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Sample records for replicator event mark

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

    Science.gov (United States)

    Jasencakova, Zuzana; Scharf, Annette N D; Ask, Katrine; Corpet, Armelle; Imhof, Axel; Almouzni, Geneviève; Groth, Anja

    2010-03-12

    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 that replication stress interferes with predeposition marking and histone recycling with potential impact on epigenetic stability.

  2. The spatiotemporal program of DNA replication is associated with specific combinations of chromatin marks in human cells.

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    Franck Picard

    2014-05-01

    Full Text Available The duplication of mammalian genomes is under the control of a spatiotemporal program that orchestrates the positioning and the timing of firing of replication origins. The molecular mechanisms coordinating the activation of about [Formula: see text] predicted origins remain poorly understood, partly due to the intrinsic rarity of replication bubbles, making it difficult to purify short nascent strands (SNS. The precise identification of origins based on the high-throughput sequencing of SNS constitutes a new methodological challenge. We propose a new statistical method with a controlled resolution, adapted to the detection of replication origins from SNS data. We detected an average of 80,000 replication origins in different cell lines. To evaluate the consistency between different protocols, we compared SNS detections with bubble trapping detections. This comparison demonstrated a good agreement between genome-wide methods, with 65% of SNS-detected origins validated by bubble trapping, and 44% of bubble trapping origins validated by SNS origins, when compared at the same resolution. We investigated the interplay between the spatial and the temporal programs of replication at fine scales. We show that most of the origins detected in regions replicated in early S phase are shared by all the cell lines investigated whereas cell-type-specific origins tend to be replicated in late S phase. We shed a new light on the key role of CpG islands, by showing that 80% of the origins associated with CGIs are constitutive. Our results further show that at least 76% of CGIs are origins of replication. The analysis of associations with chromatin marks at different timing of cell division revealed new potential epigenetic regulators driving the spatiotemporal activity of replication origins. We highlight the potential role of H4K20me1 and H3K27me3, the coupling of which is correlated with increased efficiency of replication origins, clearly identifying those

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

    DEFF Research Database (Denmark)

    Jasencakova, Zusana; Groth, Anja

    2010-01-01

    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...... and information from recycled parental histones....

  4. 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...

  5. 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...

  6. Early events in alphavirus replication determine the outcome of infection.

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    Frolov, Ilya; Akhrymuk, Maryna; Akhrymuk, Ivan; Atasheva, Svetlana; Frolova, Elena I

    2012-05-01

    Alphaviruses are a group of important human and animal pathogens. They efficiently replicate to high titers in vivo and in many commonly used cell lines of vertebrate origin. They have also evolved effective means of interfering with development of the innate immune response. Nevertheless, most of the alphaviruses are known to induce a type I interferon (IFN) response in vivo. The results of this study demonstrate that the first hours postinfection play a critical role in infection spread and development of the antiviral response. During this window, a balance is struck between virus replication and spread in vertebrate cells and IFN response development. The most important findings are as follows: (i) within the first 2 to 4 h postinfection, alphavirus-infected cells become unable to respond to IFN-β, and this occurs before the virus-induced decrease in STAT1 phosphorylation in response to IFN treatment. (ii) Most importantly, very low, subprotective doses of IFN-β, which do not induce the antiviral response in uninfected cells, have a very strong stimulatory effect on the cells' ability to express type I IFN and activate interferon-stimulated genes during subsequent infection with Sindbis virus (SINV). (iii) Small changes in SINV nsP2 protein affect its ability to inhibit cellular transcription and IFN release. Thus, the balance between type I IFN induction and the ability of the virus to develop further rounds of infection is determined in the first few hours of virus replication, when only low numbers of cells and infectious virus are involved.

  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

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    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. GEOLOGICAL MARKS OF A POSSIBLE EXTRATERRESTRIAL IMPACT EVENT ON THE BOUNDARY BETWEEN SINIAN/CAMBRIAN IN TIANMENSHAN IN WESTERN HUNAN

    Institute of Scientific and Technical Information of China (English)

    HUANG Huaiyong; WANG Daojing; CHEN Guanghao; YIN Hanhui

    2004-01-01

    Geologic marks related to extraterrestrial impact events, such as impact split gravels, impact brecciate layers, impact dikes, microirghizites, microtektites, especially meteoritic residues, were discovered on the boundary between Sinian/Cambrian at Tianmenshan of Western Hunan, which may possibly demonstrate that an extraterrestrial impact event has ever occurred there on the S/C boundary.

  10. The Lomagundi Event Marks Post-Pasteur Point Evolution of Aerobic Respiration: A Hypothesis

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    Raub, T. D.; Kirschvink, J. L.; Nash, C. Z.; Raub, T. M.; Kopp, R. E.; Hilburn, I. A.

    2009-05-01

    All published early Earth carbon cycle models assume that aerobic respiration is as ancient as oxygenic photosynthesis. However, aerobic respiration shuts down at oxygen concentrations below the Pasteur Point, (.01 of the present atmospheric level, PAL). As geochemical processes are unable to produce even local oxygen concentrations above .001 PAL, it follows that aerobic respiration could only have evolved after oxygenic photosynthesis, implying a time gap. The evolution of oxygen reductase-utilizing metabolisms presumably would have occupied this interval. During this time the PS-II-generated free oxygen would have been largely unavailable for remineralization of dissolved organic carbon and so would have profoundly shifted the burial ratio of organic/inorganic carbon. We argue that the sequential geological record of the Makganyene (Snowball?) glaciation (2.3-2.22), the exessively aerobic Hekpoort and coeval paleosols, the Lomagundi-Jatuli carbon isotopic excursion (ending 2.056 Ga), and the deposition of concentrated, sedimentary organic carbon (shungite) mark this period of a profoundly unbalanced global carbon cycle. The Kopp et al. (2005) model for oxyatmoversion agrees with phylogenetic evidence for the radiation of cyanobacteria followed closely by the radiation of gram-negative lineages containing magnetotactic bacteria, which depend upon vertical oxygen gradients. These organisms include delta-Proteobacteria from which the mitochondrial ancestor originated. The Precambrian carbon cycle was rebalanced after a series of biological innovations allowed utilization of the high redox potential of free oxygen. Aerobic respiration in mitochondria required the evolution of a unique family of Fe-Cu oxidases, one of many factors contributing to the >210 Myr delay between the Makganyene deglaciation and the end of the Lomagundi-Jatuli event. We speculate that metalliferious fluids associated with the eruption of the Bushveld complex facilitated evolution of these

  11. In Vitro Studies Show that Sequence Variability Contributes to Marked Variation in Hepatitis B Virus Replication, Protein Expression, and Function Observed across Genotypes.

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    Sozzi, Vitina; Walsh, Renae; Littlejohn, Margaret; Colledge, Danni; Jackson, Kathy; Warner, Nadia; Yuen, Lilly; Locarnini, Stephen A; Revill, Peter A

    2016-11-15

    The hepatitis B virus (HBV) exists as 9 major genotypes (A to I), one minor strain (designated J) and multiple subtypes. Marked differences in HBV natural history, disease progression and treatment response are exhibited by many of these genotypes and subtypes. For example, HBV genotype C is associated with later hepatitis B e antigen (HBeAg) seroconversion and high rates of liver cancer compared to other HBV genotypes, whereas genotype A2 is rarely associated with HBeAg-negative disease or liver cancer. The reasons for these and other differences in HBV natural history are yet to be determined but could in part be due to sequence differences in the HBV genome that alter replicative capacity and/or gene expression. Direct comparative studies on HBV replication and protein expression have been limited to date due largely to the absence of infectious HBV cDNA clones for each of the HBV genotypes present in the same genetic arrangement. We have produced replication-competent infectious cDNA clones of the most common subtypes of genotypes A to D, namely, A2, B2, C2, D3, and the minor strain J, and compared their HBV replication phenotype using transient-transfection models. We identified striking differences in HBV replicative capacity as well as HBeAg and surface (HBsAg) protein expression across genotypes, which may in part be due to sequence variability in regulatory regions of the HBV genome. Functional analysis showed that sequence differences in the major upstream regulatory region across genotypes impacted promoter activity. There have been very few studies directly comparing the replication phenotype of different HBV genotypes, for which there are marked differences in natural history and disease progression worldwide. We have generated replication-competent 1.3-mer cDNA clones of the major genotypes A2, B2, C2, and D3, as well as a recently identified strain J, and identified striking differences in replicative capacity and protein expression that may

  12. Co occurrence of Hepatitis B Virus Infection and Autoimmune Hepatitis with Marked Hepatitis B Virus Replication Following Treatment of Autoimmune Hepatitis

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    Tyagi I

    2015-10-01

    Full Text Available Background: Children have different natural history of Hepatitis B virus (HBV infection. They commonly develop asymptomatic chronic carrier state which is less frequently seen in adults. We describe a rare case of acute on chronic liver failure (ACLF in the course of concurrent autoimmune hepatitis (AIH and HBV infection and replication of HBV following the treatment for autoimmune hepatitis. Case Report: A 15 year old male child presented with jaundice and altered sensorium. Physical examination showed hepatosplenomegaly. The liver function tests were markedly altered. Serology was positive for anti liver kidney microsomal antibody (LKM, hepatitis B surface antigen (HBsAg and immunoglobulin M (IgM anti hepatitis B core antigen (HBc Ag. Liver biopsy showed chronic hepatitis with features of acute exacerbation. Patient was started on treatment with azathioprine and prednisolone for AIH following which clinical and biochmemical improvement was noted. After two years of continued treatment a repeat biopsy performed showed fairly reduced histological activity, but marked replication of the HBV (immunohistochemistry for HBsAg and anti HBcAg showed diffuse cytoplasmic and nuclear positivity respectively. These findings suggest viral replication although the patient was clinically stable. At six months follow-up after the second biopsy and cessation of azathioprine and prednisolone, there were raised liver enzymes and viral load, hence the patient was started on antiviral drug Entecavir to which there was good response and the patient is presently doing well. Conclusion: We describethe rare co occurrence of HBV infection and AIH with marked HBV replication following the treatment for AIH

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

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    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.

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

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    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

  15. A spectral method for numerical elastodynamic fracture analysis without spatial replication of the rupture event

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    Cochard, Alain; Rice, James R.

    1997-08-01

    Perrin et al. (1995) and Geubelle and Rice (1995) have introduced a spectral method for numerical solution of two- and three-dimensional elastodynamic fracture problems. The method applies for ruptures confined to a plane separating homogeneous elastic half spaces. In this method, the physical variables, such as the traction components of stress and displacement discontinuity on the rupture plane, are represented as Fourier series in space with time-dependent coefficients. An analytical solution is found for each Fourier mode, in that each Fourier coefficient for stress is expressed by the time convolution of the corresponding coefficient for displacement with a convolution kernel specific to the rupture mode. Once the 2D formulation of the method is known, the method is readily generalizable to 3D problems in that it involves only linear combinations of the convolution kernels found for each rupture mode in 2D. This conceptual simplicity has, however, a major drawback : due to the Fourier series representations of the physical variables, the problem solved is in fact an infinite and periodic replication of rupture events on the fracture plane. So, in order to study the evolution of a single rupture, one has to use a spatial period large enough in order that the waves coming from the replication cracks do not enter the zone of interest during the time duration studied, or provide negligible stress alteration when they do arrive. We show here how to rigorously offset this defect while retaining the modal independence. Once expressed in the spatial domain, the method amounts to truncating in space the space-time convolution kernels, in a manner that provides an exact evaluation for all positions within the rupture domain (where the constitutive law between stress and displacement discontinuity is to be imposed), but not outside. In order for the method to be identical in structure to the method of Perrin et al. (1995) and Geubelle and Rice (1995), the period of the

  16. Hot subdwarfs: Small stars marking important events in stellar evolution. Ludwig Biermann Award Lecture 2014

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    Geier, S.

    2015-06-01

    Hot subdwarfs are considered to be the compact helium cores of red giants which lost almost their entire hydrogen envelope. What causes this enormous mass loss is still unclear. Binary interactions are invoked, and a significant fraction of the hot subdwarf population is indeed found in close binaries. In a large project we search for close binary sdBs with the most and the least massive companions. Significantly enhancing the known sample of close binary sdBs we performed the first comprehensive study of this population. Triggered by the discovery of two sdB binaries with close brown dwarf companions in the course of this project, we were able to show that the interaction of stars with substellar companions is an important channel to form sdB stars. Finally, we discovered a unique and very compact binary system consisting of an sdB and a massive white dwarf which qualifies as a progenitor candidate for a supernova of type Ia. In addition to that, we could connect those explosions to the class of hypervelocity hot subdwarf stars which we consider as the surviving companions of such events. Being the stripped cores of red giants, hot subdwarfs turned out to be important markers of peculiar events in stellar evolution ranging all the way from star-planet interactions to the progenitors of stellar explosions used to measure the expansion of our Universe.

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

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    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.

  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

    that new histones incorporated during DNA replication provide a signature of post-replicative chromatin, read by the human TONSL–MMS22L 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...... 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. 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....

  19. Mosquito saliva induced cutaneous events augment Chikungunya virus replication and disease progression.

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    Agarwal, Ankita; Joshi, Gaurav; Nagar, Durga P; Sharma, Ajay K; Sukumaran, D; Pant, Satish C; Parida, Man Mohan; Dash, Paban Kumar

    2016-06-01

    Chikungunya virus (CHIKV) is transmitted when infected mosquito probes the host skin. While probing, mosquito saliva is expectorated into host skin along with virus which contains cocktail of molecules having anti-hemostatic and immunomodulatory properties. As mosquito saliva is a critical factor during natural arboviral infection, therefore we investigated mosquito saliva induced cutaneous events that modulate CHIKV infection. The effect of mosquito saliva on CHIKV infection was examined through inoculation of suckling mice subcutaneously with either CHIKV alone or uninfected mosquito bite followed by CHIKV. Histopathological evaluation of skin revealed infiltration of transmigrated inflammatory cells. Dermal blood vessels were hyperemic and adnexa showed degenerating lesions. Severe hemorrhage was observed in dermis and hypodermis in mosquito bite+CHIKV group compared to CHIKV group. Analysis of cytokines in skin showed significant downregulation of inflammatory genes like TLR-3, IL-2, IFN-γ, TNF-α and IFN-β in mosquito bite+CHIKV group compared to CHIKV group. In contrast, significant upregulation of anti-inflammatory genes like IL-4 and IL-10 was observed. These early events might have been responsible for increased dissemination of CHIKV to serum and peripheral organs as demonstrated through >10-fold higher viremia, antigen localization, cellular infiltration and degenerative changes. Thus mosquito saliva induced early cellular infiltration and associated cytokines augment CHIKV pathogenesis in a mouse model. This mosquito improved CHIKV mouse model simulates the realistic conditions that occur naturally during infected mosquito bite to a host. It will lead to better understanding of CHIKV pathobiology and promote the evaluation of novel medical countermeasures against emerging CHIKV. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Phosphorylation of chromosome core components may serve as axis marks for the status of chromosomal events during mammalian meiosis.

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    Tomoyuki Fukuda

    2012-02-01

    Full Text Available Meiotic recombination and chromosome synapsis between homologous chromosomes are essential for proper chromosome segregation at the first meiotic division. While recombination and synapsis, as well as checkpoints that monitor these two events, take place in the context of a prophase I-specific axial chromosome structure, it remains unclear how chromosome axis components contribute to these processes. We show here that many protein components of the meiotic chromosome axis, including SYCP2, SYCP3, HORMAD1, HORMAD2, SMC3, STAG3, and REC8, become post-translationally modified by phosphorylation during the prophase I stage. We found that HORMAD1 and SMC3 are phosphorylated at a consensus site for the ATM/ATR checkpoint kinase and that the phosphorylated forms of HORMAD1 and SMC3 localize preferentially to unsynapsed chromosomal regions where synapsis has not yet occurred, but not to synapsed or desynapsed regions. We investigated the genetic requirements for the phosphorylation events and revealed that the phosphorylation levels of HORMAD1, HORMAD2, and SMC3 are dramatically reduced in the absence of initiation of meiotic recombination, whereas BRCA1 and SYCP3 are required for normal levels of phosphorylation of HORMAD1 and HORMAD2, but not of SMC3. Interestingly, reduced HORMAD1 and HORMAD2 phosphorylation is associated with impaired targeting of the MSUC (meiotic silencing of unsynapsed chromatin machinery to unsynapsed chromosomes, suggesting that these post-translational events contribute to the regulation of the synapsis surveillance system. We propose that modifications of chromosome axis components serve as signals that facilitate chromosomal events including recombination, checkpoint control, transcription, and synapsis regulation.

  1. Morphosyntax can modulate the N400 component: event related potentials to gender-marked post-nominal adjectives.

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    Guajardo, Lourdes F; Wicha, Nicole Y Y

    2014-05-01

    Event-related potential studies of grammatical gender agreement often report a left anterior negativity (LAN) when agreement violations occur. Some studies have shown that during sentence comprehension gender violations can also interact with semantic processing to modulate a negativity associated with processing meaning - the N400. Given that the LAN and N400 overlap in time, they are identified by their scalp distributions and purported functional roles. Critically, grammatical gender violations also elicit a right posterior positivity that can overlap temporally and potentially affect the scalp distribution of the LAN/N400. We measured the effect of grammatical gender violations in the LAN/N400 window and late positive component (LPC) during comprehension of Spanish sentences. A post-nominal adjective could either make sense or not, and either agree or disagree in gender with the preceding noun. We observed a negativity to gender agreement violations in the LAN/N400 window (300-500ms post stimulus onset) that was smaller than the semantic-congruity N400, but overlapped with it in time and distribution. The early portion of the LPC to gender violations was modulated by sentence constraint, occurring as early as 450ms in highly constraining sentences. A subadditive interaction occurred at the later portion of the LPC with equivalent effects for single and double violations (gender and semantics), reflecting a general stage of reprocessing. Overall, our data support models of language comprehension whereby both semantic and morphosyntactic information can affect processing at similar time points.

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

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    Shah, Jubin N.; Kirioukhova, Olga; Pawar, Pallavi; Tayyab, Muhammad; Mateo, Juan L.; Johnston, Amal J.

    2016-01-01

    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 serve as (epi)genetic 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 homologs 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, homologs 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 homologs were deregulated in Boechera seedlings upon DNA demethylation, and ASY1 in particular seems to be repressed by global DNA

  3. The key molecular events during Macrobrachium rosenbergii nodavirus (MrNV) infection and replication in Sf9 insect cells.

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    Somrit, Monsicha; Watthammawut, Atthaboon; Chotwiwatthanakun, Charoonroj; Weerachatyanukul, Wattana

    2016-09-02

    In this study we demonstrated that Macrobrachium rosenbergii nodavirus (MrNV) was able to internalize and replicate in Sf9 insect cells, with levels of infection altered by substances affecting the caveolin-(CAV) mediated endocytosis pathway. The use of Sf9 cells for efficient MrNV replication and propagation was demonstrated by confocal microscopy and PCR amplification, through which early viral binding and internalization were initially detectable at 30min post-infection; whereas at 72h, the distinguishable sign of late-MrNV infection was observable as the gradual accumulation of a cytopathic effect (CPE) in the cells, ultimately resulting in cellular disruption. Moreover, during the early period of infection, the MrNV signals were highly co-localized with CAV1 signals of the CAV-mediated endocytosis pathway. The use of genistein as an inhibitor of the CAV-mediated endocytosis pathway significantly reduced MrNV and CAV1 co-localization, and also reduced the levels of MrNV infection in Sf9 cells as shown by PCR and ELISA. Moreover, the addition of the pathway agonist okadaic acid not only recovered but also augmented both the levels of MrNV co-localization with CAV1 and of Sf9 infection in the presence of genistein inhibition; therefore demonstrating that MrNV infection in Sf9 cells was associated with the CAV-mediated endocytosis pathway machinery.

  4. Polyomavirus JC in the Context of Immunosuppression: A Series of Adaptive, DNA Replication-Driven Recombination Events in the Development of Progressive Multifocal Leukoencephalopathy

    Directory of Open Access Journals (Sweden)

    Edward M. Johnson

    2013-01-01

    Full Text Available Polyomavirus JC (JCV is the etiological agent of progressive multifocal leukoencephalopathy (PML, a demyelinating infection of oligodendrocytes in the brain. PML, a frequently fatal opportunistic infection in AIDS, has also emerged as a consequence of treatment with several new immunosuppressive therapeutic agents. Although nearly 80% of adults are seropositive, JCV attains an ability to infect glial cells in only a minority of people. Data suggest that JCV undergoes sequence alterations that accompany this ability, and these changes can be derived from an archetype strain by mutation, deletion, and duplication. While the introductory source and primary tissue reservoir of JCV remain unknown, lymphoid cells have been identified as potential intermediaries in progression of JCV to the brain. This review is focused on sequence changes in the noncoding control region (NCCR of the virus. We propose an adaptive mechanism that involves a sequential series of DNA replication-driven NCCR recombination events involving stalled DNA replication forks at NCCR palindromic secondary structures. We shall describe how the NCCR sequence changes point to a model in which viral DNA replication drives NCCR recombination, allowing JCV adaptation to different cell types in its progression to neurovirulence.

  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. The alpha, beta, gamma, delta-unsaturated aldehyde 2-trans-4-trans-decadienal disturbs DNA replication and mitotic events in early sea urchin embryos.

    Science.gov (United States)

    Hansen, Espen; Even, Yasmine; Genevière, Anne-Marie

    2004-09-01

    The polyunsaturated aldehydes are highly reactive products of fatty acid peroxidation and combustion of organic materials, and they have been documented to have diverse cyctotoxic and genotoxic effects. The alpha,beta,gamma,delta-unsaturated aldehyde 2-trans-4-trans-decadienal is produced by marine microalgae, and it is known to inhibit cell proliferation and induce apoptosis in several different cell types. However, the molecular basis for the cell cycle arrest is not fully understood. We used sea urchin embryos to examine how some of the key events of the mitotic cell division were influenced by this polyunsaturated aldehyde. We found that cell divisions in embryos of Sphaerechinus granularis were inhibited by 2-trans-4-trans-decadienal in a dose dependent manner with an EC50 of 1.3 microM. Mitotic events in the nondividing eggs were characterized using immunofluorescent staining. DNA labelling revealed that pronuclear migration was inhibited, and a total absence of incorporation of the DNA-base analogue 5-bromo-2-deoxyuridine indicated that no DNA replication had occurred. Staining of alpha-tubulin subunits showed that tubulin-polymerization was disrupted and aberrations were induced in mitotic spindles. Furthermore, we monitored the activity of the G2-M promoting complex cyclin B-Cdk1 in newly fertilized sea urchin eggs, and found that this complex was not activated in embryos treated with 2-trans-4-trans-decadienal despite the accumulation of cyclin B.

  7. Stretch Marks

    Science.gov (United States)

    ... to get rid of stretch marks, but the truth is that most don't work and are ... The Nemours Foundation, iStock, Getty Images, Corbis, Veer, Science Photo Library, Science Source Images, Shutterstock, and Clipart. ...

  8. Stretch marks

    Science.gov (United States)

    Stretch marks can appear when there is rapid stretching of the skin. They are often seen when ... often disappear after the cause of the skin stretching is gone. Avoiding rapid weight gain helps reduce ...

  9. Replication-Fork Dynamics

    NARCIS (Netherlands)

    Duderstadt, Karl E.; Reyes-Lamothe, Rodrigo; van Oijen, Antoine M.; Sherratt, David J.

    2014-01-01

    The proliferation of all organisms depends on the coordination of enzymatic events within large multiprotein replisomes that duplicate chromosomes. Whereas the structure and function of many core replisome components have been clarified, the timing and order of molecular events during replication re

  10. News Conference: The Big Bangor Day Meeting Lecture: Charterhouse plays host to a physics day Festival: Science on Stage festival 2013 arrives in Poland Event: Scottish Physics Teachers' Summer School Meeting: Researchers and educators meet at Lund University Conference: Exeter marks the spot Recognition: European Physical Society uncovers an historic site Education: Initial teacher education undergoes big changes Forthcoming events

    Science.gov (United States)

    2013-09-01

    Conference: The Big Bangor Day Meeting Lecture: Charterhouse plays host to a physics day Festival: Science on Stage festival 2013 arrives in Poland Event: Scottish Physics Teachers' Summer School Meeting: Researchers and educators meet at Lund University Conference: Exeter marks the spot Recognition: European Physical Society uncovers an historic site Education: Initial teacher education undergoes big changes Forthcoming events

  11. 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.

  12. Efficient usage of Adabas replication

    CERN Document Server

    Storr, Dieter W

    2011-01-01

    In today's IT organization replication becomes more and more an essential technology. This makes Software AG's Event Replicator for Adabas an important part of your data processing. Setting the right parameters and establishing the best network communication, as well as selecting efficient target components, is essential for successfully implementing replication. This book provides comprehensive information and unique best-practice experience in the field of Event Replicator for Adabas. It also includes sample codes and configurations making your start very easy. It describes all components ne

  13. 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

  14. 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

  15. Telicity marking in Hungarian

    Directory of Open Access Journals (Sweden)

    Éva Kardos

    2016-10-01

    Full Text Available This paper explores the encoding of telicity in Hungarian. While proposing a mereological, scalar semantic analysis, it shows that Hungarian uses a telicity-marking strategy in which it contrasts with English, where telicity is not the direct consequence of an overt marker but arises as a cumulative effect of specific, well-definable properties of various components of verbal predicates including the head verb and its argument(s. A major contribution of the analysis, which mainly addresses telicity marking in the class of non-creation/non-consumption predicates in neutral sentences, lies in the fact that it reveals important cross-linguistic differences with respect to the aspectual role of verbal particles and resultative/locative expressions and the referential properties of telic verbal predicates. As for the former, it is demonstrated that Hungarian verbal particles and resultative/locative expressions mark telicity by directly placing bounds on events by virtue of serving an event maximalizing function, whereas the English counterparts of these elements do not have such direct event-bounding effects. As for the latter, it emerges that in Hungarian quantized reference is a necessary and sufficient condition for telicity in cases where in English it is only sufficient.

  16. Early events in the generation of autophagosomes are required for the formation of membrane structures involved in hepatitis C virus genome replication.

    Science.gov (United States)

    Mohl, Bjorn-Patrick; Bartlett, Christopher; Mankouri, Jamel; Harris, Mark

    2016-03-01

    Hepatitis C virus (HCV) infection has been shown to induce autophagy but the mechanisms underpinning this process remain to be elucidated. Induction of autophagy requires the class III phosphatidylinositol 3-kinase, Vps34, which produces phosphatidylinositol 3-phosphate (PI3P) within the endoplasmic reticulum (ER) membrane. This recruits proteins with PI3P binding domains such as the double-FYVE-containing protein 1 (DFCP1). DFCP1 generates cup-shaped protrusions from the ER membrane, termed omegasomes, which provide a platform for the production of autophagosomes. Here we present data demonstrating that both Vps34 and DFCP1 are required for HCV genome replication, in the context of both a subgenomic replicon and virus infection, but did not affect virus entry or initial translation. Using live cell fluorescence microscopy we demonstrated that early during HCV infection the nascent viral genome replication complexes (identified by using non-structural protein NS5A as a marker) transiently colocalize with DFCP1-positive punctae (omegasomes), before the two structures move apart from each other. This observation is reminiscent of the transient association of LC3 and DFCP1 during omegasome formation, and therefore we propose that omegasomes are utilized by HCV to generate the double-membrane vesicles which are the hallmark of HCV replication complexes.

  17. Diversification of genes encoding granule-bound starch synthase in monocots and dicots is marked by multiple genome-wide duplication events.

    Directory of Open Access Journals (Sweden)

    Jun Cheng

    Full Text Available Starch is one of the major components of cereals, tubers, and fruits. Genes encoding granule-bound starch synthase (GBSS, which is responsible for amylose synthesis, have been extensively studied in cereals but little is known about them in fruits. Due to their low copy gene number, GBSS genes have been used to study plant phylogenetic and evolutionary relationships. In this study, GBSS genes have been isolated and characterized in three fruit trees, including apple, peach, and orange. Moreover, a comprehensive evolutionary study of GBSS genes has also been conducted between both monocots and eudicots. Results have revealed that genomic structures of GBSS genes in plants are conserved, suggesting they all have evolved from a common ancestor. In addition, the GBSS gene in an ancestral angiosperm must have undergone genome duplication ∼251 million years ago (MYA to generate two families, GBSSI and GBSSII. Both GBSSI and GBSSII are found in monocots; however, GBSSI is absent in eudicots. The ancestral GBSSII must have undergone further divergence when monocots and eudicots split ∼165 MYA. This is consistent with expression profiles of GBSS genes, wherein these profiles are more similar to those of GBSSII in eudicots than to those of GBSSI genes in monocots. In dicots, GBSSII must have undergone further divergence when rosids and asterids split from each other ∼126 MYA. Taken together, these findings suggest that it is GBSSII rather than GBSSI of monocots that have orthologous relationships with GBSS genes of eudicots. Moreover, diversification of GBSS genes is mainly associated with genome-wide duplication events throughout the evolutionary course of history of monocots and eudicots.

  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. The Caulobacter crescentus ctrA P1 promoter is essential for the coordination of cell cycle events that prevent the overinitiation of DNA replication.

    Science.gov (United States)

    Schredl, Alexander T; Perez Mora, Yannet G; Herrera, Anabel; Cuajungco, Math P; Murray, Sean R

    2012-10-01

    The master regulator CtrA oscillates during the Caulobacter cell cycle due to temporally regulated proteolysis and transcription. It is proteolysed during the G1-S transition and reaccumulates in predivisional cells as a result of transcription from two sequentially activated promoters, P1 and P2. CtrA reinforces its own synthesis by directly mediating the activation of P2 concurrently with repression of P1. To explore the role of P1 in cell cycle control, we engineered a mutation into the native ctrA locus that prevents transcription from P1 but not P2. As expected, the ctrA P1 mutant exhibits striking growth, morphological and DNA replication defects. Unexpectedly, we found CtrA and its antagonist SciP, but not DnaA, GcrA or CcrM accumulation to be dramatically reduced in the ctrA P1 mutant. SciP levels closely paralleled CtrA accumulation, suggesting that CtrA acts as a rheostat to modulate SciP abundance. Furthermore, the reappearance of CtrA and CcrM in predivisional cells was delayed in the P1 mutant by 0.125 cell cycle unit in synchronized cultures. High levels of ccrM transcription despite low levels of CtrA and increased transcription of ctrA P2 in the ctrA P1 mutant are two examples of robustness in the cell cycle. Thus, Caulobacter can adjust regulatory pathways to partially compensate for reduced and delayed CtrA accumulation in the ctrA P1 mutant.

  20. Mastering Marking Madness

    Science.gov (United States)

    Moore, Brooke

    2009-01-01

    Teachers are smart people, so why does marking reduce them to stressed and soulless messes? Because in their hearts they know that students do not learn from it, and that drives them nuts. Researchers like Lorna Earl and Dylan Wiliam have looked closely at marking systems and have proven what teachers already know deep down: marking student work…

  1. 77 FR 4271 - Special Permit Marking Removal

    Science.gov (United States)

    2012-01-27

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF TRANSPORTATION... Administration (FRA), Department of Transportation (DOT). ACTION: Removal of obsolete Special Permit markings... first shopping event, whichever occurred first. This document relieves tank car owners from that...

  2. 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...

  3. Archaeal DNA replication.

    Science.gov (United States)

    Kelman, Lori M; Kelman, Zvi

    2014-01-01

    DNA replication is essential for all life forms. Although the process is fundamentally conserved in the three domains of life, bioinformatic, biochemical, structural, and genetic studies have demonstrated that the process and the proteins involved in archaeal DNA replication are more similar to those in eukaryal DNA replication than in bacterial DNA replication, but have some archaeal-specific features. The archaeal replication system, however, is not monolithic, and there are some differences in the replication process between different species. In this review, the current knowledge of the mechanisms governing DNA replication in Archaea is summarized. The general features of the replication process as well as some of the differences are discussed.

  4. News CERN Celebration: CERN marks 20 years of the Web Workshops: Physics Teachers' Day aired live on Web Teacher Programme: Physics Teachers at CERN 2009 leaves attendees thirsty for more GIREP: Registration open for GIREP '09 Science and Creationism: Telegraph headline leads readers down wrong path Recruitment: Is recession proving to be good news for science teaching? Forthcoming Events

    Science.gov (United States)

    2009-05-01

    CERN Celebration: CERN marks 20 years of the Web Workshops: Physics Teachers' Day aired live on Web Teacher Programme: Physics Teachers at CERN 2009 leaves attendees thirsty for more GIREP: Registration open for GIREP '09 Science and Creationism: Telegraph headline leads readers down wrong path Recruitment: Is recession proving to be good news for science teaching? Forthcoming Events

  5. On denture marking.

    Science.gov (United States)

    Borrman, H I; DiZinno, J A; Wasén, J; René, N

    1999-06-01

    During the last decades in Sweden dentures have been permanently marked with a stainless steel metal band incorporated into the acrylic and containing the patient's birth date, a special number, and "S" for Sweden. The last recommendation issued by the National Board of Health and Welfare states that "the patients shall always be offered denture marking and be informed about the benefit thereof. Denture marking is not permitted if the patient refuses it". Requirements for denture markers have been that they should be biologically inert (when incorporated into the denture), not be expensive, be easy to inscribe, be possible to retrieve after an accident, and survive elevated temperatures for a reasonable time under normal circumstances. Although the frequency of edentulousness has decreased in recent years due to the improvement in oral health there remains a need to address the issue of marking of complete dentures, because there is a large variation in the oral status of populations in different countries. Given that only one marked denture can reveal the identity of a deceased person when all other methods fail to do so, makes it worthwhile. Furthermore, denture marking is important in long-term care facilities. We have investigated the issue of denture marking in Europe and in the United States. The results from the European survey show that denture marking is, to our knowledge regulated by law only in Sweden and Iceland. In the US denture marking is so far mandatory in 21 states while New York State requires dentures to be marked if the patient requests it and several other states impose the obligation to mark dentures on long-term care facilities. Since there is no international consensus regarding the issue of denture marking it is important to address it. A survey from the Nordic countries has shown that if denture marking was in general use, the contribution to the establishment of identity by forensic odontology in cases of fire would increase by about 10

  6. Marking as Judgment

    Science.gov (United States)

    Brooks, Val

    2012-01-01

    An aspect of assessment which has received little attention compared with perennial concerns, such as standards or reliability, is the role of judgment in marking. This paper explores marking as an act of judgment, paying particular attention to the nature of judgment and the processes involved. It brings together studies which have explored…

  7. Marking as Judgment

    Science.gov (United States)

    Brooks, Val

    2012-01-01

    An aspect of assessment which has received little attention compared with perennial concerns, such as standards or reliability, is the role of judgment in marking. This paper explores marking as an act of judgment, paying particular attention to the nature of judgment and the processes involved. It brings together studies which have explored…

  8. Bite Mark Analysis

    Directory of Open Access Journals (Sweden)

    SK Padmakumar

    2014-07-01

    Full Text Available Bite mark analysis plays an important role in personal identi- fi cation in forensic odontology. They are commonly seen in violent crimes such as sexual assaults, homicides, child abuse, etc. Human bites are common on the face and are usually seen on prominent locations of the face such as the ears, nose and lips. Individual characteristics recorded in the bite marks such as fractures, rotations, attrition, and congenital malformations are helpful in identifying the individual who caused it. We are reporting the case of a 55-year-old lady with bite marks on her left ear, who was allegedly assaulted by the suspect. On the basis of characteristic features of the suspect’s dentition, it was concluded that the bite marks seen on the victim was most probably caused by the suspect.

  9. 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

  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 IVA microprocessor support

    Science.gov (United States)

    Burford, A. L.

    1982-01-01

    The requirements and plans for the maintenance support of microprocessor-based controllers in the Deep Space Network Mark IVA System are discussed. Additional new interfaces and 16-bit processors have introduced problems not present in the Mark III System. The need for continuous training of maintenance personnel to maintain a level of expertise consistent with the sophistication of the required tools is also emphasized.

  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. A dynamic stochastic model for DNA replication initiation in early embryos.

    Directory of Open Access Journals (Sweden)

    Arach Goldar

    Full Text Available BACKGROUND: Eukaryotic cells seem unable to monitor replication completion during normal S phase, yet must ensure a reliable replication completion time. This is an acute problem in early Xenopus embryos since DNA replication origins are located and activated stochastically, leading to the random completion problem. DNA combing, kinetic modelling and other studies using Xenopus egg extracts have suggested that potential origins are much more abundant than actual initiation events and that the time-dependent rate of initiation, I(t, markedly increases through S phase to ensure the rapid completion of unreplicated gaps and a narrow distribution of completion times. However, the molecular mechanism that underlies this increase has remained obscure. METHODOLOGY/PRINCIPAL FINDINGS: Using both previous and novel DNA combing data we have confirmed that I(t increases through S phase but have also established that it progressively decreases before the end of S phase. To explore plausible biochemical scenarios that might explain these features, we have performed comparisons between numerical simulations and DNA combing data. Several simple models were tested: i recycling of a limiting replication fork component from completed replicons; ii time-dependent increase in origin efficiency; iii time-dependent increase in availability of an initially limiting factor, e.g. by nuclear import. None of these potential mechanisms could on its own account for the data. We propose a model that combines time-dependent changes in availability of a replication factor and a fork-density dependent affinity of this factor for potential origins. This novel model quantitatively and robustly accounted for the observed changes in initiation rate and fork density. CONCLUSIONS/SIGNIFICANCE: This work provides a refined temporal profile of replication initiation rates and a robust, dynamic model that quantitatively explains replication origin usage during early embryonic S phase

  14. 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...

  15. Replication Restart in Bacteria.

    Science.gov (United States)

    Michel, Bénédicte; Sandler, Steven J

    2017-07-01

    In bacteria, replication forks assembled at a replication origin travel to the terminus, often a few megabases away. They may encounter obstacles that trigger replisome disassembly, rendering replication restart from abandoned forks crucial for cell viability. During the past 25 years, the genes that encode replication restart proteins have been identified and genetically characterized. In parallel, the enzymes were purified and analyzed in vitro, where they can catalyze replication initiation in a sequence-independent manner from fork-like DNA structures. This work also revealed a close link between replication and homologous recombination, as replication restart from recombination intermediates is an essential step of DNA double-strand break repair in bacteria and, conversely, arrested replication forks can be acted upon by recombination proteins and converted into various recombination substrates. In this review, we summarize this intense period of research that led to the characterization of the ubiquitous replication restart protein PriA and its partners, to the definition of several replication restart pathways in vivo, and to the description of tight links between replication and homologous recombination, responsible for the importance of replication restart in the maintenance of genome stability. Copyright © 2017 American Society for Microbiology.

  16. 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.

  17. Regulation of chromosomal replication in Caulobacter crescentus.

    Science.gov (United States)

    Collier, Justine

    2012-03-01

    The alpha-proteobacterium Caulobacter crescentus is characterized by its asymmetric cell division, which gives rise to a replicating stalked cell and a non-replicating swarmer cell. Thus, the initiation of chromosomal replication is tightly regulated, temporally and spatially, to ensure that it is coordinated with cell differentiation and cell cycle progression. Waves of DnaA and CtrA activities control when and where the initiation of DNA replication will take place in C. crescentus cells. The conserved DnaA protein initiates chromosomal replication by directly binding to sites within the chromosomal origin (Cori), ensuring that DNA replication starts once and only once per cell cycle. The CtrA response regulator represses the initiation of DNA replication in swarmer cells and in the swarmer compartment of pre-divisional cells, probably by competing with DnaA for binding to Cori. CtrA and DnaA are controlled by multiple redundant regulatory pathways that include DNA methylation-dependent transcriptional regulation, temporally regulated proteolysis and the targeting of regulators to specific locations within the cell. Besides being critical regulators of chromosomal replication, CtrA and DnaA are also master transcriptional regulators that control the expression of many genes, thus connecting DNA replication with other events of the C. crescentus cell cycle. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. 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

  19. Fathoming Mark Twain.

    Science.gov (United States)

    Biggar, Joanna

    1988-01-01

    Relates the efforts of completing two collections of the works and papers of Mark Twain. Describes the combined efforts of the University of Iowa and the University of California to publish both a scholarly edition and a reader's edition devoted to Twain. (KO)

  20. Teaching with Mark Dion

    Science.gov (United States)

    Fusaro, Joe

    2011-01-01

    Mark Dion creates sculptures, installations, and interactive environments that sometimes seem contrary to what one expects from visual artists. Remarkable curiosity cabinets and carefully arranged artifacts from specific places and time periods make up a large part of his work. His work does not neatly fit into traditional lessons about elements…

  1. Marked metric measure spaces

    CERN Document Server

    Depperschmidt, Andrej; Pfaffelhuber, Peter

    2011-01-01

    A marked metric measure space (mmm-space) is a triple (X,r,mu), where (X,r) is a complete and separable metric space and mu is a probability measure on XxI for some Polish space I of possible marks. We study the space of all (equivalence classes of) marked metric measure spaces for some fixed I. It arises as state space in the construction of Markov processes which take values in random graphs, e.g. tree-valued dynamics describing randomly evolving genealogical structures in population models. We derive here the topological properties of the space of mmm-spaces needed to study convergence in distribution of random mmm-spaces. Extending the notion of the Gromov-weak topology introduced in (Greven, Pfaffelhuber and Winter, 2009), we define the marked Gromov-weak topology, which turns the set of mmm-spaces into a Polish space. We give a characterization of tightness for families of distributions of random mmm- spaces and identify a convergence determining algebra of functions, called polynomials.

  2. Marked PCP is decidable

    NARCIS (Netherlands)

    Halava, V.; Hirvensalo, M.; de Wolf, R.

    2001-01-01

    We show that the marked version of the Post Correspondence Problem, where the words on a list are required to differ in the first letter, is decidable. On the other hand, we prove that the PCP remains undecidable if we only require the words to differ in the first two letters. Thus we locate the

  3. 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.

  4. 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....

  5. 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.

  6. Mark Twain on phrenology.

    Science.gov (United States)

    Stone, James L

    2003-12-01

    Mark Twain was a noted 19th century American writer and humorist. He often elaborated upon the personalities of his characters, and his observational skills reflected a strong interest in psychology. Similarly, he found an interest in phrenology, a pseudoscience that purported to characterize personality traits according to elevations or depressions on the head. Twain's style is clearly reflected in the interesting essay he wrote regarding his personal experience with phrenology.

  7. Mechanism of chromosomal DNA replication initiation and replication fork stabilization in eukaryotes.

    Science.gov (United States)

    Wu, LiHong; Liu, Yang; Kong, DaoChun

    2014-05-01

    Chromosomal DNA replication is one of the central biological events occurring inside cells. Due to its large size, the replication of genomic DNA in eukaryotes initiates at hundreds to tens of thousands of sites called DNA origins so that the replication could be completed in a limited time. Further, eukaryotic DNA replication is sophisticatedly regulated, and this regulation guarantees that each origin fires once per S phase and each segment of DNA gets duplication also once per cell cycle. The first step of replication initiation is the assembly of pre-replication complex (pre-RC). Since 1973, four proteins, Cdc6/Cdc18, MCM, ORC and Cdt1, have been extensively studied and proved to be pre-RC components. Recently, a novel pre-RC component called Sap1/Girdin was identified. Sap1/Girdin is required for loading Cdc18/Cdc6 to origins for pre-RC assembly in the fission yeast and human cells, respectively. At the transition of G1 to S phase, pre-RC is activated by the two kinases, cyclindependent kinase (CDK) and Dbf4-dependent kinase (DDK), and subsequently, RPA, primase-polα, PCNA, topoisomerase, Cdc45, polδ, and polɛ are recruited to DNA origins for creating two bi-directional replication forks and initiating DNA replication. As replication forks move along chromatin DNA, they frequently stall due to the presence of a great number of replication barriers on chromatin DNA, such as secondary DNA structures, protein/DNA complexes, DNA lesions, gene transcription. Stalled forks must require checkpoint regulation for their stabilization. Otherwise, stalled forks will collapse, which results in incomplete DNA replication and genomic instability. This short review gives a concise introduction regarding the current understanding of replication initiation and replication fork stabilization.

  8. 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.

  9. 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.

  10. 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.

  11. Oncogene v-jun modulates DNA replication.

    Science.gov (United States)

    Wasylyk, C; Schneikert, J; Wasylyk, B

    1990-07-01

    Cell transformation leads to alterations in both transcription and DNA replication. Activation of transcription by the expression of a number of transforming oncogenes is mediated by the transcription factor AP1 (Herrlich & Ponta, 1989; Imler & Wasylyk, 1989). AP1 is a composite transcription factor, consisting of members of the jun and fos gene-families. c-jun and c-fos are progenitors of oncogenes, suggestion that an important transcriptional event in cell transformation is altered activity of AP1, which may arise either indirectly by oncogene expression or directly by structural modification of AP1. We report here that the v-jun oncogene and its progenitor c-jun, as fusion proteins with the lex-A-repressor DNA binding domain, can activate DNA replication from the Polyoma virus (Py) origin of replication, linked to the lex-A operator. The transcription-activation region of v-jun is required for activation of replication. When excess v-jun is expressed in the cell, replication is inhibited or 'squelched'. These results suggest that one consequence of deregulated jun activity could be altered DNA replication and that there are similarities in the way v-jun activates replication and transcription.

  12. H3K4me3 demethylation by the histone demethylase KDM5C/JARID1C promotes DNA replication origin firing.

    Science.gov (United States)

    Rondinelli, Beatrice; Schwerer, Hélène; Antonini, Elena; Gaviraghi, Marco; Lupi, Alessio; Frenquelli, Michela; Cittaro, Davide; Segalla, Simona; Lemaitre, Jean-Marc; Tonon, Giovanni

    2015-03-11

    DNA replication is a tightly regulated process that initiates from multiple replication origins and leads to the faithful transmission of the genetic material. For proper DNA replication, the chromatin surrounding origins needs to be remodeled. However, remarkably little is known on which epigenetic changes are required to allow the firing of replication origins. Here, we show that the histone demethylase KDM5C/JARID1C is required for proper DNA replication at early origins. JARID1C dictates the assembly of the pre-initiation complex, driving the binding to chromatin of the pre-initiation proteins CDC45 and PCNA, through the demethylation of the histone mark H3K4me3. Fork activation and histone H4 acetylation, additional early events involved in DNA replication, are not affected by JARID1C downregulation. All together, these data point to a prominent role for JARID1C in a specific phase of DNA replication in mammalian cells, through its demethylase activity on H3K4me3.

  13. 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

  14. 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)

  15. 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.

  16. Abiotic self-replication.

    Science.gov (United States)

    Meyer, Adam J; Ellefson, Jared W; Ellington, Andrew D

    2012-12-18

    The key to the origins of life is the replication of information. Linear polymers such as nucleic acids that both carry information and can be replicated are currently what we consider to be the basis of living systems. However, these two properties are not necessarily coupled. The ability to mutate in a discrete or quantized way, without frequent reversion, may be an additional requirement for Darwinian evolution, in which case the notion that Darwinian evolution defines life may be less of a tautology than previously thought. In this Account, we examine a variety of in vitro systems of increasing complexity, from simple chemical replicators up to complex systems based on in vitro transcription and translation. Comparing and contrasting these systems provides an interesting window onto the molecular origins of life. For nucleic acids, the story likely begins with simple chemical replication, perhaps of the form A + B → T, in which T serves as a template for the joining of A and B. Molecular variants capable of faster replication would come to dominate a population, and the development of cycles in which templates could foster one another's replication would have led to increasingly complex replicators and from thence to the initial genomes. The initial genomes may have been propagated by RNA replicases, ribozymes capable of joining oligonucleotides and eventually polymerizing mononucleotide substrates. As ribozymes were added to the genome to fill gaps in the chemistry necessary for replication, the backbone of a putative RNA world would have emerged. It is likely that such replicators would have been plagued by molecular parasites, which would have been passively replicated by the RNA world machinery without contributing to it. These molecular parasites would have been a major driver for the development of compartmentalization/cellularization, as more robust compartments could have outcompeted parasite-ridden compartments. The eventual outsourcing of metabolic

  17. Adenovirus DNA Replication

    OpenAIRE

    Hoeben, Rob C.; Uil, Taco G.

    2013-01-01

    Adenoviruses have attracted much attention as probes to study biological processes such as DNA replication, transcription, splicing, and cellular transformation. More recently these viruses have been used as gene-transfer vectors and oncolytic agents. On the other hand, adenoviruses are notorious pathogens in people with compromised immune functions. This article will briefly summarize the basic replication strategy of adenoviruses and the key proteins involved and will deal with the new deve...

  18. The Genomic Replication of the Crenarchaeal Virus SIRV2

    DEFF Research Database (Denmark)

    Martinez Alvarez, Laura

    of the crenarchaeal virus SIRV2, a model among archaeal viruses. SIRV2 was found to employ multiple replication mechanisms, with DNA synthesis starting by a strand-displacement mode that later derived in a rolling-circle replication from a circular intermediate. Interestingly, evidence for a secondary, bidirectional...... 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......-related proteins are concentrated. Our data indicates that the host DNA polymerase Dpo1 is also the viral replicative polymerase. Moreover, additional data suggests that other processes, such as translation, are also reorganized after infection. Based on our results, a model for the organization of viral...

  19. Decreased replication origin activity in temporal transition regions.

    Science.gov (United States)

    Guan, Zeqiang; Hughes, Christina M; Kosiyatrakul, Settapong; Norio, Paolo; Sen, Ranjan; Fiering, Steven; Allis, C David; Bouhassira, Eric E; Schildkraut, Carl L

    2009-11-30

    In the mammalian genome, early- and late-replicating domains are often separated by temporal transition regions (TTRs) with novel properties and unknown functions. We identified a TTR in the mouse immunoglobulin heavy chain (Igh) locus, which contains replication origins that are silent in embryonic stem cells but activated during B cell development. To investigate which factors contribute to origin activation during B cell development, we systematically modified the genetic and epigenetic status of the endogenous Igh TTR and used a single-molecule approach to analyze DNA replication. Introduction of a transcription unit into the Igh TTR, activation of gene transcription, and enhancement of local histone modifications characteristic of active chromatin did not lead to origin activation. Moreover, very few replication initiation events were observed when two ectopic replication origin sequences were inserted into the TTR. These findings indicate that the Igh TTR represents a repressive compartment that inhibits replication initiation, thus maintaining the boundaries between early and late replication domains.

  20. 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.

  1. Minichromosome replication in vitro: inhibition of re-replication by replicatively assembled nucleosomes.

    Science.gov (United States)

    Krude, T; Knippers, R

    1994-08-19

    Single-stranded circular DNA, containing the SV40 origin sequence, was used as a template for complementary DNA strand synthesis in cytosolic extracts from HeLa cells. In the presence of the replication-dependent chromatin assembly factor CAF-1, defined numbers of nucleosomes were assembled during complementary DNA strand synthesis. These minichromosomes were then induced to semiconservatively replicate by the addition of the SV40 initiator protein T antigen (re-replication). The results indicate that re-replication of minichromosomes appears to be inhibited by two independent mechanisms. One acts at the initiation of minichromosome re-replication, and the other affects replicative chain elongation. To directly demonstrate the inhibitory effect of replicatively assembled nucleosomes, two types of minichromosomes were prepared: (i) post-replicative minichromosomes were assembled in a reaction coupled to replication as above; (ii) pre-replicative minichromosomes were assembled independently of replication on double-stranded DNA. Both types of minichromosomes were used as templates for DNA replication under identical conditions. Replicative fork movement was found to be impeded only on post-replicative minichromosome templates. In contrast, pre-replicative minichromosomes allowed one unconstrained replication cycle, but re-replication was inhibited due to a block in fork movement. Thus, replicatively assembled chromatin may have a profound influence on the re-replication of DNA.

  2. 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...

  3. 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 number of times an event happened, a history of past trauma, and psychological problems before the ...

  4. Investigating variation in replicability: A "Many Labs" replication project

    NARCIS (Netherlands)

    Klein, R.A.; Ratliff, K.A.; Vianello, M.; Adams, R.B.; Bahnik, S.; Bernstein, M.J.; Bocian, K.; Brandt, M.J.; Brooks, B.; Brumbaugh, C.C.; Cemalcilar, Z.; Chandler, J.; Cheong, W.; Davis, W.E.; Devos, T.; Eisner, M.; Frankowska, N.; Furrow, D.; Galliani, E.M.; Hasselman, F.W.; Hicks, J.A.; Hovermale, J.F.; Hunt, S.J.; Huntsinger, J.R.; IJzerman, H.; John, M.S.; Joy-Gaba, J.A.; Kappes, H.B.; Krueger, L.E.; Kurtz, J.; Levitan, C.A.; Mallett, R.K.; Morris, W.L.; Nelson, A.J.; Nier, J.A.; Packard, G.; Pilati, R.; Rutchick, A.M.; Schmidt, K.; Skorinko, J.L.M.; Smith, R.; Steiner, T.G.; Storbeck, J.; Van Swol, L.M.; Thompson, D.; Veer, A.E. van 't; Vaughn, L.A.; Vranka, M.; Wichman, A.L.; Woodzicka, J.A.; Nosek, B.A.

    2014-01-01

    Although replication is a central tenet of science, direct replications are rare in psychology. This research tested variation in the replicability of 13 classic and contemporary effects across 36 independent samples totaling 6,344 participants. In the aggregate, 10 effects replicated consistently.

  5. Hepatitis B virus replication

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Hepadnaviruses, including human hepatitis B virus (HBV), replicate through reverse transcription of an RNA intermediate, the pregenomic RNA (pgRNA). Despite this kinship to retroviruses, there are fundamental differences beyond the fact that hepadnavirions contain DNA instead of RNA. Most peculiar is the initiation of reverse transcription: it occurs by protein-priming, is strictly committed to using an RNA hairpin on the pgRNA,ε, as template, and depends on cellular chaperones;moreover, proper replication can apparently occur only in the specialized environment of intact nucleocapsids.This complexity has hampered an in-depth mechanistic understanding. The recent successful reconstitution in the test tube of active replication initiation complexes from purified components, for duck HBV (DHBV),now allows for the analysis of the biochemistry of hepadnaviral replication at the molecular level. Here we review the current state of knowledge at all steps of the hepadnaviral genome replication cycle, with emphasis on new insights that turned up by the use of such cellfree systems. At this time, they can, unfortunately,not be complemented by three-dimensional structural information on the involved components. However, at least for the s RNA element such information is emerging,raising expectations that combining biophysics with biochemistry and genetics will soon provide a powerful integrated approach for solving the many outstanding questions. The ultimate, though most challenging goal,will be to visualize the hepadnaviral reverse transcriptase in the act of synthesizing DNA, which will also have strong implications for drug development.

  6. Practical Time Mark Estimators for Multichannel Digital Silicon Photomultipliers

    NARCIS (Netherlands)

    Venialgo, E.; Mandai, S.; Gong, T.; Schaart, D.R.; Charbon, E.

    2015-01-01

    Multiple time-to-digital converters coupled with silicon photomultipliers allow to timestamp several light photons generated by a scintillation event. Multichannel digital silicon photomultipliers opened the possibility to estimate a gammaphoton time mark by using several photoelectrons timestamps.

  7. Ergodicity Conditions and Cesaro Limit Results for Marked Point Processes

    NARCIS (Netherlands)

    Nieuwenhuis, G.

    1996-01-01

    In Palm theory it is very common to consider several distributions to describe the characteristics of the system.To study a stationary marked point process, the time-stationary distribution P and its event-stationary Palm distributions P 0 L with respect to sets L of marks can all be used as startin

  8. Psychology, replication & beyond.

    Science.gov (United States)

    Laws, Keith R

    2016-06-01

    Modern psychology is apparently in crisis and the prevailing view is that this partly reflects an inability to replicate past findings. If a crisis does exists, then it is some kind of 'chronic' crisis, as psychologists have been censuring themselves over replicability for decades. While the debate in psychology is not new, the lack of progress across the decades is disappointing. Recently though, we have seen a veritable surfeit of debate alongside multiple orchestrated and well-publicised replication initiatives. The spotlight is being shone on certain areas and although not everyone agrees on how we should interpret the outcomes, the debate is happening and impassioned. The issue of reproducibility occupies a central place in our whig history of psychology.

  9. 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

  10. 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

  11. DNA replication origins in archaea

    OpenAIRE

    Zhenfang eWu; Jingfang eLiu; Haibo eYang; Hua eXiang

    2014-01-01

    DNA replication initiation, which starts at specific chromosomal site (known as replication origins), is the key regulatory stage of chromosome replication. Archaea, the third domain of life, use a single or multiple origin(s) to initiate replication of their circular chromosomes. The basic structure of replication origins is conserved among archaea, typically including an AT-rich unwinding region flanked by several conserved repeats (origin recognition box, ORB) that are located adjacent to ...

  12. 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...

  13. Coronavirus Attachment and Replication

    Science.gov (United States)

    1988-03-28

    synthesis during RNA replication of vesicular stomatitis virus. J. Virol. 49:303-309. Pedersen, N.C. 1976a. Feline infectious peritonitis: Something old...receptors on intestinal brush border membranes from normal host species were developed for canine (CCV), feline (FIPV), porcine (TGEV), human (HCV...gastroenteritis receptor on pig BBMs ...... ................. ... 114 Feline infectious peritonitis virus receptor on cat BBMs ... .............. 117 Human

  14. Improving Marking Quality through a Taxonomy of Mark Schemes

    Science.gov (United States)

    Ahmed, Ayesha; Pollitt, Alastair

    2011-01-01

    At the heart of most assessments lies a set of questions, and those who write them must achieve "two" things. Not only must they ensure that each question elicits the kind of performance that shows how "good" pupils are at the subject, but they must also ensure that each mark scheme gives more marks to those who are…

  15. Reversible Switching of Cooperating Replicators

    Science.gov (United States)

    Urtel, Georg C.; Rind, Thomas; Braun, Dieter

    2017-02-01

    How can molecules with short lifetimes preserve their information over millions of years? For evolution to occur, information-carrying molecules have to replicate before they degrade. Our experiments reveal a robust, reversible cooperation mechanism in oligonucleotide replication. Two inherently slow replicating hairpin molecules can transfer their information to fast crossbreed replicators that outgrow the hairpins. The reverse is also possible. When one replication initiation site is missing, single hairpins reemerge from the crossbreed. With this mechanism, interacting replicators can switch between the hairpin and crossbreed mode, revealing a flexible adaptation to different boundary conditions.

  16. Chromatin replication and epigenome maintenance

    DEFF Research Database (Denmark)

    Alabert, Constance; Groth, Anja

    2012-01-01

    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...

  17. Chromatin replication and epigenome maintenance

    DEFF Research Database (Denmark)

    Alabert, Constance; Groth, Anja

    2012-01-01

    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...

  18. Initiation of adenovirus DNA replication.

    OpenAIRE

    Reiter, T; Fütterer, J; Weingärtner, B; Winnacker, E L

    1980-01-01

    In an attempt to study the mechanism of initiation of adenovirus DNA replication, an assay was developed to investigate the pattern of DNA synthesis in early replicative intermediates of adenovirus DNA. By using wild-type virus-infected cells, it was possible to place the origin of adenovirus type 2 DNA replication within the terminal 350 to 500 base pairs from either of the two molecular termini. In addition, a variety of parameters characteristic of adenovirus DNA replication were compared ...

  19. 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...

  20. Mark-specific hazard ratio model with missing multivariate marks.

    Science.gov (United States)

    Juraska, Michal; Gilbert, Peter B

    2016-10-01

    An objective of randomized placebo-controlled preventive HIV vaccine efficacy (VE) trials is to assess the relationship between vaccine effects to prevent HIV acquisition and continuous genetic distances of the exposing HIVs to multiple HIV strains represented in the vaccine. The set of genetic distances, only observed in failures, is collectively termed the 'mark.' The objective has motivated a recent study of a multivariate mark-specific hazard ratio model in the competing risks failure time analysis framework. Marks of interest, however, are commonly subject to substantial missingness, largely due to rapid post-acquisition viral evolution. In this article, we investigate the mark-specific hazard ratio model with missing multivariate marks and develop two inferential procedures based on (i) inverse probability weighting (IPW) of the complete cases, and (ii) augmentation of the IPW estimating functions by leveraging auxiliary data predictive of the mark. Asymptotic properties and finite-sample performance of the inferential procedures are presented. This research also provides general inferential methods for semiparametric density ratio/biased sampling models with missing data. We apply the developed procedures to data from the HVTN 502 'Step' HIV VE trial.

  1. 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…

  2. 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…

  3. Replication data collection highlights value in diversity of replication attempts

    Science.gov (United States)

    DeSoto, K. Andrew; Schweinsberg, Martin

    2017-01-01

    Researchers agree that replicability and reproducibility are key aspects of science. A collection of Data Descriptors published in Scientific Data presents data obtained in the process of attempting to replicate previously published research. These new replication data describe published and unpublished projects. The different papers in this collection highlight the many ways that scientific replications can be conducted, and they reveal the benefits and challenges of crucial replication research. The organizers of this collection encourage scientists to reuse the data contained in the collection for their own work, and also believe that these replication examples can serve as educational resources for students, early-career researchers, and experienced scientists alike who are interested in learning more about the process of replication. PMID:28291224

  4. Coordination between chromosome replication, segregation, and cell division in Caulobacter crescentus

    DEFF Research Database (Denmark)

    Jensen, Rasmus Bugge

    2006-01-01

    Progression through the Caulobacter crescentus cell cycle is coupled to a cellular differentiation program. The swarmer cell is replicationally quiescent, and DNA replication initiates at the swarmer-to-stalked cell transition. There is a very short delay between initiation of DNA replication......, and the completely replicated terminus regions stay associated with each other after chromosome replication is completed, disassociating very late in the cell cycle shortly before the final cell division event. Invagination of the cytoplasmic membrane occurs earlier than separation of the replicated terminus regions...

  5. Multifork chromosome replication in slow-growing bacteria

    Science.gov (United States)

    Trojanowski, Damian; Hołówka, Joanna; Ginda, Katarzyna; Jakimowicz, Dagmara; Zakrzewska-Czerwińska, Jolanta

    2017-01-01

    The growth rates of bacteria must be coordinated with major cell cycle events, including chromosome replication. When the doubling time (Td) is shorter than the duration of chromosome replication (C period), a new round of replication begins before the previous round terminates. Thus, newborn cells inherit partially duplicated chromosomes. This phenomenon, which is termed multifork replication, occurs among fast-growing bacteria such as Escherichia coli and Bacillus subtilis. In contrast, it was historically believed that slow-growing bacteria (including mycobacteria) do not reinitiate chromosome replication until the previous round has been completed. Here, we use single-cell time-lapse analyses to reveal that mycobacterial cell populations exhibit heterogeneity in their DNA replication dynamics. In addition to cells with non-overlapping replication rounds, we observed cells in which the next replication round was initiated before completion of the previous replication round. We speculate that this heterogeneity may reflect a relaxation of cell cycle checkpoints, possibly increasing the ability of slow-growing mycobacteria to adapt to environmental conditions. PMID:28262767

  6. Surgical skin-marking techniques.

    Science.gov (United States)

    Granick, M S; Heckler, F R; Jones, E W

    1987-04-01

    Surgical skin-marking inks and dyes are in everyday use for designing and planning incisions in plastic and reconstructive surgery. We have traced the historical development of surgical skin-marking techniques from ancient times to the present. The biochemical characteristics of the commonly used marking agents are discussed. A three-part experiment utilizing a pig model was carried out to test the tissue inflammatory response to the various dyes and inks when used intradermally as tattoos, the persistence of such tattoos, and the ease of skin erasure for each of eight stains. Methylene blue and gentian violet are recommended as the best all-purpose marking agents. The use of proprietary inks is discouraged.

  7. Eesti vajab riigiarhitekti / Mark Soosaar

    Index Scriptorium Estoniae

    Soosaar, Mark, 1946-

    2006-01-01

    Linnade tekkimisest Eestis, linnaehitusest ja linnaplaneerimisest. Pärnu muinsuskaitsealast ja uute korruselamute ehitamisest. Arhitektuuriameti loomise ja riigiarhitekti ametikoha vajalikkusest. Kommenteerivad Ülar Mark, Triin Ojari, Harry Liivrand, Karin Paulus

  8. Anatomy of Mammalian Replication Domains

    Science.gov (United States)

    Takebayashi, Shin-ichiro; Ogata, Masato; Okumura, Katsuzumi

    2017-01-01

    Genetic information is faithfully copied by DNA replication through many rounds of cell division. In mammals, DNA is replicated in Mb-sized chromosomal units called “replication domains.” While genome-wide maps in multiple cell types and disease states have uncovered both dynamic and static properties of replication domains, we are still in the process of understanding the mechanisms that give rise to these properties. A better understanding of the molecular basis of replication domain regulation will bring new insights into chromosome structure and function. PMID:28350365

  9. Lane marking aided vehicle localization

    OpenAIRE

    2013-01-01

    International audience; A localization system that exploits L1-GPS estimates, vehicle data, and features from a video camera as well as lane markings embedded in digital navigation maps is presented. A sensitivity analysis of the detected lane markings is proposed in order to quantify both the lateral and longitudinal errors caused by 2D-world hypothesis violation. From this, a camera observation model for vehicle localization is proposed. The paper presents also a method to build a map of th...

  10. 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....

  11. DNA methyltransferases are required to induce heterochromatic re-replication in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Hume Stroud

    2012-07-01

    Full Text Available The relationship between epigenetic marks on chromatin and the regulation of DNA replication is poorly understood. Mutations of the H3K27 methyltransferase genes, Arabidopsis trithorax-related protein5 (ATXR5 and ATXR6, result in re-replication (repeated origin firing within the same cell cycle. Here we show that mutations that reduce DNA methylation act to suppress the re-replication phenotype of atxr5 atxr6 mutants. This suggests that DNA methylation, a mark enriched at the same heterochromatic regions that re-replicate in atxr5/6 mutants, is required for aberrant re-replication. In contrast, RNA sequencing analyses suggest that ATXR5/6 and DNA methylation cooperatively transcriptionally silence transposable elements (TEs. Hence our results suggest a complex relationship between ATXR5/6 and DNA methylation in the regulation of DNA replication and transcription of TEs.

  12. Inflectional marking in Hungarian aphasics.

    Science.gov (United States)

    MacWhinney, B; Osmán-Sági, J

    1991-08-01

    How do aphasics deal with the rich inflectional marking available in agglutinative languages like Hungarian? For the Hungarian noun alone, aphasics have to deal with over 15 basic case markings and dozens of possible combinations of these basic markings. Using the picture description task of MacWhinney and Bates (1978), this study examined the use of inflectional markings in nine Broca's and five Wernicke's aphasic speakers of Hungarian. The analysis focused on subject, direct object, indirect object, and locative nominal arguments. Compared to normals, both groups had a much higher rate of omission of all argument types. Subject ellipsis was particularly strong, as it is in normal Hungarian. There was a tendency for Broca's to omit the indirect object and for Wernicke's to omit the direct object. Across argument types, Wernicke's had a much higher level of pronoun usage than did Broca's. Broca's also showed a very high level of article omission. Compared to similar data reported by Slobin (this issue) for Turkish, the Hungarian aphasics showed an elevated level of omission of case markings. Addition errors were quite rare, but there were 14 substitutions of one case marking for another. These errors all involved the substitution of some close semantic competitor. There were no errors in the basic rules for vowel harmony or morpheme order. Overall the results paint a picture of a group of individuals whose grammatical abilities are damaged and noisy, but still largely functional. Neither the view of Broca's as agrammatic nor the view of Wernicke's as paragrammatic was strongly supported.

  13. 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.

  14. 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....

  15. Systematic determination of replication activity type highlights interconnections between replication, chromatin structure and nuclear localization.

    Directory of Open Access Journals (Sweden)

    Shlomit Farkash-Amar

    Full Text Available DNA replication is a highly regulated process, with each genomic locus replicating at a distinct time of replication (ToR. Advances in ToR measurement technology enabled several genome-wide profiling studies that revealed tight associations between ToR and general genomic features and a remarkable ToR conservation in mammals. Genome wide studies further showed that at the hundreds kb-to-megabase scale the genome can be divided into constant ToR regions (CTRs in which the replication process propagates at a faster pace due to the activation of multiple origins and temporal transition regions (TTRs in which the replication process propagates at a slower pace. We developed a computational tool that assigns a ToR to every measured locus and determines its replication activity type (CTR versus TTR. Our algorithm, ARTO (Analysis of Replication Timing and Organization, uses signal processing methods to fit a constant piece-wise linear curve to the measured raw data. We tested our algorithm and provide performance and usability results. A Matlab implementation of ARTO is available at http://bioinfo.cs.technion.ac.il/people/zohar/ARTO/. Applying our algorithm to ToR data measured in multiple mouse and human samples allowed precise genome-wide ToR determination and replication activity type characterization. Analysis of the results highlighted the plasticity of the replication program. For example, we observed significant ToR differences in 10-25% of the genome when comparing different tissue types. Our analyses also provide evidence for activity type differences in up to 30% of the probes. Integration of the ToR data with multiple aspects of chromosome organization characteristics suggests that ToR plays a role in shaping the regional chromatin structure. Namely, repressive chromatin marks, are associated with late ToR both in TTRs and CTRs. Finally, characterization of the differences between TTRs and CTRs, with matching ToR, revealed that TTRs are

  16. Replicated Spectrographs in Astronomy

    CERN Document Server

    Hill, Gary J

    2014-01-01

    As telescope apertures increase, the challenge of scaling spectrographic astronomical instruments becomes acute. The next generation of extremely large telescopes (ELTs) strain the availability of glass blanks for optics and engineering to provide sufficient mechanical stability. While breaking the relationship between telescope diameter and instrument pupil size by adaptive optics is a clear path for small fields of view, survey instruments exploiting multiplex advantages will be pressed to find cost-effective solutions. In this review we argue that exploiting the full potential of ELTs will require the barrier of the cost and engineering difficulty of monolithic instruments to be broken by the use of large-scale replication of spectrographs. The first steps in this direction have already been taken with the soon to be commissioned MUSE and VIRUS instruments for the Very Large Telescope and the Hobby-Eberly Telescope, respectively. MUSE employs 24 spectrograph channels, while VIRUS has 150 channels. We compa...

  17. 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.

  18. 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.

  19. 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

  20. Vastab Mark Lubotski / Mark Lubotski ; interv. Toomas Velmet

    Index Scriptorium Estoniae

    Lubotski, Mark

    2008-01-01

    Hamburgi Muusikakõrgkooli viiuliprofessor Mark Lubotskist, kes viibis Tallinnas oktoobris 2008 ja oli IV rahvusvahelise Heino Elleri nimelise viiuldajate konkursi žürii esimeheks. Tema sidemetest Eesti muusikutega, pagemisest Läände, Heino Elleri nimelisest konkursist ja tööst žüriis

  1. 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

  2. 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.

  3. 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.

  4. Solving the Telomere Replication Problem

    Science.gov (United States)

    Maestroni, Laetitia; Matmati, Samah; Coulon, Stéphane

    2017-01-01

    Telomeres are complex nucleoprotein structures that protect the extremities of linear chromosomes. Telomere replication is a major challenge because many obstacles to the progression of the replication fork are concentrated at the ends of the chromosomes. This is known as the telomere replication problem. In this article, different and new aspects of telomere replication, that can threaten the integrity of telomeres, will be reviewed. In particular, we will focus on the functions of shelterin and the replisome for the preservation of telomere integrity. PMID:28146113

  5. Two Stories about Mark Twain

    Institute of Scientific and Technical Information of China (English)

    张策; 李秀云

    2004-01-01

    ⅠAsyouknow,MarkTwainwasafamousAmericanwriterandJamesWhistlerwasafa-mouspainter.TwainlikedWhistler’sworkverymuch,andthere’sastoryaboutthedayhevisitedWhistlerinhisstudio.Whistlerwasaratherseriousperson,butTwainen-joyedjokes.TwainwalkedroundthestudiolookingatWhistler’swonderfulpaintings.“Ilikethispictureofthesea,”Twainsaid.“Yes,Ipainteditsometimeago.It’scalled‘AngrySea’.”“Thecolorsarebeautiful,”Twainsaid.Thenhepointedatanotherpicture.“Ilikethewaythewomanisstandinginthepicture.Ilikethewayshe’slookingoutofthewin...

  6. Business Education Receives High Marks.

    Science.gov (United States)

    Yopp, Martha C.; Brumley, Debbie

    1996-01-01

    A national survey of state superintendents of public instruction (n=35) and state directors of employment and training (n=28) gives business education programs, courses, and competencies high marks. Suggests that business educators should take advantage of this support by becoming more active in professional organizations. (JOW)

  7. Visual marking of old objects

    NARCIS (Netherlands)

    Theeuwes, J.; Kramer, A.F.; Atchley, P.

    1998-01-01

    Watson and Humphreys (1997) presented evidence that selection of new elements can be prioritized by on-line top-down attentional inhibition of old stimuli already in the visual field (visual marking). The experiments on which this evidence was based always presented old elements in green and new ele

  8. Splitting the Notion of "Agent": Case-Marking in Early Child Hindi

    Science.gov (United States)

    Narasimhan, Bhuvana

    2005-01-01

    Two construals of agency are evaluated as possible innate biases guiding case-marking in children. A BROAD construal treats agentive arguments of multi-participant and single-participant events as being similar. A NARROWER construal is restricted to agents of multi-participant events. In Hindi, ergative case-marking is associated with agentive…

  9. 49 CFR 1520.13 - Marking SSI.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 9 2010-10-01 2010-10-01 false Marking SSI. 1520.13 Section 1520.13... SECURITY INFORMATION § 1520.13 Marking SSI. (a) Marking of paper records. In the case of paper records containing SSI, a covered person must mark the record by placing the protective marking conspicuously on the...

  10. Identifying and preserving high-water mark data

    Science.gov (United States)

    Koenig, Todd A.; Bruce, Jennifer L.; O'Connor, Jim; McGee, Benton D.; Holmes, Jr., Robert R.; Hollins, Ryan; Forbes, Brandon T.; Kohn, Michael S.; Schellekens, Mathew; Martin, Zachary W.; Peppler, Marie C.

    2016-03-08

    High-water marks provide valuable data for understanding recent and historical flood events. The proper collection and recording of high-water mark data from perishable and preserved evidence informs flood assessments, research, and water resource management. Given the high cost of flooding in developed areas, experienced hydrographers, using the best available techniques, can contribute high-quality data toward efforts such as public education of flood risk, flood inundation mapping, flood frequency computations, indirect streamflow measurement, and hazard assessments.This manual presents guidance for skilled high-water mark identification, including marks left behind in natural and man-made environments by tranquil and rapid flowing water. This manual also presents pitfalls and challenges associated with various types of flood evidence that help hydrographers identify the best high-water marks and assess the uncertainty associated with a given mark. Proficient high-water mark data collection contributes to better understanding of the flooding process and reduces risk through greater ability to estimate flood probability.The U.S. Geological Survey, operating the Nation’s premier water data collection network, encourages readers of this manual to familiarize themselves with the art and science of high-water mark collection. The U.S. Geological survey maintains a national database at http://water.usgs.gov/floods/FEV/ that includes high-water mark information for many flood events, and local U.S. Geological Survey Water Science Centers can provide information to interested readers about participation in data collection and flood documentation efforts as volunteers or observers.

  11. 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…

  12. 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.

  13. DATABASE REPLICATION IN HETEROGENOUS PLATFORM

    Directory of Open Access Journals (Sweden)

    Hendro Nindito

    2014-01-01

    Full Text Available 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 MySQL running on Linux as the destination. The method applied in this research is prototyping in which the processes of development and testing can be done interactively and repeatedly. The key result of this research is that the replication technology applied, which is called Oracle GoldenGate, can successfully manage to do its task in replicating data in real-time and heterogeneous platforms.

  14. LHCb experience with LFC replication

    CERN Document Server

    Carbone, Angelo; Dafonte Perez, Eva; D'Apice, Antimo; dell'Agnello, Luca; Duellmann, Dirk; Girone, Maria; Lo Re, Giuseppe; Martelli, Barbara; Peco, Gianluca; Ricci, Pier Paolo; Sapunenko, Vladimir; Vagnoni, Vincenzo; Vitlacil, Dejan

    2007-01-01

    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. 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 Informations (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.

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

  16. 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

  17. 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…

  18. 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.

  19. DNA ligase I, the replicative DNA ligase.

    Science.gov (United States)

    Howes, Timothy R L; Tomkinson, Alan E

    2012-01-01

    Multiple DNA ligation events are required to join the Okazaki fragments generated during lagging strand DNA synthesis. In eukaryotes, this is primarily carried out by members of the DNA ligase I family. The C-terminal catalytic region of these enzymes is composed of three domains: a DNA binding domain, an adenylation domain and an OB-fold domain. In the absence of DNA, these domains adopt an extended structure but transition into a compact ring structure when they engage a DNA nick, with each of the domains contacting the DNA. The non-catalytic N-terminal region of eukaryotic DNA ligase I is responsible for the specific participation of these enzymes in DNA replication. This proline-rich unstructured region contains the nuclear localization signal and a PCNA interaction motif that is critical for localization to replication foci and efficient joining of Okazaki fragments. DNA ligase I initially engages the PCNA trimer via this interaction motif which is located at the extreme N-terminus of this flexible region. It is likely that this facilitates an additional interaction between the DNA binding domain and the PCNA ring. The similar size and shape of the rings formed by the PCNA trimer and the DNA ligase I catalytic region when it engages a DNA nick suggest that these proteins interact to form a double-ring structure during the joining of Okazaki fragments. DNA ligase I also interacts with replication factor C, the factor that loads the PCNA trimeric ring onto DNA. This interaction, which is regulated by phosphorylation of the non-catalytic N-terminus of DNA ligase I, also appears to be critical for DNA replication.

  20. International Expansion through Flexible Replication

    DEFF Research Database (Denmark)

    Jonsson, Anna; Foss, Nicolai Juul

    2011-01-01

    to local environments and under the impact of new learning. To illuminate these issues, we draw on a longitudinal in-depth study of Swedish home furnishing giant IKEA, involving more than 70 interviews. We find that IKEA has developed organizational mechanisms that support an ongoing learning process aimed......, 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....

  1. The Psychology of Replication and Replication in Psychology.

    Science.gov (United States)

    Francis, Gregory

    2012-11-01

    Like other scientists, psychologists believe experimental replication to be the final arbiter for determining the validity of an empirical finding. Reports in psychology journals often attempt to prove the validity of a hypothesis or theory with multiple experiments that replicate a finding. Unfortunately, these efforts are sometimes misguided because in a field like experimental psychology, ever more successful replication does not necessarily ensure the validity of an empirical finding. When psychological experiments are analyzed with statistics, the rules of probability dictate that random samples should sometimes be selected that do not reject the null hypothesis, even if an effect is real. As a result, it is possible for a set of experiments to have too many successful replications. When there are too many successful replications for a given set of experiments, a skeptical scientist should be suspicious that null or negative findings have been suppressed, the experiments were run improperly, or the experiments were analyzed improperly. This article describes the implications of this observation and demonstrates how to test for too much successful replication by using a set of experiments from a recent research paper.

  2. Regulation of Replication Recovery and Genome Integrity

    DEFF Research Database (Denmark)

    Colding, Camilla Skettrup

    Preserving genome integrity is essential for cell survival. To this end, mechanisms that supervise DNA replication and respond to replication perturbations have evolved. One such mechanism is the replication checkpoint, which responds to DNA replication stress and acts to ensure replication pausing...

  3. Laser therapy of stretch marks.

    Science.gov (United States)

    McDaniel, David H

    2002-01-01

    Striae distensae, better known as stretch marks, are a common disfiguring skin disorder of significant cosmetic concern. Many sources have reported the use of lasers to diminish the appearance of striae. Controlled clinical studies of the various treatment modalities available for striae are relatively uncommon, and much of the clinical data are anecdotal. The use of lasers alone or in combination with other therapeutic modalities can provide a safe and effective reduction in the appearance of both red and white striae distensae. Many of these therapies require special measures for darker skin phototypes. This article reviews the historical use of laser therapy for this disorder and discusses current therapeutic options.

  4. 49 CFR 221.14 - Marking devices.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Marking devices. 221.14 Section 221.14..., DEPARTMENT OF TRANSPORTATION REAR END MARKING DEVICE-PASSENGER, COMMUTER AND FREIGHT TRAINS Marking Devices § 221.14 Marking devices. (a) As prescribed in § 221.13, passenger, commuter and freight trains shall...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. Event Management

    OpenAIRE

    Havlenová, Tereza

    2016-01-01

    Event is an experience that is perceived by all the senses. Event management is a process involving the various activities that are assigned to staffers. Organizing special events became an individual field. If the manager understand the events as a communication platform gets into the hands of a modern, multifunctional and very impressive tool. The procedure to implement a successful event in a particular area is part of this work. The first part explains the issues of event management on th...

  10. 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).

  11. Design of Arabic Diacritical Marks

    CERN Document Server

    Hssini, Mohamed

    2011-01-01

    Diacritical marks play a crucial role in meeting the criteria of usability of typographic text, such as: homogeneity, clarity and legibility. To change the diacritic of a letter in a word could completely change its semantic. The situation is very complicated with multilingual text. Indeed, the problem of design becomes more difficult by the presence of diacritics that come from various scripts; they are used for different purposes, and are controlled by various typographic rules. It is quite challenging to adapt rules from one script to another. This paper aims to study the placement and sizing of diacritical marks in Arabic script, with a comparison with the Latin's case. The Arabic script is cursive and runs from right-to-left; its criteria and rules are quite distinct from those of the Latin script. In the beginning, we compare the difficulty of processing diacritics in both scripts. After, we will study the limits of Latin resolution strategies when applied to Arabic. At the end, we propose an approach t...

  12. 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...... with their chronological age and present health status, help define their current rate of aging and contribute to establish personalized therapy plans to reduce, counteract or even avoid the appearance of aging biomarkers....

  13. Nucleotide Metabolism and DNA Replication.

    Science.gov (United States)

    Warner, Digby F; Evans, Joanna C; Mizrahi, Valerie

    2014-10-01

    The development and application of a highly versatile suite of tools for mycobacterial genetics, coupled with widespread use of "omics" approaches to elucidate the structure, function, and regulation of mycobacterial proteins, has led to spectacular advances in our understanding of the metabolism and physiology of mycobacteria. In this article, we provide an update on nucleotide metabolism and DNA replication in mycobacteria, highlighting key findings from the past 10 to 15 years. In the first section, we focus on nucleotide metabolism, ranging from the biosynthesis, salvage, and interconversion of purine and pyrimidine ribonucleotides to the formation of deoxyribonucleotides. The second part of the article is devoted to DNA replication, with a focus on replication initiation and elongation, as well as DNA unwinding. We provide an overview of replication fidelity and mutation rates in mycobacteria and summarize evidence suggesting that DNA replication occurs during states of low metabolic activity, and conclude by suggesting directions for future research to address key outstanding questions. Although this article focuses primarily on observations from Mycobacterium tuberculosis, it is interspersed, where appropriate, with insights from, and comparisons with, other mycobacterial species as well as better characterized bacterial models such as Escherichia coli. Finally, a common theme underlying almost all studies of mycobacterial metabolism is the potential to identify and validate functions or pathways that can be exploited for tuberculosis drug discovery. In this context, we have specifically highlighted those processes in mycobacterial DNA replication that might satisfy this critical requirement.

  14. Plasmid Rolling-Circle Replication.

    Science.gov (United States)

    Ruiz-Masó, J A; MachóN, C; Bordanaba-Ruiseco, L; Espinosa, M; Coll, M; Del Solar, G

    2015-02-01

    Plasmids are DNA entities that undergo controlled replication independent of the chromosomal DNA, a crucial step that guarantees the prevalence of the plasmid in its host. DNA replication has to cope with the incapacity of the DNA polymerases to start de novo DNA synthesis, and different replication mechanisms offer diverse solutions to this problem. Rolling-circle replication (RCR) is a mechanism adopted by certain plasmids, among other genetic elements, that represents one of the simplest initiation strategies, that is, the nicking by a replication initiator protein on one parental strand to generate the primer for leading-strand initiation and a single priming site for lagging-strand synthesis. All RCR plasmid genomes consist of a number of basic elements: leading strand initiation and control, lagging strand origin, phenotypic determinants, and mobilization, generally in that order of frequency. RCR has been mainly characterized in Gram-positive bacterial plasmids, although it has also been described in Gram-negative bacterial or archaeal plasmids. Here we aim to provide an overview of the RCR plasmids' lifestyle, with emphasis on their characteristic traits, promiscuity, stability, utility as vectors, etc. While RCR is one of the best-characterized plasmid replication mechanisms, there are still many questions left unanswered, which will be pointed out along the way in this review.

  15. 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, ...

  16. 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, ...

  17. The Werner and Bloom syndrome proteins help resolve replication blockage by converting (regressed) holliday junctions to functional replication forks.

    Science.gov (United States)

    Machwe, Amrita; Karale, Rajashree; Xu, Xioahua; Liu, Yilun; Orren, David K

    2011-08-16

    Cells cope with blockage of replication fork progression in a manner that allows DNA synthesis to be completed and genomic instability minimized. Models for resolution of blocked replication involve fork regression to form Holliday junction structures. The human RecQ helicases WRN and BLM (deficient in Werner and Bloom syndromes, respectively) are critical for maintaining genomic stability and thought to function in accurate resolution of replication blockage. Consistent with this notion, WRN and BLM localize to sites of blocked replication after certain DNA-damaging treatments and exhibit enhanced activity on replication and recombination intermediates. Here we examine the actions of WRN and BLM on a special Holliday junction substrate reflective of a regressed replication fork. Our results demonstrate that, in reactions requiring ATP hydrolysis, both WRN and BLM convert this Holliday junction substrate primarily to a four-stranded replication fork structure, suggesting they target the Holliday junction to initiate branch migration. In agreement, the Holliday junction binding protein RuvA inhibits the WRN- and BLM-mediated conversion reactions. Importantly, this conversion product is suitable for replication with its leading daughter strand readily extended by DNA polymerases. Furthermore, binding to and conversion of this Holliday junction are optimal at low MgCl(2) concentrations, suggesting that WRN and BLM preferentially act on the square planar (open) conformation of Holliday junctions. Our findings suggest that, subsequent to fork regression events, WRN and/or BLM could re-establish functional replication forks to help overcome fork blockage. Such a function is highly consistent with phenotypes associated with WRN- and BLM-deficient cells.

  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. Dialectica Interpretation with Marked Counterexamples

    CERN Document Server

    Trifonov, Trifon

    2011-01-01

    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.

  20. Ku stabilizes replication forks in the absence of Brc1.

    Directory of Open Access Journals (Sweden)

    Arancha Sánchez

    Full Text Available DNA replication errors are a major source of genome instability in all organisms. In the fission yeast Schizosaccharomyces pombe, the DNA damage response protein Brc1 binds phospho-histone H2A (γH2A-marked chromatin during S-phase, but how Brc1 protects genome integrity remains unclear. Here we report that the non-homologous end-joining (NHEJ protein Ku becomes critical for survival of replication stress in brc1∆ cells. Ku's protective activity in brc1∆ cells does not involve its canonical NHEJ function or its roles in protecting telomeres or shielding DNA ends from Exo1 exonuclease. In brc1∆ pku80∆ cells, nuclear foci of Rad52 homologous recombination (HR protein increase and Mus81-Eme1 Holliday junction resolvase becomes critical, indicating increased replication fork instability. Ku's localization at a ribosomal DNA replication fork barrier associated with frequent replisome-transcriptosome collisions increases in brc1∆ cells and increased collisions correlate with an enhanced requirement for Brc1. These data indicate that Ku stabilizes replication forks in the absence of Brc1.

  1. Event marketing

    OpenAIRE

    Novotná, Michaela

    2008-01-01

    This study aims to analyze event-marketing activities of the small firm and propose new events. At first the theoretical part describes marketing and communication mix and then especially planning and development of event marketing campaign. Research data were collected by the method of survey to propose the new events. Randomly selected customers were asked to fill the questionnaire. Its results were integrated into the proposal of the new events. The interview was realized with the owner of...

  2. A replicator was not involved in the origin of life.

    Science.gov (United States)

    Shapiro, R

    2000-03-01

    Many scientific theories of the origin of life suggest that life began with the spontaneous formation of a replicator (a self-copying organic polymer) within an unorganized chemical mixture, or "soup." A profound difficulty exists, however, with the idea of RNA, or any other replicator, at the start of life. Existing replicators can serve as templates for the synthesis of additional copies of themselves, but this device cannot be used for the preparation of the very first such molecule, which must arise spontaneously from an unorganized mixture. The formation of an information-bearing homopolymer through undirected chemical synthesis appears very improbable. The difficulties involved in such a synthesis are illustrated by considering the prospects for the assembly of a polypeptide of L-alpha-amino acids, based on the contents of the Murchison meteorite as an example of a mixture of abiotic origin. In that mixture, potential replicator components would be accompanied by a host of interfering substances, which include chain terminators (simple carboxylic acids and amines), branch-formers, D-amino acids, and many classes of substances for which incorporation would disrupt the necessary structural regularity of the replicator. Laboratory experiments dealing with the nonenzymatic synthesis of biopolymers have not addressed the specificity problem. The possibility that formation of the first replicator took place through a very improbable event cannot be excluded, but greater attention should be given to metabolism-first theories, which avoid this difficulty.

  3. The research of laser marking control technology

    Science.gov (United States)

    Zhang, Qiue; Zhang, Rong

    2009-08-01

    In the area of Laser marking, the general control method is insert control card to computer's mother board, it can not support hot swap, it is difficult to assemble or it. Moreover, the one marking system must to equip one computer. In the system marking, the computer can not to do the other things except to transmit marking digital information. Otherwise it can affect marking precision. Based on traditional control methods existed some problems, introduced marking graphic editing and digital processing by the computer finish, high-speed digital signal processor (DSP) control marking the whole process. The laser marking controller is mainly contain DSP2812, digital memorizer, DAC (digital analog converting) transform unit circuit, USB interface control circuit, man-machine interface circuit, and other logic control circuit. Download the marking information which is processed by computer to U disk, DSP read the information by USB interface on time, then processing it, adopt the DSP inter timer control the marking time sequence, output the scanner control signal by D/A parts. Apply the technology can realize marking offline, thereby reduce the product cost, increase the product efficiency. The system have good effect in actual unit markings, the marking speed is more quickly than PCI control card to 20 percent. It has application value in practicality.

  4. 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.

  5. 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. PMID:26710261

  6. Defects of mitochondrial DNA replication.

    Science.gov (United States)

    Copeland, William C

    2014-09-01

    Mitochondrial DNA is replicated by DNA polymerase γ in concert with accessory proteins such as the mitochondrial DNA helicase, single-stranded DNA binding protein, topoisomerase, and initiating factors. Defects in mitochondrial DNA replication or nucleotide metabolism can cause mitochondrial genetic diseases due to mitochondrial DNA deletions, point mutations, or depletion, which ultimately cause loss of oxidative phosphorylation. These genetic diseases include mitochondrial DNA depletion syndromes such as Alpers or early infantile hepatocerebral syndromes, and mitochondrial DNA deletion disorders, such as progressive external ophthalmoplegia, ataxia-neuropathy, or mitochondrial neurogastrointestinal encephalomyopathy. This review focuses on our current knowledge of genetic defects of mitochondrial DNA replication (POLG, POLG2, C10orf2, and MGME1) that cause instability of mitochondrial DNA and mitochondrial disease.

  7. 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...

  8. Shell Separation for Mirror Replication

    Science.gov (United States)

    1999-01-01

    NASA's Space Optics Manufacturing Center has been working to expand our view of the universe via sophisticated new telescopes. The Optics Center's goal is to develop low-cost, advanced space optics technologies for the NASA program in the 21st century - including the long-term goal of imaging Earth-like planets in distant solar systems. To reduce the cost of mirror fabrication, Marshall Space Flight Center (MSFC) has developed replication techniques, the machinery, and materials to replicate electro-formed nickel mirrors. Optics replication uses reusable forms, called mandrels, to make telescope mirrors ready for final finishing. MSFC optical physicist Bill Jones monitors a device used to chill a mandrel, causing it to shrink and separate from the telescope mirror without deforming the mirror's precisely curved surface.

  9. Readers of histone methylarginine marks.

    Science.gov (United States)

    Gayatri, Sitaram; Bedford, Mark T

    2014-08-01

    Arginine methylation is a common posttranslational modification (PTM) that alters roughly 0.5% of all arginine residues in the cells. There are three types of arginine methylation: monomethylarginine (MMA), asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA). These three PTMs are enriched on RNA-binding proteins and on histones, and also impact signal transduction cascades. To date, over thirty arginine methylation sites have been cataloged on the different core histones. These modifications alter protein structure, impact interactions with DNA, and also generate docking sites for effector molecules. The primary "readers" of methylarginine marks are Tudor domain-containing proteins. The complete family of thirty-six Tudor domain-containing proteins has yet to be fully characterized, but at least ten bind methyllysine motifs and eight bind methylarginine motifs. In this review, we will highlight the biological roles of the Tudor domains that interact with arginine methylated motifs, and also address other types of interactions that are regulated by these particular PTMs. This article is part of a Special Issue entitled: Molecular mechanisms of histone modification function. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. EDMS - Reaching the Million Mark

    CERN Document Server

    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...

  11. 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…

  12. 46 CFR 160.005-6 - Marking.

    Science.gov (United States)

    2010-10-01

    ...: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Life Preservers, Fibrous Glass, Adult and Child (Jacket Type), Models 52 and 56 § 160.005-6 Marking. Each life preserver must have the following clearly marked in...

  13. 46 CFR 160.002-6 - Marking.

    Science.gov (United States)

    2010-10-01

    ...: SPECIFICATIONS AND APPROVAL LIFESAVING EQUIPMENT Life Preservers, Kapok, Adult and Child (Jacket Type), Models 3 and 5 § 160.002-6 Marking. Each life preserver must have the following clearly marked in waterproof...

  14. 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...

  15. Replication Termination: Containing Fork Fusion-Mediated Pathologies in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Juachi U. Dimude

    2016-07-01

    Full Text Available Duplication of bacterial chromosomes is initiated via the assembly of two replication forks at a single defined origin. Forks proceed bi-directionally until they fuse in a specialised termination area opposite the origin. This area is flanked by polar replication fork pause sites that allow forks to enter but not to leave. The precise function of this replication fork trap has remained enigmatic, as no obvious phenotypes have been associated with its inactivation. However, the fork trap becomes a serious problem to cells if the second fork is stalled at an impediment, as replication cannot be completed, suggesting that a significant evolutionary advantage for maintaining this chromosomal arrangement must exist. Recently, we demonstrated that head-on fusion of replication forks can trigger over-replication of the chromosome. This over-replication is normally prevented by a number of proteins including RecG helicase and 3’ exonucleases. However, even in the absence of these proteins it can be safely contained within the replication fork trap, highlighting that multiple systems might be involved in coordinating replication fork fusions. Here, we discuss whether considering the problems associated with head-on replication fork fusion events helps us to better understand the important role of the replication fork trap in cellular metabolism.

  16. 19 CFR 18.27 - Port marks.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Port marks. 18.27 Section 18.27 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY TRANSPORTATION... Port marks. Port marks may be added by authority of the port director and under the supervision of...

  17. 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...

  18. 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... Export marks. In addition to the marks and brands required to be placed on packages or other bulk... “Export” on the Government side of each case or Government head of each container before removal for...

  19. 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...

  20. Replication domains are self-interacting structural chromatin units of human chromosomes

    Science.gov (United States)

    Arneodo, Alain

    2011-03-01

    In higher eukaryotes, the absence of specific sequence motifs marking the origins of replication has been a serious hindrance to the understanding of the mechanisms that regulate the initiation and the maintenance of the replication program in different cell types. In silico analysis of nucleotide compositional skew has predicted the existence, in the germline, of replication N-domains bordered by putative replication origins and where the skew decreases rather linearly as the signature of a progressive inversion of the average fork polarity. Here, from the demonstration that the average fork polarity can be directly extracted from the derivative of replication timing profiles, we develop a wavelet-based pattern recognition methodology to delineate replication U-domains where the replication timing profile is shaped as a U and its derivative as a N. Replication U-domains are robustly found in seven cell lines as covering a significant portion (40-50%) of the human genome where the replication timing data actually displays some plasticity between cell lines. The early replication initiation zones at U-domains borders are found to be hypersensitive to DNase I cleavage, to be associated with transcriptional activity and to present a significant enrichment in insular-binding proteins CTCF, the hallmark of an open chromatin structure. A comparative analysis of genome-wide chromatin interaction (HiC) data shows that replication-U domains correspond to self-interacting structural high order chromatin units of megabase characteristic size. Taken together, these findings provide evidence that the epigenetic compartmentalization of the human genome into autonomous replication U-domains comes along with an extensive remodelling of the threedimensional chromosome architecture during development or in specific diseases. The observed cell specific conservation of the replication timing between the human and mouse genomes strongly suggests that this chromosome organization into

  1. Regulation of Replication Recovery and Genome Integrity

    DEFF Research Database (Denmark)

    Colding, Camilla Skettrup

    facilitate replication recovery after MMS-induced replication stress. Our data reveal that control of Mrc1 turnover through the interplay between posttranslational modifications and INQ localization adds another layer of regulation to the replication checkpoint. We also add replication recovery to the list...... is mediated by Mrc1, which ensures Mec1 presence at the stalled replication fork thus facilitating Rad53 phosphorylation. When replication can be resumed safely, the replication checkpoint is deactivated and replication forks restart. One mechanism for checkpoint deactivation is the ubiquitin......-targeted proteasomal degradation of Mrc1. In this study, we describe a novel nuclear structure, the intranuclear quality control compartment (INQ), which regulates protein turnover and is important for recovery after replication stress. We find that upon methyl methanesulfonate (MMS)-induced replication stress, INQ...

  2. 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.

  3. Hyperthermia stimulates HIV-1 replication.

    Science.gov (United States)

    Roesch, Ferdinand; Meziane, Oussama; Kula, Anna; Nisole, Sébastien; Porrot, Françoise; Anderson, Ian; Mammano, Fabrizio; Fassati, Ariberto; Marcello, Alessandro; Benkirane, Monsef; Schwartz, Olivier

    2012-01-01

    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.

  4. Cellular Responses to Replication Problems

    NARCIS (Netherlands)

    M. Budzowska (Magdalena)

    2008-01-01

    textabstractDuring every S-phase cells need to duplicate their genomes so that both daughter cells inherit complete copies of genetic information. It is a tremendous task, given the large sizes of mammalian genomes and the required precision of DNA replication. A major threat to the accuracy and eff

  5. Covert Reinforcement: A Partial Replication.

    Science.gov (United States)

    Ripstra, Constance C.; And Others

    A partial replication of an investigation of the effect of covert reinforcement on a perceptual estimation task is described. The study was extended to include an extinction phase. There were five treatment groups: covert reinforcement, neutral scene reinforcement, noncontingent covert reinforcement, and two control groups. Each subject estimated…

  6. 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

  7. Bromodeoxyuridine does not contribute to sister chromatid exchange events in normal or Bloom syndrome cells.

    Science.gov (United States)

    van Wietmarschen, Niek; Lansdorp, Peter M

    2016-08-19

    Sister chromatid exchanges (SCEs) are considered sensitive indicators of genome instability. Detection of SCEs typically requires cells to incorporate bromodeoxyuridine (BrdU) during two rounds of DNA synthesis. Previous studies have suggested that SCEs are induced by DNA replication over BrdU-substituted DNA and that BrdU incorporation alone could be responsible for the high number of SCE events observed in cells from patients with Bloom syndrome (BS), a rare genetic disorder characterized by marked genome instability and high SCE frequency. Here we show using Strand-seq, a single cell DNA template strand sequencing technique, that the presence of variable BrdU concentrations in the cell culture medium and in DNA template strands has no effect on SCE frequency in either normal or BS cells. We conclude that BrdU does not induce SCEs and that SCEs detected in either normal or BS cells reflect DNA repair events that occur spontaneously.

  8. 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.…

  9. Replication-Uncoupled Histone Deposition during Adenovirus DNA Replication

    OpenAIRE

    Komatsu, Tetsuro; Nagata, Kyosuke

    2012-01-01

    In infected cells, the chromatin structure of the adenovirus genome DNA plays critical roles in its genome functions. Previously, we reported that in early phases of infection, incoming viral DNA is associated with both viral core protein VII and cellular histones. Here we show that in late phases of infection, newly synthesized viral DNA is also associated with histones. We also found that the knockdown of CAF-1, a histone chaperone that functions in the replication-coupled deposition of his...

  10. REPLICATION TOOL AND METHOD OF PROVIDING A REPLICATION TOOL

    DEFF Research Database (Denmark)

    2016-01-01

    structured master surface (3a, 3b, 3c, 3d) having a lateral master pattern and a vertical master profile. The microscale structured master surface (3a, 3b, 3c, 3d) has been provided by localized pulsed laser treatment to generate microscale phase explosions. A method for producing a part with microscale......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...

  11. 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.

  12. High contrast laser marking of alumina

    Energy Technology Data Exchange (ETDEWEB)

    Penide, J. [Applied Physics Department, University of Vigo, EEI, Lagoas-Marcosende, 9, Vigo 36310 (Spain); Quintero, F., E-mail: fquintero@uvigo.es [Applied Physics Department, University of Vigo, EEI, Lagoas-Marcosende, 9, Vigo 36310 (Spain); Riveiro, A. [Applied Physics Department, University of Vigo, EEI, Lagoas-Marcosende, 9, Vigo 36310 (Spain); Fernández, A. [Department of Engineering Design, University of Vigo, Escuela de Ingeniería Industrial, Campus Universitario, Vigo E-36310 (Spain); Val, J. del [Applied Physics Department, University of Vigo, EEI, Lagoas-Marcosende, 9, Vigo 36310 (Spain); Comesaña, R. [Materials Engineering, Applied Mechanics and Construction Department, University of Vigo, EEI, Lagoas-Marcosende, Vigo E-36310 (Spain); Lusquiños, F.; Pou, J. [Applied Physics Department, University of Vigo, EEI, Lagoas-Marcosende, 9, Vigo 36310 (Spain)

    2015-05-01

    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.

  13. 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

  14. Choosing a suitable method for the identification of replication origins in microbial genomes

    Directory of Open Access Journals (Sweden)

    Chengcheng eSong

    2015-09-01

    Full Text Available As the replication of genomic DNA is arguably the most important task performed by a cell and given that it is controlled at the initiation stage, the events that occur at the replication origin play a central role in the cell cycle. Making sense of DNA replication origins is important for improving our capacity to study cellular processes and functions in the regulation of gene expression, genome integrity in much finer detail. Thus, clearly comprehending the positions and sequences of replication origins which are fundamental to chromosome organization and duplication is the first priority of all. In view of such important roles of replication origins, tremendous work has been aimed at identifying and testing the specificity of replication origins. A number of computational tools based on various skew types have been developed to predict replication origins. Using various in silico approaches such as Ori-Finder 2, and databases such as DoriC and oriDB, researchers have predicted the locations of replication origins sites for thousands bacterial chromosomes and archaeal genomes. Based on the predicted results, we should choose an effective method for identifying and confirming the interactions at origins of replication. Here we describe the main existing experimental methods that aimed to determine the replication origin regions and list some of the many the practical applications of these methods.

  15. 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...

  16. 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...

  17. 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...

  18. Therapeutic targeting of replicative immortality

    OpenAIRE

    Yaswen, Paul; MacKenzie, Karen L.; Keith, W. Nicol; Hentosh, Patricia; Rodier, Francis; Zhu, Jiyue; Firestone, Gary L.; Matheu, Ander; Carnero, Amancio; Bilsland, Alan; Sundin, Tabetha; Honoki, Kanya; Fujii, Hiromasa; Georgakilas, Alexandros G.; Amedei, Amedeo

    2015-01-01

    One of the hallmarks of malignant cell populations is the ability to undergo continuous proliferation. This property allows clonal lineages to acquire sequential aberrations that can fuel increasingly autonomous growth, invasiveness, and therapeutic resistance. Innate cellular mechanisms have evolved to regulate replicative potential as a hedge against malignant progression. When activated in the absence of normal terminal differentiation cues, these mechanisms can result in a state of persis...

  19. Alphavirus polymerase and RNA replication.

    Science.gov (United States)

    Pietilä, Maija K; Hellström, Kirsi; Ahola, Tero

    2017-01-16

    Alphaviruses are typically arthropod-borne, and many are important pathogens such as chikungunya virus. Alphaviruses encode four nonstructural proteins (nsP1-4), initially produced as a polyprotein P1234. nsP4 is the core RNA-dependent RNA polymerase but all four nsPs are required for RNA synthesis. The early replication complex (RC) formed by the polyprotein P123 and nsP4 synthesizes minus RNA strands, and the late RC composed of fully processed nsP1-nsP4 is responsible for the production of genomic and subgenomic plus strands. Different parts of nsP4 recognize the promoters for minus and plus strands but the binding also requires the other nsPs. The alphavirus polymerase has been purified and is capable of de novo RNA synthesis only in the presence of the other nsPs. The purified nsP4 also has terminal adenylyltransferase activity, which may generate the poly(A) tail at the 3' end of the genome. Membrane association of the nsPs is vital for replication, and alphaviruses induce membrane invaginations called spherules, which form a microenvironment for RNA synthesis by concentrating replication components and protecting double-stranded RNA intermediates. The RCs isolated as crude membrane preparations are active in RNA synthesis in vitro, but high-resolution structure of the RC has not been achieved, and thus the arrangement of viral and possible host components remains unknown. For some alphaviruses, Ras-GTPase-activating protein (Src-homology 3 (SH3) domain)-binding proteins (G3BPs) and amphiphysins have been shown to be essential for RNA replication and are present in the RCs. Host factors offer an additional target for antivirals, as only few alphavirus polymerase inhibitors have been described.

  20. Dynamic replication of Web contents

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The phenomenal growth of the World Wide Web has brought huge increase in the traffic to the popular web sites.Long delays and denial of service experienced by the end-users,especially during the peak hours,continues to be the common problem while accessing popular sites.Replicating some of the objects at multiple sites in a distributed web-server environment is one of the possible solutions to improve the response time/Iatency. The decision of what and where to replicate requires solving a constraint optimization problem,which is NP-complete in general.In this paper, we consider the problem of placing copies of objects in a distributed web server system to minimize the cost of serving read and write requests when the web servers have Iimited storage capacity.We formulate the problem as a 0-1 optimization problem and present a polynomial time greedy algorithm with backtracking to dynamically replicate objects at the appropriate sites to minimize a cost function.To reduce the solution search space,we present necessary condi tions for a site to have a replica of an object jn order to minimize the cost function We present simulation resuIts for a variety of problems to illustrate the accuracy and efficiency of the proposed algorithms and compare them with those of some well-known algorithms.The simulation resuIts demonstrate the superiority of the proposed algorithms.

  1. Aluminum alloy nanosecond vs femtosecond laser marking

    Indian Academy of Sciences (India)

    S Rusu; A Buzaianu; D G Galusca; L Ionel; D Ursescu

    2013-11-01

    Based on the lack of consistent literature publications that analyse the effects of laser marking for traceability on various materials, the present paper proposes a study of the influence of such radiation processing on an aluminum alloy, a vastly used material base within several industry fields. For the novelty impact, femtolaser marking has been carried out, besides the standard commercial nanosecond engraving. All the marks have been analysed using profilometry, overhead and cross-section SEM microscopy, respectively and EDAX measurements.

  2. Briefs & Events

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Total installation capacity exceeds 800 GW in China At the National Power Working Conference held on August 16,it was declared that the Unit 6 of Laxiwa Hydropower Station aff iliated to China Power Investment Corporation was commissioned,which marks the milestone of 800 GW total generation capacity in China.

  3. Evaluating replicability of laboratory experiments in economics.

    Science.gov (United States)

    Camerer, Colin F; Dreber, Anna; Forsell, Eskil; Ho, Teck-Hua; Huber, Jürgen; Johannesson, Magnus; Kirchler, Michael; Almenberg, Johan; Altmejd, Adam; Chan, Taizan; Heikensten, Emma; Holzmeister, Felix; Imai, Taisuke; Isaksson, Siri; Nave, Gideon; Pfeiffer, Thomas; Razen, Michael; Wu, Hang

    2016-03-25

    The replicability of some scientific findings has recently been called into question. To contribute data about replicability in economics, we replicated 18 studies published in the American Economic Review and the Quarterly Journal of Economics between 2011 and 2014. All of these replications followed predefined analysis plans that were made publicly available beforehand, and they all have a statistical power of at least 90% to detect the original effect size at the 5% significance level. We found a significant effect in the same direction as in the original study for 11 replications (61%); on average, the replicated effect size is 66% of the original. The replicability rate varies between 67% and 78% for four additional replicability indicators, including a prediction market measure of peer beliefs.

  4. 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...

  5. Appropriating Apocalyptic: Paul Ricoeur's Hermeneutics and the Discourse of Mark 13

    Science.gov (United States)

    de Vries, Peter C.

    2010-01-01

    Mark 13 predicts that certain events will occur literally within the generation of Jesus' contemporaries, and today's reader recognizes that some of these events have not taken place. The reader therefore appropriates the text as a false configuration of the world because it describes the world differently from how it is. However, the hermeneutics…

  6. Dengue virus binding and replication by platelets.

    Science.gov (United States)

    Simon, Ayo Y; Sutherland, Michael R; Pryzdial, Edward L G

    2015-07-16

    Dengue virus (DENV) infection causes ∼200 million cases of severe flulike illness annually, escalating to life-threatening hemorrhagic fever or shock syndrome in ∼500,000. Although thrombocytopenia is typical of both mild and severe diseases, the mechanism triggering platelet reduction is incompletely understood. As a probable initiating event, direct purified DENV-platelet binding was followed in the current study by quantitative reverse transcription-polymerase chain reaction and confirmed antigenically. Approximately 800 viruses specifically bound per platelet at 37°C. Fewer sites were observed at 25°C, the blood bank storage temperature (∼350 sites), or 4°C, known to attenuate virus cell entry (∼200 sites). Dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) and heparan sulfate proteoglycan were implicated as coreceptors because only the combination of anti-DC-SIGN and low-molecular-weight heparin prevented binding. Interestingly, at 37°C and 25°C, platelets replicated the positive sense single-stranded RNA genome of DENV by up to ∼4-fold over 7 days. Further time course experiments demonstrated production of viral NS1 protein, which is known to be highly antigenic in patient serum. The infectivity of DENV intrinsically decayed in vitro, which was moderated by platelet-mediated generation of viable progeny. This was shown using a transcription inhibitor and confirmed by freeze-denatured platelets being incapable of replicating the DENV genome. For the first time, these data demonstrate that platelets directly bind DENV saturably and produce infectious virus. Thus, expression of antigen encoded by DENV is a novel consideration in the pathogen-induced thrombocytopenia mechanism. These results furthermore draw attention to the possibility that platelets may produce permissive RNA viruses in addition to DENV.

  7. Genome-scale analysis of metazoan replication origins reveals their organization in specific but flexible sites defined by conserved features

    Science.gov (United States)

    Cayrou, Christelle; Coulombe, Philippe; Vigneron, Alice; Stanojcic, Slavica; Ganier, Olivier; Peiffer, Isabelle; Rivals, Eric; Puy, Aurore; Laurent-Chabalier, Sabine; Desprat, Romain; Méchali, Marcel

    2011-01-01

    In metazoans, thousands of DNA replication origins (Oris) are activated at each cell cycle. Their genomic organization and their genetic nature remain elusive. Here, we characterized Oris by nascent strand (NS) purification and a genome-wide analysis in Drosophila and mouse cells. We show that in both species most CpG islands (CGI) contain Oris, although methylation is nearly absent in Drosophila, indicating that this epigenetic mark is not crucial for defining the activated origin. Initiation of DNA synthesis starts at the borders of CGI, resulting in a striking bimodal distribution of NS, suggestive of a dual initiation event. Oris contain a unique nucleotide skew around NS peaks, characterized by G/T and C/A overrepresentation at the 5′ and 3′ of Ori sites, respectively. Repeated GC-rich elements were detected, which are good predictors of Oris, suggesting that common sequence features are part of metazoan Oris. In the heterochromatic chromosome 4 of Drosophila, Oris correlated with HP1 binding sites. At the chromosome level, regions rich in Oris are early replicating, whereas Ori-poor regions are late replicating. The genome-wide analysis was coupled with a DNA combing analysis to unravel the organization of Oris. The results indicate that Oris are in a large excess, but their activation does not occur at random. They are organized in groups of site-specific but flexible origins that define replicons, where a single origin is activated in each replicon. This organization provides both site specificity and Ori firing flexibility in each replicon, allowing possible adaptation to environmental cues and cell fates. PMID:21750104

  8. Growth factor-dependent initiation of DNA replication in nuclei isolated from an interleukin 3-dependent murine myeloid cell line.

    Science.gov (United States)

    Munshi, N C; Gabig, T G

    1990-01-01

    To study the proliferative response of hematopoietic cells to growth factors at the molecular level, we developed a cell-free system for growth factor-dependent initiation of genomic DNA replication. Nuclei were isolated from the IL-3-dependent cell line NFS/N1-H7 after a 10-h period of IL-3 deprivation. Cytosolic and membrane-containing subcellular fractions were prepared from proliferating NFS/N1-H7 cells. Nuclei from the nonproliferating cells (+/- IL-3) showed essentially no incorporation of [3H]thymidine during a 16-h incubation with a mixture of unlabeled GTP, ATP, UTP, CTP, dGTP, dATP, dCTP, and [3H]dTTP. When the combination of IL-3, a cytosolic fraction, and a membrane-containing fraction from proliferating cells was added to nuclei from nonproliferating cells, a burst of [3H]thymidine incorporation into DNA began after a 12-h lag period, attained a maximal rate at 16 h, and reached a level of 860 pmol thymidine/10(6) nuclei at 24 h (corresponding to replication of approximately 56% total mouse genomic DNA). This DNA synthesis was inhibited approximately 90% by the specific DNA polymerase alpha inhibitor aphidicolin. Deletion of a single cellular component or IL-3 from the system resulted in a marked reduction of DNA replication (-membrane, 80 +/- 4%; -cytosol, 90% +/- 4%; -IL-3, 74 +/- 7% inhibition). This model requires a growth factor (IL-3), a sedimentable cell fraction containing its receptor and possibly additional membrane-associated components, and a cytosolic fraction. It appears to recapitulate the molecular events required for progression from early G1 to S phase of the cell cycle induced by IL-3 binding to its receptor.

  9. Replication Origin Specification Gets a Push.

    Science.gov (United States)

    Plosky, Brian S

    2015-12-03

    During the gap between G1 and S phases when replication origins are licensed and fired, it is possible that DNA translocases could disrupt pre-replicative complexes (pre-RCs). In this issue of Molecular Cell, Gros et al. (2015) find that pre-RCs can be pushed along DNA and retain the ability to support replication.

  10. Exploiting replicative stress to treat cancer

    DEFF Research Database (Denmark)

    Dobbelstein, Matthias; Sørensen, Claus Storgaard

    2015-01-01

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

  11. Fantasy and Reality in Mark Twain's Aggression.

    Science.gov (United States)

    Sears, Robert R.

    Psychoanalysis, a favorite method for studying personality and motivation, cannot be used on the dead. Instead, biographical analysis must be employed. This study examines Mark Twain's aggression by analyzing his writings, social behavior, and environmental aspects of his life. In viewing Mark Twain's novels as representing fantasy, 17 categories…

  12. Effects of heat on cut mark characteristics.

    Science.gov (United States)

    Waltenberger, Lukas; Schutkowski, Holger

    2017-02-01

    Cut marks on bones provide crucial information about tools used and their mode of application, both in archaeological and forensic contexts. Despite a substantial amount of research on cut mark analysis and the influence of fire on bones (shrinkage, fracture pattern, recrystallisation), there is still a lack of knowledge in cut mark analysis on burnt remains. This study provides information about heat alteration of cut marks and whether consistent features can be observed that allow direct interpretation of the implemented tools used. In a controlled experiment, cut marks (n=25) were inflicted on pig ribs (n=7) with a kitchen knife and examined using micro-CT and digital microscopy. The methods were compared in terms of their efficacy in recording cut marks on native and heat-treated bones. Statistical analysis demonstrates that floor angles and the maximum slope height of cuts undergo significant alteration, whereas width, depth, floor radius, slope, and opening angle remain stable. Micro-CT and digital microscopy are both suitable methods for cut mark analysis. However, significant differences in measurements were detected between both methods, as micro-CT is less accurate due to the lower resolution. Moreover, stabbing led to micro-fissures surrounding the cuts, which might also influence the alteration of cut marks.

  13. Mark formation modeling in optical rewritable recording

    NARCIS (Netherlands)

    Brusche, J.H.; Segal, A.; Vuik, C.; Urbach, H.P.

    2006-01-01

    In optical rewritable recording media, such as the Blu-ray Disc, amorphous marks are formed on a crystalline background of a phase-change layer, by means of short, high power laser pulses. In order to improve this data storage concept, it is of great importance to understand the mark formation

  14. Mark Blaug: rebel with many causes

    NARCIS (Netherlands)

    M. Boumans; M. Klaes

    2013-01-01

    This book celebrates the immense contributions of Mark Blaug to every aspect of economics, a discipline in which his influence and relevance still resonate today, particularly in the field of the economics of education. This collection of eminent contributions discusses the ideas and works of Mark B

  15. Recent Discoveries on Antwerp Panel Makers' Marks

    DEFF Research Database (Denmark)

    Wadum, Jørgen

    1993-01-01

    There still exist today uncertainties and misunderstandings in our interpretation of panel makers' marks from early 17th century Antwerp. In the future, panel marks and the panels on which they can be found will certainly render much more information concerning the technology of that time. Still...

  16. 76 FR 490 - Marking Meteorological Evaluation Towers

    Science.gov (United States)

    2011-01-05

    ... Federal Aviation Administration 14 CFR Part 77 Marking Meteorological Evaluation Towers AGENCY: Federal.... SUMMARY: The FAA is considering revising its current Advisory Circular on Obstruction Marking and Lighting to include guidance for Meteorological Evaluation Towers (METs). These towers are erected in...

  17. 76 FR 36983 - Marking Meteorological Evaluation Towers

    Science.gov (United States)

    2011-06-24

    ... terrain. Without a similar evaluation process, the FAA cannot recommend lighting for METs. It is important... Federal Aviation Administration 14 CFR Part 77 Marking Meteorological Evaluation Towers AGENCY: Federal... recommended guidance for the voluntary marking of Meteorological Evaluation Towers (METs) erected in...

  18. 40 CFR 761.40 - Marking requirements.

    Science.gov (United States)

    2010-07-01

    ... time of removal from use if not already marked. ; (3) PCB Large High Voltage Capacitors at the time of... Capacitor at the time of manufacture, at the time of distribution in commerce if not already marked, and at... Capacitors at the time of removal from use (see also paragraph (k) of this section). (6) Electric...

  19. 49 CFR 15.13 - Marking SSI.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Marking SSI. 15.13 Section 15.13 Transportation... SSI. (a) Marking of paper records. In the case of paper records containing SSI, a covered person must... types of records. In the case of non-paper records that contain SSI, including motion picture films...

  20. Mark formation modeling in optical rewritable recording

    NARCIS (Netherlands)

    Brusche, J.H.; Segal, A.; Vuik, C.; Urbach, H.P.

    2006-01-01

    In optical rewritable recording media, such as the Blu-ray Disc, amorphous marks are formed on a crystalline background of a phase-change layer, by means of short, high power laser pulses. In order to improve this data storage concept, it is of great importance to understand the mark formation proce

  1. Credit Documentation and the Mark 15 Subroutine

    Energy Technology Data Exchange (ETDEWEB)

    McAllister, J.E.

    2001-08-16

    This report documents the rewrite of the heat transfer subroutine. Part of the process of preparing the Mark 15 assembly for production operation is the development of thermal-hydraulic limits for the assembly. These limits require, among other items, the development of a Mark 15 assembly subroutine for the CREDIT code.

  2. Teaching Mark through a postcolonial optic

    African Journals Online (AJOL)

    2015-07-16

    Jul 16, 2015 ... But empire (or anti-empire) studies and postcolonial studies are not one and the same. .... presence in Mark 1:1.8 As one scholar put it, 'Mark appears ... back to villages of Galilee (presumably to continue the project inaugurated in Jesus' ... A few chapters later, it is possible to let students see through.

  3. 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...

  4. 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...

  5. 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.

  6. Fast temporal event integration in the visual domain demonstrated by event-related potentials

    NARCIS (Netherlands)

    Akyürek, Elkan G.; Schubö, Anna; Hommel, Bernhard

    Four experiments are reported that investigated visual event integration by using a variant of the missing element paradigm. Good performance on this task depends on whether two brief successive stimulus displays are perceived as (or integrated into) one single event. We replicated the classic

  7. Replication of micro and nano surface geometries

    DEFF Research Database (Denmark)

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

    2011-01-01

    : 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....

  8. Replication of prions in differentiated muscle cells.

    Science.gov (United States)

    Herbst, Allen; Aiken, Judd M; McKenzie, Debbie

    2014-01-01

    We have demonstrated that prions accumulate to high levels in non-proliferative C2C12 myotubes. C2C12 cells replicate as myoblasts but can be differentiated into myotubes. Earlier studies indicated that C2C12 myoblasts are not competent for prion replication. (1) We confirmed that observation and demonstrated, for the first time, that while replicative myoblasts do not accumulate PrP(Sc), differentiated post-mitotic myotube cultures replicate prions robustly. Here we extend our observations and describe the implication and utility of this system for replicating prions.

  9. DNA replication stress: causes, resolution and disease.

    Science.gov (United States)

    Mazouzi, Abdelghani; Velimezi, Georgia; Loizou, Joanna I

    2014-11-15

    DNA replication is a fundamental process of the cell that ensures accurate duplication of the genetic information and subsequent transfer to daughter cells. Various pertubations, originating from endogenous or exogenous sources, can interfere with proper progression and completion of the replication process, thus threatening genome integrity. Coordinated regulation of replication and the DNA damage response is therefore fundamental to counteract these challenges and ensure accurate synthesis of the genetic material under conditions of replication stress. In this review, we summarize the main sources of replication stress and the DNA damage signaling pathways that are activated in order to preserve genome integrity during DNA replication. We also discuss the association of replication stress and DNA damage in human disease and future perspectives in the field. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Replication Stress: A Lifetime of Epigenetic Change

    Directory of Open Access Journals (Sweden)

    Simran Khurana

    2015-09-01

    Full Text Available DNA replication is essential for cell division. Challenges to the progression of DNA polymerase can result in replication stress, promoting the stalling and ultimately collapse of replication forks. The latter involves the formation of DNA double-strand breaks (DSBs and has been linked to both genome instability and irreversible cell cycle arrest (senescence. Recent technological advances have elucidated many of the factors that contribute to the sensing and repair of stalled or broken replication forks. In addition to bona fide repair factors, these efforts highlight a range of chromatin-associated changes at and near sites of replication stress, suggesting defects in epigenome maintenance as a potential outcome of aberrant DNA replication. Here, we will summarize recent insight into replication stress-induced chromatin-reorganization and will speculate on possible adverse effects for gene expression, nuclear integrity and, ultimately, cell function.

  11. 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.

  12. Viral interactions in human lymphoid tissue: Human herpesvirus 7 suppresses the replication of CCR5-tropic human immunodeficiency virus type 1 via CD4 modulation.

    Science.gov (United States)

    Lisco, Andrea; Grivel, Jean-Charles; Biancotto, Angélique; Vanpouille, Christophe; Origgi, Francesco; Malnati, Mauro S; Schols, Dominique; Lusso, Paolo; Margolis, Leonid B

    2007-01-01

    Human immunodeficiency virus (HIV) infection is often accompanied by infection with other pathogens that affect the clinical course of HIV disease. Here, we identified another virus, human herpesvirus 7 (HHV-7) that interferes with HIV type 1 (HIV-1) replication in human lymphoid tissue, where critical events of HIV disease occur. Like the closely related HHV-6, HHV-7 suppresses the replication of CCR5-tropic (R5) HIV-1 in coinfected blocks of human lymphoid tissue. Unlike HHV-6, which affects HIV-1 by upregulating RANTES, HHV-7 did not upregulate any CCR5-binding chemokine. Rather, the inhibition of R5 HIV-1 by HHV-7 was associated with a marked downregulation of CD4, the cellular receptor shared by HHV-7 and HIV-1. HHV-7-induced CD4 downregulation was sufficient for HIV-1 inhibition, since comparable downregulation of CD4 with cyclotriazadisulfonamide, a synthetic macrocycle that specifically modulates expression of CD4, resulted in the suppression of HIV infection similar to that seen in HHV-7-infected tissues. In contrast to R5 HIV-1, CXCR4-tropic (X4) HIV-1 was only minimally suppressed by HHV-7 coinfection. This selectivity in suppression of R5 and X4 HIV-1 is explained by a suppression of HHV-7 replication in X4- but not in R5-coinfected tissues. These results suggest that HIV-1 and HHV-7 may interfere in lymphoid tissue in vivo, thus potentially affecting the progression of HIV-1 disease. Knowledge of the mechanisms of interaction of HIV-1 with HHV-7, as well as with other pathogens that modulate HIV-1 replication, may provide new insights into HIV pathogenesis and lead to the development of new anti-HIV therapeutic strategies.

  13. HBV replication is significantly reduced by IL-6

    Directory of Open Access Journals (Sweden)

    Jeng King-Song

    2009-04-01

    Full Text Available Abstract Interleukin-6 (IL-6 is a pleiotropic cytokine with pivotal functions in the regulation of the biological responses of several target cells including hepatocytes. The level of serum IL-6 has been reported to be elevated in patients with chronic hepatitis B, cirrhosis and hepatocellular carcinoma and represents the best marker of HBV-related clinical progression as compared with several other cytokines. In this study, we found that IL-6 was able to effectively suppress hepatitis B virus (HBV replication and prevent the accumulation of HBV covalently closed circular DNA (cccDNA in a human hepatoma cell line. We also demonstrated that the suppression of HBV replication by IL-6 requires concurrently a moderate reduction of viral transcripts/core proteins and a marked decrease in viral genome-containing nucleocapsids. Studies on the stability of existing viral capsids suggest that the IL-6 effect on the reduction of genome-containing nucleocapsids is mediated through the prevention of the formation of genome-containing nucleocapsids, which is similar to the effect of interferons. However, IFN-α/β and IFN-γ did not participate in the IL-6-induced suppression of HBV replication. Taken together, our results will provide important information to better understand the role of IL-6 in the course of HBV infection.

  14. Dynamics of Nucleosome Positioning Maturation following Genomic Replication

    Directory of Open Access Journals (Sweden)

    Pauline Vasseur

    2016-09-01

    Full Text Available Chromatin is thought to carry epigenetic information from one generation to the next, although it is unclear how such information survives the disruptions of nucleosomal architecture occurring during genomic replication. Here, we measure a key aspect of chromatin structure dynamics during replication—how rapidly nucleosome positions are established on the newly replicated daughter genomes. By isolating newly synthesized DNA marked with 5-ethynyl-2′-deoxyuridine (EdU, we characterize nucleosome positions on both daughter genomes of S. cerevisiae during chromatin maturation. We find that nucleosomes rapidly adopt their mid-log positions at highly transcribed genes, which is consistent with a role for transcription in positioning nucleosomes in vivo. Additionally, experiments in hir1Δ mutants reveal a role for HIR in nucleosome spacing. We also characterized nucleosome positions on the leading and lagging strands, uncovering differences in chromatin maturation dynamics at hundreds of genes. Our data define the maturation dynamics of newly replicated chromatin and support a role for transcription in sculpting the chromatin template.

  15. A model for transmission of the H3K27me3 epigenetic mark.

    Science.gov (United States)

    Hansen, Klaus H; Bracken, Adrian P; Pasini, Diego; Dietrich, Nikolaj; Gehani, Simmi S; Monrad, Astrid; Rappsilber, Juri; Lerdrup, Mads; Helin, Kristian

    2008-11-01

    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. Here we provide a model to explain how trimethylated Lys 27 of histone 3 (H3K27me3), which is catalysed by the EZH2-containing Polycomb Repressive Complex 2 (PRC2), is maintained in proliferating cells. We show that the PRC2 complex binds to the H3K27me3 mark and colocalizes with this mark in G1 phase and with sites of ongoing DNA replication. Efficient binding requires an intact trimeric PRC2 complex containing EZH2, EED and SUZ12, but is independent of the catalytic SET domain of EZH2. Using a heterologous reporter system, we show that transient recruitment of the PRC2 complex to chromatin, upstream of the transcriptional start site, is sufficient to maintain repression through endogenous PRC2 during subsequent cell divisions. Thus, we suggest that once the H3K27me3 is established, it recruits the PRC2 complex to maintain the mark at sites of DNA replication, leading to methylation of H3K27 on the daughter strands 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 and transcriptional programs.

  16. 30 CFR 7.409 - Approval marking.

    Science.gov (United States)

    2010-07-01

    ... approval number in addition to the number and size (gauge) of conductors and cable type. For cables containing electric conductors, the marking shall also include the voltage rating. For splices, the...

  17. 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)

  18. Mark Making: Methodologies and methods (innovative practice).

    Science.gov (United States)

    Zeilig, Hannah

    2016-09-01

    Mark Making is a recently completed AHRC-funded review exploring the role of the participative arts for people with dementia in the UK. Key concerns underlying Mark Making were both how to privilege the views and feelings of people with a dementia and also how best to understand the value of the arts for people with a dementia. These issues were tackled using a variety of qualitative methods. Methods included a rigorous literature review, the development of a unique web-based map locating many participative arts projects and above all working with people with a dementia to ascertain their views. This brief article will concentrate on some of the innovative methods that the Mark Making team used, with particular reference to comics as a mode of engagement as used in the Descartes project. The article will provide an insight into some of the methodological challenges confronted by Mark Making as well as the inspirations and successes that were enjoyed.

  19. Mark Twain National Wildlife Refuge: Sign Plan

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — The Mark Twain NWR (including the Louisa District, the Annada District, and the Brussels District) Sign Plan explains how signs are used on the Refuge to help guide...

  20. Mark Twain National Wildlife Refuge Complex : 1980

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for Mark Twain National Wildlife Refuge summarizes Refuge activities during the 1980 calendar year. The report begins with a summary of...

  1. 46 CFR 122.602 - Hull markings.

    Science.gov (United States)

    2010-10-01

    ... height, with its upper edge passing through the point of maximum draft. The loading mark must be painted in a contrasting color to the sideshell paint. (e) On a vessel that has a load line, the...

  2. Smoking Leaves Lasting Marks on DNA: Study

    Science.gov (United States)

    ... fullstory_161060.html Smoking Leaves Lasting Marks on DNA: Study Changes related to disease found in more ... cigarettes can leave a lasting imprint on human DNA, altering more than 7,000 genes in ways ...

  3. Self-replication of DNA rings

    Science.gov (United States)

    Kim, Junghoon; Lee, Junwye; Hamada, Shogo; Murata, Satoshi; Ha Park, Sung

    2015-06-01

    Biology provides numerous examples of self-replicating machines, but artificially engineering such complex systems remains a formidable challenge. In particular, although simple artificial self-replicating systems including wooden blocks, magnetic systems, modular robots and synthetic molecular systems have been devised, such kinematic self-replicators are rare compared with examples of theoretical cellular self-replication. One of the principal reasons for this is the amount of complexity that arises when you try to incorporate self-replication into a physical medium. In this regard, DNA is a prime candidate material for constructing self-replicating systems due to its ability to self-assemble through molecular recognition. Here, we show that DNA T-motifs, which self-assemble into ring structures, can be designed to self-replicate through toehold-mediated strand displacement reactions. The inherent design of these rings allows the population dynamics of the systems to be controlled. We also analyse the replication scheme within a universal framework of self-replication and derive a quantitative metric of the self-replicability of the rings.

  4. DNA Replication via Entanglement Swapping

    CERN Document Server

    Pusuluk, Onur

    2010-01-01

    Quantum effects are mainly used for the determination of molecular shapes in molecular biology, but quantum information theory may be a more useful tool to understand the physics of life. Molecular biology assumes that function is explained by structure, the complementary geometries of molecules and weak intermolecular hydrogen bonds. However, both this assumption and its converse are possible if organic molecules and quantum circuits/protocols are considered as hardware and software of living systems that are co-optimized during evolution. In this paper, we try to model DNA replication as a multiparticle entanglement swapping with a reliable qubit representation of nucleotides. In the model, molecular recognition of a nucleotide triggers an intrabase entanglement corresponding to a superposition state of different tautomer forms. Then, base pairing occurs by swapping intrabase entanglements with interbase entanglements.

  5. 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.

  6. Strain measurement based on laser mark automatic tracking line mark on specimen

    Science.gov (United States)

    Tian, Qiuhong; Sun, Zhengrong; Le, Zhongping; Liu, Yanna; Zhang, Lijian; Xie, Sendong

    2014-12-01

    Conventional video extensometers, using a measurement mark on specimen to obtain material strain, have a problem with deformation of the measurement mark. Therefore, the accurate position of the measurement mark is difficult to evaluate, and measurement accuracy is limited. To solve this problem, a strain measurement method based on a laser mark automatically tracking a line mark on the specimen is proposed. This method is using an undeformed laser mark to replace the line mark to calculate the specimen strain and eliminates the measurement error induced by the deformation of specimen marks. The positions of the laser mark and the line mark are achieved by using digital image processing. Automatic tracking is realized by means of an intelligent motor control. Also, the strain of the specimen is obtained by analyzing the movement trace of the laser mark. A video extensometer experimental setup based on the proposed method is constructed. Two experiments were carried out. The first experiment verified the validity and the repeatability of the method via tensile testing of the specimens of low-carbon steel and cast iron. The second one demonstrated the high measurement accuracy of the method by comparing with a clip-on extensometer.

  7. 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.

  8. Therapeutic targeting of replicative immortality.

    Science.gov (United States)

    Yaswen, Paul; MacKenzie, Karen L; Keith, W Nicol; Hentosh, Patricia; Rodier, Francis; Zhu, Jiyue; Firestone, Gary L; Matheu, Ander; Carnero, Amancio; Bilsland, Alan; Sundin, Tabetha; Honoki, Kanya; Fujii, Hiromasa; Georgakilas, Alexandros G; Amedei, Amedeo; Amin, Amr; Helferich, Bill; Boosani, Chandra S; Guha, Gunjan; Ciriolo, Maria Rosa; Chen, Sophie; Mohammed, Sulma I; Azmi, Asfar S; Bhakta, Dipita; Halicka, Dorota; Niccolai, Elena; Aquilano, Katia; Ashraf, S Salman; Nowsheen, Somaira; Yang, Xujuan

    2015-12-01

    One of the hallmarks of malignant cell populations is the ability to undergo continuous proliferation. This property allows clonal lineages to acquire sequential aberrations that can fuel increasingly autonomous growth, invasiveness, and therapeutic resistance. Innate cellular mechanisms have evolved to regulate replicative potential as a hedge against malignant progression. When activated in the absence of normal terminal differentiation cues, these mechanisms can result in a state of persistent cytostasis. This state, termed "senescence," can be triggered by intrinsic cellular processes such as telomere dysfunction and oncogene expression, and by exogenous factors such as DNA damaging agents or oxidative environments. Despite differences in upstream signaling, senescence often involves convergent interdependent activation of tumor suppressors p53 and p16/pRB, but can be induced, albeit with reduced sensitivity, when these suppressors are compromised. Doses of conventional genotoxic drugs required to achieve cancer cell senescence are often much lower than doses required to achieve outright cell death. Additional therapies, such as those targeting cyclin dependent kinases or components of the PI3K signaling pathway, may induce senescence specifically in cancer cells by circumventing defects in tumor suppressor pathways or exploiting cancer cells' heightened requirements for telomerase. Such treatments sufficient to induce cancer cell senescence could provide increased patient survival with fewer and less severe side effects than conventional cytotoxic regimens. This positive aspect is countered by important caveats regarding senescence reversibility, genomic instability, and paracrine effects that may increase heterogeneity and adaptive resistance of surviving cancer cells. Nevertheless, agents that effectively disrupt replicative immortality will likely be valuable components of new combinatorial approaches to cancer therapy. Copyright © 2015 The Authors

  9. Confidently estimating the number of DNA replication origins.

    Science.gov (United States)

    Bhaskar, Anand; Keich, Uri

    2010-01-01

    We present a method for estimating and providing a confidence interval for the number of DNA replication origins in the genome of the yeast Kluyveromyces lactis. The method requires an initial set of verified sites from which a position specific frequency matrix (PSFM) can be constructed. We further assume that we have access to a sparingly used experimental procedure which can verify the functionality of a few, but not all, computationally predicted sites. While our motivation comes from estimating the number of autonomously replicating sequences (ARSs), our method can also be applied to estimating the genome-wide number of "functional" transcription factor binding sites, where functionality is determined by experimental verification of the transcription factor binding event using, for example, ChIP data. The reliability of our method is demonstrated by correctly predicting the known number of Saccharomyces cerevisiae ARSs as well as the number of S. cerevisiae probes that bind to the transcription factor ABF1.

  10. Regulation of Unperturbed DNA Replication by Ubiquitylation

    Directory of Open Access Journals (Sweden)

    Sara Priego Moreno

    2015-06-01

    Full Text Available Posttranslational modification of proteins by means of attachment of a small globular protein ubiquitin (i.e., ubiquitylation represents one of the most abundant and versatile mechanisms of protein regulation employed by eukaryotic cells. Ubiquitylation influences almost every cellular process and its key role in coordination of the DNA damage response is well established. In this review we focus, however, on the ways ubiquitylation controls the process of unperturbed DNA replication. We summarise the accumulated knowledge showing the leading role of ubiquitin driven protein degradation in setting up conditions favourable for replication origin licensing and S-phase entry. Importantly, we also present the emerging major role of ubiquitylation in coordination of the active DNA replication process: preventing re-replication, regulating the progression of DNA replication forks, chromatin re-establishment and disassembly of the replisome at the termination of replication forks.

  11. Chromosome replication and segregation in bacteria.

    Science.gov (United States)

    Reyes-Lamothe, Rodrigo; Nicolas, Emilien; Sherratt, David J

    2012-01-01

    In dividing cells, chromosome duplication once per generation must be coordinated with faithful segregation of newly replicated chromosomes and with cell growth and division. Many of the mechanistic details of bacterial replication elongation are well established. However, an understanding of the complexities of how replication initiation is controlled and coordinated with other cellular processes is emerging only slowly. In contrast to eukaryotes, in which replication and segregation are separate in time, the segregation of most newly replicated bacterial genetic loci occurs sequentially soon after replication. We compare the strategies used by chromosomes and plasmids to ensure their accurate duplication and segregation and discuss how these processes are coordinated spatially and temporally with growth and cell division. We also describe what is known about the three conserved families of ATP-binding proteins that contribute to chromosome segregation and discuss their inter-relationships in a range of disparate bacteria.

  12. Semiconservative replication in the quasispecies model

    Science.gov (United States)

    Tannenbaum, Emmanuel; Deeds, Eric J.; Shakhnovich, Eugene I.

    2004-06-01

    This paper extends Eigen’s quasispecies equations to account for the semiconservative nature of DNA replication. We solve the equations in the limit of infinite sequence length for the simplest case of a static, sharply peaked fitness landscape. We show that the error catastrophe occurs when μ , the product of sequence length and per base pair mismatch probability, exceeds 2 ln [2/ ( 1+1/k ) ] , where k>1 is the first-order growth rate constant of the viable “master” sequence (with all other sequences having a first-order growth rate constant of 1 ). This is in contrast to the result of ln k for conservative replication. In particular, as k→∞ , the error catastrophe is never reached for conservative replication, while for semiconservative replication the critical μ approaches 2 ln 2 . Semiconservative replication is therefore considerably less robust than conservative replication to the effect of replication errors. We also show that the mean equilibrium fitness of a semiconservatively replicating system is given by k ( 2 e-μ/2 -1 ) below the error catastrophe, in contrast to the standard result of k e-μ for conservative replication (derived by Kimura and Maruyama in 1966). From this result it is readily shown that semiconservative replication is necessary to account for the observation that, at sufficiently high mutagen concentrations, faster replicating cells will die more quickly than more slowly replicating cells. Thus, in contrast to Eigen’s original model, the semiconservative quasispecies equations are able to provide a mathematical basis for explaining the efficacy of mutagens as chemotherapeutic agents.

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

    OpenAIRE

    Piotte Olivier; Boura Céline; Cazaubon Anaïs; Chaléon Carine; Chambon Dominique; Guillevic Gwenaël; Pasquet Fabien; Perherin Céline; Raimbault Emmanuel

    2016-01-01

    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 organiza...

  14. Sol-gel replicated optics made from single point diamond turned masters exhibit fractal surface roughness

    Energy Technology Data Exchange (ETDEWEB)

    Bernacki, B.E.; Miller, A.C. Jr.; Evans, B.M. III [Oak Ridge National Lab., TN (United States); Moreshead, W.V.; Nogues, J.L.R. [GELTECH, Inc., Alachua, FL (United States)

    1996-05-01

    Deterministic optics manufacturing, notably single point diamond turning (SPDT) has matured such that the current generation of machines is capable of producing refractive and reflective optics for the visible wavelength region that are quite acceptable for many applications. However, spiral tool marks are still produced that result in unwanted diffractive scattering from grating-like features having a spatial frequency determined by the machine feed, tool radius, and other influences such as vibration and material removal effects. Such regular artifacts are the characteristic of deterministic manufacturing methods such as SPDT. The authors present some initial findings suggesting that fractal, or non-deterministic surfaces can be produced by SPDT through sol-gel replication. The key is the large isotropic shrinkage that occurs through monolithic sol-gel replication (a factor of 2.5) that results in all features, including tooling marks, being reduced by that amount. The large shrinkage itself would be a laudable-enough feature of the replication process. However, by an as-yet-not understood manner, the replication process itself seems to alter the roughness character of the replicated surface such that it appears to be fractal when analyzed using contact profilometry and the power spectrum approach.

  15. Comparison of three replication strategies in complex multicellular organisms: Asexual replication, sexual replication with identical gametes, and sexual replication with distinct sperm and egg gametes

    Science.gov (United States)

    Tannenbaum, Emmanuel

    2008-01-01

    This paper studies the mutation-selection balance in three simplified replication models. The first model considers a population of organisms replicating via the production of asexual spores. The second model considers a sexually replicating population that produces identical gametes. The third model considers a sexually replicating population that produces distinct sperm and egg gametes. All models assume diploid organisms whose genomes consist of two chromosomes, each of which is taken to be functional if equal to some master sequence, and defective otherwise. In the asexual population, the asexual diploid spores develop directly into adult organisms. In the sexual populations, the haploid gametes enter a haploid pool, where they may fuse with other haploids. The resulting immature diploid organisms then proceed to develop into mature organisms. Based on an analysis of all three models, we find that, as organism size increases, a sexually replicating population can only outcompete an asexually replicating population if the adult organisms produce distinct sperm and egg gametes. A sexual replication strategy that is based on the production of large numbers of sperm cells to fertilize a small number of eggs is found to be necessary in order to maintain a sufficiently low cost for sex for the strategy to be selected for over a purely asexual strategy. We discuss the usefulness of this model in understanding the evolution and maintenance of sexual replication as the preferred replication strategy in complex, multicellular organisms.

  16. 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.

  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.

  18. LANE MARKING DETECTION IN CLUTTERED ENVIRONMENT

    Institute of Scientific and Technical Information of China (English)

    李青; 郑南宁; 程洪

    2003-01-01

    Objective To determine the positions of marking in the presence of distracting shadows, highlight, pavement cracks, etc. Methods RGB color space is transformed into I1I2I3 color space and I2 component was used to form a new image with less effect of the clutter. Using an improved edge detection operator, an edge strength map was produced, and binarilized by adaptive thresholds. The binary image was labeled and circularity of all connected components is calculated. The Self-Organizing Mapping is adopted to extract regions which imply potential marking. Finally the position of marking was obtained by curve fitting. Results Color information was utilized fully, all thresholds were set adaptively and lane marking could be detected in challenging images with shadows, highlight or other cars. Conclusion The method based on circularity of connected components shows its outstanding robustness to lane marking detection and has a wide variety of applications in the areas of vehicle autonomous navigation and driver assistance system.

  19. Evolution of Nucleotide Punctuation Marks: From Structural to Linear Signals.

    Science.gov (United States)

    El Houmami, Nawal; Seligmann, Hervé

    2017-01-01

    We present an evolutionary hypothesis assuming that signals marking nucleotide synthesis (DNA replication and RNA transcription) evolved from multi- to unidimensional structures, and were carried over from transcription to translation. This evolutionary scenario presumes that signals combining secondary and primary nucleotide structures are evolutionary transitions. Mitochondrial replication initiation fits this scenario. Some observations reported in the literature corroborate that several signals for nucleotide synthesis function in translation, and vice versa. (a) Polymerase-induced frameshift mutations occur preferentially at translational termination signals (nucleotide deletion is interpreted as termination of nucleotide polymerization, paralleling the role of stop codons in translation). (b) Stem-loop hairpin presence/absence modulates codon-amino acid assignments, showing that translational signals sometimes combine primary and secondary nucleotide structures (here codon and stem-loop). (c) Homopolymer nucleotide triplets (AAA, CCC, GGG, TTT) cause transcriptional and ribosomal frameshifts. Here we find in recently described human mitochondrial RNAs that systematically lack mono-, dinucleotides after each trinucleotide (delRNAs) that delRNA triplets include 2x more homopolymers than mitogenome regions not covered by delRNA. Further analyses of delRNAs show that the natural circular code X (a little-known group of 20 translational signals enabling ribosomal frame retrieval consisting of 20 codons {AAC, AAT, ACC, ATC, ATT, CAG, CTC, CTG, GAA, GAC, GAG, GAT, GCC, GGC, GGT, GTA, GTC, GTT, TAC, TTC} universally overrepresented in coding versus other frames of gene sequences), regulates frameshift in transcription and translation. This dual transcription and translation role confirms for X the hypothesis that translational signals were carried over from transcriptional signals.

  20. 77 FR 16098 - In the Matter of All Operating Boiling Water Reactor Licensees With Mark I and Mark II...

    Science.gov (United States)

    2012-03-19

    ... the Matter of All Operating Boiling Water Reactor Licensees With Mark I and Mark II Containments... operate boiling-water reactors (BWRs) with Mark I and Mark II containment designs. II On March 11, 2011, a... Nuclear Reactor Regulation. Operating Boiling Water Reactor Licenses With Mark I and Mark II Containments...

  1. 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.

  2. Reliable Date-Replication Using Grid Computing Tools

    CERN Document Server

    Sonnick, D

    2009-01-01

    The LHCb detector at CERN is a physical experiment to measure rare b-decays after the collision of protons in the Large Hadron Collider ring. The measured collisions are called “Events”. These events are containing the data which are necessary to analyze and reconstruct the decays. The events are send to speed optimized writer processes which are writing the events into files on a local hard disk cluster. Because the space is limited on the hard disk cluster, the data needs to be replicated to a long term storage system. This diploma thesis will present the design and implementation of a software which replicates the data in a reliable manner. In addition this software registers the data in special databases to prepare the following analyzes and reconstructions. Because the software which is used in the LHCb experiment is still under development, there is a special need for reliability to deal with error situations or inconsistent data. The subject of this diploma thesis was also presented at the “17th ...

  3. 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.

  4. 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.

  5. High-resolution profiling of Drosophila replication start sites reveals a DNA shape and chromatin signature of metazoan origins.

    Science.gov (United States)

    Comoglio, Federico; Schlumpf, Tommy; Schmid, Virginia; Rohs, Remo; Beisel, Christian; Paro, Renato

    2015-05-05

    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.

  6. 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.

  7. The Mark II Vertex Drift Chamber

    Energy Technology Data Exchange (ETDEWEB)

    Alexander, J.P.; Baggs, R.; Fujino, D.; Hayes, K.; Hoard, C.; Hower, N.; Hutchinson, D.; Jaros, J.A.; Koetke, D.; Kowalski, L.A.

    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 {mu}m spatial resolution and <1000 {mu}m track-pair resolution in pressurized CO{sub 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{sub 2} mixtures are presented. 10 refs., 12 figs., 1 tab.

  8. MARK5:n asiakaslupaus ja myynnin argumentaatio

    OpenAIRE

    2015-01-01

    Opinnäytetyön tarkoituksena on rakentaa kohdeyritykselle MARK5:n asiakaslupaus ja myynnin argumentaatio sekä esittää ehdotus asiakaslupauksen ja myynnin argumentaation tuottotavasta, jota kohdeyritys voisi hyödyntää muiden tuotteidensa tai palveluidensa asiakaslupausten ja myynnin argumentaatioiden rakentamisessa. Opinnäytetyö aloitetaan esittelemällä kohdeyritys ja MARK5 sekä määrittelemällä liiketoimintaongelma ja työn tavoitteet. Opinnäytetyön ongelmana on, että kohdeyrityksellä ei ole...

  9. 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.

  10. DNA intercalator stimulates influenza transcription and virus replication.

    Science.gov (United States)

    Li, Olive T W; Poon, Leo L M

    2011-03-15

    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 RNAPII(a) in infected cells was due to the shift of nonphosphorylated RNAPII (RNAPII(a)) to hyperphosphorylated RNAPII (RNAPII(o)).

  11. Surface micro topography replication in injection moulding

    DEFF Research Database (Denmark)

    Arlø, Uffe Rolf

    of the mechanisms controlling topography replication. Surface micro topography replication in injection moulding depends on the main elements of  Process conditions  Plastic material  Mould topography In this work, the process conditions is the main factor considered, but the impact of plastic material...

  12. 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…

  13. Completion of DNA replication in Escherichia coli.

    Science.gov (United States)

    Wendel, Brian M; Courcelle, Charmain T; Courcelle, Justin

    2014-11-18

    The mechanism by which cells recognize and complete replicated regions at their precise doubling point must be remarkably efficient, occurring thousands of times per cell division along the chromosomes of humans. However, this process remains poorly understood. Here we show that, in Escherichia coli, the completion of replication involves an enzymatic system that effectively counts pairs and limits cellular replication to its doubling point by allowing converging replication forks to transiently continue through the doubling point before the excess, over-replicated regions are incised, resected, and joined. Completion requires RecBCD and involves several proteins associated with repairing double-strand breaks including, ExoI, SbcDC, and RecG. However, unlike double-strand break repair, completion occurs independently of homologous recombination and RecA. In some bacterial viruses, the completion mechanism is specifically targeted for inactivation to allow over-replication to occur during lytic replication. The results suggest that a primary cause of genomic instabilities in many double-strand-break-repair mutants arises from an impaired ability to complete replication, independent from DNA damage.

  14. 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…

  15. 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…

  16. How frog embryos replicate their DNA reliably

    Science.gov (United States)

    Bechhoefer, John; Marshall, Brandon

    2007-03-01

    Frog embryos contain three billion base pairs of DNA. In early embryos (cycles 2-12), DNA replication is extremely rapid, about 20 min., and the entire cell cycle lasts only 25 min., meaning that mitosis (cell division) takes place in about 5 min. In this stripped-down cell cycle, there are no efficient checkpoints to prevent the cell from dividing before its DNA has finished replication - a disastrous scenario. Even worse, the many origins of replication are laid down stochastically and are also initiated stochastically throughout the replication process. Despite the very tight time constraints and despite the randomness introduced by origin stochasticity, replication is extremely reliable, with cell division failing no more than once in 10,000 tries. We discuss a recent model of DNA replication that is drawn from condensed-matter theories of 1d nucleation and growth. Using our model, we discuss different strategies of replication: should one initiate all origins as early as possible, or is it better to hold back and initiate some later on? Using concepts from extreme-value statistics, we derive the distribution of replication times given a particular scenario for the initiation of origins. We show that the experimentally observed initiation strategy for frog embryos meets the reliability constraint and is close to the one that requires the fewest resources of a cell.

  17. 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 depl...

  18. 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.

  19. Mark Twain's Nemesis: The Paige Compositor.

    Science.gov (United States)

    Goble, Corban

    Samuel Clemens (Mark Twain), who had set type by hand in his youth, had believed that a mechanical composer was beyond the realm of possibility. In 1880, however, he invested $2,000 in an early typesetter invented by James W. Paige. Both Clemens and Paige dreamed of immense wealth that would be generated by selling thousands of Paige Compositors.…

  20. Mark Twain and "The Awful German Language."

    Science.gov (United States)

    Hedderich, Norbert

    2003-01-01

    Analyzes Mark Twain's 1869 essay "The Awful German Language" in terms of Twain's comments on morphological, syntactical, lexical, and phonological features of German. The topic is presented in the context of Twain's German language learning experience. Relevance of the article for German language instruction today is also described. (Author/VWL)

  1. Mark Twain National Wildlife Refuge : Sign Plan

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — The Mark Twain NWR Sign Plan explains how signs are used on the Refuge to help guide and educate visitors. An inventory of current signs is given as well as a list...

  2. Mark Twain: An Introduction and Interpretation.

    Science.gov (United States)

    Baldanza, Frank

    One of a series of works aimed at presenting contemporary critical opinion on major American authors, this volume contains critical studies of Mark Twain. Designed for use by both literary critics and secondary and college teachers of English, this work would also be of value to undergraduate and graduate students of literature. Topics covered…

  3. Mark Twain and American Humor [Lesson Plan].

    Science.gov (United States)

    2000

    In this three-part lesson, students examine structure and characterization in the short story and consider the significance of humor through a study of Mark Twain's "The Celebrated Jumping Frog of Calaveras County." In Part I, through skits and storytelling, students first examine the structure of Twain's story and the role he creates for his…

  4. 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...

  5. 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

  6. Eesti oma idamaa kunstnik / Mark Soosaar

    Index Scriptorium Estoniae

    Soosaar, Mark, 1946-

    1999-01-01

    8. apr.-st Pärnu Uue Kunsti Muuseumis veebruaris Soulis idamaise maalikunsti alal magistrikraadi kaitsnud Kati Kalda (sünd. 1971) maalinäitus "Elu korea moodi", Kalev Mark Kostabi maalide väljapanek ning loodusfoto konkursi parimate tööde näitus.

  7. 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

  8. 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.…

  9. 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

  10. Marks, forfeiture and a constitutional conundrum

    NARCIS (Netherlands)

    Ramalho, A.

    2009-01-01

    In Autumn 2008 a US district court ordered the forfeiture of marks owned by a gang known as the Mongols on the grounds that the gang engaged in illegal activities. While the forfeiture of property is provided for under various US statutes, this case raises more than its fair share of legal and const

  11. Action Research at St Mark's Academy 2013

    Science.gov (United States)

    Elwick, Alex, Ed.; Riggall, Anna, Ed.

    2013-01-01

    St Mark's Church of England Academy is an 11-18 academy situated in Mitcham, South London. It offers a commitment to high achievement within a community of care, underpinned by the Christian values of hope, love and trust. The academy encourages the development of the moral and spiritual well-being of students, alongside their academic success.…

  12. Mark the Evangelist: His African memory

    Directory of Open Access Journals (Sweden)

    Willem Oliver

    2016-05-01

    Full Text Available Mark is the author of the oldest gospel in the Christian Bible. Not much is known about him or his family except for a few references in the Bible. The general assumption, originating in the West, is that Mark was born and bred in Palestine. One of the main proponents of the Western view is Walter Bauer, a German theologian of the first half of the 20th century. His views rely heavily on the argument from silence, as Africa had – and to a great extent still has – an oral culture. Contrary to the Western view, Thomas Oden, an American theologian, did research on the oral culture and investigated the African memory of Mark. This article presents a critical discussion and a review of the book written by Oden in 2011 titled The African memory of Mark. Oden seems to be very subjective in his remarks in favour of Africa, as is also clear from his book titled How Africa shaped the Christian mind, written in 2007, and the question is if he really has enough grounds for his postulations.

  13. Laser Marked Codes For Paperless Tracking Applications

    Science.gov (United States)

    Crater, David

    1987-01-01

    The application of laser markers for marking machine readable codes is described. Use of such codes for automatic tracking and considerations for marker performance and features are discussed. Available laser marker types are reviewed. Compatibility of laser/material combinations and material/code/reader systems are reviewed.

  14. E. Mark Stern (1929-2014).

    Science.gov (United States)

    Vande Kemp, Hendrika

    2014-12-01

    This article memorializes E. Mark Stern (1929 -2014), a clinical psychologist who found his ideological home in humanistic and existential psychology. Highlights of Stern's career and professional contributions are noted. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

  15. Prosodic focus marking in Dali Mandarin

    NARCIS (Netherlands)

    Liu, L.Z.H.; van de Velde, H.; Chen, A.

    2016-01-01

    This study investigated prosodic marking of focus in Dali Mandarin, a variety of Xinan Guanhua (Southwestern Mandarin) spoken in Dali city, the capital of Dali Bai Autonomous Prefecture, China. Dali Mandarin as a variety of Mandarin has had heavy contact with Bai, a Tibeto-Burman language, for a lon

  16. 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....

  17. 49 CFR 172.304 - Marking requirements.

    Science.gov (United States)

    2010-10-01

    ... could substantially reduce its effectiveness. (b) [Reserved] [Amdt. 172-29, 41 FR 15996, Apr. 15, 1976... 49 Transportation 2 2010-10-01 2010-10-01 false Marking requirements. 172.304 Section 172.304... PROVISIONS, HAZARDOUS MATERIALS COMMUNICATIONS, EMERGENCY RESPONSE INFORMATION, TRAINING REQUIREMENTS, AND...

  18. Recent Discoveries on Antwerp Panel Makers' Marks

    DEFF Research Database (Denmark)

    Wadum, Jørgen

    1993-01-01

    more can be added to our comprehension of the way the panel makers worked in Antwerp. In the following paper I shall give a brief summary of the present state of research, as well as outline the complicated task of interpreting these marks and their use as a dating tool. The ready-made supports...

  19. 22 CFR 226.91 - Marking.

    Science.gov (United States)

    2010-04-01

    ... funding, USAID Agreement Officers will request Apparent Successful Applicants to submit a Branding Strategy, defined in § 226.2. The proposed Branding Strategy will not be evaluated competitively. The... marked with the USAID Identity. (1) Any “public communications” as defined in § 226.2, funded by USAID...

  20. 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

  1. 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.…

  2. 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.

  3. Dormant origins licensed by excess Mcm2-7 are required for human cells to survive replicative stress.

    Science.gov (United States)

    Ge, Xin Quan; Jackson, Dean A; Blow, J Julian

    2007-12-15

    In late mitosis and early G1, Mcm2-7 complexes are loaded onto DNA to license replication origins for use in the upcoming S phase. However, the amount of Mcm2-7 loaded is in significant excess over the number of origins normally used. We show here that in human cells, excess chromatin-bound Mcm2-7 license dormant replication origins that do not fire during normal DNA replication, in part due to checkpoint activity. Dormant origins were activated within active replicon clusters if replication fork progression was inhibited, despite the activation of S-phase checkpoints. After lowering levels of chromatin-bound Mcm2-7 in human cells by RNA interference (RNAi), the use of dormant origins was suppressed in response to replicative stress. Although cells with lowered chromatin-bound Mcm2-7 replicated at normal rates, when challenged with replication inhibitors they had dramatically reduced rates of DNA synthesis and reduced viability. These results suggest that the use of dormant origins licensed by excess Mcm2-7 is a new and physiologically important mechanism that cells utilize to maintain DNA replication rates under conditions of replicative stress. We propose that checkpoint kinase activity can preferentially suppress initiation within inactive replicon clusters, thereby directing new initiation events toward active clusters that are experiencing replication problems.

  4. Do clinicians use more question marks?

    Science.gov (United States)

    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*, med* or patient* were found anywhere in the paper’s title, abstract or the journal’s name. Other papers were considered controls. As a verification, clinical journals were compared to non-clinical journals in two different approaches. Also, 50 highest impact journals were explored for publisher group dependent differences. Main outcome measure Total number of question marks in titles. Results A total of 368,362 papers were classified as clinical and 596,889 as controls. Clinical papers had question marks in 3.9% (95% confidence interval 3.8–4.0%) of titles and other papers in 2.3% (confidence interval 2.3–2.3%; p < 0.001). These findings could be verified for clinical journals compared to non-clinical journals. Different percentages between four publisher groups were found (p < 0.01). Conclusion We found more question marks in titles of clinical papers than in other papers. This could suggest that clinicians often have a question-driven approach to research and scientists in more fundamental research a hypothesis-driven approach. An alternative explanation is that clinicians like catchy titles. Publishing groups might have pro- and anti-question mark policies. PMID:26085937

  5. 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...

  6. 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.

  7. 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.

  8. Temporal order of evolution of DNA replication systems inferred by comparison of cellular and viral DNA polymerases

    Directory of Open Access Journals (Sweden)

    Koonin Eugene V

    2006-12-01

    Full Text Available Abstract Background The core enzymes of the DNA replication systems show striking diversity among cellular life forms and more so among viruses. In particular, and counter-intuitively, given the central role of DNA in all cells and the mechanistic uniformity of replication, the core enzymes of the replication systems of bacteria and archaea (as well as eukaryotes are unrelated or extremely distantly related. Viruses and plasmids, in addition, possess at least two unique DNA replication systems, namely, the protein-primed and rolling circle modalities of replication. This unexpected diversity makes the origin and evolution of DNA replication systems a particularly challenging and intriguing problem in evolutionary biology. Results I propose a specific succession for the emergence of different DNA replication systems, drawing argument from the differences in their representation among viruses and other selfish replicating elements. In a striking pattern, the DNA replication systems of viruses infecting bacteria and eukaryotes are dominated by the archaeal-type B-family DNA polymerase (PolB whereas the bacterial replicative DNA polymerase (PolC is present only in a handful of bacteriophage genomes. There is no apparent mechanistic impediment to the involvement of the bacterial-type replication machinery in viral DNA replication. Therefore, I hypothesize that the observed, markedly unequal distribution of the replicative DNA polymerases among the known cellular and viral replication systems has a historical explanation. I propose that, among the two types of DNA replication machineries that are found in extant life forms, the archaeal-type, PolB-based system evolved first and had already given rise to a variety of diverse viruses and other selfish elements before the advent of the bacterial, PolC-based machinery. Conceivably, at that stage of evolution, the niches for DNA-viral reproduction have been already filled with viruses replicating with the

  9. 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...

  10. 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.

  11. On objectivity and validity of oral examinations in psychology – A replication

    Directory of Open Access Journals (Sweden)

    Karl Westhoff

    2010-09-01

    Full Text Available A hierarchy of requirements applying to practising psychologists is the basis of a concept for oral examinations in psychological assessment. A study on the objectivity of oral examinations was replicated. We found very high correlations between the evaluations of examiner and assessor and high correlations between the examinees’ self-evaluations after the exam. Examinees’ self-evaluations before the examinations correlated at about 0.48 with the marks in the oral examina-tion. The results concerning preparation do not uniformly show that preparation in a group and mutual examination lead to better marks compared to preparation alone.

  12. Replication forks reverse at high frequency upon replication stress in Physarum polycephalum.

    Science.gov (United States)

    Maric, Chrystelle; Bénard, Marianne

    2014-12-01

    The addition of hydroxyurea after the onset of S phase allows replication to start and permits the successive detecting of replication-dependent joint DNA molecules and chicken foot structures in the synchronous nuclei of Physarum polycephalum. We find evidence for a very high frequency of reversed replication forks upon replication stress. The formation of these reversed forks is dependent on the presence of joint DNA molecules, the impediment of the replication fork progression by hydroxyurea, and likely on the propensity of some replication origins to reinitiate replication to counteract the action of this compound. As hydroxyurea treatment enables us to successively detect the appearance of joint DNA molecules and then of reversed replication forks, we propose that chicken foot structures are formed both from the regression of hydroxyurea-frozen joint DNA molecules and from hydroxyurea-stalled replication forks. These experiments underscore the transient nature of replication fork regression, which becomes detectable due to the hydroxyurea-induced slowing down of replication fork progression.

  13. 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.

  14. Regulated Transport into the Nucleus of Herpesviridae DNA Replication Core Proteins

    Directory of Open Access Journals (Sweden)

    Alessandro Ripalti

    2013-09-01

    Full Text Available The Herpesvirdae family comprises several major human pathogens belonging to three distinct subfamilies. Their double stranded DNA genome is replicated in the nuclei of infected cells by a number of host and viral products. Among the latter the viral replication complex, whose activity is strictly required for viral replication, is composed of six different polypeptides, including a two-subunit DNA polymerase holoenzyme, a trimeric primase/helicase complex and a single stranded DNA binding protein. The study of herpesviral DNA replication machinery is extremely important, both because it provides an excellent model to understand processes related to eukaryotic DNA replication and it has important implications for the development of highly needed antiviral agents. Even though all known herpesviruses utilize very similar mechanisms for amplification of their genomes, the nuclear import of the replication complex components appears to be a heterogeneous and highly regulated process to ensure the correct spatiotemporal localization of each protein. The nuclear transport process of these enzymes is controlled by three mechanisms, typifying the main processes through which protein nuclear import is generally regulated in eukaryotic cells. These include cargo post-translational modification-based recognition by the intracellular transporters, piggy-back events allowing coordinated nuclear import of multimeric holoenzymes, and chaperone-assisted nuclear import of specific subunits. In this review we summarize these mechanisms and discuss potential implications for the development of antiviral compounds aimed at inhibiting the Herpesvirus life cycle by targeting nuclear import of the Herpesvirus DNA replicating enzymes.

  15. A quantitative model of DNA replication in Xenopus embryos: reliable replication despite stochasticity

    Science.gov (United States)

    Cheng-Hsin Yang, Scott; Bechhoefer, John

    2008-03-01

    DNA synthesis in Xenopus frog embryos initiates stochastically in time at many sites (origins) along the chromosome. Stochastic initiation implies fluctuations in the replication time and may lead to cell death if replication takes longer than the cell cycle time (˜ 25 min.). Surprisingly, although the typical replication time is about 20 min., in vivo experiments show that replication fails to complete only about 1 in 250 times. How is replication timing accurately controlled despite the stochasticity? Biologists have proposed two mechanisms: the first uses a regular spatial distribution of origins, while the second uses randomly located origins but increases their probability of initiation as the cell cycle proceeds. Here, we show that both mechanisms yield similar end-time distributions, implying that regular origin spacing is not needed for control of replication time. Moreover, we show that the experimentally inferred time-dependent initiation rate satisfies the observed low failure probability and nearly optimizes the use of replicative proteins.

  16. Schizophrenia-specific basic symptoms. A successful replication.

    Science.gov (United States)

    Mass, R; Weigel, S; Schneider, S; Klepsch, R

    1998-01-01

    Several investigations showed that the Frankfurt Complaint Questionnaire (FCQ) has no diagnostic specificity. However, in a preceding study two new FCQ subscales were developed: FCQ-S, sensitive to schizophrenia, and FCQ-A, sensitive to alcoholism. The aim of the present study was to replicate the diagnostic sensitivity of those subscales. Four groups were considered: schizophrenics with marked negative symptoms (n = 25); schizophrenics with no or mild negative symptoms (n = 25); alcoholics (n = 25); patients with obsessive-compulsive disorder (n = 15). FCQ original subscales and total score did not differ between groups. As expected, in FCQ-S both schizophrenic groups had significantly higher scores than the other groups; FCQ-A failed to show group differences but was significantly related to alcoholism markers.

  17. Targeting DNA Replication Stress for Cancer Therapy

    Science.gov (United States)

    Zhang, Jun; Dai, Qun; Park, Dongkyoo; Deng, Xingming

    2016-01-01

    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. PMID:27548226

  18. 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.

  19. Chromosome catastrophes involve replication mechanisms generating complex genomic rearrangements.

    Science.gov (United States)

    Liu, Pengfei; Erez, Ayelet; Nagamani, Sandesh C Sreenath; Dhar, Shweta U; Kołodziejska, Katarzyna E; Dharmadhikari, Avinash V; Cooper, M Lance; Wiszniewska, Joanna; Zhang, Feng; Withers, Marjorie A; Bacino, Carlos A; Campos-Acevedo, Luis Daniel; Delgado, Mauricio R; Freedenberg, Debra; Garnica, Adolfo; Grebe, Theresa A; Hernández-Almaguer, Dolores; Immken, LaDonna; Lalani, Seema R; McLean, Scott D; Northrup, Hope; Scaglia, Fernando; Strathearn, Lane; Trapane, Pamela; Kang, Sung-Hae L; Patel, Ankita; Cheung, Sau Wai; Hastings, P J; Stankiewicz, Paweł; Lupski, James R; Bi, Weimin

    2011-09-16

    Complex genomic rearrangements (CGRs) consisting of two or more breakpoint junctions have been observed in genomic disorders. Recently, a chromosome catastrophe phenomenon termed chromothripsis, in which numerous genomic rearrangements are apparently acquired in one single catastrophic event, was described in multiple cancers. Here, we show that constitutionally acquired CGRs share similarities with cancer chromothripsis. In the 17 CGR cases investigated, we observed localization and multiple copy number changes including deletions, duplications, and/or triplications, as well as extensive translocations and inversions. Genomic rearrangements involved varied in size and complexities; in one case, array comparative genomic hybridization revealed 18 copy number changes. Breakpoint sequencing identified characteristic features, including small templated insertions at breakpoints and microhomology at breakpoint junctions, which have been attributed to replicative processes. The resemblance between CGR and chromothripsis suggests similar mechanistic underpinnings. Such chromosome catastrophic events appear to reflect basic DNA metabolism operative throughout an organism's life cycle.

  20. A whole genome RNAi screen identifies replication stress response genes.

    Science.gov (United States)

    Kavanaugh, Gina; Ye, Fei; Mohni, Kareem N; Luzwick, Jessica W; Glick, Gloria; Cortez, David

    2015-11-01

    Proper DNA replication is critical to maintain genome stability. When the DNA replication machinery encounters obstacles to replication, replication forks stall and the replication stress response is activated. This response includes activation of cell cycle checkpoints, stabilization of the replication fork, and DNA damage repair and tolerance mechanisms. Defects in the replication stress response can result in alterations to the DNA sequence causing changes in protein function and expression, ultimately leading to disease states such as cancer. To identify additional genes that control the replication stress response, we performed a three-parameter, high content, whole genome siRNA screen measuring DNA replication before and after a challenge with replication stress as well as a marker of checkpoint kinase signalling. We identified over 200 replication stress response genes and subsequently analyzed how they influence cellular viability in response to replication stress. These data will serve as a useful resource for understanding the replication stress response.

  1. Event extraction for DNA methylation

    Directory of Open Access Journals (Sweden)

    Ohta Tomoko

    2011-10-01

    Full Text Available Abstract Background We consider the task of automatically extracting DNA methylation events from the biomedical domain literature. DNA methylation is a key mechanism of epigenetic control of gene expression and implicated in many cancers, but there has been little study of automatic information extraction for DNA methylation. Results We present an annotation scheme for DNA methylation following the representation of the BioNLP shared task on event extraction, select a set of 200 abstracts including a representative sample of all PubMed citations relevant to DNA methylation, and introduce manual annotation for this corpus marking nearly 3000 gene/protein mentions and 1500 DNA methylation and demethylation events. We retrain a state-of-the-art event extraction system on the corpus and find that automatic extraction of DNA methylation events, the methylated genes, and their methylation sites can be performed at 78% precision and 76% recall. Conclusions Our results demonstrate that reliable extraction methods for DNA methylation events can be created through corpus annotation and straightforward retraining of a general event extraction system. The introduced resources are freely available for use in research from the GENIA project homepage http://www-tsujii.is.s.u-tokyo.ac.jp/GENIA.

  2. Study on the micro-replication of shark skin

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Direct replication of creatural scarfskins to form biomimetic surfaces with relatively vivid morphology is a new attempt of the bio-replicated forming technology at animal body. Taking shark skins as the replication templates, and the micro-embossing and micro-molding as the material forming methods, the micro-replicating technology of the outward morphology on shark skins was demonstrated. The preliminary analysis on replication precision indicates that the bio-replicated forming technology can replicate the outward morphology of the shark scales with good precision, which validates the application of the bio-replicated forming technology in the direct morphology replication of the firm creatural scarfskins.

  3. Inhibition of IκB kinase by thalidomide increases hepatitis C virus RNA replication.

    Science.gov (United States)

    Rance, E; Tanner, J E; Alfieri, C

    2012-02-01

    Hepatic fibrosis is an integral element in the progression of chronic liver disease. Elevated hepatic interleukin (IL)-8 is an important contributor to fibrosis in patients chronically infected with the hepatitis C virus (HCV). Thalidomide has been used to reduce liver inflammation and fibrosis in HCV-infected patients, but its impact on HCV replication remains unclear. This study examined the effect of thalidomide on HCV replication in vitro. Results revealed that while thalidomide reduced IL-8 and nuclear factor kappa B (NF-κB) activity by 95% and 46% in Huh-7 cells, increasing concentrations of thalidomide correlated with a linear rise in HCV replication (17-fold at 200 μm). The NF-κB inhibitors, wedelolactone and NF-κB activation inhibitor-1, which mimic the actions of thalidomide by preventing phosphorylation and activation of IκB kinase (IKK) and hence block NF-κB activity, increased HCV RNA by 18- and 19-fold, respectively. During in vitro HCV replication in Huh-7 cells, we observed a 30% increase in IKKα protein and 55% decrease in NF-κB(p65)/RelA protein relative to cellular β-actin. Ectopic expression of IKKα to enhance the inactive form of IKK in cells undergoing virus replication led to a 13-fold increase in HCV RNA. Conversely, enhanced expression of NF-κB(p65)/RelA in infected cells resulted in a 17-fold reduction in HCV RNA. In conclusion, HCV RNA replication was significantly augmented by the inhibition of IKK activation and subsequent NF-κB signalling, whereas a restoration of NF-κB activity by the addition of NF-κB/RelA markedly reduced HCV replication. This study lends added importance to the role of the NF-κB signalling pathway in controlling HCV replication.

  4. 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

  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. Forensic odontology, part 4. Human bite marks.

    Science.gov (United States)

    Hinchliffe, J

    2011-04-23

    The aim of this paper is to give a brief overview of bite mark analysis: its usefulness and limitations. The study and analysis of such injuries is challenging and complex. The correct protocols for collection, management, preservation, analysis and interpretation of this evidence should be employed if useful information is to be obtained for the courts. It is now possible, with advances in digital technology, to produce more accurate and reproducible comparison techniques which go some way to preventing and reducing problems such as photographic distortions. Research needs to be continued to increase our knowledge of the behaviour of skin when bitten. However, when presented with a high quality bite mark showing good dental detail, and a limited, accessible number of potential biters, it can be extremely useful in establishing a link between the bitten person and the biter or excluding the innocent.

  7. 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...

  8. The Bionic Clicker Mark I & II.

    Science.gov (United States)

    Magee, Elliott G; Ourselin, S; Nikitichev, Daniil; Vercauteren, T; Vanhoestenberghe, Anne

    2017-08-14

    In this manuscript, we present two 'Bionic Clicker' systems, the first designed to demonstrate electromyography (EMG) based control systems for educational purposes and the second for research purposes. EMG based control systems pick up electrical signals generated by muscle activation and use these as inputs for controllers. EMG controllers are widely used in prosthetics to control limbs. The Mark I (MK I) clicker allows the wearer to change the slide of a presentation by raising their index finger. It is built around a microcontroller and a bio-signals shield. It generated a lot of interest from both the public and research community. The Mark II (MK II) device presented here was designed to be a cheaper, sleeker, and more customizable system that can be easily modified and directly transmit EMG data. It is built using a wireless capable microcontroller and a muscle sensor.

  9. Dynamic molecular networks: from synthetic receptors to self-replicators.

    Science.gov (United States)

    Otto, Sijbren

    2012-12-18

    Dynamic combinatorial libraries (DCLs) are molecular networks in which the network members exchange building blocks. The resulting product distribution is initially under thermodynamic control. Addition of a guest or template molecule tends to shift the equilibrium towards compounds that are receptors for the guest. This Account gives an overview of our work in this area. We have demonstrated the template-induced amplification of synthetic receptors, which has given rise to several high-affinity binders for cationic and anionic guests in highly competitive aqueous solution. The dynamic combinatorial approach allows for the identification of new receptors unlikely to be obtained through rational design. Receptor discovery is possible and more efficient in larger libraries. The dynamic combinatorial approach has the attractive characteristic of revealing interesting structures, such as catenanes, even when they are not specifically targeted. Using a transition-state analogue as a guest we can identify receptors with catalytic activity. Although DCLs were initially used with the reductionistic view of identifying new synthetic receptors or catalysts, it is becoming increasingly apparent that DCLs are also of interest in their own right. We performed detailed computational studies of the effect of templates on the product distributions of DCLs using DCLSim software. Template effects can be rationalized by considering the entire network: the system tends to maximize global host-guest binding energy. A data-fitting analysis of the response of the global position of the DCLs to the addition of the template using DCLFit software allowed us to disentangle individual host-guest binding constants. This powerful procedure eliminates the need for isolation and purification of the various individual receptors. Furthermore, local network binding events tend to propagate through the entire network and may be harnessed for transmitting and processing of information. We demonstrated

  10. Ispra Mark-10 water splitting process

    Science.gov (United States)

    1975-01-01

    A thermochemical water splitting process, the Ispra Mark-10 chemical reaction cycle, was chosen for examining the possibility of using water to produce hydrogen on a large scale for fuel and major industrial chemical uses. The assumed energy source for the process is an HTGR (helium cooled). A process flow diagram, a material balance, and an energy balance were developed for the thermochemical reaction cycle. Principal reactions which constitute the cycle are included.

  11. Mucocele and pyocele with marked intracranial extension

    Energy Technology Data Exchange (ETDEWEB)

    Tsuchiya, Kazuhiro; Machida, Tohru; Iio, Masahiro

    1984-08-01

    Two cases are presented with frontal sinus pyocele and fronto-ethmoid sinus mucocele in which marked intracranial extension is shown. Their intracranial part appeared as a large biconvex mass, which showed iso or slightly low density homogeneously and had gross calcification in the posterior rim. The findings of the paranasal sinuses and the orbit in tomograms and CT scans are thought to be useful in the differential diagnosis of chronic subdural hematoma.

  12. Chorionic Villus Sampling and Marked Membrane Separation

    Directory of Open Access Journals (Sweden)

    Sh. Akhlaghpoor

    2010-12-01

    Full Text Available Background/Objective: The major concern about the invasive prenatal diagnostic tests is the"nfrequency of procedure induced pregnancy loss. Chorionic Villus Sampling (CVS is the invasive"ntest of choice in the first trimester after the 10th gestational week. Our experience suggests"nmarked chorioamniotic separation is an uncommon finding after the 10th gestational week. This"nstudy assesses the rate of marked membrane separation in a 10 to 14-week gestational period"nand its effect on post CVS fetal loss."nPatients and Methods: Forty-one patients (5.2% were selected among 782 patients as cases"nwith marked membrane separation (mean maternal age, 26.9 years. CVS procedures were"nperformed with a 20-gauge Chiba needle attached to a 20-ml syringe under ultrasound guidance."nFollow-up was performed by phone call and clinical visits until 24 weeks of gestation. For the"ncontrol group, the follow-up was performed for only 2 weeks. Early fetal loss in the first two"nweeks of post procedural period, and late fetal loss from 2 weeks after procedure till the 24th"ngestational week were considered as CVS complications."nResults: We detected 2.4% early fetal losses after the procedure. Fourteen cases voluntarily"nunderwent therapeutic abortion due to beta-thalassemia or hemophilia. One fetus with"nmicrocephaly was spontaneously aborted in the 21st gestational week. Twenty-five neonates"nwere delivered alive at term and one prematurely at the 32nd week. Marked membrane separation"nhad no significant effect on early post CVS fetal loss rate."nConclusion: The procedure does not have a major impact on the early post CVS fetal loss in"npatients with marked membrane separation.

  13. Exhibition by Gozitan artist Mark Sagona

    OpenAIRE

    Calleja, Joseph

    2004-01-01

    Mark Sagona's exhibition, entitled "Recent Insights" was held at the Banca Giuratale in Victoria, Gozo between the 24th January and the 8th February 2004. It brought together twenty-four paintings, all produced in 2003 and the majority of which were realised in oil on canvas. The exhibition was curated by Dr Joseph Paul Cassar, and inaugurated by the Minister for Gozo, the Hon. Giovanna Debono.

  14. Transcriptional coactivator HCF-1 couples the histone chaperone Asf1b to HSV-1 DNA replication components.

    Science.gov (United States)

    Peng, Hua; Nogueira, Mauricio L; Vogel, Jodi L; Kristie, Thomas M

    2010-02-01

    The cellular transcriptional coactivator HCF-1 interacts with numerous transcription factors as well as other coactivators and is a component of multiple chromatin modulation complexes. The protein is essential for the expression of the immediate early genes of both herpes simplex virus (HSV) and varicella zoster virus and functions, in part, by coupling chromatin modification components including the Set1 or MLL1 histone methyltransferases and the histone demethylase LSD1 to promote the installation of positive chromatin marks and the activation of viral immediately early gene transcription. Although studies have investigated the role of HCF-1 in both cellular and viral transcription, little is known about other processes that the protein may be involved in. Here we demonstrate that HCF-1 localizes to sites of HSV replication late in infection. HCF-1 interacts directly and simultaneously with both HSV DNA replication proteins and the cellular histone chaperone Asf1b, a protein that regulates the progression of cellular DNA replication forks via chromatin reorganization. Asf1b localizes with HCF-1 in viral replication foci and depletion of Asf1b results in significantly reduced viral DNA accumulation. The results support a model in which the transcriptional coactivator HCF-1 is a component of the HSV DNA replication assembly and promotes viral DNA replication by coupling Asf1b to DNA replication components. This coupling provides a novel function for HCF-1 and insights into the mechanisms of modulating chromatin during DNA replication.

  15. Laser treatment of stretch marks: preliminary results

    Science.gov (United States)

    Longo, Leonardo; Piccinetti, A. L.; Monache, G. D.; Botta, G.; Mancini, S.

    2000-06-01

    The best treatment of these stretch mark is still unknown. Some authors proposed the treatment with flash-lamp-pumped dye laser 585 nm, with fluence over 8 J/cm2. Reviewing our experiences on no-surgical effects of lasers in the various phases of the wound healing, including the re- epithelization, we would like to apply the no-surgical laser therapy treating the stretch marks of breast, abdomen and lumbo-sacral region. The goal is to inhibit the fibrous tissue metabolism, encouraging the destruction of the collagen fibers with inflammatory mechanism, and increasing the reconstitution of the superficial dermis layers. We treated five cases of stretch marks in women 22-35 years old, since May 1999, with a cycle of applications of double lasers, 511 and 577 nm, with energy of 20 Joule for spot, respecting the maximum thermal relaxation times of the skin. We waited two weeks interval between the applications. Results obtained after five applications are very positive, and we are encouraged to continue this experimentation.

  16. 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...

  17. 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

  18. A transcription and translation-coupled DNA replication system using rolling-circle replication.

    Science.gov (United States)

    Sakatani, Yoshihiro; Ichihashi, Norikazu; Kazuta, Yasuaki; Yomo, Tetsuya

    2015-05-27

    All living organisms have a genome replication system in which genomic DNA is replicated by a DNA polymerase translated from mRNA transcribed from the genome. The artificial reconstitution of this genome replication system is a great challenge in in vitro synthetic biology. In this study, we attempted to construct a transcription- and translation-coupled DNA replication (TTcDR) system using circular genomic DNA encoding phi29 DNA polymerase and a reconstituted transcription and translation system. In this system, phi29 DNA polymerase was translated from the genome and replicated the genome in a rolling-circle manner. When using a traditional translation system composition, almost no DNA replication was observed, because the tRNA and nucleoside triphosphates included in the translation system significantly inhibited DNA replication. To minimize these inhibitory effects, we optimized the composition of the TTcDR system and improved replication by approximately 100-fold. Using our system, genomic DNA was replicated up to 10 times in 12 hours at 30 °C. This system provides a step toward the in vitro construction of an artificial genome replication system, which is a prerequisite for the construction of an artificial cell.

  19. Using autonomous replication to physically and genetically define human origins of replication

    Energy Technology Data Exchange (ETDEWEB)

    Krysan, P.J.

    1993-01-01

    The author previously developed a system for studying autonomous replication in human cells involving the use of sequences from the Epstein-Barr virus (EBV) genome to provide extrachromosomal plasmids with a nuclear retention function. Using this system, it was demonstrated that large fragments of human genomic DNA could be isolated which replicate autonomously in human cells. In this study the DNA sequences which function as origins of replication in human cells are defined physically and genetically. These experiments demonstrated that replication initiates at multiple locations distributed throughout the plasmid. Another line of experiments addressed the DNA sequence requirements for autonomous replication in human cells. These experiments demonstrated that human DNA fragments have a higher replication activity than bacterial fragments do. It was also found, however, that the bacterial DNA sequence could support efficient replication if enough copies of it were present on the plasmid. These findings suggested that autonomous replication in human cells does not depend on extensive, specific DNA sequences. The autonomous replication system which the author has employed for these experiments utilizes a cis-acting sequence from the EBV origin and the trans-acting EBNA-1 protein to provide plasmids with a nuclear retention function. It was therefore relevant to verify that the autonomous replication of human DNA fragments did not depend on the replication activity associated with the EBV sequences utilized for nuclear retention. To accomplish this goal, the author demonstrated that plasmids carrying the EBV sequences and large fragments of human DNA could support long-term autonomous replication in hamster cells, which are not permissive for EBV replication.

  20. 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...

  1. Control of chromosome replication in caulobacter crescentus.

    Science.gov (United States)

    Marczynski, Gregory T; Shapiro, Lucy

    2002-01-01

    Caulobacter crescentus permits detailed analysis of chromosome replication control during a developmental cell cycle. Its chromosome replication origin (Cori) may be prototypical of the large and diverse class of alpha-proteobacteria. Cori has features that both affiliate and distinguish it from the Escherichia coli chromosome replication origin. For example, requirements for DnaA protein and RNA transcription affiliate both origins. However, Cori is distinguished by several features, and especially by five binding sites for the CtrA response regulator protein. To selectively repress and limit chromosome replication, CtrA receives both protein degradation and protein phosphorylation signals. The signal mediators, proteases, response regulators, and kinases, as well as Cori DNA and the replisome, all show distinct patterns of temporal and spatial organization during cell cycle progression. Future studies should integrate our knowledge of biochemical activities at Cori with our emerging understanding of cytological dynamics in C. crescentus and other bacteria.

  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. 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...

  4. Surface Micro Topography Replication in Injection Moulding

    DEFF Research Database (Denmark)

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

    2005-01-01

    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...

  5. Exonuclease mutations in DNA polymerase epsilon reveal replication strand specific mutation patterns and human origins of replication.

    Science.gov (United States)

    Shinbrot, Eve; Henninger, Erin E; Weinhold, Nils; Covington, Kyle R; Göksenin, A Yasemin; Schultz, Nikolaus; Chao, Hsu; Doddapaneni, HarshaVardhan; Muzny, Donna M; Gibbs, Richard A; Sander, Chris; Pursell, Zachary F; Wheeler, David A

    2014-11-01

    Tumors with somatic mutations in the proofreading exonuclease domain of DNA polymerase epsilon (POLE-exo*) exhibit a novel mutator phenotype, with markedly elevated TCT→TAT and TCG→TTG mutations and overall mutation frequencies often exceeding 100 mutations/Mb. Here, we identify POLE-exo* tumors in numerous cancers and classify them into two groups, A and B, according to their mutational properties. Group A mutants are found only in POLE, whereas Group B mutants are found in POLE and POLD1 and appear to be nonfunctional. In Group A, cell-free polymerase assays confirm that mutations in the exonuclease domain result in high mutation frequencies with a preference for C→A mutation. We describe the patterns of amino acid substitutions caused by POLE-exo* and compare them to other tumor types. The nucleotide preference of POLE-exo* leads to increased frequencies of recurrent nonsense mutations in key tumor suppressors such as TP53, ATM, and PIK3R1. We further demonstrate that strand-specific mutation patterns arise from some of these POLE-exo* mutants during genome duplication. This is the first direct proof of leading strand-specific replication by human POLE, which has only been demonstrated in yeast so far. Taken together, the extremely high mutation frequency and strand specificity of mutations provide a unique identifier of eukaryotic origins of replication.

  6. Flood marks of the 1813 flood in the Central Europe

    Science.gov (United States)

    Miklanek, Pavol; Pekárová, Pavla; Halmová, Dana; Pramuk, Branislav; Bačová Mitková, Veronika

    2014-05-01

    In August 2013, 200 years have passed since the greatest and most destructive floods known in the Slovak river basins. The flood affected almost the entire territory of Slovakia, northeastern Moravia, south of Poland. River basins of Váh (Orava, Kysuca), Poprad, Nitra, Hron, Torysa, Hornád, upper and middle Vistula, Odra have been most affected. The aim of this paper is to map the flood marks documenting this catastrophic flood in Slovakia. Flood marks and registrations on the 1813 flood in the Váh river basin are characterized by great diversity and are written in Bernolák modification of Slovak, in Latin, German and Hungarian. Their descriptions are stored in municipal chronicles and Slovak and Hungarian state archives. The flood in 1813 devastated the entire Váh valley, as well as its tributaries. Following flood marks were known in the Vah river basin: Dolná Lehota village in the Orava river basin, historical map from 1817 covering the Sučany village and showing three different cross-sections of the Váh river during the 1813 flood, flood mark in the city of Trenčín, Flood mark in the gate of the Brunovce mansion, cross preserved at the old linden tree at Drahovce, and some records in written documents, e.g. Cifer village. The second part of the study deals with flood marks mapping in the Hron, Hnilec and Poprad River basins, and Vistula River basin in Krakow. On the basis of literary documents and the actual measurement, we summarize the peak flow rates achieved during the floods in 1813 in the profile Hron: Banská Bystrica. According to recent situation the 1813 flood peak was approximately by 1.22 m higher, than the flood in 1974. Also in the Poprad basin is the August 1813 flood referred as the most devastating flood in last 400 years. The position of the flood mark is known, but the building was unfortunately removed later. The water level in 1813 was much higher than the water level during the recent flood in June 2010. In Cracow the water level

  7. 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"

  8. 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"

  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. Mycobacterium tuberculosis replicates within necrotic human macrophages

    Science.gov (United States)

    Lerner, Thomas R.; Repnik, Urska; Herbst, Susanne; Collinson, Lucy M.; Griffiths, Gareth

    2017-01-01

    Mycobacterium tuberculosis modulation of macrophage cell death is a well-documented phenomenon, but its role during bacterial replication is less characterized. In this study, we investigate the impact of plasma membrane (PM) integrity on bacterial replication in different functional populations of human primary macrophages. We discovered that IFN-γ enhanced bacterial replication in macrophage colony-stimulating factor–differentiated macrophages more than in granulocyte–macrophage colony-stimulating factor–differentiated macrophages. We show that permissiveness in the different populations of macrophages to bacterial growth is the result of a differential ability to preserve PM integrity. By combining live-cell imaging, correlative light electron microscopy, and single-cell analysis, we found that after infection, a population of macrophages became necrotic, providing a niche for M. tuberculosis replication before escaping into the extracellular milieu. Thus, in addition to bacterial dissemination, necrotic cells provide first a niche for bacterial replication. Our results are relevant to understanding the environment of M. tuberculosis replication in the host. PMID:28242744

  11. Aedes Aegypti saliva enhances chikungunya virus replication in human skin fibroblasts via inhibition of the type I interferon signaling pathway.

    Science.gov (United States)

    Wichit, Sineewanlaya; Diop, Fodé; Hamel, Rodolphe; Talignani, Loïc; Ferraris, Pauline; Cornelie, Sylvie; Liegeois, Florian; Thomas, Frédéric; Yssel, Hans; Missé, Dorothée

    2017-09-01

    Chikungunya virus (CHIKV) transmission occurs through the bite of an infected Aedes mosquito which injects virus-containing saliva into the skin of the human host during blood feeding. In the present study, we have determined the effect of Aedes aegypti saliva on CHIKV replication in human skin fibroblasts, a major cell type for viral entry, which mimics the events that occur during natural transmission. A significant increase in the expression of viral transcripts and infectious viral particles was observed in fibroblasts infected with CHIKV in the presence of saliva, as compared with those infected with virus alone. CHIKV-infected human fibroblasts were found to express significantly increased levels of various type I IFN-responsive genes, as demonstrated by specific PCR array analysis. In contrast, the expression of these genes was markedly decreased in cells infected with CHIKV in the presence of mosquito saliva. Moreover, Western blotting analysis revealed that STAT2 and its phosphorylated form were down-regulated in the presence of mosquito saliva. Our data demonstrate for the first time the significance of Aedes aegypti saliva in promoting CHIKV infection via down-regulation of several type I IFN-responsive genes in infected human skin fibroblasts via the JAK-STAT signaling pathway. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. 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

  13. 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...

  14. The Mark II detector for the SLC

    Energy Technology Data Exchange (ETDEWEB)

    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. (Lawrence Berkeley Lab., CA (USA); California Univ., Berkeley (USA). Dept. of Physics); Adolphsen, C.E.; Burchat, P.R.; Dorfan, D.E.; Gatto, C.; Gomez Cadenas, J.J.; Gratta, G.; Heusch, C.A.; Kent, J.; King, M.; Koepke, L.; Labarga, L.; Litke, A.M.; Sadrozinski, H.F.W.; Schwarz, A.S.; Seiden, A.; Turala, M.; Watson, S.; Weisz, S.; Zaccardelli, C.; Von Zanthier, C. (California Univ., Santa Cruz (USA)); 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. (Michigan Univ., Ann Arbor (USA)); Alexander, J.P.; Ballam, J.; Barklow, T.; Bartelt, J.; De Boe

    1989-08-20

    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 ({radical}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.).

  15. 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

  16. Method of marking an animal or plant

    Energy Technology Data Exchange (ETDEWEB)

    Guy, R.J.

    1994-04-27

    This patent describes a method of marking (non-human) animals and plants, involving the use of isotopes, in order to verify the authenticity of animal or plant products in subsequent use, for example free range meat, eggs or other foods. Most elements exist in more than one atomic form in nature. By altering the ratios of the stable isotopes of one or more elements naturally present in the plant or animal, it is possible to differentiate between true and counterfeit products. Altering the isotopic balance leaves the products suitability for human consumption unchanged. (UK).

  17. Mark Zuckerberg biography of an accidental billionaire

    CERN Document Server

    Melendez, Macie

    2012-01-01

    ABOUT THE BOOK Mark Zuckerberg is one of the world's youngest billionaires, thanks to his role in co-founding social networking site, Facebook. As Facebook has grown exponentially since its founding in 2004 (with 845 million monthly active users as of the end of December 2011 according to Facebook), Zuckerberg's popularity has also flown through the roof. Interesting on so many levels, Zuckerberg's quick rise to fame is one that the mass media and general public just can't get enough of. There's his Harvard education, his invention of one of the most popular Internet sites this world has ev

  18. MARK II end cap calorimeter electronics

    Energy Technology Data Exchange (ETDEWEB)

    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%/..sqrt..E was achieved.

  19. Citation Analysis with Mark-and-Recapture

    CERN Document Server

    Loe, Chuan Wen

    2015-01-01

    Mark-and-Recapture is a methodology from Population Biology to estimate the number of a species without counting every individual. This is done by multiple samplings of the species using traps and discounting the instances that were caught repeated. In this paper we show that this methodology is applicable for citation analysis as it is also not feasible to count all the relevant publications of a research topic. In addition this estimation also allows us to propose a stopping rule for researchers to decide how far one should extend their search for relevant literature.

  20. Marking Space and Making Place in Barcelona

    DEFF Research Database (Denmark)

    Hau, Mark Friis

    2016-01-01

    of Catalonia problematizes the role of ‘the city’ in the Catalan independence movement. Through the actors’ narrative inscriptions of certain spaces as Catalan and active markings of the cityscape, the city itself helps to orient understandings of national identity. Visual cues, both in architecture...... ideas of nation and state are encountered and contested in Barcelona through activists’ spatial engagements, exploring how the city, the nation, and the political are connected in Catalonia. The position of Barcelona in activists’ narratives as both ‘less Catalan’ and as the undeniable capital...

  1. The positive behavioral momentum of Mark Ylvisaker.

    Science.gov (United States)

    Turkstra, Lyn S

    2010-08-01

    Mark Ylvisaker inspired many people to believe they had the skills to help children and adults with brain injury live a meaningful life. He was thoroughly multidisciplinary in his approach, but also felt strongly that communication was the cornerstone of effective behavior management and that speech-language pathologists could make a unique contribution in the everyday lives of individuals with cognitive-communication disorders. This article recognizes his profound influence on the author's research, teaching, and clinical practice and was written in the spirit of paying forward the knowledge he shared.

  2. Laser controlled singlet oxygen generation in mitochondria to promote mitochondrial DNA replication in vitro.

    Science.gov (United States)

    Zhou, Xin; Wang, Yupei; Si, Jing; Zhou, Rong; Gan, Lu; Di, Cuixia; Xie, Yi; Zhang, Hong

    2015-11-18

    Reports have shown that a certain level of reactive oxygen species (ROS) can promote mitochondrial DNA (mtDNA) replication. However, it is unclear whether it is the mitochondrial ROS that stimulate mtDNA replication and this requires further investigation. Here we employed a photodynamic system to achieve controlled mitochondrial singlet oxygen ((1)O2) generation. HeLa cells incubated with 5-aminolevulinic acid (ALA) were exposed to laser irradiation to induce (1)O2 generation within mitochondria. Increased mtDNA copy number was detected after low doses of 630 nm laser light in ALA-treated cells. The stimulated mtDNA replication was directly linked to mitochondrial (1)O2 generation, as verified using specific ROS scavengers. The stimulated mtDNA replication was regulated by mitochondrial transcription factor A (TFAM) and mtDNA polymerase γ. MtDNA control region modifications were induced by (1)O2 generation in mitochondria. A marked increase in 8-Oxoguanine (8-oxoG) level was detected in ALA-treated cells after irradiation. HeLa cell growth stimulation and G1-S cell cycle transition were also observed after laser irradiation in ALA-treated cells. These cellular responses could be due to a second wave of ROS generation detected in mitochondria. In summary, we describe a controllable method of inducing mtDNA replication in vitro.

  3. 33 CFR 62.27 - Safe water marks.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Safe water marks. 62.27 Section... UNITED STATES AIDS TO NAVIGATION SYSTEM The U.S. Aids to Navigation System § 62.27 Safe water marks. Safe water marks indicate that there is navigable water all around the mark. They are often used to...

  4. 14 CFR 45.31 - Marking of export aircraft.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Marking of export aircraft. 45.31 Section 45.31 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT IDENTIFICATION AND REGISTRATION MARKING Nationality and Registration Marks § 45.31 Marking of export aircraft. A...

  5. 19 CFR 134.45 - Approved markings of country name.

    Science.gov (United States)

    2010-04-01

    ... OF THE TREASURY COUNTRY OF ORIGIN MARKING Method and Location of Marking Imported Articles § 134.45 Approved markings of country name. (a) Language. (1) Except as otherwise provided in paragraph (a)(2) of this section, the markings required by this part shall include the full English name of the country...

  6. 46 CFR 108.646 - Marking of stowage locations.

    Science.gov (United States)

    2010-10-01

    ... AND EQUIPMENT Equipment Markings and Instructions § 108.646 Marking of stowage locations. (a) Containers, brackets, racks, and other similar stowage locations for lifesaving equipment, must be marked... 46 Shipping 4 2010-10-01 2010-10-01 false Marking of stowage locations. 108.646 Section...

  7. 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

  8. MARKS OF ETHNICITY IN PURPLE HIBISCUS TRANSLATION

    Directory of Open Access Journals (Sweden)

    Fernanda de Oliveira Müller

    2016-10-01

    Full Text Available This study gives an analysis of the English – Brazilian Portuguese translation of Chimamanda Ngozi Adichie’s novel, Purple Hibiscus, made by Julia Romeu. It is an attempt to analyze how traces of ethnic identities marked in the source text are reproduced in the Brazilian version Hibisco Roxo, published in 2011. Initially, is a brief biography of the writer is presented together with her history towards the construction of a new paradigm for the literature about Africa and Nigeria. Adichie challenges Western stereotypes about that continent, which tend to report poverty, war and disease scenarios. Secondly, a summary of the story was made and the main characters were described. Thirdly, a collection of recorded words and phrases in the Igbo language was compiled from the original text and an analysis of the translation of those terms into Brazilian Portuguese was performed. Afterwards, the concept of ethnicity described by the sociologist Anthony Giddens was presented. Based on that concept, it was concluded that the terms previously selected could be considered as marks of ethnicity, reflecting the presence of the Igbo ethnic group in the British colonial culture. Finally, taking Antoine Berman’s proposition for an ethical translation, which embraces the foreign and rejects ethnocentrism, the conclusion to be drawn is that the translator’s option to keep Igbo terms in her work respected the author’s manifest intention of, through her work, showing the readers from other countries a bit of Nigeria’s culture and history.

  9. The Five Marks of the Mental

    Directory of Open Access Journals (Sweden)

    Tuomas K. Pernu

    2017-07-01

    Full Text Available 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.

  10. Control of helicase loading in the coupled DNA replication and recombination systems of bacteriophage T4.

    Science.gov (United States)

    Branagan, Amy M; Klein, Jenny A; Jordan, Christian S; Morrical, Scott W

    2014-01-31

    The Gp59 protein of bacteriophage T4 promotes DNA replication by loading the replicative helicase, Gp41, onto replication forks and recombination intermediates. Gp59 also blocks DNA synthesis by Gp43 polymerase until Gp41 is loaded, ensuring that synthesis is tightly coupled to unwinding. The distinct polymerase blocking and helicase loading activities of Gp59 likely involve different binding interactions with DNA and protein partners. Here, we investigate how interactions of Gp59 with DNA and Gp32, the T4 single-stranded DNA (ssDNA)-binding protein, are related to these activities. A previously characterized mutant, Gp59-I87A, exhibits markedly reduced affinity for ssDNA and pseudo-fork DNA substrates. We demonstrate that on Gp32-covered ssDNA, the DNA binding defect of Gp59-I87A is not detrimental to helicase loading and translocation. In contrast, on pseudo-fork DNA the I87A mutation is detrimental to helicase loading and unwinding in the presence or absence of Gp32. Other results indicate that Gp32 binding to lagging strand ssDNA relieves the blockage of Gp43 polymerase activity by Gp59, whereas the inhibition of Gp43 exonuclease activity is maintained. Our findings suggest that Gp59-Gp32 and Gp59-DNA interactions perform separate but complementary roles in T4 DNA metabolism; Gp59-Gp32 interactions are needed to load Gp41 onto D-loops, and other nucleoprotein structures containing clusters of Gp32. Gp59-DNA interactions are needed to load Gp41 onto nascent or collapsed replication forks lacking clusters of Gp32 and to coordinate bidirectional replication from T4 origins. The dual functionalities of Gp59 allow it to promote the initiation or re-start of DNA replication from a wide variety of recombination and replication intermediates.

  11. Future Events

    Directory of Open Access Journals (Sweden)

    Adli Tıp Uzmanları Derneği ATUD

    2006-12-01

    : Cambridge Healthtech Institute 250 First Avenue, Suite 300 Needham, MA 02494 (781 972-5400 or (888 999-6288 - Fax: (781 972-5425 www.healthtech.com SCANNING 2007 “Scanning Microscopy In Forensics Science” 10-12 April 2007 CA,USA Further information S. Frank Platek, Forensic Chemistry Center, US Food and Drug Administration, 6751 Steger Drive, Cincinnati, OH Tel: 513-679-2700 x254 - Email: fplatek@ora.fda.gov Web: www.fams.org The 9th Annual Conference of BAHID 12-14 April 2007, United Kingdom University of Surrey, Guildford Further information: Web:www.bahid.org AFDIL’s International Training Course 16-20 April 2007, USA Extraction of DNA from Aged Skeletal Remains and Forensic Mitochondrial DNA Sequence Further information: The Armed Forces DNA Identification Laboratory, 1413 Research Blvd, Bldg, 101, Rockville, MD 20850 25th Annual CME Symposium in Forensic Psychiatry April 26-29, 2007 Santa Fe, New Mexico - Inn and Spa at Loretto Further information: American College of Forensic Psychiatry PO Box 5870, Balboa Island CA 92662 Tel: (949 673-7773 - www.forensicpsychonline.com Scanning Microscopy in Forensic Science - A 3-Day Symposium at SCANNING 2007 10-12 April To be held at the Portola Plaza Hotel at Monterey Bay in Monterey, CA. Mark K. Sullivan Program Planning Committee SCANNING 2007 PO Box 485 Mahwah, NJ 07430-0485 (201 818-1010 Fax: (201 818-0086 mks@fams.org - www.fams.org -www.scanning2007.org 7th Annual Proteomic and Genomic Sample Preparation Conference - Optimizing Samples for Diagnostics and Drug Discovery 11-13 April To be held at the World Trade Center in Boston, MA. Margit Eder, PhD Conference Director Cambridge Healthtech Institute (781 972-5478 - Fax: (781 972-5425 meder@healthtech.com - www.GOTSummit.com Forensic Medical Investigation Comprehensive Review Course 11-13 April To be held in Atlantic City, NJ. CONTACT: Michael Henderson or Mary Dudley, MD Forensic Medical Investigation Institute 6505 East Central; PMB#176 Wichita, KS 67206-1924 mike

  12. Replicating function of the RS1 element associated with Vibrio cholerae CTX phi prophage.

    Science.gov (United States)

    Campos, J; Fando, R; Silva, A; Rodriguez, B L; Benitez, J A

    1998-07-01

    The RS1 element associated with Vibrio cholerae CTX phi prophage was cloned from an E1 Tor biotype Vibrio cholerae strain. We used the recA- vaccine strain Peru-15, that lacks the target for RS-mediated site-specific integration, to show that RS1 promotes autonomous replication of a suicide vector. A linker insertion in the rstR open reading frame abolished autonomous replication in Peru-15 but not in a strain containing an RS1 in the chromosome. An AT-rich region containing cis-acting elements involved in autonomous replication was identified by deletion. This region was sufficient to support autonomous replication in a strain containing an RS1 in the chromosome. DNA sequence analysis of a region present in RS1 and not RS2 revealed the presence of putative binding sites for host proteins involved in plasmid replication. These results indicate that RS1 contains a replicon distinct from RS2 which could be involved in replicative recombination events associated with tandem amplification of the CTX element.

  13. Characteristics of DNA replication in isolated nuclei initiated by an aprotinin-binding protein.

    Science.gov (United States)

    Coffman, F D; Fresa, K L; Hameed, M; Cohen, S

    1993-02-01

    Isolated cell nuclei were used as the source of template DNA to investigate the role of a cytosolic aprotinin-binding protein (ADR) in the initiation of eukaryotic DNA replication. Computerized image cytometry demonstrated that the DNA content of individual nuclei increased significantly following incubation with ADR-containing preparations, and the extent of DNA synthesis is consistent with that allowed by the limiting concentration of dTTP. Thus, dTTP incorporation into isolated nuclei represents DNA synthesis and not parent strand repair. We found that dTTP incorporation into the isolated nuclei is dependent on DNA polymerase alpha (a principal polymerase in DNA replication) but that DNA polymerase beta (a principal polymerase in DNA repair processes) does not play a significant role in this system. Finally, neither aprotinin nor a previously described cytosolic ADR inhibitor can block the replication of nuclease-treated calf thymus DNA, while both strongly inhibit replication of DNA in isolated nuclei. This result, coupled with the relative ineffectiveness of nuclease-treated DNA compared with nuclear DNA to serve as a replicative template in this assay, argues against a significant contribution from repair or synthesis which initiates at a site of DNA damage. These data indicate that ADR-mediated incorporation of 3H-dTTP into isolated nuclei results from DNA replicative processes that are directly relevant to in vivo S phase events.

  14. Dynamics of Escherichia coli chromosome segregation during multifork replication.

    Science.gov (United States)

    Nielsen, Henrik J; Youngren, Brenda; Hansen, Flemming G; Austin, Stuart

    2007-12-01

    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 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 cohesion of sister DNA regions was seen at any growth rate. We conclude that segregation is driven by the progression of the replication forks.

  15. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Graves, C.E.

    1997-09-29

    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.

  17. 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).

  18. Self-replication with magnetic dipolar colloids.

    Science.gov (United States)

    Dempster, Joshua M; Zhang, Rui; Olvera de la Cruz, Monica

    2015-10-01

    Colloidal self-replication represents an exciting research frontier in soft matter physics. Currently, all reported self-replication schemes involve coating colloidal particles with stimuli-responsive molecules to allow switchable interactions. In this paper, we introduce a scheme using ferromagnetic dipolar colloids and preprogrammed external magnetic fields to create an autonomous self-replication system. Interparticle dipole-dipole forces and periodically varying weak-strong magnetic fields cooperate to drive colloid monomers from the solute onto templates, bind them into replicas, and dissolve template complexes. We present three general design principles for autonomous linear replicators, derived from a focused study of a minimalist sphere-dimer magnetic system in which single binding sites allow formation of dimeric templates. We show via statistical models and computer simulations that our system exhibits nonlinear growth of templates and produces nearly exponential growth (low error rate) upon adding an optimized competing electrostatic potential. We devise experimental strategies for constructing the required magnetic colloids based on documented laboratory techniques. We also present qualitative ideas about building more complex self-replicating structures utilizing magnetic colloids.

  19. A Self-Replicating Ligase Ribozyme

    Science.gov (United States)

    Paul, Natasha; Joyce, Gerald F.

    2002-01-01

    A self-replicating molecule directs the covalent assembly of component molecules to form a product that is of identical composition to the parent. When the newly formed product also is able to direct the assembly of product molecules, the self-replicating system can be termed autocatalytic. A self-replicating system was developed based on a ribozyme that catalyzes the assembly of additional copies of Itself through an RNA-catalyzed RNA ligation reaction. The R3C ligase ribozyme was redesigned so that it would ligate two substrates to generate an exact copy of itself, which then would behave in a similar manner. This self-replicating system depends on the catalytic nature of the RNA for the generation of copies. A linear dependence was observed between the initial rate of formation of new copies and the starting concentration of ribozyme, consistent with exponential growth. The autocatalytic rate constant was 0.011 per min, whereas the initial rate of reaction in the absence of pre-existing ribozyme was only 3.3 x 10(exp -11) M per min. Exponential growth was limited, however, because newly formed ribozyme molecules had greater difficulty forming a productive complex with the two substrates. Further optimization of the system may lead to the sustained exponential growth of ribozymes that undergo self-replication.

  20. Spacetime replication of continuous variable quantum information

    Science.gov (United States)

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

    2016-08-01

    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.

  1. 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.

  2. 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.

  3. Inhibition of vesicular stomatitis virus replication in the course of HIV infection in patients with different stages of immunodeficiency.

    Science.gov (United States)

    Piasecki, Egbert; Knysz, Brygida; Zwolińska, Katarzyna; Gąsiorowski, Jacek; Lorenc, Maria; Zalewska, Małgorzata; Gładysz, Andrzej; Siemieniec, Iwona; Pazgan-Simon, Monika

    2010-12-01

    The replication of vesicular stomatitis virus (VSV) in isolated human leukocytes has been used to measure the level of nonspecific antiviral immunity. However, during infection with some pathogens, the main effect observed is caused by interaction between the pathogen and VSV. This was also noted in advanced stages of HIV infection, when an inverse association between HIV viral load and VSV replication was found. The mutual effect was markedly stronger than the correlation between the VSV replication level and CD4(+) T-cell count. Since successful antiretroviral therapy is associated with a decrease in HIV viremia to undetectable levels, the effect of such therapy on VSV replication was expected and confirmed in this investigation. In fact, increased VSV titers were observed together with decreased HIV viral load, particularly in the case of efficient therapeutic schemes, for example those including lopinavir/ritonavir. The results showed that VSV replication capacity reflected the progression of HIV infection. Moreover, the presence of interferon in the plasma of AIDS patients was found to be only partially responsible for the inhibition of VSV replication. The results suggest a specific HIV-VSV interaction, whether direct or indirect. Thus the VSV replication assay may be applied in evaluating the stage of HIV infection.

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

    OpenAIRE

    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 ...

  5. Bulletin Board Ideas: Worldwide Scientific Events

    Science.gov (United States)

    Schiffman, Maurice K.

    1977-01-01

    Describes a bulletin board activity that identifies scientific phenomena occurring worldwide during the school year. A map of the world is marked with colored pins as students find news information of places and kind of event (e.g.; volcanoes, floods, crop failures, human epidemics). (CS)

  6. Content replication and placement in mobile networks

    CERN Document Server

    La, Chi-Anh; Casetti, Claudio; Chiasserini, Carla-Fabiana; Fiore, Marco

    2011-01-01

    Performance and reliability of content access in mobile networks is conditioned by the number and location of content replicas deployed at the network nodes. Location theory has been the traditional, centralized approach to study content replication: computing the number and placement of replicas in a static network can be cast as a facility location problem. The endeavor of this work is to design a practical solution to the above joint optimization problem that is suitable for mobile wireless environments. We thus seek a replication algorithm that is lightweight, distributed, and reactive to network dynamics. We devise a solution that lets nodes (i) share the burden of storing and providing content, so as to achieve load balancing, and (ii) autonomously decide whether to replicate or drop the information, so as to adapt the content availability to dynamic demands and time-varying network topologies. We evaluate our mechanism through simulation, by exploring a wide range of settings, including different node ...

  7. 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.

  8. Replicating Cardiovascular Condition-Birth Month Associations

    Science.gov (United States)

    Li, Li; Boland, Mary Regina; Miotto, Riccardo; Tatonetti, Nicholas P.; Dudley, Joel T.

    2016-01-01

    Independent replication is vital for study findings drawn from Electronic Health Records (EHR). This replication study evaluates the relationship between seasonal effects at birth and lifetime cardiovascular condition risk. We performed a Season-wide Association Study on 1,169,599 patients from Mount Sinai Hospital (MSH) to compute phenome-wide associations between birth month and CVD. We then evaluated if seasonal patterns found at MSH matched those reported at Columbia University Medical Center. Coronary arteriosclerosis, essential hypertension, angina, and pre-infarction syndrome passed phenome-wide significance and their seasonal patterns matched those previously reported. Atrial fibrillation, cardiomyopathy, and chronic myocardial ischemia had consistent patterns but were not phenome-wide significant. We confirm that CVD risk peaks for those born in the late winter/early spring among the evaluated patient populations. The replication findings bolster evidence for a seasonal birth month effect in CVD. Further study is required to identify the environmental and developmental mechanisms. PMID:27624541

  9. 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.

  10. GFLV replication in electroporated grapevine protoplasts.

    Science.gov (United States)

    Valat; Toutain; Courtois; Gaire; Decout; Pinck; Mauro; Burrus

    2000-06-29

    Grapevine fanleaf virus (GFLV), responsible for the economically important court-noué disease, is exclusively transmitted to its natural host in the vineyards through Xiphinema nematodes. We have developed direct inoculation of GFLV into grapevine through protoplast electroporation. Protoplasts were isolated from mesophyll of in vitro-grown plants and from embryogenic cell suspensions. Permeation conditions were determined by monitoring calcein uptake. Low salt poration medium was selected. Electrical conditions leading to strong transient gene expression were also tested for GFLV inoculation (isolate F13). GFLV replication was detected with either virus particles (2 µg) or viral RNA (10 ng) in both protoplast populations, as shown by anti-P38 Western blotting. Direct inoculation and replication were also observed with Arabis mosaic virus (ArMV), a closely related nepovirus, as well as with another GFLV isolate. These results will be valuable in grapevine biotechnology, for GFLV replication studies, transgenic plant screening for GFLV resistance, and biorisk evaluation.

  11. An interview with Mark G. Hans.

    Science.gov (United States)

    Hans, Mark G; Nojima, Matilde da Cunha Gonçalves

    2014-01-01

    It is a great honor to conduct an interview with Professor Mark G. Hans, after following his outstanding work ahead of the Bolton-Brush Growth Study Center and the Department of Orthodontics at the prestigious Case Western Reserve School of Dental Medicine (CWRU) in Cleveland, Ohio. Born in Berea, Ohio, Professor Mark Hans attended Yale University in New Haven, CT, and earned his Bachelor of Science Degree in Chemistry. Upon graduation, Dr. Hans received his DDS and Masters Degree of Science in Dentistry with specialty certification in Orthodontics at Case Western Reserve University. During his education, Dr. Hans’ Master’s Thesis won the Harry Sicher Award for Best Research by an Orthodontic Student and being granted a Presidential Teaching Fellowship. As one of the youngest doctors ever certified by the American Board of Orthodontics, Dr. Hans continues to maintain his board certification. He has worked through academics on a variety of research interests, that includes the demographics of orthodontic practice, digital radiographic data, dental and craniofacial genetics, as obstructive sleep apnea syndrome, with selected publications in these fields. One of his noteworthy contributions to the orthodontic literature came along with Dr. Donald Enlow on the pages of “Essentials of Facial Growth”, being reference on the study of craniofacial growth and development. Dr. Mark Hans’s academic career is linked to CWRU, recognized as the renowned birthplace of research on craniofacial growth and development, where the classic Bolton-Brush Growth Study was historically set. Today, Dr. Hans is the Director of The Bolton-Brush Growth Study Center, performing, with great skill and dedication, the handling of the larger longitudinal sample of bone growth study. He is Associate Dean for Graduate Studies, Professor and Chairman of the Department of Orthodontics, working in clinical and theoretical activities with students of the Undergraduate Course from the School of

  12. Marking Streets to Improve Parking Density

    CERN Document Server

    Xu, Chao

    2015-01-01

    Street parking spots for automobiles are a scarce commodity in most urban environments. The heterogeneity of car sizes makes it inefficient to rigidly define fixed-sized spots. Instead, unmarked streets in cities like New York leave placement decisions to individual drivers, who have no direct incentive to maximize street utilization. In this paper, we explore the effectiveness of two different behavioral interventions designed to encourage better parking, namely (1) educational campaigns to encourage parkers to "kiss the bumper" and reduce the distance between themselves and their neighbors, or (2) painting appropriately-spaced markings on the street and urging drivers to "hit the line". Through analysis and simulation, we establish that the greatest densities are achieved when lines are painted to create spots roughly twice the length of average-sized cars. Kiss-the-bumper campaigns are in principle more effective than hit-the-line for equal degrees of compliance, although we believe that the visual cues of...

  13. Marked Seizure Reduction after MCT Supplementation

    Directory of Open Access Journals (Sweden)

    Raed Azzam

    2013-01-01

    Full Text Available We report the case of a 43-year-old man with history of nonsurgical partial epilepsy who previously failed multiple trials of antiepileptic drugs. Medium-chain triglycerides (MCT were added to his regular diet in the form of pure oil. Subsequently, his seizure frequency was markedly reduced from multiple daily seizures to one seizure every four days. His seizures recurred after transient discontinuation of MCT over a period of ten days. His seizure improvement was achieved at a dose of four tablespoons of MCT twice daily with no reported side effects. He developed significant diarrhea and flatulence at higher doses. We conclude that MCT oil supplementation to regular diet may provide better seizure control in some patients. MCT oil supplementation may be a more tolerable alternative to the standard ketogenic diet.

  14. TRIGA Mark-III reactor dismantling program

    Energy Technology Data Exchange (ETDEWEB)

    Chung, U. S.; Lee, B. J.; Paik, S. T.; Jung, K. J. [TRIGA Research Reactor D and D Project Team, Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1999-07-01

    The activation assessment of the main parts of the TRIGA Mark-III (KRR-2) was estimated to effectively dismantle the activated and contaminated areas. All of the method and the order for decommissioning the KRR-2 have been chosen as a result of the examination of the physical structure and radiological conditions of the reactor component. These decommissioning methods and orders were reviewed as part of the Hazard and Operability (HAZOP) studies for the project. Radiological assessment is also done to protect the workers and the environment from the dismantling work. License documents were submitted to the Ministry of Science and Technology (MOST) at the end of 1998. Practical work of the D and D will start at the end of 1999 once the government issues the license. Radiation protection plan was also set up to control the workers and environment. This paper summarized the main lines of those studies. (author)

  15. Mark IVA DSN 26-meter Subnet

    Science.gov (United States)

    Gordon, D. D.

    1984-01-01

    The Office of Space Tracking and Data Systems' Networks Consolidation Program (NCP), managed by the Jet Propulsion Laboratory (JPL), includes the implementation of a 26-meter Tracking and Communications Subnet as a part of the Mark IV A Deep Space Network (DSN). The incorporatin of this subnet into the DSN will contribute to the NCP goal of consolidating the two NASA ground tracking networks into one tracking network. The 26-meter Tracking and Communication Subnet was designed to provide the capability to support, at each Deep Space Communication Complex, the tracking and data communication requirements of the earth-orbital missions that cannot be supported by the Tracking and Data Relay Satellite System when it becomes operational. Implementation activities and planned capabilities of the subnet are discussed.

  16. An interview with Mark G. Hans

    Science.gov (United States)

    Bolognese, Ana Maria; Palomo, Juan Martin; Miyashita, Kunihiko; Nojima, Lincoln Issamu; Nojima, Matilde da Cunha Gonçalves

    2014-01-01

    It is a great honor to conduct an interview with Professor Mark G. Hans, after following his outstanding work ahead of the Bolton-Brush Growth Study Center and the Department of Orthodontics at the prestigious Case Western Reserve School of Dental Medicine (CWRU) in Cleveland, Ohio. Born in Berea, Ohio, Professor Mark Hans attended Yale University in New Haven, CT, and earned his Bachelor of Science Degree in Chemistry. Upon graduation, Dr. Hans received his DDS and Masters Degree of Science in Dentistry with specialty certification in Orthodontics at Case Western Reserve University. During his education, Dr. Hans' Master's Thesis won the Harry Sicher Award for Best Research by an Orthodontic Student and being granted a Presidential Teaching Fellowship. As one of the youngest doctors ever certified by the American Board of Orthodontics, Dr. Hans continues to maintain his board certification. He has worked through academics on a variety of research interests, that includes the demographics of orthodontic practice, digital radiographic data, dental and craniofacial genetics, as obstructive sleep apnea syndrome, with selected publications in these fields. One of his noteworthy contributions to the orthodontic literature came along with Dr. Donald Enlow on the pages of "Essentials of Facial Growth", being reference on the study of craniofacial growth and development. Dr. Mark Hans's academic career is linked to CWRU, recognized as the renowned birthplace of research on craniofacial growth and development, where the classic Bolton-Brush Growth Study was historically set. Today, Dr. Hans is the Director of The Bolton-Brush Growth Study Center, performing, with great skill and dedication, the handling of the larger longitudinal sample of bone growth study. He is Associate Dean for Graduate Studies, Professor and Chairman of the Department of Orthodontics, working in clinical and theoretical activities with students of the Undergraduate Course from the School of Dental

  17. Event Index - an LHCb Event Search System

    CERN Document Server

    Ustyuzhanin, Andrey

    2015-01-01

    During LHC Run 1, the LHCb experiment recorded around 1011 collision events. This paper describes Event Index | an event search system. Its primary function is to quickly select subsets of events from a combination of conditions, such as the estimated decay channel or number of hits in a subdetector. Event Index is essentially Apache Lucene [1] optimized for read-only indexes distributed over independent shards on independent nodes.

  18. Mark-recapture and mark-resight methods for estimating abundance with remote cameras: a carnivore case study

    Science.gov (United States)

    Alanso, Robert S.; McClintock, Brett T.; Lyren, Lisa M.; Boydston, Erin E.; Crooks, Kevin R.

    2015-01-01

    Abundance estimation of carnivore populations is difficult and has prompted the use of non-invasive detection methods, such as remotely-triggered cameras, to collect data. To analyze photo data, studies focusing on carnivores with unique pelage patterns have utilized a mark-recapture framework and studies of carnivores without unique pelage patterns have used a mark-resight framework. We compared mark-resight and mark-recapture estimation methods to estimate bobcat (Lynx rufus) population sizes, which motivated the development of a new "hybrid" mark-resight model as an alternative to traditional methods. We deployed a sampling grid of 30 cameras throughout the urban southern California study area. Additionally, we physically captured and marked a subset of the bobcat population with GPS telemetry collars. Since we could identify individual bobcats with photos of unique pelage patterns and a subset of the population was physically marked, we were able to use traditional mark-recapture and mark-resight methods, as well as the new “hybrid” mark-resight model we developed to estimate bobcat abundance. We recorded 109 bobcat photos during 4,669 camera nights and physically marked 27 bobcats with GPS telemetry collars. Abundance estimates produced by the traditional mark-recapture, traditional mark-resight, and “hybrid” mark-resight methods were similar, however precision differed depending on the models used. Traditional mark-recapture and mark-resight estimates were relatively imprecise with percent confidence interval lengths exceeding 100% of point estimates. Hybrid mark-resight models produced better precision with percent confidence intervals not exceeding 57%. The increased precision of the hybrid mark-resight method stems from utilizing the complete encounter histories of physically marked individuals (including those never detected by a camera trap) and the encounter histories of naturally marked individuals detected at camera traps. This new estimator

  19. Mark-recapture and mark-resight methods for estimating abundance with remote cameras: a carnivore case study.

    Directory of Open Access Journals (Sweden)

    Robert S Alonso

    Full Text Available Abundance estimation of carnivore populations is difficult and has prompted the use of non-invasive detection methods, such as remotely-triggered cameras, to collect data. To analyze photo data, studies focusing on carnivores with unique pelage patterns have utilized a mark-recapture framework and studies of carnivores without unique pelage patterns have used a mark-resight framework. We compared mark-resight and mark-recapture estimation methods to estimate bobcat (Lynx rufus population sizes, which motivated the development of a new "hybrid" mark-resight model as an alternative to traditional methods. We deployed a sampling grid of 30 cameras throughout the urban southern California study area. Additionally, we physically captured and marked a subset of the bobcat population with GPS telemetry collars. Since we could identify individual bobcats with photos of unique pelage patterns and a subset of the population was physically marked, we were able to use traditional mark-recapture and mark-resight methods, as well as the new "hybrid" mark-resight model we developed to estimate bobcat abundance. We recorded 109 bobcat photos during 4,669 camera nights and physically marked 27 bobcats with GPS telemetry collars. Abundance estimates produced by the traditional mark-recapture, traditional mark-resight, and "hybrid" mark-resight methods were similar, however precision differed depending on the models used. Traditional mark-recapture and mark-resight estimates were relatively imprecise with percent confidence interval lengths exceeding 100% of point estimates. Hybrid mark-resight models produced better precision with percent confidence intervals not exceeding 57%. The increased precision of the hybrid mark-resight method stems from utilizing the complete encounter histories of physically marked individuals (including those never detected by a camera trap and the encounter histories of naturally marked individuals detected at camera traps. This new

  20. Suppression of Adenovirus Replication by Cardiotonic Steroids.

    Science.gov (United States)

    Grosso, Filomena; Stoilov, Peter; Lingwood, Clifford; Brown, Martha; Cochrane, Alan

    2017-02-01

    The dependence of adenovirus on the host pre-RNA splicing machinery for expression of its complete genome potentially makes it vulnerable to modulators of RNA splicing, such as digoxin and digitoxin. Both drugs reduced the yields of four human adenoviruses (HAdV-A31, -B35, and -C5 and a species D conjunctivitis isolate) by at least 2 to 3 logs by affecting one or more steps needed for genome replication. Immediate early E1A protein levels are unaffected by the drugs, but synthesis of the delayed protein E4orf6 and the major late capsid protein hexon is compromised. Quantitative reverse transcription-PCR (qRT-PCR) analyses revealed that both drugs altered E1A RNA splicing (favoring the production of 13S over 12S RNA) early in infection and partially blocked the transition from 12S and 13S to 9S RNA at late stages of virus replication. Expression of multiple late viral protein mRNAs was lost in the presence of either drug, consistent with the observed block in viral DNA replication. The antiviral effect was dependent on the continued presence of the drug and was rapidly reversible. RIDK34, a derivative of convallotoxin, although having more potent antiviral activity, did not show an improved selectivity index. All three drugs reduced metabolic activity to some degree without evidence of cell death. By blocking adenovirus replication at one or more steps beyond the onset of E1A expression and prior to genome replication, digoxin and digitoxin show potential as antiviral agents for treatment of serious adenovirus infections. Furthermore, understanding the mechanism(s) by which digoxin and digitoxin inhibit adenovirus replication will guide the development of novel antiviral therapies.

  1. Gastrointestinal events with clopidogrel

    DEFF Research Database (Denmark)

    Grove, Erik Lerkevang; Würtz, Morten; Schwarz, Peter

    2013-01-01

    Clopidogrel prevents cardiovascular events, but has been linked with adverse gastrointestinal (GI) complications, particularly bleeding events.......Clopidogrel prevents cardiovascular events, but has been linked with adverse gastrointestinal (GI) complications, particularly bleeding events....

  2. (Ubi)quitin' the h2bit: recent insights into the roles of H2B ubiquitylation in DNA replication and transcription.

    Science.gov (United States)

    Wright, Duncan E; Kao, Cheng-Fu

    2015-01-01

    The reversible ubiquitylation of histone H2B has long been known to regulate gene transcription, and is now understood to modulate DNA replication as well. In this review, we describe how recent, genome-wide analyses have demonstrated that this histone mark has further reaching effects on transcription and replication than once thought. We also consider the ongoing efforts to elucidate the molecular mechanisms by which H2B ubiquitylation affects processes on the DNA template, and outline the various hypothetical scenarios.

  3. The replication of expansive production knowledge

    DEFF Research Database (Denmark)

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

    2012-01-01

    . Design/methodology/approach – Two case studies are introduced. Empirical data were collected over a period of two years based on interviews and participating observations. Findings – The findings show that (1) knowledge transfer within the replication of a production line is a stepwise expansive process......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 principles to transfer productive knowledge in a specific context, which, in this paper, is a production line....

  4. Chromatin challenges during DNA replication and repair

    DEFF Research Database (Denmark)

    Groth, Anja; Rocha, Walter; Verreault, Alain

    2007-01-01

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

  5. 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.

  6. Replication, recombination, and repair: going for the gold.

    Science.gov (United States)

    Klein, Hannah L; Kreuzer, Kenneth N

    2002-03-01

    DNA recombination is now appreciated to be integral to DNA replication and cell survival. Recombination allows replication to successfully maneuver through the roadblocks of damaged or collapsed replication forks. The signals and controls that permit cells to transition between replication and recombination modes are now being identified.

  7. Direct visualization of replication dynamics in early zebrafish embryos.

    Science.gov (United States)

    Kuriya, Kenji; Higashiyama, Eriko; Avşar-Ban, Eriko; Okochi, Nanami; Hattori, Kaede; Ogata, Shin; Takebayashi, Shin-Ichiro; Ogata, Masato; Tamaru, Yutaka; Okumura, Katsuzumi

    2016-05-01

    We analyzed DNA replication in early zebrafish embryos. The replicating DNA of whole embryos was labeled with the thymidine analog 5-ethynyl-2'-deoxyuridine (EdU), and spatial regulation of replication sites was visualized in single embryo-derived cells. The results unveiled uncharacterized replication dynamics during zebrafish early embryogenesis.

  8. A structural and functional perspective of alphavirus replication and assembly.

    Science.gov (United States)

    Jose, Joyce; Snyder, Jonathan E; Kuhn, Richard J

    2009-09-01

    Alphaviruses are small, spherical, enveloped, positive-sense ssRNA viruses responsible for a considerable number of human and animal diseases. Alphavirus members include Chikungunya virus, Sindbis virus, Semliki Forest virus, the western, eastern and Venezuelan equine encephalitis viruses, and the Ross River virus. Alphaviruses can cause arthritic diseases and encephalitis in humans and animals and continue to be a worldwide threat. The viruses are transmitted by blood-sucking arthropods, and replicate in both arthropod and vertebrate hosts. Alphaviruses form spherical particles (65-70 nm in diameter) with icosahedral symmetry and a triangulation number of four. The icosahedral structures of alphaviruses have been defined to very high resolutions by cryo-electron microscopy and crystallographic studies. In this review, we summarize the major events in alphavirus infection: entry, replication, assembly and budding. We focus on data acquired from structural and functional studies of the alphaviruses. These structural and functional data provide a broader perspective of the virus lifecycle and structure, and allow additional insight into these important viruses.

  9. End of the beginning: elongation and termination features of alternative modes of chromosomal replication initiation in bacteria.

    Directory of Open Access Journals (Sweden)

    Jayaraman Gowrishankar

    2015-01-01

    Full Text Available In bacterial cells, bidirectional replication of the circular chromosome is initiated from a single origin (oriC and terminates in an antipodal terminus region such that movement of the pair of replication forks is largely codirectional with transcription. The terminus region is flanked by discrete Ter sequences that act as polar, or direction-dependent, arrest sites for fork progression. Alternative oriC-independent modes of replication initiation are possible, one of which is constitutive stable DNA replication (cSDR from transcription-associated RNA-DNA hybrids or R-loops. Here, I discuss the distinctive attributes of fork progression and termination associated with different modes of bacterial replication initiation. Two hypothetical models are proposed: that head-on collisions between pairs of replication forks, which are a feature of replication termination in all kingdoms of life, provoke bilateral fork reversal reactions; and that cSDR is characterized by existence of distinct subpopulations in bacterial cultures and a widespread distribution of origins in the genome, each with a small firing potential. Since R-loops are known to exist in eukaryotic cells and to inflict genome damage in G1 phase, it is possible that cSDR-like events promote aberrant replication initiation even in eukaryotes.

  10. Creating Special Events

    Science.gov (United States)

    deLisle, Lee

    2009-01-01

    "Creating Special Events" is organized as a systematic approach to festivals and events for students who seek a career in event management. This book looks at the evolution and history of festivals and events and proceeds to the nuts and bolts of event management. The book presents event management as the means of planning, organizing, directing,…

  11. Spatial regulation and organization of DNA replication within the nucleus.

    Science.gov (United States)

    Natsume, Toyoaki; Tanaka, Tomoyuki U

    2010-01-01

    Duplication of chromosomal DNA is a temporally and spatially regulated process. The timing of DNA replication initiation at various origins is highly coordinated; some origins fire early and others late during S phase. Moreover, inside the nuclei, the bulk of DNA replication is physically organized in replication factories, consisting of DNA polymerases and other replication proteins. In this review article, we discuss how DNA replication is organized and regulated spatially within the nucleus and how this spatial organization is linked to temporal regulation. We focus on DNA replication in budding yeast and fission yeast and, where applicable, compare yeast DNA replication with that in bacteria and metazoans.

  12. Regulation of eukaryotic DNA replication and nuclear structure

    Institute of Scientific and Technical Information of China (English)

    WUJIARUI

    1999-01-01

    In eukaryote,nuclear structure is a key component for the functions of eukaryotic cells.More and more evidences show that the nuclear structure plays important role in regulating DNA replication.The nuclear structure provides a physical barrier for the replication licensing,participates in the decision where DNA replication initiates,and organizes replication proteins as replication factory for DNA replication.Through these works,new concepts on the regulation of DNA replication have emerged,which will be discussed in this minireview.

  13. 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.

  14. 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

  15. Pinnuks silmas - Mark Soosaar 60 / Mark Soosaar ; interv. Jüri Aarma

    Index Scriptorium Estoniae

    Soosaar, Mark, 1946-

    2006-01-01

    Mark Soosaare vastused olematutele küsimustele (J. Aarma küsimused vahelt ära võetud). Endast, oma uuest filmist "Vabatahtlikud" ja muust. Lisatud Sirje Niitra artikkel "Valutab südant" Soosaare muredest ja võitlustest seoses Pärnu linnaga

  16. Pinnuks silmas - Mark Soosaar 60 / Mark Soosaar ; interv. Jüri Aarma

    Index Scriptorium Estoniae

    Soosaar, Mark, 1946-

    2006-01-01

    Mark Soosaare vastused olematutele küsimustele (J. Aarma küsimused vahelt ära võetud). Endast, oma uuest filmist "Vabatahtlikud" ja muust. Lisatud Sirje Niitra artikkel "Valutab südant" Soosaare muredest ja võitlustest seoses Pärnu linnaga

  17. Spatial regulation and organization of DNA replication within the nucleus

    OpenAIRE

    2009-01-01

    Duplication of chromosomal DNA is a temporally and spatially regulated process. The timing of DNA replication initiation at various origins is highly coordinated; some origins fire early and others late during S phase. Moreover, inside the nuclei, the bulk of DNA replication is physically organized in replication factories, consisting of DNA polymerases and other replication proteins. In this review article, we discuss how DNA replication is organized and regulated spatially within the nucleu...

  18. POTENT Reconstruction from Mark III Velocities

    Science.gov (United States)

    Dekel, A.; Eldar, A.; Kolatt, T.; Yahil, A.; Willick, J. A.; Faber, S. M.; Courteau, S.; Burstein, D.

    1999-09-01

    We present an improved version of the POTENT method for reconstructing the cosmological velocity and mass density fields from radial peculiar velocities, test it with mock catalogs, and apply it to the Mark III Catalog of Galaxy Peculiar Velocities. The method is improved in several ways: (1) the inhomogeneous Malmquist bias is reduced by grouping and corrected statistically in either forward or inverse analyses of inferred distances, (2) the smoothing into a radial velocity field is optimized such that window and sampling biases are reduced, (3) the density field is derived from the velocity field using an improved weakly nonlinear approximation in Eulerian space, and (4) the computational errors are made negligible compared to the other errors. The method is carefully tested and optimized using realistic mock catalogs based on an N-body simulation that mimics our cosmological neighborhood, and the remaining systematic and random errors are evaluated quantitatively. The Mark III catalog, with ~3300 grouped galaxies, allows a reliable reconstruction with fixed Gaussian smoothing of 10-12 h-1 Mpc out to ~60 h-1 Mpc and beyond in some directions. We present maps of the three-dimensional velocity and mass-density fields and the corresponding errors. The typical systematic and random errors in the density fluctuations inside 40 h-1 Mpc are +/-0.13 and +/-0.18 (for Ω=1). In its gross features, the recovered mass distribution resembles the galaxy distribution in redshift surveys and the mass distribution in a similar POTENT analysis of a complementary velocity catalog (SFI), including such features as the Great Attractor, Perseus-Pisces, and the large void in between. The reconstruction inside ~40 h-1 Mpc is not affected much by a revised calibration of the distance indicators (VM2, tailored to match the velocities from the IRAS 1.2 Jy redshift survey). The volume-weighted bulk velocity within the sphere of radius 50 h-1 Mpc about the Local Group is V50=370+/-110 km s-1

  19. Replication of biotinylated human immunodeficiency viruses.

    Science.gov (United States)

    Belshan, Michael; Matthews, John M; Madson, Christian J

    2011-01-01

    Previous work demonstrated recently the adaptation of the Escherichia coli biotin ligase BirA - biotin acceptor sequence (BAS) labeling system to produce human immunodeficiency virus type 1 viruses with biotinylated integrase (NLXIN(B)) and matrix (NLXMA(B)) proteins (Belshan et al., 2009). This report describes the construction of an HIV permissive cell line stably expressing BirA (SupT1.BirA). Consistent with the results in the previous report, NLXMA(B) replicated similar to wild-type levels and expressed biotinylated Gag and MA proteins in the SupT1.BirA cells, whereas the replication of NLXIN(B) was reduced severely. Three additional HIV type 2 (HIV-2) viruses were constructed with the BAS inserted into the vpx and vpr accessory genes. Two BAS insertions were made into the C-terminal half of the Vpx, including one internal insertion, and one at the N-terminus of Vpr. All three viruses were replication competent in the SupT1.BirA cells and their target proteins biotinylated efficiently and incorporated into virions. These results demonstrate the potential utility of the biotinylation system to label and capture HIV protein complexes in the context of replicating virus.

  20. Chemistry: Small molecular replicators go organic

    Science.gov (United States)

    Taylor, Annette F.

    2016-09-01

    The emergence of complex, dynamic molecular behaviour might have had a role in the origin of life. Such behaviour has now been seen in a reaction network involving small, organic, self-replicating molecules of biological relevance. See Letter p.656

  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...

  2. The replication of expansive production knowledge

    DEFF Research Database (Denmark)

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

    2012-01-01

    exploration, the small sample size is an obvious limitation for generalisation. Practical implications – A roadmap for knowledge transfer within the replication of a production line is suggested, which, together with four managerial suggestions, provides strong support and clear directions to managers...

  3. 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.

  4. Representation dimension of m-replicated algebras

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Let A be a finite-dimensional hereditary algebra over an algebraically closed field and A(m) be the m-replicated algebra of A.We prove that the representation dimension of A(m) is at most 3,and that the dominant dimension of A(m) is at least m.

  5. Multiseason occupancy models for correlated replicate surveys

    Science.gov (United States)

    Hines, James; Nichols, James; Collazo, Jaime

    2014-01-01

    Occupancy surveys collecting data from adjacent (sometimes correlated) spatial replicates have become relatively popular for logistical reasons. Hines et al. (2010) presented one approach to modelling such data for single-season occupancy surveys. Here, we present a multiseason analogue of this model (with corresponding software) for inferences about occupancy dynamics. We include a new parameter to deal with the uncertainty associated with the first spatial replicate for both single-season and multiseason models. We use a case study, based on the brown-headed nuthatch, to assess the need for these models when analysing data from the North American Breeding Bird Survey (BBS), and we test various hypotheses about occupancy dynamics for this species in the south-eastern United States. The new model permits inference about local probabilities of extinction, colonization and occupancy for sampling conducted over multiple seasons. The model performs adequately, based on a small simulation study and on results of the case study analysis. The new model incorporating correlated replicates was strongly favoured by model selection for the BBS data for brown-headed nuthatch (Sitta pusilla). Latitude was found to be an important source of variation in local colonization and occupancy probabilities for brown-headed nuthatch, with both probabilities being higher near the centre of the species range, as opposed to more northern and southern areas. We recommend this new occupancy model for detection–nondetection studies that use potentially correlated replicates.

  6. Structure and replication of hepatitis delta virus

    African Journals Online (AJOL)

    STORAGESEVER

    2008-12-29

    Dec 29, 2008 ... Unidade de Biologia Molecular, Centro de Malária e outras Doenças Tropicais, Instituto de Higiene e Medicina Tropical, ... molecules of both delta antigens (Ryu et al., 1993). This ..... Glenn JS, Watson JA, Havel CM, White JO (1992). ... HDV RNA encoding the large delta antigen cannot replicate. J. Gen.

  7. Are renal ciliopathies (replication) stressed out?

    NARCIS (Netherlands)

    Slaats, Gisela G; Giles, R

    2015-01-01

    Juvenile renal failure is commonly caused by the ciliopathy nephronophthisis (NPHP). Since all NPHP genes regulate cilia function, it has been assumed that NPHP onset is due to cilia loss. However, recent data suggest that DNA damage caused by replication stress, possibly concomitant with or upstrea

  8. 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.

  9. Chromatin determinants of the inner-centromere rely on replication factors with functions that impart cohesion.

    Science.gov (United States)

    Abe, Takuya; Kawasumi, Ryotaro; Arakawa, Hiroshi; Hori, Tetsuya; Shirahige, Katsuhiko; Losada, Ana; Fukagawa, Tatsuo; Branzei, Dana

    2016-10-18

    Replication fork-associated factors promote genome integrity and protect against cancer. Mutations in the DDX11 helicase and the ESCO2 acetyltransferase also cause related developmental disorders classified as cohesinopathies. Here we generated vertebrate model cell lines of these disorders and cohesinopathies-related genes. We found that vertebrate DDX11 and Tim-Tipin are individually needed to compensate for ESCO2 loss in chromosome segregation, with DDX11 also playing complementary roles with ESCO2 in centromeric cohesion. Our study reveals that overt centromeric cohesion loss does not necessarily precede chromosome missegregation, while both these problems correlate with, and possibly originate from, inner-centromere defects involving reduced phosphorylation of histone H3T3 (pH3T3) in the region. Interestingly, the mitotic pH3T3 mark was defective in all analyzed replication-related mutants with functions in cohesion. The results pinpoint mitotic pH3T3 as a postreplicative chromatin mark that is sensitive to replication stress and conducts with different kinetics to robust centromeric cohesion and correct chromosome segregation.

  10. Pfh1 Is an Accessory Replicative Helicase that Interacts with the Replisome to Facilitate Fork Progression and Preserve Genome Integrity.

    Directory of Open Access Journals (Sweden)

    Karin R McDonald

    2016-09-01

    Full Text Available Replicative DNA helicases expose the two strands of the double helix to the replication apparatus, but accessory helicases are often needed to help forks move past naturally occurring hard-to-replicate sites, such as tightly bound proteins, RNA/DNA hybrids, and DNA secondary structures. Although the Schizosaccharomyces pombe 5'-to-3' DNA helicase Pfh1 is known to promote fork progression, its genomic targets, dynamics, and mechanisms of action are largely unknown. Here we address these questions by integrating genome-wide identification of Pfh1 binding sites, comprehensive analysis of the effects of Pfh1 depletion on replication and DNA damage, and proteomic analysis of Pfh1 interaction partners by immunoaffinity purification mass spectrometry. Of the 621 high confidence Pfh1-binding sites in wild type cells, about 40% were sites of fork slowing (as marked by high DNA polymerase occupancy and/or DNA damage (as marked by high levels of phosphorylated H2A. The replication and integrity of tRNA and 5S rRNA genes, highly transcribed RNA polymerase II genes, and nucleosome depleted regions were particularly Pfh1-dependent. The association of Pfh1 with genomic integrity at highly transcribed genes was S phase dependent, and thus unlikely to be an artifact of high transcription rates. Although Pfh1 affected replication and suppressed DNA damage at discrete sites throughout the genome, Pfh1 and the replicative DNA polymerase bound to similar extents to both Pfh1-dependent and independent sites, suggesting that Pfh1 is proximal to the replication machinery during S phase. Consistent with this interpretation, Pfh1 co-purified with many key replisome components, including the hexameric MCM helicase, replicative DNA polymerases, RPA, and the processivity clamp PCNA in an S phase dependent manner. Thus, we conclude that Pfh1 is an accessory DNA helicase that interacts with the replisome and promotes replication and suppresses DNA damage at hard-to-replicate

  11. ReplicationDomain: a visualization tool and comparative database for genome-wide replication timing data

    Directory of Open Access Journals (Sweden)

    Yokochi Tomoki

    2008-12-01

    Full Text Available Abstract Background Eukaryotic DNA replication is regulated at the level of large chromosomal domains (0.5–5 megabases in mammals within which replicons are activated relatively synchronously. These domains replicate in a specific temporal order during S-phase and our genome-wide analyses of replication timing have demonstrated that this temporal order of domain replication is a stable property of specific cell types. Results We have developed ReplicationDomain http://www.replicationdomain.org as a web-based database for analysis of genome-wide replication timing maps (replication profiles from various cell lines and species. This database also provides comparative information of transcriptional expression and is configured to display any genome-wide property (for instance, ChIP-Chip or ChIP-Seq data via an interactive web interface. Our published microarray data sets are publicly available. Users may graphically display these data sets for a selected genomic region and download the data displayed as text files, or alternatively, download complete genome-wide data sets. Furthermore, we have implemented a user registration system that allows registered users to upload their own data sets. Upon uploading, registered users may choose to: (1 view their data sets privately without sharing; (2 share with other registered users; or (3 make their published or "in press" data sets publicly available, which can fulfill journal and funding agencies' requirements for data sharing. Conclusion ReplicationDomain is a novel and powerful tool to facilitate the comparative visualization of replication timing in various cell types as well as other genome-wide chromatin features and is considerably faster and more convenient than existing browsers when viewing multi-megabase segments of chromosomes. Furthermore, the data upload function with the option of private viewing or sharing of data sets between registered users should be a valuable resource for the

  12. 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.

  13. Mark 3 interactive data analysis system

    Science.gov (United States)

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

    1980-01-01

    The interactive data analysis system, a major subset of the total Mark 3 very long baseline interferometry (VLBI) software system is described. The system consists of two major and a number of small programs. These programs provide for the scientific analysis of the observed values of delay and delay rate generated by the VLBI data reduction programs and product the geophysical and astrometric parameters which are among the ultimate products of VLBI. The two major programs are CALC and SOLVE. CALC generates the theoretical values of VLBI delay rate as well as partial derivatives based on apriori values of the geophysical and astronometric parameters. SOLVE is a least squares parameters estimation program which yields the geophysical and astrometric parameters using the observed values by the data processing system and theoretical values and partial derivatives provided by CALC. SOLVE is a highly interactive program in which the user selects the exact form of the recovered parameters and the data to be accepted into the solution.

  14. Precision markedly attenuates repetitive lift capacity.

    Science.gov (United States)

    Collier, Brooke R; Holland, Laura; McGhee, Deirdre; Sampson, John A; Bell, Alison; Stapley, Paul J; Groeller, Herbert

    2014-01-01

    This study investigated the effect of precision on time to task failure in a repetitive whole-body manual handling task. Twelve participants were required to repetitively lift a box weighing 65% of their single repetition maximum to shoulder height using either precise or unconstrained box placement. Muscle activity, forces exerted at the ground, 2D body kinematics, box acceleration and psychophysical measures of performance were recorded until task failure was reached. With precision, time to task failure for repetitive lifting was reduced by 72%, whereas the duration taken to complete a single lift and anterior deltoid muscle activation increased by 39% and 25%, respectively. Yet, no significant difference was observed in ratings of perceived exertion or heart rate at task failure. In conclusion, our results suggest that when accuracy is a characteristic of a repetitive manual handling task, physical work capacity will decline markedly. The capacity to lift repetitively to shoulder height was reduced by 72% when increased accuracy was required to place a box upon a shelf. Lifting strategy and muscle activity were also modified, confirming practitioners should take into consideration movement precision when evaluating the demands of repetitive manual handling tasks.

  15. Typehusbranchens organisation, produktion og marked og innovation

    DEFF Research Database (Denmark)

    Haugbølle, Kim; Forman, Marianne

    Denne dokumentationsrapport beskriver resultaterne af et survey af typehusbranchens organisering, produktion, marked og innovation. På trods af eller måske netop på grund af den aktuelle finanskrise vil en fortsat udvikling af typehusbyggeriet og det industrialiserede byggeri generelt kræve en øget...... forståelse af, hvordan bygherrens og brugernes ønsker, krav og forventninger er med til at forme producenternes produkter og udviklingsstrategier og vice versa. Baseret på et omfattende webbaseret survey via SurveyXact besvarer rapporten fire spørgsmål vedrørende typehusindustrien: - Hvilke karakteristika...... har producenterne? - Hvem er bygherrerne? - Hvilke typer af innovation finder sted? - Hvordan forløber innovationsprocessen? Undersøgelsen yder således et bidrag til en forståelse af byggeriets processer og innovation indenfor et område, som er relativt upåagtet i både dansk og international...

  16. Infrared and visible combat identification marking materials

    Science.gov (United States)

    O'Keefe, Eoin; Shohet, Adam; Swan, Martin

    2007-04-01

    Historically, it is believed that fratricide accounts for up to 15% of friendly casualties during operations and a UK MoD report identifies that almost half of all such casualties occur in situations involving ground units only. Such risks can be mitigated, to an extent, via operational awareness and effective communications. However, recent conflicts have involved a much more dynamic, complex and technically sophisticated battlefield than previously experienced. For example, Operation Telic (Desert Storm) involved almost one million combatants and ten thousand armoured vehicles in the coalition force, advancing across an extensive battlefront at high speed during daylight and at night, making effective use of a range of electro-optic sensors. The accelerated tempo of battle means that front lines can undergo rapid, punctuated advances that can leave individual combat units with a much degraded situational awareness, particularly of where they are in relation to other 'friendly' combatants. Consequently, there is a need for a robust, low cost, low weight, compact, unpowered, interoperable, Combat Identification technique for use with popular electro-optic sensors which can be deployed, and is effective, at the individual combat unit level. In this paper we discuss ground-to-ground combat identification materials that meet these requirements, all of which are based on the air-to-ground Mirage TM vehicle marking material. We show some preliminary ground-to-ground data collected from the new variant Mirage TM material in recent experimental trials conducted during the day, evening and at night.

  17. Habitat Management Plan for St. Marks National Wildlife Refuge

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — The St. Marks NWR Habitat Management Plan provides a long-term vision and specific guidance on managing habitats for the resources of concern at St. Marks NWR, to...

  18. Mark 6 16-Gbps Next-Generation VLBI Data System

    Science.gov (United States)

    Whitney, Alan R.; Cappallo, Roger J.; Ruszczyk, Chester A.; SooHoo, Jason; Crew, Geoffrey B.

    2014-12-01

    The Mark 6 VLBI data system has been developed as a next-generation disk-based VLBI data system capable of supporting the goals of VLBI2010 and other very-high-data-rate VLBI applications, with a maximum sustained recording rate of 16 Gbps. Based on COTS data hardware and open-source software, the Mark 6 is designed to transition easily from the widely used Mark 5 system. Its features include a `scatter/gather' gather algorithm to ensure that data recording is not slowed by one or more slow or bad disks. The first field demonstration of a 16 Gbps/station VLBI experiment using Mark 6 in 2012 is reported. Existing Mark 5 systems are upgradeable to Mark 6, and existing Mark 5 SATA modules are upgradeable for compatibility with Mark 6.

  19. 14 CFR 45.29 - Size of marks.

    Science.gov (United States)

    2010-01-01

    ... weight-shift-control aircraft must be at least 3 inches high; and (3) Rotorcraft, must be at least 12...-control aircraft must display marks at least 3 inches high. (g) Uniformity. The marks required by...

  20. Minimization of sink mark defects in injection molding process ...

    African Journals Online (AJOL)

    Minimization of sink mark defects in injection molding process – Taguchi approach. ... plays a very important role in controlling the quality of the injection molded products. ... of injection molding variables on sink marks using Taguchi approach.

  1. 46 CFR 199.176 - Markings on lifesaving appliances.

    Science.gov (United States)

    2010-10-01

    ... the boat belongs, such as the vessel's name, must be plainly marked or painted so that the markings... and numbers at least 100 millimeters (4 inches) high and in a color contrasting to that of...

  2. 33 CFR 62.29 - Isolated danger marks.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Isolated danger marks. 62.29... NAVIGATION UNITED STATES AIDS TO NAVIGATION SYSTEM The U.S. Aids to Navigation System § 62.29 Isolated danger marks. Isolated danger marks indicate an isolated danger which may be passed on all sides. As...

  3. A J-function for marked point patterns

    NARCIS (Netherlands)

    Lieshout, M.N.M. van

    2004-01-01

    We propose a new summary statistic for marked point patterns. The underlying principle is to compare the distance from a marked point to the nearest other marked point in the pattern to the same distance seen from an arbitrary point in space. Information about the range of interaction can be inferre

  4. 25 CFR 304.3 - Classifying and marking of silver.

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false Classifying and marking of silver. 304.3 Section 304.3 Indians INDIAN ARTS AND CRAFTS BOARD, DEPARTMENT OF THE INTERIOR NAVAJO, PUEBLO, AND HOPI SILVER, USE OF GOVERNMENT MARK § 304.3 Classifying and marking of silver. For the present the Indian Arts and Crafts...

  5. 7 CFR 51.2927 - Marking and packing requirements.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Marking and packing requirements. 51.2927 Section 51... STANDARDS) United States Standards for Grades of Apricots Marking and Packing Requirements § 51.2927 Marking and packing requirements. The minimum size or numerical count of the apricots in any package shall...

  6. The Nature of Object Marking in American Sign Language

    Science.gov (United States)

    Gokgoz, Kadir

    2013-01-01

    In this dissertation, I examine the nature of object marking in American Sign Language (ASL). I investigate object marking by means of directionality (the movement of the verb towards a certain location in signing space) and by means of handling classifiers (certain handshapes accompanying the verb). I propose that object marking in ASL is…

  7. 33 CFR 64.33 - Marking by the Coast Guard.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Marking by the Coast Guard. 64.33 Section 64.33 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY AIDS TO... Marking by the Coast Guard. (a) The District Commander may mark for the protection of maritime...

  8. 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... container except by an inspector or under the supervision of an inspector or other person authorized by...

  9. Marking Strategies in Metacognition-Evaluated Computer-Based Testing

    Science.gov (United States)

    Chen, Li-Ju; Ho, Rong-Guey; Yen, Yung-Chin

    2010-01-01

    This study aimed to explore the effects of marking and metacognition-evaluated feedback (MEF) in computer-based testing (CBT) on student performance and review behavior. Marking is a strategy, in which students place a question mark next to a test item to indicate an uncertain answer. The MEF provided students with feedback on test results…

  10. 19 CFR 134.11 - Country of origin marking required.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Country of origin marking required. 134.11 Section... OF THE TREASURY COUNTRY OF ORIGIN MARKING Articles Subject to Marking § 134.11 Country of origin... English name of the country of origin of the article, at the time of importation into the...

  11. 16 CFR 300.9 - Abbreviations, ditto marks, and asterisks.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Abbreviations, ditto marks, and asterisks..., ditto marks, and asterisks. (a) In disclosing required information, words or terms shall not be designated by ditto marks or appear in footnotes referred to by asterisks or other symbols in...

  12. 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...

  13. 47 CFR 74.30 - Antenna structure, marking and lighting.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 4 2010-10-01 2010-10-01 false Antenna structure, marking and lighting. 74.30... Applicable to All Services in Part 74 § 74.30 Antenna structure, marking and lighting. The provisions of part 17 of the FCC rules (Construction, Marking, and Lighting of Antenna Structures) require...

  14. A Review on Denture Marking Systems: A Mark in Forensic Dentistry.

    Science.gov (United States)

    Kareker, Nikita; Aras, Meena; Chitre, Vidya

    2014-12-01

    "Identification through forensic science is an art of giving the corpse a name A real life detective work that would put even Sherlock Homes to shame." Forensic dentistry deals with proper handling and examination of dental evidence and proper evaluation and presentation of dental findings in interest of justice. The Prosthodontists are playing a very important role in forensic dentistry as they are concerned with fabrication of various prosthesis which can serve as an important tool for identification. Identification is essential requirement of any medico-legal investigation because a wrong identity may pose a problem in delivering justice. This article describes the different methods for identification/marking of the complete dentures, removable partial dentures and fixed partial dentures and the importance of denture marking in forensic investigatory purposes. The PubMed, Ebsco and Google search engines were used to gather the articles.

  15. Study on the micro-replication of shark skin

    Institute of Scientific and Technical Information of China (English)

    HAN Xin; ZHANG DeYuan

    2008-01-01

    Direct replication of creatural scarfskins to form biomimetic surfaces with relatively vivid morphology is a new attempt of the bio-replicated forming technology at animal body.Taking shark skins as the replication templates,and the micro-em-bossing and micro-molding as the material forming methods,the micro-replicating technology of the outward morphology on shark skins was demonstrated.The pre-liminary analysis on replication precision indicates that the bio-replicated forming technology can replicate the outward morphology of the shark scales with good precision,which validates the application of the bio-replicated forming technology in the direct morphology replication of the firm creatural scarfskins.

  16. 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.

  17. A replication-time-controlling sequence element in Schizosaccharomyces pombe.

    Science.gov (United States)

    Tripathi, Vishnu P; Dubey, Dharani D

    2017-08-01

    Eukaryotic replication origins are highly variable in their activity and replication timing. The nature and role of cis-acting regulatory sequences that control chromosomal replication timing is not well defined. In the fission yeast, Schizosaccharomyces pombe, a 200-bp late-replication-enforcing element (LRE), has been shown to enforce late replication of ARS elements in plasmids. Here, we show that a short (133-bp) fragment of the LRE (shLRE) is required for causing late replication of adjoining origins in its native as well as in an ectopic early-replicating chromosomal location. Active from both sides of an early-replicating origin, the shLRE is a bona fide cis-acting regulatory element that imposes late replication timing in the chromosome.

  18. 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.

  19. 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.

  20. Single molecule analysis of Trypanosoma brucei DNA replication dynamics.

    Science.gov (United States)

    Calderano, Simone Guedes; Drosopoulos, William C; Quaresma, Marina Mônaco; Marques, Catarina A; Kosiyatrakul, Settapong; McCulloch, Richard; Schildkraut, Carl L; Elias, Maria Carolina

    2015-03-11

    Eukaryotic genome duplication relies on origins of replication, distributed over multiple chromosomes, to initiate DNA replication. A recent genome-wide analysis of Trypanosoma brucei, the etiological agent of sleeping sickness, localized its replication origins to the boundaries of multigenic transcription units. To better understand genomic replication in this organism, we examined replication by single molecule analysis of replicated DNA. We determined the average speed of replication forks of procyclic and bloodstream form cells and we found that T. brucei DNA replication rate is similar to rates seen in other eukaryotes. We also analyzed the replication dynamics of a central region of chromosome 1 in procyclic forms. We present evidence for replication terminating within the central part of the chromosome and thus emanating from both sides, suggesting a previously unmapped origin toward the 5' extremity of chromosome 1. Also, termination is not at a fixed location in chromosome 1, but is rather variable. Importantly, we found a replication origin located near an ORC1/CDC6 binding site that is detected after replicative stress induced by hydroxyurea treatment, suggesting it may be a dormant origin activated in response to replicative stress. Collectively, our findings support the existence of more replication origins in T. brucei than previously appreciated.

  1. 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

  2. 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

  3. 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.

  4. Murine gamma-herpesvirus 68 hijacks MAVS and IKKbeta to initiate lytic replication.

    Directory of Open Access Journals (Sweden)

    Xiaonan Dong

    2010-07-01

    Full Text Available Upon viral infection, the mitochondrial antiviral signaling (MAVS-IKKbeta pathway is activated to restrict viral replication. Manipulation of immune signaling events by pathogens has been an outstanding theme of host-pathogen interaction. Here we report that the loss of MAVS or IKKbeta impaired the lytic replication of gamma-herpesvirus 68 (gammaHV68, a model herpesvirus for human Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus. gammaHV68 infection activated IKKbeta in a MAVS-dependent manner; however, IKKbeta phosphorylated and promoted the transcriptional activation of the gammaHV68 replication and transcription activator (RTA. Mutational analyses identified IKKbeta phosphorylation sites, through which RTA-mediated transcription was increased by IKKbeta, within the transactivation domain of RTA. Moreover, the lytic replication of recombinant gammaHV68 carrying mutations within the IKKbeta phosphorylation sites was greatly impaired. These findings support the conclusion that gammaHV68 hijacks the antiviral MAVS-IKKbeta pathway to promote viral transcription and lytic infection, representing an example whereby viral replication is coupled to host immune activation.

  5. 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

  6. The Rtt107 BRCT scaffold and its partner modification enzymes collaborate to promote replication.

    Science.gov (United States)

    Hang, Lisa; Zhao, Xiaolan

    2016-07-03

    Faithful duplication of the entire genome during each cell cycle is key for genome maintenance. Each stage of DNA replication, including initiation, progression, and termination, is tightly regulated. Some of these regulations enable replisomes to overcome tens of thousands of template obstacles that block DNA synthesis. Previous studies have identified a large number of proteins that are dedicated to this mission, including protein modification enzymes and scaffold proteins. Protein modification enzymes can bestow fast and reversible changes on many substrates, and thus are ideal for coordinating multiple events needed to promptly overcome replication impediments. Scaffold proteins can support specific protein-protein interactions that enable protein complex formation, protein recruitment, and partner enzyme functions. Taken together with previous studies, our recent work elucidates that a group of modification and scaffold proteins form several complexes to aid replication progression and are particularly important for synthesizing large replicons. Additionally, our work reveals that the intrinsic plasticity of the replication initiation program can be used to compensate for deficient replication progression. (1).

  7. 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.

  8. Novel Mutant AAV2 Rep Proteins Support AAV2 Replication without Blocking HSV-1 Helpervirus Replication

    Science.gov (United States)

    Seyffert, Michael; Glauser, Daniel L.; Schraner, Elisabeth M.; de Oliveira, Anna-Paula; Mansilla-Soto, Jorge; Vogt, Bernd; Büning, Hildegard; Linden, R. Michael; Ackermann, Mathias; Fraefel, Cornel

    2017-01-01

    As their names imply, parvoviruses of the genus Dependovirus rely for their efficient replication on the concurrent presence of a helpervirus, such as herpesvirus, adenovirus, or papilloma virus. Adeno-associated virus 2 (AAV2) is such an example, which in turn can efficiently inhibit the replication of each helpervirus by distinct mechanisms. In a previous study we have shown that expression of the AAV2 rep gene is not compatible with efficient replication of herpes simplex virus 1 (HSV-1). In particular, the combined DNA-binding and ATPase/helicase activities of the Rep68/78 proteins have been shown to exert opposite effects on the replication of AAV2 and HSV-1. While essential for AAV2 DNA replication these protein activities account for the Rep-mediated inhibition of HSV-1 replication. Here, we describe a novel Rep mutant (Rep-D371Y), which displayed an unexpected phenotype. Rep-D371Y did not block HSV-1 replication, but still supported efficient AAV2 replication, at least when a double-stranded AAV2 genome template was used. We also found that the capacity of Rep-D371Y to induce apoptosis and a Rep-specific DNA damage response was significantly reduced compared to wild-type Rep. These findings suggest that AAV2 Rep-helicase subdomains exert diverging activities, which contribute to distinct steps of the AAV2 life cycle. More important, the novel AAV2 mutant Rep-D371Y may allow deciphering yet unsolved activities of the AAV2 Rep proteins such as DNA second-strand synthesis, genomic integration or packaging, which all involve the Rep-helicase activity. PMID:28125695

  9. 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.

    2013-01-01

    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 79 years 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. PMID:23942350

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

    Science.gov (United States)

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

    2017-01-01

    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. PMID:28270517

  11. Replicative Homeostasis: A fundamental mechanism mediating selective viral replication and escape mutation

    Directory of Open Access Journals (Sweden)

    Sallie Richard

    2005-02-01

    Full Text Available Abstract Hepatitis C (HCV, hepatitis B (HBV, the human immunodeficiency viruses (HIV, and other viruses that replicate via RNA intermediaries, cause an enormous burden of disease and premature death worldwide. These viruses circulate within infected hosts as vast populations of closely related, but genetically diverse, molecules known as "quasispecies". The mechanism(s by which this extreme genetic and antigenic diversity is stably maintained are unclear, but are fundamental to understanding viral persistence and pathobiology. The persistence of HCV, an RNA virus, is especially problematic and HCV stability, maintained despite rapid genomic mutation, is highly paradoxical. This paper presents the hypothesis, and evidence, that viruses capable of persistent infection autoregulate replication and the likely mechanism mediating autoregulation – Replicative Homeostasis – is described. Replicative homeostasis causes formation of stable, but highly reactive, equilibria that drive quasispecies expansion and generates escape mutation. Replicative homeostasis explains both viral kinetics and the enigma of RNA quasispecies stability and provides a rational, mechanistic basis for all observed viral behaviours and host responses. More importantly, this paradigm has specific therapeutic implication and defines, precisely, new approaches to antiviral therapy. Replicative homeostasis may also modulate cellular gene expression.

  12. Cultural Differences in the Translation of Trade Marks

    Institute of Scientific and Technical Information of China (English)

    何懿文

    2008-01-01

    As more and more Chinese products are getting into foreign markets, it is important to translate a Chinese trade mark into English properly. This paper points out what is a trade mark and its importance in the modern world. It then gives reason why it is necessary to translate the Chinese trade marks properly into English. It also gives the standard of a good trade mark. Furthermore it analyses several kinds of improper translation and the cause of these mistakes, last it introduces the main rules and three main skills of translation of trade marks.

  13. Escalation of error catastrophe for enzymatic self-replicators

    Science.gov (United States)

    Obermayer, B.; Frey, E.

    2009-11-01

    It is a long-standing question in origin-of-life research whether the information content of replicating molecules can be maintained in the presence of replication errors. Extending standard quasispecies models of non-enzymatic replication, we analyze highly specific enzymatic self-replication mediated through an otherwise neutral recognition region, which leads to frequency-dependent replication rates. We find a significant reduction of the maximally tolerable error rate, because the replication rate of the fittest molecules decreases with the fraction of functional enzymes. Our analysis is extended to hypercyclic couplings as an example for catalytic networks.

  14. 9 CFR 317.10 - Reuse of official inspection marks; reuse of containers bearing official marks, labels, etc.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Reuse of official inspection marks; reuse of containers bearing official marks, labels, etc. 317.10 Section 317.10 Animals and Animal... DEVICES, AND CONTAINERS General § 317.10 Reuse of official inspection marks; reuse of containers...

  15. 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......-like, artificial, molecular aggregate (i.e. protocell) that has been proposed by Steen Rasussen and coworkers and is currently pursued both experimentally and computationally in interdisciplinary international research projects. We develop a space-time continuous physically motivated simulation framework based...... computational models. This allows us to address key issues of the replicating subsystems – container, genome, and metabolism – both individually and in mutual coupling. We analyze each step in the life-cycle of the molecular aggregate, and a final integrated simulation of the entire life-cycle is prepared. Our...

  16. Choreography of bacteriophage T7 DNA replication.

    Science.gov (United States)

    Lee, Seung-Joo; Richardson, Charles C

    2011-10-01

    The replication system of phage T7 provides a model for DNA replication. Biochemical, structural, and single-molecule analyses together provide insight into replisome mechanics. A complex of polymerase, a processivity factor, and helicase mediates leading strand synthesis. Establishment of the complex requires an interaction of the C-terminal tail of the helicase with the polymerase. During synthesis the complex is stabilized by other interactions to provide for a processivity of 5 kilobase (kb). The C-terminal tail also interacts with a distinct region of the polymerase to captures dissociating polymerase to increase the processivity to >17kb. The lagging strand is synthesized discontinuously within a loop that forms and resolves during each cycle of Okazaki fragment synthesis. The synthesis of a primer as well as the termination of a fragment signal loop resolution.

  17. Surface micro topography replication in injection moulding

    DEFF Research Database (Denmark)

    Arlø, Uffe Rolf

    , the topography itself, and other factors were also investigated. The experimental work is based on a multi-purpose experimental injection mould with a collection of test surface inserts manufactured by EDM (electrical discharge machining). Experimental production took place with an injection moulding machine......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...... in a clean room environment. The mould and the injection moulding machine were fitted with transducers for subsequent process analysis. A total of 13 different plastic material grades were applied. Topographical characterisation was performed with an optical laser focus detection instrument. Replication...

  18. Entropy involved in fidelity of DNA replication

    CERN Document Server

    Arias-Gonzalez, J Ricardo

    2012-01-01

    Information has an entropic character which can be analyzed within the Statistical Theory in molecular systems. R. Landauer and C.H. Bennett showed that a logical copy can be carried out in the limit of no dissipation if the computation is performed sufficiently slowly. Structural and recent single-molecule assays have provided dynamic details of polymerase machinery with insight into information processing. We introduce a rigorous characterization of Shannon Information in biomolecular systems and apply it to DNA replication in the limit of no dissipation. Specifically, we devise an equilibrium pathway in DNA replication to determine the entropy generated in copying the information from a DNA template in the absence of friction. Both the initial state, the free nucleotides randomly distributed in certain concentrations, and the final state, a polymerized strand, are mesoscopic equilibrium states for the nucleotide distribution. We use empirical stacking free energies to calculate the probabilities of incorpo...

  19. The Solution to Science's Replication Crisis

    CERN Document Server

    Knuteson, Bruce

    2016-01-01

    The solution to science's replication crisis is a new ecosystem in which scientists sell what they learn from their research. In each pairwise transaction, the information seller makes (loses) money if he turns out to be correct (incorrect). Responsibility for the determination of correctness is delegated, with appropriate incentives, to the information purchaser. Each transaction is brokered by a central exchange, which holds money from the anonymous information buyer and anonymous information seller in escrow, and which enforces a set of incentives facilitating the transfer of useful, bluntly honest information from the seller to the buyer. This new ecosystem, capitalist science, directly addresses socialist science's replication crisis by explicitly rewarding accuracy and penalizing inaccuracy.

  20. Experimental Replication of an Aeroengine Combustion Instability

    Science.gov (United States)

    Cohen, J. M.; Hibshman, J. R.; Proscia, W.; Rosfjord, T. J.; Wake, B. E.; McVey, J. B.; Lovett, J.; Ondas, M.; DeLaat, J.; Breisacher, K.

    2000-01-01

    Combustion instabilities in gas turbine engines are most frequently encountered during the late phases of engine development, at which point they are difficult and expensive to fix. The ability to replicate an engine-traceable combustion instability in a laboratory-scale experiment offers the opportunity to economically diagnose the problem (to determine the root cause), and to investigate solutions to the problem, such as active control. The development and validation of active combustion instability control requires that the causal dynamic processes be reproduced in experimental test facilities which can be used as a test bed for control system evaluation. This paper discusses the process through which a laboratory-scale experiment was designed to replicate an instability observed in a developmental engine. The scaling process used physically-based analyses to preserve the relevant geometric, acoustic and thermo-fluid features. The process increases the probability that results achieved in the single-nozzle experiment will be scalable to the engine.

  1. Competition and cooperation in dynamic replication networks.

    Science.gov (United States)

    Dadon, Zehavit; Wagner, Nathaniel; Alasibi, Samaa; Samiappan, Manickasundaram; Mukherjee, Rakesh; Ashkenasy, Gonen

    2015-01-07

    The simultaneous replication of six coiled-coil peptide mutants by reversible thiol-thioester exchange reactions is described. Experimental analysis of the time dependent evolution of networks formed by the peptides under different conditions reveals a complex web of molecular interactions and consequent mutant replication, governed by competition for resources and by autocatalytic and/or cross-catalytic template-assisted reactions. A kinetic model, first of its kind, is then introduced, allowing simulation of varied network behaviour as a consequence of changing competition and cooperation scenarios. We suggest that by clarifying the kinetic description of these relatively complex dynamic networks, both at early stages of the reaction far from equilibrium and at later stages approaching equilibrium, one lays the foundation for studying dynamic networks out-of-equilibrium in the near future.

  2. 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.

  3. 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.

  4. 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.

  5. Holter and Event Monitors

    Science.gov (United States)

    ... Share this page from the NHLBI on Twitter. Holter and Event Monitors Also known as ambulatory EKG; continuous EKG; EKG event monitors. Holter and event monitors are small, portable electrocardiogram devices ...

  6. Advanced Patient Data Replication and Recovery

    Science.gov (United States)

    2010-10-01

    able to “dial” the bandwidth back down to the 10Mbps range to reduce 8 the cost of the data link back to EMC. EMC2 Centera replication is the...automation robot (which fills pharmacy orders) and the drug dispensing kiosks located near the nurse stations in the hospital. These systems have...with appropriate workspaces, including telephone and internet service, for several weeks if needed. 11. Hotels must be available within 15

  7. 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

  8. Ultrastructural Characterization of Zika Virus Replication Factories

    Directory of Open Access Journals (Sweden)

    Mirko Cortese

    2017-02-01

    Full Text Available 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.

  9. Break-Induced Replication and Genome Stability

    Directory of Open Access Journals (Sweden)

    Anna Malkova

    2012-10-01

    Full Text Available Genetic instabilities, including mutations and chromosomal rearrangements, lead to cancer and other diseases in humans and play an important role in evolution. A frequent cause of genetic instabilities is double-strand DNA breaks (DSBs, which may arise from a wide range of exogeneous and endogeneous cellular factors. Although the repair of DSBs is required, some repair pathways are dangerous because they may destabilize the genome. One such pathway, break-induced replication (BIR, is the mechanism for repairing DSBs that possesses only one repairable end. This situation commonly arises as a result of eroded telomeres or collapsed replication forks. Although BIR plays a positive role in repairing DSBs, it can alternatively be a dangerous source of several types of genetic instabilities, including loss of heterozygosity, telomere maintenance in the absence of telomerase, and non-reciprocal translocations. Also, mutation rates in BIR are about 1000 times higher as compared to normal DNA replication. In addition, micro-homology-mediated BIR (MMBIR, which is a mechanism related to BIR, can generate copy-number variations (CNVs as well as various complex chromosomal rearrangements. Overall, activation of BIR may contribute to genomic destabilization resulting in substantial biological consequences including those affecting human health.

  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.

  11. Continuously Cumulating Meta-Analysis and Replicability.

    Science.gov (United States)

    Braver, Sanford L; Thoemmes, Felix J; Rosenthal, Robert

    2014-05-01

    The current crisis in scientific psychology about whether our findings are irreproducible was presaged years ago by Tversky and Kahneman (1971), who noted that even sophisticated researchers believe in the fallacious Law of Small Numbers-erroneous intuitions about how imprecisely sample data reflect population phenomena. Combined with the low power of most current work, this often leads to the use of misleading criteria about whether an effect has replicated. Rosenthal (1990) suggested more appropriate criteria, here labeled the continuously cumulating meta-analytic (CCMA) approach. For example, a CCMA analysis on a replication attempt that does not reach significance might nonetheless provide more, not less, evidence that the effect is real. Alternatively, measures of heterogeneity might show that two studies that differ in whether they are significant might have only trivially different effect sizes. We present a nontechnical introduction to the CCMA framework (referencing relevant software), and then explain how it can be used to address aspects of replicability or more generally to assess quantitative evidence from numerous studies. We then present some examples and simulation results using the CCMA approach that show how the combination of evidence can yield improved results over the consideration of single studies.

  12. Early steps of retrovirus replicative cycle

    Directory of Open Access Journals (Sweden)

    Saïb Ali

    2004-05-01

    Full Text Available Abstract During the last two decades, the profusion of HIV research due to the urge to identify new therapeutic targets has led to a wealth of information on the retroviral replication cycle. However, while the late stages of the retrovirus life cycle, consisting of virus replication and egress, have been partly unraveled, the early steps remain largely enigmatic. These early steps consist of a long and perilous journey from the cell surface to the nucleus where the proviral DNA integrates into the host genome. Retroviral particles must bind specifically to their target cells, cross the plasma membrane, reverse-transcribe their RNA genome, while uncoating the cores, find their way to the nuclear membrane and penetrate into the nucleus to finally dock and integrate into the cellular genome. Along this journey, retroviruses hijack the cellular machinery, while at the same time counteracting cellular defenses. Elucidating these mechanisms and identifying which cellular factors are exploited by the retroviruses and which hinder their life cycle, will certainly lead to the discovery of new ways to inhibit viral replication and to improve retroviral vectors for gene transfer. Finally, as proven by many examples in the past, progresses in retrovirology will undoubtedly also provide some priceless insights into cell biology.

  13. Keterlibatan Event Stakeholders pada Keberhasilan Event PR

    Directory of Open Access Journals (Sweden)

    Lidya Wati Evelina

    2013-03-01

    Full Text Available The objective of this article is to determine how event organizers collaborate with stakeholders including the media, particular community, sponsors, participants, venue providers, accommodation providers, carteres, legal and finance personnel, production, local trade, transportation providers, government and associations for implementation Public Relations event. This paper discusses about the things that must be done for the cooperation and the benefits of cooperation undertaken. The method used in this paper is qualitative research method based on observations, literature and case studies. The results of this research note that the event organizers or companies can together with the stakeholders (the other party make an event as mutually beneficial Public Relations. This means that all parties can achieve through the event. At the conclusion of an event Public Relations, all stakeholders involved for their own purposes. Event organizer must ensure that all stakeholders work together effectively in accordance with the agreed schedule and budget. One important feature of the agreement is to maintain a good flow of communication according to the needs of its stakeholders. All information is documented to avoid misunderstandings. Collaboration between stakeholders continuously until the event is completed. Discussion of issues that arise during the event takes place between the committee with various stakeholders is an important thing for the evaluation and response to the events that occurred.

  14. Absence of RNase H allows replication of pBR322 in Escherichia coli mutants lacking DNA polymerase I.

    Science.gov (United States)

    Kogoma, T

    1984-12-01

    rnh (formerly termed sdrA) mutants of Escherichia coli K-12, capable of continuous DNA replication in the absence of protein synthesis (stable DNA replication), are devoid of ribonuclease H (RNase H, EC 3.1.26.4) activity. Plasmid pBR322 was found to replicate in rnh mutants in the absence of DNA polymerase I, the polA gene product, which is normally required for replication of this plasmid. The plasmid copy number in polA rnh double mutants was as high as in the wild-type strains. When a chimeric construct between pBR322 and pSC101 was introduced into a polA rnh double mutant, the replication of the plasmid via the pBR322 replicon was inhibited if the plasmid also carried an rnh+ gene or if the host harbored an F' plasmid carrying an rnh+ gene. Thus, DNA polymerase I-independent replication of pBR322 requires the absence of RNase H activity. This alternative mechanism requiring neither DNA polymerase I nor RNase H appears to involve a transcriptional event in the region of the normal origin of replication.

  15. Cardiac event monitors

    Science.gov (United States)

    ... ECG) - ambulatory; Continuous electrocardiograms (EKGs); Holter monitors; Transtelephonic event monitors ... attached. You can carry or wear a cardiac event monitor up to 30 days. You carry the ...

  16. 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/

  17. Amplified and Persistent Immune Responses Generated by Single-Cycle Replicating Adenovirus Vaccines

    Science.gov (United States)

    Crosby, Catherine M.; Nehete, Pramod; Sastry, K. Jagannadha

    2014-01-01

    ABSTRACT Replication-competent adenoviral (RC-Ad) vectors generate exceptionally strong gene-based vaccine responses by amplifying the antigen transgenes they carry. While they are potent, they also risk causing adenovirus infections. More common replication-defective Ad (RD-Ad) vectors with deletions of E1 avoid this risk but do not replicate their transgene and generate markedly weaker vaccine responses. To amplify vaccine transgenes while avoiding production of infectious progeny viruses, we engineered “single-cycle” adenovirus (SC-Ad) vectors by deleting the gene for IIIa capsid cement protein of lower-seroprevalence adenovirus serotype 6. In mouse, human, hamster, and macaque cells, SC-Ad6 still replicated its genome but prevented genome packaging and virion maturation. When used for mucosal intranasal immunization of Syrian hamsters, both SC-Ad and RC-Ad expressed transgenes at levels hundreds of times higher than that of RD-Ad. Surprisingly, SC-Ad, but not RC-Ad, generated higher levels of transgene-specific antibody than RD-Ad, which notably climbed in serum and vaginal wash samples over 12 weeks after single mucosal immunization. When RD-Ad and SC-Ad were tested by single sublingual immunization in rhesus macaques, SC-Ad generated higher gamma interferon (IFN-γ) responses and higher transgene-specific serum antibody levels. These data suggest that SC-Ad vectors may have utility as mucosal vaccines. IMPORTANCE This work illustrates the utility of our recently developed single-cycle adenovirus (SC-Ad6) vector as a new vaccine platform. Replication-defective (RD-Ad6) vectors produce low levels of transgene protein, which leads to minimal antibody responses in vivo. This study shows that replicating SC-Ad6 produces higher levels of luciferase and induces higher levels of green fluorescent protein (GFP)-specific antibodies than RD in a permissive Syrian hamster model. Surprisingly, although a replication-competent (RC-Ad6) vector produces more luciferase

  18. Replicative intermediates of maize streak virus found during leaf development.

    Science.gov (United States)

    Erdmann, Julia B; Shepherd, Dionne N; Martin, Darren P; Varsani, Arvind; Rybicki, Edward P; Jeske, Holger

    2010-04-01

    Geminiviruses of the genera Begomovirus and Curtovirus utilize three replication modes: complementary-strand replication (CSR), rolling-circle replication (RCR) and recombination-dependent replication (RDR). Using two-dimensional gel electrophoresis, we now show for the first time that maize streak virus (MSV), the type member of the most divergent geminivirus genus, Mastrevirus, does the same. Although mastreviruses have fewer regulatory genes than other geminiviruses and uniquely express their replication-associated protein (Rep) from a spliced transcript, the replicative intermediates of CSR, RCR and RDR could be detected unequivocally within infected maize tissues. All replicative intermediates accumulated early and, to varying degrees, were already present in the shoot apex and leaves at different maturation stages. Relative to other replicative intermediates, those associated with RCR increased in prevalence during leaf maturation. Interestingly, in addition to RCR-associated DNA forms seen in other geminiviruses, MSV also apparently uses dimeric open circular DNA as a template for RCR.

  19. On the scattering of DNA replication completion times

    Science.gov (United States)

    Meilikhov, E. Z.; Farzetdinova, R. M.

    2015-07-01

    Stochasticity of Eukaryotes' DNA replication should not lead to large fluctuations of replication times, which could result in mitotic catastrophes. Fundamental problem that cells face is how to be ensured that entire genome is replicated on time. We develop analytic approach of calculating DNA replication times, that being simplified and approximate, leads, nevertheless, to results practically coincident with those that were obtained by some sophisticated methods. In the framework of that model we consider replication times' scattering and discuss the influence of repair stopping on kinetics of DNA replication. Our main explicit formulae for DNA replication time t r ∝ ( N is the total number of DNA base pairs) is of general character and explains basic features of DNA replication kinetics.

  20. Mark 6 Next-Generation VLBI Data System

    Science.gov (United States)

    Whitney, A.; Lapsley, D.

    2012-12-01

    The Mark 6 VLBI data system is being developed by MIT Haystack Observatory as a next-generation disk-based VLBI data system capable of supporting the goals of VLBI2010, with a maximum sustained recording rate of 16 Gbps writing to an array of 32 magnetic disks. The Mark 6 is based on COTS hardware and open-source code and is being designed to transition easily from the widely used Mark 5 system. A successful 16 Gbps per station VLBI demonstration experiment was conducted with Mark 6 in late 2011 as a proof-of-concept. Haystack Observatory is collaborating with the NASA/GSFC High-End Network Computing Group in the selection of high-performance COTS hardware platforms and with Conduant Corporation in the development of a high-performance disk module for Mark 6. Existing Mark 5 systems will be upgradable to Mark 6, and existing Mark 5 SATA modules will be upgradeable for compatibility with Mark 6. The Mark 6 system is projected to be available to the VLBI community in late 2012.