WorldWideScience

Sample records for replicator event mark

  1. ATAD2 is an epigenetic reader of newly synthesized histone marks during DNA replication.

    Science.gov (United States)

    Koo, Seong Joo; Fernández-Montalván, Amaury E; Badock, Volker; Ott, Christopher J; Holton, Simon J; von Ahsen, Oliver; Toedling, Joern; Vittori, Sarah; Bradner, James E; Gorjánácz, Mátyás

    2016-10-25

    ATAD2 (ATPase family AAA domain-containing protein 2) is a chromatin regulator harboring an AAA+ ATPase domain and a bromodomain, previously proposed to function as an oncogenic transcription co-factor. Here we suggest that ATAD2 is also required for DNA replication. ATAD2 is co-expressed with genes involved in DNA replication in various cancer types and predominantly expressed in S phase cells where it localized on nascent chromatin (replication sites). Our extensive biochemical and cellular analyses revealed that ATAD2 is recruited to replication sites through a direct interaction with di-acetylated histone H4 at K5 and K12, indicative of newly synthesized histones during replication-coupled chromatin reassembly. Similar to ATAD2-depletion, ectopic expression of ATAD2 mutants that are deficient in binding to these di-acetylation marks resulted in reduced DNA replication and impaired loading of PCNA onto chromatin, suggesting relevance of ATAD2 in DNA replication. Taken together, our data show a novel function of ATAD2 in cancer and for the first time identify a reader of newly synthesized histone di-acetylation-marks during replication.

  2. Transcription and replication result in distinct epigenetic marks following repression of early gene expression

    OpenAIRE

    Kallestad, Les; Woods, Emily; Christensen, Kendra; Gefroh, Amanda; Balakrishnan, Lata; Milavetz, Barry

    2013-01-01

    Simian Virus 40 (SV40) early transcription is repressed when the product of early transcription, T-antigen, binds to its cognate regulatory sequence, Site I, in the promoter of the SV40 minichromosome. Because SV40 minichromosomes undergo replication and transcription potentially repression could occur during active transcription or during DNA replication. Since repression is frequently epigenetically marked by the introduction of specific forms of methylated histone H3, we characterized th...

  3. Replication stress interferes with histone recycling and predeposition marking of new histones

    DEFF Research Database (Denmark)

    Jasencakova, Zuzana; Scharf, Annette N D; Ask, Katrine

    2010-01-01

    To restore chromatin on new DNA during replication, recycling of histones evicted ahead of the fork is combined with new histone deposition. The Asf1 histone chaperone, which buffers excess histones under stress, is a key player in this process. Yet how histones handled by human Asf1 are modified...... remains unclear. Here we identify marks on histones H3-H4 bound to Asf1 and changes induced upon replication stress. In S phase, distinct cytosolic and nuclear Asf1b complexes show ubiquitous H4K5K12diAc and heterogeneous H3 marks, including K9me1, K14ac, K18ac, and K56ac. Upon acute replication arrest......, the predeposition mark H3K9me1 and modifications typical of chromatin accumulate in Asf1 complexes. In parallel, ssDNA is generated at replication sites, consistent with evicted histones being trapped with Asf1. During recovery, histones stored with Asf1 are rapidly used as replication resumes. This shows...

  4. Restoring chromatin after replication: How new and old histone marks come together

    DEFF Research Database (Denmark)

    Jasencakova, Zusana; Groth, Anja

    2010-01-01

    In dividing cells genome stability and function rely on faithful transmission of both DNA sequence and its organization into chromatin. In the course of DNA replication chromatin undergoes transient genome-wide disruption followed by restoration on new DNA. This involves tight coordination of DNA...... replication and chromatin assembly processes in time and space. Dynamic recycling and de novo deposition of histones are fundamental for chromatin restoration. Histone post-translational modifications (PTMs) are thought to have a causal role in establishing distinct chromatin structures. Here we discuss PTMs...... present on new and parental histones and how they influence genome stability and restoration of epigenetically defined domains. Newly deposited histones must change their signature in the process of chromatin restoration, this may occur in a step-wise fashion involving replication-coupled processes...

  5. Transcriptional repression is epigenetically marked by H3K9 methylation during SV40 replication

    OpenAIRE

    Kallestad, Les; Christensen, Kendra; Woods, Emily; Milavetz, Barry

    2014-01-01

    Background We have recently shown that T-antigen binding to Site I results in the replication-dependent introduction of H3K9me1 into SV40 chromatin late in infection. Since H3K9me2 and H3K9me3 are also present late in infection, we determined whether their presence was also related to the status of ongoing transcription and replication. Transcription was either inhibited with 5,6-dichloro-1-beta-D-ribofuranosylbenzimidizole (DRB) or stimulated with sodium butyrate and the effects on histone m...

  6. A transgenic mouse marking live replicating cells reveals in vivo transcriptional program of proliferation

    DEFF Research Database (Denmark)

    Klochendler, Agnes; Weinberg-Corem, Noa; Moran, Maya

    2012-01-01

    Most adult mammalian tissues are quiescent, with rare cell divisions serving to maintain homeostasis. At present, the isolation and study of replicating cells from their in vivo niche typically involves immunostaining for intracellular markers of proliferation, causing the loss of sensitive biolo...

  7. H4K20me0 marks post-replicative chromatin and recruits the TONSL₋MMS22L DNA repair complex

    Energy Technology Data Exchange (ETDEWEB)

    Saredi, Giulia; Huang, Hongda; Hammond, Colin M.; Alabert, Constance; Bekker-Jensen, Simon; Forne, Ignasi; Reverón-Gómez, Nazaret; Foster, Benjamin M.; Mlejnkova, Lucie; Bartke, Till; Cejka, Petr; Mailand, Niels; Imhof, Axel; Patel, Dinshaw J.; Groth, Anja [UCopenhagen; (MSKCC); (ICL); (LMU); (Zurich)

    2016-06-22

    Here, we report that after DNA replication, chromosomal processes including DNA repair and transcription take place in the context of sister chromatids. While cell cycle regulation can guide these processes globally, mechanisms to distinguish pre- and post-replicative states locally remain unknown. In this paper we reveal that new histones incorporated during DNA replication provide a signature of post-replicative chromatin, read by the human TONSL–MMS22L1, 2, 3, 4 homologous recombination complex. We identify the TONSL ankyrin repeat domain (ARD) as a reader of histone H4 tails unmethylated at K20 (H4K20me0), which are specific to new histones incorporated during DNA replication and mark post-replicative chromatin until the G2/M phase of the cell cycle. Accordingly, TONSL–MMS22L binds new histones H3–H4 both before and after incorporation into nucleosomes, remaining on replicated chromatin until late G2/M. H4K20me0 recognition is required for TONSL–MMS22L binding to chromatin and accumulation at challenged replication forks and DNA lesions. Consequently, TONSL ARD mutants are toxic, compromising genome stability, cell viability and resistance to replication stress. Finally, together, these data reveal a histone-reader-based mechanism for recognizing the post-replicative state, offering a new angle to understand DNA repair with the potential for targeted cancer therapy.

  8. Logistic regression applied to natural hazards: rare event logistic regression with replications

    Directory of Open Access Journals (Sweden)

    M. Guns

    2012-06-01

    Full Text Available Statistical analysis of natural hazards needs particular attention, as most of these phenomena are rare events. This study shows that the ordinary rare event logistic regression, as it is now commonly used in geomorphologic studies, does not always lead to a robust detection of controlling factors, as the results can be strongly sample-dependent. In this paper, we introduce some concepts of Monte Carlo simulations in rare event logistic regression. This technique, so-called rare event logistic regression with replications, combines the strength of probabilistic and statistical methods, and allows overcoming some of the limitations of previous developments through robust variable selection. This technique was here developed for the analyses of landslide controlling factors, but the concept is widely applicable for statistical analyses of natural hazards.

  9. Logistic regression applied to natural hazards: rare event logistic regression with replications

    Science.gov (United States)

    Guns, M.; Vanacker, V.

    2012-06-01

    Statistical analysis of natural hazards needs particular attention, as most of these phenomena are rare events. This study shows that the ordinary rare event logistic regression, as it is now commonly used in geomorphologic studies, does not always lead to a robust detection of controlling factors, as the results can be strongly sample-dependent. In this paper, we introduce some concepts of Monte Carlo simulations in rare event logistic regression. This technique, so-called rare event logistic regression with replications, combines the strength of probabilistic and statistical methods, and allows overcoming some of the limitations of previous developments through robust variable selection. This technique was here developed for the analyses of landslide controlling factors, but the concept is widely applicable for statistical analyses of natural hazards.

  10. Work-family enrichment and job performance: a constructive replication of affective events theory.

    Science.gov (United States)

    Carlson, Dawn; Kacmar, K Michele; Zivnuska, Suzanne; Ferguson, Merideth; Whitten, Dwayne

    2011-07-01

    Based on affective events theory (AET), we hypothesize a four-step model of the mediating mechanisms of positive mood and job satisfaction in the relationship between work-family enrichment and job performance. We test this model for both directions of enrichment (work-to-family and family-to-work). We used two samples to test the model using structural equation modeling. Results from Study 1, which included 240 full-time employees, were replicated in Study 2, which included 189 matched subordinate-supervisor dyads. For the work-to-family direction, results from both samples support our conceptual model and indicate mediation of the enrichment-performance relationship for the work-to-family direction of enrichment. For the family-to-work direction, results from the first sample support our conceptual model but results from the second sample do not. Our findings help elucidate mixed findings in the enrichment and job performance literatures and contribute to an understanding of the mechanisms linking these concepts. We conclude with a discussion of the practical and theoretical implications of our findings.

  11. Replisome stall events have shaped the distribution of replication origins in the genomes of yeasts

    Science.gov (United States)

    Newman, Timothy J.; Mamun, Mohammed A.; Nieduszynski, Conrad A.; Blow, J. Julian

    2013-01-01

    During S phase, the entire genome must be precisely duplicated, with no sections of DNA left unreplicated. Here, we develop a simple mathematical model to describe the probability of replication failing due to the irreversible stalling of replication forks. We show that the probability of complete genome replication is maximized if replication origins are evenly spaced, the largest inter-origin distances are minimized, and the end-most origins are positioned close to chromosome ends. We show that origin positions in the yeast Saccharomyces cerevisiae genome conform to all three predictions thereby maximizing the probability of complete replication if replication forks stall. Origin positions in four other yeasts—Kluyveromyces lactis, Lachancea kluyveri, Lachancea waltii and Schizosaccharomyces pombe—also conform to these predictions. Equating failure rates at chromosome ends with those in chromosome interiors gives a mean per nucleotide fork stall rate of ∼5 × 10−8, which is consistent with experimental estimates. Using this value in our theoretical predictions gives replication failure rates that are consistent with data from replication origin knockout experiments. Our theory also predicts that significantly larger genomes, such as those of mammals, will experience a much greater probability of replication failure genome-wide, and therefore will likely require additional compensatory mechanisms. PMID:23963700

  12. Definition of herpes simplex virus type 1 helper activities for adeno-associated virus early replication events.

    Directory of Open Access Journals (Sweden)

    Nathalie Alazard-Dany

    2009-03-01

    Full Text Available The human parvovirus Adeno-Associated Virus (AAV type 2 can only replicate in cells co-infected with a helper virus, such as Adenovirus or Herpes Simplex Virus type 1 (HSV-1; whereas, in the absence of a helper virus, it establishes a latent infection. Previous studies demonstrated that the ternary HSV-1 helicase/primase (HP complex (UL5/8/52 and the single-stranded DNA-Binding Protein (ICP8 were sufficient to induce AAV-2 replication in transfected cells. We independently showed that, in the context of a latent AAV-2 infection, the HSV-1 ICP0 protein was able to activate rep gene expression. The present study was conducted to integrate these observations and to further explore the requirement of other HSV-1 proteins during early AAV replication steps, i.e. rep gene expression and AAV DNA replication. Using a cellular model that mimics AAV latency and composite constructs coding for various sets of HSV-1 genes, we first confirmed the role of ICP0 for rep gene expression and demonstrated a synergistic effect of ICP4 and, to a lesser extent, ICP22. Conversely, ICP27 displayed an inhibitory effect. Second, our analyses showed that the effect of ICP0, ICP4, and ICP22 on rep gene expression was essential for the onset of AAV DNA replication in conjunction with the HP complex and ICP8. Third, and most importantly, we demonstrated that the HSV-1 DNA polymerase complex (UL30/UL42 was critical to enhance AAV DNA replication to a significant level in transfected cells and that its catalytic activity was involved in this process. Altogether, this work represents the first comprehensive study recapitulating the series of early events taking place during HSV-1-induced AAV replication.

  13. "The man who committed a hundred burglaries": Mark Benney's strange and eventful sociological career.

    Science.gov (United States)

    Lee, Raymond M

    2015-01-01

    This article examines the life and career of the sociologist Mark Benney. It describes the processes, not all of them edifying, by which he made the transition from life as a career criminal, via literature, to become a sociologist first at the London School of Economics and then at the University of Chicago. Benney's career is then used to illuminate particular episodes in the history of sociology, including the attempt to introduce into British sociology in the period after the Second World War quantitative survey techniques of the kind that were then becoming more widely used in the United States, and his work with David Riesman on the Interview Project, Riesman's attempt to develop a empirically based sociology of the interview. © 2015 Wiley Periodicals, Inc.

  14. H3S10ph broadly marks early-replicating domains in interphase ESCs and shows reciprocal antagonism with H3K9me2.

    Science.gov (United States)

    Chen, Carol C L; Goyal, Preeti; Karimi, Mohammad M; Abildgaard, Marie H; Kimura, Hiroshi; Lorincz, Matthew C

    2018-01-01

    Phosphorylation of histone H3 at serine 10 (H3S10ph) by Aurora kinases plays an important role in mitosis; however, H3S10ph also marks regulatory regions of inducible genes in interphase mammalian cells, implicating mitosis-independent functions. Using the fluorescent ubiquitin-mediated cell cycle indicator (FUCCI), we found that 30% of the genome in interphase mouse embryonic stem cells (ESCs) is marked with H3S10ph. H3S10ph broadly demarcates gene-rich regions in G1 and is positively correlated with domains of early DNA replication timing (RT) but negatively correlated with H3K9me2 and lamin-associated domains (LADs). Consistent with mitosis-independent kinase activity, this pattern was preserved in ESCs treated with Hesperadin, a potent inhibitor of Aurora B/C kinases. Disruption of H3S10ph by expression of nonphosphorylatable H3.3S10A results in ectopic spreading of H3K9me2 into adjacent euchromatic regions, mimicking the phenotype observed in Drosophila JIL-1 kinase mutants . Conversely, interphase H3S10ph domains expand in Ehmt1 (also known as Glp ) null ESCs, revealing that H3S10ph deposition is restricted by H3K9me2. Strikingly, spreading of H3S10ph at RT transition regions (TTRs) is accompanied by aberrant transcription initiation of genes co-oriented with the replication fork in Ehmt1 -/- and Ehmt2 -/- ESCs, indicating that establishment of repressive chromatin on the leading strand following DNA synthesis may depend upon these lysine methyltransferases. H3S10ph is also anti-correlated with H3K9me2 in interphase murine embryonic fibroblasts (MEFs) and is restricted to intragenic regions of actively transcribing genes by EHMT2. Taken together, these observations reveal that H3S10ph may play a general role in restricting the spreading of repressive chromatin in interphase mammalian cells. © 2018 Chen et al.; Published by Cold Spring Harbor Laboratory Press.

  15. Discrete gene replication events drive coupling between the cell cycle and circadian clocks.

    Science.gov (United States)

    Paijmans, Joris; Bosman, Mark; Ten Wolde, Pieter Rein; Lubensky, David K

    2016-04-12

    Many organisms possess both a cell cycle to control DNA replication and a circadian clock to anticipate changes between day and night. In some cases, these two rhythmic systems are known to be coupled by specific, cross-regulatory interactions. Here, we use mathematical modeling to show that, additionally, the cell cycle generically influences circadian clocks in a nonspecific fashion: The regular, discrete jumps in gene-copy number arising from DNA replication during the cell cycle cause a periodic driving of the circadian clock, which can dramatically alter its behavior and impair its function. A clock built on negative transcriptional feedback either phase-locks to the cell cycle, so that the clock period tracks the cell division time, or exhibits erratic behavior. We argue that the cyanobacterium Synechococcus elongatus has evolved two features that protect its clock from such disturbances, both of which are needed to fully insulate it from the cell cycle and give it its observed robustness: a phosphorylation-based protein modification oscillator, together with its accompanying push-pull read-out circuit that responds primarily to the ratios of different phosphoform concentrations, makes the clock less susceptible to perturbations in protein synthesis; the presence of multiple, asynchronously replicating copies of the same chromosome diminishes the effect of replicating any single copy of a gene.

  16. Logistic regression applied to natural hazards: rare event logistic regression with replications

    OpenAIRE

    Guns, M.; Vanacker, Veerle

    2012-01-01

    Statistical analysis of natural hazards needs particular attention, as most of these phenomena are rare events. This study shows that the ordinary rare event logistic regression, as it is now commonly used in geomorphologic studies, does not always lead to a robust detection of controlling factors, as the results can be strongly sample-dependent. In this paper, we introduce some concepts of Monte Carlo simulations in rare event logistic regression. This technique, so-called rare event logisti...

  17. Examining the Structure of the Schedule of Sexist Events: Replication and Extension

    National Research Council Canada - National Science Library

    Matteson, Alicia

    2004-01-01

    ... at Work/School," and "Unfair Treatment in Distant and Close Relationships" subscales Recommendations are made for the future use of these proposed subscales in conjunction with total scale scores in research using the SSE to examine links between reported experiences of sexist events and women's health and well-being.

  18. H4K20me0 marks post-replicative chromatin and recruits the TONSL–MMS22L DNA repair complex

    DEFF Research Database (Denmark)

    Saredi, Giulia; Huang, Hongda; Hammond, Colin M

    2016-01-01

    After DNA replication, chromosomal processes including DNA repair and transcription take place in the context of sister chromatids. While cell cycle regulation can guide these processes globally, mechanisms to distinguish pre- and post-replicative states locally remain unknown. Here we reveal...

  19. The use of water marks mapping to understand flood overflow events inside karstic cavities: Cueva Fría and Cueva Rosa (Asturias, NW Spain)

    Science.gov (United States)

    González Lemos, Saúl; Stoll, Heather M.

    2014-05-01

    Several karst systems in Asturias (NW Spain) present evidence of fluvial deposits cemented in speleothems that may provide good chronology of past flood events inside the caves. This flood record is under research in two karstic caves of this region, Cueva Fría and Cueva Rosa, which have in common the presence of a perennial stream inside the cave and a low gradient of the cave passage. Immediately after a flood overflow event, water marks, foam and detritus are visible at different heights on the cave walls and correspond to heights of bottlenecks in overflow drainage through the cave passage. Flood events also deposit sand and gravel on terraces on the cave wall and move large volumes of sand in the cave bed. We have noted that detrital particles (like sand or silt particles) are preserved as inclusions inside the stalagmites and that their abundance inside coeval stalagmites decreases as altitude and distance from the perennial stream increase, supporting its fluvial affinity. However, not all the stalagmites that contain detrital particles are located close to the perennial streams. In this work, we have mapped the water marks preserved in the cave walls to reconstruct water levels associated to flood overflow events of different magnitude. We have found that water mark correlation along the cave passage is very useful to define the hydrological behaviour and flood model of the cave during these extreme events. The water mark mapping and correlation have been also useful to prove that during periods of high rainfall, the movement of the sand-bars inside the cave can cover partially or completely active stalagmites, facilitating the cementation process and trapping abundant detrital material inside the stalagmite carbonate. 14C and U/Th dating of the stalagmites can provide a chronology for the detrital rich layers, so that the abundance of fluvial material in the stalagmites can reveal periods of enhanced vs. reduced flooding in the cave over the past several

  20. Track-match procedure criteria in the reference mark plane for quality control of event measurements from the JINR measuring devices

    International Nuclear Information System (INIS)

    Stepanenko, V.A.

    1978-01-01

    A new technique to preselect potential tracks of events in a reference plane is described. This technique allows to log bench marks used in track projections which connect two tops or a top and a break point in the TRACK-MATCH procedure. The above technique is implemented in a modular measurement quality control program. The results of measurement quality control obtained using a geometry restoration program are compared with those of the measurement quality control program

  1. Timing and sequencing of events marking the transition to adulthood in two informal settlements in Nairobi, Kenya.

    Science.gov (United States)

    Beguy, Donatien; Kabiru, Caroline W; Zulu, Eliya M; Ezeh, Alex C

    2011-06-01

    Young people living in poor urban informal settlements face unique challenges as they transition to adulthood. This exploratory paper uses retrospective information from the baseline survey of a 3-year prospective study to examine the timing and sequencing of four key markers (first sex, marriage, birth, and independent housing) of the transition to adulthood among 3,944 adolescents in two informal settlements in Nairobi city, Kenya. Event history analysis techniques are employed to examine the timing of the events. Results indicate that there is no significant gender difference with regard to first sexual debut among adolescents. For many boys and girls, the first sexual experience occurs outside of marriage or other union. For males, the sequencing of entry begins with entry into first sex, followed by independent housing. Conversely, for females, the sequencing begins with first sex and then parenthood. Apart from sexual debut, the patterns of entry into union and parenthood do not differ much from what was observed for Nairobi as a whole. The space constraints that typify the two slums may have influenced the pattern of leaving home observed. We discuss these and other findings in light of their implications for young people's health and well-being in resource-poor settings in urban areas.

  2. Depletion of Key Meiotic Genes and Transcriptome-Wide Abiotic Stress Reprogramming Mark Early Preparatory Events Ahead of Apomeiotic Transition

    Directory of Open Access Journals (Sweden)

    Jubin N Shah

    2016-10-01

    Full Text Available Molecular dissection of apomixis - an asexual reproductive mode - is anticipated to solve the enigma of loss of meiotic sex, and to help fixing elite agronomic traits. The Brassicaceae genus Boechera comprises of both sexual and apomictic species, permitting comparative analyses of meiotic circumvention (apomeiosis and parthenogenesis. Whereas previous studies reported local transcriptome changes during these events, it remained unclear whether global changes associated with hybridization, polyploidy and environmental adaptation that arose during evolution of Boechera might hint as (epigenetic regulators of early development prior apomictic initiation. To identify these signatures during vegetative stages, we compared seedling RNA-seq transcriptomes of an obligate triploid apomict and a diploid sexual, both isolated from a drought-prone habitat. Uncovered were several genes differentially expressed between sexual and apomictic seedlings, including homologues of meiotic genes ASYNAPTIC 1 (ASY1 and MULTIPOLAR SPINDLE 1 (MPS1 that were down-regulated in apomicts. An intriguing class of apomict-specific deregulated genes included several NAC transcription factors, homologues of which are known to be transcriptionally reprogrammed during abiotic stress in other plants. Deregulation of both meiotic and stress-response genes during seedling stages might possibly be important in preparation for meiotic circumvention, as similar transcriptional alteration was discernible in apomeiotic floral buds too. Furthermore, we noted that the apomict showed better tolerance to osmotic stress in vitro than the sexual, in conjunction with significant upregulation of a subset of NAC genes. In support of the current model that DNA methylation epigenetically regulates stress, ploidy, hybridization and apomixis, we noted that ASY1, MPS1 and NAC019 homologues were deregulated in Boechera seedlings upon DNA demethylation, and ASY1 in particular seems to be repressed by

  3. Hydrocarbon Biomarker Stratigraphy of C-Isotopic Excursions Marking Chemical Changes in the Ocean with Contemporanious Biotic Extinction-Radiation Events

    Science.gov (United States)

    Summons, Roger E.

    2004-01-01

    One paper recording progress in this topic has been accepted for publication. We report a method for the rigorous identification of biomarkers (crocetane and PMI) that may be specific for methanotrophic and methanogenic archaea and, perhaps, the process of anaerobic oxidation of methane. If catastrophic methane efflux from sub-sea methane hydrate is responsible for extinction events, as has been hypothesized by many workers, then we might expect to find biomarkers for methane oxidation in sediments marking some extinction boundaries. Unfortunately, identifying crocetane and PMI with certainty is not a trivial exercise and these biomarkers appear to have been mis-identified in a recent publication by workers from Curtin University. Barber et al. (2001) identified crocetane and PMI in sediments deposited in the basal Triassic of the Perth Basin, Australia. However, Barber et al. (2001) also found crocetane and PMI in many other sediments and oils in a way that was inconsistent with our knowledge of these systems.

  4. Event-based stochastic point rainfall resampling for statistical replication and climate projection of historical rainfall series

    DEFF Research Database (Denmark)

    Thorndahl, Søren; Korup Andersen, Aske; Larsen, Anders Badsberg

    2017-01-01

    Continuous and long rainfall series are a necessity in rural and urban hydrology for analysis and design purposes. Local historical point rainfall series often cover several decades, which makes it possible to estimate rainfall means at different timescales, and to assess return periods of extreme...... includes climate changes projected to a specific future period. This paper presents a framework for resampling of historical point rainfall series in order to generate synthetic rainfall series, which has the same statistical properties as an original series. Using a number of key target predictions...... for the future climate, such as winter and summer precipitation, and representation of extreme events, the resampled historical series are projected to represent rainfall properties in a future climate. Climate-projected rainfall series are simulated by brute force randomization of model parameters, which leads...

  5. Early events in the pathogenesis of foot-and-mouth disease in pigs; identification of oropharyngeal tonsils as sites of primary and sustained viral replication.

    Directory of Open Access Journals (Sweden)

    Carolina Stenfeldt

    Full Text Available A time-course study was performed to elucidate the early events of foot-and-mouth disease virus (FMDV infection in pigs subsequent to simulated natural, intra-oropharyngeal, inoculation. The earliest detectable event was primary infection in the lingual and paraepiglottic tonsils at 6 hours post inoculation (hpi characterized by regional localization of viral RNA, viral antigen, and infectious virus. At this time FMDV antigen was localized in cytokeratin-positive epithelial cells and CD172a-expressing leukocytes of the crypt epithelium of the paraepiglottic tonsils. De novo replication of FMDV was first detected in oropharyngeal swab samples at 12 hpi and viremia occurred at 18-24 hpi, approximately 24 hours prior to the appearance of vesicular lesions. From 12 through 78 hpi, microscopic detection of FMDV was consistently localized to cytokeratin-positive cells within morphologically characteristic segments of oropharyngeal tonsil crypt epithelium. During this period, leukocyte populations expressing CD172a, SLA-DQ class II and/or CD8 were found in close proximity to infected epithelial cells, but with little or no co-localization with viral proteins. Similarly, M-cells expressing cytokeratin-18 did not co-localize with FMDV proteins. Intra-epithelial micro-vesicles composed of acantholytic epithelial cells expressing large amounts of structural and non-structural FMDV proteins were present within crypts of the tonsil of the soft palate during peak clinical infection. These findings inculpate the paraepiglottic tonsils as the primary site of FMDV infection in pigs exposed via the gastrointestinal tract. Furthermore, the continuing replication of FMDV in the oropharyngeal tonsils during viremia and peak clinical infection with no concurrent amplification of virus occurring in the lower respiratory tract indicates that these sites are the major source of shedding of FMDV from pigs.

  6. 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...

  7. Lateralized delay period activity marks the focus of spatial attention in working memory: evidence from somatosensory event-related brain potentials.

    Science.gov (United States)

    Katus, Tobias; Eimer, Martin

    2015-04-29

    The short-term retention of sensory information in working memory (WM) is known to be associated with a sustained enhancement of neural activity. What remains controversial is whether this neural trace indicates the sustained storage of information or the allocation of attention. To evaluate the storage and attention accounts, we examined sustained tactile contralateral delay activity (tCDA component) of the event-related potential. The tCDA manifests over somatosensory cortex contralateral to task-relevant tactile information during stimulus retention. Two tactile sample sets (S1, S2) were presented sequentially, separated by 1.5 s. Each set comprised two stimuli, one per hand. Human participants memorized the location of one task-relevant stimulus per sample set and judged whether one of these locations was stimulated again at memory test. The two relevant pulses were unpredictably located on the same hand (stay trials) or on different hands (shift trials). Initially, tCDA components emerged contralateral to the relevant S1 pulse. Sequential loading of WM enhanced the tCDA after S2 was presented on stay trials. On shift trials, the tCDA's polarity reversed after S2 presentation, resulting in delay activity that was now contralateral to the task-relevant S2 pulse. The disappearance of a lateralized neural trace for the relevant S1 pulse did not impair memory accuracy for this stimulus on shift trials. These results contradict the storage account and suggest that delay period activity indicates the sustained engagement of an attention-based rehearsal mechanism. In conclusion, somatosensory delay period activity marks the current focus of attention in tactile WM. Copyright © 2015 the authors 0270-6474/15/356689-07$15.00/0.

  8. Evidence of systematic bias in sexual over- and underperception of naturally occurring events: a direct replication of Haselton (2003) in a more gender-equal culture.

    Science.gov (United States)

    Bendixen, Mons

    2014-11-17

    Error Management Theory (Haselton and Buss, 2000; Haselton and Nettle, 2006) maintains that natural selection has engineered adaptations for judgment under uncertainty to minimize the overall cost of making errors, leading to universal biases in judgments of sexual interest in men and women. This study, using a sample of het erosexual Norwegian students (n = 308), was carried out as a direct replication of Haselton's (2003) original study of naturally occurring events of sexual misperception. The results strongly supported the main hypotheses in the original study, showing that women reported being subject to opposite-sex sexual overperception far more often relative to underperception, and that this difference was small for men. In support of Error Management Theory, and in contrast to Social Role / Structure Theory expectations, the pattern of misperception for women and men was largely invariant across studies and across demographic groups within a culture. The findings suggest that cross-national differences in the level of gender inequality do not influence reports of sexual over- and underperception in women and men. Beyond sex, factors associated with more sexual overperception relative to underperception were being single, young, and having attitudes condoning casual sex.

  9. Evidence of Systematic Bias in Sexual Over- and Underperception of Naturally Occurring Events: A Direct Replication of Haselton (2003 in a more Gender-Equal Culture

    Directory of Open Access Journals (Sweden)

    Mons Bendixen

    2014-04-01

    Full Text Available Error Management Theory (Haselton and Buss, 2000; Haselton and Nettle, 2006 maintains that natural selection has engineered adaptations for judgment under uncertainty to minimize the overall cost of making errors, leading to universal biases in judgments of sexual interest in men and women. This study, using a sample of heterosexual Norwegian students (n = 308, was carried out as a direct replication of Haselton's (2003 original study of naturally occurring events of sexual misperception. The results strongly supported the main hypotheses in the original study, showing that women reported being subject to opposite-sex sexual overperception far more often relative to underperception, and that this difference was small for men. In support of Error Management Theory, and in contrast to Social Role / Structure Theory expectations, the pattern of misperception for women and men was largely invariant across studies and across demographic groups within a culture. The findings suggest that cross-national differences in the level of gender inequality do not influence reports of sexual over- and underperception in women and men. Beyond sex, factors associated with more sexual overperception relative to underperception were being single, young, and having attitudes condoning casual sex.

  10. 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...

  11. Stretch Marks

    Science.gov (United States)

    ... completely without the help of a dermatologist or plastic surgeon. These doctors may use one of many types of treatments — from actual surgery to techniques like microdermabrasion and laser treatment — to reduce the appearance of stretch marks. These techniques are ...

  12. 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

  13. Events

    Directory of Open Access Journals (Sweden)

    Igor V. Karyakin

    2016-02-01

    Full Text Available The 9th ARRCN Symposium 2015 was held during 21st–25th October 2015 at the Novotel Hotel, Chumphon, Thailand, one of the most favored travel destinations in Asia. The 10th ARRCN Symposium 2017 will be held during October 2017 in the Davao, Philippines. International Symposium on the Montagu's Harrier (Circus pygargus «The Montagu's Harrier in Europe. Status. Threats. Protection», organized by the environmental organization «Landesbund für Vogelschutz in Bayern e.V.» (LBV was held on November 20-22, 2015 in Germany. The location of this event was the city of Wurzburg in Bavaria.

  14. Different rates of DNA replication at early versus late S-phase sections: multiscale modeling of stochastic events related to DNA content/EdU (5-ethynyl-2'deoxyuridine) incorporation distributions.

    Science.gov (United States)

    Li, Biao; Zhao, Hong; Rybak, Paulina; Dobrucki, Jurek W; Darzynkiewicz, Zbigniew; Kimmel, Marek

    2014-09-01

    Mathematical modeling allows relating molecular events to single-cell characteristics assessed by multiparameter cytometry. In the present study we labeled newly synthesized DNA in A549 human lung carcinoma cells with 15-120 min pulses of EdU. All DNA was stained with DAPI and cellular fluorescence was measured by laser scanning cytometry. The frequency of cells in the ascending (left) side of the "horseshoe"-shaped EdU/DAPI bivariate distributions reports the rate of DNA replication at the time of entrance to S phase while their frequency in the descending (right) side is a marker of DNA replication rate at the time of transition from S to G2 phase. To understand the connection between molecular-scale events and scatterplot asymmetry, we developed a multiscale stochastic model, which simulates DNA replication and cell cycle progression of individual cells and produces in silico EdU/DAPI scatterplots. For each S-phase cell the time points at which replication origins are fired are modeled by a non-homogeneous Poisson Process (NHPP). Shifted gamma distributions are assumed for durations of cell cycle phases (G1, S and G2 M), Depending on the rate of DNA synthesis being an increasing or decreasing function, simulated EdU/DAPI bivariate graphs show predominance of cells in left (early-S) or right (late-S) side of the horseshoe distribution. Assuming NHPP rate estimated from independent experiments, simulated EdU/DAPI graphs are nearly indistinguishable from those experimentally observed. This finding proves consistency between the S-phase DNA-replication rate based on molecular-scale analyses, and cell population kinetics ascertained from EdU/DAPI scatterplots and demonstrates that DNA replication rate at entrance to S is relatively slow compared with its rather abrupt termination during S to G2 transition. Our approach opens a possibility of similar modeling to study the effect of anticancer drugs on DNA replication/cell cycle progression and also to quantify other

  15. Prayer marks.

    Science.gov (United States)

    Abanmi, Abdullah A; Al Zouman, Abdulrahman Y; Al Hussaini, Husa; Al-Asmari, Abdulrahman

    2002-07-01

    Prayer marks (PMs) are asymptomatic, chronic skin changes that consist mainly of thickening, lichenification, and hyperpigmentation, and develop over a long period of time as a consequence of repeated, extended pressure on bony prominences during prayer. Three hundred and forty-nine Muslims and 24 non-Muslims were examined for the appearance of PMs at different body sites. The prospective study of 349 Muslims (both males and females) with regular praying habits showed the occurrence of PMs on specific locations, such as the forehead, knees, ankles, and dorsa of the feet, leading to dermatologic changes consisting of lichenification and hyperpigmentation. The incidence of PMs was significantly higher in males than in females. Older subjects (over 50 years of age) demonstrated a significantly higher frequency of lichenification and hyperpigmentation, suggesting that repeated pressure and friction for prolonged periods are the causative factors for the development of PMs. Histologic examination of skin biopsies from the affected sites showed compact orthokeratosis, hypergranulosis, dermal papillary fibrosis, and dermal vascularization. PMs were not associated with any risk of secondary complications, such as erythema, bullous formation, and infections. PMs are commonly occurring dermatologic changes in Muslims who pray for prolonged periods.

  16. Investigation of adverse events associated with an off-label use of arterial stents and CE-marked iliac vein stents in the iliac vein: insights into developing a better iliac vein stent.

    Science.gov (United States)

    Shida, Takuya; Umezu, Mitsuo; Iwasaki, Kiyotaka

    2018-06-01

    We analyzed the adverse events associated with an off-label use of arterial stents and CE-marked iliac vein stents for the treatment of iliac venous thromboembolism and investigated their relationships with the anatomical features of the iliac vein, to gain insights into the development of a better iliac vein stent. Reports of adverse events following the use of stents in the iliac vein were retrieved from the Manufacturer and User Facility Device Experience (MAUDE) database that contain suspected device-associated complications reported to the Food and Drug Administration. Data from 2006 to 2016 were investigated. The literature analysis was also conducted using PubMed, Cochrane Library, EMBASE, and Web of Science focusing on English articles published up to 4 October 2016. The analysis of 88 adverse events from the MAUDE database and 182 articles from the literature revealed that a higher number of adverse events had been reported following the use of arterial stents in the iliac vein compared to CE-marked iliac vein stents. While stent migration and shortening were reported only for the arterial stents, stent fracture and compression occurred regardless of the stent type, even though a vein does not pulsate. A study of the anatomical features of the iliac vein implies that bending, compression, and kink loads are applied to the iliac vein stents in vivo. For designing, developing, and pre-clinical testing of stents intended for use in the iliac vein, the above mechanical load environments induced by the anatomical features should be considered.

  17. 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

  18. Serotonin Transporter-Linked Polymorphic Region (5-HTTLPR) Genotype and Stressful Life Events Interact to Predict Preschool-Onset Depression: A Replication and Developmental Extension

    Science.gov (United States)

    Bogdan, Ryan; Agrawal, Arpana; Gaffrey, Michael S.; Tillman, Rebecca; Luby, Joan L.

    2014-01-01

    Background: Scientific enthusiasm about gene × environment interactions, spurred by the 5-HTTLPR (serotonin transporter-linked polymorphic region) × SLEs (stressful life events) interaction predicting depression, have recently been tempered by sober realizations of small effects and meta-analyses reaching opposing conclusions. These mixed findings…

  19. A constructive replication of White's alleged refutation of Nisbett and Wilson and of Bem: Limitations on verbal reports of internal events.

    NARCIS (Netherlands)

    Srpangers, M.; van den Brink, W.P.; van Heerden, J.; Hoogstraten, J.

    1987-01-01

    Critiques P. White's analysis of R. Nisbett and T. Wilson's work on the limitations to conscious awareness of mental processes. A reanalysis of White's data demonstrated no evidence for his hypothesis that report accuracy is improved by memory for the events of the relevant process. In addition,

  20. 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...

  1. 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....

  2. 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...

  3. Reconfiguring trade mark law

    DEFF Research Database (Denmark)

    Elsmore, Matthew James

    2013-01-01

    -border setting, with a particular focus on small business and consumers. The article's overall message is to call for a rethink of received wisdom suggesting that trade marks are effective trade-enabling devices. The case is made for reassessing how we think about European trade mark law.......First, this article argues that trade mark law should be approached in a supplementary way, called reconfiguration. Second, the article investigates such a reconfiguration of trade mark law by exploring the interplay of trade marks and service transactions in the Single Market, in the cross...

  4. 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...

  5. Mark Tompkins Canaccord

    OpenAIRE

    Mark Tompkins Canaccord

    2018-01-01

    Mark Tompkins Canaccord is a senior technologist for ecosystem and water resources management in SEC SAID Oakland, California office. In his career which lasts over fifteen years Mark has worked on project involving lake restorations, clean water engineering, ecological engineering and management, hydrology, hydraulics, sediment transport and other projects for environmental planning all over the country. Mark Tompkins Canaccord tries to blend his skills of planning and engineering with s...

  6. Lujan Mark-4

    Energy Technology Data Exchange (ETDEWEB)

    Mocko, Michael Jeffrey [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Zavorka, Lukas [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Koehler, Paul E. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-11-13

    This is a review of Mark-IV target neutronics design. It involved the major redesign of the upper tier, offering harder neutron spectra for upper-tier FPs; a redesign of the high-resolution (HR) moderator; and a preservation of the rest of Mark-III features.

  7. Mark Stock | NREL

    Science.gov (United States)

    Stock Mark Stock Scientific Visualization Specialist Mark.Stock@nrel.gov | 303-275-4174 Dr. Stock , virtual reality, parallel computing, and manipulation of large spatial data sets. As an artist, he creates . Stock built the SUNLIGHT artwork that is installed on the Webb Building in downtown Denver. In addition

  8. 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.

  9. The Design of Finite State Machine for Asynchronous Replication Protocol

    Science.gov (United States)

    Wang, Yanlong; Li, Zhanhuai; Lin, Wei; Hei, Minglei; Hao, Jianhua

    Data replication is a key way to design a disaster tolerance system and to achieve reliability and availability. It is difficult for a replication protocol to deal with the diverse and complex environment. This means that data is less well replicated than it ought to be. To reduce data loss and to optimize replication protocols, we (1) present a finite state machine, (2) run it to manage an asynchronous replication protocol and (3) report a simple evaluation of the asynchronous replication protocol based on our state machine. It's proved that our state machine is applicable to guarantee the asynchronous replication protocol running in the proper state to the largest extent in the event of various possible events. It also can helpful to build up replication-based disaster tolerance systems to ensure the business continuity.

  10. Mark 1 Test Facility

    Data.gov (United States)

    Federal Laboratory Consortium — The Mark I Test Facility is a state-of-the-art space environment simulation test chamber for full-scale space systems testing. A $1.5M dollar upgrade in fiscal year...

  11. Mark Raidpere portreefotod Kielis

    Index Scriptorium Estoniae

    1999-01-01

    Kieli Linnagaleriis avatud 2. Ars Baltica fototriennaalil 'Can You Hear Me?' esindab Eestit Mark Raidpere seeriaga 'Portreed 1998'. Näituse Eesti-poolne kuraator Anu Liivak, kataloogiteksti kirjutas Anders Härm. Tuntumaid osalejaid triennaalil Wolfgang Tillmans

  12. Marks of Metal Copenhell

    DEFF Research Database (Denmark)

    2015-01-01

    Planchebaseret udendørs udstilling på musikfestivalen Copenhell 18-20/6 2015. En mindre udgave af udstillingen Marks of Metal - Logodesign og visualitet i heavy metal. Udarbejdet i samarbejde med Mediemuseet.......Planchebaseret udendørs udstilling på musikfestivalen Copenhell 18-20/6 2015. En mindre udgave af udstillingen Marks of Metal - Logodesign og visualitet i heavy metal. Udarbejdet i samarbejde med Mediemuseet....

  13. COMPUTER HARDWARE MARKING

    CERN Multimedia

    Groupe de protection des biens

    2000-01-01

    As part of the campaign to protect CERN property and for insurance reasons, all computer hardware belonging to the Organization must be marked with the words 'PROPRIETE CERN'.IT Division has recently introduced a new marking system that is both economical and easy to use. From now on all desktop hardware (PCs, Macintoshes, printers) issued by IT Division with a value equal to or exceeding 500 CHF will be marked using this new system.For equipment that is already installed but not yet marked, including UNIX workstations and X terminals, IT Division's Desktop Support Service offers the following services free of charge:Equipment-marking wherever the Service is called out to perform other work (please submit all work requests to the IT Helpdesk on 78888 or helpdesk@cern.ch; for unavoidable operational reasons, the Desktop Support Service will only respond to marking requests when these coincide with requests for other work such as repairs, system upgrades, etc.);Training of personnel designated by Division Leade...

  14. 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....

  15. 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.

  16. Augmented marked graphs

    CERN Document Server

    Cheung, King Sing

    2014-01-01

    Petri nets are a formal and theoretically rich model for the modelling and analysis of systems. A subclass of Petri nets, augmented marked graphs possess a structure that is especially desirable for the modelling and analysis of systems with concurrent processes and shared resources.This monograph consists of three parts: Part I provides the conceptual background for readers who have no prior knowledge on Petri nets; Part II elaborates the theory of augmented marked graphs; finally, Part III discusses the application to system integration. The book is suitable as a first self-contained volume

  17. USP37 deubiquitinates Cdt1 and contributes to regulate DNA replication.

    Science.gov (United States)

    Hernández-Pérez, Santiago; Cabrera, Elisa; Amoedo, Hugo; Rodríguez-Acebes, Sara; Koundrioukoff, Stephane; Debatisse, Michelle; Méndez, Juan; Freire, Raimundo

    2016-10-01

    DNA replication control is a key process in maintaining genomic integrity. Monitoring DNA replication initiation is particularly important as it needs to be coordinated with other cellular events and should occur only once per cell cycle. Crucial players in the initiation of DNA replication are the ORC protein complex, marking the origin of replication, and the Cdt1 and Cdc6 proteins, that license these origins to replicate by recruiting the MCM2-7 helicase. To accurately achieve its functions, Cdt1 is tightly regulated. Cdt1 levels are high from metaphase and during G1 and low in S/G2 phases of the cell cycle. This control is achieved, among other processes, by ubiquitination and proteasomal degradation. In an overexpression screen for Cdt1 deubiquitinating enzymes, we isolated USP37, to date the first ubiquitin hydrolase controlling Cdt1. USP37 overexpression stabilizes Cdt1, most likely a phosphorylated form of the protein. In contrast, USP37 knock down destabilizes Cdt1, predominantly during G1 and G1/S phases of the cell cycle. USP37 interacts with Cdt1 and is able to de-ubiquitinate Cdt1 in vivo and, USP37 is able to regulate the loading of MCM complexes onto the chromatin. In addition, downregulation of USP37 reduces DNA replication fork speed. Taken together, here we show that the deubiquitinase USP37 plays an important role in the regulation of DNA replication. Whether this is achieved via Cdt1, a central protein in this process, which we have shown to be stabilized by USP37, or via additional factors, remains to be tested. Copyright © 2016 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  18. 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.

  19. 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…

  20. Identification markings for gemstones

    International Nuclear Information System (INIS)

    Dreschhoff, G.A.M.; Zeller, E.J.

    1980-01-01

    A method is described of providing permanent identification markings to gemstones such as diamond crystals by irradiating the cooled gemstone with protons in the desired pattern. The proton bombardment results in a reaction limited to a defined plane and converting the bombarded area of the plane into a different crystal lattice from that of the preirradiated stone. (author)

  1. 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

  2. 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...

  3. Effect of deoxyribonucleic acid replication inhibitors on bacterial recombination

    International Nuclear Information System (INIS)

    Canosi, U.; Siccardi, A.G.; Falaschi, A.; Mazza, G.

    1976-01-01

    Two inhibitors of replicative deoxyribonucleic acid (DNA) synthesis, nalidixic acid (NAL) and 6-(p-hydroxyphenylazo)-uracil (HPUra), showed different effects on genetic recombination and DNA repair in Bacillus subtilis. Previous work (Pedrini et al., 1972) showed that NAL does not interfere with the transformation process of B. subtilis. The results reported in this work demonstrated that the drug was also without effect on the transfection SPP1 or SPO-1 phage DNA (a process that requires a recombination event). The drug was also ineffective on the host cell reactivation of ultraviolet-irradiated SPP1 phage, as well as on transfection with ultraviolet-irradiated DNA of the same phage. HPUra instead markedly reduced the transformation process, as well as transfection, by SPO-1 DNA, but it did not affect the host cell reactivation of SPO-1 phage. In conclusion, whereas the NAL target seems to be specific for replicative DNA synthesis, the HPUra target (i.e., the DNA polymerase III of B. subtilis) seems to be involved also in recombination, but not in the excision repair process. The mutations conferring NAL and HPUra resistance used in this work were mapped by PBS-1 transduction

  4. Interview with Mark Watson

    Directory of Open Access Journals (Sweden)

    Katy Shaw

    2016-04-01

    Full Text Available Mark Watson is a British comedian and novelist. His five novels to date – 'Bullet Points' (2004, 'A Light-Hearted Look At Murder' (2007, 'Eleven' (2010, 'The Knot' (2012 and 'Hotel Alpha' (2014 – explore human relationships and communities in contemporary society. His latest novel Hotel Alpha tells the story of an extraordinary hotel in London and two mysterious disappearances that raise questions no one seems willing to answer. External to the novel, readers can also discover more about the hotel and its inhabitants in one hundred extra stories that expand the world of the novel and can be found at http://www.hotelalphastories.com. In conversation here with Dr Katy Shaw, Mark offers some reflections on his writing process, the field of contemporary literature, and the vitality of the novel form in the twenty-first century.

  5. 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

  6. 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

  7. 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.

  8. 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)

  9. 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 ...

  10. Use of nonpathogenic, green fluorescent protein-marked Escherichia coli Biotype I cultures to evaluate the self-cleansing capabilities of a commercial beef grinding system after a contamination event.

    Science.gov (United States)

    Wages, Jennifer A; Williams, Jennifer; Adams, Jacquelyn; George, Bruce; Oxford, Eric; Zelenka, Dan

    2014-11-01

    Inoculated beef trim containing a cocktail of green fluorescent protein-marked Escherichia coli biotype I cultures as surrogates for E. coli O157:H7 was introduced into two large, commercial grinding facilities capable of producing 180,000 kg of ground product in 1 day. Three repetitions were performed over 3 days. Sampling occurred at three different points within the process: postprimary grind, postsecondary grind-blender, and postpackaging. Resulting data show that, as the inoculated meat passes through the system, the presence of the marked surrogate quickly diminishes. The depletion rates are directly related to the amount of product in kilograms (represented by time) that has passed through the system, but these rates vary with each step of the process. The primary grinder appears to rid itself of the contaminant the most quickly; in all repetitions, the contaminant was not detected within 5 min of introduction of the contaminated combo bin into the system, which in all cases, was prior to the introduction of a second combo bin and within 1,800 kg of product. After the blending step and subsequent secondary grinding, the contaminant was detected in product produced from both the parent combo and the combo bin added directly after the parent combo bin; however, for those days on which three combo bins (approximately 2,700 kg) were available for sampling, the contaminant was not detected from product representing the third combo bin. Similarly, at the packaging step, the contaminant was detected in the product produced by both the parent and second combo bins; however, on those days when a third combo bin was available for sampling (repetitions 2 and 3), the contaminant was not detected from product produced from the third combo bin.

  11. Isotopic marking and tracers

    International Nuclear Information System (INIS)

    Morel, F.

    1997-01-01

    The use of radioactive isotopes as tracers in biology has been developed thanks to the economic generation of the required isotopes in accelerators and nuclear reactors, and to the multiple applications of tracers in the life domain; the most usual isotopes employed in biology are carbon, hydrogen, phosphorus and sulfur isotopes, because these elements are present in most of organic molecules. Most of the life science knowledge appears to be dependent to the extensive use of nuclear tools and radioactive tracers; the example of the utilization of radioactive phosphorus marked ATP to study the multiple reactions with proteins, nucleic acids, etc., is given

  12. Ceremony marking Einstein Year

    CERN Multimedia

    2005-01-01

    Sunday 13th November at 10:00amat Geneva's St. Peter's Cathedral To mark Einstein Year and the importance of the intercultural dialogue of which it forms a part, a religious service will take place on Sunday 13 November at 10 a.m. in St. Peter's Cathedral, to which CERN members and colleagues are warmly welcomed. Pastor Henry Babel, senior minister at the Cathedral, will speak on the theme: 'God in Einstein's Universe'. Diether Blechschmidt will convey a message on behalf of the scientific community.

  13. Minimal Marking: A Success Story

    Science.gov (United States)

    McNeilly, Anne

    2014-01-01

    The minimal-marking project conducted in Ryerson's School of Journalism throughout 2012 and early 2013 resulted in significantly higher grammar scores in two first-year classes of minimally marked university students when compared to two traditionally marked classes. The "minimal-marking" concept (Haswell, 1983), which requires…

  14. Checkpoint responses to replication stalling: inducing tolerance and preventing mutagenesis

    Energy Technology Data Exchange (ETDEWEB)

    Kai, Mihoko; Wang, Teresa S.-F

    2003-11-27

    Replication mutants often exhibit a mutator phenotype characterized by point mutations, single base frameshifts, and the deletion or duplication of sequences flanked by homologous repeats. Mutation in genes encoding checkpoint proteins can significantly affect the mutator phenotype. Here, we use fission yeast (Schizosaccharomyces pombe) as a model system to discuss the checkpoint responses to replication perturbations induced by replication mutants. Checkpoint activation induced by a DNA polymerase mutant, aside from delay of mitotic entry, up-regulates the translesion polymerase DinB (Pol{kappa}). Checkpoint Rad9-Rad1-Hus1 (9-1-1) complex, which is loaded onto chromatin by the Rad17-Rfc2-5 checkpoint complex in response to replication perturbation, recruits DinB onto chromatin to generate the point mutations and single nucleotide frameshifts in the replication mutator. This chain of events reveals a novel checkpoint-induced tolerance mechanism that allows cells to cope with replication perturbation, presumably to make possible restarting stalled replication forks. Fission yeast Cds1 kinase plays an essential role in maintaining DNA replication fork stability in the face of DNA damage and replication fork stalling. Cds1 kinase is known to regulate three proteins that are implicated in maintaining replication fork stability: Mus81-Eme1, a hetero-dimeric structure-specific endonuclease complex; Rqh1, a RecQ-family helicase involved in suppressing inappropriate recombination during replication; and Rad60, a protein required for recombinational repair during replication. These Cds1-regulated proteins are thought to cooperatively prevent mutagenesis and maintain replication fork stability in cells under replication stress. These checkpoint-regulated processes allow cells to survive replication perturbation by preventing stalled replication forks from degenerating into deleterious DNA structures resulting in genomic instability and cancer development.

  15. Checkpoint responses to replication stalling: inducing tolerance and preventing mutagenesis

    International Nuclear Information System (INIS)

    Kai, Mihoko; Wang, Teresa S.-F.

    2003-01-01

    Replication mutants often exhibit a mutator phenotype characterized by point mutations, single base frameshifts, and the deletion or duplication of sequences flanked by homologous repeats. Mutation in genes encoding checkpoint proteins can significantly affect the mutator phenotype. Here, we use fission yeast (Schizosaccharomyces pombe) as a model system to discuss the checkpoint responses to replication perturbations induced by replication mutants. Checkpoint activation induced by a DNA polymerase mutant, aside from delay of mitotic entry, up-regulates the translesion polymerase DinB (Polκ). Checkpoint Rad9-Rad1-Hus1 (9-1-1) complex, which is loaded onto chromatin by the Rad17-Rfc2-5 checkpoint complex in response to replication perturbation, recruits DinB onto chromatin to generate the point mutations and single nucleotide frameshifts in the replication mutator. This chain of events reveals a novel checkpoint-induced tolerance mechanism that allows cells to cope with replication perturbation, presumably to make possible restarting stalled replication forks. Fission yeast Cds1 kinase plays an essential role in maintaining DNA replication fork stability in the face of DNA damage and replication fork stalling. Cds1 kinase is known to regulate three proteins that are implicated in maintaining replication fork stability: Mus81-Eme1, a hetero-dimeric structure-specific endonuclease complex; Rqh1, a RecQ-family helicase involved in suppressing inappropriate recombination during replication; and Rad60, a protein required for recombinational repair during replication. These Cds1-regulated proteins are thought to cooperatively prevent mutagenesis and maintain replication fork stability in cells under replication stress. These checkpoint-regulated processes allow cells to survive replication perturbation by preventing stalled replication forks from degenerating into deleterious DNA structures resulting in genomic instability and cancer development

  16. Probabilistic Safety Assessment Of It TRIGA Mark-II Reactor

    International Nuclear Information System (INIS)

    Ergun, E; Kadiroglu, O.S.

    1999-01-01

    The probabilistic safety assessment for Istanbul Technical University (ITU) TRIGA Mark-II reactor is performed. Qualitative analysis, which includes fault and event trees and quantitative analysis which includes the collection of data for basic events, determination of minimal cut sets, calculation of quantitative values of top events, sensitivity analysis and importance measures, uncertainty analysis and radiation release from fuel elements are considered

  17. 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

  18. 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...

  19. SLARette Mark 2 system

    International Nuclear Information System (INIS)

    Burnett, D.J.

    1992-01-01

    The SLAR (Spacer Location and Repositioning) program has developed the technology and tooling necessary to locate and reposition the fuel channel spacers that separate the pressure tube from the calandria tube in a CANDU reactor. The in-channel SLAR tool contains all the inspection probes, and is capable of moving spacers under remote control. The SLAR inspection computer system translates all eddy currents and ultrasonic signals from the in-channel tool into various graphic displays. The in-channel SLAR tool can be delivered and manipulated in a fuel channel by either a SLAR delivery machine or a SLARette delivery machine. The SLAR delivery machine consists of a modified fuelling machine, and is capable of operating under totally remote control in automatic or semi-automatic mode. The SLARette delivery machine is a smaller less automated version, which was designed to be quickly installed, operated, and removed from a limited number of fuel channels during regular annual maintenance outages. This paper describes the design and operation of the SLARette Mark 2 system. 5 figs

  20. Mechanisms and regulation of DNA replication initiation in eukaryotes.

    Science.gov (United States)

    Parker, Matthew W; Botchan, Michael R; Berger, James M

    2017-04-01

    Cellular DNA replication is initiated through the action of multiprotein complexes that recognize replication start sites in the chromosome (termed origins) and facilitate duplex DNA melting within these regions. In a typical cell cycle, initiation occurs only once per origin and each round of replication is tightly coupled to cell division. To avoid aberrant origin firing and re-replication, eukaryotes tightly regulate two events in the initiation process: loading of the replicative helicase, MCM2-7, onto chromatin by the origin recognition complex (ORC), and subsequent activation of the helicase by its incorporation into a complex known as the CMG. Recent work has begun to reveal the details of an orchestrated and sequential exchange of initiation factors on DNA that give rise to a replication-competent complex, the replisome. Here, we review the molecular mechanisms that underpin eukaryotic DNA replication initiation - from selecting replication start sites to replicative helicase loading and activation - and describe how these events are often distinctly regulated across different eukaryotic model organisms.

  1. Mark Kostabi soovib muuta inimesi õnnelikumaks / Kalev Mark Kostabi

    Index Scriptorium Estoniae

    Kostabi, Kalev Mark, 1960-

    2008-01-01

    Kalev Mark Kostabi oma sisekujunduslikest eelistustest, ameeriklaste ja itaallaste kodude sisekujunduse erinevustest, kunstist kui ruumikujunduse ühest osast, oma New Yorgi ja Rooma korterite kujundusest

  2. 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.

  3. 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...

  4. 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…

  5. NotaMark industrial laser marking system: a new security marking technology

    Science.gov (United States)

    Moreau, Vincent G.

    2004-06-01

    Up until now, the only variable alphanumeric data which could be added to banknotes was the number, applied by means of impact typographical numbering boxes. As an additional process or an alternative to this mechanical method, a non-contact laser marking process can be used offering high quality and greater levels of flexibility. For this purpose KBA-GIORI propose an exclusive laser marking solution called NotaMark. The laser marking process NotaMark is the ideal solution for applying variable data and personalizing banknotes (or any other security documents) with a very high resolution, for extremely large production volumes. A completely integrated solution has been developed comprised of laser light sources, marking head units, and covers and extraction systems. NotaMark allows the marking of variable data by removing locally and selectively, specific printed materials leaving the substrate itself untouched. A wide range of materials has already been tested extensively. NotaMark is a new security feature which is easy to identify and difficult to counterfeit, and which complies with the standard mechanical and chemical resistance tests in the security printing industry as well as with other major soiling tests. The laser marking process opens up a whole new range of design possibilities and can be used to create a primary security feature such as numbering, or to enhance the value of existing features.

  6. Preoperative Site Marking: Are We Adhering to Good Surgical Practice?

    Science.gov (United States)

    Bathla, Sonia; Chadwick, Michael; Nevins, Edward J; Seward, Joanna

    2017-06-29

    Wrong-site surgery is a never event and a serious, preventable patient safety incident. Within the United Kingdom, national guidance has been issued to minimize the risk of such events. The mandate includes preoperative marking of all surgical patients. This study aimed to quantify regional variation in practice within general surgery and opinions of the surgeons, to help guide the formulation and implementation of a regional general surgery preoperative marking protocol. A SurveyMonkey questionnaire was designed and distributed to 120 surgeons within the Mersey region, United Kingdom. This included all surgical trainees in Mersey (47 registrars, 56 core trainees), 15 consultants, and 2 surgical care practitioners. This sought to ascertain their routine practice and how they would choose to mark for 12 index procedures in general surgery, if mandated to do so. A total of 72 responses (60%) were obtained to the SurveyMonkey questionnaire. Only 26 (36.1%) said that they routinely marked all of their patients preoperatively. The operating surgeon marked the patient in 69% of responses, with the remainder delegating this task. Markings were visible after draping in only 55.6% of marked cases. Based on our findings, surgeons may not be adhering to "Good Surgical Practice"; practice is widely variable and surgeons are largely opposed and resistant to marking patients unless laterality is involved. We suggest that all surgeons need to be actively engaged in the design of local marking protocols to gain support, change practice, and reduce errors.

  7. Statement at Event Marking 50th Anniversary of G77

    International Nuclear Information System (INIS)

    Amano, Y.

    2014-01-01

    The G77 is a very important body within the IAEA. It is effective in making its voice heard. I am grateful for the role which the G77 plays in the work of the Agency and for the support which you have given to the IAEA. The IAEA is often described as the world's nuclear watchdog. But, in fact, we do much more than helping to prevent the spread of nuclear weapons. An equally important part of our mandate is to make peaceful nuclear science and technology available to all countries, including in the developing world. We help countries to improve human health, fight cancer and improve nutrition. We help to improve access to electricity. We help to increase food production, manage scarce water resources and monitor environmental pollution. All of these are areas where nuclear techniques have an important role to play. As a scientific and technical organisation, the IAEA is an important partner in development. Through our technical cooperation programme, we assist developing countries in addressing the basic human needs of their people through technology transfer and capacity-building. I visit around 30 countries every year. Everywhere I go, I see IAEA technical cooperation projects in action. I meet farmers, fishermen and cancer patients whose lives have changed for the better thanks to the work of the IAEA. This is one of the most gratifying aspects of my work. The IAEA makes an important and unique contribution to achieving the Millennium Development Goals. This is not always recognised. I am doing my best to raise awareness of our role. I would like to see better recognition of the importance of science and technology, including nuclear related technology, in the global development agenda. It is, of course, Member States who decide the development agenda. But G77 countries can play a decisive role in raising awareness of the important role of nuclear technology in development

  8. 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...

  9. 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.

  10. Fusion events

    International Nuclear Information System (INIS)

    Aboufirassi, M; Angelique, J.C.; Bizard, G.; Bougault, R.; Brou, R.; Buta, A.; Colin, J.; Cussol, D.; Durand, D.; Genoux-Lubain, A.; Horn, D.; Kerambrun, A.; Laville, J.L.; Le Brun, C.; Lecolley, J.F.; Lefebvres, F.; Lopez, O.; Louvel, M.; Meslin, C.; Metivier, V.; Nakagawa, T.; Peter, J.; Popescu, R.; Regimbart, R.; Steckmeyer, J.C.; Tamain, B.; Vient, E.; Wieloch, A.; Yuasa-Nakagawa, K.

    1998-01-01

    The fusion reactions between low energy heavy ions have a very high cross section. First measurements at energies around 30-40 MeV/nucleon indicated no residue of either complete or incomplete fusion, thus demonstrating the disappearance of this process. This is explained as being due to the high amount o energies transferred to the nucleus, what leads to its total dislocation in light fragments and particles. Exclusive analyses have permitted to mark clearly the presence of fusion processes in heavy systems at energies above 30-40 MeV/nucleon. Among the complete events of the Kr + Au reaction at 60 MeV/nucleon the majority correspond to binary collisions. Nevertheless, for the most considerable energy losses, a class of events do occur for which the detected fragments appears to be emitted from a unique source. These events correspond to an incomplete projectile-target fusion followed by a multifragmentation. Such events were singled out also in the reaction Xe + Sn at 50 MeV/nucleon. For the events in which the energy dissipation was maximal it was possible to isolate an isotropic group of events showing all the characteristics of fusion nuclei. The fusion is said to be incomplete as pre-equilibrium Z = 1 and Z = 2 particles are emitted. The cross section is of the order of 25 mb. Similar conclusions were drown for the systems 36 Ar + 27 Al and 64 Zn + nat Ti. A cross section value of ∼ 20 mb was determined at 55 MeV/nucleon in the first case, while the measurement of evaporation light residues in the last system gave an upper limit of 20-30 mb for the cross section at 50 MeV/nucleon

  11. Replication stress, a source of epigenetic aberrations in cancer?

    DEFF Research Database (Denmark)

    Jasencakova, Zusana; Groth, Anja

    2010-01-01

    . Chromatin organization is transiently disrupted during DNA replication and maintenance of epigenetic information thus relies on faithful restoration of chromatin on the new daughter strands. Acute replication stress challenges proper chromatin restoration by deregulating histone H3 lysine 9 mono......-methylation on new histones and impairing parental histone recycling. This could facilitate stochastic epigenetic silencing by laying down repressive histone marks at sites of fork stalling. Deregulation of replication in response to oncogenes and other tumor-promoting insults is recognized as a significant source...... of genome instability in cancer. We propose that replication stress not only presents a threat to genome stability, but also jeopardizes chromatin integrity and increases epigenetic plasticity during tumorigenesis....

  12. 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.

  13. Centromere replication timing determines different forms of genomic instability in Saccharomyces cerevisiae checkpoint mutants during replication stress.

    Science.gov (United States)

    Feng, Wenyi; Bachant, Jeff; Collingwood, David; Raghuraman, M K; Brewer, Bonita J

    2009-12-01

    Yeast replication checkpoint mutants lose viability following transient exposure to hydroxyurea, a replication-impeding drug. In an effort to understand the basis for this lethality, we discovered that different events are responsible for inviability in checkpoint-deficient cells harboring mutations in the mec1 and rad53 genes. By monitoring genomewide replication dynamics of cells exposed to hydroxyurea, we show that cells with a checkpoint deficient allele of RAD53, rad53K227A, fail to duplicate centromeres. Following removal of the drug, however, rad53K227A cells recover substantial DNA replication, including replication through centromeres. Despite this recovery, the rad53K227A mutant fails to achieve biorientation of sister centromeres during recovery from hydroxyurea, leading to secondary activation of the spindle assembly checkpoint (SAC), aneuploidy, and lethal chromosome segregation errors. We demonstrate that cell lethality from this segregation defect could be partially remedied by reinforcing bipolar attachment. In contrast, cells with the mec1-1 sml1-1 mutations suffer from severely impaired replication resumption upon removal of hydroxyurea. mec1-1 sml1-1 cells can, however, duplicate at least some of their centromeres and achieve bipolar attachment, leading to abortive segregation and fragmentation of incompletely replicated chromosomes. Our results highlight the importance of replicating yeast centromeres early and reveal different mechanisms of cell death due to differences in replication fork progression.

  14. Chromatin Constrains the Initiation and Elongation of DNA Replication.

    Science.gov (United States)

    Devbhandari, Sujan; Jiang, Jieqing; Kumar, Charanya; Whitehouse, Iestyn; Remus, Dirk

    2017-01-05

    Eukaryotic chromosomal DNA is faithfully replicated in a complex series of cell-cycle-regulated events that are incompletely understood. Here we report the reconstitution of DNA replication free in solution with purified proteins from the budding yeast Saccharomyces cerevisiae. The system recapitulates regulated bidirectional origin activation; synthesis of leading and lagging strands by the three replicative DNA polymerases Pol α, Pol δ, and Pol ε; and canonical maturation of Okazaki fragments into continuous daughter strands. We uncover a dual regulatory role for chromatin during DNA replication: promoting origin dependence and determining Okazaki fragment length by restricting Pol δ progression. This system thus provides a functional platform for the detailed mechanistic analysis of eukaryotic chromosome replication. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. 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.

  16. 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.

  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. Civilsamfundets ABC: M for Marked

    DEFF Research Database (Denmark)

    Lund, Anker Brink; Meyer, Gitte

    2016-01-01

    Bogstaveligt talt: Hvad er civilsamfundet? Anker Brink Lund og Gitte Meyer fra CBS Center for Civil Society Studies gennemgår civilsamfundet bogstav for bogstav. Vi er nået til M for Marked.......Bogstaveligt talt: Hvad er civilsamfundet? Anker Brink Lund og Gitte Meyer fra CBS Center for Civil Society Studies gennemgår civilsamfundet bogstav for bogstav. Vi er nået til M for Marked....

  19. Marks on the petroleum fiscality

    International Nuclear Information System (INIS)

    2007-02-01

    This document offers some marks on the petroleum fiscality in France: the taxes as the 'accises' and the 'TVA', the part of the taxes in the sale price at the service station, the comparison with other countries of Europe, the tax revenues and the Government budget. It provides also marks on the fuels prices formation (margins), the world petroleum markets (supply and demand) and the part of the petroleum companies on the petroleum market. (A.L.B.)

  20. The DNA Replication Stress Hypothesis of Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Yuri B. Yurov

    2011-01-01

    Full Text Available A well-recognized theory of Alzheimer’s disease (AD pathogenesis suggests ectopic cell cycle events to mediate neurodegeneration. Vulnerable neurons of the AD brain exhibit biomarkers of cell cycle progression and DNA replication suggesting a reentry into the cell cycle. Chromosome reduplication without proper cell cycle completion and mitotic division probably causes neuronal cell dysfunction and death. However, this theory seems to require some inputs in accordance with the generally recognized amyloid cascade theory as well as to explain causes and consequences of genomic instability (aneuploidy in the AD brain. We propose that unscheduled and incomplete DNA replication (replication stress destabilizes (epigenomic landscape in the brain and leads to DNA replication “catastrophe” causing cell death during the S phase (replicative cell death. DNA replication stress can be a key element of the pathogenetic cascade explaining the interplay between ectopic cell cycle events and genetic instabilities in the AD brain. Abnormal cell cycle reentry and somatic genome variations can be used for updating the cell cycle theory introducing replication stress as a missing link between cell genetics and neurobiology of AD.

  1. Murine leukemia virus (MLV replication monitored with fluorescent proteins

    Directory of Open Access Journals (Sweden)

    Bittner Alexandra

    2004-12-01

    Full Text Available Abstract Background Cancer gene therapy will benefit from vectors that are able to replicate in tumor tissue and cause a bystander effect. Replication-competent murine leukemia virus (MLV has been described to have potential as cancer therapeutics, however, MLV infection does not cause a cytopathic effect in the infected cell and viral replication can only be studied by immunostaining or measurement of reverse transcriptase activity. Results We inserted the coding sequences for green fluorescent protein (GFP into the proline-rich region (PRR of the ecotropic envelope protein (Env and were able to fluorescently label MLV. This allowed us to directly monitor viral replication and attachment to target cells by flow cytometry. We used this method to study viral replication of recombinant MLVs and split viral genomes, which were generated by replacement of the MLV env gene with the red fluorescent protein (RFP and separately cloning GFP-Env into a retroviral vector. Co-transfection of both plasmids into target cells resulted in the generation of semi-replicative vectors, and the two color labeling allowed to determine the distribution of the individual genomes in the target cells and was indicative for the occurrence of recombination events. Conclusions Fluorescently labeled MLVs are excellent tools for the study of factors that influence viral replication and can be used to optimize MLV-based replication-competent viruses or vectors for gene therapy.

  2. BWR Mark I pressure suppression study: bench mark experiments

    International Nuclear Information System (INIS)

    Lai, W.; McCauley, E.W.

    1977-01-01

    Computer simulations representative of the wetwell of Mark I BWR's have predicted pressures and related phenomena. However, calculational predictions for purposes of engineering decision will be possible only if the code can be verified, i.e., shown to compute in accord with measured values. Described in the report is a set of single downcomer spherical flask bench mark experiments designed to produce quantitative data to validate various air-water dynamic computations; the experiments were performed since relevant bench mark data were not available from outside sources. Secondary purposes of the study were to provide a test bed for the instrumentation and post-experiment data processing techniques to be used in the Laboratory's reactor safety research program and to provide additional masurements for the air-water scaling study

  3. 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

  4. 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

  5. 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…

  6. 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

  7. 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.

  8. Mark Napier / Mark Napier ; interv. Tilman Baumgärtel

    Index Scriptorium Estoniae

    Napier, Mark

    2006-01-01

    Ameerika kunstnikust Mark Napierist (sünd. 1961) ja tema loomingust, 2001. a. tehtud meiliintervjuu kunstnikuga. Võrguteosest "The Digital Landfill" (1998), koos Andy Deckiga loodud tööst "GrafficJam" (1999), töödest "Shredder" (1998), "Feed", "Riot", "P-Soup" (2000), võrgukunstist ja muust

  9. Minimal Marking: A Success Story

    Directory of Open Access Journals (Sweden)

    Anne McNeilly

    2014-11-01

    Full Text Available The minimal-marking project conducted in Ryerson’s School of Journalism throughout 2012 and early 2013 resulted in significantly higher grammar scores in two first-year classes of minimally marked university students when compared to two traditionally marked classes. The “minimal-marking” concept (Haswell, 1983, which requires dramatically more student engagement, resulted in more successful learning outcomes for surface-level knowledge acquisition than the more traditional approach of “teacher-corrects-all.” Results suggest it would be effective, not just for grammar, punctuation, and word usage, the objective here, but for any material that requires rote-memory learning, such as the Associated Press or Canadian Press style rules used by news publications across North America.

  10. Percentage Retail Mark-Ups

    OpenAIRE

    Thomas von Ungern-Sternberg

    1999-01-01

    A common assumption in the literature on the double marginalization problem is that the retailer can set his mark-up only in the second stage of the game after the producer has moved. To the extent that the sequence of moves is designed to reflect the relative bargaining power of the two parties it is just as plausible to let the retailer move first. Furthermore, retailers frequently calculate their selling prices by adding a percentage mark-up to their wholesale prices. This allows a retaile...

  11. 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…

  12. Prosodic Focus Marking in Bai.

    NARCIS (Netherlands)

    Liu, Zenghui; Chen, A.; Van de Velde, Hans

    2014-01-01

    This study investigates prosodic marking of focus in Bai, a Sino-Tibetan language spoken in the Southwest of China, by adopting a semi-spontaneous experimental approach. Our data show that Bai speakers increase the duration of the focused constituent and reduce the duration of the post-focus

  13. Better marking means cheaper pruning.

    Science.gov (United States)

    Kenneth R. Eversole

    1953-01-01

    Careful selection of trees to be pruned can make the difference between profit and loss on the pruning investment, especially in stands where no thinning is contemplated. Expert marking is required to make sure that the pruned trees will grow rapidly. The most important variable influencing the cost of clear wood produced by pruning is growth rate. For example, at 3...

  14. Laser marking method and device

    International Nuclear Information System (INIS)

    Okazaki, Yuki; Aoki, Nobutada; Mukai, Narihiko; Sano, Yuji; Yamamoto, Seiji.

    1997-01-01

    An object is disposed in laser beam permeating liquid or gaseous medium. Laser beams such as CW laser or pulse laser oscillated from a laser device are emitted to the object to apply laser markings with less degradation of identification and excellent corrosion resistance on the surface of the object simply and easily. Upon applying the laser markings, a liquid or gas as a laser beam permeating medium is blown onto the surface of the object, or the liquid or gas in the vicinity of the object is sucked, the laser beam-irradiated portion on the surface can be cooled positively. Accordingly, the laser marking can be formed on the surface of the object with less heat affection to the object. In addition, if the content of a nitrogen gas in the laser beam permeating liquid medium is reduced by degassing to lower than a predetermined value, or the laser beam permeating gaseous medium is formed by an inert gas, a laser marking having high corrosion resistance and reliability can be formed on the surface of the objective member. (N.H.)

  15. Non‐Canonical Replication Initiation: You’re Fired!

    Directory of Open Access Journals (Sweden)

    Bazilė Ravoitytė

    2017-01-01

    Full Text Available The division of prokaryotic and eukaryotic cells produces two cells that inherit a perfect copy of the genetic material originally derived from the mother cell. The initiation of canonical DNA replication must be coordinated to the cell cycle to ensure the accuracy of genome duplication. Controlled replication initiation depends on a complex interplay of cis‐acting DNA sequences, the so‐called origins of replication (ori, with trans‐acting factors involved in the onset of DNA synthesis. The interplay of cis‐acting elements and trans‐acting factors ensures that cells initiate replication at sequence‐specific sites only once, and in a timely order, to avoid chromosomal endoreplication. However, chromosome breakage and excessive RNA:DNA hybrid formation can cause breakinduced (BIR or transcription‐initiated replication (TIR, respectively. These non‐canonical replication events are expected to affect eukaryotic genome function and maintenance, and could be important for genome evolution and disease development. In this review, we describe the difference between canonical and non‐canonical DNA replication, and focus on mechanistic differences and common features between BIR and TIR. Finally, we discuss open issues on the factors and molecular mechanisms involved in TIR.

  16. Cell lethality after selective irradiation of the DNA replication fork

    International Nuclear Information System (INIS)

    Hofer, K.G.; Warters, R.L.

    1985-01-01

    It has been suggested that nascent DNA located at the DNA replication fork may exhibit enhanced sensitivity to radiation damage. To evaluate this hypothesis, Chinese hamster ovary cells (CHO) were labeled with 125 I-iododeoxyuridine ( 125 IUdR) either in the presence or absence of aphidicolin. Aphidicolin (5 μg/ml) reduced cellular 125 IUdR incorporation to 3-5% of the control value. The residual 125 I incorporation appeared to be restricted to low molecular weight (sub-replicon sized) fragments of DNA which were more sensitive to micrococcal nuclease attack and less sensitive to high salt DNase I digestion than randomly labeled DNA. These findings suggest that DNA replicated in the presence of aphidicolin remains localized at the replication fork adjacent to the nuclear matrix. Based on these observations an attempt was made to compare the lethal consequences of 125 I decays at the replication fork to that of 125 I decays randomly distributed over the entire genome. Regardless of the distribution of decay events, all treatment groups exhibited identical dose-response curves (D 0 : 101 125 I decays/cell). Since differential irradiation of the replication complex did not result in enhanced cell lethality, it can be concluded that neither the nascent DNA nor the protein components (replicative enzymes, nuclear protein matrix) associated with the DNA replication site constitute key radiosensitive targets within the cellular genome. (orig.)

  17. Megabase replication domains along the human genome: relation to chromatin structure and genome organisation.

    Science.gov (United States)

    Audit, Benjamin; Zaghloul, Lamia; Baker, Antoine; Arneodo, Alain; Chen, Chun-Long; d'Aubenton-Carafa, Yves; Thermes, Claude

    2013-01-01

    In higher eukaryotes, the absence of specific sequence motifs, marking the origins of replication has been a serious hindrance to the understanding of (i) the mechanisms that regulate the spatio-temporal replication program, and (ii) the links between origins activation, chromatin structure and transcription. In this chapter, we review the partitioning of the human genome into megabased-size replication domains delineated as N-shaped motifs in the strand compositional asymmetry profiles. They collectively span 28.3% of the genome and are bordered by more than 1,000 putative replication origins. We recapitulate the comparison of this partition of the human genome with high-resolution experimental data that confirms that replication domain borders are likely to be preferential replication initiation zones in the germline. In addition, we highlight the specific distribution of experimental and numerical chromatin marks along replication domains. Domain borders correspond to particular open chromatin regions, possibly encoded in the DNA sequence, and around which replication and transcription are highly coordinated. These regions also present a high evolutionary breakpoint density, suggesting that susceptibility to breakage might be linked to local open chromatin fiber state. Altogether, this chapter presents a compartmentalization of the human genome into replication domains that are landmarks of the human genome organization and are likely to play a key role in genome dynamics during evolution and in pathological situations.

  18. Fluoxetine Is a Potent Inhibitor of Coxsackievirus Replication

    OpenAIRE

    Zuo, Jun; Quinn, Kevin K.; Kye, Steve; Cooper, Paige; Damoiseaux, Robert; Krogstad, Paul

    2012-01-01

    No antiviral drugs currently exist for the treatment of enterovirus infections, which are often severe and potentially life threatening. Molecular screening of small molecule libraries identified fluoxetine, a selective serotonin reuptake inhibitor, as a potent inhibitor of coxsackievirus replication. Fluoxetine did not interfere with either viral entry or translation of the viral genome. Instead, fluoxetine and its metabolite norfluoxetine markedly reduced the synthesis of viral RNA and prot...

  19. Coping with a Traumatic Event

    Science.gov (United States)

    ... Traumatic events are marked by a sense of horror, helplessness, serious injury, or the threat of serious ... The symptoms of PTSD fall into three broad types: re-living, avoidance and increased arousal. • Symptoms of ...

  20. Automated road marking recognition system

    Science.gov (United States)

    Ziyatdinov, R. R.; Shigabiev, R. R.; Talipov, D. N.

    2017-09-01

    Development of the automated road marking recognition systems in existing and future vehicles control systems is an urgent task. One way to implement such systems is the use of neural networks. To test the possibility of using neural network software has been developed with the use of a single-layer perceptron. The resulting system based on neural network has successfully coped with the task both when driving in the daytime and at night.

  1. Mark Twain: inocente ou pecador? = Mark Twain: innocent or sinner?

    Directory of Open Access Journals (Sweden)

    Heloisa Helou Doca

    2009-01-01

    Full Text Available A leitura cuidadosa do texto do “Tratado de Paris”, em 1900, leva Mark Twain a concluir que a intenção política norte-americana era, claramente, a de subjugação. Declara-se, abertamente, antiimperialista, nesse momento, apesar das inúmeras críticasrecebidas por antagonistas políticos que defendiam o establishment dos Estados Unidos. Após viajar para a Europa e Oriente, em 1867, como correspondente do jornal Daily Alta Califórnia, Mark Twain publica, em 1869, seu relato de viagem, The Innocents Abroad or TheNew Pilgrim’s Progress. Nosso estudo demonstra que o autor, apesar das diversas máscaras usadas em seus relatos, narra histórias, culturas e tradições, tanto da Europa quanto do Oriente, já com os olhos bem abertos pelo viés antiimperialista. Faz uso da paródia, sátira, ironia e humor para dessacralizar impérios, monarcas e a Igreja que subjugavam os mais fracos, iluminando, desde então, os estudos sobre culturas. Nosso estudo, outrossim, faz uma reflexão sobre cultura, tradição e o olhar do viajante, justificando o “olhar inocente” do narrador em seu relato.After carefully reading the Treaty of Paris in 1900, Mark Twain concluded that the goal of U.S. policy was clearly one ofsubjugation. He openly declared himself an anti-imperialist at that time, in spite of the numerous criticisms he received from political opponents who supported the United States status quo. After traveling to Europe and the East in 1867 as a correspondent for The DailyAlta California newspaper, Mark Twain published his travel report, The Innocents Abroad or The New Pilgrim’s Progress in 1869. Our study demonstrates that the author, in spite of using different guises in his reports, narrated histories, cultures and traditions – from both Europe and the East – with a viewpoint already imbued by his anti-imperialistic ideals. Twain made use of parody, satire, irony and humor within his texts in order to desecrate empires,monarchs and

  2. 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...

  3. Studies on the effects of persistent RNA priming on DNA replication and genomic stability

    OpenAIRE

    Stuckey, Ruth

    2014-01-01

    [EN]: DNA replication and transcription take place on the same DNA template, and the correct interplay between these processes ensures faithful genome duplication. DNA replication must be highly coordinated with other cell cycle events, such as segregation of fully replicated DNA in order to maintain genomic integrity. Transcription generates RNA:DNA hybrids, transient intermediate structures that are degraded by the ribonuclease H (RNaseH) class of enzymes. RNA:DNA hybrids can form R-loops, ...

  4. Recent results for Mark III

    International Nuclear Information System (INIS)

    Brient, J.C.

    1987-12-01

    This paper presents recent results from the Mark III detector at SPEAR, in the open charm sector. The first topic discussed is the reanalysis of the direct measurement of the D hadronic branching fractions, where a detailed study has been made of the Cabibbo suppressed and multi-π 0 's D decays backgrounds in the double tag sample. Next, the Dalitz plot analysis of the D decays to Kππ is presented, leading to the relative fractions of three-body versus pseudoscalarvector decays. 7 refs., 5 figs

  5. The Mark III vertex chamber

    International Nuclear Information System (INIS)

    Adler, J.; Bolton, T.; Bunnell, K.

    1987-07-01

    The design and construction of the new Mark III vertex chamber is described. Initial tests with cosmic rays prove the ability of track reconstruction and yield triplet resolutions below 50 μm at 3 atm using argon/ethane (50:50). Also performed are studies using a prototype of a pressurized wire vertex chamber with 8 mm diameter straw geometry. Spatial resolution of 35mm was obtained using dimethyl ether (DME) at 1 atm and 30 μm using argon/ethane (50/50 mixture) at 4 atm. Preliminary studies indicate the DME to adversely affect such materials as aluminized Mylar and Delrin

  6. 46 CFR 185.602 - Hull markings.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Hull markings. 185.602 Section 185.602 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) SMALL PASSENGER VESSELS (UNDER 100 GROSS TONS) OPERATIONS Markings Required § 185.602 Hull markings. (a) Each vessel must be marked as required by part 67...

  7. 27 CFR 28.193 - Export marks.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Export marks. 28.193... Drawback Filing of Notice and Removal § 28.193 Export marks. In addition to the marks and brands required... chapter, the exporter shall mark the word “Export” on the Government side of each case or Government head...

  8. 27 CFR 28.103 - Export marks.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Export marks. 28.103... Manufacturing Bonded Warehouse § 28.103 Export marks. (a) General. In addition to the marks and brands required... provisions of part 19 of this chapter, the proprietor shall mark the word “Export” on the Government side of...

  9. 27 CFR 28.144 - Export marks.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Export marks. 28.144... § 28.144 Export marks. (a) General Requirement. In addition to the marks and brands required to be... brewer shall mark the word “Export” on each container or case of beer, or the words “Beer concentrate for...

  10. 27 CFR 28.154 - Export marks.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Export marks. 28.154..., for Exportation or Transfer to a Foreign-Trade Zone § 28.154 Export marks. In addition to the marks... provisions of part 19 of this chapter, the proprietor shall mark the word “Export” on the Government side of...

  11. 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...

  12. 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...

  13. Replicative intermediates in UV-irradiated Simian virus 40

    International Nuclear Information System (INIS)

    Clark, J.M.; Hanawalt, P.C.

    1984-01-01

    The authors have used Simian virus 40 (SV40) as a probe to study the replication of UV-damaged DNA in mammalian cells. Viral DNA replication in infected monkey kidney cells was synchronized by incubating a mutant of SV40 (tsA58) temperature-sensitive for the initiation of DNA synthesis at the restrictive temperature and then adding aphidicolin to temporarily inhibit DNA synthesis at the permissive temperature while permitting pre-replicative events to occur. After removal of the drug, the infected cells were irradiated at 100 J/m 2 (254 nm) to produce 6-7 pyrimidine dimers per SV40 genome, and returned to the restrictive temperature to prevent reinitiation of replication from the SV40 origin. Replicative intermediates (RI) were labeled with [ 3 H]thymidine. The size distribution of daughter DNA strands in RI isolated shortly after irradiation was skewed towards lengths less than the interdimer spacing in parental DNA; this bias persisted for at least 1 h after irradiation, but disappeared within 3 h by which time the size of the newly-synthesized DNA exceeded the interdimer distance. Evidence was obtained for the generation at late times after irradiation, of Form I molecules in which the daughter DNA strand contain dimers. Thus DNA strand exchange as well as trans-dimer synthesis may be involved in the generation of supercoiled Form I DNA from 0V-damaged SV40 replicative intermediates. (Auth.)

  14. Interview with Professor Mark Wilcox.

    Science.gov (United States)

    Wilcox, Mark

    2016-08-01

    Mark Wilcox speaks to Georgia Patey, Commissioning Editor: Professor Mark Wilcox is a Consultant Microbiologist and Head of Microbiology at the Leeds Teaching Hospitals (Leeds, UK), the Professor of Medical Microbiology at the University of Leeds (Leeds, UK), and is the Lead on Clostridium difficile and the Head of the UK C. difficile Reference Laboratory for Public Health England (PHE). He was the Director of Infection Prevention (4 years), Infection Control Doctor (8 years) and Clinical Director of Pathology (6 years) at the Leeds Teaching Hospitals. He is Chair of PHE's Rapid Review Panel (reviews utility of infection prevention and control products for National Health Service), Deputy Chair of the UK Department of Health's Antimicrobial Resistance and Healthcare Associated Infection Committee and a member of PHE's HCAI/AR Programme Board. He is a member of UK/European/US working groups on C. difficile infection. He has provided clinical advice as part of the FDA/EMA submissions for the approval of multiple novel antimicrobial agents. He heads a healthcare-associated infection research team at University of Leeds, comprising approximately 30 doctors, scientists and nurses; projects include multiple aspects of C. difficile infection, diagnostics, antimicrobial resistance and the clinical development of new antimicrobial agents. He has authored more than 400 publications, and is the coeditor of Antimicrobial Chemotherapy (5th/6th/7th Editions, 15 December 2007).

  15. 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…

  16. Insights into the Initiation of Eukaryotic DNA Replication.

    Science.gov (United States)

    Bruck, Irina; Perez-Arnaiz, Patricia; Colbert, Max K; Kaplan, Daniel L

    2015-01-01

    The initiation of DNA replication is a highly regulated event in eukaryotic cells to ensure that the entire genome is copied once and only once during S phase. The primary target of cellular regulation of eukaryotic DNA replication initiation is the assembly and activation of the replication fork helicase, the 11-subunit assembly that unwinds DNA at a replication fork. The replication fork helicase, called CMG for Cdc45-Mcm2-7, and GINS, assembles in S phase from the constituent Cdc45, Mcm2-7, and GINS proteins. The assembly and activation of the CMG replication fork helicase during S phase is governed by 2 S-phase specific kinases, CDK and DDK. CDK stimulates the interaction between Sld2, Sld3, and Dpb11, 3 initiation factors that are each required for the initiation of DNA replication. DDK, on the other hand, phosphorylates the Mcm2, Mcm4, and Mcm6 subunits of the Mcm2-7 complex. Sld3 recruits Cdc45 to Mcm2-7 in a manner that depends on DDK, and recent work suggests that Sld3 binds directly to Mcm2-7 and also to single-stranded DNA. Furthermore, recent work demonstrates that Sld3 and its human homolog Treslin substantially stimulate DDK phosphorylation of Mcm2. These data suggest that the initiation factor Sld3/Treslin coordinates the assembly and activation of the eukaryotic replication fork helicase by recruiting Cdc45 to Mcm2-7, stimulating DDK phosphorylation of Mcm2, and binding directly to single-stranded DNA as the origin is melted.

  17. H3K56me1 marks a spot for PCNA

    DEFF Research Database (Denmark)

    Lee, Sung-Po; Jasencakova, Zusana; Groth, Anja

    2012-01-01

    In the current issue of Molecular Cell, Yu et al. (2012) establish H3K56 monomethylation (H3K56me1) as a new mammalian chromatin mark, imposed by the G9a methyltransferase and recognized by the replication clamp PCNA....

  18. Dialectica Interpretation with Marked Counterexamples

    Directory of Open Access Journals (Sweden)

    Trifon Trifonov

    2011-01-01

    Full Text Available Goedel's functional "Dialectica" interpretation can be used to extract functional programs from non-constructive proofs in arithmetic by employing two sorts of higher-order witnessing terms: positive realisers and negative counterexamples. In the original interpretation decidability of atoms is required to compute the correct counterexample from a set of candidates. When combined with recursion, this choice needs to be made for every step in the extracted program, however, in some special cases the decision on negative witnesses can be calculated only once. We present a variant of the interpretation in which the time complexity of extracted programs can be improved by marking the chosen witness and thus avoiding recomputation. The achieved effect is similar to using an abortive control operator to interpret computational content of non-constructive principles.

  19. 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…

  20. 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.

  1. 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...

  2. 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

  3. 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.

  4. Cavernous hemangioma presenting marked hyperostosis

    International Nuclear Information System (INIS)

    Kobata, Hitoshi; Miyake, Hiroji; Kitamura, Junji; Kajikawa, Hiroshi; Ohta, Tomio

    1988-01-01

    The authors report here a case of hemangioma of the left parietal bone which presented headache and papilledema. This patient is a 37-year-old female who had, prior to admission, complained of increasing headache for one year and blurred vision for three months. She had no history of head injury. Local physical examinations revealed a slight bulging in her left parietal region which was insensitive to palpation and not adherent to the overlying scalp. Neurological examinations revealed bilateral papilledema and an incongruous bitemporal upper quadrant defect in the visual field. All the other neurological and laboratory data were normal. A plain skull roentogenogram showed a 9 x 9 cm osteolytic and characteristic honeycomb lesion in the parietal region. Systemic bone survey revealed a similar lesion in the right tibia which was not histologically examined. A marked accumulation of isotopes was detected on the bone scintigrams at both lesions. Selective external carotid angiograms demonstrated a tumor stain fed by the superficial temporal, occipital, and middle meningial arteries. CT scans of the brain and skull clearly showed a local thickening of and structural changes in the skull bone and also a mass effect on the brain and lateral ventricle. The lesioned bone was removed en bloc and replaced by an artificial bone. It was highly vascular, but not adherent to the overlying dura. The post-operative course was uneventful, and the headache and papilledema disappeared. Hemangioma of the skull presenting marked hyperostosis, as reported above, seems to be rare. In addition, in this case, skeletal angioma without any clinical manifestation was detected. Clinical and radiological pictures of the hemangioma of the skull and other bones were briefly discussed. (author)

  5. 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

  6. Regulation of DNA replication in irradiated cells by trans-acting factors

    International Nuclear Information System (INIS)

    Wang, Y.; Huq, M.S.; Cheng, X.; Iliakis, G.

    1995-01-01

    We compared DNA replication activity in cytoplasmic extracts prepared from irradiated and nonirradiated HeLa cells using a simian virus 40 (SV40)-based in vitro replication assay. The assay measures semi-conservative DNA replication in a plasmid carrying the SV40 origin of replication and requires SV40 T antigen as the sole noncellular protein. The plasmid DNA used in the replication reaction is never exposed to radiation. We find that replication of plasmid DNA is significantly reduced when cytoplasmic extracts from irradiated cells are used. Since plasmid replication proceeds to completion in extracts from irradiated cells, the observed reduction in the overall replication activity is probably due to a reduction in the efficiency of initiation events. The degree of inhibition of DNA replication after exposure to 10, 30 and 50 Gy X rays as measured in vitro using this assay is similar to that measured in intact cells immediately before processing for extract preparation. These observations are compatible with the induction or activation by ionizing radiation of a factor(s) that inhibits in trans DNA replication. The results contribute to our understanding of the mechanism(s) developed by the cells to regulate DNA replication when exposed to clastogenic agents. Such processes may be of significance in the restoration of DNA integrity, and may define yet another checkpoint operating during S at the level of clusters of replicons. 26 refs., 4 figs

  7. Adeno-associated virus type 2 enhances goose parvovirus replication in embryonated goose eggs

    International Nuclear Information System (INIS)

    Malkinson, Mertyn; Winocour, Ernest

    2005-01-01

    The autonomous goose parvovirus (GPV) and the human helper-dependent adeno-associated virus type 2 (AAV2) share a high degree of homology. To determine if this evolutionary relationship has a biological impact, we studied viral replication in human 293 cells and in embryonated goose eggs coinfected with both viruses. Similar experiments were performed with the minute virus of mice (MVM), an autonomous murine parvovirus with less homology to AAV2. In human 293 cells, both GPV and MVM augmented AAV2 replication. In contrast, AAV2 markedly enhanced GPV replication in embryonated goose eggs under conditions where a similar effect was not observed with MVM. AAV2 did not replicate in embryonated goose eggs and AAV2 inactivated by UV-irradiation also enhanced GPV replication. To our knowledge, this is the first report that a human helper-dependent member of the Parvoviridae can provide helper activity for an autonomous parvovirus in a natural host

  8. Cooperative Shark Mark Recapture Database (MRDBS)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Shark Mark Recapture Database is a Cooperative Research Program database system used to keep multispecies mark-recapture information in a common format for...

  9. On-road Bicycle Pavement Markings

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — A mile by mile breakdown of the on-street bicycle pavement markings installed within the City of Pittsburgh. These include bike lanes, shared lane markings...

  10. Serviceable pavement marking retroreflectivity levels : technical report.

    Science.gov (United States)

    2009-03-01

    This research addressed an array of issues related to measuring pavement markings retroreflectivity, factors : related to pavement marking performance, subjective evaluation process, best practices for using mobile : retroreflectometers, sampling pav...

  11. Construction and updating of event models in auditory event processing.

    Science.gov (United States)

    Huff, Markus; Maurer, Annika E; Brich, Irina; Pagenkopf, Anne; Wickelmaier, Florian; Papenmeier, Frank

    2018-02-01

    Humans segment the continuous stream of sensory information into distinct events at points of change. Between 2 events, humans perceive an event boundary. Present theories propose changes in the sensory information to trigger updating processes of the present event model. Increased encoding effort finally leads to a memory benefit at event boundaries. Evidence from reading time studies (increased reading times with increasing amount of change) suggest that updating of event models is incremental. We present results from 5 experiments that studied event processing (including memory formation processes and reading times) using an audio drama as well as a transcript thereof as stimulus material. Experiments 1a and 1b replicated the event boundary advantage effect for memory. In contrast to recent evidence from studies using visual stimulus material, Experiments 2a and 2b found no support for incremental updating with normally sighted and blind participants for recognition memory. In Experiment 3, we replicated Experiment 2a using a written transcript of the audio drama as stimulus material, allowing us to disentangle encoding and retrieval processes. Our results indicate incremental updating processes at encoding (as measured with reading times). At the same time, we again found recognition performance to be unaffected by the amount of change. We discuss these findings in light of current event cognition theories. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  12. [Marked hemosiderosis in myelodysplastic syndrome].

    Science.gov (United States)

    Klinz, C

    1999-01-29

    A 68-year-old man was admitted because of symptoms of lumbar pain. He was known to have chronic anemia with ring sideroblasts and diabetes melitus and to be in heart failure. Three months before he had been given 7 units of red cell concentrate. On admission the outstanding features were brown discoloration of the skin, absent body hair, tachycardia, hepatomegaly and small testicles. He had a normocytic anemia, hyperglycemia and raised transaminases, hypogonadism and vitamin D3 deficiency. The serum levels of iron, transferrin saturation and feritin were markedly elevated. Liver iron content/g dried liver was 4.2 g (by biomagnetometer). Radiology of the lumbar vertebrae showed osteoporosis and sonography confirmed hepatomegaly. The known myelodysplastic syndrome (MDS) had fed to secondary hemosiderosis with heart failure, liver involvement, diabetes mellitus, hypogonadism and osteoporosis. Symptomatic treatment was unsuccessfully complemented by desferoxamine (up to 4 g/12 h) to release iron. But very good iron excretion was then achieved with deferiprone (3 x 1 g/d). The patient later died of the sequelae of hemosiderosis. Even when they have not required transfusions, patients with long-standing MDS should be examined regularly for the possible development of secondary hemosiderosis so that iron-chelating agents can be administered as needed.

  13. EDMS - Reaching the Million Mark

    CERN Multimedia

    2009-01-01

    When Christophe Seith from the company Cegelec sat down to work on 14 May 2009 at 10:09 a.m. to create the EDMS document entitled "Rapport tournée PH semaine 20", little did he know that he would be the proud creator of the millionth EDMS document and the happy prize winner of a celebratory bottle of champagne to mark the occasion. In the run up to the creation of the millionth EDMS document the EDMS team had been closely monitoring the steady rise in the EDMS number generator, so as to ensure the switch from the six figured i.d. to seven figures would run smoothly and of course, to be able to congratulate the creator of the millionth EDMS document. From left to right: Stephan Petit (GS-ASE- EDS Section Leader), Christophe Delamare (GS- ASE Group Leader), Christophe Seith, creator of the millionth EDMS document, David Widegren, (GS-ASE- EPS Section Leader). The millionth EDMS document. For t...

  14. Structural Insights into the Coupling of Virion Assembly and Rotavirus Replication

    Science.gov (United States)

    Trask, Shane D.; McDonald, Sarah M.; Patton, John T.

    2013-01-01

    Preface Viral replication is rapid and robust, but it is far from a chaotic process. Instead, successful production of infectious progeny requires that events occur in the correct place and at the correct time. Rotavirus, a segmented double-stranded RNA virus of the Reoviridae family, seems to govern its replication through ordered disassembly and assembly of a triple-layered icosahedral capsid. In recent years, high-resolution structural data have provided unprecedented insight into these events. In this Review, we explore the current understanding of rotavirus replication and how it compares to other Reoviridae family members. PMID:22266782

  15. 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.

  16. 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...

  17. 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.

  18. 46 CFR 122.602 - Hull markings.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Hull markings. 122.602 Section 122.602 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) SMALL PASSENGER VESSELS CARRYING MORE THAN 150....602 Hull markings. (a) Each vessel must be marked as required by part 67, subpart I, of this chapter...

  19. 7 CFR 160.32 - Marking containers.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false Marking containers. 160.32 Section 160.32 Agriculture... STANDARDS FOR NAVAL STORES Analysis, Inspection, and Grading on Request § 160.32 Marking containers. The interested person shall provide any labor necessary for marking the containers, after the contents have been...

  20. 46 CFR 160.176-23 - Marking.

    Science.gov (United States)

    2010-10-01

    ... of the vessel. (2) The type of vessel. (3) Specific purpose or limitation approved by the Coast Guard...: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Inflatable Lifejackets § 160.176-23 Marking. (a) General. Each inflatable lifejacket must be marked with the information required by this section. Each marking must be...

  1. 27 CFR 28.123 - Export marks.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Export marks. 28.123..., or Transportation to a Manufacturing Bonded Warehouse § 28.123 Export marks. (a) General. In addition... filled under the provisions of part 24 of this chapter, the proprietor shall mark the word “Export” on...

  2. 27 CFR 28.223 - Export marks.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Export marks. 28.223... Export marks. In addition to the marks and brands required to be placed on kegs, barrels, cases, crates... “Export” on each container or case before removal for export, for use on vessels or aircraft, or for...

  3. 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...

  4. 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

  5. Identifying Cancer Driver Genes Using Replication-Incompetent Retroviral Vectors

    Directory of Open Access Journals (Sweden)

    Victor M. Bii

    2016-10-01

    Full Text Available Identifying novel genes that drive tumor metastasis and drug resistance has significant potential to improve patient outcomes. High-throughput sequencing approaches have identified cancer genes, but distinguishing driver genes from passengers remains challenging. Insertional mutagenesis screens using replication-incompetent retroviral vectors have emerged as a powerful tool to identify cancer genes. Unlike replicating retroviruses and transposons, replication-incompetent retroviral vectors lack additional mutagenesis events that can complicate the identification of driver mutations from passenger mutations. They can also be used for almost any human cancer due to the broad tropism of the vectors. Replication-incompetent retroviral vectors have the ability to dysregulate nearby cancer genes via several mechanisms including enhancer-mediated activation of gene promoters. The integrated provirus acts as a unique molecular tag for nearby candidate driver genes which can be rapidly identified using well established methods that utilize next generation sequencing and bioinformatics programs. Recently, retroviral vector screens have been used to efficiently identify candidate driver genes in prostate, breast, liver and pancreatic cancers. Validated driver genes can be potential therapeutic targets and biomarkers. In this review, we describe the emergence of retroviral insertional mutagenesis screens using replication-incompetent retroviral vectors as a novel tool to identify cancer driver genes in different cancer types.

  6. Minority games, evolving capitals and replicator dynamics

    International Nuclear Information System (INIS)

    Galla, Tobias; Zhang, Yi-Cheng

    2009-01-01

    We discuss a simple version of the minority game (MG) in which agents hold only one strategy each, but in which their capitals evolve dynamically according to their success and in which the total trading volume varies in time accordingly. This feature is known to be crucial for MGs to reproduce stylized facts of real market data. The stationary states and phase diagram of the model can be computed, and we show that the ergodicity breaking phase transition common for MGs, and marked by a divergence of the integrated response, is present also in this simplified model. An analogous majority game turns out to be relatively void of interesting features, and the total capital is found to diverge in time. Introducing a restraining force leads to a model akin to the replicator dynamics of evolutionary game theory, and we demonstrate that here a different type of phase transition is observed. Finally we briefly discuss the relation of this model with one strategy per player to more sophisticated minority games with dynamical capitals and several trading strategies per agent

  7. Mark-II Data Acquisition and Trigger system

    International Nuclear Information System (INIS)

    Breidenbach, M.

    1984-06-01

    The Mark-II Data Acquisition and Trigger system requirements and general solution are described. The solution takes advantage of the synchronous crossing times and low event rates of an electron positron collider to permit a very highly multiplexed analog scheme to be effective. The system depends on a two level trigger to operate with acceptable dead time. The trigger, multiplexing, data reduction, calibration, and CAMAC systems are described

  8. Distribution of DNA replication proteins in Drosophila cells

    Science.gov (United States)

    Easwaran, Hariharan P; Leonhardt, Heinrich; Cardoso, M Cristina

    2007-01-01

    Background DNA replication in higher eukaryotic cells is organized in discrete subnuclear sites called replication foci (RF). During the S phase, most replication proteins assemble at the RF by interacting with PCNA via a PCNA binding domain (PBD). This has been shown to occur for many mammalian replication proteins, but it is not known whether this mechanism is conserved in evolution. Results Fluorescent fusions of mammalian replication proteins, Dnmt1, HsDNA Lig I and HsPCNA were analyzed for their ability to target to RF in Drosophila cells. Except for HsPCNA, none of the other proteins and their deletions showed any accumulation at RF in Drosophila cells. We hypothesized that in Drosophila cells there might be some other peptide sequence responsible for targeting proteins to RF. To test this, we identified the DmDNA Lig I and compared the protein sequence with HsDNA Lig I. The two orthologs shared the PBD suggesting a functionally conserved role for this domain in the Drosophila counterpart. A series of deletions of DmDNA Lig I were analyzed for their ability to accumulate at RF in Drosophila and mammalian cells. Surprisingly, no accumulation at RF was observed in Drosophila cells, while in mammalian cells DmDNA Lig I accumulated at RF via its PBD. Further, GFP fusions with the PBD domains from Dnmt1, HsDNA Lig I and DmDNA Lig I, were able to target to RF only in mammalian cells but not in Drosophila cells. Conclusion We show that S phase in Drosophila cells is characterized by formation of RF marked by PCNA like in mammalian cells. However, other than PCNA none of the replication proteins and their deletions tested here showed accumulation at RF in Drosophila cells while the same proteins and deletions are capable of accumulating at RF in mammalian cells. We hypothesize that unlike mammalian cells, in Drosophila cells, replication proteins do not form long-lasting interactions with the replication machinery, and rather perform their functions via very

  9. 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....

  10. 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...

  11. 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....

  12. 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...

  13. 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...

  14. 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.

  15. High contrast laser marking of alumina

    International Nuclear Information System (INIS)

    Penide, J.; Quintero, F.; Riveiro, A.; Fernández, A.; Val, J. del; Comesaña, R.; Lusquiños, F.; Pou, J.

    2015-01-01

    Highlights: • Laser marking of alumina using near infrared (NIR) lasers was experimentally analyzed. • Color change produced by NIR lasers is due to thermally induced oxygen vacancies. • Laser marking results obtained using NIR lasers and green laser are compared. • High contrast marks on alumina were achieved. - Abstract: Alumina serves as raw material for a broad range of advanced ceramic products. These elements should usually be identified by some characters or symbols printed directly on them. In this sense, laser marking is an efficient, reliable and widely implemented process in industry. However, laser marking of alumina still leads to poor results since the process is not able to produce a dark mark, yielding bad contrast. In this paper, we present an experimental study on the process of marking alumina by three different lasers working in two wavelengths: 1064 nm (Near-infrared) and 532 nm (visible, green radiation). A colorimetric analysis has been carried out in order to compare the resulting marks and its contrast. The most suitable laser operating conditions were also defined and are reported here. Moreover, the physical process of marking by NIR lasers is discussed in detail. Field Emission Scanning Electron Microscopy, High Resolution Transmission Electron Microscopy and X-ray Photoelectron Spectroscopy were also employed to analyze the results. Finally, we propose an explanation for the differences of the coloration induced under different atmospheres and laser parameters. We concluded that the atmosphere is the key parameter, being the inert one the best choice to produce the darkest marks

  16. 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.

  17. 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.)

  18. 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.

  19. 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....

  20. 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.

  1. Initiation of DNA replication: functional and evolutionary aspects

    Science.gov (United States)

    Bryant, John A.; Aves, Stephen J.

    2011-01-01

    Background The initiation of DNA replication is a very important and highly regulated step in the cell division cycle. It is of interest to compare different groups of eukaryotic organisms (a) to identify the essential molecular events that occur in all eukaryotes, (b) to start to identify higher-level regulatory mechanisms that are specific to particular groups and (c) to gain insights into the evolution of initiation mechanisms. Scope This review features a wide-ranging literature survey covering replication origins, origin recognition and usage, modification of origin usage (especially in response to plant hormones), assembly of the pre-replication complex, loading of the replisome, genomics, and the likely origin of these mechanisms and proteins in Archaea. Conclusions In all eukaryotes, chromatin is organized for DNA replication as multiple replicons. In each replicon, replication is initiated at an origin. With the exception of those in budding yeast, replication origins, including the only one to be isolated so far from a plant, do not appear to embody a specific sequence; rather, they are AT-rich, with short tracts of locally bent DNA. The proteins involved in initiation are remarkably similar across the range of eukaryotes. Nevertheless, their activity may be modified by plant-specific mechanisms, including regulation by plant hormones. The molecular features of initiation are seen in a much simpler form in the Archaea. In particular, where eukaryotes possess a number of closely related proteins that form ‘hetero-complexes’ (such as the origin recognition complex and the MCM complex), archaeans typically possess one type of protein (e.g. one MCM) that forms a homo-complex. This suggests that several eukaryotic initiation proteins have evolved from archaeal ancestors by gene duplication and divergence. PMID:21508040

  2. Mark II magnetic detector for SPEAR

    International Nuclear Information System (INIS)

    Larsen, R.R.

    1975-01-01

    The Mark II Detector, presently in the design stage, is a SLAC/LBL detector project to replace the Mark I now in operation at SPEAR. While similar in concept to the Mark I it will have improved momentum resolution, shower detection, solid angle coverage for both triggering and tracking and a magnet design providing easier access to those particles transmitted through the aluminum coil

  3. An analysis of hospital brand mark clusters.

    Science.gov (United States)

    Vollmers, Stacy M; Miller, Darryl W; Kilic, Ozcan

    2010-07-01

    This study analyzed brand mark clusters (i.e., various types of brand marks displayed in combination) used by hospitals in the United States. The brand marks were assessed against several normative criteria for creating brand marks that are memorable and that elicit positive affect. Overall, results show a reasonably high level of adherence to many of these normative criteria. Many of the clusters exhibited pictorial elements that reflected benefits and that were conceptually consistent with the verbal content of the cluster. Also, many clusters featured icons that were balanced and moderately complex. However, only a few contained interactive imagery or taglines communicating benefits.

  4. Event Investigation

    International Nuclear Information System (INIS)

    Korosec, D.

    2000-01-01

    The events in the nuclear industry are investigated from the license point of view and from the regulatory side too. It is well known the importance of the event investigation. One of the main goals of such investigation is to prevent the circumstances leading to the event and the consequences of the event. The protection of the nuclear workers against nuclear hazard, and the protection of general public against dangerous effects of an event could be achieved by systematic approach to the event investigation. Both, the nuclear safety regulatory body and the licensee shall ensure that operational significant events are investigated in a systematic and technically sound manner to gather information pertaining to the probable causes of the event. One of the results should be appropriate feedback regarding the lessons of the experience to the regulatory body, nuclear industry and general public. In the present paper a general description of systematic approach to the event investigation is presented. The systematic approach to the event investigation works best where cooperation is present among the different divisions of the nuclear facility or regulatory body. By involving management and supervisors the safety office can usually improve their efforts in the whole process. The end result shall be a program which serves to prevent events and reduce the time and efforts solving the root cause which initiated each event. Selection of the proper method for the investigation and an adequate review of the findings and conclusions lead to the higher level of the overall nuclear safety. (author)

  5. Eyewitness Suggestibility and Source Similarity: Intrusions of Details from One Event into Memory Reports of Another Event

    Science.gov (United States)

    Lindsay, D. Stephen; Allen, Bem P.; Chan, Jason C. K.; Dahl, Leora C.

    2004-01-01

    We explored the effect of the degree of conceptual similarity between a witnessed event and an extra-event narrative on eyewitness suggestibility. Experiments 1A and 1B replicated Allen and Lindsay's (1998) finding that subjects sometimes intrude details from a narrative description of one event into their reports of a different visual event.…

  6. A model for transmission of the H3K27me3 epigenetic mark

    DEFF Research Database (Denmark)

    Hansen, Klaus H; Bracken, Adrian P; Pasini, Diego

    2008-01-01

    Organization of chromatin by epigenetic mechanisms is essential for establishing and maintaining cellular identity in developing and adult organisms. A key question that remains unresolved about this process is how epigenetic marks are transmitted to the next cell generation during cell division...... during incorporation of newly synthesized histones. This mechanism ensures maintenance of the H3K27me3 epigenetic mark in proliferating cells, not only during DNA replication when histones synthesized de novo are incorporated, but also outside S phase, thereby preserving chromatin structure...

  7. Social learning and the replication process: an experimental investigation.

    Science.gov (United States)

    Derex, Maxime; Feron, Romain; Godelle, Bernard; Raymond, Michel

    2015-06-07

    Human cultural traits typically result from a gradual process that has been described as analogous to biological evolution. This observation has led pioneering scholars to draw inspiration from population genetics to develop a rigorous and successful theoretical framework of cultural evolution. Social learning, the mechanism allowing information to be transmitted between individuals, has thus been described as a simple replication mechanism. Although useful, the extent to which this idealization appropriately describes the actual social learning events has not been carefully assessed. Here, we used a specifically developed computer task to evaluate (i) the extent to which social learning leads to the replication of an observed behaviour and (ii) the consequences it has for fitness landscape exploration. Our results show that social learning does not lead to a dichotomous choice between disregarding and replicating social information. Rather, it appeared that individuals combine and transform information coming from multiple sources to produce new solutions. As a consequence, landscape exploration was promoted by the use of social information. These results invite us to rethink the way social learning is commonly modelled and could question the validity of predictions coming from models considering this process as replicative. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  8. 49 CFR 1520.13 - Marking SSI.

    Science.gov (United States)

    2010-10-01

    ... SECURITY INFORMATION § 1520.13 Marking SSI. (a) Marking of paper records. In the case of paper records... back cover, including a binder cover or folder, if the document has a front and back cover; (2) Any.... 552 and 49 CFR parts 15 and 1520. (d) Other types of records. In the case of non-paper records that...

  9. Lessons learned : pavement marking warranty contract.

    Science.gov (United States)

    2013-12-01

    In 2012, UDOT implemented a performance-based warranty on a portion of an I-15 pavement marking : project. The awarded contract requested a contractor warranty on the implemented markings for a total : duration of six years. This is the first time th...

  10. 49 CFR 178.338-18 - Marking.

    Science.gov (United States)

    2010-10-01

    ... pounds. (7) Maximum design density of lading (Max. Lading density), in pounds per gallon. (8) Material... cryogenic liquid, in hours, and the name of that cryogenic liquid (MRHT __ hrs, name of cryogenic liquid). Marked rated holding marking for additional cryogenic liquids may be displayed on or adjacent to the...

  11. 25 CFR 141.16 - Price marking.

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Price marking. 141.16 Section 141.16 Indians BUREAU OF... AND ZUNI RESERVATIONS General Business Practices § 141.16 Price marking. The price of each article... visible to the customer and that affords the customer a reasonable opportunity to learn the price of the...

  12. Do employers prefer Mark over Mohammed?

    NARCIS (Netherlands)

    Iris Andriessen; Eline Nievers; Laila Faulk; Jaco Dagevos

    2010-01-01

    Original title: Liever Mark dan Mohammed? Does Mohammed have less chance of succeeding on the Dutch labour market than Mark, even though they both have the same qualifications and work experience? And are employers less friendly towards Sonaya than Paula? This study investigates the

  13. 7 CFR 956.162 - Container markings.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 8 2010-01-01 2010-01-01 false Container markings. 956.162 Section 956.162... WALLA VALLEY OF SOUTHEAST WASHINGTON AND NORTHEAST OREGON Rules and Regulations § 956.162 Container markings. Effective April 15, 1997, no handler shall ship any container of Walla Walla Sweet Onions except...

  14. 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.

  15. Definition of distance for nonlinear time series analysis of marked point process data

    Energy Technology Data Exchange (ETDEWEB)

    Iwayama, Koji, E-mail: koji@sat.t.u-tokyo.ac.jp [Research Institute for Food and Agriculture, Ryukoku Univeristy, 1-5 Yokotani, Seta Oe-cho, Otsu-Shi, Shiga 520-2194 (Japan); Hirata, Yoshito; Aihara, Kazuyuki [Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505 (Japan)

    2017-01-30

    Marked point process data are time series of discrete events accompanied with some values, such as economic trades, earthquakes, and lightnings. A distance for marked point process data allows us to apply nonlinear time series analysis to such data. We propose a distance for marked point process data which can be calculated much faster than the existing distance when the number of marks is small. Furthermore, under some assumptions, the Kullback–Leibler divergences between posterior distributions for neighbors defined by this distance are small. We performed some numerical simulations showing that analysis based on the proposed distance is effective. - Highlights: • A new distance for marked point process data is proposed. • The distance can be computed fast enough for a small number of marks. • The method to optimize parameter values of the distance is also proposed. • Numerical simulations indicate that the analysis based on the distance is effective.

  16. Genome-wide Control of Heterochromatin Replication by the Telomere Capping Protein TRF2.

    Science.gov (United States)

    Mendez-Bermudez, Aaron; Lototska, Liudmyla; Bauwens, Serge; Giraud-Panis, Marie-Josèphe; Croce, Olivier; Jamet, Karine; Irizar, Agurtzane; Mowinckel, Macarena; Koundrioukoff, Stephane; Nottet, Nicolas; Almouzni, Genevieve; Teulade-Fichou, Mare-Paule; Schertzer, Michael; Perderiset, Mylène; Londoño-Vallejo, Arturo; Debatisse, Michelle; Gilson, Eric; Ye, Jing

    2018-05-03

    Hard-to-replicate regions of chromosomes (e.g., pericentromeres, centromeres, and telomeres) impede replication fork progression, eventually leading, in the event of replication stress, to chromosome fragility, aging, and cancer. Our knowledge of the mechanisms controlling the stability of these regions is essentially limited to telomeres, where fragility is counteracted by the shelterin proteins. Here we show that the shelterin subunit TRF2 ensures progression of the replication fork through pericentromeric heterochromatin, but not centromeric chromatin. In a process involving its N-terminal basic domain, TRF2 binds to pericentromeric Satellite III sequences during S phase, allowing the recruitment of the G-quadruplex-resolving helicase RTEL1 to facilitate fork progression. We also show that TRF2 is required for the stability of other heterochromatic regions localized throughout the genome, paving the way for future research on heterochromatic replication and its relationship with aging and cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Characterization of the replication timing program of 6 human model cell lines

    Directory of Open Access Journals (Sweden)

    Djihad Hadjadj

    2016-09-01

    Full Text Available During the S-phase, the DNA replication process is finely orchestrated and regulated by two programs: the spatial program that determines where replication will start in the genome (Cadoret et al. (2008 Oct 14, Cayrou et al. (2011 Sep, Picard et al. (2014 May 1 [1–3], and the temporal program that determines when during the S phase different parts of the genome are replicated and when origins are activated. The temporal program is so well conserved for each cell type from independent individuals [4] that it is possible to identify a cell type from an unknown sample just by determining its replication timing program. Moreover, replicative domains are strongly correlated with the partition of the genome into topological domains (determined by the Hi-C method, Lieberman-Aiden et al. (2009 Oct 9, Pope et al. (2014 Nov 20 [5,6]. On the one hand, replicative areas are well defined and participate in shaping the spatial organization of the genome for a given cell type. On the other hand, studies on the timing program during cell differentiation showed a certain plasticity of this program according to the stage of cell differentiation Hiratani et al. (2008 Oct 7, 2010 Feb [7,8]. Domains where a replication timing change was observed went through a nuclear re-localization. Thus the temporal program of replication can be considered as an epigenetic mark Hiratani and Gilbert (2009 Feb 16 [9]. We present the genomic data of replication timing in 6 human model cell lines: U2OS (GSM2111308, RKO (GSM2111309, HEK 293T (GSM2111310, HeLa (GSM2111311, MRC5-SV (GSM2111312 and K562 (GSM2111313. A short comparative analysis was performed that allowed us to define regions common to the 6 cell lines. These replication timing data can be taken into account when performing studies that use these model cell lines.

  18. SENTINEL EVENTS

    Directory of Open Access Journals (Sweden)

    Andrej Robida

    2004-09-01

    Full Text Available Background. The Objective of the article is a two year statistics on sentinel events in hospitals. Results of a survey on sentinel events and the attitude of hospital leaders and staff are also included. Some recommendations regarding patient safety and the handling of sentinel events are given.Methods. In March 2002 the Ministry of Health introduce a voluntary reporting system on sentinel events in Slovenian hospitals. Sentinel events were analyzed according to the place the event, its content, and root causes. To show results of the first year, a conference for hospital directors and medical directors was organized. A survey was conducted among the participants with the purpose of gathering information about their view on sentinel events. One hundred questionnaires were distributed.Results. Sentinel events. There were 14 reports of sentinel events in the first year and 7 in the second. In 4 cases reports were received only after written reminders were sent to the responsible persons, in one case no reports were obtained. There were 14 deaths, 5 of these were in-hospital suicides, 6 were due to an adverse event, 3 were unexplained. Events not leading to death were a suicide attempt, a wrong side surgery, a paraplegia after spinal anaesthesia, a fall with a femoral neck fracture, a damage of the spleen in the event of pleural space drainage, inadvertent embolization with absolute alcohol into a femoral artery and a physical attack on a physician by a patient. Analysis of root causes of sentinel events showed that in most cases processes were inadequate.Survey. One quarter of those surveyed did not know about the sentinel events reporting system. 16% were having actual problems when reporting events and 47% beleived that there was an attempt to blame individuals. Obstacles in reporting events openly were fear of consequences, moral shame, fear of public disclosure of names of participants in the event and exposure in mass media. The majority of

  19. Transgene Expression and Host Cell Responses to Replication-Defective, Single-Cycle, and Replication-Competent Adenovirus Vectors

    Directory of Open Access Journals (Sweden)

    Catherine M. Crosby

    2017-02-01

    Full Text Available Most adenovirus (Ad vectors are E1 gene deleted replication defective (RD-Ad vectors that deliver one transgene to the cell and all expression is based on that one gene. In contrast, E1-intact replication-competent Ad (RC-Ad vectors replicate their DNA and their transgenes up to 10,000-fold, amplifying transgene expression markedly higher than RD-Ad vectors. While RC-Ad are more potent, they run the real risk of causing adenovirus infections in vector recipients and those that administer them. To gain the benefits of transgene amplification, but avoid the risk of Ad infections, we developed “single cycle” Ad (SC-Ad vectors. SC-Ads amplify transgene expression and generated markedly stronger and more persistent immune responses than RD-Ad as expected. However, they also unexpectedly generated stronger immune responses than RC-Ad vectors. To explore the basis of this potency here, we compared gene expression and the cellular responses to infection to these vectors in vitro and in vivo. In vitro, in primary human lung epithelial cells, SC- and RC-Ad amplified their genomes more than 400-fold relative to RD-Ad with higher replication by SC-Ad. This replication translated into higher green fluorescent protein (GFP expression for 48 h by SC- and RC-Ad than by RD-Ad. In vitro, in the absence of an immune system, RD-Ad expression became higher by 72 h coincident with cell death mediated by SC- and RC-Ad and release of transgene product from the dying cells. When the vectors were compared in human THP-1 Lucia- interferon-stimulated gene (ISG cells, which are a human monocyte cell line that have been modified to quantify ISG activity, RC-Ad6 provoked significantly stronger ISG responses than RD- or SC-Ad. In mice, intravenous or intranasal injection produced up to 100-fold genome replication. Under these in vivo conditions in the presence of the immune system, luciferase expression by RC and SC-Ad was markedly higher than that by RD-Ad. In

  20. 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...

  1. Event Modeling

    DEFF Research Database (Denmark)

    Bækgaard, Lars

    2001-01-01

    The purpose of this chapter is to discuss conceptual event modeling within a context of information modeling. Traditionally, information modeling has been concerned with the modeling of a universe of discourse in terms of information structures. However, most interesting universes of discourse...... are dynamic and we present a modeling approach that can be used to model such dynamics.We characterize events as both information objects and change agents (Bækgaard 1997). When viewed as information objects events are phenomena that can be observed and described. For example, borrow events in a library can...

  2. 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...

  3. Energy risk management through self-exciting marked point process

    International Nuclear Information System (INIS)

    Herrera, Rodrigo

    2013-01-01

    Crude oil is a dynamically traded commodity that affects many economies. We propose a collection of marked self-exciting point processes with dependent arrival rates for extreme events in oil markets and related risk measures. The models treat the time among extreme events in oil markets as a stochastic process. The main advantage of this approach is its capability to capture the short, medium and long-term behavior of extremes without involving an arbitrary stochastic volatility model or a prefiltration of the data, as is common in extreme value theory applications. We make use of the proposed model in order to obtain an improved estimate for the Value at Risk in oil markets. Empirical findings suggest that the reliability and stability of Value at Risk estimates improve as a result of finer modeling approach. This is supported by an empirical application in the representative West Texas Intermediate (WTI) and Brent crude oil markets. - Highlights: • We propose marked self-exciting point processes for extreme events in oil markets. • This approach captures the short and long-term behavior of extremes. • We improve the estimates for the VaR in the WTI and Brent crude oil markets

  4. High contrast laser marking of alumina

    Science.gov (United States)

    Penide, J.; Quintero, F.; Riveiro, A.; Fernández, A.; del Val, J.; Comesaña, R.; Lusquiños, F.; Pou, J.

    2015-05-01

    Alumina serves as raw material for a broad range of advanced ceramic products. These elements should usually be identified by some characters or symbols printed directly on them. In this sense, laser marking is an efficient, reliable and widely implemented process in industry. However, laser marking of alumina still leads to poor results since the process is not able to produce a dark mark, yielding bad contrast. In this paper, we present an experimental study on the process of marking alumina by three different lasers working in two wavelengths: 1064 nm (Near-infrared) and 532 nm (visible, green radiation). A colorimetric analysis has been carried out in order to compare the resulting marks and its contrast. The most suitable laser operating conditions were also defined and are reported here. Moreover, the physical process of marking by NIR lasers is discussed in detail. Field Emission Scanning Electron Microscopy, High Resolution Transmission Electron Microscopy and X-ray Photoelectron Spectroscopy were also employed to analyze the results. Finally, we propose an explanation for the differences of the coloration induced under different atmospheres and laser parameters. We concluded that the atmosphere is the key parameter, being the inert one the best choice to produce the darkest marks.

  5. Court presentation of bite mark evidence.

    Science.gov (United States)

    Drinnan, A J; Melton, M J

    1985-12-01

    The uniqueness of an individual's bite mark is generally accepted. The use of bite mark analysis to identify or exclude those suspected of crimes is now a well established activity in forensic dentistry. Although the techniques for evaluating bite mark evidence are extremely sophisticated, it is important that the courtroom presentation of such evidence should be as simple as possible and be directed towards those who must judge it. Dentists likely to be involved in the courtroom presentation of bite mark evidence should: be certain that their local law enforcement personnel are frequently updated on the techniques to be used for producing the optimum evidence needed to evaluate bite marks; become acquainted with the current techniques of evaluating bite mark evidence and understand their difficulties and pitfalls; meet with the lawyers (prosecution or defence) before a courtroom appearance, briefing them on the significance of the particular findings; prepare clear and easily understandable visual aids to present to the court the techniques used in the analysis and the bases for the conclusion reached; and offer conclusions derived from the bite mark investigation.

  6. Inhibition of rotavirus replication by downregulation of fatty acid synthesis.

    Science.gov (United States)

    Gaunt, Eleanor R; Cheung, Winsome; Richards, James E; Lever, Andrew; Desselberger, Ulrich

    2013-06-01

    Recently the recruitment of lipid droplets (LDs) to sites of rotavirus (RV) replication was reported. LDs are polymorphic organelles that store triacylglycerols, cholesterol and cholesterol esters. The neutral fats are derived from palmitoyl-CoA, synthesized via the fatty acid biosynthetic pathway. RV-infected cells were treated with chemical inhibitors of the fatty acid biosynthetic pathway, and the effects on viral replication kinetics were assessed. Treatment with compound C75, an inhibitor of the fatty acid synthase enzyme complex (FASN), reduced RV infectivity 3.2-fold (P = 0.07) and modestly reduced viral RNA synthesis (1.2-fold). Acting earlier in the fatty acid synthesis pathway, TOFA [5-(Tetradecyloxy)-2-furoic acid] inhibits the enzyme acetyl-CoA carboxylase 1 (ACC1). TOFA reduced the infectivity of progeny RV 31-fold and viral RNA production 6-fold. The effect of TOFA on RV infectivity and RNA replication was dose-dependent, and infectivity was reduced by administering TOFA up to 4 h post-infection. Co-treatment of RV-infected cells with C75 and TOFA synergistically reduced viral infectivity. Knockdown by siRNA of FASN and ACC1 produced findings similar to those observed by inhibiting these proteins with the chemical compounds. Inhibition of fatty acid synthesis using a range of approaches uniformly had a more marked impact on viral infectivity than on viral RNA yield, inferring a role for LDs in virus assembly and/or egress. Specific inhibitors of fatty acid metabolism may help pinpoint the critical structural and biochemical features of LDs that are essential for RV replication, and facilitate the development of antiviral therapies.

  7. Changing Context of Trade Mark Protection in India: A Review of the Trade Marks Act, 1999

    OpenAIRE

    Pathak, Akhileshwar

    2004-01-01

    With liberalisation and globalisation of the Indian economy, it has become possible for anyone to get into production and services in most of the sectors. This has led to rampant misuse and appropriation of trade marks. In an insulated economy, with monopoly markets, law protecting trade marks had a limited role. In the changed context, however, trade mark law will be a field of much interest for academics and practitioners. Towards this, the paper explores the formation of trade mark law in ...

  8. 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

  9. A Marked Point Process Framework for Extracellular Electrical Potentials

    Directory of Open Access Journals (Sweden)

    Carlos A. Loza

    2017-12-01

    Full Text Available Neuromodulations are an important component of extracellular electrical potentials (EEP, such as the Electroencephalogram (EEG, Electrocorticogram (ECoG and Local Field Potentials (LFP. This spatially temporal organized multi-frequency transient (phasic activity reflects the multiscale spatiotemporal synchronization of neuronal populations in response to external stimuli or internal physiological processes. We propose a novel generative statistical model of a single EEP channel, where the collected signal is regarded as the noisy addition of reoccurring, multi-frequency phasic events over time. One of the main advantages of the proposed framework is the exceptional temporal resolution in the time location of the EEP phasic events, e.g., up to the sampling period utilized in the data collection. Therefore, this allows for the first time a description of neuromodulation in EEPs as a Marked Point Process (MPP, represented by their amplitude, center frequency, duration, and time of occurrence. The generative model for the multi-frequency phasic events exploits sparseness and involves a shift-invariant implementation of the clustering technique known as k-means. The cost function incorporates a robust estimation component based on correntropy to mitigate the outliers caused by the inherent noise in the EEP. Lastly, the background EEP activity is explicitly modeled as the non-sparse component of the collected signal to further improve the delineation of the multi-frequency phasic events in time. The framework is validated using two publicly available datasets: the DREAMS sleep spindles database and one of the Brain-Computer Interface (BCI competition datasets. The results achieve benchmark performance and provide novel quantitative descriptions based on power, event rates and timing in order to assess behavioral correlates beyond the classical power spectrum-based analysis. This opens the possibility for a unifying point process framework of

  10. Elemental marking of arthropod pests in agricultural systems: single and multigenerational marking

    Science.gov (United States)

    Jane Leslie Hayes

    1991-01-01

    Use of elemental markers to study movement of arthropod pests of field crops is reviewed. Trace elements, rubidium (Rb) and cesium (Cs), have provided a nondisruptive method of marking natural adult populations via developmental stage consumption of treated host plants. Multigenerational marking occurs with the transfer of elemental markers from marked adults to...

  11. 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.

  12. First results from Mark III at SPEAR

    International Nuclear Information System (INIS)

    Einsweiler, K.F.

    The paper presents data on meson decays obtained using the MARK III detector operating at SPEAR. Results on hadronic decays; decays of the etasub(e); and results on radiative decays; are all described. (U.K.)

  13. User's guide : pavement marking management system database.

    Science.gov (United States)

    2011-12-01

    Pavement markings play a critical role in maintaining a safe and efficient driving environment for road users, especially during nighttime conditions. The Texas Department of Transportation (TxDOT) spends millions of dollars each year for installatio...

  14. Mark Twain, Fenimore Cooper, and Batman.

    Science.gov (United States)

    Crick, Robert Alan

    1992-01-01

    Describes how Mark Twain's essay "Fenimore Cooper's Literary Offenses" helped students to get interested in writing and inspired them to write a similar essay critiquing the movie "Batman." Provides excerpts from students' essays. (PRA)

  15. 46 CFR 160.054-6 - Marking.

    Science.gov (United States)

    2010-10-01

    ... “To Close, Press Together Full Length”. The marking may be applied to the container by the silk screen process, using a suitable ink or paint, or may be applied by other means shown to be acceptable. (b...

  16. 49 CFR 180.213 - Requalification markings.

    Science.gov (United States)

    2010-10-01

    ... eddy current examination combined with a visual inspection, the marking is as illustrated in paragraph..., securely affixed in a manner prescribed by the cylinder manufacturer, near the original manufacturer's...

  17. Microscopic saw mark analysis: an empirical approach.

    Science.gov (United States)

    Love, Jennifer C; Derrick, Sharon M; Wiersema, Jason M; Peters, Charles

    2015-01-01

    Microscopic saw mark analysis is a well published and generally accepted qualitative analytical method. However, little research has focused on identifying and mitigating potential sources of error associated with the method. The presented study proposes the use of classification trees and random forest classifiers as an optimal, statistically sound approach to mitigate the potential for error of variability and outcome error in microscopic saw mark analysis. The statistical model was applied to 58 experimental saw marks created with four types of saws. The saw marks were made in fresh human femurs obtained through anatomical gift and were analyzed using a Keyence digital microscope. The statistical approach weighed the variables based on discriminatory value and produced decision trees with an associated outcome error rate of 8.62-17.82%. © 2014 American Academy of Forensic Sciences.

  18. 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.

  19. Enamel-based mark performance for marking Chinese mystery snail Bellamya chinensis

    Science.gov (United States)

    Wong, Alec; Allen, Craig R.; Hart, Noelle M.; Haak, Danielle M.; Pope, Kevin L.; Smeenk, Nicholas A.; Stephen, Bruce J.; Uden, Daniel R.

    2013-01-01

    The exoskeleton of gastropods provides a convenient surface for carrying marks, and i the interest of improving future marking methods our laboratory assessed the performance of an enamel paint. The endurance of the paint was also compared to other marking methods assessed in the past. We marked the shells of 30 adult Chinese mystery snails Bellamya chinensis and held them in an aquarium for 181 days. We observed no complete degradation of any enamel-paint mark during the 181 days. The enamel-paint mark was superior to a nai;-polish mark, which lasted a median of 100 days. Enamel-paint marks also have a lower rate of loss (0.00 month-1 181 days) than plastic bee tags (0.01 month-1, 57 days), gouache paint (0.07 month-1, 18.5 days), or car body paint from studies found in scientific literature. Legibility of enamel-paint marks had a median lifetime of 102 days. The use of enamel paint on the shells of gastropods is a viable option for studies lasting up to 6 months. Furthermore, visits to capture-mark-recapture site 1 year after application of enamel-paint marks on B. chinesnis shells produced several individuals on which the enamel paint was still visible, although further testing is required to clarify durability over longer periods.

  20. PREOPERATIVE ENDOSCOPIC MARKING OF UNPALPABLE COLONIC TUMORS

    Directory of Open Access Journals (Sweden)

    A. L. Goncharov

    2013-01-01

    Full Text Available The identification of small colon lesions is one of the major problems in laparoscopic colonic resection.Research objective: to develop a technique of visualization of small tumors of a colon by preoperative endoscopic marking of a tumor.Materials and methods. In one day prior to operation to the patient after bowel preparation the colonoscopy is carried out. In the planned point near tumor on antimesentery edge the submucous infiltration of marking solution (Micky Sharpz blue tattoo pigment, UK is made. The volume of entered solution of 1–3 ml. In only 5 months of use of a technique preoperative marking to 14 patients with small (the size of 1–3 cm malignant tumors of the left colon is performed.Results. The tattoo mark was well visualized by during operation at 13 of 14 patients. In all cases we recorded no complications. Time of operation with preoperative marking averaged 108 min, that is significantly less in comparison with average time of operation with an intra-operative colonoscopy – 155 min (р < 0.001.Conclusions. The first experience of preoperative endoscopic marking of non palpable small tumors of a colon is encouraging. Performance of a technique wasn't accompanied by complications and allowed to reduce significantly time of operation and to simplify conditions of performance of operation.

  1. The BAH domain of ORC1 links H4K20me2 to DNA replication licensing and Meier-Gorlin syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Kuo, Alex J; Song, Jikui; Cheung, Peggie; Ishibe-Murakami, Satoko; Yamazoe, Sayumi; Chen, James K; Patel, Dinshaw J; Gozani, Or [Stanford; (MSKCC); (Stanford-MED)

    2012-07-11

    The recognition of distinctly modified histones by specialized 'effector' proteins constitutes a key mechanism for transducing molecular events at chromatin to biological outcomes. Effector proteins influence DNA-templated processes, including transcription, DNA recombination and DNA repair; however, no effector functions have yet been identified within the mammalian machinery that regulate DNA replication. Here we show that ORC1 - a component of ORC (origin of replication complex), which mediates pre-DNA replication licensing - contains a bromo adjacent homology (BAH) domain that specifically recognizes histone H4 dimethylated at lysine 20 (H4K20me2). Recognition of H4K20me2 is a property common to BAH domains present within diverse metazoan ORC1 proteins. Structural studies reveal that the specificity of the BAH domain for H4K20me2 is mediated by a dynamic aromatic dimethyl-lysine-binding cage and multiple intermolecular contacts involving the bound peptide. H4K20me2 is enriched at replication origins, and abrogating ORC1 recognition of H4K20me2 in cells impairs ORC1 occupancy at replication origins, ORC chromatin loading and cell-cycle progression. Mutation of the ORC1 BAH domain has been implicated in the aetiology of Meier-Gorlin syndrome (MGS), a form of primordial dwarfism, and ORC1 depletion in zebrafish results in an MGS-like phenotype. We find that wild-type human ORC1, but not ORC1-H4K20me2-binding mutants, rescues the growth retardation of orc1 morphants. Moreover, zebrafish depleted of H4K20me2 have diminished body size, mirroring the phenotype of orc1 morphants. Together, our results identify the BAH domain as a novel methyl-lysine-binding module, thereby establishing the first direct link between histone methylation and the metazoan DNA replication machinery, and defining a pivotal aetiological role for the canonical H4K20me2 mark, via ORC1, in primordial dwarfism.

  2. High-Resolution Profiling of Drosophila Replication Start Sites Reveals a DNA Shape and Chromatin Signature of Metazoan Origins

    Directory of Open Access Journals (Sweden)

    Federico Comoglio

    2015-05-01

    Full Text Available At every cell cycle, faithful inheritance of metazoan genomes requires the concerted activation of thousands of DNA replication origins. However, the genetic and chromatin features defining metazoan replication start sites remain largely unknown. Here, we delineate the origin repertoire of the Drosophila genome at high resolution. We address the role of origin-proximal G-quadruplexes and suggest that they transiently stall replication forks in vivo. We dissect the chromatin configuration of replication origins and identify a rich spatial organization of chromatin features at initiation sites. DNA shape and chromatin configurations, not strict sequence motifs, mark and predict origins in higher eukaryotes. We further examine the link between transcription and origin firing and reveal that modulation of origin activity across cell types is intimately linked to cell-type-specific transcriptional programs. Our study unravels conserved origin features and provides unique insights into the relationship among DNA topology, chromatin, transcription, and replication initiation across metazoa.

  3. 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…

  4. 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…

  5. 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…

  6. 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

  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. 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.

  15. DNA intercalator stimulates influenza transcription and virus replication

    Directory of Open Access Journals (Sweden)

    Poon Leo LM

    2011-03-01

    Full Text Available Abstract Influenza A virus uses its host transcription machinery to facilitate viral RNA synthesis, an event that is associated with cellular RNA polymerase II (RNAPII. In this study, various RNAPII transcription inhibitors were used to investigate the effect of RNAPII phosphorylation status on viral RNA transcription. A low concentration of DNA intercalators, such as actinomycin D (ActD, was found to stimulate viral polymerase activity and virus replication. This effect was not observed in cells treated with RNAPII kinase inhibitors. In addition, the loss of RNAPIIa in infected cells was due to the shift of nonphosphorylated RNAPII (RNAPIIa to hyperphosphorylated RNAPII (RNAPIIo.

  16. 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.

  17. Forensic surface metrology: tool mark evidence.

    Science.gov (United States)

    Gambino, Carol; McLaughlin, Patrick; Kuo, Loretta; Kammerman, Frani; Shenkin, Peter; Diaczuk, Peter; Petraco, Nicholas; Hamby, James; Petraco, Nicholas D K

    2011-01-01

    Over the last several decades, forensic examiners of impression evidence have come under scrutiny in the courtroom due to analysis methods that rely heavily on subjective morphological comparisons. Currently, there is no universally accepted system that generates numerical data to independently corroborate visual comparisons. Our research attempts to develop such a system for tool mark evidence, proposing a methodology that objectively evaluates the association of striated tool marks with the tools that generated them. In our study, 58 primer shear marks on 9 mm cartridge cases, fired from four Glock model 19 pistols, were collected using high-resolution white light confocal microscopy. The resulting three-dimensional surface topographies were filtered to extract all "waviness surfaces"-the essential "line" information that firearm and tool mark examiners view under a microscope. Extracted waviness profiles were processed with principal component analysis (PCA) for dimension reduction. Support vector machines (SVM) were used to make the profile-gun associations, and conformal prediction theory (CPT) for establishing confidence levels. At the 95% confidence level, CPT coupled with PCA-SVM yielded an empirical error rate of 3.5%. Complementary, bootstrap-based computations for estimated error rates were 0%, indicating that the error rate for the algorithmic procedure is likely to remain low on larger data sets. Finally, suggestions are made for practical courtroom application of CPT for assigning levels of confidence to SVM identifications of tool marks recorded with confocal microscopy. Copyright © 2011 Wiley Periodicals, Inc.

  18. Mark 4A project training evaluation

    Science.gov (United States)

    Stephenson, S. N.

    1985-11-01

    A participant evaluation of a Deep Space Network (DSN) is described. The Mark IVA project is an implementation to upgrade the tracking and data acquisition systems of the dSN. Approximately six hundred DSN operations and engineering maintenance personnel were surveyed. The survey obtained a convenience sample including trained people within the population in order to learn what training had taken place and to what effect. The survey questionnaire used modifications of standard rating scales to evaluate over one hundred items in four training dimensions. The scope of the evaluation included Mark IVA vendor training, a systems familiarization training seminar, engineering training classes, a on-the-job training. Measures of central tendency were made from participant rating responses. Chi square tests of statistical significance were performed on the data. The evaluation results indicated that the effects of different Mark INA training methods could be measured according to certain ratings of technical training effectiveness, and that the Mark IVA technical training has exhibited positive effects on the abilities of DSN personnel to operate and maintain new Mark IVA equipment systems.

  19. Mark 4A project training evaluation

    Science.gov (United States)

    Stephenson, S. N.

    1985-01-01

    A participant evaluation of a Deep Space Network (DSN) is described. The Mark IVA project is an implementation to upgrade the tracking and data acquisition systems of the dSN. Approximately six hundred DSN operations and engineering maintenance personnel were surveyed. The survey obtained a convenience sample including trained people within the population in order to learn what training had taken place and to what effect. The survey questionnaire used modifications of standard rating scales to evaluate over one hundred items in four training dimensions. The scope of the evaluation included Mark IVA vendor training, a systems familiarization training seminar, engineering training classes, a on-the-job training. Measures of central tendency were made from participant rating responses. Chi square tests of statistical significance were performed on the data. The evaluation results indicated that the effects of different Mark INA training methods could be measured according to certain ratings of technical training effectiveness, and that the Mark IVA technical training has exhibited positive effects on the abilities of DSN personnel to operate and maintain new Mark IVA equipment systems.

  20. Biological evolution of replicator systems: towards a quantitative approach.

    Science.gov (United States)

    Martin, Osmel; Horvath, J E

    2013-04-01

    The aim of this work is to study the features of a simple replicator chemical model of the relation between kinetic stability and entropy production under the action of external perturbations. We quantitatively explore the different paths leading to evolution in a toy model where two independent replicators compete for the same substrate. To do that, the same scenario described originally by Pross (J Phys Org Chem 17:312-316, 2004) is revised and new criteria to define the kinetic stability are proposed. Our results suggest that fast replicator populations are continually favored by the effects of strong stochastic environmental fluctuations capable to determine the global population, the former assumed to be the only acting evolution force. We demonstrate that the process is continually driven by strong perturbations only, and that population crashes may be useful proxies for these catastrophic environmental fluctuations. As expected, such behavior is particularly enhanced under very large scale perturbations, suggesting a likely dynamical footprint in the recovery patterns of new species after mass extinction events in the Earth's geological past. Furthermore, the hypothesis that natural selection always favors the faster processes may give theoretical support to different studies that claim the applicability of maximum principles like the Maximum Metabolic Flux (MMF) or Maximum Entropy Productions Principle (MEPP), seen as the main goal of biological evolution.

  1. Maintaining epigenetic inheritance during DNA replication in plants

    Directory of Open Access Journals (Sweden)

    Francisco eIglesias

    2016-02-01

    Full Text Available Biotic and abiotic stresses alter the pattern of gene expression in plants. Depending on the frequency and duration of stress events, the effects on the transcriptional state of genes are remembered temporally or transmitted to daughter cells and, in some instances, even to offspring (transgenerational epigenetic inheritance. This memory effect, which can be found even in the absence of the original stress, has an epigenetic basis, through molecular mechanisms that take place at the chromatin and DNA level but do not imply changes in the DNA sequence. Many epigenetic mechanisms have been described and involve covalent modifications on the DNA and histones, such as DNA methylation, histone acetylation and methylation, and RNAi dependent silencing mechanisms. Some of these chromatin modifications need to be stable through cell division in order to be truly epigenetic. During DNA replication, histones are recycled during the formation of the new nucleosomes and this process is tightly regulated. Perturbations to the DNA replication process and/or the recycling of histones lead to epigenetic changes. In this mini-review, we discuss recent evidence aimed at linking DNA replication process to epigenetic inheritance in plants.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. Edit distance for marked point processes revisited: An implementation by binary integer programming

    Energy Technology Data Exchange (ETDEWEB)

    Hirata, Yoshito; Aihara, Kazuyuki [Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8505 (Japan)

    2015-12-15

    We implement the edit distance for marked point processes [Suzuki et al., Int. J. Bifurcation Chaos 20, 3699–3708 (2010)] as a binary integer program. Compared with the previous implementation using minimum cost perfect matching, the proposed implementation has two advantages: first, by using the proposed implementation, we can apply a wide variety of software and hardware, even spin glasses and coherent ising machines, to calculate the edit distance for marked point processes; second, the proposed implementation runs faster than the previous implementation when the difference between the numbers of events in two time windows for a marked point process is large.

  7. The national hydrologic bench-mark network

    Science.gov (United States)

    Cobb, Ernest D.; Biesecker, J.E.

    1971-01-01

    The United States is undergoing a dramatic growth of population and demands on its natural resources. The effects are widespread and often produce significant alterations of the environment. The hydrologic bench-mark network was established to provide data on stream basins which are little affected by these changes. The network is made up of selected stream basins which are not expected to be significantly altered by man. Data obtained from these basins can be used to document natural changes in hydrologic characteristics with time, to provide a better understanding of the hydrologic structure of natural basins, and to provide a comparative base for studying the effects of man on the hydrologic environment. There are 57 bench-mark basins in 37 States. These basins are in areas having a wide variety of climate and topography. The bench-mark basins and the types of data collected in the basins are described.

  8. 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

  9. 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

  10. Replication of each copy of the yeast 2 micron DNA plasmid occurs during the S phase.

    Science.gov (United States)

    Zakian, V A; Brewer, B J; Fangman, W L

    1979-08-01

    Saccharomyces cerevisiae contains 50-100 copies per cell of a circular plasmid called 2 micron DNA. Replication of this DNA was studied in two ways. The distribution of replication events among 2 micron DNA molecules was examined by density transfer experiments with asynchronous cultures. The data show that 2 micron DNA replication is similar to chromosomal DNA replication: essentially all 2 micron duplexes were of hybrid density at one cell doubling after the density transfer, with the majority having one fully dense strand and one fully light strand. The results show that replication of 2 micron DNA occurs by a semiconservative mechanism where each of the plasmid molecules replicates once each cell cycle. 2 micron DNA is the only known example of a multiple-copy, extrachromosomal DNA in which every molecule replicates in each cell cycle. Quantitative analysis of the data indicates that 2 micron DNA replication is limited to a fraction of the cell cycle. The period in the cell cycle when 2 micron DNA replicates was examined directly with synchronous cell cultures. Synchronization was accomplished by sequentially arresting cells in G1 phase using the yeast pheromone alpha-factor and incubating at the restrictive temperature for a cell cycle (cdc 7) mutant. Replication was monitored by adding 3H-uracil to cells previously labeled with 14C-uracil, and determining the 3H/14C ratio for purified DNA species. 2 micron DNA replication did not occur during the G1 arrest periods. However, the population of 2 micron DNA doubled during the synchronous S phase at the permissive temperature, with most of the replication occurring in the first third of S phase. Our results indicate that a mechanism exists which insures that the origin of replication of each 2 micron DNA molecule is activated each S phase. As with chromosomal DNA, further activation is prevented until the next cell cycle. We propose that the mechanism which controls the replication initiation of each 2 micron DNA

  11. The Mark II Vertex Drift Chamber

    International Nuclear Information System (INIS)

    Alexander, J.P.; Baggs, R.; Fujino, D.

    1989-03-01

    We have completed constructing and begun operating the Mark II Drift Chamber Vertex Detector. The chamber, based on a modified jet cell design, achieves 30 μm spatial resolution and 2 gas mixtures. Special emphasis has been placed on controlling systematic errors including the use of novel construction techniques which permit accurate wire placement. Chamber performance has been studied with cosmic ray tracks collected with the chamber located both inside and outside the Mark II. Results on spatial resolution, average pulse shape, and some properties of CO 2 mixtures are presented. 10 refs., 12 figs., 1 tab

  12. THE MARK I BUSINESS SYSTEM SIMULATION MODEL

    Science.gov (United States)

    of a large-scale business simulation model as a vehicle for doing research in management controls. The major results of the program were the...development of the Mark I business simulation model and the Simulation Package (SIMPAC). SIMPAC is a method and set of programs facilitating the construction...of large simulation models. The object of this document is to describe the Mark I Corporation model, state why parts of the business were modeled as they were, and indicate the research applications of the model. (Author)

  13. The Escherichia coli Tus-Ter replication fork barrier causes site-specific DNA replication perturbation in yeast.

    Science.gov (United States)

    Larsen, Nicolai B; Sass, Ehud; Suski, Catherine; Mankouri, Hocine W; Hickson, Ian D

    2014-04-07

    Replication fork (RF) pausing occurs at both 'programmed' sites and non-physiological barriers (for example, DNA adducts). Programmed RF pausing is required for site-specific DNA replication termination in Escherichia coli, and this process requires the binding of the polar terminator protein, Tus, to specific DNA sequences called Ter. Here, we demonstrate that Tus-Ter modules also induce polar RF pausing when engineered into the Saccharomyces cerevisiae genome. This heterologous RF barrier is distinct from a number of previously characterized, protein-mediated, RF pause sites in yeast, as it is neither Tof1-dependent nor counteracted by the Rrm3 helicase. Although the yeast replisome can overcome RF pausing at Tus-Ter modules, this event triggers site-specific homologous recombination that requires the RecQ helicase, Sgs1, for its timely resolution. We propose that Tus-Ter can be utilized as a versatile, site-specific, heterologous DNA replication-perturbing system, with a variety of potential applications.

  14. Recent advances in the genome-wide study of DNA replication origins in yeast

    Directory of Open Access Journals (Sweden)

    Chong ePeng

    2015-02-01

    Full Text Available DNA replication, one of the central events in the cell cycle, is the basis of biological inheritance. In order to be duplicated, a DNA double helix must be opened at defined sites, which are called DNA replication origins (ORIs. Unlike in bacteria, where replication initiates from a single replication origin, multiple origins are utilized in the eukaryotic genome. Among them, the ORIs in budding yeast Saccharomyces cerevisiae and the fission yeast Schizosaccharomyces pombe have been best characterized. In recent years, advances in DNA microarray and next-generation sequencing technologies have increased the number of yeast species involved in ORIs research dramatically. The ORIs in some nonconventional yeast species such as Kluyveromyces lactis and Pichia pastoris have also been genome-widely identified. Relevant databases of replication origins in yeast were constructed, then the comparative genomic analysis can be carried out. Here, we review several experimental approaches that have been used to map replication origins in yeast and some of the available web resources related to yeast ORIs. We also discuss the sequence characteristics and chromosome structures of ORIs in the four yeast species, which can be utilized to improve the replication origins prediction.

  15. Recent advances in the genome-wide study of DNA replication origins in yeast

    Science.gov (United States)

    Peng, Chong; Luo, Hao; Zhang, Xi; Gao, Feng

    2015-01-01

    DNA replication, one of the central events in the cell cycle, is the basis of biological inheritance. In order to be duplicated, a DNA double helix must be opened at defined sites, which are called DNA replication origins (ORIs). Unlike in bacteria, where replication initiates from a single replication origin, multiple origins are utilized in the eukaryotic genomes. Among them, the ORIs in budding yeast Saccharomyces cerevisiae and the fission yeast Schizosaccharomyces pombe have been best characterized. In recent years, advances in DNA microarray and next-generation sequencing technologies have increased the number of yeast species involved in ORIs research dramatically. The ORIs in some non-conventional yeast species such as Kluyveromyces lactis and Pichia pastoris have also been genome-widely identified. Relevant databases of replication origins in yeast were constructed, then the comparative genomic analysis can be carried out. Here, we review several experimental approaches that have been used to map replication origins in yeast and some of the available web resources related to yeast ORIs. We also discuss the sequence characteristics and chromosome structures of ORIs in the four yeast species, which can be utilized to improve yeast replication origins prediction. PMID:25745419

  16. Regional differences in DNA replication in nasal epithelium following acute ozone or cigarette smoke exposure

    International Nuclear Information System (INIS)

    Johnson, N.F.; Hotchkiss, J.A.; Harkema, J.R.; Henderson, R.F.; Mauderly, J.L.; Cuddihy, R.G.

    1988-01-01

    The epithelium of the anterior nasal cavity is composed of four cell types, squamous, respiratory, cuboidal, and olfactory cells. We monitored proliferation In these tissues by bromodeoxy-uridine (BrdUrd) incorporation; the labeled cells were identified by using a monoclonal antibody that recognizes BrdUrd. The respiratory, cuboidal and olfactory epithelia had low cell turnover (1-labeled ceIl/mm basal lamina). Squamous epithelium contained 40-labeled cells per mm basal lamina. Following exposure to diluted mainstream cigarette smoke, a transient, but marked increase in DNA replication was seen in the cuboidal epithelium. In contrast, ozone exposure was associated with DNA replication in the olfactory and respiratory epithelium, as well as in the cuboidal epithelium. These studies show that the sensitivity of nasal epithelium to irritants can be assayed by measuring DNA replication. (author)

  17. Regional differences in DNA replication in nasal epithelium following acute ozone or cigarette smoke exposure

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, N F; Hotchkiss, J A; Harkema, J R; Henderson, R F; Mauderly, J L; Cuddihy, R G

    1988-12-01

    The epithelium of the anterior nasal cavity is composed of four cell types, squamous, respiratory, cuboidal, and olfactory cells. We monitored proliferation In these tissues by bromodeoxy-uridine (BrdUrd) incorporation; the labeled cells were identified by using a monoclonal antibody that recognizes BrdUrd. The respiratory, cuboidal and olfactory epithelia had low cell turnover (1-labeled ceIl/mm basal lamina). Squamous epithelium contained 40-labeled cells per mm basal lamina. Following exposure to diluted mainstream cigarette smoke, a transient, but marked increase in DNA replication was seen in the cuboidal epithelium. In contrast, ozone exposure was associated with DNA replication in the olfactory and respiratory epithelium, as well as in the cuboidal epithelium. These studies show that the sensitivity of nasal epithelium to irritants can be assayed by measuring DNA replication. (author)

  18. 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.

  19. 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.

  20. 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.

  1. 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...

  2. 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.

  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. 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...

  5. Regionaalpoliitika ja arhitektuur / Ülar Mark

    Index Scriptorium Estoniae

    Mark, Ülar

    1999-01-01

    Kagu-Eesti Regionaalarengu Programmi raames Eesti Kunstiakadeemia arhitektuurikateedri IV kursuse eriala valikaines 1998/99 tehtud tööst "HyperMobiilne Reaalsus & Kagu Eesti" (juhendajad Ralf Tamm, Ülar Mark). Ühises töös osalesid Tartu Ülikooli geograafiatudengid (juhendaja Rein Ahas). 4 illustratsiooni

  6. Nekroloog turundusele / Mark Earls ; interv. Margo Kokerov

    Index Scriptorium Estoniae

    Earls, Mark

    2003-01-01

    Turunduskommunikatsioonifirma Ogilvy & Mather suunajuht Mark Earls leiab, et kuna turg on üle ujutatud võrdselt heade toodetega ja tarbija teab, et tegelikult pole oluline, millise toote ta valib, muutub turundusrevolutsiooni keskne idee - tarbijavajaduste kindlakstegemine ja rahuldamine - tähtsusetuks.

  7. 49 CFR 15.13 - Marking SSI.

    Science.gov (United States)

    2010-10-01

    ... SSI. (a) Marking of paper records. In the case of paper records containing SSI, a covered person must... limitation statement on the bottom, of— (1) The outside of any front and back cover, including a binder cover... types of records. In the case of non-paper records that contain SSI, including motion picture films...

  8. Monopoly, Pareto and Ramsey mark-ups

    NARCIS (Netherlands)

    Ten Raa, T.

    2009-01-01

    Monopoly prices are too high. It is a price level problem, in the sense that the relative mark-ups have Ramsey optimal proportions, at least for independent constant elasticity demands. I show that this feature of monopoly prices breaks down the moment one demand is replaced by the textbook linear

  9. Globaalne palavik ja Nord Stream / Mark Soosaar

    Index Scriptorium Estoniae

    Soosaar, Mark, 1946-

    2009-01-01

    Riigikogu keskkonnakomisjoni liikme Mark Soosaare sõnul peaks Eesti Taani eeskujul jõudma parlamentaarse otsuseni loobuda tuumajaamaehitusest, vähendada tuleks märgatavalt Eesti metsade raiumist. Vene-Saksa gaasitarneleppe vastu töötamise asemel tuleks otsida ühisosa nii Venemaa kui teiste Läänemeremaadega

  10. Teaching Mark through a postcolonial optic

    African Journals Online (AJOL)

    2015-07-16

    Jul 16, 2015 ... question, eliciting answers that range from Mark as in direct and open ... or armed response, especially in a context where such actions were unrealistic. (whether ..... identity; social memory; to name a few) of power. It implies ... an elite-driven enterprise in the simplistic sense of the word, although the elite's ...

  11. First results from Mark II at SPEAR

    International Nuclear Information System (INIS)

    Abrams, G.S.; Alam, M.S.; Blocker, C.A.

    1979-05-01

    First results from the SLAC-LBL Mark II magnetic detector at SPEAR are presented. The performance of the detector is discussed and preliminary results are given on inclusive baryon production R/sub p + anti p/, R/sub Λ + anti Λ/, on decay modes of the D mesons and on two-photon production of eta' mesons

  12. 15 CFR 1150.3 - Approved markings.

    Science.gov (United States)

    2010-01-01

    ... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Approved markings. 1150.3 Section 1150.3 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued... permanently affixed to the exterior surface of the barrel, covering the circumference of the barrel from the...

  13. 22 CFR 226.91 - Marking.

    Science.gov (United States)

    2010-04-01

    ... Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ADMINISTRATION OF ASSISTANCE AWARDS TO U.S. NON-GOVERNMENTAL ORGANIZATIONS Miscellaneous § 226.91 Marking. (a) USAID policy is that all programs, projects, activities... support of the American people through the United States Agency for International Development (USAID). The...

  14. Fingerprint Analysis with Marked Point Processes

    DEFF Research Database (Denmark)

    Forbes, Peter G. M.; Lauritzen, Steffen; Møller, Jesper

    We present a framework for fingerprint matching based on marked point process models. An efficient Monte Carlo algorithm is developed to calculate the marginal likelihood ratio for the hypothesis that two observed prints originate from the same finger against the hypothesis that they originate from...... different fingers. Our model achieves good performance on an NIST-FBI fingerprint database of 258 matched fingerprint pairs....

  15. A Collar for Marking Big Game Animals

    Science.gov (United States)

    Robert L. Phillips

    1970-01-01

    A Simple, inexpensive collar made of Armor-tite (a vinyl-coated nylon fabric) was designed for marking white-tailed deer (Odocoileus virginianus) and moose (Alces alces). Field tests showed that the material is easily seen and extrememly durable. It may be suitable for use on other large mammals. The collar can be quickly fitted to individual animals under field...

  16. The Four Marks of Holistic Kinesiology

    Science.gov (United States)

    Twietmeyer, Gregg

    2012-01-01

    What, to borrow a theological phrase, are the marks of a truly holistic kinesiology department? "In Kinesis and the Nature of the Human Person" (2010), I examined the theoretical impact of Aristotle's definition of "kinesis" and Polanyi's theory of "tacit knowledge" on kinesiology. The intention here, however, is practical rather than theoretical.…

  17. Marks & Spencer loob ELis maksupretsedenti / Sirje Rank

    Index Scriptorium Estoniae

    Rank, Sirje, 1966-

    2005-01-01

    Ilmunud ka: Delovõje Vedomosti 13. apr. lk. 6. Briti rõivakett Marks & Spencer kaebas, et Briti maksuseadused, mis ei lubanud emafirma Suurbritannias maksustavast tulust maha kanda Saksamaal, Prantsusmaal ja Belgias asunud tütarfirmade suuri kahjumeid üheksakümnendate aastate lõpus, on vastuolus EL-i ühisturu seadustega

  18. Do clinicians use more question marks?

    NARCIS (Netherlands)

    Zijlmans, Maeike; Otte, Willem M; Van't Klooster, Maryse A; van Diessen, Eric; Leijten, Frans Ss; Sander, Josemir W

    2015-01-01

    OBJECTIVE: To quantify the use of question marks in titles of published studies. DESIGN AND SETTING: Literature review. PARTICIPANTS: All Pubmed publications between 1 January 2013 and 31 December 2013 with an available abstract. Papers were classified as being clinical when the search terms clin*,

  19. 27 CFR 28.216 - Export marks.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Export marks. 28.216 Section 28.216 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS EXPORTATION OF ALCOHOL Exportation of Wine With Benefit of Drawback § 28.216...

  20. Primary Science Quality Mark--2016 Update

    Science.gov (United States)

    Turner, Jane

    2016-01-01

    Back in May 2011, an article in "Primary Science" described how the idea for a quality mark for primary science was developed from an initial conversation at an Association for Science Education annual conference (Turner, Marshall and Elsmore, 2011). Its intention then, as now, was to support and champion good practice and raise the…

  1. 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...

  2. 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...

  3. 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...

  4. Recovery of arrested replication forks by homologous recombination is error-prone.

    Directory of Open Access Journals (Sweden)

    Ismail Iraqui

    Full Text Available Homologous recombination is a universal mechanism that allows repair of DNA and provides support for DNA replication. Homologous recombination is therefore a major pathway that suppresses non-homology-mediated genome instability. Here, we report that recovery of impeded replication forks by homologous recombination is error-prone. Using a fork-arrest-based assay in fission yeast, we demonstrate that a single collapsed fork can cause mutations and large-scale genomic changes, including deletions and translocations. Fork-arrest-induced gross chromosomal rearrangements are mediated by inappropriate ectopic recombination events at the site of collapsed forks. Inverted repeats near the site of fork collapse stimulate large-scale genomic changes up to 1,500 times over spontaneous events. We also show that the high accuracy of DNA replication during S-phase is impaired by impediments to fork progression, since fork-arrest-induced mutation is due to erroneous DNA synthesis during recovery of replication forks. The mutations caused are small insertions/duplications between short tandem repeats (micro-homology indicative of replication slippage. Our data establish that collapsed forks, but not stalled forks, recovered by homologous recombination are prone to replication slippage. The inaccuracy of DNA synthesis does not rely on PCNA ubiquitination or trans-lesion-synthesis DNA polymerases, and it is not counteracted by mismatch repair. We propose that deletions/insertions, mediated by micro-homology, leading to copy number variations during replication stress may arise by progression of error-prone replication forks restarted by homologous recombination.

  5. Distinguishing butchery cut marks from crocodile bite marks through machine learning methods.

    Science.gov (United States)

    Domínguez-Rodrigo, Manuel; Baquedano, Enrique

    2018-04-10

    All models of evolution of human behaviour depend on the correct identification and interpretation of bone surface modifications (BSM) on archaeofaunal assemblages. Crucial evolutionary features, such as the origin of stone tool use, meat-eating, food-sharing, cooperation and sociality can only be addressed through confident identification and interpretation of BSM, and more specifically, cut marks. Recently, it has been argued that linear marks with the same properties as cut marks can be created by crocodiles, thereby questioning whether secure cut mark identifications can be made in the Early Pleistocene fossil record. Powerful classification methods based on multivariate statistics and machine learning (ML) algorithms have previously successfully discriminated cut marks from most other potentially confounding BSM. However, crocodile-made marks were marginal to or played no role in these comparative analyses. Here, for the first time, we apply state-of-the-art ML methods on crocodile linear BSM and experimental butchery cut marks, showing that the combination of multivariate taphonomy and ML methods provides accurate identification of BSM, including cut and crocodile bite marks. This enables empirically-supported hominin behavioural modelling, provided that these methods are applied to fossil assemblages.

  6. 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.)

  7. 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).

  8. 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.

  9. 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.

  10. 19 CFR 11.9 - Special marking on certain articles.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Special marking on certain articles. 11.9 Section... OF THE TREASURY PACKING AND STAMPING; MARKING Marking § 11.9 Special marking on certain articles. (a... of additional U.S. Note 4, Chapter 91. If any article so required to be marked is found not to be...

  11. 19 CFR 134.43 - Methods of marking specific articles.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Methods of marking specific articles. 134.43...; DEPARTMENT OF THE TREASURY COUNTRY OF ORIGIN MARKING Method and Location of Marking Imported Articles § 134.43 Methods of marking specific articles. (a) Marking previously required by certain provisions of the...

  12. 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

  13. 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

  14. 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

  15. A study of an adaptive replication framework for orchestrated composite web services.

    Science.gov (United States)

    Mohamed, Marwa F; Elyamany, Hany F; Nassar, Hamed M

    2013-01-01

    Replication is considered one of the most important techniques to improve the Quality of Services (QoS) of published Web Services. It has achieved impressive success in managing resource sharing and usage in order to moderate the energy consumed in IT environments. For a robust and successful replication process, attention should be paid to suitable time as well as the constraints and capabilities in which the process runs. The replication process is time-consuming since outsourcing some new replicas into other hosts is lengthy. Furthermore, nowadays, most of the business processes that might be implemented over the Web are composed of multiple Web services working together in two main styles: Orchestration and Choreography. Accomplishing a replication over such business processes is another challenge due to the complexity and flexibility involved. In this paper, we present an adaptive replication framework for regular and orchestrated composite Web services. The suggested framework includes a number of components for detecting unexpected and unhappy events that might occur when consuming the original published web services including failure or overloading. It also includes a specific replication controller to manage the replication process and select the best host that would encapsulate a new replica. In addition, it includes a component for predicting the incoming load in order to decrease the time needed for outsourcing new replicas, enhancing the performance greatly. A simulation environment has been created to measure the performance of the suggested framework. The results indicate that adaptive replication with prediction scenario is the best option for enhancing the performance of the replication process in an online business environment.

  16. Real-time single-molecule observation of rolling-circle DNA replication

    NARCIS (Netherlands)

    Tanner, Nathan A.; Loparo, Joseph J.; Hamdan, Samir M.; Jergic, Slobodan; Dixon, Nicholas E.; Oijen, Antoine M. van

    2009-01-01

    We present a simple technique for visualizing replication of individual DNA molecules in real time. By attaching a rolling-circle substrate to a TIRF microscope-mounted flow chamber, we are able to monitor the progression of single-DNA synthesis events and accurately measure rates and processivities

  17. 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.

  18. 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

  19. 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.)

  20. Minnesota Local Agency Pavement Marking : Mining Existing Data

    Science.gov (United States)

    2017-11-01

    Pavement marking is important for safety. Maximizing pavement marking performance in terms of increased retroreflectivity, within limited budget constraints, allows agencies to make better decisions toward providing more effective pavement marking pe...

  1. 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.

  2. Revised Mark 22 coolant temperature coefficients

    International Nuclear Information System (INIS)

    Graves, W.E.

    1987-01-01

    Coolant temperature coefficients for the Mark 22 charge published previously are non-conservative because of the neglect of a significant mechanism which has a positive contribution to reactivity. Even after correcting for this effect, dynamic tests made on a Mark VIB charge in the early 60's suggest the results are still non-conservative. This memorandum takes both of these sources of information into account in making a best estimate of the prompt (coolant plus metal) temperature coefficient. Although no safety issues arise from this work (the overall temperature coefficient still strongly contributes to reactor stability), it is obviously desirable to use best estimates for prompt coefficients in limits and other calculations

  3. EcoMark 2.0

    DEFF Research Database (Denmark)

    Guo, Chenjuan; Yang, Bin; Andersen, Ove

    2015-01-01

    Eco-routing is a simple yet effective approach to substantially reducing the environmental impact, e.g., fuel consumption and greenhouse gas (GHG) emissions, of vehicular transportation. Eco-routing relies on the ability to reliably quantify the environmental impact of vehicles as they travel...... in a spatial network. The procedure of quantifying such vehicular impact for road segments of a spatial network is called eco-weight assignment. EcoMark 2.0 proposes a general framework for eco-weight assignment to enable eco-routing. It studies the abilities of six instantaneous and five aggregated models......, and experiments for assessing the utility of the impact models in assigning eco-weights. The application of EcoMark 2.0 indicates that the instantaneous model EMIT and the aggregated model SIDRA-Running are suitable for assigning eco-weights under varying circumstances. In contrast, other instantaneous models...

  4. Geologic bench marks by terrestrial photography

    Science.gov (United States)

    Malde, Harold E.

    1973-01-01

    A photograph made with a level camera, if taken at a known height above a permanent mark on the ground, can be later repeated with exactness for measurement of changes in terrain. Such a photograph is one of several means for establishing a geologic bench mark and is especially useful for monitoring the subtle qualities of a landscape that are otherwise hard to map and describe, including the effects of man's use. Moreover, the geometry of such a photograph provides the same angular measurements between objects as can be made with a transit. A measurement of distance on a single photograph, however, requires control points. These can be surveyed at any convenient time, not necessarily when the initial photograph is made. Distances can also be determined by simple stereophotography from a base line of suitable length.

  5. Identification marking by means of laser peening

    Science.gov (United States)

    Hackel, Lloyd A.; Dane, C. Brent; Harris, Fritz

    2002-01-01

    The invention is a method and apparatus for marking components by inducing a shock wave on the surface that results in an indented (strained) layer and a residual compressive stress in the surface layer. One embodiment of the laser peenmarking system rapidly imprints, with single laser pulses, a complete identification code or three-dimensional pattern and leaves the surface in a state of deep residual compressive stress. A state of compressive stress in parts made of metal or other materials is highly desirable to make them resistant to fatigue failure and stress corrosion cracking. This process employs a laser peening system and beam spatial modulation hardware or imaging technology that can be setup to impress full three dimensional patterns into metal surfaces at the pulse rate of the laser, a rate that is at least an order of magnitude faster than competing marking technologies.

  6. Monopoly, Pareto and Ramsey mark-ups

    OpenAIRE

    Ten Raa, T.

    2009-01-01

    Monopoly prices are too high. It is a price level problem, in the sense that the relative mark-ups have Ramsey optimal proportions, at least for independent constant elasticity demands. I show that this feature of monopoly prices breaks down the moment one demand is replaced by the textbook linear demand or, even within the constant elasticity framework, dependence is introduced. The analysis provides a single Generalized Inverse Elasticity Rule for the problems of monopoly, Pareto and Ramsey.

  7. Utilization of Slovenian TRIGA Mark II reactor

    International Nuclear Information System (INIS)

    Snoj, L.; Smodis, B.

    2010-01-01

    TRIGA Mark II research reactor at the Jozef Stefan Institute [JSI] is extensively used for various applications, such as: irradiation of various samples, training and education, verification and validation of nuclear data and computer codes, testing and development of experimental equipment used for core physics tests at a nuclear power plant. The paper briefly describes the aforementioned activities and shows that even such small reactors are still indispensable in nuclear science and technology. (author)

  8. High efficiency metal marking with CO2 laser and glass marking with excimer laser

    DEFF Research Database (Denmark)

    Bastue, Jens; Olsen, Flemmming Ove

    1997-01-01

    with a thoroughly tested ray-tracing model is presented and compared with experimental results. Special emphasis is put on two different applications namely marking in metal with TEA-CO2 laser and marking in glass with excimer laser. The results are evaluated on the basis of the achievable energy enhancement......Today, mask based laser materials processing and especially marking is widely used. However, the energy efficiency in such processes is very low [1].This paper gives a review of the results, that may be obtained using the energy enhancing technique [1]. Results of simulations performed...

  9. 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

  10. 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)

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. Dynamic remodeling of lipids coincides with dengue virus replication in the midgut of Aedes aegypti mosquitoes.

    Directory of Open Access Journals (Sweden)

    Nunya Chotiwan

    2018-02-01

    Full Text Available We describe the first comprehensive analysis of the midgut metabolome of Aedes aegypti, the primary mosquito vector for arboviruses such as dengue, Zika, chikungunya and yellow fever viruses. Transmission of these viruses depends on their ability to infect, replicate and disseminate from several tissues in the mosquito vector. The metabolic environments within these tissues play crucial roles in these processes. Since these viruses are enveloped, viral replication, assembly and release occur on cellular membranes primed through the manipulation of host metabolism. Interference with this virus infection-induced metabolic environment is detrimental to viral replication in human and mosquito cell culture models. Here we present the first insight into the metabolic environment induced during arbovirus replication in Aedes aegypti. Using high-resolution mass spectrometry, we have analyzed the temporal metabolic perturbations that occur following dengue virus infection of the midgut tissue. This is the primary site of infection and replication, preceding systemic viral dissemination and transmission. We identified metabolites that exhibited a dynamic-profile across early-, mid- and late-infection time points. We observed a marked increase in the lipid content. An increase in glycerophospholipids, sphingolipids and fatty acyls was coincident with the kinetics of viral replication. Elevation of glycerolipid levels suggested a diversion of resources during infection from energy storage to synthetic pathways. Elevated levels of acyl-carnitines were observed, signaling disruptions in mitochondrial function and possible diversion of energy production. A central hub in the sphingolipid pathway that influenced dihydroceramide to ceramide ratios was identified as critical for the virus life cycle. This study also resulted in the first reconstruction of the sphingolipid pathway in Aedes aegypti. Given conservation in the replication mechanisms of several

  16. Dynamic remodeling of lipids coincides with dengue virus replication in the midgut of Aedes aegypti mosquitoes.

    Science.gov (United States)

    Chotiwan, Nunya; Andre, Barbara G; Sanchez-Vargas, Irma; Islam, M Nurul; Grabowski, Jeffrey M; Hopf-Jannasch, Amber; Gough, Erik; Nakayasu, Ernesto; Blair, Carol D; Belisle, John T; Hill, Catherine A; Kuhn, Richard J; Perera, Rushika

    2018-02-01

    We describe the first comprehensive analysis of the midgut metabolome of Aedes aegypti, the primary mosquito vector for arboviruses such as dengue, Zika, chikungunya and yellow fever viruses. Transmission of these viruses depends on their ability to infect, replicate and disseminate from several tissues in the mosquito vector. The metabolic environments within these tissues play crucial roles in these processes. Since these viruses are enveloped, viral replication, assembly and release occur on cellular membranes primed through the manipulation of host metabolism. Interference with this virus infection-induced metabolic environment is detrimental to viral replication in human and mosquito cell culture models. Here we present the first insight into the metabolic environment induced during arbovirus replication in Aedes aegypti. Using high-resolution mass spectrometry, we have analyzed the temporal metabolic perturbations that occur following dengue virus infection of the midgut tissue. This is the primary site of infection and replication, preceding systemic viral dissemination and transmission. We identified metabolites that exhibited a dynamic-profile across early-, mid- and late-infection time points. We observed a marked increase in the lipid content. An increase in glycerophospholipids, sphingolipids and fatty acyls was coincident with the kinetics of viral replication. Elevation of glycerolipid levels suggested a diversion of resources during infection from energy storage to synthetic pathways. Elevated levels of acyl-carnitines were observed, signaling disruptions in mitochondrial function and possible diversion of energy production. A central hub in the sphingolipid pathway that influenced dihydroceramide to ceramide ratios was identified as critical for the virus life cycle. This study also resulted in the first reconstruction of the sphingolipid pathway in Aedes aegypti. Given conservation in the replication mechanisms of several flaviviruses transmitted

  17. CHARITY EVENT

    CERN Multimedia

    STAFF ASSOCIATION

    2010-01-01

    Fund raising Pakistan     Dear Colleagues, Following the monsoon rains that have caused devastating flooding in Pakistan, taken the lives of more than 1500 people, displaced 20 million and destroyed hundreds of thousands of homes, CERN Management and the Staff Association are organizing a collection to help the victims of what UN Secretary General, Ban Ki-moon, has described as a disaster worse than any he has witnessed before. The money collected will be transferred equally to Caritas (www.caritas.ch) and to the Swiss Labour Assistance (www.sah.ch) guaranteeing proper use of the funds. From today you can pay your donations into a special UBS account, marking “Pakistan flooding” as the reason for payment.   BIC:        UBSWCHZH80A IBAN:    CH85 0027 9279 HU10 6832 1 Account number: 279-HU106832.1 Account Holder: Association du personnel CERN, 1211 GENEVA 23   Mr Ban went on to sa...

  18. Mark Raidpere näitused Pariisis ja Napolis / Mark Raidpere ; interv. Harry Liivrand

    Index Scriptorium Estoniae

    Raidpere, Mark

    2008-01-01

    Mark Raidpere videod "Vekovka", "Dedication / Pühendus", "Majestoso Mystico" näitusel Pariisis Michel Reini galeriis. Osaleb koos saksa fotograafi Sven Johnega näitusel Napolis. Kreekas Thessalonikis valminud filmist "1:1:1"

  19. Mirror-mark tests performed on jackdaws reveal potential methodological problems in the use of stickers in avian mark-test studies.

    Directory of Open Access Journals (Sweden)

    Manuel Soler

    Full Text Available Some animals are capable of recognizing themselves in a mirror, which is considered to be demonstrated by passing the mark test. Mirror self-recognition capacity has been found in just a few mammals having very large brains and only in one bird, the magpie (Pica pica. The results obtained in magpies have enormous biological and cognitive implications because the fact that magpies were able to pass the mark test meant that this species is at the same cognitive level with great apes, that mirror self-recognition has evolved independently in the magpie and great apes (which diverged 300 million years ago, and that the neocortex (which is not present in the bird's brains is not a prerequisite for mirror self-recognition as previously believed. Here, we have replicated the experimental design used on magpies to determine whether jackdaws (Corvus monedula are also capable of mirror self-recognition by passing the mark test. We found that our nine jackdaws showed a very high interest towards the mirror and exhibited self-contingent behavior as soon as mirrors were introduced. However, jackdaws were not able to pass the mark test: both sticker-directed actions and sticker removal were performed with a similar frequency in both the cardboard (control and the mirror conditions. We conclude that our jackdaws' behaviour raises non-trivial questions about the methodology used in the avian mark test. Our study suggests that the use of self-adhesive stickers on sensitive throat feathers may open the way to artefactual results because birds might perceive the stickers tactilely.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. Hda inactivation of DnaA is the predominant mechanism preventing hyperinitiation of Escherichia coli DNA replication.

    Science.gov (United States)

    Camara, Johanna E; Breier, Adam M; Brendler, Therese; Austin, Stuart; Cozzarelli, Nicholas R; Crooke, Elliott

    2005-08-01

    Initiation of DNA replication from the Escherichia coli chromosomal origin is highly regulated, assuring that replication occurs precisely once per cell cycle. Three mechanisms for regulation of replication initiation have been proposed: titration of free DnaA initiator protein by the datA locus, sequestration of newly replicated origins by SeqA protein and regulatory inactivation of DnaA (RIDA), in which active ATP-DnaA is converted to the inactive ADP-bound form. DNA microarray analyses showed that the level of initiation in rapidly growing cells that lack datA was indistinguishable from that in wild-type cells, and that the absence of SeqA protein caused only a modest increase in initiation, in agreement with flow-cytometry data. In contrast, cells lacking Hda overinitiated replication twofold, implicating RIDA as the predominant mechanism preventing extra initiation events in a cell cycle.

  6. Genome-wide mapping reveals single-origin chromosome replication in Leishmania, a eukaryotic microbe.

    Science.gov (United States)

    Marques, Catarina A; Dickens, Nicholas J; Paape, Daniel; Campbell, Samantha J; McCulloch, Richard

    2015-10-19

    DNA replication initiates on defined genome sites, termed origins. Origin usage appears to follow common rules in the eukaryotic organisms examined to date: all chromosomes are replicated from multiple origins, which display variations in firing efficiency and are selected from a larger pool of potential origins. To ask if these features of DNA replication are true of all eukaryotes, we describe genome-wide origin mapping in the parasite Leishmania. Origin mapping in Leishmania suggests a striking divergence in origin usage relative to characterized eukaryotes, since each chromosome appears to be replicated from a single origin. By comparing two species of Leishmania, we find evidence that such origin singularity is maintained in the face of chromosome fusion or fission events during evolution. Mapping Leishmania origins suggests that all origins fire with equal efficiency, and that the genomic sites occupied by origins differ from related non-origins sites. Finally, we provide evidence that origin location in Leishmania displays striking conservation with Trypanosoma brucei, despite the latter parasite replicating its chromosomes from multiple, variable strength origins. The demonstration of chromosome replication for a single origin in Leishmania, a microbial eukaryote, has implications for the evolution of origin multiplicity and associated controls, and may explain the pervasive aneuploidy that characterizes Leishmania chromosome architecture.

  7. Event Index - a LHCb Event Search System

    CERN Document Server

    INSPIRE-00392208; Kazeev, Nikita; Redkin, Artem

    2015-12-23

    LHC experiments generate up to $10^{12}$ events per year. This paper describes Event Index - an event search system. Event Index's primary function is quickly selecting subsets of events from a combination of conditions, such as the estimated decay channel or stripping lines output. Event Index is essentially Apache Lucene optimized for read-only indexes distributed over independent shards on independent nodes.

  8. 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.

  9. 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.

  10. 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....

  11. 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.

  12. 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.

  13. 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...

  14. Radiation-induced mutation frequency in marked chromosome of Macaca mulatta

    International Nuclear Information System (INIS)

    Dzhemilev, Z.A.; Machavariani, M.G.

    1976-01-01

    The symmetric and asymmetric exchange frequencies of marked (nucleolus forming) chromosomes were studied in the lymphocytes and epithelial kidney cells irradiated by X-rays at G 0 , both in vivo and in vitro. Symmetric and asymmetric exchange frequencies were found to be equal. In both the types of Macaca mulatta cells, the exchange frequency in the long arm appeared to be higher than theoretically expected. The increased exchange in the long arm is thought to be due to a greater quantity of late replicating heterochromatin in it. The short arm of marked chromosome of epithelial kidney cells enters the exchange in accordance to its length in mitosis, but exchange number in the short arm chromosome in lymphocytes is lower than in epithelial cells. This difference is caused likely by different functioning of the nucleolus forming heterochromatin. (author)

  15. 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

  16. Decontamination of TRIGA Mark II reactor, Indonesia

    International Nuclear Information System (INIS)

    Suseno, H.; Daryoko, M.; Goeritno, A.

    2002-01-01

    The TRIGA Mark II Reactor in the Centre for Research and Development Nuclear Technique Bandung has been partially decommissioned as part of an upgrading project. The upgrading project was carried out from 1995 to 2000 and is being commissioned in 2001. The decommissioning portion of the project included disassembly of some components of the reactor core, producing contaminated material. This contaminated material (grid plate, reflector, thermal column, heat exchanger and pipe) will be sent to the Decontamination Facility at the Radioactive Waste Management Development Centre. (author)

  17. The Mark II detector for the SLC

    International Nuclear Information System (INIS)

    Abrams, G.; Baden, A.R.; Boyer, J.; Butler, F.; Drell, P.S.; Fay, J.; Gidal, G.; Goldhaber, G.; Haggerty, J.; Harr, R.; Hearty, C.; Herrup, D.; Holmgren, S.O.; Jaffre, M.; Juricic, I.; Kadyk, J.A.; Kral, J.F.; Levi, M.E.; Lynch, G.R.; Richman, J.D.; Rouse, F.R.; Schaad, M.W.; Schmidke, W.B.; Schumm, B.A.; Trilling, G.H.; Wood, D.R.; Akerlof, C.; Bonvicini, G.; Chapman, J.; Chmeissani, M.; Frey, R.; Gero, E.; Hong, S.J.; Koska, W.; Nitz, D.; Petradza, M.; Thun, R.; Tschirhart, R.; Veltman, H.; Alexander, J.P.; Ballam, J.; Barklow, T.; Bartelt, J.; De Boer, W.; Boyarski, A.; Braune, K.; Bulos, F.; Burke, D.L.; Cords, D.; Coupal, D.P.; Destaebler, H.C.; Dorfan, J.M.; Feldman, G.J.; Fernandes, D.; Field, R.C.; Fordham, C.; Fujino, D.; Gan, K.K.; Glanzman, T.; Grosse-Wiesmann, P.; Hanson, G.; Hayes, K.; Himel, T.; Hutchinson, D.; Innes, W.R.; Jacobsen, R.G.; Jaros, J.A.; Jung, C.K.; Karlen, D.; Klein, S.R.; Koetke, D.; Komamiya, M.; Kowalski, L.A.; Kozanecki, W.; Lankford, A.J.; Larsen, R.R.; Lueth, V.; Mattison, T.; Moffeit, K.C.; Mueller, L.; Munger, C.T.; Nash, J.; Ong, R.A.; O'Shaughnessy, K.F.; Perl, J.; Perl, M.L.; Perrier, F.; Petersen, A.; Pitthan, R.; Riles, K.; Swartz, M.; Taylor, R.E.; Van Kooten, R.; Voruganti, P.; Weigend, A.; Woods, M.; Wormser, G.; Wright, R.; Alvarez, M.; Calvino, F.; Fernandez, E.; Ford, W.T.; Hinshaw, D.A.; Rankin, P.; Smith, J.G.; Wagner, S.R.; Weber, P.; White, S.L.; Averill, D.; Blockus, D.; Brabson, B.; Brom, J.M.; Murray, W.N.; Ogren, H.; Rust, D.R.; Snyder, A.; Yurko, M.; Barish, B.C.; Hawkes, C.M.; Hoenk, M.; Kuhlen, M.; Li, Z.; McKenna, J.A.; Milliken, B.D.; Nelson, M.E.; Peck, C.; Porter, F.C.; Soderstrom, E.; Stroynowski, R.; Weinstein, A.J.; Weir, A.J.; Wicklund, E.; Wolf, R.C.; Wu, D.Y.; Barnett, B.A.; Boswell, C.; Dauncey, P.; Drewer, D.C.; Harral, B.; Hylen, J.; Matthews, J.A.J.; Stoker, D.P.; Vejcik, S.; Breakstone, A.; Cence, R.J.; Gong, X.; Harris, F.A.; Koide, A.; Parker, S.I.; Green, A.; Lawrence Berkeley Lab., CA; California Univ., Berkeley

    1989-01-01

    The Mark II detector has been upgraded in preparation for its role as the first detector to take data at the Stanford Linear Collider. The new detector components include the central drift chamber, the time-of-flight system, the coil, the endcap electromagnetic calorimeters and the beam energy and luminosity measuring devices. There have also been improvements in detector hermeticity. All of the major components were installed for a test run at the PEP storage ring (√s=29 GeV) in 1985. This paper describes the upgraded detector, including its trigger and data acquisition systems, and gives performance figures for its components. Future improvements are also discussed. (orig.)

  18. Kuosheng Mark III containment analyses using GOTHIC

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Ansheng, E-mail: samuellin1999@iner.gov.tw; Chen, Yen-Shu; Yuann, Yng-Ruey

    2013-10-15

    Highlights: • The Kuosheng Mark III containment model is established using GOTHIC. • Containment pressure and temperature responses due to LOCA are presented. • The calculated results are all below the design values and compared with the FSAR results. • The calculated results can be served as an analysis reference for an SPU project in the future. -- Abstract: Kuosheng nuclear power plant in Taiwan is a twin-unit BWR/6 plant, and both units utilize the Mark III containment. Currently, the plant is performing a stretch power uprate (SPU) project to increase the core thermal power to 103.7% OLTP (original licensed thermal power). However, the containment response in the Kuosheng Final Safety Analysis Report (FSAR) was completed more than twenty-five years ago. The purpose of this study is to establish a Kuosheng Mark III containment model using the containment program GOTHIC. The containment pressure and temperature responses under the design-basis accidents, which are the main steam line break (MSLB) and the recirculation line break (RCLB) accidents, are investigated. Short-term and long-term analyses are presented in this study. The short-term analysis is to calculate the drywell peak pressure and temperature which happen in the early stage of the LOCAs. The long-term analysis is to calculate the peak pressure and temperature of the reactor building space. In the short-term analysis, the calculated peak drywell to wetwell differential pressure is 140.6 kPa for the MSLB, which is below than the design value of 189.6 kPa. The calculated peak drywell temperature is 158 °C, which is still below the design value of 165.6 °C. In addition, in the long-term analysis, the calculated peak containment pressure is 47 kPa G, which is below the design value of 103.4 kPa G. The calculated peak values of containment temperatures are 74.7 °C, which is lower than the design value of 93.3 °C. Therefore, the Kuosheng Mark III containment can maintain the integrity after

  19. MARK II end cap calorimeter electronics

    International Nuclear Information System (INIS)

    Jared, R.C.; Haggerty, J.S.; Herrup, D.A.; Kirsten, F.A.; Lee, K.L.; Olson, S.R.; Wood, D.R.

    1985-10-01

    An end cap calorimeter system has been added to the MARK II detector in preparation for its use at the SLAC Linear Collider. The calorimeter uses 8744 rectangular proportional counter tubes. This paper describes the design features of the data acquisition electronics that has been installed on the calorimeter. The design and use of computer-based test stands for the amplification and signal-shaping components is also covered. A portion of the complete system has been tested in a beam at SLAC. In these initial tests, using only the calibration provided by the test stands, a resolution of 18%/√E was achieved

  20. 46 CFR 78.50-5 - Hull markings.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 3 2010-10-01 2010-10-01 false Hull markings. 78.50-5 Section 78.50-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) PASSENGER VESSELS OPERATIONS Markings on Vessels § 78.50-5 Hull markings. Vessels shall be marked as required by parts 67 and 69 of this chapter. [CGD 72...

  1. 46 CFR 196.40-5 - Hull markings.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Hull markings. 196.40-5 Section 196.40-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Markings on Vessels § 196.40-5 Hull markings. Vessels shall be marked as required by parts 67 and 69 of this chapter...

  2. 46 CFR 97.40-5 - Hull markings.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Hull markings. 97.40-5 Section 97.40-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CARGO AND MISCELLANEOUS VESSELS OPERATIONS Markings on Vessels § 97.40-5 Hull markings. Vessels shall be marked as required by parts 67 and 69 of this...

  3. Circulatory Markings at Double-Lane Traffic Roundabout.

    NARCIS (Netherlands)

    Bie, Jing; Lo, Hong K.; Wong, S.C.

    2008-01-01

    This paper compares two types of circulatory markings at a double-lane traffic roundabout: the concentric marking scheme and the Alberta marking scheme. The effects of these two marking schemes on drivers' lane choice behavior, delay, and safety, are compared based on data collected from before and

  4. Simulating events

    Energy Technology Data Exchange (ETDEWEB)

    Ferretti, C; Bruzzone, L [Techint Italimpianti, Milan (Italy)

    2000-06-01

    The Petacalco Marine terminal on the Pacific coast in the harbour of Lazaro Carclenas (Michoacan) in Mexico, provides coal to the thermoelectric power plant at Pdte Plutarco Elias Calles in the port area. The plant is being converted from oil to burn coal to generate 2100 MW of power. The article describes the layout of the terminal and equipment employed in the unloading, coal stacking, coal handling areas and the receiving area at the power plant. The contractor Techint Italimpianti has developed a software system, MHATIS, for marine terminal management which is nearly complete. The discrete event simulator with its graphic interface provides a real-type decision support system for simulating changes to the terminal operations and evaluating impacts. The article describes how MHATIS is used. 7 figs.

  5. Event generators

    International Nuclear Information System (INIS)

    Durand, D.; Gulminelli, F.; Lopez, O.; Vient, E.

    1998-01-01

    The results concerning the heavy ion collision simulations at Fermi energies by means of phenomenological models obtained in the last two years ar presented. The event generators are essentially following the phase of elaboration of analysis methods of data obtained by INDRA or NAUTILUS 4 π multidetectors. To identify and correctly quantify a phenomenon or a physical quantity it is necessary to verify by simulation the feasibility and validity of the analysis and also to estimate the bias introduced by the experimental filter. Many studies have shown this, for instance: the determination of the collision reaction plan for flow studies, determination of kinematical characteristics of the quasi-projectiles, and the excitation energy measurement stored in the hot nuclei. To Eugene, the currently utilised generator, several improvements were added: introduction of space-time correlations between the different products emitted in the decay of excited nuclei by calculating the trajectories of the particles in the final phase of the reaction; taking into account in the decay cascade of the discrete levels of the lighter fragments; the possibility of the schematically description of the explosion of the nucleus by simultaneous emission of multi-fragments. Thus, by comparing the calculations with the data relative to heavy systems studied with the NAUTILUS assembly it was possible to extract the time scales in the nuclear fragmentation. The utilisation of these event generators was extended to the analysis of INDRA data concerning the determination of the vaporization threshold in the collisions Ar + Ni and also the research of the expansion effects in the collisions Xe + Sn at 50 MeV/u

  6. 1L Mark-IV Target Design Review

    Energy Technology Data Exchange (ETDEWEB)

    Koehler, Paul E. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-11-16

    This presentation includes General Design Considerations; Current (Mark-III) Lower Tier; Mark-III Upper Tier; Performance Metrics; General Improvements for Material Science; General Improvements for Nuclear Science; Improving FOM for Nuclear Science; General Design Considerations Summary; Design Optimization Studies; Expected Mark-IV Performance: Material Science; Expected Mark-IV Performance: Nuclear Science (Disk); Mark IV Enables Much Wider Range of Nuclear-Science FOM Gains than Mark III; Mark-IV Performance Summary; Rod or Disk? Center or Real FOV?; and Project Cost and Schedule.

  7. Nuclear particle track-etched anti-bogus mark

    International Nuclear Information System (INIS)

    He Xiangming; Yan Yushun; Zhang Quanrong

    2003-01-01

    Nuclear particle track-etched anti-bogus mark is a new type of forgery-proof product after engraving gravure printing, thermocolour, fluorescence, laser hologram and metal concealed anti-bogus mark. The mark is manufactured by intricate high technology and the state strictly controlled sensitive nuclear facilities to ensure the mark not to be copied. The pattern of the mark is specially characterized by permeability of liquid to be discriminated from forgery. The genuine mark can be distinguished from sham one by transparent liquid (e.g. water), colorful pen and chemical reagent. The mark has passed the official examination of health safety. It is no danger of nuclear irradiation. (author)

  8. Risk analysis of brachytherapy events

    International Nuclear Information System (INIS)

    Buricova, P.; Zackova, H.; Hobzova, L.; Novotny, J.; Kindlova, A.

    2005-01-01

    For prevention radiological events it is necessary to identify hazardous situation and to analyse the nature of committed errors. Though the recommendation on the classification and prevention of radiological events: Radiological accidents has been prepared in the framework of Czech Society of Radiation Oncology, Biology and Physics and it was approved by Czech regulatory body (SONS) in 1999, only a few reports have been submitted up to now from brachytherapy practice. At the radiotherapy departments attention has been paid more likely to the problems of dominant teletherapy treatments. But in the two last decades the usage of brachytherapy methods has gradually increased because .nature of this treatment well as the possibilities of operating facility have been completely changed: new radionuclides of high activity are introduced and sophisticate afterloading systems controlled by computers are used. Consequently also the nature of errors, which can occurred in the clinical practice, has been changing. To determine the potentially hazardous parts of procedure the so-called 'process tree', which follows the flow of entire treatment process, has been created for most frequent type of applications. Marking the location of errors on the process tree indicates where failures occurred and accumulation of marks along branches show weak points in the process. Analysed data provide useful information to prevent medical events in brachytherapy .The results strength the requirements given in Recommendations of SONS and revealed the need for its amendment. They call especially for systematic registration of the events. (authors)

  9. Chromosome Replication in Escherichia coli: Life on the Scales

    Science.gov (United States)

    Norris, Vic; Amar, Patrick

    2012-01-01

    At all levels of Life, systems evolve on the 'scales of equilibria'. At the level of bacteria, the individual cell must favor one of two opposing strategies and either take risks to grow or avoid risks to survive. It has been proposed in the Dualism hypothesis that the growth and survival strategies depend on non-equilibrium and equilibrium hyperstructures, respectively. It has been further proposed that the cell cycle itself is the way cells manage to balance the ratios of these types of hyperstructure so as to achieve the compromise solution of living on the two scales. Here, we attempt to re-interpret a major event, the initiation of chromosome replication in Escherichia coli, in the light of scales of equilibria. This entails thinking in terms of hyperstructures as responsible for intensity sensing and quantity sensing and how this sensing might help explain the role of the DnaA protein in initiation of replication. We outline experiments and an automaton approach to the cell cycle that should test and refine the scales concept. PMID:25371267

  10. Deposition in St. Mark's Basilica of Venice.

    Science.gov (United States)

    Morabito, E; Zendri, E; Piazza, R; Ganzerla, R; Montalbani, S; Marcoleoni, E; Bonetto, F; Scandella, A; Barbante, C; Gambaro, A

    2013-04-01

    Atmospheric pollutants may cause damage to monuments and historical buildings. Besides air contaminants, soluble salts are also responsible for stone deterioration and decay in outdoor and indoor monuments. The problem of how to conserve works of arts thus requires a deep knowledge of contaminants' concentration and distribution inside buildings. In this work, water-soluble ions inside St. Mark's Basilica in Venice were studied, with the aim of understanding their principal source and distribution inside the building. With the aid of Fourier transform infrared spectroscopy and scanning electron microscopy analysis, the interaction between ions and surface's material was also investigated. Ion chromatographic analysis of depositions highlighted a large amount of "deteriorating agents" such as sulphates and chlorides. A possible source in the innermost area of the basilica has been found for formates and nitrates. On the contrary, a decrease of chloride, from the entrance to the innermost area, has been found, which indicates that the source is outside the building. It is emphasized that different contaminants behave differently on different material, and the effect of pollution inside churches and monuments is not easy to predict. Wood and brick seem to react differently than stone and mortar to the damaging action of salts and pollutants. The present work should be considered a useful tool for the future preservation of St. Mark's Basilica in Venice.

  11. The Five Marks of the Mental

    Science.gov (United States)

    Pernu, Tuomas K.

    2017-01-01

    The mental realm seems different to the physical realm; the mental is thought to be dependent on, yet distinct from the physical. But how, exactly, are the two realms supposed to be different, and what, exactly, creates the seemingly insurmountable juxtaposition between the mental and the physical? This review identifies and discusses five marks of the mental, features that set characteristically mental phenomena apart from the characteristically physical phenomena. These five marks (intentionality, consciousness, free will, teleology, and normativity) are not presented as a set of features that define mentality. Rather, each of them is something we seem to associate with phenomena we consider mental, and each of them seems to be in tension with the physical view of reality in its own particular way. It is thus suggested how there is no single mind-body problem, but a set of distinct but interconnected problems. Each of these separate problems is analyzed, and their differences, similarities and connections are identified. This provides a useful basis for future theoretical work on psychology and philosophy of mind, that until now has too often suffered from unclarities, inadequacies, and conflations. PMID:28736537

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. Marked heterogeneity in growth characteristics of myoblast clonal cultures and myoblast mixed cultures obtained from the same individual.

    Science.gov (United States)

    Maier, Andrea B; Cohen, Ron; Blom, Joke; van Heemst, Diana; Westendorp, Rudi G J

    2012-01-01

    Sarcopenia is defined as an age-related decrease in skeletal muscle mass and function while adjacent satellite cells are unable to compensate for this loss. However, myoblast cultures can be established even in the presence of sarcopenia. It is yet unknown whether satellite cells from failing muscle in older age are equally affected, as human satellite cells have been assessed using myoblast mixed cultures and not by using myoblast clonal cultures. We questioned to what extent myoblast mixed cultures reflect the in vivo characteristics of single satellite cells from adult skeletal muscle. We established a myoblast mixed culture and three myoblast clonal cultures out of the same muscle biopsy and cultured these cells for 100 days. Replicative capacity and oxidative stress resistance were compared. We found marked heterogeneity between the myoblast clonal cultures that all had a significantly lower replicative capacity when compared to the mixed culture. Replicative capacity of the clonal cultures was inversely related to the β-galactosidase activity after exposure to oxidative stress. Addition of L-carnosine enhanced the remaining replicative capacity in all cultures with a concomitant marginal decrease in β-galactosidase activity. It is concluded that myoblast mixed cultures in vitro do not reflect the marked heterogeneity between single isolated satellite cells. The consequences of the heterogeneity on muscle performance remain to be established. Copyright © 2011 S. Karger AG, Basel.

  18. 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.

  19. Evaluation of copper for divider subassembly in MCO Mark IA and Mark IV scrap fuel baskets

    International Nuclear Information System (INIS)

    Graves, C.E.

    1997-01-01

    The K Basin Spent Nuclear Fuel (SNF) Project Multi-Canister Overpack (MCO) subprojection eludes the design and fabrication of a canister that will be used to confine, contain, and maintain fuel in a critically safe array to enable its removal from the K Basins, vacuum drying, transport, staging, hot conditioning, and interim storage (Goldinann 1997). Each MCO consists of a shell, shield plug, fuel baskets (Mark IA or Mark IV), and other incidental equipment. The Mark IA intact and scrap fuel baskets are a safety class item for criticality control and components necessary for criticality control will be constructed from 304L stainless steel. It is proposed that a copper divider subassembly be used in both Mark IA and Mark IV scrap baskets to increase the safety basis margin during cold vacuum drying. The use of copper would increase the heat conducted away from hot areas in the baskets out to the wall of the MCO by both radiative and conductive heat transfer means. Thus copper subassembly will likely be a safety significant component of the scrap fuel baskets. This report examines the structural, cost and corrosion consequences associated with using a copper subassembly in the stainless steel MCO scrap fuel baskets

  20. Events diary

    Science.gov (United States)

    2000-01-01

    as Imperial College, the Royal Albert Hall, the Royal College of Art, the Natural History and Science Museums and the Royal Geographical Society. Under the heading `Shaping the future together' BA2000 will explore science, engineering and technology in their wider cultural context. Further information about this event on 6 - 12 September may be obtained from Sandra Koura, BA2000 Festival Manager, British Association for the Advancement of Science, 23 Savile Row, London W1X 2NB (tel: 0171 973 3075, e-mail: sandra.koura@britassoc.org.uk ). Details of the creating SPARKS events may be obtained from creating.sparks@britassoc.org.uk or from the website www.britassoc.org.uk . Other events 3 - 7 July, Porto Alegre, Brazil VII Interamerican conference on physics education: The preparation of physicists and physics teachers in contemporary society. Info: IACPE7@if.ufrgs.br or cabbat1.cnea.gov.ar/iacpe/iacpei.htm 27 August - 1 September, Barcelona, Spain GIREP conference: Physics teacher education beyond 2000. Info: www.blues.uab.es/phyteb/index.html

  1. Geophysical events

    Science.gov (United States)

    This is a summary of SEAN Bulletin, 13(3), March 31, 1988, a publication of the Smithsonian Institution's Scientific Event Alert Network. The complete bulletin is available in the microfiche edition of Eos as a microfiche supplement or as a paper reprint. For the microfiche, order document E88-002 at $2.50 (U.S.) by writing to AGU Orders, 2000 Florida Avenue, N.W., Washington, DC 20009 or by calling toll free on 800-424-2488. For the paper reprint, order SEAN Bulletin (giving volume and issue numbers and issue date) through the same address; the price is $3.50 for one copy of each issue number for those who do not have a deposit account, $2 for those who do; additional copies of each issue number are $1. Subscriptions to SEAN Bulletin are also available from AGU-Orders; the price is $18 for 12 monthly issues mailed to a U.S. address, $28 if mailed elsewhere, and must be prepaid.

  2. Differential Signature of the Centrosomal MARK4 Isoforms in Glioma

    Directory of Open Access Journals (Sweden)

    Ivana Magnani

    2011-01-01

    Full Text Available Background: MAP/microtubule affinity-regulating kinase 4 (MARK4 is a serine-threonine kinase expressed in two spliced isoforms, MARK4L and MARK4S, of which MARK4L is a candidate for a role in neoplastic transformation. Methods: We performed mutation analysis to identify sequence alterations possibly affecting MARK4 expression. We then investigated the MARK4L and MARK4S expression profile in 21 glioma cell lines and 36 tissues of different malignancy grades, glioblastoma-derived cancer stem cells (GBM CSCs and mouse neural stem cells (NSCs by real-time PCR, immunoblotting and immunohistochemistry. We also analyzed the sub-cellular localisation of MARK4 isoforms in glioma and normal cell lines by immunofluorescence. Results: Mutation analysis rules out sequence variations as the cause of the altered MARK4 expression in glioma. Expression profiling confirms that MARK4L is the predominant isoform, whereas MARK4S levels are significantly decreased in comparison and show an inverse correlation with tumour grade. A high MARK4L/MARK4S ratio also characterizes undifferentiated cells, such as GBM CSCs and NSCs. Accordingly, only MARK4L is expressed in brain neurogenic regions. Moreover, while both MARK4 isoforms are localised to the centrosome and midbody in glioma and normal cells, the L isoform exhibits an additional nucleolar localisation in tumour cells. Conclusions: The observed switch towards MARK4L suggests that the balance between the MARK4 isoforms is carefully guarded during neural differentiation but may be subverted in gliomagenesis. Moreover, the MARK4L nucleolar localisation in tumour cells features this MARK4 isoform as a nucleolus-associated tumour marker.

  3. Decommissioning of TRIGA Mark II type reactor

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Dooseong; Jeong, Gyeonghwan; Moon, Jeikwon [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2012-10-15

    The first research reactor in Korea, KRR 1, is a TRIGA Mark II type with open pool and fixed core. Its power was 100 kWth at its construction and it was upgraded to 250 kWth. Its construction was started in 1957. The first criticality was reached in 1962 and it had been operated for 36,000 hours. The second reactor, KRR 2, is a TRIGA Mark III type with open pool and movable core. These reactors were shut down in 1995, and the decision was made to decommission both reactors. The aim of the decommissioning activities is to decommission the KRR 2 reactor and decontaminate the residual building structures and site, and to release them as unrestricted areas. The KRR 1 reactor was decided to be preserve as a historical monument. A project was launched for the decommissioning of these reactors in 1997, and approved by the regulatory body in 2000. A total budget for the project was 20.0 million US dollars. It was anticipated that this project would be completed and the site turned over to KEPCO by 2010. However, it was discovered that the pool water of the KRR 1 reactor was leaked into the environment in 2009. As a result, preservation of the KRR 1 reactor as a monument had to be reviewed, and it was decided to fully decommission the KRR 1 reactor. Dismantling of the KRR 1 reactor takes place from 2011 to 2014 with a budget of 3.25 million US dollars. The scope of the work includes licensing of the decommissioning plan change, removal of pool internals including the reactor core, removal of the thermal and thermalizing columns, removal of beam port tubes and the aluminum liner in the reactor tank, removal of the radioactive concrete (the entire concrete structure will not be demolished), sorting the radioactive waste (concrete and soil) and conditioning the radioactive waste for final disposal, and final statuses of the survey and free release of the site and building, and turning over the site to KEPCO. In this paper, the current status of the TRIGA Mark-II type reactor

  4. Aluminum-Oxide Temperatures on the Mark VB, VE, VR, 15, and Mark 25 Assemblies

    International Nuclear Information System (INIS)

    Aleman, S.E.

    2001-01-01

    The task was to compute the maximum aluminum-oxide and oxide-coolant temperatures of assemblies cladded in 99+ percent aluminum. The assemblies considered were the Mark VB, VE, V5, 15 and 25. These assemblies consist of nested slug columns with individual uranium slugs cladded in aluminum cans. The CREDIT code was modified to calculate the oxide film thickness and the aluminum-oxide temperature at each axial increment. This information in this report will be used to evaluate the potential for cladding corrosion of the Mark 25 assembly

  5. Mutational analysis of the hypervariable region of hepatitis e virus reveals its involvement in the efficiency of viral RNA replication.

    Science.gov (United States)

    Pudupakam, R S; Kenney, Scott P; Córdoba, Laura; Huang, Yao-Wei; Dryman, Barbara A; Leroith, Tanya; Pierson, F William; Meng, Xiang-Jin

    2011-10-01

    The RNA genome of the hepatitis E virus (HEV) contains a hypervariable region (HVR) in ORF1 that tolerates small deletions with respect to infectivity. To further investigate the role of the HVR in HEV replication, we constructed a panel of mutants with overlapping deletions in the N-terminal, central, and C-terminal regions of the HVR by using a genotype 1 human HEV luciferase replicon and analyzed the effects of deletions on viral RNA replication in Huh7 cells. We found that the replication levels of the HVR deletion mutants were markedly reduced in Huh7 cells, suggesting a role of the HVR in viral replication efficiency. To further verify the results, we constructed HVR deletion mutants by using a genetically divergent, nonmammalian avian HEV, and similar effects on viral replication efficiency were observed when the avian HEV mutants were tested in LMH cells. Furthermore, the impact of complete HVR deletion on virus infectivity was tested in chickens, using an avian HEV mutant with a complete HVR deletion. Although the deletion mutant was still replication competent in LMH cells, the complete HVR deletion resulted in a loss of avian HEV infectivity in chickens. Since the HVR exhibits extensive variations in sequence and length among different HEV genotypes, we further examined the interchangeability of HVRs and demonstrated that HVR sequences are functionally exchangeable between HEV genotypes with regard to viral replication and infectivity in vitro, although genotype-specific HVR differences in replication efficiency were observed. The results showed that although the HVR tolerates small deletions with regard to infectivity, it may interact with viral and host factors to modulate the efficiency of HEV replication.

  6. Genetic exchanges caused by ultraviolet photoproducts in phage lamda DNA molecules: the role of DNA replication

    International Nuclear Information System (INIS)

    Lin, P.F.; Howard-Flanders, P.; Yale Univ., New Haven, Conn.

    1976-01-01

    Genetic recombination induced by structural damage in DNA molecules was investigated in E. coli K12(lamda) lysogens infected with genetically marked phage lamda. Photoproducts were induced in the phage DNA before infection by exposing them either to 313 nm light in the presence of acetophenone or to 254 nm light. To test the role of the replication of the damage phage DNA on the frequency of the induced recombination , both heteroimmune and homoimmune crosses were performed, and scored for P + recombinants. In heteroimmune crosses, recombination was less frequent in infected cells exposed to visible light and in wild type cells able to perform excision repair than in excision-defective lysogens. Therefore, much of the induced recombination can be attributed to the pyrimidine dimers in the phage DNA. In homoimmune crosses, replication of the phage DNA containing ultraviolet photoproducts was represented by lamda immunity, and was further blocked by the lack of the P gene product needed for replication. The 254 nm photoproducts increased the frequency of recombination in these homoimmune crosses, even though phage DNA replication was blocked. Irradiation with 313 nm light and acetophenone M, which produces dimers and unknown photoproducts, was not as effective per dimer as the 254 nm light. It is concluded from these results that certain unidentified 254 nm photoproducts can cause recombination even in the absence of DNA replication. They are not pyrimidine dimers, as they are not susceptible to excision repair or photoreactivation. In contrast, pyrimidine dimers appear to cause recombination only when the DNA containing them undergoes replication. (orig./MG) [de

  7. Oxygen binding to nitric oxide marked hemoglobin

    International Nuclear Information System (INIS)

    Louro, S.R.W.; Ribeiro, P.C.; Bemski, G.

    1979-04-01

    Electron spin resonance spectra of organic phosphate free human hemoglobin marked with nitric oxide at the sixth coordination position of one of the four hemes allow to observe the transition from the tense (T) to the relaxed (R) conformation, as a function of parcial oxygen pressure. The spectra are composites of contributions from α sub(T), α sub(R) and β chains spectra, showing the presence of only two conformations: T and R. In the absence of organic phosphates NO binds to α and β chains with the same probability, but in the presence of phosphates NO combines preferentially with α chains. The dissociation of NO proceeds at least an order of magnitude faster in T than in R configuration. (author) [pt

  8. Results on the iota from Mark III

    International Nuclear Information System (INIS)

    Richman, J.D.

    1985-01-01

    A survey is presented of Mark III results on the iota(1440), a possible glueball state observed in radiative J/psi decays. The measurements include a spin-parity determination using both the iota → Ksub(s) 0 K +- π +- and iota → K + K - π 0 decay modes; an upper limit on the K*anti-K content of the Kanti-Kπ Dalitz plot; branching fractions and isospin; stringent upper limits for several hadronic channels, including iota → zetaπ→etaππ; and results from a search for iota radiative decays into vector mesons. These measurements are discussed in the context of theoretical ideas about the iota and results on the E(1420), a state observed in hadronic interactions. 11 refs., 7 figs

  9. Decommissioning plan for the TRIGA mark-3

    International Nuclear Information System (INIS)

    Park, S. K.; Jung, W. S.; Jung, K. H.; Baek, S. T.; Jung, K. J.

    1999-01-01

    TRIGA Mark-III (KRR-2) is the second research reactor in Korea. Construction of KRR-2 was started in 1969 and first criticality was achieved in 1972. After 24 years operation, KRR-2 has stopped its operation at the end of 1995 due to normal operation of HANARO. KRR-2 was then decided to decommission in 1996 by government. Decontamination and decommissioning (D and D) will be conducted in accordance with domestic laws and international regulations. Selected method of D and D will be devoted to protect workers and environment and to minimize radioactive wastes produced. The major D and D work will be conducted safely by using conventional industrial equipment because of relatively low radioactivity and contamination in the facility. When removing activated concrete from reactor pool, it will be installed a temporary containment and ventilation system. In this paper, structure of KRR-2 and method of D and D in each step are presented and discussed

  10. Dihydralazine induces marked cerebral vasodilation in man

    DEFF Research Database (Denmark)

    Schroeder, T; Sillesen, H

    1987-01-01

    of dihydralazine was of the same order of magnitude as the effect of 5% CO2 inhalation. These results in normal subjects should be extrapolated to diseased persons only with extreme caution. Still, the very marked and long lasting vasodilation observed suggests that dihydralazine, from a theoretical point of view.......v. xenon-133 technique in seven young, normotensive volunteers before and 15, 60 and 180 min after 6.25 mg i.v. dihydralazine, corresponding approximately to 0.1 mg kg-1 body weight. For comparison the CBF reactivity to inhalation of 5% CO2 in air was investigated. Dihydralazine increased CBF throughout...... the period of study, in median 16, 27 and 23% at the three periods of measurements, respectively. The arterial blood pressure remained unchanged, whereas heart rate increased significantly. During CO2 inhalation, CBF increased on average 29%. Thus, the cerebral vasodilation exerted by a small i.v. dose...

  11. Z0 physics from the Mark II at the SLC [SLAC Linear Collider

    International Nuclear Information System (INIS)

    Abrams, G.S.

    1989-06-01

    The MARK II detector has started to take data at the new SLAC Linear Collider. The novel aspects of the accelerator and of the MARK II are briefly described. Displays of event pictures from some of the early-on data are presented to illustrate the quality of the data. A first presentation of the results of an energy scan near the Z 0 mass that is currently in progress shows the expected resonant enhancement near 91 GeV. 2 refs., 23 figs., 1 tab

  12. DNA replication and post-replication repair in U.V.-sensitive mouse neuroblastoma cells

    International Nuclear Information System (INIS)

    Lavin, M.F.; McCombe, P.; Kidson, C.

    1976-01-01

    Mouse neuroblastoma cells differentiated when grown in the absence of serum; differentiation was reversed on the addition of serum. Differentiated cells were more sensitive to U.V.-radiation than proliferating cells. Whereas addition of serum to differentiated neuroblastoma cells normally resulted in immediate, synchronous entry into S phase, irradiation just before the addition of serum resulted in a long delay in the onset of DNA replication. During this lag period, incorporated 3 H-thymidine appeared in the light density region of CsCl gradients, reflecting either repair synthesis or abortive replication. Post-replication repair (gap-filling) was found to be present in proliferating cells and at certain times in differentiated cells. It is suggested that the sensitivity of differentiated neuroblastoma cells to U.V.-radiation may have been due to ineffective post-replication repair or to deficiencies in more than one repair mechanism, with reduction in repair capacity beyond a critical threshold. (author)

  13. The Role of the Transcriptional Response to DNA Replication Stress.

    Science.gov (United States)

    Herlihy, Anna E; de Bruin, Robertus A M

    2017-03-02

    During DNA replication many factors can result in DNA replication stress. The DNA replication stress checkpoint prevents the accumulation of replication stress-induced DNA damage and the potential ensuing genome instability. A critical role for post-translational modifications, such as phosphorylation, in the replication stress checkpoint response has been well established. However, recent work has revealed an important role for transcription in the cellular response to DNA replication stress. In this review, we will provide an overview of current knowledge of the cellular response to DNA replication stress with a specific focus on the DNA replication stress checkpoint transcriptional response and its role in the prevention of replication stress-induced DNA damage.

  14. The Role of the Transcriptional Response to DNA Replication Stress

    Science.gov (United States)

    Herlihy, Anna E.; de Bruin, Robertus A.M.

    2017-01-01

    During DNA replication many factors can result in DNA replication stress. The DNA replication stress checkpoint prevents the accumulation of replication stress-induced DNA damage and the potential ensuing genome instability. A critical role for post-translational modifications, such as phosphorylation, in the replication stress checkpoint response has been well established. However, recent work has revealed an important role for transcription in the cellular response to DNA replication stress. In this review, we will provide an overview of current knowledge of the cellular response to DNA replication stress with a specific focus on the DNA replication stress checkpoint transcriptional response and its role in the prevention of replication stress-induced DNA damage. PMID:28257104

  15. Replication Protein A (RPA) Phosphorylation Prevents RPA Association with Replication Centers

    OpenAIRE

    Vassin, Vitaly M.; Wold, Marc S.; Borowiec, James A.

    2004-01-01

    Mammalian replication protein A (RPA) undergoes DNA damage-dependent phosphorylation at numerous sites on the N terminus of the RPA2 subunit. To understand the functional significance of RPA phosphorylation, we expressed RPA2 variants in which the phosphorylation sites were converted to aspartate (RPA2D) or alanine (RPA2A). Although RPA2D was incorporated into RPA heterotrimers and supported simian virus 40 DNA replication in vitro, the RPA2D mutant was selectively unable to associate with re...

  16. Functions of Ubiquitin and SUMO in DNA Replication and Replication Stress

    Science.gov (United States)

    García-Rodríguez, Néstor; Wong, Ronald P.; Ulrich, Helle D.

    2016-01-01

    Complete and faithful duplication of its entire genetic material is one of the essential prerequisites for a proliferating cell to maintain genome stability. Yet, during replication DNA is particularly vulnerable to insults. On the one hand, lesions in replicating DNA frequently cause a stalling of the replication machinery, as most DNA polymerases cannot cope with defective templates. This situation is aggravated by the fact that strand separation in preparation for DNA synthesis prevents common repair mechanisms relying on strand complementarity, such as base and nucleotide excision repair, from working properly. On the other hand, the replication process itself subjects the DNA to a series of hazardous transformations, ranging from the exposure of single-stranded DNA to topological contortions and the generation of nicks and fragments, which all bear the risk of inducing genomic instability. Dealing with these problems requires rapid and flexible responses, for which posttranslational protein modifications that act independently of protein synthesis are particularly well suited. Hence, it is not surprising that members of the ubiquitin family, particularly ubiquitin itself and SUMO, feature prominently in controlling many of the defensive and restorative measures involved in the protection of DNA during replication. In this review we will discuss the contributions of ubiquitin and SUMO to genome maintenance specifically as they relate to DNA replication. We will consider cases where the modifiers act during regular, i.e., unperturbed stages of replication, such as initiation, fork progression, and termination, but also give an account of their functions in dealing with lesions, replication stalling and fork collapse. PMID:27242895

  17. A unique epigenetic signature is associated with active DNA replication loci in human embryonic stem cells.

    Science.gov (United States)

    Li, Bing; Su, Trent; Ferrari, Roberto; Li, Jing-Yu; Kurdistani, Siavash K

    2014-02-01

    The cellular epigenetic landscape changes as pluripotent stem cells differentiate to somatic cells or when differentiated cells transform to a cancerous state. These epigenetic changes are commonly correlated with differences in gene expression. Whether active DNA replication is also associated with distinct chromatin environments in these developmentally and phenotypically diverse cell types has not been known. Here, we used BrdU-seq to map active DNA replication loci in human embryonic stem cells (hESCs), normal primary fibroblasts and a cancer cell line, and correlated these maps to the epigenome. In all cell lines, the majority of BrdU peaks were enriched in euchromatin and at DNA repetitive elements, especially at microsatellite repeats, and coincided with previously determined replication origins. The most prominent BrdU peaks were shared between all cells but a sizable fraction of the peaks were specific to each cell type and associated with cell type-specific genes. Surprisingly, the BrdU peaks that were common to all cell lines were associated with H3K18ac, H3K56ac, and H4K20me1 histone marks only in hESCs but not in normal fibroblasts or cancer cells. Depletion of the histone acetyltransferases for H3K18 and H3K56 dramatically decreased the number and intensity of BrdU peaks in hESCs. Our data reveal a unique epigenetic signature that distinguishes active replication loci in hESCs from normal somatic or malignant cells.

  18. ATLAS event featuring two charm jets and missing energy

    CERN Multimedia

    ATLAS Collaboration

    2012-01-01

    Proton collision event in the ATLAS detector featuring two tagged charm jets and missing transverse energy. The zoomed view in the bottom right panel shows a displaced vertex of one of the c-tagged jets (marked in blue).

  19. DNA Replication in Engineered Escherichia coli Genomes with Extra Replication Origins.

    Science.gov (United States)

    Milbredt, Sarah; Farmani, Neda; Sobetzko, Patrick; Waldminghaus, Torsten

    2016-10-21

    The standard outline of bacterial genomes is a single circular chromosome with a single replication origin. From the bioengineering perspective, it appears attractive to extend this basic setup. Bacteria with split chromosomes or multiple replication origins have been successfully constructed in the last few years. The characteristics of these engineered strains will largely depend on the respective DNA replication patterns. However, the DNA replication has not been investigated systematically in engineered bacteria with multiple origins or split replicons. Here we fill this gap by studying a set of strains consisting of (i) E. coli strains with an extra copy of the native replication origin (oriC), (ii) E. coli strains with an extra copy of the replication origin from the secondary chromosome of Vibrio cholerae (oriII), and (iii) a strain in which the E. coli chromosome is split into two linear replicons. A combination of flow cytometry, microarray-based comparative genomic hybridization (CGH), and modeling revealed silencing of extra oriC copies and differential timing of ectopic oriII copies compared to the native oriC. The results were used to derive construction rules for future multiorigin and multireplicon projects.

  20. Mcm10 regulates DNA replication elongation by stimulating the CMG replicative helicase.

    Science.gov (United States)

    Lõoke, Marko; Maloney, Michael F; Bell, Stephen P

    2017-02-01

    Activation of the Mcm2-7 replicative DNA helicase is the committed step in eukaryotic DNA replication initiation. Although Mcm2-7 activation requires binding of the helicase-activating proteins Cdc45 and GINS (forming the CMG complex), an additional protein, Mcm10, drives initial origin DNA unwinding by an unknown mechanism. We show that Mcm10 binds a conserved motif located between the oligonucleotide/oligosaccharide fold (OB-fold) and A subdomain of Mcm2. Although buried in the interface between these domains in Mcm2-7 structures, mutations predicted to separate the domains and expose this motif restore growth to conditional-lethal MCM10 mutant cells. We found that, in addition to stimulating initial DNA unwinding, Mcm10 stabilizes Cdc45 and GINS association with Mcm2-7 and stimulates replication elongation in vivo and in vitro. Furthermore, we identified a lethal allele of MCM10 that stimulates initial DNA unwinding but is defective in replication elongation and CMG binding. Our findings expand the roles of Mcm10 during DNA replication and suggest a new model for Mcm10 function as an activator of the CMG complex throughout DNA replication. © 2017 Lõoke et al.; Published by Cold Spring Harbor Laboratory Press.

  1. MarkIT büroo = Offices of MarkIT

    Index Scriptorium Estoniae

    2010-01-01

    Tallinnas Pärnu mnt. 102C asuvas büroohoones paikneva MarkIT büroo sisekujundusest. Sisearhitektid Kard Männil (SAB Miu Miu Miu) ja Loreida Hein (Studio La), nende tähtsamate tööde loetelu. Valge büroomööbel on sisearhitektide projekteeritud. Graafika on sisearhitektid ise joonistanud

  2. DNA replication and repair in Tilapia cells

    International Nuclear Information System (INIS)

    Yew, F.H.; Chang, L.M.

    1984-01-01

    The effect of ultraviolet radiation on a cell line established from the warm water fish Tilapia has been assessed by measuring the rate of DNA synthesis, excision repair, post-replication repair and cell survival. The cells tolerate ultraviolet radiation better than mammalian cells with respect to DNA synthesis, post-replication repair and cell survival. They are also efficient in excision repair, which in other fish cell lines has been found to be at a low level or absent. Their response to the inhibitors hydroxyurea and 1-β-D-arabinofuranosylcytosine is less sensitive than that of other cell lines, yet the cells seem to have very small pools of DNA precursor. (author)

  3. Circus: A Replicated Procedure Call Facility

    Science.gov (United States)

    1984-08-01

    298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 client client stubs ...... ...... ..... ..... runtime libary stub compiler binding agent...runtime libary Figure 1: Structure of the Circus system replicated procedure call paired message protocol unreliable datagrams Figure 2: Circus...114-121. [11) Digit &! Equipment Corporation, Intel Corporation, a.nd Xerox Corporation. The Ethernet: A Local Area Networlc. September 1080. [12

  4. Nonequilibrium Phase Transitions Associated with DNA Replication

    Science.gov (United States)

    2011-02-11

    polymerases) catalyzing the growth of a DNA primer strand (the nascent chain of nucleotides complementary to the template strand) based on the Watson ...the fraction (error rate) of monomers for which y, where y is the correct Watson - Crick complementary base of , can be obtained by ¼ X...Nonequilibrium Phase Transitions Associated with DNA Replication Hyung-June Woo* and Anders Wallqvist Biotechnology High Performance Computing

  5. Recursion vs. Replication in Simple Cryptographic Protocols

    DEFF Research Database (Denmark)

    Huttel, Hans; Srba, Jiri

    2005-01-01

    We use some recent techniques from process algebra to draw several conclusions about the well studied class of ping-pong protocols introduced by Dolev and Yao. In particular we show that all nontrivial properties, including reachability and equivalence checking wrt. the whole van Glabbeek's spect...... of messages in the sense of Amadio, Lugiez and Vanackere. We conclude by showing that reachability analysis for a replicative variant of the protocol becomes decidable....

  6. Theoretical models for the regulation of DNA replication in fast-growing bacteria

    Science.gov (United States)

    Creutziger, Martin; Schmidt, Mischa; Lenz, Peter

    2012-09-01

    Growing in always changing environments, Escherichia coli cells are challenged by the task to coordinate growth and division. In particular, adaption of their growth program to the surrounding medium has to guarantee that the daughter cells obtain fully replicated chromosomes. Replication is therefore to be initiated at the right time, which is particularly challenging in media that support fast growth. Here, the mother cell initiates replication not only for the daughter but also for the granddaughter cells. This is possible only if replication occurs from several replication forks that all need to be correctly initiated. Despite considerable efforts during the last 40 years, regulation of this process is still unknown. Part of the difficulty arises from the fact that many details of the relevant molecular processes are not known. Here, we develop a novel theoretical strategy for dealing with this general problem: instead of analyzing a single model, we introduce a wide variety of 128 different models that make different assumptions about the unknown processes. By comparing the predictions of these models we are able to identify the key quantities that allow the experimental discrimination of the different models. Analysis of these quantities yields that out of the 128 models 94 are not consistent with available experimental data. From the remaining 34 models we are able to conclude that mass growth and DNA replication need either to be truly coupled, by coupling DNA replication initiation to the event of cell division, or to the amount of accumulated mass. Finally, we make suggestions for experiments to further reduce the number of possible regulation scenarios.

  7. Inhibition of Hepatitis B virus cccDNA replication by siRNA

    International Nuclear Information System (INIS)

    Li Guiqiu; Gu Hongxi; Li Di; Xu Weizhen

    2007-01-01

    The development of an effective therapy for Hepatitis B virus (HBV) infection is still a challenge. Progress in RNA interference (RNAi) has shed slight on developing a new anti-HBV strategy. Here, we present a series of experiments showing a significant reduction in HBV transcripts and replication intermediates in HepG2.2.15 cells by vector-based siRNA targeted nuclear localization signal (NLS) region. More importantly, we showed that siRNA1 markedly inhibited HBV covalently closed circular DNA (cccDNA) replication. Our results indicated that HBV NLS may serve as a novel RNAi target to combat HBV infection, which can enhance anti-HBV efficacy and overcome the drawbacks of current therapies

  8. Registered Replication Report: Strack, Martin, & Stepper (1988).

    Science.gov (United States)

    Acosta, Alberto; Adams, Reginald B; Albohn, Daniel N; Allard, Eric S; Beek, Titia; Benning, Stephen D; Blouin- Hudon, Eve-Marie; Bulnes, Luis Carlo; Caldwell, Tracy L; Calin-Jageman, Robert J; Capaldi, Colin A; Carfagno, Nicholas S; Chasten, Kelsie T; Cleeremans, Axel; Connell, Louise; DeCicco, Jennifer M.; Dijkhoff, Laura; Dijkstra, Katinka; Fischer, Agneta H; Foroni, Francesco; Gronau, Quentin F; Hess, Ursula; Holmes, Kevin J; Jones, Jacob L H; Klein, Olivier; Koch, Christopher; Korb, Sebastian; Lewinski, Peter; Liao, Julia D; Lund, Sophie; Lupiáñez, Juan; Lynott, Dermot; Nance, Christin N; Oosterwijk, Suzanne; Özdog˘ru, Asil Ali; Pacheco-Unguetti, Antonia Pilar; Pearson, Bethany; Powis, Christina; Riding, Sarah; Roberts, Tomi-Ann; Rumiati, Raffaella I; Senden, Morgane; Shea-Shumsky, Noah B; Sobocko, Karin; Soto, Jose A; Steiner, Troy G; Talarico, Jennifer M; vanAllen, Zack M; Wagenmakers, E-J; Vandekerckhove, Marie; Wainwright, Bethany; Wayand, Joseph F; Zeelenberg, Rene; Zetzer, Emily E; Zwaan, Rolf A

    2016-11-01

    According to the facial feedback hypothesis, people's affective responses can be influenced by their own facial expression (e.g., smiling, pouting), even when their expression did not result from their emotional experiences. For example, Strack, Martin, and Stepper (1988) instructed participants to rate the funniness of cartoons using a pen that they held in their mouth. In line with the facial feedback hypothesis, when participants held the pen with their teeth (inducing a "smile"), they rated the cartoons as funnier than when they held the pen with their lips (inducing a "pout"). This seminal study of the facial feedback hypothesis has not been replicated directly. This Registered Replication Report describes the results of 17 independent direct replications of Study 1 from Strack et al. (1988), all of which followed the same vetted protocol. A meta-analysis of these studies examined the difference in funniness ratings between the "smile" and "pout" conditions. The original Strack et al. (1988) study reported a rating difference of 0.82 units on a 10-point Likert scale. Our meta-analysis revealed a rating difference of 0.03 units with a 95% confidence interval ranging from -0.11 to 0.16. © The Author(s) 2016.

  9. The Anisotropy of Replicated Aluminum Foams

    Directory of Open Access Journals (Sweden)

    Eugeny L. Furman

    2014-01-01

    Full Text Available The replication casting process gives the open-cell aluminum foams that can be used in many industrial applications as well as in filtering technology. The essential requirement for filters is the uniformity of filtering degree which is defined by the minimal pore size. However the structure of replication castings is often inhomogeneous and the minimal pore radius is decreasing in the direction of melt infiltration. The objective of this investigation is to study the dynamics of melt impregnation of the porous medium by vacuum suction to identify the possibility of reducing the anisotropy. Theoretical data illustrate the processes at the boundary between melt and gas medium. The experiments were carried out using the replication aluminum samples produced according to commercial technology. It was found that the permeability coefficient varies throughout the height of castings. A method for estimation of pressure on the line of melt movement was proposed. The resistance of NaCl layer and circular vents of the mold causes the inhomogeneity of castings. Finally the ways of minimizing the anisotropy were offered.

  10. The molecular biology of Bluetongue virus replication.

    Science.gov (United States)

    Patel, Avnish; Roy, Polly

    2014-03-01

    The members of Orbivirus genus within the Reoviridae family are arthropod-borne viruses which are responsible for high morbidity and mortality in ruminants. Bluetongue virus (BTV) which causes disease in livestock (sheep, goat, cattle) has been in the forefront of molecular studies for the last three decades and now represents the best understood orbivirus at a molecular and structural level. The complex nature of the virion structure has been well characterised at high resolution along with the definition of the virus encoded enzymes required for RNA replication; the ordered assembly of the capsid shell as well as the protein and genome sequestration required for it; and the role of host proteins in virus entry and virus release. More recent developments of Reverse Genetics and Cell-Free Assembly systems have allowed integration of the accumulated structural and molecular knowledge to be tested at meticulous level, yielding higher insight into basic molecular virology, from which the rational design of safe efficacious vaccines has been possible. This article is centred on the molecular dissection of BTV with a view to understanding the role of each protein in the virus replication cycle. These areas are important in themselves for BTV replication but they also indicate the pathways that related viruses, which includes viruses that are pathogenic to man and animals, might also use providing an informed starting point for intervention or prevention. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Singlet Oxygen-Mediated Oxidation during UVA Radiation Alters the Dynamic of Genomic DNA Replication.

    Directory of Open Access Journals (Sweden)

    Dany Graindorge

    Full Text Available UVA radiation (320-400 nm is a major environmental agent that can exert its deleterious action on living organisms through absorption of the UVA photons by endogenous or exogenous photosensitizers. This leads to the production of reactive oxygen species (ROS, such as singlet oxygen (1O2 and hydrogen peroxide (H2O2, which in turn can modify reversibly or irreversibly biomolecules, such as lipids, proteins and nucleic acids. We have previously reported that UVA-induced ROS strongly inhibit DNA replication in a dose-dependent manner, but independently of the cell cycle checkpoints activation. Here, we report that the production of 1O2 by UVA radiation leads to a transient inhibition of replication fork velocity, a transient decrease in the dNTP pool, a quickly reversible GSH-dependent oxidation of the RRM1 subunit of ribonucleotide reductase and sustained inhibition of origin firing. The time of recovery post irradiation for each of these events can last from few minutes (reduction of oxidized RRM1 to several hours (replication fork velocity and origin firing. The quenching of 1O2 by sodium azide prevents the delay of DNA replication, the decrease in the dNTP pool and the oxidation of RRM1, while inhibition of Chk1 does not prevent the inhibition of origin firing. Although the molecular mechanism remains elusive, our data demonstrate that the dynamic of replication is altered by UVA photosensitization of vitamins via the production of singlet oxygen.

  12. Singlet Oxygen-Mediated Oxidation during UVA Radiation Alters the Dynamic of Genomic DNA Replication

    Science.gov (United States)

    Graindorge, Dany; Martineau, Sylvain; Machon, Christelle; Arnoux, Philippe; Guitton, Jérôme; Francesconi, Stefania; Frochot, Céline; Sage, Evelyne; Girard, Pierre-Marie

    2015-01-01

    UVA radiation (320–400 nm) is a major environmental agent that can exert its deleterious action on living organisms through absorption of the UVA photons by endogenous or exogenous photosensitizers. This leads to the production of reactive oxygen species (ROS), such as singlet oxygen (1O2) and hydrogen peroxide (H2O2), which in turn can modify reversibly or irreversibly biomolecules, such as lipids, proteins and nucleic acids. We have previously reported that UVA-induced ROS strongly inhibit DNA replication in a dose-dependent manner, but independently of the cell cycle checkpoints activation. Here, we report that the production of 1O2 by UVA radiation leads to a transient inhibition of replication fork velocity, a transient decrease in the dNTP pool, a quickly reversible GSH-dependent oxidation of the RRM1 subunit of ribonucleotide reductase and sustained inhibition of origin firing. The time of recovery post irradiation for each of these events can last from few minutes (reduction of oxidized RRM1) to several hours (replication fork velocity and origin firing). The quenching of 1O2 by sodium azide prevents the delay of DNA replication, the decrease in the dNTP pool and the oxidation of RRM1, while inhibition of Chk1 does not prevent the inhibition of origin firing. Although the molecular mechanism remains elusive, our data demonstrate that the dynamic of replication is altered by UVA photosensitization of vitamins via the production of singlet oxygen. PMID:26485711

  13. DNA Replication Control During Drosophila Development: Insights into the Onset of S Phase, Replication Initiation, and Fork Progression

    Science.gov (United States)

    Hua, Brian L.; Orr-Weaver, Terry L.

    2017-01-01

    Proper control of DNA replication is critical to ensure genomic integrity during cell proliferation. In addition, differential regulation of the DNA replication program during development can change gene copy number to influence cell size and gene expression. Drosophila melanogaster serves as a powerful organism to study the developmental control of DNA replication in various cell cycle contexts in a variety of differentiated cell and tissue types. Additionally, Drosophila has provided several developmentally regulated replication models to dissect the molecular mechanisms that underlie replication-based copy number changes in the genome, which include differential underreplication and gene amplification. Here, we review key findings and our current understanding of the developmental control of DNA replication in the contexts of the archetypal replication program as well as of underreplication and differential gene amplification. We focus on the use of these latter two replication systems to delineate many of the molecular mechanisms that underlie the developmental control of replication initiation and fork elongation. PMID:28874453

  14. Inhibition of influenza virus replication by targeting broad host cell pathways.

    Directory of Open Access Journals (Sweden)

    Isabelle Marois

    Full Text Available Antivirals that are currently used to treat influenza virus infections target components of the virus which can mutate rapidly. Consequently, there has been an increase in the number of resistant strains to one or many antivirals in recent years. Here we compared the antiviral effects of lysosomotropic alkalinizing agents (LAAs and calcium modulators (CMs, which interfere with crucial events in the influenza virus replication cycle, against avian, swine, and human viruses of different subtypes in MDCK cells. We observed that treatment with LAAs, CMs, or a combination of both, significantly inhibited viral replication. Moreover, the drugs were effective even when they were administered 8 h after infection. Finally, analysis of the expression of viral acidic polymerase (PA revealed that both drugs classes interfered with early events in the viral replication cycle. This study demonstrates that targeting broad host cellular pathways can be an efficient strategy to inhibit influenza replication. Furthermore, it provides an interesting avenue for drug development where resistance by the virus might be reduced since the virus is not targeted directly.

  15. Riverscape genetics identifies replicated ecological divergence across an Amazonian ecotone.

    Science.gov (United States)

    Cooke, Georgina M; Landguth, Erin L; Beheregaray, Luciano B

    2014-07-01

    Ecological speciation involves the evolution of reproductive isolation and niche divergence in the absence of a physical barrier to gene flow. The process is one of the most controversial topics of the speciation debate, particularly in tropical regions. Here, we investigate ecologically based divergence across an Amazonian ecotone in the electric fish, Steatogenys elegans. We combine phylogenetics, genome scans, and population genetics with a recently developed individual-based evolutionary landscape genetics approach that incorporates selection. This framework is used to assess the relative contributions of geography and divergent natural selection between environments as biodiversity drivers. We report on two closely related and sympatric lineages that exemplify how divergent selection across a major Amazonian aquatic ecotone (i.e., between rivers with markedly different hydrochemical properties) may result in replicated ecologically mediated speciation. The results link selection across an ecological gradient with reproductive isolation and we propose that assortative mating based on water color may be driving the divergence. Divergence resulting from ecologically driven selection highlights the importance of considering environmental heterogeneity in studies of speciation in tropical regions. Furthermore, we show that framing ecological speciation in a spatially explicit evolutionary landscape genetics framework provides an important first step in exploring a wide range of the potential effects of spatial dependence in natural selection. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

  16. Response of sublethally irradiated monkeys to a replicating viral antigen

    International Nuclear Information System (INIS)

    Hilmas, D.E.; Spertzel, R.O.

    1975-01-01

    Temporal effects of exposure to sublethal, total-body x radiation (400 R) on responses to vaccination with the attenuated Venezuelan equine encephalomyelitis vaccine virus, TC-83, were examined in rhesus monkeys. Viremia, often with delayed onset, was prolonged even when irradiation preceded vaccination by 28 days. Virus titers were increased, particularly in groups irradiated 4 or 7 days before vaccination. Delay in appearance of hemagglutination-inhibition and serum-neutralizing antibody correlated closely with persistence of viremia in irradiated-vaccinated monkeys. The temporal course of antibody response was markedly affected by the interval between irradiation and injection of this replicating antigen. With longer intervals between irradiation and vaccination, the somewhat depressed antibody responses approached normal or surpassed those of nonirradiated monkeys. Vaccination 14 days after radiation exposure resulted in lethality to 8 of 12 monkeys, apparently as a result of secondary infection. The additional lymphopenic stress due to the effect of TC-83, superimposed on the severely depressed hematopoietic competence at 14 days, undoubtedly contributed to this increased susceptibility to latent infection

  17. Dynamics of Escherichia coli Chromosome Segregation during Multifork Replication

    DEFF Research Database (Denmark)

    Nielsen, Henrik Jørck; Youngren, Brenda; Hansen, Flemming G.

    2007-01-01

    Slowly growing Escherichia coli cells have a simple cell cycle, with replication and progressive segregation of the chromosome completed before cell division. In rapidly growing cells, initiation of replication occurs before the previous replication rounds are complete. At cell division, the chro......Slowly growing Escherichia coli cells have a simple cell cycle, with replication and progressive segregation of the chromosome completed before cell division. In rapidly growing cells, initiation of replication occurs before the previous replication rounds are complete. At cell division......, the chromosomes contain multiple replication forks and must be segregated while this complex pattern of replication is still ongoing. Here, we show that replication and segregation continue in step, starting at the origin and progressing to the replication terminus. Thus, early-replicated markers on the multiple......-branched chromosomes continue to separate soon after replication to form separate protonucleoids, even though they are not segregated into different daughter cells until later generations. The segregation pattern follows the pattern of chromosome replication and does not follow the cell division cycle. No extensive...

  18. The probability of Mark-1 liner failure

    International Nuclear Information System (INIS)

    Theofanous, T.G.; Yan, H.; Ratnam, U.; Amarasooriya, W.H.

    1991-01-01

    The authors are proposing a probabilistic methodology, the risk-oriented accident analysis methodology (ROAAM) as an overall systematic, disciplined approach for addressing the Mark-1 liner attack issue. The probabilistic framework encompasses the key features of the phenomenology, yet it is flexible enough to allow independent quantification of individual components as it may arise from independent research efforts. As a first step in this direction, the authors assembled, discussed, and took into consideration in the quantification proposed all relevant prior work. Furthermore, as an essential aspect of the overall methodology, most of those whose work has been referenced and/or used in this report have been asked to comment. The details of this work, the comments received, and the authors' responses are included in NUREG/CR-5423. As an even more important characteristic of the methodology, it is hoped that other quantifications (or information relevant to such) of independent components will become available in the future so that one can aim for convergence and closure

  19. SRS reactor stack plume marking tests

    International Nuclear Information System (INIS)

    Petry, S.F.

    1992-03-01

    Tests performed in 105-K in 1987 and 1988 demonstrated that the stack plume can successfully be made visible (i.e., marked) by introducing smoke into the stack breech. The ultimate objective of these tests is to provide a means during an emergency evacuation so that an evacuee can readily identify the stack plume and evacuate in the opposite direction, thus minimizing the potential of severe radiation exposure. The EPA has also requested DOE to arrange for more tests to settle a technical question involving the correct calculation of stack downwash. New test canisters were received in 1988 designed to produce more smoke per unit time; however, these canisters have not been evaluated, because normal ventilation conditions have not been reestablished in K Area. Meanwhile, both the authorization and procedure to conduct the tests have expired. The tests can be performed during normal reactor operation. It is recommended that appropriate authorization and procedure approval be obtained to resume testing after K Area restart

  20. The Mark 3 data base handler

    Science.gov (United States)

    Ryan, J. W.; Ma, C.; Schupler, B. R.

    1980-01-01

    A data base handler which would act to tie Mark 3 system programs together is discussed. The data base handler is written in FORTRAN and is implemented on the Hewlett-Packard 21MX and the IBM 360/91. The system design objectives were to (1) provide for an easily specified method of data interchange among programs, (2) provide for a high level of data integrity, (3) accommodate changing requirments, (4) promote program accountability, (5) provide a single source of program constants, and (6) provide a central point for data archiving. The system consists of two distinct parts: a set of files existing on disk packs and tapes; and a set of utility subroutines which allow users to access the information in these files. Users never directly read or write the files and need not know the details of how the data are formatted in the files. To the users, the storage medium is format free. A user does need to know something about the sequencing of his data in the files but nothing about data in which he has no interest.

  1. Trade Mark Cluttering: An Exploratory Report Commissioned by UKIPO

    OpenAIRE

    von Graevenitz, Georg; Greenhalgh, Christine; Helmers, Christian; Schautschick, Philipp

    2012-01-01

    This report explores the problem of “cluttering” of trade mark registers. The report consists of two parts: the first presents a conceptual discussion of “cluttering” of trade mark registers. The second part provides an exploratory empirical analysis of trade mark applications at the UK Intellectual Property Office (UKIPO) and the European trade mark office (OHIM). This part contains results of a descriptive and an econometric analysis. According to our definition, cluttering arises where fir...

  2. Forging Ahead through Darkness: PCNA, Still the Principal Conductor at the Replication Fork.

    Science.gov (United States)

    Choe, Katherine N; Moldovan, George-Lucian

    2017-02-02

    Proliferating cell nuclear antigen (PCNA) lies at the center of the faithful duplication of eukaryotic genomes. With its distinctive doughnut-shaped molecular structure, PCNA was originally studied for its role in stimulating DNA polymerases. However, we now know that PCNA does much more than promote processive DNA synthesis. Because of the complexity of the events involved, cellular DNA replication poses major threats to genomic integrity. Whatever predicament lies ahead for the replication fork, PCNA is there to orchestrate the events necessary to handle it. Through its many protein interactions and various post-translational modifications, PCNA has far-reaching impacts on a myriad of cellular functions. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. 9 CFR 590.418 - Supervision of marking and packaging.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Supervision of marking and packaging...) Identifying and Marking Product § 590.418 Supervision of marking and packaging. (a) Evidence of label approval... has on file evidence that such official identification or packaging material bearing such official...

  4. 14 CFR 1203.501 - Applying derivative classification markings.

    Science.gov (United States)

    2010-01-01

    ... INFORMATION SECURITY PROGRAM Derivative Classification § 1203.501 Applying derivative classification markings. Persons who apply derivative classification markings shall: (a) Observe and respect original... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Applying derivative classification markings...

  5. 46 CFR 199.176 - Markings on lifesaving appliances.

    Science.gov (United States)

    2010-10-01

    ... ARRANGEMENTS LIFESAVING SYSTEMS FOR CERTAIN INSPECTED VESSELS Requirements for All Vessels § 199.176 Markings on lifesaving appliances. (a) Lifeboats and rescue boats. Each lifeboat and rescue boat must be plainly marked as follows: (1) Each side of each lifeboat and rescue boat bow must be marked in block...

  6. 27 CFR 19.612 - Authorized abbreviations to identify marks.

    Science.gov (United States)

    2010-04-01

    ... T Tax Determined TD Wine Spirits Addition WSA (Sec. 201, Pub. L. 85-859, 72 Stat. 1360, as amended... TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS DISTILLED SPIRITS PLANTS Containers and Marks... to identify certain marks: Mark Abbreviation Completely Denatured Alcohol CDA Distilled Spirits...

  7. 9 CFR 316.13 - Marking of outside containers.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Marking of outside containers. 316.13... INSPECTION AND CERTIFICATION MARKING PRODUCTS AND THEIR CONTAINERS § 316.13 Marking of outside containers. (a... domestic commerce is moved from an official establishment, the outside container shall bear an official...

  8. Survival and reproduction of radio-marked adult spotted owls.

    Science.gov (United States)

    C.C. Foster; E.D. Forsman; E.C. Meslow; G.S. Miller; J.A. Reid; F.F. Wagner; A.B. Carey; J.B. Lint

    1992-01-01

    We compared survival, reproduction, and body mass of radio-marked and non radio-marked spotted owls (Strix occidentalis) to determine if backpack radios influenced reproduction or survival. In most study areas and years, there were no differences (P > 0.05) in survival of males and females or in survival of radio-marked versus banded owls. There...

  9. Marking for Structure using Boolean Feedback | Louw | Journal for ...

    African Journals Online (AJOL)

    This paper presents evidence that marking student texts with well considered checklists is more effective than marking by hand. An experiment conducted on first-year students illustrated that the checklists developed to mark introductions, conclusions and paragraphs yielded better revision results than handwritten ...

  10. Tooth-marked small theropod bone: an extremely rare trace

    DEFF Research Database (Denmark)

    Jacobsen, Aase Roland

    2001-01-01

    Tooth-marked dinosaur bones provide insight into feeding behaviours and biting strategies of theropod dinosaurs. The majority of theropod tooth marks reported to date have been found on herbivorous dinosaur bones, although some tyrannosaurid bones with tooth marks have also been reported. In 1988...

  11. 46 CFR 108.645 - Markings on lifesaving appliances.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 false Markings on lifesaving appliances. 108.645 Section 108.645 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) A-MOBILE OFFSHORE DRILLING UNITS DESIGN AND EQUIPMENT Equipment Markings and Instructions § 108.645 Markings on lifesaving appliances. (a...

  12. Darwinian Evolution of Mutualistic RNA Replicators with Different Genes

    Science.gov (United States)

    Mizuuchi, R.; Ichihashi, N.

    2017-07-01

    We report a sustainable long-term replication and evolution of two distinct cooperative RNA replicators encoding different genes. One of the RNAs evolved to maintain or increase the cooperativity, despite selective advantage of selfish mutations.

  13. Replication assessment of surface texture at sub-micrometre scale

    DEFF Research Database (Denmark)

    Quagliotti, Danilo; Tosello, Guido; Hansen, Hans Nørgaard

    2017-01-01

    [2]. A replication process requires reproducing a master geometry by conveying it to a substrate material. It is typically induced by means of different energy sources (usually heat and force) and a direct physical contact between the master and the substrate. Furthermore, concepts of advanced......, because of the replication nature of molding processes, the required specifications for the manufacture of micro molded components must be ensured by means of a metrological approach to surface replication and dimensional control of both master geometry and replicated substrate [3]-[4]. Therefore...... replication was assessed by the replication fidelity, i.e., comparing the produced parts with the tool used to replicate the geometry. Furthermore, the uncertainty of the replication fidelity was achieved by propagating the uncertainties evaluated for both masters and replicas. Finally, despite the specimens...

  14. Chromosome biology: conflict management for replication and transcription.

    Science.gov (United States)

    Dewar, James M; Walter, Johannes C

    2013-03-04

    A recent study has uncovered a new mechanism that attenuates DNA replication during periods of heightened gene expression to avoid collisions between replication and transcription. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Topology of a Membrane Associated Regulator of Prokaryotic DNA Replication

    National Research Council Canada - National Science Library

    Firshein, William

    1998-01-01

    This proposal has focused on a broad host range plasmid, RK2, as a model system to study how a pair of initiation proteins encoded by the plasmid for DNA replication function when replication occurs...

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

    Science.gov (United States)

    Moolman, M Charl; Tiruvadi Krishnan, Sriram; Kerssemakers, Jacob W J; de Leeuw, Roy; Lorent, Vincent; Sherratt, David J; Dekker, Nynke H

    2016-07-27

    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 Tus-ter barriers in the cell are poorly understood. By performing quantitative fluorescence microscopy with microfuidics, we investigate the effect on the replisome when encountering these barriers in live Escherichia coli cells. We make use of an E. coli variant that includes only an ectopic origin of replication that is positioned such that one of the two replisomes encounters a Tus-ter barrier before the other replisome. This enables us to single out the effect of encountering a Tus-ter roadblock on an individual replisome. We demonstrate that the replisome remains stably bound after encountering a Tus-ter complex from the non-permissive direction. Furthermore, the replisome is only transiently blocked, and continues replication beyond the barrier. Additionally, we demonstrate that these barriers affect sister chromosome segregation by visualizing specific chromosomal loci in the presence and absence of the Tus protein. These observations demonstrate the resilience of the replication fork to natural barriers and the sensitivity of chromosome alignment to fork progression. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  17. Addressing the "Replication Crisis": Using Original Studies to Design Replication Studies with Appropriate Statistical Power.

    Science.gov (United States)

    Anderson, Samantha F; Maxwell, Scott E

    2017-01-01

    Psychology is undergoing a replication crisis. The discussion surrounding this crisis has centered on mistrust of previous findings. Researchers planning replication studies often use the original study sample effect size as the basis for sample size planning. However, this strategy ignores uncertainty and publication bias in estimated effect sizes, resulting in overly optimistic calculations. A psychologist who intends to obtain power of .80 in the replication study, and performs calculations accordingly, may have an actual power lower than .80. We performed simulations to reveal the magnitude of the difference between actual and intended power based on common sample size planning strategies and assessed the performance of methods that aim to correct for effect size uncertainty and/or bias. Our results imply that even if original studies reflect actual phenomena and were conducted in the absence of questionable research practices, popular approaches to designing replication studies may result in a low success rate, especially if the original study is underpowered. Methods correcting for bias and/or uncertainty generally had higher actual power, but were not a panacea for an underpowered original study. Thus, it becomes imperative that 1) original studies are adequately powered and 2) replication studies are designed with methods that are more likely to yield the intended level of power.

  18. Checkpoint independence of most DNA replication origins in fission yeast

    OpenAIRE

    Mickle, Katie L; Ramanathan, Sunita; Rosebrock, Adam; Oliva, Anna; Chaudari, Amna; Yompakdee, Chulee; Scott, Donna; Leatherwood, Janet; Huberman, Joel A

    2007-01-01

    Abstract Background In budding yeast, the replication checkpoint slows progress through S phase by inhibiting replication origin firing. In mammals, the replication checkpoint inhibits both origin firing and replication fork movement. To find out which strategy is employed in the fission yeast, Schizosaccharomyces pombe, we used microarrays to investigate the use of origins by wild-type and checkpoint-mutant strains in the presence of hydroxyurea (HU), which limits the pool of deoxyribonucleo...

  19. Chromatin Heterogeneity and Distribution of Regulatory Elements in the Late-Replicating Intercalary Heterochromatin Domains of Drosophila melanogaster Chromosomes.

    Directory of Open Access Journals (Sweden)

    Varvara A Khoroshko

    Full Text Available Late-replicating domains (intercalary heterochromatin in the Drosophila genome display a number of features suggesting their organization is quite unique. Typically, they are quite large and encompass clusters of functionally unrelated tissue-specific genes. They correspond to the topologically associating domains and conserved microsynteny blocks. Our study aims at exploring further details of molecular organization of intercalary heterochromatin and has uncovered surprising heterogeneity of chromatin composition in these regions. Using the 4HMM model developed in our group earlier, intercalary heterochromatin regions were found to host chromatin fragments with a particular epigenetic profile. Aquamarine chromatin fragments (spanning 0.67% of late-replicating regions are characterized as a class of sequences that appear heterogeneous in terms of their decompactization. These fragments are enriched with enhancer sequences and binding sites for insulator proteins. They likely mark the chromatin state that is related to the binding of cis-regulatory proteins. Malachite chromatin fragments (11% of late-replicating regions appear to function as universal transitional regions between two contrasting chromatin states. Namely, they invariably delimit intercalary heterochromatin regions from the adjacent active chromatin of interbands. Malachite fragments also flank aquamarine fragments embedded in the repressed chromatin of late-replicating regions. Significant enrichment of insulator proteins CP190, SU(HW, and MOD2.2 was observed in malachite chromatin. Neither aquamarine nor malachite chromatin types appear to correlate with the positions of highly conserved non-coding elements (HCNE that are typically replete in intercalary heterochromatin. Malachite chromatin found on the flanks of intercalary heterochromatin regions tends to replicate earlier than the malachite chromatin embedded in intercalary heterochromatin. In other words, there exists a

  20. Mark Leonard : EL ei peakski olema suurvõim / Mark Leonard ; interv. Erkki Bahovski

    Index Scriptorium Estoniae

    Leonard, Mark

    2008-01-01

    Intervjuu Euroopa Välissuhete Nõukogu tegevdirektoriga, kes vastab küsimustele, mis puudutavad USA ja Euroopa suhteid, Euroopa Liidu välispoliitikat, Venemaa ja Euroopa Liidu suhteid pärast Gruusia konflikti. Ta peab murettekitavaks, et Venemaa üritab takistada euroopalike väärtuste levitamist oma naaberriikides. Vt. samas: Mark Leonard. Ilmunud ka Sirp : Diplomaatia 14. nov. nr. 11 lk. 13-14

  1. Vaccine Adverse Events

    Science.gov (United States)

    ... for Biologics Evaluation & Research Vaccine Adverse Events Vaccine Adverse Events Share Tweet Linkedin Pin it More sharing ... in the primary immunization series in infants Report Adverse Event Report a Vaccine Adverse Event Contact FDA ( ...

  2. Laying a Solid Foundation: Strategies for Effective Program Replication

    Science.gov (United States)

    Summerville, Geri

    2009-01-01

    The replication of proven social programs is a cost-effective and efficient way to achieve large-scale, positive social change. Yet there has been little guidance available about how to approach program replication and limited development of systems--at local, state or federal levels--to support replication efforts. "Laying a Solid Foundation:…

  3. Geminin: a major DNA replication safeguard in higher eukaryotes

    DEFF Research Database (Denmark)

    Melixetian, Marina; Helin, Kristian

    2004-01-01

    Eukaryotes have evolved multiple mechanisms to restrict DNA replication to once per cell cycle. These mechanisms prevent relicensing of origins of replication after initiation of DNA replication in S phase until the end of mitosis. Most of our knowledge of mechanisms controlling prereplication...

  4. Anaphase onset before complete DNA replication with intact checkpoint responses

    DEFF Research Database (Denmark)

    Torres-Rosell, Jordi; De Piccoli, Giacomo; Cordon-Preciado, Violeta

    2007-01-01

    Cellular checkpoints prevent mitosis in the presence of stalled replication forks. Whether checkpoints also ensure the completion of DNA replication before mitosis is unknown. Here, we show that in yeast smc5-smc6 mutants, which are related to cohesin and condensin, replication is delayed, most...

  5. Uncoupling of Sister Replisomes during Eukaryotic DNA Replication

    NARCIS (Netherlands)

    Yardimci, Hasan; Loveland, Anna B.; Habuchi, Satoshi; van Oijen, Antoine M.; Walter, Johannes C.

    2010-01-01

    The duplication of eukaryotic genomes involves the replication of DNA from multiple origins of replication. In S phase, two sister replisomes assemble at each active origin, and they replicate DNA in opposite directions. Little is known about the functional relationship between sister replisomes.

  6. Visualizing Single-molecule DNA Replication with Fluorescence Microscopy

    NARCIS (Netherlands)

    Tanner, Nathan A.; Loparo, Joseph J.; Oijen, Antoine M. van

    2009-01-01

    We describe a simple fluorescence microscopy-based real-time method for observing DNA replication at the single-molecule level. A circular, forked DNA template is attached to a functionalized glass coverslip and replicated extensively after introduction of replication proteins and nucleotides. The

  7. Mapping autonomously replicating sequence elements in a 73-kb ...

    Indian Academy of Sciences (India)

    Autonomously replicating sequence (ARS) elements are the genetic determinants of replication origin function in yeasts. They can be easily identified as the plasmids containing them transform yeast cells at a high frequency. As the first step towards identifying all potential replication origins in a 73-kb region of the long arm ...

  8. Evidence of a genetic instability induced by the incorporation of a DNA precursor marked with tritium

    International Nuclear Information System (INIS)

    Saintigny, Y.; Laurent, D.; Lahayel, J.B.; Roche, St.; Meynard, D.; Lopez, B.S.

    2009-01-01

    The authors report a molecular geno-toxicology investigation which allowed molecular events induced par intracellular incorporation of tritium to be studied, and the genetic instability resulting from a chronic exposure even at low dose to be analysed. For this purpose, they developed cell models (hamster tumorous cells and human fibroblasts) in which they know how to incorporate given quantities of marked nucleotides in the DNA. They show that the incorporation of tritium, even with doses which are said to be non toxic, causes a prolonged exposure of the cell to a genotoxic stress, and maybe a genetic instability due to a too great number of recombination events

  9. Prosodic Marking of Narrow Focus in Seoul Korean

    Directory of Open Access Journals (Sweden)

    Hae-Sung Jeon

    2017-01-01

    Full Text Available This paper explores prosodic marking of narrow (corrective focus in Seoul Korean. Korean lacks lexical stress and it has a phonologized association between the Accentual Phrase (AP initial segment and intonation. In the experiment, 4 speakers read sentences including a two-item list which were designed to elicit either an L or H AP-initial tone. The durational variations, the pitch events at prosodic boundaries, and 'F''0 'span in 32 sentences read neutrally and 64 sentences read with one of the items under focus were analyzed. The results show that the focused constituent consistently initiates a new prosodic phrase. In comparison to the neutrally spoken or defocused counterpart, the focused constituent was more likely to be realized as an Intonational Phrase (IP in some contexts. Bitonal IP boundary tones were more likely to occur under focus than monotonal tones. In addition, in focused constituents, durational expansion particularly at the phrase-edges, expansion in 'F''0 'span, and raising of the phrase-initial pitch were observed. On the other hand, defocused constituents were not phonetically reduced compared to the neutral counterparts. The results imply that the phonetic cues spreading over the focused constituent complement the exaggerated prosodic boundaries.

  10. Synchronous contextual irregularities affect early scene processing: replication and extension.

    Science.gov (United States)

    Mudrik, Liad; Shalgi, Shani; Lamy, Dominique; Deouell, Leon Y

    2014-04-01

    Whether contextual regularities facilitate perceptual stages of scene processing is widely debated, and empirical evidence is still inconclusive. Specifically, it was recently suggested that contextual violations affect early processing of a scene only when the incongruent object and the scene are presented a-synchronously, creating expectations. We compared event-related potentials (ERPs) evoked by scenes that depicted a person performing an action using either a congruent or an incongruent object (e.g., a man shaving with a razor or with a fork) when scene and object were presented simultaneously. We also explored the role of attention in contextual processing by using a pre-cue to direct subjects׳ attention towards or away from the congruent/incongruent object. Subjects׳ task was to determine how many hands the person in the picture used in order to perform the action. We replicated our previous findings of frontocentral negativity for incongruent scenes that started ~ 210 ms post stimulus presentation, even earlier than previously found. Surprisingly, this incongruency ERP effect was negatively correlated with the reaction times cost on incongruent scenes. The results did not allow us to draw conclusions about the role of attention in detecting the regularity, due to a weak attention manipulation. By replicating the 200-300 ms incongruity effect with a new group of subjects at even earlier latencies than previously reported, the results strengthen the evidence for contextual processing during this time window even when simultaneous presentation of the scene and object prevent the formation of prior expectations. We discuss possible methodological limitations that may account for previous failures to find this an effect, and conclude that contextual information affects object model selection processes prior to full object identification, with semantic knowledge activation stages unfolding only later on. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Lattice gas simulations of replicating domains

    International Nuclear Information System (INIS)

    Dawson, S.P.; Hasslacher, B.; Pearson, J.E.

    1993-01-01

    We use the lattice gas cellular automation (LGCA) developed to simulate a process of pattern-formation recently observed in reaction-diffusion systems. We study the reaction mechanism, which is an extension of the Selkov model for glycolytic oscillations. We are able to reproduce the self-replicating domains observed in this work. We use the LGCA simulation to estimate the smallest length-scale on which this process can occur under conditions encountered in the cell. These estimates are similar to those obtained for Turing patterns in the same setting

  12. Lattice gas simulations of replicating domains

    Energy Technology Data Exchange (ETDEWEB)

    Dawson, S.P.; Hasslacher, B.; Pearson, J.E.

    1993-12-31

    We use the lattice gas cellular automation (LGCA) developed to simulate a process of pattern-formation recently observed in reaction-diffusion systems. We study the reaction mechanism, which is an extension of the Selkov model for glycolytic oscillations. We are able to reproduce the self-replicating domains observed in this work. We use the LGCA simulation to estimate the smallest length-scale on which this process can occur under conditions encountered in the cell. These estimates are similar to those obtained for Turing patterns in the same setting.

  13. Physically Embedded Minimal Self-Replicating Systems

    DEFF Research Database (Denmark)

    Fellermann, Harold

    Self-replication is a fundamental property of all living organisms, yet has only been accomplished to limited extend in manmade systems. This thesis is part of the ongoing research endeavor to bridge the two sides of this gap. In particular, we present simulation results of a minimal life...... for any model above the atomistic scale. This is achieved by deriving an alternative scaling procedure for interaction parameters in the model. We perform system-level simulations of the design which attempt to account for theoretical, and experimental knowledge, as well as results from other...

  14. Replication of DNA during barley endosperm development

    DEFF Research Database (Denmark)

    Giese, H.

    1992-01-01

    The incorporation of [6-H-3]-thymidine into DNA of developing barley end sperm was examined by autoradiography of cross sections of seeds and DNA analysis. The majority of nuclear divisions took place in the very young endosperm, but as late as 25 days after anthesis there was evidence for DNA...... replication. The DNA content of the endosperm increases during development and in response to nitrogen application in parallel to the storage protein synthesis profile. The hordein genes were hypersensitive to DNase I treatment throughout development....

  15. The Nature of Stability in Replicating Systems

    Directory of Open Access Journals (Sweden)

    Addy Pross

    2011-02-01

    Full Text Available We review the concept of dynamic kinetic stability, a type of stability associated specifically with replicating entities, and show how it differs from the well-known and established (static kinetic and thermodynamic stabilities associated with regular chemical systems. In the process we demonstrate how the concept can help bridge the conceptual chasm that continues to separate the physical and biological sciences by relating the nature of stability in the animate and inanimate worlds, and by providing additional insights into the physicochemical nature of abiogenesis.

  16. Statistical methods for the forensic analysis of striated tool marks

    Energy Technology Data Exchange (ETDEWEB)

    Hoeksema, Amy Beth [Iowa State Univ., Ames, IA (United States)

    2013-01-01

    In forensics, fingerprints can be used to uniquely identify suspects in a crime. Similarly, a tool mark left at a crime scene can be used to identify the tool that was used. However, the current practice of identifying matching tool marks involves visual inspection of marks by forensic experts which can be a very subjective process. As a result, declared matches are often successfully challenged in court, so law enforcement agencies are particularly interested in encouraging research in more objective approaches. Our analysis is based on comparisons of profilometry data, essentially depth contours of a tool mark surface taken along a linear path. In current practice, for stronger support of a match or non-match, multiple marks are made in the lab under the same conditions by the suspect tool. We propose the use of a likelihood ratio test to analyze the difference between a sample of comparisons of lab tool marks to a field tool mark, against a sample of comparisons of two lab tool marks. Chumbley et al. (2010) point out that the angle of incidence between the tool and the marked surface can have a substantial impact on the tool mark and on the effectiveness of both manual and algorithmic matching procedures. To better address this problem, we describe how the analysis can be enhanced to model the effect of tool angle and allow for angle estimation for a tool mark left at a crime scene. With sufficient development, such methods may lead to more defensible forensic analyses.

  17. Zika virus preferentially replicates in the female reproductive tract after vaginal inoculation of rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Timothy Carroll

    2017-07-01

    Full Text Available Zika virus (ZIKV is a mosquito-transmitted virus that can cause severe defects in an infected fetus. ZIKV is also transmitted by sexual contact, although the relative importance of sexual transmission is unclear. To better understand the role of sexual transmission in ZIKV pathogenesis, a nonhuman primate (NHP model of vaginal transmission was developed. ZIKV was readily transmitted to mature cycling female rhesus macaque (RM by vaginal inoculation with 104-106 plaque-forming units (PFU. However, there was variability in susceptibility between the individual RM with 1->8 vaginal inoculations required to establish infection. After treatment with Depoprovera, a widely used contraceptive progestin, two RM that initially resisted 8 vaginal ZIKV inoculations became infected after one ZIKV inoculation. Thus, Depoprovera seemed to enhance susceptibility to vaginal ZIKV transmission. Unexpectedly, the kinetics of virus replication and dissemination after intravaginal ZIKV inoculation were markedly different from RM infected with ZIKV by subcutaneous (SQ virus inoculation. Several groups have reported that after SQ ZIKV inoculation vRNA is rapidly detected in blood plasma with vRNA less common in urine and saliva and only rarely detected in female reproductive tract (FRT secretions. In contrast, in vaginally inoculated RM, plasma vRNA is delayed for several days and ZIKV replication in, and vRNA shedding from, the FRT was found in all 6 animals. Further, after intravaginal transmission ZIKV RNA shedding from FRT secretions was detected before or simultaneously with plasma vRNA, and persisted for at least as long. Thus, ZIKV replication in the FRT was independent of, and often preceded virus replication in the tissues contributing to plasma vRNA. These results support the conclusion that ZIKV preferentially replicates in the FRT after vaginal transmission, but not after SQ transmission, and raise the possibility that there is enhanced fetal infection and

  18. Zika virus preferentially replicates in the female reproductive tract after vaginal inoculation of rhesus macaques.

    Science.gov (United States)

    Carroll, Timothy; Lo, Ming; Lanteri, Marion; Dutra, Joseph; Zarbock, Katie; Silveira, Paola; Rourke, Tracy; Ma, Zhong-Min; Fritts, Linda; O'Connor, Shelby; Busch, Michael; Miller, Christopher J

    2017-07-01

    Zika virus (ZIKV) is a mosquito-transmitted virus that can cause severe defects in an infected fetus. ZIKV is also transmitted by sexual contact, although the relative importance of sexual transmission is unclear. To better understand the role of sexual transmission in ZIKV pathogenesis, a nonhuman primate (NHP) model of vaginal transmission was developed. ZIKV was readily transmitted to mature cycling female rhesus macaque (RM) by vaginal inoculation with 104-106 plaque-forming units (PFU). However, there was variability in susceptibility between the individual RM with 1->8 vaginal inoculations required to establish infection. After treatment with Depoprovera, a widely used contraceptive progestin, two RM that initially resisted 8 vaginal ZIKV inoculations became infected after one ZIKV inoculation. Thus, Depoprovera seemed to enhance susceptibility to vaginal ZIKV transmission. Unexpectedly, the kinetics of virus replication and dissemination after intravaginal ZIKV inoculation were markedly different from RM infected with ZIKV by subcutaneous (SQ) virus inoculation. Several groups have reported that after SQ ZIKV inoculation vRNA is rapidly detected in blood plasma with vRNA less common in urine and saliva and only rarely detected in female reproductive tract (FRT) secretions. In contrast, in vaginally inoculated RM, plasma vRNA is delayed for several days and ZIKV replication in, and vRNA shedding from, the FRT was found in all 6 animals. Further, after intravaginal transmission ZIKV RNA shedding from FRT secretions was detected before or simultaneously with plasma vRNA, and persisted for at least as long. Thus, ZIKV replication in the FRT was independent of, and often preceded virus replication in the tissues contributing to plasma vRNA. These results support the conclusion that ZIKV preferentially replicates in the FRT after vaginal transmission, but not after SQ transmission, and raise the possibility that there is enhanced fetal infection and pathology

  19. Bite marks on skin and clay: A comparative analysis

    Directory of Open Access Journals (Sweden)

    R.K. Gorea

    2014-12-01

    Full Text Available Bite marks are always unique because teeth are distinctive. Bite marks are often observed at the crime scene in sexual and in physical assault cases on the skin of the victims and sometimes on edible leftovers in burglary cases. This piece of evidence is often ignored, but if properly harvested and investigated, bite marks may prove useful in apprehending and successfully prosecuting the criminals. Due to the importance of bite marks, we conducted a progressive randomised experimental study conducted on volunteers. A total of 188 bite marks on clay were studied. Based on these findings, 93.34% of the volunteers could be identified from the bite marks on the clay. In addition, 201 impressions on skin were studied, and out of these cases, 41.01% of the same volunteers could be identified based on the bite mark impressions on the skin.

  20. Teacher Correction versus Peer-Marking

    Directory of Open Access Journals (Sweden)

    Mourente Miguel Mariana Correia

    2004-08-01

    Full Text Available Written language is undoubtedly more often used than oral language in a variety of contexts, including both the professional and academic life. Consequently, developing strategies for correcting compositions and improving students’ written production is of vital importance. This article describes an experiment aimed at assessing the two most widely used methods of correction for compositions –traditional teacher correction and peer marking and their effect on the frequency of errors. Data was collected by asking students to write and revise a text. Statistical tests were performed to analyse it. At the end of the experiment, it was found that no significant difference in efficiency existed between the two methods, contradicting expectations (cf. Davies, 2002; Levine et al., 2002 and Ward, 2001. Key words: English-Teaching, Foreign Language-Teaching Writing, Evaluation, Assessment El lenguaje escrito es sin duda usado con más frecuencia que el lenguaje oral en una variedad de situaciones o contextos, incluyendo tanto la vida profesional como la académica. En consecuencia, el desarrollo de estrategias para corregir composiciones y mejorar la producción escrita de los estudiantes es de suma importancia. Este artículo describe un experimento cuyo objetivo es evaluar los dos métodos más usados para la corrección de composiciones, la corrección tradicional por el maestro y la corrección por revisión de pares, con respecto a su efecto en la frecuencia de errores. Se recogió información haciendo que estudiantes escribieran y revisaran un texto y sobre esos textos se aplicaron pruebas estadísticas para analizar los errores. Contrario a lo esperado, al final del experimento, no se encontró ninguna diferencia significativa entre los resultados encontrados por los dos métodos, (cfr. Davies, 2002; Levine et al., 2002 y Ward, 2001. Palabras claves: Inglés-Enseñanza, Idioma Extranjero-Enseñanza, Composición, Evaluación

  1. Subtype-Specific Differences in Gag-Protease-Driven Replication Capacity Are Consistent with Intersubtype Differences in HIV-1 Disease Progression.

    Science.gov (United States)

    Kiguoya, Marion W; Mann, Jaclyn K; Chopera, Denis; Gounder, Kamini; Lee, Guinevere Q; Hunt, Peter W; Martin, Jeffrey N; Ball, T Blake; Kimani, Joshua; Brumme, Zabrina L; Brockman, Mark A; Ndung'u, Thumbi

    2017-07-01

    There are marked differences in the spread and prevalence of HIV-1 subtypes worldwide, and differences in clinical progression have been reported. However, the biological reasons underlying these differences are unknown. Gag-protease is essential for HIV-1 replication, and Gag-protease-driven replication capacity has previously been correlated with disease progression. We show that Gag-protease replication capacity correlates significantly with that of whole isolates ( r = 0.51; P = 0.04), indicating that Gag-protease is a significant contributor to viral replication capacity. Furthermore, we investigated subtype-specific differences in Gag-protease-driven replication capacity using large well-characterized cohorts in Africa and the Americas. Patient-derived Gag-protease sequences were inserted into an HIV-1 NL4-3 backbone, and the replication capacities of the resulting recombinant viruses were measured in an HIV-1-inducible reporter T cell line by flow cytometry. Recombinant viruses expressing subtype C Gag-proteases exhibited substantially lower replication capacities than those expressing subtype B Gag-proteases ( P identified Gag residues 483 and 484, located within the Alix-binding motif involved in virus budding, as major contributors to subtype-specific replicative differences. In East African cohorts, we observed a hierarchy of Gag-protease-driven replication capacities, i.e., subtypes A/C differences in disease progression. We thus hypothesize that the lower Gag-protease-driven replication capacity of subtypes A and C slows disease progression in individuals infected with these subtypes, which in turn leads to greater opportunity for transmission and thus increased prevalence of these subtypes. IMPORTANCE HIV-1 subtypes are unevenly distributed globally, and there are reported differences in their rates of disease progression and epidemic spread. The biological determinants underlying these differences have not been fully elucidated. Here, we show that

  2. The Escherichia coli Tus-Ter replication fork barrier causes site-specific DNA replication perturbation in yeast

    DEFF Research Database (Denmark)

    Larsen, Nicolai B; Sass, Ehud; Suski, Catherine

    2014-01-01

    Replication fork (RF) pausing occurs at both 'programmed' sites and non-physiological barriers (for example, DNA adducts). Programmed RF pausing is required for site-specific DNA replication termination in Escherichia coli, and this process requires the binding of the polar terminator protein, Tus...... as a versatile, site-specific, heterologous DNA replication-perturbing system, with a variety of potential applications....

  3. Multifaceted regulation of translational readthrough by RNA replication elements in a tombusvirus.

    Directory of Open Access Journals (Sweden)

    Peter A Cimino

    2011-12-01

    Full Text Available Translational readthrough of stop codons by ribosomes is a recoding event used by a variety of viruses, including plus-strand RNA tombusviruses. Translation of the viral RNA-dependent RNA polymerase (RdRp in tombusviruses is mediated using this strategy and we have investigated this process using a variety of in vitro and in vivo approaches. Our results indicate that readthrough generating the RdRp requires a novel long-range RNA-RNA interaction, spanning a distance of ∼3.5 kb, which occurs between a large RNA stem-loop located 3'-proximal to the stop codon and an RNA replication structure termed RIV at the 3'-end of the viral genome. Interestingly, this long-distance RNA-RNA interaction is modulated by mutually-exclusive RNA structures in RIV that represent a type of RNA switch. Moreover, a different long-range RNA-RNA interaction that was previously shown to be necessary for viral RNA replicase assembly was also required for efficient readthrough production of the RdRp. Accordingly, multiple replication-associated RNA elements are involved in modulating the readthrough event in tombusviruses and we propose an integrated mechanistic model to describe how this regulatory network could be advantageous by (i providing a quality control system for culling truncated viral genomes at an early stage in the replication process, (ii mediating cis-preferential replication of viral genomes, and (iii coordinating translational readthrough of the RdRp with viral genome replication. Based on comparative sequence analysis and experimental data, basic elements of this regulatory model extend to other members of Tombusviridae, as well as to viruses outside of this family.

  4. Molecular analysis of the replication program in unicellular model organisms.

    Science.gov (United States)

    Raghuraman, M K; Brewer, Bonita J

    2010-01-01

    Eukaryotes have long been reported to show temporal programs of replication, different portions of the genome being replicated at different times in S phase, with the added possibility of developmentally regulated changes in this pattern depending on species and cell type. Unicellular model organisms, primarily the budding yeast Saccharomyces cerevisiae, have been central to our current understanding of the mechanisms underlying the regulation of replication origins and the temporal program of replication in particular. But what exactly is a temporal program of replication, and how might it arise? In this article, we explore this question, drawing again on the wealth of experimental information in unicellular model organisms.

  5. Materials Chemistry and Performance of Silicone-Based Replicating Compounds.

    Energy Technology Data Exchange (ETDEWEB)

    Brumbach, Michael T.; Mirabal, Alex James; Kalan, Michael; Trujillo, Ana B; Hale, Kevin

    2014-11-01

    Replicating compounds are used to cast reproductions of surface features on a variety of materials. Replicas allow for quantitative measurements and recordkeeping on parts that may otherwise be difficult to measure or maintain. In this study, the chemistry and replicating capability of several replicating compounds was investigated. Additionally, the residue remaining on material surfaces upon removal of replicas was quantified. Cleaning practices were tested for several different replicating compounds. For all replicating compounds investigated, a thin silicone residue was left by the replica. For some compounds, additional inorganic species could be identified in the residue. Simple solvent cleaning could remove some residue.

  6. Regulation of replication fork progression through histone supply and demand

    DEFF Research Database (Denmark)

    Groth, Anja; Corpet, Armelle; Cook, Adam J L

    2007-01-01

    DNA replication in eukaryotes requires nucleosome disruption ahead of the replication fork and reassembly behind. An unresolved issue concerns how histone dynamics are coordinated with fork progression to maintain chromosomal stability. Here, we characterize a complex in which the human histone c...... progression and histone supply and demand.......1 chaperone function, histone supply, and replicative unwinding of DNA in chromatin. We propose that Asf1, as a histone acceptor and donor, handles parental and new histones at the replication fork via an Asf1-(H3-H4)-MCM2-7 intermediate and thus provides a means to fine-tune replication fork...

  7. From structure to mechanism—understanding initiation of DNA replication

    Science.gov (United States)

    Riera, Alberto; Barbon, Marta; Noguchi, Yasunori; Reuter, L. Maximilian; Schneider, Sarah; Speck, Christian

    2017-01-01

    DNA replication results in the doubling of the genome prior to cell division. This process requires the assembly of 50 or more protein factors into a replication fork. Here, we review recent structural and biochemical insights that start to explain how specific proteins recognize DNA replication origins, load the replicative helicase on DNA, unwind DNA, synthesize new DNA strands, and reassemble chromatin. We focus on the minichromosome maintenance (MCM2–7) proteins, which form the core of the eukaryotic replication fork, as this complex undergoes major structural rearrangements in order to engage with DNA, regulate its DNA-unwinding activity, and maintain genome stability. PMID:28717046

  8. Replicative DNA polymerase mutations in cancer☆

    Science.gov (United States)

    Heitzer, Ellen; Tomlinson, Ian

    2014-01-01

    Three DNA polymerases — Pol α, Pol δ and Pol ɛ — are essential for DNA replication. After initiation of DNA synthesis by Pol α, Pol δ or Pol ɛ take over on the lagging and leading strand respectively. Pol δ and Pol ɛ perform the bulk of replication with very high fidelity, which is ensured by Watson–Crick base pairing and 3′exonuclease (proofreading) activity. Yeast models have shown that mutations in the exonuclease domain of Pol δ and Pol ɛ homologues can cause a mutator phenotype. Recently, we identified germline exonuclease domain mutations (EDMs) in human POLD1 and POLE that predispose to ‘polymerase proofreading associated polyposis’ (PPAP), a disease characterised by multiple colorectal adenomas and carcinoma, with high penetrance and dominant inheritance. Moreover, somatic EDMs in POLE have also been found in sporadic colorectal and endometrial cancers. Tumors with EDMs are microsatellite stable and show an ‘ultramutator’ phenotype, with a dramatic increase in base substitutions. PMID:24583393

  9. Replicative DNA polymerase mutations in cancer.

    Science.gov (United States)

    Heitzer, Ellen; Tomlinson, Ian

    2014-02-01

    Three DNA polymerases - Pol α, Pol δ and Pol ɛ - are essential for DNA replication. After initiation of DNA synthesis by Pol α, Pol δ or Pol ɛ take over on the lagging and leading strand respectively. Pol δ and Pol ɛ perform the bulk of replication with very high fidelity, which is ensured by Watson-Crick base pairing and 3'exonuclease (proofreading) activity. Yeast models have shown that mutations in the exonuclease domain of Pol δ and Pol ɛ homologues can cause a mutator phenotype. Recently, we identified germline exonuclease domain mutations (EDMs) in human POLD1 and POLE that predispose to 'polymerase proofreading associated polyposis' (PPAP), a disease characterised by multiple colorectal adenomas and carcinoma, with high penetrance and dominant inheritance. Moreover, somatic EDMs in POLE have also been found in sporadic colorectal and endometrial cancers. Tumors with EDMs are microsatellite stable and show an 'ultramutator' phenotype, with a dramatic increase in base substitutions. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Education: DNA replication using microscale natural convection.

    Science.gov (United States)

    Priye, Aashish; Hassan, Yassin A; Ugaz, Victor M

    2012-12-07

    There is a need for innovative educational experiences that unify and reinforce fundamental principles at the interface between the physical, chemical, and life sciences. These experiences empower and excite students by helping them recognize how interdisciplinary knowledge can be applied to develop new products and technologies that benefit society. Microfluidics offers an incredibly versatile tool to address this need. Here we describe our efforts to create innovative hands-on activities that introduce chemical engineering students to molecular biology by challenging them to harness microscale natural convection phenomena to perform DNA replication via the polymerase chain reaction (PCR). Experimentally, we have constructed convective PCR stations incorporating a simple design for loading and mounting cylindrical microfluidic reactors between independently controlled thermal plates. A portable motion analysis microscope enables flow patterns inside the convective reactors to be directly visualized using fluorescent bead tracers. We have also developed a hands-on computational fluid dynamics (CFD) exercise based on modeling microscale thermal convection to identify optimal geometries for DNA replication. A cognitive assessment reveals that these activities strongly impact student learning in a positive way.

  11. Le Chatelier's principle in replicator dynamics

    Science.gov (United States)

    Allahverdyan, Armen E.; Galstyan, Aram

    2011-10-01

    The Le Chatelier principle states that physical equilibria are not only stable, but they also resist external perturbations via short-time negative-feedback mechanisms: a perturbation induces processes tending to diminish its results. The principle has deep roots, e.g., in thermodynamics it is closely related to the second law and the positivity of the entropy production. Here we study the applicability of the Le Chatelier principle to evolutionary game theory, i.e., to perturbations of a Nash equilibrium within the replicator dynamics. We show that the principle can be reformulated as a majorization relation. This defines a stability notion that generalizes the concept of evolutionary stability. We determine criteria for a Nash equilibrium to satisfy the Le Chatelier principle and relate them to mutualistic interactions (game-theoretical anticoordination) showing in which sense mutualistic replicators can be more stable than (say) competing ones. There are globally stable Nash equilibria, where the Le Chatelier principle is violated even locally: in contrast to the thermodynamic equilibrium a Nash equilibrium can amplify small perturbations, though both types of equilibria satisfy the detailed balance condition.

  12. Why threefold-replication of families?

    Science.gov (United States)

    Fitzpatrick, Gerald L.

    1998-04-01

    In spite of the many successes of the standard model of particle physics, the observed proliferation of matter-fields, in the form of ``replicated'' generations or families, is a major unsolved problem. In this paper, I explore some of the algebraic, geometric and physical consequences of a new organizing principle for fundamental fermions (quarks and leptons)(Gerald L. Fitzpatrick, phThe Family Problem--New Internal Algebraic and Geometric Regularities), Nova Scientific Press, Issaquah, Washington, 1997. Read more about this book (ISBN 0--9655695--0--0) and its subject matter at: http://www.tp.umu.se/TIPTOP and/or amazon.com>http://www.amazon.com.. The essence of the new organizing principle is the idea that the standard-model concept of scalar fermion numbers f can be generalized. In particular, a ``generalized fermion number,'' which consists of a 2× 2 matrix F that ``acts'' on an internal 2-space, instead of spacetime, is taken to describe certain internal properties of fundamental fermions. This generalization automatically introduces internal degrees of freedom that ``explain,'' among other things, family replication and the number (three) of families observed in nature.

  13. Endoplasmic reticulum stress causes EBV lytic replication.

    Science.gov (United States)

    Taylor, Gwen Marie; Raghuwanshi, Sandeep K; Rowe, David T; Wadowsky, Robert M; Rosendorff, Adam

    2011-11-17

    Endoplasmic reticulum (ER) stress triggers a homeostatic cellular response in mammalian cells to ensure efficient folding, sorting, and processing of client proteins. In lytic-permissive lymphoblastoid cell lines (LCLs), pulse exposure to the chemical ER-stress inducer thapsigargin (TG) followed by recovery resulted in the activation of the EBV immediate-early (BRLF1, BZLF1), early (BMRF1), and late (gp350) genes, gp350 surface expression, and virus release. The protein phosphatase 1 a (PP1a)-specific phosphatase inhibitor Salubrinal (SAL) synergized with TG to induce EBV lytic genes; however, TG treatment alone was sufficient to activate EBV lytic replication. SAL showed ER-stress-dependent and -independent antiviral effects, preventing virus release in human LCLs and abrogating gp350 expression in 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated B95-8 cells. TG resulted in sustained BCL6 but not BLIMP1 or CD138 expression, which is consistent with maintenance of a germinal center B-cell, rather than plasma-cell, phenotype. Microarray analysis identified candidate genes governing lytic replication in LCLs undergoing ER stress.

  14. How to securely replicate services (preliminary version)

    Science.gov (United States)

    Reiter, Michael; Birman, Kenneth

    1992-01-01

    A method is presented for constructing replicated services that retain their availability and integrity despite several servers and clients being corrupted by an intruder, in addition to others failing benignly. More precisely, a service is replicated by 'n' servers in such a way that a correct client will accept a correct server's response if, for some prespecified parameter, k, at least k servers are correct and fewer than k servers are correct. The issue of maintaining causality among client requests is also addressed. A security breach resulting from an intruder's ability to effect a violation of causality in the sequence of requests processed by the service is illustrated. An approach to counter this problem is proposed that requires that fewer than k servers are corrupt and, to ensure liveness, that k is less than or = n - 2t, where t is the assumed maximum total number of both corruptions and benign failures suffered by servers in any system run. An important and novel feature of these schemes is that the client need not be able to identify or authenticate even a single server. Instead, the client is required only to possess at most two public keys for the service.

  15. Strategic role of the ubiquitin-dependent segregase p97 (VCP or Cdc48) in DNA replication.

    Science.gov (United States)

    Ramadan, Kristijan; Halder, Swagata; Wiseman, Katherine; Vaz, Bruno

    2017-02-01

    Genome amplification (DNA synthesis) is one of the most demanding cellular processes in all proliferative cells. The DNA replication machinery (also known as the replisome) orchestrates genome amplification during S-phase of the cell cycle. Genetic material is particularly vulnerable to various events that can challenge the replisome during its assembly, activation (firing), progression (elongation) and disassembly from chromatin (termination). Any disturbance of the replisome leads to stalling of the DNA replication fork and firing of dormant replication origins, a process known as DNA replication stress. DNA replication stress is considered to be one of the main causes of sporadic cancers and other pathologies related to tissue degeneration and ageing. The mechanisms of replisome assembly and elongation during DNA synthesis are well understood. However, once DNA synthesis is complete, the process of replisome disassembly, and its removal from chromatin, remains unclear. In recent years, a growing body of evidence has alluded to a central role in replisome regulation for the ubiquitin-dependent protein segregase p97, also known as valosin-containing protein (VCP) in metazoans and Cdc48 in lower eukaryotes. By orchestrating the spatiotemporal turnover of the replisome, p97 plays an essential role in DNA replication. In this review, we will summarise our current knowledge about how p97 controls the replisome from replication initiation, to elongation and finally termination. We will also further examine the more recent findings concerning the role of p97 and how mutations in p97 cofactors, also known as adaptors, cause DNA replication stress induced genomic instability that leads to cancer and accelerated ageing. To our knowledge, this is the first comprehensive review concerning the mechanisms involved in the regulation of DNA replication by p97.

  16. Reactivation and Lytic Replication of Kaposi’s Sarcoma-Associated Herpesvirus: An Update

    Science.gov (United States)

    Aneja, Kawalpreet K.; Yuan, Yan

    2017-01-01

    The life cycle of Kaposi’s sarcoma-associated herpesvirus (KSHV) consists of two phases, latent and lytic. The virus establishes latency as a strategy for avoiding host immune surveillance and fusing symbiotically with the host for lifetime persistent infection. However, latency can be disrupted and KSHV is reactivated for entry into the lytic replication. Viral lytic replication is crucial for efficient dissemination from its long-term reservoir to the sites of disease and for the spread of the virus to new hosts. The balance of these two phases in the KSHV life cycle is important for both the virus and the host and control of the switch between these two phases is extremely complex. Various environmental factors such as oxidative stress, hypoxia, and certain chemicals have been shown to switch KSHV from latency to lytic reactivation. Immunosuppression, unbalanced inflammatory cytokines, and other viral co-infections also lead to the reactivation of KSHV. This review article summarizes the current understanding of the initiation and regulation of KSHV reactivation and the mechanisms underlying the process of viral lytic replication. In particular, the central role of an immediate-early gene product RTA in KSHV reactivation has been extensively investigated. These studies revealed multiple layers of regulation in activation of RTA as well as the multifunctional roles of RTA in the lytic replication cascade. Epigenetic regulation is known as a critical layer of control for the switch of KSHV between latency and lytic replication. The viral non-coding RNA, PAN, was demonstrated to play a central role in the epigenetic regulation by serving as a guide RNA that brought chromatin remodeling enzymes to the promoters of RTA and other lytic genes. In addition, a novel dimension of regulation by microPeptides emerged and has been shown to regulate RTA expression at the protein level. Overall, extensive investigation of KSHV reactivation and lytic replication has revealed

  17. A new MCM modification cycle regulates DNA replication initiation.

    Science.gov (United States)

    Wei, Lei; Zhao, Xiaolan

    2016-03-01

    The MCM DNA helicase is a central regulatory target during genome replication. MCM is kept inactive during G1, and it initiates replication after being activated in S phase. During this transition, the only known chemical change to MCM is the gain of multisite phosphorylation that promotes cofactor recruitment. Because replication initiation is intimately linked to multiple biological cues, additional changes to MCM can provide further regulatory points. Here, we describe a yeast MCM SUMOylation cycle that regulates replication. MCM subunits undergo SUMOylation upon loading at origins in G1 before MCM phosphorylation. MCM SUMOylation levels then decline as MCM phosphorylation levels rise, thus suggesting an inhibitory role of MCM SUMOylation during replication. Indeed, increasing MCM SUMOylation impairs replication initiation, partly through promoting the recruitment of a phosphatase that decreases MCM phosphorylation and activation. We propose that MCM SUMOylation counterbalances kinase-based regulation, thus ensuring accurate control of replication initiation.

  18. Replication, falsification, and the crisis of confidence in social psychology.

    Science.gov (United States)

    Earp, Brian D; Trafimow, David

    2015-01-01

    The (latest) crisis in confidence in social psychology has generated much heated discussion about the importance of replication, including how it should be carried out as well as interpreted by scholars in the field. For example, what does it mean if a replication attempt "fails"-does it mean that the original results, or the theory that predicted them, have been falsified? And how should "failed" replications affect our belief in the validity of the original research? In this paper, we consider the replication debate from a historical and philosophical perspective, and provide a conceptual analysis of both replication and falsification as they pertain to this important discussion. Along the way, we highlight the importance of auxiliary assumptions (for both testing theories and attempting replications), and introduce a Bayesian framework for assessing "failed" replications in terms of how they should affect our confidence in original findings.

  19. Replication, falsification, and the crisis of confidence in social psychology

    Science.gov (United States)

    Earp, Brian D.; Trafimow, David

    2015-01-01

    The (latest) crisis in confidence in social psychology has generated much heated discussion about the importance of replication, including how it should be carried out as well as interpreted by scholars in the field. For example, what does it mean if a replication attempt “fails”—does it mean that the original results, or the theory that predicted them, have been falsified? And how should “failed” replications affect our belief in the validity of the original research? In this paper, we consider the replication debate from a historical and philosophical perspective, and provide a conceptual analysis of both replication and falsification as they pertain to this important discussion. Along the way, we highlight the importance of auxiliary assumptions (for both testing theories and attempting replications), and introduce a Bayesian framework for assessing “failed” replications in terms of how they should affect our confidence in original findings. PMID:26042061

  20. Topology of Event Horizon

    OpenAIRE

    Siino, Masaru

    1997-01-01

    The topologies of event horizons are investigated. Considering the existence of the endpoint of the event horizon, it cannot be differentiable. Then there are the new possibilities of the topology of the event horizon though they are excluded in smooth event horizons. The relation between the topology of the event horizon and the endpoint of it is revealed. A torus event horizon is caused by two-dimensional endpoints. One-dimensional endpoints provide the coalescence of spherical event horizo...

  1. Studies on the mechanism of replication of adenovirus DNA. III. Electron microscopy of replicating DNA

    NARCIS (Netherlands)

    Ellens, D.J.; Sussenbach, J.S.; Jansz, H.S.

    1974-01-01

    Replicating Ad5 DNA was isolated from nuclei of infected KB cells and studied by electron microscopy. Branched as well as unbranched linear intermediates were observed containing extended regions of single-stranded DNA. The relationship between the branched and unbranched structures was studied

  2. 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.

  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. A CI-Independent Form of Replicative Inhibition: Turn Off of Early Replication of Bacteriophage Lambda

    Science.gov (United States)

    Hayes, Sidney; Horbay, Monique A.; Hayes, Connie

    2012-01-01

    Several earlier studies have described an unusual exclusion phenotype exhibited by cells with plasmids carrying a portion of the replication region of phage lambda. Cells exhibiting this inhibition phenotype (IP) prevent the plating of homo-immune and hybrid hetero-immune lambdoid phages. We have attempted to define aspects of IP, and show that it is directed to repλ phages. IP was observed in cells with plasmids containing a λ DNA fragment including oop, encoding a short OOP micro RNA, and part of the lambda origin of replication, oriλ, defined by iteron sequences ITN1-4 and an adjacent high AT-rich sequence. Transcription of the intact oop sequence from its promoter, pO is required for IP, as are iterons ITN3–4, but not the high AT-rich portion of oriλ. The results suggest that IP silencing is directed to theta mode replication initiation from an infecting repλ genome, or an induced repλ prophage. Phage mutations suppressing IP, i.e., Sip, map within, or adjacent to cro or in O, or both. Our results for plasmid based IP suggest the hypothesis that there is a natural mechanism for silencing early theta-mode replication initiation, i.e. the buildup of λ genomes with oop + oriλ+ sequence. PMID:22590552

  5. Grammatical Aspect in uences Event Duration Estimations: Evidence from Dutch

    NARCIS (Netherlands)

    Flecken, M.E.P.; Gerwien, J.; Knauff, M.; Pauen, M.; Sebanz, N.; Wachsmuth, I.

    2013-01-01

    This study investigates the effect of grammatical aspect marking in Dutch sentences, on speakers’ estimations of the duration of highly familiar, everyday events. We first established the ‘inherent’ or natural duration of different events (Exp. 1). This was then used for the manipulation of aspect

  6. DNA replication events during larval silk gland development in the silkworm, Bombyx mori.

    Science.gov (United States)

    Zhang, Chun-Dong; Li, Fang-Fang; Chen, Xiang-Yun; Huang, Mao-Hua; Zhang, Jun; Cui, Hongjuan; Pan, Min-Hui; Lu, Cheng

    2012-07-01

    The silk gland is an important organ in silkworm as it synthesizes silk proteins and is critical to spinning. The genomic DNA content of silk gland cells dramatically increases 200-400 thousand times for the larval life span through the process of endomitosis. Using in vitro culture, DNA synthesis was measured using BrdU labeling during the larval molt and intermolt periods. We found that the cell cycle of endomitosis was activated during the intermolt and was inhibited during the molt phase. The anterior silk gland, middle silk gland, and posterior silk gland cells asynchronously exit the endomitotic cycle after day 6 in 5th instar larvae, which correlated with the reduced expression of the cell cycle-related cdt1, pcna, cyclin E, cdk2 and cdk1 mRNAs in the wandering phase. Additional starvation had no effect on the initiation of silk gland DNA synthesis of the freshly ecdysed larvae. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Cutthroat trout virus as a surrogate in vitro infection model for testing inhibitors of hepatitis E virus replication

    Science.gov (United States)

    Debing, Yannick; Winton, James; Neyts, Johan; Dallmeier, Kai

    2013-01-01

    Hepatitis E virus (HEV) is one of the most important causes of acute hepatitis worldwide. Although most infections are self-limiting, mortality is particularly high in pregnant women. Chronic infections can occur in transplant and other immune-compromised patients. Successful treatment of chronic hepatitis E has been reported with ribavirin and pegylated interferon-alpha, however severe side effects were observed. We employed the cutthroat trout virus (CTV), a non-pathogenic fish virus with remarkable similarities to HEV, as a potential surrogate for HEV and established an antiviral assay against this virus using the Chinook salmon embryo (CHSE-214) cell line. Ribavirin and the respective trout interferon were found to efficiently inhibit CTV replication. Other known broad-spectrum inhibitors of RNA virus replication such as the nucleoside analog 2′-C-methylcytidine resulted only in a moderate antiviral activity. In its natural fish host, CTV levels largely fluctuate during the reproductive cycle with the virus detected mainly during spawning. We wondered whether this aspect of CTV infection may serve as a surrogate model for the peculiar pathogenesis of HEV in pregnant women. To that end the effect of three sex steroids on in vitro CTV replication was evaluated. Whereas progesterone resulted in marked inhibition of virus replication, testosterone and 17β-estradiol stimulated viral growth. Our data thus indicate that CTV may serve as a surrogate model for HEV, both for antiviral experiments and studies on the replication biology of the Hepeviridae.

  8. Interaction of the retinoblastoma protein with Orc1 and its recruitment to human origins of DNA replication.

    Directory of Open Access Journals (Sweden)

    Ramiro Mendoza-Maldonado

    Full Text Available BACKGROUND: The retinoblastoma protein (Rb is a crucial regulator of cell cycle progression by binding with E2F transcription factor and repressing the expression of a variety of genes required for the G1-S phase transition. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that Rb and E2F1 directly participate in the control of initiation of DNA replication in human HeLa, U2OS and T98G cells by specifically binding to origins of DNA replication in a cell cycle regulated manner. We show that, both in vitro and inside the cells, the largest subunit of the origin recognition complex (Orc1 specifically binds hypo-phosphorylated Rb and that this interaction is competitive with the binding of Rb to E2F1. The displacement of Rb-bound Orc1 by E2F1 at origins of DNA replication marks the progression of the G1 phase of the cell cycle toward the G1-S border. CONCLUSIONS/SIGNIFICANCE: The participation of Rb and E2F1 in the formation of the multiprotein complex that binds origins of DNA replication in mammalian cells appears to represent an effective mechanism to couple the expression of genes required for cell cycle progression to the activation of DNA replication.

  9. The Things of Caesar: Mark-ing the Plural (Mk 12:13–17

    Directory of Open Access Journals (Sweden)

    Warren Carter

    2014-09-01

    Full Text Available This article observes the rarely-discussed phenomenon that the Marcan paying-the-tax scene refers to tax in the singular, whilst the concluding saying uses the plural ‘the things of Caesar and of God’. The article accounts for this phenomenon by means of developing traditions. The section under the heading ‘Mark’s scene and saying about taxes (12:13–17’ counters the common claim that scene and saying originated as a unit from the historical Jesus. It proposes that whilst the saying may have originated with Jesus, the scene as we have it did not. The section under the heading ‘Social memory, orality, and a multi-referential saying?’ suggests some contexts that the saying about the things of Caesar addressed pre-Mark. And under the section ‘Trauma and Mark’s scene’ it is argued that Mark created a unit comprising scene and saying to negotiate the ‘ trauma’ of the 66–70 war. The unit evaluates freshly-asserted Roman power as idolatrous and blasphemous whilst simultaneously authorising the continued involvement of Jesus-believers in imperial society.

  10. Radio-marking and in vivo imagery of oligonucleotides

    International Nuclear Information System (INIS)

    Kuehnast, Bertrand

    2000-01-01

    This research thesis is part of activities aimed at the development of new molecules like oligonucleotides. Its first objective was the development and validation of a marking method with fluorine-18 of oligonucleotides for their in-vivo pharmacological assessment with positron emission tomography (PET). Further investigations addressed the use of iodine-125 for oligonucleotide marking purpose. This radio-marking, and in vivo and ex vivo imagery techniques are described, and their potential is highlighted for the pharmacological assessment of different oligonucleotides

  11. The naming of gender-marked pronouns supports interactivity in models of lexical access

    Directory of Open Access Journals (Sweden)

    Albert Costa

    2009-01-01

    Full Text Available When a speaker names an object using a gender-marked pronominal form, the referent word corresponding to the target object has to be selected in order to access the grammatical gender. By contrast, the phonological content of the referent word is not needed. In two picture-naming interference experiments we explored whether the lexical selection of a referent word is affected by its phonological properties. In Experiment 1, Spanish participants named pictures using a sentence with a noun or a pronoun while ignoring words semantically or phonologically related. The results showed a semantic interference effect and a Phonological Facilitation Effect (PFE in both type of utterances. In Experiment 2 the PFE was replicated with Italian participants in a different pronominal utterance. The PFE suggests that the lexical selection of the referent word is facilitated by the presentation of a distractor word phonologically related. These findings are consistent with the predictions of interactive models of lexical access.

  12. Reduced genetic distance and high replication levels increase the RNA recombination rate of hepatitis delta virus.

    Science.gov (United States)

    Lin, Chia-Chi; Yang, Zhi-Wei; Iang, Shan-Bei; Chao, Mei

    2015-01-02

    Hepatitis delta virus (HDV) replication is carried out by host RNA polymerases. Since homologous inter-genotypic RNA recombination is known to occur in HDV, possibly via a replication-dependent process, we hypothesized that the degree of sequence homology and the replication level should be related to the recombination frequency in cells co-expressing two HDV sequences. To confirm this, we separately co-transfected cells with three different pairs of HDV genomic RNAs and analyzed the obtained recombinants by RT-PCR followed by restriction fragment length polymorphism and sequencing analyses. The sequence divergence between the clones ranged from 24% to less than 0.1%, and the difference in replication levels was as high as 100-fold. As expected, significant differences were observed in the recombination frequencies, which ranged from 0.5% to 47.5%. Furthermore, varying the relative amounts of parental RNA altered the dominant recombinant species produced, suggesting that template switching occurs frequently during the synthesis of genomic HDV RNA. Taken together, these data suggest that during the host RNA polymerase-driven RNA recombination of HDV, both inter- and intra-genotypic recombination events are important in shaping the genetic diversity of HDV. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Genetic response to metabolic fluctuations: correlation between central carbon metabolism and DNA replication in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Szalewska-Pałasz Agnieszka

    2011-03-01

    Full Text Available Abstract Background Until now, the direct link between central carbon metabolism and DNA replication has been demonstrated only in Bacillus. subtilis. Therefore, we asked if this is a specific phenomenon, characteristic for this bacterium and perhaps for its close relatives, or a more general biological rule. Results We found that temperature-sensitivity of mutants in particular genes coding for replication proteins could be suppressed by deletions of certain genes coding for enzymes of the central carbon metabolism. Namely, the effects of dnaA46(ts mutation could be suppressed by dysfunction of pta or ackA, effects of dnaB(ts by dysfunction of pgi or pta, effects of dnaE486(ts by dysfunction of tktB, effects of dnaG(ts by dysfunction of gpmA, pta or ackA, and effects of dnaN159(ts by dysfunction of pta or ackA. The observed suppression effects were not caused by a decrease in bacterial growth rate. Conclusions The genetic correlation exists between central carbon metabolism and DNA replication in the model Gram-negative bacterium, E. coli. This link exists at the steps of initiation and elongation of DNA replication, indicating the important global correlation between metabolic status of the cell and the events leading to cell reproduction.

  14. Oncogenic Herpesvirus Utilizes Stress-Induced Cell Cycle Checkpoints for Efficient Lytic Replication.

    Directory of Open Access Journals (Sweden)

    Giuseppe Balistreri

    2016-02-01

    Full Text Available Kaposi's sarcoma herpesvirus (KSHV causes Kaposi's sarcoma and certain lymphoproliferative malignancies. Latent infection is established in the majority of tumor cells, whereas lytic replication is reactivated in a small fraction of cells, which is important for both virus spread and disease progression. A siRNA screen for novel regulators of KSHV reactivation identified the E3 ubiquitin ligase MDM2 as a negative regulator of viral reactivation. Depletion of MDM2, a repressor of p53, favored efficient activation of the viral lytic transcription program and viral reactivation. During lytic replication cells activated a p53 response, accumulated DNA damage and arrested at G2-phase. Depletion of p21, a p53 target gene, restored cell cycle progression and thereby impaired the virus reactivation cascade delaying the onset of virus replication induced cytopathic effect. Herpesviruses are known to reactivate in response to different kinds of stress, and our study now highlights the molecular events in the stressed host cell that KSHV has evolved to utilize to ensure efficient viral lytic replication.

  15. RTEL1 contributes to DNA replication and repair and telomere maintenance.

    Science.gov (United States)

    Uringa, Evert-Jan; Lisaingo, Kathleen; Pickett, Hilda A; Brind'Amour, Julie; Rohde, Jan-Hendrik; Zelensky, Alex; Essers, Jeroen; Lansdorp, Peter M

    2012-07-01

    Telomere maintenance and DNA repair are important processes that protect the genome against instability. mRtel1, an essential helicase, is a dominant factor setting telomere length in mice. In addition, mRtel1 is involved in DNA double-strand break repair. The role of mRtel1 in telomere maintenance and genome stability is poorly understood. Therefore we used mRtel1-deficient mouse embryonic stem cells to examine the function of mRtel1 in replication, DNA repair, recombination, and telomere maintenance. mRtel1-deficient mouse embryonic stem cells showed sensitivity to a range of DNA-damaging agents, highlighting its role in replication and genome maintenance. Deletion of mRtel1 increased the frequency of sister chromatid exchange events and suppressed gene replacement, demonstrating the involvement of the protein in homologous recombination. mRtel1 localized transiently at telomeres and is needed for efficient telomere replication. Of interest, in the absence of mRtel1, telomeres in embryonic stem cells appeared relatively stable in length, suggesting that mRtel1 is required to allow extension by telomerase. We propose that mRtel1 is a key protein for DNA replication, recombination, and repair and efficient elongation of telomeres by telomerase.

  16. Regulation of adeno-associated virus DNA replication by the cellular TAF-I/set complex.

    Science.gov (United States)

    Pegoraro, Gianluca; Marcello, Alessandro; Myers, Michael P; Giacca, Mauro

    2006-07-01

    The Rep proteins of the adeno-associated virus (AAV) are required for viral replication in the presence of adenovirus helper functions and as yet poorly characterized cellular factors. In an attempt to identify such factors, we purified Flag-Rep68-interacting proteins from human cell lysates. Several polypeptides were identified by mass spectrometry, among which was ANP32B, a member of the acidic nuclear protein 32 family which takes part in the formation of the template-activating factor I/Set oncoprotein (TAF-I/Set) complex. The N terminus of Rep was found to specifically bind the acidic domain of ANP32B; through this interaction, Rep was also able to recruit other members of the TAF-I/Set complex, including the ANP32A protein and the histone chaperone TAF-I/Set. Further experiments revealed that silencing of ANP32A and ANP32B inhibited AAV replication, while overexpression of all of the components of the TAF-I/Set complex increased de novo AAV DNA synthesis in permissive cells. Besides being the first indication that the TAF-I/Set complex participates in wild-type AAV replication, these findings have important implications for the generation of recombinant AAV vectors since overexpression of the TAF-I/Set components was found to markedly increase viral vector production.

  17. Replicability and generalizability of PTSD networks

    DEFF Research Database (Denmark)

    Eiko I., Fried; Eidhof, Marloes B.; Palic, Sabina

    2018-01-01

    The growing literature conceptualizing mental disorders like Posttraumatic Stress Disorder (PTSD) as networks of interacting symptoms faces three key challenges. Prior studies predominantly used (a) small samples with low power for precise estimation, (b) non-clinical samples, and (c) single...... samples. This renders network structures in clinical data, and the extent to which networks replicate across datasets, unknown. To overcome these limitations, the present cross-cultural multisite study estimated regularized partial correlation networks of 16 PTSD symptoms across four datasets...... of traumatized patients receiving treatment for PTSD (total N=2,782). Despite differences in culture, trauma-type and severity of the samples, considerable similarities emerged, with moderate to high correlations between symptom profiles (0.43-0.82), network structures (0.62-0.74), and centrality estimates (0...

  18. Archaeal Viruses: Diversity, Replication, and Structure.

    Science.gov (United States)

    Dellas, Nikki; Snyder, Jamie C; Bolduc, Benjamin; Young, Mark J

    2014-11-01

    The Archaea-and their viruses-remain the most enigmatic of life's three domains. Once thought to inhabit only extreme environments, archaea are now known to inhabit diverse environments. Even though the first archaeal virus was described over 40 years ago, only 117 archaeal viruses have been discovered to date. Despite this small number, these viruses have painted a portrait of enormous morphological and genetic diversity. For example, research centered around the various steps of the archaeal virus life cycle has led to the discovery of unique mechanisms employed by archaeal viruses during replication, maturation, and virion release. In many instances, archaeal virus proteins display very low levels of sequence homology to other proteins listed in the public database, and therefore, structural characterization of these proteins has played an integral role in functional assignment. These structural studies have not only provided insights into structure-function relationships but have also identified links between viruses across all three domains of life.

  19. Data Service: Distributed Data Capture and Replication

    Science.gov (United States)

    Warner, P. B.; Pietrowicz, S. R.

    2007-10-01

    Data Service is a critical component of the NOAO Data Management and Science Support (DMaSS) Solutions Platform, which is based on a service-oriented architecture, and is to replace the current NOAO Data Transport System. Its responsibilities include capturing data from NOAO and partner telescopes and instruments and replicating the data across multiple (currently six) storage sites. Java 5 was chosen as the implementation language, and Java EE as the underlying enterprise framework. Application metadata persistence is performed using EJB and Hibernate on the JBoss Application Server, with PostgreSQL as the persistence back-end. Although potentially any underlying mass storage system may be used as the Data Service file persistence technology, DTS deployments and Data Service test deployments currently use the Storage Resource Broker from SDSC. This paper presents an overview and high-level design of the Data Service, including aspects of deployment, e.g., for the LSST Data Challenge at the NCSA computing facilities.

  20. Security in a Replicated Metadata Catalogue

    CERN Document Server

    Koblitz, B

    2007-01-01

    The gLite-AMGA metadata has been developed by NA4 to provide simple relational metadata access for the EGEE user community. As advanced features, which will be the focus of this presentation, AMGA provides very fine-grained security also in connection with the built-in support for replication and federation of metadata. AMGA is extensively used by the biomedical community to store medical images metadata, digital libraries, in HEP for logging and bookkeeping data and in the climate community. The biomedical community intends to deploy a distributed metadata system for medical images consisting of various sites, which range from hospitals to computing centres. Only safe sharing of the highly sensitive metadata as provided in AMGA makes such a scenario possible. Other scenarios are digital libraries, which federate copyright protected (meta-) data into a common catalogue. The biomedical and digital libraries have been deployed using a centralized structure already for some time. They now intend to decentralize ...

  1. Suggestibility and negative priming: two replication studies.

    Science.gov (United States)

    David, Daniel; Brown, Richard J

    2002-07-01

    Research suggests that inhibiting the effect of irrelevant stimuli on subsequent thought and action (cognitive inhibition) may be an important component of suggestibility. Two small correlation studies were conducted to address the relationship between different aspects of suggestibility and individual differences in cognitive inhibition, operationalized as the degree of negative priming generated by to-be-ignored stimuli in a semantic categorization task. The first study found significant positive correlations between negative priming, hypnotic suggestibility, and creative imagination; a significant negative correlation was obtained between negative priming and interrogative suggestibility, demonstrating the discriminant validity of the study results. The second study replicated the correlation between negative priming and hypnotic suggestibility, using a different suggestibility measurement procedure that assessed subjective experience and hypnotic involuntariness as well as objective responses to suggestions. These studies support the notion that the ability to engage in cognitive inhibition may be an important component of hypnotic responsivity and maybe of other forms of suggestibility.

  2. Experimenter gender and replicability in science.

    Science.gov (United States)

    Chapman, Colin D; Benedict, Christian; Schiöth, Helgi B

    2018-01-01

    There is a replication crisis spreading through the annals of scientific inquiry. Although some work has been carried out to uncover the roots of this issue, much remains unanswered. With this in mind, this paper investigates how the gender of the experimenter may affect experimental findings. Clinical trials are regularly carried out without any report of the experimenter's gender and with dubious knowledge of its influence. Consequently, significant biases caused by the experimenter's gender may lead researchers to conclude that therapeutics or other interventions are either overtreating or undertreating a variety of conditions. Bearing this in mind, this policy paper emphasizes the importance of reporting and controlling for experimenter gender in future research. As backdrop, it explores what we know about the role of experimenter gender in influencing laboratory results, suggests possible mechanisms, and suggests future areas of inquiry.

  3. Event segmentation ability uniquely predicts event memory.

    Science.gov (United States)

    Sargent, Jesse Q; Zacks, Jeffrey M; Hambrick, David Z; Zacks, Rose T; Kurby, Christopher A; Bailey, Heather R; Eisenberg, Michelle L; Beck, Taylor M

    2013-11-01

    Memory for everyday events plays a central role in tasks of daily living, autobiographical memory, and planning. Event memory depends in part on segmenting ongoing activity into meaningful units. This study examined the relationship between event segmentation and memory in a lifespan sample to answer the following question: Is the ability to segment activity into meaningful events a unique predictor of subsequent memory, or is the relationship between event perception and memory accounted for by general cognitive abilities? Two hundred and eight adults ranging from 20 to 79years old segmented movies of everyday events and attempted to remember the events afterwards. They also completed psychometric ability tests and tests measuring script knowledge for everyday events. Event segmentation and script knowledge both explained unique variance in event memory above and beyond the psychometric measures, and did so as strongly in older as in younger adults. These results suggest that event segmentation is a basic cognitive mechanism, important for memory across the lifespan. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Inhibition of Zika Virus Replication by Silvestrol

    Directory of Open Access Journals (Sweden)

    Fabian Elgner

    2018-03-01

    Full Text Available The Zika virus (ZIKV outbreak in 2016 in South America with specific pathogenic outcomes highlighted the need for new antiviral substances with broad-spectrum activities to react quickly to unexpected outbreaks of emerging viral pathogens. Very recently, the natural compound silvestrol isolated from the plant Aglaia foveolata was found to have very potent antiviral effects against the (−-strand RNA-virus Ebola virus as well as against Corona- and Picornaviruses with a (+-strand RNA-genome. This antiviral activity is based on the impaired translation of viral RNA by the inhibition of the DEAD-box RNA helicase eukaryotic initiation factor-4A (eIF4A which is required to unwind structured 5´-untranslated regions (5′-UTRs of several proto-oncogenes and thereby facilitate their translation. Zika virus is a flavivirus with a positive-stranded RNA-genome harboring a 5′-capped UTR with distinct secondary structure elements. Therefore, we investigated the effects of silvestrol on ZIKV replication in A549 cells and primary human hepatocytes. Two different ZIKV strains were used. In both infected A549 cells and primary human hepatocytes, silvestrol has the potential to exert a significant inhibition of ZIKV replication for both analyzed strains, even though the ancestor strain from Uganda is less sensitive to silvestrol. Our data might contribute to identify host factors involved in the control of ZIKV infection and help to develop antiviral concepts that can be used to treat a variety of viral infections without the risk of resistances because a host protein is targeted.

  5. Direct Visualization of DNA Replication Dynamics in Zebrafish Cells.

    Science.gov (United States)

    Kuriya, Kenji; Higashiyama, Eriko; Avşar-Ban, Eriko; Tamaru, Yutaka; Ogata, Shin; Takebayashi, Shin-ichiro; Ogata, Masato; Okumura, Katsuzumi

    2015-12-01

    Spatiotemporal regulation of DNA replication in the S-phase nucleus has been extensively studied in mammalian cells because it is tightly coupled with the regulation of other nuclear processes such as transcription. However, little is known about the replication dynamics in nonmammalian cells. Here, we analyzed the DNA replication processes of zebrafish (Danio rerio) cells through the direct visualization of replicating DNA in the nucleus and on DNA fiber molecules isolated from the nucleus. We found that zebrafish chromosomal DNA at the nuclear interior was replicated first, followed by replication of DNA at the nuclear periphery, which is reminiscent of the spatiotemporal regulation of mammalian DNA replication. However, the relative duration of interior DNA replication in zebrafish cells was longer compared to mammalian cells, possibly reflecting zebrafish-specific genomic organization. The rate of replication fork progression and ori-to-ori distance measured by the DNA combing technique were ∼ 1.4 kb/min and 100 kb, respectively, which are comparable to those in mammalian cells. To our knowledge, this is a first report that measures replication dynamics in zebrafish cells.

  6. 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.

  7. Early intranuclear replication of African swine fever virus genome modifies the landscape of the host cell nucleus.

    Science.gov (United States)

    Simões, Margarida; Martins, Carlos; Ferreira, Fernando

    2015-12-02

    Although African swine fever virus (ASFV) replicates in viral cytoplasmic factories, the presence of viral DNA within the host cell nucleus has been previously reported to be essential for productive infection. Herein, we described, for the first time, the intranuclear distribution patterns of viral DNA replication events, preceding those that occur in the cytoplasmic compartment. Using BrdU pulse-labelling experiments, newly synthesized ASFV genomes were exclusively detected inside the host cell nucleus at the early phase of infection, both in swine monocyte-derived macrophages (MDMs) and Vero cells. From 8hpi onwards, BrdU labelling was only observed in ASFV cytoplasmic factories. Our results also show that ASFV specifically activates the Ataxia Telangiectasia Mutated Rad-3 related (ATR) pathway in ASFV-infected swine MDMs from the early phase of infection, most probably because ASFV genome is recognized as foreign DNA. Morphological changes of promyelocytic leukaemia nuclear bodies (PML-NBs), nuclear speckles and Cajal bodies were also found in ASFV-infected swine MDMs, strongly suggesting the viral modulation of cellular antiviral responses and cellular transcription, respectively. As described for other viral infections, the nuclear reorganization that takes place during ASFV infection may also provide an environment that favours its intranuclear replication events. Altogether, our results contribute for a better understanding of ASFV replication strategies, starting with an essential intranuclear DNA replication phase which induces host nucleus changes towards a successful viral infection. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Control of Genome Integrity by RFC Complexes; Conductors of PCNA Loading onto and Unloading from Chromatin during DNA Replication

    Directory of Open Access Journals (Sweden)

    Yasushi Shiomi

    2017-01-01

    Full Text Available During cell division, genome integrity is maintained by faithful DNA replication during S phase, followed by accurate segregation in mitosis. Many DNA metabolic events linked with DNA replication are also regulated throughout the cell cycle. In eukaryotes, the DNA sliding clamp, proliferating cell nuclear antigen (PCNA, acts on chromatin as a processivity factor for DNA polymerases. Since its discovery, many other PCNA binding partners have been identified that function during DNA replication, repair, recombination, chromatin remodeling, cohesion, and proteolysis in cell-cycle progression. PCNA not only recruits the proteins involved in such events, but it also actively controls their function as chromatin assembles. Therefore, control of PCNA-loading onto chromatin is fundamental for various replication-coupled reactions. PCNA is loaded onto chromatin by PCNA-loading replication factor C (RFC complexes. Both RFC1-RFC and Ctf18-RFC fundamentally function as PCNA loaders. On the other hand, after DNA synthesis, PCNA must be removed from chromatin by Elg1-RFC. Functional defects in RFC complexes lead to chromosomal abnormalities. In this review, we summarize the structural and functional relationships among RFC complexes, and describe how the regulation of PCNA loading/unloading by RFC complexes contributes to maintaining genome integrity.

  9. FBH1 co-operates with MUS81 in inducing DNA double-strand breaks and cell death following replication stress

    DEFF Research Database (Denmark)

    Fugger, Kasper; Chu, Wai Kit; Haahr, Peter

    2013-01-01

    The molecular events occurring following the disruption of DNA replication forks are poorly characterized, despite extensive use of replication inhibitors such as hydroxyurea in the treatment of malignancies. Here, we identify a key role for the FBH1 helicase in mediating DNA double-strand break...... formation following replication inhibition. We show that FBH1-deficient cells are resistant to killing by hydroxyurea, and exhibit impaired activation of the pro-apoptotic factor p53, consistent with decreased DNA double-strand break formation. Similar findings were obtained in murine ES cells carrying...... of replication stress. Our data suggest that FBH1 helicase activity is required to eliminate cells with excessive replication stress through the generation of MUS81-induced DNA double-strand breaks....

  10. An amphipathic alpha-helix controls multiple roles of brome mosaic virus protein 1a in RNA replication complex assembly and function.

    Directory of Open Access Journals (Sweden)

    Ling Liu

    2009-03-01

    Full Text Available Brome mosaic virus (BMV protein 1a has multiple key roles in viral RNA replication. 1a localizes to perinuclear endoplasmic reticulum (ER membranes as a peripheral membrane protein, induces ER membrane invaginations in which RNA replication complexes form, and recruits and stabilizes BMV 2a polymerase (2a(Pol and RNA replication templates at these sites to establish active replication complexes. During replication, 1a provides RNA capping, NTPase and possibly RNA helicase functions. Here we identify in BMV 1a an amphipathic alpha-helix, helix A, and use NMR analysis to define its structure and propensity to insert in hydrophobic membrane-mimicking micelles. We show that helix A is essential for efficient 1a-ER membrane association and normal perinuclear ER localization, and that deletion or mutation of helix A abolishes RNA replication. Strikingly, mutations in helix A give rise to two dramatically opposite 1a function phenotypes, implying that helix A acts as a molecular switch regulating the intricate balance between separable 1a functions. One class of helix A deletions and amino acid substitutions markedly inhibits 1a-membrane association and abolishes ER membrane invagination, viral RNA template recruitment, and replication, but doubles the 1a-mediated increase in 2a(Pol accumulation. The second class of helix A mutations not only maintains efficient 1a-membrane association but also amplifies the number of 1a-induced membrane invaginations 5- to 8-fold and enhances viral RNA template recruitment, while failing to stimulate 2a(Pol accumulation. The results provide new insights into the pathways of RNA replication complex assembly and show that helix A is critical for assembly and function of the viral RNA replication complex, including its central role in targeting replication components and controlling modes of 1a action.

  11. Significant Tsunami Events

    Science.gov (United States)

    Dunbar, P. K.; Furtney, M.; McLean, S. J.; Sweeney, A. D.

    2014-12-01

    Tsunamis have inflicted death and destruction on the coastlines of the world throughout history. The occurrence of tsunamis and the resulting effects have been collected and studied as far back as the second millennium B.C. The knowledge gained from cataloging and examining these events has led to significant changes in our understanding of tsunamis, tsunami sources, and methods to mitigate the effects of tsunamis. The most significant, not surprisingly, are often the most devastating, such as the 2011 Tohoku, Japan earthquake and tsunami. The goal of this poster is to give a brief overview of the occurrence of tsunamis and then focus specifically on several significant tsunamis. There are various criteria to determine the most significant tsunamis: the number of deaths, amount of damage, maximum runup height, had a major impact on tsunami science or policy, etc. As a result, descriptions will include some of the most costly (2011 Tohoku, Japan), the most deadly (2004 Sumatra, 1883 Krakatau), and the highest runup ever observed (1958 Lituya Bay, Alaska). The discovery of the Cascadia subduction zone as the source of the 1700 Japanese "Orphan" tsunami and a future tsunami threat to the U.S. northwest coast, contributed to the decision to form the U.S. National Tsunami Hazard Mitigation Program. The great Lisbon earthquake of 1755 marked the beginning of the modern era of seismology. Knowledge gained from the 1964 Alaska earthquake and tsunami helped confirm the theory of plate tectonics. The 1946 Alaska, 1952 Kuril Islands, 1960 Chile, 1964 Alaska, and the 2004 Banda Aceh, tsunamis all resulted in warning centers or systems being established.The data descriptions on this poster were extracted from NOAA's National Geophysical Data Center (NGDC) global historical tsunami database. Additional information about these tsunamis, as well as water level data can be found by accessing the NGDC website www.ngdc.noaa.gov/hazard/

  12. Replicative age induces mitotic recombination in the ribosomal RNA gene cluster of Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Derek L Lindstrom

    2011-03-01

    Full Text Available Somatic mutations contribute to the development of age-associated disease. In earlier work, we found that, at high frequency, aging Saccharomyces cerevisiae diploid cells produce daughters without mitochondrial DNA, leading to loss of respiration competence and increased loss of heterozygosity (LOH in the nuclear genome. Here we used the recently developed Mother Enrichment Program to ask whether aging cells that maintain the ability to produce respiration-competent daughters also experience increased genomic instability. We discovered that this population exhibits a distinct genomic instability phenotype that primarily affects the repeated ribosomal RNA gene array (rDNA array. As diploid cells passed their median replicative life span, recombination rates between rDNA arrays on homologous chromosomes progressively increased, resulting in mutational events that generated LOH at >300 contiguous open reading frames on the right arm of chromosome XII. We show that, while these recombination events were dependent on the replication fork block protein Fob1, the aging process that underlies this phenotype is Fob1-independent. Furthermore, we provide evidence that this aging process is not driven by mechanisms that modulate rDNA recombination in young cells, including loss of cohesion within the rDNA array or loss of Sir2 function. Instead, we suggest that the age-associated increase in rDNA recombination is a response to increasing DNA replication stress generated in aging cells.

  13. Marked bengal pink. A dynamic test using marking doses; its value in jaundice diagnosis

    International Nuclear Information System (INIS)

    Kellershohn, C.; Desgrez, A.; Delaloye, B.

    1961-01-01

    The authors do a historic calling back of the differential study of jaundices thanks to the semi logarithmic gradients of expurgation of bromine sulphone-phthalein and thanks to the time of appearance of this material in the bile collected by duodenal tubing. They sum up likewise the foreign works which lead to take the place of this test, the outside count at the level of the head, the liver, and the abdomen after intravenous injection of a running dose of marked Rose Bengal. They specify the technical conditions of this test and report an experience which corroborate its value, its accuracy and the interest of its using in the different types of jaundices (hepatitis and obstructive types). (author) [fr

  14. Induction of UV-resistant DNA replication in Escherichia coli: Induced stable DNA replication as an SOS function

    International Nuclear Information System (INIS)

    Kogoma, T.; Torrey, T.A.; Connaughton, M.J.

    1979-01-01

    The striking similarity between the treatments that induce SOS functions and those that result in stable DNA replication (continuous DNA replication in the absence of protein synthesis) prompted us to examine the possibility of stable DNA replication being a recA + lexA + -dependent SOS function. In addition to the treatments previously reported, ultraviolet (UV) irradiation or treatment with mitomycin C was also found to induce stable DNA replication. The thermal treatment of tif-1 strains did not result in detectable levels of stable DNA replication, but nalidixic acid readily induced the activity in these strains. The induction of stable DNA replication with nalidixic acid was severely suppressed in tif-1 lex A mutant strains. The inhibitory activity of lexA3 was negated by the presence of the spr-5l mutation, an intragenic suppressor of lexA3. Induced stable DNA replication was found to be considerably more resistant to UV irradiation than normal replication both in a uvr A6 strain and a uvr + strain. The UV-resistant replication occurred mostly in the semiconservative manner. The possible roles of stable DNA replication in repair of damaged DNA are discussed. (orig.)

  15. Effector-Triggered Self-Replication in Coupled Subsystems.

    Science.gov (United States)

    Komáromy, Dávid; Tezcan, Meniz; Schaeffer, Gaël; Marić, Ivana; Otto, Sijbren

    2017-11-13

    In living systems processes like genome duplication and cell division are carefully synchronized through subsystem coupling. If we are to create life de novo, similar control over essential processes such as self-replication need to be developed. Here we report that coupling two dynamic combinatorial subsystems, featuring two separate building blocks, enables effector-mediated control over self-replication. The subsystem based on the first building block shows only self-replication, whereas that based on the second one is solely responsive toward a specific external effector molecule. Mixing the subsystems arrests replication until the effector molecule is added, resulting in the formation of a host-effector complex and the liberation of the building block that subsequently engages in self-replication. The onset, rate and extent of self-replication is controlled by the amount of effector present. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Causation and the origin of life. Metabolism or replication first?

    Science.gov (United States)

    Pross, Addy

    2004-06-01

    The conceptual gulf that separates the 'metabolism first' and 'replication first' mechanisms for the emergence of life continues to cloud the origin of life debate. In the present paper we analyze this aspect of the origin of life problem and offer arguments in favor of the 'replication first' school. Utilizing Wicken's two-tier approach to causation we argue that a causal connection between replication and metabolism can only be demonstrated if replication would have preceded metabolism. In conjunction with existing empirical evidence and theoretical reasoning, our analysis concludes that there is no substantive evidence for a 'metabolism first' mechanism for life's emergence, while a coherent case can be made for the 'replication first' group of mechanisms. The analysis reaffirms our conviction that life is an extreme expression of kinetic control, and that the emergence of metabolic pathways can be understood by considering life as a manifestation of 'replicative chemistry'.

  17. Regulated eukaryotic DNA replication origin firing with purified proteins.

    Science.gov (United States)

    Yeeles, Joseph T P; Deegan, Tom D; Janska, Agnieszka; Early, Anne; Diffley, John F X

    2015-03-26

    Eukaryotic cells initiate DNA replication from multiple origins, which must be tightly regulated to promote precise genome duplication in every cell cycle. To accomplish this, initiation is partitioned into two temporally discrete steps: a double hexameric minichromosome maintenance (MCM) complex is first loaded at replication origins during G1 phase, and then converted to the active CMG (Cdc45-MCM-GINS) helicase during S phase. Here we describe the reconstitution of budding yeast DNA replication initiation with 16 purified replication factors, made from 42 polypeptides. Origin-dependent initiation recapitulates regulation seen in vivo. Cyclin-dependent kinase (CDK) inhibits MCM loading by phosphorylating the origin recognition complex (ORC) and promotes CMG formation by phosphorylating Sld2 and Sld3. Dbf4-dependent kinase (DDK) promotes replication by phosphorylating MCM, and can act either before or after CDK. These experiments define the minimum complement of proteins, protein kinase substrates and co-factors required for regulated eukaryotic DNA replication.

  18. Ülar Mark: loome uut ja iga loomisega lammutame midagi / Ülar Mark ; intervjueerinud Mikk Salu

    Index Scriptorium Estoniae

    Mark, Ülar, 1968-

    2010-01-01

    Eesti Arhitektuurikeskuse juhatuse esimees, arhitekt Ülar Mark Tallinna arhitektuurist ja linna arengust, demokraatlikust linnaruumist. Pikemalt Solarise keskusest, vabadussambast, väikepoodide asemele suurte kaubanduskeskuste tulekust

  19. Collection, storage and management of high-water marks data: praxis and recommendations

    Directory of Open Access Journals (Sweden)

    Piotte Olivier

    2016-01-01

    Full Text Available High-water marks data, in its most general definition, is a precious source of information for the many stakeholders involved in risk culture, inundation mapping, river, estuarine or coastal studies, etc. Although there have already been many initiatives to collect and exploit existing data, as well as collecting new marks after flood events, a lack of harmonization and coordination remains. The French flood forecasting services, together with Cerema, decided to provide technical and organizational solutions in order to set up a collaborative management approach of high-water marks data. On the one hand, a methodological handbook has been produced, giving recommendations for post-flood field investigations. It comes with a dedicated PDA tool and a PC desktop software. On the other hand, a national repository has been built, making it possible to gather the large range of informations usually needed. This repository is combined with a collaborative web platform, which aims to be a way of public access to the available information, a working tool for technical users, and a front door to contribute to the inventory. The last step of this approach is the setting of an organization blue-print including all the stakeholders directly or indirectly involved in high-water marks knowledge.

  20. Marked point process for modelling seismic activity (case study in Sumatra and Java)

    Science.gov (United States)

    Pratiwi, Hasih; Sulistya Rini, Lia; Wayan Mangku, I.

    2018-05-01

    Earthquake is a natural phenomenon that is random, irregular in space and time. Until now the forecast of earthquake occurrence at a location is still difficult to be estimated so that the development of earthquake forecast methodology is still carried out both from seismology aspect and stochastic aspect. To explain the random nature phenomena, both in space and time, a point process approach can be used. There are two types of point processes: temporal point process and spatial point process. The temporal point process relates to events observed over time as a sequence of time, whereas the spatial point process describes the location of objects in two or three dimensional spaces. The points on the point process can be labelled with additional information called marks. A marked point process can be considered as a pair (x, m) where x is the point of location and m is the mark attached to the point of that location. This study aims to model marked point process indexed by time on earthquake data in Sumatra Island and Java Island. This model can be used to analyse seismic activity through its intensity function by considering the history process up to time before t. Based on data obtained from U.S. Geological Survey from 1973 to 2017 with magnitude threshold 5, we obtained maximum likelihood estimate for parameters of the intensity function. The estimation of model parameters shows that the seismic activity in Sumatra Island is greater than Java Island.