WorldWideScience

Sample records for replicate similar science

  1. 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.

  2. Similarity and Modeling in Science and Engineering

    CERN Document Server

    Kuneš, Josef

    2012-01-01

    The present text sets itself in relief to other titles on the subject in that it addresses the means and methodologies versus a narrow specific-task oriented approach. Concepts and their developments which evolved to meet the changing needs of applications are addressed. This approach provides the reader with a general tool-box to apply to their specific needs. Two important tools are presented: dimensional analysis and the similarity analysis methods. The fundamental point of view, enabling one to sort all models, is that of information flux between a model and an original expressed by the similarity and abstraction. Each chapter includes original examples and ap-plications. In this respect, the models can be divided into several groups. The following models are dealt with separately by chapter; mathematical and physical models, physical analogues, deterministic, stochastic, and cybernetic computer models. The mathematical models are divided into asymptotic and phenomenological models. The phenomenological m...

  3. Predicting Lexical Priming Effects from Distributional Semantic Similarities: A Replication with Extension.

    Science.gov (United States)

    Günther, Fritz; Dudschig, Carolin; Kaup, Barbara

    2016-01-01

    In two experiments, we attempted to replicate and extend findings by Günther et al. (2016) that word similarity measures obtained from distributional semantics models-Latent Semantic Analysis (LSA) and Hyperspace Analog to Language (HAL)-predict lexical priming effects. To this end, we used the pseudo-random method to generate item material while systematically controlling for word similarities introduced by Günther et al. (2016) which was based on LSA cosine similarities (Experiment 1) and HAL cosine similarities (Experiment 2). Extending the original study, we used semantic spaces created from far larger corpora, and implemented several additional methodological improvements. In Experiment 1, we only found a significant effect of HAL cosines on lexical decision times, while we found significant effects for both LSA and HAL cosines in Experiment 2. As further supported by an analysis of the pooled data from both experiments, this indicates that HAL cosines are a better predictor of priming effects than LSA cosines. Taken together, the results replicate the finding that priming effects can be predicted from distributional semantic similarity measures.

  4. Predicting lexical priming effects from distributional semantic similarities: A replication with extension

    Directory of Open Access Journals (Sweden)

    Fritz Günther

    2016-10-01

    Full Text Available In two experiments, we attempted to replicate findings by Günther, Dudschig &Kaup (2016 that word similarity measures obtained from distributional semantics models -Latent Semantic Analysis (LSA and Hyperspace Analogue to Language (HAL - predictlexical priming effects. To this end, we used the pseudo-random method to generate itemmaterial while systematically controlling for word similarities introduced by Günther et al.,which was based on LSA cosine similarities (Experiment 1 and HAL cosine similarities(Experiment 2. Contrary to the original study, we used semantic spaces created from farlarger corpora, and implemented several additional methodological improvements. InExperiment 1, we only found a significant effect of HAL cosines on lexical decision times,while we found significant effects for both LSA and HAL cosines in Experiment 2. Asfurther supported by an analysis of the pooled data from both experiments, this indicatesthat HAL cosines are a better predictor of priming effects than LSA cosines. Takentogether, the results replicate the finding that priming effects can be predicted fromdistributional semantic similarity measures.

  5. Transforming genes among three different oncogenic subgroups of human adenoviruses have similar replicative functions.

    Science.gov (United States)

    Brusca, J S; Chinnadurai, G

    1981-01-01

    We have examined the functional similarity of the transforming genes for replicative functions among three different subgroups of human adenoviruses (A, B, and C), using mutant complementation as an assay. A host range deletion mutant (dl201.2) of Ad2 (nononcogenic subgroup C) lacking about 5% of the viral DNA covering two early gene blocks (E1a and E1b) involved in cellular transformation was isolated and tested for its ability to replicate in nonpermissive KB cells in the presence of Ad7 (weakly oncogenic group B) or ad12 (highly oncogenic group A). The complementation of the mutant defect was demonstrated by cleaving the viral DNA extracted from mixed infected cells or the DNA extracted from purified virions from mixed infected cells with restriction endonuclease BamHI, which produces a different cleavage pattern with the DNA of each serotype. It was found that the defects in E1a plus E1b of dl201.2 could be complemented by Ad7 and Ad12, indicating that these genes in Ad2, Ad7, and Ad12 have similar functions during productive infection. Images PMID:7277578

  6. Similarity solutions of a replicator dynamics equation associated with a continuum of pure strategies

    Directory of Open Access Journals (Sweden)

    Vassilis G. Papanicolaou

    2015-09-01

    Full Text Available We introduce a nonlinear degenerate parabolic equation containing a nonlocal term. The equation serves as a replicator dynamics model where the set of strategies is a continuum. In our model the payoff operator (which is the continuous analog of the payoff matrix is nonsymmetric and, also, evolves with time. We are interested in solutions u(t, x of our equation which are positive and their integral (with respect to x over the whole space is 1, for any t > 0. These solutions, being probability densities, can serve as time-evolving mixed strategies of a player. We show that for our model there is an one-parameter family of self-similar such solutions $u(t, x$, all approaching the Dirac delta function $\\delta(x$ as $t \\to 0^+$.

  7. The Acid Test for Biological Science: STAP Cells, Trust, and Replication.

    Science.gov (United States)

    Lancaster, Cheryl

    2016-02-01

    In January 2014, a letter and original research article were published in Nature describing a process whereby somatic mouse cells could be converted into stem cells by subjecting them to stress. These "stimulus-triggered acquisition of pluripotency" (STAP) cells were shown to be capable of contributing to all cell types of a developing embryo, and extra-embryonic tissues. The lead author of the publications, Haruko Obokata, became an overnight celebrity in Japan, where she was dubbed the new face of Japanese science. However, in the weeks that followed publication of the research, issues arose. Other laboratories and researchers (including authors on the original papers) found that they were unable to replicate Obokata et al.'s work. Closer scrutiny of the papers by the scientific community also suggested that there was manipulation of images that had been published, and Obokata was accused of misconduct. Those who should have been supervising her work (also her co-authors on the publications) were also heavily criticised. The STAP cell saga of 2014 is used as an example to highlight the importance of trust and replication in twenty-first century biological science. The role of trust in the scientific community is highlighted, and the effects on interactions between science and the public examined. Similarly, this essay aims to highlight the importance of replication, and how this is understood by researchers, the media, and the public. The expected behaviour of scientists in the twenty-first century is now more closely scrutinised.

  8. Similarity of TIMSS Math and Science Achievement of Nations

    Directory of Open Access Journals (Sweden)

    Algirdas Zabulionis

    2001-09-01

    Full Text Available In 1991-97, the International Association for the Evaluation of Educational Achievement (IEA undertook a Third International Mathematics and Science Study (TIMSS in which data about the mathematics and science achievement of the thirteen year-old students in more than 40 countries were collected. These data provided the opportunity to search for patterns of students' answers to the test items: which group of items was relatively more difficult (or more easy for the students from a particular country (or group of countries. Using this massive data set an attempt was made to measure the similarities among country profiles of how students responded to the test items.

  9. [Similarities in periodical structures in the position of nucleotides in regions of initiation of replication of bacterial genomes].

    Science.gov (United States)

    Kravatskaia, G I; Frank, G K; Makeev, V Iu; Esipova, N G

    2002-01-01

    The regions of initiation of replication of some bacterial genomes were studied by the method of Fourier matrix analysis. A generalized spectral portrait of the primary structures of E. coli-like regions of initiation of replication in bacteria was obtained, which reflects the features of their structural and functional organization. It contains well-pronounced peaks that correspond to the periods T = 2, 11, 17, 27, 86-105 of nucleotides. The peaks corresponding to T = 9, 13, 14, 18, 19, 33-35, 45-47, 74-85, 106-110 are less pronounced. The uniqueness of the Fourier spectrum corresponding to the region of initiation of replication of E. coli oriC was considered by the example of the complete genome of E. coli. Some regions of the E. coli genome were identified that differ from oriC in the primary structure but have Fourier spectra resembling the spectrum of oriC. A number of these regions are alternative points of initiation of replication in sdrA(rnh) mutants of E. coli, the others are localized in yet unidentified regions of the E. coli genome but are capable, in our opinion, to participate in the initiation of replication. Thus, from the similarity of spectral portraits of different regions of the genome, it was possible to reveal several regions that have similar functions, i.e., are involved in initiation of replication.

  10. The replication initiator of the cholera pathogen's second chromosome shows structural similarity to plasmid initiators.

    Science.gov (United States)

    Orlova, Natalia; Gerding, Matthew; Ivashkiv, Olha; Olinares, Paul Dominic B; Chait, Brian T; Waldor, Matthew K; Jeruzalmi, David

    2016-12-27

    The conserved DnaA-oriC system is used to initiate replication of primary chromosomes throughout the bacterial kingdom; however, bacteria with multipartite genomes evolved distinct systems to initiate replication of secondary chromosomes. In the cholera pathogen, Vibrio cholerae, and in related species, secondary chromosome replication requires the RctB initiator protein. Here, we show that RctB consists of four domains. The structure of its central two domains resembles that of several plasmid replication initiators. RctB contains at least three DNA binding winged-helix-turn-helix motifs, and mutations within any of these severely compromise biological activity. In the structure, RctB adopts a head-to-head dimeric configuration that likely reflects the arrangement in solution. Therefore, major structural reorganization likely accompanies complex formation on the head-to-tail array of binding sites in oriCII Our findings support the hypothesis that the second Vibrionaceae chromosome arose from an ancestral plasmid, and that RctB may have evolved additional regulatory features.

  11. Derivatives. Replication and (auto)plagiarism in the social sciences

    NARCIS (Netherlands)

    R. Tweehuysen (Rolandt ); J. den Haan (Joost); K. Berkhout (Karel ); P.A.G. van Bergeijk (Peter)

    2012-01-01

    textabstractThis working paper reports on the travelling exhibition “Derivatives”. This exhibition investigates the issue of originality in the context of (self) plagiarism and replication. The different views in the Arts and the scientific discourse form the point of departure for discovering how i

  12. Derivatives. Replication and (auto)plagiarism in the social sciences

    NARCIS (Netherlands)

    R. Tweehuysen (Rolandt ); J. den Haan (Joost); K. Berkhout (Karel ); P.A.G. van Bergeijk (Peter)

    2012-01-01

    textabstractThis working paper reports on the travelling exhibition “Derivatives”. This exhibition investigates the issue of originality in the context of (self) plagiarism and replication. The different views in the Arts and the scientific discourse form the point of departure for discovering how

  13. Derivatives. Replication and (auto)plagiarism in the social sciences

    NARCIS (Netherlands)

    R. Tweehuysen (Rolandt ); J. den Haan (Joost); K. Berkhout (Karel ); P.A.G. van Bergeijk (Peter)

    2012-01-01

    textabstractThis working paper reports on the travelling exhibition “Derivatives”. This exhibition investigates the issue of originality in the context of (self) plagiarism and replication. The different views in the Arts and the scientific discourse form the point of departure for discovering how i

  14. Replicative bypass of abasic site in Escherichia coli and human cells: similarities and differences.

    Directory of Open Access Journals (Sweden)

    Savithri Weerasooriya

    Full Text Available Abasic [apurinic/apyrimidinic (AP] sites are the most common DNA damages, opposite which dAMP is frequently inserted ('A-rule' in Escherichia coli. Nucleotide insertion opposite the AP-site in eukaryotic cells depends on the assay system and the type of cells. Accordingly, a 'C-rule', 'A-rule', or the lack of specificity has been reported. DNA sequence context also modulates nucleotide insertion opposite AP-site. Herein, we have compared replication of tetrahydrofuran (Z, a stable analog of AP-site, in E. coli and human embryonic kidney 293T cells in two different sequences. The efficiency of translesion synthesis or viability of the AP-site construct in E. coli was less than 1%, but it was 7- to 8-fold higher in the GZGTC sequence than in the GTGZC sequence. The difference in viability increased even more in pol V-deficient strains. Targeted one-base deletions occurred in 63% frequency in the GZG and 68% frequency in GZC sequence, which dropped to 49% and 21%, respectively, upon induction of SOS. The full-length products with SOS primarily involved dAMP insertion opposite the AP-site, which occurred in 49% and 71% frequency, respectively, in the GZG and GZC sequence. dAMP insertion, largely carried out by pol V, was more efficient when the AP-site was a stronger replication block. In contrast to these results in E. coli, viability was 2 to 3 orders of magnitude higher in human cells, and the 'A-rule' was more rigidly followed. The AP-site in the GZG and GZC sequences gave 76% and 89%, respectively, Z → T substitutions. In human cells, targeted one-base deletion was undetectable, and dTMP>dCMP were the next preferred nucleotides inserted opposite Z. siRNA knockdown of Rev1 or pol ζ established that both these polymerases are vital for AP-site bypass, as demonstrated by 36-67% reduction in bypass efficiency. However, neither polymerase was indispensable, suggesting roles of additional DNA polymerases in AP-site bypass in human cells.

  15. Similarity

    Science.gov (United States)

    Apostol, Tom M. (Editor)

    1990-01-01

    In this 'Project Mathematics! series, sponsored by the California Institute for Technology (CalTech), the mathematical concept of similarity is presented. he history of and real life applications are discussed using actual film footage and computer animation. Terms used and various concepts of size, shape, ratio, area, and volume are demonstrated. The similarity of polygons, solids, congruent triangles, internal ratios, perimeters, and line segments using the previous mentioned concepts are shown.

  16. Medical students from natural science and nonscience undergraduate backgrounds. Similar academic performance and residency selection.

    Science.gov (United States)

    Dickman, R L; Sarnacki, R E; Schimpfhauser, F T; Katz, L A

    1980-06-27

    The majority of matriculating US medical students continue to major in the natural sciences as college undergraduates in the belief that this will enhance their chances of admission to and their performance in medical school. The present study compared the academic performance and residency selection of natural science and nonscience majors in three separate medical school classes at the State University of New York at Buffalo. Statistical analysis of grades in the first two years of medical school, clinical performance in the third year, and part I and part II National Board Medical Examination scores revealed no significant differences across three class replications. Residency selection among graduating seniors was also independent of undergraduate major. It is suggested that admissions committees, premedical advisors, and students reconsider their attitudes about the necessity of concentration in the natural sciences before entering medical school.

  17. Dot/Icm Effector Translocation by Legionella longbeachae Creates a Replicative Vacuole Similar to That of Legionella pneumophila despite Translocation of Distinct Effector Repertoires.

    Science.gov (United States)

    Wood, Rebecca E; Newton, Patrice; Latomanski, Eleanor A; Newton, Hayley J

    2015-10-01

    Legionella organisms are environmental bacteria and accidental human pathogens that can cause severe pneumonia, termed Legionnaires' disease. These bacteria replicate within a pathogen-derived vacuole termed the Legionella-containing vacuole (LCV). Our understanding of the development and dynamics of this vacuole is based on extensive analysis of Legionella pneumophila. Here, we have characterized the Legionella longbeachae replicative vacuole (longbeachae-LCV) and demonstrated that, despite important genomic differences, key features of the replicative LCV are comparable to those of the LCV of L. pneumophila (pneumophila-LCV). We constructed a Dot/Icm-deficient strain by deleting dotB and demonstrated the inability of this mutant to replicate inside THP-1 cells. L. longbeachae does not enter THP-1 cells as efficiently as L. pneumophila, and this is reflected in the observation that translocation of BlaM-RalFLLO (where RalFLLO is the L. longbeachae homologue of RalF) into THP-1 cells by the L. longbeachae Dot/Icm system is less efficient than that by L. pneumophila. This difference is negated in A549 cells where L. longbeachae and L. pneumophila infect with similar entry dynamics. A β-lactamase assay was employed to demonstrate the translocation of a novel family of proteins, the Rab-like effector (Rle) proteins. Immunofluorescence analysis confirmed that these proteins enter the host cell during infection and display distinct subcellular localizations, with RleA and RleC present on the longbeachae-LCV. We observed that the host Rab GTPase, Rab1, and the v-SNARE Sec22b are also recruited to the longbeachae-LCV during the early stages of infection, coinciding with the LCV avoiding endocytic maturation. These studies further our understanding of the L. longbeachae replicative vacuole, highlighting phenotypic similarities to the vacuole of L. pneumophila as well as unique aspects of LCV biology.

  18. Semantic Similarity Computation and Concept Mapping in Earth and Environmental Science

    Science.gov (United States)

    Zheng, J.; Ma, X.; Fox, P. A.

    2013-12-01

    Ontologies have been widely adopted and used by Earth and Environmental Science community to capture and represent knowledge in the domain. One of the major problem that prevent us to combine and reuse these ontologies to solve more interesting problems is semantic heterogeneity problem, for example, same vocabularies from different ontologies may refer to different concept; or different terms from different ontologies may have same meaning. In this proposed work, we will address the problem by (1) developing a semantic similarity computation model to compute similarity among the concepts in Earth and Environmental Science; (2) based on the computation model, we will implement concept mapping tool that creates alignment for concepts that are semantically the same; (3) we will demonstrate the effectiveness of the tool using GCMD and CLEAN vocabularies and other earth science related ontologies.

  19. Re-Examining the Similarities between Teacher and Student Conceptions about Physical Science

    Science.gov (United States)

    Burgoon, Jacob N.; Heddle, Mandy L.; Duran, Emilio

    2010-01-01

    There is a large body of research that has explored students' misconceptions about science phenomena. Less research, however, has been devoted to identifying teachers' misconceptions, but the results of the few existing studies demonstrate that teachers and students possess similar misconceptions. This study explored the physical science…

  20. Home and Motivational Factors Related to Science-Career Pursuit: Gender differences and gender similarities

    Science.gov (United States)

    Shin, Jongho; Lee, Hyunjoo; McCarthy-Donovan, Alexander; Hwang, Hyeyoung; Yim, Sonyoung; Seo, EunJin

    2015-06-01

    The purpose of the study was to examine whether gender differences exist in the mean levels of and relations between adolescents' home environments (parents' view of science, socio-economic status (SES)), motivations (intrinsic and instrumental motivations, self-beliefs), and pursuit of science careers. For the purpose, the Programmed for International Student Assessment 2006 data of Korean 15-year-old students were analysed. The results of the study showed that girls had lower levels of science intrinsic and instrumental motivations, self-beliefs, and science-career pursuit (SCP) as well as their parents' values in science less than boys. Gender similarities, rather than gender differences, existed in patterns of causal relationship among home environments, motivations, and SCP. The results showed positive effects for parents' higher value in science and SES on motivations, SCP, and for intrinsic and instrumental motivations on SCP for girls and boys. These results provide implications for educational interventions to decrease gender differences in science motivations and SCP, and to decrease adolescents' gender stereotypes.

  1. Replication Rate, Framing, and Format Affect Attitudes and Decisions about Science Claims

    Directory of Open Access Journals (Sweden)

    Ralph M. Barnes

    2016-11-01

    Full Text Available A series of five experiments examined how the evaluation of a scientific finding was influenced by information about the number of studies that had successfully replicated the initial finding. The experiments also tested the impact of frame (negative, positive and numeric format (percentage, natural frequency on the evaluation of scientific findings. In Experiments 1 through 4, an attitude difference score served as the dependent measure, while a measure of choice served as the dependent measure in Experiment 5. Results from a diverse sample of 188 non-institutionalized U.S. adults (Experiment 2 and 730 undergraduate college students (Experiments 1, 3, and 4 indicated that attitudes became more positive as the replication rate increased and attitudes were more positive when the replication information was framed positively. The results also indicate that the manner in which replication rate was framed had a greater impact on attitude than the replication rate itself. The large effect for frame was attenuated somewhat when information about replication was presented in the form of natural frequencies rather than percentages. A fifth study employing 662 undergraduate college students in a task in which choice served as the dependent measure confirmed the framing effect and replicated the replication rate effect in the positive frame condition, but provided no evidence that the use of natural frequencies diminished the effect.

  2. Replication Rate, Framing, and Format Affect Attitudes and Decisions about Science Claims.

    Science.gov (United States)

    Barnes, Ralph M; Tobin, Stephanie J; Johnston, Heather M; MacKenzie, Noah; Taglang, Chelsea M

    2016-01-01

    A series of five experiments examined how the evaluation of a scientific finding was influenced by information about the number of studies that had successfully replicated the initial finding. The experiments also tested the impact of frame (negative, positive) and numeric format (percentage, natural frequency) on the evaluation of scientific findings. In Experiments 1 through 4, an attitude difference score served as the dependent measure, while a measure of choice served as the dependent measure in Experiment 5. Results from a diverse sample of 188 non-institutionalized U.S. adults (Experiment 2) and 730 undergraduate college students (Experiments 1, 3, and 4) indicated that attitudes became more positive as the replication rate increased and attitudes were more positive when the replication information was framed positively. The results also indicate that the manner in which replication rate was framed had a greater impact on attitude than the replication rate itself. The large effect for frame was attenuated somewhat when information about replication was presented in the form of natural frequencies rather than percentages. A fifth study employing 662 undergraduate college students in a task in which choice served as the dependent measure confirmed the framing effect and replicated the replication rate effect in the positive frame condition, but provided no evidence that the use of natural frequencies diminished the effect.

  3. The Cultural Argument for Understanding Nature of Science - A Chance to Reflect on Similarities and Differences Between Science and Humanities

    Science.gov (United States)

    Reiners, Christiane S.; Bliersbach, Markus; Marniok, Karl

    2017-08-01

    , and the role of technology. Thus, the cultural argument for understanding science invites us not only to consider domain-specific concepts but also to reflect on similarities between science and the humanities by way of examples.

  4. A New Orbivirus Isolated from Mosquitoes in North-Western Australia Shows Antigenic and Genetic Similarity to Corriparta Virus but Does Not Replicate in Vertebrate Cells

    Directory of Open Access Journals (Sweden)

    Jessica J. Harrison

    2016-05-01

    Full Text Available The discovery and characterisation of new mosquito-borne viruses provides valuable information on the biodiversity of vector-borne viruses and important insights into their evolution. In this study, a broad-spectrum virus screening system, based on the detection of long double-stranded RNA in inoculated cell cultures, was used to investigate the presence of novel viruses in mosquito populations of northern Australia. We detected and isolated a new virus (tentatively named Parry’s Lagoon virus, PLV from Culex annulirostris, Culex pullus, Mansonia uniformis and Aedes normanensis mosquitoes that shares genomic sequence similarities to Corriparta virus (CORV, a member of the Orbivirus genus of the family Reoviridae. Despite moderate to high (72.2% to 92.2% amino acid identity across all proteins when compared to CORV, and demonstration of antigenic relatedness, PLV did not replicate in several vertebrate cell lines that were permissive to CORV. This striking phenotypic difference suggests that PLV has evolved to have a very restricted host range, indicative of a mosquito-only life cycle.

  5. How to compare movement? A review of physical movement similarity measures in geographic information science and beyond

    OpenAIRE

    Ranacher, Peter; Tzavella, Katerina

    2014-01-01

    In geographic information science, a plethora of different approaches and methods is used to assess the similarity of movement. Some of these approaches term two moving objects similar if they share akin paths. Others require objects to move at similar speed and yet others consider movement similar if it occurs at the same time. We believe that a structured and comprehensive classification of movement comparison measures is missing. We argue that such a classification not only depicts the sta...

  6. 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.

  7. Proteins in similarity relationship with the cluster - Gclust Server | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available Gclust Server Proteins in similarity relationship with the cluster Data detail Data name Proteins in similarity relationship wit...t Us Proteins in similarity relationship with the cluster - Gclust Server | LSDB Archive ...

  8. Soil Science in tropical and temperate regions - some differences and similarities

    NARCIS (Netherlands)

    Hartemink, A.E.

    2002-01-01

    Little has been written about geographical differences in the progress and development of soil science, whereas such information is of interest for determining research priorities and for an improved understanding of the impact of soil science in various parts of the globe. This paper reviews some o

  9. Soil Science in tropical and temperate regions - some differences and similarities

    NARCIS (Netherlands)

    Hartemink, A.E.

    2002-01-01

    Little has been written about geographical differences in the progress and development of soil science, whereas such information is of interest for determining research priorities and for an improved understanding of the impact of soil science in various parts of the globe. This paper reviews some

  10. Merton and Ziman's modes of science: the case of biological and similar material transfer agreements

    NARCIS (Netherlands)

    Rodriguez, Victor

    2007-01-01

    This paper makes a connection between recent studies on research materials exchange and its effect on the progress of science. Academia fears that scientific development could be hampered by the privatised practices of research material exchange. Since post-academic science represents a sufficient d

  11. Home and Motivational Factors Related to Science-Career Pursuit: Gender Differences and Gender Similarities

    Science.gov (United States)

    Shin, Jongho; Lee, Hyunjoo; McCarthy-Donovan, Alexander; Hwang, Hyeyoung; Yim, Sonyoung; Seo, EunJin

    2015-01-01

    The purpose of the study was to examine whether gender differences exist in the mean levels of and relations between adolescents' home environments (parents' view of science, socio-economic status (SES)), motivations (intrinsic and instrumental motivations, self-beliefs), and pursuit of science careers. For the purpose, the Programmed for…

  12. Development of a replicable process for translating science into practical health education messages.

    Science.gov (United States)

    Tyus, Nadra C; Freeman, Randall J; Gibbons, M Christopher

    2006-09-01

    There has been considerable discussion about translating science into practical messages, especially among urban minority and "hard-to-reach" populations. Unfortunately, many research findings rarely make it back in useful format to the general public. Few innovative techniques have been established that provide researchers with a systematic process for developing health awareness and prevention messages for priority populations. The purpose of this paper is to describe the early development and experience of a unique community-based participatory process used to develop health promotion messages for a predominantly low-income, black and African-American community in Baltimore, MD. Scientific research findings from peer-reviewed literature were identified by academic researchers. Researchers then taught the science to graphic design students and faculty. The graphic design students and faculty then worked with both community residents and researchers to transform this information into evidence-based public health education messages. The final products were culturally and educationally appropriate, health promotion messages reflecting urban imagery that were eagerly desired by the community. This early outcome is in contrast to many previously developed messages and materials created through processes with limited community involvement and by individuals with limited practical knowledge of local community culture or expertise in marketing or mass communication. This process may potentially be utilized as a community-based participatory approach to enhance the translation of scientific research into desirable and appropriate health education messages.

  13. Innovation or Replication? Crossing and Criss-Crossing in Social Science

    Science.gov (United States)

    Strathern, Marilyn

    2014-01-01

    What does it mean to find echoes of an innovatory moment in the past, or a discipline's cutting edge in another's worn down tool, or people in different fields quite unknown to one another following a similar intellectual trajectory over the same three or four years? A short case study of what looks uncannily like "independent…

  14. Innovation or Replication? Crossing and Criss-Crossing in Social Science

    Science.gov (United States)

    Strathern, Marilyn

    2014-01-01

    What does it mean to find echoes of an innovatory moment in the past, or a discipline's cutting edge in another's worn down tool, or people in different fields quite unknown to one another following a similar intellectual trajectory over the same three or four years? A short case study of what looks uncannily like "independent invention"…

  15. Innovation or Replication? Crossing and Criss-Crossing in Social Science

    Science.gov (United States)

    Strathern, Marilyn

    2014-01-01

    What does it mean to find echoes of an innovatory moment in the past, or a discipline's cutting edge in another's worn down tool, or people in different fields quite unknown to one another following a similar intellectual trajectory over the same three or four years? A short case study of what looks uncannily like "independent invention"…

  16. Promises and pitfalls of Web-based experimentation in the advance of replicable psychological science: A reply to Plant (2015).

    Science.gov (United States)

    van Steenbergen, Henk; Bocanegra, Bruno R

    2016-12-01

    In a recent letter, Plant (2015) reminded us that proper calibration of our laboratory experiments is important for the progress of psychological science. Therefore, carefully controlled laboratory studies are argued to be preferred over Web-based experimentation, in which timing is usually more imprecise. Here we argue that there are many situations in which the timing of Web-based experimentation is acceptable and that online experimentation provides a very useful and promising complementary toolbox to available lab-based approaches. We discuss examples in which stimulus calibration or calibration against response criteria is necessary and situations in which this is not critical. We also discuss how online labor markets, such as Amazon's Mechanical Turk, allow researchers to acquire data in more diverse populations and to test theories along more psychological dimensions. Recent methodological advances that have produced more accurate browser-based stimulus presentation are also discussed. In our view, online experimentation is one of the most promising avenues to advance replicable psychological science in the near future.

  17. Science Student Teachers' Preferences for Ways of Learning: Differences and Similarities

    Science.gov (United States)

    Efe, Rifat; Gonen, Selahattin; Maskan, A. Kadir; Hevedanli, Murat

    2011-01-01

    Knowing an individual's learning style is considered important because it can help educators to prepare and develop learning environments in which the individual can enhance his/her learning. In this study, Biology, Physics, Chemistry and Primary science student teachers' learning styles were investigated. The participants were 387 student…

  18. [The personal context of a museum experience: similarities and differences between science and art museums].

    Science.gov (United States)

    Almeida, Adriana Mortara

    2005-01-01

    The article focuses on the development of research that illuminates not only the socioeconomic profiles of museum visitors and non-visitors but also their cultural habits, general entertainment interests, and their perceptions of art, science, and other topics addressed at these institutes. The more we know about a visitor's personal context, the more we can enhance his or her museum experience, thereby encouraging further museum visits during which his or her expectations, wishes, and needs will be more fully met. The article also focuses on how local culture plays an important part in shaping both personal context as well as each museum experience. Some examples are provided from the literature, above all concerning studies in Brazil and the contributions that research at art museums may have for science museums.

  19. 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.

  20. Algorithmic aspects of analysis, prediction, and control in science and engineering an approach based on symmetry and similarity

    CERN Document Server

    Nava, Jaime

    2015-01-01

    This book demonstrates how to describe and analyze a system's behavior and extract the desired prediction and control algorithms from this analysis. A typical prediction is based on observing similar situations in the past, knowing the outcomes of these past situations, and expecting that the future outcome of the current situation will be similar to these past observed outcomes. In mathematical terms, similarity corresponds to symmetry, and similarity of outcomes to invariance.   This book shows how symmetries can be used in all classes of algorithmic problems of sciences and engineering: from analysis to prediction to control. Applications cover chemistry, geosciences, intelligent control, neural networks, quantum physics, and thermal physics. Specifically, it is shown how the approach based on symmetry and similarity can be used in the analysis of real-life systems, in the algorithms of prediction, and in the algorithms of control.

  1. How to compare movement? A review of physical movement similarity measures in geographic information science and beyond.

    Science.gov (United States)

    Ranacher, Peter; Tzavella, Katerina

    2014-05-27

    In geographic information science, a plethora of different approaches and methods is used to assess the similarity of movement. Some of these approaches term two moving objects similar if they share akin paths. Others require objects to move at similar speed and yet others consider movement similar if it occurs at the same time. We believe that a structured and comprehensive classification of movement comparison measures is missing. We argue that such a classification not only depicts the status quo of qualitative and quantitative movement analysis, but also allows for identifying those aspects of movement for which similarity measures are scarce or entirely missing. In this review paper we, first, decompose movement into its spatial, temporal, and spatiotemporal movement parameters. A movement parameter is a physical quantity of movement, such as speed, spatial path, or temporal duration. For each of these parameters we then review qualitative and quantitative methods of how to compare movement. Thus, we provide a systematic and comprehensive classification of different movement similarity measures used in geographic information science. This classification is a valuable first step toward a GIS toolbox comprising all relevant movement comparison methods.

  2. Alien or Alike? How the Perceived Similarity Between the Typical Science Teacher and a Student's Self-Image Correlates with Choosing Science at School

    Science.gov (United States)

    Kessels, Ursula; Taconis, Ruurd

    2012-12-01

    By applying the self-to-prototype matching theory to students' academic choices, this study links the unpopularity of science in many industrialized countries with the perceived gap between typical persons representing science (e.g. physics teachers) on the one hand and students' self-image on the other. A sample of N = 308 Dutch and German students described both themselves and typical teachers representing different school subjects using 65 trait adjectives. The following hypotheses were tested: The typical hard sciences teacher and the typical languages teacher will be perceived as differing in their personal characteristics. The typical physics teachers will be perceived as being less similar to students' own self-image than teachers representing languages. Actual choices students make during secondary school should correlate with the perceived fit between students' self-image and the prototype of teachers representing different school subjects, especially in the less frequent and less popular choices of a math or physics major/profile. The findings supported these hypotheses. The discussion stresses that students acquire not only knowledge about science but also about science culture (sensu Aikenhead) in their science classes and that students' image of science teachers can influence their academic choices.

  3. Transfer of Nature of Science Understandings into Similar Contexts: Promises and Possibilities of an Explicit Reflective Approach

    Science.gov (United States)

    Khishfe, Rola

    2013-11-01

    The purpose of this study was to (a) investigate the effectiveness of explicit nature of science (NOS) instruction in the context of controversial socioscientific issues and (b) explore whether the transfer of acquired NOS understandings, which were explicitly taught in the context of one socioscientific context, into other similar contexts (familiar and unfamiliar) was possible. Participants were 10th grade students in two intact sections at one high school. The treatment involved teaching a six-week unit about genetic engineering. For one group (non-NOS group), there was no explicit instruction about NOS. For the other group (NOS group), explicit instruction about three NOS aspects (subjective, empirical, and tentative) was dispersed across the genetic engineering unit. A questionnaire including two open-ended scenarios, in conjunction with semi-structured interviews, was used to assess the change in participants' understandings of NOS and their ability to transfer their acquired understandings into similar contexts. The first scenario involved a familiar context about genetically modified food and the second one focused on an unfamiliar context about water fluoridation. Results showed no improvement in NOS understandings of participants in the non-NOS group in relation to the familiar and unfamiliar contexts. On the other hand, there was a general improvement in the NOS understandings of participants in the NOS group in relation to both the familiar and unfamiliar contexts. Implications about the transfer of participants' acquired NOS understandings on the basis of the distance between the context of learning and that of application are highlighted and discussed in link with the classroom learning environment.

  4. Emergent Themes from Recent Research Syntheses in Science Education and Their Implications for Research Design, Replication, and Reporting Practices

    Science.gov (United States)

    Taylor, Joseph; Furtak, Erin; Kowalski, Susan; Martinez, Alina; Slavin, Robert; Stuhlsatz, Molly; Wilson, Christopher

    2016-01-01

    This article draws upon the experiences of four recent efforts to synthesize the findings of quantitative studies in science education research. After establishing the need for research syntheses in advancing generalizable knowledge and causal effects research in our field, we identify a set themes that emerged in the process of conducting these…

  5. 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

  6. 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

  7. Creation and Application of a Replicable Analytic Method to Determine Attitudes and Beliefs of Undergraduate Science Professors Toward the Discipline of Education

    Directory of Open Access Journals (Sweden)

    Katherine Fogelberg

    2016-07-01

    Full Text Available Detailed here is the creation and application of a replicable method bricolage that brings together Discourse Analysis, discourse analysis, and the theory of reasoned action to examine attitudes and beliefs of university science professors toward the discipline of education. This method used a two-phase method for analysis. The first phase looked for phrases that could be defined as either an attitude or a belief based on definitions taken from the social psychology and communication studies literature. The second phase interpreted the overall data to explore the influences on the formation of the attitudes and beliefs as well as to support or refute the findings from Phase 1. The need for a replicable Discourse Analysis method is apparent in the education literature, as is a solid definition of what constitutes an attitude or a belief. The method outlined here provides good definitions for attitudes and beliefs, a method for extracting both constructs from the data, and incorporates an internal crystallization process for looking at and comparing emergent themes from both phases of analysis.

  8. Organic synthesis: the art and science of replicating the molecules of living nature and creating others like them in the laboratory.

    Science.gov (United States)

    Nicolaou, K C

    2014-03-01

    Synthetic organic chemists have the power to replicate some of the most intriguing molecules of living nature in the laboratory and apply their developed synthetic strategies and technologies to construct variations of them. Such molecules facilitate biology and medicine, as they often find uses as biological tools and drug candidates for clinical development. In addition, by employing sophisticated catalytic reactions and appropriately designed synthetic processes, they can synthesize not only the molecules of nature and their analogues, but also myriad other organic molecules for potential applications in many areas of science, technology and everyday life. After a short historical introduction, this article focuses on recent advances in the field of organic synthesis with demonstrative examples of total synthesis of complex bioactive molecules, natural or designed, from the author's laboratories, and their impact on chemistry, biology and medicine.

  9. Organic synthesis: the art and science of replicating the molecules of living nature and creating others like them in the laboratory

    Science.gov (United States)

    Nicolaou, K. C.

    2014-01-01

    Synthetic organic chemists have the power to replicate some of the most intriguing molecules of living nature in the laboratory and apply their developed synthetic strategies and technologies to construct variations of them. Such molecules facilitate biology and medicine, as they often find uses as biological tools and drug candidates for clinical development. In addition, by employing sophisticated catalytic reactions and appropriately designed synthetic processes, they can synthesize not only the molecules of nature and their analogues, but also myriad other organic molecules for potential applications in many areas of science, technology and everyday life. After a short historical introduction, this article focuses on recent advances in the field of organic synthesis with demonstrative examples of total synthesis of complex bioactive molecules, natural or designed, from the author’s laboratories, and their impact on chemistry, biology and medicine. PMID:24611027

  10. Alien or Alike? How the Perceived Similarity between the Typical Science Teacher and a Student's Self-Image Correlates with Choosing Science at School

    Science.gov (United States)

    Kessels, Ursula; Taconis, Ruurd

    2012-01-01

    By applying the self-to-prototype matching theory to students' academic choices, this study links the unpopularity of science in many industrialized countries with the perceived gap between typical persons representing science (e.g. physics teachers) on the one hand and students' self-image on the other. A sample of N = 308 Dutch and German…

  11. Similarities and Contrasts between Writing during a Writers' Workshop and Writing in Science: Examining the Teacher's Role. Elementary Subjects Center Series No. 94.

    Science.gov (United States)

    Rosaen, Cheryl L.; Roth, Kathleen J.

    A study investigated what was possible in terms of student learning when a conceptual change model of teaching science and a writers' workshop model of teaching writing were used consistently across time. Similarities and contrasts in the curriculum, learning communities, and teachers' roles when the two instructional models were used (by two…

  12. Data Analytics vs. Data Science: A Study of Similarities and Differences in Undergraduate Programs Based on Course Descriptions

    Science.gov (United States)

    Aasheim, Cheryl L.; Williams, Susan; Rutner, Paige; Gardiner, Adrian

    2015-01-01

    The rate at which data is produced and accumulated today is greater than at any point in history with little prospect of slowing. As organizations attempt to collect and analyze this data, there is a tremendous unmet demand for appropriately skilled knowledge workers. In response, universities are developing degree programs in data science and…

  13. Data Analytics vs. Data Science: A Study of Similarities and Differences in Undergraduate Programs Based on Course Descriptions

    Science.gov (United States)

    Aasheim, Cheryl L.; Williams, Susan; Rutner, Paige; Gardiner, Adrian

    2015-01-01

    The rate at which data is produced and accumulated today is greater than at any point in history with little prospect of slowing. As organizations attempt to collect and analyze this data, there is a tremendous unmet demand for appropriately skilled knowledge workers. In response, universities are developing degree programs in data science and…

  14. Number Theory in Science and Communication With Applications in Cryptography, Physics, Digital Information, Computing, and Self-Similarity

    CERN Document Server

    Schroeder, Manfred R

    2006-01-01

    "Number Theory in Science and Communication" is a well-known introduction for non-mathematicians to this fascinating and useful branch of applied mathematics . It stresses intuitive understanding rather than abstract theory and highlights important concepts such as continued fractions, the golden ratio, quadratic residues and Chinese remainders, trapdoor functions, pseudoprimes and primitive elements. Their applications to problems in the real world are one of the main themes of the book. This revised fourth edition is augmented by recent advances in primes in progressions, twin primes, prime triplets, prime quadruplets and quintruplets, factoring with elliptic curves, quantum factoring, Golomb rulers and "baroque" integers. From reviews of earlier editions – "I continue to find [Schroeder’s] Number Theory a goldmine of valuable information. It is a marvellous book, in touch with the most recent applications of number theory and written with great clarity and humor.’ Philip Morrison (Scientific American...

  15. Number Theory in Science and Communication With Applications in Cryptography, Physics, Digital Information, Computing, and Self-Similarity

    CERN Document Server

    Schroeder, Manfred

    2009-01-01

    "Number Theory in Science and Communication" is a well-known introduction for non-mathematicians to this fascinating and useful branch of applied mathematics . It stresses intuitive understanding rather than abstract theory and highlights important concepts such as continued fractions, the golden ratio, quadratic residues and Chinese remainders, trapdoor functions, pseudoprimes and primitive elements. Their applications to problems in the real world are one of the main themes of the book. This revised fifth edition is augmented by recent advances in coding theory, permutations and derangements and a chapter in quantum cryptography. From reviews of earlier editions – "I continue to find [Schroeder’s] Number Theory a goldmine of valuable information. It is a marvellous book, in touch with the most recent applications of number theory and written with great clarity and humor.’ Philip Morrison (Scientific American) "A light-hearted and readable volume with a wide range of applications to which the author ha...

  16. Social approach behaviors are similar on conventional versus reverse lighting cycles, and in replications across cohorts, in BTBR T+ tf/J, C57BL/6J, and vasopressin receptor 1B mutant mice

    Directory of Open Access Journals (Sweden)

    Mu Yang

    2007-11-01

    Full Text Available Mice are a nocturnal species, whose social behaviors occur primarily during the dark phase of the circadian cycle. However, laboratory rodents are frequently tested during their light phase, for practical reasons. We investigated the question of whether light phase testing presents a methodological pitfall for investigating mouse social approach behaviors. Three lines of mice were systematically compared. One cohort of each line was raised in a conventional lighting schedule and tested during the light phase, under white light illumination; another cohort was raised in a reverse lighting schedule and tested during their dark phase, under dim red light. Male C57BL/6J (B6 displayed high levels of sociability in our three-chambered automated social approach task when tested in either phase. BTBR T+ tf/J (BTBR displayed low levels of sociability in either phase. Five cohorts of vasopressin receptor subtype 1b (Avpr1b null mutants, heterozygotes, and wildtype littermate controls were tested in the same social approach paradigm: three in the dark phase and two in the light phase. All three genotypes displayed normal sociability in four out of the five replications. In the juvenile play test, testing phase had no effect on play soliciting behaviors in Avpr1b mice, but had modest effects on nose sniff and huddling. Taken together, these findings indicate that testing phase is not a crucial factor for studying some forms of social approach in juvenile and adult mice.

  17. Web Similarity

    NARCIS (Netherlands)

    Cohen, A.R.; Vitányi, P.M.B.

    2015-01-01

    Normalized web distance (NWD) is a similarity or normalized semantic distance based on the World Wide Web or any other large electronic database, for instance Wikipedia, and a search engine that returns reliable aggregate page counts. For sets of search terms the NWD gives a similarity on a scale fr

  18. New Similarity Functions

    DEFF Research Database (Denmark)

    Yazdani, Hossein; Ortiz-Arroyo, Daniel; Kwasnicka, Halina

    2016-01-01

    In data science, there are important parameters that affect the accuracy of the algorithms used. Some of these parameters are: the type of data objects, the membership assignments, and distance or similarity functions. This paper discusses similarity functions as fundamental elements in membership...

  19. 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.

  20. Organic synthesis: the art and science of replicating the molecules of living nature and creating others like them in the laboratory

    OpenAIRE

    Nicolaou, K. C.

    2014-01-01

    Synthetic organic chemists have the power to replicate some of the most intriguing molecules of living nature in the laboratory and apply their developed synthetic strategies and technologies to construct variations of them. Such molecules facilitate biology and medicine, as they often find uses as biological tools and drug candidates for clinical development. In addition, by employing sophisticated catalytic reactions and appropriately designed synthetic processes, they can synthesize not on...

  1. Um replicador em movimento: aproximações entre a poética narrativa de Borges e o programa de pesquisa dos memes A replicator in movement: similarities between Borges' poetic narrative and the memes research agenda

    Directory of Open Access Journals (Sweden)

    Ricardo Waizbort

    2008-03-01

    Full Text Available A extensa obra fantástica de Jorge Luis Borges tem sido lida como uma crítica contra a ciência tradicional e a lógica, como tendo repudiado a importância do indivíduo, a pressuposição da própria realidade e conseqüentemente, as formas de conhecimento que nos são acessíveis. Neste trabalho, procuramos mostrar um novo ângulo de compreensão da narrativa poética borgeana, evidenciando a capacidade dessa narrativa de apreender fenômenos culturais sob um ponto de vista científico. Apresentamos uma analogia entre a poética narrativa de Borges e a memética, sendo esta uma tentativa de interpretar a natureza humana em termos tanto de genes quanto de memes, ou seja, idéias compreendidas como padrões culturais. Embora qualquer obra literária seja veículo de idéias, acreditamos que Borges, escrevendo de forma extremamente crítica, parece estar especialmente consciente da independência das idéias, e seus personagens poderiam ser vistos como prisioneiros de labirintos de memes.Jorge Luis Borges' extensive fantasy writings have been read as a critique of traditional science and logic and as a repudiation of the individual's importance, of the presumption of reality itself, and, consequently, of the forms of knowledge accessible to us. The article presents a new way of understanding Borges' poetic narrative, evincing this narrative's ability to grasp cultural phenomenon from a scientific perspective. An analogy is drawn between Borges' poetic narrative and memetics, the latter being an attempt to interpret human nature in terms not only of genes but also of memes - that is, ideas understood as cultural patterns. Although any literary work is a vehicle for ideas, Borges, who writes in an extraordinarily critical fashion, seems particularly aware of the independence of ideas and therefore, the article asserts, his characters can be seen as prisoners inside labyrinths of memes.

  2. Similarity Scaling

    Science.gov (United States)

    Schnack, Dalton D.

    In Lecture 10, we introduced a non-dimensional parameter called the Lundquist number, denoted by S. This is just one of many non-dimensional parameters that can appear in the formulations of both hydrodynamics and MHD. These generally express the ratio of the time scale associated with some dissipative process to the time scale associated with either wave propagation or transport by flow. These are important because they define regions in parameter space that separate flows with different physical characteristics. All flows that have the same non-dimensional parameters behave in the same way. This property is called similarity scaling.

  3. 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.

  4. New Similarity Functions

    DEFF Research Database (Denmark)

    Yazdani, Hossein; Ortiz-Arroyo, Daniel; Kwasnicka, Halina

    2016-01-01

    In data science, there are important parameters that affect the accuracy of the algorithms used. Some of these parameters are: the type of data objects, the membership assignments, and distance or similarity functions. This paper discusses similarity functions as fundamental elements in membership...... assignments. The paper introduces Weighted Feature Distance (WFD), and Prioritized Weighted Feature Distance (PWFD), two new distance functions that take into account the diversity in feature spaces. WFD functions perform better in supervised and unsupervised methods by comparing data objects on their feature...... spaces, in addition to their similarity in the vector space. Prioritized Weighted Feature Distance (PWFD) works similarly as WFD, but provides the ability to give priorities to desirable features. The accuracy of the proposed functions are compared with other similarity functions on several data sets...

  5. 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.

  6. Similar or Different?: A Comparative Analysis of Higher Education Research in Political Science and International Relations between the United States of America and the United Kingdom

    Science.gov (United States)

    Blair, Alasdair

    2015-01-01

    This article focuses on the nature of the writing in 73 articles published in six U.S. and U.K. political science and international relations journals that focus on teaching and learning. A comparative analysis is made of the articles through a review of the characteristics of the authors, the themes researched, the analytical focus, the research…

  7. Similar or Different?: A Comparative Analysis of Higher Education Research in Political Science and International Relations between the United States of America and the United Kingdom

    Science.gov (United States)

    Blair, Alasdair

    2015-01-01

    This article focuses on the nature of the writing in 73 articles published in six U.S. and U.K. political science and international relations journals that focus on teaching and learning. A comparative analysis is made of the articles through a review of the characteristics of the authors, the themes researched, the analytical focus, the research…

  8. 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....

  9. 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.

  10. 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.

  11. Nutrition, Food Science, and Dietetics Faculty Have Information Needs Similar to Basic and Medical Sciences Faculty – Online Access to Electronic Journals, PubMed/Medline, and Google. A Review of: Shpilko, I. (2011. Assessing information-seeking patterns and needs of nutrition, food science, and dietetics faculty. Library & Information Science Research, 33(2, 151-157.

    Directory of Open Access Journals (Sweden)

    Mê-Linh Lê

    2011-01-01

    .1%. Databases were cited as the most effective way to locate relevant information (63.1%; PubMed was the most heavily used database (73.7%, although Medline (via EBSCO, Science Direct, and Academic Search Premier were also used.Respondents were asked how they preferred to obtain online research skills (e.g., on their own, via a colleague, via a librarian, or in some other way. The linked data does not answer this question, however, and instead supplies figures on what types of sessions respondents had attended in the past (44.4% attended library instruction sessions, while others were self-taught, consulted colleagues, attended seminars, or obtained skills through their PhD research.Conclusion – Strong public interest in nutritional issues is a growing trend in the Western world. For those faculty members and scholars researching and teaching on nutrition and related areas, more work on their information needs is required. This study begins to address that gap and found that nutrition, food science, and dietetics faculty share strong similarities with researchers in medicine and the other basic sciences with regard to information needs and behaviours. The focus is on electronic journals, PubMed/Medline, and online access to resources. Important insights include the fact that print journals are still in modest use, researchers use grey literature (e.g., government sources and other non-traditional formats (e.g., conference proceedings and electronic mail lists as information sources, and training sessions need to be offered in a variety of formats in order to address individual preferences.

  12. 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.

  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. General Didactics and Instructional Design: eyes like twins A transatlantic dialogue about similarities and differences, about the past and the future of two sciences of learning and teaching.

    Science.gov (United States)

    Zierer, Klaus; Seel, Norbert M

    2012-01-01

    Although General Didactics (GD) and Instructional Design (ID) have not shown many points of contact in the past, there are some obvious parellels from the perspective of their historical development. This will be examined in detail in this article. More specifically, we speak about model building, which has characterized General Didactics and Instructional Design for some decades. However, the models of General Didactics and Instructional Design are not problem-free with regard to the continuity and advancement of both disciplines. First, we will describe the historical roots of both disciplines and examine which elements of theory are of central importance. Second, we will try to answer the question of which kind of model building could be considered as predominant and what problems result from this predominance. In order to do this, we will describe empirical studies on the use of instructional models and discuss these studies from the perspective of the philosophy of science. Third, we will draw inferences for future processes of model building in order to prevent the same problems that happened in the past from happening again. Finally, we will discuss the issue of what General Didactics can learn from Instructional Design and vice versa.

  15. 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)

  16. 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.

  17. 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

  18. 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...

  19. "It's Funny that We Don't See the Similarities when that's what We're Aiming for"—Visualizing and Challenging Teachers' Stereotypes of Gender and Science

    Science.gov (United States)

    Andersson, Kristina

    2012-04-01

    This study illuminates teachers' conceptions of gender and science and possibilities to challenge these conceptions. Since 2005, a group of teachers (K-6) in Sweden have met approximately once a month in two-hour seminars to discuss and develop their instruction in science and technology based on a gender perspective. The present data consist mainly of audio-recordings of the teacher seminars and video-recordings of science activities with students. Analysis of the empirical data has been carried out in several stages and was inspired by thematic analysis, the theoretical framework of which is based on Hirdman's and Beauvoir's theories of gender. The results show that the teachers' ideas about gender/equity and science exist on several levels, within which various conceptions are represented. On the one hand, "reasoning around similarity", where teachers consider that both girls and boys should have the same prerequisites for working with science. In contrast, stereotypical conceptions of girls and boys occur when the teachers evaluate their activities with students, and condescending attitudes toward girls are also observed. The girls' ways of working with science are not as highly valued as the boys', and this outlook on children can ultimately have consequences for girls' attitudes towards the subject. When teachers are allowed to read their own statements about the girls, they get "a glimpse of themselves", and their condescending ideas about girls are made visible. In this way, the teachers can begin their active work towards change, which may lead to new outlooks on and attitudes towards students.

  20. 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.

  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. 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.

  3. 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.

  4. Assembly of alphavirus replication complexes from RNA and protein components in a novel trans-replication system in mammalian cells.

    Science.gov (United States)

    Spuul, Pirjo; Balistreri, Giuseppe; Hellström, Kirsi; Golubtsov, Andrey V; Jokitalo, Eija; Ahola, Tero

    2011-05-01

    For positive-strand RNA viruses, the viral genomic RNA also acts as an mRNA directing the translation of the replicase proteins of the virus. Replication takes place in association with cytoplasmic membranes, which are heavily modified to create specific replication compartments. Here we have expressed by plasmid DNA transfection the large replicase polyprotein of Semliki Forest virus (SFV) in mammalian cells from a nonreplicating mRNA and provided a separate RNA containing the replication signals. The replicase proteins were able to efficiently and specifically replicate the template in trans, leading to accumulation of RNA and marker gene products expressed from the template RNA. The replicase proteins and double-stranded RNA replication intermediates localized to structures similar to those seen in SFV-infected cells. Using correlative light electron microscopy (CLEM) with fluorescent marker proteins to relocate those transfected cells, in which active replication was ongoing, abundant membrane modifications, representing the replication complex spherules, were observed both at the plasma membrane and in intracellular endolysosomes. Thus, replication complexes are faithfully assembled and localized in the trans-replication system. We demonstrated, using CLEM, that the replication proteins alone or a polymerase-negative polyprotein mutant together with the template did not give rise to spherule formation. Thus, the trans-replication system is suitable for cell biological dissection and examination in a mammalian cell environment, and similar systems may be possible for other positive-strand RNA viruses.

  5. 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 ...

  6. Replication intermediate analysis confirms that chromosomal replication origin initiates from an unusual intergenic region in Caulobacter crescentus.

    Science.gov (United States)

    Brassinga, A K; Marczynski, G T

    2001-11-01

    The alpha-proteobacterium Caulobacter crescentus possesses a developmental cell cycle that restricts chromosome replication to a stalked cell type. The proposed C.crescentus chromosome replication origin (Cori) lies between hemE and RP001, an unusual intergenic region not previously associated with bacterial replication origins, although a similar genomic arrangement is also present at the putative replication origin in the related bacterium Rickettsia prowazekii. The cloned Cori supports autonomous plasmid replication selectively in the stalked cell type implying that replication of the entire chromosome also initiates between hemE and RP001. To confirm this location, we applied the 2-D (N/N) agarose gel electrophoresis technique to resolve and identify chromosome replication intermediates throughout a 30 kb region spanning Cori. Replication initiation in Cori was uniquely characterized by an 'origin bubble and Y-arc' pattern and this observation was supported by simple replication fork 'Y-arc' patterns that characterized the regions flanking Cori. These replication forks originated bi-directionally from within Cori as determined by the fork direction assay. Therefore, chromosomal replication initiates from the unusual hemE/RP001 intergenic region that we propose represents a new class of replication origins.

  7. 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...

  8. 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

  9. 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

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    DNA replication in eukaryotes requires nucleosome disruption ahead of the replication fork and reassembly behind. An unresolved issue concerns how histone dynamics are coordinated with fork progression to maintain chromosomal stability. Here, we characterize a complex in which the human histone...... chaperone Asf1 and MCM2-7, the putative replicative helicase, are connected through a histone H3-H4 bridge. Depletion of Asf1 by RNA interference impedes DNA unwinding at replication sites, and similar defects arise from overproduction of new histone H3-H4 that compromises Asf1 function. These data link Asf......1 chaperone function, histone supply, and replicative unwinding of DNA in chromatin. We propose that Asf1, as a histone acceptor and donor, handles parental and new histones at the replication fork via an Asf1-(H3-H4)-MCM2-7 intermediate and thus provides a means to fine-tune replication fork...

  11. 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.

  12. An Inadvertent Concurrent Replication: Same Roadmap, Different Journey

    Science.gov (United States)

    Lemons, Christopher J.; King, Seth A.; Davidson, Kimberly A.; Berryessa, Teresa L.; Gajjar, Shimul A.; Sacks, Lia H.

    2016-01-01

    Replication is a critical aspect of scientific inquiry that presents a variety of challenges to researchers, even under the best of conditions. We conducted a review of replication rates in special education journals similar to the review conducted by Makel et al. in this issue. Unknowingly conducting independent reviews allowed for an unexpected…

  13. 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...

  14. 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...

  15. 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 ...

  16. 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...

  17. 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…

  18. 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…

  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. 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

  1. 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.

  2. Intracellular Detection of Viral Transcription and Replication Using RNA FISH

    Science.gov (United States)

    2016-05-26

    Chapter 14. Intracellular detection of viral transcription and replication using RNA FISH i. Summary/Abstract Many hemorrhagic fever viruses...examine the mechanisms in which viruses replicate, assemble, and traffic through the cell. An additional benefit of this method is that the robust...Visualization of single RNA transcripts in situ. Science, 1998. 280(5363): p. 585-90. 4. Jambo, K.C., et al., Small alveolar macrophages are infected

  3. 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...

  4. 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.

  5. Publication bias and the failure of replication in experimental psychology.

    Science.gov (United States)

    Francis, Gregory

    2012-12-01

    Replication of empirical findings plays a fundamental role in science. Among experimental psychologists, successful replication enhances belief in a finding, while a failure to replicate is often interpreted to mean that one of the experiments is flawed. This view is wrong. Because experimental psychology uses statistics, empirical findings should appear with predictable probabilities. In a misguided effort to demonstrate successful replication of empirical findings and avoid failures to replicate, experimental psychologists sometimes report too many positive results. Rather than strengthen confidence in an effect, too much successful replication actually indicates publication bias, which invalidates entire sets of experimental findings. Researchers cannot judge the validity of a set of biased experiments because the experiment set may consist entirely of type I errors. This article shows how an investigation of the effect sizes from reported experiments can test for publication bias by looking for too much successful replication. Simulated experiments demonstrate that the publication bias test is able to discriminate biased experiment sets from unbiased experiment sets, but it is conservative about reporting bias. The test is then applied to several studies of prominent phenomena that highlight how publication bias contaminates some findings in experimental psychology. Additional simulated experiments demonstrate that using Bayesian methods of data analysis can reduce (and in some cases, eliminate) the occurrence of publication bias. Such methods should be part of a systematic process to remove publication bias from experimental psychology and reinstate the important role of replication as a final arbiter of scientific findings.

  6. When Science Replaces Religion: Science as a Secular Authority Bolsters Moral Sensitivity.

    Science.gov (United States)

    Yilmaz, Onurcan; Bahçekapili, Hasan G

    2015-01-01

    Scientific and religious thinking compete with each other on several levels. For example, activating one generally weakens the other. Since priming religion is known to increase moral behaviour and moral sensitivity, priming science might be expected to have the opposite effect. However, it was recently demonstrated that, on the contrary, science priming increases moral sensitivity as well. The present set of studies sought to replicate this effect and test two explanations for it. Study 1 used a sentence unscrambling task for implicitly priming the concept of science but failed to replicate its effect on moral sensitivity, presumably due to a ceiling effect. Study 2 replicated the effect with a new measure of moral sensitivity. Study 3 tested whether science-related words create this effect by activating the idea of secular authority or by activating analytic thinking. It was demonstrated that words related to secular authority, but not words related to analytic thinking, produced a similar increase in moral sensitivity. Religiosity level of the participants did not influence this basic finding. The results are consistent with the hypothesis that science as a secular institution has overtaken some of the functions of religion in modern societies.

  7. Roget's Thesaurus and Semantic Similarity

    CERN Document Server

    Jarmasz, Mario

    2012-01-01

    We have implemented a system that measures semantic similarity using a computerized 1987 Roget's Thesaurus, and evaluated it by performing a few typical tests. We compare the results of these tests with those produced by WordNet-based similarity measures. One of the benchmarks is Miller and Charles' list of 30 noun pairs to which human judges had assigned similarity measures. We correlate these measures with those computed by several NLP systems. The 30 pairs can be traced back to Rubenstein and Goodenough's 65 pairs, which we have also studied. Our Roget's-based system gets correlations of .878 for the smaller and .818 for the larger list of noun pairs; this is quite close to the .885 that Resnik obtained when he employed humans to replicate the Miller and Charles experiment. We further evaluate our measure by using Roget's and WordNet to answer 80 TOEFL, 50 ESL and 300 Reader's Digest questions: the correct synonym must be selected amongst a group of four words. Our system gets 78.75%, 82.00% and 74.33% of ...

  8. 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

  9. 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

  10. 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.

  11. Interpersonal attraction and personality: what is attractive--self similarity, ideal similarity, complementarity or attachment security?

    Science.gov (United States)

    Klohnen, Eva C; Luo, Shanhong

    2003-10-01

    Little is known about whether personality characteristics influence initial attraction. Because adult attachment differences influence a broad range of relationship processes, the authors examined their role in 3 experimental attraction studies. The authors tested four major attraction hypotheses--self similarity, ideal-self similarity, complementarity, and attachment security--and examined both actual and perceptual factors. Replicated analyses across samples, designs, and manipulations showed that actual security and self similarity predicted attraction. With regard to perceptual factors, ideal similarity, self similarity, and security all were significant predictors. Whereas perceptual ideal and self similarity had incremental predictive power, perceptual security's effects were subsumed by perceptual ideal similarity. Perceptual self similarity fully mediated actual attachment similarity effects, whereas ideal similarity was only a partial mediator.

  12. The Nature of Stability in Replicating Systems

    Directory of Open Access Journals (Sweden)

    Addy Pross

    2011-02-01

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

  13. 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…

  14. Replication, Communication, and the Population Dynamics of Scientific Discovery.

    Directory of Open Access Journals (Sweden)

    Richard McElreath

    Full Text Available Many published research results are false (Ioannidis, 2005, and controversy continues over the roles of replication and publication policy in improving the reliability of research. Addressing these problems is frustrated by the lack of a formal framework that jointly represents hypothesis formation, replication, publication bias, and variation in research quality. We develop a mathematical model of scientific discovery that combines all of these elements. This model provides both a dynamic model of research as well as a formal framework for reasoning about the normative structure of science. We show that replication may serve as a ratchet that gradually separates true hypotheses from false, but the same factors that make initial findings unreliable also make replications unreliable. The most important factors in improving the reliability of research are the rate of false positives and the base rate of true hypotheses, and we offer suggestions for addressing each. Our results also bring clarity to verbal debates about the communication of research. Surprisingly, publication bias is not always an obstacle, but instead may have positive impacts-suppression of negative novel findings is often beneficial. We also find that communication of negative replications may aid true discovery even when attempts to replicate have diminished power. The model speaks constructively to ongoing debates about the design and conduct of science, focusing analysis and discussion on precise, internally consistent models, as well as highlighting the importance of population dynamics.

  15. Replication, Communication, and the Population Dynamics of Scientific Discovery.

    Science.gov (United States)

    McElreath, Richard; Smaldino, Paul E

    2015-01-01

    Many published research results are false (Ioannidis, 2005), and controversy continues over the roles of replication and publication policy in improving the reliability of research. Addressing these problems is frustrated by the lack of a formal framework that jointly represents hypothesis formation, replication, publication bias, and variation in research quality. We develop a mathematical model of scientific discovery that combines all of these elements. This model provides both a dynamic model of research as well as a formal framework for reasoning about the normative structure of science. We show that replication may serve as a ratchet that gradually separates true hypotheses from false, but the same factors that make initial findings unreliable also make replications unreliable. The most important factors in improving the reliability of research are the rate of false positives and the base rate of true hypotheses, and we offer suggestions for addressing each. Our results also bring clarity to verbal debates about the communication of research. Surprisingly, publication bias is not always an obstacle, but instead may have positive impacts-suppression of negative novel findings is often beneficial. We also find that communication of negative replications may aid true discovery even when attempts to replicate have diminished power. The model speaks constructively to ongoing debates about the design and conduct of science, focusing analysis and discussion on precise, internally consistent models, as well as highlighting the importance of population dynamics.

  16. 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.

  17. 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.

  18. 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.

  19. Universal Temporal Profile of Replication Origin Activation in Eukaryotes

    Science.gov (United States)

    Goldar, Arach

    2011-03-01

    The complete and faithful transmission of eukaryotic genome to daughter cells involves the timely duplication of mother cell's DNA. DNA replication starts at multiple chromosomal positions called replication origin. From each activated replication origin two replication forks progress in opposite direction and duplicate the mother cell's DNA. While it is widely accepted that in eukaryotic organisms replication origins are activated in a stochastic manner, little is known on the sources of the observed stochasticity. It is often associated to the population variability to enter S phase. We extract from a growing Saccharomyces cerevisiae population the average rate of origin activation in a single cell by combining single molecule measurements and a numerical deconvolution technique. We show that the temporal profile of the rate of origin activation in a single cell is similar to the one extracted from a replicating cell population. Taking into account this observation we exclude the population variability as the origin of observed stochasticity in origin activation. We confirm that the rate of origin activation increases in the early stage of S phase and decreases at the latter stage. The population average activation rate extracted from single molecule analysis is in prefect accordance with the activation rate extracted from published micro-array data, confirming therefore the homogeneity and genome scale invariance of dynamic of replication process. All these observations point toward a possible role of replication fork to control the rate of origin activation.

  20. Enzymes involved in organellar DNA replication in photosynthetic eukaryotes

    Directory of Open Access Journals (Sweden)

    Takashi eMoriyama

    2014-09-01

    Full Text Available Plastids and mitochondria possess their own genomes. Although the replication mechanisms of these organellar genomes remain unclear in photosynthetic eukaryotes, several organelle-localized enzymes related to genome replication, including DNA polymerase, DNA primase, DNA helicase, DNA topoisomerase, single-stranded DNA maintenance protein, DNA ligase, primer removal enzyme, and several DNA recombination-related enzymes, have been identified. In the reference Eudicot plant Arabidopsis thaliana, the replication-related enzymes of plastids and mitochondria are similar because many of them are dual targeted to both organelles, whereas in the red alga Cyanidioschyzon merolae, plastids and mitochondria contain different replication machinery components. The enzymes involved in organellar genome replication in green plants and red algae were derived from different origins, including proteobacterial, cyanobacterial, and eukaryotic lineages. In the present review, we summarize the available data for enzymes related to organellar genome replication in green plants and red algae. In addition, based on the type and distribution of replication enzymes in photosynthetic eukaryotes, we discuss the transitional history of replication enzymes in the organelles of plants.

  1. 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…

  2. Similarity transformations of MAPs

    Directory of Open Access Journals (Sweden)

    Andersen Allan T.

    1999-01-01

    Full Text Available We introduce the notion of similar Markovian Arrival Processes (MAPs and show that the event stationary point processes related to two similar MAPs are stochastically equivalent. This holds true for the time stationary point processes too. We show that several well known stochastical equivalences as e.g. that between the H 2 renewal process and the Interrupted Poisson Process (IPP can be expressed by the similarity transformations of MAPs. In the appendix the valid region of similarity transformations for two-state MAPs is characterized.

  3. Revisiting Mental Simulation in Language Comprehension: Six Replication Attempts

    NARCIS (Netherlands)

    R.A. Zwaan (Rolf); D. Pecher (Diane)

    2012-01-01

    textabstractThe notion of language comprehension as mental simulation has become popular in cognitive science. We revisit some of the original empirical evidence for this. Specifically, we attempted to replicate the findings from earlier studies that examined the mental simulation of object orientat

  4. 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....

  5. 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.

  6. 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...

  7. Clustering by Pattern Similarity

    Institute of Scientific and Technical Information of China (English)

    Hai-xun Wang; Jian Pei

    2008-01-01

    The task of clustering is to identify classes of similar objects among a set of objects. The definition of similarity varies from one clustering model to another. However, in most of these models the concept of similarity is often based on such metrics as Manhattan distance, Euclidean distance or other Lp distances. In other words, similar objects must have close values in at least a set of dimensions. In this paper, we explore a more general type of similarity. Under the pCluster model we proposed, two objects are similar if they exhibit a coherent pattern on a subset of dimensions. The new similarity concept models a wide range of applications. For instance, in DNA microarray analysis, the expression levels of two genes may rise and fall synchronously in response to a set of environmental stimuli. Although the magnitude of their expression levels may not be close, the patterns they exhibit can be very much alike. Discovery of such clusters of genes is essential in revealing significant connections in gene regulatory networks. E-commerce applications, such as collaborative filtering, can also benefit from the new model, because it is able to capture not only the closeness of values of certain leading indicators but also the closeness of (purchasing, browsing, etc.) patterns exhibited by the customers. In addition to the novel similarity model, this paper also introduces an effective and efficient algorithm to detect such clusters, and we perform tests on several real and synthetic data sets to show its performance.

  8. Judgments of brand similarity

    NARCIS (Netherlands)

    Bijmolt, THA; Wedel, M; Pieters, RGM; DeSarbo, WS

    This paper provides empirical insight into the way consumers make pairwise similarity judgments between brands, and how familiarity with the brands, serial position of the pair in a sequence, and the presentation format affect these judgments. Within the similarity judgment process both the

  9. Judgments of brand similarity

    NARCIS (Netherlands)

    Bijmolt, THA; Wedel, M; Pieters, RGM; DeSarbo, WS

    1998-01-01

    This paper provides empirical insight into the way consumers make pairwise similarity judgments between brands, and how familiarity with the brands, serial position of the pair in a sequence, and the presentation format affect these judgments. Within the similarity judgment process both the formatio

  10. The semantic similarity ensemble

    Directory of Open Access Journals (Sweden)

    Andrea Ballatore

    2013-12-01

    Full Text Available Computational measures of semantic similarity between geographic terms provide valuable support across geographic information retrieval, data mining, and information integration. To date, a wide variety of approaches to geo-semantic similarity have been devised. A judgment of similarity is not intrinsically right or wrong, but obtains a certain degree of cognitive plausibility, depending on how closely it mimics human behavior. Thus selecting the most appropriate measure for a specific task is a significant challenge. To address this issue, we make an analogy between computational similarity measures and soliciting domain expert opinions, which incorporate a subjective set of beliefs, perceptions, hypotheses, and epistemic biases. Following this analogy, we define the semantic similarity ensemble (SSE as a composition of different similarity measures, acting as a panel of experts having to reach a decision on the semantic similarity of a set of geographic terms. The approach is evaluated in comparison to human judgments, and results indicate that an SSE performs better than the average of its parts. Although the best member tends to outperform the ensemble, all ensembles outperform the average performance of each ensemble's member. Hence, in contexts where the best measure is unknown, the ensemble provides a more cognitively plausible approach.

  11. Biomarkers of replicative senescence revisited

    DEFF Research Database (Denmark)

    Nehlin, Jan

    2016-01-01

    Biomarkers of replicative senescence can be defined as those ultrastructural and physiological variations as well as molecules whose changes in expression, activity or function correlate with aging, as a result of the gradual exhaustion of replicative potential and a state of permanent cell cycle...... 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....

  12. Similar component analysis

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hong; WANG Xin; LI Junwei; CAO Xianguang

    2006-01-01

    A new unsupervised feature extraction method called similar component analysis (SCA) is proposed in this paper. SCA method has a self-aggregation property that the data objects will move towards each other to form clusters through SCA theoretically,which can reveal the inherent pattern of similarity hidden in the dataset. The inputs of SCA are just the pairwise similarities of the dataset,which makes it easier for time series analysis due to the variable length of the time series. Our experimental results on many problems have verified the effectiveness of SCA on some engineering application.

  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. Gender similarities and differences.

    Science.gov (United States)

    Hyde, Janet Shibley

    2014-01-01

    Whether men and women are fundamentally different or similar has been debated for more than a century. This review summarizes major theories designed to explain gender differences: evolutionary theories, cognitive social learning theory, sociocultural theory, and expectancy-value theory. The gender similarities hypothesis raises the possibility of theorizing gender similarities. Statistical methods for the analysis of gender differences and similarities are reviewed, including effect sizes, meta-analysis, taxometric analysis, and equivalence testing. Then, relying mainly on evidence from meta-analyses, gender differences are reviewed in cognitive performance (e.g., math performance), personality and social behaviors (e.g., temperament, emotions, aggression, and leadership), and psychological well-being. The evidence on gender differences in variance is summarized. The final sections explore applications of intersectionality and directions for future research.

  16. 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.

  17. Analysis of the Occurrence of "Applications/Replications" in Ten Published Papers

    Science.gov (United States)

    Fahy, Patrick J.

    2017-01-01

    "Application" or "replication" research, already rare, is diminishing in both quantity and quality, for a variety of reasons ("How science goes wrong," 2013; "For my next trick," 2016). In this study of "replications" and "applications," 351 papers that included a reference to any one of…

  18. Involvement of proliferating cell nuclear antigen (Cyclin) in DNA replication in living cells

    Energy Technology Data Exchange (ETDEWEB)

    Zuber, M.; Tan, E.M.; Ryoji, M.

    1989-01-01

    Proliferating cell nuclear antigen (PCNA) (also called cyclin) is known to stimulate the activity of DNA polymerase /delta/ but not the other DNA polymerases in vitro. The authors injected a human autoimmune antibody against PCNA into unfertilized eggs of Xenopus laevis and examined the effects of this antibody on the replication of injected plasmid DNA as well as egg chromosomes. The anti-PCNA antibody inhibited plasmid replication by up to 67%, demonstrating that PCNA is involved in plasmid replication in living cells. This result further implies that DNA polymerase /delta/ is necessary for plasmid replication in vivo, Anti-PCNA antibody alone did not block plasmid replication completely, but the residual replication was abolished by coinjection of a monoclonal antibody against DNA polymerase /alpha/. Anti-DNA polymerase /alpha/ alone inhibited plasmid replication by 63%. Thus, DNA ploymerase /alpha/ is also required for plasmid replication in this system. In similar studies on the replication of egg chromosomes, the inhibition by anti-PCNA antibody was only 30%, while anti-DNA polymerase /alpha/ antibody blocked 73% of replication. They concluded that the replication machineries of chromosomes and plasmid differ in their relative content of DNA polymerase /delta/. In addition, they obtained evidence through the use of phenylbutyl deoxyguanosine, an inhibitor of DNA polymearse /alpha/, that the structure of DNA polymerase /alpha/ holoenzyme for chromosome replication is significantly different from that for plasmid replication.

  19. SMARCAL1 maintains telomere integrity during DNA replication.

    Science.gov (United States)

    Poole, Lisa A; Zhao, Runxiang; Glick, Gloria G; Lovejoy, Courtney A; Eischen, Christine M; Cortez, David

    2015-12-01

    The SMARCAL1 (SWI/SNF related, matrix-associated, actin-dependent, regulator of chromatin, subfamily A-like 1) DNA translocase is one of several related enzymes, including ZRANB3 (zinc finger, RAN-binding domain containing 3) and HLTF (helicase-like transcription factor), that are recruited to stalled replication forks to promote repair and restart replication. These enzymes can perform similar biochemical reactions such as fork reversal; however, genetic studies indicate they must have unique cellular activities. Here, we present data showing that SMARCAL1 has an important function at telomeres, which present an endogenous source of replication stress. SMARCAL1-deficient cells accumulate telomere-associated DNA damage and have greatly elevated levels of extrachromosomal telomere DNA (C-circles). Although these telomere phenotypes are often found in tumor cells using the alternative lengthening of telomeres (ALT) pathway for telomere elongation, SMARCAL1 deficiency does not yield other ALT phenotypes such as elevated telomere recombination. The activity of SMARCAL1 at telomeres can be separated from its genome-maintenance activity in bulk chromosomal replication because it does not require interaction with replication protein A. Finally, this telomere-maintenance function is not shared by ZRANB3 or HLTF. Our results provide the first identification, to our knowledge, of an endogenous source of replication stress that requires SMARCAL1 for resolution and define differences between members of this class of replication fork-repair enzymes.

  20. 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.

  1. Social Values as Arguments: Similar is Convincing

    Directory of Open Access Journals (Sweden)

    Gregory R Maio

    2014-08-01

    Full Text Available Politicians, philosophers, and rhetors engage in co-value argumentation: appealing to one value in order to support another value (e.g., equality leads to freedom. Across four experiments in the United Kingdom and India, we found that the psychological relatedness of values affects the persuasiveness of the arguments that bind them. Experiment 1 found that participants were more persuaded by arguments citing values that fulfilled similar motives than by arguments citing opposing values. Experiments 2 and 3 replicated this result using a wider variety of values, while finding that the effect is stronger among people higher in need for cognition and that the effect is mediated by the greater plausibility of co-value arguments that link motivationally compatible values. Experiment 4 extended the effect to real-world arguments taken from political propaganda and replicated the mediating effect of argument plausibility. The findings highlight the importance of value relatedness in argument persuasiveness.

  2. Compression-based Similarity

    CERN Document Server

    Vitanyi, Paul M B

    2011-01-01

    First we consider pair-wise distances for literal objects consisting of finite binary files. These files are taken to contain all of their meaning, like genomes or books. The distances are based on compression of the objects concerned, normalized, and can be viewed as similarity distances. Second, we consider pair-wise distances between names of objects, like "red" or "christianity." In this case the distances are based on searches of the Internet. Such a search can be performed by any search engine that returns aggregate page counts. We can extract a code length from the numbers returned, use the same formula as before, and derive a similarity or relative semantics between names for objects. The theory is based on Kolmogorov complexity. We test both similarities extensively experimentally.

  3. Similarity or difference?

    DEFF Research Database (Denmark)

    Villadsen, Anders Ryom

    2013-01-01

    While the organizational structures and strategies of public organizations have attracted substantial research attention among public management scholars, little research has explored how these organizational core dimensions are interconnected and influenced by pressures for similarity....... In this paper I address this topic by exploring the relation between expenditure strategy isomorphism and structure isomorphism in Danish municipalities. Different literatures suggest that organizations exist in concurrent pressures for being similar to and different from other organizations in their field......-shaped relation exists between expenditure strategy isomorphism and structure isomorphism in a longitudinal quantitative study of Danish municipalities....

  4. Segmentation Similarity and Agreement

    CERN Document Server

    Fournier, Chris

    2012-01-01

    We propose a new segmentation evaluation metric, called segmentation similarity (S), that quantifies the similarity between two segmentations as the proportion of boundaries that are not transformed when comparing them using edit distance, essentially using edit distance as a penalty function and scaling penalties by segmentation size. We propose several adapted inter-annotator agreement coefficients which use S that are suitable for segmentation. We show that S is configurable enough to suit a wide variety of segmentation evaluations, and is an improvement upon the state of the art. We also propose using inter-annotator agreement coefficients to evaluate automatic segmenters in terms of human performance.

  5. A subset of replication proteins enhances origin recognition and lytic replication by the Epstein-Barr virus ZEBRA protein.

    Directory of Open Access Journals (Sweden)

    Ayman El-Guindy

    Full Text Available ZEBRA is a site-specific DNA binding protein that functions as a transcriptional activator and as an origin binding protein. Both activities require that ZEBRA recognizes DNA motifs that are scattered along the viral genome. The mechanism by which ZEBRA discriminates between the origin of lytic replication and promoters of EBV early genes is not well understood. We explored the hypothesis that activation of replication requires stronger association between ZEBRA and DNA than does transcription. A ZEBRA mutant, Z(S173A, at a phosphorylation site and three point mutants in the DNA recognition domain of ZEBRA, namely Z(Y180E, Z(R187K and Z(K188A, were similarly deficient at activating lytic DNA replication and expression of late gene expression but were competent to activate transcription of viral early lytic genes. These mutants all exhibited reduced capacity to interact with DNA as assessed by EMSA, ChIP and an in vivo biotinylated DNA pull-down assay. Over-expression of three virally encoded replication proteins, namely the primase (BSLF1, the single-stranded DNA-binding protein (BALF2 and the DNA polymerase processivity factor (BMRF1, partially rescued the replication defect in these mutants and enhanced ZEBRA's interaction with oriLyt. The findings demonstrate a functional role of replication proteins in stabilizing the association of ZEBRA with viral DNA. Enhanced binding of ZEBRA to oriLyt is crucial for lytic viral DNA replication.

  6. Incremental Similarity and Turbulence

    DEFF Research Database (Denmark)

    Barndorff-Nielsen, Ole E.; Hedevang, Emil; Schmiegel, Jürgen

    This paper discusses the mathematical representation of an empirically observed phenomenon, referred to as Incremental Similarity. We discuss this feature from the viewpoint of stochastic processes and present a variety of non-trivial examples, including those that are of relevance for turbulence...

  7. 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.

  8. 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...

  9. 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.

  10. 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…

  11. Rapid transient production in plants by replicating and non-replicating vectors yields high quality functional anti-HIV antibody.

    Directory of Open Access Journals (Sweden)

    Frank Sainsbury

    Full Text Available The capacity of plants and plant cells to produce large amounts of recombinant protein has been well established. Due to advantages in terms of speed and yield, attention has recently turned towards the use of transient expression systems, including viral vectors, to produce proteins of pharmaceutical interest in plants. However, the effects of such high level expression from viral vectors and concomitant effects on host cells may affect the quality of the recombinant product.To assess the quality of antibodies transiently expressed to high levels in plants, we have expressed and characterised the human anti-HIV monoclonal antibody, 2G12, using both replicating and non-replicating systems based on deleted versions of Cowpea mosaic virus (CPMV RNA-2. The highest yield (approximately 100 mg/kg wet weight leaf tissue of affinity purified 2G12 was obtained when the non-replicating CPMV-HT system was used and the antibody was retained in the endoplasmic reticulum (ER. Glycan analysis by mass-spectrometry showed that the glycosylation pattern was determined exclusively by whether the antibody was retained in the ER and did not depend on whether a replicating or non-replicating system was used. Characterisation of the binding and neutralisation properties of all the purified 2G12 variants from plants showed that these were generally similar to those of the Chinese hamster ovary (CHO cell-produced 2G12.Overall, the results demonstrate that replicating and non-replicating CPMV-based vectors are able to direct the production of a recombinant IgG similar in activity to the CHO-produced control. Thus, a complex recombinant protein was produced with no apparent effect on its biochemical properties using either high-level expression or viral replication. The speed with which a recombinant pharmaceutical with excellent biochemical characteristics can be produced transiently in plants makes CPMV-based expression vectors an attractive option for

  12. 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...

  13. Science Bubbles

    DEFF Research Database (Denmark)

    Hendricks, Vincent Fella; Pedersen, David Budtz

    2013-01-01

    Much like the trade and trait sof bubbles in financial markets,similar bubbles appear on the science market. When economic bubbles burst, the drop in prices causes the crash of unsustainable investments leading to an investor confidence crisis possibly followed by a financial panic. But when...... bubbles appear in science, truth and reliability are the first victims. This paper explores how fashions in research funding and research management may turn science into something like a bubble economy....

  14. More Similar Than Different

    DEFF Research Database (Denmark)

    Pedersen, Mogens Jin

    2015-01-01

    What role do employee features play into the success of different personnel management practices for serving high performance? Using data from a randomized survey experiment among 5,982 individuals of all ages, this article examines how gender conditions the compliance effects of different...... incentive treatments—each relating to the basic content of distinct types of personnel management practices. The findings show that males and females are more similar than different in terms of the incentive treatments’ effects: Significant average effects are found for three out of five incentive...

  15. 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.

  16. 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.

  17. 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

  18. 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…

  19. 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

  20. Similar dissection of sets

    CERN Document Server

    Akiyama, Shigeki; Okazaki, Ryotaro; Steiner, Wolfgang; Thuswaldner, Jörg

    2010-01-01

    In 1994, Martin Gardner stated a set of questions concerning the dissection of a square or an equilateral triangle in three similar parts. Meanwhile, Gardner's questions have been generalized and some of them are already solved. In the present paper, we solve more of his questions and treat them in a much more general context. Let $D\\subset \\mathbb{R}^d$ be a given set and let $f_1,...,f_k$ be injective continuous mappings. Does there exist a set $X$ such that $D = X \\cup f_1(X) \\cup ... \\cup f_k(X)$ is satisfied with a non-overlapping union? We prove that such a set $X$ exists for certain choices of $D$ and $\\{f_1,...,f_k\\}$. The solutions $X$ often turn out to be attractors of iterated function systems with condensation in the sense of Barnsley. Coming back to Gardner's setting, we use our theory to prove that an equilateral triangle can be dissected in three similar copies whose areas have ratio $1:1:a$ for $a \\ge (3+\\sqrt{5})/2$.

  1. Replication initiatives will not salvage the trustworthiness of psychology.

    Science.gov (United States)

    Coyne, James C

    2016-05-31

    Replication initiatives in psychology continue to gather considerable attention from far outside the field, as well as controversy from within. Some accomplishments of these initiatives are noted, but this article focuses on why they do not provide a general solution for what ails psychology. There are inherent limitations to mass replications ever being conducted in many areas of psychology, both in terms of their practicality and their prospects for improving the science. Unnecessary compromises were built into the ground rules for design and publication of the Open Science Collaboration: Psychology that undermine its effectiveness. Some ground rules could actually be flipped into guidance for how not to conduct replications. Greater adherence to best publication practices, transparency in the design and publishing of research, strengthening of independent post-publication peer review and firmer enforcement of rules about data sharing and declarations of conflict of interest would make many replications unnecessary. Yet, it has been difficult to move beyond simple endorsement of these measures to consistent implementation. Given the strong institutional support for questionable publication practices, progress will depend on effective individual and collective use of social media to expose lapses and demand reform. Some recent incidents highlight the necessity of this.

  2. Some more similarities between Peirce and Skinner

    OpenAIRE

    Moxley, Roy A.

    2002-01-01

    C. S. Peirce is noted for pioneering a variety of views, and the case is made here for the similarities and parallels between his views and B. F. Skinner's radical behaviorism. In addition to parallels previously noted, these similarities include an advancement of experimental science, a behavioral psychology, a shift from nominalism to realism, an opposition to positivism, a selectionist account for strengthening behavior, the importance of a community of selves, a recursive approach to meth...

  3. Similarity transformed semiclassical dynamics

    Science.gov (United States)

    Van Voorhis, Troy; Heller, Eric J.

    2003-12-01

    In this article, we employ a recently discovered criterion for selecting important contributions to the semiclassical coherent state propagator [T. Van Voorhis and E. J. Heller, Phys. Rev. A 66, 050501 (2002)] to study the dynamics of many dimensional problems. We show that the dynamics are governed by a similarity transformed version of the standard classical Hamiltonian. In this light, our selection criterion amounts to using trajectories generated with the untransformed Hamiltonian as approximate initial conditions for the transformed boundary value problem. We apply the new selection scheme to some multidimensional Henon-Heiles problems and compare our results to those obtained with the more sophisticated Herman-Kluk approach. We find that the present technique gives near-quantitative agreement with the the standard results, but that the amount of computational effort is less than Herman-Kluk requires even when sophisticated integral smoothing techniques are employed in the latter.

  4. 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...

  5. 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...

  6. Role of Cellular Components of Mosquito Cells in Viral Replication and Transmission.

    Science.gov (United States)

    1981-03-17

    replicating in mosquito cells, experiments similar to those described above were conducted employing Eastern equine encephalitis virus ( alphavirus ...7 D-R126 612 ROLE OF CELLULAR COMPONENTS OF MOSQUITO CELLS IN VIRAL 1/1 REPLICATION AND TRANSMISSION(U) INDIANA UNIV AT INDIANAPOLIS SCHOOL OF...MOSQUITO CELLS IN VIRAL REPLICATION AND TRANSMISSION Annual Report Final Report Robert H. Schloemer March 17, 1981 Supported by U.S. Army Medical

  7. La inserción profesional de los graduados en Ciencias de la Educación : panorama en Iberoamérica y configuraciones en Argentina = Employability of graduates in Sciences Education : similarities and differences in Ibero-America

    Directory of Open Access Journals (Sweden)

    María Eugenia Vicente

    2014-09-01

    Full Text Available El campo profesional de las Ciencias de la Educación es caracterizado como heterogéneo, difuso y fragmentado debido a las tendencias de diversificación de los espacios de inserción profesional en Iberoamérica. En este sentido, el presente estudio pretende aportar datos sobre las características comunes y diferentes de los mecanismos de inserción profesional y del campo profesional de las Ciencias de la Educación en el plano internacional. Para ello, se lleva a cabo un análisis comparativo de fuentes secundarias a partir de las siguientes dimensiones: I la situación de empleabilidad, II el tiempo que tardaron en conseguir el primer empleo, III las formas de ingreso a los espacios de trabajo IV la formación recibida.The professional field of Sciences Education is characterized as heterogeneous, diffuse and fragmented due to diversification of the employment spaces in Iberoamerica. The present study aim is to provide data on the common and different features of mechanisms employability and professional field of Educational Sciences at the international level. For that purpose, this study developed a comparative analysis of secondary sources around the following dimensions: I the situation of employability, II the time that graduates get the first job, III the forms of access to the employment spaces, and IV training.

  8. UTeach Replication: Impacting Teacher Preparation at a University Near You

    Science.gov (United States)

    Marshall, Jill

    2008-03-01

    In 2007 the National Mathematics and Science Initiative, with a grant from Exxon-Mobil, launched two major programs to improve science and mathematics education in the US: an Advanced Placement initiative and replication of the UTeach program. Twelve colleges and universities, from Florida to California, have been selected to receive grants of up to 2.4 million to start UTeach-type programs. I will report on the requirements for these grants, what it really means to have a ``UTeach-type'' program and the evidence that such programs can affect the quantity and quality of physics teachers in the US.

  9. 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...

  10. 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...

  11. 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.

  12. 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.

  13. DEVELOPMENT OF TRANSPORT SUBSYSTEM STREAMING DATA REPLICATION CLUSTER IN CORBA-SYSTEM WITH ZEROMQ TECHNOLOGY

    Directory of Open Access Journals (Sweden)

    F. A. Kozlov

    2013-03-01

    Full Text Available The article deals with the peculiarities of distributed cluster system creation with streaming data replication. Ways of replication cluster implementation in CORBA-systems with ZeroMq technology are presented. Major advantages of ZeroMQ technology over similar technologies are considered in this type distributed systems creation.

  14. Arabidopsis thaliana chromosome 4 replicates in two phases that correlate with chromatin state.

    Science.gov (United States)

    Lee, Tae-Jin; Pascuzzi, Pete E; Settlage, Sharon B; Shultz, Randall W; Tanurdzic, Milos; Rabinowicz, Pablo D; Menges, Margit; Zheng, Ping; Main, Dorrie; Murray, James A H; Sosinski, Bryon; Allen, George C; Martienssen, Robert A; Hanley-Bowdoin, Linda; Vaughn, Matthew W; Thompson, William F

    2010-06-10

    DNA replication programs have been studied extensively in yeast and animal systems, where they have been shown to correlate with gene expression and certain epigenetic modifications. Despite the conservation of core DNA replication proteins, little is known about replication programs in plants. We used flow cytometry and tiling microarrays to profile DNA replication of Arabidopsis thaliana chromosome 4 (chr4) during early, mid, and late S phase. Replication profiles for early and mid S phase were similar and encompassed the majority of the euchromatin. Late S phase exhibited a distinctly different profile that includes the remaining euchromatin and essentially all of the heterochromatin. Termination zones were consistent between experiments, allowing us to define 163 putative replicons on chr4 that clustered into larger domains of predominately early or late replication. Early-replicating sequences, especially the initiation zones of early replicons, displayed a pattern of epigenetic modifications specifying an open chromatin conformation. Late replicons, and the termination zones of early replicons, showed an opposite pattern. Histone H3 acetylated on lysine 56 (H3K56ac) was enriched in early replicons, as well as the initiation zones of both early and late replicons. H3K56ac was also associated with expressed genes, but this effect was local whereas replication time correlated with H3K56ac over broad regions. The similarity of the replication profiles for early and mid S phase cells indicates that replication origin activation in euchromatin is stochastic. Replicon organization in Arabidopsis is strongly influenced by epigenetic modifications to histones and DNA. The domain organization of Arabidopsis is more similar to that in Drosophila than that in mammals, which may reflect genome size and complexity. The distinct patterns of association of H3K56ac with gene expression and early replication provide evidence that H3K56ac may be associated with initiation zones

  15. Arabidopsis thaliana chromosome 4 replicates in two phases that correlate with chromatin state.

    Directory of Open Access Journals (Sweden)

    Tae-Jin Lee

    2010-06-01

    Full Text Available DNA replication programs have been studied extensively in yeast and animal systems, where they have been shown to correlate with gene expression and certain epigenetic modifications. Despite the conservation of core DNA replication proteins, little is known about replication programs in plants. We used flow cytometry and tiling microarrays to profile DNA replication of Arabidopsis thaliana chromosome 4 (chr4 during early, mid, and late S phase. Replication profiles for early and mid S phase were similar and encompassed the majority of the euchromatin. Late S phase exhibited a distinctly different profile that includes the remaining euchromatin and essentially all of the heterochromatin. Termination zones were consistent between experiments, allowing us to define 163 putative replicons on chr4 that clustered into larger domains of predominately early or late replication. Early-replicating sequences, especially the initiation zones of early replicons, displayed a pattern of epigenetic modifications specifying an open chromatin conformation. Late replicons, and the termination zones of early replicons, showed an opposite pattern. Histone H3 acetylated on lysine 56 (H3K56ac was enriched in early replicons, as well as the initiation zones of both early and late replicons. H3K56ac was also associated with expressed genes, but this effect was local whereas replication time correlated with H3K56ac over broad regions. The similarity of the replication profiles for early and mid S phase cells indicates that replication origin activation in euchromatin is stochastic. Replicon organization in Arabidopsis is strongly influenced by epigenetic modifications to histones and DNA. The domain organization of Arabidopsis is more similar to that in Drosophila than that in mammals, which may reflect genome size and complexity. The distinct patterns of association of H3K56ac with gene expression and early replication provide evidence that H3K56ac may be associated

  16. 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.

  17. 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...

  18. Internal RNA Replication Elements are Prevalent in Tombusviridae

    Directory of Open Access Journals (Sweden)

    Beth L Nicholson

    2012-08-01

    Full Text Available Internal replication elements (IREs are RNA structures that are present at internal positions in the genomes of different types of plus-strand RNA viruses. Members of the genus Tombusvirus (family Tombusviridae contain an IRE within the polymerase coding region of their genomes and this RNA element participates in both genome targeting to sites of replication and replicase complex assembly. Here we propose that other members of the virus family Tombusviridae also possess comparable IREs. Through sequence and structural analyses, candidate IREs in several genera of this family were identified, including aureusviruses, necroviruses, carmoviruses and pelarspoviruses. The results from subsequent mutational analysis of selected proposed IREs were consistent with a critical role for these structures in viral genome accumulation during infections. Our study supports the existence of IREs in several genera in Tombusviridae and points to previously unappreciated similarities in genome replication strategies between members of this virus family.

  19. Characterization of human chromosomal DNA sequences which replicate autonomously in Saccharomyces cerevisiae.

    Science.gov (United States)

    Montiel, J F; Norbury, C J; Tuite, M F; Dobson, M J; Mills, J S; Kingsman, A J; Kingsman, S M

    1984-01-01

    We have characterised two restriction fragments, isolated from a "shotgun" collection of human DNA, which function as autonomously replicating sequences (ARSs) in Saccharomyces cerevisiae. Functional domains of these fragments have been defined by subcloning and exonuclease (BAL 31) deletion analysis. Both fragments contain two spatially distinct domains. One is essential for high frequency transformation and is termed the Replication Sequence (RS) domain, the other, termed the Replication Enhancer (RE) domain, has no inherent replication competence but is essential for ensuring maximum function of the RS domain. The nucleotide sequence of these domains reveals several conserved sequences one of which is strikingly similar to the yeast ARS consensus sequence. PMID:6320114

  20. 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.

  1. 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...

  2. Once in a lifetime: strategies for preventing re-replication in prokaryotic and eukaryotic cells.

    Science.gov (United States)

    Nielsen, Olaf; Løbner-Olesen, Anders

    2008-02-01

    DNA replication is an extremely accurate process and cells have evolved intricate control mechanisms to ensure that each region of their genome is replicated only once during S phase. Here, we compare what is known about the processes that prevent re-replication in prokaryotic and eukaryotic cells by using the model organisms Escherichia coli and Schizosaccharomyces pombe as examples. Although the underlying molecular details are different, the logic behind the control mechanisms is similar. For example, after initiation, crucial molecules required for the loading of replicative helicases in both prokaryotes and eukaryotes are inactivated until the next cell cycle. Furthermore, in both systems the beta-clamp of the replicative polymerase associates with enzymatic activities that contribute to the inactivation of the helicase loaders. Finally, recent studies suggest that the control mechanism that prevents re-replication in both systems also increases the synthesis of DNA building blocks.

  3. Identification of 30 protein species involved in replicative senescence and stress-induced premature senescence

    DEFF Research Database (Denmark)

    Dierick, Jean François; Kalume, Dário E; Wenders, Frédéric

    2002-01-01

    Exposure of human proliferative cells to subcytotoxic stress triggers stress-induced premature senescence (SIPS) which is characterized by many biomarkers of replicative senescence. Proteomic comparison of replicative senescence and stress-induced premature senescence indicates that, at the level....... These changes affect different cell functions, including energy metabolism, defense systems, maintenance of the redox potential, cell morphology and transduction pathways.......Exposure of human proliferative cells to subcytotoxic stress triggers stress-induced premature senescence (SIPS) which is characterized by many biomarkers of replicative senescence. Proteomic comparison of replicative senescence and stress-induced premature senescence indicates that, at the level...... of protein expression, stress-induced premature senescence and replicative senescence are different phenotypes sharing however similarities. In this study, we identified 30 proteins showing changes of expression level specific or common to replicative senescence and/or stress-induced premature senescence...

  4. 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....

  5. 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.

  6. PSYCHOLOGY. Estimating the reproducibility of psychological science.

    Science.gov (United States)

    2015-08-28

    Reproducibility is a defining feature of science, but the extent to which it characterizes current research is unknown. We conducted replications of 100 experimental and correlational studies published in three psychology journals using high-powered designs and original materials when available. Replication effects were half the magnitude of original effects, representing a substantial decline. Ninety-seven percent of original studies had statistically significant results. Thirty-six percent of replications had statistically significant results; 47% of original effect sizes were in the 95% confidence interval of the replication effect size; 39% of effects were subjectively rated to have replicated the original result; and if no bias in original results is assumed, combining original and replication results left 68% with statistically significant effects. Correlational tests suggest that replication success was better predicted by the strength of original evidence than by characteristics of the original and replication teams.

  7. Data from a pre-publication independent replication initiative examining ten moral judgement effects

    Science.gov (United States)

    Tierney, Warren; Schweinsberg, Martin; Jordan, Jennifer; Kennedy, Deanna M.; Qureshi, Israr; Sommer, S. Amy; Thornley, Nico; Madan, Nikhil; Vianello, Michelangelo; Awtrey, Eli; Zhu, Luke Lei; Diermeier, Daniel; Heinze, Justin E.; Srinivasan, Malavika; Tannenbaum, David; Bivolaru, Eliza; Dana, Jason; Davis-Stober, Clintin P.; du Plessis, Christilene; Gronau, Quentin F.; Hafenbrack, Andrew C.; Liao, Eko Yi; Ly, Alexander; Marsman, Maarten; Murase, Toshio; Schaerer, Michael; Tworek, Christina M.; Wagenmakers, Eric-Jan; Wong, Lynn; Anderson, Tabitha; Bauman, Christopher W.; Bedwell, Wendy L.; Brescoll, Victoria; Canavan, Andrew; Chandler, Jesse J.; Cheries, Erik; Cheryan, Sapna; Cheung, Felix; Cimpian, Andrei; Clark, Mark A.; Cordon, Diana; Cushman, Fiery; Ditto, Peter H.; Amell, Alice; Frick, Sarah E.; Gamez-Djokic, Monica; Grady, Rebecca Hofstein; Graham, Jesse; Gu, Jun; Hahn, Adam; Hanson, Brittany E.; Hartwich, Nicole J.; Hein, Kristie; Inbar, Yoel; Jiang, Lily; Kellogg, Tehlyr; Legate, Nicole; Luoma, Timo P.; Maibeucher, Heidi; Meindl, Peter; Miles, Jennifer; Mislin, Alexandra; Molden, Daniel C.; Motyl, Matt; Newman, George; Ngo, Hoai Huong; Packham, Harvey; Ramsay, P. Scott; Ray, Jennifer L.; Sackett, Aaron M.; Sellier, Anne-Laure; Sokolova, Tatiana; Sowden, Walter; Storage, Daniel; Sun, Xiaomin; Van Bavel, Jay J.; Washburn, Anthony N.; Wei, Cong; Wetter, Erik; Wilson, Carlos T.; Darroux, Sophie-Charlotte; Uhlmann, Eric Luis

    2016-01-01

    We present the data from a crowdsourced project seeking to replicate findings in independent laboratories before (rather than after) they are published. In this Pre-Publication Independent Replication (PPIR) initiative, 25 research groups attempted to replicate 10 moral judgment effects from a single laboratory’s research pipeline of unpublished findings. The 10 effects were investigated using online/lab surveys containing psychological manipulations (vignettes) followed by questionnaires. Results revealed a mix of reliable, unreliable, and culturally moderated findings. Unlike any previous replication project, this dataset includes the data from not only the replications but also from the original studies, creating a unique corpus that researchers can use to better understand reproducibility and irreproducibility in science. PMID:27727246

  8. 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.

  9. 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.

  10. Mathematical Analysis of Replication by Cash Flow Matching

    Directory of Open Access Journals (Sweden)

    Jan Natolski

    2017-02-01

    Full Text Available The replicating portfolio approach is a well-established approach carried out by many life insurance companies within their Solvency II framework for the computation of risk capital. In this note,weelaborateononespecificformulationofareplicatingportfolioproblem. Incontrasttothetwo most popular replication approaches, it does not yield an analytic solution (if, at all, a solution exists andisunique. Further,althoughconvex,theobjectivefunctionseemstobenon-smooth,andhencea numericalsolutionmightthusbemuchmoredemandingthanforthetwomostpopularformulations. Especially for the second reason, this formulation did not (yet receive much attention in practical applications, in contrast to the other two formulations. In the following, we will demonstrate that the (potential non-smoothness can be avoided due to an equivalent reformulation as a linear second order cone program (SOCP. This allows for a numerical solution by efficient second order methods like interior point methods or similar. We also show that—under weak assumptions—existence and uniqueness of the optimal solution can be guaranteed. We additionally prove that—under a further similarly weak condition—the fair value of the replicating portfolio equals the fair value of liabilities. Based on these insights, we argue that this unloved stepmother child within the replication problem family indeed represents an equally good formulation for practical purposes.

  11. Estimating similarity of XML Schemas using path similarity measure

    Directory of Open Access Journals (Sweden)

    Veena Trivedi

    2012-07-01

    Full Text Available In this paper, an attempt has been made to develop an algorithm which estimates the similarity for XML Schemas using multiple similarity measures. For performing the task, the XML Schema element information has been represented in the form of string and four different similarity measure approaches have been employed. To further improve the similarity measure, an overall similarity measure has also been calculated. The approach used in this paper is a distinguished one, as it calculates the similarity between two XML schemas using four approaches and gives an integrated values for the similarity measure. Keywords-componen

  12. Survey of Search and Replication Schemes in Unstructured P2P Networks

    CERN Document Server

    Thampi, Sabu M

    2010-01-01

    P2P computing lifts taxing issues in various areas of computer science. The largely used decentralized unstructured P2P systems are ad hoc in nature and present a number of research challenges. In this paper, we provide a comprehensive theoretical survey of various state-of-the-art search and replication schemes in unstructured P2P networks for file-sharing applications. The classifications of search and replication techniques and their advantages and disadvantages are briefly explained. Finally, the various issues on searching and replication for unstructured P2P networks are discussed.

  13. Replication of Vibrio cholerae chromosome I in Escherichia coli: dependence on dam methylation

    DEFF Research Database (Denmark)

    Koch, Birgit; Ma, Xiaofang; Løbner-Olesen, Anders

    2010-01-01

    We successfully substituted Escherichia coli's origin of replication oriC with the origin region of Vibrio cholerae chromosome I (oriCIVc). Replication from oriCIVc initiated at a similar or slightly reduced cell mass compared to that of normal E. coli oriC. With respect to sequestration....... cholerae chromosome I replication, which similar to what is observed for E. coli. No hda homologue has been identified in V. cholerae yet. In V. cholerae, dam is essential for viability, whereas in E. coli, dam mutants are viable. Replacement of E. coli oriC with oriCIVc allowed us to specifically address...

  14. 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.

  15. 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.

  16. 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

  17. Widening Disparity and its Suppression in a Stochastic Replicator Model

    CERN Document Server

    Sakaguchi, Hidetsugu

    2016-01-01

    Winner-take-all phenomena are observed in various competitive systems. We find similar phenomena in replicator models with randomly fluctuating growth rates. The disparity between winners and losers increases indefinitely, even if all elements are statistically equivalent. A lognormal distribution describes well the nonstationary time evolution. If a nonlinear load corresponding to progressive taxation is introduced, a stationary distribution is obtained and disparity widening is suppressed.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-04-15

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

  19. 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.

  20. 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.

  1. Chk1 inhibits replication factory activation but allows dormant origin firing in existing factories

    Science.gov (United States)

    Ge, Xin Quan

    2010-01-01

    Replication origins are licensed by loading MCM2-7 hexamers before entry into S phase. However, only ∼10% of licensed origins are normally used in S phase, with the others remaining dormant. When fork progression is inhibited, dormant origins initiate nearby to ensure that all of the DNA is eventually replicated. In apparent contrast, replicative stress activates ataxia telangiectasia and rad-3–related (ATR) and Chk1 checkpoint kinases that inhibit origin firing. In this study, we show that at low levels of replication stress, ATR/Chk1 predominantly suppresses origin initiation by inhibiting the activation of new replication factories, thereby reducing the number of active factories. At the same time, inhibition of replication fork progression allows dormant origins to initiate within existing replication factories. The inhibition of new factory activation by ATR/Chk1 therefore redirects replication toward active factories where forks are inhibited and away from regions that have yet to start replication. This minimizes the deleterious consequences of fork stalling and prevents similar problems from arising in unreplicated regions of the genome. PMID:21173116

  2. 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.

  3. 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.

  4. 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.

  5. Effects of 60 Hz electromagnetic fields on early growth in three plant species and a replication of previous results

    Energy Technology Data Exchange (ETDEWEB)

    Davis, M.S. [Univ. of Sunderland (United Kingdom). Ecology Centre

    1996-05-01

    In an attempt to replicate the findings of Smith et al., seeds of Raphanus sativus L. (radish), Sinapsis alba L. (mustard), and Hordeum vulgare L. (barley) were grown for between 9 and 21 days in continuous electromagnetic fields (EMFs) at ion-cyclotron resonance conditions for stimulation of Ca{sup 2+} (B{sub H} = 78.3 {micro}T, B{sub HAC} = 40 {micro}T peak-peak at 60 Hz, B{sub v} = 0). On harvesting, radish showed results similar to those of Smith et al. Dry stem weight and plant height were both significantly greater (Mann-Whitney tests, Ps < 0.05) in EMF-exposed plants than in control plants in each EMF experiment. Wet root weight was significantly greater in EMF-exposed plants in two out of three experiments, as were dry leaf weight, dry whole weight, and stem diameter. Dry root weight, wet leaf weight, and wet whole weight were significantly greater in EMF-exposed plants in one of three experiments. All significant differences indicated an increase in weight or size in the EMF-exposed plants. In each of the sham experiments, no differences between exposed and control plants were evident. Mustard plants failed to respond to the EMFs in any of the plant parameters measured. In one experiment, barley similarly failed to respond; but in another showed significantly greater wet root weight and significantly smaller stem diameter and dry seed weight at the end of the experiment in exposed plants compared to control plants. Although these results give no clue about the underlying bioelectromagnetic mechanism, they demonstrate that, at least for one EMF-sensitive biosystem, results can be independently replicated in another laboratory. Such replication is crucial in establishing the validity of bioelectromagnetic science.

  6. Effects of 60 Hz electromagnetic fields on early growth in three plant species and a replication of previous results.

    Science.gov (United States)

    Davies, M S

    1996-01-01

    In an attempt to replicate the findings of Smith et al., seeds of Raphanus sativus L. (radish), Sinapsis alba L. (mustard), and Hordeum vulgare L. (barley) were grown for between 9 and 21 days in continuous electromagnetic fields (EMFs) at "ion-cyclotron resonance" conditions for stimulation of Ca(2+) (B(H) = 78.3 mu T, B(HAC) = 40 mu T peak-peak at 60 Hz, B(V) = 0). On harvesting, radish showed results similar to those of Smith et al. Dry stem weight and plant height were both significantly greater (Mann-Whitney tests, Ps < 0.05) in EMF-exposed plants than in control plants in each EMF experiment. Wet root weight was significantly greater in EMF-exposed plants in two out of three experiments, as were dry leaf weight, dry whole weight, and stem diameter. Dry root weight, wet leaf weight, and wet whole weight were significantly greater in EMF-exposed plants in one of three experiments. All significant differences indicated an increase in weight or size in the EMF-exposed plants. In each of the sham experiments, no differences between exposed and control plants were evident. Mustard plants failed to respond to the EMFs in any of the plant parameters measured. In one experiment, barley similarly failed to respond; but in another showed significantly greater wet root weight and significantly smaller stem diameter and dry seed weight at the end of the experiment in exposed plants compared to control plants. Although these results give no clue about the underlying bioelectromagnetic mechanism, they demonstrate that, at least for one EMF-sensitive biosystem, results can be independently replicated in another laboratory. Such replication is crucial in establishing the validity of bioelectromagnetic science.

  7. 18β-glycyrrhetinic acid inhibits rotavirus replication in culture

    Directory of Open Access Journals (Sweden)

    Hardy Michele E

    2012-05-01

    Full Text Available Abstract Background Glycyrrhizin (GA and primary metabolite 18β-glycyrrhetinic acid (GRA are pharmacologically active components of the medicinal licorice root, and both have been shown to have antiviral and immunomodulatory properties. Although these properties are well established, the mechanisms of action are not completely understood. In this study, GA and GRA were tested for the ability to inhibit rotavirus replication in cell culture, toward a long term goal of discovering natural compounds that may complement existing vaccines. Methods Epithelial cells were treated with GA or GRA various times pre- or post-infection and virus yields were measured by immunofluorescent focus assay. Levels of viral proteins VP2, VP6, and NSP2 in GRA treated cells were measured by immunoblot to determine if there was an effect of GRA treatment on the accumulation of viral protein. Results GRA treatment reduced rotavirus yields by 99% when added to infected cultures post-- virus adsorption, whereas virus yields in GA treated cultures were similar to mock treated controls. Time of addition experiments indicated that GRA-mediated replication inhibition likely occurs at a step or steps subsequent to virus entry. The amounts of VP2, VP6 and NSP2 were substantially reduced when GRA was added to cultures up to two hours post-entry. Conclusions GRA, but not GA, has significant antiviral activity against rotavirus replication in vitro, and studies to determine whether GRA attenuates rotavirus replication in vivo are underway.

  8. The replication timing of the amplified dihydrofolate reductase genes in the Chinese hamster ovary cell line CHOC 400.

    Science.gov (United States)

    Caddle, M S; Heintz, N H

    1990-07-16

    We have examined the timing of replication of the amplified dihydrofolate reductase genes in the methotrexate-resistant Chinese hamster ovary cell line CHOC 400 using two synchronization procedures. DNA replicated in the presence of 5-bromodeoxyuridine was collected from cells of various times during the DNA synthesis phase and the extent of replication for defined sequences was determined by Southern blotting analysis of CsCl density gradient fractions. We report that under these conditions the DHFR gene replicates throughout the course of S phase in a mode similar to the bulk of the replicated genomic DNA. This contrasts with previous data that shows the non-amplified DHFR gene replicates during the first quarter of S phase. Therefore, we conclude that gene amplification alters the replication timing of the DHFR gene in CHOC 400 cells.

  9. Similarity measures for protein ensembles

    DEFF Research Database (Denmark)

    Lindorff-Larsen, Kresten; Ferkinghoff-Borg, Jesper

    2009-01-01

    Analyses of similarities and changes in protein conformation can provide important information regarding protein function and evolution. Many scores, including the commonly used root mean square deviation, have therefore been developed to quantify the similarities of different protein conformatio...

  10. 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.

  11. Functional Similarity and Interpersonal Attraction.

    Science.gov (United States)

    Neimeyer, Greg J.; Neimeyer, Robert A.

    1981-01-01

    Students participated in dyadic disclosure exercises over a five-week period. Results indicated members of high functional similarity dyads evidenced greater attraction to one another than did members of low functional similarity dyads. "Friendship" pairs of male undergraduates displayed greater functional similarity than did…

  12. Functional Similarity and Interpersonal Attraction.

    Science.gov (United States)

    Neimeyer, Greg J.; Neimeyer, Robert A.

    1981-01-01

    Students participated in dyadic disclosure exercises over a five-week period. Results indicated members of high functional similarity dyads evidenced greater attraction to one another than did members of low functional similarity dyads. "Friendship" pairs of male undergraduates displayed greater functional similarity than did "nominal" pairs from…

  13. Interbehavioral psychology and radical behaviorism: Some similarities and differences

    Science.gov (United States)

    Morris, Edward K.

    1984-01-01

    Both J. R. Kantor's interbehavioral psychology and B. F. Skinner's radical behaviorism represent wellarticulated approaches to a natural science of behavior. As such, they share a number of similar features, yet they also differ on a number of dimensions. Some of these similarities and differences are examined by describing their emergence in the professional literature and by comparing the respective units of analysis of the two approaches—the interbehavioral field and the three-term contingency. An evaluation of the similarities and differences shows the similarities to be largely fundamental, and the differences largely ones of emphasis. Nonetheless, the two approaches do make unique contributions to a natural science of behavior, the integration of which can facilitate the development of that science and its acceptance among other sciences and within society at large. PMID:22478612

  14. Representation of Semantic Similarity in the Left Intraparietal Sulcus : Functional Magnetic Resonance Imaging Evidence

    NARCIS (Netherlands)

    Neyens, Veerle; Bruffaerts, Rose; Liuzzi, Antonietta Gabriella; Kalfas, Ioannis; Peeters, Ronald; Keuleers, Emmanuel; Vogels, Rufin; De Deyne, Simon; Storms, Gert; Dupont, Patrick; Vandenberghe, Rik

    2017-01-01

    According to a recent study, semantic similarity between concrete entities correlates with the similarity of activity patterns in left middle IPS during category naming. We examined the replicability of this effect under passive viewing conditions, the potential role of visuoperceptual similarity,

  15. Once in a lifetime: strategies for preventing re-replication in prokaryotic and eukaryotic cells

    DEFF Research Database (Denmark)

    Nielsen, Olaf; Løbner-Olesen, Anders

    2008-01-01

    DNA replication is an extremely accurate process and cells have evolved intricate control mechanisms to ensure that each region of their genome is replicated only once during S phase. Here, we compare what is known about the processes that prevent re-replication in prokaryotic and eukaryotic cells...... prokaryotes and eukaryotes are inactivated until the next cell cycle. Furthermore, in both systems the beta-clamp of the replicative polymerase associates with enzymatic activities that contribute to the inactivation of the helicase loaders. Finally, recent studies suggest that the control mechanism...... by using the model organisms Escherichia coli and Schizosaccharomyces pombe as examples. Although the underlying molecular details are different, the logic behind the control mechanisms is similar. For example, after initiation, crucial molecules required for the loading of replicative helicases in both...

  16. Dual interaction of a geminivirus replication accessory factor with a viral replication protein and a plant cell cycle regulator.

    Science.gov (United States)

    Settlage, S B; Miller, A B; Gruissem, W; Hanley-Bowdoin, L

    2001-01-20

    Geminiviruses replicate their small, single-stranded DNA genomes through double-stranded DNA intermediates in plant nuclei using host replication machinery. Like most dicot-infecting geminiviruses, tomato golden mosaic virus encodes a protein, AL3 or C3, that greatly enhances viral DNA accumulation through an unknown mechanism. Earlier studies showed that AL3 forms oligomers and interacts with the viral replication initiator AL1. Experiments reported here established that AL3 also interacts with a plant homolog of the mammalian tumor suppressor protein, retinoblastoma (pRb). Analysis of truncated AL3 proteins indicated that pRb and AL1 bind to similar regions of AL3, whereas AL3 oligomerization is dependent on a different region of the protein. Analysis of truncated AL1 proteins located the AL3-binding domain between AL1 amino acids 101 and 180 to a region that also includes the AL1 oligomerization domain and the catalytic site for initiation of viral DNA replication. Interestingly, the AL3-binding domain was fully contiguous with the domain that mediates AL1/pRb interactions. The potential significance of AL3/pRb binding and the coincidence of the domains responsible for AL3, AL1, and pRb interactions are discussed.

  17. Science and Science Fiction

    Science.gov (United States)

    Oravetz, David

    2005-01-01

    This article is for teachers looking for new ways to motivate students, increase science comprehension, and understanding without using the old standard expository science textbook. This author suggests reading a science fiction novel in the science classroom as a way to engage students in learning. Using science fiction literature and language…

  18. 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...

  19. Replication and Robustness in Developmental Research

    Science.gov (United States)

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

    2014-01-01

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

  20. 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.

  1. 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…

  2. 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…

  3. 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.

  4. 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...

  5. 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.

  6. Hypotension and Environmental Noise: A Replication Study

    Science.gov (United States)

    Lercher, Peter; Widmann, Ulrich; Thudium, Jürg

    2014-01-01

    Up to now, traffic noise effect studies focused on hypertension as health outcome. Hypotension has not been considered as a potential health outcome although in experiments some people also responded to noise with decreases of blood pressure. Currently, the characteristics of these persons are not known and whether this down regulation of blood pressure is an experimental artifact, selection, or can also be observed in population studies is unanswered. In a cross-sectional replication study, we randomly sampled participants (age 20–75, N = 807) from circular areas (radius = 500 m) around 31 noise measurement sites from four noise exposure strata (35–44, 45–54, 55–64, >64 Leq, dBA). Repeated blood pressure measurements were available for a smaller sample (N = 570). Standardized information on socio-demographics, housing, life style and health was obtained by door to door visits including anthropometric measurements. Noise and air pollution exposure was assigned by GIS based on both calculation and measurements. Reported hypotension or hypotension medication past year was the main outcome studied. Exposure-effect relationships were modeled with multiple non-linear logistic regression techniques using separate noise estimations for total, highway and rail exposure. Reported hypotension was significantly associated with rail and total noise exposure and strongly modified by weather sensitivity. Reported hypotension medication showed associations of similar size with rail and total noise exposure without effect modification by weather sensitivity. The size of the associations in the smaller sample with BMI as additional covariate was similar. Other important cofactors (sex, age, BMI, health) and moderators (weather sensitivity, adjacent main roads and associated annoyance) need to be considered as indispensible part of the observed relationship. This study confirms a potential new noise effect pathway and discusses potential patho-physiological routes of actions

  7. Hypotension and Environmental Noise: A Replication Study

    Directory of Open Access Journals (Sweden)

    Peter Lercher

    2014-08-01

    Full Text Available Up to now, traffic noise effect studies focused on hypertension as health outcome. Hypotension has not been considered as a potential health outcome although in experiments some people also responded to noise with decreases of blood pressure. Currently, the characteristics of these persons are not known and whether this down regulation of blood pressure is an experimental artifact, selection, or can also be observed in population studies is unanswered. In a cross-sectional replication study, we randomly sampled participants (age 20–75, N = 807 from circular areas (radius = 500 m around 31 noise measurement sites from four noise exposure strata (35–44, 45–54, 55–64, >64 Leq, dBA. Repeated blood pressure measurements were available for a smaller sample (N = 570. Standardized information on socio-demographics, housing, life style and health was obtained by door to door visits including anthropometric measurements. Noise and air pollution exposure was assigned by GIS based on both calculation and measurements. Reported hypotension or hypotension medication past year was the main outcome studied. Exposure-effect relationships were modeled with multiple non-linear logistic regression techniques using separate noise estimations for total, highway and rail exposure. Reported hypotension was significantly associated with rail and total noise exposure and strongly modified by weather sensitivity. Reported hypotension medication showed associations of similar size with rail and total noise exposure without effect modification by weather sensitivity. The size of the associations in the smaller sample with BMI as additional covariate was similar. Other important cofactors (sex, age, BMI, health and moderators (weather sensitivity, adjacent main roads and associated annoyance need to be considered as indispensible part of the observed relationship. This study confirms a potential new noise effect pathway and discusses potential patho

  8. Effect of CD4 gene expression on adenovirus replication.

    Science.gov (United States)

    Hotta, J; Shi, L; Ginsberg, H S

    1994-11-01

    The gene encoding the CD4 receptor was introduced into KB cells to establish the KBT4 cell line, a cell line susceptible to infection with human immunodeficiency virus type 1. Adenovirus replication was found to be significantly less in these cells than in the parental KB cells. Similar decreased adenovirus type 5 (Ad5) replication occurred in HeLaT4 cells compared with the original HeLa cells. The presence of CD4 did not alter the cell surface population of KB cell adenovirus receptors, since viral adsorption was similar in the two cell lines. Moreover, addition of soluble CD4 did not reduce viral replication in either KB or KBT4 infected cells. Uncoating of viral DNA was also unchanged in KBT4 cells compared with the parental KB cells. In contrast, migration to or entrance of viral DNA into nuclei and synthesis of early viral RNAs was delayed and reduced in KBT4 cells. These effects were more pronounced for Ad7 than for Ad5. The yields of infectious viruses were the same in both cell lines, however, after transfection of naked viral DNAs to initiate infection. These results imply that the expression of the CD4 gene in KBT4 cells interfered with passage of uncoated virus across endosomal vesicles and/or transfer of uncoated core viral DNA into the nucleus.

  9. Quasispecies spatial models for RNA viruses with different replication modes and infection strategies.

    Directory of Open Access Journals (Sweden)

    Josep Sardanyés

    Full Text Available Empirical observations and theoretical studies suggest that viruses may use different replication strategies to amplify their genomes, which impact the dynamics of mutation accumulation in viral populations and therefore, their fitness and virulence. Similarly, during natural infections, viruses replicate and infect cells that are rarely in suspension but spatially organized. Surprisingly, most quasispecies models of virus replication have ignored these two phenomena. In order to study these two viral characteristics, we have developed stochastic cellular automata models that simulate two different modes of replication (geometric vs stamping machine for quasispecies replicating and spreading on a two-dimensional space. Furthermore, we explored these two replication models considering epistatic fitness landscapes (antagonistic vs synergistic and different scenarios for cell-to-cell spread, one with free superinfection and another with superinfection inhibition. We found that the master sequences for populations replicating geometrically and with antagonistic fitness effects vanished at low critical mutation rates. By contrast, the highest critical mutation rate was observed for populations replicating geometrically but with a synergistic fitness landscape. Our simulations also showed that for stamping machine replication and antagonistic epistasis, a combination that appears to be common among plant viruses, populations further increased their robustness by inhibiting superinfection. We have also shown that the mode of replication strongly influenced the linkage between viral loci, which rapidly reached linkage equilibrium at increasing mutations for geometric replication. We also found that the strategy that minimized the time required to spread over the whole space was the stamping machine with antagonistic epistasis among mutations. Finally, our simulations revealed that the multiplicity of infection fluctuated but generically increased along

  10. Statistical correction of the Winner's Curse explains replication variability in quantitative trait genome-wide association studies.

    Directory of Open Access Journals (Sweden)

    Cameron Palmer

    2017-07-01

    Full Text Available Genome-wide association studies (GWAS have identified hundreds of SNPs responsible for variation in human quantitative traits. However, genome-wide-significant associations often fail to replicate across independent cohorts, in apparent inconsistency with their apparent strong effects in discovery cohorts. This limited success of replication raises pervasive questions about the utility of the GWAS field. We identify all 332 studies of quantitative traits from the NHGRI-EBI GWAS Database with attempted replication. We find that the majority of studies provide insufficient data to evaluate replication rates. The remaining papers replicate significantly worse than expected (p < 10-14, even when adjusting for regression-to-the-mean of effect size between discovery- and replication-cohorts termed the Winner's Curse (p < 10-16. We show this is due in part to misreporting replication cohort-size as a maximum number, rather than per-locus one. In 39 studies accurately reporting per-locus cohort-size for attempted replication of 707 loci in samples with similar ancestry, replication rate matched expectation (predicted 458, observed 457, p = 0.94. In contrast, ancestry differences between replication and discovery (13 studies, 385 loci cause the most highly-powered decile of loci to replicate worse than expected, due to difference in linkage disequilibrium.

  11. A COMPARISON OF SEMANTIC SIMILARITY MODELS IN EVALUATING CONCEPT SIMILARITY

    Directory of Open Access Journals (Sweden)

    Q. X. Xu

    2012-08-01

    Full Text Available The semantic similarities are important in concept definition, recognition, categorization, interpretation, and integration. Many semantic similarity models have been established to evaluate semantic similarities of objects or/and concepts. To find out the suitability and performance of different models in evaluating concept similarities, we make a comparison of four main types of models in this paper: the geometric model, the feature model, the network model, and the transformational model. Fundamental principles and main characteristics of these models are introduced and compared firstly. Land use and land cover concepts of NLCD92 are employed as examples in the case study. The results demonstrate that correlations between these models are very high for a possible reason that all these models are designed to simulate the similarity judgement of human mind.

  12. a Comparison of Semantic Similarity Models in Evaluating Concept Similarity

    Science.gov (United States)

    Xu, Q. X.; Shi, W. Z.

    2012-08-01

    The semantic similarities are important in concept definition, recognition, categorization, interpretation, and integration. Many semantic similarity models have been established to evaluate semantic similarities of objects or/and concepts. To find out the suitability and performance of different models in evaluating concept similarities, we make a comparison of four main types of models in this paper: the geometric model, the feature model, the network model, and the transformational model. Fundamental principles and main characteristics of these models are introduced and compared firstly. Land use and land cover concepts of NLCD92 are employed as examples in the case study. The results demonstrate that correlations between these models are very high for a possible reason that all these models are designed to simulate the similarity judgement of human mind.

  13. Learning Multi-modal Similarity

    CERN Document Server

    McFee, Brian

    2010-01-01

    In many applications involving multi-media data, the definition of similarity between items is integral to several key tasks, e.g., nearest-neighbor retrieval, classification, and recommendation. Data in such regimes typically exhibits multiple modalities, such as acoustic and visual content of video. Integrating such heterogeneous data to form a holistic similarity space is therefore a key challenge to be overcome in many real-world applications. We present a novel multiple kernel learning technique for integrating heterogeneous data into a single, unified similarity space. Our algorithm learns an optimal ensemble of kernel transfor- mations which conform to measurements of human perceptual similarity, as expressed by relative comparisons. To cope with the ubiquitous problems of subjectivity and inconsistency in multi- media similarity, we develop graph-based techniques to filter similarity measurements, resulting in a simplified and robust training procedure.

  14. Renewing the Respect for Similarity

    Directory of Open Access Journals (Sweden)

    Shimon eEdelman

    2012-07-01

    Full Text Available In psychology, the concept of similarity has traditionally evoked a mixture of respect, stemmingfrom its ubiquity and intuitive appeal, and concern, due to its dependence on the framing of the problemat hand and on its context. We argue for a renewed focus on similarity as an explanatory concept, bysurveying established results and new developments in the theory and methods of similarity-preservingassociative lookup and dimensionality reduction — critical components of many cognitive functions, aswell as of intelligent data management in computer vision. We focus in particular on the growing familyof algorithms that support associative memory by performing hashing that respects local similarity, andon the uses of similarity in representing structured objects and scenes. Insofar as these similarity-basedideas and methods are useful in cognitive modeling and in AI applications, they should be included inthe core conceptual toolkit of computational neuroscience.

  15. Recruitment of wild-type and recombinant adeno-associated virus into adenovirus replication centers.

    Science.gov (United States)

    Weitzman, M D; Fisher, K J; Wilson, J M

    1996-03-01

    Replication of a human parvovirus, adeno-associated virus (AAV), is facilitated by coinfection with adeno-virus to provide essential helper functions. We have used the techniques of in situ hybridization and immunocytochemistry to characterize the localization of AAV replication within infected cells, Previous studies have shown that adenovirus establishes foci called replication centers within the nucleus, where adenoviral replication and transcription occur. Our studies indicate that AAV is colocalized with the adenovirus replication centers, where it may utilize adenovirus and cellular proteins for its own replication. Expression of the AAV Rep protein inhibits the normal maturation of the adenovirus centers. Similar experiments were performed with recombinant AAV (rAAV) to establish a relationship between intranuclear localization and rAAV transduction. rAAV efficiently entered the cell, and its genome was faintly detectable in a perinuclear distribution and was mobilized to replication centers when the cell was infected with adenovirus. The recruitment of the replication-defective genome into the intranuclear adenovirus domains resulted in enhanced transduction. These studies illustrate the importance of intracellular compartmentalization for such complex interactions as the relationship between AAV and adenovirus.

  16. The replication origin of a repABC plasmid

    Directory of Open Access Journals (Sweden)

    Cevallos Miguel A

    2011-06-01

    Full Text Available Abstract Background repABC operons are present on large, low copy-number plasmids and on some secondary chromosomes in at least 19 α-proteobacterial genera, and are responsible for the replication and segregation properties of these replicons. These operons consist, with some variations, of three genes: repA, repB, and repC. RepA and RepB are involved in plasmid partitioning and in the negative regulation of their own transcription, and RepC is the limiting factor for replication. An antisense RNA encoded between the repB-repC genes modulates repC expression. Results To identify the minimal region of the Rhizobium etli p42d plasmid that is capable of autonomous replication, we amplified different regions of the repABC operon using PCR and cloned the regions into a suicide vector. The resulting vectors were then introduced into R. etli strains that did or did not contain p42d. The minimal replicon consisted of a repC open reading frame under the control of a constitutive promoter with a Shine-Dalgarno sequence that we designed. A sequence analysis of repC revealed the presence of a large A+T-rich region but no iterons or DnaA boxes. Silent mutations that modified the A+T content of this region eliminated the replication capability of the plasmid. The minimal replicon could not be introduced into R. etli strain containing p42d, but similar constructs that carried repC from Sinorhizobium meliloti pSymA or the linear chromosome of Agrobacterium tumefaciens replicated in the presence or absence of p42d, indicating that RepC is an incompatibility factor. A hybrid gene construct expressing a RepC protein with the first 362 amino acid residues from p42d RepC and the last 39 amino acid residues of RepC from SymA was able to replicate in the presence of p42d. Conclusions RepC is the only element encoded in the repABC operon of the R. etli p42d plasmid that is necessary and sufficient for plasmid replication and is probably the initiator protein. The ori

  17. Ultrastructure of the replication sites of positive-strand RNA viruses

    Energy Technology Data Exchange (ETDEWEB)

    Harak, Christian; Lohmann, Volker, E-mail: volker_lohmann@med.uni-heidelberg.de

    2015-05-15

    Positive strand RNA viruses replicate in the cytoplasm of infected cells and induce intracellular membranous compartments harboring the sites of viral RNA synthesis. These replication factories are supposed to concentrate the components of the replicase and to shield replication intermediates from the host cell innate immune defense. Virus induced membrane alterations are often generated in coordination with host factors and can be grouped into different morphotypes. Recent advances in conventional and electron microscopy have contributed greatly to our understanding of their biogenesis, but still many questions remain how viral proteins capture membranes and subvert host factors for their need. In this review, we will discuss different representatives of positive strand RNA viruses and their ways of hijacking cellular membranes to establish replication complexes. We will further focus on host cell factors that are critically involved in formation of these membranes and how they contribute to viral replication. - Highlights: • Positive strand RNA viruses induce massive membrane alterations. • Despite the great diversity, replication complexes share many similarities. • Host factors play a pivotal role in replication complex biogenesis. • Use of the same host factors by several viruses hints to similar functions.

  18. Similarity Learning of Manifold Data.

    Science.gov (United States)

    Chen, Si-Bao; Ding, Chris H Q; Luo, Bin

    2015-09-01

    Without constructing adjacency graph for neighborhood, we propose a method to learn similarity among sample points of manifold in Laplacian embedding (LE) based on adding constraints of linear reconstruction and least absolute shrinkage and selection operator type minimization. Two algorithms and corresponding analyses are presented to learn similarity for mix-signed and nonnegative data respectively. The similarity learning method is further extended to kernel spaces. The experiments on both synthetic and real world benchmark data sets demonstrate that the proposed LE with new similarity has better visualization and achieves higher accuracy in classification.

  19. 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.

  20. 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

  1. 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.

  2. Note---Mintzberg was Right!: A Replication and Extension of The Nature of Managerial Work

    OpenAIRE

    Lance B. Kurke; Howard E. Aldrich

    1983-01-01

    This paper reports a replication of Mintzberg (McCall M. W., Jr. A. M. Morrison, R. L. Hannan. 1978. Studies of managerial work: results and methods. Technical Report #9, Center for Creative Leadership.). Structured observation with supplemental unstructured interviewing was used to study four top managers for one week each. Mintzberg's field study was supported by our replication in all important dimensions. Explanations for similarities and differences between organizations and industries a...

  3. Replication of Equine Infectious Anemia Virus in Engineered Mouse NIH 3T3 Cells ▿

    OpenAIRE

    Zhang, Baoshan; Montelaro, Ronald C.

    2008-01-01

    We employed the equine lentivirus equine infectious anemia virus (EIAV) to investigate the cellular restrictions for lentivirus replication in murine NIH 3T3 cells. The results of these studies demonstrate that NIH 3T3 cells expressing the EIAV receptor ELR1 and equine cyclin T1 supported productive replication of EIAV and produced infectious virions at levels similar to those found in a reference permissive equine cell line. The studies presented here demonstrate, for the first time, differe...

  4. Dynamic similarity in erosional processes

    Science.gov (United States)

    Scheidegger, A.E.

    1963-01-01

    A study is made of the dynamic similarity conditions obtaining in a variety of erosional processes. The pertinent equations for each type of process are written in dimensionless form; the similarity conditions can then easily be deduced. The processes treated are: raindrop action, slope evolution and river erosion. ?? 1963 Istituto Geofisico Italiano.

  5. Wavelet transform in similarity paradigm

    NARCIS (Netherlands)

    Z.R. Struzik; A.P.J.M. Siebes (Arno)

    1998-01-01

    textabstract[INS-R9802] Searching for similarity in time series finds still broader applications in data mining. However, due to the very broad spectrum of data involved, there is no possibility of defining one single notion of similarity suitable to serve all applications. We present a powerful

  6. Visual Representations of DNA Replication: Middle Grades Students' Perceptions and Interpretations

    Science.gov (United States)

    Patrick, Michelle D.; Carter, Glenda; Wiebe, Eric N.

    2005-01-01

    Visual representations play a critical role in the communication of science concepts for scientists and students alike. However, recent research suggests that novice students experience difficulty extracting relevant information from representations. This study examined students' interpretations of visual representations of DNA replication. Each…

  7. 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.

  8. Computational investigations on polymerase actions in gene transcription and replication: Combining physical modeling and atomistic simulations

    Science.gov (United States)

    Jin, Yu

    2016-01-01

    Polymerases are protein enzymes that move along nucleic acid chains and catalyze template-based polymerization reactions during gene transcription and replication. The polymerases also substantially improve transcription or replication fidelity through the non-equilibrium enzymatic cycles. We briefly review computational efforts that have been made toward understanding mechano-chemical coupling and fidelity control mechanisms of the polymerase elongation. The polymerases are regarded as molecular information motors during the elongation process. It requires a full spectrum of computational approaches from multiple time and length scales to understand the full polymerase functional cycle. We stay away from quantum mechanics based approaches to the polymerase catalysis due to abundant former surveys, while addressing statistical physics modeling approaches along with all-atom molecular dynamics simulation studies. We organize this review around our own modeling and simulation practices on a single subunit T7 RNA polymerase, and summarize commensurate studies on structurally similar DNA polymerases as well. For multi-subunit RNA polymerases that have been actively studied in recent years, we leave systematical reviews of the simulation achievements to latest computational chemistry surveys, while covering only representative studies published very recently, including our own work modeling structure-based elongation kinetic of yeast RNA polymerase II. In the end, we briefly go through physical modeling on elongation pauses and backtracking activities of the multi-subunit RNAPs. We emphasize on the fluctuation and control mechanisms of the polymerase actions, highlight the non-equilibrium nature of the operation system, and try to build some perspectives toward understanding the polymerase impacts from the single molecule level to a genome-wide scale. Project supported by the National Natural Science Foundation (Grant No. 11275022).

  9. 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.

  10. 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

  11. Similarity and rules United: similarity- and rule-based processing in a single neural network.

    Science.gov (United States)

    Verguts, Tom; Fias, Wim

    2009-03-01

    A central controversy in cognitive science concerns the roles of rules versus similarity. To gain some leverage on this problem, we propose that rule- versus similarity-based processes can be characterized as extremes in a multidimensional space that is composed of at least two dimensions: the number of features (Pothos, 2005) and the physical presence of features. The transition of similarity- to rule-based processing is conceptualized as a transition in this space. To illustrate this, we show how a neural network model uses input features (and in this sense produces similarity-based responses) when it has a low learning rate or in the early phases of training, but it switches to using self-generated, more abstract features (and in this sense produces rule-based responses) when it has a higher learning rate or is in the later phases of training. Relations with categorization and the psychology of learning are pointed out.

  12. Achieving Full Dynamic Similarity with Small-Scale Wind Turbine Models

    Science.gov (United States)

    Miller, Mark; Kiefer, Janik; Westergaard, Carsten; Hultmark, Marcus

    2016-11-01

    Power and thrust data as a function of Reynolds number and Tip Speed Ratio are presented at conditions matching those of a full scale turbine. Such data has traditionally been very difficult to acquire due to the large length-scales of wind turbines, and the limited size of conventional wind tunnels. Ongoing work at Princeton University employs a novel, high-pressure wind tunnel (up to 220 atmospheres of static pressure) which uses air as the working fluid. This facility allows adjustment of the Reynolds number (via the fluid density) independent of the Tip Speed Ratio, up to a Reynolds number (based on chord and velocity at the tip) of over 3 million. Achieving dynamic similarity using this approach implies very high power and thrust loading, which results in mechanical loads greater than 200 times those experienced by a similarly sized model in a conventional wind tunnel. In order to accurately report the power coefficients, a series of tests were carried out on a specially designed model turbine drive-train using an external testing bench to replicate tunnel loading. An accurate map of the drive-train performance at various operating conditions was determined. Finally, subsequent corrections to the power coefficient are discussed in detail. Supported by: National Science Foundation Grant CBET-1435254 (program director Gregory Rorrer).

  13. Similarity of samples and trimming

    CERN Document Server

    Álvarez-Esteban, Pedro C; Cuesta-Albertos, Juan A; Matrán, Carlos; 10.3150/11-BEJ351

    2012-01-01

    We say that two probabilities are similar at level $\\alpha$ if they are contaminated versions (up to an $\\alpha$ fraction) of the same common probability. We show how this model is related to minimal distances between sets of trimmed probabilities. Empirical versions turn out to present an overfitting effect in the sense that trimming beyond the similarity level results in trimmed samples that are closer than expected to each other. We show how this can be combined with a bootstrap approach to assess similarity from two data samples.

  14. 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.

  15. 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.

  16. 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.

  17. 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...

  18. 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.

  19. 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.

  20. 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...

  1. 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...

  2. Partial order similarity based on mutual information

    CERN Document Server

    Tibély, Gergely; Palla, Gergely

    2016-01-01

    Comparing the ranking of candidates by different voters is an important topic in social and information science with a high relevance from the point of view of practical applications. In general, ties and pairs of incomparable candidates may occur, thus, the alternative rankings are described by partial orders. Various distance measures between partial orders have already been introduced, where zero distance is corresponding to a perfect match between a pair of partial orders, and larger values signal greater differences. Here we take a different approach and propose a similarity measure based on adjusted mutual information. In general, the similarity value of unity is corresponding to exactly matching partial orders, while a low similarity is associated to a pair of independent partial orders. The time complexity of the computation of this similarity measure is $\\mathcal{O}(\\left|{\\mathcal C}\\right|^3)$ in the worst case, and $\\mathcal{O}(\\left|{\\mathcal C}\\right|^2\\ln \\left|{\\mathcal C}\\right|)$ in the typi...

  3. Diversity of eukaryotic DNA replication origins revealed by genome-wide analysis of chromatin structure.

    Directory of Open Access Journals (Sweden)

    Nicolas M Berbenetz

    2010-09-01

    Full Text Available Eukaryotic DNA replication origins differ both in their efficiency and in the characteristic time during S phase when they become active. The biological basis for these differences remains unknown, but they could be a consequence of chromatin structure. The availability of genome-wide maps of nucleosome positions has led to an explosion of information about how nucleosomes are assembled at transcription start sites, but no similar maps exist for DNA replication origins. Here we combine high-resolution genome-wide nucleosome maps with comprehensive annotations of DNA replication origins to identify patterns of nucleosome occupancy at eukaryotic replication origins. On average, replication origins contain a nucleosome depleted region centered next to the ACS element, flanked on both sides by arrays of well-positioned nucleosomes. Our analysis identified DNA sequence properties that correlate with nucleosome occupancy at replication origins genome-wide and that are correlated with the nucleosome-depleted region. Clustering analysis of all annotated replication origins revealed a surprising diversity of nucleosome occupancy patterns. We provide evidence that the origin recognition complex, which binds to the origin, acts as a barrier element to position and phase nucleosomes on both sides of the origin. Finally, analysis of chromatin reconstituted in vitro reveals that origins are inherently nucleosome depleted. Together our data provide a comprehensive, genome-wide view of chromatin structure at replication origins and suggest a model of nucleosome positioning at replication origins in which the underlying sequence occludes nucleosomes to permit binding of the origin recognition complex, which then (likely in concert with nucleosome modifiers and remodelers positions nucleosomes adjacent to the origin to promote replication origin function.

  4. Scaling, similarity, and the fourth paradigm for hydrology

    Science.gov (United States)

    Peters-Lidard, Christa D.; Clark, Martyn; Samaniego, Luis; Verhoest, Niko E. C.; van Emmerik, Tim; Uijlenhoet, Remko; Achieng, Kevin; Franz, Trenton E.; Woods, Ross

    2017-07-01

    In this synthesis paper addressing hydrologic scaling and similarity, we posit that roadblocks in the search for universal laws of hydrology are hindered by our focus on computational simulation (the third paradigm) and assert that it is time for hydrology to embrace a fourth paradigm of data-intensive science. Advances in information-based hydrologic science, coupled with an explosion of hydrologic data and advances in parameter estimation and modeling, have laid the foundation for a data-driven framework for scrutinizing hydrological scaling and similarity hypotheses. We summarize important scaling and similarity concepts (hypotheses) that require testing; describe a mutual information framework for testing these hypotheses; describe boundary condition, state, flux, and parameter data requirements across scales to support testing these hypotheses; and discuss some challenges to overcome while pursuing the fourth hydrological paradigm. We call upon the hydrologic sciences community to develop a focused effort towards adopting the fourth paradigm and apply this to outstanding challenges in scaling and similarity.

  5. Contextual Bandits with Similarity Information

    CERN Document Server

    Slivkins, Aleksandrs

    2009-01-01

    In a multi-armed bandit (MAB) problem, an online algorithm makes a sequence of choices. In each round it chooses from a time-invariant set of alternatives and receives the payoff associated with this alternative. While the case of small strategy sets is by now well-understood, a lot of recent work has focused on MAB problems with exponentially or infinitely large strategy sets, where one needs to assume extra structure in order to make the problem tractable. In particular, recent literature considered information on similarity between arms. We consider similarity information in the setting of "contextual bandits", a natural extension of the basic MAB problem where before each round an algorithm is given the "context" -- a hint about the payoffs in this round. Contextual bandits are directly motivated by placing advertisements on webpages, one of the crucial problems in sponsored search. A particularly simple way to represent similarity information in the contextual bandit setting is via a "similarity distance...

  6. Self-similar aftershock rates

    Science.gov (United States)

    Davidsen, Jörn; Baiesi, Marco

    2016-08-01

    In many important systems exhibiting crackling noise—an intermittent avalanchelike relaxation response with power-law and, thus, self-similar distributed event sizes—the "laws" for the rate of activity after large events are not consistent with the overall self-similar behavior expected on theoretical grounds. This is particularly true for the case of seismicity, and a satisfying solution to this paradox has remained outstanding. Here, we propose a generalized description of the aftershock rates which is both self-similar and consistent with all other known self-similar features. Comparing our theoretical predictions with high-resolution earthquake data from Southern California we find excellent agreement, providing particularly clear evidence for a unified description of aftershocks and foreshocks. This may offer an improved framework for time-dependent seismic hazard assessment and earthquake forecasting.

  7. Unmixing of spectrally similar minerals

    CSIR Research Space (South Africa)

    Debba, Pravesh

    2009-01-01

    Full Text Available -bearing oxide/hydroxide/sulfate minerals in complex mixtures be obtained using hyperspectral data? Debba (CSIR) Unmixing of spectrally similar minerals MERAKA 2009 3 / 18 Method of spectral unmixing Old method: problem Linear Spectral Mixture Analysis (LSMA...

  8. Self-similar aftershock rates

    CERN Document Server

    Davidsen, Jörn

    2016-01-01

    In many important systems exhibiting crackling noise --- intermittent avalanche-like relaxation response with power-law and, thus, self-similar distributed event sizes --- the "laws" for the rate of activity after large events are not consistent with the overall self-similar behavior expected on theoretical grounds. This is in particular true for the case of seismicity and a satisfying solution to this paradox has remained outstanding. Here, we propose a generalized description of the aftershock rates which is both self-similar and consistent with all other known self-similar features. Comparing our theoretical predictions with high resolution earthquake data from Southern California we find excellent agreement, providing in particular clear evidence for a unified description of aftershocks and foreshocks. This may offer an improved way of time-dependent seismic hazard assessment and earthquake forecasting.

  9. Community Detection by Neighborhood Similarity

    Institute of Scientific and Technical Information of China (English)

    LIU Xu; XIE Zheng; YI Dong-Yun

    2012-01-01

    Detection of the community structure in a network is important for understanding the structure and dynamics of the network.By exploring the neighborhood of vertices,a local similarity metric is proposed,which can be quickly computed.The resulting similarity matrix retains the same support as the adjacency matrix.Based on local similarity,an agglomerative hierarchical clustering algorithm is proposed for community detection.The algorithm is implemented by an efficient max-heap data structure and runs in nearly linear time,thus is capable of dealing with large sparse networks with tens of thousands of nodes.Experiments on synthesized and real-world networks demonstrate that our method is efficient to detect community structures,and the proposed metric is the most suitable one among all the tested similarity indices.%Detection of the community structure in a network is important for understanding the structure and dynamics of the network. By exploring the neighborhood of vertices, a local similarity metric is proposed, which can be quickly computed. The resulting similarity matrix retains the same support as the adjacency matrix. Based on local similarity, an agglomerative hierarchical clustering algorithm is proposed for community detection. The algorithm is implemented by an efficient max-heap data structure and runs in nearly linear time, thus is capable of dealing with large sparse networks with tens of thousands of nodes. Experiments on synthesized and real-world networks demonstrate that our method is efficient to detect community structures, and the proposed metric is the most suitable one among all the tested similarity indices.

  10. Similarity measures for protein ensembles

    DEFF Research Database (Denmark)

    Lindorff-Larsen, Kresten; Ferkinghoff-Borg, Jesper

    2009-01-01

    Analyses of similarities and changes in protein conformation can provide important information regarding protein function and evolution. Many scores, including the commonly used root mean square deviation, have therefore been developed to quantify the similarities of different protein conformations...... a synthetic example from molecular dynamics simulations. We then apply the algorithms to revisit the problem of ensemble averaging during structure determination of proteins, and find that an ensemble refinement method is able to recover the correct distribution of conformations better than standard single...

  11. Science or Art? How Aesthetic Standards Grease the Way Through the Publication Bottleneck but Undermine Science.

    Science.gov (United States)

    Giner-Sorolla, Roger

    2012-11-01

    The current crisis in psychological research involves issues of fraud, replication, publication bias, and false positive results. I argue that this crisis follows the failure of widely adopted solutions to psychology's similar crisis of the 1970s. The untouched root cause is an information-economic one: Too many studies divided by too few publication outlets equals a bottleneck. Articles cannot pass through just by showing theoretical meaning and methodological rigor; their results must appear to support the hypothesis perfectly. Consequently, psychologists must master the art of presenting perfect-looking results just to survive in the profession. This favors aesthetic criteria of presentation in a way that harms science's search for truth. Shallow standards of statistical perfection distort analyses and undermine the accuracy of cumulative data; narrative expectations encourage dishonesty about the relationship between results and hypotheses; criteria of novelty suppress replication attempts. Concerns about truth in research are emerging in other sciences and may eventually descend on our heads in the form of difficult and insensitive regulations. I suggest a more palatable solution: to open the bottleneck, putting structures in place to reward broader forms of information sharing beyond the exquisite art of present-day journal publication. © The Author(s) 2012.

  12. Identification of the minimal replicon and the origin of replication of the crenarchaeal plasmid pRN1.

    Science.gov (United States)

    Berkner, Silvia; Hinojosa, Mery Pina; Prangishvili, David; Lipps, Georg

    2014-10-01

    We have determined the minimal replicon of the crenarchaeal plasmid pRN1. It consists of 3097 base pairs amounting to 58% of the genome of pRN1. The minimal replicon comprises replication operon orf56/orf904 coding for a transcriptional repressor and the replication protein of pRN1. An upstream region of 64 bp that contains the promoter of the replication operon is essential as well as 166 bp of sequence downstream of the orf904 gene. This region contains a putative transcriptional terminator and a 100 nucleotides long stem-loop structure. Only the latter structure was shown to be required for replication. In addition replication was sustained when the stem-loop was displaced to another part of the pRN1 sequence. By mutational analysis we also find that the integrity of the stem-loop structure is required to maintain the replication of pRN1-derived constructs. As similar stem-loop structures are also present in other members of the pRN family, we suggest that this conserved structural element could be the origin of replication for the pRN plasmids. Further bioinformatic analysis revealed that the domain structure of the replication protein and the presence of a similar stem-loop structure as the putative replication origin are also found in several bacteriophages.

  13. 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.

  14. 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

  15. 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

  16. 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...

  17. 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.

  18. Single molecular biology: coming of age in DNA replication.

    Science.gov (United States)

    Liu, Xiao-Jing; Lou, Hui-Qiang

    2017-09-20

    DNA replication is an essential process of the living organisms. To achieve precise and reliable replication, DNA polymerases play a central role in DNA synthesis. Previous investigations have shown that the average rates of DNA synthesis on the leading and lagging strands in a replisome must be similar to avoid the formation of significant gaps in the nascent strands. The underlying mechanism has been assumed to be coordination between leading- and lagging-strand polymerases. However, Kowalczykowski's lab members recently performed single molecule techniques in E. coli and showed the real-time behavior of a replisome. The leading- and lagging-strand polymerases function stochastically and independently. Furthermore, when a DNA polymerase is paused, the helicase slows down in a self-regulating fail-safe mechanism, akin to a ''dead-man's switch''. Based on the real-time single-molecular observation, the authors propose that leading- and lagging-strand polymerases synthesize DNA stochastically within a Gaussian distribution. Along with the development and application of single-molecule techniques, we will witness a new age of DNA replication and other biological researches.

  19. Domain similarity based orthology detection.

    Science.gov (United States)

    Bitard-Feildel, Tristan; Kemena, Carsten; Greenwood, Jenny M; Bornberg-Bauer, Erich

    2015-05-13

    Orthologous protein detection software mostly uses pairwise comparisons of amino-acid sequences to assert whether two proteins are orthologous or not. Accordingly, when the number of sequences for comparison increases, the number of comparisons to compute grows in a quadratic order. A current challenge of bioinformatic research, especially when taking into account the increasing number of sequenced organisms available, is to make this ever-growing number of comparisons computationally feasible in a reasonable amount of time. We propose to speed up the detection of orthologous proteins by using strings of domains to characterize the proteins. We present two new protein similarity measures, a cosine and a maximal weight matching score based on domain content similarity, and new software, named porthoDom. The qualities of the cosine and the maximal weight matching similarity measures are compared against curated datasets. The measures show that domain content similarities are able to correctly group proteins into their families. Accordingly, the cosine similarity measure is used inside porthoDom, the wrapper developed for proteinortho. porthoDom makes use of domain content similarity measures to group proteins together before searching for orthologs. By using domains instead of amino acid sequences, the reduction of the search space decreases the computational complexity of an all-against-all sequence comparison. We demonstrate that representing and comparing proteins as strings of discrete domains, i.e. as a concatenation of their unique identifiers, allows a drastic simplification of search space. porthoDom has the advantage of speeding up orthology detection while maintaining a degree of accuracy similar to proteinortho. The implementation of porthoDom is released using python and C++ languages and is available under the GNU GPL licence 3 at http://www.bornberglab.org/pages/porthoda .

  20. Enrichment of Phosphatidylethanolamine in Viral Replication Compartments via Co-opting the Endosomal Rab5 Small GTPase by a Positive-Strand RNA Virus

    Science.gov (United States)

    Xu, Kai; Nagy, Peter D.

    2016-01-01

    Positive-strand RNA viruses build extensive membranous replication compartments to support replication and protect the virus from antiviral responses by the host. These viruses require host factors and various lipids to form viral replication complexes (VRCs). The VRCs built by Tomato bushy stunt virus (TBSV) are enriched with phosphatidylethanolamine (PE) through a previously unknown pathway. To unravel the mechanism of PE enrichment within the TBSV replication compartment, in this paper, the authors demonstrate that TBSV co-opts the guanosine triphosphate (GTP)-bound active form of the endosomal Rab5 small GTPase via direct interaction with the viral replication protein. Deletion of Rab5 orthologs in a yeast model host or expression of dominant negative mutants of plant Rab5 greatly decreases TBSV replication and prevents the redistribution of PE to the sites of viral replication. We also show that enrichment of PE in the viral replication compartment is assisted by actin filaments. Interestingly, the closely related Carnation Italian ringspot virus, which replicates on the boundary membrane of mitochondria, uses a similar strategy to the peroxisomal TBSV to hijack the Rab5-positive endosomes into the viral replication compartments. Altogether, usurping the GTP-Rab5–positive endosomes allows TBSV to build a PE-enriched viral replication compartment, which is needed to support peak-level replication. Thus, the Rab family of small GTPases includes critical host factors assisting VRC assembly and genesis of the viral replication compartment. PMID:27760128

  1. Similarity of atoms in molecules

    Energy Technology Data Exchange (ETDEWEB)

    Cioslowski, J.; Nanayakkara, A. (Florida State Univ., Tallahassee, FL (United States))

    1993-12-01

    Similarity of atoms in molecules is quantitatively assessed with a measure that employs electron densities within respective atomic basins. This atomic similarity measure does not rely on arbitrary assumptions concerning basis functions or 'atomic orbitals', is relatively inexpensive to compute, and has straightforward interpretation. Inspection of similarities between pairs of carbon, hydrogen, and fluorine atoms in the CH[sub 4], CH[sub 3]F, CH[sub 2]F[sub 2], CHF[sub 3], CF[sub 4], C[sub 2]H[sub 2], C[sub 2]H[sub 4], and C[sub 2]H[sub 6] molecules, calculated at the MP2/6-311G[sup **] level of theory, reveals that the atomic similarity is greatly reduced by a change in the number or the character of ligands (i.e. the atoms with nuclei linked through bond paths to the nucleus of the atom in question). On the other hand, atoms with formally identical (i.e. having the same nuclei and numbers of ligands) ligands resemble each other to a large degree, with the similarity indices greater than 0.95 for hydrogens and 0.99 for non-hydrogens. 19 refs., 6 tabs.

  2. Quantifying Similarity in Seismic Polarizations

    Science.gov (United States)

    Eaton, D. W. S.; Jones, J. P.; Caffagni, E.

    2015-12-01

    Measuring similarity in seismic attributes can help identify tremor, low S/N signals, and converted or reflected phases, in addition to diagnosing site noise and sensor misalignment in arrays. Polarization analysis is a widely accepted method for studying the orientation and directional characteristics of seismic phases via. computed attributes, but similarity is ordinarily discussed using qualitative comparisons with reference values. Here we introduce a technique for quantitative polarization similarity that uses weighted histograms computed in short, overlapping time windows, drawing on methods adapted from the image processing and computer vision literature. Our method accounts for ambiguity in azimuth and incidence angle and variations in signal-to-noise (S/N) ratio. Using records of the Mw=8.3 Sea of Okhotsk earthquake from CNSN broadband sensors in British Columbia and Yukon Territory, Canada, and vertical borehole array data from a monitoring experiment at Hoadley gas field, central Alberta, Canada, we demonstrate that our method is robust to station spacing. Discrete wavelet analysis extends polarization similarity to the time-frequency domain in a straightforward way. Because histogram distance metrics are bounded by [0 1], clustering allows empirical time-frequency separation of seismic phase arrivals on single-station three-component records. Array processing for automatic seismic phase classification may be possible using subspace clustering of polarization similarity, but efficient algorithms are required to reduce the dimensionality.

  3. 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.

  4. Similarity measures for face recognition

    CERN Document Server

    Vezzetti, Enrico

    2015-01-01

    Face recognition has several applications, including security, such as (authentication and identification of device users and criminal suspects), and in medicine (corrective surgery and diagnosis). Facial recognition programs rely on algorithms that can compare and compute the similarity between two sets of images. This eBook explains some of the similarity measures used in facial recognition systems in a single volume. Readers will learn about various measures including Minkowski distances, Mahalanobis distances, Hansdorff distances, cosine-based distances, among other methods. The book also summarizes errors that may occur in face recognition methods. Computer scientists "facing face" and looking to select and test different methods of computing similarities will benefit from this book. The book is also useful tool for students undertaking computer vision courses.

  5. Stalled replication forks within heterochromatin require ATRX for protection.

    Science.gov (United States)

    Huh, M S; Ivanochko, D; Hashem, L E; Curtin, M; Delorme, M; Goodall, E; Yan, K; Picketts, D J

    2016-05-12

    Expansive growth of neural progenitor cells (NPCs) is a prerequisite to the temporal waves of neuronal differentiation that generate the six-layered neocortex, while also placing a heavy burden on proteins that regulate chromatin packaging and genome integrity. This problem is further reflected by the growing number of developmental disorders caused by mutations in chromatin regulators. ATRX gene mutations cause a severe intellectual disability disorder (α-thalassemia mental retardation X-linked (ATRX) syndrome; OMIM no. 301040), characterized by microcephaly, urogenital abnormalities and α-thalassemia. Although the ATRX protein is required for the maintenance of repetitive DNA within heterochromatin, how this translates to disease pathogenesis remain poorly understood and was a focus of this study. We demonstrate that Atrx(FoxG1Cre) forebrain-specific conditional knockout mice display poly(ADP-ribose) polymerase-1 (Parp-1) hyperactivation during neurogenesis and generate fewer late-born Cux1- and Brn2-positive neurons that accounts for the reduced cortical size. Moreover, DNA damage, induced Parp-1 and Atm activation is elevated in progenitor cells and contributes to their increased level of cell death. ATRX-null HeLa cells are similarly sensitive to hydroxyurea-induced replication stress, accumulate DNA damage and proliferate poorly. Impaired BRCA1-RAD51 colocalization and PARP-1 hyperactivation indicated that stalled replication forks are not efficiently protected. DNA fiber assays confirmed that MRE11 degradation of stalled replication forks was rampant in the absence of ATRX or DAXX. Indeed, fork degradation in ATRX-null cells could be attenuated by treatment with the MRE11 inhibitor mirin, or exacerbated by inhibiting PARP-1 activity. Taken together, these results suggest that ATRX is required to limit replication stress during cellular proliferation, whereas upregulation of PARP-1 activity functions as a compensatory mechanism to protect stalled forks

  6. The rightful place of science science on the verge

    CERN Document Server

    2016-01-01

    A crisis looms over the scientific enterprise. Not a day passes without news of retractions, failed replications, fraudulent peer reviews, or misinformed science-based policies. The social implications are enormous, yet this crisis has remained largely uncharted—until now. In Science on the Verge, luminaries in the field of post-normal science and scientific governance focus attention on worrying fault-lines in the use of science for policymaking, and the dramatic crisis within science itself. This provocative new volume in The Rightful Place of Science also explores the concepts that need to be unlearned, and the skills that must be relearned and enhanced, if we are to restore the legitimacy and integrity of science.

  7. Science in Science Fiction.

    Science.gov (United States)

    Allday, Jonathan

    2003-01-01

    Offers some suggestions as to how science fiction, especially television science fiction programs such as "Star Trek" and "Star Wars", can be drawn into physics lessons to illuminate some interesting issues. (Author/KHR)

  8. Distance learning for similarity estimation

    NARCIS (Netherlands)

    Yu, J.; Amores, J.; Sebe, N.; Radeva, P.; Tian, Q.

    2008-01-01

    In this paper, we present a general guideline to find a better distance measure for similarity estimation based on statistical analysis of distribution models and distance functions. A new set of distance measures are derived from the harmonic distance, the geometric distance, and their generalized

  9. Distance learning for similarity estimation.

    Science.gov (United States)

    Yu, Jie; Amores, Jaume; Sebe, Nicu; Radeva, Petia; Tian, Qi

    2008-03-01

    In this paper, we present a general guideline to find a better distance measure for similarity estimation based on statistical analysis of distribution models and distance functions. A new set of distance measures are derived from the harmonic distance, the geometric distance, and their generalized variants according to the Maximum Likelihood theory. These measures can provide a more accurate feature model than the classical Euclidean and Manhattan distances. We also find that the feature elements are often from heterogeneous sources that may have different influence on similarity estimation. Therefore, the assumption of single isotropic distribution model is often inappropriate. To alleviate this problem, we use a boosted distance measure framework that finds multiple distance measures which fit the distribution of selected feature elements best for accurate similarity estimation. The new distance measures for similarity estimation are tested on two applications: stereo matching and motion tracking in video sequences. The performance of boosted distance measure is further evaluated on several benchmark data sets from the UCI repository and two image retrieval applications. In all the experiments, robust results are obtained based on the proposed methods.

  10. Revisiting Inter-Genre Similarity

    DEFF Research Database (Denmark)

    Sturm, Bob L.; Gouyon, Fabien

    2013-01-01

    We revisit the idea of ``inter-genre similarity'' (IGS) for machine learning in general, and music genre recognition in particular. We show analytically that the probability of error for IGS is higher than naive Bayes classification with zero-one loss (NB). We show empirically that IGS does...

  11. Comparison of hydrological similarity measures

    Science.gov (United States)

    Rianna, Maura; Ridolfi, Elena; Manciola, Piergiorgio; Napolitano, Francesco; Russo, Fabio

    2016-04-01

    The use of a traditional at site approach for the statistical characterization and simulation of spatio-temporal precipitation fields has a major recognized drawback. Indeed, the weakness of the methodology is related to the estimation of rare events and it involves the uncertainty of the at-site sample statistical inference, because of the limited length of records. In order to overcome the lack of at-site observations, regional frequency approach uses the idea of substituting space for time to estimate design floods. The conventional regional frequency analysis estimates quantile values at a specific site from multi-site analysis. The main idea is that homogeneous sites, once pooled together, have similar probability distribution curves of extremes, except for a scaling factor. The method for pooling groups of sites can be based on geographical or climatological considerations. In this work the region of influence (ROI) pooling method is compared with an entropy-based one. The ROI is a flexible pooling group approach which defines for each site its own "region" formed by a unique set of similar stations. The similarity is found through the Euclidean distance metric in the attribute space. Here an alternative approach based on entropy is introduced to cluster homogeneous sites. The core idea is that homogeneous sites share a redundant (i.e. similar) amount of information. Homogeneous sites are pooled through a hierarchical selection based on the mutual information index (i.e. a measure of redundancy). The method is tested on precipitation data in Central Italy area.

  12. HOW DISSIMILARLY SIMILAR ARE BIOSIMILARS?

    Directory of Open Access Journals (Sweden)

    Ramshankar Vijayalakshmi

    2012-05-01

    Full Text Available Recently Biopharmaceuticals are the new chemotherapeutical agents that are called as “Biosimilars” or “follow on protein products” by the European Medicines Agency (EMA and the American regulatory agencies (Food and Drug Administration respectively. Biosimilars are extremely similar to the reference molecule but not identical, however close their similarities may be. A regulatory framework is therefore in place to assess the application for marketing authorisation of biosimilars. When a biosimilar is similar to the reference biopharmaceutical in terms of safety, quality, and efficacy, it can be registered. It is important to document data from clinical trials with a view of similar safety and efficacy. If the development time for a generic medicine is around 3 years, a biosimilar takes about 6-9 years. Generic medicines need to demonstrate bioequivalence only unlike biosimilars that need to conduct phase I and Phase III clinical trials. In this review, different biosimilars that are already being used successfully in the field on Oncology is discussed. Their similarity, differences and guidelines to be followed before a clinically informed decision to be taken, is discussed. More importantly the regulatory guidelines that are operational in India with a work flow of making a biosimilar with relevant dos and dont’s are discussed. For a large populous country like India, where with improved treatments in all sectors including oncology, our ageing population is increasing. For the health care of this sector, we need more newer, cheaper and effective biosimilars in the market. It becomes therefore important to understand the regulatory guidelines and steps to come up with more biosimilars for the existing population and also more information is mandatory for the practicing clinicians to translate these effectively into clinical practice.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. The Caulobacter crescentus chromosome replication origin evolved two classes of weak DnaA binding sites.

    Science.gov (United States)

    Taylor, James A; Ouimet, Marie-Claude; Wargachuk, Richard; Marczynski, Gregory T

    2011-10-01

    The Caulobacter crescentus replication initiator DnaA and essential response regulator CtrA compete to control chromosome replication. The C. crescentus replication origin (Cori) contains five strong CtrA binding sites but only two apparent DnaA boxes, termed G-boxes (with a conserved second position G, TGATCCACA). Since clusters of DnaA boxes typify bacterial replication origins, this discrepancy suggested that C. crescentus DnaA recognizes different DNA sequences or compensates with novel DNA-binding proteins. We searched for novel DNA sites by scanning mutagenesis of the most conserved Cori DNA. Autonomous replication assays showed that G-boxes and novel W-boxes (TCCCCA) are essential for replication. Further analyses showed that C. crescentus DnaA binds G-boxes with moderate and W-boxes with very weak affinities significantly below DnaA's capacity for high-affinity Escherichia coli-boxes (TTATCCACA). Cori has five conserved W-boxes. Increasing W-box affinities increases or decreases autonomous replication depending on their strategic positions between the G-boxes. In vitro, CtrA binding displaces DnaA from proximal G-boxes and from distal W-boxes implying CtrA-DnaA competition and DnaA-DnaA cooperation between G-boxes and W-boxes. Similarly, during cell cycle progression, CtrA proteolysis coincides with DnaA binding to Cori. We also observe highly conserved W-boxes in other replication origins lacking E. coli-boxes. Therefore, strategically weak DnaA binding can be a general means of replication control. © 2011 Blackwell Publishing Ltd.

  20. Establishment and primary application of a mouse model with hepatitis B virus replication

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To establish a rapid and convenient animal model with hepatitis B virus (HBV) replication. METHODS: A naked DNA solution of HBV-replicationcompetent plasmid was transferred to BALB/C mice via the tail vein, using a hydrodynamic in vivo transfection procedure. After injection, these mice were sacrificed on d 1, 3, 4, 5, 7 and 10. HBV DNA replication intermediates in the liver were analyzed by Southern blot hybridization. The expression of hepatitis B core antigen (HBcAg) and hepatitis B surface antigen (HBsAg) in the liver was checked by immunohistochemistry. Serum HBsAg and hepatitis B e antigen (HBeAg) was detected by enzymelinked immunosorbent assay (ELISA). Inhibition of HBV replication was compared in HBV replication model mice treated intraperitoneally with polyinosinic-polytidylin acid (polyIC) or phosphate-buffered saline (PBS). RESULTS: After hydrodynamicin vivo transfection, HBV DNA replication intermediates in the mouse liver were detectable on d 1 and abundant on d 3 and 4, the levels were slightly decreased and remained relatively stable between d 5 and 7, and were almost undetectable on d 10. The expression patterns of HBcAg and HBsAg were similar to that of HBV replication intermediate DNA, except that they reached a peak on d 1 after injection. No obvious differences in HBV DNA replication intermediates were observed in the left, right and middle lobes of the liver. After treatment with polyIC, the level of HBV intermediate DNA in the liver was lower than that in the control mice injected with PBS. CONCLUSION: A rapid and convenient mouse model with a high level of HBV replication was developed and used to investigate the inhibitory effect of polyIC on HBV replication, which provides a useful tool for future functional studies of the HBV genome.

  1. Mitochondrial swinger replication: DNA replication systematically exchanging nucleotides and short 16S ribosomal DNA swinger inserts.

    Science.gov (United States)

    Seligmann, Hervé

    2014-11-01

    Assuming systematic exchanges between nucleotides (swinger RNAs) resolves genomic 'parenthood' of some orphan mitochondrial transcripts. Twenty-three different systematic nucleotide exchanges (bijective transformations) exist. Similarities between transcription and replication suggest occurrence of swinger DNA. GenBank searches for swinger DNA matching the 23 swinger versions of human and mouse mitogenomes detect only vertebrate mitochondrial swinger DNA for swinger type AT+CG (from five different studies, 149 sequences) matching three human and mouse mitochondrial genes: 12S and 16S ribosomal RNAs, and cytochrome oxidase subunit I. Exchange AT+CG conserves self-hybridization properties, putatively explaining swinger biases for rDNA, against protein coding genes. Twenty percent of the regular human mitochondrial 16S rDNA consists of short swinger repeats (from 13 exchanges). Swinger repeats could originate from recombinations between regular and swinger DNA: duplicated mitochondrial genes of the parthenogenetic gecko Heteronotia binoei include fewer short AT+CG swinger repeats than non-duplicated mitochondrial genomes of that species. Presumably, rare recombinations between female and male mitochondrial genes (and in parthenogenetic situations between duplicated genes), favors reverse-mutations of swinger repeat insertions, probably because most inserts affect negatively ribosomal function. Results show that swinger DNA exists, and indicate that swinger polymerization contributes to the genesis of genetic material and polymorphism.

  2. Replicating DNA by cell factories: roles of central carbon metabolism and transcription in the control of DNA replication in microbes, and implications for understanding this process in human cells.

    Science.gov (United States)

    Barańska, Sylwia; Glinkowska, Monika; Herman-Antosiewicz, Anna; Maciąg-Dorszyńska, Monika; Nowicki, Dariusz; Szalewska-Pałasz, Agnieszka; Węgrzyn, Alicja; Węgrzyn, Grzegorz

    2013-05-29

    Precise regulation of DNA replication is necessary to ensure the inheritance of genetic features by daughter cells after each cell division. Therefore, determining how the regulatory processes operate to control DNA replication is crucial to our understanding and application to biotechnological processes. Contrary to early concepts of DNA replication, it appears that this process is operated by large, stationary nucleoprotein complexes, called replication factories, rather than by single enzymes trafficking along template molecules. Recent discoveries indicated that in bacterial cells two processes, central carbon metabolism (CCM) and transcription, significantly and specifically influence the control of DNA replication of various replicons. The impact of these discoveries on our understanding of the regulation of DNA synthesis is discussed in this review. It appears that CCM may influence DNA replication by either action of specific metabolites or moonlighting activities of some enzymes involved in this metabolic pathway. The role of transcription in the control of DNA replication may arise from either topological changes in nucleic acids which accompany RNA synthesis or direct interactions between replication and transcription machineries. Due to intriguing similarities between some prokaryotic and eukaryotic regulatory systems, possible implications of studies on regulation of microbial DNA replication on understanding such a process occurring in human cells are discussed.

  3. Reproducible research in computational science.

    Science.gov (United States)

    Peng, Roger D

    2011-12-02

    Computational science has led to exciting new developments, but the nature of the work has exposed limitations in our ability to evaluate published findings. Reproducibility has the potential to serve as a minimum standard for judging scientific claims when full independent replication of a study is not possible.

  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. Self-similarity Driven Demosaicking

    Directory of Open Access Journals (Sweden)

    Antoni Buades

    2011-06-01

    Full Text Available Digital cameras record only one color component per pixel, red, green or blue. Demosaicking is the process by which one can infer a whole color matrix from such a matrix of values, thus interpolating the two missing color values per pixel. In this article we propose a demosaicking method based on the property of non-local self-similarity of images.

  6. Sparse Similarity-Based Fisherfaces

    DEFF Research Database (Denmark)

    Fagertun, Jens; Gomez, David Delgado; Hansen, Mads Fogtmann;

    2011-01-01

    In this work, the effect of introducing Sparse Principal Component Analysis within the Similarity-based Fisherfaces algorithm is examined. The technique aims at mimicking the human ability to discriminate faces by projecting the faces in a highly discriminative and easy interpretative way. Pixel...... obtain the same recognition results as the technique in a dense version using only a fraction of the input data. Furthermore, the presented results suggest that using SPCA in the technique offers robustness to occlusions....

  7. 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 ...

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. Active browsing using similarity pyramids

    Science.gov (United States)

    Chen, Jau-Yuen; Bouman, Charles A.; Dalton, John C.

    1998-12-01

    In this paper, we describe a new approach to managing large image databases, which we call active browsing. Active browsing integrates relevance feedback into the browsing environment, so that users can modify the database's organization to suit the desired task. Our method is based on a similarity pyramid data structure, which hierarchically organizes the database, so that it can be efficiently browsed. At coarse levels, the similarity pyramid allows users to view the database as large clusters of similar images. Alternatively, users can 'zoom into' finer levels to view individual images. We discuss relevance feedback for the browsing process, and argue that it is fundamentally different from relevance feedback for more traditional search-by-query tasks. We propose two fundamental operations for active browsing: pruning and reorganization. Both of these operations depend on a user-defined relevance set, which represents the image or set of images desired by the user. We present statistical methods for accurately pruning the database, and we propose a new 'worm hole' distance metric for reorganizing the database, so that members of the relevance set are grouped together.

  13. Self-Similar Collisionless Shocks

    CERN Document Server

    Katz, B; Waxman, E; Katz, Boaz; Keshet, Uri; Waxman, Eli

    2006-01-01

    Observations of gamma-ray burst afterglows suggest that the correlation length of magnetic field fluctuations downstream of relativistic non-magnetized collisionless shocks grows with distance from the shock to scales much larger than the plasma skin depth. We argue that this indicates that the plasma properties are described by a self-similar solution, and derive constraints on the scaling properties of the solution. For example, we find that the scaling of the characteristic magnetic field amplitude with distance from the shock is B \\propto D^{s_B} with -1 \\propto x^{2s_B} (for x>>D). We show that the plasma may be approximated as a combination of two self-similar components: a kinetic component of energetic particles and an MHD-like component representing "thermal" particles. We argue that the latter may be considered as infinitely conducting, in which case s_B=0 and the scalings are completely determined (e.g. dn/dE \\propto E^{-2} and B \\propto D^0). Similar claims apply to non- relativistic shocks such a...

  14. Contextual Factors for Finding Similar Experts

    DEFF Research Database (Denmark)

    Hofmann, Katja; Balog, Krisztian; Bogers, Toine;

    2010-01-01

    Expertise-seeking research studies how people search for expertise and choose whom to contact in the context of a specific task. An important outcome are models that identify factors that influence expert finding. Expertise retrieval addresses the same problem, expert finding, but from a system......-seeking models, are rarely taken into account. In this article, we extend content-based expert-finding approaches with contextual factors that have been found to influence human expert finding. We focus on a task of science communicators in a knowledge-intensive environment, the task of finding similar experts......, given an example expert. Our approach combines expertise-seeking and retrieval research. First, we conduct a user study to identify contextual factors that may play a role in the studied task and environment. Then, we design expert retrieval models to capture these factors. We combine these with content...

  15. Generalized entropies and the similarity of texts

    Science.gov (United States)

    Altmann, Eduardo G.; Dias, Laércio; Gerlach, Martin

    2017-01-01

    We show how generalized Gibbs–Shannon entropies can provide new insights on the statistical properties of texts. The universal distribution of word frequencies (Zipf’s law) implies that the generalized entropies, computed at the word level, are dominated by words in a specific range of frequencies. Here we show that this is the case not only for the generalized entropies but also for the generalized (Jensen–Shannon) divergences, used to compute the similarity between different texts. This finding allows us to identify the contribution of specific words (and word frequencies) for the different generalized entropies and also to estimate the size of the databases needed to obtain a reliable estimation of the divergences. We test our results in large databases of books (from the google n-gram database) and scientific papers (indexed by Web of Science).

  16. Generalized Entropies and the Similarity of Texts

    CERN Document Server

    Altmann, Eduardo G; Gerlach, Martin

    2016-01-01

    We show how generalized Gibbs-Shannon entropies can provide new insights on the statistical properties of texts. The universal distribution of word frequencies (Zipf's law) implies that the generalized entropies, computed at the word level, are dominated by words in a specific range of frequencies. Here we show that this is the case not only for the generalized entropies but also for the generalized (Jensen-Shannon) divergences, used to compute the similarity between different texts. This finding allows us to identify the contribution of specific words (and word frequencies) for the different generalized entropies and also to estimate the size of the databases needed to obtain a reliable estimation of the divergences. We test our results in large databases of books (from the Google n-gram database) and scientific papers (indexed by Web of Science).

  17. Contextual Factors for Finding Similar Experts

    DEFF Research Database (Denmark)

    Hofmann, Katja; Balog, Krisztian; Bogers, Toine

    2010-01-01

    -seeking models, are rarely taken into account. In this article, we extend content-based expert-finding approaches with contextual factors that have been found to influence human expert finding. We focus on a task of science communicators in a knowledge-intensive environment, the task of finding similar experts......, given an example expert. Our approach combines expertise-seeking and retrieval research. First, we conduct a user study to identify contextual factors that may play a role in the studied task and environment. Then, we design expert retrieval models to capture these factors. We combine these with content......-based retrieval models and evaluate them in a retrieval experiment. Our main finding is that while content-based features are the most important, human participants also take contextual factors into account, such as media experience and organizational structure. We develop two principled ways of modeling...

  18. The Gestalt principle of similarity benefits visual working memory.

    Science.gov (United States)

    Peterson, Dwight J; Berryhill, Marian E

    2013-12-01

    Visual working memory (VWM) is essential for many cognitive processes, yet it is notably limited in capacity. Visual perception processing is facilitated by Gestalt principles of grouping, such as connectedness, similarity, and proximity. This introduces the question, do these perceptual benefits extend to VWM? If so, can this be an approach to enhance VWM function by optimizing the processing of information? Previous findings have demonstrated that several Gestalt principles (connectedness, common region, and spatial proximity) do facilitate VWM performance in change detection tasks (Jiang, Olson, & Chun, 2000; Woodman, Vecera, & Luck, 2003; Xu, 2002, 2006; Xu & Chun, 2007). However, one prevalent Gestalt principle, similarity, has not been examined with regard to facilitating VWM. Here, we investigated whether grouping by similarity benefits VWM. Experiment 1 established the basic finding that VWM performance could benefit from grouping. Experiment 2 replicated and extended this finding by showing that similarity was only effective when the similar stimuli were proximal. In short, the VWM performance benefit derived from similarity was constrained by spatial proximity, such that similar items need to be near each other. Thus, the Gestalt principle of similarity benefits visual perception, but it can provide benefits to VWM as well.

  19. 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.

  20. Genome-scale cluster analysis of replicated microarrays using shrinkage correlation coefficient.

    Science.gov (United States)

    Yao, Jianchao; Chang, Chunqi; Salmi, Mari L; Hung, Yeung Sam; Loraine, Ann; Roux, Stanley J

    2008-06-18

    Currently, clustering with some form of correlation coefficient as the gene similarity metric has become a popular method for profiling genomic data. The Pearson correlation coefficient and the standard deviation (SD)-weighted correlation coefficient are the two most widely-used correlations as the similarity metrics in clustering microarray data. However, these two correlations are not optimal for analyzing replicated microarray data generated by most laboratories. An effective correlation coefficient is needed to provide statistically sufficient analysis of replicated microarray data. In this study, we describe a novel correlation coefficient, shrinkage correlation coefficient (SCC), that fully exploits the similarity between the replicated microarray experimental samples. The methodology considers both the number of replicates and the variance within each experimental group in clustering expression data, and provides a robust statistical estimation of the error of replicated microarray data. The value of SCC is revealed by its comparison with two other correlation coefficients that are currently the most widely-used (Pearson correlation coefficient and SD-weighted correlation coefficient) using statistical measures on both synthetic expression data as well as real gene expression data from Saccharomyces cerevisiae. Two leading clustering methods, hierarchical and k-means clustering were applied for the comparison. The comparison indicated that using SCC achieves better clustering performance. Applying SCC-based hierarchical clustering to the replicated microarray data obtained from germinating spores of the fern Ceratopteris richardii, we discovered two clusters of genes with shared expression patterns during spore germination. Functional analysis suggested that some of the genetic mechanisms that control germination in such diverse plant lineages as mosses and angiosperms are also conserved among ferns. This study shows that SCC is an alternative to the Pearson

  1. Genome-scale cluster analysis of replicated microarrays using shrinkage correlation coefficient

    Directory of Open Access Journals (Sweden)

    Loraine Ann

    2008-06-01

    Full Text Available Abstract Background Currently, clustering with some form of correlation coefficient as the gene similarity metric has become a popular method for profiling genomic data. The Pearson correlation coefficient and the standard deviation (SD-weighted correlation coefficient are the two most widely-used correlations as the similarity metrics in clustering microarray data. However, these two correlations are not optimal for analyzing replicated microarray data generated by most laboratories. An effective correlation coefficient is needed to provide statistically sufficient analysis of replicated microarray data. Results In this study, we describe a novel correlation coefficient, shrinkage correlation coefficient (SCC, that fully exploits the similarity between the replicated microarray experimental samples. The methodology considers both the number of replicates and the variance within each experimental group in clustering expression data, and provides a robust statistical estimation of the error of replicated microarray data. The value of SCC is revealed by its comparison with two other correlation coefficients that are currently the most widely-used (Pearson correlation coefficient and SD-weighted correlation coefficient using statistical measures on both synthetic expression data as well as real gene expression data from Saccharomyces cerevisiae. Two leading clustering methods, hierarchical and k-means clustering were applied for the comparison. The comparison indicated that using SCC achieves better clustering performance. Applying SCC-based hierarchical clustering to the replicated microarray data obtained from germinating spores of the fern Ceratopteris richardii, we discovered two clusters of genes with shared expression patterns during spore germination. Functional analysis suggested that some of the genetic mechanisms that control germination in such diverse plant lineages as mosses and angiosperms are also conserved among ferns. Conclusion

  2. 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....

  3. 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...

  4. 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.

  5. Replicating and understanding successful innovations: Implementing tutorials in introductory physics

    Directory of Open Access Journals (Sweden)

    S. J. Pollock

    2005-09-01

    Full Text Available We report a detailed study of the implementation of Tutorials in Introductory Physics at a large-scale research institution. Based on two successive semesters of evaluation, we observe students’ improved conceptual mastery (force and motion concept evaluation median normalized gain 0.77, N=336 , albeit with some student discontent. We replicate the results of original studies of tutorial effectiveness and document how and why these results occur. Additionally, using the Colorado Learning Attitudes about Science Survey we measure the support of students’ expertlike beliefs about learning physics in our environment. We examine this implementation from a viewpoint that emphasizes varying contextual levels of this implementation, from students’ engagement in individual tasks, to the situations in which these tasks are embedded, to the broader classroom, departmental, and educational structures. We document both obvious and subtle features that help ensure the successful implementation of these reforms.

  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. 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.

  9. 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.

  10. 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.

  11. Assessing protein kinase target similarity

    DEFF Research Database (Denmark)

    Gani, Osman A; Thakkar, Balmukund; Narayanan, Dilip

    2015-01-01

    : focussed chemical libraries, drug repurposing, polypharmacological design, to name a few. Protein kinase target similarity is easily quantified by sequence, and its relevance to ligand design includes broad classification by key binding sites, evaluation of resistance mutations, and the use of surrogate......" of sequence and crystal structure information, with statistical methods able to identify key correlates to activity but also here, "the devil is in the details." Examples from specific repurposing and polypharmacology applications illustrate these points. This article is part of a Special Issue entitled...

  12. Science in Computational Sciences

    Directory of Open Access Journals (Sweden)

    Jameson Cerrosen

    2012-12-01

    Full Text Available The existing theory in relation to science presents the physics as an ideal, although many sciences not approach the same, so that the current philosophy of science-Theory of Science- is not much help when it comes to analyze the computer science, an emerging field of knowledge that aims investigation of computers, which are included in the materialization of the ideas that try to structure the knowledge and information about the world. Computer Science is based on logic and mathematics, but both theoretical research methods and experimental follow patterns of classical scientific fields. Modeling and computer simulation, as a method, are specific to the discipline and will be further developed in the near future, not only applied to computers but also to other scientific fields. In this article it is analyze the aspects of science in computer science, is presenting an approach to the definition of science and the scientific method in general and describes the relationships between science, research, development and technology.

  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. Characterization of the replicon from the lactococcal theta-replicating plasmid pJW563.

    Science.gov (United States)

    Gravesen, A; Josephsen, J; von Wright, A; Vogensen, F K

    1995-09-01

    The replication region of the lactococcal plasmid pJW563 was localized to a 2.3-kb EcoRI fragment. This DNA fragment was sequenced ans a 1155-bp open reading frame, repB563, encoding a putative protein RepB563 of 385 amino acids was found. An AT-rich noncoding region, repA563, was found upstream of repB563. This segment included several direct and inverted repeats. A downstream 591-bp open reading frame, ORF X, which was not necessary for replication, was putatively translationally coupled to repB563, RepB563 supplied in trans could support replication of a plasmid containing repA563 and a truncated repB563. This observation suggests that RepB563 is a trans-acting replication protein, and repA563 the cis-acting origin of replication, repA563, repB563, and the beginning of ORF X showed high homology to similar regions in a family of lactococcal theta-replicating plasmids. The repA DNA sequences and the RepB amino acid sequences of the plasmids were aligned and the consensus sequences generated. The comparison revealed highly conserved areas among this family of plasmids. In addition, variable domains emerged, presumably having a plasmid specific function, pVS40 and pC1305 were plasmids with replication proteins showing high homology to RepB563. Despite this homology, replication from repA563 could not be supported by the pVS40 or pC1305 replication protein supplied in trans. Likewise the pJW563 protein could not support replication from the pVS40 origin. pJW563 was found to be compatible with the pVS40 and pC1305 replicons. The results indicate that pJW563 belongs to the widespread family of lactococcal theta-replicating pladmids. Despite the high homology between their replicons, the interaction between the replication origin and the protein is highly specific in many cases rendering the plasmids compatible.

  15. Mechanisms for similarity based cooperation

    Science.gov (United States)

    Traulsen, A.

    2008-06-01

    Cooperation based on similarity has been discussed since Richard Dawkins introduced the term “green beard” effect. In these models, individuals cooperate based on an aribtrary signal (or tag) such as the famous green beard. Here, two different models for such tag based cooperation are analysed. As neutral drift is important in both models, a finite population framework is applied. The first model, which we term “cooperative tags” considers a situation in which groups of cooperators are formed by some joint signal. Defectors adopting the signal and exploiting the group can lead to a breakdown of cooperation. In this case, conditions are derived under which the average abundance of the more cooperative strategy exceeds 50%. The second model considers a situation in which individuals start defecting towards others that are not similar to them. This situation is termed “defective tags”. It is shown that in this case, individuals using tags to cooperate exclusively with their own kind dominate over unconditional cooperators.

  16. 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...

  17. 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

  18. 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...

  19. 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...

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. Interneurons targeting similar layers receive synaptic inputs with similar kinetics.

    Science.gov (United States)

    Cossart, Rosa; Petanjek, Zdravko; Dumitriu, Dani; Hirsch, June C; Ben-Ari, Yehezkel; Esclapez, Monique; Bernard, Christophe

    2006-01-01

    GABAergic interneurons play diverse and important roles in controlling neuronal network dynamics. They are characterized by an extreme heterogeneity morphologically, neurochemically, and physiologically, but a functionally relevant classification is still lacking. Present taxonomy is essentially based on their postsynaptic targets, but a physiological counterpart to this classification has not yet been determined. Using a quantitative analysis based on multidimensional clustering of morphological and physiological variables, we now demonstrate a strong correlation between the kinetics of glutamate and GABA miniature synaptic currents received by CA1 hippocampal interneurons and the laminar distribution of their axons: neurons that project to the same layer(s) receive synaptic inputs with similar kinetics distributions. In contrast, the kinetics distributions of GABAergic and glutamatergic synaptic events received by a given interneuron do not depend upon its somatic location or dendritic arborization. Although the mechanisms responsible for this unexpected observation are still unclear, our results suggest that interneurons may be programmed to receive synaptic currents with specific temporal dynamics depending on their targets and the local networks in which they operate.

  7. 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

  8. Semantically enabled image similarity search

    Science.gov (United States)

    Casterline, May V.; Emerick, Timothy; Sadeghi, Kolia; Gosse, C. A.; Bartlett, Brent; Casey, Jason

    2015-05-01

    Georeferenced data of various modalities are increasingly available for intelligence and commercial use, however effectively exploiting these sources demands a unified data space capable of capturing the unique contribution of each input. This work presents a suite of software tools for representing geospatial vector data and overhead imagery in a shared high-dimension vector or embedding" space that supports fused learning and similarity search across dissimilar modalities. While the approach is suitable for fusing arbitrary input types, including free text, the present work exploits the obvious but computationally difficult relationship between GIS and overhead imagery. GIS is comprised of temporally-smoothed but information-limited content of a GIS, while overhead imagery provides an information-rich but temporally-limited perspective. This processing framework includes some important extensions of concepts in literature but, more critically, presents a means to accomplish them as a unified framework at scale on commodity cloud architectures.

  9. SIMILARITIES AND DIFFERENCES BETWEEN COMPANIES

    Directory of Open Access Journals (Sweden)

    NAGY CRISTINA MIHAELA

    2015-05-01

    Full Text Available act: Similarities between the accounting of companies and territorial administrative units accounting are the following: organizing double entry accounting; accounting method both in terms of fundamental theoretical principles and specific practical tools. The differences between the accounting of companies and of territorial administrative units refer to: the accounting of territorial administrative units includes besides general accounting (financial also budgetary accounting, and the accounts system of the budgetary accounting is completely different from that of companies; financial statements of territorial administrative units to which leaders are not main authorizing officers are submitted to the hierarchically superior body (not at MPF; the accounts of territorial administrative units are opened at treasury and financial institutions, accounts at commercial banks being prohibited; equity accounts in territorial administrative units are structured into groups of funds; long term debts have a specific structure in territorial administrative units (internal local public debt and external local public debt.

  10. Performance Indexes: Similarities and Differences

    Directory of Open Access Journals (Sweden)

    André Machado Caldeira

    2013-06-01

    Full Text Available The investor of today is more rigorous on monitoring a financial assets portfolio. He no longer thinks only in terms of the expected return (one dimension, but in terms of risk-return (two dimensions. Thus new perception is more complex, since the risk measurement can vary according to anyone’s perception; some use the standard deviation for that, others disagree with this measure by proposing others. In addition to this difficulty, there is the problem of how to consider these two dimensions. The objective of this essay is to study the main performance indexes through an empirical study in order to verify the differences and similarities for some of the selected assets. One performance index proposed in Caldeira (2005 shall be included in this analysis.

  11. Features Based Text Similarity Detection

    CERN Document Server

    Kent, Chow Kok

    2010-01-01

    As the Internet help us cross cultural border by providing different information, plagiarism issue is bound to arise. As a result, plagiarism detection becomes more demanding in overcoming this issue. Different plagiarism detection tools have been developed based on various detection techniques. Nowadays, fingerprint matching technique plays an important role in those detection tools. However, in handling some large content articles, there are some weaknesses in fingerprint matching technique especially in space and time consumption issue. In this paper, we propose a new approach to detect plagiarism which integrates the use of fingerprint matching technique with four key features to assist in the detection process. These proposed features are capable to choose the main point or key sentence in the articles to be compared. Those selected sentence will be undergo the fingerprint matching process in order to detect the similarity between the sentences. Hence, time and space usage for the comparison process is r...

  12. HIV Replication at Low Copy Number and its Correlation with the HIV Reservoir: A Clinical Perspective.

    Science.gov (United States)

    Sarmati, Loredana; D'Ettorre, Gabriella; Parisi, Saverio Giuseppe; Andreoni, Massimo

    2015-01-01

    The efficacy of combination therapy (antiretroviral therapy--ARV) is demonstrated by the high rates of viral suppression achieved in most treated HIV patients. Whereas contemporary treatments may continuously suppress HIV replication, they do not eliminate the latent reservoir, which can reactivate HIV infection if ARV is discontinued. The persistence of HIV proviral DNA and infectious viruses in CD4+ T cells and others cells has long been considered a major obstacle in eradicating the HIV virus in treated patients. Moreover, recent studies have demonstrated the persistence of HIV replication at low copies in most patients on suppressive ARV. The source of this 'residual viraemia' and whether it declines over years of therapy remain unknown. Similarly, little is known regarding the biological relationships between the HIV reservoir and viral replication at low copies. The question of whether this 'residual viraemia' represents active replication or the release of non-productive virus from the reservoir has not been adequately resolved. From a clinical perspective, both the quantification of the HIV reservoir and the detection of low levels of replication in full-responder patients on prolonged ARV may provide important information regarding the effectiveness of treatment and the eradication of HIV. To date, the monitoring of these two parameters has been conducted only for research purposes; the routine use of standardised tests procedure is lacking. This review aims to assess the current data regarding the correlation between HIV replication at low copies and the HIV reservoir and to provide useful information for clinicians.

  13. Replication efficiency of soil-bound prions varies with soil type.

    Science.gov (United States)

    Saunders, Samuel E; Shikiya, Ronald A; Langenfeld, Katie; Bartelt-Hunt, Shannon L; Bartz, Jason C

    2011-06-01

    Prion sorption to soil is thought to play an important role in the transmission of scrapie and chronic wasting disease (CWD) via the environment. Sorption of PrP to soil and soil minerals is influenced by the strain and species of PrP(Sc) and by soil characteristics. However, the ability of soil-bound prions to convert PrP(c) to PrP(Sc) under these wide-ranging conditions remains poorly understood. We developed a semiquantitative protein misfolding cyclic amplification (PMCA) protocol to evaluate replication efficiency of soil-bound prions. Binding of the hyper (HY) strain of transmissible mink encephalopathy (TME) (hamster) prions to a silty clay loam soil yielded a greater-than-1-log decrease in PMCA replication efficiency with a corresponding 1.3-log reduction in titer. The increased binding of PrP(Sc) to soil over time corresponded with a decrease in PMCA replication efficiency. The PMCA efficiency of bound prions varied with soil type, where prions bound to clay and organic surfaces exhibited significantly lower replication efficiencies while prions bound to sand exhibited no apparent difference in replication efficiency compared to unbound controls. PMCA results from hamster and CWD agent-infected elk prions yielded similar findings. Given that PrP(Sc) adsorption affinity varies with soil type, the overall balance between prion adsorption affinity and replication efficiency for the dominant soil types of an area may be a significant determinant in the environmental transmission of prion diseases.

  14. The quaternary structure of the eukaryotic DNA replication proteins Sld7 and Sld3.

    Science.gov (United States)

    Itou, Hiroshi; Shirakihara, Yasuo; Araki, Hiroyuki

    2015-08-01

    The initiation of eukaryotic chromosomal DNA replication requires the formation of an active replicative helicase at the replication origins of chromosomes. Yeast Sld3 and its metazoan counterpart treslin are the hub proteins mediating protein associations critical for formation of the helicase. The Sld7 protein interacts with Sld3, and the complex formed is thought to regulate the function of Sld3. Although Sld7 is a non-essential DNA replication protein that is found in only a limited range of yeasts, its depletion slowed the growth of cells and caused a delay in the S phase. Recently, the Mdm2-binding protein was found to bind to treslin in humans, and its depletion causes defects in cells similar to the depletion of Sld7 in yeast, suggesting their functional relatedness and importance during the initiation step of DNA replication. Here, the crystal structure of Sld7 in complex with Sld3 is presented. Sld7 comprises two structural domains. The N-terminal domain of Sld7 binds to Sld3, and the C-terminal domains connect two Sld7 molecules in an antiparallel manner. The quaternary structure of the Sld3-Sld7 complex shown from the crystal structures appears to be suitable to activate two helicase molecules loaded onto replication origins in a head-to-head manner.

  15. Mycobacterium tuberculosis Ser/Thr protein kinase B mediates an oxygen-dependent replication switch

    Energy Technology Data Exchange (ETDEWEB)

    Ortega, Corrie; Liao, Reiling; Anderson, Lindsey N.; Rustad, Tige; Ollodart, Anja R.; Wright, Aaron T.; Sherman, David R.; Grundner, Christoph

    2014-01-07

    In the majority of cases, Mycobacterium tuberculosis (Mtb) infections are clinically latent, characterized by little or no bacterial replication and drug tolerance. Low oxygen tension is a major host factor inducing bacteriostasis, but the molecular mechanisms driving oxygen-dependent replication are poorly understood. Mtb encodes eleven serine/threonine protein kinases, a family of signaling molecules known to regulate similar replicative adaptations in other bacteria. Here, we tested the role of serine/threonine phosphorylation in the Mtb response to altered oxygen status, using an in vitro model of latency (hypoxia) and reactivation (reaeration). Broad kinase inhibition compromised survival of Mtb in hypoxia. Activity-based protein profiling and genetic mutation identified PknB as the kinase critical for surviving hypoxia. Mtb replication was highly sensitive to changes in PknB levels in aerated culture, and even more so in hypoxia. A mutant overexpressing PknB specifically in hypoxia showed a 10-fold loss in viability in low oxygen conditions. In contrast, chemically reducing PknB activity during hypoxia specifically compromised resumption of growth during reaeration. These data support a model in which PknB activity is reduced to achieve bacteriostasis, and elevated when replication resumes. Together, these data show that phosphosignaling controls replicative transitions associated with latency and reactivation, that PknB is a major regulator of these transitions, and that PknB could provide a highly vulnerable therapeutic target at every step of the Mtb life cycle - active disease, latency, and reactivation.

  16. Exponential growth and selection in self-replicating materials from DNA origami rafts

    Science.gov (United States)

    He, Xiaojin; Sha, Ruojie; Zhuo, Rebecca; Mi, Yongli; Chaikin, Paul M.; Seeman, Nadrian C.

    2017-10-01

    Self-replication and evolution under selective pressure are inherent phenomena in life, and but few artificial systems exhibit these phenomena. We have designed a system of DNA origami rafts that exponentially replicates a seed pattern, doubling the copies in each diurnal-like cycle of temperature and ultraviolet illumination, producing more than 7 million copies in 24 cycles. We demonstrate environmental selection in growing populations by incorporating pH-sensitive binding in two subpopulations. In one species, pH-sensitive triplex DNA bonds enable parent-daughter templating, while in the second species, triplex binding inhibits the formation of duplex DNA templating. At pH 5.3, the replication rate of species I is ~1.3-1.4 times faster than that of species II. At pH 7.8, the replication rates are reversed. When mixed together in the same vial, the progeny of species I replicate preferentially at pH 7.8 similarly at pH 5.3, the progeny of species II take over the system. This addressable selectivity should be adaptable to the selection and evolution of multi-component self-replicating materials in the nanoscopic-to-microscopic size range.

  17. Active RNA replication of hepatitis C virus downregulates CD81 expression.

    Science.gov (United States)

    Ke, Po-Yuan; Chen, Steve S-L

    2013-01-01

    So far how hepatitis C virus (HCV) replication modulates subsequent virus growth and propagation still remains largely unknown. Here we determine the impact of HCV replication status on the consequential virus growth by comparing normal and high levels of HCV RNA expression. We first engineered a full-length, HCV genotype 2a JFH1 genome containing a blasticidin-resistant cassette inserted at amino acid residue of 420 in nonstructural (NS) protein 5A, which allowed selection of human hepatoma Huh7 cells stably-expressing HCV. Short-term establishment of HCV stable cells attained a highly-replicating status, judged by higher expressions of viral RNA and protein as well as higher titer of viral infectivity as opposed to cells harboring the same genome without selection. Interestingly, maintenance of highly-replicating HCV stable cells led to decreased susceptibility to HCV pseudotyped particle (HCVpp) infection and downregulated cell surface level of CD81, a critical HCV entry (co)receptor. The decreased CD81 cell surface expression occurred through reduced total expression and cytoplasmic retention of CD81 within an endoplasmic reticulum -associated compartment. Moreover, productive viral RNA replication in cells harboring a JFH1 subgenomic replicon containing a similar blasticidin resistance gene cassette in NS5A and in cells robustly replicating full-length infectious genome also reduced permissiveness to HCVpp infection through decreasing the surface expression of CD81. The downregulation of CD81 surface level in HCV RNA highly-replicating cells thus interfered with reinfection and led to attenuated viral amplification. These findings together indicate that the HCV RNA replication status plays a crucial determinant in HCV growth by modulating the expression and intracellular localization of CD81.

  18. A Role of hIPI3 in DNA Replication Licensing in Human Cells.

    Science.gov (United States)

    Huang, Yining; Amin, Aftab; Qin, Yan; Wang, Ziyi; Jiang, Huadong; Liang, Lu; Shi, Linjing; Liang, Chun

    2016-01-01

    The yeast Ipi3p is required for DNA replication and cell viability in Sacharomyces cerevisiae. It is an essential component of the Rix1 complex (Rix1p/Ipi2p-Ipi1p-Ipi3p) that is required for the processing of 35S pre-rRNA in pre-60S ribosomal particles and for the initiation of DNA replication. The human IPI3 homolog is WDR18 (WD repeat domain 18), which shares significant homology with yIpi3p. Here we report that knockdown of hIPI3 resulted in substantial defects in the chromatin association of the MCM complex, DNA replication, cell cycle progression and cell proliferation. Importantly, hIPI3 silencing did not result in a reduction of the protein level of hCDC6, hMCM7, or the ectopically expressed GFP protein, indicating that protein synthesis was not defective in the same time frame of the DNA replication and cell cycle defects. Furthermore, the mRNA and protein levels of hIPI3 fluctuate in the cell cycle, with the highest levels from M phase to early G1 phase, similar to other pre-replicative (pre-RC) proteins. Moreover, hIPI3 interacts with other replication-initiation proteins, co-localizes with hMCM7 in the nucleus, and is important for the nuclear localization of hMCM7. We also found that hIPI3 preferentially binds to the origins of DNA replication including those at the c-Myc, Lamin-B2 and β-Globin loci. These results indicate that hIPI3 is involved in human DNA replication licensing independent of its role in ribosome biogenesis.

  19. Active RNA replication of hepatitis C virus downregulates CD81 expression.

    Directory of Open Access Journals (Sweden)

    Po-Yuan Ke

    Full Text Available So far how hepatitis C virus (HCV replication modulates subsequent virus growth and propagation still remains largely unknown. Here we determine the impact of HCV replication status on the consequential virus growth by comparing normal and high levels of HCV RNA expression. We first engineered a full-length, HCV genotype 2a JFH1 genome containing a blasticidin-resistant cassette inserted at amino acid residue of 420 in nonstructural (NS protein 5A, which allowed selection of human hepatoma Huh7 cells stably-expressing HCV. Short-term establishment of HCV stable cells attained a highly-replicating status, judged by higher expressions of viral RNA and protein as well as higher titer of viral infectivity as opposed to cells harboring the same genome without selection. Interestingly, maintenance of highly-replicating HCV stable cells led to decreased susceptibility to HCV pseudotyped particle (HCVpp infection and downregulated cell surface level of CD81, a critical HCV entry (coreceptor. The decreased CD81 cell surface expression occurred through reduced total expression and cytoplasmic retention of CD81 within an endoplasmic reticulum -associated compartment. Moreover, productive viral RNA replication in cells harboring a JFH1 subgenomic replicon containing a similar blasticidin resistance gene cassette in NS5A and in cells robustly replicating full-length infectious genome also reduced permissiveness to HCVpp infection through decreasing the surface expression of CD81. The downregulation of CD81 surface level in HCV RNA highly-replicating cells thus interfered with reinfection and led to attenuated viral amplification. These findings together indicate that the HCV RNA replication status plays a crucial determinant in HCV growth by modulating the expression and intracellular localization of CD81.

  20. Once in a lifetime: strategies for preventing re-replication in prokaryotic and eukaryotic cells

    DEFF Research Database (Denmark)

    Nielsen, Olaf; Løbner-Olesen, Anders

    2008-01-01

    by using the model organisms Escherichia coli and Schizosaccharomyces pombe as examples. Although the underlying molecular details are different, the logic behind the control mechanisms is similar. For example, after initiation, crucial molecules required for the loading of replicative helicases in both...

  1. Empirically Derived Learning Disability Subtypes: A Replication Attempt and Longitudinal Patterns over 15 Years.

    Science.gov (United States)

    Spreen, Otfried; Haaf, Robert G.

    1986-01-01

    Test scores of two groups of learning disabled children (N=63 and N=96) were submitted to cluster analysis in an attempt to replicate previously described subtypes. All three subtypes (visuo-perceptual, linguistic, and articulo-graphomotor types) were identified along with minimally and severely impaired subtypes. Similar clusters in the same…

  2. Empirically Derived Learning Disability Subtypes: A Replication Attempt and Longitudinal Patterns over 15 Years.

    Science.gov (United States)

    Spreen, Otfried; Haaf, Robert G.

    1986-01-01

    Test scores of two groups of learning disabled children (N=63 and N=96) were submitted to cluster analysis in an attempt to replicate previously described subtypes. All three subtypes (visuo-perceptual, linguistic, and articulo-graphomotor types) were identified along with minimally and severely impaired subtypes. Similar clusters in the same…

  3. Inclusion bodies are a site of ebolavirus replication.

    Science.gov (United States)

    Hoenen, Thomas; Shabman, Reed S; Groseth, Allison; Herwig, Astrid; Weber, Michaela; Schudt, Gordian; Dolnik, Olga; Basler, Christopher F; Becker, Stephan; Feldmann, Heinz

    2012-11-01

    Inclusion bodies are a characteristic feature of ebolavirus infections in cells. They contain large numbers of preformed nucleocapsids, but their biological significance has been debated, and they have been suggested to be aggregates of viral proteins without any further biological function. However, recent data for other viruses that produce similar structures have suggested that inclusion bodies might be involved in genome replication and transcription. In order to study filovirus inclusion bodies, we fused mCherry to the ebolavirus polymerase L, which is found in inclusion bodies. The resulting L-mCherry fusion protein was functional in minigenome assays and incorporated into virus-like particles. Importantly, L-mCherry fluorescence in transfected cells was readily detectable and distributed in a punctate pattern characteristic for inclusion bodies. A recombinant ebolavirus encoding L-mCherry instead of L was rescued and showed virtually identical growth kinetics and endpoint titers to those for wild-type virus. Using this virus, we showed that the onset of inclusion body formation corresponds to the onset of viral genome replication, but that viral transcription occurs prior to inclusion body formation. Live-cell imaging further showed that inclusion bodies are highly dynamic structures and that they can undergo dramatic reorganization during cell division. Finally, by labeling nascent RNAs using click technology we showed that inclusion bodies are indeed the site of viral RNA synthesis. Based on these data we conclude that, rather than being inert aggregates of nucleocapsids, ebolavirus inclusion bodies are in fact complex and dynamic structures and an important site at which viral RNA replication takes place.

  4. 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.

  5. 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.

  6. 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.

  7. Similar compositional biases are caused by very different mutational effects

    Science.gov (United States)

    Rocha, Eduardo P.C.; Touchon, Marie; Feil, Edward J.

    2006-01-01

    Compositional replication strand bias, commonly referred to as GC skew, is present in many genomes of prokaryotes, eukaryotes, and viruses. Although cytosine deamination in ssDNA (resulting in C→T changes on the leading strand) is often invoked as its major cause, the precise contributions of this and other substitution types are currently unknown. It is also unclear if the underlying mutational asymmetries are the same among taxa, are stable over time, or how closely the observed biases are to mutational equilibrium. We analyzed nearly neutral sites of seven taxa each with between three and six complete bacterial genomes, and inferred the substitution spectra of fourfold degenerate positions in nonhighly expressed genes. Using a bootstrap procedure, we extracted compositional biases associated with replication and identified the significant asymmetries. Although all taxa showed an overrepresentation of G relative to C on the leading strand (and imbalances between A and T), widely variable substitution asymmetries are noted. Surprisingly, all substitution types show significant asymmetry in at least one taxon, but none were universally biased in all taxa. Notably, in the two most biased genomes, A→G, rather than C→T, shapes the compositional bias. Given the variability in these biases, we propose that the process is multifactorial. Finally, we also find that most genomes are not at compositional equilibrium, and suggest that mutational-based heterotachy is deeply imprinted in the history of biological macromolecules. This shows that similar compositional biases associated with the same essential well-conserved process, replication, do not reflect similar mutational processes in different genomes, and that caution is required in inferring the roles of specific mutational biases on the basis of contemporary patterns of sequence composition. PMID:17068325

  8. High-Resolution Replication Profiles Define the Stochastic Nature of Genome Replication Initiation and Termination

    Directory of Open Access Journals (Sweden)

    Michelle Hawkins

    2013-11-01

    Full Text Available Eukaryotic genome replication is stochastic, and each cell uses a different cohort of replication origins. We demonstrate that interpreting high-resolution Saccharomyces cerevisiae genome replication data with a mathematical model allows quantification of the stochastic nature of genome replication, including the efficiency of each origin and the distribution of termination events. Single-cell measurements support the inferred values for stochastic origin activation time. A strain, in which three origins were inactivated, confirmed that the distribution of termination events is primarily dictated by the stochastic activation time of origins. Cell-to-cell variability in origin activity ensures that termination events are widely distributed across virtually the whole genome. We propose that the heterogeneity in origin usage contributes to genome stability by limiting potentially deleterious events from accumulating at particular loci.

  9. 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

  10. Replicative nature of Indian research, essence of scientific temper, and future of scientific progress

    Directory of Open Access Journals (Sweden)

    Ajai R. Singh

    2004-05-01

    Full Text Available A lot of Indian research is replicative in nature. This is because originality is at a premium here and mediocrity is in great demand. But replication has its merit as well because it helps in corroboration. And that is the bedrock on which many a fancied scientific hypothesis or theory stands, or falls. However, to go from replicative to original research will involve a massive effort to restructure the Indian psyche and an all round effort from numerous quarters. The second part of this paper deals with the essence of scientific temper,which need not have any basic friendship, or animosity, with religion, faith, superstition and other such entities. A true scientist follows two cardinal rules. He is never unwilling to accept the worth of evidence, howsoever damning to the most favourite of his theories. Second, and perhaps more important, for want of evidence, he withholds comment. He says neither yes nor no. Where will Science ultimately lead Man is the third part of this essay. One argument is that the conflict between Man and Science will continue tilleither of them is exhausted or wiped out. The other believes that it is Science which has to be harnessed for Man and not Man used for Science. And with the numerous checks and balances in place, Science will remain an effective tool for man's progress. The essential value-neutrality of Science will have to be supplemented by the values that man has upheld for centuries as fundamental, and which religious thought and moral philosophy have continuously professed.

  11. Science enrichment through informal science. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Katz, P.

    1996-07-01

    Hands On Science Outreach (HOSO) is a program of informal science education. Its mission is to bring to communities the option of out-of-school science explorations to small groups of children from the ages of 4-12. Such experiences encourage children to enjoy science without the fear of the consequences of failure that can occur in a formal school setting. It can start them on a life long pattern of participation, awareness and perhaps career interest, motivated by this kind of pleasurable learning. Since HOSO binds together adult training, materials and written guides, many of those not professionally employed in education, including parents, can and do become involved in {open_quotes}science for the fun of it.{close_quotes} The DOE grant to the HOSO program has funded the delivery of HOSO programming to five selected sites over the 1992-96 school years. It is the intention of both the DOE and HOSO to reach children who might otherwise not be able to afford the programming, with emphasis on underrepresented minorities. HOSO has developed fall, winter and spring theme-oriented informal science sessions on four age/grade levels. One hour classes take place once a week for eight weeks per session. At the original Washington, D.C. site, the program uses a mentoring model named STEPS (Successful Teaming for Educational Partnerships in Science) in partnership with the District of Columbia Schools, as well as HOSO and the DOE. That model continues to work in Washington, D.C. and has been replicated in parts of the Sacramento and Denver sites.

  12. Defining multiple, distinct, and shared spatiotemporal patterns of DNA replication and endoreduplication from 3D image analysis of developing maize (Zea mays L.) root tip nuclei.

    Science.gov (United States)

    Bass, Hank W; Hoffman, Gregg G; Lee, Tae-Jin; Wear, Emily E; Joseph, Stacey R; Allen, George C; Hanley-Bowdoin, Linda; Thompson, William F

    2015-11-01

    Spatiotemporal patterns of DNA replication have been described for yeast and many types of cultured animal cells, frequently after cell cycle arrest to aid in synchronization. However, patterns of DNA replication in nuclei from plants or naturally developing organs remain largely uncharacterized. Here we report findings from 3D quantitative analysis of DNA replication and endoreduplication in nuclei from pulse-labeled developing maize root tips. In both early and middle S phase nuclei, flow-sorted on the basis of DNA content, replicative labeling was widely distributed across euchromatic regions of the nucleoplasm. We did not observe the perinuclear or perinucleolar replicative labeling patterns characteristic of middle S phase in mammals. Instead, the early versus middle S phase patterns in maize could be distinguished cytologically by correlating two quantitative, continuous variables, replicative labeling and DAPI staining. Early S nuclei exhibited widely distributed euchromatic labeling preferentially localized to regions with weak DAPI signals. Middle S nuclei also exhibited widely distributed euchromatic labeling, but the label was preferentially localized to regions with strong DAPI signals. Highly condensed heterochromatin, including knobs, replicated during late S phase as previously reported. Similar spatiotemporal replication patterns were observed for both mitotic and endocycling maize nuclei. These results revealed that maize euchromatin exists as an intermingled mixture of two components distinguished by their condensation state and replication timing. These different patterns might reflect a previously described genome organization pattern, with "gene islands" mostly replicating during early S phase followed by most of the intergenic repetitive regions replicating during middle S phase.

  13. 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

  14. 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.

  15. Accessory Genes Confer a High Replication Rate to Virulent Feline Immunodeficiency Virus

    OpenAIRE

    Troyer, Ryan M.; Thompson, Jesse; Elder, John H.; VandeWoude, Sue

    2013-01-01

    Feline immunodeficiency virus (FIV) is a lentivirus that causes AIDS in domestic cats, similar to human immunodeficiency virus (HIV)/AIDS in humans. The FIV accessory protein Vif abrogates the inhibition of infection by cat APOBEC3 restriction factors. FIV also encodes a multifunctional OrfA accessory protein that has characteristics similar to HIV Tat, Vpu, Vpr, and Nef. To examine the role of vif and orfA accessory genes in FIV replication and pathogenicity, we generated chimeras between tw...

  16. 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.

  17. Enzyme-like replication de novo in a microcontroller environment.

    Science.gov (United States)

    Tangen, Uwe

    2010-01-01

    The desire to start evolution from scratch inside a computer memory is as old as computing. Here we demonstrate how viable computer programs can be established de novo in a Precambrian environment without supplying any specific instantiation, just starting with random bit sequences. These programs are not self-replicators, but act much more like catalysts. The microcontrollers used in the end are the result of a long series of simplifications. The objective of this simplification process was to produce universal machines with a human-readable interface, allowing software and/or hardware evolution to be studied. The power of the instruction set can be modified by introducing a secondary structure-folding mechanism, which is a state machine, allowing nontrivial replication to emerge with an instruction width of only a few bits. This state-machine approach not only attenuates the problems of brittleness and encoding functionality (too few bits available for coding, and too many instructions needed); it also enables the study of hardware evolution as such. Furthermore, the instruction set is sufficiently powerful to permit external signals to be processed. This information-theoretic approach forms one vertex of a triangle alongside artificial cell research and experimental research on the creation of life. Hopefully this work helps develop an understanding of how information—in a similar sense to the account of functional information described by Hazen et al.—is created by evolution and how this information interacts with or is embedded in its physico-chemical environment.

  18. A New Shuttle Plasmid That Stably Replicates in Clostridium acetobutylicum.

    Science.gov (United States)

    Lee, Sang-Hyun; Kwon, Min-A; Choi, Sunwha; Kim, Sooah; Kim, Jungyeon; Shin, Yong-An; Kim, Kyoung Heon

    2015-10-01

    We have developed a new shuttle plasmid, designated as pLK1-MCS that can replicate in both Clostridium acetobutylicum and Escherichia coli, by combining the pUB110 and pUC19 plasmids. Plasmid pLK1-MCS replicated more stably than previously reported plasmids containing either the pIM13 or the pAMβ1 replicon in the absence of antibiotic selective pressure. The transfer frequency of pLK1-MCS into C. acetobutylicum was similar to the transfer frequency of other shuttle plasmids. We complemented C. acetobutylicum ML1 (that does not produce solvents such as acetone, butanol, and ethanol owing to loss of the megaplasmid pSOL1 harboring the adhE1-ctfAB-adc operon) by introducing pLK1-MCS carrying the adhE1-ctfAB-adc operon into C. acetobutylicum ML1. The transformed cells were able to resume anaerobic solvent production, indicating that the new shuttle plasmid has the potential for practical use in microbial biotechnology.

  19. Host Phylogeny Determines Viral Persistence and Replication in Novel Hosts

    Science.gov (United States)

    Longdon, Ben; Hadfield, Jarrod D.; Webster, Claire L.

    2011-01-01

    Pathogens switching to new hosts can result in the emergence of new infectious diseases, and determining which species are likely to be sources of such host shifts is essential to understanding disease threats to both humans and wildlife. However, the factors that determine whether a pathogen can infect a novel host are poorly understood. We have examined the ability of three host-specific RNA-viruses (Drosophila sigma viruses from the family Rhabdoviridae) to persist and replicate in 51 different species of Drosophilidae. Using a novel analytical approach we found that the host phylogeny could explain most of the variation in viral replication and persistence between different host species. This effect is partly driven by viruses reaching a higher titre in those novel hosts most closely related to the original host. However, there is also a strong effect of host phylogeny that is independent of the distance from the original host, with viral titres being similar in groups of related hosts. Most of this effect could be explained by variation in general susceptibility to all three sigma viruses, as there is a strong phylogenetic correlation in the titres of the three viruses. These results suggest that the source of new emerging diseases may often be predictable from the host phylogeny, but that the effect may be more complex than simply causing most host shifts to occur between closely related hosts. PMID:21966271

  20. Studies on the mechanism of DNA replication in Physarum polycephalum

    Energy Technology Data Exchange (ETDEWEB)

    Brewer, E.N.; Evans, T.E.; Evans, H.H.

    1974-01-01

    The synthesis of single-stranded DNA subunits (4 x 10/sup 7/ daltons) in Physarum polycephalum was studied by alkaline sucrose density gradient centrifugation. The results were compared with the synthesis of the double-stranded DNA molecules (2.3 x 10/sup 8/ daltons) which they comprise, as determined from neutral sucrose density gradient centrifugation patterns. Although the initiation of synthesis of most double-stranded DNA molecules takes place relatively early in the S period, synthesis of the subunits within them is initiated throughout at least the first two hours of this period. Similarly, replicating (presumably forked) DNA molecules appear to split into daughter DNA molecules prior to the completion of synthesis of the subunits therein. The average rate of DNA chain elongation within subunits is 0.3 x 10/sup 6/ daltons/minute. It is suggested that alkaline sucrose density gradient centrifugation may be a more sensitive method for determining the time required for the completion of replication than other methods based solely on the incorporation of radioactive DNA precursors into an acid-insoluble product.

  1. Mechanisms Governing DDK Regulation of the Initiation of DNA Replication

    Directory of Open Access Journals (Sweden)

    Larasati

    2016-12-01

    Full Text Available The budding yeast Dbf4-dependent kinase (DDK complex—comprised of cell division cycle (Cdc7 kinase and its regulatory subunit dumbbell former 4 (Dbf4—is required to trigger the initiation of DNA replication through the phosphorylation of multiple minichromosome maintenance complex subunits 2-7 (Mcm2-7. DDK is also a target of the radiation sensitive 53 (Rad53 checkpoint kinase in response to replication stress. Numerous investigations have determined mechanistic details, including the regions of Mcm2, Mcm4, and Mcm6 phosphorylated by DDK, and a number of DDK docking sites. Similarly, the way in which the Rad53 forkhead-associated 1 (FHA1 domain binds to DDK—involving both canonical and non-canonical interactions—has been elucidated. Recent work has revealed mutual promotion of DDK and synthetic lethal with dpb11-1 3 (Sld3 roles. While DDK phosphorylation of Mcm2-7 subunits facilitates their interaction with Sld3 at origins, Sld3 in turn stimulates DDK phosphorylation of Mcm2. Details of a mutually antagonistic relationship between DDK and Rap1-interacting factor 1 (Rif1 have also recently come to light. While Rif1 is able to reverse DDK-mediated Mcm2-7 complex phosphorylation by targeting the protein phosphatase glycogen 7 (Glc7 to origins, there is evidence to suggest that DDK can counteract this activity by binding to and phosphorylating Rif1.

  2. Transient fibril structures facilitating nonenzymatic self-replication.

    Science.gov (United States)

    Rubinov, Boris; Wagner, Nathaniel; Matmor, Maayan; Regev, Oren; Ashkenasy, Nurit; Ashkenasy, Gonen

    2012-09-25

    An emerging new direction of research focuses on developing "self-synthesizing materials", those supramolecular structures that can promote their own formation by accelerating the synthesis of building blocks and/or an entire assembly. It was postulated recently that practical design of such systems can benefit from the ability to control the assembly of amphiphilic molecules into nanostructures. We describe here the self-assembly pathway of short amphiphilic peptides into various forms of soluble β-sheet structures--β-plates, fibrils, and hollow nanotubes--and their consequent activity as autocatalysts for the synthesis of monomeric peptides from simpler building blocks. A detailed kinetic analysis of both the self-assembly and self-replication processes allows us to suggest a full model and simulate the replication process, revealing that only specific structures, primarily fibrils that are stable within the solution for a time shorter than a few hours, can be active as catalysts. Interestingly, we have found that such a process also induces fibril reproduction, in a mechanism very similar to the propagation of prion proteins by transmission of misfolded states.

  3. 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...

  4. 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.

  5. 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...

  6. 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...

  7. 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.

  8. 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.

  9. Replicative DNA polymerase mutations in cancer.

    Science.gov (United States)

    Heitzer, Ellen; Tomlinson, Ian

    2014-02-01

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

  10. 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

  11. Aminoguanidine delays the replicative senescence of human diploid fibroblasts

    Institute of Scientific and Technical Information of China (English)

    WANG Pei-chang; ZHANG Jian; ZHANG Zong-yu; TONG Tan-jun

    2007-01-01

    advanced glycation end products; comet assayBackground The accumulation of free radicals and advanced glycation end products (AGEs) in cell plays a very important role in replicative senescence. Aminoguanidine (AG) has potential antioxidant effects and decreases AGE levels. This study aimed to investigate its effect on replicative senescence in vitro.Methods The effects of aminoguanidine on morphology, replicative lifespan, cell growth and proliferation, AGEs, DNA damage, DNA repair ability and telomere length were observed in human fetal lung diploid fibroblasts (2BS).Results Aminoguanidine maintained the non-senescent phenotype of 2BS cells even at late population doubling (PD) and increased cumulative population doublings by at least 17-21 PDs. Aminoguanidine also improved the potentials of growth and proliferation of 2BS cells as detected by the MTT assay. The AGE levels of late PD cells grown from early PD in DMEM containing aminiguanidine decreased significantly compared with those of late PD control cells and were similar to those of young control cells. In addition, the cells pretreated with aminoguanidine had a significant reduction in DNA strand breaks when they were exposed to 200 μmol/L H2O2 for 5 minutes which indicated that the compound had a strong potential to protect genomic DNA against oxidative stress. And most of the cells exposed to 100 μmol/L H2O2 had much shorter comet tails and smaller tail areas after incubation with aminoguanidine-supplemented DMEM, which indicated that the compound strongly improved the DNA repair abilities of 2BS cells. Moreover, PD55 cells grown from PD28 in 2 mmol/L or 4 mmol/L aminoguanidine retain telomere lengths of 7.94 kb or 8.12 kb, which was 0.83 kb or 1.11kb longer than that of the control cells.Conclusion Aminoguanidine delays replicative senescence of 2BS cells and the senescence-delaying effect of aminoguanidine appear to be due to its many biological properties including its potential for proliferation

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. The Problem of False Discovery: Many Scientific Results Can't Be Replicated, Leading to Serious Questions about What's True and False in the World of Research.

    Science.gov (United States)

    Foster, Kenneth R; Skufca, Joseph

    2016-01-01

    Is there a Cheshire Cat in science? One might believe so, given the many published scientific discoveries that cannot be independently reproduced. The ?replication crisis? in science has become a widely discussed issue among scientists and the lay media and even has its own entry in Wikipedia.

  17. Science or Science Fiction?

    DEFF Research Database (Denmark)

    Lefsrud, Lianne M.; Meyer, Renate

    2012-01-01

    This paper examines the framings and identity work associated with professionals’ discursive construction of climate change science, their legitimation of themselves as experts on ‘the truth’, and their attitudes towards regulatory measures. Drawing from survey responses of 1077 professional......, legitimation strategies, and use of emotionality and metaphor. By linking notions of the science or science fiction of climate change to the assessment of the adequacy of global and local policies and of potential organizational responses, we contribute to the understanding of ‘defensive institutional work...

  18. p53-Mediated Cellular Response to DNA Damage in Cells with Replicative Hepatitis B Virus

    Science.gov (United States)

    Puisieux, Alain; Ji, Jingwei; Guillot, Celine; Legros, Yann; Soussi, Thierry; Isselbacher, Kurt; Ozturk, Mehmet

    1995-02-01

    Wild-type p53 acts as a tumor suppressor gene by protecting cells from deleterious effects of genotoxic agents through the induction of a G_1/S arrest or apoptosis as a response to DNA damage. Transforming proteins of several oncogenic DNA viruses inactivate tumor suppressor activity of p53 by blocking this cellular response. To test whether hepatitis B virus displays a similar effect, we studied the p53-mediated cellular response to DNA damage in 2215 hepatoma cells with replicative hepatitis B virus. We demonstrate that hepatitis B virus replication does not interfere with known cellular functions of p53 protein.

  19. Rhinovirus uses a phosphatidylinositol 4-phosphate/cholesterol counter-current for the formation of replication compartments at the ER-Golgi interface

    NARCIS (Netherlands)

    Roulin, Pascal S; Lötzerich, Mark; Torta, Federico; Tanner, Lukas B; van Kuppeveld, Frank J M; Wenk, Markus R; Greber, Urs F

    2014-01-01

    Similar to other positive-strand RNA viruses, rhinovirus, the causative agent of the common cold, replicates on a web of cytoplasmic membranes, orchestrated by host proteins and lipids. The host pathways that facilitate the formation and function of the replication membranes and complexes are poorly

  20. Replicability and heterogeneity of awake unrestrained canine FMRI responses.

    Directory of Open Access Journals (Sweden)

    Gregory S Berns

    Full Text Available Previously, we demonstrated the possibility of fMRI in two awake and unrestrained dogs. Here, we determined the replicability and heterogeneity of these results in an additional 11 dogs for a total of 13 subjects. Based on an anatomically placed region-of-interest, we compared the caudate response to a hand signal indicating the imminent availability of a food reward to a hand signal indicating no reward. 8 of 13 dogs had a positive differential caudate response to the signal indicating reward. The mean differential caudate response was 0.09%, which was similar to a comparable human study. These results show that canine fMRI is reliable and can be done with minimal stress to the dogs.

  1. Replicability and heterogeneity of awake unrestrained canine FMRI responses.

    Science.gov (United States)

    Berns, Gregory S; Brooks, Andrew; Spivak, Mark

    2013-01-01

    Previously, we demonstrated the possibility of fMRI in two awake and unrestrained dogs. Here, we determined the replicability and heterogeneity of these results in an additional 11 dogs for a total of 13 subjects. Based on an anatomically placed region-of-interest, we compared the caudate response to a hand signal indicating the imminent availability of a food reward to a hand signal indicating no reward. 8 of 13 dogs had a positive differential caudate response to the signal indicating reward. The mean differential caudate response was 0.09%, which was similar to a comparable human study. These results show that canine fMRI is reliable and can be done with minimal stress to the dogs.

  2. 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.

  3. 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.

  4. Reconceptualising Inquiry in Science Education

    Science.gov (United States)

    Bevins, Stuart; Price, Gareth

    2016-01-01

    Decades of discussion and debate about how science is most effectively taught and learned have resulted in a number of similar but competing inquiry models. These aim to develop students learning of science through approaches which reflect the authenticity of science as practiced by professional scientists while being practical and manageable…

  5. Replication of plasmids in gram-negative bacteria.

    OpenAIRE

    1989-01-01

    Replication of plasmid deoxyribonucleic acid (DNA) is dependent on three stages: initiation, elongation, and termination. The first stage, initiation, depends on plasmid-encoded properties such as the replication origin and, in most cases, the replication initiation protein (Rep protein). In recent years the understanding of initiation and regulation of plasmid replication in Escherichia coli has increased considerably, but it is only for the ColE1-type plasmids that significant biochemical d...

  6. PCNA Modifications for Regulation of Post-Replication Repair Pathways

    OpenAIRE

    2008-01-01

    Stalled DNA replication forks activate specific DNA repair mechanism called post-replication repair (PRR) pathways that simply bypass DNA damage. The bypassing of DNA damage by PRR prevents prolonged stalling of DNA replication that could result in double strand breaks (DSBs). Proliferating cell nuclear antigen (PCNA) functions to initiate and choose different bypassing pathways of PRR. In yeast, DNA replication forks stalled by DNA damage induces monoubiquitination of PCNA at K164, which is ...

  7. Mathematical Framework for A Novel Database Replication Algorithm

    Directory of Open Access Journals (Sweden)

    Divakar Singh Yadav

    2013-10-01

    Full Text Available In this paper, the detailed overview of the database replication is presented. Thereafter, PDDRA (Pre-fetching based dynamic data replication algorithm algorithm as recently published is detailed. In this algorithm, further, modifications are suggested to minimize the delay in data replication. Finally a mathematical framework is presented to evaluate mean waiting time before a data can be replicated on the requested site.

  8. 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.

  9. 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

  10. Americans Still Overestimate Social Class Mobility: A Pre-Registered Self-Replication

    Directory of Open Access Journals (Sweden)

    Michael W. Kraus

    2015-11-01

    Full Text Available Kraus and Tan (2015 hypothesized that Americans tend to overestimate social class mobility in society, and do so because they seek to protect the self. This paper reports a pre-registered exact replication of Study 3 from this original paper and finds, consistent with the original study, that Americans substantially overestimate social class mobility, that people provide greater overestimates when made while thinking of similar others, and that high perceived social class is related to greater overestimates. The current results provide additional evidence consistent with the idea that people overestimate class mobility to protect their beliefs in the promise of equality of opportunity. Discussion considers the utility of pre-registered self-replications as one tool for encouraging replication efforts and assessing the robustness of effect sizes.

  11. Reduced rate of DNA replication fork movement in megaloblastic anemia.

    Science.gov (United States)

    Wickremasinghe, R G; Hoffbrand, A V

    1980-01-01

    Chromatography on benzoylated naphthoylated DEAE-cellulose has been used to fractionate fully double-stranded from partially single-stranded DNA molecules. DNA was extracted from phytohemagglutinin-stimulated lymphocytes from patients with megaloblastic anemia resulting from vitamin B12 or folate deficiency after pulse-labeling the cells with [3H]thymidine for 5 min and chasing in unlabeled medium for 24 h. No gross accumulation of partially single-stranded material was observed in the DNA of these cells when compared with DNA from similarly labeled control cells obtained by the addition of 5-formyl tetrahydrofolic acid to the culture medium. When DNA from lymphocytes labeled with a 5-min pulse of [3H]thymidine and sheared to fragments of an average length of 18 micrometer was chromatographed on benzoylated naphthoylated DEAE-cellulose, approximately 80% of the label was recovered in the partially single-stranded fraction. After chasing in unlabeled medium the label was progressively transferred to the double-stranded fraction over a period of 2--3 h. The rate of transfer was slower in megaloblastic lymphocytes than in controls. The difference in rate suggested a slower rate of replication fork movement in megaloblastic lymphocytes and so the density shift technique of Painter and schaeffer (J. Mol. Biol. 45: 467--479, 1969) was used to measure the fork rate directly. [3H]Deoxycytidine was used as the labeled nucleoside to avoid possible complications arising from [3H]thymidine labeling of megaloblastic cells. Investigations on the lymphocytes from four patients showed that the replication fork rate in vitamin-treated control lyphocytes was about 1 micrometer/min. The fork rates in the corresponding untreated cells were invariably lower and rates ranging from 40 to 92% of those of controls were observed. Normal lymphocytes treated with the deoxynucleotide pool-depleting drugs methotrexate or hydroxyurea displayed defects in DNA synthesis similar to those of

  12. Influence of Plasmid Type on the Replication of Rhodococcus equi in Host Macrophages.

    Science.gov (United States)

    Willingham-Lane, Jennifer M; Berghaus, Londa J; Giguère, Steeve; Hondalus, Mary K

    2016-01-01

    The soil-dwelling, saprophytic actinomycete Rhodococcus equi is a multihost, facultative intracellular pathogen of macrophages. When inhaled by susceptible foals, it causes severe bronchopneumonia. It is also a pathogen of pigs, which may develop submaxillary lymphadenitis upon exposure. R. equi isolates obtained from foals and pigs possess conjugative plasmids housing a pathogenicity island (PAI) containing a novel family of genes of unknown function called the virulence-associated protein or vap family. The PAI regions of the equine and swine plasmids differ in vap gene composition, with equine isolates possessing six vap genes, including the major virulence determinant vapA, while the PAIs of swine isolates house vapB and five other unique vap genes. Possession of the pVAPA-type virulence plasmid by equine isolates bestows the capacity for intramacrophage replication essential for disease development in vivo. Swine isolates of R. equi are largely unstudied. Here, we show that R. equi isolates from pigs, carrying pVAPB-type plasmids, are able to replicate in a plasmid-dependent manner in macrophages obtained from a variety of species (murine, swine, and equine) and anatomical locations. Similarly, equine isolates carrying pVAPA-type plasmids are capable of replication in swine macrophages. Plasmid swapping between equine and swine strains through conjugation did not alter the intracellular replication capacity of the parental strain, indicating that coevolution of the plasmid and chromosome is not crucial for this attribute. These results demonstrate that while distinct plasmid types exist among R. equi isolates obtained from equine and swine sources, this tropism is not determined by host species-specific intramacrophage replication capabilities. IMPORTANCE This work greatly advances our understanding of the opportunistic pathogen Rhodococcus equi, a disease agent of animals and immunocompromised people. Clinical isolates from diseased foals carry a

  13. Budding Yeast Rif1 Controls Genome Integrity by Inhibiting rDNA Replication.

    Science.gov (United States)

    Shyian, Maksym; Mattarocci, Stefano; Albert, Benjamin; Hafner, Lukas; Lezaja, Aleksandra; Costanzo, Michael; Boone, Charlie; Shore, David

    2016-11-01

    The Rif1 protein is a negative regulator of DNA replication initiation in eukaryotes. Here we show that budding yeast Rif1 inhibits DNA replication initiation at the rDNA locus. Absence of Rif1, or disruption of its interaction with PP1/Glc7 phosphatase, leads to more intensive rDNA replication. The effect of Rif1-Glc7 on rDNA replication is similar to that of the Sir2 deacetylase, and the two would appear to act in the same pathway, since the rif1Δ sir2Δ double mutant shows no further increase in rDNA replication. Loss of Rif1-Glc7 activity is also accompanied by an increase in rDNA repeat instability that again is not additive with the effect of sir2Δ. We find, in addition, that the viability of rif1Δ cells is severely compromised in combination with disruption of the MRX or Ctf4-Mms22 complexes, both of which are implicated in stabilization of stalled replication forks. Significantly, we show that removal of the rDNA replication fork barrier (RFB) protein Fob1, alleviation of replisome pausing by deletion of the Tof1/Csm3 complex, or a large deletion of the rDNA repeat array all rescue this synthetic growth defect of rif1Δ cells lacking in addition either MRX or Ctf4-Mms22 activity. These data suggest that the repression of origin activation by Rif1-Glc7 is important to avoid the deleterious accumulation of stalled replication forks at the rDNA RFB, which become lethal when fork stability is compromised. Finally, we show that Rif1-Glc7, unlike Sir2, has an important effect on origin firing outside of the rDNA locus that serves to prevent activation of the DNA replication checkpoint. Our results thus provide insights into a mechanism of replication control within a large repetitive chromosomal domain and its importance for the maintenance of genome stability. These findings may have important implications for metazoans, where large blocks of repetitive sequences are much more common.

  14. Budding Yeast Rif1 Controls Genome Integrity by Inhibiting rDNA Replication.

    Directory of Open Access Journals (Sweden)

    Maksym Shyian

    2016-11-01

    Full Text Available The Rif1 protein is a negative regulator of DNA replication initiation in eukaryotes. Here we show that budding yeast Rif1 inhibits DNA replication initiation at the rDNA locus. Absence of Rif1, or disruption of its interaction with PP1/Glc7 phosphatase, leads to more intensive rDNA replication. The effect of Rif1-Glc7 on rDNA replication is similar to that of the Sir2 deacetylase, and the two would appear to act in the same pathway, since the rif1Δ sir2Δ double mutant shows no further increase in rDNA replication. Loss of Rif1-Glc7 activity is also accompanied by an increase in rDNA repeat instability that again is not additive with the effect of sir2Δ. We find, in addition, that the viability of rif1Δ cells is severely compromised in combination with disruption of the MRX or Ctf4-Mms22 complexes, both of which are implicated in stabilization of stalled replication forks. Significantly, we show that removal of the rDNA replication fork barrier (RFB protein Fob1, alleviation of replisome pausing by deletion of the Tof1/Csm3 complex, or a large deletion of the rDNA repeat array all rescue this synthetic growth defect of rif1Δ cells lacking in addition either MRX or Ctf4-Mms22 activity. These data suggest that the repression of origin activation by Rif1-Glc7 is important to avoid the deleterious accumulation of stalled replication forks at the rDNA RFB, which become lethal when fork stability is compromised. Finally, we show that Rif1-Glc7, unlike Sir2, has an important effect on origin firing outside of the rDNA locus that serves to prevent activation of the DNA replication checkpoint. Our results thus provide insights into a mechanism of replication control within a large repetitive chromosomal domain and its importance for the maintenance of genome stability. These findings may have important implications for metazoans, where large blocks of repetitive sequences are much more common.

  15. Chromatin Dynamics During DNA Replication and Uncharacterized Replication Factors determined by Nascent Chromatin Capture (NCC) Proteomics

    Science.gov (United States)

    Alabert, Constance; Bukowski-Wills, Jimi-Carlo; Lee, Sung-Bau; Kustatscher, Georg; Nakamura, Kyosuke; de Lima Alves, Flavia; Menard, Patrice; Mejlvang, Jakob; Rappsilber, Juri; Groth, Anja

    2014-01-01

    SUMMARY To maintain genome function and stability, DNA sequence and its organization into chromatin must be duplicated during cell division. Understanding how entire chromosomes are copied remains a major challenge. Here, we use Nascent Chromatin Capture (NCC) to profile chromatin proteome dynamics during replication in human cells. NCC relies on biotin-dUTP labelling of replicating DNA, affinity-purification and quantitative proteomics. Comparing nascent chromatin with mature post-replicative chromatin, we provide association dynamics for 3995 proteins. The replication machinery and 485 chromatin factors like CAF-1, DNMT1, SUV39h1 are enriched in nascent chromatin, whereas 170 factors including histone H1, DNMT3, MBD1-3 and PRC1 show delayed association. This correlates with H4K5K12diAc removal and H3K9me1 accumulation, while H3K27me3 and H3K9me3 remain unchanged. Finally, we combine NCC enrichment with experimentally derived chromatin probabilities to predict a function in nascent chromatin for 93 uncharacterized proteins and identify FAM111A as a replication factor required for PCNA loading. Together, this provides an extensive resource to understand genome and epigenome maintenance. PMID:24561620

  16. Isolation and characterization of highly replicable hepatitis C virus genotype 1a strain HCV-RMT.

    Science.gov (United States)

    Arai, Masaaki; Tokunaga, Yuko; Takagi, Asako; Tobita, Yoshimi; Hirata, Yuichi; Ishida, Yuji; Tateno, Chise; Kohara, Michinori

    2013-01-01

    Multiple genotype 1a clones have been reported, including the very first hepatitis C virus (HCV) clone called H77. The replication ability of some of these clones has been confirmed in vitro and in vivo, although this ability is somehow compromised. We now report a newly isolated genotype 1a clone, designated HCV-RMT, which has the ability to replicate efficiently in patients, chimeric mice with humanized liver, and cultured cells. An authentic subgenomic replicon cell line was established from the HCV-RMT sequence with spontaneous introduction of three adaptive mutations, which were later confirmed to be responsible for efficient replication in HuH-7 cells as both subgenomic replicon RNA and viral genome RNA. Following transfection, the HCV-RMT RNA genome with three adaptive mutations was maintained for more than 2 months in HuH-7 cells. One clone selected from the transfected cells had a high copy number, and its supernatant could infect naïve HuH-7 cells. Direct injection of wild-type HCV-RMT RNA into the liver of chimeric mice with humanized liver resulted in vigorous replication, similar to inoculation with the parental patient's serum. A study of virus replication using HCV-RMT derivatives with various combinations of adaptive mutations revealed a clear inversely proportional relationship between in vitro and in vivo replication abilities. Thus, we suggest that HCV-RMT and its derivatives are important tools for HCV genotype 1a research and for determining the mechanism of HCV replication in vitro and in vivo.

  17. Isolation and characterization of highly replicable hepatitis C virus genotype 1a strain HCV-RMT.

    Directory of Open Access Journals (Sweden)

    Masaaki Arai

    Full Text Available Multiple genotype 1a clones have been reported, including the very first hepatitis C virus (HCV clone called H77. The replication ability of some of these clones has been confirmed in vitro and in vivo, although this ability is somehow compromised. We now report a newly isolated genotype 1a clone, designated HCV-RMT, which has the ability to replicate efficiently in patients, chimeric mice with humanized liver, and cultured cells. An authentic subgenomic replicon cell line was established from the HCV-RMT sequence with spontaneous introduction of three adaptive mutations, which were later confirmed to be responsible for efficient replication in HuH-7 cells as both subgenomic replicon RNA and viral genome RNA. Following transfection, the HCV-RMT RNA genome with three adaptive mutations was maintained for more than 2 months in HuH-7 cells. One clone selected from the transfected cells had a high copy number, and its supernatant could infect naïve HuH-7 cells. Direct injection of wild-type HCV-RMT RNA into the liver of chimeric mice with humanized liver resulted in vigorous replication, similar to inoculation with the parental patient's serum. A study of virus replication using HCV-RMT derivatives with various combinations of adaptive mutations revealed a clear inversely proportional relationship between in vitro and in vivo replication abilities. Thus, we suggest that HCV-RMT and its derivatives are important tools for HCV genotype 1a research and for determining the mechanism of HCV replication in vitro and in vivo.

  18. Tracking replicability as a method of post-publication open evaluation.

    Science.gov (United States)

    Hartshorne, Joshua K; Schachner, Adena

    2012-01-01

    Recent reports have suggested that many published results are unreliable. To increase the reliability and accuracy of published papers, multiple changes have been proposed, such as changes in statistical methods. We support such reforms. However, we believe that the incentive structure of scientific publishing must change for such reforms to be successful. Under the current system, the quality of individual scientists is judged on the basis of their number of publications and citations, with journals similarly judged via numbers of citations. Neither of these measures takes into account the replicability of the published findings, as false or controversial results are often particularly widely cited. We propose tracking replications as a means of post-publication evaluation, both to help researchers identify reliable findings and to incentivize the publication of reliable results. Tracking replications requires a database linking published studies that replicate one another. As any such database is limited by the number of replication attempts published, we propose establishing an open-access journal dedicated to publishing replication attempts. Data quality of both the database and the affiliated journal would be ensured through a combination of crowd-sourcing and peer review. As reports in the database are aggregated, ultimately it will be possible to calculate replicability scores, which may be used alongside citation counts to evaluate the quality of work published in individual journals. In this paper, we lay out a detailed description of how this system could be implemented, including mechanisms for compiling the information, ensuring data quality, and incentivizing the research community to participate.

  19. Epigallocatechin gallate inhibits HBV DNA synthesis in a viral replication - inducible cell line

    Institute of Scientific and Technical Information of China (English)

    Wei He; Li-Xia Li; Qing-Jiao Liao; Chun-Lan Liu; Xu-Lin Chen

    2011-01-01

    AIM: To analyze the antiviral mechanism of Epigallocatechin gallate (EGCG) against hepatitis B virus (HBV) replication. METHODS: In this research, the HBV-replicating cell line HepG2.117 was used to investigate the antiviral mechanism of EGCG. Cytotoxicity of EGCG was analyzed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Hepatitis B virus e antigen (HBeAg) and hepatitis B virus surface antigen (HBsAg) in the supernatant were detected by enzyme-linked immunosorbent assay. Precore mRNA and pregenomic RNA (pgRNA) levels were determined by semi-quantitative reverse transcription polymerase chain reaction (PCR) assay. The effect of EGCG on HBV core promoter activity was measured by dual luciferase reporter assay. HBV covalently closed circular DNA and replicative intermediates of DNA were quantified by real-time PCR assay. RESULTS: When HepG2.117 cells were grown in the presence of EGCG, the expression of HBeAg was suppressed, however, the expression of HBsAg was not affected. HBV precore mRNA level was also downregulated by EGCG, while the transcription of precore mRNA was not impaired. The synthesis of both HBV covalently closed circular DNA and replicative intermediates of DNA were reduced by EGCG treatment to a similar extent, however, HBV pgRNA transcripted from chromosome-integrated HBV genome was not affected by EGCG treatment, indicating that EGCG targets only replicative intermediates of DNA synthesis. CONCLUSION: In HepG2.117 cells, EGCG inhibits HBV replication by impairing HBV replicative intermediates of DNA synthesis and such inhibition results in reduced production of HBV covalently closed circular DNA.

  20. Tracking replicability as a method of post-publication open evaluation

    Directory of Open Access Journals (Sweden)

    Joshua eHartshorne

    2012-03-01

    Full Text Available Recent reports have suggested that many published results are unreliable. To increase the reliability and accuracy of published papers, multiple changes have been proposed, such as changes in statistical methods. We support such reforms. However, we believe that the incentive structure of scientific publishing must change for such reforms to be successful. Under the current system, the quality of individual scientists is judged on the basis of their number of publications and citations, with journals similarly judged via numbers of citations. Neither of these measures takes into account the replicability of the published findings, as false or controversial results are often particularly widely cited. We propose tracking replications as a means of post-publication evaluation, both to help researchers identify reliable findings and to incentivize the publication of reliable results.Tracking replications requires a database linking published studies that replicate one another. As any such database is limited by the number of replication attempts published, we propose establishing an open-access journal dedicated to publishing replication attempts. Data quality of both the database and the affiliated journal would be ensured through a combination of crowd-sourcing and peer review. As reports in the database are aggregated, ultimately it will be possible to calculate replicability scores, which may be used alongside citation counts to evaluate the quality of work published in individual journals. In this paper, we lay out a detailed description of how this system could be implemented, including mechanisms for compiling the information, ensuring data quality, and incentivizing the research community to participate.

  1. Building up and breaking down: mechanisms controlling recombination during replication.

    Science.gov (United States)

    Branzei, Dana; Szakal, Barnabas

    2017-08-01

    The complete and faithful duplication of the genome is an essential prerequisite for proliferating cells to maintain genome integrity. This objective is greatly challenged by DNA damage encountered during replication, which causes fork stalling and in certain cases, fork breakage. DNA damage tolerance (DDT) pathways mitigate the effects on fork stability induced by replication fork stalling by mediating damage-bypass and replication fork restart. These DDT mechanisms, largely relying on homologous recombination (HR) and specialized polymerases, can however contribute to genome rearrangements and mutagenesis. There is a profound connection between replication and recombination: recombination proteins protect replication forks from nuclease-mediated degradation of the nascent DNA strands and facilitate replication completion in cells challenged by DNA damage. Moreover, in case of fork collapse and formation of double strand breaks (DSBs), the recombination factors present or recruited to the fork facilitate HR-mediated DSB repair, which is primarily error-free. Disruption of HR is inexorably linked to genome instability, but the premature activation of HR during replication often leads to genome rearrangements. Faithful replication necessitates the downregulation of HR and disruption of active RAD51 filaments at replication forks, but upon persistent fork stalling, building up of HR is critical for the reorganization of the replication fork and for filling-in of the gaps associated with discontinuous replication induced by DNA lesions. Here we summarize and reflect on our understanding of the mechanisms that either suppress recombination or locally enhance it during replication, and the principles that underlie this regulation.

  2. Uncoupling of Sister Replisomes during Eukaryotic DNA Replication

    NARCIS (Netherlands)

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

    2010-01-01

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

  3. Visualizing Single-molecule DNA Replication with Fluorescence Microscopy

    NARCIS (Netherlands)

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

    2009-01-01

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

  4. Uncoupling of Sister Replisomes during Eukaryotic DNA Replication

    NARCIS (Netherlands)

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

    2010-01-01

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

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

    DEFF Research Database (Denmark)

    Melixetian, Marina; Helin, Kristian

    2004-01-01

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

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  7. Visualizing Single-molecule DNA Replication with Fluorescence Microscopy

    NARCIS (Netherlands)

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

    2009-01-01

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

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

    DEFF Research Database (Denmark)

    Melixetian, Marina; Helin, Kristian

    2004-01-01

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

  9. Replication NAND gate with light as input and output.

    Science.gov (United States)

    Samiappan, Manickasundaram; Dadon, Zehavit; Ashkenasy, Gonen

    2011-01-14

    Logic operations can highlight information transfer within complex molecular networks. We describe here the design of a peptide-based replication system that can be detected by following its fluorescence quenching. This process is used to negate the signal of light-activated replication, and thus to prepare the first replication NAND gate.

  10. ASAR15, A cis-acting locus that controls chromosome-wide replication timing and stability of human chromosome 15.

    Directory of Open Access Journals (Sweden)

    Nathan Donley

    2015-01-01

    Full Text Available DNA replication initiates at multiple sites along each mammalian chromosome at different times during each S phase, following a temporal replication program. We have used a Cre/loxP-based strategy to identify cis-acting elements that control this replication-timing program on individual human chromosomes. In this report, we show that rearrangements at a complex locus at chromosome 15q24.3 result in delayed replication and structural instability of human chromosome 15. Characterization of this locus identified long, RNA transcripts that are retained in the nucleus and form a "cloud" on one homolog of chromosome 15. We also found that this locus displays asynchronous replication that is coordinated with other random monoallelic genes on chromosome 15. We have named this locus ASynchronous replication and Autosomal RNA on chromosome 15, or ASAR15. Previously, we found that disruption of the ASAR6 lincRNA gene results in delayed replication, delayed mitotic condensation and structural instability of human chromosome 6. Previous studies in the mouse found that deletion of the Xist gene, from the X chromosome in adult somatic cells, results in a delayed replication and instability phenotype that is indistinguishable from the phenotype caused by disruption of either ASAR6 or ASAR15. In addition, delayed replication and chromosome instability were detected following structural rearrangement of many different human or mouse chromosomes. These observations suggest that all mammalian chromosomes contain similar cis-acting loci. Thus, under this scenario, all mammalian chromosomes contain four distinct types of essential cis-acting elements: origins, telomeres, centromeres and "inactivation/stability centers", all functioning to promote proper replication, segregation and structural stability of each chromosome.

  11. Control of Initiation of DNA Replication in Bacillus subtilis and Escherichia coli

    Directory of Open Access Journals (Sweden)

    Katie H. Jameson

    2017-01-01

    Full Text Available Initiation of DNA Replication is tightly regulated in all cells since imbalances in chromosomal copy number are deleterious and often lethal. In bacteria such as Bacillus subtilis and Escherichia coli, at the point of cytokinesis, there must be two complete copies of the chromosome to partition into the daughter cells following division at mid-cell during vegetative growth. Under conditions of rapid growth, when the time taken to replicate the chromosome exceeds the doubling time of the cells, there will be multiple initiations per cell cycle and daughter cells will inherit chromosomes that are already undergoing replication. In contrast, cells entering the sporulation pathway in B. subtilis can do so only during a short interval in the cell cycle when there are two, and only two, chromosomes per cell, one destined for the spore and one for the mother cell. Here, we briefly describe the overall process of DNA replication in bacteria before reviewing initiation of DNA replication in detail. The review covers DnaA-directed assembly of the replisome at oriC and the multitude of mechanisms of regulation of initiation, with a focus on the similarities and differences between E. coli and B. subtilis.

  12. ETAA1 acts at stalled replication forks to maintain genome integrity.

    Science.gov (United States)

    Bass, Thomas E; Luzwick, Jessica W; Kavanaugh, Gina; Carroll, Clinton; Dungrawala, Huzefa; Glick, Gloria G; Feldkamp, Michael D; Putney, Reid; Chazin, Walter J; Cortez, David

    2016-11-01

    The ATR checkpoint kinase coordinates cellular responses to DNA replication stress. Budding yeast contain three activators of Mec1 (the ATR orthologue); however, only TOPBP1 is known to activate ATR in vertebrates. We identified ETAA1 as a replication stress response protein in two proteomic screens. ETAA1-deficient cells accumulate double-strand breaks, sister chromatid exchanges, and other hallmarks of genome instability. They are also hypersensitive to replication stress and have increased frequencies of replication fork collapse. ETAA1 contains two RPA-interaction motifs that localize ETAA1 to stalled replication forks. It also interacts with several DNA damage response proteins including the BLM/TOP3α/RMI1/RMI2 and ATR/ATRIP complexes. It binds ATR/ATRIP directly using a motif with sequence similarity to the TOPBP1 ATR-activation domain; and like TOPBP1, ETAA1 acts as a direct ATR activator. ETAA1 functions in parallel to the TOPBP1/RAD9/HUS1/RAD1 pathway to regulate ATR and maintain genome stability. Thus, vertebrate cells contain at least two ATR-activating proteins.

  13. Control of Initiation of DNA Replication in Bacillus subtilis and Escherichia coli.

    Science.gov (United States)

    Jameson, Katie H; Wilkinson, Anthony J

    2017-01-10

    Initiation of DNA Replication is tightly regulated in all cells since imbalances in chromosomal copy number are deleterious and often lethal. In bacteria such as Bacillus subtilis and Escherichia coli, at the point of cytokinesis, there must be two complete copies of the chromosome to partition into the daughter cells following division at mid-cell during vegetative growth. Under conditions of rapid growth, when the time taken to replicate the chromosome exceeds the doubling time of the cells, there will be multiple initiations per cell cycle and daughter cells will inherit chromosomes that are already undergoing replication. In contrast, cells entering the sporulation pathway in B. subtilis can do so only during a short interval in the cell cycle when there are two, and only two, chromosomes per cell, one destined for the spore and one for the mother cell. Here, we briefly describe the overall process of DNA replication in bacteria before reviewing initiation of DNA replication in detail. The review covers DnaA-directed assembly of the replisome at oriC and the multitude of mechanisms of regulation of initiation, with a focus on the similarities and differences between E. coli and B. subtilis.

  14. Identification and functional characterization of Bet protein as a negative regulator of BFV3026 replication.

    Science.gov (United States)

    Bing, Tiejun; Wu, Kai; Cui, Xiaoxu; Shao, Peng; Zhang, Qicheng; Bai, Xiaobo; Tan, Juan; Qiao, Wentao

    2014-06-01

    Foamy virus (FV) establishes persistent infection in the host without causing apparent disease. Besides the transactivator Tas protein, another auxiliary protein--Bet--has been reported in prototype foamy virus, equine foamy virus, and feline foamy virus. Here, we found the putative bbet gene in clone C74 from a cDNA library of bovine foamy virus strain 3026 (BFV3026) by comparison of gene localization, composition, and splicing features with other known bet genes. Subsequently, BBet protein was detected in BFV3026-infected cells by Western blot and immunofluorescence analyses. Analysis of the BBet mutant infectious clone (pBS-BFVdelBBet) revealed that BBet could inhibit BFV3026 replication. Consistent with this result, overexpression of BBet in Cf2Th cells reduced BFV replication by approximately threefold. Furthermore, virus replication levels similarly were reduced by approximately threefold in pBS-BFV-transfected and BFV3026-infected Cf2Th cells stably expressing BBet compared with control cells. After three passages, BFV3026 replicated more slowly in BBet-expressing cells. This study implicates BBet as a negative regulator of BFV replication and provides a resource for future studies on the function of this protein in the virus lifecycle.

  15. Assembling semiconductor nanocomposites using DNA replication technologies.

    Energy Technology Data Exchange (ETDEWEB)

    Heimer, Brandon W.; Crown, Kevin K.; Bachand, George David

    2005-11-01

    Deoxyribonucleic acid (DNA) molecules represent Nature's genetic database, encoding the information necessary for all cellular processes. From a materials engineering perspective, DNA represents a nanoscale scaffold with highly refined structure, stability across a wide range of environmental conditions, and the ability to interact with a range of biomolecules. The ability to mass-manufacture functionalized DNA strands with Angstrom-level resolution through DNA replication technology, however, has not been explored. The long-term goal of the work presented in this report is focused on exploiting DNA and in vitro DNA replication processes to mass-manufacture nanocomposite materials. The specific objectives of this project were to: (1) develop methods for replicating DNA strands that incorporate nucleotides with ''chemical handles'', and (2) demonstrate attachment of nanocrystal quantum dots (nQDs) to functionalized DNA strands. Polymerase chain reaction (PCR) and primer extension methodologies were used to successfully synthesize amine-, thiol-, and biotin-functionalized DNA molecules. Significant variability in the efficiency of modified nucleotide incorporation was observed, and attributed to the intrinsic properties of the modified nucleotides. Noncovalent attachment of streptavidin-coated nQDs to biotin-modified DNA synthesized using the primer extension method was observed by epifluorescence microscopy. Data regarding covalent attachment of nQDs to amine- and thiol-functionalized DNA was generally inconclusive; alternative characterization tools are necessary to fully evaluate these attachment methods. Full realization of this technology may facilitate new approaches to manufacturing materials at the nanoscale. In addition, composite nQD-DNA materials may serve as novel recognition elements in sensor devices, or be used as diagnostic tools for forensic analyses. This report summarizes the results obtained over the course of this 1-year

  16. Effecting change in elementary school science education

    Energy Technology Data Exchange (ETDEWEB)

    Parravano, C.

    1994-12-31

    The mission of the Merck Institute for Science Education is to improve the quality of science education during the formative years of kindergarten through eighth grade. To accomplish this mission, the Institute has three primary goals: Transform the teaching of science to communicate the excitement and relevance of science; Reform the education of teachers to instill in tomorrow`s teachers an understanding and appreciation of science; and Create a consensus on the importance of elementary science education among leaders in education, business, and science. Merck has made a minimum ten year commitment of funding and resources to the Institute. The Institute will work very closely with faculty, administration, and community leaders in target school districts to enhance science education in the elementary grades of their schools. Once the Institute`s goals have been achieved in these initial partner districts, the Institute will replicate its programs in other districts.

  17. Semantic Referencing - Determining Context Weights for Similarity Measurement

    Science.gov (United States)

    Janowicz, Krzysztof; Adams, Benjamin; Raubal, Martin

    Semantic similarity measurement is a key methodology in various domains ranging from cognitive science to geographic information retrieval on the Web. Meaningful notions of similarity, however, cannot be determined without taking additional contextual information into account. One way to make similarity measures context-aware is by introducing weights for specific characteristics. Existing approaches to automatically determine such weights are rather limited or require application specific adjustments. In the past, the possibility to tweak similarity theories until they fit a specific use case has been one of the major criticisms for their evaluation. In this work, we propose a novel approach to semi-automatically adapt similarity theories to the user's needs and hence make them context-aware. Our methodology is inspired by the process of georeferencing images in which known control points between the image and geographic space are used to compute a suitable transformation. We propose to semi-automatically calibrate weights to compute inter-instance and inter-concept similarities by allowing the user to adjust pre-computed similarity rankings. These known control similarities are then used to reference other similarity values.

  18. The IFITMs Inhibit Zika Virus Replication

    Directory of Open Access Journals (Sweden)

    George Savidis

    2016-06-01

    Full Text Available Zika virus has emerged as a severe health threat with a rapidly expanding range. The IFITM family of restriction factors inhibits the replication of a broad range of viruses, including the closely related flaviruses West Nile virus and dengue virus. Here, we show that IFITM1 and IFITM3 inhibit Zika virus infection early in the viral life cycle. Moreover, IFITM3 can prevent Zika-virus-induced cell death. These results suggest that strategies to boost the actions and/or levels of the IFITMs might be useful for inhibiting a broad range of emerging viruses.

  19. Multiscale modeling of virus replication and spread.

    Science.gov (United States)

    Kumberger, Peter; Frey, Felix; Schwarz, Ulrich S; Graw, Frederik

    2016-07-01

    Replication and spread of human viruses is based on the simultaneous exploitation of many different host functions, bridging multiple scales in space and time. Mathematical modeling is essential to obtain a systems-level understanding of how human viruses manage to proceed through their life cycles. Here, we review corresponding advances for viral systems of large medical relevance, such as human immunodeficiency virus-1 (HIV-1) and hepatitis C virus (HCV). We will outline how the combination of mathematical models and experimental data has advanced our quantitative knowledge about various processes of these pathogens, and how novel quantitative approaches promise to fill remaining gaps.

  20. Accounting for PDMS shrinkage when replicating structures

    DEFF Research Database (Denmark)

    Madsen, Morten Hannibal; Feidenhans'l, Nikolaj Agentoft; Hansen, Poul-Erik

    2014-01-01

    are seldom applied to counteract the shrinkage of PDMS. Also, to perform metrological measurements using replica techniques one has to take the shrinkage into account. Thus we report a study of the shrinkage of PDMS with several different mixing ratios and curing temperatures. The shrinkage factor, with its...... associated uncertainty, for PDMS in the range 40 to 120 °C is provided. By applying this correction factor, it is possible to replicate structures with a standard uncertainty of less than 0.2% in lateral dimensions using typical curing temperatures and PDMS mixing ratios in the range 1:6 to 1:20 (agent:base)....

  1. Replication of DNA during barley endosperm development

    DEFF Research Database (Denmark)

    Giese, H.

    1992-01-01

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

  2. Simulation Studies in Data Replication Strategies

    Institute of Scientific and Technical Information of China (English)

    HarveyB.Newman; IosifC.Legrand

    2001-01-01

    The aim of this work is to present the simulation studies in evaluating different data replication strategies between Regional Centers.The simulation Framework developed within the "Models of Networked Analysis at Rgional Centers”(MONARC) project,as a design and optimization tool for large scale distributed systems,has been used for these modeling studies.Remote client-serer access to database servers as well as ftp-like data transfers have been ralistically simulated and the performance and limitations are presented as a function of the characteristics of the protocol used and the network parameters.

  3. Method of producing an item with enhanced wetting properties by fast replication and replication tool used in the method

    DEFF Research Database (Denmark)

    2016-01-01

    The invention relates to a replication tool (1) for producing an item (4) with enhanced wetting properties by fast replication, such as injection moulding or extrusion coating. The replication tool (1) comprises a tool surface (2a, 2b) defining a general shape of the item (4). The tool surface (2a...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-11-01

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

  5. DNA replication origin activation in space and time.

    Science.gov (United States)

    Fragkos, Michalis; Ganier, Olivier; Coulombe, Philippe; Méchali, Marcel

    2015-06-01

    DNA replication begins with the assembly of pre-replication complexes (pre-RCs) at thousands of DNA replication origins during the G1 phase of the cell cycle. At the G1-S-phase transition, pre-RCs are converted into pre-initiation complexes, in which the replicative helicase is activated, leading to DNA unwinding and initiation of DNA synthesis. However, only a subset of origins are activated during any S phase. Recent insights into the mechanisms underlying this choice reveal how flexibility in origin usage and temporal activation are linked to chromosome structure and organization, cell growth and differentiation, and replication stress.

  6. Science as Performance: A Proactive Strategy to Communicate and Educate Through Theater, Music and Dance

    Science.gov (United States)

    Schwartz, Brian

    2006-03-01

    Theater, music, dance, the literary and the visual arts can convey the joys and controversies of science. We describe a program at the Graduate Center entitled Science as Performance which is designed to communicate to the public the excitement and wonder of science, technology, engineering and mathematics. Over the past few years there have been major successes in communicating science to the public through the arts. This is especially evident in theater and film with such recent plays as Copenhagen and the Oscar winning film A Beautiful Mind. The performance series Science and the Arts has been developed and tested at the Graduate Center of the City University of New York (CUNY) in mid-Manhattan for more than four years, see http://web.gc.cuny.edu/sciart/ . We have developed working relationships with actors, playwrights, dancers, choreographers, musicians, composers, artists and scientists who work at the intersection of science and the arts. In this presentation we will illustrate many of our collaborations in theater, dance, music and art. The response to the series has shown that the arts can make the sciences accessible, relevant, and exciting to diverse audiences in ways that provide both scientific content and significant artistic and entertainment values. The National Science Foundation has awarded a grant to the Graduate Center to help replicate similar Science and the Arts programs on other campuses by involving both their science departments and their performing arts departments. Some results of campus visits will be described. The author will also describe his involvement with producing two musical versions of a play, Einstein’s Dreams based on the novel by Alan Lightman. One production opened at the Teatro da Trindade in Lisbon, Portugal at on October 21, 2005 for a four month run and a second and different production opens at the Prince Music Theater in Philadelphia in March 2006.

  7. Inequalities between similarities for numerical data

    NARCIS (Netherlands)

    Warrens, Matthijs J.

    2016-01-01

    Similarity measures are entities that can be used to quantify the similarity between two vectors with real numbers. We present inequalities between seven well known similarities. The inequalities are valid if the vectors contain non-negative real numbers.

  8. Optimal Allocation of Replicates for Measurement Evaluation Studies

    Institute of Scientific and Technical Information of China (English)

    Stanislav O.Zakharkin; Kyoungmi Kim; Alfred A.Bartolucci; Grier P.Page; David B.Allison

    2006-01-01

    Optimal experimental design is important for the efficient use of modern highthroughput technologies such as microarrays and proteomics. Multiple factors including the reliability of measurement system, which itself must be estimated from prior experimental work, could influence design decisions. In this study, we describe how the optimal number of replicate measures (technical replicates) for each biological sample (biological replicate) can be determined. Different allocations of biological and technical replicates were evaluated by minimizing the variance of the ratio of technical variance (measurement error) to the total variance (sum of sampling error and measurement error). We demonstrate that if the number of biological replicates and the number of technical replicates per biological sample are variable, while the total number of available measures is fixed, then the optimal allocation of replicates for measurement evaluation experiments requires two technical replicates for each biological replicate. Therefore, it is recommended to use two technical replicates for each biological replicate if the goal is to evaluate the reproducibility of measurements.

  9. Failed Replication of Oxytocin Effects on Trust: The Envelope Task Case.

    Directory of Open Access Journals (Sweden)

    Anthony Lane

    Full Text Available The neurohormone Oxytocin (OT has been one of the most studied peptides in behavioral sciences over the past two decades. Many studies have suggested that OT could increase trusting behaviors. A previous study, based on the "Envelope Task" paradigm, where trust is assessed by the degree of openness of an envelope containing participant's confidential information, showed that OT increases trusting behavior and reported one of the most powerful effects of OT on a behavioral variable. In this paper we present two failed replications of this effect, despite sufficient power to replicate the original large effect. The non-significant results of these two failed replications clearly exclude a large effect of OT on trust in this paradigm but are compatible with either a null effect of OT on trust, or a small effect, undetectable with small sample size (N = 95 and 61 in Study 1 and 2, respectively. Taken together, our results question the purported size of OT's effect on trust and emphasize the need for replications.

  10. 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...

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

    Directory of Open Access Journals (Sweden)

    Brian D. Earp

    2015-05-01

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

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

    Science.gov (United States)

    Earp, Brian D; Trafimow, David

    2015-01-01

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

  13. The Alleged Crisis and the Illusion of Exact Replication.

    Science.gov (United States)

    Stroebe, Wolfgang; Strack, Fritz

    2014-01-01

    There has been increasing criticism of the way psychologists conduct and analyze studies. These critiques as well as failures to replicate several high-profile studies have been used as justification to proclaim a "replication crisis" in psychology. Psychologists are encouraged to conduct more "exact" replications of published studies to assess the reproducibility of psychological research. This article argues that the alleged "crisis of replicability" is primarily due to an epistemological misunderstanding that emphasizes the phenomenon instead of its underlying mechanisms. As a consequence, a replicated phenomenon may not serve as a rigorous test of a theoretical hypothesis because identical operationalizations of variables in studies conducted at different times and with different subject populations might test different theoretical constructs. Therefore, we propose that for meaningful replications, attempts at reinstating the original circumstances are not sufficient. Instead, replicators must ascertain that conditions are realized that reflect the theoretical variable(s) manipulated (and/or measured) in the original study.

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

    Science.gov (United States)

    Earp, Brian D.; Trafimow, David

    2015-01-01

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

  15. Prevention of DNA re-replication in eukaryotic cells

    Institute of Scientific and Technical Information of China (English)

    Lan N. Truong; Xiaohua Wu

    2011-01-01

    DNA replication is a highly regulated process involving a number of licensing and replication factors that function in a carefully orchestrated manner to faithfully replicate DNA during every cell cycle. Loss of proper licensing control leads to deregulated DNA replication including DNA re-replication, which can cause genome instability and tumorigenesis. Eukaryotic organisms have established several conserved mechanisms to prevent DNA re-replication and to counteract its potentially harmful effects. These mechanisms include tightly controlled regulation of licensing factors and activation of cell cycle and DNA damage checkpoints.Deregulated licensing control and its associated compromised checkpoints have both been observed in tumor cells, indicating that proper functioning of these pathways is essential for maintaining genome stability. In this review, we discuss the regulatory mechanisms of licensing control, the deleterious consequences when both licensing and checkpoints are compromised, and present possible mechanisms to prevent re-replication in order to maintain genome stability.

  16. Eukaryotic Mismatch Repair in Relation to DNA Replication.

    Science.gov (United States)

    Kunkel, Thomas A; Erie, Dorothy A

    2015-01-01

    Three processes act in series to accurately replicate the eukaryotic nuclear genome. The major replicative DNA polymerases strongly prevent mismatch formation, occasional mismatches that do form are proofread during replication, and rare mismatches that escape proofreading are corrected by mismatch repair (MMR). This review focuses on MMR in light of increasing knowledge about nuclear DNA replication enzymology and the rate and specificity with which mismatches are generated during leading- and lagging-strand replication. We consider differences in MMR efficiency in relation to mismatch recognition, signaling to direct MMR to the nascent strand, mismatch removal, and the timing of MMR. These studies are refining our understanding of relationships between generating and repairing replication errors to achieve accurate replication of both DNA strands of the nuclear genome.

  17. Control of DNA replication by anomalous reaction-diffusion kinetics

    Science.gov (United States)

    Bechhoefer, John; Gauthier, Michel

    2010-03-01

    DNA replication requires two distinct processes: the initiation of pre-licensed replication origins and the propagation of replication forks away from the fired origins. Experiments indicate that these origins are triggered over the whole genome at a rate I(t) (the number of initiations per unreplicated length per time) that increases throughout most of the synthesis (S) phase, before rapidly decreasing to zero at the end of the replication process. We propose a simple model for the control of DNA replication in which the rate of initiation of replication origins is controlled by protein-DNA interactions. Analyzing recent data from Xenopus frog embryos, we find that the initiation rate is reaction limited until nearly the end of replication, when it becomes diffusion limited. Initiation of origins is suppressed when the diffusion-limited search time dominates. To fit the experimental data, we find that the interaction between DNA and the rate-limiting protein must be subdiffusive.

  18. 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.

  19. Le Chatelier's principle in replicator dynamics

    Science.gov (United States)

    Allahverdyan, Armen E.; Galstyan, Aram

    2011-10-01

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

  20. DNA instability in replicating Huntington's disease lymphoblasts

    Directory of Open Access Journals (Sweden)

    Frati Luigi

    2009-02-01

    Full Text Available Abstract Background The expanded CAG repeat in the Huntington's disease (HD gene may display tissue-specific variability (e.g. triplet mosaicism in repeat length, the longest mutations involving mitotic (germ and glial cells and postmitotic (neurons cells. What contributes to the triplet mutability underlying the development of HD nevertheless remains unknown. We investigated whether, besides the increased DNA instability documented in postmitotic neurons, possible environmental and genetic mechanisms, related to cell replication, may concur to determine CAG repeat mutability. To test this hypothesis we used, as a model, cultured HD patients' lymphoblasts with various CAG repeat lengths. Results Although most lymphoblastoid cell lines (88% showed little or no repeat instability even after six or more months culture, in lymphoblasts with large expansion repeats beyond 60 CAG repeats the mutation size and triplet mosaicism always increased during replication, implying that the repeat mutability for highly expanded mutations may quantitatively depend on the triplet expansion size. None of the investigated genetic factors, potentially acting in cis to the mutation, significantly influence the repeat changes. Finally, in our experiments certain drugs controlled triplet expansion in two prone-to-expand HD cell lines carrying large CAG mutations. Conclusion Our data support quantitative evidence that the inherited CAG length of expanded alleles has a major influence on somatic repeat variation. The longest triplet expansions show wide somatic variations and may offer a mechanistic model to study triplet drug-controlled instability and genetic factors influencing it.

  1. Why threefold-replication of families?

    Science.gov (United States)

    Fitzpatrick, Gerald L.

    1998-04-01

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

  2. Replicative DNA polymerase mutations in cancer☆

    Science.gov (United States)

    Heitzer, Ellen; Tomlinson, Ian

    2014-01-01

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

  3. Cholesterol-rich lipid rafts play an important role in the Cyprinid herpesvirus 3 replication cycle.

    Science.gov (United States)

    Brogden, Graham; Adamek, Mikołaj; Proepsting, Marcus J; Ulrich, Reiner; Naim, Hassan Y; Steinhagen, Dieter

    2015-09-30

    The Cyprinus herpesvirus 3 (CyHV-3) is a member of the new Alloherpesviridae virus family in the Herpesvirales order. CyHV-3 has been implicated in a large number of disease outbreaks in carp populations causing up to 100% mortality. The aim of this study was to investigate the requirement of cholesterol-rich lipid rafts in CyHV-3 entry and replication in carp cells. Plasma membrane cholesterol was depleted from common carp brain (CCB) cells with methyl-β-cyclodextrin (MβCD). Treated and non-treated cells were infected with CyHV-3 and virus binding and infection parameters were assessed using RT-qPCR, immunocytochemistry and virus titration. The effect of cholesterol reduction severely stunted virus entry in vitro, however after cholesterol replenishment virus entry and subsequent replication rates were similar to the control infection. Furthermore, cholesterol depletion did not significantly influence virus binding and the subsequent post-entry replication stage, however had an impact on virus egress. Comparative analysis of the lipid compositions of CyHV-3 and CCB membrane fractions revealed strong similarities between the lipid composition of the CyHV-3 and CCB lipid rafts. The results presented here show that cholesterol-rich lipid rafts are important for the CyHV-3 replication cycle especially during entry and egress.

  4. Replication of M13 single—stranded DNA bearing a sitespecific ethenocytosine lesion by Escherichia coil cell extracts

    Institute of Scientific and Technical Information of China (English)

    WANGGE; PAULMDUNMAN; 等

    1997-01-01

    Previous investigation on the mutagenic effects of 3,N4-Ethenocytosine (εC),a nonpairing DNA lesion,revealed the existence of a novel SOS-independent inducible mutagenic mechanism in E.coli termed UVM for UV modulation of mutagenesis.To investigate whether UVM is mediated by an alteration of DNA replication,we have set up an in vitro replication system in which phage M13 viral single-stranded DNA bearing a single site-specific (εC) residue is replicated by soluble protein extracts from E.coli cells.Replication products were analyzed by agarose gel electrophoresis and the frequency of translesion synthesis was determined by restriction endonuclease analyses.Our data indicate that DNA replication is strongly inhibited by εC,but that translesion DNA synthesis does occur in about 14% of the replicated DNA molecules.These results are very similar to those observed previously in vivo,and suggest that this experimental system may be suitable for evaluating alterations in DNA replication in UVM-induced cells.

  5. Inhibition of RNA recruitment and replication of an RNA virus by acridine derivatives with known anti-prion activities.

    Directory of Open Access Journals (Sweden)

    Zsuzsanna Sasvari

    Full Text Available BACKGROUND: Small molecule inhibitors of RNA virus replication are potent antiviral drugs and useful to dissect selected steps in the replication process. To identify antiviral compounds against Tomato bushy stunt virus (TBSV, a model positive stranded RNA virus, we tested acridine derivatives, such as chlorpromazine (CPZ and quinacrine (QC, which are active against prion-based diseases. METHODOLOGY/PRINCIPAL FINDINGS: Here, we report that CPZ and QC compounds inhibited TBSV RNA accumulation in plants and in protoplasts. In vitro assays revealed that the inhibitory effects of these compounds were manifested at different steps of TBSV replication. QC was shown to have an effect on multiple steps, including: (i inhibition of the selective binding of the p33 replication protein to the viral RNA template, which is required for recruitment of viral RNA for replication; (ii reduction of minus-strand synthesis by the tombusvirus replicase; and (iii inhibition of translation of the uncapped TBSV genomic RNA. In contrast, CPZ was shown to inhibit the in vitro assembly of the TBSV replicase, likely due to binding of CPZ to intracellular membranes, which are important for RNA virus replication. CONCLUSION/SIGNIFICANCE: Since we found that CPZ was also an effective inhibitor of other plant viruses, including Tobacco mosaic virus and Turnip crinkle virus, it seems likely that CPZ has a broad range of antiviral activity. Thus, these inhibitors constitute effective tools to study similarities in replication strategies of various RNA viruses.

  6. Mammalian chromosomes contain cis-acting elements that control replication timing, mitotic condensation, and stability of entire chromosomes.

    Science.gov (United States)

    Thayer, Mathew J

    2012-09-01

    Recent studies indicate that mammalian chromosomes contain discrete cis-acting loci that control replication timing, mitotic condensation, and stability of entire chromosomes. Disruption of the large non-coding RNA gene ASAR6 results in late replication, an under-condensed appearance during mitosis, and structural instability of human chromosome 6. Similarly, disruption of the mouse Xist gene in adult somatic cells results in a late replication and instability phenotype on the X chromosome. ASAR6 shares many characteristics with Xist, including random mono-allelic expression and asynchronous replication timing. Additional "chromosome engineering" studies indicate that certain chromosome rearrangements affecting many different chromosomes display this abnormal replication and instability phenotype. These observations suggest that all mammalian chromosomes contain "inactivation/stability centers" that control proper replication, condensation, and stability of individual chromosomes. Therefore, mammalian chromosomes contain four types of cis-acting elements, origins, telomeres, centromeres, and "inactivation/stability centers", all functioning to ensure proper replication, condensation, segregation, and stability of individual chromosomes.

  7. Clustering Similarity Digest Bloom Filters in Self-Organizing Maps

    Science.gov (United States)

    2012-12-01

    Science Foundation. xv THIS PAGE INTENTIONALLY LEFT BLANK xvi CHAPTER 1: Introduction In the late 1980s, IBM’s 3390 Model 1 direct access storage device...information autonomously. From there, we look at a specific type of artificial neural network, the self-organizing map, as a appropriate model to build...training was not thorough enough for significant similarity scor - ing with the untrained document collection. In Section 4.1 we saw that each SOM had a

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

    Directory of Open Access Journals (Sweden)

    Tunin Karen

    2002-01-01

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

  9. Replication regions of two pairs of incompatible lactococcal theta-replicating plasmids.

    Science.gov (United States)

    Gravesen, A; von Wright, A; Josephsen, J; Vogensen, F K

    1997-01-01

    Incompatibility tests were performed employing 12 replicons belonging to a family of homologous lactococcal theta-replicating plasmids. Two pairs of incompatible plasmids were found, namely, pFV1001 and pFV1201, and pJW565 and pFW094. The replicons of plasmids pFV1001, pFV1201, pJW565, pJW566, and pFW094 were sequenced. Alignments were made of the replicational origins (repA) and putative replication proteins (RepB) of these and 11 related plasmid sequences. Comparison of the alignments with the incompatibility data indicated that the incompatibility determinant could be contained within the 22-bp tandem repeats DRII and/or the inverted repeat IR1 in repA. In support, the incompatibility determinant of pJW563 was localized to a 743-bp fragment encompassing repA. A stretch of 13 amino acids of RepB was proposed to be responsible for the plasmid-specific initiation of replication. This stretch is part of a domain containing features that are highly conserved within the proposed DNA binding regions of the initiation proteins from several well-characterized plasmids from Gram-negative bacteria, including pSC101, R6K, and mini-F.

  10. Communicating Science

    Science.gov (United States)

    Russell, Nicholas

    2009-10-01

    Introduction: what this book is about and why you might want to read it; Prologue: three orphans share a common paternity: professional science communication, popular journalism, and literary fiction are not as separate as they seem; Part I. Professional Science Communication: 1. Spreading the word: the endless struggle to publish professional science; 2. Walk like an Egyptian: the alien feeling of professional science writing; 3. The future's bright? Professional science communication in the age of the internet; 4. Counting the horse's teeth: professional standards in science's barter economy; 5. Separating the wheat from the chaff: peer review on trial; Part II. Science for the Public: What Science Do People Need and How Might They Get It?: 6. The Public Understanding of Science (PUS) movement and its problems; 7. Public engagement with science and technology (PEST): fine principle, difficult practice; 8. Citizen scientists? Democratic input into science policy; 9. Teaching and learning science in schools: implications for popular science communication; Part III. Popular Science Communication: The Press and Broadcasting: 10. What every scientist should know about mass media; 11. What every scientist should know about journalists; 12. The influence of new media; 13. How the media represents science; 14. How should science journalists behave?; Part IV. The Origins of Science in Cultural Context: Five Historic Dramas: 15. A terrible storm in Wittenberg: natural knowledge through sorcery and evil; 16. A terrible storm in the Mediterranean: controlling nature with white magic and religion; 17. Thieving magpies: the subtle art of false projecting; 18. Foolish virtuosi: natural philosophy emerges as a distinct discipline but many cannot take it seriously; 19. Is scientific knowledge 'true' or should it just be 'truthfully' deployed?; Part V. Science in Literature: 20. Science and the Gothic: the three big nineteenth-century monster stories; 21. Science fiction: serious

  11. Similarity-Based Solution of the Generalized Boussinesq Equation

    Science.gov (United States)

    Olsen, J. S.; Mortensen, J.; Telyakovskiy, A. S.; Wheatcraft, S. W.

    2013-12-01

    The generalized Boussinesq equation is a nonlinear diffusion equation where hydraulic conductivity is a power-law function of hydraulic head. In the traditional Boussinesq equation it is a linear function of hydraulic head. The generalized Boussinesq equation models flows of gases through porous media and flows of water in forest soils and concretes. Also, when the hydraulic conductivity is a power-law function of elevation we obtain this equation. We model a one-dimensional semi-infinite initially empty aquifer with boundary conditions at the inlet in rectangular coordinates. We introduce similarity variables to reduce the initial-boundary value problem to a boundary value problem for a nonlinear ordinary differential equation. We construct an approximate solution that preserves certain properties of the true solution and replicated known exact solutions.

  12. RNA interference targets arbovirus replication in Culicoides cells.

    Science.gov (United States)

    Schnettler, Esther; Ratinier, Maxime; Watson, Mick; Shaw, Andrew E; McFarlane, Melanie; Varela, Mariana; Elliott, Richard M; Palmarini, Massimo; Kohl, Alain

    2013-03-01

    Arboviruses are transmitted to vertebrate hosts by biting arthropod vectors such as mosquitoes, ticks, and midges. These viruses replicate in both arthropods and vertebrates and are thus exposed to different antiviral responses in these organisms. RNA interference (RNAi) is a sequence-specific RNA degradation mechanism that has been shown to play a major role in the antiviral response against arboviruses in mosquitoes. Culicoides midges are important vectors of arboviruses, known to transmit pathogens of humans and livestock such as bluetongue virus (BTV) (Reoviridae), Oropouche virus (Bunyaviridae), and likely the recently discovered Schmallenberg virus (Bunyaviridae). In this study, we investigated whether Culicoides cells possess an antiviral RNAi response and whether this is effective against arboviruses, including those with double-stranded RNA (dsRNA) genomes, such as BTV. Using reporter gene-based assays, we established the presence of a functional RNAi response in Culicoides sonorensis-derived KC cells which is effective in inhibiting BTV infection. Sequencing of small RNAs from KC and Aedes aegypti-derived Aag2 cells infected with BTV or the unrelated Schmallenberg virus resulted in the production of virus-derived small interfering RNAs (viRNAs) of 21 nucleotides, similar to the viRNAs produced during arbovirus infections of mosquitoes. In addition, viRNA profiles strongly suggest that the BTV dsRNA genome is accessible to a Dicer-type nuclease. Thus, we show for the first time that midge cells target arbovirus replication by mounting an antiviral RNAi response mainly resembling that of other insect vectors of arboviruses.

  13. Short hairpin-loop-structured oligodeoxynucleotides reduce HSV-1 replication

    Directory of Open Access Journals (Sweden)

    Heinrich Jochen

    2009-04-01

    Full Text Available Abstract The Herpes simplex virus (HSV is known as an infectious agent and widespread in the human population. The symptoms of HSV infections can range from mild to life threatening, especially in immune-compromised individuals. HSV infections are commonly treated with the guanosine analogue Aciclovir, but reports of resistance are increasing. Efforts are made to establish single-stranded antisense oligodeoxynucleotides (as and small interfering ribonucleic acids (siRNAs for antiviral treatment. Recently, another class of short interfering nucleic acids, partially double-stranded hairpin loop-structured 54 mer oligodeoxynucleotides (ODNs, was shown to allow hydrolysis of HIV RNA by binding to the viral RNA. This leads to a substrate for the viral RNase H. To assess the potential of such ODNs for inhibition of HSV-1 replication, five partially double-stranded ODNs were designed based on the sequences of known siRNAs against HSV-1 with antiviral activity. Three of them are directed against early and two against leaky late genes. Primary human lung fibroblasts, MRC-5, and African green monkey kidney cells, Vero, were transfected with ODNs and subsequently infected. The effect on HSV-1 replication was determined by analyzing the virus titer in cell culture supernatants by quantitative PCR and plaque assays. An inhibitory effect was observed with all five selected ODNs, with two cases showing statistical significance in both cell types. The observed effect was sequence-specific and dose dependent. In one case the ODN was more efficient than a previously described siRNA directed against the same target site in the mRNA of UL5, a component of the helicase/primase complex. HSV-1 virions and ODNs can be applied simultaneously without transfection reagent, but at a 50-fold higher concentration to Vero cells with similar efficiencies. The results underline the potential of partially double-stranded hairpin loop-structured ODNs as antiviral agents.

  14. DNA replication and transcription: An innovative teaching strategy.

    Science.gov (United States)

    Fossey, Annabel; Hancock, Carolyn

    2005-11-01

    First-year students in genetics at the University of KwaZulu-Natal, South Africa, attend two general biology modules, one in each semester. Teaching involves four formal lectures per week of 45 min each, one 3-h practical, and one lecture period tutorial. These students, graduating from secondary education, are well schooled in rote leaning but are limited in critical thinking and find assessment questions belonging to the higher levels of Bloom's taxonomy difficult. All students attend the formal lectures together, up to 300 students, whereas for the tutorials they are grouped into small groups, no more than 40 students in a tutorial class, allowing for innovative teaching strategies. Students find the processes of DNA replication and transcription difficult because of the sequential steps involved in the processes together with limitations imposed by the enzymes involved. Furthermore, they find the significance and relationships between the different components of the processes very difficult. A tutorial was developed in which students are requested to demonstrate replication with line drawings, which are then used in various iterations of transcription. The tutorial is administered in the presence of a tutor that guides the step by step execution of the tutorial while stimulating active participation. In the past 2 years, the presentation of this and other similar tutorials in genetics has improved overall class performance on average by 15%. Furthermore, students seem to display a greater retention from the first year to the second, which was previously rather limited. A survey among first-year students revealed that the implementation of this tutorial facilitated studying and recall by helping students to organize thoughts, picture the sequence of events, understand fundamental concepts, and create a feeling of confidence.

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

    Science.gov (United States)

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

    2015-12-01

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

  16. SV40 utilizes ATM kinase activity to prevent non-homologous end joining of broken viral DNA replication products.

    Directory of Open Access Journals (Sweden)

    Gregory A Sowd

    2014-12-01

    Full Text Available Simian virus 40 (SV40 and cellular DNA replication rely on host ATM and ATR DNA damage signaling kinases to facilitate DNA repair and elicit cell cycle arrest following DNA damage. During SV40 DNA replication, ATM kinase activity prevents concatemerization of the viral genome whereas ATR activity prevents accumulation of aberrant genomes resulting from breakage of a moving replication fork as it converges with a stalled fork. However, the repair pathways that ATM and ATR orchestrate to prevent these aberrant SV40 DNA replication products are unclear. Using two-dimensional gel electrophoresis and Southern blotting, we show that ATR kinase activity, but not DNA-PK(cs kinase activity, facilitates some aspects of double strand break (DSB repair when ATM is inhibited during SV40 infection. To clarify which repair factors associate with viral DNA replication centers, we examined the localization of DSB repair proteins in response to SV40 infection. Under normal conditions, viral replication centers exclusively associate with homology-directed repair (HDR and do not colocalize with non-homologous end joining (NHEJ factors. Following ATM inhibition, but not ATR inhibition, activated DNA-PK(cs and KU70/80 accumulate at the viral replication centers while CtIP and BLM, proteins that initiate 5' to 3' end resection during HDR, become undetectable. Similar to what has been observed during cellular DSB repair in S phase, these data suggest that ATM kinase influences DSB repair pathway choice by preventing the recruitment of NHEJ factors to replicating viral DNA. These data may explain how ATM prevents concatemerization of the viral genome and promotes viral propagation. We suggest that inhibitors of DNA damage signaling and DNA repair could be used during infection to disrupt productive viral DNA replication.

  17. SV40 utilizes ATM kinase activity to prevent non-homologous end joining of broken viral DNA replication products.

    Science.gov (United States)

    Sowd, Gregory A; Mody, Dviti; Eggold, Joshua; Cortez, David; Friedman, Katherine L; Fanning, Ellen

    2014-12-01

    Simian virus 40 (SV40) and cellular DNA replication rely on host ATM and ATR DNA damage signaling kinases to facilitate DNA repair and elicit cell cycle arrest following DNA damage. During SV40 DNA replication, ATM kinase activity prevents concatemerization of the viral genome whereas ATR activity prevents accumulation of aberrant genomes resulting from breakage of a moving replication fork as it converges with a stalled fork. However, the repair pathways that ATM and ATR orchestrate to prevent these aberrant SV40 DNA replication products are unclear. Using two-dimensional gel electrophoresis and Southern blotting, we show that ATR kinase activity, but not DNA-PK(cs) kinase activity, facilitates some aspects of double strand break (DSB) repair when ATM is inhibited during SV40 infection. To clarify which repair factors associate with viral DNA replication centers, we examined the localization of DSB repair proteins in response to SV40 infection. Under normal conditions, viral replication centers exclusively associate with homology-directed repair (HDR) and do not colocalize with non-homologous end joining (NHEJ) factors. Following ATM inhibition, but not ATR inhibition, activated DNA-PK(cs) and KU70/80 accumulate at the viral replication centers while CtIP and BLM, proteins that initiate 5' to 3' end resection during HDR, become undetectable. Similar to what has been observed during cellular DSB repair in S phase, these data suggest that ATM kinase influences DSB repair pathway choice by preventing the recruitment of NHEJ factors to replicating viral DNA. These data may explain how ATM prevents concatemerization of the viral genome and promotes viral propagation. We suggest that inhibitors of DNA damage signaling and DNA repair could be used during infection to disrupt productive viral DNA replication.

  18. Turning the hands of time again: a purely confirmatory replication study and a Bayesian analysis.

    Science.gov (United States)

    Wagenmakers, Eric-Jan; Beek, Titia F; Rotteveel, Mark; Gierholz, Alex; Matzke, Dora; Steingroever, Helen; Ly, Alexander; Verhagen, Josine; Selker, Ravi; Sasiadek, Adam; Gronau, Quentin F; Love, Jonathon; Pinto, Yair

    2015-01-01

    In a series of four experiments, Topolinski and Sparenberg (2012) found support for the conjecture that clockwise movements induce psychological states of temporal progression and an orientation toward the future and novelty. Here we report the results of a preregistered replication attempt of Experiment 2 from Topolinski and Sparenberg (2012). Participants turned kitchen rolls either clockwise or counterclockwise while answering items from a questionnaire assessing openness to experience. Data from 102 participants showed that the effect went slightly in the direction opposite to that predicted by Topolinski and Sparenberg (2012), and a preregistered Bayes factor hypothesis test revealed that the data were 10.76 times more likely under the null hypothesis than under the alternative hypothesis. Our findings illustrate the theoretical importance and practical advantages of preregistered Bayes factor replication studies, both for psychological science and for empirical work in general.

  19. Turning the Hands of Time Again: A Purely Confirmatory Replication Study and a Bayesian Analysis

    Directory of Open Access Journals (Sweden)

    Eric-Jan eWagenmakers

    2015-04-01

    Full Text Available In a series of four experiments, Topolinski and Sparenberg (2012; TS found support for the conjecture that clockwise movements induce psychological states of temporal progression and an orientation toward the future and novelty. Here we report the results of a preregistered replication attempt of Experiment 2 from TS. Participants turned kitchen rolls either clockwise or counterclockwise while answering items from a questionnaire assessing openness to experience. Data from 102 participants showed that the effect went slightly in the direction opposite to that predicted by TS, and a preregistered Bayes factor hypothesis test revealed that the data were 10.76 times more likely under the null hypothesis than under the alternative hypothesis. Our findings illustrate the theoretical importance and practical advantages of preregistered Bayes factor replication studies, both for psychological science and for empirical work in general.

  20. Replication Regulates Volume Weighting in Quantum Cosmology

    CERN Document Server

    Hartle, James

    2009-01-01

    Probabilities for observations in cosmology are conditioned both on the universe's quantum state and on local data specifying the observational situation. We show the quantum state defines a measure for prediction through such conditional probabilities that is well behaved for spatially large or infinite universes when the probabilities that our data is replicated are taken into account. In histories where our data are rare volume weighting connects top-down probabilities conditioned on both the data and the quantum state to the bottom-up probabilities conditioned on the quantum state alone. We apply these principles to a calculation of the number of inflationary e-folds in a homogeneous, isotropic minisuperspace model with a single scalar field moving in a quadratic potential. We find that volume weighting is justified and the top-down probabilities favor a large number of e-folds.

  1. Star Trek replicators and diatom nanotechnology.

    Science.gov (United States)

    Drum, Ryan W; Gordon, Richard

    2003-08-01

    Diatoms are single celled algae, the 10(5)-10(6) species of which create a wide variety of three-dimensional amorphous silica shells. If we could get them to produce useful structures, perhaps by compustat selection experiments (i.e. forced evolution of development or evodevo), their exponential growth in suspension cultures could compete with the lithography techniques of present day nanotechnology, which have limited 3D capabilities. Alternatively, their fine detail could be used for templates for MEMS (micro electro mechanical systems), or their silica deposition systems isolated for guiding silica deposition. A recent paper has demonstrated that silica can be replaced atom for atom without change of shape--a step towards the Star Trek replicator.

  2. Replicator dynamics for optional public good games

    DEFF Research Database (Denmark)

    Hauert, C.; De Monte, Silvia; Hofbauer, J.;

    2002-01-01

    The public goods game represents a straightforward generalization of the prisoner's dilemma to an arbitrary number of players. Since the dominant strategy is to defect, both classical and evolutionary game theory predict the asocial outcome that no player contributes to the public goods....... In contrast to the compulsory public goods game, optional participation provides a natural way to avoid deadlocks in the state of mutual defection. The three resulting strategies-collaboration or defection in the public goods game, as well as not joining at all-are studied by means of a replicator dynamics...... participation makes cooperation feasible. But for each strategy, the average payoff value remains equal to the earnings of those not participating in the public goods game....

  3. Dynamic combinatorial self-replicating systems.

    Science.gov (United States)

    Moulin, Emilie; Giuseppone, Nicolas

    2012-01-01

    Thanks to their intrinsic network topologies, dynamic combinatorial libraries (DCLs) represent new tools for investigating fundamental aspects related to self-organization and adaptation processes. Very recently the first examples integrating self-replication features within DCLs have pushed even further the idea of implementing dynamic combinatorial chemistry (DCC) towards minimal systems capable of self-construction and/or evolution. Indeed, feedback loop processes - in particular in the form of autocatalytic reactions - are keystones to build dynamic supersystems which could possibly approach the roots of "Darwinian" evolvability at mesoscale. This topic of current interest also shows significant potentialities beyond its fundamental character, because truly smart and autonomous materials for the future will have to respond to changes of their environment by selecting and by exponentially amplifying their fittest constituents.

  4. Entanglement Swapping Model of DNA Replication

    CERN Document Server

    Pusuluk, Onur

    2011-01-01

    Molecular biology explains function of molecules by their geometric and electronic structures which are mainly determined by utilization of quantum effects in chemistry. However, further quantum effects are not thought to play any significant role in the essential processes of life. On the contrary, consideration of quantum circuits/protocols and organic molecules as software and hardware of living systems that are co-optimized during evolution, may be useful to pass over the difficulties raised by biochemical complexity and to understand the physics of life. In this sense, we model DNA replication with a reliable qubit representation of the nucleotides: 1) molecular recognition of a nucleotide is assumed to trigger an intrabase entanglement corresponding to a superposition of different tautomer forms and 2) pairing of complementary nucleotides is described by swapping intrabase entanglements with interbase entanglements. We examine possible realizations of quantum circuits/protocols to be used to obtain intr...

  5. Suggestibility and negative priming: two replication studies.

    Science.gov (United States)

    David, Daniel; Brown, Richard J

    2002-07-01

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

  6. Self-replicating alphavirus RNA vaccines.

    Science.gov (United States)

    Ljungberg, Karl; Liljeström, Peter

    2015-02-01

    Recombinant nucleic acids are considered as promising next-generation vaccines. These vaccines express the native antigen upon delivery into tissue, thus mimicking live attenuated vaccines without having the risk of reversion to pathogenicity. They also stimulate the innate immune system, thus potentiating responses. Nucleic acid vaccines are easy to produce at reasonable cost and are stable. During the past years, focus has been on the use of plasmid DNA for vaccination. Now mRNA and replicon vaccines have come into focus as promising technology platforms for vaccine development. This review discusses self-replicating RNA vaccines developed from alphavirus expression vectors. These replicon vaccines can be delivered as RNA, DNA or as recombinant virus particles. All three platforms have been pre-clinically evaluated as vaccines against a number of infectious diseases and cancer. Results have been very encouraging and propelled the first human clinical trials, the results of which have been promising.

  7. Security in a Replicated Metadata Catalogue

    CERN Document Server

    Koblitz, B

    2007-01-01

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

  8. A replicating adenovirus capsid display recombinant elicits antibodies against Plasmodium falciparum sporozoites in Aotus nancymaae monkeys.

    Science.gov (United States)

    Karen, Kasey A; Deal, Cailin; Adams, Robert J; Nielsen, Carolyn; Ward, Cameron; Espinosa, Diego A; Xie, Jane; Zavala, Fidel; Ketner, Gary

    2015-01-01

    Decades of success with live adenovirus vaccines suggest that replication-competent recombinant adenoviruses (rAds) could serve as effective vectors for immunization against other pathogens. To explore the potential of a live rAd vaccine against malaria, we prepared a viable adenovirus 5 (Ad5) recombinant that displays a B-cell epitope from the circumsporozoite protein (CSP) of Plasmodium falciparum on the virion surface. The recombinant induced P. falciparum sporozoite-neutralizing antibodies in mice. Human adenoviruses do not replicate in mice. Therefore, to examine immunogenicity in a system in which, as in humans, the recombinant replicates, we constructed a similar recombinant in an adenovirus mutant that replicates in monkey cells and immunized four Aotus nancymaae monkeys. The recombinant replicated in the monkeys after intratracheal instillation, the first demonstration of replication of human adenoviruses in New World monkeys. Immunization elicited antibodies both to the Plasmodium epitope and the Ad5 vector. Antibodies from all four monkeys recognized CSP on intact parasites, and plasma from one monkey neutralized sporozoites in vitro and conferred partial protection against P. falciparum sporozoite infection after passive transfer to mice. Prior enteric inoculation of two animals with antigenically wild-type adenovirus primed a response to the subsequent intratracheal inoculation, suggesting a route to optimizing performance. A vaccine is not yet available against P. falciparum, which induces the deadliest form of malaria and kills approximately one million children each year. The live capsid display recombinant described here may constitute an early step in a critically needed novel approach to malaria immunization. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  9. Enhancing visuospatial performance through video game training to increase learning in visuospatial science domains.

    Science.gov (United States)

    Sanchez, Christopher A

    2012-02-01

    Although previous research has demonstrated that performance on visuospatial assessments can be enhanced through relevant experience, an unaddressed question is whether such experience also produces a similar increase in target domains (such as science learning) where visuospatial abilities are directly relevant for performance. In the present study, participants completed either spatial or nonspatial training via interaction with video games and were then asked to read and learn about the geologic topic of plate tectonics. Results replicate the benefit of playing appropriate video games in enhancing visuospatial performance and demonstrate that this facilitation also manifests itself in learning science topics that are visuospatial in nature. This novel result suggests that visuospatial training not only can impact performance on measures of spatial functioning, but also can affect performance in content areas in which these abilities are utilized.

  10. Strange science takes time

    CERN Multimedia

    2008-01-01

    The late astronomer Carl Sagan popularized the saying that "extraordinary claims require extraordinary evidence," in reference to reports of alien visitations. Generating low-cost commercial fusion power, isolating antimatter and tracing reverse-time causality aren't as far out there as UFOs, but a similar rule might well apply: Extraordinary science requires extraordinary effort. With that in mind, here's a progress report on three extraordinary science projects that have popped up in the news...

  11. 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.

  12. Representation of Semantic Similarity in the Left Intraparietal Sulcus: Functional Magnetic Resonance Imaging Evidence

    Directory of Open Access Journals (Sweden)

    Veerle Neyens

    2017-08-01

    Full Text Available According to a recent study, semantic similarity between concrete entities correlates with the similarity of activity patterns in left middle IPS during category naming. We examined the replicability of this effect under passive viewing conditions, the potential role of visuoperceptual similarity, where the effect is situated compared to regions that have been previously implicated in visuospatial attention, and how it compares to effects of object identity and location. Forty-six subjects participated. Subjects passively viewed pictures from two categories, musical instruments and vehicles. Semantic similarity between entities was estimated based on a concept-feature matrix obtained in more than 1,000 subjects. Visuoperceptual similarity was modeled based on the HMAX model, the AlexNet deep convolutional learning model, and thirdly, based on subjective visuoperceptual similarity ratings. Among the IPS regions examined, only left middle IPS showed a semantic similarity effect. The effect was significant in hIP1, hIP2, and hIP3. Visuoperceptual similarity did not correlate with similarity of activity patterns in left middle IPS. The semantic similarity effect in left middle IPS was significantly stronger than in the right middle IPS and also stronger than in the left or right posterior IPS. The semantic similarity effect was similar to that seen in the angular gyrus. Object identity effects were much more widespread across nearly all parietal areas examined. Location effects were relatively specific for posterior IPS and area 7 bilaterally. To conclude, the current findings replicate the semantic similarity effect in left middle IPS under passive viewing conditions, and demonstrate its anatomical specificity within a cytoarchitectonic reference frame. We propose that the semantic similarity effect in left middle IPS reflects the transient uploading of semantic representations in working memory.

  13. The human rhinovirus internal cis-acting replication element (cre) exhibits disparate properties among serotypes.

    Science.gov (United States)

    McKnight, K L

    2003-12-01

    It has been reported previously that the Human rhinovirus 14 (HRV-14) RNA genome contains a cis-acting replication element (cre) that maps to the capsid coding (P1) sequence [19]. Further characterization of the HRV-14 cre in the present study established that by moving the cre stem-loop structure downstream, adjacent to the 3'NCR, that its position is not critical for function. When the P1 sequences of two closely related serotypes of HRV-14 were analyzed for the presence of a cre, both HRV-3 and HRV-72 were found to contain similar sequence at the same positions as HRV-14. Moreover, sequence at these positions produced structures from MFOLD analysis that closely resembled the HRV-14 cre. It was also discovered that neither HRV serotypes 1a or 16 harbor replication elements that map to the P1 segments of their genomes. Computer and mutational analyses suggest that the cre in these latter HRV serotypes map instead to the 2A gene, as has been reported for HRV-2. The putative HRV-3 cre was determined to be unable to support replication when placed in an HRV-14 replicon background. Similarly, the previously identified HRV-2 cre was unable to support replication of the HRV-14 genome. This finding is in contrast to the cardiovirus cre, which has been shown to be functionally active between two members of its family, and further suggests that there is a close link between the evolution of the human rhinoviruses and the mechanisms of RNA replication.

  14. An optimal replication strategy for data grid systems

    Institute of Scientific and Technical Information of China (English)

    JIANG Jianjin; YANG Guangwen

    2007-01-01

    Data access latency is an important metric of system performance in data grid.By means of efficient replication strategy,the amount of data transferred in a wide area network will decrease,and the average access latency of data will decrease ultimately.The motivation of our research is to solve the optimized replica distribution problem in a data grid;that is,the system should utilize many replicas for every data with storage constraints to minimize the average access latency of data.This paper proposes a model of replication strategy in federated data grid and gives the optimized solution.The analysis results and simulation results show that the optimized replication strategy proposed in this paper is superior to LRU caching strategy,uniform replication strategy,proportional replication strategy and square root replication strategy in terms of wide area network bandwidth requirement and in the average access latency of data.

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

    Science.gov (United States)

    Pross, Addy

    2004-06-01

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

  16. Replication of Avocado Sunblotch Viroid in the Yeast Saccharomyces cerevisiae▿

    Science.gov (United States)

    Delan-Forino, Clémentine; Maurel, Marie-Christine; Torchet, Claire

    2011-01-01

    Viroids are the smallest known pathogenic agents. They are noncoding, single-stranded, closed-circular, “naked” RNAs, which replicate through RNA-RNA transcription. Viroids of the Avsunviroidae family possess a hammerhead ribozyme in their sequence, allowing self-cleavage during their replication. To date, viroids have only been detected in plant cells. Here, we investigate the replication of Avocado sunblotch viroid (ASBVd) of the Avsunviroidae family in a nonconventional host, the yeast Saccharomyces cerevisiae. We demonstrate that ASBVd RNA strands of both polarities are able to self-cleave and to replicate in a unicellular eukaryote cell. We show that the viroid monomeric RNA is destabilized by the nuclear 3′ and the cytoplasmic 5′ RNA degradation pathways. For the first time, our results provide evidence that viroids can replicate in other organisms than plants and that yeast contains all of the essential cellular elements for the replication of ASBVd. PMID:21270165

  17. Evidence for sequential and increasing activation of replication origins along replication timing gradients in the human genome.

    Science.gov (United States)

    Guilbaud, Guillaume; Rappailles, Aurélien; Baker, Antoine; Chen, Chun-Long; Arneodo, Alain; Goldar, Arach; d'Aubenton-Carafa, Yves; Thermes, Claude; Audit, Benjamin; Hyrien, Olivier

    2011-12-01

    Genome-wide replication timing studies have suggested that mammalian chromosomes consist of megabase-scale domains of coordinated origin firing separated by large originless transition regions. Here, we report a quantitative genome-wide analysis of DNA replication kinetics in several human cell types that contradicts this view. DNA combing in HeLa cells sorted into four temporal compartments of S phase shows that replication origins are spaced at 40 kb intervals and fire as small clusters whose synchrony increases during S phase and that replication fork velocity (mean 0.7 kb/min, maximum 2.0 kb/min) remains constant and narrowly distributed through S phase. However, multi-scale analysis of a genome-wide replication timing profile shows a broad distribution of replication timing gradients with practically no regions larger than 100 kb replicating at less than 2 kb/min. Therefore, HeLa cells lack large regions of unidirectional fork progression. Temporal transition regions are replicated by sequential activation of origins at a rate that increases during S phase and replication timing gradients are set by the delay and the spacing between successive origin firings rather than by the velocity of single forks. Activation of internal origins in a specific temporal transition region is directly demonstrated by DNA combing of the IGH locus in HeLa cells. Analysis of published origin maps in HeLa cells and published replication timing and DNA combing data in several other cell types corroborate these findings, with the interesting exception of embryonic stem cells where regions of unidirectional fork progression seem more abundant. These results can be explained if origins fire independently of each other but under the control of long-range chromatin structure, or if replication forks progressing from early origins stimulate initiation in nearby unreplicated DNA. These findings shed a new light on the replication timing program of mammalian genomes and provide a general

  18. Estimating the reproducibility of psychological science

    NARCIS (Netherlands)

    Anderson, Joanna E.; Aarts, Alexander A.; Anderson, Christopher J.; Attridge, Peter R.; Attwood, Angela; Axt, Jordan; Babel, Molly; Bahník, Štěpán; Baranski, Erica; Barnett-Cowan, Michael; Bartmess, Elizabeth; Beer, Jennifer; Bell, Raoul; Bentley, Heather; Beyan, Leah; Binion, Grace; Borsboom, Denny; Bosch, Annick; Bosco, Frank A.; Bowman, Sara D.; Brandt, Mark J.; Braswell, Erin; Brohmer, Hilmar; Brown, Benjamin T.; Brown, Kristina; Brüning, Jovita; Calhoun-Sauls, Ann; Callahan, Shannon P.; Chagnon, Elizabeth; Chandler, Jesse; Chartier, Christopher R.; Cheung, Felix; Christopherson, Cody D.; Cillessen, Linda; Clay, Russ; Cleary, Hayley; Cloud, Mark D.; Conn, Michael; Cohoon, Johanna; Columbus, Simon; Cordes, Andreas; Costantini, Giulio; Alvarez, Leslie D Cramblet; Cremata, Ed; Crusius, Jan; DeCoster, Jamie; DeGaetano, Michelle A.; Penna, Nicolás Delia; Den Bezemer, Bobby; Deserno, Marie K.; Devitt, Olivia; Dewitte, Laura; Dobolyi, David G.; Dodson, Geneva T.; Donnellan, M. Brent; Donohue, Ryan; Dore, Rebecca A.; Dorrough, Angela; Dreber, Anna; Dugas, Michelle; Dunn, Elizabeth W.; Easey, Kayleigh; Eboigbe, Sylvia; Eggleston, Casey; Embley, Jo; Epskamp, Sacha; Errington, Timothy M.; Estel, Vivien; Farach, Frank J.; Feather, Jenelle; Fedor, Anna; Fernández-Castilla, Belén; Fiedler, Susann; Field, James G.; Fitneva, Stanka A.; Flagan, Taru; Forest, Amanda L.; Forsell, Eskil; Foster, Joshua D.; Frank, Michael C.; Frazier, Rebecca S.; Fuchs, Heather; Gable, Philip; Galak, Jeff; Galliani, Elisa Maria; Gampa, Anup; Garcia, Sara; Gazarian, Douglas; Gilbert, Elizabeth; Giner-Sorolla, Roger; Glöckner, Andreas; Goellner, Lars; Goh, Jin X.; Goldberg, Rebecca; Goodbourn, Patrick T.; Gordon-McKeon, Shauna; Gorges, Bryan; Gorges, Jessie; Goss, Justin; Graham, Jesse; Grange, James A.; Gray, Jeremy; Hartgerink, Chris; Hartshorne, Joshua; Hasselman, Fred; Hayes, Timothy; Heikensten, Emma; Henninger, Felix; Hodsoll, John; Holubar, Taylor; Hoogendoorn, Gea; Humphries, Denise J.; Hung, Cathy O Y; Immelman, Nathali; Irsik, Vanessa C.; Jahn, Georg; Jäkel, Frank; Jekel, Marc; Johannesson, Magnus; Johnson, Larissa G.; Johnson, David J.; Johnson, Kate M.; Johnston, William J.; Jonas, Kai; Joy-Gaba, Jennifer A.; Kappes, Heather Barry; Kelso, Kim; Kidwell, Mallory C.; Kim, Seung Kyung; Kirkhart, Matthew; Kleinberg, Bennett; Knežević, Goran; Kolorz, Franziska Maria; Kossakowski, Jolanda J.; Krause, Robert Wilhelm; Krijnen, Job; Kuhlmann, Tim; Kunkels, Yoram K.; Kyc, Megan M.; Lai, Calvin K.; Laique, Aamir; Lakens, Daniël|info:eu-repo/dai/nl/298811855; Lane, Kristin A.; Lassetter, Bethany; Lazarević, Ljiljana B.; Le Bel, Etienne P.; Lee, Key Jung; Lee, Minha; Lemm, Kristi; Levitan, Carmel A.; Lewis, Melissa; Lin, Lin; Lin, Stephanie; Lippold, Matthias; Loureiro, Darren; Luteijn, Ilse; MacKinnon, Sean; Mainard, Heather N.; Marigold, Denise C.; Martin, Daniel P.; Martinez, Tylar; Masicampo, E. J.; Matacotta, Josh; Mathur, Maya; May, Michael; Mechin, Nicole; Mehta, Pranjal; Meixner, Johannes; Melinger, Alissa; Miller, Jeremy K.; Miller, Mallorie; Moore, Katherine; Möschl, Marcus; Motyl, Matt; Müller, Stephanie M.; Munafo, Marcus; Neijenhuijs, Koen I.; Nervi, Taylor; Nicolas, Gandalf; Nilsonne, Gustav; Nosek, Brian A.; Nuijten, Michèle B.; Olsson, Catherine; Osborne, Colleen; Ostkamp, Lutz; Pavel, Misha; Penton-Voak, Ian S.; Perna, Olivia; Pernet, Cyril; Perugini, Marco; Pipitone, R. Nathan; Pitts, Michael; Plessow, Franziska; Prenoveau, Jason M.; Rahal, Rima Maria; Ratliff, Kate A.; Reinhard, David; Renkewitz, Frank; Ricker, Ashley A.; Rigney, Anastasia; Rivers, Andrew M.; Roebke, Mark; Rutchick, Abraham M.; Ryan, Robert S.; Sahin, Onur; Saide, Anondah; Sandstrom, Gillian M.; Santos, David; Saxe, Rebecca; Schlegelmilch, René; Schmidt, Kathleen; Scholz, Sabine; Seibel, Larissa; Selterman, Dylan Faulkner; Shaki, Samuel; Simpson, William B.; Sinclair, H. Colleen; Skorinko, Jeanine L M; Slowik, Agnieszka; Snyder, Joel S.; Soderberg, Courtney; Sonnleitner, Carina; Spencer, Nick; Spies, Jeffrey R.; Steegen, Sara; Stieger, Stefan; Strohminger, Nina; Sullivan, Gavin B.; Talhelm, Thomas; Tapia, Megan; Te Dorsthorst, Anniek; Thomae, Manuela; Thomas, Sarah L.; Tio, Pia; Traets, Frits; Tsang, Steve; Tuerlinckx, Francis; Turchan, Paul; Valášek, Milan; Van't Veer, Anna E.; Van Aert, Robbie; Van Assen, Marcel|info:eu-repo/dai/nl/407629971; Van Bork, Riet; Van De Ven, Mathijs; Van Den Bergh, Don; Van Der Hulst, Marije; Van Dooren, Roel; Van Doorn, Johnny; Van Renswoude, Daan R.; Van Rijn, Hedderik; Vanpaemel, Wolf; Echeverría, Alejandro Vásquez; Vazquez, Melissa; Velez, Natalia; Vermue, Marieke; Verschoor, Mark; Vianello, Michelangelo; Voracek, Martin; Vuu, Gina; Wagenmakers, Eric Jan; Weerdmeester, Joanneke; Welsh, Ashlee; Westgate, Erin C.; Wissink, Joeri; Wood, Michael; Woods, Andy; Wright, Emily; Wu, Sining; Zeelenberg, Marcel; Zuni, Kellylynn

    2015-01-01

    Reproducibility is a defining feature of science, but the extent to which it characterizes current research is unknown. We conducted replications of 100 experimental and correlational studies published in three psychology journals using high-powered designs and original materials when available. Rep

  19. Estimating the reproducibility of psychological science

    NARCIS (Netherlands)

    Anderson, Joanna E.; Aarts, Alexander A.; Anderson, Christopher J.; Attridge, Peter R.; Attwood, Angela; Axt, Jordan; Babel, Molly; Bahník, Štěpán; Baranski, Erica; Barnett-Cowan, Michael; Bartmess, Elizabeth; Beer, Jennifer; Bell, Raoul; Bentley, Heather; Beyan, Leah; Binion, Grace; Borsboom, Denny; Bosch, Annick; Bosco, Frank A.; Bowman, Sara D.; Brandt, Mark J.; Braswell, Erin; Brohmer, Hilmar; Brown, Benjamin T.; Brown, Kristina; Brüning, Jovita; Calhoun-Sauls, Ann; Callahan, Shannon P.; Chagnon, Elizabeth; Chandler, Jesse; Chartier, Christopher R.; Cheung, Felix; Christopherson, Cody D.; Cillessen, Linda; Clay, Russ; Cleary, Hayley; Cloud, Mark D.; Conn, Michael; Cohoon, Johanna; Columbus, Simon; Cordes, Andreas; Costantini, Giulio; Alvarez, Leslie D Cramblet; Cremata, Ed; Crusius, Jan; DeCoster, Jamie; DeGaetano, Michelle A.; Penna, Nicolás Delia; Den Bezemer, Bobby; Deserno, Marie K.; Devitt, Olivia; Dewitte, Laura; Dobolyi, David G.; Dodson, Geneva T.; Donnellan, M. Brent; Donohue, Ryan; Dore, Rebecca A.; Dorrough, Angela; Dreber, Anna; Dugas, Michelle; Dunn, Elizabeth W.; Easey, Kayleigh; Eboigbe, Sylvia; Eggleston, Casey; Embley, Jo; Epskamp, Sacha; Errington, Timothy M.; Estel, Vivien; Farach, Frank J.; Feather, Jenelle; Fedor, Anna; Fernández-Castilla, Belén; Fiedler, Susann; Field, James G.; Fitneva, Stanka A.; Flagan, Taru; Forest, Amanda L.; Forsell, Eskil; Foster, Joshua D.; Frank, Michael C.; Frazier, Rebecca S.; Fuchs, Heather; Gable, Philip; Galak, Jeff; Galliani, Elisa Maria; Gampa, Anup; Garcia, Sara; Gazarian, Douglas; Gilbert, Elizabeth; Giner-Sorolla, Roger; Glöckner, Andreas; Goellner, Lars; Goh, Jin X.; Goldberg, Rebecca; Goodbourn, Patrick T.; Gordon-McKeon, Shauna; Gorges, Bryan; Gorges, Jessie; Goss, Justin; Graham, Jesse; Grange, James A.; Gray, Jeremy; Hartgerink, Chris; Hartshorne, Joshua; Hasselman, Fred; Hayes, Timothy; Heikensten, Emma; Henninger, Felix; Hodsoll, John; Holubar, Taylor; Hoogendoorn, Gea; Humphries, Denise J.; Hung, Cathy O Y; Immelman, Nathali; Irsik, Vanessa C.; Jahn, Georg; Jäkel, Frank; Jekel, Marc; Johannesson, Magnus; Johnson, Larissa G.; Johnson, David J.; Johnson, Kate M.; Johnston, William J.; Jonas, Kai; Joy-Gaba, Jennifer A.; Kappes, Heather Barry; Kelso, Kim; Kidwell, Mallory C.; Kim, Seung Kyung; Kirkhart, Matthew; Kleinberg, Bennett; Knežević, Goran; Kolorz, Franziska Maria; Kossakowski, Jolanda J.; Krause, Robert Wilhelm; Krijnen, Job; Kuhlmann, Tim; Kunkels, Yoram K.; Kyc, Megan M.; Lai, Calvin K.; Laique, Aamir; Lakens, Daniël|info:eu-repo/dai/nl/298811855; Lane, Kristin A.; Lassetter, Bethany; Lazarević, Ljiljana B.; Le Bel, Etienne P.; Lee, Key Jung; Lee, Minha; Lemm, Kristi; Levitan, Carmel A.; Lewis, Melissa; Lin, Lin; Lin, Stephanie; Lippold, Matthias; Loureiro, Darren; Luteijn, Ilse; MacKinnon, Sean; Mainard, Heather N.; Marigold, Denise C.; Martin, Daniel P.; Martinez, Tylar; Masicampo, E. J.; Matacotta, Josh; Mathur, Maya; May, Michael; Mechin, Nicole; Mehta, Pranjal; Meixner, Johannes; Melinger, Alissa; Miller, Jeremy K.; Miller, Mallorie; Moore, Katherine; Möschl, Marcus; Motyl, Matt; Müller, Stephanie M.; Munafo, Marcus; Neijenhuijs, Koen I.; Nervi, Taylor; Nicolas, Gandalf; Nilsonne, Gustav; Nosek, Brian A.; Nuijten, Michèle B.; Olsson, Catherine; Osborne, Colleen; Ostkamp, Lutz; Pavel, Misha; Penton-Voak, Ian S.; Perna, Olivia; Pernet, Cyril; Perugini, Marco; Pipitone, R. Nathan; Pitts, Michael; Plessow, Franziska; Prenoveau, Jason M.; Rahal, Rima Maria; Ratliff, Kate A.; Reinhard, David; Renkewitz, Frank; Ricker, Ashley A.; Rigney, Anastasia; Rivers, Andrew M.; Roebke, Mark; Rutchick, Abraham M.; Ryan, Robert S.; Sahin, Onur; Saide, Anondah; Sandstrom, Gillian M.; Santos, David; Saxe, Rebecca; Schlegelmilch, René; Schmidt, Kathleen; Scholz, Sabine; Seibel, Larissa; Selterman, Dylan Faulkner; Shaki, Samuel; Simpson, William B.; Sinclair, H. Colleen; Skorinko, Jeanine L M; Slowik, Agnieszka; Snyder, Joel S.; Soderberg, Courtney; Sonnleitner, Carina; Spencer, Nick; Spies, Jeffrey R.; Steegen, Sara; Stieger, Stefan; Strohminger, Nina; Sullivan, Gavin B.; Talhelm, Thomas; Tapia, Megan; Te Dorsthorst, Anniek; Thomae, Manuela; Thomas, Sarah L.; Tio, Pia; Traets, Frits; Tsang, Steve; Tuerlinckx, Francis; Turchan, Paul; Valášek, Milan; Van't Veer, Anna E.; Van Aert, Robbie; Van Assen, Marcel|info:eu-repo/dai/nl/407629971; Van Bork, Riet; Van De Ven, Mathijs; Van Den Bergh, Don; Van Der Hulst, Marije; Van Dooren, Roel; Van Doorn, Johnny; Van Renswoude, Daan R.; Van Rijn, Hedderik; Vanpaemel, Wolf

    2015-01-01

    Reproducibility is a defining feature of science, but the extent to which it characterizes current research is unknown. We conducted replications of 100 experimental and correlational studies published in three psychology journals using high-powered designs and original materials when available.

  20. Estimating the reproducibility of psychological science

    NARCIS (Netherlands)

    Aarts, Alexander A.; Anderson, Joanna E.; Anderson, Christopher J.; Attridge, Peter R.; Attwood, Angela; Axt, Jordan; Babel, Molly; Bahnik, Stepan; Baranski, Erica; Barnett-Cowan, Michael; Bartmess, Elizabeth; Beer, Jennifer; Bell, Raoul; Bentley, Heather; Beyan, Leah; Binion, Grace; Borsboom, Denny; Bosch, Annick; Bosco, Frank A.; Bowman, Sara D.; Brandt, Mark J.; Braswell, Erin; Brohmer, Hilmar; Brown, Benjamin T.; Brown, Kristina; Bruening, Jovita; Calhoun-Sauls, Ann; Chagnon, Elizabeth; Callahan, Shannon P.; Chandler, Jesse; Chartier, Christopher R.; Cheung, Felix; Cillessen, Linda; Christopherson, Cody D.; Clay, Russ; Cleary, Hayley; Cloud, Mark D.; Cohn, Michael; Cohoon, Johanna; Columbus, Simon; Cordes, Andreas; Costantini, Giulio; Alvarez, Leslie D. Cramblet; Cremata, Ed; Crusius, Jan; DeCoster, Jamie; DeGaetano, Michelle A.; Della Penna, Nicolas; den Bezemer, Bobby; Deserno, Marie K.; Devitt, Olivia; Dewitte, Laura; Dobolyi, David G.; Dodson, Geneva T.; Donnellan, M. Brent; Donohue, Ryan; Dore, Rebecca A.; Dorrough, Angela; Dreber, Anna; Dugas, Michelle; Dunn, Elizabeth W.; Easey, Kayleigh; Eboigbe, Sylvia; Eggleston, Casey; Embley, Jo; Epskamp, Sacha; Errington, Timothy M.; Estel, Vivien; Farach, Frank J.; Feather, Jenelle; Fedor, Anna; Fernandez-Castilla, Belen; Fiedler, Susann; Field, James G.; Fitneva, Stanka A.; Flagan, Taru; Forest, Amanda L.; Forsell, Eskil; Foster, Joshua D.; Frank, Michael C.; Frazier, Rebecca S.; Fuchs, Heather; Gable, Philip; Galak, Jeff; Galliani, Elisa Maria; Gampa, Anup; Garcia, Sara; Gazarian, Douglas; Gilbert, Elizabeth; Giner-Sorolla, Roger; Gloeckner, Andreas; Goellner, Lars; Goh, Jin X.; Goldberg, Rebecca; Goodbourn, Patrick T.; Gordon-McKeon, Shauna; Gorges, Bryan; Gorges, Jessie; Goss, Justin; Graham, Jesse; Grange, James A.; Gray, Jeremy; Hartgerink, Chris; Hartshorne, Joshua; Hasselman, Fred; Hayes, Timothy; Heikensten, Emma; Henninger, Felix; Hodsoll, John; Holubar, Taylor; Hoogendoorn, Gea; Humphries, Denise J.; Hung, Cathy O. -Y.; Immelman, Nathali; Irsik, Vanessa C.; Jahn, Georg; Jaekel, Frank; Jekel, Marc; Johannesson, Magnus; Johnson, Larissa G.; Johnson, David J.; Johnson, Kate M.; Johnston, William J.; Jonas, Kai; Joy-Gaba, Jennifer A.; Kappes, Heather Barry; Kelso, Kim; Kidwell, Mallory C.; Kim, Seung Kyung; Kirkhart, Matthew; Kleinberg, Bennett; Knezevic, Goran; Kolorz, Franziska Maria; Kossakowski, Jolanda J.; Krause, Robert Wilhelm; Krijnen, Job; Kuhlmann, Tim; Kunkels, Yoram K.; Kyc, Megan M.; Lai, Calvin K.; Laique, Aamir; Lakens, Daniel; Lane, Kristin A.; Lassetter, Bethany; Lazarevic, Ljiljana B.; LeBel, Etienne P.; Lee, Key Jung; Lee, Minha; Lemm, Kristi; Levitan, Carmel A.; Lewis, M.; Lin, Lin; Lin, Stephanie; Lippold, Matthias; Loureiro, Darren; Luteijn, Ilse; Mackinnon, Sean; Mainard, Heather N.; Marigold, Denise C.; Martin, Daniel P.; Martinez, Tylar; Masicampo, E. J.; Matacotta, Josh; Mathur, Maya; May, Michael; Mechin, Nicole; Mehta, Pranjal; Meixner, Johannes; Melinger, Alissa; Miller, Jeremy K.; Miller, Mallorie; Moore, Katherine; Moeschl, Marcus; Motyl, Matt; Mueller, Stephanie M.; Munafo, Marcus; Neijenhuijs, Koen I.; Nervi, Taylor; Nicolas, Gandalf; Nilsonne, Gustav; Nosek, Brian A.; Nuijten, Michele B.; Olsson, Catherine; Osborne, Colleen; Ostkamp, Lutz; Pavel, Misha; Penton-Voak, Ian S.; Perna, Olivia; Pernet, Cyril; Perugini, Marco; Pipitone, R. Nathan; Pitts, Michael; Plessow, Franziska; Prenoveau, Jason M.; Rahal, Rima-Maria; Ratliff, Kate A.; Reinhard, David; Renkewitz, Frank; Ricker, Ashley A.; Rigney, Anastasia; Rivers, Andrew M.; Roebke, Mark; Rutchick, Abraham M.; Ryan, Robert S.; Sahin, Onur; Saide, Anondah; Sandstrom, Gillian M.; Santos, David; Saxe, Rebecca; Schmidt, Kathleen; Schlegelmilch, Rene; Seibel, Larissa; Scholz, Sabine; Selterman, Dylan Faulkner; Shaki, Samuel; Simpson, William B.; Sinclair, H. Colleen; Skorinko, Jeanine L. M.; Slowik, Agnieszka; Snyder, Joel S.; Soderberg, Courtney; Sonnleitner, Carina; Spencer, Nick; Spies, Jeffrey R.; Steegen, Sara; Stieger, Stefan; Strohminger, Nina; Sullivan, Gavin B.; Talhelm, Thomas; Tapia, Megan; te Dorsthorst, Anniek; Thomae, Manuela; Thomas, Sarah L.; Tio, Pia; Traets, Frits; Tsang, Steve; Tuerlinckx, Francis; Turchan, Paul; Valasek, Milan; van 't Veer, Anna E.; Van Aert, Robbie; van Assen, M.A.L.M.; van Bork, Riet; van de Ven, Mathijs; van den Bergh, Don; van der Hulst, Marije; van Dooren, Roel; van Doorn, Johnny; van Renswoude, Daan R.; van Rijn, Hedderik; Vanpaemel, Wolf; Echeverria, Alejandro Vasquez; Vazquez, Melissa; Velez, Natalia; Vermue, Marieke; Verschoor, Mark

    2015-01-01

    INTRODUCTION Reproducibility is a defining feature of science, but the extent to which it characterizes current research is unknown. Scientific claims should not gain credence because of the status or authority of their originator but by the replicability of their supporting evidence. Even research