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Sample records for replicated top signals

  1. Signal replication in a DNA nanostructure

    Science.gov (United States)

    Mendoza, Oscar; Houmadi, Said; Aimé, Jean-Pierre; Elezgaray, Juan

    2017-01-01

    Logic circuits based on DNA strand displacement reaction are the basic building blocks of future nanorobotic systems. The circuits tethered to DNA origami platforms present several advantages over solution-phase versions where couplings are always diffusion-limited. Here we consider a possible implementation of one of the basic operations needed in the design of these circuits, namely, signal replication. We show that with an appropriate preparation of the initial state, signal replication performs in a reproducible way. We also show the existence of side effects concomitant to the high effective concentrations in tethered circuits, such as slow leaky reactions and cross-activation.

  2. Levels of the E2 interacting protein TopBP1 modulate papillomavirus maintenance stage replication

    Energy Technology Data Exchange (ETDEWEB)

    Kanginakudru, Sriramana, E-mail: skangina@iu.edu [Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN (United States); DeSmet, Marsha, E-mail: mdesmet@iupui.edu [Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN (United States); Thomas, Yanique, E-mail: ysthomas@umail.iu.edu [Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN (United States); Morgan, Iain M., E-mail: immorgan@vcu.edu [VCU Philips Institute for Oral Health Research, Virginia Commonwealth University, Richmond, Virginia (United States); Androphy, Elliot J., E-mail: eandro@iu.edu [Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN (United States); Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN (United States)

    2015-04-15

    The evolutionarily conserved DNA topoisomerase II beta-binding protein 1 (TopBP1) functions in DNA replication, DNA damage response, and cell survival. We analyzed the role of TopBP1 in human and bovine papillomavirus genome replication. Consistent with prior reports, TopBP1 co-localized in discrete nuclear foci and was in complex with papillomavirus E2 protein. Similar to E2, TopBP1 is recruited to the region of the viral origin of replication during G1/S and early S phase. TopBP1 knockdown increased, while over-expression decreased transient virus replication, without affecting cell cycle. Similarly, using cell lines harboring HPV-16 or HPV-31 genome, TopBP1 knockdown increased while over-expression reduced viral copy number relative to genomic DNA. We propose a model in which TopBP1 serves dual roles in viral replication: it is essential for initiation of replication yet it restricts viral copy number. - Highlights: • Protein interaction study confirmed In-situ interaction between TopBP1 and E2. • TopBP1 present at papillomavirus ori in G1/S and early S phase of cell cycle. • TopBP1 knockdown increased, over-expression reduced virus replication. • TopBP1 protein level change did not influence cell survival or cell cycle. • TopBP1 displaced from papillomavirus ori after initiation of replication.

  3. Levels of the E2 interacting protein TopBP1 modulate papillomavirus maintenance stage replication

    International Nuclear Information System (INIS)

    Kanginakudru, Sriramana; DeSmet, Marsha; Thomas, Yanique; Morgan, Iain M.; Androphy, Elliot J.

    2015-01-01

    The evolutionarily conserved DNA topoisomerase II beta-binding protein 1 (TopBP1) functions in DNA replication, DNA damage response, and cell survival. We analyzed the role of TopBP1 in human and bovine papillomavirus genome replication. Consistent with prior reports, TopBP1 co-localized in discrete nuclear foci and was in complex with papillomavirus E2 protein. Similar to E2, TopBP1 is recruited to the region of the viral origin of replication during G1/S and early S phase. TopBP1 knockdown increased, while over-expression decreased transient virus replication, without affecting cell cycle. Similarly, using cell lines harboring HPV-16 or HPV-31 genome, TopBP1 knockdown increased while over-expression reduced viral copy number relative to genomic DNA. We propose a model in which TopBP1 serves dual roles in viral replication: it is essential for initiation of replication yet it restricts viral copy number. - Highlights: • Protein interaction study confirmed In-situ interaction between TopBP1 and E2. • TopBP1 present at papillomavirus ori in G1/S and early S phase of cell cycle. • TopBP1 knockdown increased, over-expression reduced virus replication. • TopBP1 protein level change did not influence cell survival or cell cycle. • TopBP1 displaced from papillomavirus ori after initiation of replication

  4. Mutant p53 perturbs DNA replication checkpoint control through TopBP1 and Treslin.

    Science.gov (United States)

    Liu, Kang; Lin, Fang-Tsyr; Graves, Joshua D; Lee, Yu-Ju; Lin, Weei-Chin

    2017-05-09

    Accumulating evidence supports the gain-of-function of mutant forms of p53 (mutp53s). However, whether mutp53 directly perturbs the DNA replication checkpoint remains unclear. Previously, we have demonstrated that TopBP1 forms a complex with mutp53s and mediates their gain-of-function through NF-Y and p63/p73. Akt phosphorylates TopBP1 and induces its oligomerization, which inhibits its ATR-activating function. Here we show that various contact and conformational mutp53s bypass Akt to induce TopBP1 oligomerization and attenuate ATR checkpoint response during replication stress. The effect on ATR response caused by mutp53 can be exploited in a synthetic lethality strategy, as depletion of another ATR activator, DNA2, in mutp53-R273H-expressing cancer cells renders cells hypersensitive to cisplatin. Expression of mutp53-R273H also makes cancer cells more sensitive to DNA2 depletion or DNA2 inhibitors. In addition to ATR-activating function during replication stress, TopBP1 interacts with Treslin in a Cdk-dependent manner to initiate DNA replication during normal growth. We find that mutp53 also interferes with TopBP1 replication function. Several contact, but not conformational, mutp53s enhance the interaction between TopBP1 and Treslin and promote DNA replication despite the presence of a Cdk2 inhibitor. Together, these data uncover two distinct mechanisms by which mutp53 enhances DNA replication: ( i ) Both contact and conformational mutp53s can bind TopBP1 and attenuate the checkpoint response to replication stress, and ( ii ) during normal growth, contact (but not conformational) mutp53s can override the Cdk2 requirement to promote replication by facilitating the TopBP1/Treslin interaction.

  5. GEMC1 is a TopBP1-interacting protein required for chromosomal DNA replication.

    Science.gov (United States)

    Balestrini, Alessia; Cosentino, Claudia; Errico, Alessia; Garner, Elizabeth; Costanzo, Vincenzo

    2010-05-01

    Many of the factors required for chromosomal DNA replication have been identified in unicellular eukaryotes. However, DNA replication is poorly understood in multicellular organisms. Here, we report the identification of GEMC1 (geminin coiled-coil containing protein 1), a novel vertebrate protein required for chromosomal DNA replication. GEMC1 is highly conserved in vertebrates and is preferentially expressed in proliferating cells. Using Xenopus laevis egg extract we show that Xenopus GEMC1 (xGEMC1) binds to the checkpoint and replication factor TopBP1, which promotes binding of xGEMC1 to chromatin during pre-replication complex (pre-RC) formation. We demonstrate that xGEMC1 interacts directly with replication factors such as Cdc45 and the kinase Cdk2-CyclinE, through which it is heavily phosphorylated. Phosphorylated xGEMC1 stimulates initiation of DNA replication, whereas depletion of xGEMC1 prevents the onset of DNA replication owing to the impairment of Cdc45 loading onto chromatin. Similarly, inhibition of GEMC1 expression with morpholino and siRNA oligos prevents DNA replication in embryonic and somatic vertebrate cells. These data suggest that GEMC1 promotes initiation of chromosomal DNA replication in multicellular organisms by mediating TopBP1- and Cdk2-dependent recruitment of Cdc45 onto replication origins.

  6. GEMC1 is a TopBP1 interacting protein required for chromosomal DNA replication

    Science.gov (United States)

    Balestrini, Alessia; Cosentino, Claudia; Errico, Alessia; Garner, Elizabeth; Costanzo, Vincenzo

    2010-01-01

    Many factors required for chromosomal DNA replication have been identified in unicellular eukaryotes. However, DNA replication in complex multicellular organisms is poorly understood. Here, we report the identification of GEMC1, a novel vertebrate protein required for chromosomal DNA replication. GEMC1 is highly conserved in vertebrates and is preferentially expressed in proliferating cells. Using Xenopus egg extract we show that Xenopus GEMC1 (xGEMC1) binds to checkpoint and replication factor TopBP1, which promotes xGEMC1 binding to chromatin during pre-replication complex (pre-RC) formation. We demonstrate that xGEMC1 directly interacts with replication factors such as Cdc45 and Cdk2-CyclinE by which it is heavily phosphorylated. Phosphorylated xGEMC1 stimulates initiation of DNA replication whereas depletion of xGEMC1 prevents DNA replication onset due to impairment of Cdc45 loading onto chromatin. Likewise, inhibition of GEMC1 expression by morpholino and siRNA oligos prevents DNA replication in embryonic and somatic vertebrate cells. These data suggest that GEMC1 promotes initiation of chromosomal DNA replication in higher eukaryotes by mediating TopBP1 and Cdk2 dependent recruitment of Cdc45 onto replication origins. PMID:20383140

  7. Assembly of Slx4 signaling complexes behind DNA replication forks.

    Science.gov (United States)

    Balint, Attila; Kim, TaeHyung; Gallo, David; Cussiol, Jose Renato; Bastos de Oliveira, Francisco M; Yimit, Askar; Ou, Jiongwen; Nakato, Ryuichiro; Gurevich, Alexey; Shirahige, Katsuhiko; Smolka, Marcus B; Zhang, Zhaolei; Brown, Grant W

    2015-08-13

    Obstructions to replication fork progression, referred to collectively as DNA replication stress, challenge genome stability. In Saccharomyces cerevisiae, cells lacking RTT107 or SLX4 show genome instability and sensitivity to DNA replication stress and are defective in the completion of DNA replication during recovery from replication stress. We demonstrate that Slx4 is recruited to chromatin behind stressed replication forks, in a region that is spatially distinct from that occupied by the replication machinery. Slx4 complex formation is nucleated by Mec1 phosphorylation of histone H2A, which is recognized by the constitutive Slx4 binding partner Rtt107. Slx4 is essential for recruiting the Mec1 activator Dpb11 behind stressed replication forks, and Slx4 complexes are important for full activity of Mec1. We propose that Slx4 complexes promote robust checkpoint signaling by Mec1 by stably recruiting Dpb11 within a discrete domain behind the replication fork, during DNA replication stress. © 2015 The Authors.

  8. Dpb11/TopBP1 plays distinct roles in DNA replication, checkpoint response and homologous recombination

    DEFF Research Database (Denmark)

    Germann, Susanne Manuela; Østergaard, Vibe Hallundbæk; Haas, Caroline

    2011-01-01

    DPB11/TopBP1 is an essential evolutionarily conserved gene involved in initiation of DNA replication and checkpoint signaling. Here, we show that Saccharomyces cerevisiae Dpb11 forms nuclear foci that localize to sites of DNA damage in G1, S and G2 phase, a recruitment that is conserved for its...... and Tel1, and of the checkpoint mediator Rad9. In a site-directed mutagenesis screen, we identify a separation-of-function mutant, dpb11-PF, that is sensitive to DSB-inducing agents yet remains proficient for DNA replication and the S-phase checkpoint at the permissive temperature. The dpb11-PF mutant...... homologue TopBP1 in Gallus gallus. Damage-induced Dpb11 foci are distinct from Sld3 replication initiation foci. Further, Dpb11 foci are dependent on the checkpoint proteins Mec3 (9-1-1 complex) and Rad24, and require the C-terminal domain of Dpb11. Dpb11 foci are independent of the checkpoint kinases Mec1...

  9. Direct Binding to Replication Protein A (RPA)-coated Single-stranded DNA Allows Recruitment of the ATR Activator TopBP1 to Sites of DNA Damage*

    Science.gov (United States)

    Acevedo, Julyana; Yan, Shan; Michael, W. Matthew

    2016-01-01

    A critical event for the ability of cells to tolerate DNA damage and replication stress is activation of the ATR kinase. ATR activation is dependent on the BRCT (BRCA1 C terminus) repeat-containing protein TopBP1. Previous work has shown that recruitment of TopBP1 to sites of DNA damage and stalled replication forks is necessary for downstream events in ATR activation; however, the mechanism for this recruitment was not known. Here, we use protein binding assays and functional studies in Xenopus egg extracts to show that TopBP1 makes a direct interaction, via its BRCT2 domain, with RPA-coated single-stranded DNA. We identify a point mutant that abrogates this interaction and show that this mutant fails to accumulate at sites of DNA damage and that the mutant cannot activate ATR. These data thus supply a mechanism for how the critical ATR activator, TopBP1, senses DNA damage and stalled replication forks to initiate assembly of checkpoint signaling complexes. PMID:27129245

  10. Repeatability study of replicate crash tests: A signal analysis approach.

    Science.gov (United States)

    Seppi, Jeremy; Toczyski, Jacek; Crandall, Jeff R; Kerrigan, Jason

    2017-10-03

    To provide an objective basis on which to evaluate the repeatability of vehicle crash test methods, a recently developed signal analysis method was used to evaluate correlation of sensor time history data between replicate vehicle crash tests. The goal of this study was to evaluate the repeatability of rollover crash tests performed with the Dynamic Rollover Test System (DRoTS) relative to other vehicle crash test methods. Test data from DRoTS tests, deceleration rollover sled (DRS) tests, frontal crash tests, frontal offset crash tests, small overlap crash tests, small overlap impact (SOI) crash tests, and oblique crash tests were obtained from the literature and publicly available databases (the NHTSA vehicle database and the Insurance Institute for Highway Safety TechData) to examine crash test repeatability. Signal analysis of the DRoTS tests showed that force and deformation time histories had good to excellent repeatability, whereas vehicle kinematics showed only fair repeatability due to the vehicle mounting method for one pair of tests and slightly dissimilar mass properties (2.2%) in a second pair of tests. Relative to the DRS, the DRoTS tests showed very similar or higher levels of repeatability in nearly all vehicle kinematic data signals with the exception of global X' (road direction of travel) velocity and displacement due to the functionality of the DRoTS fixture. Based on the average overall scoring metric of the dominant acceleration, DRoTS was found to be as repeatable as all other crash tests analyzed. Vertical force measures showed good repeatability and were on par with frontal crash barrier forces. Dynamic deformation measures showed good to excellent repeatability as opposed to poor repeatability seen in SOI and oblique deformation measures. Using the signal analysis method as outlined in this article, the DRoTS was shown to have the same or better repeatability of crash test methods used in government regulatory and consumer evaluation test

  11. Evading the top-quark mass bound at the Fermilab Tevatron: New signals for the top quark

    International Nuclear Information System (INIS)

    Mukhopadhyaya, B.; Nandi, S.

    1991-01-01

    If an SU(2)-singlet charge-2/3 quark exists, current data allow a wide range for the parameters of the 4x4 mixing matrix in which the usual ''hard-lepton'' signal of the top quark is suppressed. For a light Higgs boson, the top quark decays predominantly via the flavor-changing Yukawa interaction, thus evading the Fermilab Tevatron bounds on its mass. For a heavier Higgs boson, flavor-changing neutral-current decays become important, giving rise to anomalous Z-pair production, testable at the upgraded Tevetron, at the CERN Large Hardon Collider, and at the Superconducting Super Collider

  12. Dpb11/TopBP1 contributes to genomicstability via homologous recombinationand checkpoint signaling

    DEFF Research Database (Denmark)

    Germann, Susanne Manuela

    for recruitment. Also, the chicken homologue TopBP1 colocalizes with RPA1 as well as Rad51 when DNA damage is induced. Previously, dpb11 mutants have been shown to be sensitive to DNA-damaging agents that cause DSBs, DNA alkylation and stalled replication forks. Interestingly, we found the point mutants dpb11-PF...

  13. Signals Involved in Regulation of Hepatitis C Virus RNA Genome Translation and Replication

    Directory of Open Access Journals (Sweden)

    Michael Niepmann

    2018-03-01

    Full Text Available Hepatitis C virus (HCV preferentially replicates in the human liver and frequently causes chronic infection, often leading to cirrhosis and liver cancer. HCV is an enveloped virus classified in the genus Hepacivirus in the family Flaviviridae and has a single-stranded RNA genome of positive orientation. The HCV RNA genome is translated and replicated in the cytoplasm. Translation is controlled by the Internal Ribosome Entry Site (IRES in the 5′ untranslated region (5′ UTR, while also downstream elements like the cis-replication element (CRE in the coding region and the 3′ UTR are involved in translation regulation. The cis-elements controlling replication of the viral RNA genome are located mainly in the 5′- and 3′-UTRs at the genome ends but also in the protein coding region, and in part these signals overlap with the signals controlling RNA translation. Many long-range RNA–RNA interactions (LRIs are predicted between different regions of the HCV RNA genome, and several such LRIs are actually involved in HCV translation and replication regulation. A number of RNA cis-elements recruit cellular RNA-binding proteins that are involved in the regulation of HCV translation and replication. In addition, the liver-specific microRNA-122 (miR-122 binds to two target sites at the 5′ end of the viral RNA genome as well as to at least three additional target sites in the coding region and the 3′ UTR. It is involved in the regulation of HCV RNA stability, translation and replication, thereby largely contributing to the hepatotropism of HCV. However, we are still far from completely understanding all interactions that regulate HCV RNA genome translation, stability, replication and encapsidation. In particular, many conclusions on the function of cis-elements in HCV replication have been obtained using full-length HCV genomes or near-full-length replicon systems. These include both genome ends, making it difficult to decide if a cis-element in

  14. Signals Involved in Regulation of Hepatitis C Virus RNA Genome Translation and Replication.

    Science.gov (United States)

    Niepmann, Michael; Shalamova, Lyudmila A; Gerresheim, Gesche K; Rossbach, Oliver

    2018-01-01

    Hepatitis C virus (HCV) preferentially replicates in the human liver and frequently causes chronic infection, often leading to cirrhosis and liver cancer. HCV is an enveloped virus classified in the genus Hepacivirus in the family Flaviviridae and has a single-stranded RNA genome of positive orientation. The HCV RNA genome is translated and replicated in the cytoplasm. Translation is controlled by the Internal Ribosome Entry Site (IRES) in the 5' untranslated region (5' UTR), while also downstream elements like the cis -replication element (CRE) in the coding region and the 3' UTR are involved in translation regulation. The cis -elements controlling replication of the viral RNA genome are located mainly in the 5'- and 3'-UTRs at the genome ends but also in the protein coding region, and in part these signals overlap with the signals controlling RNA translation. Many long-range RNA-RNA interactions (LRIs) are predicted between different regions of the HCV RNA genome, and several such LRIs are actually involved in HCV translation and replication regulation. A number of RNA cis -elements recruit cellular RNA-binding proteins that are involved in the regulation of HCV translation and replication. In addition, the liver-specific microRNA-122 (miR-122) binds to two target sites at the 5' end of the viral RNA genome as well as to at least three additional target sites in the coding region and the 3' UTR. It is involved in the regulation of HCV RNA stability, translation and replication, thereby largely contributing to the hepatotropism of HCV. However, we are still far from completely understanding all interactions that regulate HCV RNA genome translation, stability, replication and encapsidation. In particular, many conclusions on the function of cis -elements in HCV replication have been obtained using full-length HCV genomes or near-full-length replicon systems. These include both genome ends, making it difficult to decide if a cis -element in question acts on HCV

  15. Baculovirus LEF-11 nuclear localization signal is important for viral DNA replication.

    Science.gov (United States)

    Chen, Tingting; Dong, Zhanqi; Hu, Nan; Hu, Zhigang; Dong, Feifan; Jiang, Yaming; Li, Jun; Chen, Peng; Lu, Cheng; Pan, Minhui

    2017-06-15

    Baculovirus LEF-11 is a small nuclear protein that is involved in viral late gene transcription and DNA replication. However, the characteristics of its nuclear localization signal and its impact on viral DNA replication are unknown. In the present study, systemic bioinformatics analysis showed that the baculovirus LEF-11 contains monopartite and bipartite classical nuclear localization signal sequences (cNLSs), which were also detected in a few alphabaculovirus species. Localization of representative LEF-11 proteins of four baculovirus genera indicated that the nuclear localization characteristics of baculovirus LEF-11 coincided with the predicted results. Moreover, Bombyx mori nucleopolyhedrovirus (BmNPV) LEF-11 could be transported into the nucleus during viral infection in the absence of a cNLSs. Further investigations demonstrated that the NLS of BmNPV LEF-11 is important for viral DNA replication. The findings of the present study indicate that the characteristics of the baculovirus LEF-11 protein and the NLS is essential to virus DNA replication and nuclear transport mechanisms. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Replication stress, DNA damage signalling, and cytomegalovirus infection in human medulloblastomas

    DEFF Research Database (Denmark)

    Bartek, Jiri; Fornara, Olesja; Merchut-Maya, Joanna Maria

    2017-01-01

    suppressor activation, across our medulloblastoma cohort. Most tumours showed high proliferation (Ki67 marker), variable oxidative DNA damage (8-oxoguanine lesions) and formation of 53BP1 nuclear 'bodies', the latter indicating (along with ATR-Chk1 signalling) endogenous replication stress. The bulk...... cell replication stress and DNA repair. Collectively, the scenario we report here likely fuels genomic instability and evolution of medulloblastoma resistance to standard-of-care genotoxic treatments....... eight established immunohistochemical markers to assess the status of the DDR machinery, we found pronounced endogenous DNA damage signalling (γH2AX marker) and robust constitutive activation of both the ATM-Chk2 and ATR-Chk1 DNA damage checkpoint kinase cascades, yet unexpectedly modest p53 tumour...

  17. Persistent Amplification of DNA Damage Signal Involved in Replicative Senescence of Normal Human Diploid Fibroblasts

    Directory of Open Access Journals (Sweden)

    Masatoshi Suzuki

    2012-01-01

    Full Text Available Foci of phosphorylated histone H2AX and ATM are the surrogate markers of DNA double strand breaks. We previously reported that the residual foci increased their size after irradiation, which amplifies DNA damage signals. Here, we addressed whether amplification of DNA damage signal is involved in replicative senescence of normal human diploid fibroblasts. Large phosphorylated H2AX foci (>1.5 μm diameter were specifically detected in presenescent cells. The frequency of cells with large foci was well correlated with that of cells positive for senescence-associated β-galactosidase staining. Hypoxic cell culture condition extended replicative life span of normal human fibroblast, and we found that the formation of large foci delayed in those cells. Our immuno-FISH analysis revealed that large foci partially localized at telomeres in senescent cells. Importantly, large foci of phosphorylated H2AX were always colocalized with phosphorylated ATM foci. Furthermore, Ser15-phosphorylated p53 showed colocalization with the large foci. Since the treatment of senescent cells with phosphoinositide 3-kinase inhibitor, wortmannin, suppressed p53 phosphorylation, it is suggested that amplification of DNA damage signaling sustains persistent activation of ATM-p53 pathway, which is essential for replicative senescence.

  18. Optimizing the top quark signal to background ratio at hadron colliders

    International Nuclear Information System (INIS)

    Field, R.D.; Kanev, Y.; Tayebnejad, M.

    1996-01-01

    We investigate the event signature of the ell νb bar bq bar q decay mode of top-pair production in proton-antiproton collisions at 1.8 TeV. Neural networks and Fisher discriminates are used in conjunction with modified Fox-Wolfram open-quotes shapeclose quotes variables to help distinguish the top-pair signal from the W + jets and b bar b+jets background. Instead of requiring at least four jets in the event, we find that it is faster and better to simply cut on the number of calorimeter cells with transverse energy greater than some minimum. By combining these cell cuts with the event shape information, we are able to obtain a signal to background ratio of around 9 while keeping 30% of the signal. This corresponds to a signal to background enhancement of around 370

  19. Top down and bottom up selection drives variations in frequency and form of a visual signal

    OpenAIRE

    Yeh, Chien-Wei; Blamires, Sean J.; Liao, Chen-Pan; Tso, I.-Min

    2015-01-01

    The frequency and form of visual signals can be shaped by selection from predators, prey or both. When a signal simultaneously attracts predators and prey, selection may favour a strategy that minimizes risks while attracting prey. Accordingly, varying the frequency and form of the silken decorations added to their web may be a way that Argiope spiders minimize predation while attracting prey. Nonetheless, the role of extraneous factors renders the influences of top down and bottom up selecti...

  20. Are Luxury Brand Labels and "Green" Labels Costly Signals of Social Status? An Extended Replication.

    Science.gov (United States)

    Berger, Joël

    2017-01-01

    Costly signaling theory provides an explanation for why humans are willing to a pay a premium for conspicuous products such as luxury brand-labeled clothing or conspicuous environmentally friendly cars. According to the theory, the extra cost of such products is a signal of social status and wealth and leads to advantages in social interactions for the signaler. A previous study found positive evidence for the case of luxury brand labels. However, an issue of this study was that some of the experiments were not conducted in a perfectly double-blind manner. I resolved this by replicating variations of the original design in a double-blind procedure. Additionally, besides the luxury label condition, I introduced a "green" label condition. Thus, the hypothesis that signaling theory is able to explain pro-environmental behavior was tested for the first time in a natural field setting. Further, I conducted experiments in both average and below-average socioeconomic neighborhoods, where, according to signaling theory, the effects of luxury signals should be even stronger. In contrast to the original study, I did not find positive effects of the luxury brand label in any of the five experiments. Nor did I find evidence for a green-signaling effect. Moreover, in poor neighborhoods a negative tendency of the luxury label actually became evident. This suggests that a signaling theory explanation of costly labels must take into account the characteristics of the observers, e.g. their social status.

  1. Are Luxury Brand Labels and "Green" Labels Costly Signals of Social Status? An Extended Replication.

    Directory of Open Access Journals (Sweden)

    Joël Berger

    Full Text Available Costly signaling theory provides an explanation for why humans are willing to a pay a premium for conspicuous products such as luxury brand-labeled clothing or conspicuous environmentally friendly cars. According to the theory, the extra cost of such products is a signal of social status and wealth and leads to advantages in social interactions for the signaler. A previous study found positive evidence for the case of luxury brand labels. However, an issue of this study was that some of the experiments were not conducted in a perfectly double-blind manner. I resolved this by replicating variations of the original design in a double-blind procedure. Additionally, besides the luxury label condition, I introduced a "green" label condition. Thus, the hypothesis that signaling theory is able to explain pro-environmental behavior was tested for the first time in a natural field setting. Further, I conducted experiments in both average and below-average socioeconomic neighborhoods, where, according to signaling theory, the effects of luxury signals should be even stronger. In contrast to the original study, I did not find positive effects of the luxury brand label in any of the five experiments. Nor did I find evidence for a green-signaling effect. Moreover, in poor neighborhoods a negative tendency of the luxury label actually became evident. This suggests that a signaling theory explanation of costly labels must take into account the characteristics of the observers, e.g. their social status.

  2. Suppression of Rac1 Signaling by Influenza A Virus NS1 Facilitates Viral Replication

    Science.gov (United States)

    Jiang, Wei; Sheng, Chunjie; Gu, Xiuling; Liu, Dong; Yao, Chen; Gao, Shijuan; Chen, Shuai; Huang, Yinghui; Huang, Wenlin; Fang, Min

    2016-01-01

    Influenza A virus (IAV) is a major human pathogen with the potential to become pandemic. IAV contains only eight RNA segments; thus, the virus must fully exploit the host cellular machinery to facilitate its own replication. In an effort to comprehensively characterize the host machinery taken over by IAV in mammalian cells, we generated stable A549 cell lines with over-expression of the viral non-structural protein (NS1) to investigate the potential host factors that might be modulated by the NS1 protein. We found that the viral NS1 protein directly interacted with cellular Rac1 and facilitated viral replication. Further research revealed that NS1 down-regulated Rac1 activity via post-translational modifications. Therefore, our results demonstrated that IAV blocked Rac1-mediated host cell signal transduction through the NS1 protein to facilitate its own replication. Our findings provide a novel insight into the mechanism of IAV replication and indicate new avenues for the development of potential therapeutic targets. PMID:27869202

  3. Utilizing ras signaling pathway to direct selective replication of herpes simplex virus-1.

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    Weihong Pan

    Full Text Available Re-engineering the tropism of viruses is an attractive translational strategy for targeting cancer cells. The Ras signal transduction pathway is a central hub for a variety of pro-oncogenic events with a fundamental role in normal and neoplastic physiology. In this work we were interested in linking Ras activation to HSV-1 replication in a direct manner in order to generate a novel oncolytic herpes virus which can target cancer cells. To establish such link, we developed a mutant HSV-1 in which the expression of ICP4 (infected cell protein-4, a viral protein necessary for replication is controlled by activation of ELK, a transcription factor down-stream of the Ras pathway and mainly activated by ERK (extracellular signal-regulated kinase, an important Ras effector pathway. This mutant HSV-1 was named as Signal-Smart 1 (SS1. A series of prostate cells were infected with the SS1 virus. Cells with elevated levels of ELK activation were preferentially infected by the SS1 virus, as demonstrated by increased levels of viral progeny, herpetic glycoprotein C and overall SS1 viral protein production. Upon exposure to SS1, the proliferation, invasiveness and colony formation capabilities of prostate cancer cells with increased ELK activation were significantly decreased (p<0.05, while the rate of apoptosis/necrosis in these cells was increased. Additionally, high Ras signaling cells infected with SS1 showed a prominent arrest in the G1 phase of the cell cycle as compared to cells exposed to parental HSV-1. The results of this study reveal the potential for re-modeling the host-herpes interaction to specifically interfere with the life of cancer cells with increased Ras signaling. SS1 also serves as a "prototype" for development of a family of signal-smart viruses which can target cancer cells on the basis of their signaling portfolio.

  4. Triple top signal as a probe of charged Higgs in a 2HDM

    Science.gov (United States)

    Patrick, Riley; Sharma, Pankaj; Williams, Anthony G.

    2018-05-01

    Within the framework of the type-II Two Higgs Doublet Model (2HDM-II) we study the production of three top quarks at the Large Hadron Collider (LHC). In the Standard Model the production cross section of three tops is low (≈3 fb), while it is expected to be significant in the 2HDM-II for reasonable choices of the parameters. We study the production of a charged Higgs in association with a top quark, followed by the decays H± →W± A and A → t t bar . We undertake a full detector simulation of the signal, and use simple conservative cuts, focussing on the final states that contain three or more leptons, and exactly one same sign di-lepton pair. Finally, we present the exclusion bounds dependent on charged Higgs and pseudoscalar Higgs masses expected in the near future at the 14 TeV LHC.

  5. A SELEX-screened aptamer of human hepatitis B virus RNA encapsidation signal suppresses viral replication.

    Directory of Open Access Journals (Sweden)

    Hui Feng

    Full Text Available BACKGROUND: The specific interaction between hepatitis B virus (HBV polymerase (P protein and the ε RNA stem-loop on pregenomic (pg RNA is crucial for viral replication. It triggers both pgRNA packaging and reverse transcription and thus represents an attractive antiviral target. RNA decoys mimicking ε in P protein binding but not supporting replication might represent novel HBV inhibitors. However, because generation of recombinant enzymatically active HBV polymerase is notoriously difficult, such decoys have as yet not been identified. METHODOLOGY/PRINCIPAL FINDINGS: Here we used a SELEX approach, based on a new in vitro reconstitution system exploiting a recombinant truncated HBV P protein (miniP, to identify potential ε decoys in two large ε RNA pools with randomized upper stem. Selection of strongly P protein binding RNAs correlated with an unexpected strong enrichment of A residues. Two aptamers, S6 and S9, displayed particularly high affinity and specificity for miniP in vitro, yet did not support viral replication when part of a complete HBV genome. Introducing S9 RNA into transiently HBV producing HepG2 cells strongly suppressed pgRNA packaging and DNA synthesis, indicating the S9 RNA can indeed act as an ε decoy that competitively inhibits P protein binding to the authentic ε signal on pgRNA. CONCLUSIONS/SIGNIFICANCE: This study demonstrates the first successful identification of human HBV ε aptamers by an in vitro SELEX approach. Effective suppression of HBV replication by the S9 aptamer provides proof-of-principle for the ability of ε decoy RNAs to interfere with viral P-ε complex formation and suggests that S9-like RNAs may further be developed into useful therapeutics against chronic hepatitis B.

  6. Enhancing the top-quark signal at Fermilab Tevatron using neural nets

    International Nuclear Information System (INIS)

    Ametller, L.; Garrido, L.; Talavera, P.

    1994-01-01

    We show, in agreement with previous studies, that neural nets can be useful for top-quark analysis at the Fermilab Tevatron. The main features of t bar t and background events in a mixed sample are projected on a single output, which controls the efficiency, purity, and statistical significance of the t bar t signal. We consider a feed-forward multilayer neural net for the CDF reported top-quark mass, using six kinematical variables as inputs. Our main results are based on the exhaustive comparison of the neural net performances with those obtainable from the standard experimental analysis, by imposing different sets of linear cuts over the same variables, showing how the neural net approach improves the standard analysis results

  7. Replication stress and oxidative damage contribute to aberrant constitutive activation of DNA damage signalling in human gliomas

    DEFF Research Database (Denmark)

    Bartkova, J; Hamerlik, P; Stockhausen, Marie

    2010-01-01

    brain and grade II astrocytomas, despite the degree of DDR activation was higher in grade II tumors. Markers indicative of ongoing DNA replication stress (Chk1 activation, Rad17 phosphorylation, replication protein A foci and single-stranded DNA) were present in GBM cells under high- or low...... and indicate that replication stress, rather than oxidative stress, fuels the DNA damage signalling in early stages of astrocytoma development.......Malignant gliomas, the deadliest of brain neoplasms, show rampant genetic instability and resistance to genotoxic therapies, implicating potentially aberrant DNA damage response (DDR) in glioma pathogenesis and treatment failure. Here, we report on gross, aberrant constitutive activation of DNA...

  8. The cis-acting replication signal at the 3' end of Flock House virus RNA2 is RNA3-dependent

    International Nuclear Information System (INIS)

    Albarino, Cesar G.; Eckerle, Lance D.; Ball, L. Andrew

    2003-01-01

    The nodavirus Flock House virus has a bipartite positive-sense RNA genome consisting of RNAs 1 and 2, which encode the viral RNA-dependent RNA polymerase (RdRp) and capsid protein precursor, respectively. The RdRp catalyzes replication of both genome segments and produces from RNA1 a subgenomic RNA (RNA3) that transactivates RNA2 replication. Here, we replaced internal sequences of RNAs 1 and 2 with a common heterologous core and were thereby able to test the RNA termini for compatibility in supporting the replication of chimeric RNAs. The results showed that the 3' 50 nt of RNA2 contained an RNA3-dependent cis-acting replication signal. Since covalent RNA dimers can direct the synthesis of monomeric replication products, the RdRp can evidently respond to cis-acting replication signals located internally. Accordingly, RNA templates containing the 3' termini of both RNAs 1 and 2 in tandem generated different replication products depending on the presence or absence of RNA3

  9. Top down and bottom up selection drives variations in frequency and form of a visual signal.

    Science.gov (United States)

    Yeh, Chien-Wei; Blamires, Sean J; Liao, Chen-Pan; Tso, I-Min

    2015-03-30

    The frequency and form of visual signals can be shaped by selection from predators, prey or both. When a signal simultaneously attracts predators and prey selection may favour a strategy that minimizes risks while attracting prey. Accordingly, varying the frequency and form of the silken decorations added to their web may be a way that Argiope spiders minimize predation while attracting prey. Nonetheless, the role of extraneous factors renders the influences of top down and bottom up selection on decoration frequency and form variation difficult to discern. Here we used dummy spiders and decorations to simulate four possible strategies that the spider Argiope aemula may choose and measured the prey and predator attraction consequences for each in the field. The strategy of decorating at a high frequency with a variable form attracted the most prey, while that of decorating at a high frequency with a fixed form attracted the most predators. These results suggest that mitigating the cost of attracting predators while maintaining prey attraction drives the use of variation in decoration form by many Argiope spp. when decorating frequently. Our study highlights the importance of considering top-down and bottom up selection pressure when devising evolutionary ecology experiments.

  10. Top-Down Control of Visual Alpha Oscillations: Sources of Control Signals and Their Mechanisms of Action

    Science.gov (United States)

    Wang, Chao; Rajagovindan, Rajasimhan; Han, Sahng-Min; Ding, Mingzhou

    2016-01-01

    Alpha oscillations (8–12 Hz) are thought to inversely correlate with cortical excitability. Goal-oriented modulation of alpha has been studied extensively. In visual spatial attention, alpha over the region of visual cortex corresponding to the attended location decreases, signifying increased excitability to facilitate the processing of impending stimuli. In contrast, in retention of verbal working memory, alpha over visual cortex increases, signifying decreased excitability to gate out stimulus input to protect the information held online from sensory interference. According to the prevailing model, this goal-oriented biasing of sensory cortex is effected by top-down control signals from frontal and parietal cortices. The present study tests and substantiates this hypothesis by (a) identifying the signals that mediate the top-down biasing influence, (b) examining whether the cortical areas issuing these signals are task-specific or task-independent, and (c) establishing the possible mechanism of the biasing action. High-density human EEG data were recorded in two experimental paradigms: a trial-by-trial cued visual spatial attention task and a modified Sternberg working memory task. Applying Granger causality to both sensor-level and source-level data we report the following findings. In covert visual spatial attention, the regions exerting top-down control over visual activity are lateralized to the right hemisphere, with the dipoles located at the right frontal eye field (FEF) and the right inferior frontal gyrus (IFG) being the main sources of top-down influences. During retention of verbal working memory, the regions exerting top-down control over visual activity are lateralized to the left hemisphere, with the dipoles located at the left middle frontal gyrus (MFG) being the main source of top-down influences. In both experiments, top-down influences are mediated by alpha oscillations, and the biasing effect is likely achieved via an inhibition

  11. Common RNA replication signals exist among group 2 coronaviruses: evidence for in vivo recombination between animal and human coronavius molecules

    International Nuclear Information System (INIS)

    Wu, H.-Y.; Guy, James S.; Yoo, Dongwan; Vlasak, Reinhard; Urbach, Ena; Brian, David A.

    2003-01-01

    5' and 3' UTR sequences on the coronavirus genome are known to carry cis-acting elements for DI RNA replication and presumably also virus genome replication. 5' UTR-adjacent coding sequences are also thought to harbor cis-acting elements. Here we have determined the 5' UTR and adjacent 289-nt sequences, and 3' UTR sequences, for six group 2 coronaviruses and have compared them to each other and to three previously reported group 2 members. Extensive regions of highly similar UTR sequences were found but small regions of divergence were also found indicating group 2 coronaviruses could be subdivided into those that are bovine coronavirus (BCoV)-like (BCoV, human respiratory coronavirus-OC43, human enteric coronavirus, porcine hemagglutinating encephalomyelitis virus, and equine coronavirus) and those that are murine hepatitis virus (MHV)-like (A59, 2, and JHM strains of MHV, puffinosis virus, and rat sialodacryoadenitis virus). The 3' UTRs of BCoV and MHV have been previously shown to be interchangeable. Here, a reporter-containing BCoV DI RNA was shown to be replicated by all five BCoV-like helper viruses and by MHV-H2 (a human cell-adapted MHV strain), a representative of the MHV-like subgroup, demonstrating group 2 common 5' and 3' replication signaling elements. BCoV DI RNA, furthermore, acquired the leader of HCoV-OC43 by leader switching, demonstrating for the first time in vivo recombination between animal and human coronavirus molecules. These results indicate that common replication signaling elements exist among group 2 coronaviruses despite a two-cluster pattern within the group and imply there could exist a high potential for recombination among group members

  12. ASCIZ/ATMIN is dispensable for ATM signaling in response to replication stress.

    Science.gov (United States)

    Liu, Rui; King, Ashleigh; Hoch, Nicolas C; Chang, Catherine; Kelly, Gemma L; Deans, Andrew J; Heierhorst, Jörg

    2017-09-01

    The ATM kinase plays critical roles in the response to DNA double-strand breaks, and can also be activated by prolonged DNA replication blocks. It has recently been proposed that replication stress-dependent ATM activation is mediated by ASCIZ (also known as ATMIN, ZNF822), an essential developmental transcription factor. In contrast, we show here that ATM activation, and phosphorylation of its substrates KAP1, p53 and H2AX in response to the replication blocking agent aphidicolin was unaffected in both immortalized and primary ASCIZ/ATMIN-deficient murine embryonic fibroblasts compared to control cells. Similar results were also obtained in human ASCIZ/ATMIN-deleted lymphoma cells. The results demonstrate that ASCIZ/ATMIN is dispensable for ATM activation, and contradict the previously reported dependence of ATM on ASCIZ/ATMIN. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  13. Evidence supporting a role for TopBP1 and Brd4 in the initiation but not continuation of human papillomavirus 16 E1/E2-mediated DNA replication.

    Science.gov (United States)

    Gauson, Elaine J; Donaldson, Mary M; Dornan, Edward S; Wang, Xu; Bristol, Molly; Bodily, Jason M; Morgan, Iain M

    2015-05-01

    To replicate the double-stranded human papillomavirus 16 (HPV16) DNA genome, viral proteins E1 and E2 associate with the viral origin of replication, and E2 can also regulate transcription from adjacent promoters. E2 interacts with host proteins in order to regulate both transcription and replication; TopBP1 and Brd4 are cellular proteins that interact with HPV16 E2. Previous work with E2 mutants demonstrated the Brd4 requirement for the transactivation properties of E2, while TopBP1 is required for DNA replication induced by E2 from the viral origin of replication in association with E1. More-recent studies have also implicated Brd4 in the regulation of DNA replication by E2 and E1. Here, we demonstrate that both TopBP1 and Brd4 are present at the viral origin of replication and that interaction with E2 is required for optimal initiation of DNA replication. Both cellular proteins are present in E1-E2-containing nuclear foci, and the viral origin of replication is required for the efficient formation of these foci. Short hairpin RNA (shRNA) against either TopBP1 or Brd4 destroys the E1-E2 nuclear bodies but has no effect on E1-E2-mediated levels of DNA replication. An E2 mutation in the context of the complete HPV16 genome that compromises Brd4 interaction fails to efficiently establish episomes in primary human keratinocytes. Overall, the results suggest that interactions between TopBP1 and E2 and between Brd4 and E2 are required to correctly initiate DNA replication but are not required for continuing DNA replication, which may be mediated by alternative processes such as rolling circle amplification and/or homologous recombination. Human papillomavirus 16 (HPV16) is causative in many human cancers, including cervical and head and neck cancers, and is responsible for the annual deaths of hundreds of thousands of people worldwide. The current vaccine will save lives in future generations, but antivirals targeting HPV16 are required for the alleviation of disease

  14. Are Luxury Brand Labels and “Green” Labels Costly Signals of Social Status? An Extended Replication

    Science.gov (United States)

    2017-01-01

    Costly signaling theory provides an explanation for why humans are willing to a pay a premium for conspicuous products such as luxury brand-labeled clothing or conspicuous environmentally friendly cars. According to the theory, the extra cost of such products is a signal of social status and wealth and leads to advantages in social interactions for the signaler. A previous study found positive evidence for the case of luxury brand labels. However, an issue of this study was that some of the experiments were not conducted in a perfectly double-blind manner. I resolved this by replicating variations of the original design in a double-blind procedure. Additionally, besides the luxury label condition, I introduced a “green” label condition. Thus, the hypothesis that signaling theory is able to explain pro-environmental behavior was tested for the first time in a natural field setting. Further, I conducted experiments in both average and below-average socioeconomic neighborhoods, where, according to signaling theory, the effects of luxury signals should be even stronger. In contrast to the original study, I did not find positive effects of the luxury brand label in any of the five experiments. Nor did I find evidence for a green-signaling effect. Moreover, in poor neighborhoods a negative tendency of the luxury label actually became evident. This suggests that a signaling theory explanation of costly labels must take into account the characteristics of the observers, e.g. their social status. PMID:28170399

  15. Shock, stress or signal? Implications of freshwater flows for a top-level estuarine predator.

    Directory of Open Access Journals (Sweden)

    Matthew D Taylor

    Full Text Available Physicochemical variability in estuarine systems plays an important role in estuarine processes and in the lifecycles of estuarine organisms. In particular, seasonality of freshwater inflow to estuaries may be important in various aspects of fish lifecycles. This study aimed to further understand these relationships by studying the movements of a top-level estuarine predator in response to physicochemical variability in a large, temperate south-east Australian estuary (Shoalhaven River. Mulloway (Argyrosomus japonicus, 47-89 cm total length were surgically implanted with acoustic transmitters, and their movements and migrations monitored over two years via fixed-position VR2W acoustic receivers configured in a linear array along the length of the estuary. The study period included a high degree of abiotic variability, with multiple pulses (exponentially high flows over a short period of time in fresh water to the estuary, as well as broader seasonal variation in flow, temperature and conductivity. The relative deviation of fish from their modal location in the estuary was affected primarily by changes in conductivity, and smaller fish (n = 4 tended to deviate much further downstream from their modal position in the estuary than larger fish (n = 8. High-flow events which coincided with warmer temperatures tended to drive mature fish down the estuary and potentially provided a spawning signal to stimulate aggregation of adults near the estuary mouth; however, this relationship requires further investigation. These findings indicate that pulse and press effects of freshwater inflow and associated physicochemical variability play a role in the movements of mulloway, and that seasonality of large freshwater flows may be important in spawning. The possible implications of river regulation and the extraction of freshwater for consumptive uses on estuarine fishes are discussed.

  16. Replication stress and oxidative damage contribute to aberrant constitutive activation of DNA damage signalling in human gliomas

    DEFF Research Database (Denmark)

    Bartkova, J; Hamerlik, P; Stockhausen, Marie

    2010-01-01

    damage signalling in low- and high-grade human gliomas, and analyze the sources of such endogenous genotoxic stress. Based on analyses of human glioblastoma multiforme (GBM) cell lines, normal astrocytes and clinical specimens from grade II astrocytomas (n=41) and grade IV GBM (n=60), we conclude...... that the DDR machinery is constitutively activated in gliomas, as documented by phosphorylated histone H2AX (gammaH2AX), activation of the ATM-Chk2-p53 pathway, 53BP1 foci and other markers. Oxidative DNA damage (8-oxoguanine) was high in some GBM cell lines and many GBM tumors, while it was low in normal...... brain and grade II astrocytomas, despite the degree of DDR activation was higher in grade II tumors. Markers indicative of ongoing DNA replication stress (Chk1 activation, Rad17 phosphorylation, replication protein A foci and single-stranded DNA) were present in GBM cells under high- or low...

  17. CD200R1 supports HSV-1 viral replication and licenses pro-inflammatory signaling functions of TLR2.

    Directory of Open Access Journals (Sweden)

    Roy J Soberman

    Full Text Available The CD200R1:CD200 axis is traditionally considered to limit tissue inflammation by down-regulating pro-inflammatory signaling in myeloid cells bearing the receptor. We generated CD200R1(-/- mice and employed them to explore both the role of CD200R1 in regulating macrophage signaling via TLR2 as well as the host response to an in vivo, TLR2-dependent model, herpes simplex virus 1 (HSV-1 infection. CD200R1(-/- peritoneal macrophages demonstrated a 70-75% decrease in the generation of IL-6 and CCL5 (Rantes in response to the TLR2 agonist Pam(2CSK(4 and to HSV-1. CD200R1(-/- macrophages could neither up-regulate the expression of TLR2, nor assemble a functional inflammasome in response to HSV-1. CD200R1(-/- mice were protected from HSV-1 infection and exhibited dysfunctional TLR2 signaling. Finally, both CD200R1(-/- mice and CD200R1(-/- fibroblasts and macrophages showed a markedly reduced ability to support HSV-1 replication. In summary, our data demonstrate an unanticipated and novel requirement for CD200R1 in "licensing" pro-inflammatory functions of TLR2 and in limiting viral replication that are supported by ex vivo and in vivo evidence.

  18. Top-down design and verification methodology for analog mixed-signal integrated circuits

    NARCIS (Netherlands)

    Beviz, P.

    2016-01-01

    The current report contains the introduction of a novel Top-Down Design and Verification methodology for AMS integrated circuits. With the introduction of new design and verification flow, more reliable and efficient development of AMS ICs is possible. The assignment incorporated the research on the

  19. Flat-top pulse generation by the optical Fourier transform technique for ultrahigh speed signal processing

    DEFF Research Database (Denmark)

    Palushani, Evarist; Oxenløwe, Leif Katsuo; Galili, Michael

    2009-01-01

    This paper reports on the generation of 1.6-ps fullwidth at half-maximum flat-top pulses by the optical Fourier transform technique, and the utilization of these pulses in a 320-Gb/s demultiplexing experiment. It is demonstrated how a narrow pulse having a 15-nm wide third-order super-Gaussian sp......This paper reports on the generation of 1.6-ps fullwidth at half-maximum flat-top pulses by the optical Fourier transform technique, and the utilization of these pulses in a 320-Gb/s demultiplexing experiment. It is demonstrated how a narrow pulse having a 15-nm wide third-order super...

  20. Higgs and supersymmetric particle signals at the infrared fixed point of the top quark mass

    International Nuclear Information System (INIS)

    Carena, M.; Wagner, C.E.M.

    1995-01-01

    We study the properties of the Higgs and supersymmetric particle spectrum, associated with the infrared fixed point solution of the top quark mass in the Minimal Supersymmetric Standard Model. We concentrate on the possible detection of these particles, analysing the deviations from the Standard Model predictions for the leptonic and hadronic variables measured at LEP and for the b→sγ decay rate. We consider the low and moderate tan β regime, imposing the constraints derived from a proper radiative SU(2) L xU(1) Y symmetry breaking, and we study both the cases of universal and non-universal soft supersymmetry-breaking parameters at high energies. In the first case, for any given value of the top quark mass, the Higgs and supersymmetric particle spectrum is completely determined as a function of only two soft supersymmetry-breaking parameters, implying very definite experimental signatures. In the case of non-universal mass parameters at M GUT , instead, the strong correlations between the sparticle masses are relaxed, allowing a richer structure for the precision data variables. As a general feature, whenever a significant deviation from the Standard Model value of the precision data parameters is predicted, a light sparticle, which should be visible at LEP2, appears in the model. (orig.)

  1. Reliability-Weighted Integration of Audiovisual Signals Can Be Modulated by Top-down Attention

    Science.gov (United States)

    Noppeney, Uta

    2018-01-01

    Abstract Behaviorally, it is well established that human observers integrate signals near-optimally weighted in proportion to their reliabilities as predicted by maximum likelihood estimation. Yet, despite abundant behavioral evidence, it is unclear how the human brain accomplishes this feat. In a spatial ventriloquist paradigm, participants were presented with auditory, visual, and audiovisual signals and reported the location of the auditory or the visual signal. Combining psychophysics, multivariate functional MRI (fMRI) decoding, and models of maximum likelihood estimation (MLE), we characterized the computational operations underlying audiovisual integration at distinct cortical levels. We estimated observers’ behavioral weights by fitting psychometric functions to participants’ localization responses. Likewise, we estimated the neural weights by fitting neurometric functions to spatial locations decoded from regional fMRI activation patterns. Our results demonstrate that low-level auditory and visual areas encode predominantly the spatial location of the signal component of a region’s preferred auditory (or visual) modality. By contrast, intraparietal sulcus forms spatial representations by integrating auditory and visual signals weighted by their reliabilities. Critically, the neural and behavioral weights and the variance of the spatial representations depended not only on the sensory reliabilities as predicted by the MLE model but also on participants’ modality-specific attention and report (i.e., visual vs. auditory). These results suggest that audiovisual integration is not exclusively determined by bottom-up sensory reliabilities. Instead, modality-specific attention and report can flexibly modulate how intraparietal sulcus integrates sensory signals into spatial representations to guide behavioral responses (e.g., localization and orienting). PMID:29527567

  2. Intracellular expression of IRF9 Stat fusion protein overcomes the defective Jak-Stat signaling and inhibits HCV RNA replication

    Directory of Open Access Journals (Sweden)

    Balart Luis A

    2010-10-01

    Full Text Available Abstract Interferon alpha (IFN-α binds to a cell surface receptor that activates the Jak-Stat signaling pathway. A critical component of this pathway is the translocation of interferon stimulated gene factor 3 (a complex of three proteins Stat1, Stat2 and IRF9 to the nucleus to activate antiviral genes. A stable sub-genomic replicon cell line resistant to IFN-α was developed in which the nuclear translocation of Stat1 and Stat2 proteins was prevented due to the lack of phosphorylation; whereas the nuclear translocation of IRF9 protein was not affected. In this study, we sought to overcome defective Jak-Stat signaling and to induce an antiviral state in the IFN-α resistant replicon cell line by developing a chimera IRF9 protein fused with the trans activating domain (TAD of either a Stat1 (IRF9-S1C or Stat2 (IRF9-S2C protein. We show here that intracellular expression of fusion proteins using the plasmid constructs of either IRF9-S1C or IRF9-S2C, in the IFN-α resistant cells, resulted in an increase in Interferon Stimulated Response Element (ISRE luciferase promoter activity and significantly induced HLA-1 surface expression. Moreover, we show that transient transfection of IRF9-S1C or IRF9-S2C plasmid constructs into IFN-α resistant replicon cells containing sub-genomic HCV1b and HCV2a viruses resulted in an inhibition of viral replication and viral protein expression independent of IFN-α treatment. The results of this study indicate that the recombinant fusion proteins of IRF9-S1C, IRF9-S2C alone, or in combination, have potent antiviral properties against the HCV in an IFN-α resistant cell line with a defective Jak-Stat signaling.

  3. Cyclosporin A Inhibits Rotavirus Replication and Restores Interferon-Beta Signaling Pathway In Vitro and In Vivo

    Science.gov (United States)

    He, Haiyang; Wu, Yuzhang

    2013-01-01

    Rotavirus (RV) is the most common cause of severe diarrhea among infants and young children. Currently, there is no specific drug available against rotavirus, largely due to the lack of an ideal target molecule which has hampered drug development. Our previous studies have revealed that cyclosporin A (CsA) might be potentially useful as an anti-RV drug. We therefore used both cellular and mouse models to study the immunological safety and effectiveness of CsA as an anti-RV drug. We found that CsA treatment of HT-29 cells before, during, and after viral infection efficiently inhibited Wa strain RV replication and restored IFN-β expression in a HT-29 cell line model. Exploring the underlying mechanisms showed that CsA promoted Interferon Regulatory Factor-5 (IRF-5) expression (a key positive regulator of the type I IFN signaling pathway), but not IRF-1, IRF-3, or IRF-7. Additionally, CsA inhibited SOCS-1 expression (the key negative regulator of IFN-α/β), but not SOCS-2 or SOCS-3. The antiviral effect of CsA was confirmed in an RV-infected neonatal mouse model by evaluation of antigen clearance and assessment of changes in intestinal tissue pathology. Also, no differences in T cell frequency or proliferation between the CsA- and vehicle-treated groups were observed. Thus, both our in vitro and in vivo findings suggest that CsA, through modulating the expression of key regulators in IFN signaling pathway, promote type I IFN-based intracellular innate immunity in RV host cells. These findings suggest that CsA may be a useful candidate to develop a new anti-RV strategy, although further evaluation and characterization of CsA on RV-induced diarrhea are warranted. PMID:23990993

  4. Inhibition of tobacco mosaic virus replication in lateral roots is dependent on an activated meristem-derived signal.

    Science.gov (United States)

    Valentine, T A; Roberts, I M; Oparka, K J

    2002-05-01

    Viral invasion of the root system of Nicotiana benthamiana was studied noninvasively with a tobacco mosaic virus (TMV) vector expressing the green-fluorescent protein (GFP). Lateral root primordia, which developed from the pericycle of primary roots, became heavily infected as they emerged from the root cortex. However, following emergence, a progressive wave of viral inhibition occurred that originated in the lateral-root meristem and progressed towards its base. Excision of source and sink tissues suggested that the inhibition of virus replication was brought about by the basipetal movement of a root meristem signal. When infected plants were inoculated with tobacco rattle virus (TRV) expressing the red-fluorescent protein, DsRed, TRV entered the lateral roots and suppressed the host response, leading to a reestablishment of TMV infection in lateral roots. By infecting GFP-expressing transgenic plants with TMV carrying the complementary GFP sequence it was possible to silence the host GFP, leading to the complete loss of fluorescence in lateral roots. The data suggest that viral inhibition in lateral roots occurs by a gene-silencing-like mechanism that is dependent on the activation of a lateral-root meristem.

  5. Forsythoside A Inhibits BVDV Replication via TRAF2-Dependent CD28-4-1BB Signaling in Bovine PBMCs.

    Directory of Open Access Journals (Sweden)

    Quan-Jiang Song

    Full Text Available Bovine viral diarrhea virus (BVDV, the causative agent of bovine viral diarrhea/mucosal disease (BVD/MD, is an important pathogen of cattle and other wild animals throughout the world. BVDV infection typically leads to an impaired immune response in cattle. In the present study, we investigated the effect of Forsythoside A (FTA on BVDV infection of bovine peripheral blood mononuclear cells (PBMCs. We found that Forsythoside A could not only promote proliferation of PBMCs and T cells activation but also inhibit the replication of BVDV as well as apoptosis induced by BVDV. FTA treatment could counteract the BVDV-induced overproduction of IFN-γ to maintain the immune homeostasis in bovine PBMCs. At same time, FTA can enhance the secretion of IL-2. What's more, BVDV promotes the expression of CD28, 4-1BB and TRAF-2, which can be modulated by FTA. Our data suggest that FTA protects PBMCs from BVDV infection possibly via TRAF2-dependent CD28-4-1BB signaling, which may activate PBMCs in response to BVDV infection. Therefore, this aids in the development of an effective adjuvant for vaccines against BVDV and other specific FTA-based therapies for preventing BVDV infection.

  6. Forsythoside A Inhibits BVDV Replication via TRAF2-Dependent CD28–4-1BB Signaling in Bovine PBMCs

    Science.gov (United States)

    Song, Quan-Jiang; Weng, Xiao-Gang; Cai, Dong-Jie; Zhang, Wang; Wang, Jiu-Feng

    2016-01-01

    Bovine viral diarrhea virus (BVDV), the causative agent of bovine viral diarrhea/mucosal disease (BVD/MD), is an important pathogen of cattle and other wild animals throughout the world. BVDV infection typically leads to an impaired immune response in cattle. In the present study, we investigated the effect of Forsythoside A (FTA) on BVDV infection of bovine peripheral blood mononuclear cells (PBMCs). We found that Forsythoside A could not only promote proliferation of PBMCs and T cells activation but also inhibit the replication of BVDV as well as apoptosis induced by BVDV. FTA treatment could counteract the BVDV-induced overproduction of IFN-γ to maintain the immune homeostasis in bovine PBMCs. At same time, FTA can enhance the secretion of IL-2. What’s more, BVDV promotes the expression of CD28, 4-1BB and TRAF-2, which can be modulated by FTA. Our data suggest that FTA protects PBMCs from BVDV infection possibly via TRAF2-dependent CD28–4-1BB signaling, which may activate PBMCs in response to BVDV infection. Therefore, this aids in the development of an effective adjuvant for vaccines against BVDV and other specific FTA-based therapies for preventing BVDV infection. PMID:27617959

  7. Lepton number violating signals of the top quark partners in the left-right twin Higgs model

    International Nuclear Information System (INIS)

    Goh, Hock-Seng; Krenke, Christopher A.

    2010-01-01

    We study the collider signatures of the left-right twin Higgs model in the case that the right-handed neutrino mass is less than the mass of the right-handed gauge boson. In this scenario, new leptonic decay chains open up, allowing the particles which cancel the one-loop quadratic divergences of the Higgs, the right-handed gauge bosons and top-partners, to be discovered. Half of these events contain same-sign leptons without missing energy, which have no genuine standard model background and for which the backgrounds are purely instrumental. These signals may be used to complement other collider searches and, in certain regions of parameter space, may be the only way to observe the particles responsible for natural electroweak symmetry breaking in the left-right twin Higgs model.

  8. Cellular Hsp27 interacts with classical swine fever virus NS5A protein and negatively regulates viral replication by the NF-κB signaling pathway.

    Science.gov (United States)

    Ling, Shifeng; Luo, Mingyang; Jiang, Shengnan; Liu, Jiayu; Ding, Chunying; Zhang, Qinghuan; Guo, Huancheng; Gong, Wenjie; Tu, Changchun; Sun, Jinfu

    2018-05-01

    Classical swine fever virus (CSFV) nonstructural protein NS5A is a multifunctional protein functioning in regulation of viral genome replication, protein translation and assembly by interaction with viral or host proteins. Here, heat shock protein 27 (Hsp27) has been identified as a novel binding partner of NS5A by using His tag "pull down" coupled with shotgun LC-MS/MS, with interaction of both proteins further confirmed by co-immunoprecipitation and laser confocal assays. In PK-15 cells, silencing of Hsp27 expression by siRNA enhanced CSFV replication, and upregulation of Hsp27 inhibited viral proliferation. Additionally, we have shown that overexpression of Hsp27 increased NF-κB signaling induced by TNFα. Blocking NF-κB signaling in PK-15 cells overexpressing Hsp27 by ammonium pyrrolidinedithiocarbamate (PDTC) eliminated the inhibition of CSFV replication by Hsp27. These findings clearly demonstrate that the inhibition of CSFV replication by Hsp27 is mediated via the NF-κB signaling pathway. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. RPA mediates recombination repair during replication stress and is displaced from DNA by checkpoint signalling in human cells

    DEFF Research Database (Denmark)

    Sleeth, Kate M; Sørensen, Claus Storgaard; Issaeva, Natalia

    2007-01-01

    The replication protein A (RPA) is involved in most, if not all, nuclear metabolism involving single-stranded DNA. Here, we show that RPA is involved in genome maintenance at stalled replication forks by the homologous recombination repair system in humans. Depletion of the RPA protein inhibited...... the formation of RAD51 nuclear foci after hydroxyurea-induced replication stalling leading to persistent unrepaired DNA double-strand breaks (DSBs). We demonstrate a direct role of RPA in homology directed recombination repair. We find that RPA is dispensable for checkpoint kinase 1 (Chk1) activation...... and that RPA directly binds RAD52 upon replication stress, suggesting a direct role in recombination repair. In addition we show that inhibition of Chk1 with UCN-01 decreases dissociation of RPA from the chromatin and inhibits association of RAD51 and RAD52 with DNA. Altogether, our data suggest a direct role...

  10. Mutations within the nuclear localization signal of the porcine reproductive and respiratory syndrome virus nucleocapsid protein attenuate virus replication

    International Nuclear Information System (INIS)

    Lee, Changhee; Hodgins, Douglas; Calvert, Jay G.; Welch, Siao-Kun W.; Jolie, Rika; Yoo, Dongwan

    2006-01-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) is an RNA virus replicating in the cytoplasm, but the nucleocapsid (N) protein is specifically localized to the nucleus and nucleolus in virus-infected cells. A 'pat7' motif of 41-PGKK(N/S)KK has previously been identified in the N protein as the functional nuclear localization signal (NLS); however, the biological consequences of N protein nuclear localization are unknown. In the present study, the role of N protein nuclear localization during infection was investigated in pigs using an NLS-null mutant virus. When two lysines at 43 and 44 at the NLS locus were substituted to glycines, the modified NLS with 41-PGGGNKK restricted the N protein to the cytoplasm. This NLS-null mutation was introduced into a full-length infectious cDNA clone of PRRSV. Upon transfection of cells, the NLS-null full-length clone induced cytopathic effects and produced infectious progeny. The NLS-null virus grew to a titer 100-fold lower than that of wild-type virus. To examine the response to NLS-null PRRSV in the natural host, three groups of pigs, consisting of seven animals per group, were intranasally inoculated with wild-type, placebo, or NLS-null virus, and the animals were maintained for 4 weeks. The NLS-null-infected pigs had a significantly shorter mean duration of viremia than wild-type-infected pigs but developed significantly higher titers of neutralizing antibodies. Mutations occurred at the NLS locus in one pig during viremia, and four types of mutations were identified: 41-PGRGNKK, 41-PGGRNKK, and 41-PGRRNKK, and 41-PGKKSKK. Both wild-type and NLS-null viruses persisted in the tonsils for at least 4 weeks, and the NLS-null virus persisting in the tonsils was found to be mutated to either 41-PGRGNKK or 41-PGGRNKK in all pigs. No other mutation was found in the N gene. All types of reversions which occurred during viremia and persistence were able to translocate the mutated N proteins to the nucleus, indicating a

  11. Characterization of a Non-Canonical Signal Peptidase Cleavage Site in a Replication Protein from Tomato Ringspot Virus.

    Directory of Open Access Journals (Sweden)

    Ting Wei

    Full Text Available The NTB-VPg polyprotein from tomato ringspot virus is an integral membrane replication protein associated with endoplasmic reticulum membranes. A signal peptidase (SPase cleavage was previously detected in the C-terminal region of NTB-VPg downstream of a 14 amino acid (aa-long hydrophobic region (termed TM2. However, the exact location of the cleavage site was not determined. Using in vitro translation assays, we show that the SPase cleavage site is conserved in the NTB-VPg protein from various ToRSV isolates, although the rate of cleavage varies from one isolate to another. Systematic site-directed mutagenesis of the NTB-VPg SPase cleavage sites of two ToRSV isolates allowed the identification of sequences that affect cleavage efficiency. We also present evidence that SPase cleavage in the ToRSV-Rasp2 isolate occurs within a GAAGG sequence likely after the AAG (GAAG/G. Mutation of a downstream MAAV sequence to AAAV resulted in SPase cleavage at both the natural GAAG/G and the mutated AAA/V sequences. Given that there is a distance of seven aa between the two cleavage sites, this indicates that there is flexibility in the positioning of the cleavage sites relative to the inner surface of the membrane and the SPase active site. SPase cleavage sites are typically located 3-7 aa downstream of the hydrophobic region. However, the NTB-VPg GAAG/G cleavage site is located 17 aa downstream of the TM2 hydrophobic region, highlighting unusual features of the NTB-VPg SPase cleavage site. A putative 11 aa-long amphipathic helix was identified immediately downstream of the TM2 region and five aa upstream of the GAAG/G cleavage site. Based on these results, we present an updated topology model in which the hydrophobic and amphipathic domains form a long tilted helix or a bent helix in the membrane lipid bilayer, with the downstream cleavage site(s oriented parallel to the membrane inner surface.

  12. Inhibition of cyclophilin A suppresses H2O2-enhanced replication of HCMV through the p38 MAPK signaling pathway.

    Science.gov (United States)

    Xiao, Jun; Song, Xin; Deng, Jiang; Lv, Liping; Ma, Ping; Gao, Bo; Zhou, Xipeng; Zhang, Yanyu; Xu, Jinbo

    2016-09-01

    Human cytomegalovirus (HCMV) infection can be accelerated by intracellular and extracellular hydrogen peroxide (H2O2) stimulation, mediated by the activation of the p38 mitogen-activated protein kinase (MAPK) pathway. However, it remains unknown whether host gene expression is involved in H2O2-upregulated HCMV replication. Here, we show that the expression of the host gene, cyclophilin A (CyPA), could be facilitated by treatment with H2O2 in a dose-dependent manner. Experiments with CyPA-specific siRNA, or with cyclosporine A, an inhibitor of CyPA, confirmed that H2O2-mediated upregulation of HCMV replication is specifically mediated by upregulation of CyPA expression. Furthermore, depletion or inhibition of CyPA reduced H2O2-induced p38 activation, consistent with that of H2O2-upregulated HCMV lytic replication. These results show that H2O2 is capable of activating ROS-CyPA-p38 MAPK interactions to enhance HCMV replication.

  13. In vitro analysis of the role of replication protein A (RPA) and RPA phosphorylation in ATR-mediated checkpoint signaling.

    Science.gov (United States)

    Lindsey-Boltz, Laura A; Reardon, Joyce T; Wold, Marc S; Sancar, Aziz

    2012-10-19

    Replication protein A (RPA) plays essential roles in DNA metabolism, including replication, checkpoint, and repair. Recently, we described an in vitro system in which the phosphorylation of human Chk1 kinase by ATR (ataxia telangiectasia mutated and Rad3-related) is dependent on RPA bound to single-stranded DNA. Here, we report that phosphorylation of other ATR targets, p53 and Rad17, has the same requirements and that RPA is also phosphorylated in this system. At high p53 or Rad17 concentrations, RPA phosphorylation is inhibited and, in this system, RPA with phosphomimetic mutations cannot support ATR kinase function, whereas a non-phosphorylatable RPA mutant exhibits full activity. Phosphorylation of these ATR substrates depends on the recruitment of ATR and the substrates by RPA to the RPA-ssDNA complex. Finally, mutant RPAs lacking checkpoint function exhibit essentially normal activity in nucleotide excision repair, revealing RPA separation of function for checkpoint and excision repair.

  14. In Vitro Analysis of the Role of Replication Protein A (RPA) and RPA Phosphorylation in ATR-mediated Checkpoint Signaling*

    Science.gov (United States)

    Lindsey-Boltz, Laura A.; Reardon, Joyce T.; Wold, Marc S.; Sancar, Aziz

    2012-01-01

    Replication protein A (RPA) plays essential roles in DNA metabolism, including replication, checkpoint, and repair. Recently, we described an in vitro system in which the phosphorylation of human Chk1 kinase by ATR (ataxia telangiectasia mutated and Rad3-related) is dependent on RPA bound to single-stranded DNA. Here, we report that phosphorylation of other ATR targets, p53 and Rad17, has the same requirements and that RPA is also phosphorylated in this system. At high p53 or Rad17 concentrations, RPA phosphorylation is inhibited and, in this system, RPA with phosphomimetic mutations cannot support ATR kinase function, whereas a non-phosphorylatable RPA mutant exhibits full activity. Phosphorylation of these ATR substrates depends on the recruitment of ATR and the substrates by RPA to the RPA-ssDNA complex. Finally, mutant RPAs lacking checkpoint function exhibit essentially normal activity in nucleotide excision repair, revealing RPA separation of function for checkpoint and excision repair. PMID:22948311

  15. Evaluating the Effects of Traffic on Driver Stopping and Turn Signal Use at a Stop Sign: A Systematic Replication

    Science.gov (United States)

    Lebbon, Angela R.; Austin, John; Van Houten, Ron; Malenfant, Louis E.

    2007-01-01

    The current analyses of observational data found that oncoming traffic substantially affected driver stopping patterns and turn signal use at the target stop sign. The percentage of legal stops and turn signal use by drivers in the presence and absence of traffic was analyzed using a multi-element design. The results showed that legal stops were…

  16. Transmissible gastroenteritis coronavirus genome packaging signal is located at the 5' end of the genome and promotes viral RNA incorporation into virions in a replication-independent process.

    Science.gov (United States)

    Morales, Lucia; Mateos-Gomez, Pedro A; Capiscol, Carmen; del Palacio, Lorena; Enjuanes, Luis; Sola, Isabel

    2013-11-01

    Preferential RNA packaging in coronaviruses involves the recognition of viral genomic RNA, a crucial process for viral particle morphogenesis mediated by RNA-specific sequences, known as packaging signals. An essential packaging signal component of transmissible gastroenteritis coronavirus (TGEV) has been further delimited to the first 598 nucleotides (nt) from the 5' end of its RNA genome, by using recombinant viruses transcribing subgenomic mRNA that included potential packaging signals. The integrity of the entire sequence domain was necessary because deletion of any of the five structural motifs defined within this region abrogated specific packaging of this viral RNA. One of these RNA motifs was the stem-loop SL5, a highly conserved motif in coronaviruses located at nucleotide positions 106 to 136. Partial deletion or point mutations within this motif also abrogated packaging. Using TGEV-derived defective minigenomes replicated in trans by a helper virus, we have shown that TGEV RNA packaging is a replication-independent process. Furthermore, the last 494 nt of the genomic 3' end were not essential for packaging, although this region increased packaging efficiency. TGEV RNA sequences identified as necessary for viral genome packaging were not sufficient to direct packaging of a heterologous sequence derived from the green fluorescent protein gene. These results indicated that TGEV genome packaging is a complex process involving many factors in addition to the identified RNA packaging signal. The identification of well-defined RNA motifs within the TGEV RNA genome that are essential for packaging will be useful for designing packaging-deficient biosafe coronavirus-derived vectors and providing new targets for antiviral therapies.

  17. DNA Damage Signaling Is Induced in the Absence of Epstein-Barr Virus (EBV) Lytic DNA Replication and in Response to Expression of ZEBRA.

    Science.gov (United States)

    Wang'ondu, Ruth; Teal, Stuart; Park, Richard; Heston, Lee; Delecluse, Henri; Miller, George

    2015-01-01

    Epstein Barr virus (EBV), like other oncogenic viruses, modulates the activity of cellular DNA damage responses (DDR) during its life cycle. Our aim was to characterize the role of early lytic proteins and viral lytic DNA replication in activation of DNA damage signaling during the EBV lytic cycle. Our data challenge the prevalent hypothesis that activation of DDR pathways during the EBV lytic cycle occurs solely in response to large amounts of exogenous double stranded DNA products generated during lytic viral DNA replication. In immunofluorescence or immunoblot assays, DDR activation markers, specifically phosphorylated ATM (pATM), H2AX (γH2AX), or 53BP1 (p53BP1), were induced in the presence or absence of viral DNA amplification or replication compartments during the EBV lytic cycle. In assays with an ATM inhibitor and DNA damaging reagents in Burkitt lymphoma cell lines, γH2AX induction was necessary for optimal expression of early EBV genes, but not sufficient for lytic reactivation. Studies in lytically reactivated EBV-positive cells in which early EBV proteins, BGLF4, BGLF5, or BALF2, were not expressed showed that these proteins were not necessary for DDR activation during the EBV lytic cycle. Expression of ZEBRA, a viral protein that is necessary for EBV entry into the lytic phase, induced pATM foci and γH2AX independent of other EBV gene products. ZEBRA mutants deficient in DNA binding, Z(R183E) and Z(S186E), did not induce foci of pATM. ZEBRA co-localized with HP1β, a heterochromatin associated protein involved in DNA damage signaling. We propose a model of DDR activation during the EBV lytic cycle in which ZEBRA induces ATM kinase phosphorylation, in a DNA binding dependent manner, to modulate gene expression. ATM and H2AX phosphorylation induced prior to EBV replication may be critical for creating a microenvironment of viral and cellular gene expression that enables lytic cycle progression.

  18. Ekspedeerimisfirmade TOP

    Index Scriptorium Estoniae

    2008-01-01

    Ekspedeerimisfirmade TOP 57. Vt. samas: Tanel Raig. Majandus kukutab ekspedeerimisturgu. Diagramm: Väliskaubanduse statistika; Katrin Raie. Ekspedeerijad hakkavad rohkem koostööle rõhuma. Kommenteerib Jaan Lepp; Müügitulu TOP 10; Müügitulu kasvu TOP 10; Kasumi TOP 10; Kasumi kasvu TOP 10; Rentaabluse TOP 10; Omakapitali tootlikkuse TOP 10; Eestis registreeritud Vene hiiglane; Ekspedeerimisturu kasumiliider kaotas 20 miljonit; Küsimustele vastab OÜ Contimer juht Dmitri Redkin

  19. Distributional Replication

    OpenAIRE

    Beare, Brendan K.

    2009-01-01

    Suppose that X and Y are random variables. We define a replicating function to be a function f such that f(X) and Y have the same distribution. In general, the set of replicating functions for a given pair of random variables may be infinite. Suppose we have some objective function, or cost function, defined over the set of replicating functions, and we seek to estimate the replicating function with the lowest cost. We develop an approach to estimating the cheapest replicating function that i...

  20. PERK Signal-Modulated Protein Translation Promotes the Survivability of Dengue 2 Virus-Infected Mosquito Cells and Extends Viral Replication.

    Science.gov (United States)

    Hou, Jiun-Nan; Chen, Tien-Huang; Chiang, Yi-Hsuan; Peng, Jing-Yun; Yang, Tsong-Han; Cheng, Chih-Chieh; Sofiyatun, Eny; Chiu, Cheng-Hsun; Chiang-Ni, Chuan; Chen, Wei-June

    2017-09-20

    Survival of mosquitoes from dengue virus (DENV) infection is a prerequisite of viral transmission to the host. This study aimed to see how mosquito cells can survive the infection during prosperous replication of the virus. In C6/36 cells, global protein translation was shut down after infection by DENV type 2 (DENV2). However, it returned to a normal level when infected cells were treated with an inhibitor of the protein kinase RNA (PKR)-like ER kinase (PERK) signaling pathway. Based on a 7-Methylguanosine 5'-triphosphate (m7GTP) pull-down assay, the eukaryotic translation initiation factor 4F (eIF4F) complex was also identified in DENV2-infected cells. This suggests that most mosquito proteins are synthesized via canonical cap-dependent translation. When the PERK signal pathway was inhibited, both accumulation of reactive oxygen species and changes in the mitochondrial membrane potential increased. This suggested that ER stress response was alleviated through the PERK-mediated shutdown of global proteins in DENV2-infected C6/36 cells. In the meantime, the activities of caspases-9 and -3 and the apoptosis-related cell death rate increased in C6/36 cells with PERK inhibition. This reflected that the PERK-signaling pathway is involved in determining cell survival, presumably by reducing DENV2-induced ER stress. Looking at the PERK downstream target, α-subunit of eukaryotic initiation factor 2 (eIF2α), an increased phosphorylation status was only shown in infected C6/36 cells. This indicated that recruitment of ribosome binding to the mRNA 5'-cap structure could have been impaired in cap-dependent translation. It turned out that shutdown of cellular protein translation resulted in a pro-survival effect on mosquito cells in response to DENV2 infection. As synthesis of viral proteins was not affected by the PERK signal pathway, an alternate mode other than cap-dependent translation may be utilized. This finding provides insights into elucidating how the PERK signal

  1. Replication Catastrophe

    DEFF Research Database (Denmark)

    Toledo, Luis; Neelsen, Kai John; Lukas, Jiri

    2017-01-01

    Proliferating cells rely on the so-called DNA replication checkpoint to ensure orderly completion of genome duplication, and its malfunction may lead to catastrophic genome disruption, including unscheduled firing of replication origins, stalling and collapse of replication forks, massive DNA...... breakage, and, ultimately, cell death. Despite many years of intensive research into the molecular underpinnings of the eukaryotic replication checkpoint, the mechanisms underlying the dismal consequences of its failure remain enigmatic. A recent development offers a unifying model in which the replication...... checkpoint guards against global exhaustion of rate-limiting replication regulators. Here we discuss how such a mechanism can prevent catastrophic genome disruption and suggest how to harness this knowledge to advance therapeutic strategies to eliminate cancer cells that inherently proliferate under...

  2. The lytic origin of herpesvirus papio is highly homologous to Epstein-Barr virus ori-Lyt: evolutionary conservation of transcriptional activation and replication signals.

    Science.gov (United States)

    Ryon, J J; Fixman, E D; Houchens, C; Zong, J; Lieberman, P M; Chang, Y N; Hayward, G S; Hayward, S D

    1993-01-01

    Herpesvirus papio (HVP) is a B-lymphotropic baboon virus with an estimated 40% homology to Epstein-Barr virus (EBV). We have cloned and sequenced ori-Lyt of herpesvirus papio and found a striking degree of nucleotide homology (89%) with ori-Lyt of EBV. Transcriptional elements form an integral part of EBV ori-Lyt. The promoter and enhancer domains of EBV ori-Lyt are conserved in herpesvirus papio. The EBV ori-Lyt promoter contains four binding sites for the EBV lytic cycle transactivator Zta, and the enhancer includes one Zta and two Rta response elements. All five of the Zta response elements and one of the Rta motifs are conserved in HVP ori-Lyt, and the HVP DS-L leftward promoter and the enhancer were activated in transient transfection assays by the EBV Zta and Rta transactivators. The EBV ori-Lyt enhancer contains a palindromic sequence, GGTCAGCTGACC, centered on a PvuII restriction site. This sequence, with a single base change, is also present in the HVP ori-Lyt enhancer. DNase I footprinting demonstrated that the PvuII sequence was bound by a protein present in a Raji nuclear extract. Mobility shift and competition assays using oligonucleotide probes identified this sequence as a binding site for the cellular transcription factor MLTF. Mutagenesis of the binding site indicated that MLTF contributes significantly to the constitutive activity of the ori-Lyt enhancer. The high degree of conservation of cis-acting signal sequences in HVP ori-Lyt was further emphasized by the finding that an HVP ori-Lyt-containing plasmid was replicated in Vero cells by a set of cotransfected EBV replication genes. The central domain of EBV ori-Lyt contains two related AT-rich palindromes, one of which is partially duplicated in the HVP sequence. The AT-rich palindromes are functionally important cis-acting motifs. Deletion of these palindromes severely diminished replication of an ori-Lyt target plasmid. Images PMID:8389916

  3. Database Replication

    CERN Document Server

    Kemme, Bettina

    2010-01-01

    Database replication is widely used for fault-tolerance, scalability and performance. The failure of one database replica does not stop the system from working as available replicas can take over the tasks of the failed replica. Scalability can be achieved by distributing the load across all replicas, and adding new replicas should the load increase. Finally, database replication can provide fast local access, even if clients are geographically distributed clients, if data copies are located close to clients. Despite its advantages, replication is not a straightforward technique to apply, and

  4. Emerging role of Hippo signalling in pancreatic biology: YAP re-expression and plausible link to islet cell apoptosis and replication.

    Science.gov (United States)

    Sharma, Anjana; Yerra, Veera Ganesh; Kumar, Ashutosh

    2017-02-01

    Diabetes mellitus is an ailment that develops when the functional capacity of the pancreas does not meet the metabolic requirements of the whole body, either due to insulin insufficiency or resistance to insulin action. Current therapies that control glycaemia are limited by their unwanted effects or their inability to prevent the development of long-term complications. Regeneration and replacement of beta cell therapies are shaping the goals of future management of diabetes. The Hippo pathway, first discovered in Drosophila melanogaster, plays a vital role in controlling the organ size. Nuclear recruitment of YAP/TAZ (Yes-associated protein/transcriptional co-activator with PDZ-binding motif), a mammalian analogue of Yorkie protein found in Drosophila, activates cell proliferation and inhibits apoptosis. YAP was found to regulate early pancreatic development followed by downregulation during Ngn3-specific endocrine lineage maturation corresponding to their mitotic quiescence. Recent evidences have shown that optimum modulation of upstream kinases in the Hippo signalling pathway may lead to apoptosis inhibition and renewal of progenitor as well as stem cells in case of tissue or cell injury. This article reviews the evidences linking the role of various components of the Hippo pathway to pancreatic regeneration. In particular, the focus is on the beneficial role of induced YAP expression and its nuclear distribution on apoptosis and replication of adult pancreatic β islets. This approach may be of immense significance towards our fight against diabetes; thus, more insightful research is warranted in the area of Hippo signalling pathway and its involvement in pancreatic regeneration. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  5. Activation of PI3K/AKT and ERK MAPK signal pathways is required for the induction of lytic cycle replication of Kaposi's Sarcoma-associated herpesvirus by herpes simplex virus type 1

    Directory of Open Access Journals (Sweden)

    Lv Zhigang

    2011-10-01

    Full Text Available Abstract Background Kaposi's sarcoma-associated herpesvirus (KSHV is causally linked to several acquired immunodeficiency syndrome-related malignancies, including Kaposi's sarcoma (KS, primary effusion lymphoma (PEL and a subset of multicentric Castleman's disease. Regulation of viral lytic replication is critical to the initiation and progression of KS. Recently, we reported that herpes simplex virus type 1 (HSV-1 was an important cofactor that activated lytic cycle replication of KSHV. Here, we further investigated the possible signal pathways involved in HSV-1-induced reactivation of KSHV. Results By transfecting a series of dominant negative mutants and protein expressing constructs and using pharmacologic inhibitors, we found that either Janus kinase 1 (JAK1/signal transducer and activator of transcription 3 (STAT3 or JAK1/STAT6 signaling failed to regulate HSV-1-induced KSHV replication. However, HSV-1 infection of BCBL-1 cells activated phosphatidylinositol 3-kinase (PI3K/protein kinase B (PKB, also called AKT pathway and inactivated phosphatase and tensin homologue deleted on chromosome ten (PTEN and glycogen synthase kinase-3β (GSK-3β. PTEN/PI3K/AKT/GSK-3β pathway was found to be involved in HSV-1-induced KSHV reactivation. Additionally, extracellular signal-regulated protein kinase (ERK mitogen-activated protein kinase (MAPK pathway also partially contributed to HSV-1-induced KSHV replication. Conclusions HSV-1 infection stimulated PI3K/AKT and ERK MAPK signaling pathways that in turn contributed to KSHV reactivation, which provided further insights into the molecular mechanism controlling KSHV lytic replication, particularly in the context of HSV-1 and KSHV co-infection.

  6. Top physics at CDF

    Energy Technology Data Exchange (ETDEWEB)

    Hughes, R.E. [Univ. of Rochester, NY (United States)

    1997-01-01

    We report on top physics results using a 100 pb{sup -1} data sample of p{bar p} collisions at {radical}s = 1.8 TeV collected with the Collider Detector at Fermilab (CDF). We have identified top signals in a variety of decay channels, and used these channels to extract a measurement of the top mass and production cross section. A subset of the data (67 pb{sup -1}) is used to determine M{sub top} = 176 {+-} 8(stat) {+-} 10(syst) and {sigma}(tt) = 7.6 {sub -2.0}{sup +2.4} pb. We present studies of the kinematics of t{bar t} events and extract the first direct measurement of V{sub tb}. Finally, we indicate prospects for future study of top physics at the Tevatron.

  7. Boosted tops at ATLAS

    CERN Document Server

    Villaplana, M; The ATLAS collaboration

    2011-01-01

    A sample of candidate events for highly boosted top quarks is selected following the standard ATLAS selection for semi-leptonic ttbar events plus a requirement that the invariant mass of the reconstructed ttbar pair is greater than 700 GeV. Event displays are presented for the most promising candidates, as well as quantitative results for observables designed to isolate a boosted top quark signal.

  8. Kinnisvarafirmade TOP 90

    Index Scriptorium Estoniae

    2002-01-01

    TOP 90. Kinnisvara valdkondade TOP 5. Käibe TOP 30. Käibe kasvu TOP 30. Rentaabluse TOP 30. Kasumi TOP 30. Kasumi kasvu TOP 30. Varade tootlikkuse TOP 30. Kinnisvarafirmade üldandmed. Kinnisvarafirmade finantsandmed

  9. Top quark mass measurement

    International Nuclear Information System (INIS)

    Maki, Tuula; Helsinki Inst. of Phys.; Helsinki U. of Tech.

    2008-01-01

    The top quark is the heaviest elementary particle. Its mass is one of the fundamental parameters of the standard model of particle physics, and an important input to precision electroweak tests. This thesis describes three measurements of the top-quark mass in the dilepton decay channel. The dilepton events have two neutrinos in the final state; neutrinos are weakly interacting particles that cannot be detected with a multipurpose experiment. Therefore, the signal of dilepton events consists of a large amount of missing energy and momentum carried off by the neutrinos. The top-quark mass is reconstructed for each event by assuming an additional constraint from a top mass independent distribution. Template distributions are constructed from simulated samples of signal and background events, and parameterized to form continuous probability density functions. The final top-quark mass is derived using a likelihood fit to compare the reconstructed top mass distribution from data to the parameterized templates. One of the analyses uses a novel technique to add top mass information from the observed number of events by including a cross-section-constraint in the likelihood function. All measurements use data samples collected by the CDF II detector

  10. Exploiting replicative stress to treat cancer

    DEFF Research Database (Denmark)

    Dobbelstein, Matthias; Sørensen, Claus Storgaard

    2015-01-01

    DNA replication in cancer cells is accompanied by stalling and collapse of the replication fork and signalling in response to DNA damage and/or premature mitosis; these processes are collectively known as 'replicative stress'. Progress is being made to increase our understanding of the mechanisms...

  11. Kinnisvarafirmade TOP 90

    Index Scriptorium Estoniae

    2003-01-01

    Kinnisvarafirmade TOP 90. Rentaabluse TOP 30. Käibe TOP 30. Käibe kasvu TOP 30. Kasumi TOP 30. Kasumi kasvu TOP 30. Varade tootlikkuse TOP 30. Kinnisvarafirmade üldandmed. Kinnisvarafirmade finantsandmed

  12. Teedeehitusfirmade TOP 24

    Index Scriptorium Estoniae

    2006-01-01

    Teedeehitusfirmade TOP. Vt. samas: Käibe TOP 10; Käibe kasvu TOP 10; Kasumi TOP 10; Kasumi Kasvu TOP 10; Rentaabluse TOP 10; Omakapitali tootlikkuse TOP 10; Teedeehitusfirmade üld- ja finantsandmed

  13. Koolitusfirmade TOP 50

    Index Scriptorium Estoniae

    2006-01-01

    Koolitusfirmade TOP. Vt. samas: Käibe TOP 10; Käibe kasvu TOP 10; Majandustegevuse kasumi TOP 10; Kasumi kasvu TOP 10; Rentaabluse TOP 10; Omakapitali tootlikkuse TOP 10; Koolitusfirmade üld- ja finantsandmed

  14. Telekommunikatsiooni TOP aastal 2003

    Index Scriptorium Estoniae

    2004-01-01

    Telekommunikatsiooni TOP aastal 2003. Käibe TOP 10. Käibe kasvu TOP 10. Rentaabluse TOP 10. Kasumi TOP 10. Kasumi kasvu TOP 10. Omakapitali tootlikkuse TOP 10. Telekommunikatsioonifirmade üldandmed. Telekommunikatsioonifirmade finantsandmed

  15. Põllumajandustootjate TOP 50

    Index Scriptorium Estoniae

    2006-01-01

    Põllumajandustootjate TOP. Vt. samas: Käibe TOP 10; Käibe kasvu TOP 10; Majandustegevuse kasumi TOP 10; Kasumi kasvu TOP 10; Rentaabluse TOP 10; Omakapitali tootlikkuse TOP 10; Põllumajandustootjate üld- ja finantsandmed

  16. Ehitusmaterjalitootjate TOP 95

    Index Scriptorium Estoniae

    2006-01-01

    Ehitusmaterjalitootjate TOP. Vt. samas: Käibe TOP 10; Käibe kasvu TOP 10; Kasumi TOP 10; Kasumi kasvu TOP 10; Rentaabluse TOP 10; Omakapitali tootlikkuse TOP 10; Ehitusmaterjalitootjate üld- ja finantsandmed

  17. Top quark discovered

    International Nuclear Information System (INIS)

    Anon.

    1995-01-01

    Nine months after a careful announcement of tentative evidence for the long-awaited sixth 'top' quark, physicists from the CDF and DO experiments at Fermilab's Tevatron proton-antiproton collider declared on 2 March that they had finally discovered the top quark. Last year (June 1994, page 1), the CDF experiment at the Tevatron reported a dozen candidate top events. These, said CDF, had all the characteristics expected of top, but the difficulties of extracting the tiny signal from a trillion proton-antiproton collisions made them shy of claiming a discovery. For its part, the companion DO Tevatron experiment reported a few similar events but were even more guarded about their interpretation as top quarks. Just after these hesitant announcements, performance at the Tevatron improved dramatically last summer. After the commissioning of a new linear accelerator and a magnet realignment, the machine reached a new world record proton-antiproton collision luminosity of 1.28 x 10 31 per sq cm per s, ten times that originally planned. Data began to pour in at an unprecedented rate and the data sample grew to six trillion collisions. Luminosity has subsequently climbed to 1.7 x 10 31 . The top quark is the final letter in the alphabet of Standard Model particles. According to this picture, all matter is composed of six stronglyinteracting subnuclear particles, the quarks, and six weakly interacting particles, the leptons. Both sextets are neatly arranged as three pairs in order of increasing mass. The fifth quark, the 'beauty' or 'b' quark, was also discovered at Fermilab, back in 1977. Since then physicists have been eagerly waiting for the top to turn up, but have been frustrated by its heaviness - the top is some 40 times the mass of its 'beautiful' partner. Not only is the top quark the heaviest by far, but it is the only quark which has been actively hunted. After the quarry was glimpsed last year, the net has now been

  18. Top Earners

    DEFF Research Database (Denmark)

    Badel, Alejandro; Daly, Moira; Huggett, Mark

    of the earnings distribution becomes thicker with age, and (3) the growth rate of earnings over the working lifetime is larger for groups with higher lifetime earnings. Models of top earners should account for these qualitative patterns and, importantly, for how they quantitatively differ across countries....

  19. Vitamin D Potentiates the Inhibitory Effect of MicroRNA-130a in Hepatitis C Virus Replication Independent of Type I Interferon Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Xiaoqiong Duan

    2015-01-01

    Full Text Available Calcitriol, the bioactive metabolite of vitamin D, was reported to inhibit HCV production in a synergistic fashion with interferon, a treatment in vitro. Our previous study established that miR-130a inhibits HCV replication by restoring the host innate immune response. We aimed to determine whether there is additive inhibitory effect of calcitriol and miR-130a on HCV replication. Here we showed that calcitriol potentiates the anti-HCV effect of miR-130a in both Con1b replicon and J6/JFH1 culture systems. Intriguingly, this potentiating effect of calcitriol on miR-130a was not through upregulating the expression of cellular miR-130a or through increasing the miR-130a-mediated IFNα/β production. All these findings may contribute to the development of novel anti-HCV therapeutic strategies although the antiviral mechanism needs to be further investigated.

  20. A dual character of flavonoids in influenza A virus replication and spread through modulating cell-autonomous immunity by MAPK signaling pathways

    Science.gov (United States)

    Dong, Wenjuan; Wei, Xiuli; Zhang, Fayun; Hao, Junfeng; Huang, Feng; Zhang, Chunling; Liang, Wei

    2014-01-01

    Flavonoids are well known as a large class of polyphenolic compounds, which have a variety of physiological activities, including anti-influenza virus activity. The influenza A/WSN/33 infected A549 cells have been used to screen anti-influenza virus drugs from natural flavonoid compounds library. Unexpectedly, some flavonoid compounds significantly inhibited virus replication, while the others dramatically promoted virus replication. In this study, we attempted to understand these differences between flavonoid compounds in their antivirus mechanisms. Hesperidin and kaempferol were chosen as representatives of both sides, each of which exhibited the opposite effects on influenza virus replication. Our investigation revealed that the opposite effects produced by hesperidin and kaempferol on influenza virus were due to inducing the opposite cell-autonomous immune responses by selectively modulating MAP kinase pathways: hesperidin up-regulated P38 and JNK expression and activation, thus resulting in the enhanced cell-autonomous immunity; while kaempferol dramatically down-regulated p38 and JNK expression and activation, thereby suppressing cell-autonomous immunity. In addition, hesperidin restricted RNPs export from nucleus by down-regulating ERK activation, but kaempferol promoted RNPs export by up-regulating ERK activation. Our findings demonstrate that a new generation of anti-influenza virus drugs could be developed based on selective modulation of MAP kinase pathways to stimulate cell-autonomous immunity. PMID:25429875

  1. Fluorescent reporter signals, EGFP and DsRed, encoded in HIV-1 facilitate the detection of productively infected cells and cell-associated viral replication levels

    Directory of Open Access Journals (Sweden)

    Kazutaka eTerahara

    2012-01-01

    Full Text Available Flow cytometric analysis is a reliable and convenient method for investigating molecules at the single cell level. Previously, recombinant human immunodeficiency virus type 1 (HIV-1 strains were constructed that express a fluorescent reporter, either enhanced green fluorescent protein or DsRed, which allow the monitoring of HIV-1-infected cells by flow cytometry. The present study further investigated the potential of these recombinant viruses in terms of whether the HIV-1 fluorescent reporters would be helpful in evaluating viral replication based on fluorescence intensity. When primary CD4+ T cells were infected with recombinant viruses, the fluorescent reporter intensity measured by flow cytometry was associated with the level of CD4 downmodulation and Gag p24 expression in infected cells. Interestingly, some HIV-1-infected cells, in which CD4 was only moderately downmodulated, were reporter-positive but Gag p24-negative. Furthermore, when the activation status of primary CD4+ T cells was modulated by T cell receptor-mediated stimulation, we confirmed the preferential viral production upon strong stimulation and showed that the intensity of the fluorescent reporter within a proportion of HIV-1-infected cells was correlated with the viral replication level. These findings indicate that a fluorescent reporter encoded within HIV-1 is useful for the sensitive detection of productively-infected cells at different stages of infection and for evaluating cell-associated viral replication at the single cell level.

  2. TopBP1 associates with NBS1 and is involved in homologous recombination repair

    International Nuclear Information System (INIS)

    Morishima, Ken-ichi; Sakamoto, Shuichi; Kobayashi, Junya; Izumi, Hideki; Suda, Tetsuji; Matsumoto, Yoshiyuki; Tauchi, Hiroshi; Ide, Hiroshi; Komatsu, Kenshi; Matsuura, Shinya

    2007-01-01

    TopBP1 is involved in DNA replication and DNA damage checkpoint. Recent studies have demonstrated that TopBP1 is a direct positive effecter of ATR. However, it is not known how TopBP1 recognizes damaged DNA. Here, we show that TopBP1 formed nuclear foci after exposure to ionizing radiation, but such TopBP1 foci were abolished in Nijmegen breakage syndrome cells. We also show that TopBP1 physically associated with NBS1 in vivo. These results suggested that NBS1 might regulate TopBP1 recruitment to the sites of DNA damage. TopBP1-depleted cells showed hypersensitivity to Mitomycin C and ionizing radiation, an increased frequency of sister-chromatid exchange level, and a reduced frequency of DNA double-strand break induced homologous recombination repair. Together, these results suggested that TopBP1 might be a mediator of DNA damage signaling from NBS1 to ATR and promote homologous recombination repair

  3. Comparative analysis of seven viral nuclear export signals (NESs reveals the crucial role of nuclear export mediated by the third NES consensus sequence of nucleoprotein (NP in influenza A virus replication.

    Directory of Open Access Journals (Sweden)

    Nopporn Chutiwitoonchai

    Full Text Available The assembly of influenza virus progeny virions requires machinery that exports viral genomic ribonucleoproteins from the cell nucleus. Currently, seven nuclear export signal (NES consensus sequences have been identified in different viral proteins, including NS1, NS2, M1, and NP. The present study examined the roles of viral NES consensus sequences and their significance in terms of viral replication and nuclear export. Mutation of the NP-NES3 consensus sequence resulted in a failure to rescue viruses using a reverse genetics approach, whereas mutation of the NS2-NES1 and NS2-NES2 sequences led to a strong reduction in viral replication kinetics compared with the wild-type sequence. While the viral replication kinetics for other NES mutant viruses were also lower than those of the wild-type, the difference was not so marked. Immunofluorescence analysis after transient expression of NP-NES3, NS2-NES1, or NS2-NES2 proteins in host cells showed that they accumulated in the cell nucleus. These results suggest that the NP-NES3 consensus sequence is mostly required for viral replication. Therefore, each of the hydrophobic (Φ residues within this NES consensus sequence (Φ1, Φ2, Φ3, or Φ4 was mutated, and its viral replication and nuclear export function were analyzed. No viruses harboring NP-NES3 Φ2 or Φ3 mutants could be rescued. Consistent with this, the NP-NES3 Φ2 and Φ3 mutants showed reduced binding affinity with CRM1 in a pull-down assay, and both accumulated in the cell nucleus. Indeed, a nuclear export assay revealed that these mutant proteins showed lower nuclear export activity than the wild-type protein. Moreover, the Φ2 and Φ3 residues (along with other Φ residues within the NP-NES3 consensus were highly conserved among different influenza A viruses, including human, avian, and swine. Taken together, these results suggest that the Φ2 and Φ3 residues within the NP-NES3 protein are important for its nuclear export function

  4. Autotranspordifirmade TOP 100

    Index Scriptorium Estoniae

    2006-01-01

    Ilmunud ka: Delovõje Vedomosti : Transport i Logistika 29. nov. lk. 10-11. Autofirmade TOP 100. Vt. samas: Käibe TOP 10; Käibe kasvu TOP 10; Majandustegevuse kasumi TOP 10; Kasumi kasvu TOP 10; Rentaabluse TOP 10; Omakapitali tootlikkuse TOP 10; Autotranspordifirmade üld- ja finantsandmed. Delovõje Vedomosti : Transport i Logistika sisaldab tabelit Autofirmade TOP 100

  5. Transmissible Gastroenteritis Coronavirus Genome Packaging Signal Is Located at the 5′ End of the Genome and Promotes Viral RNA Incorporation into Virions in a Replication-Independent Process

    Science.gov (United States)

    Morales, Lucia; Mateos-Gomez, Pedro A.; Capiscol, Carmen; del Palacio, Lorena; Sola, Isabel

    2013-01-01

    Preferential RNA packaging in coronaviruses involves the recognition of viral genomic RNA, a crucial process for viral particle morphogenesis mediated by RNA-specific sequences, known as packaging signals. An essential packaging signal component of transmissible gastroenteritis coronavirus (TGEV) has been further delimited to the first 598 nucleotides (nt) from the 5′ end of its RNA genome, by using recombinant viruses transcribing subgenomic mRNA that included potential packaging signals. The integrity of the entire sequence domain was necessary because deletion of any of the five structural motifs defined within this region abrogated specific packaging of this viral RNA. One of these RNA motifs was the stem-loop SL5, a highly conserved motif in coronaviruses located at nucleotide positions 106 to 136. Partial deletion or point mutations within this motif also abrogated packaging. Using TGEV-derived defective minigenomes replicated in trans by a helper virus, we have shown that TGEV RNA packaging is a replication-independent process. Furthermore, the last 494 nt of the genomic 3′ end were not essential for packaging, although this region increased packaging efficiency. TGEV RNA sequences identified as necessary for viral genome packaging were not sufficient to direct packaging of a heterologous sequence derived from the green fluorescent protein gene. These results indicated that TGEV genome packaging is a complex process involving many factors in addition to the identified RNA packaging signal. The identification of well-defined RNA motifs within the TGEV RNA genome that are essential for packaging will be useful for designing packaging-deficient biosafe coronavirus-derived vectors and providing new targets for antiviral therapies. PMID:23966403

  6. Trovafloxacin-induced replication stress sensitizes HepG2 cells to tumor necrosis factor-alpha-induced cytotoxicity mediated by extracellular signal-regulated kinase and ataxia telangiectasia and Rad3-related

    International Nuclear Information System (INIS)

    Beggs, Kevin M.; Maiuri, Ashley R.; Fullerton, Aaron M.; Poulsen, Kyle L.; Breier, Anna B.; Ganey, Patricia E.; Roth, Robert A.

    2015-01-01

    Use of the fluoroquinolone antibiotic trovafloxacin (TVX) was restricted due to idiosyncratic, drug-induced liver injury (IDILI). Previous studies demonstrated that tumor necrosis factor-alpha (TNF) and TVX interact to cause death of hepatocytes in vitro that was associated with prolonged activation of c-Jun N-terminal kinase (JNK), activation of caspases 9 and 3, and DNA damage. The purpose of this study was to explore further the mechanism by which TVX interacts with TNF to cause cytotoxicity. Treatment with TVX caused cell cycle arrest, enhanced expression of p21 and impaired proliferation, but cell death only occurred after cotreatment with TVX and TNF. Cell death involved activation of extracellular signal-related kinase (ERK), which in turn activated caspase 3 and ataxia telangiectasia and Rad3-related (ATR), both of which contributed to cytotoxicity. Cotreatment of HepG2 cells with TVX and TNF caused double-strand breaks in DNA, and ERK contributed to this effect. Inhibition of caspase activity abolished the DNA strand breaks. The data suggest a complex interaction of TVX and TNF in which TVX causes replication stress, and the downstream effects are exacerbated by TNF, leading to hepatocellular death. These results raise the possibility that IDILI from TVX results from MAPK and ATR activation in hepatocytes initiated by interaction of cytokine signaling with drug-induced replication stress

  7. Database Replication Prototype

    OpenAIRE

    Vandewall, R.

    2000-01-01

    This report describes the design of a Replication Framework that facilitates the implementation and com-parison of database replication techniques. Furthermore, it discusses the implementation of a Database Replication Prototype and compares the performance measurements of two replication techniques based on the Atomic Broadcast communication primitive: pessimistic active replication and optimistic active replication. The main contributions of this report can be split into four parts....

  8. Autotranspordi TOP aastal 2007

    Index Scriptorium Estoniae

    2008-01-01

    TOP 50. Vt. samas: Käibe TOP 10; Käibe kasvu TOP 10; Kasumi TOP 10; Kasumi kasvu TOP 10; Rentaabluse TOP 10; Omakapitali tootlikkuse TOP 10; Marika Roomere. Täisteenuse pakkumine kergitas tulemusi; Jupiter Plus otsib järjest uusi kasvuvõimalusi; EST-Trans Kaubaveod teenib kasumit toiduvedamisega

  9. Koolitusfirmade TOP aastal 2007

    Index Scriptorium Estoniae

    2008-01-01

    Koolitusfirmade TOP. Vt. samas: Käibe TOP 10; Käibekasvu TOP 10; Kasumi TOP 10; Kasumi kasvu TOP 10; Rentaabluse TOP 10; Omakapitali tootlikkuse TOP 10; Signe Sillasoo. Invicta tahab lähiaastail laieneda Eestis ja mujalgi; Ketlin Priilinn. Addenda kasutas ära majanduse soodsa seisu. Kommenteerib Heli Sõmer. Juhtide hoiakute muutmisega tõus esikolmikusse

  10. Audiitorfirmade TOP aastal 2007

    Index Scriptorium Estoniae

    2008-01-01

    Audiitorfirmade TOP 51. Vt. samas: Urve Vilk. Audiitoriteni pole majanduslangus jõudnud; Intervjuu I.S. Audiitorteenuste OÜ omaniku Irina Somovaga; Käibe TOP 10; Käibe kasvu TOP 10; Kasumi TOP 10; Kasumi kasvu TOP 10; Rentaabluse TOP 10; Omakapitali tootlikkuse TOP 10

  11. Koolitusfirmade TOP aastal 2006

    Index Scriptorium Estoniae

    2007-01-01

    Koolitusfirmade TOP. Vt. samas: Käibe TOP10; Käibe kasvu TOP 10; Kasumi TOP 10; Kasumi kasvu TOP 10; Rentaabluse TOP 10; Varade tootlikkuse TOP 10; Pille Rõivas. Võtmetegur meeskond; Vain & Partnerid: uudsus peitub sisus; Kristo Kiviorg. Teel Baltimaade koolitajate tippu

  12. Top reconstruction and boosted top experimental overview

    CERN Document Server

    Skinnari, Louise

    2015-01-01

    An overview of techniques used to reconstruct resolved and boosted top quarks is presented. Techniques for resolved top quark reconstruction include kinematic likelihood fitters and pseudo- top reconstruction. Many tools and methods are available for the reconstruction of boosted top quarks, such as jet grooming techniques, jet substructure variables, and dedicated top taggers. Different techniques as used by ATLAS and CMS analyses are described and the performance of different variables and top taggers are shown.

  13. Top quark properties at ATLAS

    CERN Document Server

    Dilip, Jana

    2008-01-01

    The ATLAS potential for the study of the top quark properties and physics beyond the Standard Model in the top quark sector, is described. The measurements of the top quark charge, the spin and spin correlations, the Standard Model decay (t-> bW), rare top quark decays associated to flavour changing neutral currents (t-> qX with X = gluon, Z, photon) and ttbar resonances are discussed. The sensitivity of the ATLAS experiment is estimated for an expected luminosity of 1fb-1 at the LHC. The full simulation of the ATLAS detector is used. For the Standard Model measurements the expected precision is presented. For the tests of physics beyond the Standard Model, the 5 sigma discovery potential (in the presence of a signal) and the 95% Confidence Level (CL) limit (in the absence of a signal) are given.

  14. Prelife catalysts and replicators

    OpenAIRE

    Ohtsuki, Hisashi; Nowak, Martin A.

    2009-01-01

    Life is based on replication and evolution. But replication cannot be taken for granted. We must ask what there was prior to replication and evolution. How does evolution begin? We have proposed prelife as a generative system that produces information and diversity in the absence of replication. We model prelife as a binary soup of active monomers that form random polymers. ‘Prevolutionary’ dynamics can have mutation and selection prior to replication. Some sequences might have catalytic acti...

  15. Regulation of beta cell replication

    DEFF Research Database (Denmark)

    Lee, Ying C; Nielsen, Jens Høiriis

    2008-01-01

    Beta cell mass, at any given time, is governed by cell differentiation, neogenesis, increased or decreased cell size (cell hypertrophy or atrophy), cell death (apoptosis), and beta cell proliferation. Nutrients, hormones and growth factors coupled with their signalling intermediates have been...... suggested to play a role in beta cell mass regulation. In addition, genetic mouse model studies have indicated that cyclins and cyclin-dependent kinases that determine cell cycle progression are involved in beta cell replication, and more recently, menin in association with cyclin-dependent kinase...... inhibitors has been demonstrated to be important in beta cell growth. In this review, we consider and highlight some aspects of cell cycle regulation in relation to beta cell replication. The role of cell cycle regulation in beta cell replication is mostly from studies in rodent models, but whether...

  16. Inhibition of Dengue Virus Replication by a Class of Small-Molecule Compounds That Antagonize Dopamine Receptor D4 and Downstream Mitogen-Activated Protein Kinase Signaling

    Science.gov (United States)

    Smith, Jessica L.; Stein, David A.; Shum, David; Fischer, Matthew A.; Radu, Constantin; Bhinder, Bhavneet; Djaballah, Hakim; Nelson, Jay A.; Früh, Klaus

    2014-01-01

    ABSTRACT Dengue viruses (DENV) are endemic pathogens of tropical and subtropical regions that cause significant morbidity and mortality worldwide. To date, no vaccines or antiviral therapeutics have been approved for combating DENV-associated disease. In this paper, we describe a class of tricyclic small-molecule compounds—dihydrodibenzothiepines (DHBTs), identified through high-throughput screening—with potent inhibitory activity against DENV serotype 2. SKI-417616, a highly active representative of this class, displayed activity against all four serotypes of DENV, as well as against a related flavivirus, West Nile virus (WNV), and an alphavirus, Sindbis virus (SINV). This compound was characterized to determine its mechanism of antiviral activity. Investigation of the stage of the viral life cycle affected revealed that an early event in the life cycle is inhibited. Due to the structural similarity of the DHBTs to known antagonists of the dopamine and serotonin receptors, we explored the roles of two of these receptors, serotonin receptor 2A (5HTR2A) and the D4 dopamine receptor (DRD4), in DENV infection. Antagonism of DRD4 and subsequent downstream phosphorylation of epidermal growth factor receptor (EGFR)-related kinase (ERK) were found to impact DENV infection negatively, and blockade of signaling through this network was confirmed as the mechanism of anti-DENV activity for this class of compounds. IMPORTANCE The dengue viruses are mosquito-borne, reemerging human pathogens that are the etiological agents of a spectrum of febrile diseases. Currently, there are no approved therapeutic treatments for dengue-associated disease, nor is there a vaccine. This study identifies a small molecule, SKI-417616, with potent anti-dengue virus activity. Further analysis revealed that SKI-417616 acts through antagonism of the host cell dopamine D4 receptor and subsequent repression of the ERK phosphorylation pathway. These results suggest that SKI-417616, or other

  17. Arvutifirmade TOP 101 aastal 2004

    Index Scriptorium Estoniae

    2005-01-01

    Arvutifirmade TOP 101; Käibe TOP 20; Käibe kasvu TOP 15; Kasumi TOP 15; Rentaabluse TOP 20; Kasumi kasvu TOP 15; Omakapiali tootlikkuse TOP 15; Eesti arvutifirmade finantsandmed; Arvutifirmade üldandmed

  18. Jaekaubanduse TOP 100 aastal 2001

    Index Scriptorium Estoniae

    2002-01-01

    TOP 100. Käibe TOP 30. Käibe kasvu TOP 30. Kasumi TOP 30. Kasumi kasvu TOP 30. Rentaabluse TOP 30. Varade tootlikkuse TOP 30. Jaekaubandusettevõtete finantsseadmed. Jaekaubandusettevõtete üldandmed

  19. Jaekaubandusettevõtete TOP 70

    Index Scriptorium Estoniae

    2005-01-01

    Jaekaubandusettevõtete TOP 70; Käibe TOP 25; Kasumi TOP 25; Käibe kasvu TOP 20; Kasumi kasvu TOP 20; Rentaabluse TOP 20; Omakapitali tootlikkuse TOP 20; Jaekaubandusettevõtete üld- ja finantsandmed

  20. Majutusasutuste TOP 40 aastal 2002

    Index Scriptorium Estoniae

    2003-01-01

    Majutusasutuste TOP 40 aastal 2002. Käibe TOP 40. Kasumi TOP 40. Käibe kasvu TOP 20. Kasumi kasvu TOP 20. Rentaabluse TOP 20. Omakapitali tootlikkuse TOP 20. Majutusasutuste üldandmed. Majutusasutuste finantsandmed

  1. SUMO and KSHV Replication

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Pei-Ching [Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 112, Taiwan (China); Kung, Hsing-Jien, E-mail: hkung@nhri.org.tw [Institute for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan (China); Department of Biochemistry and Molecular Medicine, University of California, Davis, CA 95616 (United States); UC Davis Cancer Center, University of California, Davis, CA 95616 (United States); Division of Molecular and Genomic Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 35053, Taiwan (China)

    2014-09-29

    Small Ubiquitin-related MOdifier (SUMO) modification was initially identified as a reversible post-translational modification that affects the regulation of diverse cellular processes, including signal transduction, protein trafficking, chromosome segregation, and DNA repair. Increasing evidence suggests that the SUMO system also plays an important role in regulating chromatin organization and transcription. It is thus not surprising that double-stranded DNA viruses, such as Kaposi’s sarcoma-associated herpesvirus (KSHV), have exploited SUMO modification as a means of modulating viral chromatin remodeling during the latent-lytic switch. In addition, SUMO regulation allows the disassembly and assembly of promyelocytic leukemia protein-nuclear bodies (PML-NBs), an intrinsic antiviral host defense, during the viral replication cycle. Overcoming PML-NB-mediated cellular intrinsic immunity is essential to allow the initial transcription and replication of the herpesvirus genome after de novo infection. As a consequence, KSHV has evolved a way as to produce multiple SUMO regulatory viral proteins to modulate the cellular SUMO environment in a dynamic way during its life cycle. Remarkably, KSHV encodes one gene product (K-bZIP) with SUMO-ligase activities and one gene product (K-Rta) that exhibits SUMO-targeting ubiquitin ligase (STUbL) activity. In addition, at least two viral products are sumoylated that have functional importance. Furthermore, sumoylation can be modulated by other viral gene products, such as the viral protein kinase Orf36. Interference with the sumoylation of specific viral targets represents a potential therapeutic strategy when treating KSHV, as well as other oncogenic herpesviruses. Here, we summarize the different ways KSHV exploits and manipulates the cellular SUMO system and explore the multi-faceted functions of SUMO during KSHV’s life cycle and pathogenesis.

  2. Uncovering the single top: observation of electroweak top quark production

    Energy Technology Data Exchange (ETDEWEB)

    Benitez, Jorge Armando [Michigan State Univ., East Lansing, MI (United States)

    2009-01-01

    The top quark is generally produced in quark and anti-quark pairs. However, the Standard Model also predicts the production of only one top quark which is mediated by the electroweak interaction, known as 'Single Top'. Single Top quark production is important because it provides a unique and direct way to measure the CKM matrix element Vtb, and can be used to explore physics possibilities beyond the Standard Model predictions. This dissertation presents the results of the observation of Single Top using 2.3 fb-1 of Data collected with the D0 detector at the Fermilab Tevatron collider. The analysis includes the Single Top muon+jets and electron+jets final states and employs Boosted Decision Tress as a method to separate the signal from the background. The resulting Single Top cross section measurement is: (1) σ(p$\\bar{p}$→ tb + X, tqb + X) = 3.74-0.74+0.95 pb, where the errors include both statistical and systematic uncertainties. The probability to measure a cross section at this value or higher in the absence of signal is p = 1.9 x 10-6. This corresponds to a standard deviation Gaussian equivalence of 4.6. When combining this result with two other analysis methods, the resulting cross section measurement is: (2) σ(p$\\bar{p}$ → tb + X, tqb + X) = 3.94 ± 0.88 pb, and the corresponding measurement significance is 5.0 standard deviations.

  3. Molecular Mechanisms of DNA Replication Checkpoint Activation

    Directory of Open Access Journals (Sweden)

    Bénédicte Recolin

    2014-03-01

    Full Text Available The major challenge of the cell cycle is to deliver an intact, and fully duplicated, genetic material to the daughter cells. To this end, progression of DNA synthesis is monitored by a feedback mechanism known as replication checkpoint that is untimely linked to DNA replication. This signaling pathway ensures coordination of DNA synthesis with cell cycle progression. Failure to activate this checkpoint in response to perturbation of DNA synthesis (replication stress results in forced cell division leading to chromosome fragmentation, aneuploidy, and genomic instability. In this review, we will describe current knowledge of the molecular determinants of the DNA replication checkpoint in eukaryotic cells and discuss a model of activation of this signaling pathway crucial for maintenance of genomic stability.

  4. Targeting DNA Replication Stress for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Jun Zhang

    2016-08-01

    Full Text Available The human cellular genome is under constant stress from extrinsic and intrinsic factors, which can lead to DNA damage and defective replication. In normal cells, DNA damage response (DDR mediated by various checkpoints will either activate the DNA repair system or induce cellular apoptosis/senescence, therefore maintaining overall genomic integrity. Cancer cells, however, due to constitutive growth signaling and defective DDR, may exhibit “replication stress” —a phenomenon unique to cancer cells that is described as the perturbation of error-free DNA replication and slow-down of DNA synthesis. Although replication stress has been proven to induce genomic instability and tumorigenesis, recent studies have counterintuitively shown that enhancing replicative stress through further loosening of the remaining checkpoints in cancer cells to induce their catastrophic failure of proliferation may provide an alternative therapeutic approach. In this review, we discuss the rationale to enhance replicative stress in cancer cells, past approaches using traditional radiation and chemotherapy, and emerging approaches targeting the signaling cascades induced by DNA damage. We also summarize current clinical trials exploring these strategies and propose future research directions including the use of combination therapies, and the identification of potential new targets and biomarkers to track and predict treatment responses to targeting DNA replication stress.

  5. DNA replication and cancer

    DEFF Research Database (Denmark)

    Boyer, Anne-Sophie; Walter, David; Sørensen, Claus Storgaard

    2016-01-01

    A dividing cell has to duplicate its DNA precisely once during the cell cycle to preserve genome integrity avoiding the accumulation of genetic aberrations that promote diseases such as cancer. A large number of endogenous impacts can challenge DNA replication and cells harbor a battery of pathways...... causing DNA replication stress and genome instability. Further, we describe cellular and systemic responses to these insults with a focus on DNA replication restart pathways. Finally, we discuss the therapeutic potential of exploiting intrinsic replicative stress in cancer cells for targeted therapy....

  6. Reisifirmade TOP 40 aastal 2002

    Index Scriptorium Estoniae

    2003-01-01

    Reisifirmade TOP 40 aastal 2002. Reisifirmade TOP-i esikümme. Käibe TOP 40. Kasumi TOP 40. Käibe kasvu TOP 20. Kasumi kasvu TOP 20. Rentaabluse TOP 20. Omakapitali tootlikkuse TOP 20. Reisifirmade üldandmed. Reisifirmade finantsandmed. Tehnilise käibe alusel arvutatud edetabelid: Reisifirmade TOP 25; Käibe TOP 40; Rentaabluse TOP 10; Käibe kasvu TOP 10

  7. Activation of human herpesvirus replication by apoptosis.

    Science.gov (United States)

    Prasad, Alka; Remick, Jill; Zeichner, Steven L

    2013-10-01

    A central feature of herpesvirus biology is the ability of herpesviruses to remain latent within host cells. Classically, exposure to inducing agents, like activating cytokines or phorbol esters that stimulate host cell signal transduction events, and epigenetic agents (e.g., butyrate) was thought to end latency. We recently showed that Kaposi's sarcoma-associated herpesvirus (KSHV, or human herpesvirus-8 [HHV-8]) has another, alternative emergency escape replication pathway that is triggered when KSHV's host cell undergoes apoptosis, characterized by the lack of a requirement for the replication and transcription activator (RTA) protein, accelerated late gene kinetics, and production of virus with decreased infectivity. Caspase-3 is necessary and sufficient to initiate the alternative replication program. HSV-1 was also recently shown to initiate replication in response to host cell apoptosis. These observations suggested that an alternative apoptosis-triggered replication program might be a general feature of herpesvirus biology and that apoptosis-initiated herpesvirus replication may have clinical implications, particularly for herpesviruses that almost universally infect humans. To explore whether an alternative apoptosis-initiated replication program is a common feature of herpesvirus biology, we studied cell lines latently infected with Epstein-Barr virus/HHV-4, HHV-6A, HHV-6B, HHV-7, and KSHV. We found that apoptosis triggers replication for each HHV studied, with caspase-3 being necessary and sufficient for HHV replication. An alternative apoptosis-initiated replication program appears to be a common feature of HHV biology. We also found that commonly used cytotoxic chemotherapeutic agents activate HHV replication, which suggests that treatments that promote apoptosis may lead to activation of latent herpesviruses, with potential clinical significance.

  8. Sheep response to sugar cane tops supplemented with varying ...

    African Journals Online (AJOL)

    Twenty WAD sheep averaging 10.14kg were randomly divided into four groups of 5 replicates, and each group was fed sugarcane tops (SCT) supplemented with varying levels (0%, 25%, 50 and 75%) of Leucaena leucocephala foliage (LLF) in a completely randomized design. Results showed that sugarcane tops (SCT) ...

  9. Intergenerational Top Income Persistence

    DEFF Research Database (Denmark)

    Munk, Martin D.; Bonke, Jens; Hussain, M. Azhar

    2016-01-01

    In this paper, we investigate intergenerational top earnings and top income mobility in Denmark. Access to administrative registers allowed us to look at very small fractions of the population. We find that intergenerational mobility is lower in the top when including capital income in the income...... measure— for the rich top 0.1% fathers and sons the elasticity is 0.466. Compared with Sweden, however, the intergenerational top income persistence is about half the size in Denmark....

  10. Replicating animal mitochondrial DNA

    Directory of Open Access Journals (Sweden)

    Emily A. McKinney

    2013-01-01

    Full Text Available The field of mitochondrial DNA (mtDNA replication has been experiencing incredible progress in recent years, and yet little is certain about the mechanism(s used by animal cells to replicate this plasmid-like genome. The long-standing strand-displacement model of mammalian mtDNA replication (for which single-stranded DNA intermediates are a hallmark has been intensively challenged by a new set of data, which suggests that replication proceeds via coupled leading-and lagging-strand synthesis (resembling bacterial genome replication and/or via long stretches of RNA intermediates laid on the mtDNA lagging-strand (the so called RITOLS. The set of proteins required for mtDNA replication is small and includes the catalytic and accessory subunits of DNA polymerase y, the mtDNA helicase Twinkle, the mitochondrial single-stranded DNA-binding protein, and the mitochondrial RNA polymerase (which most likely functions as the mtDNA primase. Mutations in the genes coding for the first three proteins are associated with human diseases and premature aging, justifying the research interest in the genetic, biochemical and structural properties of the mtDNA replication machinery. Here we summarize these properties and discuss the current models of mtDNA replication in animal cells.

  11. Who Needs Replication?

    Science.gov (United States)

    Porte, Graeme

    2013-01-01

    In this paper, the editor of a recent Cambridge University Press book on research methods discusses replicating previous key studies to throw more light on their reliability and generalizability. Replication research is presented as an accepted method of validating previous research by providing comparability between the original and replicated…

  12. Top quark property measurements in single top

    CERN Document Server

    AUTHOR|(INSPIRE)INSPIRE-00386283; The ATLAS collaboration

    2016-01-01

    A review of the recent results on measurements of top quark properties in single top quark processes, performed at the LHC by ATLAS and CMS is presented. The measurements are in good agreement with predictions and no deviations from Standard Model expectations have been observed.

  13. Inhibition of DNA2 nuclease as a therapeutic strategy targeting replication stress in cancer cells.

    Science.gov (United States)

    Kumar, S; Peng, X; Daley, J; Yang, L; Shen, J; Nguyen, N; Bae, G; Niu, H; Peng, Y; Hsieh, H-J; Wang, L; Rao, C; Stephan, C C; Sung, P; Ira, G; Peng, G

    2017-04-17

    Replication stress is a characteristic feature of cancer cells, which is resulted from sustained proliferative signaling induced by activation of oncogenes or loss of tumor suppressors. In cancer cells, oncogene-induced replication stress manifests as replication-associated lesions, predominantly double-strand DNA breaks (DSBs). An essential mechanism utilized by cells to repair replication-associated DSBs is homologous recombination (HR). In order to overcome replication stress and survive, cancer cells often require enhanced HR repair capacity. Therefore, the key link between HR repair and cellular tolerance to replication-associated DSBs provides us with a mechanistic rationale for exploiting synthetic lethality between HR repair inhibition and replication stress. DNA2 nuclease is an evolutionarily conserved essential enzyme in replication and HR repair. Here we demonstrate that DNA2 is overexpressed in pancreatic cancers, one of the deadliest and more aggressive forms of human cancers, where mutations in the KRAS are present in 90-95% of cases. In addition, depletion of DNA2 significantly reduces pancreatic cancer cell survival and xenograft tumor growth, suggesting the therapeutic potential of DNA2 inhibition. Finally, we develop a robust high-throughput biochemistry assay to screen for inhibitors of the DNA2 nuclease activity. The top inhibitors were shown to be efficacious against both yeast Dna2 and human DNA2. Treatment of cancer cells with DNA2 inhibitors recapitulates phenotypes observed upon DNA2 depletion, including decreased DNA double strand break end resection and attenuation of HR repair. Similar to genetic ablation of DNA2, chemical inhibition of DNA2 selectively attenuates the growth of various cancer cells with oncogene-induced replication stress. Taken together, our findings open a new avenue to develop a new class of anticancer drugs by targeting druggable nuclease DNA2. We propose DNA2 inhibition as new strategy in cancer therapy by targeting

  14. Beyond Standard Model searches with top quarks at ATLAS

    International Nuclear Information System (INIS)

    Chevalier, F.

    2008-01-01

    At the Lhc, the top quark is expected to provide a huge and clean signal. With about eight millions of expected top pairs and three millions of single top events produced per year in the low luminosity runs, and with a low level of backgrounds, the Lhc will open a new opportunity for precision measurements of the top quark properties and for exotic topology searches involving top quarks. As the ATLAS discovery potential on new physics with top quarks is being assessed with many analyses, this paper focuses on two particular topics: heavy neutral resonance and charged Higgs boson searches with top quarks. The analyses and the ATLAS expectations are described.

  15. Registered Replication Report

    DEFF Research Database (Denmark)

    Bouwmeester, S.; Verkoeijen, P. P.J.L.; Aczel, B.

    2017-01-01

    and colleagues. The results of studies using time pressure have been mixed, with some replication attempts observing similar patterns (e.g., Rand et al., 2014) and others observing null effects (e.g., Tinghög et al., 2013; Verkoeijen & Bouwmeester, 2014). This Registered Replication Report (RRR) assessed...... the size and variability of the effect of time pressure on cooperative decisions by combining 21 separate, preregistered replications of the critical conditions from Study 7 of the original article (Rand et al., 2012). The primary planned analysis used data from all participants who were randomly assigned...

  16. Audiitorfirmade TOP 50 aastal 2000

    Index Scriptorium Estoniae

    2001-01-01

    Audiitorfirmade käibe TOP 50, käibe kasvu TOP 25, käibe languse TOP 15, kasumi TOP 50, kasumi kasvu TOP 10, kasumi languse TOP 10, audiitorfirmade finantsnäitajad. Rentaabluse TOP 50, varade tootlikkuse TOP 50

  17. The significance of the heavy top quark

    International Nuclear Information System (INIS)

    Simmons, Elizabeth H.

    1997-01-01

    Experiment shows that the top quark is far heavier than the other elementary fermions. This finding has stimulated research on theories of electroweak and flavor symmetry breaking that include physics beyond the standard model. Efforts to accommodate a heavy top quark within existing frameworks have revealed constraints on model-building. Other investigations have started from the premise that a large top quark mass could signal a qualitative difference between the top quark and other fermions, perhaps in the form of new interactions peculiar to the top quark. Such new dynamics may also help answer existing questions about electroweak and flavor physics. This talk explores the implications of the heavy top quark in the context of weakly-coupled (e.g., SUSY) and strongly-coupled (e.g., technicolor) theories of electroweak symmetry breaking

  18. Top Production at LHCb

    CERN Multimedia

    Santana Rangel, Murilo

    2015-01-01

    Single and pair top production in the forward direction at the LHC allows for precision tests of the Standard Model. The observation of top quarks in 7 and 8 TeV data and prospects for precision measurements are shown.

  19. The replication recipe : What makes for a convincing replication?

    NARCIS (Netherlands)

    Brandt, M.J.; IJzerman, H.; Dijksterhuis, Ap; Farach, Frank J.; Geller, Jason; Giner-Sorolla, Roger; Grange, James A.; Perugini, Marco; Spies, Jeffrey R.; van 't Veer, Anna

    Psychological scientists have recently started to reconsider the importance of close replications in building a cumulative knowledge base; however, there is no consensus about what constitutes a convincing close replication study. To facilitate convincing close replication attempts we have developed

  20. The Replication Recipe: What makes for a convincing replication?

    NARCIS (Netherlands)

    Brandt, M.J.; IJzerman, H.; Dijksterhuis, A.J.; Farach, F.J.; Geller, J.; Giner-Sorolla, R.; Grange, J.A.; Perugini, M.; Spies, J.R.; Veer, A. van 't

    2014-01-01

    Psychological scientists have recently started to reconsider the importance of close replications in building a cumulative knowledge base; however, there is no consensus about what constitutes a convincing close replication study. To facilitate convincing close replication attempts we have developed

  1. Eukaryotic DNA Replication Fork.

    Science.gov (United States)

    Burgers, Peter M J; Kunkel, Thomas A

    2017-06-20

    This review focuses on the biogenesis and composition of the eukaryotic DNA replication fork, with an emphasis on the enzymes that synthesize DNA and repair discontinuities on the lagging strand of the replication fork. Physical and genetic methodologies aimed at understanding these processes are discussed. The preponderance of evidence supports a model in which DNA polymerase ε (Pol ε) carries out the bulk of leading strand DNA synthesis at an undisturbed replication fork. DNA polymerases α and δ carry out the initiation of Okazaki fragment synthesis and its elongation and maturation, respectively. This review also discusses alternative proposals, including cellular processes during which alternative forks may be utilized, and new biochemical studies with purified proteins that are aimed at reconstituting leading and lagging strand DNA synthesis separately and as an integrated replication fork.

  2. Modeling DNA Replication.

    Science.gov (United States)

    Bennett, Joan

    1998-01-01

    Recommends the use of a model of DNA made out of Velcro to help students visualize the steps of DNA replication. Includes a materials list, construction directions, and details of the demonstration using the model parts. (DDR)

  3. Chromatin Immunoprecipitation of Replication Factors Moving with the Replication Fork

    OpenAIRE

    Rapp, Jordan B.; Ansbach, Alison B.; Noguchi, Chiaki; Noguchi, Eishi

    2009-01-01

    Replication of chromosomes involves a variety of replication proteins including DNA polymerases, DNA helicases, and other accessory factors. Many of these proteins are known to localize at replication forks and travel with them as components of the replisome complex. Other proteins do not move with replication forks but still play an essential role in DNA replication. Therefore, in order to understand the mechanisms of DNA replication and its controls, it is important to examine localization ...

  4. Top Physics at Atlas

    CERN Document Server

    Romano, M; The ATLAS collaboration

    2013-01-01

    This talk is an overview of recent results on top-quark physics obtained by the ATLAS collaboration from the analysis of p-p collisions at 7 and 8 TeV at the Large Hadron Collider. Total and differential top pair cross section, single top cross section and mass measurements are presented.

  5. CDF Top Physics

    Science.gov (United States)

    Tartarelli, G. F.; CDF Collaboration

    1996-05-01

    The authors present the latest results about top physics obtained by the CDF experiment at the Fermilab Tevatron collider. The data sample used for these analysis (about 110 pb{sup{minus}1}) represents almost the entire statistics collected by CDF during four years (1992--95) of data taking. This large data size has allowed detailed studies of top production and decay properties. The results discussed here include the determination of the top quark mass, the measurement of the production cross section, the study of the kinematics of the top events and a look at top decays.

  6. Turismifirmade 2000. a. TOP 30

    Index Scriptorium Estoniae

    2001-01-01

    Turismiettevõtete üldandmed: turismiettevõtete finantsnäitajad; käibe TOP 30; käibe kasvu TOP 10; kasumi TOP 20; kasumi kasvu TOP 10; kasumi languse TOP; rentaabluse TOP 10; varade tootlikkuse TOP 10

  7. Ehitusmaterjalitootjate TOP 70 aastal 2003

    Index Scriptorium Estoniae

    2004-01-01

    Ilmunud ka: Delovõje Vedomosti : Stroitelstvo, 29. sept. 2004, lk. 2,4. Ehitusmaterjalitootjate TOP 70; Käibe TOP 10; Käibe kasvu TOP 10; Kasumi TOP 10; Kasumi kasvu TOP 10; Rentaabluse TOP 10; Omakapitali tootlikkuse TOP. Ehitusmaterjalitootjate üldandmed

  8. Chromatin Structure and Replication Origins: Determinants Of Chromosome Replication And Nuclear Organization

    Science.gov (United States)

    Smith, Owen K.; Aladjem, Mirit I.

    2014-01-01

    The DNA replication program is, in part, determined by the epigenetic landscape that governs local chromosome architecture and directs chromosome duplication. Replication must coordinate with other biochemical processes occurring concomitantly on chromatin, such as transcription and remodeling, to insure accurate duplication of both genetic and epigenetic features and to preserve genomic stability. The importance of genome architecture and chromatin looping in coordinating cellular processes on chromatin is illustrated by two recent sets of discoveries. First, chromatin-associated proteins that are not part of the core replication machinery were shown to affect the timing of DNA replication. These chromatin-associated proteins could be working in concert, or perhaps in competition, with the transcriptional machinery and with chromatin modifiers to determine the spatial and temporal organization of replication initiation events. Second, epigenetic interactions are mediated by DNA sequences that determine chromosomal replication. In this review we summarize recent findings and current models linking spatial and temporal regulation of the replication program with epigenetic signaling. We discuss these issues in the context of the genome’s three-dimensional structure with an emphasis on events occurring during the initiation of DNA replication. PMID:24905010

  9. Observation of the Top Quark

    Science.gov (United States)

    Kim, S. B.

    1995-08-01

    Top quark production is observed in{bar p}p collisions at{radical}s= 1.8 TeV at the Fermilab Tevatron. The Collider Detector at Fermilab (CDF) and D{O} observe signals consistent with t{bar t} to WWb{bar b}, but inconsistent with the background prediction by 4.8{sigma} (CDF), 4.6a (D{O}). Additional evidence for the top quark Is provided by a peak in the reconstructed mass distribution. The kinematic properties of the excess events are consistent with the top quark decay. They measure the top quark mass to be 176{plus_minus}8(stat.){plus_minus}10(sys.) GeV/c{sup 2} (CDF), 199{sub -21}{sup+19}(stat.){plus_minus}22(sys.) GeV/c{sup 2} (D{O}), and the t{bar t} production cross section to be 6.8{sub -2.4}{sup+3.6}pb (CDF), 6.4{plus_minus}2.2 pb (D{O}).

  10. Top searches and R-parity violation at hadron colliders

    International Nuclear Information System (INIS)

    Dreiner, H.

    1991-07-01

    In R p -violating supersymmetric theories there are new 2-body top quark decays which can substantially suppress the branching fraction of the Standard Model process t → bW + → bl + υ 1 . With some choices of the dominant R p -violating operator the CDF top-quark mass bound can be lowered below the LEP bound. With other choices, however, leptonic signals from top decay become much stronger; in such scenarios the bounds on the top quark mass become more stringent than the Standard Model bounds. In future top quark searches R p -violating decays could lead to the most prominent signals. (author)

  11. Search for single top production at HERA

    International Nuclear Information System (INIS)

    Brandt, G.

    2008-01-01

    A search for single top production in e p collisions using the complete high-energy data from HERA is presented. This search is based on the analysis of events containing isolated leptons (electronic or muons) and missing transverse momentum P T miss . In the absence of a signal, an upper limit on the top production cross-section σ ep→etX tuγ T miss and the measurements of W boson polarisation fractions.

  12. TOP LINAC design; Progetto del TOP LINAC

    Energy Technology Data Exchange (ETDEWEB)

    Picardi, L; Ronsivalle, C; Vignati, A [ENEA, Centro Ricerche Frascati, Rome (Italy). Dip. Innovazione

    1997-11-01

    The report describes a linear accelerator for protons named TOP LINAC designed for the TOP (Terapia Oncologica con Protoni, Oncological Protontherapy) project launched by the Italian National Institute of Health (Istituto Superiore di Sanita`, ISS) to explore in collaboration with the biggest Oncological Hospital in Rome (Istituto Regina Elena, IRE) the potentialities of the therapy with accelerated protons and establish guide lines for the application of this new type of radiotherapy in comparison with the more traditional electron and x-rays radiotherapy. The concept of a compact accelerator for protontherapy applications bore within the Italian Hadrontherapy Collaboration (TERA Collaboration) with the aim to diffuse the protontherapy on the National territory. The ISS program plans to use the TOP linac proton beam also for production of PET (Positron Emission Tomography) radioisotopes and radiobiology studies. Official agreements are in course between ISS and ENEA which provides its experience in the industrial and medical accelerators for the design and the construction of the TOP linac. The accelerator that will be the first 3 GHz proton linac in the world, will be composed of a 428.3 MHz 7 Me V RFQ + DTL injector followed by a 7-65 Me V section of a 3 GHz SCDTL structure and a 65 - 200 Me V variable energy SCL 3 GHz structure. In particular the SCDTL section uses a highly innovative accelerating structure patented by ENEA. In this report the clinical and physical requests are discussed and a preliminary design of the whole machine is given.

  13. Top quark pair production in ATLAS

    CERN Document Server

    Moreno Llacer, M; The ATLAS collaboration

    2010-01-01

    Top-quark pairs are expected to be produced at the LHC, even at the lower beam energy and luminosity in the first years of running. Establishing the top-pair signal and measuring the production cross-section are important benchmarks for ATLAS, and will help understand the detector performance for events with high-pT leptons, high jet multiplicity, missing transverse energy. The prospects for early top physics measurements will be shown, with a particular emphasis on the progress achieved with data so far.

  14. Evolution of Replication Machines

    Science.gov (United States)

    Yao, Nina Y.; O'Donnell, Mike E.

    2016-01-01

    The machines that decode and regulate genetic information require the translation, transcription and replication pathways essential to all living cells. Thus, it might be expected that all cells share the same basic machinery for these pathways that were inherited from the primordial ancestor cell from which they evolved. A clear example of this is found in the translation machinery that converts RNA sequence to protein. The translation process requires numerous structural and catalytic RNAs and proteins, the central factors of which are homologous in all three domains of life, bacteria, archaea and eukarya. Likewise, the central actor in transcription, RNA polymerase, shows homology among the catalytic subunits in bacteria, archaea and eukarya. In contrast, while some “gears” of the genome replication machinery are homologous in all domains of life, most components of the replication machine appear to be unrelated between bacteria and those of archaea and eukarya. This review will compare and contrast the central proteins of the “replisome” machines that duplicate DNA in bacteria, archaea and eukarya, with an eye to understanding the issues surrounding the evolution of the DNA replication apparatus. PMID:27160337

  15. Replication studies in longevity

    DEFF Research Database (Denmark)

    Varcasia, O; Garasto, S; Rizza, T

    2001-01-01

    In Danes we replicated the 3'APOB-VNTR gene/longevity association study previously carried out in Italians, by which the Small alleles (less than 35 repeats) had been identified as frailty alleles for longevity. In Danes, neither genotype nor allele frequencies differed between centenarians and 20...

  16. Ekspedeerimisettevõtete TOP 50

    Index Scriptorium Estoniae

    2006-01-01

    Ilmunud ka: Delovõje Vedomosti : Transport i Logistika nr. 11, 29. nov. lk. 32-35. Ekspedeerimisettevõtete TOP. Vt. samas: Käibe TOP 10; Käibekasvu TOP 10; Kasumi TOP 10; Kasumikasvu TOP 10; Rentaabluse TOP 10; ROE TOP 10; Ekspedeerimisettevõtete üld- ja finantsandmed. Ajal. Delovõje Vedomosti : Transport i Logistika toodud ainult Ekspedeerimisettevõtete TOP 50

  17. Top Quark Physics

    International Nuclear Information System (INIS)

    Larios, F.

    2006-01-01

    We give an overview of the physics of the Top quark, from the experimental discovery to the studies of its properties. We review some of the work done on the Electroweak and Flavor Changing couplings associated with the Top quark in the Standard Model and beyond. We will focus on the specific contribution of phycisits working in Mexico and Mexican physicists working abroad

  18. Top quark theory

    NARCIS (Netherlands)

    Laenen, E.

    2012-01-01

    The theoretical aspects of a number of top quark properties such as its mass and its couplings are reviewed. Essential aspects in the theoretical description of top quark production, singly, in pairs and in association, as well as its decay related to spin and angular correlations are discussed.

  19. Top Quark Mass

    CERN Document Server

    Mulders, Martijn

    2016-01-01

    Ever since the discovery of the top quark at the Tevatron collider in 1995 the measurement of its mass has been a high priority. As one of the fundamental parameters of the Standard Theory of particle physics, the precise value of the top quark mass together with other inputs provides a test for the self-consistency of the theory, and has consequences for the stability of the Higgs field that permeates the Universe. In this review I will briefly summarize the experimental techniques used at the Tevatron and the LHC experiments throughout the years to measure the top quark mass with ever improving accuracy, and highlight the recent progress in combining all measurements in a single world average combination. As experimental measurements became more precise, the question of their theoretical interpretation has become important. The difficulty of relating the measured quantity to the fundamental top mass parameter has inspired alternative measurement methods that extract the top mass in complementary ways. I wil...

  20. Measurement of the Top Quark Mass in Dilepton Final States with the Neutrino Weighting Method

    Energy Technology Data Exchange (ETDEWEB)

    Ilchenko, Yuriy [Southern Methodist Univ., Dallas, TX (United States)

    2012-12-15

    The top quark is the heaviest fundamental particle observed to date. The mass of the top quark is a free parameter in the Standard Model (SM). A precise measurement of its mass is particularly important as it sets an indirect constraint on the mass of the Higgs boson. It is also a useful constraint on contributions from physics beyond the SM and may play a fundamental role in the electroweak symmetry breaking mechanism. I present a measurement of the top quark mass in the dilepton channel using the Neutrino Weighting Method. The data sample corresponds to an integrated luminosity of 4.3 fb-1 of p$\\bar{p}$ collisions at Tevatron with √s = 1.96 TeV, collected with the DØ detector. Kinematically under-constrained dilepton events are analyzed by integrating over neutrino rapidity. Weight distributions of t$\\bar{t}$ signal and background are produced as a function of the top quark mass for different top quark mass hypotheses. The measurement is performed by constructing templates from the moments of the weight distributions and input top quark mass, followed by a subsequent likelihood t to data. The dominant systematic uncertainties from jet energy calibration is reduced by using a correction from `+jets channel. To replicate the quark avor dependence of the jet response in data, jets in the simulated events are additionally corrected. The result is combined with our preceding measurement on 1 fb-1 and yields mt = 174.0± 2.4 (stat.) ±1.4 (syst.) GeV.

  1. Discovery of single top quark production

    Energy Technology Data Exchange (ETDEWEB)

    Gillberg, Dag [Simon Fraser Univ., Burnaby, BC (Canada)

    2009-04-01

    The top quark is by far the heaviest known fundamental particle with a mass nearing that of a gold atom. Because of this strikingly high mass, the top quark has several unique properties and might play an important role in electroweak symmetry breaking - the mechanism that gives all elementary particles mass. Creating top quarks requires access to very high energy collisions, and at present only the Tevatron collider at Fermilab is capable of reaching these energies. Until now, top quarks have only been observed produced in pairs via the strong interaction. At hadron colliders, it should also be possible to produce single top quarks via the electroweak interaction. Studies of single top quark production provide opportunities to measure the top quark spin, how top quarks mix with other quarks, and to look for new physics beyond the standard model. Because of these interesting properties, scientists have been looking for single top quarks for more than 15 years. This thesis presents the first discovery of single top quark production. An analysis is performed using 2.3 fb-1 of data recorded by the D0 detector at the Fermilab Tevatron Collider at centre-of-mass energy √s = 1.96 TeV. Boosted decision trees are used to isolate the single top signal from background, and the single top cross section is measured to be σ(p$\\bar{p}$ → tb + X, tqb + X) = 3.74-0.74+0.95 pb. Using the same analysis, a measurement of the amplitude of the CKM matrix element Vtb, governing how top and b quarks mix, is also performed. The measurement yields: |V{sub tb}|f1L| = 1.05 -0.12+0.13, where f1L is the left-handed Wtb coupling. The separation of signal from background is improved by combining the boosted decision trees with two other multivariate techniques. A new cross section measurement is performed, and the significance for the excess over the predicted background exceeds 5

  2. Top physics in WHIZARD

    Energy Technology Data Exchange (ETDEWEB)

    Reuter, Juergen; Chokoufe Nejad, Bijan [DESY, Hamburg (Germany). Theory Group; Bach, Fabian [European Commission, Eurostat, Luxembourg (Luxembourg); Hoang, Andre [Vienna Univ. (Austria). Faculty of Physics; Vienna Univ. (Austria). Erwin Schroedinger International Inst. for Mathematical Physics; Kilian, Wolfgang [Siegen Univ. (Germany); Stahlhofen, Maximilian [Mainz Univ. (Germany). PRISMA Cluster of Excellence; Teubner, Thomas [Liverpool Univ. (United Kingdom). Dept. of Mathematical Sciences; Weiss, Christian [DESY, Hamburg (Germany). Theory Group; Siegen Univ. (Germany)

    2016-03-15

    In this talk we summarize the top physics setup in the event generator WHIZARD with a main focus on lepton colliders. This includes full six-, eight- and ten-fermion processes, factorized processes and spin correlations. For lepton colliders, QCD NLO processes for top quark physics are available and discussed. A special focus is on the top-quark pair threshold, where a special implementation combines a non-relativistic effective field theory calculation augmented by a next-to-leading threshold logarithm resummation with a continuum relativistic fixed-order QCD NLO simulation.

  3. Top physics in WHIZARD

    International Nuclear Information System (INIS)

    Reuter, Juergen; Chokoufe Nejad, Bijan; Hoang, Andre; Stahlhofen, Maximilian

    2016-03-01

    In this talk we summarize the top physics setup in the event generator WHIZARD with a main focus on lepton colliders. This includes full six-, eight- and ten-fermion processes, factorized processes and spin correlations. For lepton colliders, QCD NLO processes for top quark physics are available and discussed. A special focus is on the top-quark pair threshold, where a special implementation combines a non-relativistic effective field theory calculation augmented by a next-to-leading threshold logarithm resummation with a continuum relativistic fixed-order QCD NLO simulation.

  4. Transmissible Gastroenteritis Coronavirus Genome Packaging Signal Is Located at the 5′ End of the Genome and Promotes Viral RNA Incorporation into Virions in a Replication-Independent Process

    OpenAIRE

    Morales, Lucia; Mateos-Gomez, Pedro A.; Capiscol, Carmen; del Palacio, Lorena; Enjuanes, Luis; Sola, Isabel

    2013-01-01

    Preferential RNA packaging in coronaviruses involves the recognition of viral genomic RNA, a crucial process for viral particle morphogenesis mediated by RNA-specific sequences, known as packaging signals. An essential packaging signal component of transmissible gastroenteritis coronavirus (TGEV) has been further delimited to the first 598 nucleotides (nt) from the 5′ end of its RNA genome, by using recombinant viruses transcribing subgenomic mRNA that included potential packaging signals. Th...

  5. Audiitorite TOP 50 aastal 2005

    Index Scriptorium Estoniae

    2006-01-01

    Audiitorite TOP. Vt. samas: Käibe TOP 10; Käibe kasvu TOP 10; Kasumi TOP 10; Kasumi kasvu TOP 10; Rentaabluse TOP 10; ROE TOP 10; Ketlin Priilinn. Kasvu tagavad lojaalsed kliendid; Klient on audiitori parim müügimees; Teeli Remmelg. Kliendid vaatavad pigem kvaliteeti kui madalat hinda. Kommenteerivad Signe Keernik ja Kalle Lahe. Tabel: Audiitoriettevõtete üld- ja finantsandmed

  6. FBH1 Catalyzes Regression of Stalled Replication Forks

    Directory of Open Access Journals (Sweden)

    Kasper Fugger

    2015-03-01

    Full Text Available DNA replication fork perturbation is a major challenge to the maintenance of genome integrity. It has been suggested that processing of stalled forks might involve fork regression, in which the fork reverses and the two nascent DNA strands anneal. Here, we show that FBH1 catalyzes regression of a model replication fork in vitro and promotes fork regression in vivo in response to replication perturbation. Cells respond to fork stalling by activating checkpoint responses requiring signaling through stress-activated protein kinases. Importantly, we show that FBH1, through its helicase activity, is required for early phosphorylation of ATM substrates such as CHK2 and CtIP as well as hyperphosphorylation of RPA. These phosphorylations occur prior to apparent DNA double-strand break formation. Furthermore, FBH1-dependent signaling promotes checkpoint control and preserves genome integrity. We propose a model whereby FBH1 promotes early checkpoint signaling by remodeling of stalled DNA replication forks.

  7. Mechanisms of DNA replication termination.

    Science.gov (United States)

    Dewar, James M; Walter, Johannes C

    2017-08-01

    Genome duplication is carried out by pairs of replication forks that assemble at origins of replication and then move in opposite directions. DNA replication ends when converging replication forks meet. During this process, which is known as replication termination, DNA synthesis is completed, the replication machinery is disassembled and daughter molecules are resolved. In this Review, we outline the steps that are likely to be common to replication termination in most organisms, namely, fork convergence, synthesis completion, replisome disassembly and decatenation. We briefly review the mechanism of termination in the bacterium Escherichia coli and in simian virus 40 (SV40) and also focus on recent advances in eukaryotic replication termination. In particular, we discuss the recently discovered E3 ubiquitin ligases that control replisome disassembly in yeast and higher eukaryotes, and how their activity is regulated to avoid genome instability.

  8. Jõgevamaa ettevõtete TOP 55

    Index Scriptorium Estoniae

    2004-01-01

    Jõgevamaa ettevõtete TOP 55 aastal 2003. Käibe TOP 40. Kasumi TOP 40. Käibe kasvu TOP 20. Kasumi kasvu TOP 20. Rentaabluse TOP 20. Omakapitali tootlikkuse TOP 20. Jõgevamaa firmade üld- ja finantsandmed

  9. Põlvamaa ettevõtete TOP 50

    Index Scriptorium Estoniae

    2004-01-01

    Ettevõtete TOP 50. Käibe TOP 40. Kasumi TOP 40. Käibe kasvu TOP 20. Kasumi kasvu TOP 20. Rentaabluse TOP 20. Omakapitali tootlikkuse TOP 20. Põlvamaa firmade üldandmed. Põlvamaa firmade finantsandmed

  10. Viljandimaa ettevõtete TOP 50

    Index Scriptorium Estoniae

    2005-01-01

    Viljandimaa ettevõtete TOP 50; Käibe TOP 35; Kasumi TOP 35; Käibe kasvu TOP 20; Kasumi kasvu TOP 20; Rentaabluse TOP 20; Omakapitali tootlikkuse TOP 20; Viljandimaa ettevõtete üld- ja finantsandmed

  11. Jõgevamaa ettevõtete TOP 50

    Index Scriptorium Estoniae

    2005-01-01

    Jõgevamaa ettevõtete TOP 50; Käibe TOP 35; Kasumi TOP 35; Käibe kasvu TOP 20; Kasumi kasvu TOP 20; Rentaabluse TOP 20; Omakapitali tootlikkuse TOP 20; Jõgevamaa ettevõtete üld- ja finantsandmed

  12. Telekommunikatsiooni & arvutitootjate TOP

    Index Scriptorium Estoniae

    2006-01-01

    Telekommunikatsiooni TOP 30. Tabelid. Vt. samas: Indrek Kald. Elisa ka tänavu esikohal; Väike Tele2 võidab paindlikkusest; Kernel läks üle piiri. Diagrammid. Arvutifirmade TOP 100. Tabelid. Vt. samas: Enn Heinsoo. Esikoha tõi kontori müük; Proeksperdil suund välisturgudele;¡ Ida-Eesti turg arenevale firmale kitsas. Diagrammid. Nimekiri: Omanikud

  13. Chromatin replication and epigenome maintenance

    DEFF Research Database (Denmark)

    Alabert, Constance; Groth, Anja

    2012-01-01

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

  14. Top quark mass measurement in dilepton channel

    International Nuclear Information System (INIS)

    Lysak, R.

    2007-01-01

    In this work, we measured the top quark mass in tt'-' events produced in pp'-' interactions at the center-of-mass energy 1.96 TeV using CDF detector. We used dilepton in tt'-' events where both W bosons from top quarks are decaying into leptons. The data sample corresponds to 340 pb -1 . We found there 33 tt'-' candidates while expecting 10.5 ± 1.9 background events. In the measurement, we reconstruct one, representative mass for each event using the assumption about longitudinal momentum of in tt'-' system, in order to be able to kinematically solve the under-constrained system. The mass distributions (templates) are created for simulated signal and background events. Templates are parametrized in order to obtain smooth probability density functions. Likelihood maximization which includes these parametrized templates is then performed on reconstructed masses obtained from data sample in order to obtain final top quark mass estimate. The result of applying this procedure on data events is top quark mass estimate 169.5 +7. 7 - 7.2 (stat.) ± 4.0(syst.) GeV/c 2 for 30 out of 33 candidates, where the solution for top quark mass was found. This measurement was a part of first top quark mass measurement in dilepton channel at CDF in Run II. The top quark mass measured here is consistent with the CDF measurement in dilepton channel from Run I M top = 167.4 ± 10.3(stat.) ± 4.8(syst.) GeV/c 2 . Moreover, the combined result of four top quark mass measurements in dilepton channel from Run II (one of these four measurements is our measurement) M top = 167.9 ± 5.2(stat.) ± 3.7(syst.) GeV/c 2 significantly (by ∼ 40%) improved the precision of top quark mass determination from Run I. It should be also noted, that this combined result is consistent with measurement obtained in 'lepton+jets' channel at CDF in Run II (M top = 173.5 +3.9 -3.8 GeV/c 2 ). So, we don't have yet any indication about new physics beyond the Standard Model. My main contribution in this analysis was

  15. Replication Research and Special Education

    Science.gov (United States)

    Travers, Jason C.; Cook, Bryan G.; Therrien, William J.; Coyne, Michael D.

    2016-01-01

    Replicating previously reported empirical research is a necessary aspect of an evidence-based field of special education, but little formal investigation into the prevalence of replication research in the special education research literature has been conducted. Various factors may explain the lack of attention to replication of special education…

  16. Top Quark Mass Measurement in Dilepton Channel

    Energy Technology Data Exchange (ETDEWEB)

    Lysak, Roman [Inst. of Experimental Physics, Kosice (Slovak Republic)

    2007-06-01

    We present a measurement of the top quark mass from events produced in p$\\bar{p}$ collisions at a center-of-mass energy of 1.96 TeV, using the Collider Detector at Fermilab. We identify t$\\bar{t}$ candidates where both W bosons from the top quarks decay into leptons (eν, µν, τν) from a data sample of 340 pb-1. The top quark mass is reconstructed in each event separately by the method which draw upon simulated distribution of t$\\bar{t}$ longitudinal momentum in order to extract probability distribution for the top quark mass. Representative distributions, or templates, are constructed from simulated samples of signal and background events, and parametrized to form continuous probability density functions. A likelihood fit incorporating these parametrized templates is then performed on the data sample masses in order to derive a final top quark mass. Measured top quark mass is Mtop = 169.5$+7.7\\atop{-7.2}$(stat.) ± 4.0(syst.) GeV/c2.

  17. Measurement of the Mass Difference Between Top and Anti-top Quarks at CDF

    CERN Document Server

    Aaltonen, T.; Amerio, S.; Amidei, D.; Anastassov, A.; Annovi, A.; Antos, J.; Apollinari, G.; Appel, J.A.; Arisawa, T.; Artikov, A.; Asaadi, J.; Ashmanskas, W.; Auerbach, B.; Aurisano, A.; Azfar, F.; Badgett, W.; Bae, T.; Barbaro-Galtieri, A.; Barnes, V.E.; Barnett, B.A.; Barria, P.; Bartos, P.; Bauce, M.; Bedeschi, F.; Behari, S.; Bellettini, G.; Bellinger, J.; Benjamin, D.; Beretvas, A.; Bhatti, A.; Bisello, D.; Bizjak, I.; Bland, K.R.; Blumenfeld, B.; Bocci, A.; Bodek, A.; Bortoletto, D.; Boudreau, J.; Boveia, A.; Brigliadori, L.; Bromberg, C.; Brucken, E.; Budagov, J.; Budd, H.S.; Burkett, K.; Busetto, G.; Bussey, P.; Buzatu, A.; Calamba, A.; Calancha, C.; Camarda, S.; Campanelli, M.; Campbell, M.; Canelli, F.; Carls, B.; Carlsmith, D.; Carosi, R.; Carrillo, S.; Carron, S.; Casal, B.; Casarsa, M.; Castro, A.; Catastini, P.; Cauz, D.; Cavaliere, V.; Cavalli-Sforza, M.; Cerri, A.; Cerrito, L.; Chen, Y.C.; Chertok, M.; Chiarelli, G.; Chlachidze, G.; Chlebana, F.; Cho, K.; Chokheli, D.; Chung, W.H.; Chung, Y.S.; Ciocci, M.A.; Clark, A.; Clarke, C.; Compostella, G.; Convery, M.E.; Conway, J.; Corbo, M.; Cordelli, M.; Cox, C.A.; Cox, D.J.; Crescioli, F.; Cuevas, J.; Culbertson, R.; Dagenhart, D.; d'Ascenzo, N.; Datta, M.; de Barbaro, P.; Dell'Orso, M.; Demortier, L.; Deninno, M.; Devoto, F.; d'Errico, M.; Di Canto, A.; Di Ruzza, B.; Dittmann, J.R.; D'Onofrio, M.; Donati, S.; Dong, P.; Dorigo, M.; Dorigo, T.; Ebina, K.; Elagin, A.; Eppig, A.; Erbacher, R.; Errede, S.; Ershaidat, N.; Eusebi, R.; Farrington, S.; Feindt, M.; Fernandez, J.P.; Field, R.; Flanagan, G.; Forrest, R.; Frank, M.J.; Franklin, M.; Freeman, J.C.; Funakoshi, Y.; Furic, I.; Gallinaro, M.; Garcia, J.E.; Garfinkel, A.F.; Garosi, P.; Gerberich, H.; Gerchtein, E.; Giagu, S.; Giakoumopoulou, V.; Giannetti, P.; Gibson, K.; Ginsburg, C.M.; Giokaris, N.; Giromini, P.; Giurgiu, G.; Glagolev, V.; Glenzinski, D.; Gold, M.; Goldin, D.; Goldschmidt, N.; Golossanov, A.; Gomez, G.; Gomez-Ceballos, G.; Goncharov, M.; Gonzalez, O.; Gorelov, I.; Goshaw, A.T.; Goulianos, K.; Grinstein, S.; Grosso-Pilcher, C.; Group, R.C.; Guimaraes da Costa, J.; Hahn, S.R.; Halkiadakis, E.; Hamaguchi, A.; Han, J.Y.; Happacher, F.; Hara, K.; Hare, D.; Hare, M.; Harr, R.F.; Hatakeyama, K.; Hays, C.; Heck, M.; Heinrich, J.; Herndon, M.; Hewamanage, S.; Hocker, A.; Hopkins, W.; Horn, D.; Hou, S.; Hughes, R.E.; Hurwitz, M.; Husemann, U.; Hussain, N.; Hussein, M.; Huston, J.; Introzzi, G.; Iori, M.; Ivanov, A.; James, E.; Jang, D.; Jayatilaka, B.; Jeon, E.J.; Jindariani, S.; Jones, M.; Joo, K.K.; Jun, S.Y.; Junk, T.R.; Kamon, T.; Karchin, P.E.; Kasmi, A.; Kato, Y.; Ketchum, W.; Keung, J.; Khotilovich, V.; Kilminster, B.; Kim, D.H.; Kim, H.S.; Kim, J.E.; Kim, M.J.; Kim, S.B.; Kim, S.H.; Kim, Y.K.; Kim, Y.J.; Kimura, N.; Kirby, M.; Klimenko, S.; Knoepfel, K.; Kondo, K.; Kong, D.J.; Konigsberg, J.; Kotwal, A.V.; Kreps, M.; Kroll, J.; Krop, D.; Kruse, M.; Krutelyov, V.; Kuhr, T.; Kurata, M.; Kwang, S.; Laasanen, A.T.; Lami, S.; Lammel, S.; Lancaster, M.; Lander, R.L.; Lannon, K.; Lath, A.; Latino, G.; LeCompte, T.; Lee, E.; Lee, H.S.; Lee, J.S.; Lee, S.W.; Leo, S.; Leone, S.; Lewis, J.D.; Limosani, A.; Lin, C.J.; Lindgren, M.; Lipeles, E.; Lister, A.; Litvintsev, D.O.; Liu, C.; Liu, H.; Liu, Q.; Liu, T.; Lockwitz, S.; Loginov, A.; Lucchesi, D.; Lueck, J.; Lujan, P.; Lukens, P.; Lungu, G.; Lys, J.; Lysak, R.; Madrak, R.; Maeshima, K.; Maestro, P.; Malik, S.; Manca, G.; Manousakis-Katsikakis, A.; Margaroli, F.; Marino, C.; Martinez, M.; Mastrandrea, P.; Matera, K.; Mattson, M.E.; Mazzacane, A.; Mazzanti, P.; McFarland, K.S.; McIntyre, P.; McNulty, R.; Mehta, A.; Mehtala, P.; Mesropian, C.; Miao, T.; Mietlicki, D.; Mitra, A.; Miyake, H.; Moed, S.; Moggi, N.; Mondragon, M.N.; Moon, C.S.; Moore, R.; Morello, M.J.; Morlock, J.; Movilla Fernandez, P.; Mukherjee, A.; Muller, Th.; Murat, P.; Mussini, M.; Nachtman, J.; Nagai, Y.; Naganoma, J.; Nakano, I.; Napier, A.; Nett, J.; Neu, C.; Neubauer, M.S.; Nielsen, J.; Nodulman, L.; Noh, S.Y.; Norniella, O.; Oakes, L.; Oh, S.H.; Oh, Y.D.; Oksuzian, I.; Okusawa, T.; Orava, R.; Ortolan, L.; Pagan Griso, S.; Pagliarone, C.; Palencia, E.; Papadimitriou, V.; Paramonov, A.A.; Patrick, J.; Pauletta, G.; Paulini, M.; Paus, C.; Pellett, D.E.; Penzo, A.; Phillips, T.J.; Piacentino, G.; Pianori, E.; Pilot, J.; Pitts, K.; Plager, C.; Pondrom, L.; Poprocki, S.; Potamianos, K.; Prokoshin, F.; Pranko, A.; Ptohos, F.; Punzi, G.; Rahaman, A.; Ramakrishnan, V.; Ranjan, N.; Redondo, I.; Renton, P.; Rescigno, M.; Riddick, T.; Rimondi, F.; Ristori, L.; Robson, A.; Rodrigo, T.; Rodriguez, T.; Rogers, E.; Rolli, S.; Roser, R.; Ruffini, F.; Ruiz, A.; Russ, J.; Rusu, V.; Safonov, A.; Sakumoto, W.K.; Sakurai, Y.; Santi, L.; Sato, K.; Saveliev, V.; Savoy-Navarro, A.; Schlabach, P.; Schmidt, A.; Schmidt, E.E.; Schwarz, T.; Scodellaro, L.; Scribano, A.; Scuri, F.; Seidel, S.; Seiya, Y.; Semenov, A.; Sforza, F.; Shalhout, S.Z.; Shears, T.; Shepard, P.F.; Shimojima, M.; Shochet, M.; Shreyber-Tecker, I.; Simonenko, A.; Sinervo, P.; Sliwa, K.; Smith, J.R.; Snider, F.D.; Soha, A.; Sorin, V.; Song, H.; Squillacioti, P.; Stancari, M.; St. Denis, R.; Stelzer, B.; Stelzer-Chilton, O.; Stentz, D.; Strologas, J.; Strycker, G.L.; Sudo, Y.; Sukhanov, A.; Suslov, I.; Takemasa, K.; Takeuchi, Y.; Tang, J.; Tecchio, M.; Teng, P.K.; Thom, J.; Thome, J.; Thompson, G.A.; Thomson, E.; Toback, D.; Tokar, S.; Tollefson, K.; Tomura, T.; Tonelli, D.; Torre, S.; Torretta, D.; Totaro, P.; Trovato, M.; Ukegawa, F.; Uozumi, S.; Varganov, A.; Vazquez, F.; Velev, G.; Vellidis, C.; Vidal, M.; Vila, I.; Vilar, R.; Vizan, J.; Vogel, M.; Volpi, G.; Wagner, P.; Wagner, R.L.; Wakisaka, T.; Wallny, R.; Wang, S.M.; Warburton, A.; Waters, D.; Wester, W.C., III; Whiteson, D.; Wicklund, A.B.; Wicklund, E.; Wilbur, S.; Wick, F.; Williams, H.H.; Wilson, J.S.; Wilson, P.; Winer, B.L.; Wittich, P.; Wolbers, S.; Wolfe, H.; Wright, T.; Wu, X.; Wu, Z.; Yamamoto, K.; Yamato, D.; Yang, T.; Yang, U.K.; Yang, Y.C.; Yao, W.M.; Yeh, G.P.; Yi, K.; Yoh, J.; Yorita, K.; Yoshida, T.; Yu, G.B.; Yu, I.; Yu, S.S.; Yun, J.C.; Zanetti, A.; Zeng, Y.; Zhou, C.; Zucchelli, S.

    2013-03-18

    We present a measurement of the mass difference between top ($t$) and anti-top ($\\bar{t}$) quarks using $t\\bar{t}$ candidate events reconstructed in the final state with one lepton and multiple jets. We use the full data set of Tevatron $\\sqrt{s} = 1.96$ TeV proton-antiproton collisions recorded by the CDF II detector, corresponding to an integrated luminosity of 8.7 fb$^{-1}$. We estimate event-by-event the mass difference to construct templates for top-quark signal events and background events. The resulting mass difference distribution of data compared to signal and background templates using a likelihood fit yields $\\Delta M_{top} = {M}_{t} - {M}_{\\bar{t}} = -1.95 $pm$ 1.11 (stat) $pm$ 0.59 (syst)$ and is in agreement with the standard model prediction of no mass difference.

  18. International Expansion through Flexible Replication

    DEFF Research Database (Denmark)

    Jonsson, Anna; Foss, Nicolai Juul

    2011-01-01

    Business organizations may expand internationally by replicating a part of their value chain, such as a sales and marketing format, in other countries. However, little is known regarding how such “international replicators” build a format for replication, or how they can adjust it in order to ada......, etc.) are replicated in a uniform manner across stores, and change only very slowly (if at all) in response to learning (“flexible replication”). We conclude by discussing the factors that influence the approach to replication adopted by an international replicator.......Business organizations may expand internationally by replicating a part of their value chain, such as a sales and marketing format, in other countries. However, little is known regarding how such “international replicators” build a format for replication, or how they can adjust it in order to adapt...

  19. Modeling inhomogeneous DNA replication kinetics.

    Directory of Open Access Journals (Sweden)

    Michel G Gauthier

    Full Text Available In eukaryotic organisms, DNA replication is initiated at a series of chromosomal locations called origins, where replication forks are assembled proceeding bidirectionally to replicate the genome. The distribution and firing rate of these origins, in conjunction with the velocity at which forks progress, dictate the program of the replication process. Previous attempts at modeling DNA replication in eukaryotes have focused on cases where the firing rate and the velocity of replication forks are homogeneous, or uniform, across the genome. However, it is now known that there are large variations in origin activity along the genome and variations in fork velocities can also take place. Here, we generalize previous approaches to modeling replication, to allow for arbitrary spatial variation of initiation rates and fork velocities. We derive rate equations for left- and right-moving forks and for replication probability over time that can be solved numerically to obtain the mean-field replication program. This method accurately reproduces the results of DNA replication simulation. We also successfully adapted our approach to the inverse problem of fitting measurements of DNA replication performed on single DNA molecules. Since such measurements are performed on specified portion of the genome, the examined DNA molecules may be replicated by forks that originate either within the studied molecule or outside of it. This problem was solved by using an effective flux of incoming replication forks at the model boundaries to represent the origin activity outside the studied region. Using this approach, we show that reliable inferences can be made about the replication of specific portions of the genome even if the amount of data that can be obtained from single-molecule experiments is generally limited.

  20. TOP2017 Experimental summary

    CERN Document Server

    Giammanco, Andrea

    2017-01-01

    Thanks to the unprecedentedly fast accumulation of high-energy data at the LHC during the ongoing Run~2, most of the traditional top-quark analyses are experiencing the luxury of having to worry about how to punch through the ``Systematics Wall'', and think about new ways to maximize the utility of their data. New processes involving top quarks are being studied for the first time, and the good old pair-production processes are being explored in unusual settings, such as collisions involving heavy ions, or ``reference data'' collected by the LHC at relatively low centre-of-mass energy. The TOP2017 conference featured 37 talks delivered by experimental physicists, including seven in the ``Young Scientists Forum'' where young colleagues were given the opportunity to elaborate more deeply than usual on their own work. As it is impossible to do justice to all the experimental resu...

  1. Top-ophilia

    Energy Technology Data Exchange (ETDEWEB)

    Quigg, Chris; /Fermilab

    2008-01-01

    Almost from the moment in June 1977 when the discovery of the Upsilon resonance revealed the existence of what we now call the bottom quark, physicists began searching for its partner. Through the years, as we established the electric charge and weak isospin of the b-quark, and detected the virtual influence of its mate, it became clear that the top quark must exist. Exactly at what mass, we couldn't say, but we knew just how top events would look. We also knew that top events would be rare--if the Tevatron could make them at all--and that picking out the events would pose a real challenge for the experimenters and their detectors.

  2. Angular correlations in top quark decays in standard model extensions

    International Nuclear Information System (INIS)

    Batebi, S.; Etesami, S. M.; Mohammadi-Najafabadi, M.

    2011-01-01

    The CMS Collaboration at the CERN LHC has searched for the t-channel single top quark production using the spin correlation of the t-channel. The signal extraction and cross section measurement rely on the angular distribution of the charged lepton in the top quark decays, the angle between the charged lepton momentum and top spin in the top rest frame. The behavior of the angular distribution is a distinct slope for the t-channel single top (signal) while it is flat for the backgrounds. In this Brief Report, we investigate the contributions which this spin correlation may receive from a two-Higgs doublet model, a top-color assisted technicolor (TC2) and the noncommutative extension of the standard model.

  3. Mammalian RAD52 Functions in Break-Induced Replication Repair of Collapsed DNA Replication Forks.

    Science.gov (United States)

    Sotiriou, Sotirios K; Kamileri, Irene; Lugli, Natalia; Evangelou, Konstantinos; Da-Ré, Caterina; Huber, Florian; Padayachy, Laura; Tardy, Sebastien; Nicati, Noemie L; Barriot, Samia; Ochs, Fena; Lukas, Claudia; Lukas, Jiri; Gorgoulis, Vassilis G; Scapozza, Leonardo; Halazonetis, Thanos D

    2016-12-15

    Human cancers are characterized by the presence of oncogene-induced DNA replication stress (DRS), making them dependent on repair pathways such as break-induced replication (BIR) for damaged DNA replication forks. To better understand BIR, we performed a targeted siRNA screen for genes whose depletion inhibited G1 to S phase progression when oncogenic cyclin E was overexpressed. RAD52, a gene dispensable for normal development in mice, was among the top hits. In cells in which fork collapse was induced by oncogenes or chemicals, the Rad52 protein localized to DRS foci. Depletion of Rad52 by siRNA or knockout of the gene by CRISPR/Cas9 compromised restart of collapsed forks and led to DNA damage in cells experiencing DRS. Furthermore, in cancer-prone, heterozygous APC mutant mice, homozygous deletion of the Rad52 gene suppressed tumor growth and prolonged lifespan. We therefore propose that mammalian RAD52 facilitates repair of collapsed DNA replication forks in cancer cells. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  4. Cytoplasmic ATR Activation Promotes Vaccinia Virus Genome Replication

    Directory of Open Access Journals (Sweden)

    Antonio Postigo

    2017-05-01

    Full Text Available In contrast to most DNA viruses, poxviruses replicate their genomes in the cytoplasm without host involvement. We find that vaccinia virus induces cytoplasmic activation of ATR early during infection, before genome uncoating, which is unexpected because ATR plays a fundamental nuclear role in maintaining host genome integrity. ATR, RPA, INTS7, and Chk1 are recruited to cytoplasmic DNA viral factories, suggesting canonical ATR pathway activation. Consistent with this, pharmacological and RNAi-mediated inhibition of canonical ATR signaling suppresses genome replication. RPA and the sliding clamp PCNA interact with the viral polymerase E9 and are required for DNA replication. Moreover, the ATR activator TOPBP1 promotes genome replication and associates with the viral replisome component H5. Our study suggests that, in contrast to long-held beliefs, vaccinia recruits conserved components of the eukaryote DNA replication and repair machinery to amplify its genome in the host cytoplasm.

  5. Initiation of DNA replication requires actin dynamics and formin activity.

    Science.gov (United States)

    Parisis, Nikolaos; Krasinska, Liliana; Harker, Bethany; Urbach, Serge; Rossignol, Michel; Camasses, Alain; Dewar, James; Morin, Nathalie; Fisher, Daniel

    2017-11-02

    Nuclear actin regulates transcriptional programmes in a manner dependent on its levels and polymerisation state. This dynamics is determined by the balance of nucleocytoplasmic shuttling, formin- and redox-dependent filament polymerisation. Here, using Xenopus egg extracts and human somatic cells, we show that actin dynamics and formins are essential for DNA replication. In proliferating cells, formin inhibition abolishes nuclear transport and initiation of DNA replication, as well as general transcription. In replicating nuclei from transcriptionally silent Xenopus egg extracts, we identified numerous actin regulators, and disruption of actin dynamics abrogates nuclear transport, preventing NLS (nuclear localisation signal)-cargo release from RanGTP-importin complexes. Nuclear formin activity is further required to promote loading of cyclin-dependent kinase (CDK) and proliferating cell nuclear antigen (PCNA) onto chromatin, as well as initiation and elongation of DNA replication. Therefore, actin dynamics and formins control DNA replication by multiple direct and indirect mechanisms. © 2017 The Authors.

  6. Reconstitution of RPA-covered single-stranded DNA-activated ATR-Chk1 signaling.

    Science.gov (United States)

    Choi, Jun-Hyuk; Lindsey-Boltz, Laura A; Kemp, Michael; Mason, Aaron C; Wold, Marc S; Sancar, Aziz

    2010-08-03

    ATR kinase is a critical upstream regulator of the checkpoint response to various forms of DNA damage. Previous studies have shown that ATR is recruited via its binding partner ATR-interacting protein (ATRIP) to replication protein A (RPA)-covered single-stranded DNA (RPA-ssDNA) generated at sites of DNA damage where ATR is then activated by TopBP1 to phosphorylate downstream targets including the Chk1 signal transducing kinase. However, this critical feature of the human ATR-initiated DNA damage checkpoint signaling has not been demonstrated in a defined system. Here we describe an in vitro checkpoint system in which RPA-ssDNA and TopBP1 are essential for phosphorylation of Chk1 by the purified ATR-ATRIP complex. Checkpoint defective RPA mutants fail to activate ATR kinase in this system, supporting the conclusion that this system is a faithful representation of the in vivo reaction. Interestingly, we find that an alternative form of RPA (aRPA), which does not support DNA replication, can substitute for the checkpoint function of RPA in vitro, thus revealing a potential role for aRPA in the activation of ATR kinase. We also find that TopBP1 is recruited to RPA-ssDNA in a manner dependent on ATRIP and that the N terminus of TopBP1 is required for efficient recruitment and activation of ATR kinase.

  7. TOP LINAC design

    International Nuclear Information System (INIS)

    Picardi, L.; Ronsivalle, C.; Vignati, A.

    1997-11-01

    The report describes a linear accelerator for protons named TOP LINAC designed for the TOP (Terapia Oncologica con Protoni, Oncological Protontherapy) project launched by the Italian National Institute of Health (Istituto Superiore di Sanita', ISS) to explore in collaboration with the biggest Oncological Hospital in Rome (Istituto Regina Elena, IRE) the potentialities of the therapy with accelerated protons and establish guide lines for the application of this new type of radiotherapy in comparison with the more traditional electron and x-rays radiotherapy. The concept of a compact accelerator for protontherapy applications bore within the Italian Hadrontherapy Collaboration (TERA Collaboration) with the aim to diffuse the protontherapy on the National territory. The ISS program plans to use the TOP linac proton beam also for production of PET (Positron Emission Tomography) radioisotopes and radiobiology studies. Official agreements are in course between ISS and ENEA which provides its experience in the industrial and medical accelerators for the design and the construction of the TOP linac. The accelerator that will be the first 3 GHz proton linac in the world, will be composed of a 428.3 MHz 7 Me V RFQ + DTL injector followed by a 7-65 Me V section of a 3 GHz SCDTL structure and a 65 - 200 Me V variable energy SCL 3 GHz structure. In particular the SCDTL section uses a highly innovative accelerating structure patented by ENEA. In this report the clinical and physical requests are discussed and a preliminary design of the whole machine is given

  8. Top emitting white OLEDs

    Energy Technology Data Exchange (ETDEWEB)

    Freitag, Patricia; Luessem, Bjoern; Leo, Karl [Technische Universitaet Dresden, Institut fuer Angewandte Photophysik, George-Baehr-Strasse 1, 01069 Dresden (Germany)

    2009-07-01

    Top emitting organic light emitting diodes (TOLEDs) provide a number of interesting opportunities for new applications, such as the opportunity to fabricate ITO-free devices by using opaque substrates. This makes it possible to manufacture low cost OLEDs for signage and lighting applications. A general top emitting device consists of highly reflecting metal contacts as anode and semitransparent cathode, the latter one for better outcouling reasons. In between several organic materials are deposited as charge transporting, blocking, and emission layers. Here, we show a top emitting white organic light emitting diode with silver electrodes arranged in a p-i-n structure with p- and n-doped charge transport layers. The centrical emission layer consists of two phosphorescent (red and green) and one fluorescent (blue) emitter systems separated by an ambipolar interlayer to avoid mutual exciton quenching. By adding an additional dielectric capping layer on top of the device stack, we achieve a reduction of the strong microcavity effects which appear due to the high reflection of both metal electrodes. Therefore, the outcoupled light shows broad and nearly angle-independent emission spectra, which is essential for white light emitting diodes.

  9. Top quark theory

    Indian Academy of Sciences (India)

    2012-10-04

    Oct 4, 2012 ... The theoretical aspects of a number of top quark properties such as ... to the quadratic divergences of the Higgs self-energy, while yet, ..... given in the literature, each with the aim of recovering a well-behaved expansion in αs.

  10. Top quark properties

    Indian Academy of Sciences (India)

    eter for the tests of the electroweak theory, since radiative corrections to many ... The uncertainty due to jet energy scale (JES) is the dominating systematic .... In the Standard Model, the charge of the top quark is predicted to be that of a normal up- ..... non-negative and f+ + f0 < 1, and the star marks the expectation from the ...

  11. Anomalous top magnetic couplings

    Indian Academy of Sciences (India)

    2012-11-09

    Nov 9, 2012 ... Corresponding author. E-mail: remartinezm@unal.edu.co. Abstract. The real and imaginary parts of the one-loop electroweak contributions to the left and right tensorial anomalous couplings of the tbW vertex in the Standard Model (SM) are computed. Keywords. Top; anomalous. PACS Nos 14.65.Ha; 12.15 ...

  12. arXiv Top Quark Mass Measurements at the LHC

    CERN Document Server

    AUTHOR|(INSPIRE)INSPIRE-00220136

    2016-01-01

    The top quark mass ($m_{top}$) is a fundamental parameter of the Standard Model of Particle Physics (SM). As the heaviest of all SM particles with a mass close to the electroweak symmetry-breaking scale, the top quark plays a pivotal role in the theory of elementary particles. The exact value of the top quark mass has implications on a number of theoretical predictions, which motivates the need for precision measurements of $m_{top}$. This document highlights a number of such measurements carried out by the ATLAS and CMS collaborations based on the combined LHC Run 1 datasets at centre-of-mass energies of $\\sqrt{s}=7$ and $8$ TeV. A wide range of analysis strategies are employed for a number of final-state signatures. Measurements of both the top quark pole mass as well as the value of $m_{top}$ as defined by the Monte Carlo generator in simulated signal samples are discussed.

  13. DNA Replication Profiling Using Deep Sequencing.

    Science.gov (United States)

    Saayman, Xanita; Ramos-Pérez, Cristina; Brown, Grant W

    2018-01-01

    Profiling of DNA replication during progression through S phase allows a quantitative snap-shot of replication origin usage and DNA replication fork progression. We present a method for using deep sequencing data to profile DNA replication in S. cerevisiae.

  14. Hydroxyurea-Induced Replication Stress

    Directory of Open Access Journals (Sweden)

    Kenza Lahkim Bennani-Belhaj

    2010-01-01

    Full Text Available Bloom's syndrome (BS displays one of the strongest known correlations between chromosomal instability and a high risk of cancer at an early age. BS cells combine a reduced average fork velocity with constitutive endogenous replication stress. However, the response of BS cells to replication stress induced by hydroxyurea (HU, which strongly slows the progression of replication forks, remains unclear due to publication of conflicting results. Using two different cellular models of BS, we showed that BLM deficiency is not associated with sensitivity to HU, in terms of clonogenic survival, DSB generation, and SCE induction. We suggest that surviving BLM-deficient cells are selected on the basis of their ability to deal with an endogenous replication stress induced by replication fork slowing, resulting in insensitivity to HU-induced replication stress.

  15. CPT analysis with top physics

    Energy Technology Data Exchange (ETDEWEB)

    Cembranos, Jose A. R., E-mail: cembra@fis.ucm.es [Universidad Complutense de Madrid, Departamento de Fisica Teorica I (Spain)

    2013-03-15

    We discuss the possibility of observing CPT violation from top anti-top production in hadronic colliders. We study a general approach by analyzing constraints on the mass difference between the top and anti-top quarks. We present current bounds from Tevatron data, and comment on the prospects for improving these bounds at the LHC and the ILC.

  16. Top Quark Properties at Tevatron

    Energy Technology Data Exchange (ETDEWEB)

    Lysák, Roman [Prague, Inst. Phys.

    2017-11-27

    The latest CDF and D0 experiment measurements of the top quark properties except the top quark mass are presented. The final combination of the CDF and D0 forward-backward asymmetry measurements is shown together with the D0 measurements of the inclusive top quark pair cross-section as well as the top quark polarization.

  17. DATABASE REPLICATION IN HETEROGENOUS PLATFORM

    OpenAIRE

    Hendro Nindito; Evaristus Didik Madyatmadja; Albert Verasius Dian Sano

    2014-01-01

    The application of diverse database technologies in enterprises today is increasingly a common practice. To provide high availability and survavibality of real-time information, a database replication technology that has capability to replicate databases under heterogenous platforms is required. The purpose of this research is to find the technology with such capability. In this research, the data source is stored in MSSQL database server running on Windows. The data will be replicated to MyS...

  18. IL1-and TGF beta-Nox4 signaling, oxidative stress and DNA damage response are shared features of replicative, oncogene-induced, and drug-induced paracrine 'Bystander senescence'

    Czech Academy of Sciences Publication Activity Database

    Hubáčková, Soňa; Krejčíková, Kateřina; Bartek, Jiří; Hodný, Zdeněk

    2012-01-01

    Roč. 4, č. 12 (2012), 932-951 ISSN 1945-4589 R&D Projects: GA ČR GA204/08/1418; GA ČR GAP301/10/1525 Institutional support: RVO:68378050 Keywords : senescence-associated secretome * DNA damage response * cytokines * JAK/STAT3 * TGF beta * NF kappa B * IL6 * IL beta * Nox4 * autocrine and paracrine signaling * tumor Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.696, year: 2012

  19. Landfill Top Covers

    DEFF Research Database (Denmark)

    Scheutz, Charlotte; Kjeldsen, Peter

    2011-01-01

    The purpose of the final cover of a landfill is to contain the waste and to provide for a physical separation between the waste and the environment for protection of public health. Most landfill covers are designed with the primary goal to reduce or prevent infiltration of precipitation...... into the landfill in order to minimize leachate generation. In addition the cover also has to control the release of gases produced in the landfill so the gas can be ventilated, collected and utilized, or oxidized in situ. The landfill cover should also minimize erosion and support vegetation. Finally the cover...... is landscaped in order to fit into the surrounding area/environment or meet specific plans for the final use of the landfill. To fulfill the above listed requirements landfill covers are often multicomponent systems which are placed directly on top of the waste. The top cover may be placed immediately after...

  20. Computing Z-top

    International Nuclear Information System (INIS)

    Kashani-Poor, A.K.

    2014-01-01

    The topological string presents an arena in which many features of string theory proper, such as the interplay between world-sheet and target space descriptions or open-closed duality, can be distilled into computational techniques which yield results beyond perturbation theory. In this thesis, I will summarize my research activity in this area. The presentation is organized around computations of the topological string partition function Z-top based on various perspectives on the topological string. (author)

  1. Top of the list

    International Nuclear Information System (INIS)

    Cameron, A.; Vries, E. de

    2006-01-01

    In this article the authors look at how the major turbine suppliers fared in the year 2005, and look forward to 2006 which could be the best ever for the wind industry. The world wind turbine market continues to be dominated by ten major companies, who together account for almost 100% of the total global market. Although there are some new companies on the horizon it is the ten major companies that the authors concentrate on, in particular the top three, Vestas, Gamesa and Enercon who between them control 66% of the market. They give their overall report on business in 2005 and give their predictions for 2006. By far the leading wind turbine supplier is the Danish Company Vestas, accounting for over 30% of the global market. However all of the top ten companies report a successful year and all are expecting an even better 2006. This paper also reports on potential newcomers to the industry, one of these is California-based Clipper Windpower which commenced manufacturing the 2.5 MW Liberty turbine in Iowa. Chinese manufacturer Goldwind is also looking to enter the market having acquired a licence to produce the Vensys 1.2 MW turbine. It may well be that changes are on the way, there will be jockeying for position at the top and newcomers will want to make an impression on the market

  2. Replication of bacteriophage lambda DNA

    International Nuclear Information System (INIS)

    Tsurimoto, T.; Matsubara, K.

    1983-01-01

    In this paper results of studies on the mechanism of bacteriophage lambda replication using molecular biological and biochemical approaches are reported. The purification of the initiator proteins, O and P, and the role of the O and P proteins in the initiation of lambda DNA replication through interactions with specific DNA sequences are described. 47 references, 15 figures

  3. Pattern replication by confined dewetting

    NARCIS (Netherlands)

    Harkema, S.; Schäffer, E.; Morariu, M.D.; Steiner, U

    2003-01-01

    The dewetting of a polymer film in a confined geometry was employed in a pattern-replication process. The instability of dewetting films is pinned by a structured confining surface, thereby replicating its topographic pattern. Depending on the surface energy of the confining surface, two different

  4. Charter School Replication. Policy Guide

    Science.gov (United States)

    Rhim, Lauren Morando

    2009-01-01

    "Replication" is the practice of a single charter school board or management organization opening several more schools that are each based on the same school model. The most rapid strategy to increase the number of new high-quality charter schools available to children is to encourage the replication of existing quality schools. This policy guide…

  5. Top quark measurements at ATLAS

    CERN Document Server

    Grancagnolo, Sergio; The ATLAS collaboration

    2017-01-01

    The top quark is the heaviest known fundamental particle. As it is the only quark that decays before it hadronizes, this gives us the unique opportunity to probe the properties of bare quarks at the Large Hadron Collider. This talk will present highlights of a few recent precision measurements by the ATLAS Collaboration of the top quark using 13 TeV and 8 TeV collision data: top-quark pair and single top production cross sections including differential distributions will be presented alongside top quark properties measurements. These measurements, including results using boosted top quarks, probe our understanding of top quark production in the TeV regime. Measurements of the top quark mass and searches for rare top quark decays are also presented.

  6. Top quark measurements at ATLAS

    CERN Document Server

    AUTHOR|(INSPIRE)INSPIRE-00041686; The ATLAS collaboration

    2017-01-01

    The top quark is the heaviest known fundamental particle. As it is the only quark that decays before it hadronizes, it allows us to probe the properties of bare quarks at the Large Hadron Collider. Highlights of a few recent precision measurements by the ATLAS Collaboration of the top quark using 13 TeV and 8 TeV collision data will be presented: top-quark pair and single top production cross sections including differential distributions will be presented alongside measurements of top-quark properties, including results using boosted top quarks, probe our understanding of top-quark production in the TeV regime. Measurements of the top-quark mass and searches for rare top quark decays are also presented.

  7. Naisjuhtidega ettevõtete TOP 100

    Index Scriptorium Estoniae

    2004-01-01

    Naisjuhtidega ettevõtete TOP 100. Käibe TOP 20. Käibe kasvu TOP 20. Kasumi TOP 20. Kasumi kasvu TOP 20. Rentaabluse TOP 20. Omakapitali tootlikkuse TOP 20. Riigi- ja kohaliku omavalitsuse asutuste naisjuhtide TOP 25. Riigi- ja kohaliku omavalitsuse asutuste eelarve TOP 25. Riigi- ja kohaliku omavalitsuse asutuste töötajate arvu TOP 25. Riigi- ja kohaliku omavalitsuse asutuste naisjuhtide palga TOP 25

  8. TopBP1-mediated DNA processing during mitosis.

    Science.gov (United States)

    Gallina, Irene; Christiansen, Signe Korbo; Pedersen, Rune Troelsgaard; Lisby, Michael; Oestergaard, Vibe H

    2016-01-01

    Maintenance of genome integrity is crucial to avoid cancer and other genetic diseases. Thus faced with DNA damage, cells mount a DNA damage response to avoid genome instability. The DNA damage response is partially inhibited during mitosis presumably to avoid erroneous processing of the segregating chromosomes. Yet our recent study shows that TopBP1-mediated DNA processing during mitosis is highly important to reduce transmission of DNA damage to daughter cells. (1) Here we provide an overview of the DNA damage response and DNA repair during mitosis. One role of TopBP1 during mitosis is to stimulate unscheduled DNA synthesis at underreplicated regions. We speculated that such genomic regions are likely to hold stalled replication forks or post-replicative gaps, which become the substrate for DNA synthesis upon entry into mitosis. Thus, we addressed whether the translesion pathways for fork restart or post-replicative gap filling are required for unscheduled DNA synthesis in mitosis. Using genetics in the avian DT40 cell line, we provide evidence that unscheduled DNA synthesis in mitosis does not require the translesion synthesis scaffold factor Rev1 or PCNA ubiquitylation at K164, which serve to recruit translesion polymerases to stalled forks. In line with this finding, translesion polymerase η foci do not colocalize with TopBP1 or FANCD2 in mitosis. Taken together, we conclude that TopBP1 promotes unscheduled DNA synthesis in mitosis independently of the examined translesion polymerases.

  9. LHCb experience with LFC replication

    International Nuclear Information System (INIS)

    Bonifazi, F; Carbone, A; D'Apice, A; Dell'Agnello, L; Re, G L; Martelli, B; Ricci, P P; Sapunenko, V; Vitlacil, D; Perez, E D; Duellmann, D; Girone, M; Peco, G; Vagnoni, V

    2008-01-01

    Database replication is a key topic in the framework of the LHC Computing Grid to allow processing of data in a distributed environment. In particular, the LHCb computing model relies on the LHC File Catalog, i.e. a database which stores information about files spread across the GRID, their logical names and the physical locations of all the replicas. The LHCb computing model requires the LFC to be replicated at Tier-1s. The LCG 3D project deals with the database replication issue and provides a replication service based on Oracle Streams technology. This paper describes the deployment of the LHC File Catalog replication to the INFN National Center for Telematics and Informatics (CNAF) and to other LHCb Tier-1 sites. We performed stress tests designed to evaluate any delay in the propagation of the streams and the scalability of the system. The tests show the robustness of the replica implementation with performance going much beyond the LHCb requirements

  10. LHCb experience with LFC replication

    CERN Document Server

    Bonifazi, F; Perez, E D; D'Apice, A; dell'Agnello, L; Düllmann, D; Girone, M; Re, G L; Martelli, B; Peco, G; Ricci, P P; Sapunenko, V; Vagnoni, V; Vitlacil, D

    2008-01-01

    Database replication is a key topic in the framework of the LHC Computing Grid to allow processing of data in a distributed environment. In particular, the LHCb computing model relies on the LHC File Catalog, i.e. a database which stores information about files spread across the GRID, their logical names and the physical locations of all the replicas. The LHCb computing model requires the LFC to be replicated at Tier-1s. The LCG 3D project deals with the database replication issue and provides a replication service based on Oracle Streams technology. This paper describes the deployment of the LHC File Catalog replication to the INFN National Center for Telematics and Informatics (CNAF) and to other LHCb Tier-1 sites. We performed stress tests designed to evaluate any delay in the propagation of the streams and the scalability of the system. The tests show the robustness of the replica implementation with performance going much beyond the LHCb requirements.

  11. Reliable self-replicating machines in asynchronous cellular automata.

    Science.gov (United States)

    Lee, Jia; Adachi, Susumu; Peper, Ferdinand

    2007-01-01

    We propose a self-replicating machine that is embedded in a two-dimensional asynchronous cellular automaton with von Neumann neighborhood. The machine dynamically encodes its shape into description signals, and despite the randomness of cell updating, it is able to successfully construct copies of itself according to the description signals. Self-replication on asynchronously updated cellular automata may find application in nanocomputers, where reconfigurability is an essential property, since it allows avoidance of defective parts and simplifies programming of such computers.

  12. Study of top and anti-top mass difference

    CERN Document Server

    Leedumrongwatthanakun, Saroch

    2013-01-01

    The invariance of the standard model under CPT transformations leads to the equality of particle and antiparticle masses. The recent measurements performed by the CMS experiment on the top anti-top mass difference are a test of such symmetry. In this work non-perturbative QCD effects, which may eventually lead to an apparent difference in the mass of a top and anti-top quark, are studied.

  13. NACSA Charter School Replication Guide: The Spectrum of Replication Options. Authorizing Matters. Replication Brief 1

    Science.gov (United States)

    O'Neill, Paul

    2010-01-01

    One of the most important and high-profile issues in public education reform today is the replication of successful public charter school programs. With more than 5,000 failing public schools in the United States, there is a tremendous need for strong alternatives for parents and students. Replicating successful charter school models is an…

  14. Distinct functions of human RecQ helicases during DNA replication.

    Science.gov (United States)

    Urban, Vaclav; Dobrovolna, Jana; Janscak, Pavel

    2017-06-01

    DNA replication is the most vulnerable process of DNA metabolism in proliferating cells and therefore it is tightly controlled and coordinated with processes that maintain genomic stability. Human RecQ helicases are among the most important factors involved in the maintenance of replication fork integrity, especially under conditions of replication stress. RecQ helicases promote recovery of replication forks being stalled due to different replication roadblocks of either exogenous or endogenous source. They prevent generation of aberrant replication fork structures and replication fork collapse, and are involved in proper checkpoint signaling. The essential role of human RecQ helicases in the genome maintenance during DNA replication is underlined by association of defects in their function with cancer predisposition. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Tekstiilitööstuse TOP 47

    Index Scriptorium Estoniae

    2005-01-01

    Tekstiilitööstuse TOP 47; Käibe TOP 35; Kasumi TOP 35; Käibe kasvu TOP 20; Kasumi kasvu TOP 20; Rentaabluse TOP 20; Varade tootlikkuse TOP 20; Tekstiilitööstuse TOP-i firmade üld- ja finantsandmed

  16. Rõivatööstuse TOP 50

    Index Scriptorium Estoniae

    2005-01-01

    Rõivatööstuse TOP 50; Käibe TOP 35; Kasumi TOP 35; Käibe kasvu TOP 20; Kasumi kasvu TOP 20; Rentaabluse TOP 20; Omakapitali tootlikkuse TOP 20; Rõivatööstuse TOP-i firmade üld- ja finantsandmed

  17. Eesti Ettevõtete TOP 100

    Index Scriptorium Estoniae

    2002-01-01

    TOP 100. Käibe TOP 500. Käibe kasvu TOP 100. Kasumi TOP 100. Kasumi kasvu TOP 100. Rentaabluse TOP 100. Omakapitali tootlikkuse TOP 100. Eesti edukamate ettevõtete üldandmed. Eesti edukamate ettevõtete finantsnäitajad. Valdkonna ja maakonna TOP-ide edukamate ettevõtete finantsnäitajad

  18. Treasury Offset Program (TOP) MI

    Data.gov (United States)

    Social Security Administration — The TOP MI helps OPSOS coordinate TOP case processing in the regions. The MI also helped communicate our progress and findings to BFQM and ORDP, as well as the ACOSS.

  19. Top Quark Physics with CMS

    CERN Multimedia

    CERN. Geneva

    2011-01-01

    Higgs mechanism. There are various hints at deviations from the Standard Model expectation which have been observed recently by Tevatron experiments in top final states. Several signatures of new physics accessible at the LHC either suffer from top-quark production as a significant background or contain top quarks themselves. In this talk, we present results on top quark physics obtained from the first LHC data collected by the CMS experiment.They include measurements of the top pair production cross section in various channels and their combination, measurements of the top quark mass, the single top cross section, a search for new particles decaying into top pairs, and a first look at the charge asymmetry.

  20. Top production at hadron colliders

    Indian Academy of Sciences (India)

    New results on top quark production are presented from four hadron collider experiments: CDF and D0 at the Tevatron, and ATLAS and CMS at the LHC. Cross-sections for single top and top pair production are discussed, as well as results on the top–antitop production asymmetry and searches for new physics including ...

  1. Single top t-channel

    CERN Document Server

    Faltermann, Nils

    2017-01-01

    The production of single top quarks allows to study the interplay of top quark physics and the electroweak sector of the standard model. Deviations from predictions can be a hint for physics beyond the standard model. The t-channel is the dominant production mode for single top quarks at the LHC. This talk presents the latest measurements from the ATLAS and CMS collaborations.

  2. Forward Top Physics at LHCb

    CERN Multimedia

    CERN. Geneva

    2018-01-01

    The first Run 2 measurement of top pair production in the dilepton channel at 13 TeV will be presented, along with previous Run 1 measurements in final states accessible to both single top and top pair production. Heavy flavour tagging strategies at LHCb will also be discussed.

  3. Late-replicating X-chromosome: replication patterns in mammalian females

    Directory of Open Access Journals (Sweden)

    Tunin Karen

    2002-01-01

    Full Text Available The GTG-banding and 5-BrdU incorporation patterns of the late-replicating X-chromosome were studied in female dogs and cattle, and compared to human female patterns. The replication patterns of the short arm of the X-chromosomes did not show any difference between human, dog and cattle females. As to the long arm, some bands showed differences among the three studied species regarding the replication kinetics pattern. These differences were observed in a restricted region of the X-chromosome, delimited by Xq11 -> q25 in humans, by Xq1 -> q8 in dogs, and by Xq12 -> q32 in cattle. In an attempt to find out if these differences in the replication kinetics could be a reflection of differences in the localization of genes in that region of the X-chromosome, we used the probe for the human androgen receptor gene (AR localized at Xq12, which is in the region where we observed differences among the three studied species. We did not, however, observe hybridization signals. Our study goes on, using other human probes for genes located in the region Xq11 -> Xq25.

  4. Total process surveillance: (TOPS)

    International Nuclear Information System (INIS)

    Millar, J.H.P.

    1992-01-01

    A Total Process Surveillance system is under development which can provide, in real-time, additional process information from a limited number of raw measurement signals. This is achieved by using a robust model based observer to generate estimates of the process' internal states. The observer utilises the analytical reduncancy among a diverse range of transducers and can thus accommodate off-normal conditions which lead to transducer loss or damage. The modular hierarchical structure of the system enables the maximum amount of information to be assimilated from the available instrument signals no matter how diverse. This structure also constitutes a data reduction path thus reducing operator cognitive overload from a large number of varying, and possibly contradictory, raw plant signals. (orig.)

  5. SMC1-Mediated Intra-S-Phase Arrest Facilitates Bocavirus DNA Replication

    Science.gov (United States)

    Luo, Yong; Deng, Xuefeng; Cheng, Fang; Li, Yi

    2013-01-01

    Activation of a host DNA damage response (DDR) is essential for DNA replication of minute virus of canines (MVC), a member of the genus Bocavirus of the Parvoviridae family; however, the mechanism by which DDR contributes to viral DNA replication is unknown. In the current study, we demonstrate that MVC infection triggers the intra-S-phase arrest to slow down host cellular DNA replication and to recruit cellular DNA replication factors for viral DNA replication. The intra-S-phase arrest is regulated by ATM (ataxia telangiectasia-mutated kinase) signaling in a p53-independent manner. Moreover, we demonstrate that SMC1 (structural maintenance of chromosomes 1) is the key regulator of the intra-S-phase arrest induced during infection. Either knockdown of SMC1 or complementation with a dominant negative SMC1 mutant blocks both the intra-S-phase arrest and viral DNA replication. Finally, we show that the intra-S-phase arrest induced during MVC infection was caused neither by damaged host cellular DNA nor by viral proteins but by replicating viral genomes physically associated with the DNA damage sensor, the Mre11-Rad50-Nbs1 (MRN) complex. In conclusion, the feedback loop between MVC DNA replication and the intra-S-phase arrest is mediated by ATM-SMC1 signaling and plays a critical role in MVC DNA replication. Thus, our findings unravel the mechanism underlying DDR signaling-facilitated MVC DNA replication and demonstrate a novel strategy of DNA virus-host interaction. PMID:23365434

  6. The top ten.

    Science.gov (United States)

    Davis, C

    1985-10-01

    3 lists were compiled to answer the question of what countries have experienced the most population growth from World War II to the present. The 1st list includes the 10 countries which accounted for the largest gain in world population. The 2nd list shows the 10 countries with the highest growth rates of the 150 or so most populous countries in the world. The last list also shows countries ranked by growth rate but is limited to those with a current population of at least 10 million. To deal with the fact that some countries did not exist at 1 of the reference points, a set of estimates for 1940 provided a convenient starting point. China and India headed the list of countries ranked by absolute gains. They contributed half again as much growth as the next 8 nations combined. Altogether Asia, home to almost 60% of the world's population, captured 5 of the top 10 slots. The US and the USSR are the only developed countries on the list. The Soviet Union also presents the 1st case on the list of a country with a lower ranking in population gain (6th) than in absolute size in 1985 (3rd). Many of the population giants of 1940 (Japan, Great Britain, Germany, France, and Italy) are not on the list. Despite large base populations, their growth has been slow in the intervening years. All of the countries with the highest growth rates experienced over 3% annual average growth during the last 45 years: Kuwait, United Arab Emirates, Libya, Venezuela, Costa Rica, Kenya, Ivory Coast, Mexico, Honduras, and Syria. The influence of immigration is much in evidence in this list and explains otherwise unachievable rates of growth. The top 4 countries in annual rates of growth are all oil exporters. The top 3 countries in the 3rd list -- Venezuela, Kenya, and Mexico -- are carried over from the 2nd list, sharing the characteristics of rapid population growth and substantial base populations. The geographic mix of this list is notable. Asia, Africa, and Latin America each have at least

  7. Top quark physics

    International Nuclear Information System (INIS)

    Menzione, A.

    1995-10-01

    Most of the material presented in this report, comes from contributions to the parallel session PL20 of this conference. We summarise the experimental results of direct production of Top quarks, coming from the CDF and C0 Collaborations at Fermilab, and compare these results to what one expects within current theoretical understanding. Particular attention is given to new results such as all hadronic modes of t bar t decay. As far as the mass is concerned, a comparison is made with precision measurements of related quantities, coming from LEP and other experiments. An attempt is made to look at the medium-term future and understand which variables and with what accuracy one can measure them with increased integrated luminosity

  8. Top quark pair production and top quark properties at CDF

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Chang-Seong [INFN, Pisa

    2016-06-02

    We present the most recent measurements of top quark pairs production and top quark properties in proton-antiproton collisions with center-of-mass energy of 1.96 TeV using CDF II detector at the Tevatron. The combination of top pair production cross section measurements and the direct measurement of top quark width are reported. The test of Standard Model predictions for top quark decaying into $b$-quarks, performed by measuring the ratio $R$ between the top quark branching fraction to $b$-quark and the branching fraction to any type of down quark is shown. The extraction of the CKM matrix element $|V_{tb}|$ from the ratio $R$ is discussed. We also present the latest measurements on the forward-backward asymmetry ($A_{FB}$) in top anti-top quark production. With the full CDF Run II data set, the measurements are performed in top anti-top decaying to final states that contain one or two charged leptons (electrons or muons). In addition, we combine the results of the leptonic forward-backward asymmetry in $t\\bar t$ system between the two final states. All the results show deviations from the next-to-leading order (NLO) standard model (SM) calculation.

  9. Separation of replication and transcription domains in nucleoli.

    Science.gov (United States)

    Smirnov, E; Borkovec, J; Kováčik, L; Svidenská, S; Schröfel, A; Skalníková, M; Švindrych, Z; Křížek, P; Ovesný, M; Hagen, G M; Juda, P; Michalová, K; Cardoso, M C; Cmarko, D; Raška, I

    2014-12-01

    In mammalian cells, active ribosomal genes produce the 18S, 5.8S and 28S RNAs of ribosomal particles. Transcription levels of these genes are very high throughout interphase, and the cell needs a special strategy to avoid collision of the DNA polymerase and RNA polymerase machineries. To investigate this problem, we measured the correlation of various replication and transcription signals in the nucleoli of HeLa, HT-1080 and NIH 3T3 cells using a specially devised software for analysis of confocal images. Additionally, to follow the relationship between nucleolar replication and transcription in living cells, we produced a stable cell line expressing GFP-RPA43 (subunit of RNA polymerase I, pol I) and RFP-PCNA (the sliding clamp protein) based on human fibrosarcoma HT-1080 cells. We found that replication and transcription signals are more efficiently separated in nucleoli than in the nucleoplasm. In the course of S phase, separation of PCNA and pol I signals gradually increased. During the same period, separation of pol I and incorporated Cy5-dUTP signals decreased. Analysis of single molecule localization microscopy (SMLM) images indicated that transcriptionally active FC/DFC units (i.e. fibrillar centers with adjacent dense fibrillar components) did not incorporate DNA nucleotides. Taken together, our data show that replication of the ribosomal genes is spatially separated from their transcription, and FC/DFC units may provide a structural basis for that separation. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Maternal topoisomerase II alpha, not topoisomerase II beta, enables embryonic development of zebrafish top2a-/- mutants

    LENUS (Irish Health Repository)

    Sapetto-Rebow, Beata

    2011-11-23

    Abstract Background Genetic alterations in human topoisomerase II alpha (TOP2A) are linked to cancer susceptibility. TOP2A decatenates chromosomes and thus is necessary for multiple aspects of cell division including DNA replication, chromosome condensation and segregation. Topoisomerase II alpha is also required for embryonic development in mammals, as mouse Top2a knockouts result in embryonic lethality as early as the 4-8 cell stage. The purpose of this study was to determine whether the extended developmental capability of zebrafish top2a mutants arises from maternal expression of top2a or compensation from its top2b paralogue. Results Here, we describe bloody minded (blm), a novel mutant of zebrafish top2a. In contrast to mouse Top2a nulls, zebrafish top2a mutants survive to larval stages (4-5 day post fertilization). Developmental analyses demonstrate abundant expression of maternal top2a but not top2b. Inhibition or poisoning of maternal topoisomerase II delays embryonic development by extending the cell cycle M-phase. Zygotic top2a and top2b are co-expressed in the zebrafish CNS, but endogenous or ectopic top2b RNA appear unable to prevent the blm phenotype. Conclusions We conclude that maternal top2a enables zebrafish development before the mid-zygotic transition (MZT) and that zebrafish top2a and top2b are not functionally redundant during development after activation of the zygotic genome.

  11. Maternal topoisomerase II alpha, not topoisomerase II beta, enables embryonic development of zebrafish top2a-/- mutants

    Directory of Open Access Journals (Sweden)

    Sapetto-Rebow Beata

    2011-11-01

    Full Text Available Abstract Background Genetic alterations in human topoisomerase II alpha (TOP2A are linked to cancer susceptibility. TOP2A decatenates chromosomes and thus is necessary for multiple aspects of cell division including DNA replication, chromosome condensation and segregation. Topoisomerase II alpha is also required for embryonic development in mammals, as mouse Top2a knockouts result in embryonic lethality as early as the 4-8 cell stage. The purpose of this study was to determine whether the extended developmental capability of zebrafish top2a mutants arises from maternal expression of top2a or compensation from its top2b paralogue. Results Here, we describe bloody minded (blm, a novel mutant of zebrafish top2a. In contrast to mouse Top2a nulls, zebrafish top2a mutants survive to larval stages (4-5 day post fertilization. Developmental analyses demonstrate abundant expression of maternal top2a but not top2b. Inhibition or poisoning of maternal topoisomerase II delays embryonic development by extending the cell cycle M-phase. Zygotic top2a and top2b are co-expressed in the zebrafish CNS, but endogenous or ectopic top2b RNA appear unable to prevent the blm phenotype. Conclusions We conclude that maternal top2a enables zebrafish development before the mid-zygotic transition (MZT and that zebrafish top2a and top2b are not functionally redundant during development after activation of the zygotic genome.

  12. Spin polarization in top pair production in association with two photons at NLO+PS

    CERN Document Server

    Luisoni, Gionata

    2018-01-01

    This talk focuses on the impact of top-quark spin polarization effects in Higgs boson production in association with a top-quark pair, where the Higgs boson decays to two photons. Predictions for the signal are compared with direct top-quark pair production in association with two photons at NLO+PS.

  13. Spin polarization in top pair production in association with two photons at NLO+PS

    CERN Document Server

    Luisoni, Gionata

    2017-01-01

    This talk focuses on the impact of top-quark spin polarization effects in Higgs boson production in association with a top-quark pair, where the Higgs boson decays to two photons. Predictions for the signal are compared with direct top-quark pair production in association with two photons at NLO+PS.

  14. Toitlustusettevõtete TOP 30 aastal 2002

    Index Scriptorium Estoniae

    2003-01-01

    Toitlustusettevõtete TOP 30 aastal 2002. Käibe TOP 30. Kasumi TOP 30. Käibe kasvu TOP 30. Kasumi kasvu TOP 30. Rentaabluse TOP 30. Omakapitali tootlikkuse TOP 30. Toitlustusettevõtete üldandmed. Toitlustusettevõtete finantsandmed

  15. Hiiumaa ettevõtete TOP 50

    Index Scriptorium Estoniae

    2005-01-01

    Hiiumaa ettevõtete TOP 50; Käibe TOP 35; Kasumi TOP 35; Hiiumaa ettevõtete üld- ja finantsandmed; Käibe kasvu TOP 20; Kasumi kasvu TOP 20; Rentaabluse TOP 20; Omakapitali tootlikkuse TOP 20. Vt samas: Teeli Remmalg: Hiiumaal jätkub plastitööstuse võidumarss

  16. The search for the top quark

    International Nuclear Information System (INIS)

    Barbaro-Galtieri, A.

    1989-03-01

    This paper discusses the following topics: top search in the near future, general remarks, top search at HERA, searching for the top quarks at the Z 0 machines, finding the top at Lep II, top search in UA2, top search in UA1, and top search at CDF. 58 refs., 38 figs

  17. Toiduainetööstuste TOP 100

    Index Scriptorium Estoniae

    2006-01-01

    Toiduainetööstuse TOP. Vt. samas: Käibe TOP 10; Käibekasvu TOP 10; Kasumi TOP 10; Kasumi kasvu TOP 10; Rentaabluse TOP 10; Omakapitali tootlikkuse TOP 10; Toiduainetööstuse üld- ja finantsandmed

  18. Online-kaubanduse TOP aastal 2003

    Index Scriptorium Estoniae

    2004-01-01

    Online-kaubanduse TOP aastal 2003. Käibe TOP 5. Käibe kasvu TOP 5. Rentaabluse TOP 5. Kasumi TOP 5. Kasumi kasvu TOP 5. Omakapitali tootlikkuse TOP 5. Lisa: TOPi koostamise metoodika. Online-kaubanduse firmade üldandmed. Online kaubanduse firmade finantsandmed

  19. TopView - ATLAS top physics analysis package

    CERN Document Server

    Shibata, A

    2007-01-01

    TopView is a common analysis package which is widely used in the ATLAS top physics working group. The package is fully based on the official ATLAS software Athena and EventView and playing a central role in the collaborative analysis model. It is a functional package which accounts for a broad range issues in implementing physics analysis. As well as being a modular framework suitable as a common workplace for collaborators, TopView implements numerous analysis tools including a complete top-antitop reconstruction and single top reconstruction. The package is currently used to produce common ntuple from Monte Carlo production and future use cases are under rapid development. In this paper, the design and ideas behind TopView and the performance of the analyses implemented in the package are presented with detailed documentation of the contents and instruction for using the package.

  20. REPLICATION TOOL AND METHOD OF PROVIDING A REPLICATION TOOL

    DEFF Research Database (Denmark)

    2016-01-01

    The invention relates to a replication tool (1, 1a, 1b) for producing a part (4) with a microscale textured replica surface (5a, 5b, 5c, 5d). The replication tool (1, 1a, 1b) comprises a tool surface (2a, 2b) defining a general shape of the item. The tool surface (2a, 2b) comprises a microscale...... energy directors on flange portions thereof uses the replication tool (1, 1a, 1b) to form an item (4) with a general shape as defined by the tool surface (2a, 2b). The formed item (4) comprises a microscale textured replica surface (5a, 5b, 5c, 5d) with a lateral arrangement of polydisperse microscale...

  1. Calcein represses human papillomavirus 16 E1-E2 mediated DNA replication via blocking their binding to the viral origin of replication.

    Science.gov (United States)

    Das, Dipon; Smith, Nathan W; Wang, Xu; Richardson, Stacie L; Hartman, Matthew C T; Morgan, Iain M

    2017-08-01

    Human papillomaviruses are causative agents in several human diseases ranging from genital warts to ano-genital and oropharyngeal cancers. Currently only symptoms of HPV induced disease are treated; there are no antivirals available that directly target the viral life cycle. Previously, we determined that the cellular protein TopBP1 interacts with the HPV16 replication/transcription factor E2. This E2-TopBP1 interaction is essential for optimal E1-E2 DNA replication and for the viral life cycle. The drug calcein disrupts the interaction of TopBP1 with itself and other host proteins to promote cell death. Here we demonstrate that calcein blocks HPV16 E1-E2 DNA replication via blocking the viral replication complex forming at the origin of replication. This occurs at non-toxic levels of calcein and demonstrates specificity as it does not block the ability of E2 to regulate transcription. We propose that calcein or derivatives could be developed as an anti-HPV therapeutic. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Naisjuhtidega ettevõtete TOP 70

    Index Scriptorium Estoniae

    2003-01-01

    Naisjuhtidega ettevõtete TOP 70. Käibe TOP 30. Käibe kasvu TOP 30. Kasumi TOP 30. Kasumi kasvu TOP 30. Rentaabluse TOP 30. Omakapitali tootlikkuse TOP 30. Nais- ja meesjuhtidega ettevõtted 2001. aasta 500 edukama ettevõtte hulgas. Naistegevjuhtidega firmade TOP 2001 ja 2002. Riigi- ja kohaliku omavalitsuse asutuste naisjuhtide TOP 20. Riigi- ja kohaliku omavalitsuse asutuste eelarve TOP 20. Riigi- ja kohaliku omavalitsuse asutuste töötajate arvu TOP 20. Naistegevjuhtidega firmade osakaal 2001. aastal. Riigi- ja kohaliku omavalitsuse asutuste naisjuhtide aastapalga TOP 20. Kommenteerib Tiina Raitviir.

  3. Search for scalar top and scalar bottom quarks at LEP

    CERN Document Server

    Abbiendi, G.; Akesson, P.F.; Alexander, G.; Allison, John; Amaral, P.; Anagnostou, G.; Anderson, K.J.; Arcelli, S.; Asai, S.; Axen, D.; Azuelos, G.; Bailey, I.; Barberio, E.; Barlow, R.J.; Batley, R.J.; Bechtle, P.; Behnke, T.; Bell, Kenneth Watson; Bell, P.J.; Bella, G.; Bellerive, A.; Benelli, G.; Bethke, S.; Biebel, O.; Bloodworth, I.J.; Boeriu, O.; Bock, P.; Bonacorsi, D.; Boutemeur, M.; Braibant, S.; Brigliadori, L.; Brown, Robert M.; Buesser, K.; Burckhart, H.J.; Campana, S.; Carnegie, R.K.; Caron, B.; Carter, A.A.; Carter, J.R.; Chang, C.Y.; Charlton, David G.; Csilling, A.; Cuffiani, M.; Dado, S.; Dallavalle, G.Marco; Dallison, S.; De Roeck, A.; De Wolf, E.A.; Desch, K.; Dienes, B.; Donkers, M.; Dubbert, J.; Duchovni, E.; Duckeck, G.; Duerdoth, I.P.; Elfgren, E.; Etzion, E.; Fabbri, F.; Feld, L.; Ferrari, P.; Fiedler, F.; Fleck, I.; Ford, M.; Frey, A.; Furtjes, A.; Gagnon, P.; Gary, John William; Gaycken, G.; Geich-Gimbel, C.; Giacomelli, G.; Giacomelli, P.; Giunta, Marina; Goldberg, J.; Gross, E.; Grunhaus, J.; Gruwe, M.; Gunther, P.O.; Gupta, A.; Hajdu, C.; Hamann, M.; Hanson, G.G.; Harder, K.; Harel, A.; Harin-Dirac, M.; Hauschild, M.; Hauschildt, J.; Hawkes, C.M.; Hawkings, R.; Hemingway, R.J.; Hensel, C.; Herten, G.; Heuer, R.D.; Hill, J.C.; Hoffman, Kara Dion; Homer, R.J.; Horvath, D.; Howard, R.; Huntemeyer, P.; Igo-Kemenes, P.; Ishii, K.; Jeremie, H.; Jovanovic, P.; Junk, T.R.; Kanaya, N.; Kanzaki, J.; Karapetian, G.; Karlen, D.; Kartvelishvili, V.; Kawagoe, K.; Kawamoto, T.; Keeler, R.K.; Kellogg, R.G.; Kennedy, B.W.; Kim, D.H.; Klein, K.; Klier, A.; Kluth, S.; Kobayashi, T.; Kobel, M.; Komamiya, S.; Kormos, Laura L.; Kowalewski, Robert V.; Kramer, T.; Kress, T.; Krieger, P.; von Krogh, J.; Krop, D.; Kruger, K.; Kupper, M.; Lafferty, G.D.; Landsman, H.; Lanske, D.; Layter, J.G.; Leins, A.; Lellouch, D.; Letts, J.; Levinson, L.; Lillich, J.; Lloyd, S.L.; Loebinger, F.K.; Lu, J.; Ludwig, J.; Macpherson, A.; Mader, W.; Marcellini, S.; Marchant, T.E.; Martin, A.J.; Martin, J.P.; Masetti, G.; Mashimo, T.; Mattig, Peter; McDonald, W.J.; McKenna, J.; McMahon, T.J.; McPherson, R.A.; Meijers, F.; Mendez-Lorenzo, P.; Menges, W.; Merritt, F.S.; Mes, H.; Michelini, A.; Mihara, S.; Mikenberg, G.; Miller, D.J.; Moed, S.; Mohr, W.; Mori, T.; Mutter, A.; Nagai, K.; Nakamura, I.; Neal, H.A.; Nisius, R.; O'Neale, S.W.; Oh, A.; Okpara, A.; Oreglia, M.J.; Orito, S.; Pahl, C.; Pasztor, G.; Pater, J.R.; Patrick, G.N.; Pilcher, J.E.; Pinfold, J.; Plane, David E.; Poli, B.; Polok, J.; Pooth, O.; Przybycien, M.; Quadt, A.; Rabbertz, K.; Rembser, C.; Renkel, P.; Rick, H.; Roney, J.M.; Rosati, S.; Rozen, Y.; Runge, K.; Sachs, K.; Saeki, T.; Sahr, O.; Sarkisyan, E.K.G.; Schaile, A.D.; Schaile, O.; Scharff-Hansen, P.; Schieck, J.; Schoerner-Sadenius, Thomas; Schroder, Matthias; Schumacher, M.; Schwick, C.; Scott, W.G.; Seuster, R.; Shears, T.G.; Shen, B.C.; Shepherd-Themistocleous, C.H.; Sherwood, P.; Siroli, G.; Skuja, A.; Smith, A.M.; Sobie, R.; Soldner-Rembold, S.; Spagnolo, S.; Spano, F.; Stahl, A.; Stephens, K.; Strom, David M.; Strohmer, R.; Tarem, S.; Tasevsky, M.; Taylor, R.J.; Teuscher, R.; Thomson, M.A.; Torrence, E.; Toya, D.; Tran, P.; Trefzger, T.; Tricoli, A.; Trocsanyi, Z.; Tsur, E.; Turner-Watson, M.F.; Ueda, I.; Ujvari, B.; Vachon, B.; Vollmer, C.F.; Vannerem, P.; Verzocchi, M.; Voss, H.; Vossebeld, J.; Waller, D.; Ward, C.P.; Ward, D.R.; Watkins, P.M.; Watson, A.T.; Watson, N.K.; Wells, P.S.; Wengler, T.; Wermes, N.; Wetterling, D.; Wilson, G.W.; Wilson, J.A.; Wolf, G.; Wyatt, T.R.; Yamashita, S.; Zer-Zion, D.; Zivkovic, Lidija

    2002-01-01

    Searches for a scalar top quark and a scalar bottom quark have been performed using a data sample of 438 pb-1 at centre-of-mass energies of sqrt(s) = 192 - 209 GeV collected with the OPAL detector at LEP. No evidence for a signal was found. The 95% confidence level lower limit on the scalar top quark mass is 97.6 GeV if the mixing angle between the supersymmetric partners of the left- and right-handed states of the top quark is zero. When the scalar top quark decouples from the Z0 boson, the lower limit is 95.7 GeV. These limits were obtained assuming that the scalar top quark decays into a charm quark and the lightest neutralino, and that the mass difference between the scalar top quark and the lightest neutralino is larger than 10 GeV. The complementary decay mode of the scalar top quark decaying into a bottom quark, a charged lepton and a scalar neutrino has also been studied. The lower limit on the scalar top quark mass is 93.0 GeV for this decay mode, if the mass difference between the scalar top quark a...

  4. Proteomics Reveals Global Regulation of Protein SUMOylation by ATM and ATR Kinases during Replication Stress

    DEFF Research Database (Denmark)

    Munk, Stephanie; Sigurðsson, Jón Otti; Xiao, Zhenyu

    2017-01-01

    The mechanisms that protect eukaryotic DNA during the cumbersome task of replication depend on the precise coordination of several post-translational modification (PTM)-based signaling networks. Phosphorylation is a well-known regulator of the replication stress response, and recently an essentia....... They analyze changes in the SUMO and phosphoproteome after MMC and hydroxyurea treatments and find that the DNA damage response kinases ATR and ATM globally regulate SUMOylation upon replication stress and fork breakage....

  5. RAD51 interconnects between DNA replication, DNA repair and immunity.

    Science.gov (United States)

    Bhattacharya, Souparno; Srinivasan, Kalayarasan; Abdisalaam, Salim; Su, Fengtao; Raj, Prithvi; Dozmorov, Igor; Mishra, Ritu; Wakeland, Edward K; Ghose, Subroto; Mukherjee, Shibani; Asaithamby, Aroumougame

    2017-05-05

    RAD51, a multifunctional protein, plays a central role in DNA replication and homologous recombination repair, and is known to be involved in cancer development. We identified a novel role for RAD51 in innate immune response signaling. Defects in RAD51 lead to the accumulation of self-DNA in the cytoplasm, triggering a STING-mediated innate immune response after replication stress and DNA damage. In the absence of RAD51, the unprotected newly replicated genome is degraded by the exonuclease activity of MRE11, and the fragmented nascent DNA accumulates in the cytosol, initiating an innate immune response. Our data suggest that in addition to playing roles in homologous recombination-mediated DNA double-strand break repair and replication fork processing, RAD51 is also implicated in the suppression of innate immunity. Thus, our study reveals a previously uncharacterized role of RAD51 in initiating immune signaling, placing it at the hub of new interconnections between DNA replication, DNA repair, and immunity. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  6. Financial top 100

    International Nuclear Information System (INIS)

    Jaremko, G.

    1999-01-01

    The way in which the oil industry has rebounded from a difficult financial year was discussed. In 1998, oil prices fell by about 30 per cent from 1997 prices to average US$14.40. In the second quarter of 1999, the rebounding international markets raised oil prices by about one-third to an average US$17.60. Recent surveys have shown that the oil and gas industry will experience major changes in the decade ahead. It was forecasted that in 25 years, total Canadian oil production could near three million barrels per day, an increase of 36 per cent from today's 2.2 million. However, as conventional reserves are running out, production of conventional oil is expected to be diminished by about two-thirds. Naturally-occurring, light refinery-ready oil is forecasted to come mostly from the east coast, whereas western output will be dominated by oil sands. Natural gas will continue to be a huge growth opportunity in the west because of new pipeline expansions and exports to the United States. This paper presented a list of Canada's financial top 100 oil and gas companies which emerged with the best endurance. The list included statistics from 1997 and 1998 for gross revenues, total assets, net income, cash/operating activities, capital expenditures, closing share prices (with percentage change), and market capitalization. 1 fig., 1 tab

  7. Our top priority

    CERN Multimedia

    2012-01-01

    After three years of LHC running, we are still at the beginning of a long research programme with our flagship facility, and hopefully 4 July 2012 will go down in history as the date of one of many landmark discoveries spanning several years. CERN’s top priority for the next decade and more is the full exploitation of the LHC. With speculation about potential future facilities mounting in the light of the discovery of a new Higgs-like particle, it’s important to state that most clearly. Of course, this will rely on continued global collaboration, and it’s important that CERN engage constructively with other regions.   It is important to plan ahead, particularly since the lead times for new projects in particle physics are long, and our field is increasingly global in nature. That’s why the European particle physics community is currently engaged in updating its long-term strategy. Planning ahead allowed us to be ready technologically to build the LHC whe...

  8. Three-body Supersymmetric Top Decays

    CERN Document Server

    Belyaev, A; Lola, S; Belyaev, Alexander; Ellis, John; Lola, Smaragda

    2000-01-01

    We discuss three-body supersymmetric top decays, in schemes both with andwithout R-parity conservation, assuming that sfermion masses are larger thanm_t. We find that MSSM top decays into chargino/neutralino pairs have a strongkinematic suppression in the region of the supersymmetric parameter spaceconsistent with the LEP limits, with a decay width =< 10^{-5} GeV. MSSM topdecays into neutralino pairs have less kinematical suppression, but require aflavour-changing vertex, and are likely to have a smaller rate. On the otherhand, R-violating decays to single charginos, neutralinos and conventionalfermions can be larger for values of the R-violating couplings still permittedby other upper limits. The cascade decays of the charginos and neutralinos maylead to spectacular signals with explicit lepton-number violation, such aslike-sign lepton events.

  9. Participative Design With Top Management

    DEFF Research Database (Denmark)

    Simonsen, Jesper

    2004-01-01

    meetings aimed at aligning top management with the supplier’s analysis. The article describes the MUST method’s anchoring principle and the technique of problem mapping supporting this principle. This participatory approach resulted in mutual learning processes with top management which is rarely reported...... on in the PD community. Top management participated by reviewing, challenging, and reformulating the IT designers’ central suppositions, assumptions, and hypotheses related to the causal relation between identified problems and suggested solutions....

  10. Biomarkers of replicative senescence revisited

    DEFF Research Database (Denmark)

    Nehlin, Jan

    2016-01-01

    Biomarkers of replicative senescence can be defined as those ultrastructural and physiological variations as well as molecules whose changes in expression, activity or function correlate with aging, as a result of the gradual exhaustion of replicative potential and a state of permanent cell cycle...... arrest. The biomarkers that characterize the path to an irreversible state of cell cycle arrest due to proliferative exhaustion may also be shared by other forms of senescence-inducing mechanisms. Validation of senescence markers is crucial in circumstances where quiescence or temporary growth arrest may...... be triggered or is thought to be induced. Pre-senescence biomarkers are also important to consider as their presence indicate that induction of aging processes is taking place. The bona fide pathway leading to replicative senescence that has been extensively characterized is a consequence of gradual reduction...

  11. Boosted top: experimental tools overview

    CERN Document Server

    Usai, Emanuele

    2015-01-01

    An overview of tools and methods for the reconstruction of high-boost top quark decays at the LHC is given in this report. The focus is on hadronic decays, in particular an overview of the current status of top quark taggers in physics analyses is presented. The most widely used jet substructure techniques, normally used in combination with top quark taggers, are reviewed. Special techniques to treat pileup in large cone jets are described, along with a comparison of the performance of several boosted top quark reconstruction techniques.

  12. Could stops lighten the top?

    International Nuclear Information System (INIS)

    Bilal, A.; Ellis, J.; Fogli, G.L.

    1990-01-01

    The analysis of the presently available electroweak data including radiative corrections in the standard model suggests that the top quark weighs more than the Z 0 . We examine whether squark loops in the minimal supersymmetric model, particularly those involving stops (partners of the top quark), could reduce substantially the preferred range of top quark masses. Given the present lower bounds on squark masses, we find that stop effects can reduce the central value of m t by at most a few GeV, although they do make a very heavy top quark increasingly unlikely. (orig.)

  13. Personality and Academic Motivation: Replication, Extension, and Replication

    Science.gov (United States)

    Jones, Martin H.; McMichael, Stephanie N.

    2015-01-01

    Previous work examines the relationships between personality traits and intrinsic/extrinsic motivation. We replicate and extend previous work to examine how personality may relate to achievement goals, efficacious beliefs, and mindset about intelligence. Approximately 200 undergraduates responded to the survey with a 150 participants replicating…

  14. DNA Damage Reduces the Quality, but Not the Quantity of Human Papillomavirus 16 E1 and E2 DNA Replication

    Directory of Open Access Journals (Sweden)

    Molly L. Bristol

    2016-06-01

    Full Text Available Human papillomaviruses (HPVs are causative agents in almost all cervical carcinomas. HPVs are also causative agents in head and neck cancer, the cases of which are increasing rapidly. Viral replication activates the DNA damage response (DDR pathway; associated proteins are recruited to replication foci, and this pathway may serve to allow for viral genome amplification. Likewise, HPV genome double-strand breaks (DSBs could be produced during replication and could lead to linearization and viral integration. Many studies have shown that viral integration into the host genome results in unregulated expression of the viral oncogenes, E6 and E7, promoting HPV-induced carcinogenesis. Previously, we have demonstrated that DNA-damaging agents, such as etoposide, or knocking down viral replication partner proteins, such as topoisomerase II β binding protein I (TopBP1, does not reduce the level of DNA replication. Here, we investigated whether these treatments alter the quality of DNA replication by HPV16 E1 and E2. We confirm that knockdown of TopBP1 or treatment with etoposide does not reduce total levels of E1/E2-mediated DNA replication; however, the quality of replication is significantly reduced. The results demonstrate that E1 and E2 continue to replicate under genomically-stressed conditions and that this replication is mutagenic. This mutagenesis would promote the formation of substrates for integration of the viral genome into that of the host, a hallmark of cervical cancer.

  15. DNA Damage Reduces the Quality, but Not the Quantity of Human Papillomavirus 16 E1 and E2 DNA Replication.

    Science.gov (United States)

    Bristol, Molly L; Wang, Xu; Smith, Nathan W; Son, Minkyeong P; Evans, Michael R; Morgan, Iain M

    2016-06-22

    Human papillomaviruses (HPVs) are causative agents in almost all cervical carcinomas. HPVs are also causative agents in head and neck cancer, the cases of which are increasing rapidly. Viral replication activates the DNA damage response (DDR) pathway; associated proteins are recruited to replication foci, and this pathway may serve to allow for viral genome amplification. Likewise, HPV genome double-strand breaks (DSBs) could be produced during replication and could lead to linearization and viral integration. Many studies have shown that viral integration into the host genome results in unregulated expression of the viral oncogenes, E6 and E7, promoting HPV-induced carcinogenesis. Previously, we have demonstrated that DNA-damaging agents, such as etoposide, or knocking down viral replication partner proteins, such as topoisomerase II β binding protein I (TopBP1), does not reduce the level of DNA replication. Here, we investigated whether these treatments alter the quality of DNA replication by HPV16 E1 and E2. We confirm that knockdown of TopBP1 or treatment with etoposide does not reduce total levels of E1/E2-mediated DNA replication; however, the quality of replication is significantly reduced. The results demonstrate that E1 and E2 continue to replicate under genomically-stressed conditions and that this replication is mutagenic. This mutagenesis would promote the formation of substrates for integration of the viral genome into that of the host, a hallmark of cervical cancer.

  16. The CDF top search in the multijet decay mode

    International Nuclear Information System (INIS)

    Denby, B.

    1994-01-01

    A status report on the CDF top search in the multijet channel is given. After topological cuts and the requirement of a secondary vertex in the silicon microvertex detector, about 120 events remain (21.4 pb -1 ), in which the signal to background ratio (for a nominal top mass of 160 GeV) is estimated to be 1/10. With further improvements it should be possible to improve this ratio to 1/1 while retaining good efficiency for top, which will make the multijet channel an important cross check for the leptonic modes

  17. Chameleon Chasing II: A Replication.

    Science.gov (United States)

    Newsom, Doug A.; And Others

    1993-01-01

    Replicates a 1972 survey of students, educators, and Public Relations Society of America members regarding who the public relations counselor really serves. Finds that, in 1992, most respondents thought primary responsibility was to the client, then to the client's relevant publics, then to self, then to society, and finally to media. Compares…

  18. Hyperthermia stimulates HIV-1 replication.

    Directory of Open Access Journals (Sweden)

    Ferdinand Roesch

    Full Text Available HIV-infected individuals may experience fever episodes. Fever is an elevation of the body temperature accompanied by inflammation. It is usually beneficial for the host through enhancement of immunological defenses. In cultures, transient non-physiological heat shock (42-45°C and Heat Shock Proteins (HSPs modulate HIV-1 replication, through poorly defined mechanisms. The effect of physiological hyperthermia (38-40°C on HIV-1 infection has not been extensively investigated. Here, we show that culturing primary CD4+ T lymphocytes and cell lines at a fever-like temperature (39.5°C increased the efficiency of HIV-1 replication by 2 to 7 fold. Hyperthermia did not facilitate viral entry nor reverse transcription, but increased Tat transactivation of the LTR viral promoter. Hyperthermia also boosted HIV-1 reactivation in a model of latently-infected cells. By imaging HIV-1 transcription, we further show that Hsp90 co-localized with actively transcribing provirus, and this phenomenon was enhanced at 39.5°C. The Hsp90 inhibitor 17-AAG abrogated the increase of HIV-1 replication in hyperthermic cells. Altogether, our results indicate that fever may directly stimulate HIV-1 replication, in a process involving Hsp90 and facilitation of Tat-mediated LTR activity.

  19. Adressing Replication and Model Uncertainty

    DEFF Research Database (Denmark)

    Ebersberger, Bernd; Galia, Fabrice; Laursen, Keld

    innovation survey data for France, Germany and the UK, we conduct a ‘large-scale’ replication using the Bayesian averaging approach of classical estimators. Our method tests a wide range of determinants of innovation suggested in the prior literature, and establishes a robust set of findings on the variables...

  20. Replication of kinetoplast minicircle DNA

    International Nuclear Information System (INIS)

    Sheline, C.T.

    1989-01-01

    These studies describe the isolation and characterization of early minicircle replication intermediates from Crithidia fasciculata, and Leishmania tarentolae, the mitochondrial localization of a type II topoisomerase (TIImt) in C. fasciculata, and the implication of the aforementioned TIImt in minicircle replication in L. tarentolae. Early minicircle replication intermediates from C. fasciculata were identified and characterized using isolated kinetoplasts to incorporate radiolabeled nucleotides into its DNA. The pulse-label in an apparent theta-type intermediate chase into two daughter molecules. A uniquely gapped, ribonucleotide primed, knotted molecule represents the leading strand in the model proposed, and a highly gapped molecule represents the lagging strand. This theta intermediate is repaired in vitro to a doubly nicked catenated dimer which was shown to result from the replication of a single parental molecule. Very similar intermediates were found in the heterogeneous population of minicircles of L. tarentolae. The sites of the Leishmania specific discontinuities were mapped and shown to lie within the universally conserved sequence blocks in identical positions as compared to C. fasciculata and Trypanosoma equiperdum

  1. Manual of Cupule Replication Technology

    Directory of Open Access Journals (Sweden)

    Giriraj Kumar

    2015-09-01

    Full Text Available Throughout the world, iconic rock art is preceded by non-iconic rock art. Cupules (manmade, roughly semi-hemispherical depressions on rocks form the major bulk of the early non-iconic rock art globally. The antiquity of cupules extends back to the Lower Paleolithic in Asia and Africa, hundreds of thousand years ago. When one observes these cupules, the inquisitive mind poses so many questions with regard to understanding their technology, reasons for selecting the site, which rocks were used to make the hammer stones used, the skill and cognitive abilities employed to create the different types of cupules, the objective of their creation, their age, and so on. Replication of the cupules can provide satisfactory answers to some of these questions. Comparison of the hammer stones and cupules produced by the replication process with those obtained from excavation can provide support to observations. This paper presents a manual of cupule replication technology based on our experience of cupule replication on hard quartzite rock near Daraki-Chattan in the Chambal Basin, India.

  2. Kinematics of electroweak single top quark production

    International Nuclear Information System (INIS)

    Lueck, Jan; Karlsruhe U., EKP

    2006-01-01

    In this thesis, the t-channel matching procedure of two single-top signal Monte Carlo samples is optimized. The s- and matched t-channel samples, generated by MadEvent, are validated by comparing to ZTOP next-to-leading-order calculations. We find good agreement for all kinematic distributions we investigate, except for softer light quark jets due to gluon radiation. Since this has only minor impact on the s-channel, the corresponding MadEvent sample performs its task as expected. For the t-channel, we can conclude that the applied matching procedure leads to a MadEvent sample that successfully describes the kinematic distributions and rates of the 2nd-b quark. However, small differences remain. The discrepancy in the p T -ordered 2nd-leading light jets is mainly due to the absence of initial state gluon splitting and initial and final state gluon radiation matrix elements in the MadEvent sample production. The subsequent PYTHIA showering of the partons is apparently inappropriate for modeling those contributions and not intended for this purpose. The proper way would be to produce all relevant NLO matrix elements and match them as proposed in reference [15]. At present, an NLO-MC-generator for single-top is in preparation [41]. Probably it will be available for future iterations of single-top analyses and will redundantize further matching procedures. We estimate the systematic uncertainty on the single-top acceptance due to the Monte Carlo modeling and find an uncertainty of about 1% on the t-channel acceptance. We obtain a negligible uncertainty well below 1% on the s-channel acceptance. These acceptance uncertainties are very well acceptable for the single-top analyses that are currently under way. A sensitivity study of the simultaneous cross section measurement of the s- and t-channel single-top production modes is conducted. For this purpose, only statistical uncertainties are included. For a future integrated luminosity of 1 fb -1 , we expect to obtain an s

  3. Crinivirus replication and host interactions

    Directory of Open Access Journals (Sweden)

    Zsofia A Kiss

    2013-05-01

    Full Text Available Criniviruses comprise one of the genera within the family Closteroviridae. Members in this family are restricted to the phloem and rely on whitefly vectors of the genera Bemisia and/or Trialeurodes for plant-to-plant transmission. All criniviruses have bipartite, positive-sense ssRNA genomes, although there is an unconfirmed report of one having a tripartite genome. Lettuce infectious yellows virus (LIYV is the type species of the genus, the best studied so far of the criniviruses and the first for which a reverse genetics system was available. LIYV RNA 1 encodes for proteins predicted to be involved in replication, and alone is competent for replication in protoplasts. Replication results in accumulation of cytoplasmic vesiculated membranous structures which are characteristic of most studied members of the Closteroviridae. These membranous structures, often referred to as BYV-type vesicles, are likely sites of RNA replication. LIYV RNA 2 is replicated in trans when co-infecting cells with RNA 1, but is temporally delayed relative to RNA1. Efficient RNA 2 replication also is dependent on the RNA 1-encoded RNA binding protein, P34. No LIYV RNA 2-encoded proteins have been shown to affect RNA replication, but at least four, CP, CPm, Hsp70h, and p59 are virion structural components and CPm is a determinant of whitefly transmissibility. Roles of other LIYV RNA 2-encoded proteins are largely as yet unknown, but P26 is a non-virion protein that accumulates in cells as characteristic plasmalemma deposits which in plants are localized within phloem parenchyma and companion cells over plasmodesmata connections to sieve elements. The two remaining crinivirus-conserved RNA 2-encoded proteins are P5 and P9. P5 is 39 amino acid protein and is encoded at the 5’ end of RNA 2 as ORF1 and is part of the hallmark closterovirus gene array. The orthologous gene in BYV has been shown to play a role in cell-to-cell movement and indicated to be localized to the

  4. Top Quark Mass Measurements at ATLAS and CMS

    CERN Document Server

    McCarthy, Tom; The ATLAS collaboration

    2016-01-01

    The top quark mass ($m_{top}$) is a fundamental parameter of the Standard Model of Particle Physics (SM). As the heaviest of all known SM particles with a mass close to the EW symmetry breaking scale, the top quark plays a pivotal role in the theory of elementary particles. The exact value of the top quark mass has implications on a number of theoretical predictions, which motivates the need for precision measurements of $m_{top}$. This presentation highlights a number of such precision measurements carried out by the ATLAS and CMS collaborations at centre-of-mass energies of $\\sqrt{s}=7$ and $8$ TeV from the combined LHC Run I datasets. A wide range of analysis strategies are employed in a number of channels. Measurements of both the top quark pole mass and $m_{top}$ as defined by the Monte Carlo generator in simulated signal samples are shown. Finally, a summary of combinations of the LHC measurements is presented, together with a look toward top quark mass measurements at $\\sqrt{s}=13$ TeV.

  5. Identification of Tobacco Topping Responsive Proteins in Roots

    Directory of Open Access Journals (Sweden)

    Hongxiang eGuo

    2016-04-01

    Full Text Available Tobacco plant has many responses to topping, such as the increase in ability of nicotine synthesis and secondary growth of roots. Some topping responsive miRNAs and genes had been identified in our previous work, but it is not enough to elaborate mechanism of tobacco response to topping. Here, topping responsive proteins were screened from tobacco roots with two-dimensional electrophoresis. Of these proteins, calretulin (CRT and Auxin-responsive protein IAA9 were related to the secondary growth of roots, LRR disease resistance, heat shock protein 70 and farnesyl pyrophosphate synthase 1(FPPS)were involved in wounding stress response, and F-box protein played an important role in promoting the ability of nicotine synthesis after topping. In addition, there were five tobacco bHLH proteins (NtbHLH, NtMYC1a, NtMYC1b, NtMYC2a and NtMYC2b related to nicotine synthesis. It was suggested that NtMYC2 might be the main positive transcription factor and NtbHLH protein is a negative regulator in the JA-mediating activation of nicotine synthesis after topping. Tobacco topping activates some comprehensive biology processes involving IAA and JA signaling pathway, and the identification of these proteins will be helpful to understand the process of topping response.

  6. Wave Engine Topping Cycle Assessment

    Science.gov (United States)

    Welch, Gerard E.

    1996-01-01

    The performance benefits derived by topping a gas turbine engine with a wave engine are assessed. The wave engine is a wave rotor that produces shaft power by exploiting gas dynamic energy exchange and flow turning. The wave engine is added to the baseline turboshaft engine while keeping high-pressure-turbine inlet conditions, compressor pressure ratio, engine mass flow rate, and cooling flow fractions fixed. Related work has focused on topping with pressure-exchangers (i.e., wave rotors that provide pressure gain with zero net shaft power output); however, more energy can be added to a wave-engine-topped cycle leading to greater engine specific-power-enhancement The energy addition occurs at a lower pressure in the wave-engine-topped cycle; thus the specific-fuel-consumption-enhancement effected by ideal wave engine topping is slightly lower than that effected by ideal pressure-exchanger topping. At a component level, however, flow turning affords the wave engine a degree-of-freedom relative to the pressure-exchanger that enables a more efficient match with the baseline engine. In some cases, therefore, the SFC-enhancement by wave engine topping is greater than that by pressure-exchanger topping. An ideal wave-rotor-characteristic is used to identify key wave engine design parameters and to contrast the wave engine and pressure-exchanger topping approaches. An aerodynamic design procedure is described in which wave engine design-point performance levels are computed using a one-dimensional wave rotor model. Wave engines using various wave cycles are considered including two-port cycles with on-rotor combustion (valved-combustors) and reverse-flow and through-flow four-port cycles with heat addition in conventional burners. A through-flow wave cycle design with symmetric blading is used to assess engine performance benefits. The wave-engine-topped turboshaft engine produces 16% more power than does a pressure-exchanger-topped engine under the specified topping

  7. Status of the top quark: Top production cross section and top properties

    Energy Technology Data Exchange (ETDEWEB)

    Boisvert, V.; /Rochester U.

    2006-08-01

    This report describes the latest cross section and property measurements associated with the top quark at the Tevatron Run II. The largest data sample used is 760 pb{sup -1} of integrated luminosity. Due to its large mass, the top quark might be involved in the process of electroweak symmetry breaking, making it a useful probe for signs of new physics.

  8. Observation of Single Top Quark Production

    Energy Technology Data Exchange (ETDEWEB)

    Gerber, Cecilia E.; /Illinois U., Chicago

    2009-09-01

    The author reports on the observation of electroweak production of single top quarks in p{bar p} collisions at {radical}s = 1.96 Tev using 2.3 fb{sup -1} of data collected with the D0 detector at the fermilab Tevatron Collider. Using events containing an isolated electron or muon, missing transverse energy, two, three or four jets, with one or two of them identified as originating from the fragmentation of a b quark, the measured cross section for the process p{bar p} {yields} tb + X, tqb + X is 3.94 {+-} 0.88 pb (for a top quark mass of 170 GeV). the probability to measure a cross section at this value or higher in the absence of signal is 2.5 x 10{sup -7}, corresponding to a 5.0 standard deviation significance. Using the same dataset, the measured cross sections for the t- and the s-channel processes when determined simultaneously with no assumption on their relative production rate are 3.14{sub -0.80}{sup +0.94} pb and 1.05 {+-} 0.81 pb respectively, consistent with standard model expectations. The measured t-channel cross section has a significance of 4.8 standard deviations, representing the first evidence for the production of an individual single top process to be detected.

  9. New directions in top physics

    Energy Technology Data Exchange (ETDEWEB)

    Schell, Torben Karl

    2017-02-01

    The top quark plays an important role for many aspects of particle physics. The coupling of the Higgs boson to top quarks is a key parameter to probe electroweak symmetry breaking and is important for the evolution of the Higgs potential to high energies. In addition, many models of physics beyond the Standard Model predict heavy particles that decay to top-quark pairs. Furthermore, the unexplained hierarchy of fermion masses culminates in the large top-quark mass. In this thesis, we consider resonance searches based on top quarks in the fully hadronic final state. We employ multivariate techniques in form of boosted decision trees and add several improvements to the original HEPTopTagger algorithm. These modifications and extensions result in the new HEPTopTagger2. The achieved improvements are used to estimate the precision to which the top Yukawa coupling can be measured at a future 100 TeV proton-proton collider in the fully hadronic final state of t anti tH production. We find that at such a collider a precision measurement of the top Yukawa coupling to 1% should be possible. The statistical precision is backed up by demonstrating that in the ratio σ(t anti tH)/σ(t anti tZ) theoretical uncertainties cancel to below-percent level. Finally, we propose a Froggatt-Nielsen-type model to address the hierarchy of fermion masses in the Standard Model and determine current and projected bounds on the available parameter space.

  10. Mechanisms of bacterial DNA replication restart

    Science.gov (United States)

    Windgassen, Tricia A; Wessel, Sarah R; Bhattacharyya, Basudeb

    2018-01-01

    Abstract Multi-protein DNA replication complexes called replisomes perform the essential process of copying cellular genetic information prior to cell division. Under ideal conditions, replisomes dissociate only after the entire genome has been duplicated. However, DNA replication rarely occurs without interruptions that can dislodge replisomes from DNA. Such events produce incompletely replicated chromosomes that, if left unrepaired, prevent the segregation of full genomes to daughter cells. To mitigate this threat, cells have evolved ‘DNA replication restart’ pathways that have been best defined in bacteria. Replication restart requires recognition and remodeling of abandoned replication forks by DNA replication restart proteins followed by reloading of the replicative DNA helicase, which subsequently directs assembly of the remaining replisome subunits. This review summarizes our current understanding of the mechanisms underlying replication restart and the proteins that drive the process in Escherichia coli (PriA, PriB, PriC and DnaT). PMID:29202195

  11. Periodic expression of nuclear and mitochondrial DNA replication genes during the trypanosomatid cell cycle.

    Science.gov (United States)

    Pasion, S G; Brown, G W; Brown, L M; Ray, D S

    1994-12-01

    In trypanosomatids, DNA replication in the nucleus and in the single mitochondrion (or kinetoplast) initiates nearly simultaneously, suggesting that the DNA synthesis (S) phases of the nucleus and the mitochondrion are coordinately regulated. To investigate the basis for the temporal link between nuclear and mitochondrial DNA synthesis phases the expression of the genes encoding DNA ligase I, the 51 and 28 kDa subunits of replication protein A, dihydrofolate reductase and the mitochondrial type II topoisomerase were analyzed during the cell cycle progression of synchronous cultures of Crithidia fasciculata. These DNA replication genes were all expressed periodically, with peak mRNA levels occurring just prior to or at the peak of DNA synthesis in the synchronized cultures. A plasmid clone (pdN-1) in which TOP2, the gene encoding the mitochondrial topoisomerase, was disrupted by the insertion of a NEO drug-resistance cassette was found to express both a truncated TOP2 mRNA and a truncated topoisomerase polypeptide. The truncated mRNA was also expressed periodically coordinate with the expression of the endogenous TOP2 mRNA indicating that cis elements necessary for periodic expression are contained within cloned sequences. The expression of both TOP2 and nuclear DNA replication genes at the G1/S boundary suggests that regulated expression of these genes may play a role in coordinating nuclear and mitochondrial S phases in trypanosomatids.

  12. The yeast replicative aging model.

    Science.gov (United States)

    He, Chong; Zhou, Chuankai; Kennedy, Brian K

    2018-03-08

    It has been nearly three decades since the budding yeast Saccharomyces cerevisiae became a significant model organism for aging research and it has emerged as both simple and powerful. The replicative aging assay, which interrogates the number of times a "mother" cell can divide and produce "daughters", has been a stalwart in these studies, and genetic approaches have led to the identification of hundreds of genes impacting lifespan. More recently, cell biological and biochemical approaches have been developed to determine how cellular processes become altered with age. Together, the tools are in place to develop a holistic view of aging in this single-celled organism. Here, we summarize the current state of understanding of yeast replicative aging with a focus on the recent studies that shed new light on how aging pathways interact to modulate lifespan in yeast. Copyright © 2018. Published by Elsevier B.V.

  13. Replicator dynamics in value chains

    DEFF Research Database (Denmark)

    Cantner, Uwe; Savin, Ivan; Vannuccini, Simone

    2016-01-01

    The pure model of replicator dynamics though providing important insights in the evolution of markets has not found much of empirical support. This paper extends the model to the case of firms vertically integrated in value chains. We show that i) by taking value chains into account, the replicator...... dynamics may revert its effect. In these regressive developments of market selection, firms with low fitness expand because of being integrated with highly fit partners, and the other way around; ii) allowing partner's switching within a value chain illustrates that periods of instability in the early...... stage of industry life-cycle may be the result of an 'optimization' of partners within a value chain providing a novel and simple explanation to the evidence discussed by Mazzucato (1998); iii) there are distinct differences in the contribution to market selection between the layers of a value chain...

  14. Replication confers β cell immaturity.

    Science.gov (United States)

    Puri, Sapna; Roy, Nilotpal; Russ, Holger A; Leonhardt, Laura; French, Esra K; Roy, Ritu; Bengtsson, Henrik; Scott, Donald K; Stewart, Andrew F; Hebrok, Matthias

    2018-02-02

    Pancreatic β cells are highly specialized to regulate systemic glucose levels by secreting insulin. In adults, increase in β-cell mass is limited due to brakes on cell replication. In contrast, proliferation is robust in neonatal β cells that are functionally immature as defined by a lower set point for glucose-stimulated insulin secretion. Here we show that β-cell proliferation and immaturity are linked by tuning expression of physiologically relevant, non-oncogenic levels of c-Myc. Adult β cells induced to replicate adopt gene expression and metabolic profiles resembling those of immature neonatal β that proliferate readily. We directly demonstrate that priming insulin-producing cells to enter the cell cycle promotes a functionally immature phenotype. We suggest that there exists a balance between mature functionality and the ability to expand, as the phenotypic state of the β cell reverts to a less functional one in response to proliferative cues.

  15. Chromatin replication and histone dynamics

    DEFF Research Database (Denmark)

    Alabert, Constance; Jasencakova, Zuzana; Groth, Anja

    2017-01-01

    Inheritance of the DNA sequence and its proper organization into chromatin is fundamental for genome stability and function. Therefore, how specific chromatin structures are restored on newly synthesized DNA and transmitted through cell division remains a central question to understand cell fate...... choices and self-renewal. Propagation of genetic information and chromatin-based information in cycling cells entails genome-wide disruption and restoration of chromatin, coupled with faithful replication of DNA. In this chapter, we describe how cells duplicate the genome while maintaining its proper...... organization into chromatin. We reveal how specialized replication-coupled mechanisms rapidly assemble newly synthesized DNA into nucleosomes, while the complete restoration of chromatin organization including histone marks is a continuous process taking place throughout the cell cycle. Because failure...

  16. Phosphorylated STAT5 directly facilitates parvovirus B19 DNA replication in human erythroid progenitors through interaction with the MCM complex.

    Science.gov (United States)

    Ganaie, Safder S; Zou, Wei; Xu, Peng; Deng, Xuefeng; Kleiboeker, Steve; Qiu, Jianming

    2017-05-01

    Productive infection of human parvovirus B19 (B19V) exhibits high tropism for burst forming unit erythroid (BFU-E) and colony forming unit erythroid (CFU-E) progenitor cells in human bone marrow and fetal liver. This exclusive restriction of the virus replication to human erythroid progenitor cells is partly due to the intracellular factors that are essential for viral DNA replication, including erythropoietin signaling. Efficient B19V replication also requires hypoxic conditions, which upregulate the signal transducer and activator of transcription 5 (STAT5) pathway, and phosphorylated STAT5 is essential for virus replication. In this study, our results revealed direct involvement of STAT5 in B19V DNA replication. Consensus STAT5-binding elements were identified adjacent to the NS1-binding element within the minimal origins of viral DNA replication in the B19V genome. Phosphorylated STAT5 specifically interacted with viral DNA replication origins both in vivo and in vitro, and was actively recruited within the viral DNA replication centers. Notably, STAT5 interacted with minichromosome maintenance (MCM) complex, suggesting that STAT5 directly facilitates viral DNA replication by recruiting the helicase complex of the cellular DNA replication machinery to viral DNA replication centers. The FDA-approved drug pimozide dephosphorylates STAT5, and it inhibited B19V replication in ex vivo expanded human erythroid progenitors. Our results demonstrated that pimozide could be a promising antiviral drug for treatment of B19V-related diseases.

  17. Live Replication of Paravirtual Machines

    OpenAIRE

    Stodden, Daniel

    2009-01-01

    Virtual machines offer a fair degree of system state encapsulation, which promotes practical advances in fault tolerance, system debugging, profiling and security applications. This work investigates deterministic replay and semi-active replication for system paravirtualization, a software discipline trading guest kernel binar compatibility for reduced dependency on costly trap-and-emulate techniques. A primary contribution is evidence that trace capturing under a piecewise deterministic exec...

  18. In vitro replication of poliovirus

    International Nuclear Information System (INIS)

    Lubinski, J.M.

    1986-01-01

    Poliovirus is a member of the Picornaviridae whose genome is a single stranded RNA molecule of positive polarity surrounded by a proteinaceous capsid. Replication of poliovirus occurs via negative strand intermediates in infected cells using a virally encoded RNA-dependent RNA polymerase and host cell proteins. The authors have exploited the fact that complete cDNA copies of the viral genome when transfected onto susceptible cells generate virus. Utilizing the bacteriophage SP6 DNA dependent RNA polymerase system to synthesize negative strands in vitro and using these in an in vitro reaction the authors have generated full length infectious plus strands. Mutagenesis of the 5' and 3' ends of the negative and positive strands demonstrated that replication could occur either de novo or be extensions of the templates from their 3' ends or from nicks occurring during replication. The appearance of dimeric RNA molecules generated in these reactions was not dependent upon the same protein required for de novo initiation. Full length dimeric RNA molecules using a 5' 32 P end-labelled oligo uridylic acid primer and positive strand template were demonstrated in vitro containing only the 35,000 Mr host protein and the viral RNA-dependent RNA polymerase. A model for generating positive strands without protein priming by cleavage of dimeric RNA molecules was proposed

  19. HSV-1 Remodels Host Telomeres to Facilitate Viral Replication

    Directory of Open Access Journals (Sweden)

    Zhong Deng

    2014-12-01

    Full Text Available Telomeres protect the ends of cellular chromosomes. We show here that infection with herpes simplex virus 1 (HSV-1 results in chromosomal structural aberrations at telomeres and the accumulation of telomere dysfunction-induced DNA damage foci (TIFs. At the molecular level, HSV-1 induces transcription of telomere repeat-containing RNA (TERRA, followed by the proteolytic degradation of the telomere protein TPP1 and loss of the telomere repeat DNA signal. The HSV-1-encoded E3 ubiquitin ligase ICP0 is required for TERRA transcription and facilitates TPP1 degradation. Small hairpin RNA (shRNA depletion of TPP1 increases viral replication, indicating that TPP1 inhibits viral replication. Viral replication protein ICP8 forms foci that coincide with telomeric proteins, and ICP8-null virus failed to degrade telomere DNA signal. These findings suggest that HSV-1 reorganizes telomeres to form ICP8-associated prereplication foci and to promote viral genomic replication.

  20. Boosted dibosons from mixed heavy top squarks

    Science.gov (United States)

    Ghosh, Diptimoy

    2013-12-01

    The lighter mass eigenstate (t˜1) of the two top squarks, the scalar superpartners of the top quark, is extremely difficult to discover if it is almost degenerate with the lightest neutralino (χ˜10), the lightest stable supersymmetric particle in the R-parity conserving supersymmetry. The current experimental bound on t˜1 mass in this scenario stands only around 200 GeV. For such a light t˜1, the heavier top squark (t˜2) can also be around the TeV scale. Moreover, the high value of the Higgs (h) mass prefers the left- and right-handed top squarks to be highly mixed, allowing the possibility of a considerable branching ratio for t˜2→t˜1h and t˜2→t˜1Z. In this paper, we explore the above possibility together with the pair production of t˜2 t˜2*, giving rise to the spectacular diboson+missing transverse energy final state. For an approximately 1 TeV t˜2 and a few hundred GeV t˜1 the final state particles can be moderately boosted, which encourages us to propose a novel search strategy employing the jet substructure technique to tag the boosted h and Z. The reconstruction of the h and Z momenta also allows us to construct the stransverse mass MT2, providing an additional efficient handle to fight the backgrounds. We show that a 4-5σ signal can be observed at the 14 TeV LHC for ˜1TeV t˜2 with 100fb-1 integrated luminosity.

  1. Studies of top quark production at D0

    Energy Technology Data Exchange (ETDEWEB)

    Gerber, Cecilia E.; /Illinois U., Chicago

    2011-07-01

    I present recent results on top quark production in pp collisions at a center of mass energy of 1.96 TeV. The studies were performed by the D0 collaboration using approximately 5 fb{sup -1} of data taken during Run II at the Fermilab Tevatron accelerator. The top quark is the heaviest known elementary particle and completes the quark sector of the three-generation structure of the standard model (SM). It differs from the other quarks not only by its much larger mass, but also by its lifetime which is too short to build hadronic bound states. The SM predicts that top quarks are created via two independent production mechanisms at hadron colliders. The primary mode, in which a t{bar t} pair is produced from a gtt vertex via the strong interaction, was used by the D0 and CDF collaborations to establish the existence of the top quark in 1995. The second production mode of top quarks at hadron colliders is the electroweak production of a single top quark from a Wtb vertex. The predicted cross section for single top quark production is about half that of t{bar t} pairs but the signal-to-background ratio is much worse; observation of single top quark production has therefore until recently been impeded by its low rate and difficult background environment compared to the top pair production. In the following sections I will present results for the measurement of the t{bar t} pair and the single top quark production cross section using respectively 5.3 fb{sup -1} and 5.4 fb{sup -1} of data taken by the D0 experiment.

  2. Võrumaa ettevõtete TOP 50 aastal 2003

    Index Scriptorium Estoniae

    2004-01-01

    Võrumaa ettevõtete TOP 50 aastal 2003. Käibe TOP 40. Kasumi TOP 40. Käibe kasvu TOP 20. Kasumi kasvu TOP 20. Rentaabluse TOP 20. Omakapitali tootlikkuse TOP 20. Võrumaa firmade üld- ja finantsandmed

  3. Telomeres and replicative senescence: Is it only length that counts?

    Science.gov (United States)

    von Zglinicki, T

    2001-07-26

    Telomeres are well established as a major 'replicometer', counting the population doublings in primary human cell cultures and ultimately triggering replicative senescence. However, neither is the pace of this biological clock inert, nor is there a fixed threshold telomere length acting as the universal trigger of replicative senescence. The available data suggest that opening of the telomeric loop and unscheduled exposure of the single-stranded G-rich telomeric overhang might act like a semaphore to signal senescent cell cycle arrest. Short telomere length, telomeric single-strand breaks, low levels of loop-stabilizing proteins, or other factors may trigger this opening of the loop. Thus, both telomere shortening and the ultimate signalling into senescence are able to integrate different environmental and genetic factors, especially oxidative stress-mediated damage, which might otherwise become a thread to genomic stability.

  4. Search for Top in TOTEM

    CERN Document Server

    Corrales, Alonso

    2017-01-01

    The work assigned to me during this summer (from June 19th to August 11th) was in the "Search for Top in TOTEM" project, a CMG project in collaboration with TOTEM, under the supervision of Martijn Mulders and Laurent Forthomme. The goal is to determine physical properties of the top anti top quark pair (tt) created by central exclusive processes, particularly the invariant mass. For that it is necessary to relate the measurements of the reconstructed top pair kinematics in the central detector of CMS with the detected protons in the Roman Pots of TOTEM just outside the interaction site, about 200 m from it. CMS only considers decay products from the proton collision, it does not regard the forward protons that participated in the collision. On the contrary, TOTEM does consider these protons. In this research measurements of both TOTEM and CMS were combined Figure 1 shows a diagram of the production of the top anti top pair from the interaction of the two protons. A central exclusive process occurs when the pr...

  5. Search for light top squarks with the D OE detector

    International Nuclear Information System (INIS)

    Abachi, S.

    1995-07-01

    We present preliminary results of a search for pair produced top squarks, the supersymmetric partners to the top quark, under the assumption that the two-body decay bar t 1 → b bar W 1 and three-body decay bar t 1 → bW bar Z 1 are kinematically forbidden. This scenario is realized if bar t 1 is considerably lighter than all other squarks as well as bar W 1 , all bar vs, and the top quark. Such light top squarks will dominantly decay via bar t 1 → c bar Z 1 yielding a signal of two acollinear jets with (E) T . The data reported here were taken during the 1992-1993 run of the D0 detector at the Fermilab Tevatron p bar p collider operating at √s = 1.8 TeV

  6. Replication of micro and nano surface geometries

    DEFF Research Database (Denmark)

    Hansen, Hans Nørgaard; Hocken, R.J.; Tosello, Guido

    2011-01-01

    The paper describes the state-of-the-art in replication of surface texture and topography at micro and nano scale. The description includes replication of surfaces in polymers, metals and glass. Three different main technological areas enabled by surface replication processes are presented......: manufacture of net-shape micro/nano surfaces, tooling (i.e. master making), and surface quality control (metrology, inspection). Replication processes and methods as well as the metrology of surfaces to determine the degree of replication are presented and classified. Examples from various application areas...... are given including replication for surface texture measurements, surface roughness standards, manufacture of micro and nano structured functional surfaces, replicated surfaces for optical applications (e.g. optical gratings), and process chains based on combinations of repeated surface replication steps....

  7. Adenovirus sequences required for replication in vivo.

    OpenAIRE

    Wang, K; Pearson, G D

    1985-01-01

    We have studied the in vivo replication properties of plasmids carrying deletion mutations within cloned adenovirus terminal sequences. Deletion mapping located the adenovirus DNA replication origin entirely within the first 67 bp of the adenovirus inverted terminal repeat. This region could be further subdivided into two functional domains: a minimal replication origin and an adjacent auxillary region which boosted the efficiency of replication by more than 100-fold. The minimal origin occup...

  8. Parametrised Constants and Replication for Spatial Mobility

    DEFF Research Database (Denmark)

    Hüttel, Hans; Haagensen, Bjørn

    2009-01-01

    Parametrised replication and replication are common ways of expressing infinite computation in process calculi. While parametrised constants can be encoded using replication in the π-calculus, this changes in the presence of spatial mobility as found in e.g. the distributed π- calculus...... of the distributed π-calculus with parametrised constants and replication are incomparable. On the other hand, we shall see that there exists a simple encoding of recursion in mobile ambients....

  9. ATM and KAT5 safeguard replicating chromatin against formaldehyde damage

    Science.gov (United States)

    Ortega-Atienza, Sara; Wong, Victor C.; DeLoughery, Zachary; Luczak, Michal W.; Zhitkovich, Anatoly

    2016-01-01

    Many carcinogens damage both DNA and protein constituents of chromatin, and it is unclear how cells respond to this compound injury. We examined activation of the main DNA damage-responsive kinase ATM and formation of DNA double-strand breaks (DSB) by formaldehyde (FA) that forms histone adducts and replication-blocking DNA-protein crosslinks (DPC). We found that low FA doses caused a strong and rapid activation of ATM signaling in human cells, which was ATR-independent and restricted to S-phase. High FA doses inactivated ATM via its covalent dimerization and formation of larger crosslinks. FA-induced ATM signaling showed higher CHK2 phosphorylation but much lower phospho-KAP1 relative to DSB inducers. Replication blockage by DPC did not produce damaged forks or detectable amounts of DSB during the main wave of ATM activation, which did not require MRE11. Chromatin-monitoring KAT5 (Tip60) acetyltransferase was responsible for acetylation and activation of ATM by FA. KAT5 and ATM were equally important for triggering of intra-S-phase checkpoint and ATM signaling promoted recovery of normal human cells after low-dose FA. Our results revealed a major role of the KAT5-ATM axis in protection of replicating chromatin against damage by the endogenous carcinogen FA. PMID:26420831

  10. 36 CFR 910.64 - Replication.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Replication. 910.64 Section 910.64 Parks, Forests, and Public Property PENNSYLVANIA AVENUE DEVELOPMENT CORPORATION GENERAL... DEVELOPMENT AREA Glossary of Terms § 910.64 Replication. Replication means the process of using modern methods...

  11. Variance Swap Replication: Discrete or Continuous?

    Directory of Open Access Journals (Sweden)

    Fabien Le Floc’h

    2018-02-01

    Full Text Available The popular replication formula to price variance swaps assumes continuity of traded option strikes. In practice, however, there is only a discrete set of option strikes traded on the market. We present here different discrete replication strategies and explain why the continuous replication price is more relevant.

  12. Managing Single-Stranded DNA during Replication Stress in Fission Yeast

    Directory of Open Access Journals (Sweden)

    Sarah A. Sabatinos

    2015-09-01

    Full Text Available Replication fork stalling generates a variety of responses, most of which cause an increase in single-stranded DNA. ssDNA is a primary signal of replication distress that activates cellular checkpoints. It is also a potential source of genome instability and a substrate for mutation and recombination. Therefore, managing ssDNA levels is crucial to chromosome integrity. Limited ssDNA accumulation occurs in wild-type cells under stress. In contrast, cells lacking the replication checkpoint cannot arrest forks properly and accumulate large amounts of ssDNA. This likely occurs when the replication fork polymerase and helicase units are uncoupled. Some cells with mutations in the replication helicase (mcm-ts mimic checkpoint-deficient cells, and accumulate extensive areas of ssDNA to trigger the G2-checkpoint. Another category of helicase mutant (mcm4-degron causes fork stalling in early S-phase due to immediate loss of helicase function. Intriguingly, cells realize that ssDNA is present, but fail to detect that they accumulate ssDNA, and continue to divide. Thus, the cellular response to replication stalling depends on checkpoint activity and the time that replication stress occurs in S-phase. In this review we describe the signs, signals, and symptoms of replication arrest from an ssDNA perspective. We explore the possible mechanisms for these effects. We also advise the need for caution when detecting and interpreting data related to the accumulation of ssDNA.

  13. The theory of the top

    CERN Document Server

    Klein, Felix; Nagem, Raymond J; Sandri, Guido

    The Theory of the Top. Volume IV. Technical Applications of the Theory of the Top is the fourth and final volume in a series of self-contained English translations of the classic and definitive treatment of rigid body motion. Key features: * Complete and unabridged presentation with recent advances and additional notes; * Annotations by the translators provide insights into the nature of science and mathematics in the late 19th century; * Each volume interweaves theory and applications. The Theory of the Top was originally presented by Felix Klein as an 1895 lecture at Göttingen University that was broadened in scope and clarified as a result of collaboration with Arnold Sommerfeld.  Graduate students and researchers interested in theoretical and applied mechanics will find this series of books a thorough and insightful account.  Other volumes in the series include Introduction to the Kinematics and Kinetics of the Top, Development of the Theory in the Case of the Heavy Symmetric Top, and Perturbation...

  14. Kinematic top analyses at CDF

    Energy Technology Data Exchange (ETDEWEB)

    Grassmann, H.; CDF Collaboration

    1995-03-01

    We present an update of the top quark analysis using kinematic techniques in p{bar p} collisions at {radical}s = 1.8 TeV with the Collider Detector at Fermilab (CDF). We reported before on a study which used 19.3 pb{sup {minus}1} of data from the 1992--1993 collider run, but now we use a larger data sample of 67 pb{sup {minus}1}. First, we analyze the total transverse energy of the hard collision in W+{ge}3 jet events, showing the likely presence of a t{bar t} component in the event sample. Next, we compare in more detail the kinematic structure of W+ {ge}3 jet events with expectations for top pair production and with background processes, predominantly direct W+ jet production. We again find W+ {ge} 3 jet events which cannot be explained in terms of background, but show kinematic features as expected from top. These events also show evidence for beauty quarks, in agreement with expectations from top, but not compatible with expectations from backgrounds. The findings confirm the observation of top events made earlier in the data of the 1992--1993 collider run.

  15. Replication dynamics of the yeast genome.

    Science.gov (United States)

    Raghuraman, M K; Winzeler, E A; Collingwood, D; Hunt, S; Wodicka, L; Conway, A; Lockhart, D J; Davis, R W; Brewer, B J; Fangman, W L

    2001-10-05

    Oligonucleotide microarrays were used to map the detailed topography of chromosome replication in the budding yeast Saccharomyces cerevisiae. The times of replication of thousands of sites across the genome were determined by hybridizing replicated and unreplicated DNAs, isolated at different times in S phase, to the microarrays. Origin activations take place continuously throughout S phase but with most firings near mid-S phase. Rates of replication fork movement vary greatly from region to region in the genome. The two ends of each of the 16 chromosomes are highly correlated in their times of replication. This microarray approach is readily applicable to other organisms, including humans.

  16. Chromosomal DNA replication of Vicia faba cells

    International Nuclear Information System (INIS)

    Ikushima, Takaji

    1976-01-01

    The chromosomal DNA replication of higher plant cells has been investigated by DNA fiber autoradiography. The nuclear DNA fibers of Vicia root meristematic cells are organized into many tandem arrays of replication units or replicons which exist as clusters with respect to replication. DNA is replicated bidirectionally from the initiation points at the average rate of 0.15 μm/min at 20 0 C, and the average interinitiation interval is about 16 μm. The manner of chromosomal DNA replication in this higher plant is similar to that found in other eukaryotic cells at a subchromosomal level. (auth.)

  17. Inferential misconceptions and replication crisis

    Directory of Open Access Journals (Sweden)

    Norbert Hirschauer

    2016-12-01

    Full Text Available Misinterpretations of the p value and the introduction of bias through arbitrary analytical choices have been discussed in the literature for decades. Nonetheless, they seem to have persisted in empirical research, and criticisms of p value misuses have increased in the recent past due to the non-replicability of many studies. Unfortunately, the critical concerns that have been raised in the literature are scattered over many disciplines, often linguistically confusing, and differing in their main reasons for criticisms. Misuses and misinterpretations of the p value are currently being discussed intensely under the label “replication crisis” in many academic disciplines and journals, ranging from specialized scientific journals to Nature and Science. In a drastic response to the crisis, the editors of the journal Basic and Applied Social Psychology even decided to ban the use of p values from future publications at the beginning of 2015, a fact that has certainly added fuel to the discussions in the relevant scientific forums. Finally, in early March, the American Statistical Association released a brief formal statement on p values that explicitly addresses misuses and misinterpretations. In this context, we systematize the most serious flaws related to the p value and discuss suggestions of how to prevent them and reduce the rate of false discoveries in the future.

  18. Mammalian RAD52 Functions in Break-Induced Replication Repair of Collapsed DNA Replication Forks

    DEFF Research Database (Denmark)

    Sotiriou, Sotirios K; Kamileri, Irene; Lugli, Natalia

    2016-01-01

    Human cancers are characterized by the presence of oncogene-induced DNA replication stress (DRS), making them dependent on repair pathways such as break-induced replication (BIR) for damaged DNA replication forks. To better understand BIR, we performed a targeted siRNA screen for genes whose...... RAD52 facilitates repair of collapsed DNA replication forks in cancer cells....

  19. Repair replication in replicating and nonreplicating DNA after irradiation with uv light

    Energy Technology Data Exchange (ETDEWEB)

    Slor, H.; Cleaver, J.E.

    1978-06-01

    Ultraviolet light induces more pyrimidine dimers and more repair replication in DNA that replicates within 2 to 3 h of irradiation than in DNA that does not replicate during this period. This difference may be due to special conformational changes in DNA and chromatin that might be associated with semiconservative DNA replication.

  20. The Functional Role of TopBP1 in DNA Maintenance at Mitosis

    DEFF Research Database (Denmark)

    Pedersen, Rune Troelsgaard

    When cells traverse mitosis, genome integrity of the emerging daughter cells is dependent on replication of the entire genome during the preceding S-phase and accurate chromosome segregation in mitosis. Replication stress may cause cells to enter mitosis with underreplicated loci, consisting...... can lead to anaphase bridges that impair accurate chromosome segregation. The recent decade featured many advances in our understanding of how cells cope with underreplicated loci in mitosis. A major advance was the description of ultra-fine anaphase bridges (UFBs), a class of anaphase bridges...... established Saccharomyces cerevisiae as a model organism to study anaphase bridges, and we identified Dpb11/TopBP1 as a novel UFB-associated protein in yeast and avian DT40 cells, respectively. TopBP1 localized to confined areas on replication-stress induced UFBs. Upon onset of mitosis we observed a burst...

  1. WordPress Top Plugins

    CERN Document Server

    Corbin, Brandon

    2010-01-01

    Time flies when you're having fun. This is the right way to describe this WordPress Top Plugins book by Brandon Corbin. With real world examples and by showing you the perks of having these plugins installed on your websites, the author is all set to captivate your interest from start to end. Regardless of whether this is your first time working with WordPress, or you're a seasoned WordPress coding ninja, WordPress Top Plugins will walk you through finding and installing the best plugins for generating and sharing content, building communities and reader base, and generating real advertising r

  2. Precision top-quark mass measurement at CDF.

    Science.gov (United States)

    Aaltonen, T; Alvarez González, B; Amerio, S; Amidei, D; Anastassov, A; Annovi, A; Antos, J; Apollinari, G; Appel, J A; Arisawa, T; Artikov, A; Asaadi, J; Ashmanskas, W; Auerbach, B; Aurisano, A; Azfar, F; Badgett, W; Bae, T; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Barria, P; Bartos, P; Bauce, M; Bedeschi, F; Behari, S; Bellettini, G; Bellinger, J; Benjamin, D; Beretvas, A; Bhatti, A; Bisello, D; Bizjak, I; Bland, K R; Blumenfeld, B; Bocci, A; Bodek, A; Bortoletto, D; Boudreau, J; Boveia, A; Brigliadori, L; Bromberg, C; Brucken, E; Budagov, J; Budd, H S; Burkett, K; Busetto, G; Bussey, P; Buzatu, A; Calamba, A; Calancha, C; Camarda, S; Campanelli, M; Campbell, M; Canelli, F; Carls, B; Carlsmith, D; Carosi, R; Carrillo, S; Carron, S; Casal, B; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavaliere, V; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, K; Chokheli, D; Chung, W H; Chung, Y S; Ciocci, M A; Clark, A; Clarke, C; Compostella, G; Convery, M E; Conway, J; Corbo, M; Cordelli, M; Cox, C A; Cox, D J; Crescioli, F; Cuevas, J; Culbertson, R; Dagenhart, D; d'Ascenzo, N; Datta, M; de Barbaro, P; Dell'Orso, M; Demortier, L; Deninno, M; Devoto, F; d'Errico, M; Di Canto, A; Di Ruzza, B; Dittmann, J R; D'Onofrio, M; Donati, S; Dong, P; Dorigo, M; Dorigo, T; Ebina, K; Elagin, A; Eppig, A; Erbacher, R; Errede, S; Ershaidat, N; Eusebi, R; Farrington, S; Feindt, M; Fernandez, J P; Field, R; Flanagan, G; Forrest, R; Frank, M J; Franklin, M; Freeman, J C; Funakoshi, Y; Furic, I; Gallinaro, M; Garcia, J E; Garfinkel, A F; Garosi, P; Gerberich, H; Gerchtein, E; Giagu, S; Giakoumopoulou, V; Giannetti, P; Gibson, K; Ginsburg, C M; Giokaris, N; Giromini, P; Giurgiu, G; Glagolev, V; Glenzinski, D; Gold, M; Goldin, D; Goldschmidt, N; Golossanov, A; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Goulianos, K; Grinstein, S; Grosso-Pilcher, C; Group, R C; Guimaraes da Costa, J; Hahn, S R; Halkiadakis, E; Hamaguchi, A; Han, J Y; Happacher, F; Hara, K; Hare, D; Hare, M; Harr, R F; Hatakeyama, K; Hays, C; Heck, M; Heinrich, J; Herndon, M; Hewamanage, S; Hocker, A; Hopkins, W; Horn, D; Hou, S; Hughes, R E; Hurwitz, M; Husemann, U; Hussain, N; Hussein, M; Huston, J; Introzzi, G; Iori, M; Ivanov, A; James, E; Jang, D; Jayatilaka, B; Jeon, E J; Jindariani, S; Jones, M; Joo, K K; Jun, S Y; Junk, T R; Kamon, T; Karchin, P E; Kasmi, A; Kato, Y; Ketchum, W; Keung, J; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, J E; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kim, Y J; Kimura, N; Kirby, M; Klimenko, S; Knoepfel, K; Kondo, K; Kong, D J; Konigsberg, J; Kotwal, A V; Kreps, M; Kroll, J; Krop, D; Kruse, M; Krutelyov, V; Kuhr, T; Kurata, M; Kwang, S; Laasanen, A T; Lami, S; Lammel, S; Lancaster, M; Lander, R L; Lannon, K; Lath, A; Latino, G; LeCompte, T; Lee, E; Lee, H S; Lee, J S; Lee, S W; Leo, S; Leone, S; Lewis, J D; Limosani, A; Lin, C-J; Lindgren, M; Lipeles, E; Lister, A; Litvintsev, D O; Liu, C; Liu, H; Liu, Q; Liu, T; Lockwitz, S; Loginov, A; Lucchesi, D; Lueck, J; Lujan, P; Lukens, P; Lungu, G; Lys, J; Lysak, R; Madrak, R; Maeshima, K; Maestro, P; Malik, S; Manca, G; Manousakis-Katsikakis, A; Margaroli, F; Marino, C; Martínez, M; Mastrandrea, P; Matera, K; Mattson, M E; Mazzacane, A; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Mehtala, P; Mesropian, C; Miao, T; Mietlicki, D; Mitra, A; Miyake, H; Moed, S; Moggi, N; Mondragon, M N; Moon, C S; Moore, R; Morello, M J; Morlock, J; Movilla Fernandez, P; Mukherjee, A; Muller, Th; Murat, P; Mussini, M; Nachtman, J; Nagai, Y; Naganoma, J; Nakano, I; Napier, A; Nett, J; Neu, C; Neubauer, M S; Nielsen, J; Nodulman, L; Noh, S Y; Norniella, O; Oakes, L; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Orava, R; Ortolan, L; Pagan Griso, S; Pagliarone, C; Palencia, E; Papadimitriou, V; Paramonov, A A; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Pianori, E; Pilot, J; Pitts, K; Plager, C; Pondrom, L; Poprocki, S; Potamianos, K; Prokoshin, F; Pranko, A; Ptohos, F; Punzi, G; Rahaman, A; Ramakrishnan, V; Ranjan, N; Redondo, I; Renton, P; Rescigno, M; Riddick, T; Rimondi, F; Ristori, L; Robson, A; Rodrigo, T; Rodriguez, T; Rogers, E; Rolli, S; Roser, R; Ruffini, F; Ruiz, A; Russ, J; Rusu, V; Safonov, A; Sakumoto, W K; Sakurai, Y; Santi, L; Sato, K; Saveliev, V; Savoy-Navarro, A; Schlabach, P; Schmidt, A; Schmidt, E E; Schwarz, T; Scodellaro, L; Scribano, A; Scuri, F; Seidel, S; Seiya, Y; Semenov, A; Sforza, F; Shalhout, S Z; Shears, T; Shepard, P F; Shimojima, M; Shochet, M; Shreyber-Tecker, I; Simonenko, A; Sinervo, P; Sliwa, K; Smith, J R; Snider, F D; Soha, A; Sorin, V; Song, H; Squillacioti, P; Stancari, M; St Denis, R; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Strycker, G L; Sudo, Y; Sukhanov, A; Suslov, I; Takemasa, K; Takeuchi, Y; Tang, J; Tecchio, M; Teng, P K; Thom, J; Thome, J; Thompson, G A; Thomson, E; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Totaro, P; Trovato, M; Ukegawa, F; Uozumi, S; Varganov, A; Vázquez, F; Velev, G; Vellidis, C; Vidal, M; Vila, I; Vilar, R; Vizán, J; Vogel, M; Volpi, G; Wagner, P; Wagner, R L; Wakisaka, T; Wallny, R; Wang, S M; Warburton, A; Waters, D; Wester, W C; Whiteson, D; Wicklund, A B; Wicklund, E; Wilbur, S; Wick, F; Williams, H H; Wilson, J S; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, H; Wright, T; Wu, X; Wu, Z; Yamamoto, K; Yamato, D; Yang, T; Yang, U K; Yang, Y C; Yao, W-M; Yeh, G P; Yi, K; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanetti, A; Zeng, Y; Zhou, C; Zucchelli, S

    2012-10-12

    We present a precision measurement of the top-quark mass using the full sample of Tevatron √s = 1.96 TeV proton-antiproton collisions collected by the CDF II detector, corresponding to an integrated luminosity of 8.7 fb(-1). Using a sample of tt¯ candidate events decaying into the lepton+jets channel, we obtain distributions of the top-quark masses and the invariant mass of two jets from the W boson decays from data. We then compare these distributions to templates derived from signal and background samples to extract the top-quark mass and the energy scale of the calorimeter jets with in situ calibration. The likelihood fit of the templates from signal and background events to the data yields the single most-precise measurement of the top-quark mass, M(top)=172.85±0.71(stat)±0.85(syst) GeV/c(2).

  3. Observation of the top quark with the DO detector

    Energy Technology Data Exchange (ETDEWEB)

    Hadley, N.J. [Univ. of Maryland, College Park, MD (United States)

    1997-01-01

    The DO Collaboration reports on the observation of the top quark in p{bar p} collisions at {radical}s = 1.8 TeV at the Fermilab Tevatron. We measure the top quark mass to be 199{sub -21}{sup -19}(stat){sub -21}{sup +14}(syst.) GeV/c{sup 2} and its production cross section to be 6.4 {+-}2.2 pb. Our result is based on approximately 50 pb{sup -1} of data. We observe 17 events with an expected background of 3.8 {+-} 0.6 events. The probability of an upward fluctuation of the background to produce the observed signal is 2 x 10{sup -6} (equivalent to 4.6 standard deviations). The kinematic properties of the events are consistent with top quark decay, and the distribution of events across the seven decay channels is consistent with the Standard Model top quark branching fractions. We describe the analysis that led to the observation of the top quark as well as the properties of the top quark events.

  4. Climbing back to the top

    Energy Technology Data Exchange (ETDEWEB)

    Curry, Lynn

    2010-07-01

    California - the top wind producer in the US since the 1980s lost its lead in 2008 in the face of intense competition from other states. But backed by strong financial and political support from the government, California's wind energy sector is slowly making a comeback. (orig.)

  5. Kowalevski top in quantum mechanics

    International Nuclear Information System (INIS)

    Matsuyama, A.

    2013-01-01

    The quantum mechanical Kowalevski top is studied by the direct diagonalization of the Hamiltonian. The spectra show different behaviors depending on the region divided by the bifurcation sets of the classical invariant tori. Some of these spectra are nearly degenerate due to the multiplicity of the invariant tori. The Kowalevski top has several symmetries and symmetry quantum numbers can be assigned to the eigenstates. We have also carried out the semiclassical quantization of the Kowalevski top by the EBK formulation. It is found that the semiclassical spectra are close to the exact values, thus the eigenstates can be also labeled by the integer quantum numbers. The symmetries of the system are shown to have close relations with the semiclassical quantum numbers and the near-degeneracy of the spectra. -- Highlights: •Quantum spectra of the Kowalevski top are calculated. •Semiclassical quantization is carried out by the EBK formulation. •Quantum states are labeled by the semiclassical integer quantum numbers. •Multiplicity of the classical torus makes the spectra nearly degenerate. •Symmetries, quantum numbers and near-degenerate spectra are closely related

  6. Top production at hadron colliders

    Indian Academy of Sciences (India)

    mulated by the summer of 2010, the first top quark event candidates were observed and ..... Result of combined fit to data in the exclusive three-jet bin, the exclusive .... Figure 7 shows the results of a model-independent measurement of.

  7. TEMAC, Top Event Sensitivity Analysis

    International Nuclear Information System (INIS)

    Iman, R.L.; Shortencarier, M.J.

    1988-01-01

    1 - Description of program or function: TEMAC is designed to permit the user to easily estimate risk and to perform sensitivity and uncertainty analyses with a Boolean expression such as produced by the SETS computer program. SETS produces a mathematical representation of a fault tree used to model system unavailability. In the terminology of the TEMAC program, such a mathematical representation is referred to as a top event. The analysis of risk involves the estimation of the magnitude of risk, the sensitivity of risk estimates to base event probabilities and initiating event frequencies, and the quantification of the uncertainty in the risk estimates. 2 - Method of solution: Sensitivity and uncertainty analyses associated with top events involve mathematical operations on the corresponding Boolean expression for the top event, as well as repeated evaluations of the top event in a Monte Carlo fashion. TEMAC employs a general matrix approach which provides a convenient general form for Boolean expressions, is computationally efficient, and allows large problems to be analyzed. 3 - Restrictions on the complexity of the problem - Maxima of: 4000 cut sets, 500 events, 500 values in a Monte Carlo sample, 16 characters in an event name. These restrictions are implemented through the FORTRAN 77 PARAMATER statement

  8. Top mass measurement at CDF

    International Nuclear Information System (INIS)

    Rolli, S.

    1996-06-01

    We present the measurement of the top quark mass using L = 110 pb -1 data sample of pp collisions at √s = 1.8 TeV collected with the Collider Detector at Fermilab (CDF). We show the results for the different channels and discuss with some emphasis the determination of the systematic uncertainties. 7 refs., 10 figs., 5 tabs

  9. Tree compression with top trees

    DEFF Research Database (Denmark)

    Bille, Philip; Gørtz, Inge Li; Landau, Gad M.

    2013-01-01

    We introduce a new compression scheme for labeled trees based on top trees [3]. Our compression scheme is the first to simultaneously take advantage of internal repeats in the tree (as opposed to the classical DAG compression that only exploits rooted subtree repeats) while also supporting fast...

  10. Tree compression with top trees

    DEFF Research Database (Denmark)

    Bille, Philip; Gørtz, Inge Li; Landau, Gad M.

    2015-01-01

    We introduce a new compression scheme for labeled trees based on top trees. Our compression scheme is the first to simultaneously take advantage of internal repeats in the tree (as opposed to the classical DAG compression that only exploits rooted subtree repeats) while also supporting fast...

  11. Top partners searches and composite Higgs models

    International Nuclear Information System (INIS)

    Matsedonskyi, Oleksii; Panico, Giuliano; Wulzer, Andrea

    2016-01-01

    Colored fermionic partners of the top quark are well-known signatures of the Composite Higgs scenario and for this reason they have been and will be subject of an intensive experimental study at the LHC. Performing an assessment of the theoretical implications of this experimental effort is the goal of the present paper. We proceed by analyzing a set of simple benchmark models, characterized by simple two-dimensional parameter spaces where the results of the searches are conveniently visualized and their impact quantified. We only draw exclusion contours, in the hypothesis of no signal, but of course our formalism could equally well be used to report discoveries in a theoretically useful format.

  12. CP violation and the top quark

    International Nuclear Information System (INIS)

    Atwood, D.

    1994-02-01

    We consider signals of CP violation in semi-leptonic decay of the top quark. We show that the transverse polarization asymmetries of the τ-lepton in the decay t → brv is extremely sensitive CP violation. As an illustration we consider CP phases arising from the charged Higgs exchange in the Weinberg three Higgs doublet model. Qualitatively, the polarization asymmetries are enhanced over rate or energy asymmetries by a factor of O(m t /m r ) ∼ 100 with a corresponding increase in sensitivity to CP violating parameters. We also examine τ polarization in b decays via b → cvr and find that may also be very effective in constraining CP violating effects such as those that arise from an extended Higgs sector

  13. Overcoming natural replication barriers: differential helicase requirements.

    Science.gov (United States)

    Anand, Ranjith P; Shah, Kartik A; Niu, Hengyao; Sung, Patrick; Mirkin, Sergei M; Freudenreich, Catherine H

    2012-02-01

    DNA sequences that form secondary structures or bind protein complexes are known barriers to replication and potential inducers of genome instability. In order to determine which helicases facilitate DNA replication across these barriers, we analyzed fork progression through them in wild-type and mutant yeast cells, using 2-dimensional gel-electrophoretic analysis of the replication intermediates. We show that the Srs2 protein facilitates replication of hairpin-forming CGG/CCG repeats and prevents chromosome fragility at the repeat, whereas it does not affect replication of G-quadruplex forming sequences or a protein-bound repeat. Srs2 helicase activity is required for hairpin unwinding and fork progression. Also, the PCNA binding domain of Srs2 is required for its in vivo role of replication through hairpins. In contrast, the absence of Sgs1 or Pif1 helicases did not inhibit replication through structural barriers, though Pif1 did facilitate replication of a telomeric protein barrier. Interestingly, replication through a protein barrier but not a DNA structure barrier was modulated by nucleotide pool levels, illuminating a different mechanism by which cells can regulate fork progression through protein-mediated stall sites. Our analyses reveal fundamental differences in the replication of DNA structural versus protein barriers, with Srs2 helicase activity exclusively required for fork progression through hairpin structures.

  14. Diffractive dissociation of top hadrons at collider energies

    International Nuclear Information System (INIS)

    Di Bitonto, D.

    1983-01-01

    In an optical model in which heavy-flavour production is described as coherent scattering within the nucleon, the total heavy-flavour cross-section is expected to obey a m q -2 dependence, while the partial differential cross-section dσ/dp T for top hadrons is expected to show a broad plateau above approx. 20 GeV/c in transverse momentum. The expected top hadron signal dσ/dp T is 60 nb for m t = 20 GeV/c 2 appearing in the approx. angular range of expected value of θ 10 deg - 20 deg. (author)

  15. Top Jets at the LHC

    Energy Technology Data Exchange (ETDEWEB)

    Almeida, L.G.; Lee, S.J.; Perez, G.; Sung, I.; Virzi, J.

    2008-10-06

    We investigatethe reconstruction of high pT hadronically-decaying top quarksat the Large Hadron Collider. One of the main challenges in identifying energetictop quarks is that the decay products become increasingly collimated. This reducesthe efficacy of conventional reconstruction methods that exploit the topology of thetop quark decay chain. We focus on the cases where the decay products of the topquark are reconstructed as a single jet, a"top-jet." The most basic"top-tag" methodbased on jet mass measurement is considered in detail. To analyze the feasibility ofthe top-tagging method, both theoretical and experimental aspects of the large QCDjet background contribution are examined. Based on a factorization approach, wederive a simple analytic approximation for the shape of the QCD jet mass spectrum.We observe very good agreement with the Monte Carlo simulation. We consider high pT tt bar production in the Standard Model as an example, and show that our theoretical QCD jet mass distributions can efficiently characterize the background via sideband analyses. We show that with 25 fb-1 of data, our approach allows us to resolve top-jets with pT _> 1 TeV, from the QCD background, and about 1.5 TeV top-jets with 100 fb-1, without relying on b-tagging. To further improve the significancewe consider jet shapes (recently analyzed in 0807.0234 [hep-ph]), which resolve thesubstructure of energy flow inside cone jets. A method of measuring the top quarkpolarization by using the transverse momentum of the bottom quark is also presented.The main advantages of our approach are: (i) the mass distributions are driven byfirst principle calculations, instead of relying solely on Monte Carlo simulation; (ii) for high pT jets (pT _> 1 TeV), IR-safe jet shape variables are robust against detectorresolution effects. Our analysis can be applied to other boosted massive particlessuch as the electroweak gauge bosons and the Higgs.

  16. RPA-Binding Protein ETAA1 Is an ATR Activator Involved in DNA Replication Stress Response.

    Science.gov (United States)

    Lee, Yuan-Cho; Zhou, Qing; Chen, Junjie; Yuan, Jingsong

    2016-12-19

    ETAA1 (Ewing tumor-associated antigen 1), also known as ETAA16, was identified as a tumor-specific antigen in the Ewing family of tumors. However, the biological function of this protein remains unknown. Here, we report the identification of ETAA1 as a DNA replication stress response protein. ETAA1 specifically interacts with RPA (Replication protein A) via two conserved RPA-binding domains and is therefore recruited to stalled replication forks. Interestingly, further analysis of ETAA1 function revealed that ETAA1 participates in the activation of ATR signaling pathway via a conserved ATR-activating domain (AAD) located near its N terminus. Importantly, we demonstrate that both RPA binding and ATR activation are required for ETAA1 function at stalled replication forks to maintain genome stability. Therefore, our data suggest that ETAA1 is a new ATR activator involved in replication checkpoint control. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Proteomics Reveals Global Regulation of Protein SUMOylation by ATM and ATR Kinases during Replication Stress

    Directory of Open Access Journals (Sweden)

    Stephanie Munk

    2017-10-01

    Full Text Available The mechanisms that protect eukaryotic DNA during the cumbersome task of replication depend on the precise coordination of several post-translational modification (PTM-based signaling networks. Phosphorylation is a well-known regulator of the replication stress response, and recently an essential role for SUMOs (small ubiquitin-like modifiers has also been established. Here, we investigate the global interplay between phosphorylation and SUMOylation in response to replication stress. Using SUMO and phosphoproteomic technologies, we identify thousands of regulated modification sites. We find co-regulation of central DNA damage and replication stress responders, of which the ATR-activating factor TOPBP1 is the most highly regulated. Using pharmacological inhibition of the DNA damage response kinases ATR and ATM, we find that these factors regulate global protein SUMOylation in the protein networks that protect DNA upon replication stress and fork breakage, pointing to integration between phosphorylation and SUMOylation in the cellular systems that protect DNA integrity.

  18. Entangling Higgs production associated with a single top and a top-quark pair in the presence of anomalous top-Yukawa coupling

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Jung [Physics Division, National Center for Theoretical Sciences,Hsinchu, Taiwan (China); Cheung, Kingman [Physics Division, National Center for Theoretical Sciences,Hsinchu, Taiwan (China); Division of Quantum Phases and Devices, School of Physics, Konkuk University,Seoul 143-701 (Korea, Republic of); Department of Physics, National Tsing Hua University,Hsinchu 300, Taiwan (China); Lee, Jae Sik [Physics Division, National Center for Theoretical Sciences,Hsinchu, Taiwan (China); Department of Physics, Chonnam National University, 300 Yongbong-dong, Buk-gu, Gwangju, 500-757 (Korea, Republic of); Lu, Chih-Ting [Department of Physics, National Tsing Hua University,Hsinchu 300, Taiwan (China)

    2017-04-26

    The ATLAS and CMS collaborations observed a mild excess in the associated Higgs production with a top-quark pair (tt̄h) and reported the signal strengths of μ{sub tth}{sup ATLAS}=1.81±0.80 and μ{sub tth}{sup CMS}=2.75±0.99 based on the data collected at √s= 7 and 8 TeV. Although, at the current stage, there is no obvious indication whether the excess is real or due to statistical fluctuations, here we perform a case study of this mild excess by exploiting the strong entanglement between the associated Higgs production with a single top quark (thX) and tt̄h production in the presence of anomalous top-Yukawa coupling. As well known, tt̄h production only depends on the absolute value of the top-Yukawa coupling. Meanwhile, in thX production, this degeneracy is lifted through the strong interference between the two main contributions which are proportional to the top-Yukawa and the gauge-Higgs couplings, respectively. Especially, when the relative sign of the top-Yukawa coupling with respect to the gauge-Higgs coupling is reversed, the thX cross section can be enhanced by more than one order of magnitude. We perform a detailed study of the influence of thX production on tt̄h production in the presence of the anomalous top-Yukawa coupling and point out that it is crucial to include thX production in the analysis of the tt̄h data to pin down the sign and the size of the top-Yukawa coupling in future. While assuming the Standard Model (SM) value for the gauge-Higgs coupling, we vary the top-Yukawa coupling within the range allowed by the current LHC Higgs data. We consider the Higgs decay modes into multileptons, bb̄ and γγ putting a particular emphasis on the same sign dilepton events. We also discuss the prospects for the LHC Run-2 on how to disentangle thX production from tt̄h one and how to probe the anomalous top-Yukawa coupling.

  19. TopBP1 is required at mitosis to reduce transmission of DNA damage to G1 daughter cells

    Science.gov (United States)

    Pedersen, Rune Troelsgaard; Kruse, Thomas; Nilsson, Jakob

    2015-01-01

    Genome integrity is critically dependent on timely DNA replication and accurate chromosome segregation. Replication stress delays replication into G2/M, which in turn impairs proper chromosome segregation and inflicts DNA damage on the daughter cells. Here we show that TopBP1 forms foci upon mitotic entry. In early mitosis, TopBP1 marks sites of and promotes unscheduled DNA synthesis. Moreover, TopBP1 is required for focus formation of the structure-selective nuclease and scaffold protein SLX4 in mitosis. Persistent TopBP1 foci transition into 53BP1 nuclear bodies (NBs) in G1 and precise temporal depletion of TopBP1 just before mitotic entry induced formation of 53BP1 NBs in the next cell cycle, showing that TopBP1 acts to reduce transmission of DNA damage to G1 daughter cells. Based on these results, we propose that TopBP1 maintains genome integrity in mitosis by controlling chromatin recruitment of SLX4 and by facilitating unscheduled DNA synthesis. PMID:26283799

  20. Measurement of the top quark mass in the fully hadronic top antitop decay channel with the ATLAS detector

    Energy Technology Data Exchange (ETDEWEB)

    Adomeit, Stefanie

    2013-07-30

    A measurement of the top quark mass in the fully hadronic top-antitop decay channel is presented. The measurement uses data recorded with the ATLAS detector from proton-proton collisions provided by the LHC in 2011. The data were taken at a centre-of-mass energy of {radical}(s)=7 TeV and correspond to an integrated luminosity of about 4.7 fb{sup -1}.To measure the top quark mass a template technique is used, based on the so-called R{sub 3/2} estimator which is built from the invariant mass ratio of the hadronically decaying top quarks and W bosons. A kinematic likelihood fit is performed to properly reconstruct the t anti t decay. The multijet background to the fully hadronic t anti t signal is modelled from data by means of an ABCD method, allowing for a precise prediction of kinematical distributions in background events. The top quark mass is measured to be m{sub top}=175.1{+-}1.4(stat.){+-}1.8(syst.) GeV/c{sup 2}, with the dominant sources of systematic uncertainty coming from the jet energy scale and the residual b-jet energy scale.

  1. Measurement of the top quark mass in the fully hadronic top antitop decay channel with the ATLAS detector

    International Nuclear Information System (INIS)

    Adomeit, Stefanie

    2013-01-01

    A measurement of the top quark mass in the fully hadronic top-antitop decay channel is presented. The measurement uses data recorded with the ATLAS detector from proton-proton collisions provided by the LHC in 2011. The data were taken at a centre-of-mass energy of √(s)=7 TeV and correspond to an integrated luminosity of about 4.7 fb -1 .To measure the top quark mass a template technique is used, based on the so-called R 3/2 estimator which is built from the invariant mass ratio of the hadronically decaying top quarks and W bosons. A kinematic likelihood fit is performed to properly reconstruct the t anti t decay. The multijet background to the fully hadronic t anti t signal is modelled from data by means of an ABCD method, allowing for a precise prediction of kinematical distributions in background events. The top quark mass is measured to be m top =175.1±1.4(stat.)±1.8(syst.) GeV/c 2 , with the dominant sources of systematic uncertainty coming from the jet energy scale and the residual b-jet energy scale.

  2. Measurements of Top Properties at the Tevatron

    International Nuclear Information System (INIS)

    Husemann, Ulrich; Yale U.

    2007-01-01

    The large data samples of thousands of top events collected at the Tevatron experiments CDF and D(O) allow for a variety of measurements to analyze the properties of the top quark. Guided by the question ''Is the top quark observed at the Tevatron really the top quark of the standard model,'' we present Tevatron analyses studying the top production mechanism including resonant t(bar t) production, the V -A structure of the t → Wb decay vertex, the charge of the top quark, and single-top production via flavor-changing neutral currents

  3. Surface micro topography replication in injection moulding

    DEFF Research Database (Denmark)

    Arlø, Uffe Rolf

    Thermoplastic injection moulding is a widely used industrial process that involves surface generation by replication. The surface topography of injection moulded plastic parts can be important for aesthetical or technical reasons. With the emergence of microengineering and nanotechnology additional...... importance of surface topography follows. In general the replication is not perfect and the topography of the plastic part differs from the inverse topography of the mould cavity. It is desirable to be able to control the degree of replication perfection or replication quality. This requires an understanding...... of the physical mechanisms of replication. Such understanding can lead to improved process design and facilitate in-line process quality control with respect to surface properties. The purpose of the project is to identify critical factors that affect topography replication quality and to obtain an understanding...

  4. Properties of the Top Quark

    Energy Technology Data Exchange (ETDEWEB)

    Wicke, Daniel; /Wuppertal U., Dept. Math.

    2009-08-01

    The aim of particle physics is the understanding of elementary particles and their interactions. The current theory of elementary particle physics, the Standard Model, contains twelve different types of fermions which (neglecting gravity) interact through the gauge bosons of three forces. In addition a scalar particle, the Higgs boson, is needed for theoretical consistency. These few building blocks explain all experimental results found in the context of particle physics, so far. Nevertheless, it is believed that the Standard Model is only an approximation to a more complete theory. First of all the fourth known force, gravity, has withstood all attempts to be included until now. Furthermore, the Standard Model describes several features of the elementary particles like the existence of three families of fermions or the quantisation of charges, but does not explain these properties from underlying principles. Finally, the lightness of the Higgs boson needed to explain the symmetry breaking is difficult to maintain in the presence of expected corrections from gravity at high scales. This is the so called hierarchy problem. In addition astrophysical results indicate that the universe consists only to a very small fraction of matter described by the Standard Model. Large fractions of dark energy and dark matter are needed to describe the observations. Both do not have any correspondence in the Standard Model. Also the very small asymmetry between matter and anti-matter that results in the observed universe built of matter (and not of anti-matter) cannot be explained until now. It is thus an important task of experimental particle physics to test the predictions of the Standard Model to the best possible accuracy and to search for deviations pointing to necessary extensions or modifications of our current theoretical understanding. The top quark was predicted to exist by the Standard Model as the partner of the bottom quark. It was first observed in 1995 by the

  5. Properties of the Top Quark

    International Nuclear Information System (INIS)

    Wicke, Daniel

    2009-01-01

    The aim of particle physics is the understanding of elementary particles and their interactions. The current theory of elementary particle physics, the Standard Model, contains twelve different types of fermions which (neglecting gravity) interact through the gauge bosons of three forces. In addition a scalar particle, the Higgs boson, is needed for theoretical consistency. These few building blocks explain all experimental results found in the context of particle physics, so far. Nevertheless, it is believed that the Standard Model is only an approximation to a more complete theory. First of all the fourth known force, gravity, has withstood all attempts to be included until now. Furthermore, the Standard Model describes several features of the elementary particles like the existence of three families of fermions or the quantisation of charges, but does not explain these properties from underlying principles. Finally, the lightness of the Higgs boson needed to explain the symmetry breaking is difficult to maintain in the presence of expected corrections from gravity at high scales. This is the so called hierarchy problem. In addition astrophysical results indicate that the universe consists only to a very small fraction of matter described by the Standard Model. Large fractions of dark energy and dark matter are needed to describe the observations. Both do not have any correspondence in the Standard Model. Also the very small asymmetry between matter and anti-matter that results in the observed universe built of matter (and not of anti-matter) cannot be explained until now. It is thus an important task of experimental particle physics to test the predictions of the Standard Model to the best possible accuracy and to search for deviations pointing to necessary extensions or modifications of our current theoretical understanding. The top quark was predicted to exist by the Standard Model as the partner of the bottom quark. It was first observed in 1995 by the

  6. Toiduainetööstuse TOP 95 aastal 2003

    Index Scriptorium Estoniae

    2004-01-01

    Toiduainetööstuse TOP 95; Kasumi TOP 40; Käibe TOP 40; Kasumi kasvu TOP 30; Rentaabluse TOP 30; Alkoholitootjate TOP; Pagarite TOP; Käibe kasvu TOP 30; Omakapitali tootlikkuse TOP 30; Toiduainetööstuste üld- ja finantsandmed

  7. The Hepatitis B Virus (HBV) HBx Protein Activates AKT To Simultaneously Regulate HBV Replication and Hepatocyte Survival

    Science.gov (United States)

    Rawat, Siddhartha

    2014-01-01

    ABSTRACT Chronic infection with hepatitis B virus (HBV) is a risk factor for developing liver diseases such as hepatocellular carcinoma (HCC). HBx is a multifunctional protein encoded by the HBV genome; HBx stimulates HBV replication and is thought to play an important role in the development of HBV-associated HCC. HBx can activate the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway in some cell lines; however, whether HBx regulates PI3K/AKT signaling in normal hepatocytes has not been evaluated. In studies described here, we assessed HBx activation of PI3K/AKT signaling in an ex vivo model of cultured primary hepatocytes and determined how this HBx activity affects HBV replication. We report that HBx activates AKT in primary hepatocytes and that the activation of AKT decreases HBV replication and HBV mRNA and core protein levels. We show that the transcription factor hepatocyte nuclear factor 4α (HNF4α) is a target of HBx-regulated AKT, and we link HNF4α to HBx-regulated AKT modulation of HBV transcription and replication. Although we and others have shown that HBx stimulates and is likely required for HBV replication, we now report that HBx also activates signals that can diminish the overall level of HBV replication. While this may seem counterintuitive, we show that an important effect of HBx activation of AKT is inhibition of apoptosis. Consequently, our studies suggest that HBx balances HBV replication and cell survival by stimulating signaling pathways that enhance hepatocyte survival at the expense of higher levels of HBV replication. IMPORTANCE Chronic hepatitis B virus (HBV) infection is a common cause of the development of liver cancer. Regulation of cell signaling pathways by the HBV HBx protein is thought to influence the development of HBV-associated liver cancer. HBx stimulates, and may be essential for, HBV replication. We show that HBx activates AKT in hepatocytes to reduce HBV replication. While this seems contradictory to an

  8. Top quark production at the Tevatron

    Energy Technology Data Exchange (ETDEWEB)

    Varnes, Erich W.; /Arizona U.

    2010-09-01

    The Fermilab Tevatron has, until recently, been the only accelerator with sufficient energy to produce top quarks. The CDF and D0 experiments have collected large samples of top quarks. We report on recent top quark production measurements of the single top and t{bar t} production cross sections, as well as studies of the t{bar t} invariant mass distribution and a search for highly boosted top quarks.

  9. Replicating chromatin: a tale of histones

    DEFF Research Database (Denmark)

    Groth, Anja

    2009-01-01

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

  10. Enzymatic recognition of DNA replication origins

    International Nuclear Information System (INIS)

    Stayton, M.M.; Bertsch, L.; Biswas, S.

    1983-01-01

    In this paper we discuss the process of recognition of the complementary-strand origin with emphasis on RNA polymerase action in priming M13 DNA replication, the role of primase in G4 DNA replication, and the function of protein n, a priming protein, during primosome assembly. These phage systems do not require several of the bacterial DNA replication enzymes, particularly those involved in the regulation of chromosome copy number of the initiatiion of replication of duplex DNA. 51 references, 13 figures, 1 table

  11. Thermal design of top shield

    International Nuclear Information System (INIS)

    Raghupathy, S.; Velusamy, K.; Parthasarathy, U.; Ghosh, D.; Selvaraj, P.; Chellapandi, P.; Chetal, S.C.

    2005-01-01

    Full text of publication follows: Prototype Fast Breeder Reactor (PFBR) is a 500 MWe, sodium cooled, pool type fast reactor. The top shield forms the top cover for the main vessel (MV) and includes roof slab (RS), large rotatable plug (LRP), small rotatable plug (SRP) and control Plug (CP). RS, LRP and SRP are box type structures consisting of top and bottom plates stiffened by radial stiffeners and vertical penetration shells. TS is exposed to argon cover gas provided above sodium pool on the bottom side and reactor containment building air at the top. Heat transfer takes place through the argon cover gas to the bottom plate of TS. Annular gaps are formed between the components supported on TS and the component penetrations through which cellular convection takes place. A single thermal shield provided below TS reduces the heat flux to the bottom plate to 1.15 kW/m 2 . The MV (SS 316 LN) is welded to RS (carbon steel A48 P2) through a dissimilar metal weld. A step in RS and an anti convection barrier (ACB) outside RS are provided to limit the temperature at the MV-RS junction. The MV is surrounded by safety vessel (SV) and reactor vault made of concrete. Thermal insulation is provided outside SV to limit the heat transfer to the reactor vault. The design requirements of TS are to maintain the operating temperature at 383-393 K, limit the temperature difference (ΔT) across the height of TS to 20 / 100 K under normal operation/loss of cooling, provide minimum annular gap size at the component penetrations, provide a nearly linear temperature gradient in the CP portion within the height of TS, maintain the temperature of top plate of CP > 383 K, limit the ΔT across the top plate of CP to 2 K, limit the temperature near the inflatable / backup seal to 393 K, limit the temperature at the MV-RS junction and the heat flux to the reactor vault. The total heat transferred to TS is estimated to be 210 kW. A dedicated closed loop cooling system with a total flow rate of 10

  12. Top-Down Beta Enhances Bottom-Up Gamma.

    Science.gov (United States)

    Richter, Craig G; Thompson, William H; Bosman, Conrado A; Fries, Pascal

    2017-07-12

    Several recent studies have demonstrated that the bottom-up signaling of a visual stimulus is subserved by interareal gamma-band synchronization, whereas top-down influences are mediated by alpha-beta band synchronization. These processes may implement top-down control of stimulus processing if top-down and bottom-up mediating rhythms are coupled via cross-frequency interaction. To test this possibility, we investigated Granger-causal influences among awake macaque primary visual area V1, higher visual area V4, and parietal control area 7a during attentional task performance. Top-down 7a-to-V1 beta-band influences enhanced visually driven V1-to-V4 gamma-band influences. This enhancement was spatially specific and largest when beta-band activity preceded gamma-band activity by ∼0.1 s, suggesting a causal effect of top-down processes on bottom-up processes. We propose that this cross-frequency interaction mechanistically subserves the attentional control of stimulus selection. SIGNIFICANCE STATEMENT Contemporary research indicates that the alpha-beta frequency band underlies top-down control, whereas the gamma-band mediates bottom-up stimulus processing. This arrangement inspires an attractive hypothesis, which posits that top-down beta-band influences directly modulate bottom-up gamma band influences via cross-frequency interaction. We evaluate this hypothesis determining that beta-band top-down influences from parietal area 7a to visual area V1 are correlated with bottom-up gamma frequency influences from V1 to area V4, in a spatially specific manner, and that this correlation is maximal when top-down activity precedes bottom-up activity. These results show that for top-down processes such as spatial attention, elevated top-down beta-band influences directly enhance feedforward stimulus-induced gamma-band processing, leading to enhancement of the selected stimulus. Copyright © 2017 Richter, Thompson et al.

  13. Mutations in DONSON disrupt replication fork stability and cause microcephalic dwarfism.

    Science.gov (United States)

    Reynolds, John J; Bicknell, Louise S; Carroll, Paula; Higgs, Martin R; Shaheen, Ranad; Murray, Jennie E; Papadopoulos, Dimitrios K; Leitch, Andrea; Murina, Olga; Tarnauskaitė, Žygimantė; Wessel, Sarah R; Zlatanou, Anastasia; Vernet, Audrey; von Kriegsheim, Alex; Mottram, Rachel M A; Logan, Clare V; Bye, Hannah; Li, Yun; Brean, Alexander; Maddirevula, Sateesh; Challis, Rachel C; Skouloudaki, Kassiani; Almoisheer, Agaadir; Alsaif, Hessa S; Amar, Ariella; Prescott, Natalie J; Bober, Michael B; Duker, Angela; Faqeih, Eissa; Seidahmed, Mohammed Zain; Al Tala, Saeed; Alswaid, Abdulrahman; Ahmed, Saleem; Al-Aama, Jumana Yousuf; Altmüller, Janine; Al Balwi, Mohammed; Brady, Angela F; Chessa, Luciana; Cox, Helen; Fischetto, Rita; Heller, Raoul; Henderson, Bertram D; Hobson, Emma; Nürnberg, Peter; Percin, E Ferda; Peron, Angela; Spaccini, Luigina; Quigley, Alan J; Thakur, Seema; Wise, Carol A; Yoon, Grace; Alnemer, Maha; Tomancak, Pavel; Yigit, Gökhan; Taylor, A Malcolm R; Reijns, Martin A M; Simpson, Michael A; Cortez, David; Alkuraya, Fowzan S; Mathew, Christopher G; Jackson, Andrew P; Stewart, Grant S

    2017-04-01

    To ensure efficient genome duplication, cells have evolved numerous factors that promote unperturbed DNA replication and protect, repair and restart damaged forks. Here we identify downstream neighbor of SON (DONSON) as a novel fork protection factor and report biallelic DONSON mutations in 29 individuals with microcephalic dwarfism. We demonstrate that DONSON is a replisome component that stabilizes forks during genome replication. Loss of DONSON leads to severe replication-associated DNA damage arising from nucleolytic cleavage of stalled replication forks. Furthermore, ATM- and Rad3-related (ATR)-dependent signaling in response to replication stress is impaired in DONSON-deficient cells, resulting in decreased checkpoint activity and the potentiation of chromosomal instability. Hypomorphic mutations in DONSON substantially reduce DONSON protein levels and impair fork stability in cells from patients, consistent with defective DNA replication underlying the disease phenotype. In summary, we have identified mutations in DONSON as a common cause of microcephalic dwarfism and established DONSON as a critical replication fork protein required for mammalian DNA replication and genome stability.

  14. Phosphatidic acid produced by phospholipase D promotes RNA replication of a plant RNA virus.

    Directory of Open Access Journals (Sweden)

    Kiwamu Hyodo

    2015-05-01

    Full Text Available Eukaryotic positive-strand RNA [(+RNA] viruses are intracellular obligate parasites replicate using the membrane-bound replicase complexes that contain multiple viral and host components. To replicate, (+RNA viruses exploit host resources and modify host metabolism and membrane organization. Phospholipase D (PLD is a phosphatidylcholine- and phosphatidylethanolamine-hydrolyzing enzyme that catalyzes the production of phosphatidic acid (PA, a lipid second messenger that modulates diverse intracellular signaling in various organisms. PA is normally present in small amounts (less than 1% of total phospholipids, but rapidly and transiently accumulates in lipid bilayers in response to different environmental cues such as biotic and abiotic stresses in plants. However, the precise functions of PLD and PA remain unknown. Here, we report the roles of PLD and PA in genomic RNA replication of a plant (+RNA virus, Red clover necrotic mosaic virus (RCNMV. We found that RCNMV RNA replication complexes formed in Nicotiana benthamiana contained PLDα and PLDβ. Gene-silencing and pharmacological inhibition approaches showed that PLDs and PLDs-derived PA are required for viral RNA replication. Consistent with this, exogenous application of PA enhanced viral RNA replication in plant cells and plant-derived cell-free extracts. We also found that a viral auxiliary replication protein bound to PA in vitro, and that the amount of PA increased in RCNMV-infected plant leaves. Together, our findings suggest that RCNMV hijacks host PA-producing enzymes to replicate.

  15. Replicative Intermediates of Human Papillomavirus Type 11 in Laryngeal Papillomas: Site of Replication Initiation and Direction of Replication

    Science.gov (United States)

    Auborn, K. J.; Little, R. D.; Platt, T. H. K.; Vaccariello, M. A.; Schildkraut, C. L.

    1994-07-01

    We have examined the structures of replication intermediates from the human papillomavirus type 11 genome in DNA extracted from papilloma lesions (laryngeal papillomas). The sites of replication initiation and termination utilized in vivo were mapped by using neutral/neutral and neutral/alkaline two-dimensional agarose gel electrophoresis methods. Initiation of replication was detected in or very close to the upstream regulatory region (URR; the noncoding, regulatory sequences upstream of the open reading frames in the papillomavirus genome). We also show that replication forks proceed bidirectionally from the origin and converge 180circ opposite the URR. These results demonstrate the feasibility of analysis of replication of viral genomes directly from infected tissue.

  16. Effects of camptothecin or TOP1 overexpression on genetic stability in Saccharomyces cerevisiae.

    Science.gov (United States)

    Sloan, Roketa; Huang, Shar-Yin Naomi; Pommier, Yves; Jinks-Robertson, Sue

    2017-11-01

    Topoisomerase I (Top1) removes DNA torsional stress by nicking and resealing one strand of DNA, and is essential in higher eukaryotes. The enzyme is frequently overproduced in tumors and is the sole target of the chemotherapeutic drug camptothecin (CPT) and its clinical derivatives. CPT stabilizes the covalent Top1-DNA cleavage intermediate, which leads to toxic double-strand breaks (DSBs) when encountered by a replication fork. In the current study, we examined genetic instability associated with CPT treatment or with Top1 overexpression in the yeast Saccharomyces cerevisiae. Two types of instability were monitored: Top1-dependent deletions in haploid strains, which do not require processing into a DSB, and instability at the repetitive ribosomal DNA (rDNA) locus in diploid strains, which reflects DSB formation. Three 2-bp deletion hotspots were examined and mutations at each were elevated either when a wild-type strain was treated with CPT or when TOP1 was overexpressed, with the mutation frequency correlating with the level of TOP1 overexpression. Under both conditions, deletions at novel positions were enriched. rDNA stability was examined by measuring loss-of-heterozygosity and as was observed previously upon CPT treatment of a wild-type strain, Top1 overexpression destabilized rDNA. We conclude that too much, as well as too little of Top1 is detrimental to eukaryotic genomes, and that CPT has destabilizing effects that extend beyond those associated with DSB formation. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. DNA replication and cancer: From dysfunctional replication origin activities to therapeutic opportunities.

    Science.gov (United States)

    Boyer, Anne-Sophie; Walter, David; Sørensen, Claus Storgaard

    2016-06-01

    A dividing cell has to duplicate its DNA precisely once during the cell cycle to preserve genome integrity avoiding the accumulation of genetic aberrations that promote diseases such as cancer. A large number of endogenous impacts can challenge DNA replication and cells harbor a battery of pathways to promote genome integrity during DNA replication. This includes suppressing new replication origin firing, stabilization of replicating forks, and the safe restart of forks to prevent any loss of genetic information. Here, we describe mechanisms by which oncogenes can interfere with DNA replication thereby causing DNA replication stress and genome instability. Further, we describe cellular and systemic responses to these insults with a focus on DNA replication restart pathways. Finally, we discuss the therapeutic potential of exploiting intrinsic replicative stress in cancer cells for targeted therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Top quark asymmetry from a non-Abelian horizontal symmetry

    CERN Document Server

    Jung, Sunghoon; Wells, James D

    2011-01-01

    Motivated by the persistence of a large measured top quark forward-backward asymmetry at the Tevatron, we examine a model of non-Abelian flavor gauge symmetry. The exchange of the gauge bosons in the $t$-channel can give a large $\\Afb$ due to the forward Rutherford scattering peak. We address generic constraints on non-Abelian $t$-channel physics models including flavor diagonal resonances and potentially dangerous contributions to inclusive top pair cross sections. We caution on the general difficulty of comparing theoretical predictions for top quark signals to the existing experimental results due to potentially important acceptance effects. The first signature at the Large Hadron Collider can be a large inclusive top pair cross section, or like-sign dilepton events, although the latter signal is much smaller than in Abelian models. Deviations of the invariant mass distributions at the LHC will also be promising signatures. A more direct consistency check of the Tevatron asymmetry through the LHC asymmetry...

  19. Replication and Robustness in Developmental Research

    Science.gov (United States)

    Duncan, Greg J.; Engel, Mimi; Claessens, Amy; Dowsett, Chantelle J.

    2014-01-01

    Replications and robustness checks are key elements of the scientific method and a staple in many disciplines. However, leading journals in developmental psychology rarely include explicit replications of prior research conducted by different investigators, and few require authors to establish in their articles or online appendices that their key…

  20. Three Conceptual Replication Studies in Group Theory

    Science.gov (United States)

    Melhuish, Kathleen

    2018-01-01

    Many studies in mathematics education research occur with a nonrepresentative sample and are never replicated. To challenge this paradigm, I designed a large-scale study evaluating student conceptions in group theory that surveyed a national, representative sample of students. By replicating questions previously used to build theory around student…

  1. Using Replication Projects in Teaching Research Methods

    Science.gov (United States)

    Standing, Lionel G.; Grenier, Manuel; Lane, Erica A.; Roberts, Meigan S.; Sykes, Sarah J.

    2014-01-01

    It is suggested that replication projects may be valuable in teaching research methods, and also address the current need in psychology for more independent verification of published studies. Their use in an undergraduate methods course is described, involving student teams who performed direct replications of four well-known experiments, yielding…

  2. Dynamic behavior of DNA replication domains

    NARCIS (Netherlands)

    Manders, E. M.; Stap, J.; Strackee, J.; van Driel, R.; Aten, J. A.

    1996-01-01

    Like many nuclear processes, DNA replication takes place in distinct domains that are scattered throughout the S-phase nucleus. Recently we have developed a fluorescent double-labeling procedure that allows us to visualize nascent DNA simultaneously with "newborn" DNA that had replicated earlier in

  3. Top quark studies at hadron colliders

    Energy Technology Data Exchange (ETDEWEB)

    Sinervo, P.K. [Univ. of Toronto, Ontario (Canada)

    1997-01-01

    The techniques used to study top quarks at hadron colliders are presented. The analyses that discovered the top quark are described, with emphasis on the techniques used to tag b quark jets in candidate events. The most recent measurements of top quark properties by the CDF and DO Collaborations are reviewed, including the top quark cross section, mass, branching fractions, and production properties. Future top quark studies at hadron colliders are discussed, and predictions for event yields and uncertainties in the measurements of top quark properties are presented.

  4. Top quark studies at hadron colliders

    International Nuclear Information System (INIS)

    Sinervo, P.K.

    1997-01-01

    The techniques used to study top quarks at hadron colliders are presented. The analyses that discovered the top quark are described, with emphasis on the techniques used to tag b quark jets in candidate events. The most recent measurements of top quark properties by the CDF and DO Collaborations are reviewed, including the top quark cross section, mass, branching fractions, and production properties. Future top quark studies at hadron colliders are discussed, and predictions for event yields and uncertainties in the measurements of top quark properties are presented

  5. Top quark studies at hadron colliders

    International Nuclear Information System (INIS)

    Sinervo, P.K.

    1996-08-01

    The techniques used to study top quarks at hadron colliders are presented. The analyses that discovered the top quark are described, with emphasis on the techniques used to tag b quark jets in candidate events. The most recent measurements of top quark properties by the CDF and D null collaborations are reviewed, including the top quark cross section, mass, branching fractions and production properties. Future top quark studies at hadron colliders are discussed, and predictions for event yields and uncertainties in the measurements of top quark properties are presented

  6. Aberrations of ERBB2 and TOP2A Genes in Breast Cancer

    DEFF Research Database (Denmark)

    Nielsen, Kirsten Vang; Müller, Sven; Møller, Susanne

    2009-01-01

    genes and the other by having amplification of ERBB2 and deletion of TOP2A. The characteristics are compared to findings on paired ERBB2 and TOP2A data from 649 patients with invasive breast cancer from a previously published biomarker study. The physical localization of FISH signals in metaphase...... spreads from cell lines showed that simultaneous amplification is not a simple co-amplification of a whole amplicon containing both genes. Most gene signals are translocated to abnormal marker chromosomes. ERBB2 genes but not TOP2A genes are present in tandem amplicons, leading to a higher ERBB2 ratio....... This observation was confirmed by patient FISH data: among 276 (43% of all patients) abnormal tumors, 67% had different ERBB2 and TOP2A status. ERBB2 amplification with normal TOP2A status was found in 36% of the abnormal tumors (15% of all patients). Simultaneous amplification of both genes was found in 28...

  7. A Replication by Any Other Name: A Systematic Review of Replicative Intervention Studies

    Science.gov (United States)

    Cook, Bryan G.; Collins, Lauren W.; Cook, Sara C.; Cook, Lysandra

    2016-01-01

    Replication research is essential to scientific knowledge. Reviews of replication studies often electronically search for "replicat*" as a textword, which does not identify studies that replicate previous research but do not self-identify as such. We examined whether the 83 intervention studies published in six non-categorical research…

  8. Recommendations for Replication Research in Special Education: A Framework of Systematic, Conceptual Replications

    Science.gov (United States)

    Coyne, Michael D.; Cook, Bryan G.; Therrien, William J.

    2016-01-01

    Special education researchers conduct studies that can be considered replications. However, they do not often refer to them as replication studies. The purpose of this article is to consider the potential benefits of conceptualizing special education intervention research within a framework of systematic, conceptual replication. Specifically, we…

  9. Surface Microstructure Replication in Injection Moulding

    DEFF Research Database (Denmark)

    Hansen, Hans Nørgaard; Arlø, Uffe Rolf

    2005-01-01

    topography is transcribed onto the plastic part through complex mechanisms. This replication however, is not perfect, and the replication quality depends on the plastic material properties, the topography itself, and the process conditions. This paper describes and discusses an investigation of injection...... moulding of surface microstructures. Emphasis is put on the ability to replicate surface microstructures under normal injection moulding conditions, notably with low cost materials at low mould temperatures. The replication of surface microstructures in injection moulding has been explored...... for Polypropylene at low mould temperatures. The process conditions were varied over the recommended process window for the material. The geometry of the obtained structures was analyzed. Evidence suggests that step height replication quality depends linearly on structure width in a certain range. Further...

  10. Surface microstructure replication in injection molding

    DEFF Research Database (Denmark)

    Theilade, Uffe Arlø; Hansen, Hans Nørgaard

    2006-01-01

    topography is transcribed onto the plastic part through complex mechanisms. This replication, however, is not perfect, and the replication quality depends on the plastic material properties, the topography itself, and the process conditions. This paper describes and discusses an investigation of injection...... molding of surface microstructures. The fundamental problem of surface microstructure replication has been studied. The research is based on specific microstructures as found in lab-on-a-chip products and on rough surfaces generated from EDM (electro discharge machining) mold cavities. Emphasis is put...... on the ability to replicate surface microstructures under normal injection-molding conditions, i.e., with commodity materials within typical process windows. It was found that within typical process windows the replication quality depends significantly on several process parameters, and especially the mold...

  11. Rescue from replication stress during mitosis.

    Science.gov (United States)

    Fragkos, Michalis; Naim, Valeria

    2017-04-03

    Genomic instability is a hallmark of cancer and a common feature of human disorders, characterized by growth defects, neurodegeneration, cancer predisposition, and aging. Recent evidence has shown that DNA replication stress is a major driver of genomic instability and tumorigenesis. Cells can undergo mitosis with under-replicated DNA or unresolved DNA structures, and specific pathways are dedicated to resolving these structures during mitosis, suggesting that mitotic rescue from replication stress (MRRS) is a key process influencing genome stability and cellular homeostasis. Deregulation of MRRS following oncogene activation or loss-of-function of caretaker genes may be the cause of chromosomal aberrations that promote cancer initiation and progression. In this review, we discuss the causes and consequences of replication stress, focusing on its persistence in mitosis as well as the mechanisms and factors involved in its resolution, and the potential impact of incomplete replication or aberrant MRRS on tumorigenesis, aging and disease.

  12. Suppression of Poxvirus Replication by Resveratrol.

    Science.gov (United States)

    Cao, Shuai; Realegeno, Susan; Pant, Anil; Satheshkumar, Panayampalli S; Yang, Zhilong

    2017-01-01

    Poxviruses continue to cause serious diseases even after eradication of the historically deadly infectious human disease, smallpox. Poxviruses are currently being developed as vaccine vectors and cancer therapeutic agents. Resveratrol is a natural polyphenol stilbenoid found in plants that has been shown to inhibit or enhance replication of a number of viruses, but the effect of resveratrol on poxvirus replication is unknown. In the present study, we found that resveratrol dramatically suppressed the replication of vaccinia virus (VACV), the prototypic member of poxviruses, in various cell types. Resveratrol also significantly reduced the replication of monkeypox virus, a zoonotic virus that is endemic in Western and Central Africa and causes human mortality. The inhibitory effect of resveratrol on poxviruses is independent of VACV N1 protein, a potential resveratrol binding target. Further experiments demonstrated that resveratrol had little effect on VACV early gene expression, while it suppressed VACV DNA synthesis, and subsequently post-replicative gene expression.

  13. Suppression of Poxvirus Replication by Resveratrol

    Directory of Open Access Journals (Sweden)

    Shuai Cao

    2017-11-01

    Full Text Available Poxviruses continue to cause serious diseases even after eradication of the historically deadly infectious human disease, smallpox. Poxviruses are currently being developed as vaccine vectors and cancer therapeutic agents. Resveratrol is a natural polyphenol stilbenoid found in plants that has been shown to inhibit or enhance replication of a number of viruses, but the effect of resveratrol on poxvirus replication is unknown. In the present study, we found that resveratrol dramatically suppressed the replication of vaccinia virus (VACV, the prototypic member of poxviruses, in various cell types. Resveratrol also significantly reduced the replication of monkeypox virus, a zoonotic virus that is endemic in Western and Central Africa and causes human mortality. The inhibitory effect of resveratrol on poxviruses is independent of VACV N1 protein, a potential resveratrol binding target. Further experiments demonstrated that resveratrol had little effect on VACV early gene expression, while it suppressed VACV DNA synthesis, and subsequently post-replicative gene expression.

  14. Miltefosine inhibits Chikungunya virus replication in human primary dermal fibroblasts [version 1; referees: 2 approved, 1 approved with reservations

    Directory of Open Access Journals (Sweden)

    Anuj Sharma

    2018-01-01

    Full Text Available Background: Chikungunya virus (CHIKV is a re-emerging pathogen that has caused widespread outbreaks affecting millions of people around the globe. Currently, there is no specific therapeutic drug against CHIKV, with symptomatic treatment only to manage the disease. Pi3-akt signaling has been implicated in infection of several viruses including that of CHIKV. Effect of Pi3-akt signaling inhibitors on CHIKV replication was evaluated in this study. Methods: Human primary dermal fibroblast cells were treated with inhibitors of the Pi3-akt signaling pathway. Suppression of CHIKV replication was evaluated as reduction in virus titer in cell supernatants. Effect of miltefosine (MF on CHIKV replication was evaluated in pre and post treatment regimen. Inhibition of virus replication was determined by cell growth, virus titer and western blot. Results: Inhibition of Akt-phosphorylation significantly inhibited CHIKV replication. No effect on CHIKV replication was observed after treatment with Pi3-kinase and mTOR activation inhibitors. Further, MF, an FDA-approved Akt-inhibitor, inhibited CHIKV replication in pre- and post-infection treatment regimens. Conclusion: Data suggests that Akt-phosphorylation can be an amenable target of therapy against CHIKV infection. This is the first study to show inhibition of CHIKV replication by MF, and presents a case for further development of MF as an anti-CHIKV drug.

  15. Support vector machines in analysis of top quark production

    International Nuclear Information System (INIS)

    Vaiciulis, A.

    2003-01-01

    The Support Vector Machine (SVM) learning algorithm is a new alternative to multivariate methods such as neural networks. Potential applications of SVMs in high energy physics include the common classification problem of signal/background discrimination as well as particle identification. A comparison of a conventional method and an SVM algorithm is presented here for the case of identifying top quark events in Run II physics at the CDF experiment

  16. A New Replication Norm for Psychology

    Directory of Open Access Journals (Sweden)

    Etienne P LeBel

    2015-10-01

    Full Text Available In recent years, there has been a growing concern regarding the replicability of findings in psychology, including a mounting number of prominent findings that have failed to replicate via high-powered independent replication attempts. In the face of this replicability “crisis of confidence”, several initiatives have been implemented to increase the reliability of empirical findings. In the current article, I propose a new replication norm that aims to further boost the dependability of findings in psychology. Paralleling the extant social norm that researchers should peer review about three times as many articles that they themselves publish per year, the new replication norm states that researchers should aim to independently replicate important findings in their own research areas in proportion to the number of original studies they themselves publish per year (e.g., a 4:1 original-to-replication studies ratio. I argue this simple approach could significantly advance our science by increasing the reliability and cumulative nature of our empirical knowledge base, accelerating our theoretical understanding of psychological phenomena, instilling a focus on quality rather than quantity, and by facilitating our transformation toward a research culture where executing and reporting independent direct replications is viewed as an ordinary part of the research process. To help promote the new norm, I delineate (1 how each of the major constituencies of the research process (i.e., funders, journals, professional societies, departments, and individual researchers can incentivize replications and promote the new norm and (2 any obstacles each constituency faces in supporting the new norm.

  17. Toiduainetööstuse TOP 95 aastal 2002

    Index Scriptorium Estoniae

    2003-01-01

    Toiduainetööstuse TOP 95. Käibe TOP 50. Kasumi TOP 50. Rentaabluse TOP 25. Kasumi kasvu TOP 25. Omakapitali tootlikkuse TOP 25. Käibe kasvu TOP 25. Toiduainetööstuse TOP 95 ettevõtted 2002: üldandmed ja finantsandmed

  18. Ida-Virumaa ettevõtete TOP aastal 2002

    Index Scriptorium Estoniae

    2003-01-01

    Ettevõtete TOP 55. TOP-i esikümme. Käibe TOP 40. Kasumi TOP 40. Käibe kasvu TOP 20. Kasumi kasvu TOP 20. Rentaabluse TOP 20. Omakapitali tootlikkuse TOP 20. Ida-Virumaa firmade üldandmed. Ida-Virumaa firmade finantsandmed

  19. Over the top: Experiment and the testing of hypotheses in the search for the top quark

    Science.gov (United States)

    Staley, Kent Wade

    1998-07-01

    This study presents a historical account of experiments, performed by the Collider Detector at Fermilab (CDF) collaboration, which led to the discovery of the top quark, and a discussion of philosophical issues raised by that episode. The historical discussion is based on published and unpublished documents and oral history interviews, and is presented in two parts: First, the formation of the collaboration and construction of the detector are described. The activities of the collaborators during the period of detector construction are described in terms of the development of resources for a general experimental programme. Second, the development of the means of analyzing the data for the top quark search is described, particularly aspects of the analysis that were disputed. The hypothesis that collaboration researchers have come to regard the social process of resolving disputes as a matter of methodological importance is suggested. The philosophical discussion of the experiment employs the hierarchy of models approach of Patrick Suppes and Deborah Mayo in order to examine the logic of hypothesis testing and draw some conclusions regarding the nature of scientific evidence. In an extension of an argument presented by Peter Achinstein, the account of hypothesis testing given by hypothetico-deductivist philosophers such as Karl Popper and R. B. Braithwaite is examined in light of the reasoning employed in the top search, and is found wanting. The prediction based on the hypothesis being tested in the top search is found to have been inferred inductively from the experimental data. Finally, a discussion is presented of tuning on the signal, a form of bias in the testing of hypotheses. The proscription of this form of bias resembles John Worrall's requirement of use novelty, but is shown instead to serve the aim of devising a test of the hypothesis that is severe, in the sense articulated by Deborah Mayo. It is shown that the evaluation of evidence claims, as it

  20. Table-top job analysis

    Energy Technology Data Exchange (ETDEWEB)

    1994-12-01

    The purpose of this Handbook is to establish general training program guidelines for training personnel in developing training for operation, maintenance, and technical support personnel at Department of Energy (DOE) nuclear facilities. TTJA is not the only method of job analysis; however, when conducted properly TTJA can be cost effective, efficient, and self-validating, and represents an effective method of defining job requirements. The table-top job analysis is suggested in the DOE Training Accreditation Program manuals as an acceptable alternative to traditional methods of analyzing job requirements. DOE 5480-20A strongly endorses and recommends it as the preferred method for analyzing jobs for positions addressed by the Order.

  1. Top-down cellular pyramids

    Energy Technology Data Exchange (ETDEWEB)

    Wu, A Y; Rosenfeld, A

    1983-10-01

    A cellular pyramid is an exponentially tapering stack of arrays of processors (cells), where each cell is connected to its neighbors (siblings) on its own level, to a parent on the level above, and to its children on the level below. It is shown that in some situations, if information flows top-down only, from fathers to sons, then a cellular pyramid may be no faster than a one-level cellular array; but it may be possible to use simpler cells in the pyramid case. 23 references.

  2. Search for FCNC in top-quark events in ATLAS

    CERN Document Server

    Cristinziani, Markus

    2013-01-01

    Searches for flavor changing neutral current (FCNC) processes in top-quark production and decays by the ATLAS Collaboration are presented. Data collected from $pp$ collisions at the LHC at a centre-of-mass energy of 7 TeV during 2011, corresponding to an integrated luminosity of 2.05/fb, are used. In a first analysis single top-quarks produced via FCNC are searched for. Candidate events with a semileptonic top-quark decay signature are classified as signal or background-like events by using several kinematic variables as input to a neural network. No signal is observed in the neural network output distribution and a Bayesian upper limit is placed on the production cross-section. The observed upper limit is converted using a model-independent approach into upper limits on the coupling strengths k_{ugt}/Lambda ug) cg) Zq FCNC (q=u,c) channel, and the other through the Standard Model dominant mode t-->Wb. Only the decays of the Z boson to charged leptons and leptonic W-boson decays are considered as signal. No e...

  3. Top quark forward-backward asymmetry from new t-channel physics

    CERN Document Server

    Jung, Sunghoon; Pierce, Aaron; Wells, James D

    2010-01-01

    Motivated by recent measurements of the top quark forward-backward asymmetry at the Tevatron, we study how t-channel new physics can contribute to a large value. We concentrate on a theory with an abelian gauge boson possessing flavor changing couplings between up and top quarks, but satisfies flavor physics constraints. Collider constraints are strong, but can be consistent with the aid of small flavor diagonal couplings. We find that M_Z' ~ 160 GeV can yield a total lab-frame asymmetry of ~18% without being in conflict with other observables. There are implications for future collider searches, including exotic top quark decays, like-sign top quark production, and detailed measurements of the top production cross section. An alternate model with a gauged non-Abelian flavor symmetry would have similar phenomenology, but lacks the like-sign top signal.

  4. Top quark production at the LHC

    CERN Document Server

    Gilles, Geoffrey; The ATLAS collaboration

    2018-01-01

    The top quark is the heaviest known fundamental particle. As it is the only quark that decays before it hadronizes, it gives us the unique opportunity to probe the properties of bare quarks at the Large Hadron Collider. This talk will present highlights of a few recent precision measurements of the top quark using 13 TeV and 8 TeV collision data: top-quark pair and single top production cross sections, including differential distributions and production in association with bosons, will be presented alongside top quark properties measurements. These measurements, including results using boosted top quarks, probe our understanding of top quark production in the TeV regime. Measurements of the top quark mass are also presented.

  5. Results on top-quark physics and top-quark-like signatures by CMS

    Science.gov (United States)

    Chabert, Eric; CMS Collaboration

    2017-07-01

    This report reviews the results obtained by the CMS Collaboration on top quark physics, focusing on the latest ones based on p-p collisions provided by the LHC at \\sqrt{s}=13{{TeV}} during Run II. It covers measurements of single-top, top quark pairs and associated productions as well as measurements of top quark properties. Finally several beyond the standard model searches involving top quark in the final states are presented, such as searches for supersymmetry in the third generation, heavy resonances decaying into a top quark pair, or dark matter produced in association to a single-top or a top quark pair.

  6. Data from Investigating Variation in Replicability: A “Many Labs” Replication Project

    Directory of Open Access Journals (Sweden)

    Richard A. Klein

    2014-04-01

    Full Text Available This dataset is from the Many Labs Replication Project in which 13 effects were replicated across 36 samples and over 6,000 participants. Data from the replications are included, along with demographic variables about the participants and contextual information about the environment in which the replication was conducted. Data were collected in-lab and online through a standardized procedure administered via an online link. The dataset is stored on the Open Science Framework website. These data could be used to further investigate the results of the included 13 effects or to study replication and generalizability more broadly.

  7. p53 Maintains Genomic Stability by Preventing Interference between Transcription and Replication

    Directory of Open Access Journals (Sweden)

    Constance Qiao Xin Yeo

    2016-04-01

    Full Text Available p53 tumor suppressor maintains genomic stability, typically acting through cell-cycle arrest, senescence, and apoptosis. We discovered a function of p53 in preventing conflicts between transcription and replication, independent of its canonical roles. p53 deficiency sensitizes cells to Topoisomerase (Topo II inhibitors, resulting in DNA damage arising spontaneously during replication. Topoisomerase IIα (TOP2A-DNA complexes preferentially accumulate in isogenic p53 mutant or knockout cells, reflecting an increased recruitment of TOP2A to regulate DNA topology. We propose that p53 acts to prevent DNA topological stress originating from transcription during the S phase and, therefore, promotes normal replication fork progression. Consequently, replication fork progression is impaired in the absence of p53, which is reversed by transcription inhibition. Pharmacologic inhibition of transcription also attenuates DNA damage and decreases Topo-II-DNA complexes, restoring cell viability in p53-deficient cells. Together, our results demonstrate a function of p53 that may underlie its role in tumor suppression.

  8. Search for anomalous Wtb couplings and top FCNC in t-channel single-top-quark events in the CMS experiment

    CERN Document Server

    Tsirova, Natalia

    2015-01-01

    Single-top-quark events in the t-channel are used to probe Wtb anomalous couplings and to search for top-quark Flavor-Changing Neutral Current (FCNC) interactions in proton-proton collisions with the CMS experiment. A Bayesian neural network is used to discriminate between signal and backgrounds. The observed event yields are consistent with SM prediction, and exclusion limits at 95\\% C.L. are determined.

  9. Top mass in ATLAS and CMS

    CERN Document Server

    Castro, A.

    2017-01-01

    Top quarks are produced copiously at the LHC, and a variety of related measurements has been made in the recent years by the two collaborations ATLAS and CMS. The most recent measurements of the top quark mass by the two collaborations are reported here. The top quark mass has been measured with a relative uncertainty smaller than 0.3pct, making the top quark the most accurately measured quark.

  10. New Physics in Single-Top Production

    CERN Document Server

    Kind, OM; The ATLAS collaboration

    2013-01-01

    In this presentation for TOP 2013 the latest results on searches of physics beyond the Standard Model using single-top signatures from CDF, CMS, D0 and ATLAS are collected. This includes searches for unknown resonances like W' or b*, measurements of the W helicity fractions and top polarisation in single-top events, as well as tests for CP violation, FCNC or anomalous weak couplings.

  11. Chromosome replication, cell growth, division and shape: a personal perspective

    Directory of Open Access Journals (Sweden)

    Arieh eZaritsky

    2015-08-01

    Full Text Available The origins of Molecular Biology and Bacterial Physiology are reviewed, from our personal standpoints, emphasizing the coupling between bacterial growth, chromosome replication and cell division, dimensions and shape. Current knowledge is discussed with historical perspective, summarizing past and present achievements and enlightening ideas for future studies. An interactive simulation program of the Bacterial Cell Division Cycle (BCD, described as The Central Dogma in Bacteriology, is briefly represented. The coupled process of transcription/translation of genes encoding membrane proteins and insertion into the membrane (so-called transertion is invoked as the functional relationship between the only two unique macromolecules in the cell, DNA and peptidoglycan embodying the nucleoid and the sacculus respectively. We envision that nucleoid complexity, defined as the weighted-mean DNA content associated with the replication terminus, is directly related to cell shape through the transertion process. Accordingly, the primary signal for cell division transmitted by DNA dynamics (replication, transcription and segregation to the peptidoglycan biosynthetic machinery is of a physico-chemical nature, eg stress in the plasma membrane, relieving nucleoid occlusion in the cell's center hence enabling the divisome to assemble and function between segregated daughter nucleoids.

  12. ATM supports gammaherpesvirus replication by attenuating type I interferon pathway.

    Science.gov (United States)

    Darrah, Eric J; Stoltz, Kyle P; Ledwith, Mitchell; Tarakanova, Vera L

    2017-10-01

    Ataxia-Telangiectasia mutated (ATM) kinase participates in multiple networks, including DNA damage response, oxidative stress, and mitophagy. ATM also supports replication of diverse DNA and RNA viruses. Gammaherpesviruses are prevalent cancer-associated viruses that benefit from ATM expression during replication. This proviral role of ATM had been ascribed to its signaling within the DNA damage response network; other functions of ATM have not been considered. In this study increased type I interferon (IFN) responses were observed in ATM deficient gammaherpesvirus-infected macrophages. Using a mouse model that combines ATM and type I IFN receptor deficiencies we show that increased type I IFN response in the absence of ATM fully accounts for the proviral role of ATM during gammaherpesvirus replication. Further, increased type I IFN response rendered ATM deficient macrophages more susceptible to antiviral effects of type II IFN. This study identifies attenuation of type I IFN responses as the primary mechanism underlying proviral function of ATM during gammaherpesvirus infection. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. MHD Integrated Topping Cycle Project

    Energy Technology Data Exchange (ETDEWEB)

    1992-01-01

    The overall objective of the project is to design and construct prototypical hardware for an integrated MHD topping cycle, and conduct long duration proof-of-concept tests of integrated system at the US DOE Component Development and Integration Facility in Butte, Montana. The results of the long duration tests will augment the existing engineering design data base on MHD power train reliability, availability, maintainability, and performance, and will serve as a basis for scaling up the topping cycle design to the next level of development, an early commercial scale power plant retrofit. The components of the MHD power train to be designed, fabricated, and tested include: A slagging coal combustor with a rated capacity of 50 MW thermal input, capable of operation with an Eastern (Illinois {number sign}6) or Western (Montana Rosebud) coal, a segmented supersonic nozzle, a supersonic MHD channel capable of generating at least 1.5 MW of electrical power, a segmented supersonic diffuser section to interface the channel with existing facility quench and exhaust systems, a complete set of current control circuits for local diagonal current control along the channel, and a set of current consolidation circuits to interface the channel with the existing facility inverter.

  14. Factors influencing microinjection molding replication quality

    Science.gov (United States)

    Vera, Julie; Brulez, Anne-Catherine; Contraires, Elise; Larochette, Mathieu; Trannoy-Orban, Nathalie; Pignon, Maxime; Mauclair, Cyril; Valette, Stéphane; Benayoun, Stéphane

    2018-01-01

    In recent years, there has been increased interest in producing and providing high-precision plastic parts that can be manufactured by microinjection molding: gears, pumps, optical grating elements, and so on. For all of these applications, the replication quality is essential. This study has two goals: (1) fabrication of high-precision parts using the conventional injection molding machine; (2) identification of robust parameters that ensure production quality. Thus, different technological solutions have been used: cavity vacuuming and the use of a mold coated with DLC or CrN deposits. AFM and SEM analyses were carried out to characterize the replication profile. The replication quality was studied in terms of the process parameters, coated and uncoated molds and crystallinity of the polymer. Specific studies were processed to quantify the replicability of injection molded parts (ABS, PC and PP). Analysis of the Taguchi experimental designs permits prioritization of the impact of each parameter on the replication quality. A discussion taking into account these new parameters and the thermal and spreading properties on the coatings is proposed. It appeared that, in general, increasing the mold temperature improves the molten polymer fill in submicron features except for the steel insert (for which the presence of a vacuum is the most important factor). Moreover, the DLC coating was the best coating to increase the quality of the replication. This result could be explained by the lower thermal diffusivity of this coating. We noted that the viscosity of the polymers is not a primordial factor of the replication quality.

  15. The Inherent Asymmetry of DNA Replication.

    Science.gov (United States)

    Snedeker, Jonathan; Wooten, Matthew; Chen, Xin

    2017-10-06

    Semiconservative DNA replication has provided an elegant solution to the fundamental problem of how life is able to proliferate in a way that allows cells, organisms, and populations to survive and replicate many times over. Somewhat lost, however, in our admiration for this mechanism is an appreciation for the asymmetries that occur in the process of DNA replication. As we discuss in this review, these asymmetries arise as a consequence of the structure of the DNA molecule and the enzymatic mechanism of DNA synthesis. Increasing evidence suggests that asymmetries in DNA replication are able to play a central role in the processes of adaptation and evolution by shaping the mutagenic landscape of cells. Additionally, in eukaryotes, recent work has demonstrated that the inherent asymmetries in DNA replication may play an important role in the process of chromatin replication. As chromatin plays an essential role in defining cell identity, asymmetries generated during the process of DNA replication may play critical roles in cell fate decisions related to patterning and development.

  16. Ultrastructural Characterization of Zika Virus Replication Factories

    Directory of Open Access Journals (Sweden)

    Mirko Cortese

    2017-02-01

    Full Text Available Summary: A global concern has emerged with the pandemic spread of Zika virus (ZIKV infections that can cause severe neurological symptoms in adults and newborns. ZIKV is a positive-strand RNA virus replicating in virus-induced membranous replication factories (RFs. Here we used various imaging techniques to investigate the ultrastructural details of ZIKV RFs and their relationship with host cell organelles. Analyses of human hepatic cells and neural progenitor cells infected with ZIKV revealed endoplasmic reticulum (ER membrane invaginations containing pore-like openings toward the cytosol, reminiscent to RFs in Dengue virus-infected cells. Both the MR766 African strain and the H/PF/2013 Asian strain, the latter linked to neurological diseases, induce RFs of similar architecture. Importantly, ZIKV infection causes a drastic reorganization of microtubules and intermediate filaments forming cage-like structures surrounding the viral RF. Consistently, ZIKV replication is suppressed by cytoskeleton-targeting drugs. Thus, ZIKV RFs are tightly linked to rearrangements of the host cell cytoskeleton. : Cortese et al. show that ZIKV infection in both human hepatoma and neuronal progenitor cells induces drastic structural modification of the cellular architecture. Microtubules and intermediate filaments surround the viral replication factory composed of vesicles corresponding to ER membrane invagination toward the ER lumen. Importantly, alteration of microtubule flexibility impairs ZIKV replication. Keywords: Zika virus, flavivirus, human neural progenitor cells, replication factories, replication organelles, microtubules, intermediate filaments, electron microscopy, electron tomography, live-cell imaging

  17. Variety of DNA Replication Activity Among Cyanobacteria Correlates with Distinct Respiration Activity in the Dark.

    Science.gov (United States)

    Ohbayashi, Ryudo; Yamamoto, Jun-Ya; Watanabe, Satoru; Kanesaki, Yu; Chibazakura, Taku; Miyagishima, Shin-Ya; Yoshikawa, Hirofumi

    2017-02-01

    Cyanobacteria exhibit light-dependent cell growth since most of their cellular energy is obtained by photosynthesis. In Synechococcus elongatus PCC 7942, one of the model cyanobacteria, DNA replication depends on photosynthetic electron transport. However, the critical signal for the regulatory mechanism of DNA replication has not been identified. In addition, conservation of this regulatory mechanism has not been investigated among cyanobacteria. To understand this regulatory signal and its dependence on light, we examined the regulation of DNA replication under both light and dark conditions among three model cyanobacteria, S. elongatus PCC 7942, Synechocystis sp. PCC 6803 and Anabaena sp. PCC 7120. Interestingly, DNA replication activity in Synechocystis and Anabaena was retained when cells were transferred to the dark, although it was drastically decreased in S. elongatus. Glycogen metabolism and respiration were higher in Synechocystis and Anabaena than in S. elongatus in the dark. Moreover, DNA replication activity in Synechocystis and Anabaena was reduced to the same level as that in S. elongatus by inhibition of respiratory electron transport after transfer to the dark. These results demonstrate that there is disparity in DNA replication occurring in the dark among cyanobacteria, which is caused by the difference in activity of respiratory electron transport. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  18. MYC and the Control of DNA Replication

    Science.gov (United States)

    Dominguez-Sola, David; Gautier, Jean

    2014-01-01

    The MYC oncogene is a multifunctional protein that is aberrantly expressed in a significant fraction of tumors from diverse tissue origins. Because of its multifunctional nature, it has been difficult to delineate the exact contributions of MYC’s diverse roles to tumorigenesis. Here, we review the normal role of MYC in regulating DNA replication as well as its ability to generate DNA replication stress when overexpressed. Finally, we discuss the possible mechanisms by which replication stress induced by aberrant MYC expression could contribute to genomic instability and cancer. PMID:24890833

  19. Replicated Data Management for Mobile Computing

    CERN Document Server

    Douglas, Terry

    2008-01-01

    Managing data in a mobile computing environment invariably involves caching or replication. In many cases, a mobile device has access only to data that is stored locally, and much of that data arrives via replication from other devices, PCs, and services. Given portable devices with limited resources, weak or intermittent connectivity, and security vulnerabilities, data replication serves to increase availability, reduce communication costs, foster sharing, and enhance survivability of critical information. Mobile systems have employed a variety of distributed architectures from client-server

  20. Replication-mediated disassociation of replication protein A-XPA complex upon DNA damage: implications for RPA handing off.

    Science.gov (United States)

    Jiang, Gaofeng; Zou, Yue; Wu, Xiaoming

    2012-08-01

    RPA (replication protein A), the eukaryotic ssDNA (single-stranded DNA)-binding protein, participates in most cellular processes in response to genotoxic insults, such as NER (nucleotide excision repair), DNA, DSB (double-strand break) repair and activation of cell cycle checkpoint signalling. RPA interacts with XPA (xeroderma pigmentosum A) and functions in early stage of NER. We have shown that in cells the RPA-XPA complex disassociated upon exposure of cells to high dose of UV irradiation. The dissociation required replication stress and was partially attributed to tRPA hyperphosphorylation. Treatment of cells with CPT (camptothecin) and HU (hydroxyurea), which cause DSB DNA damage and replication fork collapse respectively and also leads to the disruption of RPA-XPA complex. Purified RPA and XPA were unable to form complex in vitro in the presence of ssDNA. We propose that the competition-based RPA switch among different DNA metabolic pathways regulates the dissociation of RPA with XPA in cells after DNA damage. The biological significances of RPA-XPA complex disruption in relation with checkpoint activation, DSB repair and RPA hyperphosphorylation are discussed.

  1. Replication-mediated disassociation of replication protein A–XPA complex upon DNA damage: implications for RPA handing off

    Science.gov (United States)

    Jiang, Gaofeng; Zou, Yue; Wu, Xiaoming

    2013-01-01

    RPA (replication protein A), the eukaryotic ssDNA (single-stranded DNA)-binding protein, participates in most cellular processes in response to genotoxic insults, such as NER (nucleotide excision repair), DNA, DSB (double-strand break) repair and activation of cell cycle checkpoint signalling. RPA interacts with XPA (xeroderma pigmentosum A) and functions in early stage of NER. We have shown that in cells the RPA–XPA complex disassociated upon exposure of cells to high dose of UV irradiation. The dissociation required replication stress and was partially attributed to tRPA hyperphosphorylation. Treatment of cells with CPT (camptothecin) and HU (hydroxyurea), which cause DSB DNA damage and replication fork collapse respectively and also leads to the disruption of RPA–XPA complex. Purified RPA and XPA were unable to form complex in vitro in the presence of ssDNA. We propose that the competition-based RPA switch among different DNA metabolic pathways regulates the dissociation of RPA with XPA in cells after DNA damage. The biological significances of RPA–XPA complex disruption in relation with checkpoint activation, DSB repair and RPA hyperphosphorylation are discussed. PMID:22578086

  2. Centromeric DNA replication reconstitution reveals DNA loops and ATR checkpoint suppression.

    Science.gov (United States)

    Aze, Antoine; Sannino, Vincenzo; Soffientini, Paolo; Bachi, Angela; Costanzo, Vincenzo

    2016-06-01

    Half of the human genome is made up of repetitive DNA. However, mechanisms underlying replication of chromosome regions containing repetitive DNA are poorly understood. We reconstituted replication of defined human chromosome segments using bacterial artificial chromosomes in Xenopus laevis egg extract. Using this approach we characterized the chromatin assembly and replication dynamics of centromeric alpha-satellite DNA. Proteomic analysis of centromeric chromatin revealed replication-dependent enrichment of a network of DNA repair factors including the MSH2-6 complex, which was required for efficient centromeric DNA replication. However, contrary to expectations, the ATR-dependent checkpoint monitoring DNA replication fork arrest could not be activated on highly repetitive DNA due to the inability of the single-stranded DNA binding protein RPA to accumulate on chromatin. Electron microscopy of centromeric DNA and supercoil mapping revealed the presence of topoisomerase I-dependent DNA loops embedded in a protein matrix enriched for SMC2-4 proteins. This arrangement suppressed ATR signalling by preventing RPA hyper-loading, facilitating replication of centromeric DNA. These findings have important implications for our understanding of repetitive DNA metabolism and centromere organization under normal and stressful conditions.

  3. Search for Single Top Production at LEP

    CERN Document Server

    Achard, P; Aguilar-Benítez, M; Alcaraz, J; Alemanni, G; Allaby, James V; Aloisio, A; Alviggi, M G; Anderhub, H; Andreev, V P; Anselmo, F; Arefev, A; Azemoon, T; Aziz, T; Bagnaia, P; Bajo, A; Baksay, G; Baksay, L; Baldew, S V; Banerjee, S; Banerjee, Sw; Barczyk, A; Barillère, R; Bartalini, P; Basile, M; Batalova, N; Battiston, R; Bay, A; Becattini, F; Becker, U; Behner, F; Bellucci, L; Berbeco, R; Berdugo, J; Berges, P; Bertucci, B; Betev, B L; Biasini, M; Biglietti, M; Biland, A; Blaising, J J; Blyth, S C; Bobbink, Gerjan J; Böhm, A; Boldizsar, L; Borgia, B; Bottai, S; Bourilkov, D; Bourquin, Maurice; Braccini, S; Branson, J G; Brochu, F; Burger, J D; Burger, W J; Cai, X D; Capell, M; Cara Romeo, G; Carlino, G; Cartacci, A M; Casaus, J; Cavallari, F; Cavallo, N; Cecchi, C; Cerrada, M; Chamizo-Llatas, M; Chang, Y H; Chemarin, M; Chen, A; Chen, G; Chen, G M; Chen, H F; Chen, H S; Chiefari, G; Cifarelli, Luisa; Cindolo, F; Clare, I; Clare, R; Coignet, G; Colino, N; Costantini, S; de la Cruz, B; Cucciarelli, S; van Dalen, J A; De Asmundis, R; Déglon, P L; Debreczeni, J; Degré, A; Dehmelt, K; Deiters, K; Della Volpe, D; Delmeire, E; Denes, P; De Notaristefani, F; De Salvo, A; Diemoz, M; Dierckxsens, M; Dionisi, C; Dittmar, M; Doria, A; Dova, M T; Duchesneau, D; Echenard, B; Eline, A; El-Mamouni, H; Engler, A; Eppling, F J; Ewers, A; Extermann, P; Falagán, M A; Falciano, S; Favara, A; Fay, J; Fedin, O; Felcini, M; Ferguson, T; Fesefeldt, H S; Fiandrini, E; Field, J H; Filthaut, Frank; Fisher, P H; Fisher, W; Fisk, I; Forconi, G; Freudenreich, Klaus; Furetta, C; Galaktionov, Yu; Ganguli, S N; García-Abia, P; Gataullin, M; Gentile, S; Giagu, S; Gong, Z F; Grenier, G; Grimm, O; Grünewald, M W; Guida, M; van Gulik, R; Gupta, V K; Gurtu, A; Gutay, L J; Haas, D; Hakobyan, R S; Hatzifotiadou, D; Hebbeker, T; Hervé, A; Hirschfelder, J; Hofer, H; Hohlmann, M; Holzner, G; Hou, S R; Hu, Y; Jin, B N; Jones, L W; de Jong, P; Josa-Mutuberria, I; Käfer, D; Kaur, M; Kienzle-Focacci, M N; Kim, J K; Kirkby, Jasper; Kittel, E W; Klimentov, A; König, A C; Kopal, M; Koutsenko, V F; Kräber, M H; Krämer, R W; Krenz, W; Krüger, A; Kunin, A; Ladrón de Guevara, P; Laktineh, I; Landi, G; Lebeau, M; Lebedev, A; Lebrun, P; Lecomte, P; Lecoq, P; Le Coultre, P; Le Goff, J M; Leiste, R; Levtchenko, M; Levchenko, P M; Li, C; Likhoded, S A; Lin, C H; Lin, W T; Linde, Frank L; Lista, L; Liu, Z A; Lohmann, W; Longo, E; Lü, Y S; Lübelsmeyer, K; Luci, C; Luminari, L; Lustermann, W; Ma Wen Gan; Malgeri, L; Malinin, A; Maña, C; Mangeol, D J J; Mans, J; Martin, J P; Marzano, F; Mazumdar, K; McNeil, R R; Mele, S; Merola, L; Meschini, M; Metzger, W J; Mihul, A; Milcent, H; Mirabelli, G; Mnich, J; Mohanty, G B; Muanza, G S; Muijs, A J M; Musicar, B; Musy, M; Nagy, S; Natale, S; Napolitano, M; Nessi-Tedaldi, F; Newman, H; Niessen, T; Nisati, A; Nowak, H; Ofierzynski, R A; Organtini, G; Palomares, C; Pandoulas, D; Paolucci, P; Paramatti, R; Passaleva, G; Patricelli, S; Paul, T; Pauluzzi, M; Paus, C; Pauss, Felicitas; Pedace, M; Pensotti, S; Perret-Gallix, D; Petersen, B; Piccolo, D; Pierella, F; Pioppi, M; Piroué, P A; Pistolesi, E; Plyaskin, V; Pohl, M; Pozhidaev, V; Pothier, J; Prokofiev, D O; Prokofev, D; Quartieri, J; Rahal-Callot, G; Rahaman, M A; Raics, P; Raja, N; Ramelli, R; Rancoita, P G; Ranieri, R; Raspereza, A V; Razis, P A; Ren, D; Rescigno, M; Reucroft, S; Riemann, S; Riles, K; Roe, B P; Romero, L; Rosca, A; Rosier-Lees, S; Roth, S; Rosenbleck, C; Roux, B; Rubio, Juan Antonio; Ruggiero, G; Rykaczewski, H; Sakharov, A; Saremi, S; Sarkar, S; Salicio, J; Sánchez, E; Sanders, M P; Schäfer, C; Shchegelskii, V; Schmidt-Kärst, S; Schmitz, D; Schopper, Herwig Franz; Schotanus, D J; Schwering, G; Sciacca, C; Servoli, L; Shevchenko, S; Shivarov, N; Shoutko, V; Shumilov, E; Shvorob, A V; Siedenburg, T; Son, D; Souga, C; Spillantini, P; Steuer, M; Stickland, D P; Stoyanov, B; Strässner, A; Sudhakar, K; Sultanov, G G; Sun, L Z; Sushkov, S V; Suter, H; Swain, J D; Szillási, Z; Tang, X W; Tarjan, P; Tauscher, Ludwig; Taylor, L; Tellili, B; Teyssier, D; Timmermans, C; Ting, Samuel C C; Ting, S M; Tonwar, S C; Tóth, J; Tully, C; Tung, K L; Ulbricht, J; Valente, E; Van de Walle, R T; Vásquez, R P; Veszpremi, V; Vesztergombi, G; Vetlitskii, I; Vicinanza, D; Viertel, Gert M; Villa, S; Vivargent, M; Vlachos, S; Vodopyanov, I; Vogel, H; Vogt, H; Vorobev, I; Vorobyov, A A; Wadhwa, M; Wallraff, W; Wang, X L; Wang, Z M; Weber, M; Wienemann, P; Wilkens, H; Wynhoff, S; Xia, L; Xu, Z Z; Yamamoto, J; Yang, B Z; Yang, C G; Yang, H J; Yang, M; Yeh, S C; Zalite, A; Zalite, Yu; Zhang, Z P; Zhao, J; Zhu, G Y; Zhu, R Y; Zhuang, H L; Zichichi, A; Zimmermann, B; Zöller, M

    2002-01-01

    Single top production in e^+e^- annihilations is searched for in data collected by the L3 detector at centre-of-mass energies from 189 to 209 GeV, corresponding to a total integrated luminosity of 634 pb-1. Investigating hadronic and semileptonic top decays, no evidence of single top production at LEP is obtained and upper limits on the single top cross section as a function of the centre-of-mass energy are derived. Limits on possible anomalous couplings, as well as on the scale of contact interactions responsible for single top production are determined.

  4. Single top quark production with CMS

    Directory of Open Access Journals (Sweden)

    Piccolo Davide

    2013-11-01

    Full Text Available Measurements of single top quark production performed using the CMS experiment [1] data collected in 2011 at centre-of-mass energies of 7 TeV and in 2012 at 8 TeV, are presented. The cross sections for the electroweak production of single top quarks in the t-channel and in association with W-bosons is measured and the results are used to place constraints on the CKM matrix element Vtb. Measurements of top quark properties in single top quark production are also presented. The results include the measurement of the charge ratio in the single top t-channel.

  5. CP Violation in Single Top Quark Production

    Energy Technology Data Exchange (ETDEWEB)

    Geng, Weigang [Michigan State Univ., East Lansing, MI (United States)

    2012-01-01

    We present a search for CP violation in single top quark production with the DØ experiment at the Tevatron proton-antiproton collider. CP violation in the top electroweak interaction results in different single top quark production cross sections for top and antitop quarks. We perform the search in the single top quark final state using 5.4 fb-1 of data, in the s-channel, t-channel, and for both combined. At this time, we do not see an observable CP asymmetry.

  6. Top quark physics at the LHC

    Directory of Open Access Journals (Sweden)

    Jeong Kim Tae

    2014-04-01

    Full Text Available In 2011, an integrated luminosity of more than 5 fb−1 at 7 TeV has been delivered by the LHC. The measurement of the cross section in top quark pair production and in single top quark production, top quark mass, top quark properties and new physics searches in top quark decays have been performed at the CMS experiment with various integrated luminosities. An overview of the latest results of these measurements and searches by the time of ICFP 2012 conference will be presented.

  7. Top flooding modeling with MAAP4 code

    International Nuclear Information System (INIS)

    Brunet-Thibault, E.; Marguet, S.

    2006-01-01

    An engineering top flooding model was developed in MAAP4.04d.4, the severe accident code used in EDF, to simulate the thermal-hydraulic phenomena that should take place if emergency core cooling (ECC) water was injected in hot leg during quenching. In the framework of the ISTC (International Science and Technology Centre), a top flooding test was proposed in the PARAMETER facility (Podolsk, Russia). The MAAP calculation of the PARAMETER top flooding test is presented in this paper. A comparison between top and bottom flooding was made on the bundle test geometry. According to this study, top flooding appears to cool quickly and effectively the upper plenum internals. (author)

  8. Searching for the top at UA2

    International Nuclear Information System (INIS)

    Unal, G.

    1990-10-01

    The projects conceived for searching the quark top, predicted by the Standard Model, are described. The required existence of the quark top from the Standard Model and its production from proton-antiproton collisions are reviewed. The UA2 experimental device is described. The method applied for the search of the top is explained. The analysis of the UA2 data does not allow to conclude the existence of the top. However, the low mass limit of 69 GeV/C 2 can be established for the top mass. The results of the analysis of the W decays into supersymmetric particles are included [fr

  9. What Should Researchers Expect When They Replicate Studies? A Statistical View of Replicability in Psychological Science.

    Science.gov (United States)

    Patil, Prasad; Peng, Roger D; Leek, Jeffrey T

    2016-07-01

    A recent study of the replicability of key psychological findings is a major contribution toward understanding the human side of the scientific process. Despite the careful and nuanced analysis reported, the simple narrative disseminated by the mass, social, and scientific media was that in only 36% of the studies were the original results replicated. In the current study, however, we showed that 77% of the replication effect sizes reported were within a 95% prediction interval calculated using the original effect size. Our analysis suggests two critical issues in understanding replication of psychological studies. First, researchers' intuitive expectations for what a replication should show do not always match with statistical estimates of replication. Second, when the results of original studies are very imprecise, they create wide prediction intervals-and a broad range of replication effects that are consistent with the original estimates. This may lead to effects that replicate successfully, in that replication results are consistent with statistical expectations, but do not provide much information about the size (or existence) of the true effect. In this light, the results of the Reproducibility Project: Psychology can be viewed as statistically consistent with what one might expect when performing a large-scale replication experiment. © The Author(s) 2016.

  10. Top down electroweak dipole operators

    Science.gov (United States)

    Fuyuto, Kaori; Ramsey-Musolf, Michael

    2018-06-01

    We derive present constraints on, and prospective sensitivity to, the electric dipole moment (EDM) of the top quark (dt) implied by searches for the EDMs of the electron and nucleons. Above the electroweak scale v, the dt arises from two gauge invariant operators generated at a scale Λ ≫ v that also mix with the light fermion EDMs under renormalization group evolution at two-loop order. Bounds on the EDMs of first generation fermion systems thus imply bounds on |dt |. Working in the leading log-squared approximation, we find that the present upper bound on |dt | is 10-19 e cm for Λ = 1 TeV, except in regions of finely tuned cancellations that allow for |dt | to be up to fifty times larger. Future de and dn probes may yield an order of magnitude increase in dt sensitivity, while inclusion of a prospective proton EDM search may lead to an additional increase in reach.

  11. Mapping replication origins in yeast chromosomes.

    Science.gov (United States)

    Brewer, B J; Fangman, W L

    1991-07-01

    The replicon hypothesis, first proposed in 1963 by Jacob and Brenner, states that DNA replication is controlled at sites called origins. Replication origins have been well studied in prokaryotes. However, the study of eukaryotic chromosomal origins has lagged behind, because until recently there has been no method for reliably determining the identity and location of origins from eukaryotic chromosomes. Here, we review a technique we developed with the yeast Saccharomyces cerevisiae that allows both the mapping of replication origins and an assessment of their activity. Two-dimensional agarose gel electrophoresis and Southern hybridization with total genomic DNA are used to determine whether a particular restriction fragment acquires the branched structure diagnostic of replication initiation. The technique has been used to localize origins in yeast chromosomes and assess their initiation efficiency. In some cases, origin activation is dependent upon the surrounding context. The technique is also being applied to a variety of eukaryotic organisms.

  12. Advancing Polymerase Ribozymes Towards Self-Replication

    Science.gov (United States)

    Tjhung, K. F.; Joyce, G. F.

    2017-07-01

    Autocatalytic replication and evolution in vitro by (i) a cross-chiral RNA polymerase catalyzing polymerization of mononucleotides of the opposite handedness; (ii) non-covalent assembly of component fragments of an existing RNA polymerase ribozyme.

  13. Initiation of Replication in Escherichia coli

    DEFF Research Database (Denmark)

    Frimodt-Møller, Jakob

    The circular chromosome of Escherichia coli is replicated by two replisomes assembled at the unique origin and moving in the opposite direction until they meet in the less well defined terminus. The key protein in initiation of replication, DnaA, facilitates the unwinding of double-stranded DNA...... to single-stranded DNA in oriC. Although DnaA is able to bind both ADP and ATP, DnaA is only active in initiation when bound to ATP. Although initiation of replication, and the regulation of this, is thoroughly investigated it is still not fully understood. The overall aim of the thesis was to investigate...... the regulation of initiation, the effect on the cell when regulation fails, and if regulation was interlinked to chromosomal organization. This thesis uncovers that there exists a subtle balance between chromosome replication and reactive oxygen species (ROS) inflicted DNA damage. Thus, failure in regulation...

  14. LHCb Data Replication During SC3

    CERN Multimedia

    Smith, A

    2006-01-01

    LHCb's participation in LCG's Service Challenge 3 involves testing the bulk data transfer infrastructure developed to allow high bandwidth distribution of data across the grid in accordance with the computing model. To enable reliable bulk replication of data, LHCb's DIRAC system has been integrated with gLite's File Transfer Service middleware component to make use of dedicated network links between LHCb computing centres. DIRAC's Data Management tools previously allowed the replication, registration and deletion of files on the grid. For SC3 supplementary functionality has been added to allow bulk replication of data (using FTS) and efficient mass registration to the LFC replica catalog.Provisional performance results have shown that the system developed can meet the expected data replication rate required by the computing model in 2007. This paper details the experience and results of integration and utilisation of DIRAC with the SC3 transfer machinery.

  15. Locating Nearby Copies of Replicated Internet Servers

    National Research Council Canada - National Science Library

    Guyton, James D; Schwartz, Michael F

    1995-01-01

    In this paper we consider the problem of choosing among a collection of replicated servers focusing on the question of how to make choices that segregate client/server traffic according to network topology...

  16. Top Management Involvement in New Product Development

    DEFF Research Database (Denmark)

    Felekoglu, Burcu; Maier, Anja; Moultrie, James

    2010-01-01

    a broader conceptual space than this participation. This paper reviews the literature on top management involvement in new product development (NPD) and discusses relevance of different theoretical perspectives from other disciplines such as management, organisational behaviour and communication to analyse......Involvement of top managers in new product development (NPD) is a critical factor affecting NPD performance and frequently considered to be the participation of top management to certain activities in NPD or their NPD related behaviours. However, “Top management involvement in NPD” occupies...... antecedents, realisation and consequences of top management involvement in NPD. It is argued that top management has different involvement at different NPD levels: organisation level and project level. Resulting from this literature review, a tentative framework for top management involvement in NPD...

  17. The Dynamics of Costly Signaling

    Directory of Open Access Journals (Sweden)

    Elliott O. Wagner

    2013-04-01

    Full Text Available Costly signaling is a mechanism through which the honesty of signals can be secured in equilibrium, even in interactions where communicators have conflicting interests. This paper explores the dynamics of one such signaling game: Spence’s model of education. It is found that separating equilibria are unlikely to emerge under either the replicator or best response dynamics, but that partially communicative mixed equilibria are quite important dynamically. These mixtures are Lyapunov stable in the replicator dynamic and asymptotically stable in the best response dynamic. Moreover, they have large basins of attraction, in fact larger than those of either pooling or separating equilibria. This suggests that these mixtures may play significant, and underappreciated, roles in the explanation of the emergence and stability of information transfer.

  18. Early manifestations of replicative aging in the yeast Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Maksim I. Sorokin

    2014-01-01

    Full Text Available The yeast Saccharomyces cerevisiae is successfully used as a model organism to find genes responsible for lifespan control of higher organisms. As functional decline of higher eukaryotes can start as early as one quarter of the average lifespan, we asked whether S. cerevisiae can be used to model this manifestation of aging. While the average replicative lifespan of S. cerevisiae mother cells ranges between 15 and 30 division cycles, we found that resistances to certain stresses start to decrease much earlier. Looking into the mechanism, we found that knockouts of genes responsible for mitochondriato-nucleus (retrograde signaling, RTG1 or RTG3, significantly decrease the resistance of cells that generated more than four daughters, but not of the younger ones. We also found that even young mother cells frequently contain mitochondria with heterogeneous transmembrane potential and that the percentage of such cells correlates with replicative age. Together, these facts suggest that retrograde signaling starts to malfunction in relatively young cells, leading to accumulation of heterogeneous mitochondria within one cell. The latter may further contribute to a decline in stress resistances.

  19. DNA damage by X-rays and their impact on replication processes

    International Nuclear Information System (INIS)

    Parplys, Ann Christin; Petermann, Eva; Petersen, Cordula; Dikomey, Ekkehard; Borgmann, Kerstin

    2012-01-01

    Background: Replication-dependent radiosensitization of tumors ranks among the most promising tools for future improvements in tumor therapy. However, cell cycle checkpoint signaling during S phase is a key for maintaining genomic stability after ionizing irradiation allowing DNA damage repair by stabilizing replication forks, inhibiting new origin firing and recruiting DNA repair proteins. As the impact of the different types of DNA damage induced by ionizing radiation on replication fork functionality has not been investigated, this study was performed in tumor cells treated with various agents that induce specific DNA lesions. Methods: U2OS cells were exposed to methyl methanesulfonate (MMS) to induce base damage, low or high concentrations of hydrogen peroxide for the induction of SSBs, Topotecan to induce DSBs at replication, Mitomycin C (MMC) to induce interstrand cross-links or ionizing irradiation to analyze all damages. Chk1 phosphorylation, origin firing and replication fork progression, and cell cycle distribution were analyzed. Results: In our system, the extent of Chk1 phosphorylation was dependent on the type of damage induced and prolonged Chk1 phosphorylation correlated with the inhibition of replication initiation. Ionizing radiation, high concentrations of hydrogen peroxide, and Topotecan affected replication elongation much more strongly that the other agents. Almost all agents induced a slight increase in the S phase population but subsequent G2 arrest was only observed in response to those agents that strongly inhibited replication elongation and caused prolonged Chk1 phosphorylation. Conclusions: Our data suggest that to improve radiotherapy, radiosensitivity in S phase could be increased by combining irradiation with agents that induce secondary DSB or inhibit checkpoint signaling, such as inhibitors of PARP or Chk1.

  20. Surface Micro Topography Replication in Injection Moulding

    DEFF Research Database (Denmark)

    Arlø, Uffe Rolf; Hansen, Hans Nørgaard; Kjær, Erik Michael

    2005-01-01

    The surface micro topography of injection moulded plastic parts can be important for aesthetical and technical reasons. The quality of replication of mould surface topography onto the plastic surface depends among other factors on the process conditions. A study of this relationship has been...... carried out with rough EDM (electrical discharge machining) mould surfaces, a PS grade, and by applying established three-dimensional topography parameters. Significant quantitative relationships between process parameters and topography parameters were established. It further appeared that replication...

  1. The Legal Road To Replicating Silicon Valley

    OpenAIRE

    John Armour; Douglas Cumming

    2004-01-01

    Must policymakers seeking to replicate the success of Silicon Valley’s venture capital market first replicate other US institutions, such as deep and liquid stock markets? Or can legal reforms alone make a significant difference? In this paper, we compare the economic and legal determinants of venture capital investment, fundraising and exits. We introduce a cross-sectional and time series empirical analysis across 15 countries and 13 years of data spanning an entire business cycle. We show t...

  2. Evolution of Database Replication Technologies for WLCG

    OpenAIRE

    Baranowski, Zbigniew; Pardavila, Lorena Lobato; Blaszczyk, Marcin; Dimitrov, Gancho; Canali, Luca

    2015-01-01

    In this article we summarize several years of experience on database replication technologies used at WLCG and we provide a short review of the available Oracle technologies and their key characteristics. One of the notable changes and improvement in this area in recent past has been the introduction of Oracle GoldenGate as a replacement of Oracle Streams. We report in this article on the preparation and later upgrades for remote replication done in collaboration with ATLAS and Tier 1 databas...

  3. Modes of DNA repair and replication

    International Nuclear Information System (INIS)

    Hanawalt, P.; Kondo, S.

    1979-01-01

    Modes of DNA repair and replication require close coordination as well as some overlap of enzyme functions. Some classes of recovery deficient mutants may have defects in replication rather than repair modes. Lesions such as the pyrimidine dimers produced by ultraviolet light irradiation are the blocks to normal DNA replication in vivo and in vitro. The DNA synthesis by the DNA polymerase 1 of E. coli is blocked at one nucleotide away from the dimerized pyrimidines in template strands. Thus, some DNA polymerases seem to be unable to incorporate nucleotides opposite to the non-pairing lesions in template DNA strands. The lesions in template DNA strands may block the sequential addition of nucleotides in the synthesis of daughter strands. Normal replication utilizes a constitutive ''error-free'' mode that copies DNA templates with high fidelity, but which may be totally blocked at a lesion that obscures the appropriate base pairing specificity. It might be expected that modified replication system exhibits generally high error frequency. The error rate of DNA polymerases may be controlled by the degree of phosphorylation of the enzyme. Inducible SOS system is controlled by recA genes that also control the pathways for recombination. It is possible that SOS system involves some process other than the modification of a blocked replication apparatus to permit error-prone transdimer synthesis. (Yamashita, S.)

  4. Replication and robustness in developmental research.

    Science.gov (United States)

    Duncan, Greg J; Engel, Mimi; Claessens, Amy; Dowsett, Chantelle J

    2014-11-01

    Replications and robustness checks are key elements of the scientific method and a staple in many disciplines. However, leading journals in developmental psychology rarely include explicit replications of prior research conducted by different investigators, and few require authors to establish in their articles or online appendices that their key results are robust across estimation methods, data sets, and demographic subgroups. This article makes the case for prioritizing both explicit replications and, especially, within-study robustness checks in developmental psychology. It provides evidence on variation in effect sizes in developmental studies and documents strikingly different replication and robustness-checking practices in a sample of journals in developmental psychology and a sister behavioral science-applied economics. Our goal is not to show that any one behavioral science has a monopoly on best practices, but rather to show how journals from a related discipline address vital concerns of replication and generalizability shared by all social and behavioral sciences. We provide recommendations for promoting graduate training in replication and robustness-checking methods and for editorial policies that encourage these practices. Although some of our recommendations may shift the form and substance of developmental research articles, we argue that they would generate considerable scientific benefits for the field. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

  5. Nonequilibrium Entropic Bounds for Darwinian Replicators

    Directory of Open Access Journals (Sweden)

    Jordi Piñero

    2018-01-01

    Full Text Available Life evolved on our planet by means of a combination of Darwinian selection and innovations leading to higher levels of complexity. The emergence and selection of replicating entities is a central problem in prebiotic evolution. Theoretical models have shown how populations of different types of replicating entities exclude or coexist with other classes of replicators. Models are typically kinetic, based on standard replicator equations. On the other hand, the presence of thermodynamical constraints for these systems remain an open question. This is largely due to the lack of a general theory of statistical methods for systems far from equilibrium. Nonetheless, a first approach to this problem has been put forward in a series of novel developements falling under the rubric of the extended second law of thermodynamics. The work presented here is twofold: firstly, we review this theoretical framework and provide a brief description of the three fundamental replicator types in prebiotic evolution: parabolic, malthusian and hyperbolic. Secondly, we employ these previously mentioned techinques to explore how replicators are constrained by thermodynamics. Finally, we comment and discuss where further research should be focused on.

  6. Commercial Building Partnerships Replication and Diffusion

    Energy Technology Data Exchange (ETDEWEB)

    Antonopoulos, Chrissi A.; Dillon, Heather E.; Baechler, Michael C.

    2013-09-16

    This study presents findings from survey and interview data investigating replication efforts of Commercial Building Partnership (CBP) partners that worked directly with the Pacific Northwest National Laboratory (PNNL). PNNL partnered directly with 12 organizations on new and retrofit construction projects, which represented approximately 28 percent of the entire U.S. Department of Energy (DOE) CBP program. Through a feedback survey mechanism, along with personal interviews, PNNL gathered quantitative and qualitative data relating to replication efforts by each organization. These data were analyzed to provide insight into two primary research areas: 1) CBP partners’ replication efforts of technologies and approaches used in the CBP project to the rest of the organization’s building portfolio (including replication verification), and, 2) the market potential for technology diffusion into the total U.S. commercial building stock, as a direct result of the CBP program. The first area of this research focused specifically on replication efforts underway or planned by each CBP program participant. Factors that impact replication include motivation, organizational structure and objectives firms have for implementation of energy efficient technologies. Comparing these factors between different CBP partners revealed patterns in motivation for constructing energy efficient buildings, along with better insight into market trends for green building practices. The second area of this research develops a diffusion of innovations model to analyze potential broad market impacts of the CBP program on the commercial building industry in the United States.

  7. Human Parvovirus B19 Utilizes Cellular DNA Replication Machinery for Viral DNA Replication.

    Science.gov (United States)

    Zou, Wei; Wang, Zekun; Xiong, Min; Chen, Aaron Yun; Xu, Peng; Ganaie, Safder S; Badawi, Yomna; Kleiboeker, Steve; Nishimune, Hiroshi; Ye, Shui Qing; Qiu, Jianming

    2018-03-01

    Human parvovirus B19 (B19V) infection of human erythroid progenitor cells (EPCs) induces a DNA damage response and cell cycle arrest at late S phase, which facilitates viral DNA replication. However, it is not clear exactly which cellular factors are employed by this single-stranded DNA virus. Here, we used microarrays to systematically analyze the dynamic transcriptome of EPCs infected with B19V. We found that DNA metabolism, DNA replication, DNA repair, DNA damage response, cell cycle, and cell cycle arrest pathways were significantly regulated after B19V infection. Confocal microscopy analyses revealed that most cellular DNA replication proteins were recruited to the centers of viral DNA replication, but not the DNA repair DNA polymerases. Our results suggest that DNA replication polymerase δ and polymerase α are responsible for B19V DNA replication by knocking down its expression in EPCs. We further showed that although RPA32 is essential for B19V DNA replication and the phosphorylated forms of RPA32 colocalized with the replicating viral genomes, RPA32 phosphorylation was not necessary for B19V DNA replication. Thus, this report provides evidence that B19V uses the cellular DNA replication machinery for viral DNA replication. IMPORTANCE Human parvovirus B19 (B19V) infection can cause transient aplastic crisis, persistent viremia, and pure red cell aplasia. In fetuses, B19V infection can result in nonimmune hydrops fetalis and fetal death. These clinical manifestations of B19V infection are a direct outcome of the death of human erythroid progenitors that host B19V replication. B19V infection induces a DNA damage response that is important for cell cycle arrest at late S phase. Here, we analyzed dynamic changes in cellular gene expression and found that DNA metabolic processes are tightly regulated during B19V infection. Although genes involved in cellular DNA replication were downregulated overall, the cellular DNA replication machinery was tightly

  8. Signal Words

    Science.gov (United States)

    SIGNAL WORDS TOPIC FACT SHEET NPIC fact sheets are designed to answer questions that are commonly asked by the ... making decisions about pesticide use. What are Signal Words? Signal words are found on pesticide product labels, ...

  9. Ravimimüüjate TOP 30 aastal 2002

    Index Scriptorium Estoniae

    2003-01-01

    Ravimimüüjate TOP 30 aastal 2002. Käibe TOP 30. Kasumi TOP 30. Käibe kasvu TOP 20. Kasumi kasvu TOP 20. Rentaabluse TOP 20. Omakapitali tootlikkuse TOP 20. Ravimimüüjad 2002: üld- ja finantsandmed

  10. Tekstiilitööstuse TOP 30 aastal 2002

    Index Scriptorium Estoniae

    2003-01-01

    Tekstiilitööstuse TOP 30. Kasumi TOP 30. Käibe TOP 30. Rentaabluse TOP 20. Käibe kasvu TOP 20. Kasumi kasvu TOP 20. Omakapitali tootlikkuse TOP 20. Tekstiilitööstuse ettevõtted 2002: üld- ja finantsandmed

  11. Trükitööstuste TOP 50

    Index Scriptorium Estoniae

    2002-01-01

    Trükitööstuste TOP 50. Käibe TOP 30. Käibe kasum TOP 30. Kasvu TOP 30. Kasumi kasvu TOP 30. Rentaabluse TOP. Varade tootlikkuse TOP. Trükitööstusettevõtete üldandmed. Trükitööstusettevõtete finantsandmed

  12. Rõivatööstuse TOP 40 aastal 2002

    Index Scriptorium Estoniae

    2003-01-01

    Rõivatööstuse TOP 40. Käibe TOP 40. Kasumi TOP 40. Käibe kasvu TOP 20. Kasumi kasvu TOP 20. Rentaabluse TOP 20. Omakapitali tootlikkuse TOP 20. Rõivatööstuse ettevõtted: üldandmed ja finantsandmed

  13. Läänemaa ettevõtete TOP 50

    Index Scriptorium Estoniae

    2005-01-01

    Läänemaa ettevõtete TOP 50; Käibe TOP 35; Kasumi TOP 35; Käibe kasvu TOP 20; Kasumi kasvu TOP 20; Rentaabluse TOP 20; Omakapitali tootlikkuse TOP 20; Läänemaa ettevõtete üld- ja finantsandmed

  14. Ida-Virumaa ettevõtete TOP 50

    Index Scriptorium Estoniae

    2005-01-01

    Ilmunud ka: Delovõje Vedomosti-Severo-Vostok 7. sept. lk. 4. Ida-Virumaa ettevõtete TOP 50; Käibe TOP 35; Kasumi TOP 35; Käibe kasvu TOP 20; Kasumi kasvu TOP 20; Rentaabluse TOP 20; Omakapitali tootlikkuse TOP 20; Ida-Virumaa ettevõtete üld- ja finantsandmed

  15. Toiduainetööstuse TOP 100 aastal 2001

    Index Scriptorium Estoniae

    2002-01-01

    TOP 100. Toiduainetööstuste rentaabluse TOP 40. Varade tootlikkuse TOP 40. Käibe TOP 50. Käibe kasvu TOP 50. Kasumi TOP 50. Kasumi kasvu TOP 50. Toiduainetööstuse finantsandmed aastal 2001. Toiduainetööstuse üldandmed aastal 2001

  16. Top-philic scalar Dark Matter with a vector-like fermionic top partner

    Science.gov (United States)

    Baek, Seungwon; Ko, Pyungwon; Wu, Peiwen

    2016-10-01

    We consider a simple extension of the Standard Model with a scalar top-philic Dark Matter (DM) S coupling, apart from the Higgs portal, exclusively to the right-handed top quark t R and a colored vector-like top partner T with a Yukawa coupling y ST which we call the topVL portal. When the Higgs portal is closed and y ST is perturbative (≲1), T S → ( W + b, gt), SSto toverline{t} and Toverline{T}to (qoverline{q}, gg) provide the dominant (co) annihilation contributions to obtain ΩDM h 2 ≃ 0 .12 in light, medium and heavy DM mass range, respectively. However, large {y}_{ST}˜ O(10) can make SS → gg dominate via the loop-induced coupling C SSgg in the m S < m t region. In this model it is the C SSgg coupling that generates DM-nucleon scattering in the direct detection, which can be large and simply determined by ΩDM h 2 ≃ 0 .12 when SS → gg dominates the DM annihilation. The current LUX results can exclude the SS → gg dominating scenario and XENON-1T experiment may further test y ST ≳ 1, and 0 .5 ≲ y ST ≲ 1 may be covered in the future LUX-ZP experiment. The current indirect detection results from Fermi gamma-ray observations can also exclude the SS → gg dominating scenario and are sensitive to the heavy DM mass region, of which the improved sensitivity by one order will push DM mass to be above 400, 600, 1000 GeV for y ST = 0 .3 , 0 .5 , 1 .0, respectively. Toverline{T} pair produced at the hadron collider will decay 100% into [InlineMediaObject not available: see fulltext.] signal when kinematically open. The latest ATLAS 13 TeV 13.2 fb-1 data can excluded m T between 300 (650) and 1150 (1100) GeV for m S =40 (400) GeV and the exclusion region can reach up to m S ˜ 500 GeV.

  17. Organization of Replication of Ribosomal DNA in Saccharomyces cerevisiae

    NARCIS (Netherlands)

    Linskens, Maarten H.K.; Huberman, Joel A.

    1988-01-01

    Using recently developed replicon mapping techniques, we have analyzed the replication of the ribosomal DNA in Saccharomyces cerevisiae. The results show that (i) the functional origin of replication colocalizes with an autonomously replicating sequence element previously mapped to the

  18. Visualization and measurement of ATP levels in living cells replicating hepatitis C virus genome RNA.

    Directory of Open Access Journals (Sweden)

    Tomomi Ando

    Full Text Available Adenosine 5'-triphosphate (ATP is the primary energy currency of all living organisms and participates in a variety of cellular processes. Although ATP requirements during viral lifecycles have been examined in a number of studies, a method by which ATP production can be monitored in real-time, and by which ATP can be quantified in individual cells and subcellular compartments, is lacking, thereby hindering studies aimed at elucidating the precise mechanisms by which viral replication energized by ATP is controlled. In this study, we investigated the fluctuation and distribution of ATP in cells during RNA replication of the hepatitis C virus (HCV, a member of the Flaviviridae family. We demonstrated that cells involved in viral RNA replication actively consumed ATP, thereby reducing cytoplasmic ATP levels. Subsequently, a method to measure ATP levels at putative subcellular sites of HCV RNA replication in living cells was developed by introducing a recently-established Förster resonance energy transfer (FRET-based ATP indicator, called ATeam, into the NS5A coding region of the HCV replicon. Using this method, we were able to observe the formation of ATP-enriched dot-like structures, which co-localize with non-structural viral proteins, within the cytoplasm of HCV-replicating cells but not in non-replicating cells. The obtained FRET signals allowed us to estimate ATP concentrations within HCV replicating cells as ∼5 mM at possible replicating sites and ∼1 mM at peripheral sites that did not appear to be involved in HCV replication. In contrast, cytoplasmic ATP levels in non-replicating Huh-7 cells were estimated as ∼2 mM. To our knowledge, this is the first study to demonstrate changes in ATP concentration within cells during replication of the HCV genome and increased ATP levels at distinct sites within replicating cells. ATeam may be a powerful tool for the study of energy metabolism during replication of the viral genome.

  19. Lääne-Virumaa TOP 100 aastal 2000

    Index Scriptorium Estoniae

    2001-01-01

    Lääne-Virumaa edukamad ettevõtted; Lääne-Virumaa käibe TOP 100; Käibe kasvu TOP 20; Käibe languse TOP 10; Kasumi TOP 20; Kasumi kasvu TOP 20; Rentabluse TOP 20; ROA TOP 20; Kasumi languse TOP 10; Kahjumi TOP 10; Lääne-Virumaa käibelt suuremate ettevõtete finantsandmed. Lääne-Virumaa ettevõtete üldandmed

  20. A-Train Observations of Deep Convective Storm Tops

    Science.gov (United States)

    Setvak, Martin; Bedka, Kristopher; Lindsey, Daniel T.; Sokol, Alois; Charvat, Zdenek; Stastka, Jindrich; Wang, Pao K.

    2013-01-01

    The paper highlights simultaneous observations of tops of deep convective clouds from several space-borne instruments including the Moderate Resolution Imaging Spectroradiometer (MODIS) of the Aqua satellite, Cloud Profiling Radar (CPR) of the CloudSat satellite, and Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) flown on the CALIPSO satellite. These satellites share very close orbits, thus together with several other satellites they are referred to as the "A-Train" constellation. Though the primary responsibility of these satellites and their instrumentation is much broader than observations of fine-scale processes atop convective storms, in this study we document how data from the A-Train can contribute to a better understanding and interpretation of various storm-top features, such as overshooting tops, cold-U/V and cold ring features with their coupled embedded warm areas, above anvil ice plumes and jumping cirrus. The relationships between MODIS multi-spectral brightness temperature difference (BTD) fields and cloud top signatures observed by the CPR and CALIOP are also examined in detail to highlight the variability in BTD signals across convective storm events.

  1. Observation of top quark production using kinematic techniques

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Shinhong [Tsukuba Univ., Ibaraki (Japan); CDF Collaboration

    1995-05-17

    We present analysis results of the top quark production using kinematic techniques in p{bar p} collisions at {radical}s = 1.8 TeV with the Collider Detector at Fermilab (CDF). We analyzed a data sample corresponding to an integrated luminosity of 67 pb{sup {minus}1}. First, we compare the kinematic properties, the second and third leading jet E{sub T} of W+ > 3 jet events with expectations for t{bar t} production and its back-ground processes, predominantly direct W + jet production. The probability that backgrounds fake the excess in the signal region was found to be less than 0.26%. Next, we use a scaler sum of the transverse energies of the lepton, neutrino and jets in W+{ge}4 jet events. This analysis shows t{bar t} events exist significantly in the event sample, and enables us to estimate the top quark mass to be M{sub top} = 180 {plus_minus} 12 {sub {minus}15}{sup +19} GeV/c{sup 2}. Finally, we analyse the dijet invariant mass in the W+{ge}4 jet events. It shows a significant mass peak consistent with a mass peak of W decaying into dijet. From these results and counting experiment, we have confirmed previous evidence reported in 1994 April and observed top quark production.

  2. Single Top Quark Production at the LHC Understanding Spin

    CERN Document Server

    Mahlon, G; Mahlon, Gregory; Parke, Stephen

    2000-01-01

    We show that the single top quarks produced in the Wg-fusion channel at a proton-proton collider at a center-of-mass energy sqrt{s}=14 TeV posses a high degree of polarization in terms of a spin basis which decomposes the top quark spin in its rest frame along the direction of the spectator jet. A second useful spin basis is the eta-beamline basis, which decomposes the top quark spin along one of the two beam directions, depending on which hemisphere contains the spectator jet. We elucidate the interplay between the two- and three-body final states contributing to this production cross section in the context of determining the spin decomposition of the top quarks, and argue that the zero momentum frame helicity is undefined. We show that the usefulness of the spectator and eta-beamline spin bases is not adversely affected by the cuts required to separate the Wg-fusion signal from the background.

  3. Replication and meta-analysis of TMEM132D gene variants in panic disorder

    DEFF Research Database (Denmark)

    Erhardt, A; Akula, N; Schumacher, J

    2012-01-01

    (EA), the association of rs7309727 and the risk haplotype rs7309727-rs11060369 was, indeed, replicated, with the strongest signal coming from patients with primary PD, that is, patients without major psychiatric comorbidities (n = 1038 cases and n = 2411 controls). This finding was paralleled...

  4. TRAIP is a PCNA-binding ubiquitin ligase that protects genome stability after replication stress

    DEFF Research Database (Denmark)

    Hoffmann, Saskia; Smedegaard, Stine; Nakamura, Kyosuke

    2016-01-01

    ATR-dependent checkpoint signaling in human cells by facilitating the generation of RPA-bound single-stranded DNA regions upon replication stress in a manner that critically requires its E3 ligase activity and is potentiated by the PIP box. Consequently, loss of TRAIP function leads to enhanced...

  5. How many bootstrap replicates are necessary?

    Science.gov (United States)

    Pattengale, Nicholas D; Alipour, Masoud; Bininda-Emonds, Olaf R P; Moret, Bernard M E; Stamatakis, Alexandros

    2010-03-01

    Phylogenetic bootstrapping (BS) is a standard technique for inferring confidence values on phylogenetic trees that is based on reconstructing many trees from minor variations of the input data, trees called replicates. BS is used with all phylogenetic reconstruction approaches, but we focus here on one of the most popular, maximum likelihood (ML). Because ML inference is so computationally demanding, it has proved too expensive to date to assess the impact of the number of replicates used in BS on the relative accuracy of the support values. For the same reason, a rather small number (typically 100) of BS replicates are computed in real-world studies. Stamatakis et al. recently introduced a BS algorithm that is 1 to 2 orders of magnitude faster than previous techniques, while yielding qualitatively comparable support values, making an experimental study possible. In this article, we propose stopping criteria--that is, thresholds computed at runtime to determine when enough replicates have been generated--and we report on the first large-scale experimental study to assess the effect of the number of replicates on the quality of support values, including the performance of our proposed criteria. We run our tests on 17 diverse real-world DNA--single-gene as well as multi-gene--datasets, which include 125-2,554 taxa. We find that our stopping criteria typically stop computations after 100-500 replicates (although the most conservative criterion may continue for several thousand replicates) while producing support values that correlate at better than 99.5% with the reference values on the best ML trees. Significantly, we also find that the stopping criteria can recommend very different numbers of replicates for different datasets of comparable sizes. Our results are thus twofold: (i) they give the first experimental assessment of the effect of the number of BS replicates on the quality of support values returned through BS, and (ii) they validate our proposals for

  6. Search for FCNC in top-quark events in ATLAS

    CERN Document Server

    Cristinziani, M; The ATLAS collaboration

    2012-01-01

    Searches for flavor changing neutral current (FCNC) processes in top-quark production and decays by the ATLAS Collaboration are presented. Data collected from $pp$ collisions at the LHC at a centre-of-mass energy of $\\sqrt{s}=7$ GeV during 2011, corresponding to an integrated luminosity of 2.05 fb$^{-1}$, are used. In a first analysis single top-quarks produced via FCNC are searched for. Candidate events with a semileptonic top-quark decay signature are classified as signal or background-like events by using several kinematic variables as input to a neural network. No signal is observed in the neural network output distribution and a Bayesian upper limit is placed on the production cross-section. The observed upper limit is converted using a model-independent approach into upper limits on the coupling strengths $\\kappa_{ugt}/\\Lambda < 6.9\\cdot 10^{-3}$ TeV$^{-1}$ and $\\kappa_{cgt}/\\Lambda < 1.6 \\cdot 10^{-2}$ TeV$^{-1}$, where $\\Lambda$ is the new physics scale, and on the branching fractions ${\\cal B}(...

  7. Test Operations Procedure (TOP) 05-2-543 Enhanced Flight Termination Receiver (EFTR) Range Certification Testing

    Science.gov (United States)

    2011-07-25

    35 5.10 Signal Strength Telemetry Output ( SSTO ) (Test Number 10) ............ 38 5.11 Operational...All command outputs and monitor outputs shall respond properly. TOP 05-2-543 25 July 2011 38 5.10 Signal Strength Telemetry Output ( SSTO ...Test Number 10). a. Purpose. This test verifies that the signal strength telemetry output ( SSTO ) voltage is monotonic and directly related to the

  8. MOF Suppresses Replication Stress and Contributes to Resolution of Stalled Replication Forks.

    Science.gov (United States)

    Singh, Dharmendra Kumar; Pandita, Raj K; Singh, Mayank; Chakraborty, Sharmistha; Hambarde, Shashank; Ramnarain, Deepti; Charaka, Vijaya; Ahmed, Kazi Mokim; Hunt, Clayton R; Pandita, Tej K

    2018-03-15

    The human MOF (hMOF) protein belongs to the MYST family of histone acetyltransferases and plays a critical role in transcription and the DNA damage response. MOF is essential for cell proliferation; however, its role during replication and replicative stress is unknown. Here we demonstrate that cells depleted of MOF and under replicative stress induced by cisplatin, hydroxyurea, or camptothecin have reduced survival, a higher frequency of S-phase-specific chromosome damage, and increased R-loop formation. MOF depletion decreased replication fork speed and, when combined with replicative stress, also increased stalled replication forks as well as new origin firing. MOF interacted with PCNA, a key coordinator of replication and repair machinery at replication forks, and affected its ubiquitination and recruitment to the DNA damage site. Depletion of MOF, therefore, compromised the DNA damage repair response as evidenced by decreased Mre11, RPA70, Rad51, and PCNA focus formation, reduced DNA end resection, and decreased CHK1 phosphorylation in cells after exposure to hydroxyurea or cisplatin. These results support the argument that MOF plays an important role in suppressing replication stress induced by genotoxic agents at several stages during the DNA damage response. Copyright © 2018 American Society for Microbiology.

  9. Sterol Binding by the Tombusviral Replication Proteins Is Essential for Replication in Yeast and Plants.

    Science.gov (United States)

    Xu, Kai; Nagy, Peter D

    2017-04-01

    Membranous structures derived from various organelles are important for replication of plus-stranded RNA viruses. Although the important roles of co-opted host proteins in RNA virus replication have been appreciated for a decade, the equally important functions of cellular lipids in virus replication have been gaining full attention only recently. Previous work with Tomato bushy stunt tombusvirus (TBSV) in model host yeast has revealed essential roles for phosphatidylethanolamine and sterols in viral replication. To further our understanding of the role of sterols in tombusvirus replication, in this work we showed that the TBSV p33 and p92 replication proteins could bind to sterols in vitro The sterol binding by p33 is supported by cholesterol recognition/interaction amino acid consensus (CRAC) and CARC-like sequences within the two transmembrane domains of p33. Mutagenesis of the critical Y amino acids within the CRAC and CARC sequences blocked TBSV replication in yeast and plant cells. We also showed the enrichment of sterols in the detergent-resistant membrane (DRM) fractions obtained from yeast and plant cells replicating TBSV. The DRMs could support viral RNA synthesis on both the endogenous and exogenous templates. A lipidomic approach showed the lack of enhancement of sterol levels in yeast and plant cells replicating TBSV. The data support the notion that the TBSV replication proteins are associated with sterol-rich detergent-resistant membranes in yeast and plant cells. Together, the results obtained in this study and the previously published results support the local enrichment of sterols around the viral replication proteins that is critical for TBSV replication. IMPORTANCE One intriguing aspect of viral infections is their dependence on efficient subcellular assembly platforms serving replication, virion assembly, or virus egress via budding out of infected cells. These assembly platforms might involve sterol-rich membrane microdomains, which are

  10. X-irradiation affects all DNA replication intermediates when inhibiting replication initiation

    International Nuclear Information System (INIS)

    Loenn, U.; Karolinska Hospital, Stockholm

    1982-01-01

    When a human melanoma line was irradiated with 10 Gy, there was, after 30 to 60 min, a gradual reduction in the DNA replication rate. Ten to twelve hours after the irradiation, the DNA replication had returned to near normal rate. The results showed tht low dose-rate X-irradiation inhibits preferentially the formation of small DNA replication intermediates. There is no difference between the inhibition of these replication intermediates formed only in the irradiated cells and those formed also in untreated cells. (U.K.)

  11. Realistic Vascular Replicator for TAVR Procedures.

    Science.gov (United States)

    Rotman, Oren M; Kovarovic, Brandon; Sadasivan, Chander; Gruberg, Luis; Lieber, Baruch B; Bluestein, Danny

    2018-04-13

    Transcatheter aortic valve replacement (TAVR) is an over-the-wire procedure for treatment of severe aortic stenosis (AS). TAVR valves are conventionally tested using simplified left heart simulators (LHS). While those provide baseline performance reliably, their aortic root geometries are far from the anatomical in situ configuration, often overestimating the valves' performance. We report on a novel benchtop patient-specific arterial replicator designed for testing TAVR and training interventional cardiologists in the procedure. The Replicator is an accurate model of the human upper body vasculature for training physicians in percutaneous interventions. It comprises of fully-automated Windkessel mechanism to recreate physiological flow conditions. Calcified aortic valve models were fabricated and incorporated into the Replicator, then tested for performing TAVR procedure by an experienced cardiologist using the Inovare valve. EOA, pressures, and angiograms were monitored pre- and post-TAVR. A St. Jude mechanical valve was tested as a reference that is less affected by the AS anatomy. Results in the Replicator of both valves were compared to the performance in a commercial ISO-compliant LHS. The AS anatomy in the Replicator resulted in a significant decrease of the TAVR valve performance relative to the simplified LHS, with EOA and transvalvular pressures comparable to clinical data. Minor change was seen in the mechanical valve performance. The Replicator showed to be an effective platform for TAVR testing. Unlike a simplified geometric anatomy LHS, it conservatively provides clinically-relevant outcomes and complement it. The Replicator can be most valuable for testing new valves under challenging patient anatomies, physicians training, and procedural planning.

  12. Mutational analysis of varicella-zoster virus (VZV) immediate early protein (IE62) subdomains and their importance in viral replication

    Energy Technology Data Exchange (ETDEWEB)

    Khalil, Mohamed I., E-mail: mkhalil2@stanford.edu [Departments of Pediatrics and Microbiology & Immunology, Stan ford University School of Medicine, Stanford, CA (United States); Department of Molecular Biology, National Research Centre, El-Buhouth St., Cairo (Egypt); Che, Xibing; Sung, Phillip; Sommer, Marvin H. [Departments of Pediatrics and Microbiology & Immunology, Stan ford University School of Medicine, Stanford, CA (United States); Hay, John [Department of Microbiology and Immunology, School of Medicine and Biomedical Science, University at Buffalo, Buffalo, NY (United States); Arvin, Ann M. [Departments of Pediatrics and Microbiology & Immunology, Stan ford University School of Medicine, Stanford, CA (United States)

    2016-05-15

    VZV IE62 is an essential, immediate-early, tegument protein and consists of five domains. We generated recombinant viruses carrying mutations in the first three IE62 domains and tested their influence on VZV replication kinetics. The mutations in domain I did not affect replication kinetics while domain II mutations, disrupting the DNA binding and dimerization domain (DBD), were lethal for VZV replication. Mutations in domain III of the nuclear localization signal (NLS) and the two phosphorylation sites S686A/S722A resulted in slower growth in early and late infection respectively and were associated with IE62 accumulation in the cytoplasm and nucleus respectively. This study mapped the functional domains of IE62 in context of viral infection, indicating that DNA binding and dimerization domain is essential for VZV replication. In addition, the correct localization of IE62, whether nuclear or cytoplasmic, at different points in the viral life cycle, is important for normal progression of VZV replication. - Highlights: • Mutation of IE62 domain I did not affect VZV replication in melanoma cells. • IE62 domain II and III are important for VZV replication in melanoma cells. • Mutations of IE62 domain II (DBD) were lethal for virus replication. • Mutations of IE62 NLS and phosphorylation sites inhibited VZV replication. • NLS and S686A/S722A mutations altered localization of IE62 during early and late infection.

  13. Mutational analysis of varicella-zoster virus (VZV) immediate early protein (IE62) subdomains and their importance in viral replication

    International Nuclear Information System (INIS)

    Khalil, Mohamed I.; Che, Xibing; Sung, Phillip; Sommer, Marvin H.; Hay, John; Arvin, Ann M.

    2016-01-01

    VZV IE62 is an essential, immediate-early, tegument protein and consists of five domains. We generated recombinant viruses carrying mutations in the first three IE62 domains and tested their influence on VZV replication kinetics. The mutations in domain I did not affect replication kinetics while domain II mutations, disrupting the DNA binding and dimerization domain (DBD), were lethal for VZV replication. Mutations in domain III of the nuclear localization signal (NLS) and the two phosphorylation sites S686A/S722A resulted in slower growth in early and late infection respectively and were associated with IE62 accumulation in the cytoplasm and nucleus respectively. This study mapped the functional domains of IE62 in context of viral infection, indicating that DNA binding and dimerization domain is essential for VZV replication. In addition, the correct localization of IE62, whether nuclear or cytoplasmic, at different points in the viral life cycle, is important for normal progression of VZV replication. - Highlights: • Mutation of IE62 domain I did not affect VZV replication in melanoma cells. • IE62 domain II and III are important for VZV replication in melanoma cells. • Mutations of IE62 domain II (DBD) were lethal for virus replication. • Mutations of IE62 NLS and phosphorylation sites inhibited VZV replication. • NLS and S686A/S722A mutations altered localization of IE62 during early and late infection.

  14. Top quark mass measurement in non-tagged lepton + jets events at CDF

    International Nuclear Information System (INIS)

    Bellettini, G.; Budagov, Yu.; Chlachidze, G.; Velev, G.

    2005-01-01

    We report on the first CDF-II measurement of the top quark mass in non-tagged sample of lepton + 4 jet events from p anti p collisions at √s=1.96 TeV. The integrated luminosity of the data sample is 193.5 pb -1 . To improve the sample purity a cut at E T >21 GeV was applied on transverse energy of the jets. 39 events were reconstructed as t anti t and fitted as a superposition of top and W + jet events. The signal-constrained fit imposing a signal of 15.5±3.2 events returned a mass M top =179.1± 9.5 10.5 (stat.) ±8.5 (syst.) GeV/c 2 . The unconstrained fit returned M top =177.5± 7.7 9.1 (stat.) ±8.5 (syst.) GeV/c 2

  15. Top-of-Rail lubricant

    Energy Technology Data Exchange (ETDEWEB)

    Alzoubi, M. F.; Fenske, G. R.; Erck, R. A.; Boparai, A. S.

    2000-07-14

    Analysis of the volatile and semivolatile fractions collected after use of the TOR lubricant indicated that other than contaminants in the collection laboratory, no compounds on the EPA's Target Compound Lists (Tables 2 and 5) were detected in these fractions. The data of these qualitative analyses, given in the various tables in the text, indicate only the relative amounts of the tentatively identified compounds. The authors recommend that quantitative analysis be performed on the volatile and semivolatile fractions to allow confirmation of the tentatively identified compounds and to obtain absolute amounts of the detected compounds. Additionally, the semivolatile fraction should be analyzed by liquid chromatography/mass spectrometry to identify compounds that are not chromatographable under the temperature program used for determination of semivolatile compounds. Introducing the top-of-rail (TOR) lubricant into the wheel/rail interface results in a reduction of almost 60% of lateral friction force over the forces encountered under dry conditions. This reveals good potential for energy savings, as well as wear reduction, for railroad companies. In TOR lubrication, an increase in the angle of attack and axle load results in increased lateral friction and rate of lubricant consumption. The most efficient TOR lubricant quantity to be used in the wheel/rail interface must be calculated precisely according to the number of cars, axle loads, train speed, and angle of attack.

  16. Top medical news stories 2015

    Directory of Open Access Journals (Sweden)

    Robbins RA

    2015-12-01

    Full Text Available No abstract available. Article truncated after 150 words. Here is our list of the top seven medical news stories for 2015 with special emphasis on the Southwest. 7. Wearable health devices: A wave of wearable computing devices such as Fitbit and UP wristbands have people keeping track of how much they sit, stand, walk, climb stairs and calories they consume (1. These fitness-tracking devices herald a series of devices that will detect and monitor serious diseases. However, these so-called medical-grade wearables require approval from the U.S. Food and Drug Administration, a regulatory hurdle avoided by the fitness-tracking devices which will likely slow their introduction. 6. Caitlyn Jenner: Caitlyn Jenner became the most famous transgender woman in the world following an interview published in Vanity Fair (2. The Vanity Fair website saw 11.6 million visits curious about the former Olympic athlete. Though Jenner publicly shared her gender identity, many transgender Americans do not-12% of gender non-conforming adults said they ...

  17. Measurement of top properties in ATLAS

    CERN Document Server

    Veloso, F; The ATLAS collaboration

    2010-01-01

    The top quark may play a special role in the Standard Model of particle physics. It is, for instance, the heaviest fundamental particle known, with a mass close to the electroweak symmetry breaking scale. Millions of top quark pairs will be produced per year at the LHC at nominal luminosity. ATLAS will measure many of the top quark properties with unprecedented precision. The ATLAS sensitivity studies done with Monte Carlo for the measurements of the top quark mass, the top quark charge, rare top quark decays and flavour changing neutral currents, the $t\\bar t$ spin correlations and $W$ boson polarization, the anomalous couplings at the $Wtb$ vertex and $t\\bar t$ resonances are reviewed.

  18. Qinshan CANDU project open top construction method

    International Nuclear Information System (INIS)

    Petrunik, K.J.; Wittann, K.; Khan, A.; Ricciuti, R.; Ivanov, A.; Chen, S.

    2003-01-01

    The significant schedule reductions achieved on the Qinshan CANDU Project were due in large part to the incorporation of advanced construction technologies in project design and delivery. For the Qinshan Project, a number of key advantages were realized through the use of the 'Open Top' construction method. This paper discusses the Qinshan Phase III CANDU Project Open Top implementation method. The Open Top method allowed major equipment to be installed simply, via the use of a Very Heavy Lift (VHL) crane and permitted the use of large-scale modularization. The advantages of Open Top construction, such as simplified access, more flexible project scheduling, improved construction safety and quality, and reduced labours are presented. The large-scale modularization of the Reactor Building Dousing System and the Open Top installation method and advantages relative to traditional CANDU 6 construction practices are also presented. Finally, major improvements for future CANDU plant construction using the Open Top method are discussed. (author)

  19. Top quark mass measurements with CMS

    CERN Document Server

    Kovalchuk, Nataliia

    2017-01-01

    Measurements of the top quark mass are presented, obtained from CMS data collected in proton-proton collisions at the LHC at centre-of-mass energies of 7 TeV and 8 TeV. The mass of the top quark is measured using several methods and channels, including the reconstructed invariant mass distribution of the top quark, an analysis of endpoint spectra as well as measurements from shapes of top quark decay distributions. The dependence of the mass measurement on the kinematic phase space is investigated. The results of the various channels are combined and compared to the world average. The top mass and also $\\alpha_{\\textnormal S}$ are extracted from the top pair cross section measured at CMS.

  20. Optical tweezers reveal how proteins alter replication

    Science.gov (United States)

    Chaurasiya, Kathy

    Single molecule force spectroscopy is a powerful method that explores the DNA interaction properties of proteins involved in a wide range of fundamental biological processes such as DNA replication, transcription, and repair. We use optical tweezers to capture and stretch a single DNA molecule in the presence of proteins that bind DNA and alter its mechanical properties. We quantitatively characterize the DNA binding mechanisms of proteins in order to provide a detailed understanding of their function. In this work, we focus on proteins involved in replication of Escherichia coli (E. coli ), endogenous eukaryotic retrotransposons Ty3 and LINE-1, and human immunodeficiency virus (HIV). DNA polymerases replicate the entire genome of the cell, and bind both double-stranded DNA (dsDNA) and single-stranded DNA (ssDNA) during DNA replication. The replicative DNA polymerase in the widely-studied model system E. coli is the DNA polymerase III subunit alpha (DNA pol III alpha). We use optical tweezers to determine that UmuD, a protein that regulates bacterial mutagenesis through its interactions with DNA polymerases, specifically disrupts alpha binding to ssDNA. This suggests that UmuD removes alpha from its ssDNA template to allow DNA repair proteins access to the damaged DNA, and to facilitate exchange of the replicative polymerase for an error-prone translesion synthesis (TLS) polymerase that inserts nucleotides opposite the lesions, so that bacterial DNA replication may proceed. This work demonstrates a biophysical mechanism by which E. coli cells tolerate DNA damage. Retroviruses and retrotransposons reproduce by copying their RNA genome into the nuclear DNA of their eukaryotic hosts. Retroelements encode proteins called nucleic acid chaperones, which rearrange nucleic acid secondary structure and are therefore required for successful replication. The chaperone activity of these proteins requires strong binding affinity for both single- and double-stranded nucleic

  1. TOP500 Supercomputers for November 2004

    Energy Technology Data Exchange (ETDEWEB)

    Strohmaier, Erich; Meuer, Hans W.; Dongarra, Jack; Simon, Horst D.

    2004-11-08

    24th Edition of TOP500 List of World's Fastest Supercomputers Released: DOE/IBM BlueGene/L and NASA/SGI's Columbia gain Top Positions MANNHEIM, Germany; KNOXVILLE, Tenn.; BERKELEY, Calif. In what has become a closely watched event in the world of high-performance computing, the 24th edition of the TOP500 list of the worlds fastest supercomputers was released today (November 8, 2004) at the SC2004 Conference in Pittsburgh, Pa.

  2. TOP500 Supercomputers for June 2004

    Energy Technology Data Exchange (ETDEWEB)

    Strohmaier, Erich; Meuer, Hans W.; Dongarra, Jack; Simon, Horst D.

    2004-06-23

    23rd Edition of TOP500 List of World's Fastest Supercomputers Released: Japan's Earth Simulator Enters Third Year in Top Position MANNHEIM, Germany; KNOXVILLE, Tenn.;&BERKELEY, Calif. In what has become a closely watched event in the world of high-performance computing, the 23rd edition of the TOP500 list of the world's fastest supercomputers was released today (June 23, 2004) at the International Supercomputer Conference in Heidelberg, Germany.

  3. Top Quark Production at Hadron Colliders

    Energy Technology Data Exchange (ETDEWEB)

    Phaf, Lukas Kaj [Univ. of Amsterdam (Netherlands)

    2004-03-01

    This thesis describes both theoretical and experimental research into top quark production. The theoretical part contains a calculation of the single-top quark production cross section at hadron colliders, at Next to Leading Order (NLO) accuracy. The experimental part describes a measurement of the top quark pair production cross section in proton-antiproton collisions, at a center of mass energy of 1.96 TeV.

  4. A table top exercise and workshop

    International Nuclear Information System (INIS)

    Lakey, J.R.A.

    1992-01-01

    Table top exercises are widely applied in training for emergency preparedness and have long been a feature of Courses on Planning for Nuclear Emergencies. Experience of a large number of table top exercises is used to provide a classification of the types of exercise indicating the application and the disadvantages. The use of workshops is considered to be complementary rather than an alternative to teaching methods available from table top exercises. (author)

  5. Spacetime replication of continuous variable quantum information

    International Nuclear Information System (INIS)

    Hayden, Patrick; Nezami, Sepehr; Salton, Grant; Sanders, Barry C

    2016-01-01

    The theory of relativity requires that no information travel faster than light, whereas the unitarity of quantum mechanics ensures that quantum information cannot be cloned. These conditions provide the basic constraints that appear in information replication tasks, which formalize aspects of the behavior of information in relativistic quantum mechanics. In this article, we provide continuous variable (CV) strategies for spacetime quantum information replication that are directly amenable to optical or mechanical implementation. We use a new class of homologically constructed CV quantum error correcting codes to provide efficient solutions for the general case of information replication. As compared to schemes encoding qubits, our CV solution requires half as many shares per encoded system. We also provide an optimized five-mode strategy for replicating quantum information in a particular configuration of four spacetime regions designed not to be reducible to previously performed experiments. For this optimized strategy, we provide detailed encoding and decoding procedures using standard optical apparatus and calculate the recovery fidelity when finite squeezing is used. As such we provide a scheme for experimentally realizing quantum information replication using quantum optics. (paper)

  6. COPI is required for enterovirus 71 replication.

    Directory of Open Access Journals (Sweden)

    Jianmin Wang

    Full Text Available Enterovirus 71 (EV71, a member of the Picornaviridae family, is found in Asian countries where it causes a wide range of human diseases. No effective therapy is available for the treatment of these infections. Picornaviruses undergo RNA replication in association with membranes of infected cells. COPI and COPII have been shown to be involved in the formation of picornavirus-induced vesicles. Replication of several picornaviruses, including poliovirus and Echovirus 11 (EV11, is dependent on COPI or COPII. Here, we report that COPI, but not COPII, is required for EV71 replication. Replication of EV71 was inhibited by brefeldin A and golgicide A, inhibitors of COPI activity. Furthermore, we found EV71 2C protein interacted with COPI subunits by co-immunoprecipitation and GST pull-down assay, indicating that COPI coatomer might be directed to the viral replication complex through viral 2C protein. Additionally, because the pathway is conserved among different species of enteroviruses, it may represent a novel target for antiviral therapies.

  7. Extremal dynamics in random replicator ecosystems

    Energy Technology Data Exchange (ETDEWEB)

    Kärenlampi, Petri P., E-mail: petri.karenlampi@uef.fi

    2015-10-02

    The seminal numerical experiment by Bak and Sneppen (BS) is repeated, along with computations with replicator models, including a greater amount of features. Both types of models do self-organize, and do obey power-law scaling for the size distribution of activity cycles. However species extinction within the replicator models interferes with the BS self-organized critical (SOC) activity. Speciation–extinction dynamics ruins any stationary state which might contain a steady size distribution of activity cycles. The BS-type activity appears as a dissimilar phenomenon in comparison to speciation–extinction dynamics in the replicator system. No criticality is found from the speciation–extinction dynamics. Neither are speciations and extinctions in real biological macroevolution known to contain any diverging distributions, or self-organization towards any critical state. Consequently, biological macroevolution probably is not a self-organized critical phenomenon. - Highlights: • Extremal Dynamics organizes random replicator ecosystems to two phases in fitness space. • Replicator systems show power-law scaling of activity. • Species extinction interferes with Bak–Sneppen type mutation activity. • Speciation–extinction dynamics does not show any critical phase transition. • Biological macroevolution probably is not a self-organized critical phenomenon.

  8. Replication of cultured lung epithelial cells

    International Nuclear Information System (INIS)

    Guzowski, D.; Bienkowski, R.

    1986-01-01

    The authors have investigated the conditions necessary to support replication of lung type 2 epithelial cells in culture. Cells were isolated from mature fetal rabbit lungs (29d gestation) and cultured on feeder layers of mitotically inactivated 3T3 fibroblasts. The epithelial nature of the cells was demonstrated by indirect immunofluorescent staining for keratin and by polyacid dichrome stain. Ultrastructural examination during the first week showed that the cells contained myofilaments, microvilli and lamellar bodies (markers for type 2 cells). The following changes were observed after the first week: increase in cell size; loss of lamellar bodies and appearance of multivesicular bodies; increase in rough endoplasmic reticulum and golgi; increase in tonafilaments and well-defined junctions. General cell morphology was good for up to 10 wk. Cells cultured on plastic surface degenerated after 1 wk. Cell replication was assayed by autoradiography of cultures exposed to ( 3 H)-thymidine and by direct cell counts. The cells did not replicate during the first week; however, between 2-10 wk the cells incorporated the label and went through approximately 6 population doublings. They have demonstrated that lung alveolar epithelial cells can replicate in culture if they are maintained on an appropriate substrate. The coincidence of ability to replicate and loss of markers for differentiation may reflect the dichotomy between growth and differentiation commonly observed in developing systems

  9. The evolutionary ecology of molecular replicators.

    Science.gov (United States)

    Nee, Sean

    2016-08-01

    By reasonable criteria, life on the Earth consists mainly of molecular replicators. These include viruses, transposons, transpovirons, coviruses and many more, with continuous new discoveries like Sputnik Virophage. Their study is inherently multidisciplinary, spanning microbiology, genetics, immunology and evolutionary theory, and the current view is that taking a unified approach has great power and promise. We support this with a new, unified, model of their evolutionary ecology, using contemporary evolutionary theory coupling the Price equation with game theory, studying the consequences of the molecular replicators' promiscuous use of each others' gene products for their natural history and evolutionary ecology. Even at this simple expository level, we can make a firm prediction of a new class of replicators exploiting viruses such as lentiviruses like SIVs, a family which includes HIV: these have been explicitly stated in the primary literature to be non-existent. Closely connected to this departure is the view that multicellular organism immunology is more about the management of chronic infections rather than the elimination of acute ones and new understandings emerging are changing our view of the kind of theatre we ourselves provide for the evolutionary play of molecular replicators. This study adds molecular replicators to bacteria in the emerging field of sociomicrobiology.

  10. Top Physics at CMS/LHC

    Directory of Open Access Journals (Sweden)

    Daskalakis Georgios

    2017-01-01

    Full Text Available Recent results on the inclusive and differential production cross sections of top-quark pair and single top-quark processes are presented, obtained using data from proton-proton collisions collected with the CMS detector at the LHC. The large centre-of-mass energies available at LHC allow for the copious production of top-quark pairs in association with other final state particles at high transverse momentum. Measurements of such processes as well as of the top-quark mass and other properties will be discussed. The results are compared with the most up-to-date standard model theory predictions.

  11. Differential Top Cross-section Measurements

    CERN Document Server

    Fenton, Michael James; The ATLAS collaboration

    2017-01-01

    The top quark is the heaviest known fundamental particle. The measurement of the differential top-quark pair production cross-section provides a stringent test of advanced perturbative QCD calculations. The ATLAS collaboration has performed detailed measurements of those differential cross sections at a centre-of-mass energy of 13 TeV. This talk focuses on differential cross-section measurements in the lepton+jets final state, including using boosted top quarks to probe our understanding of top quark production in the TeV regime.

  12. Top quark production cross-section measurements

    CERN Document Server

    Chen, Ye; The ATLAS collaboration

    2017-01-01

    Measurements of the inclusive and differential cross-sections for top-quark pair and single top production cross sections in proton-proton collisions with the ATLAS detector at the Large Hadron Collider are presented at center-of-mass energies of 8 TeV and 13 TeV. The inclusive measurements reach high precision and are compared to the best available theoretical calculations. These measurements, including results using boosted tops, probe our understanding of top-pair production in the TeV regime. The results are compared to Monte Carlo generators implementing LO and NLO matrix elements matched with parton showers and NLO QCD calculations. For the t-channel single top measurement, the single top-quark and anti-top-quark total production cross-sections, their ratio, as well as differential cross sections are also presented. A measurement of the production cross-section of a single top quark in association with a W boson, the second largest single-top production mode, is also presented. Finally, measurements of ...

  13. Interplay between Selenium Levels and Replicative Senescence in WI-38 Human Fibroblasts: A Proteomic Approach.

    Science.gov (United States)

    Hammad, Ghania; Legrain, Yona; Touat-Hamici, Zahia; Duhieu, Stéphane; Cornu, David; Bulteau, Anne-Laure; Chavatte, Laurent

    2018-01-20

    Selenoproteins are essential components of antioxidant defense, redox homeostasis, and cell signaling in mammals, where selenium is found in the form of a rare amino acid, selenocysteine. Selenium, which is often limited both in food intake and cell culture media, is a strong regulator of selenoprotein expression and selenoenzyme activity. Aging is a slow, complex, and multifactorial process, resulting in a gradual and irreversible decline of various functions of the body. Several cellular aspects of organismal aging are recapitulated in the replicative senescence of cultured human diploid fibroblasts, such as embryonic lung fibroblast WI-38 cells. We previously reported that the long-term growth of young WI-38 cells with high (supplemented), moderate (control), or low (depleted) concentrations of selenium in the culture medium impacts their replicative lifespan, due to rapid changes in replicative senescence-associated markers and signaling pathways. In order to gain insight into the molecular link between selenium levels and replicative senescence, in the present work, we have applied a quantitative proteomic approach based on 2-Dimensional Differential in-Gel Electrophoresis (2D-DIGE) to the study of young and presenescent cells grown in selenium-supplemented, control, or depleted media. Applying a restrictive cut-off (spot intensity ±50% and a p value iii) spots varying in response to selenium concentration in presenescent cells. Interestingly, a 72% overlap between the impact of senescence and selenium was observed in our proteomic results, demonstrating a strong interplay between selenium, selenoproteins, and replicative senescence.

  14. Functions of mammalian Cdc7 kinase in initiation/monitoring of DNA replication and development

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jung Min; Yamada, Masayuki; Masai, Hisao

    2003-11-27

    Cdc7 kinase plays an essential role in firing of replication origins by phosphorylating components of the replication complexes. Cdc7 kinase has also been implicated in S phase checkpoint signaling downstream of the ATR and Chk1 kinases. Inactivation of Cdc7 in yeast results in arrest of cell growth with 1C DNA content after completion of the ongoing DNA replication. In contrast, conditional inactivation of Cdc7 in undifferentiated mouse embryonic stem (ES) cells leads to growth arrest with rapid cessation of DNA synthesis, suggesting requirement of Cdc7 functions for continuation of ongoing DNA synthesis. Furthermore, loss of Cdc7 function induces recombinational repair (nuclear Rad51 foci) and G2/M checkpoint responses (inhibition of Cdc2 kinase). Eventually, p53 becomes highly activated and the cells undergo massive p53-dependent apoptosis. Thus, defective origin activation in mammalian cells can generate DNA replication checkpoint signals. Efficient removal of those cells in which replication has been perturbed, through cell death, may be beneficial to maintain the highest level of genetic integrity in totipotent stem cells. Partial, rather than total, loss of Cdc7 kinase expression results in retarded growth at both cellular and whole body levels, with especially profound impairment of germ cell development.

  15. Functions of mammalian Cdc7 kinase in initiation/monitoring of DNA replication and development

    International Nuclear Information System (INIS)

    Kim, Jung Min; Yamada, Masayuki; Masai, Hisao

    2003-01-01

    Cdc7 kinase plays an essential role in firing of replication origins by phosphorylating components of the replication complexes. Cdc7 kinase has also been implicated in S phase checkpoint signaling downstream of the ATR and Chk1 kinases. Inactivation of Cdc7 in yeast results in arrest of cell growth with 1C DNA content after completion of the ongoing DNA replication. In contrast, conditional inactivation of Cdc7 in undifferentiated mouse embryonic stem (ES) cells leads to growth arrest with rapid cessation of DNA synthesis, suggesting requirement of Cdc7 functions for continuation of ongoing DNA synthesis. Furthermore, loss of Cdc7 function induces recombinational repair (nuclear Rad51 foci) and G2/M checkpoint responses (inhibition of Cdc2 kinase). Eventually, p53 becomes highly activated and the cells undergo massive p53-dependent apoptosis. Thus, defective origin activation in mammalian cells can generate DNA replication checkpoint signals. Efficient removal of those cells in which replication has been perturbed, through cell death, may be beneficial to maintain the highest level of genetic integrity in totipotent stem cells. Partial, rather than total, loss of Cdc7 kinase expression results in retarded growth at both cellular and whole body levels, with especially profound impairment of germ cell development

  16. Perceptual learning: top to bottom.

    Science.gov (United States)

    Amitay, Sygal; Zhang, Yu-Xuan; Jones, Pete R; Moore, David R

    2014-06-01

    Perceptual learning has traditionally been portrayed as a bottom-up phenomenon that improves encoding or decoding of the trained stimulus. Cognitive skills such as attention and memory are thought to drive, guide and modulate learning but are, with notable exceptions, not generally considered to undergo changes themselves as a result of training with simple perceptual tasks. Moreover, shifts in threshold are interpreted as shifts in perceptual sensitivity, with no consideration for non-sensory factors (such as response bias) that may contribute to these changes. Accumulating evidence from our own research and others shows that perceptual learning is a conglomeration of effects, with training-induced changes ranging from the lowest (noise reduction in the phase locking of auditory signals) to the highest (working memory capacity) level of processing, and includes contributions from non-sensory factors that affect decision making even on a "simple" auditory task such as frequency discrimination. We discuss our emerging view of learning as a process that increases the signal-to-noise ratio associated with perceptual tasks by tackling noise sources and inefficiencies that cause performance bottlenecks, and present some implications for training populations other than young, smart, attentive and highly-motivated college students. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  17. The progression of replication forks at natural replication barriers in live bacteria

    NARCIS (Netherlands)

    Moolman, M.C.; Tiruvadi Krishnan, S; Kerssemakers, J.W.J.; de Leeuw, R.; Lorent, V.J.F.; Sherratt, David J.; Dekker, N.H.

    2016-01-01

    Protein-DNA complexes are one of the principal barriers the replisome encounters during replication. One such barrier is the Tus-ter complex, which is a direction dependent barrier for replication fork progression. The details concerning the dynamics of the replisome when encountering these

  18. Using Replicates in Information Retrieval Evaluation.

    Science.gov (United States)

    Voorhees, Ellen M; Samarov, Daniel; Soboroff, Ian

    2017-09-01

    This article explores a method for more accurately estimating the main effect of the system in a typical test-collection-based evaluation of information retrieval systems, thus increasing the sensitivity of system comparisons. Randomly partitioning the test document collection allows for multiple tests of a given system and topic (replicates). Bootstrap ANOVA can use these replicates to extract system-topic interactions-something not possible without replicates-yielding a more precise value for the system effect and a narrower confidence interval around that value. Experiments using multiple TREC collections demonstrate that removing the topic-system interactions substantially reduces the confidence intervals around the system effect as well as increases the number of significant pairwise differences found. Further, the method is robust against small changes in the number of partitions used, against variability in the documents that constitute the partitions, and the measure of effectiveness used to quantify system effectiveness.

  19. DNA replication stress and cancer chemotherapy.

    Science.gov (United States)

    Kitao, Hiroyuki; Iimori, Makoto; Kataoka, Yuki; Wakasa, Takeshi; Tokunaga, Eriko; Saeki, Hiroshi; Oki, Eiji; Maehara, Yoshihiko

    2018-02-01

    DNA replication is one of the fundamental biological processes in which dysregulation can cause genome instability. This instability is one of the hallmarks of cancer and confers genetic diversity during tumorigenesis. Numerous experimental and clinical studies have indicated that most tumors have experienced and overcome the stresses caused by the perturbation of DNA replication, which is also referred to as DNA replication stress (DRS). When we consider therapeutic approaches for tumors, it is important to exploit the differences in DRS between tumor and normal cells. In this review, we introduce the current understanding of DRS in tumors and discuss the underlying mechanism of cancer therapy from the aspect of DRS. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  20. Evolution of Database Replication Technologies for WLCG

    CERN Document Server

    Baranowski, Zbigniew; Blaszczyk, Marcin; Dimitrov, Gancho; Canali, Luca

    2015-01-01

    In this article we summarize several years of experience on database replication technologies used at WLCG and we provide a short review of the available Oracle technologies and their key characteristics. One of the notable changes and improvement in this area in recent past has been the introduction of Oracle GoldenGate as a replacement of Oracle Streams. We report in this article on the preparation and later upgrades for remote replication done in collaboration with ATLAS and Tier 1 database administrators, including the experience from running Oracle GoldenGate in production. Moreover, we report on another key technology in this area: Oracle Active Data Guard which has been adopted in several of the mission critical use cases for database replication between online and offline databases for the LHC experiments.

  1. Synchronization of DNA array replication kinetics

    Science.gov (United States)

    Manturov, Alexey O.; Grigoryev, Anton V.

    2016-04-01

    In the present work we discuss the features of the DNA replication kinetics at the case of multiplicity of simultaneously elongated DNA fragments. The interaction between replicated DNA fragments is carried out by free protons that appears at the every nucleotide attachment at the free end of elongated DNA fragment. So there is feedback between free protons concentration and DNA-polymerase activity that appears as elongation rate dependence. We develop the numerical model based on a cellular automaton, which can simulate the elongation stage (growth of DNA strands) for DNA elongation process with conditions pointed above and we study the possibility of the DNA polymerases movement synchronization. The results obtained numerically can be useful for DNA polymerase movement detection and visualization of the elongation process in the case of massive DNA replication, eg, under PCR condition or for DNA "sequencing by synthesis" sequencing devices evaluation.

  2. Anterior Cingulate Cortex Input to the Claustrum Is Required for Top-Down Action Control

    Directory of Open Access Journals (Sweden)

    Michael G. White

    2018-01-01

    Full Text Available Summary: Cognitive abilities, such as volitional attention, operate under top-down, executive frontal cortical control of hierarchically lower structures. The circuit mechanisms underlying this process are unresolved. The claustrum possesses interconnectivity with many cortical areas and, thus, is hypothesized to orchestrate the cortical mantle for top-down control. Whether the claustrum receives top-down input and how this input may be processed by the claustrum have yet to be formally tested, however. We reveal that a rich anterior cingulate cortex (ACC input to the claustrum encodes a preparatory top-down information signal on a five-choice response assay that is necessary for optimal task performance. We further show that ACC input monosynaptically targets claustrum inhibitory interneurons and spiny glutamatergic projection neurons, the latter of which amplify ACC input in a manner that is powerfully constrained by claustrum inhibitory microcircuitry. These results demonstrate ACC input to the claustrum is critical for top-down control guiding action. : White et al. show that anterior cingulate cortex (ACC input to the claustrum encodes a top-down preparatory signal on a 5-choice response assay that is critical for task performance. Claustrum microcircuitry amplifies top-down ACC input in a frequency-dependent manner for eventual propagation to the cortex for cognitive control of action. Keywords: 5CSRTT, optogenetics, fiber photometry, microcircuit, attention, bottom-up, sensory cortices, motor cortices

  3. Temporal organization of cellular self-replication

    Science.gov (United States)

    Alexandrov, Victor; Pugatch, Rami

    Recent experiments demonstrate that single cells grow exponentially in time. A coarse grained model of cellular self-replication is presented based on a novel concept - the cell is viewed as a self-replicating queue. This allows to have a more fundamental look into various temporal organizations and, importantly, the inherent non-Markovianity of noise distributions. As an example, the distribution of doubling times can be inferred and compared to single cell experiments in bacteria. We observe data collapse upon scaling by the average doubling time for different environments and present an inherent task allocation trade-off. Support from the Simons Center for Systems Biology, IAS, Princeon.

  4. Chromatin challenges during DNA replication and repair

    DEFF Research Database (Denmark)

    Groth, Anja; Rocha, Walter; Verreault, Alain

    2007-01-01

    Inheritance and maintenance of the DNA sequence and its organization into chromatin are central for eukaryotic life. To orchestrate DNA-replication and -repair processes in the context of chromatin is a challenge, both in terms of accessibility and maintenance of chromatin organization. To meet...... the challenge of maintenance, cells have evolved efficient nucleosome-assembly pathways and chromatin-maturation mechanisms that reproduce chromatin organization in the wake of DNA replication and repair. The aim of this Review is to describe how these pathways operate and to highlight how the epigenetic...... landscape may be stably maintained even in the face of dramatic changes in chromatin structure....

  5. Iterated function systems for DNA replication

    Science.gov (United States)

    Gaspard, Pierre

    2017-10-01

    The kinetic equations of DNA replication are shown to be exactly solved in terms of iterated function systems, running along the template sequence and giving the statistical properties of the copy sequences, as well as the kinetic and thermodynamic properties of the replication process. With this method, different effects due to sequence heterogeneity can be studied, in particular, a transition between linear and sublinear growths in time of the copies, and a transition between continuous and fractal distributions of the local velocities of the DNA polymerase along the template. The method is applied to the human mitochondrial DNA polymerase γ without and with exonuclease proofreading.

  6. Involvement of Autophagy in Coronavirus Replication

    Directory of Open Access Journals (Sweden)

    Paul Britton

    2012-11-01

    Full Text Available Coronaviruses are single stranded, positive sense RNA viruses, which induce the rearrangement of cellular membranes upon infection of a host cell. This provides the virus with a platform for the assembly of viral replication complexes, improving efficiency of RNA synthesis. The membranes observed in coronavirus infected cells include double membrane vesicles. By nature of their double membrane, these vesicles resemble cellular autophagosomes, generated during the cellular autophagy pathway. In addition, coronavirus infection has been demonstrated to induce autophagy. Here we review current knowledge of coronavirus induced membrane rearrangements and the involvement of autophagy or autophagy protein microtubule associated protein 1B light chain 3 (LC3 in coronavirus replication.

  7. The replication of expansive production knowledge

    DEFF Research Database (Denmark)

    Wæhrens, Brian Vejrum; Yang, Cheng; Madsen, Erik Skov

    2012-01-01

    Purpose – With the aim to support offshore production line replication, this paper specifically aims to explore the use of templates and principles to transfer expansive productive knowledge embedded in a production line and understand the contingencies that influence the mix of these approaches......; and (2) rather than being viewed as alternative approaches, templates and principles should be seen as complementary once the transfer motive moves beyond pure replication. Research limitations – The concepts introduced in this paper were derived from two Danish cases. While acceptable for theory...

  8. Study of Vaccinia and Cowpox viruses' replication in Rac1-N17 dominant-negative cells

    Directory of Open Access Journals (Sweden)

    Ana Paula Carneiro Salgado

    2013-08-01

    Full Text Available Interfering with cellular signal transduction pathways is a common strategy used by many viruses to create a propitious intracellular environment for an efficient replication. Our group has been studying cellular signalling pathways activated by the orthopoxviruses Vaccinia (VACV and Cowpox (CPXV and their significance to viral replication. In the present study our aim was to investigate whether the GTPase Rac1 was an upstream signal that led to the activation of MEK/ERK1/2, JNK1/2 or Akt pathways upon VACV or CPXV' infections. Therefore, we generated stable murine fibroblasts exhibiting negative dominance to Rac1-N17 to evaluate viral growth and the phosphorylation status of ERK1/2, JNK1/2 and Akt. Our results demonstrated that VACV replication, but not CPXV, was affected in dominant-negative (DN Rac1-N17 cell lines in which viral yield was reduced in about 10-fold. Viral late gene expression, but not early, was also reduced. Furthermore, our data showed that Akt phosphorylation was diminished upon VACV infection in DN Rac1-N17 cells, suggesting that Rac1 participates in the phosphoinositide-3 kinase pathway leading to the activation of Akt. In conclusion, our results indicate that while Rac1 indeed plays a role in VACV biology, perhaps another GTPase may be involved in CPXV replication.

  9. Interferon lambda inhibits dengue virus replication in epithelial cells.

    Science.gov (United States)

    Palma-Ocampo, Helen K; Flores-Alonso, Juan C; Vallejo-Ruiz, Verónica; Reyes-Leyva, Julio; Flores-Mendoza, Lilian; Herrera-Camacho, Irma; Rosas-Murrieta, Nora H; Santos-López, Gerardo

    2015-09-28

    In viral disease, infection is controlled at the cellular level by type I interferon (IFN-I), but dengue virus (DENV) has the ability to inhibit this response. Type III interferon, also known as lambda IFN (IFN-III or IFN-λ), is a complementary pathway to the antiviral response by IFN-I. This work analyzed the IFN-λ (IFN-III) mediated antiviral response against DENV serotype 2 (DENV-2) infection. Dengue fever patients were sampled to determine their IFN-λ levels by ELISA. To study the IFN-λ response during DENV infection we selected the epithelial cell line C33-A, and we demonstrated that it is permissive to DENV-2 infection. The effect of IFN-λ on virus replication was determined in these cells, in parallel to the expression of IFN-stimulated genes (ISGs), and Suppressor of Cytokine Signaling (SOCS), genes measured by RT-qPCR. We found increased (~1.8 times) serological IFN-λ in dengue fever patients compared to healthy blood donors. IFN-λ inhibited DENV-2 replication in a dose-dependent manner in vitro. The reduction of viral titer corresponded with increased ISG mRNA levels (MX1 and OAS1), with the highest inhibition occurring at ISG's peak expression. Presence of IFN-negative regulators, SOCS1 and SOCS3, during DENV-2 infection was associated with reduced IFN-λ1 expression. Evidence described here suggests that IFN-λ is a good candidate inhibitor of viral replication in dengue infection. Mechanisms for the cellular and organismal interplay between DENV and IFN- λ need to be further studied as they could provide insights into strategies to treat this disease. Furthermore, we report a novel epithelial model to study dengue infection in vitro.

  10. [The effects of TorR protein on initiation of DNA replication in Escherichia coli].

    Science.gov (United States)

    Yuan, Yao; Jiaxin, Qiao; Jing, Li; Hui, Li; Morigen, Morigen

    2015-03-01

    The two-component systems, which could sense and respond to environmental changes, widely exist in bacteria as a signal transduction pathway. The bacterial CckA/CtrA, ArcA/ArcB and PhoP/PhoQ two-component systems are associated with initiation of DNA replication and cell division, however, the effects of the TorS/TorR system on cell cycle and DNA replication remains unknown. The TorS/TorR system in Escherichia coli can sense changes in trimethylamine oxide (TMAO) concentration around the cells. However, it is unknown if it also affects initiation of DNA replication. We detected DNA replication patterns in ΔtorS and ΔtorR mutant strains by flow cytometry. We found that the average number of replication origins (oriCs) per cell and doubling time in ΔtorS mutants were the same while the average number of oriCs in ΔtorR mutants was increased compared with that in wild-type cells. These results indicated that absence of TorR led to an earlier initiation of DNA replication than that in wild-type cells. Strangely, neither overexpression of TorR nor co-expression of TorR and TorS could restore ΔtorR mutant phenotype to the wild type. However, overexpression of SufD in both wild type and ΔtorR mutants promoted initiation of DNA replication, while mutation of SufD delayed it in ΔtorR mutants. Thus, TorR may affect initiation of DNA replication indirectly through regulating gene expression of sufD.

  11. Delta-9 tetrahydrocannabinol (THC inhibits lytic replication of gamma oncogenic herpesviruses in vitro

    Directory of Open Access Journals (Sweden)

    Friedman Herman

    2004-09-01

    Full Text Available Abstract Background The major psychoactive cannabinoid compound of marijuana, delta-9 tetrahydrocannabinol (THC, has been shown to modulate immune responses and lymphocyte function. After primary infection the viral DNA genome of gamma herpesviruses persists in lymphoid cell nuclei in a latent episomal circular form. In response to extracellular signals, the latent virus can be activated, which leads to production of infectious virus progeny. Therefore, we evaluated the potential effects of THC on gamma herpesvirus replication. Methods Tissue cultures infected with various gamma herpesviruses were cultured in the presence of increasing concentrations of THC and the amount of viral DNA or infectious virus yield was compared to those of control cultures. The effect of THC on Kaposi's Sarcoma Associated Herpesvirus (KSHV and Epstein-Barr virus (EBV replication was measured by the Gardella method and replication of herpesvirus saimiri (HVS of monkeys, murine gamma herpesvirus 68 (MHV 68, and herpes simplex type 1 (HSV-1 was measured by yield reduction assays. Inhibition of the immediate early ORF 50 gene promoter activity was measured by the dual luciferase method. Results Micromolar concentrations of THC inhibit KSHV and EBV reactivation in virus infected/immortalized B cells. THC also strongly inhibits lytic replication of MHV 68 and HVS in vitro. Importantly, concentrations of THC that inhibit virus replication of gamma herpesviruses have no effect on cell growth or HSV-1 replication, indicating selectivity. THC was shown to selectively inhibit the immediate early ORF 50 gene promoter of KSHV and MHV 68. Conclusions THC specifically targets viral and/or cellular mechanisms required for replication and possibly shared by these gamma herpesviruses, and the endocannabinoid system is possibly involved in regulating gamma herpesvirus latency and lytic replication. The immediate early gene ORF 50 promoter activity was specifically inhibited by THC

  12. Delta-9 tetrahydrocannabinol (THC) inhibits lytic replication of gamma oncogenic herpesviruses in vitro.

    Science.gov (United States)

    Medveczky, Maria M; Sherwood, Tracy A; Klein, Thomas W; Friedman, Herman; Medveczky, Peter G

    2004-09-15

    The major psychoactive cannabinoid compound of marijuana, delta-9 tetrahydrocannabinol (THC), has been shown to modulate immune responses and lymphocyte function. After primary infection the viral DNA genome of gamma herpesviruses persists in lymphoid cell nuclei in a latent episomal circular form. In response to extracellular signals, the latent virus can be activated, which leads to production of infectious virus progeny. Therefore, we evaluated the potential effects of THC on gamma herpesvirus replication. Tissue cultures infected with various gamma herpesviruses were cultured in the presence of increasing concentrations of THC and the amount of viral DNA or infectious virus yield was compared to those of control cultures. The effect of THC on Kaposi's Sarcoma Associated Herpesvirus (KSHV) and Epstein-Barr virus (EBV) replication was measured by the Gardella method and replication of herpesvirus saimiri (HVS) of monkeys, murine gamma herpesvirus 68 (MHV 68), and herpes simplex type 1 (HSV-1) was measured by yield reduction assays. Inhibition of the immediate early ORF 50 gene promoter activity was measured by the dual luciferase method. Micromolar concentrations of THC inhibit KSHV and EBV reactivation in virus infected/immortalized B cells. THC also strongly inhibits lytic replication of MHV 68 and HVS in vitro. Importantly, concentrations of THC that inhibit virus replication of gamma herpesviruses have no effect on cell growth or HSV-1 replication, indicating selectivity. THC was shown to selectively inhibit the immediate early ORF 50 gene promoter of KSHV and MHV 68. THC specifically targets viral and/or cellular mechanisms required for replication and possibly shared by these gamma herpesviruses, and the endocannabinoid system is possibly involved in regulating gamma herpesvirus latency and lytic replication. The immediate early gene ORF 50 promoter activity was specifically inhibited by THC. These studies may also provide the foundation for the development

  13. The Genomic Replication of the Crenarchaeal Virus SIRV2

    DEFF Research Database (Denmark)

    Martinez Alvarez, Laura

    reinitiation events may partially explain the branched topology of the viral replication intermediates. We also analyzed the intracellular location of viral replication, showing the formation of viral peripheral replication centers in SIRV2-infected cells, where viral DNA synthesis and replication...

  14. Bayesian tests to quantify the result of a replication attempt

    NARCIS (Netherlands)

    Verhagen, J.; Wagenmakers, E.-J.

    2014-01-01

    Replication attempts are essential to the empirical sciences. Successful replication attempts increase researchers’ confidence in the presence of an effect, whereas failed replication attempts induce skepticism and doubt. However, it is often unclear to what extent a replication attempt results in

  15. Scenario-based table top simulations

    DEFF Research Database (Denmark)

    Broberg, Ole; Edwards, Kasper; Nielsen, J.

    2012-01-01

    This study developed and tested a scenario-based table top simulation method in a user-driven innovation setting. A team of researchers worked together with a user group of five medical staff members from the existing clinic. Table top simulations of a new clinic were carried out in a simple model...

  16. Experimental results on SUSY searches with top

    CERN Document Server

    Eifert, Till

    2014-01-01

    Searches for supersymmetric partner particles of the top and bottom quarks at the Large Hadron Collider are reviewed. The focus is on the status of searches for a relatively light partner of the top quark performed by the CMS and ATLAS Collaborations. No excess beyond Standard Model expectations is observed and exclusion limits are set on the masses of supersymmetric particles.

  17. Top quark property measurements at the LHC

    CERN Document Server

    Hawkings, Richard; The ATLAS collaboration

    2014-01-01

    Measurements of top quark properties performed at the Large Hadron Collider are reviewed, with a particular emphasis on top-pair charge asymmetries, spin correlations and polarization measurements performed by the ATLAS and CMS collaborations. The measurements are generally in good agreement with predictions from next-to-leading-order QCD calculations, and no deviations from Standard Model expectations have been seen.

  18. Top quark distributions in hadronic collisions

    CERN Document Server

    Frixione, Stefano; Nason, P; Ridolfi, G; Frixione, S; Mangano, M L; Nason, P; Ridolfi, G

    1995-01-01

    We present kinematical distributions for top quark pairs produced at the Tevatron \\ppbar\\ Collider, as predicted within Next-to-Leading-Order QCD. We consider single and double-inclusive distributions, and compare our results to those obtained with the shower Monte Carlo HERWIG. We discuss the implications of our findings for experimental issues such as the measurement of the top quark mass.

  19. Top 12 Web Resources for 2012

    Science.gov (United States)

    Gonzales, Lisa; Vodicka, Devin

    2012-01-01

    In this article, the authors describe some of the top websites recommended by colleagues for the Association of California School Administrators. The Top 12 for 2012 are: (1) Facebook (facebook.com); (2) Twitter (twitter.com); (3) Tungle (tungle.me); (4) FCMAT (fcmat.org); (5) YouSendIt (yousendit.com); (6) Slideshare (slideshare.net); (7) QR…

  20. Latest ATLAS measurements on top quark properties

    CERN Document Server

    Derue, Frederic; The ATLAS collaboration

    2017-01-01

    The top quark is unique among the known quarks in that it decays before it has an opportunity to form hadronic bound states. This makes measurements of its properties particularly interesting as one can access directly the properties of a bare quark. The latest measurements of these properties with the ATLAS detector at the LHC are presented using 8 TeV and 13 TeV data, excluding results from single top production. Measurements of top quark spin observables in top-antitop events, each sensitive to a different coefficient of the spin density matrix, are presented and compared to the Standard Model predictions. The helicity of the W boson from the top decays and the production angles of the top quark are further discussed. New results on the measurment of color flow effects in $t{\\bar t}$ events are presented. Limits on the rate of flavour changing neutral currents in the production or decay of the top quark are reported. The cross-section measurement of photons produced in association with top-quark pairs is a...

  1. Thermal design of top shield for PFBR

    International Nuclear Information System (INIS)

    Gajapathy, R.; Jalaludeen, S.; Selvaraj, A.; Bhoje, S.B.

    1988-01-01

    India's Liquid Metal Cooled Fast Breeder Reactor programme started with the construction of loop type 13MW(e) Fast Breeder Test Reactor (FBTR) which attained criticality in October 1985. With the experience of FBTR, the design work on pool type 500 MW(e) Prototype Fast Breeder Reactor (PFBR) which will be a forerunner for future commercial fast breeder reactors, has been started. The Top Shield forms the cover for the main vessel which contains the primary circuit. Argon cover gas separates the Top Shield from the free level of hot sodium pool (803K). The Top Shield which is of box type construction consists of control plug, two rotatable plugs and roof slab, assembled together, which provide biological shielding, thermal shielding and leak tight containment at the top of the main vessel. Heat is transferred from the sodium pool to the Top Shield through argon cover gas and through components supported by it and dipped in the sodium pool. The Top Shield should be maintained at the desired operating temperature by incorporating a cooling system inside it. Insulation may be provided below the bottom plate to reduce the heat load to the cooling system, if required. The thermal design of Top Shield consists of estimation of heat transfer to the Top Shield, selection of operating temperature, assessment of insulation requirement, design of cooling system and evaluation of transient temperature changes

  2. SWFSC/MMTD/CCE: Tagging and Tracking of Physeter (T-TOP/T-TOP2) 1997

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This research was devoted to studying sperm whale (Physeter macrocephalus) behavior. The principal study area for T-TOP and T-TOP2 was the Pioneer Seamount, 50...

  3. Measuring top-quark polarization in top-pair + missing-energy events.

    Science.gov (United States)

    Berger, Edmond L; Cao, Qing-Hong; Yu, Jiang-Hao; Zhang, Hao

    2012-10-12

    The polarization of a top quark can be sensitive to new physics beyond the standard model. Since the charged lepton from top-quark decay is maximally correlated with the top-quark spin, it is common to measure the polarization from the distribution in the angle between the charged lepton and the top-quark directions. We propose a novel method based on the charged lepton energy fraction and illustrate the method with a detailed simulation of top-quark pairs produced in supersymmetric top squark pair production. We show that the lepton energy ratio distribution that we define is very sensitive to the top-quark polarization but insensitive to the precise measurement of the top-quark energy.

  4. Changing Use of Seventh Chords: A Replication of Mauch et al. (2015

    Directory of Open Access Journals (Sweden)

    Hubert Léveillé Gauvin

    2016-07-01

    Full Text Available Mauch, MacCallum, Levy, and Leroi (2015 carried out a large-scale study of changes in American popular music between 1960 and 2010. Using signal processing methods, they found evidence suggesting a decreasing use of the dominant seventh chord and increasing use of the minor-minor seventh chord. While signal analysis methods have improved substantially in recent years, the accuracy of signal-based analysis remains imperfect. Using a contrasting method and independent musical sample, this paper reports converging evidence replicating these findings.

  5. From Particle Flow to Colour Flow in Top Events

    CERN Document Server

    Lofberg, Henrik Johan

    2013-01-01

    A deeper understanding of the underlying event in $t\\overline{t}$ pair production is expected to improve the current uncertainty on the measurements of the top quark mass. By selecting events with an electron, a muon and two b-tagged jets a high purity signal is obtained. The main properties of the underlying event are isolated and compared between data and different Pythia Monte Carlo Tunes. Discrepancies between the total number of charged particles for different models is observed. Furthermore a contribution of colour reconnection to the modeling of the average transverse momentum of the charged particles is identified.

  6. Top quark studies with the ATLAS detector

    CERN Document Server

    Capua, Marcella; The ATLAS collaboration

    2015-01-01

    The latest top quark studies in proton-proton collisions at a centre-of-mass energy of 7 and 8 TeV with the ATLAS detector are reported. We present recent results on the top pair production inclusive cross-sections, top pair production differential cross-section in the resolved and boosted regimes, single top-quark production cross-sections measured in the t-channel, s-channel and W-boson associated processes, as well as the CKM matrix element $|V_{tb}|$ determination. The results are compared with theoretical expectations. Latest ATLAS results on top properties will be also shown in terms of direct and mass pole, spin correlations and charge asymmetry.

  7. Top quark studies with the ATLAS detector

    CERN Document Server

    Capua, Marcella; The ATLAS collaboration

    2015-01-01

    The latest studies of top quark production measurement in proton-proton collisions at a centre-of-mass energy of 7 and 8 TeV with the ATLAS detector are reported. The talk will present recent results on the top pair production inclusive cross sections, top pair production differential cross section in resolved and boosted regime, single top-quark productions cross sections measured for t-channel, s-channel and W-boson associated processes. as well as d the CKM matrix element |Vtb| determination. All the results are compared with theoretical expectations. Latest ATLAS results on top mass measurements will be also shown in terms of direct and mass pole results.

  8. TOP500 Supercomputers for June 2002

    Energy Technology Data Exchange (ETDEWEB)

    Strohmaier, Erich; Meuer, Hans W.; Dongarra, Jack; Simon, Horst D.

    2002-06-20

    19th Edition of TOP500 List of World's Fastest Supercomputers Released MANNHEIM, Germany; KNOXVILLE, Tenn.;&BERKELEY, Calif. In what has become a much-anticipated event in the world of high-performance computing, the 19th edition of the TOP500 list of the worlds fastest supercomputers was released today (June 20, 2002). The recently installed Earth Simulator supercomputer at the Earth Simulator Center in Yokohama, Japan, is as expected the clear new number 1. Its performance of 35.86 Tflop/s (trillions of calculations per second) running the Linpack benchmark is almost five times higher than the performance of the now No.2 IBM ASCI White system at Lawrence Livermore National Laboratory (7.2 Tflop/s). This powerful leap frogging to the top by a system so much faster than the previous top system is unparalleled in the history of the TOP500.

  9. Top quark production at the LHC

    CERN Document Server

    Ferreira da Silva, Pedro

    2016-01-01

    Twenty years past its discovery, the top quark continues attracting great interest as experiments keep unveiling its properties. An overview of the latest measurements in the domain of top quark production, performed by the ATLAS and CMS experiments at the CERN LHC, is given. The latest measurements of top quark production rates via strong and electroweak processes are reported and compared to different perturbative QCD predictions. Fundamental properties, such as the mass or the couplings of the top quark, as well as re-interpretations seeking for beyond the standard model contributions in the top quark sector, are extracted from these measurements. In each case an attempt to highlight the first results and main prospects for the on-going Run 2 of the LHC is made.

  10. D OE top quark mass analysis

    International Nuclear Information System (INIS)

    Strovink, M.

    1995-07-01

    Based on (44-48 pb -1 ) of lepton + jets data, we review D0's initial analysis of the top quark mass. The result, M top = 199 ± 19/21 (stat.) ± 22 (syst.) GeV/c 2 , is insensitive to background normalization. The errors are based on ISAJET top Monte Carlo, with its more severe gluon radiation, and allow for ISAJET/HERWIG differences. Good progress is being made in reducing the systematic error. We present a new study based on two-dimensional distributions of reconstructed top quark vs. dijet mass. With 98.7% confidence we observe a peak in the top mass - dijet mass plane. The peak and its projections are similar both in shape and magnitude to expectations based on the decay sequence 1 → bW, W → jj

  11. Top quark production at the LHC (single top and tt-bar cross sections)

    International Nuclear Information System (INIS)

    Lange, J.

    2014-01-01

    With the large number of top quarks produced at the LHC, top quark physics enters an era of precision and properties measurements. This article reviews the recent advances in top quark cross section measurements performed by ATLAS and CMS using data recorded in 2011 with integrated luminosities up to 5 fb -1 . They include precision inclusive cross sections, the establishment of challenging channels, first differential cross section measurements and single top production. An overall good agreement with Standard Model predictions is observed

  12. Direct measurement of the total decay width of the top quark.

    Science.gov (United States)

    Aaltonen, T; Amerio, S; Amidei, D; Anastassov, A; Annovi, A; Antos, J; Apollinari, G; Appel, J A; Arisawa, T; Artikov, A; Asaadi, J; Ashmanskas, W; Auerbach, B; Aurisano, A; Azfar, F; Badgett, W; Bae, T; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Barria, P; Bartos, P; Bauce, M; Bedeschi, F; Behari, S; Bellettini, G; Bellinger, J; Benjamin, D; Beretvas, A; Bhatti, A; Bland, K R; Blumenfeld, B; Bocci, A; Bodek, A; Bortoletto, D; Boudreau, J; Boveia, A; Brigliadori, L; Bromberg, C; Brucken, E; Budagov, J; Budd, H S; Burkett, K; Busetto, G; Bussey, P; Butti, P; Buzatu, A; Calamba, A; Camarda, S; Campanelli, M; Canelli, F; Carls, B; Carlsmith, D; Carosi, R; Carrillo, S; Casal, B; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavaliere, V; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Cho, K; Chokheli, D; Clark, A; Clarke, C; Convery, M E; Conway, J; Corbo, M; Cordelli, M; Cox, C A; Cox, D J; Cremonesi, M; Cruz, D; Cuevas, J; Culbertson, R; d'Ascenzo, N; Datta, M; de Barbaro, P; Demortier, L; Deninno, M; D'Errico, M; Devoto, F; Di Canto, A; Di Ruzza, B; Dittmann, J R; Donati, S; D'Onofrio, M; Dorigo, M; Driutti, A; Ebina, K; Edgar, R; Elagin, A; Erbacher, R; Errede, S; Esham, B; Farrington, S; Fernández Ramos, J P; Field, R; Flanagan, G; Forrest, R; Franklin, M; Freeman, J C; Frisch, H; Funakoshi, Y; Galloni, C; Garfinkel, A F; Garosi, P; Gerberich, H; Gerchtein, E; Giagu, S; Giakoumopoulou, V; Gibson, K; Ginsburg, C M; Giokaris, N; Giromini, P; Giurgiu, G; Glagolev, V; Glenzinski, D; Gold, M; Goldin, D; Golossanov, A; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González López, O; Gorelov, I; Goshaw, A T; Goulianos, K; Gramellini, E; Grinstein, S; Grosso-Pilcher, C; Group, R C; Guimaraes da Costa, J; Hahn, S R; Han, J Y; Happacher, F; Hara, K; Hare, M; Harr, R F; Harrington-Taber, T; Hatakeyama, K; Hays, C; Heinrich, J; Herndon, M; Hocker, A; Hong, Z; Hopkins, W; Hou, S; Hughes, R E; Husemann, U; Hussein, M; Huston, J; Introzzi, G; Iori, M; Ivanov, A; James, E; Jang, D; Jayatilaka, B; Jeon, E J; Jindariani, S; Jones, M; Joo, K K; Jun, S Y; Junk, T R; Kambeitz, M; Kamon, T; Karchin, P E; Kasmi, A; Kato, Y; Ketchum, W; Keung, J; Kilminster, B; Kim, D H; Kim, H S; Kim, J E; Kim, M J; Kim, S H; Kim, S B; Kim, Y J; Kim, Y K; Kimura, N; Kirby, M; Knoepfel, K; Kondo, K; Kong, D J; Konigsberg, J; Kotwal, A V; Kreps, M; Kroll, J; Kruse, M; Kuhr, T; Kurata, M; Laasanen, A T; Lammel, S; Lancaster, M; Lannon, K; Latino, G; Lee, H S; Lee, J S; Leo, S; Leone, S; Lewis, J D; Limosani, A; Lipeles, E; Lister, A; Liu, H; Liu, Q; Liu, T; Lockwitz, S; Loginov, A; Lucchesi, D; Lucà, A; Lueck, J; Lujan, P; Lukens, P; Lungu, G; Lys, J; Lysak, R; Madrak, R; Maestro, P; Malik, S; Manca, G; Manousakis-Katsikakis, A; Marchese, L; Margaroli, F; Marino, P; Martínez, M; Matera, K; Mattson, M E; Mazzacane, A; Mazzanti, P; McNulty, R; Mehta, A; Mehtala, P; Mesropian, C; Miao, T; Mietlicki, D; Mitra, A; Miyake, H; Moed, S; Moggi, N; Moon, C S; Moore, R; Morello, M J; Mukherjee, A; Muller, Th; Murat, P; Mussini, M; Nachtman, J; Nagai, Y; Naganoma, J; Nakano, I; Napier, A; Nett, J; Neu, C; Nigmanov, T; Nodulman, L; Noh, S Y; Norniella, O; Oakes, L; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Orava, R; Ortolan, L; Pagliarone, C; Palencia, E; Palni, P; Papadimitriou, V; Parker, W; Pauletta, G; Paulini, M; Paus, C; Phillips, T J; Piacentino, G; Pianori, E; Pilot, J; Pitts, K; Plager, C; Pondrom, L; Poprocki, S; Potamianos, K; Pranko, A; Prokoshin, F; Ptohos, F; Punzi, G; Ranjan, N; Redondo Fernández, I; Renton, P; Rescigno, M; Rimondi, F; Ristori, L; Robson, A; Rodriguez, T; Rolli, S; Ronzani, M; Roser, R; Rosner, J L; Ruffini, F; Ruiz, A; Russ, J; Rusu, V; Sakumoto, W K; Sakurai, Y; Santi, L; Sato, K; Saveliev, V; Savoy-Navarro, A; Schlabach, P; Schmidt, E E; Schwarz, T; Scodellaro, L; Scuri, F; Seidel, S; Seiya, Y; Semenov, A; Sforza, F; Shalhout, S Z; Shears, T; Shepard, P F; Shimojima, M; Shochet, M; Shreyber-Tecker, I; Simonenko, A; Sliwa, K; Smith, J R; Snider, F D; Song, H; Sorin, V; St Denis, R; Stancari, M; Stentz, D; Strologas, J; Sudo, Y; Sukhanov, A; Suslov, I; Takemasa, K; Takeuchi, Y; Tang, J; Tecchio, M; Teng, P K; Thom, J; Thomson, E; Thukral, V; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Totaro, P; Trovato, M; Ukegawa, F; Uozumi, S; Vázquez, F; Velev, G; Vellidis, C; Vernieri, C; Vidal, M; Vilar, R; Vizán, J; Vogel, M; Volpi, G; Wagner, P; Wallny, R; Wang, S M; Waters, D; Wester, W C; Whiteson, D; Wicklund, A B; Wilbur, S; Williams, H H; Wilson, J S; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, H; Wright, T; Wu, X; Wu, Z; Yamamoto, K; Yamato, D; Yang, T; Yang, U K; Yang, Y C; Yao, W-M; Yeh, G P; Yi, K; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Zanetti, A M; Zeng, Y; Zhou, C; Zucchelli, S

    2013-11-15

    We present a measurement of the total decay width of the top quark using events with top-antitop quark pair candidates reconstructed in the final state with one charged lepton and four or more hadronic jets. We use the full Tevatron run II data set of sqrt[s]=1.96  TeV proton-antiproton collisions recorded by the CDF II detector. The top quark mass and the mass of the hadronically decaying W boson are reconstructed for each event and compared with distributions derived from simulated signal and background samples to extract the top quark width (Γtop) and the energy scale of the calorimeter jets with in situ calibration. For a top quark mass Mtop=172.5  GeV/c2, we find 1.10<Γtop<4.05  GeV at 68% confidence level, which is in agreement with the standard model expectation of 1.3 GeV and is the most precise direct measurement of the top quark width to date.

  13. Challenges in New Physics searches in top-like events at the LHC

    CERN Document Server

    Lessard, J-R; The ATLAS collaboration

    2010-01-01

    These proceedings follow from the presentation ``Challenges in New Physics searches in top-like events at the LHC" given on the 4th of June 2010 at the 3rd International Workshop on Top Quark Physics held in Bruges, Belgium. The prospects of exploring physics beyond the standard model (BSM) involving top and top-like signal at the LHC based on Monte Carlo (MC) simulations at $sqrt{s} =$ 14 and 10 TeV are reviewed. A special attention will be given to results that can be expected by 2010-2011. Consequently, the first section will deal with the implications of having a center of mass energy slightly lower than what was simulated, $sqrt{s} = 7$ TeV, for the first years of the LHC running. This will be done qualitatively by discussing the impact on the cross section of various production processes. Following this discussion, many top related BSM analyses will be described: top-antitop resonances, 4th generation of quarks, top charge, W polarization, top-antitop spin correlation, anomalous Wtb vertex coupling and ...

  14. Coxsackievirus B3 2A protease promotes encephalomyocarditis virus replication.

    Science.gov (United States)

    Song, Qin-Qin; Lu, Ming-Zhi; Song, Juan; Chi, Miao-Miao; Sheng, Lin-Jun; Yu, Jie; Luo, Xiao-Nuan; Zhang, Lu; Yao, Hai-Lan; Han, Jun

    2015-10-02

    To determine whether 2A protease of the enterovirus genus with type I internal ribosome entry site (IRES) effect on the viral replication of type II IRES, coxsackievirus B3(CVB3)-encoded protease 2A and encephalomyocarditis virus (EMCV) IRES (Type II)-dependent or cap-dependent report gene were transiently co-expressed in eukaryotic cells. We found that CVB3 2A protease not only inhibited translation of cap-dependent reporter genes through the cleavage of eIF4GI, but also conferred high EMCV IRES-dependent translation ability and promoted EMCV replication. Moreover, deletions of short motif (aa13-18 RVVNRH, aa65-70 KNKHYP, or aa88-93 PRRYQSH) resembling the nuclear localization signals (NLS) or COOH-terminal acidic amino acid motif (aa133-147 DIRDLLWLEDDAMEQ) of CVB3 2A protease decreased both its EMCV IRES-dependent translation efficiency and destroy its cleavage on eukaryotic initiation factor 4G (eIF4G) I. Our results may provide better understanding into more effective interventions and treatments for co-infection of viral diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Enzyme-like replication de novo in a microcontroller environment.

    Science.gov (United States)

    Tangen, Uwe

    2010-01-01

    The desire to start evolution from scratch inside a computer memory is as old as computing. Here we demonstrate how viable computer programs can be established de novo in a Precambrian environment without supplying any specific instantiation, just starting with random bit sequences. These programs are not self-replicators, but act much more like catalysts. The microcontrollers used in the end are the result of a long series of simplifications. The objective of this simplification process was to produce universal machines with a human-readable interface, allowing software and/or hardware evolution to be studied. The power of the instruction set can be modified by introducing a secondary structure-folding mechanism, which is a state machine, allowing nontrivial replication to emerge with an instruction width of only a few bits. This state-machine approach not only attenuates the problems of brittleness and encoding functionality (too few bits available for coding, and too many instructions needed); it also enables the study of hardware evolution as such. Furthermore, the instruction set is sufficiently powerful to permit external signals to be processed. This information-theoretic approach forms one vertex of a triangle alongside artificial cell research and experimental research on the creation of life. Hopefully this work helps develop an understanding of how information—in a similar sense to the account of functional information described by Hazen et al.—is created by evolution and how this information interacts with or is embedded in its physico-chemical environment.

  16. Optical replication techniques for image slicers

    Czech Academy of Sciences Publication Activity Database

    Schmoll, J.; Robertson, D.J.; Dubbeldam, C.M.; Bortoletto, F.; Pína, L.; Hudec, René; Prieto, E.; Norrie, C.; Ramsay- Howat, S.

    2006-01-01

    Roč. 50, 4-5 (2006), s. 263-266 ISSN 1387-6473 Institutional research plan: CEZ:AV0Z10030501 Keywords : smart focal planes * image slicers * replication Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics Impact factor: 1.914, year: 2006

  17. Inhibition of DNA replication by ultraviolet light

    International Nuclear Information System (INIS)

    Edenberg, H.J.

    1976-01-01

    DNA replication in ultraviolet-irradiated HeLa cells was studied by two different techniques: measurements of the kinetics of semiconservative DNA synthesis, and DNA fiber autoradiography. In examining the kinetics of semiconservative DNA synthesis, density label was used to avoid measuring the incorporation due to repair replication. The extent of inhibition varied with time. After doses of less than 10 J/m 2 the rate was initially depressed but later showed some recovery. After higher doses, a constant, low rate of synthesis was seen for at least the initial 6 h. An analysis of these data indicated that the inhibition of DNA synthesis could be explained by replication forks halting at pyrimidine dimers. DNA fiber autoradiography was used to further characterize replication after ultraviolet irradiation. The average length of labeled segments in irradiated cells increased in the time immediately after irradiation, and then leveled off. This is the predicted pattern if DNA synthesis in each replicon continued at its previous rate until a lesion is reached, and then halted. The frequency of lesions that block synthesis is approximately the same as the frequency of pyrimidine dimers

  18. Replication and Inhibitors of Enteroviruses and Parechoviruses

    Directory of Open Access Journals (Sweden)

    Lonneke van der Linden

    2015-08-01

    Full Text Available The Enterovirus (EV and Parechovirus genera of the picornavirus family include many important human pathogens, including poliovirus, rhinovirus, EV-A71, EV-D68, and human parechoviruses (HPeV. They cause a wide variety of diseases, ranging from a simple common cold to life-threatening diseases such as encephalitis and myocarditis. At the moment, no antiviral therapy is available against these viruses and it is not feasible to develop vaccines against all EVs and HPeVs due to the great number of serotypes. Therefore, a lot of effort is being invested in the development of antiviral drugs. Both viral proteins and host proteins essential for virus replication can be used as targets for virus inhibitors. As such, a good understanding of the complex process of virus replication is pivotal in the design of antiviral strategies goes hand in hand with a good understanding of the complex process of virus replication. In this review, we will give an overview of the current state of knowledge of EV and HPeV replication and how this can be inhibited by small-molecule inhibitors.

  19. Chaotic interactions of self-replicating RNA.

    Science.gov (United States)

    Forst, C V

    1996-03-01

    A general system of high-order differential equations describing complex dynamics of replicating biomolecules is given. Symmetry relations and coordinate transformations of general replication systems leading to topologically equivalent systems are derived. Three chaotic attractors observed in Lotka-Volterra equations of dimension n = 3 are shown to represent three cross-sections of one and the same chaotic regime. Also a fractal torus in a generalized three-dimensional Lotka-Volterra Model has been linked to one of the chaotic attractors. The strange attractors are studied in the equivalent four-dimensional catalytic replicator network. The fractal torus has been examined in adapted Lotka-Volterra equations. Analytic expressions are derived for the Lyapunov exponents of the flow in the replicator system. Lyapunov spectra for different pathways into chaos has been calculated. In the generalized Lotka-Volterra system a second inner rest point--coexisting with (quasi)-periodic orbits--can be observed; with an abundance of different bifurcations. Pathways from chaotic tori, via quasi-periodic tori, via limit cycles, via multi-periodic orbits--emerging out of periodic doubling bifurcations--to "simple" chaotic attractors can be found.

  20. Suppression of Coronavirus Replication by Cyclophilin Inhibitors

    Directory of Open Access Journals (Sweden)

    Takashi Sasaki

    2013-05-01

    Full Text Available Coronaviruses infect a variety of mammalian and avian species and cause serious diseases in humans, cats, mice, and birds in the form of severe acute respiratory syndrome (SARS, feline infectious peritonitis (FIP, mouse hepatitis, and avian infectious bronchitis, respectively. No effective vaccine or treatment has been developed for SARS-coronavirus or FIP virus, both of which cause lethal diseases. It has been reported that a cyclophilin inhibitor, cyclosporin A (CsA, could inhibit the replication of coronaviruses. CsA is a well-known immunosuppressive drug that binds to cellular cyclophilins to inhibit calcineurin, a calcium-calmodulin-activated serine/threonine-specific phosphatase. The inhibition of calcineurin blocks the translocation of nuclear factor of activated T cells from the cytosol into the nucleus, thus preventing the transcription of genes encoding cytokines such as interleukin-2. Cyclophilins are peptidyl-prolyl isomerases with physiological functions that have been described for many years to include chaperone and foldase activities. Also, many viruses require cyclophilins for replication; these include human immunodeficiency virus, vesicular stomatitis virus, and hepatitis C virus. However, the molecular mechanisms leading to the suppression of viral replication differ for different viruses. This review describes the suppressive effects of CsA on coronavirus replication.

  1. Measurements and searches with top quarks

    International Nuclear Information System (INIS)

    Peters, Reinhild Yvonne

    2008-01-01

    In 1995 the last missing member of the known families of quarks, the top quark, was discovered by the CDF and D0 experiments at the Tevatron, a proton-antiproton collider at Fermilab near Chicago. Until today, the Tevatron is the only place where top quarks can be produced. The determination of top quark production and properties is crucial to understand the Standard Model of particle physics and beyond. The most striking property of the top quark is its mass--of the order of the mass of a gold atom and close to the electroweak scale--making the top quark not only interesting in itself but also as a window to new physics. Due to the high mass, much higher than of any other known fermion, it is expected that the top quark plays an important role in electroweak symmetry breaking, which is the most prominent candidate to explain the mass of particles. In the Standard Model, electroweak symmetry breaking is induced by one Higgs field, producing one additional physical particle, the Higgs boson. Although various searches have been performed, for example at the Large Electron Positron Collider (LEP), no evidence for the Higgs boson could yet be found in any experiment. At the Tevatron, multiple searches for the last missing particle of the Standard Model are ongoing with ever higher statistics and improved analysis techniques. The exclusion or verification of the Higgs boson can only be achieved by combining many techniques and many final states and production mechanisms. As part of this thesis, the search for Higgs bosons produced in association with a top quark pair (t(bar t)H) has been performed. This channel is especially interesting for the understanding of the coupling between Higgs and the top quark. Even though the Standard Model Higgs boson is an attractive candidate, there is no reason to believe that the electroweak symmetry breaking is induced by only one Higgs field. In many models more than one Higgs boson are expected to exist, opening even more channels

  2. Chromatin Controls DNA Replication Origin Selection, Lagging-Strand Synthesis, and Replication Fork Rates.

    Science.gov (United States)

    Kurat, Christoph F; Yeeles, Joseph T P; Patel, Harshil; Early, Anne; Diffley, John F X

    2017-01-05

    The integrity of eukaryotic genomes requires rapid and regulated chromatin replication. How this is accomplished is still poorly understood. Using purified yeast replication proteins and fully chromatinized templates, we have reconstituted this process in vitro. We show that chromatin enforces DNA replication origin specificity by preventing non-specific MCM helicase loading. Helicase activation occurs efficiently in the context of chromatin, but subsequent replisome progression requires the histone chaperone FACT (facilitates chromatin transcription). The FACT-associated Nhp6 protein, the nucleosome remodelers INO80 or ISW1A, and the lysine acetyltransferases Gcn5 and Esa1 each contribute separately to maximum DNA synthesis rates. Chromatin promotes the regular priming of lagging-strand DNA synthesis by facilitating DNA polymerase α function at replication forks. Finally, nucleosomes disrupted during replication are efficiently re-assembled into regular arrays on nascent DNA. Our work defines the minimum requirements for chromatin replication in vitro and shows how multiple chromatin factors might modulate replication fork rates in vivo. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  3. ATP signals

    DEFF Research Database (Denmark)

    Novak, Ivana

    2016-01-01

    The Department of Biology at the University of Copenhagen explains the function of ATP signalling in the pancreas......The Department of Biology at the University of Copenhagen explains the function of ATP signalling in the pancreas...

  4. Search for New Physics Involving Top Quarks at ATLAS

    CERN Document Server

    Golling, Tobias

    2011-01-01

    Two searches for new phenomena involving top quarks are presented: a search for a top partner in ttbar events with large missing transverse momentum, and a search for ttbar resonances in proton-proton collisions at a center-of-mass energy of 7 TeV. The measurements are based on 35 pb^-1 and 200 pb^-1 of data collected with the ATLAS detector at the LHC in 2010 and 2011, respectively. No evidence for a signal is observed. The first limits from the LHC are established on the mass of a top partner, excluding a mass of 275 GeV for a neutral particle mass less than 50 GeV and a mass of 300 GeV for a neutral particle mass less than 10 GeV. Using the reconstructed ttbar mass spectrum, limits are set on the production cross-section times branching ratio to ttbar for narrow and wide resonances. For narrow Z' models, the observed 95% C.L. limits range from approximately 38 pb to 3.2 pb for masses going from m_Z' = 500 GeV to m_Z' = 1300 GeV. In Randall-Sundrum models, Kaluza-Klein gluons with masses below 650 GeV are e...

  5. Top Mass Measurement at CLIC at 500 GeV

    CERN Document Server

    Simon, Frank; Poss, Stephane

    2012-01-01

    We present a study of the capability of a 500 GeV e+e- collider based on CLIC technology for precision measurements of top quark properties. The analysis is based on full detector simulations of the CLIC_ILD detector concept using Geant4, including realistic background contributions from two photon processes. Event reconstruction is performed using a particle flow algorithm with stringent cuts to control the influence of background. The mass and width of the top quark are studied in fully-hadronic and semi-leptonic decays of ttbar pairs using event samples of signal and standard model background processes corresponding to an integrated luminosity of 100/fb. Statistical uncertainties of the top mass given by the invariant mass of its decay products of 0.08 GeV and 0.09 GeV are obtained for the fully-hadronic and the semi-leptonic decay channel, respectively, demonstrating that similar precision to that at ILC can be achieved at CLIC despite less favorable experimental conditions.

  6. The Top Quark, QCD, And New Physics.

    Science.gov (United States)

    Dawson, S.

    2002-06-01

    The role of the top quark in completing the Standard Model quark sector is reviewed, along with a discussion of production, decay, and theoretical restrictions on the top quark properties. Particular attention is paid to the top quark as a laboratory for perturbative QCD. As examples of the relevance of QCD corrections in the top quark sector, the calculation of e{sup+}e{sup -}+ t{bar t} at next-to-leading-order QCD using the phase space slicing algorithm and the implications of a precision measurement of the top quark mass are discussed in detail. The associated production of a t{bar t} pair and a Higgs boson in either e{sup+}e{sup -} or hadronic collisions is presented at next-to-leading-order QCD and its importance for a measurement of the top quark Yulrawa coupling emphasized. Implications of the heavy top quark mass for model builders are briefly examined, with the minimal supersymmetric Standard Model and topcolor discussed as specific examples.

  7. Measurement of the top quark mass

    International Nuclear Information System (INIS)

    Blusk, Steven R.

    1998-01-01

    The first evidence and subsequent discovery of the top quark was reported nearly 4 years ago. Since then, CDF and D0 have analyzed their full Run 1 data samples, and analysis techniques have been refined to make optimal use of the information. In this paper, we report on the most recent measurements of the top quark mass, performed by the CDF and D0 collaborations at the Fermilab Tevatron. The CDF collaboration has performed measurements of the top quark mass in three decay channels from which the top quark mass is measured to be 175.5 ± 6.9 GeV=c 2 . The D0 collaboration combines measurements from two decay channels to obtain a top quark mass of 172.1 ± 7.1 GeV/c 2 . Combining the measurements from the two experiments, assuming a 2 GeV GeV/c 2 correlated systematic uncertainty, the measurement of the top quark mass at the Tevatron is 173.9 ± 5.2 GeV/c 2 . This report presents the measurements of the top quark mass from each of the decay channels which contribute to this measurement

  8. Measurements of the Top Anti-Top Production Cross Section and Top Quark Mass in the Hadronically Decaying Tau + Jets Decay Channel at CDF

    Energy Technology Data Exchange (ETDEWEB)

    Hare, Daryl Curtis [Rutgers Univ., Piscataway, NJ (United States)

    2011-01-01

    In this thesis, we present the first exclusive observation of the t-t → hadronic τ + jets decay channel. Using these events, we measure the t-t pair production cross section and the top quark mass in 2.2 fb-1 of data collected with the Collider Detector at Fermilab (CDF). The Tevatron accelerator at Fermilab provides collisions of protons and anti-protons at a center-of-mass energy of √s = 1.96 TeV and is one of only two accelerators in the world with enough energy to produce top quarks. With a branching fraction of nearly 10%, the hadronic τ + jets decay channel is the third largest t-t decay mode, and it has only been minimally explored. This the first measurement of the t-t pair production cross section in this decay channel at CDF and the first measurement of the top quark mass in this decay channel in the world. The analysis introduces a new method to recover the total momentum of the ν produced in the τ decay and an artificial neural network to reduce the contribution from the largest background source, QCD multijet background. The t-t pair production cross section is extracted by minimizing a negative log likelihood function which compares the number of observed events to the number of expected events for a given t-t cross section. The top quark mass is extracted by minimizing a negative log likelihood function built from signal and ii background probabilities which are based on the matrix elements for t-t production and decay and W + 4 parton production, respectively. Using events selected with exactly 1 hadronically decaying τ, exactly 4 jets with at least 1 identified as having originated from a b quark, and large missing transverse energy, we measure the t-t pair production cross section to be 8.8 ± 3.3 (stat.) ± 2.2 (syst.) pb and the top quark mass to be 172.7±9.3 (stat.) ±3.7 (syst.) GeV. We find both values to be in good agreement with

  9. Visibility of news items on Twitter and Facebook: comparative analysis of the most replicated news in Europe and the Americas

    Directory of Open Access Journals (Sweden)

    Gabriela da Silva Zago

    2013-06-01

    Full Text Available This paper identifies and compares the top replicated news items on Twitter and Facebook, on news websites from Brazil, Germany, Spain, the United States and United Kingdom. The data includes 8 of the newspapers with the largest circulation in the 5 countries, totaling 40 outlets. The volume of “retweets” and “likes” was used as a metric for representing the visibility of news items. Links posted on Twitter and messages posted by newspapers on Facebook were collected for a period of two weeks during October 2012. Content analysis was carried out for the top 25 replicated messages in each social network, which uncovered significant cultural traits and editorial differences across countries, based upon the content that circulated on social networks during the period. The results confirm users’ perceptions of social networking sites, with Facebook being used largely for entertainment and recreation, and Twitter for covering political, economic, and social events.

  10. Hadronization systematics and top mass reconstruction

    Directory of Open Access Journals (Sweden)

    Corcella Gennaro

    2014-01-01

    Full Text Available I discuss a few issues related to the systematic error on the top mass mea- surement at hadron colliders, due to hadronization effects. Special care is taken about the impact of bottom-quark fragmentation in top decays, especially on the reconstruction relying on final states with leptons and J/Ψ in the dilepton channel. I also debate the relation between the measured mass and its theoretical definition, and report on work in progress, based on the Monte Carlo simulation of fictitious top-flavoured hadrons, which may shed light on this issue and on the hadronization systematics.

  11. TOP500 Supercomputers for June 2005

    Energy Technology Data Exchange (ETDEWEB)

    Strohmaier, Erich; Meuer, Hans W.; Dongarra, Jack; Simon, Horst D.

    2005-06-22

    25th Edition of TOP500 List of World's Fastest Supercomputers Released: DOE/L LNL BlueGene/L and IBM gain Top Positions MANNHEIM, Germany; KNOXVILLE, Tenn.; BERKELEY, Calif. In what has become a closely watched event in the world of high-performance computing, the 25th edition of the TOP500 list of the world's fastest supercomputers was released today (June 22, 2005) at the 20th International Supercomputing Conference (ISC2005) in Heidelberg Germany.

  12. Search for top in UA2

    International Nuclear Information System (INIS)

    Repellin, J.P.

    1989-01-01

    A search for the top quark in the data collected during 1988 by the UA2 collaboration at the CERN proton-antiproton collider is presented. In UA2 the selected decay mode is t → eν-barb. The present report is limited to the study of topologies with an electron, a neutrino, and two or more jets. With an integrated luminosity of 2.5 pb -1 the data do not show any contribution from top and at this preliminary stage of the analysis a top mass between 30 and 60 GeV seems excluded. (K.A.) 9 refs.; 9 figs.; 2 tabs

  13. Precision Determination of the Top Quark Mass

    Energy Technology Data Exchange (ETDEWEB)

    Movilla Fernandez, Pedro A.; /LBL, Berkeley

    2007-05-01

    The CDF and D0 collaborations have updated their measurements of the mass of the top quark using proton-antiproton collisions at {radical}s = 1.96 TeV produced at the Tevatron. The uncertainties in each of the top-antitop decay channels have been reduced. The new Tevatron average for the mass of the top quark based on about 1 fb{sup -1} of data per experiment is 170.9 {+-} 1.8 GeV/c{sup 2}.

  14. Top quark mass measurement at the Tevatron

    Energy Technology Data Exchange (ETDEWEB)

    Guimaraes da Costa, Joao; /Harvard U.

    2004-12-01

    The authors report on the latest experimental measurements of the top quark mass by the CDF and D0 Collaborations at the Fermilab Tevatron. They present a new top mass measurement using the t{bar t} events collected by the D0 Collaboration in Run I between 1994 and 1996. This result is combined with previous measurements to yield a new world top mass average. They also describe several preliminary results using up to 193 pb{sup -1} of t{bar t} events produced in {bar p}p collisions at {radical}s = 1.96 TeV during the Run II of the Tevatron.

  15. Global constraints on top quark anomalous couplings

    Science.gov (United States)

    Déliot, Frédéric; Faria, Ricardo; Fiolhais, Miguel C. N.; Lagarelhos, Pedro; Onofre, António; Pease, Christopher M.; Vasconcelos, Ana

    2018-01-01

    The latest results on top quark physics, namely single top quark production cross sections, W -boson helicity and asymmetry measurements are used to probe the Lorentz structure of the W t b vertex. The increase of sensitivity to new anomalous physics contributions to the top quark sector of the standard model is quantified by combining the relevant results from Tevatron and the Large Hadron Collider. The results show that combining an increasing set of available precision measurements in the search for new physics phenomena beyond the standard model leads to significant sensitivity improvements, especially when compared with the current expectation for the High Luminosity run at the LHC.

  16. The de Sitter relativistic top theory

    International Nuclear Information System (INIS)

    Armenta, J.; Nieto, J.A.

    2005-01-01

    We discuss the relativistic top theory from the point of view of the de Sitter (or anti-de Sitter) group. Our treatment rests on the Hanson-Regge spherical relativistic top Lagrangian formulation. We propose an alternative method for studying spinning objects via Kaluza-Klein theory. In particular, we derive the relativistic top equations of motion starting with the geodesic equation for a point particle in 4+N dimensions. We compare our approach with Fukuyama's formulation of spinning objects, which is also based on Kaluza-Klein theory. We also report a generalization of our approach to a 4+N+D dimensional theory

  17. New Physics in Single-Top Production

    CERN Document Server

    Lohse, T; The ATLAS collaboration

    2014-01-01

    In this paper an overview of recent results on the search for physics beyond the Standard Model in the electro-weak top-quark production from the ATLAS, D0 , CDF and CMS collaborations is given. This includes searches for W' and b$^∗$ resonances as well as measurements of CP violation, the W helicity fractions and the top-quark polarisation in single-top production. A brief review on the search for flavour-changing neutral currents and cross-section measurements with respect to the CKM matrix element $V_{tb}$ is given.

  18. Top physics in ATLAS and CMS

    CERN Document Server

    Diez, Carmen

    2018-01-01

    A selection of recent results of top quark production performed by the ATLAS and CMS Collaborations at the LHC is presented. The results include measurements of top quark pair production, including inclusive and differential cross sections, as well as cross sections for ${\\rm t\\bar{t}}$ production in association with additional heavy-quark jets or additional bosons. The production of single top quarks via t-channel, tW associated production, and in association with a Z boson is also discussed. The results discussed are mostly obtained using data collected in proton-proton collisions at centre-of-mass energies of 8 and 13 TeV.

  19. Women in Top Management and Firm Performance

    DEFF Research Database (Denmark)

    Smith, Nina; Smith, Valdemar; Verner, Mette

    -observations for all Danish firms with more than 50 employees over the period 1994-2003, the analysis suggests that the proportion of women in top management jobs has from none to positive influence on firm performance. However, the results show that the strength of the effects of women in top management depends...... on how top CEOs are defined and on the method of estimation of the model. Next, the results point towards a positive influence on firm performance of the staff representation in the supervisory board of the firm but more women representing the shareholders in the supervisory board of the firm seems...

  20. High-Resolution Replication Profiles Define the Stochastic Nature of Genome Replication Initiation and Termination

    Directory of Open Access Journals (Sweden)

    Michelle Hawkins

    2013-11-01

    Full Text Available Eukaryotic genome replication is stochastic, and each cell uses a different cohort of replication origins. We demonstrate that interpreting high-resolution Saccharomyces cerevisiae genome replication data with a mathematical model allows quantification of the stochastic nature of genome replication, including the efficiency of each origin and the distribution of termination events. Single-cell measurements support the inferred values for stochastic origin activation time. A strain, in which three origins were inactivated, confirmed that the distribution of termination events is primarily dictated by the stochastic activation time of origins. Cell-to-cell variability in origin activity ensures that termination events are widely distributed across virtually the whole genome. We propose that the heterogeneity in origin usage contributes to genome stability by limiting potentially deleterious events from accumulating at particular loci.