recombination, the SUMO ligase subunit of the Smc5-Smc6 complex promotes the sumoylation of two kinetochore proteins and affects mitotic spindles. These results suggest that the Smc5-Smc6 complex regulates both recombination and kinetochore sumoylation to facilitate chromosomal maintenance during growth.

  12. CENP-C and CENP-I are key connecting factors for kinetochore and CENP-A assembly

    Science.gov (United States)

    Shono, Nobuaki; Ohzeki, Jun-ichirou; Otake, Koichiro; Martins, Nuno M. C.; Nagase, Takahiro; Kimura, Hiroshi; Larionov, Vladimir; Earnshaw, William C.; Masumoto, Hiroshi

    2015-01-01

    ABSTRACT Although it is generally accepted that chromatin containing the histone H3 variant CENP-A is an epigenetic mark maintaining centromere identity, the pathways leading to the formation and maintenance of centromere chromatin remain unclear. We previously generated human artificial chromosomes (HACs) whose centromeres contain a synthetic alpha-satellite (alphoid) DNA array containing the tetracycline operator (alphoidtetO). We also obtained cell lines bearing the alphoidtetO array at ectopic integration sites on chromosomal arms. Here, we have examined the regulation of CENP-A assembly at centromeres as well as de novo assembly on the ectopic arrays by tethering tetracycline repressor (tetR) fusions of substantial centromeric factors and chromatin modifiers. This analysis revealed four classes of factors that influence CENP-A assembly. Interestingly, many kinetochore structural components induced de novo CENP-A assembly at the ectopic site. We showed that these components work by recruiting CENP-C and subsequently recruiting M18BP1. Furthermore, we found that CENP-I can also recruit M18BP1 and, as a consequence, enhances M18BP1 assembly on centromeres in the downstream of CENP-C. Thus, we suggest that CENP-C and CENP-I are key factors connecting kinetochore to CENP-A assembly. PMID:26527398

  13. Heterogeneous nuclear ribonucleoprotein K upregulates the kinetochore complex component NUF2 and promotes the tumorigenicity of colon cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Sugimasa, Hironobu; Taniue, Kenzui [Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo, 113-0032 (Japan); Kurimoto, Akiko [Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo, 113-0032 (Japan); Oncology Research Laboratories, Daiichi Sankyo Co., Ltd, 1-2-58, Hiromachi, Shinagawa-ku, Tokyo, 140-8710 (Japan); Takeda, Yasuko; Kawasaki, Yoshihiro [Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo, 113-0032 (Japan); Akiyama, Tetsu, E-mail: akiyama@iam.u-tokyo.ac.jp [Laboratory of Molecular and Genetic Information, Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo, 113-0032 (Japan)

    2015-03-27

    Heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a multi-functional protein involved in transcription, mRNA splicing, mRNA stabilization and translation. Although hnRNP K has been suggested to play a role in the development of many cancers, its molecular function in colorectal cancer has remained elusive. Here we show that hnRNP K plays an important role in the mitotic process in HCT116 colon cancer cells. Furthermore, we demonstrate that hnRNP K directly transactivates the NUF2 gene, the product of which is a component of the NDC80 kinetochore complex and which is known to be critical for a stable spindle microtubule-kinetochore attachment. In addition, knockdown of both hnRNP K and NUF2 caused failure in metaphase chromosome alignment and drastic decrease in the growth of colon cancer cells. These results suggest that the hnRNP K-NUF2 axis is important for the mitotic process and proliferation of colon cancer cells and that this axis could be a target for the therapy of colon cancer. - Highlights: • hnRNP K is required for the tumorigenicity of colon cancer cells. • hnRNP K binds to the promoter region of NUF2 and activates its transcription. • NUF2 expression is correlated with hnRNP K expression in colorectal cancer tissue. • hnRNP K and NUF2 are required for metaphase chromosome alignment. • The hnRNP K-NUF2 axis is important for the proliferation of colon cancer cells.

  14. In vivo FRET imaging revealed a regulatory role of RanGTP in kinetochore-microtubule attachments via Aurora B kinase.

    Directory of Open Access Journals (Sweden)

    Yoke-Peng Lee

    Full Text Available Under the fluctuating circumstances provided by the innate dynamics of microtubules and opposing tensions resulted from microtubule-associated motors, it is vital to ensure stable kinetochore-microtubule attachments for accurate segregation. However, a comprehensive understanding of how this regulation is mechanistically achieved remains elusive. Using our newly designed live cell FRET time-lapse imaging, we found that post-metaphase RanGTP is crucial in the maintenance of stable kinetochore-microtubule attachments by regulating Aurora B kinase via the NES-bearing Mst1. More importantly, our study demonstrates that by ensuring stable alignment of metaphase chromosomes prior to segregation, RanGTP is indispensible in governing the genomic integrity and the fidelity of cell cycle progression. Our findings suggest an additional role of RanGTP beyond its known function in mitotic spindle assembly during the prometaphase-metaphase transition.

  15. Checkpoint genes required to delay cell division in response to nocodazole respond to impaired kinetochore function in the yeast Saccharomyces cerevisiae

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yanchang; Burke, D.J. [Univ. of Virginia, Charlottesville, VA (United States)

    1995-12-01

    This report describes the effects of antimitotic drugs on cell cycle when administered in quantities which maintain the spindle structure of microtubules. This research was carried out using the yeast Saccharomyces cerevisiae and the antimitotic drug nocodazole. Results show that a low concentration of nocodazole induces a cell cycle delay that is sensitive to impaired kinetochore function under the control of previously identified mitotic checkpoint genes. 40 refs., 6 figs., 4 tabs.

  16. Spindle checkpoint regulated by nonequilibrium collective spindle-chromosome interaction; relationship to single DNA molecule force-extension formula

    Energy Technology Data Exchange (ETDEWEB)

    Matsson, Leif, E-mail: leif.matsson@telia.co [Department of Physics, University of Gothenburg, SE-412 96 Goeteborg (Sweden)

    2009-12-16

    The spindle checkpoint, which blocks segregation until all sister chromatid pairs have been stably connected to the two spindle poles, is perhaps the biggest mystery of the cell cycle. The main reason seems to be that the spatial correlations imposed by microtubules between stably attached kinetochores and the nonlinear dependence of the system on the increasing number of such kinetochores have been disregarded in earlier spindle checkpoint studies. From these missing parts a non-equilibrium collective spindle-chromosome interaction is obtained here for budding yeast (Saccharomyces cerevisiae) cells. The interaction, which is based on a non-equilibrium statistical mechanics, can sense and count the number of stably attached kinetochores and sense the threshold for segregation. It blocks segregation until all sister chromatids pairs have been bi-oriented and regulates tension such that segregation becomes synchronized, thus explaining how the cell might decide to segregate replicated chromosomes. The model also predicts kinetochore oscillations at a frequency which agrees well with observation. Finally, a relationship between this spindle-chromosome dynamics and the force-extension formula obtained in a single DNA molecule experiment is obtained. (fast track communication)

  17. Kinetochore–microtubule attachment throughout mitosis potentiated by the elongated stalk of the kinetochore kinesin CENP-E

    Science.gov (United States)

    Vitre, Benjamin; Gudimchuk, Nikita; Borda, Ranier; Kim, Yumi; Heuser, John E.; Cleveland, Don W.; Grishchuk, Ekaterina L.

    2014-01-01

    Centromere protein E (CENP-E) is a highly elongated kinesin that transports pole-proximal chromosomes during congression in prometaphase. During metaphase, it facilitates kinetochore–microtubule end-on attachment required to achieve and maintain chromosome alignment. In vitro CENP-E can walk processively along microtubule tracks and follow both growing and shrinking microtubule plus ends. Neither the CENP-E–dependent transport along microtubules nor its tip-tracking activity requires the unusually long coiled-coil stalk of CENP-E. The biological role for the CENP-E stalk has now been identified through creation of “Bonsai” CENP-E with significantly shortened stalk but wild-type motor and tail domains. We demonstrate that Bonsai CENP-E fails to bind microtubules in vitro unless a cargo is contemporaneously bound via its C-terminal tail. In contrast, both full-length and truncated CENP-E that has no stalk and tail exhibit robust motility with and without cargo binding, highlighting the importance of CENP-E stalk for its activity. Correspondingly, kinetochore attachment to microtubule ends is shown to be disrupted in cells whose CENP-E has a shortened stalk, thereby producing chromosome misalignment in metaphase and lagging chromosomes during anaphase. Together these findings establish an unexpected role of CENP-E elongated stalk in ensuring stability of kinetochore–microtubule attachments during chromosome congression and segregation. PMID:24920822

  18. Condensin HEAT subunits required for DNA repair, kinetochore/centromere function and ploidy maintenance in fission yeast.

    Directory of Open Access Journals (Sweden)

    Xingya Xu

    Full Text Available Condensin, a central player in eukaryotic chromosomal dynamics, contains five evolutionarily-conserved subunits. Two SMC (structural maintenance of chromosomes subunits contain ATPase, hinge, and coiled-coil domains. One non-SMC subunit is similar to bacterial kleisin, and two other non-SMC subunits contain HEAT (similar to armadillo repeats. Here we report isolation and characterization of 21 fission yeast (Schizosaccharomyces pombe mutants for three non-SMC subunits, created using error-prone mutagenesis that resulted in single-amino acid substitutions. Beside condensation, segregation, and DNA repair defects, similar to those observed in previously isolated SMC and cnd2 mutants, novel phenotypes were observed for mutants of HEAT-repeats containing Cnd1 and Cnd3 subunits. cnd3-L269P is hypersensitive to the microtubule poison, thiabendazole, revealing defects in kinetochore/centromere and spindle assembly checkpoints. Three cnd1 and three cnd3 mutants increased cell size and doubled DNA content, thereby eliminating the haploid state. Five of these mutations reside in helix B of HEAT repeats. Two non-SMC condensin subunits, Cnd1 and Cnd3, are thus implicated in ploidy maintenance.

  19. Distribution of lifetimes of kinetochore-microtubule attachments: interplay of energy landscape, molecular motors and microtubule (de-)polymerization

    Science.gov (United States)

    Sharma, Ajeet K.; Shtylla, Blerta; Chowdhury, Debashish

    2014-06-01

    Before a cell divides into two daughter cells, chromosomes are replicated resulting in two sister chromosomes embracing each other. Each sister chromosome is bound to a separate proteinous structure, called kinetochore (kt), that captures the tip of a filamentous protein, called microtubule (MT). Two oppositely oriented MTs pull the two kts attached to two sister chromosomes, thereby pulling the two sisters away from each other. Here we theoretically study an even simpler system, namely an isolated kt coupled to a single MT; this system mimics an in vitro experiment where a single kt-MT attachment is reconstituted using purified extracts from budding yeast. Our models not only account for the experimentally observed ‘catch-bond-like’ behavior of the kt-MT coupling, but also make new predictions on the probability distribution of the lifetimes of the attachments. In principle, our new predictions can be tested by analyzing the data collected in the in vitro experiments, provided that the experiment is repeated a sufficiently large number of times. Our theory provides a deep insight into the effects of (a) size, (b) energetics, and (c) stochastic kinetics of the kt-MT coupling on the distribution of the lifetimes of these attachments.

  20. Spindle Checkpoint Regulated by Non-Equilibrium Collective Spindle-Chromosome Interaction; Relationship to Single DNA Molecule Force-Extension Formula

    Science.gov (United States)

    Matsson, Leif

    2010-03-01

    The spindle checkpoint, which blocks segregation until all sister chromatid pairs have been stably connected to the two spindle poles, is perhaps the biggest mystery of the cell cycle. The main reason seems to be that the spatial correlations imposed by microtubules between kinetochores and nonlinear dependence on the increasing number of such kinetochores, have been disregarded in earlier studies. From these missing parts a non-equilibrium collective spindle-chromosome interaction is obtained for budding yeast (Saccharomyces cereviciae) (J. Phys. Cond. Matter 21 (2009) 502101). The interaction, based on a non-equilibrium statistical mechanics, senses and counts the stably attached kinetochores and senses the threshold for segregation. It blocks segregation until all sister chromatids pairs are bi-oriented, regulates tension such that segregation is synchronized, explaining how the cell might decide to segregate replicated chromosomes. It also predicts kinetochore oscillations at a frequency which agrees well with observation. Finally, a relationship between this interaction and the force-extension formula of a single DNA molecule is obtained.

  1. Reduced Life- and Healthspan in Mice Carrying a Mono-Allelic BubR1 MVA Mutation

    NARCIS (Netherlands)

    Wijshake, Tobias; Malureanu, Liviu A.; Baker, Darren J.; Jeganathan, Karthik B.; van de Sluis, Bart; van Deursen, Jan M.

    2012-01-01

    Mosaic Variegated Aneuploidy (MVA) syndrome is a rare autosomal recessive disorder characterized by inaccurate chromosome segregation and high rates of near-diploid aneuploidy. Children with MVA syndrome die at an early age, are cancer prone, and have progeroid features like facial dysmorphisms,

  2. Chromosomal localization of the genes encoding the kinetochore proteins CENPE and DENPF to human chromosomes 4q24{r_arrow}q25 and 1q32{r_arrow}q41, respectively, by fluorescence in situ hybridization

    Energy Technology Data Exchange (ETDEWEB)

    Testa, J.R.; Zhou, J.Y.; Bell, D.W.; Yen, T.J. [Fox Chase Cancer Center, Philadelphia, PA (United States)

    1994-10-01

    CENPE and CENPF are human kinetochore proteins of 312 and {approximately}400 kDa, respectively. As part of an effort to characterize the functions of these two proteins, we have used their respective cDNAs to map their human chromosomal locations by fluorescence in situ hybridization. The gene that encodes CENPE, a kinetochore-associated motor protein that is postulated to segregate chromosomes during mitosis, maps to chromosome 4q24{r_arrow}q25. The CENPF gene, which encodes a structural protein of the kinetochore, maps to chromosome 1q32{r_arrow}q41 within close proximity to the genetic locus that is linked to Van der Woude syndrome. 8 refs., 1 fig.

  3. FAST TRACK COMMUNICATION: Spindle checkpoint regulated by nonequilibrium collective spindle-chromosome interaction; relationship to single DNA molecule force-extension formula

    Science.gov (United States)

    Matsson, Leif

    2009-12-01

    The spindle checkpoint, which blocks segregation until all sister chromatid pairs have been stably connected to the two spindle poles, is perhaps the biggest mystery of the cell cycle. The main reason seems to be that the spatial correlations imposed by microtubules between stably attached kinetochores and the nonlinear dependence of the system on the increasing number of such kinetochores have been disregarded in earlier spindle checkpoint studies. From these missing parts a non-equilibrium collective spindle-chromosome interaction is obtained here for budding yeast (Saccharomyces cerevisiae) cells. The interaction, which is based on a non-equilibrium statistical mechanics, can sense and count the number of stably attached kinetochores and sense the threshold for segregation. It blocks segregation until all sister chromatids pairs have been bi-oriented and regulates tension such that segregation becomes synchronized, thus explaining how the cell might decide to segregate replicated chromosomes. The model also predicts kinetochore oscillations at a frequency which agrees well with observation. Finally, a relationship between this spindle-chromosome dynamics and the force-extension formula obtained in a single DNA molecule experiment is obtained.

  4. Gamma-tubulin is required for bipolar spindle assembly and for proper kinetochore microtubule attachments during prometaphase I in Drosophila oocytes.

    Directory of Open Access Journals (Sweden)

    Stacie E Hughes

    2011-08-01

    Full Text Available In many animal species the meiosis I spindle in oocytes is anastral and lacks centrosomes. Previous studies of Drosophila oocytes failed to detect the native form of the germline-specific γ-tubulin (γTub37C in meiosis I spindles, and genetic studies have yielded conflicting data regarding the role of γTub37C in the formation of bipolar spindles at meiosis I. Our examination of living and fixed oocytes carrying either a null allele or strong missense mutation in the γtub37C gene demonstrates a role for γTub37C in the positioning of the oocyte nucleus during late prophase, as well as in the formation and maintenance of bipolar spindles in Drosophila oocytes. Prometaphase I spindles in γtub37C mutant oocytes showed wide, non-tapered spindle poles and disrupted positioning. Additionally, chromosomes failed to align properly on the spindle and showed morphological defects. The kinetochores failed to properly co-orient and often lacked proper attachments to the microtubule bundles, suggesting that γTub37C is required to stabilize kinetochore microtubule attachments in anastral spindles. Although spindle bipolarity was sometimes achieved by metaphase I in both γtub37C mutants, the resulting chromosome masses displayed highly disrupted chromosome alignment. Therefore, our data conclusively demonstrate a role for γTub37C in both the formation of the anastral meiosis I spindle and in the proper attachment of kinetochore microtubules. Finally, multispectral imaging demonstrates the presences of native γTub37C along the length of wild-type meiosis I spindles.

  5. Gamma-Tubulin Is Required for Bipolar Spindle Assembly and for Proper Kinetochore Microtubule Attachments during Prometaphase I in Drosophila Oocytes

    Science.gov (United States)

    Seat, Angela; Slaughter, Brian D.; Unruh, Jay R.; Bauerly, Elisabeth; Matthies, Heinrich J. G.; Hawley, R. Scott

    2011-01-01

    In many animal species the meiosis I spindle in oocytes is anastral and lacks centrosomes. Previous studies of Drosophila oocytes failed to detect the native form of the germline-specific γ-tubulin (γTub37C) in meiosis I spindles, and genetic studies have yielded conflicting data regarding the role of γTub37C in the formation of bipolar spindles at meiosis I. Our examination of living and fixed oocytes carrying either a null allele or strong missense mutation in the γtub37C gene demonstrates a role for γTub37C in the positioning of the oocyte nucleus during late prophase, as well as in the formation and maintenance of bipolar spindles in Drosophila oocytes. Prometaphase I spindles in γtub37C mutant oocytes showed wide, non-tapered spindle poles and disrupted positioning. Additionally, chromosomes failed to align properly on the spindle and showed morphological defects. The kinetochores failed to properly co-orient and often lacked proper attachments to the microtubule bundles, suggesting that γTub37C is required to stabilize kinetochore microtubule attachments in anastral spindles. Although spindle bipolarity was sometimes achieved by metaphase I in both γtub37C mutants, the resulting chromosome masses displayed highly disrupted chromosome alignment. Therefore, our data conclusively demonstrate a role for γTub37C in both the formation of the anastral meiosis I spindle and in the proper attachment of kinetochore microtubules. Finally, multispectral imaging demonstrates the presences of native γTub37C along the length of wild-type meiosis I spindles. PMID:21852952

  6. Yeast Interacting Proteins Database: YLR423C, YKR083C [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available of the Dam1 complex (aka DASH complex), couples kinetochores to the force produce...lex), couples kinetochores to the force produced by MT depolymerization thereby aiding in chromosome segrega

  7. Yeast Interacting Proteins Database: YGR113W, YIL144W [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available indle checkpoint activity, kinetochore assembly and clustering Rows with this prey as prey (2) Rows with thi...heckpoint activity, kinetochore assembly and clustering Rows with this prey as pr

  8. Yeast Interacting Proteins Database: YGR113W, YKR037C [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available YGR113W DAM1 Essential subunit of the Dam1 complex (aka DASH complex), couples kinetochores to the force...KR037C SPC34 Essential subunit of the Dam1 complex (aka DASH complex), couples kinetochores to the force...M1 Bait description Essential subunit of the Dam1 complex (aka DASH complex), couples kinetochores to the force...escription Essential subunit of the Dam1 complex (aka DASH complex), couples kinetochores to the force produ

  9. Yeast Interacting Proteins Database: YGL061C, YDR016C [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available YGL061C DUO1 Essential subunit of the Dam1 complex (aka DASH complex), couples kinetochores to the force...6C DAD1 Essential subunit of the Dam1 complex (aka DASH complex), couples kinetochores to the force...it description Essential subunit of the Dam1 complex (aka DASH complex), couples kinetochores to the force p... Essential subunit of the Dam1 complex (aka DASH complex), couples kinetochores to the force produced by MT

  10. Yeast Interacting Proteins Database: YKR037C, YGL061C [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available YKR037C SPC34 Essential subunit of the Dam1 complex (aka DASH complex), couples kinetochores to the force...061C DUO1 Essential subunit of the Dam1 complex (aka DASH complex), couples kinetochores to the force...Bait description Essential subunit of the Dam1 complex (aka DASH complex), couples kinetochores to the force...ion Essential subunit of the Dam1 complex (aka DASH complex), couples kinetochores to the force produced by

  11. Yeast Interacting Proteins Database: YKR083C, YKL052C [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available YKR083C DAD2 Essential subunit of the Dam1 complex (aka DASH complex), couples kinetochores to the force...2C ASK1 Essential subunit of the Dam1 complex (aka DASH complex), couples kinetochores to the force...e name DAD2 Bait description Essential subunit of the Dam1 complex (aka DASH complex), couples kinetochores to the force...ey description Essential subunit of the Dam1 complex (aka DASH complex), couples kinetochores to the force p

  12. Yeast Interacting Proteins Database: YKR083C, YDR201W [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available YKR083C DAD2 Essential subunit of the Dam1 complex (aka DASH complex), couples kinetochores to the force...1W SPC19 Essential subunit of the Dam1 complex (aka DASH complex), couples kinetochores to the force...ait description Essential subunit of the Dam1 complex (aka DASH complex), couples kinetochores to the force ...on Essential subunit of the Dam1 complex (aka DASH complex), couples kinetochores to the force produced by M

  13. Yeast Interacting Proteins Database: YKR037C, YDR201W [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available YKR037C SPC34 Essential subunit of the Dam1 complex (aka DASH complex), couples kinetochores to the force...201W SPC19 Essential subunit of the Dam1 complex (aka DASH complex), couples kinetochores to the force...34 Bait description Essential subunit of the Dam1 complex (aka DASH complex), couples kinetochores to the force...ription Essential subunit of the Dam1 complex (aka DASH complex), couples kinetochores to the force produced

  14. Yeast Interacting Proteins Database: YKR037C, YDR016C [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available YKR037C SPC34 Essential subunit of the Dam1 complex (aka DASH complex), couples kinetochores to the force...016C DAD1 Essential subunit of the Dam1 complex (aka DASH complex), couples kinetochores to the force...Bait description Essential subunit of the Dam1 complex (aka DASH complex), couples kinetochores to the force...ion Essential subunit of the Dam1 complex (aka DASH complex), couples kinetochores to the force produced by

  15. Yeast Interacting Proteins Database: YGR113W, YGL061C [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available YGR113W DAM1 Essential subunit of the Dam1 complex (aka DASH complex), couples kinetochores to the force...GL061C DUO1 Essential subunit of the Dam1 complex (aka DASH complex), couples kinetochores to the force...M1 Bait description Essential subunit of the Dam1 complex (aka DASH complex), couples kinetochores to the force...scription Essential subunit of the Dam1 complex (aka DASH complex), couples kinetochores to the force produc

  16. Yeast Interacting Proteins Database: YGR113W, YDR016C [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available YGR113W DAM1 Essential subunit of the Dam1 complex (aka DASH complex), couples kinetochores to the force...DR016C DAD1 Essential subunit of the Dam1 complex (aka DASH complex), couples kinetochores to the force... Bait description Essential subunit of the Dam1 complex (aka DASH complex), couples kinetochores to the force...ription Essential subunit of the Dam1 complex (aka DASH complex), couples kinetochores to the force produced

  17. EZH2 is required for mouse oocyte meiotic maturation by interacting with and stabilizing spindle assembly checkpoint protein BubRI

    OpenAIRE

    Qu, Yi; Lu, Danyu; Jiang, Hao; Chi, Xiaochun; Zhang, Hongquan

    2016-01-01

    Enhancer of zeste homolog 2 (EZH2) trimethylates histone H3 Lys 27 and plays key roles in a variety of biological processes. Stability of spindle assembly checkpoint protein BubR1 is essential for mitosis in somatic cells and for meiosis in oocytes. However, the role of EZH2 in oocyte meiotic maturation was unknown. Here, we presented a mechanism underlying EZH2 control of BubR1 stability in the meiosis of mouse oocytes. We identified a methyltransferase activity-independent function of EZH2 ...

  18. Multipolar spindle pole coalescence is a major source of kinetochore mis-attachment and chromosome mis-segregation in cancer cells.

    Directory of Open Access Journals (Sweden)

    William T Silkworth

    Full Text Available Many cancer cells display a CIN (Chromosome Instability phenotype, by which they exhibit high rates of chromosome loss or gain at each cell cycle. Over the years, a number of different mechanisms, including mitotic spindle multipolarity, cytokinesis failure, and merotelic kinetochore orientation, have been proposed as causes of CIN. However, a comprehensive theory of how CIN is perpetuated is still lacking. We used CIN colorectal cancer cells as a model system to investigate the possible cellular mechanism(s underlying CIN. We found that CIN cells frequently assembled multipolar spindles in early mitosis. However, multipolar anaphase cells were very rare, and live-cell experiments showed that almost all CIN cells divided in a bipolar fashion. Moreover, fixed-cell analysis showed high frequencies of merotelically attached lagging chromosomes in bipolar anaphase CIN cells, and higher frequencies of merotelic attachments in multipolar vs. bipolar prometaphases. Finally, we found that multipolar CIN prometaphases typically possessed gamma-tubulin at all spindle poles, and that a significant fraction of bipolar metaphase/early anaphase CIN cells possessed more than one centrosome at a single spindle pole. Taken together, our data suggest a model by which merotelic kinetochore attachments can easily be established in multipolar prometaphases. Most of these multipolar prometaphase cells would then bi-polarize before anaphase onset, and the residual merotelic attachments would produce chromosome mis-segregation due to anaphase lagging chromosomes. We propose this spindle pole coalescence mechanism as a major contributor to chromosome instability in cancer cells.

  19. Kinetochore of the Lepidoptera, (2). Chromosomal features and behavior in meiotic-II and in /sup 60/Co-treated cells

    Energy Technology Data Exchange (ETDEWEB)

    Maeki, K. (Kwansei Gakuin Univ., Nishinomiya, Hyogo (Japan). Faculty of Science)

    1980-10-01

    The chromosomes of Graphium Sarpedon (n, 20) and Eumeta variegata were examined by the acetoorcein squash method. In the equatorial plate of M-2 metaphase, two sister chromatids (rod-type) appeared in linear arrangement. The spindle fibers then gathered to the chromosomal part toward the cell pole, which condensed longwise on the other side. In the second anaphase, the two sister chromatids moved to the opposite poles, they appeared to move toward the pole ends-first. The M-2 metaphase and anaphase were identified only for the chromosomes equipped with the diffuse kinetochore structure. The male larvae of Graphium Sarpedon at the last-instar were irradiated with 800, 1000, 1500 or 2000 R of /sup 60/Co to induce chromosome fragmentation, and killed 18, 21, 24, 27 and 30 hrs after the irradiation. The chromosomal aberration at the meitotic stage after the irradiation of 1500 R and 2000 R was pronounced. Although the normal haploid chromosome number of G. sarpedon is 20, it was found that the irradiated larvae had 21 or 19 chromosomes at the M-1 metaphase. The aberration resulted from chromosomal fusion as well as from fragmentation during meiosis. It was suggested that the induced fragment chromosomes each carry kinetochore. In general, it is considered that the chromosomes of lepidopteran insects were characterized by holokinetic organization.

  20. A hemicentric inversion in the maize line knobless Tama flint created two sites of centromeric elements and moved the kinetochore-forming region.

    Science.gov (United States)

    Lamb, Jonathan C; Meyer, Julie M; Birchler, James A

    2007-06-01

    A maize line, knobless Tama flint (KTF), was found to contain a version of chromosome 8 with two spatially distinct regions of centromeric elements, one at the original genetic position and the other at a novel location on the long arm. The new site of centromeric elements functions as the kinetochore-forming region resulting in a change of arm length ratio. Examination of fluorescence in situ hybridization markers on chromosome 8 revealed an inversion between the two centromere sites relative to standard maize lines, indicating that this chromosome 8 resulted from a hemicentric inversion with one breakpoint approximately 20 centi-McClintocks (cMc) on the long arm (20% of the total arm length from the centromere) and the other in the original cluster of centromere repeats. This inversion moved the kinetochore-forming region but left the remainder of the centromere repeats. In a hybrid between a standard line (Mo17) and KTF, both chromosome 8 homologues were completely synapsed at pachytene despite the inversion. Although the homologous centromeres were not paired, they were always correctly oriented at anaphase and migrated to opposite poles. Additionally, recombination on 8L was severely repressed in the hybrid.

  1. DNA damage induces a kinetochore-based ATM/ATR-independent SAC arrest unique to the first meiotic division in mouse oocytes.

    Science.gov (United States)

    Lane, Simon I R; Morgan, Stephanie L; Wu, Tianyu; Collins, Josie K; Merriman, Julie A; ElInati, Elias; Turner, James M; Jones, Keith T

    2017-10-01

    Mouse oocytes carrying DNA damage arrest in meiosis I, thereby preventing creation of embryos with deleterious mutations. The arrest is dependent on activation of the spindle assembly checkpoint, which results in anaphase-promoting complex (APC) inhibition. However, little is understood about how this checkpoint is engaged following DNA damage. Here, we find that within minutes of DNA damage checkpoint proteins are assembled at the kinetochore, not at damage sites along chromosome arms, such that the APC is fully inhibited within 30 min. Despite this robust response, there is no measurable loss in k-fibres, or tension across the bivalent. Through pharmacological inhibition we observed that the response is dependent on Mps1 kinase, aurora kinase and Haspin. Using oocyte-specific knockouts we find the response does not require the DNA damage response kinases ATM or ATR. Furthermore, checkpoint activation does not occur in response to DNA damage in fully mature eggs during meiosis II, despite the divisions being separated by just a few hours. Therefore, mouse oocytes have a unique ability to sense DNA damage rapidly by activating the checkpoint at their kinetochores. © 2017. Published by The Company of Biologists Ltd.

  2. Yeast Interacting Proteins Database: YER081W, YPL233W [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available oins kinetochore subunits contacting DNA to those contacting microtubules; requir...tacting DNA to those contacting microtubules; required for accurate chromosome segr...t of the MIND kinetochore complex (Mtw1p Including Nnf1p-Nsl1p-Dsn1p) which joins kinetochore subunits con

  3. Unprotected Drosophila melanogaster telomeres activate the spindle assembly checkpoint.

    Science.gov (United States)

    Musarò, Mariarosaria; Ciapponi, Laura; Fasulo, Barbara; Gatti, Maurizio; Cenci, Giovanni

    2008-03-01

    In both yeast and mammals, uncapped telomeres activate the DNA damage response (DDR) and undergo end-to-end fusion. Previous work has shown that the Drosophila HOAP protein, encoded by the caravaggio (cav) gene, is required to prevent telomeric fusions. Here we show that HOAP-depleted telomeres activate both the DDR and the spindle assembly checkpoint (SAC). The cell cycle arrest elicited by the DDR was alleviated by mutations in mei-41 (encoding ATR), mus304 (ATRIP), grp (Chk1) and rad50 but not by mutations in tefu (ATM). The SAC was partially overridden by mutations in zw10 (also known as mit(1)15) and bubR1, and also by mutations in mei-41, mus304, rad50, grp and tefu. As expected from SAC activation, the SAC proteins Zw10, Zwilch, BubR1 and Cenp-meta (Cenp-E) accumulated at the kinetochores of cav mutant cells. Notably, BubR1 also accumulated at cav mutant telomeres in a mei-41-, mus304-, rad50-, grp- and tefu-dependent manner. Our results collectively suggest that recruitment of BubR1 by dysfunctional telomeres inhibits Cdc20-APC function, preventing the metaphase-to-anaphase transition.

  4. INTERACT

    DEFF Research Database (Denmark)

    Jochum, Elizabeth; Borggreen, Gunhild; Murphey, TD

    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...... including puppetry and dance. However, the aesthetics of these traditions vary across cultures and carry different associative and interpretive meanings. Puppetry offers a useful frame for understanding the relationship between abstract and imitative gestures and behavior, and instantiates the complex...

  5. Cyclic AMP responsive element-binding protein promotes renal cell carcinoma proliferation probably via the expression of spindle and kinetochore-associated protein 2.

    Science.gov (United States)

    Zhuang, Haihui; Meng, Xiangyu; Li, Yanyuan; Wang, Xue; Huang, Shuaishuai; Liu, Kaitai; Hehir, Michael; Fang, Rong; Jiang, Lei; Zhou, Jeff X; Wang, Ping; Ren, Yu

    2016-03-29

    Emerging evidence shows that the aberrantly expressed cyclic AMP responsive element-binding protein (CREB) is associated with tumor development and progression in several cancers. Spindle and kinetochore-associated protein 2 (SKA2) is essential for regulating the progress of mitosis. In this study, we evaluate in vitro and in vivo the functional relationship between CREB and SKA2 in renal cell carcinoma (RCC). Suppressing and replenishing CREB levels were used to manipulate SKA2 expression, observing the effects on RCC cell lines. Computational prediction and ChIP assay identified that CREB targeted ska2 by binding its CRE sequence in the human genome. Overexpression of CREB reversed the inhibited cell growth following siSKA2 treatment, and reduced the number of cells holding in mitosis. Decreased expression of CREB suppressed RCC cell growth and xenograft tumor formation, accompanied by reduced expression of SKA2. In RCC tumor samples from patients, mRNA for SKA2 were plotted near those of CREB in each sample, with significantly increased immunohistochemical staining of higher SKA2 and CREB in the higher TNM stages. The study adds evidence that CREB, a tumor oncogene, promotes RCC proliferation. It probably achieves this by increasing SKA2 expression.

  6. Establishment of cohesion at the pericentromere by the Ctf19 kinetochore subcomplex and the replication fork-associated factor, Csm3.

    Directory of Open Access Journals (Sweden)

    Josefin Fernius

    2009-09-01

    Full Text Available The cohesin complex holds sister chromatids together from the time of their duplication in S phase until their separation during mitosis. Although cohesin is found along the length of chromosomes, it is most abundant at the centromere and surrounding region, the pericentromere. We show here that the budding yeast Ctf19 kinetochore subcomplex and the replication fork-associated factor, Csm3, are both important mediators of pericentromeric cohesion, but they act through distinct mechanisms. We show that components of the Ctf19 complex direct the increased association of cohesin with the pericentromere. In contrast, Csm3 is dispensable for cohesin enrichment in the pericentromere but is essential in ensuring its functionality in holding sister centromeres together. Consistently, cells lacking Csm3 show additive cohesion defects in combination with mutants in the Ctf19 complex. Furthermore, delaying DNA replication rescues the cohesion defect observed in cells lacking Ctf19 complex components, but not Csm3. We propose that the Ctf19 complex ensures additional loading of cohesin at centromeres prior to passage of the replication fork, thereby ensuring its incorporation into functional linkages through a process requiring Csm3.

  7. Yeast Interacting Proteins Database: YDR439W, YCR086W [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available inetochores during meiosis I to mediate accurate homolog segregation; required for condensin recruitment to ...and then Mam1p at kinetochores during meiosis I to mediate accurate homolog segregation; required for condensin recruitment...p, and then Mam1p at kinetochores during meiosis I to mediate accurate homolog segregation; required for condensin recruitment...with Lrs4p and then Mam1p at kinetochores during meiosis I to mediate accurate homolog segregation; required for condensin recruitmen

  8. Yeast Interacting Proteins Database: YOL069W, YIL144W [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available complex (Ndc80p-Nuf2p-Spc24p-Spc25p); involved in chromosome segregation, spindle checkpoint activity and kinetochore clustering...vity, kinetochore assembly and clustering Rows with this prey as prey (2) Rows with this prey as bait (0) 12...-Nuf2p-Spc24p-Spc25p); involved in chromosome segregation, spindle checkpoint activity and kinetochore clustering...d coiled-coil protein involved in chromosome segregation, spindle checkpoint activity, kinetochore assembly and clustering

  9. Method to Assemble Genomic DNA Fragments or Genes on Human Artificial Chromosome with Regulated Kinetochore Using a Multi-Integrase System.

    Science.gov (United States)

    Lee, Nicholas C O; Kim, Jung-Hyun; Petrov, Nikolai S; Lee, Hee-Sheung; Masumoto, Hiroshi; Earnshaw, William C; Larionov, Vladimir; Kouprina, Natalay

    2018-01-19

    The production of cells capable of carrying multiple transgenes to Mb-size genomic loci has multiple applications in biomedicine and biotechnology. In order to achieve this goal, three key steps are required: (i) cloning of large genomic segments; (ii) insertion of multiple DNA blocks at a precise location and (iii) the capability to eliminate the assembled region from cells. In this study, we designed the iterative integration system (IIS) that utilizes recombinases Cre, ΦC31 and ΦBT1, and combined it with a human artificial chromosome (HAC) possessing a regulated kinetochore (alphoidtetO-HAC). We have demonstrated that the IIS-alphoidtetO-HAC system is a valuable genetic tool by reassembling a functional gene from multiple segments on the HAC. IIS-alphoidtetO-HAC has several notable advantages over other artificial chromosome-based systems. This includes the potential to assemble an unlimited number of genomic DNA segments; a DNA assembly process that leaves only a small insertion (<60 bp) scar between adjacent DNA, allowing genes reassembled from segments to be spliced correctly; a marker exchange system that also changes cell color, and counter-selection markers at each DNA insertion step, simplifying selection of correct clones; and presence of an error proofing mechanism to remove cells with misincorporated DNA segments, which improves the integrity of assembly. In addition, the IIS-alphoidtetO-HAC carrying a locus of interest is removable, offering the unique possibility to revert the cell line to its pretransformed state and compare the phenotypes of human cells with and without a functional copy of a gene(s). Thus, IIS-alphoidtetO-HAC allows investigation of complex biomedical pathways, gene(s) regulation, and has the potential to engineer synthetic chromosomes with a predetermined set of genes.

  10. Sequential assembly of centromeric proteins in male mouse meiosis.

    Directory of Open Access Journals (Sweden)

    María Teresa Parra

    2009-03-01

    Full Text Available The assembly of the mitotic centromere has been extensively studied in recent years, revealing the sequence and regulation of protein loading to this chromosome domain. However, few studies have analyzed centromere assembly during mammalian meiosis. This study specifically targets this approach on mouse spermatocytes. We have found that during prophase I, the proteins of the chromosomal passenger complex Borealin, INCENP, and Aurora-B load sequentially to the inner centromere before Shugoshin 2 and MCAK. The last proteins to be assembled are the outer kinetochore proteins BubR1 and CENP-E. All these proteins are not detected at the centromere during anaphase/telophase I and are then reloaded during interkinesis. The loading sequence of the analyzed proteins is similar during prophase I and interkinesis. These findings demonstrate that the interkinesis stage, regularly overlooked, is essential for centromere and kinetochore maturation and reorganization previous to the second meiotic division. We also demonstrate that Shugoshin 2 is necessary for the loading of MCAK at the inner centromere, but is dispensable for the loading of the outer kinetochore proteins BubR1 and CENP-E.

  11. Crystal structure of a PP2A B56-BubR1 complex and its implications for PP2A substrate recruitment and localization

    NARCIS (Netherlands)

    Wang, Jiao; Wang, Zhizhi; Yu, Tingting; Yang, Huan; Virshup, David M; Kops, Geert J P L; Lee, Sang Hyun; Zhou, Weihong; Li, Xin; Xu, Wenqing; Rao, Zihe

    Protein phosphatase 2A (PP2A) accounts for the majority of total Ser/Thr phosphatase activities in most cell types and regulates many biological processes. PP2A holoenzymes contain a scaffold A subunit, a catalytic C subunit, and one of the regulatory/targeting B subunits. How the B subunit controls

  12. Yeast Interacting Proteins Database: YDR034C, YGR113W [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available complex (aka DASH complex), couples kinetochores to the force produced by MT depolymerization thereby aidin...Rows with this bait as prey (0) YGR113W DAM1 Essential subunit of the Dam1 complex (aka DASH complex), coupl...es kinetochores to the force produced by MT depolymerization thereby aiding in ch

  13. Yeast Interacting Proteins Database: YKR037C, YLR423C [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available YKR037C SPC34 Essential subunit of the Dam1 complex (aka DASH complex), couples kinetochores to the force... subunit of the Dam1 complex (aka DASH complex), couples kinetochores to the force produced by MT depolymeri

  14. Yeast Interacting Proteins Database: YNL189W, YDR318W [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available ponent of the COMA complex (Ctf19p, Okp1p, Mcm21p, Ame1p) that bridges kinetochore subunits that are in contact...t of the COMA complex (Ctf19p, Okp1p, Mcm21p, Ame1p) that bridges kinetochore subunits that are in contact w

  15. Yeast Interacting Proteins Database: YOL069W, YNL086W [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available complex (Ndc80p-Nuf2p-Spc24p-Spc25p); involved in chromosome segregation, spindle checkpoint activity and kinetochore clustering...ved in chromosome segregation, spindle checkpoint activity and kinetochore clustering Rows with this bait as

  16. Yeast Interacting Proteins Database: YOL069W, YMR294W [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available complex (Ndc80p-Nuf2p-Spc24p-Spc25p); involved in chromosome segregation, spindle checkpoint activity and kinetochore clustering...heckpoint activity and kinetochore clustering Rows with this bait as bait Rows with this bait as bait (3) Ro

  17. Plk1 and Mps1 Cooperatively Regulate the Spindle Assembly Checkpoint in Human Cells

    Directory of Open Access Journals (Sweden)

    Conrad von Schubert

    2015-07-01

    Full Text Available Equal mitotic chromosome segregation is critical for genome integrity and is monitored by the spindle assembly checkpoint (SAC. We have previously shown that the consensus phosphorylation motif of the essential SAC kinase Monopolar spindle 1 (Mps1 is very similar to that of Polo-like kinase 1 (Plk1. This prompted us to ask whether human Plk1 cooperates with Mps1 in SAC signaling. Here, we demonstrate that Plk1 promotes checkpoint signaling at kinetochores through the phosphorylation of at least two Mps1 substrates, including KNL-1 and Mps1 itself. As a result, Plk1 activity enhances Mps1 catalytic activity as well as the recruitment of the SAC components Mad1:C-Mad2 and Bub3:BubR1 to kinetochores. We conclude that Plk1 strengthens the robustness of SAC establishment at the onset of mitosis and supports SAC maintenance during prolonged mitotic arrest.

  18. Yeast Interacting Proteins Database: YOR026W, YGR188C [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available res during prophase and metaphase, delays anaphase in the presence of unattached kinetochores; forms complex...b3p that is crucial in the checkpoint mechanism required to prevent cell cycle progression into anaphase in the presence...lizes to kinetochores during prophase and metaphase, delays anaphase in the presence of unattached kinetocho... and Bub3p that is crucial in the checkpoint mechanism required to prevent cell cycle progression into anaphase in the presence

  19. Dynamic autophosphorylation of mps1 kinase is required for faithful mitotic progression.

    Directory of Open Access Journals (Sweden)

    Xinghui Wang

    Full Text Available The spindle assembly checkpoint (SAC is a surveillance mechanism monitoring cell cycle progression, thus ensuring accurate chromosome segregation. The conserved mitotic kinase Mps1 is a key component of the SAC. The human Mps1 exhibits comprehensive phosphorylation during mitosis. However, the related biological relevance is largely unknown. Here, we demonstrate that 8 autophosphorylation sites within the N-terminus of Mps1, outside of the catalytic domain, are involved in regulating Mps1 kinetochore localization. The phospho-mimicking mutant of the 8 autophosphorylation sites impairs Mps1 localization to kinetochore and also affects the kinetochore recruitment of BubR1 and Mad2, two key SAC effectors, subsequently leading to chromosome segregation errors. Interestingly, the non-phosphorylatable mutant of the 8 autophosphorylation sites enhances Mps1 kinetochore localization and delays anaphase onset. We further show that the Mps1 phospho-mimicking and non-phosphorylatable mutants do not affect metaphase chromosome congression. Thus, our results highlight the importance of dynamic autophosphorylation of Mps1 in regulating accurate chromosome segregation and ensuring proper mitotic progression.

  20. Spindle assembly checkpoint signalling is uncoupled from chromosomal position in mouse oocytes.

    Science.gov (United States)

    Gui, Liming; Homer, Hayden

    2012-06-01

    The spindle assembly checkpoint (SAC) averts aneuploidy by coordinating proper bipolar chromosomal attachment with anaphase-promoting complex/cyclosome (APC/C)-mediated securin and cyclin B1 destruction required for anaphase onset. The generation of a Mad2-based signal at kinetochores is central to current models of SAC-based APC/C inhibition. During mitosis, kinetochores of polar-displaced chromosomes, which are at greatest risk of mis-segregating, recruit the highest levels of Mad2, thereby ensuring that SAC activation is proportionate to aneuploidy risk. Paradoxically, although an SAC operates in mammalian oocytes, meiosis I (MI) is notoriously error prone and polar-displaced chromosomes do not prevent anaphase onset. Here we find that Mad2 is not preferentially recruited to the kinetochores of polar chromosomes of wild-type mouse oocytes, in which polar chromosomes are rare, or of oocytes depleted of the kinesin-7 motor CENP-E, in which polar chromosomes are more abundant. Furthermore, in CENP-E-depleted oocytes, although polar chromosomal displacement intensified during MI and the capacity to form stable end-on attachments was severely compromised, all kinetochores nevertheless became devoid of Mad2. Thus, it is possible that the ability of the SAC to robustly discriminate chromosomal position might be compromised by the propensity of oocyte kinetochores to become saturated with unproductive attachments, thereby predisposing to aneuploidy. Our data also reveal novel functions for CENP-E in oocytes: first, CENP-E stabilises BubR1, thereby impacting MI progression; and second, CENP-E mediates bi-orientation by promoting kinetochore reorientation and preventing chromosomal drift towards the poles.

  1. An Arabidopsis tissue-specific RNAi method for studying genes essential to mitosis.

    Directory of Open Access Journals (Sweden)

    Brunilís Burgos-Rivera

    Full Text Available A large fraction of the genes in plants can be considered essential in the sense that when absent the plant fails to develop past the first few cell divisions. The fact that angiosperms pass through a haploid gametophyte stage can make it challenging to propagate such mutants even in the heterozygous condition. Here we describe a tissue-specific RNAi method that allows us to visualize cell division phenotypes in petals, which are large dispensable organs. Portions of the APETALA (AP3 and PISTILLATA (PI promoters confer early petal-specific expression. We show that when either promoter is used to drive the expression of a beta-glucuronidase (GUS RNAi transgene in plants uniformly expressing GUS, GUS expression is knocked down specifically in petals. We further tested the system by targeting the essential kinetochore protein CENPC and two different components of the Spindle Assembly Checkpoint (MAD2 and BUBR1. Plant lines expressing petal-specific RNAi hairpins targeting these genes exhibited an array of petal phenotypes. Cytological analyses of the affected flower buds confirmed that CENPC knockdown causes cell cycle arrest but provided no evidence that either MAD2 or BUBR1 are required for mitosis (although both genes are required for petal growth by this assay. A key benefit of the petal-specific RNAi method is that the phenotypes are not expressed in the lineages leading to germ cells, and the phenotypes are faithfully transmitted for at least four generations despite their pronounced effects on growth.

  2. Interaction between TBP and Condensin Drives the Organization and Faithful Segregation of Mitotic Chromosomes.

    Science.gov (United States)

    Iwasaki, Osamu; Tanizawa, Hideki; Kim, Kyoung-Dong; Yokoyama, Yuhki; Corcoran, Christopher J; Tanaka, Atsunari; Skordalakes, Emmanuel; Showe, Louise C; Noma, Ken-Ichi

    2015-09-03

    Genome/chromosome organization is highly ordered and controls various nuclear events, although the molecular mechanisms underlying the functional organization remain largely unknown. Here, we show that the TATA box-binding protein (TBP) interacts with the Cnd2 kleisin subunit of condensin to mediate interphase and mitotic chromosomal organization in fission yeast. TBP recruits condensin onto RNA polymerase III-transcribed (Pol III) genes and highly transcribed Pol II genes; condensin in turn associates these genes with centromeres. Inhibition of the Cnd2-TBP interaction disrupts condensin localization across the genome and the proper assembly of mitotic chromosomes, leading to severe defects in chromosome segregation and eventually causing cellular lethality. We propose that the Cnd2-TBP interaction coordinates transcription with chromosomal architecture by linking dispersed gene loci with centromeres. This chromosome arrangement can contribute to the efficient transmission of physical force at the kinetochore to chromosomal arms, thereby supporting the fidelity of chromosome segregation. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. A proteomic study of mitotic phase-specific interactors of EB1 reveals a role for SXIP-mediated protein interactions in anaphase onset

    Directory of Open Access Journals (Sweden)

    Naoka Tamura

    2015-01-01

    Full Text Available Microtubules execute diverse mitotic events that are spatially and temporally separated; the underlying regulation is poorly understood. By combining drug treatments, large-scale immunoprecipitation and mass spectrometry, we report the first comprehensive map of mitotic phase-specific protein interactions of the microtubule-end binding protein, EB1. EB1 interacts with some, but not all, of its partners throughout mitosis. We show that the interaction of EB1 with Astrin-SKAP complex, a key regulator of chromosome segregation, is enhanced during prometaphase, compared to anaphase. We find that EB1 and EB3, another EB family member, can interact directly with SKAP, in an SXIP-motif dependent manner. Using an SXIP defective mutant that cannot interact with EB, we uncover two distinct pools of SKAP at spindle microtubules and kinetochores. We demonstrate the importance of SKAP's SXIP-motif in controlling microtubule growth rates and anaphase onset, without grossly disrupting spindle function. Thus, we provide the first comprehensive map of temporal changes in EB1 interactors during mitosis and highlight the importance of EB protein interactions in ensuring normal mitosis.

  4. Interactive numerals

    Science.gov (United States)

    2017-01-01

    Although Arabic numerals (like ‘2016’ and ‘3.14’) are ubiquitous, we show that in interactive computer applications they are often misleading and surprisingly unreliable. We introduce interactive numerals as a new concept and show, like Roman numerals and Arabic numerals, interactive numerals introduce another way of using and thinking about numbers. Properly understanding interactive numerals is essential for all computer applications that involve numerical data entered by users, including finance, medicine, aviation and science. PMID:28484609

  5. ERK3 is required for metaphase-anaphase transition in mouse oocyte meiosis.

    Directory of Open Access Journals (Sweden)

    Sen Li

    2010-09-01

    Full Text Available ERK3 (extracellular signal-regulated kinase 3 is an atypical member of the mitogen-activated protein (MAP kinase family of serine/threonine kinases. Little is known about its function in mitosis, and even less about its roles in mammalian oocyte meiosis. In the present study, we examined the localization, expression and functions of ERK3 during mouse oocyte meiotic maturation. Immunofluorescent analysis showed that ERK3 localized to the spindles from the pre-MI stage to the MII stage. ERK3 co-localized with α-tubulin on the spindle fibers and asters in oocytes after taxol treatment. Deletion of ERK3 by microinjection of ERK3 morpholino (ERK3 MO resulted in oocyte arrest at the MI stage with severely impaired spindles and misaligned chromosomes. Most importantly, the spindle assembly checkpoint protein BubR1 could be detected on kinetochores even in oocytes cultured for 10 h. Low temperature treatment experiments indicated that ERK3 deletion disrupted kinetochore-microtubule (K-MT attachments. Chromosome spreading experiments showed that knock-down of ERK3 prevented the segregation of homologous chromosomes. Our data suggest that ERK3 is crucial for spindle stability and required for the metaphase-anaphase transition in mouse oocyte maturation.

  6. Cenp-meta is required for sustained spindle checkpoint

    Directory of Open Access Journals (Sweden)

    Thomas Rubin

    2014-05-01

    Full Text Available Cenp-E is a kinesin-like motor protein required for efficient end-on attachment of kinetochores to the spindle microtubules. Cenp-E immunodepletion in Xenopus mitotic extracts results in the loss of mitotic arrest and massive chromosome missegregation, whereas its depletion in mammalian cells leads to chromosome segregation defects despite the presence of a functional spindle assembly checkpoint (SAC. Cenp-meta has previously been reported to be the Drosophila homolog of vertebrate Cenp-E. In this study, we show that cenp-metaΔ mutant neuroblasts arrest in mitosis when treated with colchicine. cenp-metaΔ mutant cells display a mitotic delay. Yet, despite the persistence of the two checkpoint proteins Mad2 and BubR1 on unattached kinetochores, these cells eventually enter anaphase and give rise to highly aneuploid daughter cells. Indeed, we find that cenp-metaΔ mutant cells display a slow but continuous degradation of cyclin B, which eventually triggers the mitotic exit observed. Thus, our data provide evidence for a role of Cenp-meta in sustaining the SAC response.

  7. Floor interaction

    DEFF Research Database (Denmark)

    Petersen, Marianne Graves; Krogh, Peter; Ludvigsen, Martin

    2005-01-01

    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....

  8. Interactive Timetabling

    OpenAIRE

    Muller, Tomas; Bartak, Roman

    2001-01-01

    Timetabling is a typical application of constraint programming whose task is to allocate activities to slots in available resources respecting various constraints like precedence and capacity. In this paper we present a basic concept, a constraint model, and the solving algorithms for interactive timetabling. Interactive timetabling combines automated timetabling (the machine allocates the activities) with user interaction (the user can interfere with the process of timetabling). Because the ...

  9. 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...

  10. 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...... in the suggested benchmarking tool. The study investigates how different characteristics on dairy farms influences the technical efficiency....

  11. 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 a tool...

  12. Aesthetic Interaction

    DEFF Research Database (Denmark)

    Ludvigsen, Martin; Petersen, M.G.; Iversen, O.

    2004-01-01

    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...

  13. 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

  14. Interaction graphs

    DEFF Research Database (Denmark)

    Seiller, Thomas

    2016-01-01

    Interaction graphs were introduced as a general, uniform, construction of dynamic models of linear logic, encompassing all Geometry of Interaction (GoI) constructions introduced so far. This series of work was inspired from Girard's hyperfinite GoI, and develops a quantitative approach that should...... be understood as a dynamic version of weighted relational models. Until now, the interaction graphs framework has been shown to deal with exponentials for the constrained system ELL (Elementary Linear Logic) while keeping its quantitative aspect. Adapting older constructions by Girard, one can clearly define...... "full" exponentials, but at the cost of these quantitative features. We show here that allowing interpretations of proofs to use continuous (yet finite in a measure-theoretic sense) sets of states, as opposed to earlier Interaction Graphs constructions were these sets of states were discrete (and finite...

  15. Embarrassing Interactions

    DEFF Research Database (Denmark)

    Deterding, Sebastian; Lucero, Andrés; Holopainen, Jussi

    2015-01-01

    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 desig...... 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.......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...

  16. 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....

  17. 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 also...

  18. 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

  19. Cardiopulmonary interactions

    African Journals Online (AJOL)

    2006-08-28

    Aug 28, 2006 ... applications to a particular subspecialty,2-5 the reader is advised to have .... Using Ohm's law, it is known that PVR = (mean PAP – mean LAP)/Qp. PVR is determined by the interactions of the large capacitance vessels of the pulmonary arterial tree and ..... care setting, the application of this gas is usually.

  20. Explicit Interaction

    DEFF Research Database (Denmark)

    Löwgren, Jonas; Eriksen, Mette Agger; Linde, Per

    2006-01-01

    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...

  1. Interacting Components

    NARCIS (Netherlands)

    Orlic, B.; Broenink, Johannes F.; Welch, Peter; Kerridge, Jon; Barnes, Fred

    2006-01-01

    SystemCSP is a graphical modeling language based on both CSP and concepts of component-based software development. The component framework of SystemCSP enables specification of both interaction scenarios and relative execution ordering among components. Specification and implementation of

  2. Interactive Television.

    Science.gov (United States)

    Bisesi, Michael; Felder, B. Dell

    1986-01-01

    Universities can offer opportunities for workers in high-technology fields to gain state-of-the-art information and skills without traveling to campus, through interactive television training. Careful organization and planning of such programs, including selection of effective faculty and remote site personnel, are essential to their success. (MSE)

  3. 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...

  4. Generation of a Spindle Checkpoint Arrest from Synthetic Signaling Assemblies

    OpenAIRE

    Yuan, Ivan; Leontiou, Ioanna; Amin, Priya; May, Karen M.; Soper Ní Chafraidh, Sadhbh; Zlámalová, Eliška; Hardwick, Kevin G.

    2017-01-01

    Summary The spindle checkpoint acts as a mitotic surveillance system, monitoring interactions between kinetochores and spindle microtubules and ensuring high-fidelity chromosome segregation [1, 2, 3]. The checkpoint is activated by unattached kinetochores, and Mps1 kinase phosphorylates KNL1 on conserved MELT motifs to generate a binding site for the Bub3-Bub1 complex [4, 5, 6, 7]. This leads to dynamic kinetochore recruitment of Mad proteins [8, 9], a conformational change in Mad2 [10, 11, 1...

  5. Interactive cinema : engagement and interaction

    NARCIS (Netherlands)

    Vosmeer, Mirjam; Schouten, Ben; Mitchell, Alex; Fernández-Vara, Clara; Thue, David

    2014-01-01

    Technologies that were initially developed to be applied within the domain of video games are currently being used in experiments to explore their meaning and possibilities for cinema and cinema audiences. In this position paper we examine how narrativity, interactivity and engagement are mutually

  6. Interactive Macroeconomics

    Science.gov (United States)

    Di Guilmi, Corrado; Gallegati, Mauro; Landini, Simone

    2017-04-01

    Preface; List of tables; List of figures, 1. Introduction; Part I. Methodological Notes and Tools: 2. The state space notion; 3. The master equation; Part II. Applications to HIA Based Models: 4. Financial fragility and macroeconomic dynamics I: heterogeneity and interaction; 5. Financial fragility and macroeconomic Dynamics II: learning; Part III. Conclusions: 6. Conclusive remarks; Part IV. Appendices and Complements: Appendix A: Complements to Chapter 3; Appendix B: Solving the ME to solve the ABM; Appendix C: Specifying transition rates; Index.

  7. Interactive Governance

    DEFF Research Database (Denmark)

    Bang, Henrik

    2016-01-01

    Governance analysis has exploded in recent years, and it has become nearly impossible to tell what difference the concept and practice of governance makes from those of government and state. In addition governance analysis has been placed more and more in the shadow of the new institutionalisms and...... and growth. However, interactive governance is not a property or effect of institutions; nor does it apply solely to those individuals who seek success above everything else. It is connective more than individualistic or collectivistic in nature; and it manifests a governability capacity which...

  8. Interactive Workspaces

    DEFF Research Database (Denmark)

    Mogensen, Preben Holst

    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...... 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...

  9. 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.

  10. Attachment issues : Kinetochore transformations and spindle checkpoint silencing

    NARCIS (Netherlands)

    Etemad, Banafsheh; Kops, Geert J P L|info:eu-repo/dai/nl/226311481

    2016-01-01

    Cell division culminates in the segregation of duplicated chromosomes in opposite directions prior to cellular fission. This process is guarded by the spindle assembly checkpoint (SAC), which prevents the anaphase of cell division until stable connections between spindle microtubules and the

  11. Genetic approaches for identifying kinetochore components in Saccharomyces cerevisiae

    Energy Technology Data Exchange (ETDEWEB)

    Doheny, K.F.; Puziss, J.; Spencer, F.; Hieter, P. [John Hopkins Univ. Medical School, Baltimore, MD (United States)

    1993-12-31

    A fundamental aspect of the cell division cycle is the chromosome cycle in which each of the chromosomal DNA molecules undergoes a series of morphological changes and complex movements to ensure faithful distribution at mitosis. The gene products responsible for execution of the chromosome cycle include structural components, such as those that assemble into the mitotic spindle apparatus, and regulatory components, such as those that coordinate the ordered series of events leading to chromosome segregation within the cell cycle. We have been taking several genetic approaches to identify genes encoding determinants critical to the chromosome cycle in the budding yeast, S. cerevisiae.

  12. Attachment issues : kinetochore transformations and spindle checkpoint silencing

    NARCIS (Netherlands)

    Etemad, Banafsheh; Kops, Geert Jpl

    Cell division culminates in the segregation of duplicated chromosomes in opposite directions prior to cellular fission. This process is guarded by the spindle assembly checkpoint (SAC), which prevents the anaphase of cell division until stable connections between spindle microtubules and the

  13. OSBP-related protein 8 (ORP8) interacts with Homo sapiens sperm associated antigen 5 (SPAG5) and mediates oxysterol interference of HepG2 cell cycle

    Energy Technology Data Exchange (ETDEWEB)

    Zhong, Wenbin [Department of Biotechnology, Jinan University, Guangzhou 510632 (China); Zhou, You [Minerva Foundation Institute for Medical Research, Helsinki (Finland); Li, Jiwei [Department of Biotechnology, Jinan University, Guangzhou 510632 (China); Mysore, Raghavendra [Minerva Foundation Institute for Medical Research, Helsinki (Finland); Luo, Wei; Li, Shiqian [Department of Biotechnology, Jinan University, Guangzhou 510632 (China); Chang, Mau-Sun [Institute of Biochemical Sciences, National Taiwan University, No. 1, Taipei, Taiwan (China); Olkkonen, Vesa M. [Minerva Foundation Institute for Medical Research, Helsinki (Finland); Yan, Daoguang, E-mail: tydg@jnu.edu.cn [Department of Biotechnology, Jinan University, Guangzhou 510632 (China)

    2014-04-01

    We earlier identified OSBP-related protein 8 (ORP8) as an endoplasmic reticulum/nuclear envelope oxysterol-binding protein implicated in cellular lipid homeostasis, migration, and organization of the microtubule cytoskeleton. Here, a yeast two-hybrid screen identified Homo sapiens sperm associated antigen 5 (SPAG5)/Astrin as interaction partner of ORP8. The putative interaction was further confirmed by pull-down and co-immunoprecipitation assays. ORP8 did not colocalize with kinetochore-associated SPAG5 in mitotic HepG2 or HuH7 cells, but overexpressed ORP8 was capable of recruiting SPAG5 onto endoplasmic reticulum membranes in interphase cells. In our experiments, 25-hydroxycholesterol (25OHC) retarded the HepG2 cell cycle, causing accumulation in G2/M phase; ORP8 overexpression resulted in the same phenotype. Importantly, ORP8 knock-down dramatically inhibited the oxysterol effect on HepG2 cell cycle, suggesting a mediating role of ORP8. Furthermore, knock-down of SPAG5 significantly reduced the effects of both ORP8 overexpression and 25OHC on the cell cycle, placing SPAG5 downstream of the two cell-cycle interfering factors. Taken together, the present results suggest that ORP8 may via SPAG5 mediate oxysterol interference of the HepG2 cell cycle. - Highlights: • The oxysterol-binding protein ORP8 was found to interact with the mitotic regulator SPAG5/Astrin. • Treatment of HepG2 cells with 25-hydroxycholesterol caused cell cycle retardation in G2/M. • ORP8 overexpression caused a similar G2/M accumulation, and ORP8 knock-down reversed the 25-hydroxycholesterol effect. • Reduction of cellular of SPAG5/Astrin reversed the cell cycle effects of both 25-hydroxycholesterol and ORP8 overexpression. • Our results suggest that ORP8 mediates via SPAG5/Astrin the oxysterol interference of HepG2 cell cycle.

  14. Mps1Mph1 Kinase Phosphorylates Mad3 to Inhibit Cdc20Slp1-APC/C and Maintain Spindle Checkpoint Arrests.

    Directory of Open Access Journals (Sweden)

    Judith Zich

    2016-02-01

    Full Text Available The spindle checkpoint is a mitotic surveillance system which ensures equal segregation of sister chromatids. It delays anaphase onset by inhibiting the action of the E3 ubiquitin ligase known as the anaphase promoting complex or cyclosome (APC/C. Mad3/BubR1 is a key component of the mitotic checkpoint complex (MCC which binds and inhibits the APC/C early in mitosis. Mps1(Mph1 kinase is critical for checkpoint signalling and MCC-APC/C inhibition, yet few substrates have been identified. Here we identify Mad3 as a substrate of fission yeast Mps1(Mph1 kinase. We map and mutate phosphorylation sites in Mad3, producing mutants that are targeted to kinetochores and assembled into MCC, yet display reduced APC/C binding and are unable to maintain checkpoint arrests. We show biochemically that Mad3 phospho-mimics are potent APC/C inhibitors in vitro, demonstrating that Mad3p modification can directly influence Cdc20(Slp1-APC/C activity. This genetic dissection of APC/C inhibition demonstrates that Mps1(Mph1 kinase-dependent modifications of Mad3 and Mad2 act in a concerted manner to maintain spindle checkpoint arrests.

  15. 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...

  16. Problem of interactions: electromagnetic particles interaction

    CERN Document Server

    Sannikov-Proskuryakov, S S

    2001-01-01

    The electromagnetic interactions between charged particles are derived on the basis of the particles dynamic theory, proposed in the work of Sannikov. The electromagnetic interactions exist only in the relativistic model of the bihamiltonian system, based on the Heisenberg algebra. Existence of this type of interactions is connected with the U sub e (1)-degeneration of the basic state of the relativistic bihamiltonian system, lying in the basis of the given theory

  17. RZZ and Mad1 dynamics in Drosophila mitosis.

    Science.gov (United States)

    Défachelles, Lénaïg; Raich, Natacha; Terracol, Régine; Baudin, Xavier; Williams, Byron; Goldberg, Michael; Karess, Roger E

    2015-06-01

    The presence or absence of Mad1 at kinetochores is a major determinant of spindle assembly checkpoint (SAC) activity, the surveillance mechanism that delays anaphase onset if one or more kinetochores remain unattached to spindle fibers. Among the factors regulating the levels of Mad1 at kinetochores is the Rod, Zw10, and Zwilch (RZZ) complex, which is required for Mad1 recruitment through a mechanism that remains unknown. The relative dynamics and interactions of Mad1 and RZZ at kinetochores have not been extensively investigated, although Mad1 has been reported to be stably recruited to unattached kinetochores. In this study, we directly compare Mad1-green fluorescent protein (GFP) turnover dynamics on unattached Drosophila kinetochores with that of RZZ, tagged either with GFP-Rod or GFP-Zw10. We find that nearly 40 % of kinetochore-bound Mad1 has a significant dynamic component, turning over with a half-life of 12 s. RZZ in contrast is essentially stable on unattached kinetochores. In addition, we report that a fraction of RZZ and Mad1 can co-immunoprecipitate, indicating that the genetically determined recruitment hierarchy (in which Mad1 depends on RZZ) may reflect a physical association of the two complexes.

  18. beam-beam interaction

    CERN Multimedia

    2017-01-01

    The Beam 1 (represented in blue) and the Beam 2 (represented in red) are colliding with an angle at the Interaction Point (IP). The angle is needed to avoid unwanted multiple collisions along the interaction region. Despite of the separation introduced by the angle, the two beams interact via their electromagnetic field, the so called "beam-beam" interaction.

  19. 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....

  20. 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

  1. Interactive CFD simulations

    OpenAIRE

    Duque Lombana, Juan Fernando

    2007-01-01

    This project is about the development of an implementable Interactive Computer Fluid Dynamics methodology -- The range of this work begins with an overview of the current status of computational fluid dynamics simulation software and methodologies, continues with an introduction to what interactive and interactivity mean, develops an all original interactive CFD methodology to follow for the solution of fluid scenarios and finally, the description of the implementation of an interactive solve...

  2. Food and Drug Interactions.

    Science.gov (United States)

    Choi, Jong Hwan; Ko, Chang Mann

    2017-01-01

    Natural foods and vegetal supplements have recently become increasingly popular for their roles in medicine and as staple foods. This has, however, led to the increased risk of interaction between prescribed drugs and the bioactive ingredients contained in these foods. These interactions range from pharmacokinetic interactions (absorption, distribution, metabolism, and excretion influencing blood levels of drugs) to pharmacodynamic interactions (drug effects). In a quantitative respect, these interactions occur mainly during metabolism. In addition to the systemic metabolism that occurs mainly in the liver, recent studies have focused on the metabolism in the gastrointestinal tract endothelium before absorption. Inhibition of metabolism causes an increase in the blood levels of drugs and could have adverse reactions. The food-drug interactions causing increased blood levels of drugs may have beneficial or detrimental therapeutic effects depending on the intensity and predictability of these interactions. It is therefore important to understand the potential interactions between foods and drugs should and the specific outcomes of such interactions.

  3. Dynamic feature of mitotic arrest deficient 2-like protein 2 (MAD2L2) and structural basis for its interaction with chromosome alignment-maintaining phosphoprotein (CAMP).

    Science.gov (United States)

    Hara, Kodai; Taharazako, Shota; Ikeda, Masanori; Fujita, Hiroki; Mikami, Yoshiko; Kikuchi, Sotaro; Hishiki, Asami; Yokoyama, Hideshi; Ishikawa, Yoshinobu; Kanno, Shin-Ichiro; Tanaka, Kozo; Hashimoto, Hiroshi

    2017-10-27

    Mitotic arrest deficient 2-like protein 2 (MAD2L2), also termed MAD2B or REV7, is involved in multiple cellular functions including translesion DNA synthesis (TLS), signal transduction, transcription, and mitotic events. MAD2L2 interacts with chromosome alignment-maintaining phosphoprotein (CAMP), a kinetochore-microtubule attachment protein in mitotic cells, presumably through a novel "WK" motif in CAMP. Structures of MAD2L2 in complex with binding regions of the TLS proteins REV3 and REV1 have revealed that MAD2L2 has two faces for protein-protein interactions that are regulated by its C-terminal region; however, the mechanisms underlying the MAD2L2-CAMP interaction and the mitotic role of MAD2L2 remain unknown. Here we have determined the structures of human MAD2L2 in complex with a CAMP fragment in two crystal forms. The overall structure of the MAD2L2-CAMP complex in both crystal forms was essentially similar to that of the MAD2L2-REV3 complex. However, the residue interactions between MAD2L2 and CAMP were strikingly different from those in the MAD2L2-REV3 complex. Furthermore, structure-based interaction analyses revealed an unprecedented mechanism involving CAMP's WK motif. Surprisingly, in one of the crystal forms, the MAD2L2-CAMP complex formed a dimeric structure in which the C-terminal region of MAD2L2 was swapped and adopted an immature structure. The structure provides direct evidence for the dynamic nature of MAD2L2 structure, which in turn may have implications for the protein-protein interaction mechanism and the multiple functions of this protein. This work is the first structural study of MAD2L2 aside from its role in TLS and might pave the way to clarify MAD2L2's function in mitosis. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. 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...

  5. 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...

  6. Fundamental symmetries and interactions

    NARCIS (Netherlands)

    Jungmann, KP

    2005-01-01

    In nuclear physics numerous possibilities exist to investigate fundamental symmetries and interactions. In particular, the precise measurements of properties of fundamental fermions, searches for new interactions in beta-decays, and violations of discrete symmeties offer possibilities to search for

  7. Interactive chalk murals

    National Research Council Canada - National Science Library

    Muzzillo, Sarah; Santos, John

    2013-01-01

      Muzzillo and Santos discuss interactive chalk murals. Last summer, Apex High School art teacher Ian Sands was scrolling through his Twitter feed when he saw a tweet describing an interactive art park...

  8. Interacting agents in finance

    NARCIS (Netherlands)

    Hommes, C.; Durlauf, S.N.; Blume, L.E.

    2008-01-01

    Interacting agents in finance represent a behavioural, agent-based approach in which financial markets are viewed as complex adaptive systems consisting of many boundedly rational agents interacting through simple heterogeneous investment strategies, constantly adapting their behaviour in response

  9. Food and Drug Interactions

    OpenAIRE

    Choi, Jong Hwan; Ko, Chang Mann

    2017-01-01

    Natural foods and vegetal supplements have recently become increasingly popular for their roles in medicine and as staple foods. This has, however, led to the increased risk of interaction between prescribed drugs and the bioactive ingredients contained in these foods. These interactions range from pharmacokinetic interactions (absorption, distribution, metabolism, and excretion influencing blood levels of drugs) to pharmacodynamic interactions (drug effects). In a quantitative respect, these...

  10. Interaction Nets in Russian

    OpenAIRE

    Salikhmetov, Anton

    2013-01-01

    Draft translation to Russian of Chapter 7, Interaction-Based Models of Computation, from Models of Computation: An Introduction to Computability Theory by Maribel Fernandez. "In this chapter, we study interaction nets, a model of computation that can be seen as a representative of a class of models based on the notion of 'computation as interaction'. Interaction nets are a graphical model of computation devised by Yves Lafont in 1990 as a generalisation of the proof structures of linear logic...

  11. Device-less interaction

    NARCIS (Netherlands)

    Monaci, G.; Triki, M.; Sarroukh, B.E.

    2009-01-01

    This document describes the results of a technology survey for device-less interaction. The Device-less Interaction project (2007-307) aims at providing interaction options for future home appliances without resorting to a remote control or any other dedicated control device. The target home

  12. Interactivity: A Forgotten Art?

    Science.gov (United States)

    Sims, Rod

    1997-01-01

    This paper promotes further discussion and analysis of interactivity in learning environments and contains a classification of interaction types appropriate for consideration in multimedia settings. Through an examination of related factors associated with navigation and control, a matrix of interactive dimensions is proposed. (Author)

  13. 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...

  14. Global Interaction in Design

    Science.gov (United States)

    Bennett, Audrey Grace

    2010-01-01

    Based on a virtual conference, Glide'08 (Global Interaction in Design Education), that brought international design scholars together online, this special issue expands on the topics of cross-cultural communication and design and the technological affordances that support such interaction. The author discusses the need for global interaction in…

  15. 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...

  16. The Interactive Learning Toolkit: supporting interactive classrooms

    Science.gov (United States)

    Dutta, S.; McCauley, V.; Mazur, E.

    2004-05-01

    Research-based interactive learning techniques have dramatically improved student understanding. We have created the 'Interactive Learning Toolkit' (ILT), a web-based learning management system, to help implement two such pedagogies: Just in Time Teaching and Peer Instruction. Our main goal in developing this toolkit is to save the instructor time and effort and to use technology to facilitate the interaction between the students and the instructor (and between students themselves). After a brief review of both pedagogies, we will demonstrate the many exciting new features of the ILT. We will show how technology can not only implement, but also supplement and improve these pedagogies. We would like acknowdge grants from NSF and DEAS, Harvard University

  17. Food-drug interactions

    DEFF Research Database (Denmark)

    Schmidt, Lars E; Dalhoff, Kim

    2002-01-01

    Interactions between food and drugs may inadvertently reduce or increase the drug effect. The majority of clinically relevant food-drug interactions are caused by food-induced changes in the bioavailability of the drug. Since the bioavailability and clinical effect of most drugs are correlated......, the bioavailability is an important pharmacokinetic effect parameter. However, in order to evaluate the clinical relevance of a food-drug interaction, the impact of food intake on the clinical effect of the drug has to be quantified as well. As a result of quality review in healthcare systems, healthcare providers...... are increasingly required to develop methods for identifying and preventing adverse food-drug interactions. In this review of original literature, we have tried to provide both pharmacokinetic and clinical effect parameters of clinically relevant food-drug interactions. The most important interactions are those...

  18. 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.

  19. Cation-alkane interaction.

    Science.gov (United States)

    Premkumar, J Richard; Sastry, G Narahari

    2014-12-04

    Ab initio computations, up to CCSD(T)/CBS on model systems, and MP2/cc-pVTZ and DFT calculations are performed on cation-alkane and cation-alkene complexes, cation = Li(+), Na(+), Be(2+), Mg(2+), Ca(2+), Cu(+) and Zn(2+); alkane = C(n)H2(n+2) (n = 1-10) and C6H12; and alkene = C2H4 and C6H6. Density functional theory-symmetry adapted perturbation theory (DFT-SAPT) calculations reveal that the cation-alkane interactions are predominantly constituted of induction component. The dramatic modulation of the strength of their interaction and the topological features obtained from atoms in molecules (AIM) analysis are consistent with the characteristics of a typical noncovalent interaction. In contrast to many of the conventional noncovalent interactions, cation-alkane interactions are substantially strong and are comparable in strength to the well studied cation-π interactions.

  20. How Interactive Is the Interactive Whiteboard?

    Science.gov (United States)

    Quashie, Valerie

    2009-01-01

    An interactive whiteboard (IWB) is simply a surface onto which a computer screen can be displayed, via a projector. It is touch-sensitive and lets one use a pen like a mouse, controlling the computer from the board itself. Everything that can be displayed on a computer can be displayed onto the whiteboard and, if the computer is linked to speakers…

  1. 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...

  2. 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.)

  3. Interactive Strategy-Making

    DEFF Research Database (Denmark)

    Andersen, Torben Juul

    2015-01-01

    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......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...

  4. Food-drug interactions.

    Science.gov (United States)

    Bushra, Rabia; Aslam, Nousheen; Khan, Arshad Yar

    2011-03-01

    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 its own. These interactions may occur out of accidental misuse or due to lack of knowledge about the active ingredients involved in the relevant substances. Regarding food-drug interactions physicians and pharmacists recognize that some foods and drugs, when taken simultaneously, can alter the body's ability to utilize a particular food or drug, or cause serious side effects. Clinically significant drug interactions, which pose potential harm to the patient, may result from changes in pharmaceutical, pharmacokinetic, or pharmacodynamic properties. Some may be taken advantage of, to the benefit of patients, but more commonly drug interactions result in adverse drug events. Therefore it is advisable for patients to follow the physician and doctors instructions to obtain maximum benefits with least food-drug interactions. The literature survey was conducted by extracting data from different review and original articles on general or specific drug interactions with food. This review gives information about various interactions between different foods and drugs and will help physicians and pharmacists prescribe drugs cautiously with only suitable food supplement to get maximum benefit for the patient.

  5. Food-Drug Interactions

    Directory of Open Access Journals (Sweden)

    Arshad Yar Khan

    2011-03-01

    Full Text Available 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 its own. These interactions may occur out of accidental misuse or due to lack of knowledge about the active ingredients involved in the relevant substances. Regarding food-drug interactions physicians and pharmacists recognize that some foods and drugs, when taken simultaneously, can alter the body's ability to utilize a particular food or drug, or cause serious side effects. Clinically significant drug interactions, which pose potential harm to the patient, may result from changes in pharmaceutical, pharmacokinetic, or pharmacodynamic properties. Some may be taken advantage of, to the benefit of patients, but more commonly drug interactions result in adverse drug events. Therefore it is advisable for patients to follow the physician and doctors instructions to obtain maximum benefits with least fooddrug interactions. The literature survey was conducted by extracting data from different review and original articles on general or specific drug interactions with food. This review gives information about various interactions between different foods and drugs and will help physicians and pharmacists prescribe drugs cautiously with only suitable food supplement to get maximum benefit for the patient.

  6. 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 synergistic...

  7. Simulation of interactive games

    OpenAIRE

    Heiberg, Fredrik

    2016-01-01

    Interactive online games are increasingly popular in today's society, and the industry is growing fast. Games take place in a virtual world and involve interaction with other players. Some online games connect millions of people, and the game studios enjoy enormous revenue utilising different business models. The interactive game market has changed a lot over the years, and player demands have increased concerning functionality, content, and price. As a result, the costs related to developmen...

  8. 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

  9. 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....

  10. Drug-nutrient interactions.

    Science.gov (United States)

    Chan, Lingtak-Neander

    2013-07-01

    Drug-nutrient interactions are defined as physical, chemical, physiologic, or pathophysiologic relationships between a drug and a nutrient. The causes of most clinically significant drug-nutrient interactions are usually multifactorial. Failure to identify and properly manage drug-nutrient interactions can lead to very serious consequences and have a negative impact on patient outcomes. Nevertheless, with thorough review and assessment of the patient's history and treatment regimens and a carefully executed management strategy, adverse events associated with drug-nutrient interactions can be prevented. Based on the physiologic sequence of events after a drug or a nutrient has entered the body and the mechanism of interactions, drug-nutrient interactions can be categorized into 4 main types. Each type of interaction can be managed using similar strategies. The existing data that guide the clinical management of most drug-nutrient interactions are mostly anecdotal experience, uncontrolled observations, and opinions, whereas the science in understanding the mechanism of drug-nutrient interactions remains limited. The challenge for researchers and clinicians is to increase both basic and higher level clinical research in this field to bridge the gap between the science and practice. The research should aim to establish a better understanding of the function, regulation, and substrate specificity of the nutrient-related enzymes and transport proteins present in the gastrointestinal tract, as well as assess how the incidence and management of drug-nutrient interactions can be affected by sex, ethnicity, environmental factors, and genetic polymorphisms. This knowledge can help us develop a true personalized medicine approach in the prevention and management of drug-nutrient interactions.

  11. Interactive Presentation of Content

    Science.gov (United States)

    Magdin, Martin; Turcáni, Milan; Vrábel, Marek

    2009-01-01

    In the paper we discus about design of universal environment for solution of creating effective multimedia applications with accent on the implementation of interactive elements with the possibility of using the adaptive systems (AS). We also discuss about possibilities of offline presentation of this interactive multimedia adaptive animations…

  12. Mixed Interaction Spaces

    DEFF Research Database (Denmark)

    Lykke-Olesen, Andreas; Eriksson, E.; Hansen, T.R.

    In this paper, we describe a new interaction technique for mobile devices named Mixed Interaction Space that uses the camera of the mobile device to track the position, size and rotation of a fixed-point. In this demonstration we will present a system that uses a hand-drawn circle, colored object...

  13. Aspects, Dependencies, and Interactions

    NARCIS (Netherlands)

    Chitchyan, R; Fabry, J.; Bergmans, Lodewijk; Südholt, M.; Consel, C.

    2007-01-01

    For Aspect-Oriented Software Development (AOSD) the topic of Aspects, Dependencies and Interactions is of high importance across the whole range of development activities – from requirements engineering through to language design. Aspect interactions must be adequately addressed all across the

  14. Media Embedded Interactions.

    Science.gov (United States)

    Johnson, J. David

    A review of literature and two surveys, one of college students and one of a random sample of adults, were used to examine four aspects of media embedded interactions (social behavior in front of a TV or radio): their functions, their environment, their effects, and the reactions of the interactants to them. Television is seen as performing a…

  15. 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...

  16. 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.......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....

  17. Designs for Cooperative Interactions.

    Science.gov (United States)

    Fogarty, Robin

    Educators are moving toward models of instruction that contain a myriad of interaction patterns among teachers and students. This shift from didactic teaching models to intensely involving designs is difficult for teachers, but is made easier if seen as a gradual change. This book provides an overview of 12 cooperative interaction designs for the…

  18. Elements of interaction

    NARCIS (Netherlands)

    F. Arbab (Farhad)

    2010-01-01

    htmlabstractThe most challenging aspect of concurrency involves the study of interaction and its properties. Interaction refers to what transpires among two or more active entities whose (communication) actions mutually affect each other. In spite of the long-standing recognition of the

  19. Drug interactions: 1998 update.

    Science.gov (United States)

    1998-12-01

    (1) The 1998 edition of the Drug Interactions section of the French data sheet compendium (Dictionnaire Vidal) includes welcome updates. (2) Increasingly numerous interactions involve tramadol, clarithromycin, oral anticoagulants, antiepileptics, theophylline and various psychotropic agents. (3) An entire section is now devoted to the numerous potassium-raising drugs.

  20. Interactive Pinball Business

    DEFF Research Database (Denmark)

    Buur, Jacob; Gudiksen, Sune

    2012-01-01

    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...

  1. Interactive pinball business

    DEFF Research Database (Denmark)

    Buur, Jacob; Gudiksen, Sune Klok

    2012-01-01

    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...

  2. 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...

  3. Quantum contact interactions

    Indian Academy of Sciences (India)

    This is the transfer matrix representation [3], which has been treated as the standard form of generalized point .... the two-body interaction has no effect on identical bosons, but does have an effect on the fermions. ... We now go back to the generalU(2) representation of contact interactions, and look at the structure of the ...

  4. Acting, interacting, enacting

    DEFF Research Database (Denmark)

    Hazel, Spencer

    2015-01-01

    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...

  5. 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…

  6. Fibronectin-cell interactions

    DEFF Research Database (Denmark)

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

    1990-01-01

    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...

  7. 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...

  8. Legacy Systems Interaction Reengineering

    Science.gov (United States)

    El-Ramly, Mohammad; Stroulia, Eleni; Samir, Hani

    We present a lightweight approach for reengineering the human computer interaction (HCI) and/or interaction with other software systems. While interaction reengineering can be achieved by changing the source code and design (e.g., library replacement, refactoring, etc.) resulting in a different user interface (UI), we limit the discussion to interaction reengineering methods that do not involve changing the source code or internal design of the system. Instead, we focus on methods and techniques for wrapping and packaging the existing interaction layer to reproduce it in a different format, e.g., on a different platform or to integrate the legacy system services in another application possibly under a different architecture paradigm, e.g., service-oriented architectures (SOA).

  9. 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...

  10. Nsl1p is essential for the establishment of bipolarity and the localization of the Dam–Duo complex

    Science.gov (United States)

    Scharfenberger, Maren; Ortiz, Jennifer; Grau, Nicole; Janke, Carsten; Schiebel, Elmar; Lechner, Johannes

    2003-01-01

    We identified a physical complex consisting of Mtw1p, an established kinetochore protein, with Nnf1p, Nsl1p and Dsn1p and have demonstrated that Nnf1p, Nsl1p and Dsn1p localize to the Saccharomyces cerevisiae kinetochore. When challenged prior to metaphase, the temperature-sensitive mutants nsl1-16 and nsl1-42 as well as Nsl1p-depleted cells failed to establish a bipolar spindle–kinetochore interaction and executed monopolar segregation of sister chromatids. In contrast, an nsl1-16 defect could not be evoked after the establishment of bipolarity. The observed phenotype is characteristic of that of mutants with defects in the protein kinase Ipl1p or components of the Dam–Duo kinetochore complex. However nsl1 mutants did not exhibit a defect in microtubule–kinetochore untethering as the ipl1-321 mutant does. Instead, they exhibited a severe defect in the kinetochore localization of the Dam–Duo complex suggesting this to be the cause for the failure of nsl1 cells to establish bipolarity. Moreover the analysis of Nsl1p-depleted cells indicated that Nsl1p is required for the spindle checkpoint and kinetochore integrity. PMID:14657030

  11. Leo space plasma interactions

    Science.gov (United States)

    Ferguson, Dale C.

    1991-01-01

    Photovoltaic arrays interact with the low earth orbit (LEO) space plasma in two fundamentally different ways. One way is the steady collection of current from the plasma onto exposed conductors and semiconductors. The relative currents collected by different parts of the array will then determine the floating potential of the spacecraft. In addition, these steady state collected currents may lead to sputtering or heating of the array by the ions or electrons collected, respectively. The second kind of interaction is the short time scale arc into the space plasma, which may deplete the array and/or spacecraft of stored charge, damage solar cells, and produce EMI. Such arcs only occur at high negative potentials relative to the space plasma potential, and depend on the steady state ion currents being collected. New high voltage solar arrays being incorporated into advanced spacecraft and space platforms may be endangered by these plasma interactions. Recent advances in laboratory testing and current collection modeling promise the capability of controlling, and perhaps even using, these space plasma interactions to enable design of reliable high voltage space power systems. Some of the new results may have an impact on solar cell spacing and/or coverslide design. Planned space flight experiments are necessary to confirm the models of high voltage solar array plasma interactions. Finally, computerized, integrated plasma interactions design tools are being constructed to place plasma interactions models into the hands of the spacecraft designer.

  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. Sketches in Embodied Interaction

    DEFF Research Database (Denmark)

    Erkut, Cumhur; Dahl, Sofia; Triantafyllidis, Georgios

    2014-01-01

    We present an approach for teaching and designing embodied interaction based on interactive sketches. We have combined the mover perspective and felt experiences of movement with advanced technologies (multi-agents, physical simulations) in a generative design session. We report our activities...... and provide a simple example as a design outcome. The variety and the qualities of the initial ideas indicate that this approach might provide a better foundation for our participants, compared to the approaches that focus only on technologies. The interactive sketches were demonstrated at the conference....

  14. Interaction university and school

    Directory of Open Access Journals (Sweden)

    Gionara Tauchen

    2016-05-01

    Full Text Available Considering that the interaction between universities and middle schools is fundamental for organization and the qualification of the education system, we conducted a qualitative study on twenty public municipal schools of Rio Grande, RS, designed to investigate and understand the effectiveness of university activities (teaching, research and extension in regard to the promotion and strengthening of the interactions between these institutions. We highlight the activities related to Pibid, the Education Observatory, extension, supervised internships, and to undergraduate and postgraduate research. From comprehensions about these activities, we discuss the interaction between school and university.

  15. Drug interactions in epilepsy

    Directory of Open Access Journals (Sweden)

    Emilio Perucca

    1980-12-01

    Full Text Available Interactions with antiepileptic drugs are common and may have important clinical consequences. The physician should always consider carefully the need for and the implications of adding a new drug to any therapeutic regime and should be prepared to think about the possibility of an interaction whenever an unusual response is seen. Serum drug levels can be an invaluable tool in the recognition and the management of most types of interactions, but in no case can they be a substitute for careful observations and evaluation of the patient's symptoms and physical findings.

  16. 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...

  17. Atomic & Molecular Interactions

    Energy Technology Data Exchange (ETDEWEB)

    None

    2002-07-12

    The Gordon Research Conference (GRC) on Atomic & 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.

  18. Interaction as Negotiation

    DEFF Research Database (Denmark)

    Kristensen, Jannie Friis; Nielsen, Christina

    In this paper we discuss recent developments in interaction design principles for ubiquitous computing environments, specifically implications related to situated and mobile aspects of work. We present 'Interaction through Negotiation' as a general Human-Computer Interaction (HCI) paradigm, aimed...... at ubiquitous/pervasive technology and environments, with focus on facilitating negotiation in and between webs of different artifacts, humans and places. This approach is concerned with the way technology presents itself to us, both as physical entities and as conceptual entities, as well as the relations...... on several extensive empirical case studies, as well as co-operative design-sessions, we present a reflective analysis providing insights into results of the "Interaction through Negotiation" design approach in action. A very promising area of application is exception handling in pervasive computing...

  19. Chasing Ecological Interactions.

    Science.gov (United States)

    Jordano, Pedro

    2016-09-01

    Basic research on biodiversity has concentrated on individual species-naming new species, studying distribution patterns, and analyzing their evolutionary relationships. Yet biodiversity is more than a collection of individual species; it is the combination of biological entities and processes that support life on Earth. To understand biodiversity we must catalog it, but we must also assess the ways species interact with other species to provide functional support for the Tree of Life. Ecological interactions may be lost well before the species involved in those interactions go extinct; their ecological functions disappear even though they remain. Here, I address the challenges in studying the functional aspects of species interactions and how basic research is helping us address the fast-paced extinction of species due to human activities.

  20. Human Work Interaction Design

    DEFF Research Database (Denmark)

    . 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......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....

  1. Drug-Food Interactions

    Science.gov (United States)

    ... Devices, Prescription Medicines, Your Health ResourcesTags: adverse reactions, Food-Drug Interactions, patient education, patient information September 2000 Copyright © American Academy of Family PhysiciansThis information provides a general overview and may ...

  2. Succeeding with interactive research

    DEFF Research Database (Denmark)

    Krogh, Andreas Hagedorn; Nielsen, Morten Velsing

    2017-01-01

    the capacity for critique and ensuring that scientific standards are met. Based on our own experience and theories of interactive governance, network management and collaborative leadership, as well as on existing methodological literature, we provide guidance and suggest concrete tools and methods......Increasingly, social science research is carried out in collaboration with partners outside universities, yet research methodology is lacking on how to manoeuvre in a terrain where multiple actors set expectations for research. This article conceptualizes interactive research as research...... with and about society, and provides a set of systematic reflections on how to manage opposing pressures, tensions and dilemmas in interactive research projects. We formulate and address three major interactive research management tasks: ensuring continual commitment from external stakeholders, maintaining...

  3. Human Work Interaction Design

    DEFF Research Database (Denmark)

    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........ 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...

  4. Patient - patient interaction

    DEFF Research Database (Denmark)

    Birkelund, Regner; Søndergaard Larsen, Lene

    2013-01-01

    Aim:  The aim of this study is to provide an understanding of the significance of hospitalized patients’ interpersonal interaction with fellow patients in an infectious disease ward in a large Danish hospital. Method:  A qualitative approach was selected using participant observation and semi...... 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...

  5. 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...... includes some alpine stations located outside the Arctic. The INTERACT research stations provide an ideal platform for circumarctic research and monitoring. Activities span from small short term research projects to larger long term monitoring programmes. The stations are thus visited by many researchers...... and research groups. Therefore, INTERACT has produced a catalogue of research stations including descriptions of the physical setting, facilities and services offered at the stations. It is our hope that this catalogue will help researchers identify research stations that suit their specific needs. The 2015...

  6. 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...

  7. Socially Aware Interactive Playgrounds

    NARCIS (Netherlands)

    Moreno Celleri, Alejandro Manuel; van Delden, Robertus Wilhelmus; Poppe, Ronald Walter; Reidsma, Dennis

    Interactive playgrounds are technology-enhanced installations that aim to provide rich game experiences for children by combining the benefits of traditional playgrounds with those of digital games. These game experiences could be attained by addressing three design considerations:

  8. Transboundary water interaction III

    NARCIS (Netherlands)

    Zeitoun, Mark; Cascão, Ana Elisa; Warner, Jeroen; Mirumachi, Naho; Matthews, Nathanial; Menga, Filippo; Farnum, Rebecca

    2017-01-01

    This paper serves international water conflict resolution efforts by examining the ways that states contest hegemonic transboundary water arrangements. The conceptual framework of dynamic transboundary water interaction that it presents integrates theories about change and counter-hegemony to

  9. 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....... 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......, 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....

  10. 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...... going from personal/individual toward shared/multiuser experiences and interactions. However, computers are getting smaller, more powerful, and closer to our bodies. Therefore, mobile collocated interactions research, which originally looked at smartphones and tablets, will inevitably include ever......-smaller computers, ones that can be worn on our wrists or other parts of the body. 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 to the use of wearable devices....

  11. Interacting bosons in nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Dehesa, J.S.; Gomez, J.M.G.; Ros, J.

    1982-01-01

    These proceedings contain the lectures and articles presented at the named autumn school. These concern the interacting boson model in connection with other collective models. Separated abstracts were prepared for the articles in these proceedings.

  12. 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.

  13. 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...

  14. Interactive Design Activism

    Science.gov (United States)

    Goulev, Petar; Farrer, Joan

    The following sections are included: * Introduction * Computers and Human Well-being * To Fuzzy or Yes (No)! * Interactive Design Activism * Sensing the Sun * Personalised Public Health Advice * Modifying Human Behaviour * Transdisciplinarity, Knowledge Transfer and Multi-domain

  15. 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

  16. Designing Collaborative Interactive Spaces

    OpenAIRE

    Jetter, Hans-Christian; Geyer, Florian; Reiterer, Harald; Dachselt, Raimund; Fischer, Gerhard; Groh, Rainer; Haller, Michael; Herrmann, Thomas

    2012-01-01

    Interactive spaces are ubiquitous computing environments for computer-supported collaboration that exploit and enhance the existing cognitive, physical and social skills of users or groups of users. The workshop aims at documenting and advancing the current state-of-the-art of co-located collaboration in interactive spaces and identifying research challenges and formulating a research agenda by inviting high-quality position and research papers from HCI, Information Visualization, CSCW and CSCL.

  17. Towards interactive narrative medicine.

    Science.gov (United States)

    Cavazza, Marc; Charles, Fred

    2013-01-01

    Interactive Storytelling technologies have attracted significant interest in the field of simulation and serious gaming for their potential to provide a principled approach to improve user engagement in training scenarios. In this paper, we explore the use of Interactive Storytelling to support Narrative Medicine as a reflective practice. We describe a workflow for the generation of virtual narratives from high-level descriptions of patients' experiences as perceived by physicians, which can help to objectivize such perceptions and support various forms of analysis.

  18. 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.

  19. 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...

  20. Designing for Interaction Proxemics

    DEFF Research Database (Denmark)

    Grønbæk, Jens Emil

    2017-01-01

    Design of interactive technology provides opportunities as well as constraints in how a group of users can organize in a shared space. The core argument of interaction proxemics is to consider this in designing for collaboration. In my thesis, I focus on conceptualizing design of ubicomp...... technologies in this way. My goal with the concepts of proxemic configurations and transitions is to design for more flexibility in how users can collaborate and act socially through technology....

  1. Beam-Material Interaction

    Energy Technology Data Exchange (ETDEWEB)

    Mokhov, N. V. [Fermilab; Cerutti, F. [CERN

    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 environment in challenging current and future applications.

  2. Succeeding with interactive research

    DEFF Research Database (Denmark)

    Krogh, Andreas Hagedorn; Nielsen, Morten Velsing

    2017-01-01

    Increasingly, social science research is carried out in collaboration with partners outside universities, yet research methodology is lacking on how to manoeuvre in a terrain where multiple actors set expectations for research. This article conceptualizes interactive research as research with and......Increasingly, social science research is carried out in collaboration with partners outside universities, yet research methodology is lacking on how to manoeuvre in a terrain where multiple actors set expectations for research. This article conceptualizes interactive research as research...

  3. 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...

  4. 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

  5. Budgeted Interactive Learning

    Science.gov (United States)

    2017-06-15

    protocols that combine the benefits of online and batch learning , (2) protocols that improve interactive learning with other sources of information, and...algorithms for interactive learning with batch-like feedback (for 1) and algorithms for online digestion of representation (for 1 and 3). The team has...also addressed real-world needs for considering concept drift during online learning (for 2) and utilizing costs during deep learning , multi-label

  6. Human-machine interactions

    Science.gov (United States)

    Forsythe, J Chris [Sandia Park, NM; Xavier, Patrick G [Albuquerque, NM; Abbott, Robert G [Albuquerque, NM; Brannon, Nathan G [Albuquerque, NM; Bernard, Michael L [Tijeras, NM; Speed, Ann E [Albuquerque, NM

    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. Interactive DIF Generator

    Science.gov (United States)

    Preheim, Larry E.; Amy, Laraine; Young, Jimmie D.

    1993-01-01

    Interactive DIF Generator (IDG) computer program serves as utility to generate and manipulate directory interchange format (DIF) files. Creates and updates DIF files, sent to NASA's Master Directory, also referred to as International Global Change Directory at Goddard Space Flight Center. Many government and university data systems use Master Directory to advertise availability of research data. IDG is interactive software tool and requires mouse or trackball to operate. Written in C language.

  8. Making interactive whiteboard

    OpenAIRE

    Krivic, Tadej

    2013-01-01

    An interactive whiteboard is a modern instrument that is nowadays used in schools everywhere. A detailed description of its features, operation, usefulness, manufacture, and usage in schools will be presented in this paper. The interactive whiteboard can be used with different information and communications technology, such as digital pens, projectors, response systems, tablet computers, laptops etc. The thesis consists of the theoretical and practical part. In the theoretical part a ran...

  9. 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...

  10. The Aurora B kinase in chromosome biorientation and spindle checkpoint signalling

    Directory of Open Access Journals (Sweden)

    Veronica eKrenn

    2015-10-01

    Full Text Available Aurora B, a member of the Aurora family of serine/threonine protein kinases, is a key player in chromosome segregation. As part of a macromolecular complex known as the chromosome passenger complex, Aurora B concentrates early during mitosis in the proximity of centromeres and kinetochores, the sites of attachment of chromosomes to spindle microtubules. There, it contributes to a number of processes that impart fidelity to cell division, including kinetochore stabilization, kinetochore-microtubule attachment, and the regulation of a surveillance mechanism named the spindle assembly checkpoint. In the regulation of these processes, Aurora B is the fulcrum of a remarkably complex network of interactions that feed back on its localization and activation state. In this review we discuss the multiple roles of Aurora B during mitosis, focusing in particular on its role at centromeres and kinetochores. Many details of the network of interactions at these locations remain poorly understood, and we focus here on several crucial outstanding questions.

  11. Interaction with Machine Improvisation

    Science.gov (United States)

    Assayag, Gerard; Bloch, George; Cont, Arshia; Dubnov, Shlomo

    We describe two multi-agent architectures for an improvisation oriented musician-machine interaction systems that learn in real time from human performers. The improvisation kernel is based on sequence modeling and statistical learning. We present two frameworks of interaction with this kernel. In the first, the stylistic interaction is guided by a human operator in front of an interactive computer environment. In the second framework, the stylistic interaction is delegated to machine intelligence and therefore, knowledge propagation and decision are taken care of by the computer alone. The first framework involves a hybrid architecture using two popular composition/performance environments, Max and OpenMusic, that are put to work and communicate together, each one handling the process at a different time/memory scale. The second framework shares the same representational schemes with the first but uses an Active Learning architecture based on collaborative, competitive and memory-based learning to handle stylistic interactions. Both systems are capable of processing real-time audio/video as well as MIDI. After discussing the general cognitive background of improvisation practices, the statistical modelling tools and the concurrent agent architecture are presented. Then, an Active Learning scheme is described and considered in terms of using different improvisation regimes for improvisation planning. Finally, we provide more details about the different system implementations and describe several performances with the system.

  12. 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.

  13. 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.

  14. 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......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...... would allow devices to not only react to presence and interaction, but also other indicators, such as the interpersonal distance people naturally use in everyday life. The aim of this one-day workshop is to bring together a community of researchers, designers and practitioners who are interested...

  15. Interactive Virtual Cinematography

    DEFF Research Database (Denmark)

    Burelli, Paolo

    control of the camera by the player increases the complexity of the interaction and reduces the designer's control on game storytelling. A completely designer-driven camera releases the player from the burden of controlling the point of view, but might generate undesired camera behaviours. Furthermore......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...

  16. Fat and bone interactions.

    Science.gov (United States)

    Bermeo, Sandra; Gunaratnam, Krishanthi; Duque, Gustavo

    2014-06-01

    Fat and bone have a complicated relationship. Although obesity has been associated with low fracture risk, there is increasing evidence that some of the factors that are released by peripheral fat into the circulation may also have a deleterious effect on bone mass, thus, predisposing to fractures. More importantly, the local interaction between fat and bone within the bone marrow seems to play a significant role in the pathogenesis of age-related bone loss and osteoporosis. This "local interaction" occurs inside the bone marrow and is associated with the autocrine and paracrine release of fatty acids and adipokines, which affect the cells in their vicinity including the osteoblasts, reducing their function and survival. In this review, we explore the particularities of the fat and bone cell interactions within the bone marrow, their significance in the pathogenesis of osteoporosis, and the potential therapeutic applications that regulating marrow fat may have in the near future as a novel pharmacologic treatment for osteoporosis.

  17. Interactive Sample Book (ISB)

    DEFF Research Database (Denmark)

    Heimdal, Elisabeth Jacobsen; Lenau, Torben Anker; Guglielmi, Michel

    2009-01-01

    supervisor Torben A. Lenau. Inspiration to use smart materials Interactive textiles are still quite an unknown phenomenon to many. It is thus often difficult to communicate what kind of potentials lie within these materials. This is why the ISB project was started, as a practice based research project...... and senses in relation to integrated decoration and function primarily to indoor applications. The result of the project will be a number of interactive textiles, to be gathered in an interactive sample book (ISB), in a similar way as the sample books of wallpapers one can take home from the shop and choose...... from. In other words, it is a kind of display material, which in a simple manner can illustrate how different techniques and smart materials work. The sample book should display a number of possibilities where sensor technology, smart materials and textiles are mixed to such an extent that the textile...

  18. Interactive Topology Optimization

    DEFF Research Database (Denmark)

    Nobel-Jørgensen, Morten

    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 based......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...

  19. 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.

  20. 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).

  1. Formalising Interaction Patterns

    Science.gov (United States)

    Bottoni, Paolo; Guerra, Esther; de Lara, Juan

    The use of patterns as a way to refer to common solutions in the field of interface design is becoming widespread. However, contrary to the situation for software patterns, definitions of interaction patterns do not enjoy a common standard yet. Moreover, patterns are developed for design aspects as diverse as: user experience, layout, action coordination, or specification of entire widgets, reflecting the complexity of the field. As a consequence, research on formalisation of interaction patterns is not developed, and few attempts have been made to extend techniques developed for design pattern formalisation. We show here how an extension to an approach to pattern formalisation recently proposed by the authors can be usefully employed to formalize some classes of interaction patterns, to express relations like subtyping and composition, and to detect conflicts.

  2. 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.

  3. 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

  4. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Tospovirus-thrips interactions.

    Science.gov (United States)

    Whitfield, Anna E; Ullman, Diane E; German, Thomas L

    2005-01-01

    The complex and specific interplay between thrips, tospoviruses, and their shared plant hosts leads to outbreaks of crop disease epidemics of economic and social importance. The precise details of the processes underpinning the vector-virus-host interaction and their coordinated evolution increase our understanding of the general principles underlying pathogen transmission by insects, which in turn can be exploited to develop sustainable strategies for controlling the spread of the virus through plant populations. In this review, we focus primarily on recent progress toward understanding the biological processes and molecular interactions involved in the acquisition and transmission of Tospoviruses by their thrips vectors.

  6. Urban Interaction Design

    DEFF Research Database (Denmark)

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

    to the 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......This book is an effort to explore the newly emerging field of urban interaction design that addresses these issues. In the first part of the book, 'Foundations', we look into its origins. Where do its practitioners come from? How are they working together? What methodologies do they bring...

  7. 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

  8. Human Work Interaction Design

    DEFF Research Database (Denmark)

    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...

  9. Self-interacting polynomials

    CERN Document Server

    Vivaldi, F

    2002-01-01

    We introduce a class of dynamical systems of algebraic origin, consisting of self-interacting irreducible polynomials over a field. A polynomial $f$ is made to act on a polynomial $g$ by mapping the roots of the latter. This action identifies a new polynomial $h$, as the minimal polynomial of the displaced roots. By allowing several polynomials to act on one another, we obtain a self-interacting system with a rich dynamics and strong collective features, which affords a fresh viewpoint on some algebraic dynamical constructs. We identify the basic dynamical invariants and begin the study of periodic behaviour, organizing the polynomials into an oriented graph.

  10. A tabletop interactive storytelling system: designing for social interaction

    NARCIS (Netherlands)

    Alofs, Thijs; Theune, Mariet; Swartjes, I.M.T.

    This paper presents the Interactive Storyteller, a multi-user interface for AI-based interactive storytelling, where stories emerge from the interaction of human players with intelligent characters in a simulated story world. To support face-to-face contact and social interaction, we position users

  11. Interacting composite fermions

    DEFF Research Database (Denmark)

    nrc762, nrc762

    2016-01-01

    Numerical studies by Wójs, Yi, and Quinn have suggested that an unconventional fractional quantum Hall effect is plausible at filling factors ν=1/3 and 1/5, provided the interparticle interaction has an unusual form for which the energy of two fermions in the relative angular momentum three channel...

  12. 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 the spe...

  13. University-industry interaction

    NARCIS (Netherlands)

    Groen, Arend J.; van der Sijde, Peter

    2002-01-01

    This book addresses the question of how to organise university-industry interaction. The objective was to identify best practices and to gain insight into the conditions necessary for optimal knowledge and technology transfer from universities to industry, in particular small and medium-sized

  14. Standardizing Interaction Design Education

    Science.gov (United States)

    Thomassen, Aukje; Ozcan, Oguzhan

    2010-01-01

    The objective of this paper is to which extend the didactic format of studio-based group-work is applicable for creating a common-ground for Interaction Design Education in European Perspective. The current debate on design education shows us a landscape of different initiatives. So far difficulties have arisen in the area of accreditation and…

  15. Interactive Mold House Tour

    Science.gov (United States)

    Get a quick glimpse of some of the most important ways to protect your home from mold by this interactive tour of the Mold House. Room-by-room, you'll learn about common mold issues and how to address them.

  16. 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...

  17. 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 multitaski...

  18. Ziggy: Very Interactive Trigonometry

    NARCIS (Netherlands)

    Anjewierden, Anjo Allert; Kamp, E.T.; Kamp, Ellen T.; de Jong, Anthonius J.M.

    2013-01-01

    In this paper we describe a highly interactive touch-based application to teach the basics of trigonometry to secondary school students. The application, called Ziggy, lets students “touch” and “push” triangles, dynamically modifying the shape and size, and observe the effect on the angles, sides

  19. Human Work Interaction Design

    DEFF Research Database (Denmark)

    . 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...

  20. Experiencing affective interactive art

    NARCIS (Netherlands)

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

    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

  1. 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...

  2. Designing Interactive Learning Environments.

    Science.gov (United States)

    Akpinar, Y.; Hartley, J. R.

    1996-01-01

    Describes the design principles of computer-assisted learning (CAL) environments in which the software is interactive yet adaptable to different styles of learning and teaching, illustrated with a mathematics application. Following implementation, initial evaluation data taken from students showed marked performance improvements, and indicated how…

  3. Understanding Ancient Interactions

    Directory of Open Access Journals (Sweden)

    Edward Schortman

    2015-08-01

    Full Text Available Archaic State Interaction casts valuable new light on how extra-societal contacts may be implicated in processes of increasing social complexity. As the title makes clear, the contributors ground their discussions of interaction theory in the specific sequence of events dating to 3100-1000 BCE in that portion of the Mediterranean basin stretching from Italy to the Levantine Coast. Their goals, as stated clearly by Parkinson and Galaty in the introduction, are to consider how local social and economic changes, on the one hand, were related to: variations in the intensity of interactions occurring at differing spatial and temporal scales; changes in how, and by whom, such contacts were conducted; and, shifts in the routes these transactions followed. The result is less a consensus than a healthy, productive debate on these issues. The main points of contention concern: rates of socio-political change; how to translate patterns among static material remains into dynamic political and economic processes; whose interests drove and shaped the course of cross-border contacts; and what interpretive frameworks are best suited to modeling the latter interactions. With respect to the last point, a consistent theme running throughout the papers deals with the utility of world-systems theory (WST in describing and understanding the developmental significance of inter-polity contacts.

  4. 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 bi...

  5. Merging frameworks for interaction

    NARCIS (Netherlands)

    van Benthem, J.; Gerbrandy, J.; Hoshi, T.; Pacuit, E.

    2009-01-01

    A variety of logical frameworks have been developed to study rational agents interacting over time. This paper takes a closer look at one particular interface, between two systems that both address the dynamics of knowledge and information flow. The first is Epistemic Temporal Logic (ETL) which uses

  6. Interactive Stable Ray Tracing

    DEFF Research Database (Denmark)

    Dal Corso, Alessandro; Salviato, Marco; Kolb, Craig

    2017-01-01

    -processing filters. Our technique is based on sample reprojection and explicit hole filling, rather than relying on hole-filling heuristics that can compromise image quality. We make reprojection practical in an interactive ray tracing context through the use of a super-resolution bitmask to estimate screen space...

  7. Interactive database management (IDM).

    Science.gov (United States)

    Othman, R

    1995-08-01

    Interactive database management (IDM) is a data editing software that provides complete data editing at the time of initial data entry when information is 'fresh at hand'. Under the new interactive system, initial data recording is subjected to instant data editing by the interactive computer software logic. Data are immediately entered in final form to the database and are available for analysis. IDM continuously checks all variables for acceptability, completeness, and consistency. IDM does not allow form duplication. Many functions including backups have been automated. The interactive system can export the database to other systems. The software has been implemented for two Department of Veterans Affairs Cooperative Studies (CCSHS #5 and CSP #385) which collect data for 1400 and 1000 variables, respectively at 28 VA medical centers. IDM is extremely user friendly and simple to operate. Researchers with no computer background can be trained quickly and easily to use the system. IDM is deployed on notebook microcomputers making it portable for use anywhere in the hospital setting.

  8. Aspects, Dependencies and Interactions

    NARCIS (Netherlands)

    Sanen, F.; Chitchyan, R; Bergmans, Lodewijk; Fabry, J.; Sudholt, M.; Mehner, K.; Cebulla, M.

    2008-01-01

    The topics on aspects, dependencies and interactions are among the key remaining challenges to be tackled by the Aspect-Oriented Software Development (AOSD) community to enable a wide adoption of AOSD technology. This second workshop, organized and supported by the AOSD-Europe project, aimed to

  9. Interactive Architecture #2

    NARCIS (Netherlands)

    Oosterhuis, K.; Xia, X.

    2009-01-01

    This is the second issue (of twelve) of iA bookzine. iA brings together interdisciplinary perspectives to the topic of "Interactive Architecture" (IA) - from researchers, students, guest lecturers from Hyperbody), and experts from other organizations. This second issue, like the first, consists of

  10. 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...

  11. Multiple Interactions in Herwig++

    CERN Document Server

    Bahr, Manuel; Seymour, Michael H.

    2008-01-01

    In this contribution we describe a new model of multiple partonic interactions that has been implemented in Herwig++. Tuning its two free parameters we find a good description of CDF underlying event data. We show extrapolations to the LHC and discuss intrinsic PDF uncertainties.

  12. Sonic Interaction Design

    DEFF Research Database (Denmark)

    ) 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...

  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. 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.

  15. Affordance in Interaction

    NARCIS (Netherlands)

    Vyas, Dhaval; Chisalita, Cristina; van der Veer, Gerrit C.; Rizzo, Antonio; Grote, Gudela; Wong, William

    2006-01-01

    The concept of affordance has different interpretations in the field of Human-Computer Interaction (HCI). However, its treatment has been merely as a one-to-one relationship between a user and a technology. We believe that a broader view of affordances is needed which encompasses social and cultural

  16. 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...

  17. 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...

  18. Interactive Playgrounds for Children

    NARCIS (Netherlands)

    Poppe, Ronald Walter; van Delden, Robertus Wilhelmus; Moreno Celleri, Alejandro Manuel; Reidsma, Dennis; Nijholt, A.; Nijholt, Antinus

    Play is an important factor in the life of children. It plays a role in their cognitive, social, and physical development, and provides entertaining and fulfilling activities in itself. As with any field of human endeavor, interactive technology has a huge potential for transforming and enhancing

  19. Bub1 positions Mad1 close to KNL1 MELT repeats to promote checkpoint signalling

    DEFF Research Database (Denmark)

    Zhang, Gang; Kruse, Thomas; López-Méndez, Blanca

    2017-01-01

    Proper segregation of chromosomes depends on a functional spindle assembly checkpoint (SAC) and requires kinetochore localization of the Bub1 and Mad1/Mad2 checkpoint proteins. Several aspects of Mad1/Mad2 kinetochore recruitment in human cells are unclear and in particular the underlying direct...... interactions. Here we show that conserved domain 1 (CD1) in human Bub1 binds directly to Mad1 and a phosphorylation site exists in CD1 that stimulates Mad1 binding and SAC signalling. Importantly, fusion of minimal kinetochore-targeting Bub1 fragments to Mad1 bypasses the need for CD1, revealing that the main...... for spindle assembly checkpoint signalling at kinetochores in human cells....

  20. INTERACTIVE LEARNING: ADVANTAGES AND DISADVANTAGES

    OpenAIRE

    O. Kustovska; A. Svidenyuk

    2016-01-01

    In the article the use of interactive technologies in the educational process of the university, allowing students to develop innovative thinking, away from stereotypes, develop imagination, communication skills and expertise, intellectual, emotional, motivational and other areas of personality. Implementing the principles of technological learning, interactive educational technology and provides interactive computer learning tools, and interactivity of educational process when...

  1. 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....... 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, in which...

  2. 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.

  3. The Interactive Astronomy Textbook

    Science.gov (United States)

    Fluke, Christopher J.; Barnes, David G.

    We introduce the use of in situ interactive three-dimensional (3-d) figures in digital astronomy textbooks as a means of enhancing student learning. The recent 3-d extensions to the Adobe Portable Document Format (PDF), combined with simple JavaScript, provide new ways to present intrinsically 3-d models, data sets, and instructional diagrams in digital publications. This is an enhancement to the usual method of presenting static, two-dimensional views, or "comic strip" sequences, to indicate changes in viewpoint. Interactive figures provide opportunities for students to undertake active learning while reading a textbook: they are able to explore and uncover the connections between viewpoint, orientation, and the 3-d nature of models and data sets for themselves.

  4. Cultivating objects in interaction

    DEFF Research Database (Denmark)

    Hazel, Spencer

    2014-01-01

    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......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...... surround through a combination of vocal, visual and tactile means; once indexed one way, these objects are subsequently recycled in later multimodal turn design. By tracking recurrent participant orientations to particular objects made relevant in the surround, we are able to explore further...

  5. Theory of gravitational interactions

    CERN Document Server

    Gasperini, Maurizio

    2017-01-01

    This is the second edition of a well-received book that is a modern, self-contained introduction to the theory of gravitational interactions. The new edition includes more details on gravitational waves of cosmological origin, the so-called brane world scenario, and gravitational time-delay effects. The first part of the book follows the traditional presentation of general relativity as a geometric theory of the macroscopic gravitational field, while the second, more advanced part 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 within the traditional approach to general relativity which usually leaves students puzzled about the role of gravity. The required notions of differential geometry are reduced to the minimum, allowing room for aspects of gravitational physics of current phenomenological and theoretical interest, such as the properties of gravitational waves, the gravitational inter...

  6. Interactive Energy Planning

    DEFF Research Database (Denmark)

    Blarke, Morten Boje

    2006-01-01

    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...... 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 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...

  7. 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.

  8. Magnetic interactions through fluoride

    DEFF Research Database (Denmark)

    Pedersen, Kasper Steen; Sigrist, Marc; Weihe, Høgni

    2014-01-01

    The nature of the magnetic interaction through fluoride in a simple, dinuclear manganese(III) complex (1), bridged by a single fluoride ion in a perfectly linear fashion, is established by experiment and density functional theory. The magnitude of the antiferromagnetic exchange interaction...... and the manganese(III) zero-field-splitting parameters are unambiguously determined by inelastic neutron scattering to yield J = 33.0(2) cm(-1) (Ĥ = JŜ1·Ŝ2 Hamiltonian definition) and single-ion D = -4.0(1) cm(-1). Additionally, high-field, high-frequency electron paramagnetic resonance and magnetic measurements...... support the parameter values and resolve |E| ≈ 0.04 cm(-1). The exchange coupling constant (J) is 1 order of magnitude smaller than that found in comparable systems with linear oxide bridging but comparable to typical magnitudes through cyanide, thus underlining the potential of fluoride complexes...

  9. Interaction Design for Public Spaces

    DEFF Research Database (Denmark)

    Kortbek, Karen Johanne

    2008-01-01

    will focus on the usage of the body as an interaction device. Furthermore, the project will involve a dramaturgic take on communication and design of interactive systems in the pursuit of new ways to stage the interactive contexts. The outcome of the project will be guidelines and conceptual frameworks which...... will help interaction designers when designing for bodily movement, and communicating and staging interactive content in public spaces....

  10. INTERACTIVE LEARNING: ADVANTAGES AND DISADVANTAGES

    Directory of Open Access Journals (Sweden)

    O. Kustovska

    2016-10-01

    Full Text Available In the article the use of interactive technologies in the educational process of the university, allowing students to develop innovative thinking, away from stereotypes, develop imagination, communication skills and expertise, intellectual, emotional, motivational and other areas of personality. Implementing the principles of technological learning, interactive educational technology and provides interactive computer learning tools, and interactivity of educational process when the basic conceptual provisions defined training based on interactive communication.

  11. Student interaction in workshops

    DEFF Research Database (Denmark)

    Evers, Winie

    2014-01-01

    a task of modeling the dynamics of a firm’s supply chain. Following Gardner’s theory of multiple intelligences (1983), it is argued that each learner possesses a unique blend of diverse intelligences, and should therefore empower learners, rather than restrict them to a single modality. Consequently...... teaching should reflect this diversity by embracing and experimenting with multiple forms, including activation of students by students’ interaction and manipulation with objects....

  12. Interaction in educational games

    OpenAIRE

    Jovanovič, Vesna

    2011-01-01

    The diploma thesis is devoted to educational computer games and their use in the classroom. We want to find out the difference in knowledge that pupils gain in frontal lessons and in knowledge acquired by playing interactive educational games. This question was answered with an experiment with two experimental groups. For this experiment we created an educational game. We have found that students who were taught by frontal method, perform better in the test than students who learned on their ...

  13. Gaze interaction from bed

    DEFF Research Database (Denmark)

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

    2011-01-01

    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 lying down....... Also, gaze tracking in the bottom part of the image was found to be more precise than in the top part....

  14. Model Checking Feature Interactions

    DEFF Research Database (Denmark)

    Le Guilly, Thibaut; Olsen, Petur; Pedersen, Thomas

    2015-01-01

    This paper presents an offline approach to analyzing feature interactions in embedded systems. The approach consists of a systematic process to gather the necessary information about system components and their models. The model is first specified in terms of predicates, before being refined to t...... to timed automata. The consistency of the model is verified at different development stages, and the correct linkage between the predicates and their semantic model is checked. The approach is illustrated on a use case from home automation....

  15. Electromagnetic Interaction Equations

    OpenAIRE

    Zinoviev, Yury M.

    2009-01-01

    For the electromagnetic interaction of two particles the relativistic quantum mechanics equations are proposed. These equations are solved for the case when one particle has a small mass and moves freely. The initial wave functions are supposed to be concentrated at the coordinates origin. The energy spectrum of another particle wave function is defined by the initial wave function of the free moving particle. Choosing the initial wave function of the free moving particle it is possible to ob...

  16. Strangeness in hadronic interactions

    CERN Document Server

    Paul, S

    2000-01-01

    Strangeness has always been an important subject at all PANIC conferences as it probably constitutes the best link between particle and nuclear physics. I will thus use the theme of the conference by considering strangeness as a tourist through the world of strong interaction. During this talk we will accompany strangeness from production, to the royaume of mesons and baryons up to the complex world of nuclei.

  17. 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

  18. Amantadine-dyazide interaction.

    OpenAIRE

    Wilson, T. W.; Rajput, A. H.

    1983-01-01

    To document an interaction between amantadine hydrochloride and Dyazide that had apparently produced amantadine toxicity, a patient was given amantadine alone for 1 week, followed by amantadine plus Dyazide for another week, under controlled conditions. A diuretic effect was observed after Dyazide was added to the regimen, but the urine amantadine excretion fell, and the drug's plasma concentration increased. It was concluded that one or both of the components of Dyazide (hydrochlorothiazide ...

  19. 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.

  20. Transboundary water interaction III

    OpenAIRE

    Zeitoun, Mark; Cascão, Ana Elisa; Warner, Jeroen; Mirumachi, Naho; Matthews, Nathanial; Menga, Filippo; Farnum, Rebecca

    2017-01-01

    This paper serves international water conflict resolution efforts by examining the ways that states contest hegemonic transboundary water arrangements. The conceptual framework of dynamic transboundary water interaction that it presents integrates theories about change and counter-hegemony to ascertain coercive, leverage, and liberating mechanisms through which contest and transformation of an arrangement occur. While the mechanisms can be active through sociopolitical processes either of com...

  1. Biological Interactions of Nanomaterials

    Science.gov (United States)

    2008-12-01

    interest of scientific and technical information exchange, and its publication does not constitute the Government’s approval or disapproval of its ideas...proteins and glycoproteins, the cellular interactions of these NPs with human tissues must be considered. Because the production of viable sperm is...Billerica, MA). Then 30 μg of the immunoprecipitates were loaded onto 10 percent Tris-HCl gels for electrophoresis (Bio-Rad, Hercules, CA). The

  2. Gravitational interaction of antimatter

    OpenAIRE

    Villata, Massimo

    2010-01-01

    Until now, there is no experimental evidence on the gravitational behaviour of antimatter. While we may be confident that antimatter attracts antimatter, we do not know anything on the interaction between matter and antimatter. We investigate this issue on theoretical grounds. Starting from the CPT invariance of physical laws, we transform matter into antimatter in the equations of both electrodynamics and gravitation. In the former case, the result is the well-known change of sign of the ele...

  3. 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....

  4. 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.

  5. Nutrition-parasite interaction.

    Science.gov (United States)

    Coop, R L; Kyriazakis, I

    1999-08-01

    The interactions between host nutrition and parasitism in ruminants are viewed within a framework that accounts for the allocation of scarce nutrient resources, such as energy and protein, between the various competing body functions of the host. These include functions that are the direct result of parasitism. Since it is proposed that the host gives priority to the reversal of the pathophysiological consequences of parasitism over other body functions, it is to be expected that improved nutrition will always lead to improved resilience. On the other hand, it is proposed that the function of growth, pregnancy and lactation are prioritised over the expression of immunity. Thus, improved nutrition may affect the degree of expression of immunity during these phases. The framework is useful at highlighting areas of future research on host/parasite/nutrition interactions. Its suggestions can account for the observations of the periparturient relaxation of immunity in reproducing females, as well as the reduction in worm burden in small ruminants supplemented with additional protein. Although developed for gastrointestinal nematodes in ruminants, the concepts of the framework should be applicable to the interactions of nutrition in other parasitic diseases.

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

    Directory of Open Access Journals (Sweden)

    Charles S. White

    1993-12-01

    Full Text Available 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.

  7. Bunyavirus-Vector Interactions

    Directory of Open Access Journals (Sweden)

    Kate McElroy Horne

    2014-11-01

    Full Text Available The Bunyaviridae family is comprised of more than 350 viruses, of which many within the Hantavirus, Orthobunyavirus, Nairovirus, Tospovirus, and Phlebovirus genera are significant human or agricultural pathogens. The viruses within the Orthobunyavirus, Nairovirus, and Phlebovirus genera are transmitted by hematophagous arthropods, such as mosquitoes, midges, flies, and ticks, and their associated arthropods not only serve as vectors but also as virus reservoirs in many cases. This review presents an overview of several important emerging or re-emerging bunyaviruses and describes what is known about bunyavirus-vector interactions based on epidemiological, ultrastructural, and genetic studies of members of this virus family.

  8. Environmental Interactions Technology Status

    Science.gov (United States)

    1986-10-01

    CV) CO)z 0 0x m IIn ~ H1J ~ -cn - 77 - x, * 6 toA 0000000 x < roo- 0. CN- - E C4- LLJ V CO zz <. z. r.4. Ct HOVU HJLVI C - 78 - A A 0 9- CC LUU 400...Experienced Single Event Upsets TIROS-N DMSP Satellite Data System NAVSTAR/GPS Solar Maximum Mission Landsat D Voyager Pioneer Venus LES 8 & LES 9 Intelsat V...from this interaction. The surface changes can affect such properties as reflectivity , solar absorptivity, and secondary emission. These changes

  9. Anomalous Gauge Boson Interactions

    Energy Technology Data Exchange (ETDEWEB)

    Barklow, Timothy L

    2003-06-16

    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 {approx} 1 TeV, these low energy anomalous couplings are expected to be no larger than {Omicron}(10{sup -2}). Constraints from high precision measurements at LEP and low energy charged and neutral current processes are critically reviewed.

  10. Anomalous gauge boson interactions

    Energy Technology Data Exchange (ETDEWEB)

    Aihara, H. [Lawrence Berkeley Lab., CA (United States); Barklow, T. [Stanford Linear Accelerator Center, Menlo Park, CA (United States); Baur, U. [State Univ. of New York, Buffalo, NY (United States). Dept. of Physics]|[Florida State Univ., Tallahassee, FL (United States). Dept. of Physics] [and others

    1995-03-01

    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 {approximately} 1 TeV, these low energy anomalous couplings are expected to be no larger than {Omicron}(10{sup {minus}2}). Constraints from high precision measurements at LEP and low energy charged and neutral current processes are critically reviewed.

  11. CASSIS: Interactive spectrum analyzer

    Science.gov (United States)

    Cassis Team At Cesr/Irap

    2014-02-01

    CASSIS (Centre d'Analyse Scientifique de Spectres Infrarouges et Submillimetriques), written in Java, is suited for broad-band spectral surveys to speed up the scientific analysis of high spectral resolution observations. It uses a local spectroscopic database made of the two molecular spectroscopic databases JPL and CDMS, as well as the atomic spectroscopic database NIST. Its tools include a LTE model and the RADEX model connected to the LAMDA molecular collisional database. CASSIS can build a line list fitting the various transitions of a given species and to directly produce rotational diagrams from these lists. CASSIS is fully integrated into HIPE, the Herschel Interactive Processing Environment, as a plug-in.

  12. 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.

  13. Interactive LISREL in Practice

    CERN Document Server

    Vieira, Armando Luis

    2011-01-01

    INTERACTIVE LISREL IN PRACTICE: Getting Started with a SIMPLIS Approach is particularly appropriate for those users that are not experts in statistics, but have some basic notions of multivariate analysis that would allow them to use this handbook as a good first incursion on the realm of LISREL. Parte I introduces the topic, presents the study that serves as the background for the explanation of matters, and launches the bases for parts II and III, which, in turn, explain the process of estimation of the measurement model and the structural model, respectively. With the announcement of each p

  14. 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....... 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...

  15. 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....... 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...

  16. The interactive design collaboratorium

    DEFF Research Database (Denmark)

    Bødker, Susanne; Krogh, Peter Gall; Graves Petersen, Marianne

    2001-01-01

    This paper reports on an experimental process in which a prototype was developed of an interactive design collaboratorium, in cooperation with a group of usability designers. In a longterm research cooperation, this usability group has changed its work practice in order to work in the design coll...... in practical experimentation in projects and in design of an experimental design collaboratorium employing electronic whiteboards, 3D design documentation, etc. This experimental prototype has been evaluated in cooperative workshops. We report on the results of this evaluation....

  17. Diachronic Perspective and Interaction

    DEFF Research Database (Denmark)

    Marchetti, Emanuela; Valente, Andrea

    seem to demand for solutions: the absence of a dialogue between museums and young audiences, and ineffective approaches to convey historical processes. Typical young visitors are pupils participating to guided tours, in which guides provide oral narratives about historical artifacts and events....... 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...

  18. Interaction in Information Systems - Beyond Human-Computer Interaction

    DEFF Research Database (Denmark)

    Bækgaard, Lars

    The purpose of this paper is to discuss and analyze the role of interaction in information systems. Interaction represents dynamic relations between actors and other elements in information systems. We introduce a semi-formal notation that we use to describe a set of interaction patterns and we i...

  19. Relationality and social interaction.

    Science.gov (United States)

    Bottero, Wendy

    2009-06-01

    This paper explores Bourdieu's account of a relational social space, and his relative neglect of social interaction within this framework. Bourdieu includes social capital as one of the key relational elements of his social space, but says much less about it than economic or cultural capital, and levels of social capital are rarely measured in his work. Bourdieu is reluctant to focus on the content of social networks as part of his rejection of substantialist thinking. The neglect of substantive networks creates problems for Bourdieu's framework, because many of Bourdieu's core concepts rest upon assumptions about their interactional properties (in particular, the prevalence of homophilous differential association) which are left unexamined. It is argued here that Bourdieu's neglect of the substance of social networks is related to the criticisms that Bourdieu's framework often encounters, and that this neglect bears re-examination, since it is helpful to think of the ways in which differentiated social networks contribute to the development of habitus, help form fields, and so constitute the intersubjective social relations within which sociality, and practice more generally, occur.

  20. Interactive Biplot Construction

    Directory of Open Access Journals (Sweden)

    Frederic Udina

    2005-01-01

    Full Text Available We analyze and discuss how a generic software to produce biplot graphs should be designed. We describe a data structure appropriate to include the biplot description and we specify the algorithm(s to be used for several biplot types. We discuss the options the software should offer to the user in two different environments. In a highly interactive environment the user should be able to specify many graphical options and also to change them using the usual interactive tools. The resulting graph needs to be available in several formats, including high quality format for printing. In a web-based environment, the user submits a data file or listing together with some options specified either in a file or using a form. Then the graphic is sent back to the user in one of several possible formats according to the specifications. We review some of the already available software and we present an implementation based in XLISP-STAT. It can be run under Unix or Windows, and it is also part of a service that provides biplot graphs through the web.

  1. Cephradine antacids interaction studies.

    Science.gov (United States)

    Arayne, M Saeed; Sultana, Najma; Afzal, M

    2007-07-01

    The present work comprises of interaction studies of cephradine with antacids. Cephradine is included among the first generation cephalosporin, which is active against a wide range of Gram positive and Gram-negative bacteria including penicillinase-producing staphylococci. Since the presence of complexing ligand may affect the bioavailability of a drug in blood or tissues, therefore, in order to study the probable interaction of cephradine with antacids all the reaction conditions were simulated to natural environments. Antacids are commonly used in patients complaining of GI irritations. The behavior of cephradine in presence of seven antacids i.e., simethicone, magaldrate, magnesium carbonate, magnesium hydroxide, magnesium trisilicate, sodium bicarbonate and aluminium hydroxide was studied by using standard dissolution apparatus. Cephradine was monitored both by UV and by high performance liquid chromatography. The results revealed that antacids containing polyvalent cations retarded the in vitro availability of cephradine. Moreover, these studies indicated that cephradine was strongly adsorbed on antacids; magnesium trisilicate and simeco tablets (powdered) exhibited relatively higher adsorption capacities.

  2. Interactive Computer Graphics

    Science.gov (United States)

    Kenwright, David

    2000-01-01

    Aerospace data analysis tools that significantly reduce the time and effort needed to analyze large-scale computational fluid dynamics simulations have emerged this year. The current approach for most postprocessing and visualization work is to explore the 3D flow simulations with one of a dozen or so interactive tools. While effective for analyzing small data sets, this approach becomes extremely time consuming when working with data sets larger than one gigabyte. An active area of research this year has been the development of data mining tools that automatically search through gigabyte data sets and extract the salient features with little or no human intervention. With these so-called feature extraction tools, engineers are spared the tedious task of manually exploring huge amounts of data to find the important flow phenomena. The software tools identify features such as vortex cores, shocks, separation and attachment lines, recirculation bubbles, and boundary layers. Some of these features can be extracted in a few seconds; others take minutes to hours on extremely large data sets. The analysis can be performed off-line in a batch process, either during or following the supercomputer simulations. These computations have to be performed only once, because the feature extraction programs search the entire data set and find every occurrence of the phenomena being sought. Because the important questions about the data are being answered automatically, interactivity is less critical than it is with traditional approaches.

  3. 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 with various targets to try to understand better the physics of virtual photon interactions over a wide range of four-momentum transfer (q$^{2}$).\\\\ \\\\ The spectrometer includes a large aperture dipole magnet (2m x 1m) of bending power $\\simeq$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 $\\simeq$at 100 GeV/c, and an angular definition of $\\pm$ 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 d...

  4. Hydrophobic interactions and chemical reactivity

    NARCIS (Netherlands)

    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.

  5. Multimodal Embodied Mimicry in Interaction

    NARCIS (Netherlands)

    Sun, X.; Esposito, Anna; Vinciarelli, Alessandro; Vicsi, Klára; Pelachaud, Catherine; Nijholt, Antinus

    2011-01-01

    Nonverbal behaviors play an important role in communicating with others. One particular kind of nonverbal interaction behavior is mimicry. It has been argued that behavioral mimicry supports harmonious relationships in social interaction through creating affiliation, rapport, and liking between

  6. 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...

  7. 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 ...

  8. 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

  9. SNP interaction pattern identifier (SIPI)

    DEFF Research Database (Denmark)

    Lin, Hui-Yi; Chen, Dung-Tsa; Huang, Po-Yu

    2016-01-01

    with the exact or similar pattern in the discovery and validation sets. A similar match for external validation of SNP-SNP interaction studies is suggested. We demonstrated that SIPI not only searches for more meaningful interaction patterns but can also overcome the unstable nature of interaction patterns...

  10. Interactive Writing with Young Children.

    Science.gov (United States)

    Hall, Nigel

    2000-01-01

    Defines interactive writing and how it works. Recommends starting with the message sheet, then going on to written conversation and writing to a make-believe character. Identifies six benefits of interactive writing and asserts that interactive writing supports a basic human need of expressing one's thoughts and communicating them to others. (DLH)

  11. Ridge Regression for Interactive Models.

    Science.gov (United States)

    Tate, Richard L.

    1988-01-01

    An exploratory study of the value of ridge regression for interactive models is reported. Assuming that the linear terms in a simple interactive model are centered to eliminate non-essential multicollinearity, a variety of common models, representing both ordinal and disordinal interactions, are shown to have "orientations" that are…

  12. Interaction between learners in an interactive learning environment

    DEFF Research Database (Denmark)

    Davidsen, Jacob; Georgsen, Marianne

    interaction and participation patterns, thereby guiding their own learning activities with reference to the materials designed by the teacher. It might seem that the students direct their learning solely with technology, but this is not the case – the teacher is very important in this setup...... will transform the learning situation based on underlying learning principles such as dialogue, interaction and collaboration. Mercer et al (2010) describe what they call technical interactivity and dialogic interactivity and state that IWBs can change the interaction and participation patterns in the class....... 2010). However, such a learning design still requires a teacher to facilitate, manage and lead the participation and interaction patterns of the learners. In this paper, we present an empirical long term study of class room interaction in a setting where technology is introduced to enhance...

  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. IDG - INTERACTIVE DIF GENERATOR

    Science.gov (United States)

    Preheim, L. E.

    1994-01-01

    The Interactive DIF Generator (IDG) utility is a tool used to generate and manipulate Directory Interchange Format files (DIF). Its purpose as a specialized text editor is to create and update DIF files which can be sent to NASA's Master Directory, also referred to as the International Global Change Directory at Goddard. Many government and university data systems use the Master Directory to advertise the availability of research data. The IDG interface consists of a set of four windows: (1) the IDG main window; (2) a text editing window; (3) a text formatting and validation window; and (4) a file viewing window. The IDG main window starts up the other windows and contains a list of valid keywords. The keywords are loaded from a user-designated file and selected keywords can be copied into any active editing window. Once activated, the editing window designates the file to be edited. Upon switching from the editing window to the formatting and validation window, the user has options for making simple changes to one or more files such as inserting tabs, aligning fields, and indenting groups. The viewing window is a scrollable read-only window that allows fast viewing of any text file. IDG is an interactive tool and requires a mouse or a trackball to operate. IDG uses the X Window System to build and manage its interactive forms, and also uses the Motif widget set and runs under Sun UNIX. IDG is written in C-language for Sun computers running SunOS. This package requires the X Window System, Version 11 Revision 4, with OSF/Motif 1.1. IDG requires 1.8Mb of hard disk space. The standard distribution medium for IDG is a .25 inch streaming magnetic tape cartridge in UNIX tar format. It is also available on a 3.5 inch diskette in UNIX tar format. The program was developed in 1991 and is a copyrighted work with all copyright vested in NASA. SunOS is a trademark of Sun Microsystems, Inc. X Window System is a trademark of Massachusetts Institute of Technology. OSF/Motif is a

  15. 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.

  16. Wood–water interactions

    DEFF Research Database (Denmark)

    Engelund, Emil Tang

    2011-01-01

    is the physical behaviour on the molecular level since water interferes with wood at this level. The elastic material properties of the wood cell wall are explained by the organisation of wood constituents and their properties. The effect of water as well as temperature is incorporated by considering the amount......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...

  17. Pipeline‐Seabed Interaction

    DEFF Research Database (Denmark)

    Fredsøe, Jørgen

    2016-01-01

    A review of the existing research on the interaction between a pipeline and an erodible bed exposed to waves and/or currents is presented. The review covers three topics, i.e., scour, liquefaction and lateral stability of pipelines. The basic mechanism that leads to scour in two‐dimensional (2D......) and 3D case is firstly described. The scour processes are deduced from small‐scale laboratory experiments. The onset of scour from piping and the developing tunnel erosion are among the processes described. The lateral expansion of the scour hole along the pipe is described, also based primarily...... on small‐scale laboratory experiments.. The state of the art of the mathematical/numerical modeling of the scour processes is presented. The associated self‐burial of the pipe is described and compared to field observations. In addition to scour, liquefaction may also constitute a risk 19 for pipeline...

  18. Doing, using, interacting

    DEFF Research Database (Denmark)

    Nordin, Sara; Hjalager, Anne-Mette

    2017-01-01

    of innovation processes: science, technology, and innovation (STI) and doing, using, and interacting (DUI). DUI appears to capture the essence of innovation in tourism enterprises better than STI because it acknowledges the intrinsic nature of services and the typical size and working modes of touristic actors....... The case study of Icehotel illustrates how working in partnerships and in close cooperation with customers enhances the advantages of the DUI model. The handling of externally induced events and difficulties and the critical partnerships are better understood through the DUI than through the STI lens....... The DUI framework leads to a more correct picture of tourism innovation and could also provide a better guidance for policy processes in the field....

  19. Nekton Interaction Monitoring System

    Energy Technology Data Exchange (ETDEWEB)

    2017-03-15

    The software provides a real-time processing system for sonar to detect and track animals, and to extract water column biomass statistics in order to facilitate continuous monitoring of an underwater environment. The Nekton Interaction Monitoring System (NIMS) extracts and archives tracking and backscatter statistics data from a real-time stream of data from a sonar device. NIMS also sends real-time tracking messages over the network that can be used by other systems to generate other metrics or to trigger instruments such as an optical video camera. A web-based user interface provides remote monitoring and control. NIMS currently supports three popular sonar devices: M3 multi-beam sonar (Kongsberg), EK60 split-beam echo-sounder (Simrad) and BlueView acoustic camera (Teledyne).

  20. The interactive design collaboratorium

    DEFF Research Database (Denmark)

    Bødker, Susanne; Petersen, Marianne Graves; Krogh, Peter Gall

    2001-01-01

    This paper reports on experimental process in which a prototype was developed of an interactive design collaboatorium, in cooperation with a group of usability designers. In a longterm research cooperation, this usability group has changed its work practice in order to work in the design...... collaboratorium. The design collaboratorium was developed to move usability design away from a lab towards an open physical and organizational space where designer, users and engineers meet and collaborate, or work alongside each other. The cooperation between researchers and the usability gruop has resulted...... in practical experimentation in projects and in design of an experimental design collaboratorium emploing electronic whiteboards, 3D design documentation, etc. This experimental prototype has been evaluated in cooperative workshops. We report on the results of this evaluation....

  1. Interaction, transference, and subjectivity

    DEFF Research Database (Denmark)

    Lundgaard Andersen, Linda

    2012-01-01

    Fieldwork is one of the important methods in educational, social, and organisational research. In fieldwork, the researcher takes residence for a shorter or longer period amongst the subjects and settings to be studied. The aim of this is to study the culture of people: how people seem to make...... sense of their lives and which moral, professional, and ethical values seem to guide their behaviour and attitudes. In fieldwork, the researcher has to balance participation and observation in her attempts at representation. Consequently, the researcher’s academic and life-historical subjectivity...... 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...

  2. Interacting viscous mixtures

    CERN Document Server

    Giovannini, Massimo

    2005-01-01

    Gravitational and hydrodynamical perturbations are analysed in a relativistic plasma containing a mixture of interacting fluids characterized by a non-negligible bulk viscosity coefficient. The energy-momentum transfer between the cosmological fluids, as well as the fluctuations of the bulk viscosity coefficients, are analyzed simultaneously with the aim of deriving a generalized set of evolution equations for the entropy and curvature fluctuations. For typical length scales larger than the Hubble radius, the fluctuations of the bulk viscosity coefficients and of the decay rate provide source terms for the evolution of both the curvature and the entropy fluctuations. According to the functional dependence of the bulk viscosity coefficient on the energy densities of the fluids composing the system, the mixing of entropy and curvature perturbations is scrutinized both analytically and numerically.

  3. Interacting viscous mixtures

    Energy Technology Data Exchange (ETDEWEB)

    Giovannini, Massimo [Centro ' Enrico Fermi' , Compendio del Viminale, Via Panisperna 89/A, 00184 Rome (Italy) and Department of Physics, Theory Division, CERN, 1211 Geneva 23 (Switzerland)]. E-mail: massimo.giovannini@cern.ch

    2005-09-01

    Gravitational and hydrodynamical perturbations are analysed in a relativistic plasma containing a mixture of interacting fluids characterized by a non-negligible bulk viscosity coefficient. The energy-momentum transfer between the cosmological fluids, as well as the fluctuations of the bulk viscosity coefficients, are analyzed simultaneously with the aim of deriving a generalized set of evolution equations for the entropy and curvature fluctuations. For typical length scales larger than the Hubble radius, the fluctuations of the bulk viscosity coefficients and of the decay rate provide source terms for the evolution of both the curvature and the entropy fluctuations. According to the functional dependence of the bulk viscosity coefficient on the energy densities of the fluids composing the system, the mixing of entropy and curvature perturbations is scrutinized both analytically and numerically.

  4. Leukocyte-epithelial interactions.

    Science.gov (United States)

    Zen, Ke; Parkos, Charles A

    2003-10-01

    As a 'double-edged sword', neutrophil (polymorphonuclear leukocyte) migration across epithelial-lined organs is an important component of host defense, but it also results in epithelial pathophysiology and disease symptoms. There have been significant advances in better understanding the mechanisms of how leukocytes cross the vascular endothelium to exit the bloodstream; however, many of the mechanisms that govern polymorphonuclear leukocyte transepithelial migration are different and we are only just beginning to understand them. Recent findings include new junctional adhesion molecules and carbohydrate moieties as receptors for migrating neutrophils. In addition, new insights into leukocyte-epithelial signaling events have emerged that are beginning to shed light on the role of SIRP-CD47 interactions in regulating the rate of neutrophil transepithelial migration and how neutrophils modulate epithelial barrier function.

  5. 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...

  6. Interactive Data Visualization

    Energy Technology Data Exchange (ETDEWEB)

    Steed, Chad A [ORNL

    2017-01-01

    Interactive data visualization leverages human visual perception and cognition to improve the accuracy and effectiveness of data analysis. When combined with automated data analytics, data visualization systems orchestrate the strengths of humans with the computational power of machines to solve problems neither approach can manage in isolation. In the intelligent transportation system domain, such systems are necessary to support decision making in large and complex data streams. In this chapter, we provide an introduction to several key topics related to the design of data visualization systems. In addition to an overview of key techniques and strategies, we will describe practical design principles. The chapter is concluded with a detailed case study involving the design of a multivariate visualization tool.

  7. Multiobjective Interaction Programming Problem with Interaction Constraint for Two Players

    Directory of Open Access Journals (Sweden)

    Min Jiang

    2012-01-01

    Full Text Available This paper extends an existing cooperative multi-objective interaction programming problem with interaction constraint for two players (or two agents. First, we define an s-optimal joint solution with weight vector to multi-objective interaction programming problem with interaction constraint for two players and get some properties of it. It is proved that the s-optimal joint solution with weight vector to the multi-objective interaction programming problem can be obtained by solving a corresponding mathematical programming problem. Then, we define another s-optimal joint solution with weight value to multi-objective interaction programming problem with interaction constraint for two players and get some of its properties. It is proved that the s-optimal joint solution with weight vector to multi-objective interaction programming problem can be obtained by solving a corresponding mathematical programming problem. Finally, we build a pricing multi-objective interaction programming model for a bi-level supply chain. Numerical results show that the interaction programming pricing model is better than Stackelberg pricing model and the joint pricing model.

  8. Interactive Projector as an Interactive Teaching Tool in the Classroom: Evaluating Teaching Efficiency and Interactivity

    Science.gov (United States)

    Liu, Li-Ying; Cheng, Meng-Tzu

    2015-01-01

    This study reports on a measurement that is used to investigate interactivity in the classrooms and examines the impact of integrating the interactive projector into middle school science classes on classroom interactivity and students' biology learning. A total of 126 7th grade Taiwanese students were involved in the study and quasi-experimental…

  9. 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....... the Interaction Themes are characterised by a relatively simple and self-generated content, they have an essential function because they contain the child’s and music therapist’s joint interaction history. They make up the context within which it is possible to create meaningful interaction with a client group...

  10. 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....... the Interaction Themes are characterised by a relatively simple and self-generated content, they have an essential function because they contain the child’s and music therapist’s joint interaction history. They make up the context within which it is possible to create meaningful interaction with a client group...

  11. Interacting With Robots to Investigate the Bases of Social Interaction.

    Science.gov (United States)

    Sciutti, Alessandra; Sandini, Giulio

    2017-12-01

    Humans show a great natural ability at interacting with each other. Such efficiency in joint actions depends on a synergy between planned collaboration and emergent coordination, a subconscious mechanism based on a tight link between action execution and perception. This link supports phenomena as mutual adaptation, synchronization, and anticipation, which cut drastically the delays in the interaction and the need of complex verbal instructions and result in the establishment of joint intentions, the backbone of social interaction. From a neurophysiological perspective, this is possible, because the same neural system supporting action execution is responsible of the understanding and the anticipation of the observed action of others. Defining which human motion features allow for such emergent coordination with another agent would be crucial to establish more natural and efficient interaction paradigms with artificial devices, ranging from assistive and rehabilitative technology to companion robots. However, investigating the behavioral and neural mechanisms supporting natural interaction poses substantial problems. In particular, the unconscious processes at the basis of emergent coordination (e.g., unintentional movements or gazing) are very difficult-if not impossible-to restrain or control in a quantitative way for a human agent. Moreover, during an interaction, participants influence each other continuously in a complex way, resulting in behaviors that go beyond experimental control. In this paper, we propose robotics technology as a potential solution to this methodological problem. Robots indeed can establish an interaction with a human partner, contingently reacting to his actions without losing the controllability of the experiment or the naturalness of the interactive scenario. A robot could represent an "interactive probe" to assess the sensory and motor mechanisms underlying human-human interaction. We discuss this proposal with examples from our

  12. Cryptococcus–Epithelial Interactions

    Directory of Open Access Journals (Sweden)

    Leanne M. Taylor-Smith

    2017-10-01

    Full Text Available The fungal pathogen, Cryptococcus neoformans, causes devastating levels of morbidity and mortality. Infections with this fungus tend to be predominantly in immunocompromised individuals, such as those with HIV. Infections initiate with inhalation of cryptococcal cells and entry of the pathogen into the lungs. The bronchial epithelial cells of the upper airway and the alveolar epithelial cells of the lower airway are likely to be the first host cells that Cryptococcus engage with. Thus the interaction of cryptococci and the respiratory epithelia will be the focus of this review. C. neoformans has been shown to adhere to respiratory epithelial cells, although if the role of the capsule is in aiding or hindering this adhesion is debatable. The epithelia are also able to react to cryptococci with the release of cytokines and chemokines to start the immune response to this invading pathogen. The activity of surfactant components that line this mucosal barrier towards Cryptococcus and the metabolic and transcriptional reaction of cryptococci when encountering epithelial cells will also be discussed.

  13. Dike/Drift Interactions

    Energy Technology Data Exchange (ETDEWEB)

    E.S. Gaffney

    2003-10-08

    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.

  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. Body-turbulence interaction

    Science.gov (United States)

    Bushnell, D. M.

    1984-01-01

    The paper reviews the area of body-turbulence interaction with particular emphasis upon the influence of the body upon an incident turublent field. Cases considered include two-dimensional (high and low fineness ratio, porous, and impervious) and three-dimensional bodies in-stream, adjacent to, and attached to walls. Particular physics common to several geometric and incident flow configurations include (1) eddy severing at relatively sharp leading edges, (2) production of vorticity of the opposite sense on bluff bodies, and (3) body region production of control vortices which affect the incident turbulence field for the order of 100 boundary-layer thicknesses downstream. The major local effects of the body upon the incident turbulent field include (1) a blocking effect, (2) influence of the body momentum deficit/near wake, (3) distortion due to the body time-averaged flow field, and (4) unsteady body circulation. The review may be of particular interest for turbulence alteration/control using fixed geometry in applications such as drag reduction, separation control, noise reduction, and augmentor optimization.

  16. RJSplot: Interactive Graphs with R.

    Science.gov (United States)

    Barrios, David; Prieto, Carlos

    2017-10-05

    Data visualization techniques provide new methods for the generation of interactive graphs. These graphs allow a better exploration and interpretation of data but their creation requires advanced knowledge of graphical libraries. Recent packages have enabled the integration of interactive graphs in R. However, R provides limited graphical packages that allow the generation of interactive graphs for computational biology applications. The present project has joined the analytical power of R with the interactive graphical features of JavaScript in a new R package (RJSplot). It enables the easy generation of interactive graphs in R, provides new visualization capabilities, and contributes to the advance of computational biology analytical methods. At present, 16 interactive graphics are available in RJSplot, such as the genome viewer, Manhattan plots, 3D plots, heatmaps, dendrograms, networks, and so on. The RJSplot package is freely available online at http://rjsplot.net. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Perturbative gadgets without strong interactions

    OpenAIRE

    Cao, Yudong; Nagaj, Daniel

    2014-01-01

    Perturbative gadgets are used to construct a quantum Hamiltonian whose low-energy subspace approximates a given quantum $k$-body Hamiltonian up to an absolute error $\\epsilon$. Typically, gadget constructions involve terms with large interaction strengths of order $\\text{poly}(\\epsilon^{-1})$. Here we present a 2-body gadget construction and prove that it approximates a target many-body Hamiltonian of interaction strength $\\gamma = O(1)$ up to absolute error $\\epsilon\\ll\\gamma$ using interact...

  18. 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...

  19. 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,

  20. Interactional Psychology and Organizational Behavior.

    Science.gov (United States)

    1982-02-01

    would have the opportunity to conduct true interactionist research on leadership . Hollander’s (1978) transactional theory and Hersey and Blanchard’s...approach. In J. G. Hunt & L. L. Larson (Eds.), Leadership frontiers. Kent,OH: Kent State University Press, 1975. 47 Hersey , P., & Blanchard , K. H...Interactional psychology organizational design organization theory person x situation interaction work socialization person-environment interaction

  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. Dark patterns in proxemic interactions

    DEFF Research Database (Denmark)

    Greenberg, Saul; Boring, Sebastian; Vermeulen, Jo

    2014-01-01

    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...... to better facilitate seamless and natural interactions. To do so, both people and devices are tracked to determine their spatial relationships. While interest in proxemic interactions has increased over the last few years, it also has a dark side: knowledge of proxemics may (and likely will) be easily...

  3. Ecological interactions of marine sponges

    National Research Council Canada - National Science Library

    Wulff, Janie L

    2006-01-01

    .... Considerable creative energy has been required to study and describe the amazing variety of sponge interactions, as sponges can hide symbionts deep inside, rapidly regenerate wounds from grazers...

  4. Imaging van der Waals Interactions.

    Science.gov (United States)

    Han, Zhumin; Wei, Xinyuan; Xu, Chen; Chiang, Chi-Lun; Zhang, Yanxing; Wu, Ruqian; Ho, W

    2016-12-15

    The van der Waals interactions are responsible for a large diversity of structures and functions in chemistry, biology, and materials. Discussion of van der Waals interactions has focused on the attractive potential energy that varies as the inverse power of the distance between the two interacting partners. The origin of the attractive force is widely discussed as being due to the correlated fluctuations of electron charges that lead to instantaneous dipole-induced dipole attractions. Here, we use the inelastic tunneling probe to image the potential energy surface associated with the van der Waals interactions of xenon atoms.

  5. 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.

  6. Mobile Collocated Interactions With Wearables

    DEFF Research Database (Denmark)

    Lucero, Andrés; Wilde, Danielle; Robinson, Simon

    2015-01-01

    Research on mobile collocated interactions has been looking at situations in which collocated users engage in collaborative activities using their mobile devices, thus going from personal/individual toward shared/multiuser experiences and interactions. However, computers are getting smaller, more...... 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....

  7. 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....

  8. Interactive Television: The Influence of User Control and Interactive Structure.

    Science.gov (United States)

    Gagnon, Diana; And Others

    A series of studies underway at the Audience Research Facility at MIT (the Massachusetts Institute of Technology) are examining the influence of interactive video on learning and entertainment television viewing. The first study compared the learning of spatial content from interactive (user controlled video games) versus observational…

  9. The n→π* Interaction.

    Science.gov (United States)

    Newberry, Robert W; Raines, Ronald T

    2017-08-15

    The carbonyl group holds a prominent position in chemistry and biology not only because it allows diverse transformations but also because it supports key intermolecular interactions, including hydrogen bonding. More recently, carbonyl groups have been found to interact with a variety of nucleophiles, including other carbonyl groups, in what we have termed an n→π* interaction. In an n→π* interaction, a nucleophile donates lone-pair (n) electron density into the empty π* orbital of a nearby carbonyl group. Mixing of these orbitals releases energy, resulting in an attractive interaction. Hints of such interactions were evident in small-molecule crystal structures as early as the 1970s, but not until 2001 was the role of such interactions articulated clearly. These non-covalent interactions were first discovered during investigations into the thermostability of the proline-rich protein collagen, which achieves a robust structure despite a relatively low potential for hydrogen bonding. It was found that by modulating the distance between two carbonyl groups in the peptide backbone, one could alter the conformational preferences of a peptide bond to proline. Specifically, only the trans conformation of a peptide bond to proline allows for an attractive interaction with an adjacent carbonyl group, so when one increases the proximity of the two carbonyl groups, one enhances their interaction and promotes the trans conformation of the peptide bond, which increases the thermostability of collagen. More recently, attention has been paid to the nature of these interactions. Some have argued that rather than resulting from electron donation, carbonyl interactions are a particular example of dipolar interactions that are well-approximated by classical mechanics. However, experimental evidence has demonstrated otherwise. Numerous examples now exist where an increase in the dipole moment of a carbonyl group decreases the strength of its interactions with other carbonyl

  10. Discovering functional interaction patterns in protein-protein interaction networks

    Directory of Open Access Journals (Sweden)

    Can Tolga

    2008-06-01

    Full Text Available Abstract Background In recent years, a considerable amount of research effort has been directed to the analysis of biological networks with the availability of genome-scale networks of genes and/or proteins of an increasing number of organisms. A protein-protein interaction (PPI network is a particular biological network which represents physical interactions between pairs of proteins of an organism. Major research on PPI networks has focused on understanding the topological organization of PPI networks, evolution of PPI networks and identification of conserved subnetworks across different species, discovery of modules of interaction, use of PPI networks for functional annotation of uncharacterized proteins, and improvement of the accuracy of currently available networks. Results In this article, we map known functional annotations of proteins onto a PPI network in order to identify frequently occurring interaction patterns in the functional space. We propose a new frequent pattern identification technique, PPISpan, adapted specifically for PPI networks from a well-known frequent subgraph identification method, gSpan. Existing module discovery techniques either look for specific clique-like highly interacting protein clusters or linear paths of interaction. However, our goal is different; instead of single clusters or pathways, we look for recurring functional interaction patterns in arbitrary topologies. We have applied PPISpan on PPI networks of Saccharomyces cerevisiae and identified a number of frequently occurring functional interaction patterns. Conclusion With the help of PPISpan, recurring functional interaction patterns in an organism's PPI network can be identified. Such an analysis offers a new perspective on the modular organization of PPI networks. The complete list of identified functional interaction patterns is available at http://bioserver.ceng.metu.edu.tr/PPISpan/.

  11. Kinetochore-microtubule stability governs the metaphase requirement for Eg5

    OpenAIRE

    Gayek, A. Sophia; Ohi, Ryoma

    2014-01-01

    The mitotic spindle is a bipolar, microtubule (MT)-based cellular machine that segregates the duplicated genome into two daughter cells. The kinesin-5 Eg5 establishes the bipolar geometry of the mitotic spindle, but previous work in mammalian cells suggested that this motor is unimportant for the maintenance of spindle bipolarity. Although it is known that Kif15, a second mitotic kinesin, enforces spindle bipolarity in the absence of Eg5, how Kif15 functions in this capacity and/or whether ot...

  12. A neocentromere on human chromosome 3 without detectable alpha-satellite DNA forms morphologically normal kinetochores

    DEFF Research Database (Denmark)

    Wandall, A; Tranebjaerg, L; Tommerup, Niels

    1998-01-01

    A neocentromere at 3q26 was observed in a father and his daughter on a chromosome 3 with deleted centromeric region. No alpha-satellite DNA was detectable at the 3q26 neocentromere, but it was weakly positive with anticentromere (CREST) antibodies. Electron microscopy showed that the neocentromere...

  13. How Different Are Aromatic π Interactions from Aliphatic π Interactions and Non-π Stacking Interactions?

    Science.gov (United States)

    Kim, Kwang S; Karthikeyan, S; Singh, N Jiten

    2011-11-08

    We compare aromatic π interactions with aliphatic π interactions of double- and triple-bonded π systems and non-π stacking interactions of single-bonded σ systems. The model dimer systems of acetylene (C2H2)2, ethylene (C2H4)2, ethane (C2H6)2, benzene (C6H6)2, and cyclohexane (C6H12)2 are investigated. The ethylene dimer has large dispersion energy, while the acetylene dimer has strong electrostatic energy. The aromatic π interactions are strong with particularly large dispersion and electrostatic energies, which would explain why aromatic compounds are frequently found in crystal packing and molecular self-engineering. It should be noted that the difference in binding energy between the benzene dimer (aromatic-aromatic interactions) and the cyclohexane dimer (aliphatic-aliphatic interactions) is not properly described in most density functionals.

  14. 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

  15. Our interests in protein-protein interactions

    Indian Academy of Sciences (India)

    protein interactions. Evolution of P-P partnerships. Evolution of P-P structures. Evolutionary dynamics of P-P interactions. Dynamics of P-P interaction network. Host-pathogen interactions. CryoEM mapping of gigantic protein assemblies.

  16. Interactions between Diatoms and Bacteria

    Science.gov (United States)

    Amin, Shady A.; Parker, Micaela S.

    2012-01-01

    Summary: Diatoms and bacteria have cooccurred in common habitats for hundreds of millions of years, thus fostering specific associations and interactions with global biogeochemical consequences. Diatoms are responsible for one-fifth of the photosynthesis on Earth, while bacteria remineralize a large portion of this fixed carbon in the oceans. Through their coexistence, diatoms and bacteria cycle nutrients between oxidized and reduced states, impacting bioavailability and ultimately feeding higher trophic levels. Here we present an overview of how diatoms and bacteria interact and the implications of these interactions. We emphasize that heterotrophic bacteria in the oceans that are consistently associated with diatoms are confined to two phyla. These consistent bacterial associations result from encounter mechanisms that occur within a microscale environment surrounding a diatom cell. We review signaling mechanisms that occur in this microenvironment to pave the way for specific interactions. Finally, we discuss known interactions between diatoms and bacteria and exciting new directions and research opportunities in this field. Throughout the review, we emphasize new technological advances that will help in the discovery of new interactions. Deciphering the languages of diatoms and bacteria and how they interact will inform our understanding of the role these organisms have in shaping the ocean and how these interactions may change in future oceans. PMID:22933565

  17. 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

  18. Transformations: Mobile Interaction & Language Learning

    Science.gov (United States)

    Carroll, Fiona; Kop, Rita; Thomas, Nathan; Dunning, Rebecca

    2015-01-01

    Mobile devices and the interactions that these technologies afford have the potential to change the face and nature of education in our schools. Indeed, mobile technological advances are seen to offer better access to educational material and new interactive ways to learn. However, the question arises, as to whether these new technologies are…

  19. Urban Interaction and Affective Experience

    DEFF Research Database (Denmark)

    Fritsch, Jonas; Brynskov, Martin

    2008-01-01

    in favor of three points in that direction: First we argue that interaction – and the definition of interaction – is central to unfold the potential of digital urban media, from big, shared screens and media facades to small pri-vate, networked mobile and embedded platforms. Then we argue that an affective...

  20. Hypervideos and interactive multimedia presentations

    NARCIS (Netherlands)

    B. Meixner (Britta)

    2017-01-01

    textabstractHypervideos and interactive multimedia presentations allow the creation of fully interactive and enriched video. It is possible to organize video scenes in a nonlinear way. Additional information can be added to the video ranging from short descriptions to images and more videos.

  1. Mapping Letters through Interaction Design

    NARCIS (Netherlands)

    Iturrioz, T.; Cano, J.; Wachowicz, M.

    2009-01-01

    Many kinds of text documents (e.g. newspapers, reports and letters) provide a potential source of geo-referenced information that is often underutilized. In interaction design, the use of dynamic icons and animation plays an important role in creating a sense of interactivity and feedback with

  2. DRUG INTERACTIONS WITH TUBERCULOSIS THERAPY

    African Journals Online (AJOL)

    Kurt

    most relevant to tuberculosis drug interactions is drug metabolism, which is explained in more detail below. Drug metabolism interactions. Drugs are metabolised by two types of reactions: phase I reactions that involve oxi- dation, reduction or hydrolysis in which drugs are turned into more polar com- pounds, and phase II ...

  3. Osteopontin interaction with integrin receptors

    DEFF Research Database (Denmark)

    Kläning, Eva

    Osteopontin is a negatively charged and unstructured protein that is found in many types of tissue in humans. Osteopontin can interact with many different types of cells via interaction with integrins, which are a particular class of receptors expressed on the cellular surface. Via contact...... with integrins, osteopontin can affect cellular behaviour in both normal and disease-related contexts....

  4. 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...

  5. Beneficial interactions in the rhizosphere

    NARCIS (Netherlands)

    Hol, W.H.G.; De Boer, W.; Medina, A.; Dighton, J.; Krumins, J.A.K

    2014-01-01

    Production of plant biomass is one of the main ecosystem services delivered by soil. The area closely surrounding the root surface, the rhizosphere, is where plants interact with soil organisms. The interaction of a plant with soil microorganisms may result in several benefits to the plant,

  6. Should Music Interaction Be Easy?

    NARCIS (Netherlands)

    McDermott, J.; Gifford, T.; Bouwer, A.; Wagy, M.; Holland, S.; Wilkie, K.; Mulholland, P.; Seago, A.

    2013-01-01

    A fundamental assumption in the fields of human-computer interaction and usability studies is that interfaces should be designed for ease of use, with a few exceptions such as the trade-off with long-term power. In this chapter it is argued that in music interaction the situation is far more

  7. Interactions between diatoms and bacteria.

    Science.gov (United States)

    Amin, Shady A; Parker, Micaela S; Armbrust, E Virginia

    2012-09-01

    Diatoms and bacteria have cooccurred in common habitats for hundreds of millions of years, thus fostering specific associations and interactions with global biogeochemical consequences. Diatoms are responsible for one-fifth of the photosynthesis on Earth, while bacteria remineralize a large portion of this fixed carbon in the oceans. Through their coexistence, diatoms and bacteria cycle nutrients between oxidized and reduced states, impacting bioavailability and ultimately feeding higher trophic levels. Here we present an overview of how diatoms and bacteria interact and the implications of these interactions. We emphasize that heterotrophic bacteria in the oceans that are consistently associated with diatoms are confined to two phyla. These consistent bacterial associations result from encounter mechanisms that occur within a microscale environment surrounding a diatom cell. We review signaling mechanisms that occur in this microenvironment to pave the way for specific interactions. Finally, we discuss known interactions between diatoms and bacteria and exciting new directions and research opportunities in this field. Throughout the review, we emphasize new technological advances that will help in the discovery of new interactions. Deciphering the languages of diatoms and bacteria and how they interact will inform our understanding of the role these organisms have in shaping the ocean and how these interactions may change in future oceans.

  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. Observation of Tau Neutrino Interactions

    CERN Document Server

    Kodama, K; Andreopoulos, C; Saoulidou, N; Tzanakos, G S; Yager, P M; Baller, B R; Böhnlein, D J; Freeman, W; Lundberg, B; Mor, J; Rameika, R; Yun, J C; Song, J S; Yoon, C S; Chung, S H; Berghaus, P; Kubantsev, M A; Reay, N W; Sidwell, R A; Stanton, N; Yoshida, S; Aoki, S; Hara, T; Rhee, J T; Ciampa, D; Erickson, C; Graham, M; Heller, K; Rusack, R W; Schwienhorst, R; Siela, J; Trammell, J; Wilcox, J; Hoshino, K; Jiko, H; Miyanishi, M; Komatsu, M; Nakamura, M; Nakano, T; Niwa, K; Nonaka, N; Okada, K; Sato, O; Akdogan, T; Paolone, V; Rosenfeld, C; Kulik, A V; Kafka, T; Oliver, W; Patzak, T; Schneps, J

    2001-01-01

    The DONUT experiment has analyzed 203 neutrino interactions recorded in nuclear emulsion targets. A decay search has found evidence of four tau neutrino interactions with an estimated background of 0.34 events. This number is consistent with the Standard Model expectation.

  10. Child-Computer Interaction SIG

    DEFF Research Database (Denmark)

    Hourcade, Juan Pablo; Revelle, Glenda; Zeising, Anja

    2016-01-01

    This SIG will provide child-computer interaction researchers and practitioners an opportunity to discuss four topics that represent new challenges and opportunities for the community. The four areas are: interactive technologies for children under the age of five, technology for inclusion, privacy...

  11. 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…

  12. Mutually coordinated anticipatory multimodal interaction

    NARCIS (Netherlands)

    Nijholt, Antinus; Reidsma, Dennis; van Welbergen, H.; op den Akker, Hendrikus J.A.; Ruttkay, Z.M.; Esposito, A.; Bourbakis, N.G.; Avouris, N.; Hatzilygeroudis, I.

    2008-01-01

    We introduce our research on anticipatory and coordinated interaction between a virtual human and a human partner. Rather than adhering to the turn taking paradigm, we choose to investigate interaction where there is simultaneous expressive behavior by the human interlocutor and a humanoid. We have

  13. 3-way Anova Interactions: Deconstructed

    OpenAIRE

    Phil Ender

    2008-01-01

    Three approaches to understanding 3-way anova interactions will be presented: 1) a conceptual approach, 2) an anova approach and 3) a regression approach using dummy coding. The three approaches are illustrated through the use of a synthetic dataset with a significant 3-way interaction.

  14. Embedded Interaction 2009: final report

    CSIR Research Space (South Africa)

    Smith, Adrew C

    2009-03-01

    Full Text Available • Book proposal review....................................................................................... 14 • PhD proposal review........................................................................................ 14 • Advisory committee member... activities of children from differing socio- economic backgrounds. Typically, children attending School A interact mostly with electronic technology and books, both presenting information in a 2D format. In contrast, children from School B interact mostly...

  15. Narrative Cognition in Interactive Systems

    DEFF Research Database (Denmark)

    Bruni, Luis Emilio; Baceviciute, Sarune; Arief, Mohammed

    2014-01-01

    In this article we explore some of the methodological problems related to characterizing cognitive aspects of involvement with interactive narratives using well known EEG/ERP techniques. To exemplify this, we construct an experimental EEG-ERP set-up with an interactive narrative that considers...

  16. 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…

  17. 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...... the Interaction Themes are characterised by arelatively simple and self-generated content, they have an essentialfunction because they contain the child?s and music therapist?s jointinteraction history. They make up the context within which it ispossible to create meaningful interaction with a client group...

  18. Interaction webs in arctic ecosystems

    DEFF Research Database (Denmark)

    Schmidt, Niels Martin; Hardwick, Bess; Gilg, Olivier

    2017-01-01

    in environmental conditions. Thirdly, biotic interactions within a trophic level may affect other trophic levels, in some cases ultimately affecting land–atmosphere feedbacks. Finally, differential responses to environmental change may decouple interacting species. These insights form Zackenberg emphasize......How species interact modulate their dynamics, their response to environmental change, and ultimately the functioning and stability of entire communities. Work conducted at Zackenberg, Northeast Greenland, has changed our view on how networks of arctic biotic interactions are structured, how...... they vary in time, and how they are changing with current environmental change: firstly, the high arctic interaction webs are much more complex than previously envisaged, and with a structure mainly dictated by its arthropod component. Secondly, the dynamics of species within these webs reflect changes...

  19. Interaction Terms in Nonlinear Models

    Science.gov (United States)

    Karaca-Mandic, Pinar; Norton, Edward C; Dowd, Bryan

    2012-01-01

    Objectives To explain the use of interaction terms in nonlinear models. Study Design We discuss the motivation for including interaction terms in multivariate analyses. We then explain how the straightforward interpretation of interaction terms in linear models changes in nonlinear models, using graphs and equations. We extend the basic results from logit and probit to difference-in-differences models, models with higher powers of explanatory variables, other nonlinear models (including log transformation and ordered models), and panel data models. Empirical Application We show how to calculate and interpret interaction effects using a publicly available Stata data set with a binary outcome. Stata 11 has added several features which make those calculations easier. LIMDEP code also is provided. Conclusions It is important to understand why interaction terms are included in nonlinear models in order to be clear about their substantive interpretation. PMID:22091735

  20. Expanding the Interaction Equivalency Theorem

    Directory of Open Access Journals (Sweden)

    Brenda Cecilia Padilla Rodriguez

    2015-06-01

    Full Text Available Although interaction is recognised as a key element for learning, its incorporation in online courses can be challenging. The interaction equivalency theorem provides guidelines: Meaningful learning can be supported as long as one of three types of interactions (learner-content, learner-teacher and learner-learner is present at a high level. This study sought to apply this theorem to the corporate sector, and to expand it to include other indicators of course effectiveness: satisfaction, knowledge transfer, business results and return on expectations. A large Mexican organisation participated in this research, with 146 learners, 30 teachers and 3 academic assistants. Three versions of an online course were designed, each emphasising a different type of interaction. Data were collected through surveys, exams, observations, activity logs, think aloud protocols and sales records. All course versions yielded high levels of effectiveness, in terms of satisfaction, learning and return on expectations. Yet, course design did not dictate the types of interactions in which students engaged within the courses. Findings suggest that the interaction equivalency theorem can be reformulated as follows: In corporate settings, an online course can be effective in terms of satisfaction, learning, knowledge transfer, business results and return on expectations, as long as (a at least one of three types of interaction (learner-content, learner-teacher or learner-learner features prominently in the design of the course, and (b course delivery is consistent with the chosen type of interaction. Focusing on only one type of interaction carries a high risk of confusion, disengagement or missed learning opportunities, which can be managed by incorporating other forms of interactions.

  1. Final State Interactions Effects in Neutrino-Nucleus Interactions

    Energy Technology Data Exchange (ETDEWEB)

    Golan, Tomasz [Univ. of Wroctaw (Poland); Juszczak, Cezary [Univ. of Wroctaw (Poland); Sobczyk, Jan T. [Fermi National Accelerator Laboratory (FNAL), Batavia, IL (United States)

    2012-07-01

    Final State Interactions effects are discussed in the context of Monte Carlo simulations of neutrino-nucleus interactions. A role of Formation Time is explained and several models describing this effect are compared. Various observables which are sensitive to FSI effects are reviewed including pion-nucleus interaction and hadron yields in backward hemisphere. NuWro Monte Carlo neutrino event generator is described and its ability to understand neutral current $\\pi^0$ production data in $\\sim 1$ GeV neutrino flux experiments is demonstrated.

  2. Interactive computations: toward risk management in interactive intelligent systems.

    Science.gov (United States)

    Skowron, Andrzej; Jankowski, Andrzej

    Understanding the nature of interactions is regarded as one of the biggest challenges in projects related to complex adaptive systems. We discuss foundations for interactive computations in interactive intelligent systems (IIS), developed in the Wistech program and used for modeling complex systems. We emphasize the key role of risk management in problem solving by IIS. The considerations are based on experience gained in real-life projects concerning, e.g., medical diagnosis and therapy support, control of an unmanned helicopter, fraud detection algorithmic trading or fire commander decision support.

  3. Calculation of Rydberg interaction potentials

    Science.gov (United States)

    Weber, Sebastian; Tresp, Christoph; Menke, Henri; Urvoy, Alban; Firstenberg, Ofer; Büchler, Hans Peter; Hofferberth, Sebastian

    2017-07-01

    The strong interaction between individual Rydberg atoms provides a powerful tool exploited in an ever-growing range of applications in quantum information science, quantum simulation and ultracold chemistry. One hallmark of the Rydberg interaction is that both its strength and angular dependence can be fine-tuned with great flexibility by choosing appropriate Rydberg states and applying external electric and magnetic fields. More and more experiments are probing this interaction at short atomic distances or with such high precision that perturbative calculations as well as restrictions to the leading dipole-dipole interaction term are no longer sufficient. In this tutorial, we review all relevant aspects of the full calculation of Rydberg interaction potentials. We discuss the derivation of the interaction Hamiltonian from the electrostatic multipole expansion, numerical and analytical methods for calculating the required electric multipole moments and the inclusion of electromagnetic fields with arbitrary direction. We focus specifically on symmetry arguments and selection rules, which greatly reduce the size of the Hamiltonian matrix, enabling the direct diagonalization of the Hamiltonian up to higher multipole orders on a desktop computer. Finally, we present example calculations showing the relevance of the full interaction calculation to current experiments. Our software for calculating Rydberg potentials including all features discussed in this tutorial is available as open source.

  4. Evolutionary dynamics under interactive diversity

    Science.gov (United States)

    Su, Qi; Li, Aming; Wang, Long

    2017-10-01

    As evidenced by many cases in human societies, individuals often make different behavior decisions in different interactions, and adaptively adjust their behavior in changeable interactive scenarios. However, up to now, how such diverse interactive behavior affects cooperation dynamics has still remained unknown. Here we develop a general framework of interactive diversity, which models individuals’ separated behavior against distinct opponents and their adaptive adjustment in response to opponents’ strategies, to explore the evolution of cooperation. We find that interactive diversity enables individuals to reciprocate every single opponent, and thus sustains large-scale reciprocal interactions. Our work witnesses an impressive boost of cooperation for a notably extensive range of parameters and for all pairwise games. These results are robust against well-mixed and various networked populations, and against degree-normalized and cumulative payoff patterns. From the perspective of network dynamics, distinguished from individuals competing for nodes in most previous work, in this paper, the system evolves in the form of behavior disseminating along edges. We propose a theoretical method based on evolution of edges, which predicts well both the frequency of cooperation and the compact cooperation clusters. Our thorough investigation clarifies the positive role of interactive diversity in resolving social dilemmas and highlights the significance of understanding evolutionary dynamics from the viewpoint of edge dynamics.

  5. Adverse food-drug interactions.

    Science.gov (United States)

    de Boer, Alie; van Hunsel, Florence; Bast, Aalt

    2015-12-01

    Food supplements and herbal products are increasingly popular amongst consumers. This leads to increased risks of interactions between prescribed drugs and these products containing bioactive ingredients. From 1991 up to 2014, 55 cases of suspected adverse drug reactions due to concomitant intake of health-enhancing products and drugs were reported to Lareb, the Netherlands Pharmacovigilance Centre. An overview of these suspected interactions is presented and their potential mechanisms of action are described. Mainly during the metabolism of xenobiotics and due to the pharmacodynamics effects interactions seem to occur, which may result in adverse drug reactions. Where legislation is seen to distinct food and medicine, legislation concerning these different bioactive products is less clear-cut. This can only be resolved by increasing the molecular knowledge on bioactive substances and their potential interactions. Thereby potential interactions can be better understood and prevented on an individual level. By considering the dietary pattern and use of bioactive substances with prescribed medication, both health professionals and consumers will be increasingly aware of interactions and these interactive adverse effects can be prevented. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Interactions, Starbursts, and Star Formation

    Directory of Open Access Journals (Sweden)

    Johan H. Knapen

    2015-12-01

    Full Text Available We study how interactions between galaxies affect star formation within them by considering a sample of almost 1500 of the nearest galaxies, all within a distance of ∼45 Mpc. We use the far-IR emission to define the massive star formation rate (SFR, and then normalise the SFR by the stellar mass of the galaxy to obtain the specific star formation rate (SSFR. We explore the distribution of (SSFR with morphological type and with stellar mass. We calculate the relative enhancement of SFR and SSFR for each galaxy by normalising them by the median SFR and SSFR values of individual control samples of similar non-interacting galaxies. We find that both the median SFR and SSFR are enhanced in interacting galaxies, and more so as the degree of interaction is higher. The increase is moderate, reaching a maximum of a factor of 1.9 for the highest degree of interaction (mergers. While the SFR and SSFR are enhanced statistically by interactions, in many individual interacting galaxies they are not enhanced at all. Our study is based on a representative sample of nearby galaxies and should be used to place constraints on studies based on samples of galaxies at larger distances.

  7. [Drug interactions in pain therapy].

    Science.gov (United States)

    Syhr, K M J; Oertel, B G; Geisslinger, G

    2015-12-01

    Pain is one of the most common reasons for consulting a physician. Chronic pain patients often suffer from a variety of comorbidities, such as depression and anxiety and they are therefore often simultaneously treated with more than one drug. The probability of drug interactions increases with every additional drug. A systematic internet and literature search up to February 2015 was carried out. Systematic lists were included. In addition, the drug prescription information sheets were used and an internet search via Pubmed and google.com was carried out for drugs alone and in combination in order to find substance-specific interactions. A differentiation is made between pharmaceutical, pharmacodynamic and pharmacokinetic drug interactions. Pharmaceutical interactions are caused by chemical, physical or physicochemical incompatibility of drugs or adjuvants used. These can even occur outside the body and during concomitant administration via the same route. A pharmacodynamic interaction in pain management is for example the additive sedative effect of opioids and benzodiazepines when taken together. Pharmacokinetic interactions occur during the absorption, distribution, metabolism and in the elimination phases. Many drug interactions can be avoided by careful and continuous evaluation of pharmacotherapy and if necessary its adaptation; however, a sound knowledge of the underlying pharmacological mechanisms and the properties of currently used analgesics is necessary.

  8. Aquaporin Protein-Protein Interactions

    Directory of Open Access Journals (Sweden)

    Jennifer Virginia Roche

    2017-10-01

    Full Text Available Aquaporins are tetrameric membrane-bound channels that facilitate transport of water and other small solutes across cell membranes. In eukaryotes, they are frequently regulated by gating or trafficking, allowing for the cell to control membrane permeability in a specific manner. Protein–protein interactions play crucial roles in both regulatory processes and also mediate alternative functions such as cell adhesion. In this review, we summarize recent knowledge about aquaporin protein–protein interactions; dividing the interactions into three types: (1 interactions between aquaporin tetramers; (2 interactions between aquaporin monomers within a tetramer (hetero-tetramerization; and (3 transient interactions with regulatory proteins. We particularly focus on the structural aspects of the interactions, discussing the small differences within a conserved overall fold that allow for aquaporins to be differentially regulated in an organism-, tissue- and trigger-specific manner. A deep knowledge about these differences is needed to fully understand aquaporin function and regulation in many physiological processes, and may enable design of compounds targeting specific aquaporins for treatment of human disease.

  9. Interact-ed interwinning nature of virtual reality

    OpenAIRE

    Özenç, Kürşat Fatih; Ozenc, Kursat Fatih

    2004-01-01

    In our highly computerized world, we live in an environment which resembles an intertwining mobius of 'real' and 'virtual'. In interact-ed's visual context, the virtual and the real have been quettioned with respect to this interrelation. The investigation is moreover done with the concept of dreams. Dreams, like virtual environments, affect our life 'apperently'; not 'really'. As affective experiences, virtual (environments) and dreams are tightly related to each other. In somne conditions t...

  10. Detecting mutually exclusive interactions in protein-protein interaction maps.

    Directory of Open Access Journals (Sweden)

    Carmen Sánchez Claros

    Full Text Available Comprehensive protein interaction maps can complement genetic and biochemical experiments and allow the formulation of new hypotheses to be tested in the system of interest. The computational analysis of the maps may help to focus on interesting cases and thereby to appropriately prioritize the validation experiments. We show here that, by automatically comparing and analyzing structurally similar regions of proteins of known structure interacting with a common partner, it is possible to identify mutually exclusive interactions present in the maps with a sensitivity of 70% and a specificity higher than 85% and that, in about three fourth of the correctly identified complexes, we also correctly recognize at least one residue (five on average belonging to the interaction interface. Given the present and continuously increasing number of proteins of known structure, the requirement of the knowledge of the structure of the interacting proteins does not substantially impact on the coverage of our strategy that can be estimated to be around 25%. We also introduce here the Estrella server that embodies this strategy, is designed for users interested in validating specific hypotheses about the functional role of a protein-protein interaction and it also allows access to pre-computed data for seven organisms.

  11. Detecting mutually exclusive interactions in protein-protein interaction maps.

    KAUST Repository

    Sánchez Claros, Carmen

    2012-06-08

    Comprehensive protein interaction maps can complement genetic and biochemical experiments and allow the formulation of new hypotheses to be tested in the system of interest. The computational analysis of the maps may help to focus on interesting cases and thereby to appropriately prioritize the validation experiments. We show here that, by automatically comparing and analyzing structurally similar regions of proteins of known structure interacting with a common partner, it is possible to identify mutually exclusive interactions present in the maps with a sensitivity of 70% and a specificity higher than 85% and that, in about three fourth of the correctly identified complexes, we also correctly recognize at least one residue (five on average) belonging to the interaction interface. Given the present and continuously increasing number of proteins of known structure, the requirement of the knowledge of the structure of the interacting proteins does not substantially impact on the coverage of our strategy that can be estimated to be around 25%. We also introduce here the Estrella server that embodies this strategy, is designed for users interested in validating specific hypotheses about the functional role of a protein-protein interaction and it also allows access to pre-computed data for seven organisms.

  12. Quantum interaction. Revised selected papers

    Energy Technology Data Exchange (ETDEWEB)

    Song, Dawei; Zhang, Peng; Wang, Lei [Aberdeen Univ. (United Kingdom). School of Computing; Melucci, Massimo [Padua Univ., Padova (Italy). Dept. of Information Engineering; Frommholz, Ingo [Bedfordshire Univ. (United Kingdom); Arafat, Sachi (eds.) [Glasgow Univ. (United Kingdom). School of Computing Science

    2011-07-01

    This book constitutes the thoroughly refereed post-conference proceedings of the 5th International Symposium on Quantum Interaction, QI 2011, held in Aberdeen, UK, in June 2011. The 26 revised full papers and 6 revised poster papers, presented together with 1 tutorial and 1 invited talk were carefully reviewed and selected from numerous submissions during two rounds of reviewing and improvement. The papers show the cross-disciplinary nature of quantum interaction covering topics such as computation, cognition, mechanics, social interaction, semantic space and information representation and retrieval. (orig.)

  13. Interaction of radiation with matter

    CERN Document Server

    Nikjoo, Hooshang; Emfietzoglou, Dimitris

    2012-01-01

    Written for students approaching the subject for the first time, this text provides a solid grounding in the physics of the interactions of photons and particles with matter, which is the basis of radiological physics and radiation dosimetry. The authors first present the relevant atomic physics and then describe the interactions, emphasizing practical applications in health/medical physics and radiation biology. They cover such important topics as microdosimetry, interaction of photons with matter, electron energy loss, and dielectric response. Each chapter includes exercises and a summary.

  14. Diatomic interaction potential theory applications

    CERN Document Server

    Goodisman, Jerry

    2013-01-01

    Diatomic Interaction Potential Theory, Volume 2: Applications discusses the variety of applicable theoretical material and approaches in the calculations for diatomic systems in their ground states. The volume covers the descriptions and illustrations of modern calculations. Chapter I discusses the calculation of the interaction potential for large and small values of the internuclear distance R (separated and united atom limits). Chapter II covers the methods used for intermediate values of R, which in principle means any values of R. The Hartree-Fock and configuration interaction schemes des

  15. Research in interactive scene analysis

    Science.gov (United States)

    Tenenbaum, J. M.; Barrow, H. G.; Weyl, S. A.

    1976-01-01

    Cooperative (man-machine) scene analysis techniques were developed whereby humans can provide a computer with guidance when completely automated processing is infeasible. An interactive approach promises significant near-term payoffs in analyzing various types of high volume satellite imagery, as well as vehicle-based imagery used in robot planetary exploration. This report summarizes the work accomplished over the duration of the project and describes in detail three major accomplishments: (1) the interactive design of texture classifiers; (2) a new approach for integrating the segmentation and interpretation phases of scene analysis; and (3) the application of interactive scene analysis techniques to cartography.

  16. The Ontology of Interactive Kinds

    Directory of Open Access Journals (Sweden)

    Hauswald Rico

    2016-08-01

    Full Text Available This paper defends the notions of an interactive kind and a looping effect as features of social and human scientific classifications and aims to give a realist interpretation of them. I argue that interactive kinds can best be modeled as a special case of changing causal property cluster kinds. In order to do so, I develop a typology of looping effects according to the sort of entities that are affected, the main types of which are individual-looping, category-looping, and kind-looping. Based on this distinction, I identify interactive kinds as those causal property cluster kinds that are subjected to kind-looping.

  17. Learning Axure RP interactive prototypes

    CERN Document Server

    Krahenbuhl, John Henry

    2015-01-01

    If you are a user experience professional, designer, information architect, or business analyst who wants to gain interactive prototyping skills with Axure, then this book is ideal for you. Some familiarity with Axure is preferred but not essential.

  18. Interaction of spatial photorefractive solitons

    DEFF Research Database (Denmark)

    Królikowski, W.; Denz, C.; Stepken, A.

    1998-01-01

    We present a review of our recent theoretical and experimental results on the interaction of two-dimensional solitary beams in photorefractive SBN crystals. We show that the collision of coherent solitons may result in energy exchange, fusion of the interacting solitons, the birth of a new solita...... that a soliton pair may experience both attractive and repulsive forces; depending on their mutual separation. We also show that strong attraction leads to periodic collision or helical motion of solitons depending on initial conditions.......We present a review of our recent theoretical and experimental results on the interaction of two-dimensional solitary beams in photorefractive SBN crystals. We show that the collision of coherent solitons may result in energy exchange, fusion of the interacting solitons, the birth of a new solitary...

  19. Interactive Proof Presentations with Cobra

    National Research Council Canada - National Science Library

    Ring, Martin; Lüth, Christoph

    2017-01-01

    We present Cobra, a modern proof presentation framework, leveraging cutting-edge presentation technology together with a state of the art interactive theorem prover to present formalized mathematics as active documents...

  20. Urban Interaction and Affective Experience

    DEFF Research Database (Denmark)

    Fritsch, Jonas; Brynskov, Martin

    2008-01-01

    As interactive digital technologies become a still more integrated and complex part of the everyday physical, social and cultural spaces we inhabit, research into these spaces’ dynamics and struc-tures needs to formulate adequate methods of analysis and dis-course. In this position paper we argue...... in favor of three points in that direction: First we argue that interaction – and the definition of interaction – is central to unfold the potential of digital urban media, from big, shared screens and media facades to small pri-vate, networked mobile and embedded platforms. Then we argue that an affective...... approach holds potential to address important aspects of the design of such blended digital spaces, extending beyond traditional interaction design. And finally we argue for the importance of construction, i.e. actual interventions of consider-able scale....