WorldWideScience

Sample records for replicated prior research

  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. 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…

  3. 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…

  4. Replication Research and Special Education

    Science.gov (United States)

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

    2016-01-01

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

  5. Using Replication Projects in Teaching Research Methods

    Science.gov (United States)

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

    2014-01-01

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

  6. GENERAL ASPECTS REGARDING THE PRIOR DISCIPLINARY RESEARCH

    Directory of Open Access Journals (Sweden)

    ANDRA PURAN (DASCĂLU

    2012-05-01

    Full Text Available Disciplinary research is the first phase of the disciplinary action. According to art. 251 paragraph 1 of the Labour Code no disciplinary sanction may be ordered before performing the prior disciplinary research.These regulations provide an exception: the sanction of written warning. The current regulations in question, kept from the old regulation, provides a protection for employees against abuses made by employers, since sanctions are affecting the salary or the position held, or even the development of individual employment contract. Thus, prior research of the fact that is a misconduct, before a disciplinary sanction is applied, is an essential condition for the validity of the measure ordered. Through this study we try to highlight some general issues concerning the characteristics, processes and effects of prior disciplinary research.

  7. Hope and the interpersonal-psychological theory of suicidal behavior: replication and extension of prior findings.

    Science.gov (United States)

    Anestis, Michael D; Moberg, Fallon B; Arnau, Randolph C

    2014-04-01

    The interpersonal-psychological theory of suicidal behavior (IPTS; Joiner, 2005) posits that suicidal behavior occurs when an individual has a desire for death (due to the combination of perceived burdensomeness and thwarted belongingness) in addition to an acquired capacity for suicide, which is present when the individual has a low fear of death and high pain tolerance. Previous research has demonstrated an expected negative relation between trait hope and perceived burdensomeness and thwarted belongingness, as well as a more perplexing finding that hope is positively associated with the acquired capability. In a sample of 230 college students, measures of the three components of the IPTS were administered, along with measures of hope, depression, and painful and/or provocative events. Hierarchical regression analyses replicated the previously found associations between hope and burdensomeness and belongingness while controlling for depression and demographic variables. The positive association between hope and acquired capacity was also replicated, but a mediation analysis demonstrated that the effect was statistically accounted for by distress tolerance. The results further support the incremental validity of hope as a consideration in suicide risk assessments and suggest that hope may serve as a protective factor with respect to suicidal desire.

  8. Focus Article: Replication in Second Language Writing Research

    Science.gov (United States)

    Porte, Graeme; Richards, Keith

    2012-01-01

    This paper discusses the meaning and range of replication in L2 research from both quantitative and qualitative perspectives. In the first half of the paper, it will be argued that key quantitative studies need to be replicated to have their robustness and generalizability tested and that this is a requirement of scientific inquiry. Such research…

  9. Focus Article: Replication in Second Language Writing Research

    Science.gov (United States)

    Porte, Graeme; Richards, Keith

    2012-01-01

    This paper discusses the meaning and range of replication in L2 research from both quantitative and qualitative perspectives. In the first half of the paper, it will be argued that key quantitative studies need to be replicated to have their robustness and generalizability tested and that this is a requirement of scientific inquiry. Such research…

  10. Ku80 binds to human replication origins prior to the assembly of the ORC complex.

    Science.gov (United States)

    Sibani, Sahar; Price, Gerald B; Zannis-Hadjopoulos, Maria

    2005-05-31

    The Ku heterodimer, an abundant nuclear protein, binds DNA replication origins in a sequence-specific manner and promotes initiation. In this study, using HCT116 Ku80+/- haplo-insufficient and Orc2(delta/-) hypomorphic cells, the order of binding of Ku and the human origin recognition complex (HsORC) was determined. The nuclear expression of Ku80 was found to be decreased by 60% in Ku80+/- cells, while its general association with chromatin was decreased by 33%. Coimmunoprecipitation studies indicated that the Ku heterodimer associates specifically with the human HsOrc-2, -3, -4, and -6 subunits. Chromatin immunoprecipitation (ChIP) experiments, using cells synchronized to late G1, showed that the association of Ku80 with the lamin B2, beta-globin, and c-myc origins in vivo was decreased by 1.5-, 2.3-, and 2.5-fold, respectively, in Ku80+/- cells. The association of HsOrc-3, -4, and -6 was consistently decreased in all three origins examined in Ku80+/- cells, while that of HsOrc-2 showed no significant variation, indicating that the HsOrc-3, -4, and -6 subunits bind to the origins after Ku80. In Orc2(delta/-) cells, the association of HsOrc-2 with the lamin B2, beta-globin, and c-myc origins was decreased by 2.8-, 4.9-, and 2.8-fold, respectively, relative to wild-type HCT116 cells. Furthermore, nascent strand abundance at these three origins was decreased by 4.5-, 2.3-, and 2.6-fold in Orc2(delta/-) relative to HCT116 cells, respectively. Interestingly, the association of Ku80 with these origins was not affected in this hypomorphic cell line, indicating that Ku and HsOrc-2 bind to origins independently of each other.

  11. Developing benchmarks for prior learning assessment. Part 1: Research.

    Science.gov (United States)

    Day, M

    The aim of the study was to develop and promote national benchmarks for those engaged in accreditation of prior learning (APL) termed 'prior learning assessment and recognition' (PLAR) assessment in Canada, in all sectors and communities. The study objectives were to gain practitioner consensus on the development of benchmarks for APL (PLAR) across Canada; produce a guide to support the implementation of national benchmarks; make recommendations for the promotion of the national benchmarks; and distribute the guide. The study also investigated the feasibility of developing a system to confirm the competence of APL (PLAR) practitioners, based on nationally agreed benchmarks for practice. A qualitative research strategy was developed, which used a benchmarking survey and focus groups as the primary research tools. These were applied to a purposive sample of APL practitioners (n = 91). The participants were identified through the use of an initial screening survey. Respondents indicated that in Canada, PLAR is used in a variety of ways to assist with individual and personal growth for human resource development, the preparation of professionals and the achievement of academic credit. The findings of the focus groups are summarised using a SWOT analysis The study identified that the main functions of the PLAR practitioners are to prepare individuals for assessment and conduct assessments. Although practitioners should be made aware of the potential conflicts in undertaking combined roles, they should be encouraged to develop confidence in both functions.

  12. An Evaluation of Research Replication with Q Method and Its Utility in Market Segmentation.

    Science.gov (United States)

    Adams, R. C.

    Precipitated by questions of using Q methodology in television market segmentation and of the replicability of such research, this paper reports on both a reexamination of 1968 research by Joseph M. Foley and an attempt to replicate Foley's study. By undertaking a reanalysis of the Foley data, the question of replication in Q method is addressed.…

  13. Replicating Small Group Research Using the Functional Theory.

    Science.gov (United States)

    Cragan, John F.; Wright, David W.

    A replication study tested functional theory utilizing untrained full-fledged groups. One hundred forty undergraduate students who were enrolled in a small group communication course at a large midwestern university participated in small group discussions analyzing a plagiarism case used in an original study by R. Y. Hirokawa. Results indicated…

  14. Aggregate and Individual Replication Probability within an Explicit Model of the Research Process

    Science.gov (United States)

    Miller, Jeff; Schwarz, Wolf

    2011-01-01

    We study a model of the research process in which the true effect size, the replication jitter due to changes in experimental procedure, and the statistical error of effect size measurement are all normally distributed random variables. Within this model, we analyze the probability of successfully replicating an initial experimental result by…

  15. Aggregate and Individual Replication Probability within an Explicit Model of the Research Process

    Science.gov (United States)

    Miller, Jeff; Schwarz, Wolf

    2011-01-01

    We study a model of the research process in which the true effect size, the replication jitter due to changes in experimental procedure, and the statistical error of effect size measurement are all normally distributed random variables. Within this model, we analyze the probability of successfully replicating an initial experimental result by…

  16. Mutation of the dengue virus type 2 envelope protein heparan sulfate binding sites or the domain III lateral ridge blocks replication in Vero cells prior to membrane fusion

    Energy Technology Data Exchange (ETDEWEB)

    Roehrig, John T., E-mail: jtr1@cdc.gov [Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, CO 80521 (United States); Butrapet, Siritorn; Liss, Nathan M. [Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, CO 80521 (United States); Bennett, Susan L. [Arthropod-borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523 (United States); Luy, Betty E.; Childers, Thomas; Boroughs, Karen L.; Stovall, Janae L.; Calvert, Amanda E. [Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, CO 80521 (United States); Blair, Carol D. [Arthropod-borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523 (United States); Huang, Claire Y.-H. [Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, CO 80521 (United States)

    2013-07-05

    Using an infectious cDNA clone we engineered seven mutations in the putative heparan sulfate- and receptor-binding motifs of the envelope protein of dengue virus serotype 2, strain 16681. Four mutant viruses, KK122/123EE, E202K, G304K, and KKK305/307/310EEE, were recovered following transfection of C6/36 cells. A fifth mutant, KK291/295EE, was recovered from C6/36 cells with a compensatory E295V mutation. All mutants grew in and mediated fusion of virus-infected C6/36 cells, but three of the mutants, KK122/123EE, E202K, G304K, did not grow in Vero cells without further modification. Two Vero cell lethal mutants, KK291/295EV and KKK307/307/310EEE, failed to replicate in DC-SIGN-transformed Raji cells and did not react with monoclonal antibodies known to block DENV attachment to Vero cells. Additionally, both mutants were unable to initiate negative-strand vRNA synthesis in Vero cells by 72 h post-infection, suggesting that the replication block occurred prior to virus-mediated membrane fusion. - Highlights: • Heparan sulfate- and receptor-binding motifs of DENV2 envelope protein were mutated. • Four mutant viruses were isolated—all could fuse C6/36 cells. • Two of these mutants were lethal in Vero cells without further modification. • Lethal mutations were KK291/295EV and KKK305/307/310EEE. • Cell attachment was implicated as the replication block for both mutants.

  17. Replication in Interaction and Working Memory Research: Révész (2012) and Goo (2012)

    Science.gov (United States)

    Gass, Susan; Valmori, Lorena

    2015-01-01

    This paper argues for the replication of two studies, both of which consider feedback and working memory. In the first part of this paper, we discuss the role of interaction-based research and working memory research in second language acquisition research. We then describe two studies that have unified these two areas in recent published articles…

  18. Raising Reliability of Web Search Tool Research through Replication and Chaos Theory

    OpenAIRE

    Nicholson, Scott

    1999-01-01

    Because the World Wide Web is a dynamic collection of information, the Web search tools (or "search engines") that index the Web are dynamic. Traditional information retrieval evaluation techniques may not provide reliable results when applied to the Web search tools. This study is the result of ten replications of the classic 1996 Ding and Marchionini Web search tool research. It explores the effects that replication can have on transforming unreliable results from one iteration into replica...

  19. Viral replication in excised fin tissues (VREFT) corresponds with prior exposure of Pacific herring, Clupea pallasii (Valenciennes), to viral haemorrhagic septicaemia virus (VHSV).

    Science.gov (United States)

    Grady, C A; Gregg, J L; Wade, R M; Winton, J R; Hershberger, P K

    2011-01-01

    Procedures for a viral replication in excised fin tissue (VREFT) assay were adapted to Pacific herring, Clupea pallasii, and optimized both to reduce processing time and to provide the greatest resolution between naïve herring and those previously exposed to viral haemorrhagic septicaemia virus (VHSV), Genogroup IVa. The optimized procedures included removal of the left pectoral fin from a euthanized fish, inoculation of the fin with >10(5) plaque-forming units (PFU) mL(-1) VHSV for 1 h, rinsing the fin in fresh medium six times to remove unadsorbed virions, incubation of the fin in fresh medium for 4 days and enumeration of the viral titre in a sample of the incubation medium by plaque assay. The optimized VREFT assay was effective at identifying the prior exposure history of laboratory-reared Pacific herring to VHSV. The geometric mean VREFT value was significantly greater (P < 0.01) among naïve herring (1.2 × 10(3) PFU mL(-1) ) than among groups that survived exposure to VHSV (1.0-2.9 × 10(2) PFU mL(-1) ); additionally, the proportion of cultures with no detectable virus was significantly greater (P = 0.0002) among fish that survived exposure to VHSV (39-47%) than among naïve fish (3.3%). The optimized VREFT assay demonstrates promise for identifying VHSV exposure history and forecasting disease potential in populations of wild Pacific herring.

  20. We need more replication research - A case for test-retest reliability.

    Science.gov (United States)

    Leppink, Jimmie; Pérez-Fuster, Patricia

    2017-06-01

    Following debates in psychology on the importance of replication research, we have also started to see pleas for a more prominent role for replication research in medical education. To enable replication research, it is of paramount importance to carefully study the reliability of the instruments we use. Cronbach's alpha has been the most widely used estimator of reliability in the field of medical education, notably as some kind of quality label of test or questionnaire scores based on multiple items or of the reliability of assessment across exam stations. However, as this narrative review outlines, Cronbach's alpha or alternative reliability statistics may complement but not replace psychometric methods such as factor analysis. Moreover, multiple-item measurements should be preferred above single-item measurements, and when using single-item measurements, coefficients as Cronbach's alpha should not be interpreted as indicators of the reliability of a single item when that item is administered after fundamentally different activities, such as learning tasks that differ in content. Finally, if we want to follow up on recent pleas for more replication research, we have to start studying the test-retest reliability of the instruments we use.

  1. [Molecular combing method in the research of DNA replication parameters in isolated organs of Drosophyla melanogaster].

    Science.gov (United States)

    Ivankin, A V; Kolesnikova, T D; Demakov, S A; Andreenkov, O V; Bil'danova, E R; Andreenkova, N G; Zhimulev, I F

    2011-01-01

    Methods of physical DNA mapping and direct visualization of replication and transcription in specific regions of genome play crucial role in the researches of structural and functional organization of eukaryotic genomes. Since DNA strands in the cells are organized into high-fold structure and present as highly compacted chromosomes, the majority of these methods have lower resolution at chromosomal level. One of the approaches to enhance the resolution and mapping accuracy is the method of molecular combing. The method is based on the process of stretching and alignment of DNA molecules that are covalently attached with one of the ends to the cover glass surface. In this article we describe the major methodological steps of molecular combing and their adaptation for researches of DNA replication parameters in polyploidy and diploid tissues of Drosophyla larvae.

  2. Replicating research in ecology and evolution: feasibility, incentives, and the cost-benefit conundrum.

    Science.gov (United States)

    Nakagawa, Shinichi; Parker, Timothy H

    2015-10-28

    We believe that replicating studies in ecology and evolution is extremely valuable, but replication within species and systems is troublingly rare, and even 'quasi-replications' in different systems are often insufficient. We make a case for supporting multiple types of replications and point out that the current incentive structure needs to change if ecologists and evolutionary biologist are to value scientific replication sufficiently.

  3. 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.

  4. Making Connections: Replicating and Extending the Utility Value Intervention in the Classroom

    Science.gov (United States)

    Hulleman, Chris S.; Kosovich, Jeff J.; Barron, Kenneth E.; Daniel, David B.

    2017-01-01

    We replicated and extended prior research investigating a theoretically guided intervention based on expectancy-value theory designed to enhance student learning outcomes (e.g., Hulleman & Harackiewicz, 2009). First, we replicated prior work by demonstrating that the utility value intervention, which manipulated whether students made…

  5. A Qualitative Research on the Relationship between Prior Success and Motivation of Chinese EFL Readers

    Institute of Scientific and Technical Information of China (English)

    李艳

    2014-01-01

    In this study the author will pay attention to the relationship between the prior success of Chinese EFL readers and their motivation of reading. This essay is to investigate the question about whether prior success has a positive effect on Chinese EFL readers’motivation.

  6. Using Cinéma Vérité (Truthful Cinema to Facilitate Replication and Accountability in Psychological Research

    Directory of Open Access Journals (Sweden)

    Jerry eSuls

    2013-11-01

    Full Text Available To increase replication and accountability, it is proposed that researchers make audio/video recordings of laboratory protocols using currently available technologies, such as smart-phones. A detailed record of the procedure representing each experimental condition of the study design with simulated participants could then be posted on the internet and made accessible to researchers wanting more information about the procedures described in the research publication. Making recordings of all research participants a standard practice would be a greater challenge because of threats to internal validity and ethical concerns, however is feasible and merits a broad discussion among researchers, professional societies, IRB’s and funding organizations.

  7. Moving the Starting Line through Prior Learning Assessment (PLA). Research Brief

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    Council for Adult and Experiential Learning (NJ1), 2011

    2011-01-01

    Prior learning assessment (PLA) methods can help adult students earn college credit for what they already know. PLA can be an important offering by postsecondary degree programs because it can save students time and money. In addition, the Council for Adult and Experiential Learning's (CAEL's) "Fueling the Race to Postsecondary Success"…

  8. Studies in Historical Replication in Psychology IV: An Inquiry into the Psychological Research and Life of Gertrude Stein

    Science.gov (United States)

    Sirrine, Nicole K.; McCarthy, Shauna K.

    2008-05-01

    Gertrude Stein (1874 1946) is well known as an early twentieth century writer, but less well known is her involvement in automatic writing research. Critics of Stein’s literary works suggest that her research had a significant influence on her poetry and fiction, though Stein denied any influence. A partial replication of Stein’s 1896 study was conducted with the goal of addressing three historical questions: (1) What contributed to Stein’s involvement in automatic writing research?; (2) To what extent did Stein believe that she experienced automatic writing?; and (3) To what extent did her automatic writing research influence her later literary works?

  9. Manipulation therapy prior to diagnosis induced primary osteosarcoma metastasis--from clinical to basic research.

    Science.gov (United States)

    Wang, Jir-You; Wu, Po-Kuei; Chen, Paul Chih-Hsueh; Yen, Chuen-Chuan; Hung, Giun-Yi; Chen, Cheng-Fong; Hung, Shih-Chieh; Tsai, Shih-Fen; Liu, Chien-Lin; Chen, Tain-Hsiung; Chen, Wei-Ming

    2014-01-01

    Osteosarcoma (OS) patients who suffer manipulation therapy (MT) prior to diagnosis resulted in poor prognosis with increasing metastasis or recurrence rate. The aim of the study is to establish an in vivo model to identify the effects of MT on OS. The enrolled 235 OS patients were followed up in this study. In vivo nude mice model with tibia injection of GFP-labeled human OS cells were randomly allocated into MT(+) that with repeated massage on tumor site twice a week and no treatment as MT(-) group. The five-year survival, metastasis and recurrence rates were recorded in clinical subjects. X-ray plainfilm, micro-PET/CT scan, histopathology, serum metalloproteinase 2 (MMP2), metalloproteinase 9 (MMP9) level and human kinase domain insert receptor (KDR) pattern were assayed in mice model. The results showed that patient with MT decreased 5-year survival and higher recurrence or metastasis rate. Compatible with clinical findings, the decreased body weight (30.5 ± 0.65 g) and an increased tumor volume (8.3 ± 1.18 mm3) in MT(+) mice were observed. The increasing signal intensity over lymph node region of hind limb by micro-PET/CT and the tumor cells were detected in lung and bilateral lymph nodes only in MT(+) group. MMP2 (214 ± 9.8 ng/ml) and MMP9 (25.5 ± 1.81 ng/ml) were higher in MT(+) group than in MT(-) group (165 ± 7.8 ng/ml and 16.9 ± 1.40 ng/ml, individually) as well as KDR expression. Taking clinical observations and in vivo evidence together, MT treatment leads to poor prognosis of primary osteosarcoma; physicians should pay more attention on patients who seek MT before diagnosis.

  10. Manipulation therapy prior to diagnosis induced primary osteosarcoma metastasis--from clinical to basic research.

    Directory of Open Access Journals (Sweden)

    Jir-You Wang

    Full Text Available Osteosarcoma (OS patients who suffer manipulation therapy (MT prior to diagnosis resulted in poor prognosis with increasing metastasis or recurrence rate. The aim of the study is to establish an in vivo model to identify the effects of MT on OS. The enrolled 235 OS patients were followed up in this study. In vivo nude mice model with tibia injection of GFP-labeled human OS cells were randomly allocated into MT(+ that with repeated massage on tumor site twice a week and no treatment as MT(- group. The five-year survival, metastasis and recurrence rates were recorded in clinical subjects. X-ray plainfilm, micro-PET/CT scan, histopathology, serum metalloproteinase 2 (MMP2, metalloproteinase 9 (MMP9 level and human kinase domain insert receptor (KDR pattern were assayed in mice model. The results showed that patient with MT decreased 5-year survival and higher recurrence or metastasis rate. Compatible with clinical findings, the decreased body weight (30.5 ± 0.65 g and an increased tumor volume (8.3 ± 1.18 mm3 in MT(+ mice were observed. The increasing signal intensity over lymph node region of hind limb by micro-PET/CT and the tumor cells were detected in lung and bilateral lymph nodes only in MT(+ group. MMP2 (214 ± 9.8 ng/ml and MMP9 (25.5 ± 1.81 ng/ml were higher in MT(+ group than in MT(- group (165 ± 7.8 ng/ml and 16.9 ± 1.40 ng/ml, individually as well as KDR expression. Taking clinical observations and in vivo evidence together, MT treatment leads to poor prognosis of primary osteosarcoma; physicians should pay more attention on patients who seek MT before diagnosis.

  11. Manipulation Therapy Prior to Diagnosis Induced Primary Osteosarcoma Metastasis—From Clinical to Basic Research

    Science.gov (United States)

    Wang, Jir-You; Wu, Po-Kuei; Chen, Paul Chih-Hsueh; Yen, Chuen-Chuan; Hung, Giun-Yi; Chen, Cheng-Fong; Hung, Shih-Chieh; Tsai, Shih-Fen; Liu, Chien-Lin; Chen, Tain-Hsiung; Chen, Wei-Ming

    2014-01-01

    Osteosarcoma (OS) patients who suffer manipulation therapy (MT) prior to diagnosis resulted in poor prognosis with increasing metastasis or recurrence rate. The aim of the study is to establish an in vivo model to identify the effects of MT on OS. The enrolled 235 OS patients were followed up in this study. In vivo nude mice model with tibia injection of GFP-labeled human OS cells were randomly allocated into MT(+) that with repeated massage on tumor site twice a week and no treatment as MT(−) group. The five-year survival, metastasis and recurrence rates were recorded in clinical subjects. X-ray plainfilm, micro-PET/CT scan, histopathology, serum metalloproteinase 2 (MMP2), metalloproteinase 9 (MMP9) level and human kinase domain insert receptor (KDR) pattern were assayed in mice model. The results showed that patient with MT decreased 5-year survival and higher recurrence or metastasis rate. Compatible with clinical findings, the decreased body weight (30.5±0.65 g) and an increased tumor volume (8.3±1.18 mm3) in MT(+) mice were observed. The increasing signal intensity over lymph node region of hind limb by micro-PET/CT and the tumor cells were detected in lung and bilateral lymph nodes only in MT(+) group. MMP2 (214±9.8 ng/ml) and MMP9 (25.5±1.81 ng/ml) were higher in MT(+) group than in MT(−) group (165±7.8 ng/ml and 16.9±1.40 ng/ml, individually) as well as KDR expression. Taking clinical observations and in vivo evidence together, MT treatment leads to poor prognosis of primary osteosarcoma; physicians should pay more attention on patients who seek MT before diagnosis. PMID:24804772

  12. 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.

  13. 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.

  14. Prior authorization policies in Medicaid programs: The importance of study design and analysis on findings and outcomes from research.

    Science.gov (United States)

    Keast, Shellie L; Farmer, Kevin; Smith, Michael; Nesser, Nancy; Harrison, Donald

    2016-01-01

    U.S. State Medicaid programs for the medically indigent strive to deliver quality health care services with limited budgets. An often used cost management strategy is prior authorization of services or prescription medications. The goal of this strategy is to shape the pharmaceutical market share in the most efficient manner for the particular state Medicaid program, much like commercial managed care organizations. These policies are often scrutinized due to the population Medicaid serves, which in the past was largely composed of individuals with vulnerable health status. Unintended consequences can occur if these policies are not carried out in an appropriate manner or if they greatly restrict services. The data used for policy implementation research is prone to certain problems such as skewness and multimodality. Previous guidelines have been published regarding the best practices when analyzing these data. These guidelines were used to review the current body of literature regarding prior authorization in Medicaid. Further discussed are additional characteristics such as therapeutic areas researched and the outcomes identified. Finally, the importance of considering state-specific characteristics when reviewing individual policies and the usefulness of these results for other programs are also considered.

  15. A Call for Examining Replication and Bias in Special Education Research

    Science.gov (United States)

    Cook, Bryan G.

    2014-01-01

    Valid, scientific research is critical for ascertaining the effects of instructional techniques on learners with disabilities and for guiding effective special education practice and policy. Researchers in fields such as psychology and medicine have identified serious and widespread shortcomings in their research literatures related to replication…

  16. Incident acute pseudogout and prior bisphosphonate use: Matched case–control study in the UK-Clinical Practice Research Datalink

    Science.gov (United States)

    Roddy, Edward; Muller, Sara; Paskins, Zoe; Hider, Samantha L.; Blagojevic-Bucknall, Milisa; Mallen, Christian D.

    2017-01-01

    Abstract Oral bisphosphonates are the most commonly used drugs to treat postmenopausal osteoporosis. Acute pseudogout is anecdotally reported to occur following bisphosphonate initiation but empirical data are lacking. We investigated whether treatment with oral bisphosphonates is a risk factor for incident acute pseudogout. A matched case–control study was undertaken using data from the UK-Clinical Practice Research Datalink. Adults who consulted for incident acute pseudogout between 1987 and 2012 were each matched for gender, age at pseudogout diagnosis, and general practice to up to 4 control subjects without pseudogout. The exposure of interest was a prescription for an oral bisphosphonate issued within the 60-day period prior to the date of incident acute pseudogout. Associations between incident acute pseudogout and prior bisphosphonate prescription were examined using conditional logistic regression, adjusting for hyperparathyroidism, osteoarthritis, rheumatoid arthritis, hemochromatosis, hypophosphatasia, and prescriptions for diuretics and oral corticosteroids. Two thousand eleven acute pseudogout cases were compared with 8013 matched controls without acute pseudogout (mean age [standard deviation] 72 years [14]; 52% male). One hundred twenty-three cases (6.1%) had received an oral bisphosphonate prescription in the 60-day exposure period compared with 305 controls (3.8%) (adjusted incidence rate ratio [IRR] 1.33; 95% confidence interval [CI] 1.05–1.69). This association was stronger in females (adjusted IRR 1.49; 95% CI 1.15–1.94) and was nonsignificant in males (0.83; 0.48–1.44). Incident acute pseudogout was associated with prescription of an oral bisphosphonate in the preceding 60 days. Prescribers should be aware of acute pseudogout as a possible side effect of bisphosphonate treatment. Further research is needed to explore the risks conferred by different bisphosphonates and the mechanism underlying this association. PMID:28328803

  17. 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…

  18. Replication Research in Comparative Genre Analysis in English for Academic Purposes

    Science.gov (United States)

    Basturkmen, Helen

    2014-01-01

    In recent years a number of comparative studies based on an established approach to genre analysis have been published in the English for Academic Purposes (EAP) literature. Studies in this emerging strand of research typically aim to identify how the rhetorical structure of a particular genre (a text type) or part of a genre may vary across…

  19. Test Anxiety Reduction and Confidence Training: A Replication

    Science.gov (United States)

    Bowman, Noah; Driscoll, Richard

    2013-01-01

    This study was undertaken to replicate prior research in which a brief counter-conditioning and confidence training program was found to reduce anxiety and raise test scores. First-semester college students were screened with the Westside Test Anxiety Scale, and the 25 identified as having high or moderately-high anxiety were randomly divided…

  20. 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

  1. 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

  2. [Application of "overlay-maps" model in prior period research of ecological planning of Shanghai Expo area].

    Science.gov (United States)

    Xu, Xi; Wang, Xiao-Ming; Wang, Tian-Hou; Liu, Yi-Ning; Wang, Kai-Yun

    2009-05-01

    An ecological planning approach for Shanghai Expo 2010 was constructed based on "overlay-maps" model, and the ecological elements and GIS visualization in Shanghai Expo 2010 area were investigated and analyzed from the aspects of human comfort degree, life health, and sustainable utilization of resources. This approach included the determination of objectives for ecological planning, the selection and in situ investigation of ecological elements, the construction of eco-database, and the integrative analysis of GIS visualization, being indispensable for the prior period research of ecological planning of Expo area. Based on the present situation of soil pollution in the Expo area, a tentative scheme of soil restoration and utilization was brought forward, with the concerns of green space demand and soil secondary pollution avoidance. To protect the wild life habitats in Expo area, a demarcation of conservation areas for plants and original landscape was made. A conception of using landscape elements to optimize air temperature, humidity, and ventilation in the process of urban design was proposed, aimed to promote the human comfort degree under tropical monsoon conditions.

  3. 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.

  4. Research and Teaching: Computational Methods in General Chemistry--Perceptions of Programming, Prior Experience, and Student Outcomes

    Science.gov (United States)

    Wheeler, Lindsay B.; Chiu, Jennie L.; Grisham, Charles M.

    2016-01-01

    This article explores how integrating computational tools into a general chemistry laboratory course can influence student perceptions of programming and investigates relationships among student perceptions, prior experience, and student outcomes.

  5. Research and Teaching: Computational Methods in General Chemistry--Perceptions of Programming, Prior Experience, and Student Outcomes

    Science.gov (United States)

    Wheeler, Lindsay B.; Chiu, Jennie L.; Grisham, Charles M.

    2016-01-01

    This article explores how integrating computational tools into a general chemistry laboratory course can influence student perceptions of programming and investigates relationships among student perceptions, prior experience, and student outcomes.

  6. Adult Trade Apprentices: Exploring the Significance of Recognition of Prior Learning and Skill Sets for Earlier Completion. Research Report

    Science.gov (United States)

    Hargreaves, Jo; Blomberg, Davinia

    2015-01-01

    The nature of apprenticeships is changing. Increasing proportions of adult apprentices are prompting demand for various alternative pathways to completion. One option for an alternative pathway to accelerate completion is the use of recognition of prior learning (RPL) to identify existing skills and knowledge in combination with gap training. This…

  7. Constructing priors in synesthesia.

    Science.gov (United States)

    van Leeuwen, Tessa M

    2014-01-01

    A new theoretical framework (PPSMC) applicable to synesthesia has been proposed, in which the discrepancy between the perceptual reality of (some) synesthetic concurrents and their subjective non-veridicality is being explained. The PPSMC framework stresses the relevance of the phenomenology of synesthesia for synesthesia research-and beyond. When describing the emergence and persistence of synesthetic concurrents under PPSMC, it is proposed that precise, high-confidence priors are crucial in synesthesia. I discuss the construction of priors in synesthesia.

  8. 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.

  9. A Test-Replicate Approach to Candidate Gene Research on Addiction and Externalizing Disorders: A Collaboration Across Five Longitudinal Studies.

    Science.gov (United States)

    Samek, Diana R; Bailey, Jennifer; Hill, Karl G; Wilson, Sylia; Lee, Susanne; Keyes, Margaret A; Epstein, Marina; Smolen, Andrew; Miller, Michael; Winters, Ken C; Hawkins, J David; Catalano, Richard F; Iacono, William G; McGue, Matt

    2016-09-01

    This study presents results from a collaboration across five longitudinal studies seeking to test and replicate models of gene-environment interplay in the development of substance use and externalizing disorders (SUDs, EXT). We describe an overview of our conceptual models, plan for gene-environment interplay analyses, and present main effects results evaluating six candidate genes potentially relevant to SUDs and EXT (MAOA, 5-HTTLPR, COMT, DRD2, DAT1, and DRD4). All samples included rich longitudinal and phenotypic measurements from childhood/adolescence (ages 5-13) through early adulthood (ages 25-33); sample sizes ranged from 3487 in the test sample, to ~600-1000 in the replication samples. Phenotypes included lifetime symptom counts of SUDs (nicotine, alcohol and cannabis), adult antisocial behavior, and an aggregate externalizing disorder composite. Covariates included the first 10 ancestral principal components computed using all autosomal markers in subjects across the data sets, and age at the most recent assessment. Sex, ancestry, and exposure effects were thoroughly evaluated. After correcting for multiple testing, only one significant main effect was found in the test sample, but it was not replicated. Implications for subsequent gene-environment interplay analyses are discussed.

  10. Prior Knowledge Assessment Guide

    Science.gov (United States)

    2014-12-01

    determine the students’ extent of prior knowledge, not their reading speed or comprehension. Therefore, be sure to consider the reading and English ...backgrounds and skills to make training more effective, meaningful and efficient. Initial research in this tailored training program was on...history of developing measures of mental ability or cognitive skills for personnel selection; beginning with World War I (Zeidner & Drucker, 1988

  11. Training Of Teacher-Researcher As Prior Consideration Of Professional Training Of Pedagogues In Great Britain Abstract

    Directory of Open Access Journals (Sweden)

    Kozubovska Iryna

    2015-06-01

    Full Text Available The article is devoted to the problem of professional training of pedagogues in foreign countries. Special attention has been paid to the experience of Great Britain. It has been underlined that the teacher has to acquire thorough knowledge in profession as well as to master the methods of teaching. Nevertheless, this is not enough to reach success in a professional field. The educational system today needs a teacher-researcher. It has been proved that the process which provides scientific and educational unity by means of involving students into scientific work is stirring up in European pedagogical institutions. The problem of orientating the teachers to be on research work is considered to be the most important condition of their personal professional self-determination and professional culture. A new teacher-researcher training pattern in British higher educational system has been made. This pattern includes some interdependent components and is successful under certain pedagogic conditions: the possession of research position by a teacher-to-be; ensuring creative interaction and cooperation among students and teachers; introduction of special educative modules with research orientation; the use of project technologies; the arrangement of creative educational atmosphere; establishing friendly relationships among university teachers (lecturers, students and school teachers. The accent is made on the urgent necessity of implementation of British experience in Ukraine.

  12. Is it possible to enhance the confidence of student dietitians prior to professional placements? A design-based research model.

    Science.gov (United States)

    Ross, L J; Mitchell, L J; Williams, L T

    2017-10-01

    Student confidence is an important contributor to a successful professional placement experience. The present study aimed to evaluate a placement preparation program for student dietitians and to assess the impact on self-rated confidence with respect to commencing placements. The present study is part of a design-based research approach that involves students in a cyclic enquiry to evaluate and improve curricula. Nutrition and Dietetics students at an Australian university participated in a 1-week mandatory workshop - Pre-Placement week (PrePW), N = 98 students: in 2015 (n = 54) and 2016 (n = 44). An online survey was conducted before and after PrePW using a five-point Likert scale (1 = not confident; 5 = very confident) to assess self-rated confidence to commence placements. Mean (SD) scores were calculated. Paired and independent t-tests evaluated within- and between-group differences, respectively. Before PrePW, the mean (SD) for student confidence to commence placements overall (in all areas of practise) was 'somewhat confident' [2.9 (0.6) in 2015 and 3.0 (0.7) in 2016]. Students were least confident to commence Clinical Practice [2015: 2.5 (0.6); 2016: 2.8 (0.6)] compared to Food Service Management (FSM) [2015: 3.2 (0.9); 2016: 3.1 (0.9)] and Community and Public Health Nutrition (CPHN) [2015: 3.3 (0.9); 2016: 3.2 (0.8)]. Student feedback from PrePW 2015 was used to change the curriculum and PrePW program. The 2016 students reported significantly greater confidence within all areas of practice: Clinical Practice [3.4 (0.6)], FSM [3.7 (0.6)] and CPHN [3.8 (0.6)], including confidence to commence placements overall [3.6 (0.6)] (P confidence in preparation for professional placement. © 2017 Commonwealth of Australia. Journal of Human Nutrition and Dietetics © 2017 The British Dietetic Association Ltd.

  13. The gap between research and practice: a replication study on the HR professionals' beliefs about effective human resource practices

    NARCIS (Netherlands)

    Sanders, Karin; van Riemsdijk, Maarten; Groen, B.A.C.

    2008-01-01

    In 2002 Rynes, Colbert and Brown asked human resource (HR) professionals to what extent they agreed with various HR research findings. Responses from 959 American participants showed that there are large discrepancies between research findings and practitioners' beliefs about effective human

  14. The gap between research and practice: a replication study on the HR professionals' beliefs about effective human resource practices

    NARCIS (Netherlands)

    Sanders, Karin; Riemsdijk, van Maarten; Groen, Bianca

    2008-01-01

    In 2002 Rynes, Colbert and Brown asked human resource (HR) professionals to what extent they agreed with various HR research findings. Responses from 959 American participants showed that there are large discrepancies between research findings and practitioners' beliefs about effective human resourc

  15. 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.

  16. Fighting Prior Review.

    Science.gov (United States)

    Bowen, John

    1990-01-01

    Reviews arguments for and against prior administrative review and censorship of student expression. Suggests that prior review strips any pretense of democracy from many American educational institutions. Argues that prior review is journalistically inappropriate, educationally unsound, and practically illogical. (KEH)

  17. Modernizing Clinical Trial Eligibility Criteria: Recommendations of the American Society of Clinical Oncology-Friends of Cancer Research Organ Dysfunction, Prior or Concurrent Malignancy, and Comorbidities Working Group.

    Science.gov (United States)

    Lichtman, Stuart M; Harvey, R Donald; Damiette Smit, Marie-Anne; Rahman, Atiqur; Thompson, Michael A; Roach, Nancy; Schenkel, Caroline; Bruinooge, Suanna S; Cortazar, Patricia; Walker, Dana; Fehrenbacher, Louis

    2017-10-02

    Purpose Patients with organ dysfunction, prior or concurrent malignancies, and comorbidities are often excluded from clinical trials. Excluding patients on the basis of these factors results in clinical trial participants who are healthier and younger than the overall population of patients with cancer. Methods ASCO and Friends of Cancer Research established a multidisciplinary working group that included experts in trial design and conduct to examine how eligibility criteria could be more inclusive. The group analyzed current eligibility criteria; conducted original data analysis; considered safety concerns, potential benefits, research, and potential hurdles of this approach through discussion; and reached consensus on recommendations regarding updated eligibility criteria that prioritize inclusiveness without compromising patient safety. Results If renal toxicity and clearance are not of direct treatment-related concern, then patients with lower creatinine clearance values of > 30 mL/min should be included in trials. Inclusion of patients with mild to moderate hepatic dysfunction may be possible when the totality of the available nonclinical and clinical data indicates that inclusion is safe. Ejection fraction values should be used with investigator assessment of a patient's risk for heart failure to determine eligibility. Patients with laboratory parameters out of normal range as a result of hematologic disease should be included in trials. Measures of patient functional status should be included in trials to better assess fit versus frail patients. Conclusion Expanding inclusion of these patients will increase the number and diversity of patients in clinical trials and result in a more appropriate population of patients.

  18. 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.

  19. 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.

  20. Vector Autoregressive Models and Granger Causality in Time Series Analysis in Nursing Research: Dynamic Changes Among Vital Signs Prior to Cardiorespiratory Instability Events as an Example.

    Science.gov (United States)

    Bose, Eliezer; Hravnak, Marilyn; Sereika, Susan M

    Patients undergoing continuous vital sign monitoring (heart rate [HR], respiratory rate [RR], pulse oximetry [SpO2]) in real time display interrelated vital sign changes during situations of physiological stress. Patterns in this physiological cross-talk could portend impending cardiorespiratory instability (CRI). Vector autoregressive (VAR) modeling with Granger causality tests is one of the most flexible ways to elucidate underlying causal mechanisms in time series data. The purpose of this article is to illustrate the development of patient-specific VAR models using vital sign time series data in a sample of acutely ill, monitored, step-down unit patients and determine their Granger causal dynamics prior to onset of an incident CRI. CRI was defined as vital signs beyond stipulated normality thresholds (HR = 40-140/minute, RR = 8-36/minute, SpO2 time segment prior to onset of first CRI was chosen for time series modeling in 20 patients using a six-step procedure: (a) the uniform time series for each vital sign was assessed for stationarity, (b) appropriate lag was determined using a lag-length selection criteria, (c) the VAR model was constructed, (d) residual autocorrelation was assessed with the Lagrange Multiplier test, (e) stability of the VAR system was checked, and (f) Granger causality was evaluated in the final stable model. The primary cause of incident CRI was low SpO2 (60% of cases), followed by out-of-range RR (30%) and HR (10%). Granger causality testing revealed that change in RR caused change in HR (21%; i.e., RR changed before HR changed) more often than change in HR causing change in RR (15%). Similarly, changes in RR caused changes in SpO2 (15%) more often than changes in SpO2 caused changes in RR (9%). For HR and SpO2, changes in HR causing changes in SpO2 and changes in SpO2 causing changes in HR occurred with equal frequency (18%). Within this sample of acutely ill patients who experienced a CRI event, VAR modeling indicated that RR changes

  1. Unsuccessful attempts to replicate effects of self control operations and glucose on ego-depletion pose an interesting research question that demands explanation.

    Science.gov (United States)

    Chatzisarantis, Nikos L D; Hagger, Martin S

    2015-01-01

    The hypothesis that sugar-containing drinks counteract depletion of self-control or ego resources is elegant and provocative because it entails that the origins of ego-energy and self-control operations can be traced to a physiological substrate. However, this hypothesis has not withstood scientific scrutiny. Lange and Eggert presented two unsuccessful attempts to replicate effects of glucose on ego-depletion. Chatzisarantis and Hagger argued that inconsistent findings may be due to experimental designs that expose participants to similar acts of self-control. This methodology may not provide a rigorous test of the counteracting effects of glucose on ego-depletion because it does not control for factors (i.e., motivation) that interfere with glucose effects. In this article, we address Lange's comments and explore the possibility that findings reported by Lange and Eggert's and Hagger and Chatzisarantis' studies are consistent. In addition, we discuss a factor that researchers may wish to take into consideration when designing experiments that aim to test effects of glucose, or glucose rinsing, on ego-depletion. This factor is related to ego-depleting value of self-control tasks. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

  2. A New Replication Norm for Psychology

    Directory of Open Access Journals (Sweden)

    Etienne P LeBel

    2015-10-01

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

  3. Overcoming priors anxiety

    CERN Document Server

    D'Agostini, Giulio

    1999-01-01

    The choice of priors may become an insoluble problem if priors and Bayes' rule are not seen and accepted in the framework of subjectivism. Therefore, the meaning and the role of subjectivity in science is considered and defended from the pragmatic point of view of an ``experienced scientist''. The case for the use of subjective priors is then supported and some recommendations for routine and frontier measurement applications are given. The issue of reference priors is also considered from the practical point of view and in the general context of ``Bayesian dogmatism''.

  4. DNA replication and cancer

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  5. Arthur Prior and medieval logic

    OpenAIRE

    2012-01-01

    Though Arthur Prior is now best known for his founding of modern temporal logic and hybrid logic, much of his early philosophical career was devoted to history of logic and historical logic. This interest laid the foundations for both of his ground-breaking innovations in the 1950s and 1960s. Because of the important rôle played by Prior’s research in ancient and medieval logic in his development of temporal and hybrid logic, any student of Prior, temporal logic, or hybrid logic should be fam...

  6. Cognitive Temporal Document Priors

    NARCIS (Netherlands)

    Peetz, M.H.; de Rijke, M.

    2013-01-01

    Temporal information retrieval exploits temporal features of document collections and queries. Temporal document priors are used to adjust the score of a document based on its publication time. We consider a class of temporal document priors that is inspired by retention functions considered in cogn

  7. 数据复制在水利领域中的应用研究%Application research of data replication in water conservancy field

    Institute of Scientific and Technical Information of China (English)

    范江华

    2011-01-01

    在简要说明数据复制技术定义与特点的基础上,针对国家水利行业管理部门地理上的分布造成各个管辖区域的水利数据呈现出分散的现状,利用Oracle10g高级复制服务器,为水利资源数据分中心数据库数据维护管理系统设计了一种新的复制模型,该模型将多宿主复制模式与快照复制模式进行了有机的结合.实验结果表明,新的混合复制模型避免了传统数据复制单一模式的低效性,实现了将各个部门与总部之间以及各个部门之间的数据库联系起来,变成物理上分散、逻辑上统一的集成数据库.%Based on the brief introduction of the definition and characteristics of data replication technique, directed at the current status that the geometrically distribution of state water industry management departments results in decentralized water conservancy data, utilizing advanced replication server of Oracle l0g, a new replication model for data maintenance and management system of the branch center's database for water resources data is developed, in which multi-master replication and snapshot replication are combined organically. The results show that this new hybrid model avoids the inefficiency caused by the traditional replication model, through which databases between each department and headquarter and among them are connected to become a physically-dispersed, logically-unified integrated database.

  8. 验前信息在武器装备试验中的应用研究%Research of Application for Prior Test Information to Armament Test

    Institute of Scientific and Technical Information of China (English)

    郑锦; 张富强; 何晓明

    2011-01-01

    How to use the lots of prior test information before armament system test is the main content of this paper.It aims at distinct phyletic prior test information of armament, ascertains it distributing type, adopting parameter and non-parameter checkout method goes along the checkout of mutually contain nature.It makes that the prior test information by pretreatment can be used for test.Validating the method is science feasibility through example.This method has certain significance for the application of prior test information in the armament system test and result assessed.%针对武器装备定型试验时如何把验前积累大量的先验信息科学合理利用,根据武器装备不同种类的验前信息,确定其分布类型并采用参数和非参数检验方法进行相容性检脸,使经过预处理的验前信息能够为试验所用,并通过实例验证了该方法的科学可行性.该方法对验前信息在武器装备试验及结果评定中的应用具有一定意义.

  9. Underserved Students Who Earn Credit through Prior Learning Assessment (PLA) Have Higher Degree Completion Rates and Shorter Time-to-Degree. Research Brief

    Science.gov (United States)

    Klein-Collins, Rebecca

    2011-01-01

    In 2010, the Council for Adult and Experiential Learning (CAEL) released a report on a multi-institutional study on prior learning assessment (PLA) and adult student outcomes. The study examined data from 62,475 adult students at 48 colleges and universities, following the students' academic progress over the course of seven years. The data from…

  10. 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.

  11. 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.

  12. 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

  13. 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)

  14. 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.

  15. 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

  16. 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...

  17. 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.

  18. Comparative researches on two direct transmethylation without prior extraction methods for fatty acids analysis in vegetal matrix with low fat content

    Directory of Open Access Journals (Sweden)

    Harmanescu Monica

    2012-01-01

    Full Text Available Abstract Background The aim of our work was to compare two methods, both based on direct transmethylation with different reagents, BF3/MeOH (boron trifluoride in methanol or HCl/MeOH (hydrochloride acid in methanol, in acid catalysis, without prior extraction, to find the fast, non-expensive but enough precise method for 9 principal fatty acids (lauric, myristic, palmitic, stearic, oleic, linoleic, linolenic, arahidic and behenic acids analysis in vegetal matrix with low fat content (forage from grassland, for nutrition and agrochemical studies. Results Comparatively, between the average values obtained for all analysed fatty acids by the two methods based on direct transmethylation without prior extraction no significantly difference was identified (p > 0.05. The results of fatty acids for the same forage sample were more closely to their average value, being more homogenous for BF3/MeOH than HCl/MeOH, because of the better accuracy and repeatability of this method. Method that uses BF3/MeOH reagent produces small amounts of interfering compounds than the method using HCl/MeOH reagent, results reflected by the better statistical parameters. Conclusion The fast and non-expensive BF3/methanol method was applied with good accuracy and sensitivity for the determination of free or combined fatty acids (saturated and unsaturated in forage matrix with low fat content from grassland. Also, the final extract obtained by this method, poorer in interfering compounds, is safer to protect the injector and column from contamination with heavy or non-volatile compounds formed by transmethylation reactions.

  19. Quantitative Evidence Synthesis with Power Priors

    NARCIS (Netherlands)

    Rietbergen, C.|info:eu-repo/dai/nl/322847796

    2016-01-01

    The aim of this thesis is to provide the applied researcher with a practical approach for quantitative evidence synthesis using the conditional power prior that allows for subjective input and thereby provides an alternative tgbgo deal with the difficulties as- sociated with the joint power prior

  20. Quantitative Evidence Synthesis with Power Priors

    NARCIS (Netherlands)

    Rietbergen, C.

    2016-01-01

    The aim of this thesis is to provide the applied researcher with a practical approach for quantitative evidence synthesis using the conditional power prior that allows for subjective input and thereby provides an alternative tgbgo deal with the difficulties as- sociated with the joint power prior di

  1. Arthur Prior and 'Now'

    DEFF Research Database (Denmark)

    Blackburn, Patrick Rowan; Jørgensen, Klaus Frovin

    2015-01-01

    ’s search led him through the work of Castaneda, and back to his own work on hybrid logic: the first made temporal reference philosophically respectable, the second made it technically feasible in a modal framework. With the aid of hybrid logic, Prior built a bridge from a two-dimensional UT calculus...

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Does oxytocin affect mind-reading? A replication study.

    Science.gov (United States)

    Radke, Sina; de Bruijn, Ellen R A

    2015-10-01

    One of the most well-known findings in human oxytocin research is its beneficial effect on "mind-reading", i.e., inferring others' mental states just from the eye region in the Reading the Mind in the Eyes Test (RMET). Previous studies have partially confirmed these improvements and have further shown that they depend both on baseline social-emotional abilities and on specific item characteristics such as difficulty. Following the original design of Domes et al. (2007), the aim of the current study was to replicate and extend previous findings by thoroughly investigating the impact of oxytocin administration on RMET performance. We tested for potential moderation effects involving item difficulty, valence, intensity, sex of poser as well as individual differences in trait empathy measured with the Empathy Quotient (EQ) for a general score and the Interpersonal Reactivity Index (IRI) for a multidimensional assessment of cognitive and emotional empathy. Oxytocin did not affect mind-reading, neither in general nor when considering specific item characteristics. An association between oxytocin-induced changes in RMET performance and emotional empathy (the empathic concern scale of the IRI) was evident, with individuals low in emotional empathy showing greater improvement after oxytocin administration compared to placebo. The reproducibility and variability of these and prior findings needs to be addressed in future experiments. As true effects may not replicate across different studies for various reasons, this should not discourage, but encourage further research.

  7. 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

  8. 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.

  9. 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 ...

  10. 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...

  11. 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

  12. 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

  13. Does a single session of reading literary fiction prime enhanced mentalising performance? Four replication experiments of Kidd and Castano (2013).

    Science.gov (United States)

    Samur, Dalya; Tops, Mattie; Koole, Sander L

    2017-01-17

    Prior experiments indicated that reading literary fiction improves mentalising performance relative to reading popular fiction, non-fiction, or not reading. However, the experiments had relatively small sample sizes and hence low statistical power. To address this limitation, the present authors conducted four high-powered replication experiments (combined N = 1006) testing the causal impact of reading literary fiction on mentalising. Relative to the original research, the present experiments used the same literary texts in the reading manipulation; the same mentalising task; and the same kind of participant samples. Moreover, one experiment was pre-registered as a direct replication. In none of the experiments did reading literary fiction have any effect on mentalising relative to control conditions. The results replicate earlier findings that familiarity with fiction is positively correlated with mentalising. Taken together, the present findings call into question whether a single session of reading fiction leads to immediate improvements in mentalising.

  14. Effects of prior exposure to office noise and music on aspects of working memory.

    Science.gov (United States)

    Smith, Andrew; Waters, Beth; Jones, Hywel

    2010-01-01

    Previous research has suggested that prior exposure to noise reduces the effect of subsequent exposure due to habituation. Similarly, a number of studies have shown that exposure to Mozart's music leads to better subsequent spatial reasoning performance. Two studies were conducted to extend these findings. The first one examined whether habituation occurs to office noise (including speech) and, if so, how long it takes to develop. Thirty-six young adults participated in the first study which compared effects of office noise with quiet on the performance of a maths task. The study also examined the effects of prior exposure to the office noise on the subsequent effect of the noise. The results showed that performance was initially impaired by the office noise but that the effects of the noise were removed by 10 minutes of exposure between tasks. The second experiment attempted to replicate the "Mozart effect" which represents an improvement in spatial reasoning following listening to Mozart. The study also examined whether the Mozart effect could be explained by changes in mood. Twenty-four young adults participated in the study. The results replicated the Mozart effect and showed that it was not due to changes in mood. Overall, these results show that prior exposure to noise or music can influence aspects of working memory. Such effects need to be incorporated into models of effects of noise on cognition and attempts have to be made to eliminate alternative explanations rather than just describing changes that occur in specific contexts.

  15. Effects of prior exposure to office noise and music on aspects of working memory

    Directory of Open Access Journals (Sweden)

    Andrew Smith

    2010-01-01

    Full Text Available Previous research has suggested that prior exposure to noise reduces the effect of subsequent exposure due to habituation. Similarly, a number of studies have shown that exposure to Mozart′s music leads to better subsequent spatial reasoning performance. Two studies were conducted to extend these findings. The first one examined whether habituation occurs to office noise (including speech and, if so, how long it takes to develop. Thirty-six young adults participated in the first study which compared effects of office noise with quiet on the performance of a maths task. The study also examined the effects of prior exposure to the office noise on the subsequent effect of the noise. The results showed that performance was initially impaired by the office noise but that the effects of the noise were removed by 10 minutes of exposure between tasks. The second experiment attempted to replicate the "Mozart effect" which represents an improvement in spatial reasoning following listening to Mozart. The study also examined whether the Mozart effect could be explained by changes in mood. Twenty-four young adults participated in the study. The results replicated the Mozart effect and showed that it was not due to changes in mood. Overall, these results show that prior exposure to noise or music can influence aspects of working memory. Such effects need to be incorporated into models of effects of noise on cognition and attempts have to be made to eliminate alternative explanations rather than just describing changes that occur in specific contexts.

  16. 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.

  17. 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.

  18. Remote Acculturation of Early Adolescents in Jamaica towards European American Culture: A Replication and Extension

    Science.gov (United States)

    Ferguson, Gail M.; Bornstein, Marc H.

    2015-01-01

    Remote acculturation is a modern form of non-immigrant acculturation identified among early adolescents in Jamaica as “Americanization”. This study aimed to replicate the original remote acculturation findings in a new cohort of early adolescents in Jamaica (n = 222; M = 12.08 years) and to extend our understanding of remote acculturation by investigating potential vehicles of indirect and intermittent intercultural contact. Cluster analyses replicated prior findings: Relative to Traditional Jamaican adolescents (62%), Americanized Jamaican adolescents (38%) reported stronger European American cultural orientation, lower Jamaican orientation, lower family obligations, and greater conflict with parents. More U.S. media (girls) and less local media and local sports (all) were the primary vehicles of intercultural contact predicting higher odds of Americanization. U.S. food, U.S. tourism, and transnational communication were also linked to U.S. orientation. Findings have implications for acculturation research and for practice and policy targeting Caribbean youth and families. PMID:25709142

  19. Remote Acculturation of Early Adolescents in Jamaica towards European American Culture: A Replication and Extension.

    Science.gov (United States)

    Ferguson, Gail M; Bornstein, Marc H

    2015-03-01

    Remote acculturation is a modern form of non-immigrant acculturation identified among early adolescents in Jamaica as "Americanization". This study aimed to replicate the original remote acculturation findings in a new cohort of early adolescents in Jamaica (n = 222; M = 12.08 years) and to extend our understanding of remote acculturation by investigating potential vehicles of indirect and intermittent intercultural contact. Cluster analyses replicated prior findings: Relative to Traditional Jamaican adolescents (62%), Americanized Jamaican adolescents (38%) reported stronger European American cultural orientation, lower Jamaican orientation, lower family obligations, and greater conflict with parents. More U.S. media (girls) and less local media and local sports (all) were the primary vehicles of intercultural contact predicting higher odds of Americanization. U.S. food, U.S. tourism, and transnational communication were also linked to U.S. orientation. Findings have implications for acculturation research and for practice and policy targeting Caribbean youth and families.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. Improving public health training and research capacity in Africa: a replicable model for linking training to health and socio-demographic surveillance data

    Directory of Open Access Journals (Sweden)

    Jill R. Williams

    2010-08-01

    Full Text Available Background: Research training for public health professionals is key to the future of public health and policy in Africa. A growing number of schools of public health are connected to health and socio-demographic surveillance system field sites in developing countries, in Africa and Asia in particular. Linking training programs with these sites provides important opportunities to improve training, build local research capacity, foreground local health priorities, and increase the relevance of research to local health policy. Objective: To increase research training capacity in public health programs by providing targeted training to students and increasing the accessibility of existing data. Design: This report is a case study of an approach to linking public health research and training at the University of the Witwatersrand. We discuss the development of a sample training database from the Agincourt Health and Socio-demographic Surveillance System in South Africa and outline a concordant transnational intensive short course on longitudinal data analysis offered by the University of the Witwatersrand and the University of Colorado-Boulder. This case study highlights ways common barriers to linking research and training can be overcome. Results and Conclusions: This collaborative effort demonstrates that linking training to ongoing data collection can improve student research, accelerate student training, and connect students to an international network of scholars. Importantly, the approach can be adapted to other partnerships between schools of public health and longitudinal research sites.

  5. The interim test effect: testing prior material can facilitate the learning of new material.

    Science.gov (United States)

    Wissman, Kathryn T; Rawson, Katherine A; Pyc, Mary A

    2011-12-01

    A wealth of prior research has shown that testing can improve subsequent learning of the initially tested material. In contrast, only one recent study has shown that an interim test over prior material can improve learning of subsequent new material (i.e., an interim-test effect). Five experiments replicated and extended this initial work by exploring the extent to which interim test effects generalize to complex text material. Participants were prompted to recall each section of an expository text before moving on to study the next section, or were only prompted to recall after the final section. In all experiments, recall of the final, target section was greater when prior sections had received interim tests versus no interim tests. Experiment 3 established that the effect was due to interim testing in particular rather than to intervening activity in general. Experiment 4 established that the effect was not due to test expectancy differences. In contrast to prior research, Experiment 4 also provided evidence that the effect is not due to release from proactive interference. We discuss other possible mechanisms underlying interim-test effects with text, including shifting to more effective encoding strategies.

  6. Terminology for pregnancy loss prior to viability

    DEFF Research Database (Denmark)

    Kolte, A M; Bernardi, L A; Christiansen, O B

    2015-01-01

    Pregnancy loss prior to viability is common and research in the field is extensive. Unfortunately, terminology in the literature is inconsistent. The lack of consensus regarding nomenclature and classification of pregnancy loss prior to viability makes it difficult to compare study results from...... different centres. In our opinion, terminology and definitions should be based on clinical findings, and when possible, transvaginal ultrasound. With this Early Pregnancy Consensus Statement, it is our goal to provide clear and consistent terminology for pregnancy loss prior to viability....

  7. 条件复制型腺病毒的研究进展%Advance of research in conditionally replicating adenovirus

    Institute of Scientific and Technical Information of China (English)

    邬朝平

    2011-01-01

    条件复制型腺病毒(conditionally replicating adenovirus,CRAd)基因治疗肿瘤的研究主要集中于提高其靶向性、增强肿瘤杀伤特异性,以及降低毒性作用三个方面.在提高CRAd靶向性的研究中,早期策略主要集中在腺病毒早期复制必需基因Ela/Elb突变或缺失的调控以及肿瘤或组织特异性启动子对其转录的调控;近年来利用组织特异性microRNA对病毒早期复制必需基因的转录后调控以及病毒外壳蛋白修饰的转导调控已逐渐成为研究的热点.在提高CRAd的肿瘤杀伤方面,除删除病毒自身凋亡抑制基因与导入外源性治疗基因两种方法以外,改造外壳纤毛提高病毒对靶细胞的亲嗜性及构建靶向肿瘤干细胞的CRAd成为新的关注点.同时,随着对腺病毒结构认识的逐步加深,修饰其外壳六邻体蛋白及其他外壳蛋白以降低CRAd的肝嗜性与免疫原性也正成为降低CRAd毒性作用的研究热点.

  8. 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...

  9. 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...

  10. 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 ...

  11. 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...

  12. The Prior-project

    DEFF Research Database (Denmark)

    Engerer, Volkmar Paul; Roued-Cunliffe, Henriette; Albretsen, Jørgen

    In this paper, we present a DH research infrastructure which relies heavily on a combination of domain knowledge with information technology. The general goal is to develop tools to aid scholars in their interpretations and understanding of temporal logic. This in turn is based on an extensive di...

  13. 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

  14. Constructing an Evidence-Base for Future CALL Design with "Engineering Power": The Need for More Basic Research and Instrumental Replication

    Science.gov (United States)

    Handley, Zöe

    2014-01-01

    This paper argues that the goal of Computer-Assisted Language Learning (CALL) research should be to construct a reliable evidence-base with "engineering power" and generality upon which the design of future CALL software and activities can be based. In order to establish such an evidence base for future CALL design, it suggests that CALL…

  15. 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.

  16. 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.

  17. 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...

  18. 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…

  19. Perfectionism in Gifted Adolescents: A Replication and Extension

    Science.gov (United States)

    Margot, Kelly C.; Rinn, Anne N.

    2016-01-01

    To provide further generalizability for the results garnered by two previous studies, the authors conducted a methodological replication. In addition to adding to the body of replication research done with gifted students, the purpose of this study was to examine perfectionism differences among gifted adolescents in regards to gender, birth order,…

  20. 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.

  1. SUMO and KSHV Replication

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-09-29

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

  2. FBH1 Catalyzes Regression of Stalled Replication Forks

    Directory of Open Access Journals (Sweden)

    Kasper Fugger

    2015-03-01

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

  3. Accommodating Uncertainty in Prior Distributions

    Energy Technology Data Exchange (ETDEWEB)

    Picard, Richard Roy [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Vander Wiel, Scott Alan [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-01-19

    A fundamental premise of Bayesian methodology is that a priori information is accurately summarized by a single, precisely de ned prior distribution. In many cases, especially involving informative priors, this premise is false, and the (mis)application of Bayes methods produces posterior quantities whose apparent precisions are highly misleading. We examine the implications of uncertainty in prior distributions, and present graphical methods for dealing with them.

  4. 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

  5. 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

  6. Menarche: Prior Knowledge and Experience.

    Science.gov (United States)

    Skandhan, K. P.; And Others

    1988-01-01

    Recorded menstruation information among 305 young women in India, assessing the differences between those who did and did not have knowledge of menstruation prior to menarche. Those with prior knowledge considered menarche to be a normal physiological function and had a higher rate of regularity, lower rate of dysmenorrhea, and earlier onset of…

  7. The Importance of Prior Knowledge.

    Science.gov (United States)

    Cleary, Linda Miller

    1989-01-01

    Recounts a college English teacher's experience of reading and rereading Noam Chomsky, building up a greater store of prior knowledge. Argues that Frank Smith provides a theory for the importance of prior knowledge and Chomsky's work provided a personal example with which to interpret and integrate that theory. (RS)

  8. The Importance of Prior Knowledge.

    Science.gov (United States)

    Cleary, Linda Miller

    1989-01-01

    Recounts a college English teacher's experience of reading and rereading Noam Chomsky, building up a greater store of prior knowledge. Argues that Frank Smith provides a theory for the importance of prior knowledge and Chomsky's work provided a personal example with which to interpret and integrate that theory. (RS)

  9. 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…

  10. The effects of activating prior topic and metacognitive knowledge on text comprehension scores

    NARCIS (Netherlands)

    Kostons, Danny; van der Werf, Margaretha

    2015-01-01

    Background Research on prior knowledge activation has consistently shown that activating learners' prior knowledge has beneficial effects on learning. If learners activate their prior knowledge, this activated knowledge serves as a framework for establishing relationships between the knowledge they

  11. Depletion of acidic phospholipids influences chromosomal replication in Escherichia coli.

    Science.gov (United States)

    Fingland, Nicholas; Flåtten, Ingvild; Downey, Christopher D; Fossum-Raunehaug, Solveig; Skarstad, Kirsten; Crooke, Elliott

    2012-12-01

    In Escherichia coli, coordinated activation and deactivation of DnaA allows for proper timing of the initiation of chromosomal synthesis at the origin of replication (oriC) and assures initiation occurs once per cell cycle. In vitro, acidic phospholipids reactivate DnaA, and in vivo depletion of acidic phospholipids, results in growth arrest. Growth can be restored by the expression of a mutant form of DnaA, DnaA(L366K), or by oriC-independent DNA synthesis, suggesting acidic phospholipids are required for DnaA- and oriC-dependent replication. We observe here that when acidic phospholipids were depleted, replication was inhibited with a concomitant reduction of chromosomal content and cell mass prior to growth arrest. This global shutdown of biosynthetic activity was independent of the stringent response. Restoration of acidic phospholipid synthesis resulted in a resumption of DNA replication prior to restored growth, indicating a possible cell-cycle-specific growth arrest had occurred with the earlier loss of acidic phospholipids. Flow cytometry, thymidine uptake, and quantitative polymerase chain reaction data suggest that a deficiency in acidic phospholipids prolonged the time required to replicate the chromosome. We also observed that regardless of the cellular content of acidic phospholipids, expression of mutant DnaA(L366K) altered the DNA content-to-cell mass ratio.

  12. LHCb experience with LFC replication

    CERN Document Server

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

    2008-01-01

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

  13. 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.

  14. 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...

  15. 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…

  16. 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.

  17. 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.

  18. 新型非浸润模板法制备抗癌载药微粒的研究进展%Research progress of novel particle replication for anti-cancer biomaterials

    Institute of Scientific and Technical Information of China (English)

    罗琳; 王运灿; 王天强; 郝建原; 刘钰

    2013-01-01

    In recent years,a method to produce shape-specific nanoparticles which can load any cargo has become a hot and difficult area of research. This review starts with a brief introduction of the advanced nanoparticles,which can load any cargo. A novel method called PRINT (particle replication in non-wetting templates) can be used to design and prepare the templates through the low surface energy perfluoropolyether network. By the confined space of template,shape-controlled particles are fabricated. The method of nanofabrication and application in loading anti-cancer drug is summarized. The anti-cancer drug particles with different haspect ratios contributes to different drug release rates. This breakthrough in nanotechnology will have tremendous potential for applications in nanomedicine and diagnostics.%  近年来,能够精确控制尺寸、形态、组成的纳米微粒制备方法的研究成为科学研究的难点与热点。本文简述了一项新型的纳米微粒制备技术:非浸润模板微印制技术(PRINT,particle replication in non-wetting templates),该技术是将微细加工技术应用到材料合成领域,以不亲水不亲油的含氟材料为模板,预先根据所需微结构的尺寸、形态设计制作模板,利用模板的空间局限作用,压印制备特定尺寸、形态、取向、排布的单分散载药微粒。重点阐述了PRINT技术微粒制备的方法以及在抗癌载药微粒的制备与应用,最后总结指出由PRINT技术制备的多种不同高宽比的形态抗癌载药微粒在病体细胞中具有不同的释药效果,该项技术在纳米微粒制备领域的突破有望推动纳米医药与生物诊断研究领域的巨大发展。

  19. Universal Prior Prediction for Communication

    CERN Document Server

    Lomnitz, Yuval

    2011-01-01

    We consider the problem of communicating over an unknown and arbitrarily varying channel, using feedback. This paper focuses on the problem of determining the input behavior, or more specifically, a prior which is used to randomly generate a codebook. We pose the problem of setting the prior as a universal sequential prediction problem using information theoretic abstractions of the communication channel. For the case where the channel is block-wise constant, we show it is possible to asymptotically approach the best rate that can be attained by any system using a fixed prior. For the case where the channel may change on each symbol, we combine a rateless coding scheme with a prior predictor and asymptotically approach the capacity of the average channel universally for every sequence of channels.

  20. International Expansion through Flexible Replication

    DEFF Research Database (Denmark)

    Jonsson, Anna; Foss, Nicolai Juul

    2011-01-01

    to local environments and under the impact of new learning. To illuminate these issues, we draw on a longitudinal in-depth study of Swedish home furnishing giant IKEA, involving more than 70 interviews. We find that IKEA has developed organizational mechanisms that support an ongoing learning process aimed......, etc.) are replicated in a uniform manner across stores, and change only very slowly (if at all) in response to learning (“flexible replication”). We conclude by discussing the factors that influence the approach to replication adopted by an international replicator....

  1. Recruiting for Prior Service Market

    Science.gov (United States)

    2008-06-01

    perceptions, expectations and issues for re-enlistment • Develop potential marketing and advertising tactics and strategies targeted to the defined...01 JUN 2008 2. REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE Recruiting for Prior Service Market 5a. CONTRACT NUMBER 5b. GRANT...Command First Handshake to First Unit of Assignment An Army of One Proud to Be e e to Serve Recruiting for Prior Service Market MAJ Eric Givens / MAJ Brian

  2. Regulation of Replication Recovery and Genome Integrity

    DEFF Research Database (Denmark)

    Colding, Camilla Skettrup

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

  3. The Cell Cycle Timing of Human Papillomavirus DNA Replication.

    Science.gov (United States)

    Reinson, Tormi; Henno, Liisi; Toots, Mart; Ustav, Mart; Ustav, Mart

    2015-01-01

    Viruses manipulate the cell cycle of the host cell to optimize conditions for more efficient viral genome replication. One strategy utilized by DNA viruses is to replicate their genomes non-concurrently with the host genome; in this case, the viral genome is amplified outside S phase. This phenomenon has also been described for human papillomavirus (HPV) vegetative genome replication, which occurs in G2-arrested cells; however, the precise timing of viral DNA replication during initial and stable replication phases has not been studied. We developed a new method to quantitate newly synthesized DNA levels and used this method in combination with cell cycle synchronization to show that viral DNA replication is initiated during S phase and is extended to G2 during initial amplification but follows the replication pattern of cellular DNA during S phase in the stable maintenance phase. E1 and E2 protein overexpression changes the replication time from S only to both the S and G2 phases in cells that stably maintain viral episomes. These data demonstrate that the active synthesis and replication of the HPV genome are extended into the G2 phase to amplify its copy number and the duration of HPV genome replication is controlled by the level of the viral replication proteins E1 and E2. Using the G2 phase for genome amplification may be an important adaptation that allows exploitation of changing cellular conditions during cell cycle progression. We also describe a new method to quantify newly synthesized viral DNA levels and discuss its benefits for HPV research.

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

    NARCIS (Netherlands)

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

    2016-01-01

    textabstractWe 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

  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. Unveiling the mystery of mitochondrial DNA replication in yeasts.

    Science.gov (United States)

    Chen, Xin Jie; Clark-Walker, George Desmond

    2017-08-01

    Conventional DNA replication is initiated from specific origins and requires the synthesis of RNA primers for both the leading and lagging strands. In contrast, the replication of yeast mitochondrial DNA is origin-independent. The replication of the leading strand is likely primed by recombinational structures and proceeded by a rolling circle mechanism. The coexistent linear and circular DNA conformers facilitate the recombination-based initiation. The replication of the lagging strand is poorly understood. Re-evaluation of published data suggests that the rolling circle may also provide structures for the synthesis of the lagging-strand by mechanisms such as template switching. Thus, the coupling of recombination with rolling circle replication and possibly, template switching, may have been selected as an economic replication mode to accommodate the reductive evolution of mitochondria. Such a replication mode spares the need for conventional replicative components, including those required for origin recognition/remodelling, RNA primer synthesis and lagging-strand processing. Copyright © 2017 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

  7. 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....

  8. 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.

  9. 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.

  10. Bayesian priors for transiting planets

    CERN Document Server

    Kipping, David M

    2016-01-01

    As astronomers push towards discovering ever-smaller transiting planets, it is increasingly common to deal with low signal-to-noise ratio (SNR) events, where the choice of priors plays an influential role in Bayesian inference. In the analysis of exoplanet data, the selection of priors is often treated as a nuisance, with observers typically defaulting to uninformative distributions. Such treatments miss a key strength of the Bayesian framework, especially in the low SNR regime, where even weak a priori information is valuable. When estimating the parameters of a low-SNR transit, two key pieces of information are known: (i) the planet has the correct geometric alignment to transit and (ii) the transit event exhibits sufficient signal-to-noise to have been detected. These represent two forms of observational bias. Accordingly, when fitting transits, the model parameter priors should not follow the intrinsic distributions of said terms, but rather those of both the intrinsic distributions and the observational ...

  11. Increase in error threshold for quasispecies by heterogeneous replication accuracy

    Science.gov (United States)

    Aoki, Kazuhiro; Furusawa, Mitsuru

    2003-09-01

    In this paper we investigate the error threshold for quasispecies with heterogeneous replication accuracy. We show that the coexistence of error-free and error-prone polymerases can greatly increase the error threshold without a catastrophic loss of genetic information. We also show that the error threshold is influenced by the number of replicores. Our research suggests that quasispecies with heterogeneous replication accuracy can reduce the genetic cost of selective evolution while still producing a variety of mutants.

  12. Components of Visual Prior Entry

    Science.gov (United States)

    Schneider, Keith A.; Bavelier, Daphne

    2003-01-01

    The prior entry hypothesis contends that attention accelerates sensory processing, shortening the time to perception. Typical observations supporting the hypothesis may be explained equally well by response biases, changes in decision criteria, or sensory facilitation. In a series of experiments conducted to discriminate among the potential…

  13. Arthur Prior and medieval logic

    NARCIS (Netherlands)

    Uckelman, S.L.

    2012-01-01

    Though Arthur Prior is now best known for his founding of modern temporal logic and hybrid logic, much of his early philosophical career was devoted to history of logic and historical logic. This interest laid the foundations for both of his ground-breaking innovations in the 1950s and 1960s. Becaus

  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. 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.

  17. 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...

  18. 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.

  19. 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…

  20. 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...

  1. Quantum steganography using prior entanglement

    Energy Technology Data Exchange (ETDEWEB)

    Mihara, Takashi, E-mail: mihara@toyo.jp

    2015-06-05

    Steganography is the hiding of secret information within innocent-looking information (e.g., text, audio, image, video, etc.). A quantum version of steganography is a method based on quantum physics. In this paper, we propose quantum steganography by combining quantum error-correcting codes with prior entanglement. In many steganographic techniques, embedding secret messages in error-correcting codes may cause damage to them if the embedded part is corrupted. However, our proposed steganography can separately create secret messages and the content of cover messages. The intrinsic form of the cover message does not have to be modified for embedding secret messages. - Highlights: • Our steganography combines quantum error-correcting codes with prior entanglement. • Our steganography can separately create secret messages and the content of cover messages. • Errors in cover messages do not have affect the recovery of secret messages. • We embed a secret message in the Steane code as an example of our steganography.

  2. Hyperthermia stimulates HIV-1 replication.

    Directory of Open Access Journals (Sweden)

    Ferdinand Roesch

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

  3. Hyperthermia stimulates HIV-1 replication.

    Science.gov (United States)

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

    2012-01-01

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

  4. Cellular Responses to Replication Problems

    NARCIS (Netherlands)

    M. Budzowska (Magdalena)

    2008-01-01

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

  5. Covert Reinforcement: A Partial Replication.

    Science.gov (United States)

    Ripstra, Constance C.; And Others

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

  6. Crinivirus replication and host interactions

    Directory of Open Access Journals (Sweden)

    Zsofia A Kiss

    2013-05-01

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

  7. 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...

  8. 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...

  9. Mirror averaging with sparsity priors

    CERN Document Server

    Dalalyan, Arnak

    2010-01-01

    We consider the problem of aggregating the elements of a (possibly infinite) dictionary for building a decision procedure, that aims at minimizing a given criterion. Along with the dictionary, an independent identically distributed training sample is available, on which the performance of a given procedure can be tested. In a fairly general set-up, we establish an oracle inequality for the Mirror Averaging aggregate based on any prior distribution. This oracle inequality is applied in the context of sparse coding for different problems of statistics and machine learning such as regression, density estimation and binary classification.

  10. Panero et al. (2016): Failure to replicate methods caused the failure to replicate results.

    Science.gov (United States)

    Kidd, David Comer; Castano, Emanuele

    2017-03-01

    Contrary to Kidd and Castano (2013), Panero et al. (2016) fail to find that reading literary fiction improves performance on an advanced test of theory of mind (ToM), the Reading the Mind in the Eyes Test. However, this commentary shows that the findings presented in Panero et al. (2016) are not reliable due to two striking threats to the internal validity of their studies that were not clearly disclosed or discussed in the manuscript or supplementary materials. First, no effective strategy was implemented to ensure that participants read their assigned texts, and examination of the data revealed many participants whose reading times indicate that they were not exposed to the manipulation. Second, further examination shows that two of the largest studies contributing to Panero et al. (2016) are not valid experiments due to a clear failure of random assignment to conditions. These threats to experimental internal validity make the conclusions presented in Panero et al. (2016) untenable. After removing cases in which participants were not exposed to the manipulation and the data from the two studies without random assignment, an analysis reveals that reading literary fiction improves ToM compared to reading popular genre fiction. This result is consistent with prior studies and indicates that a failure to carefully replicate the methods of Kidd and Castano (2013) led to the failure to replicate Kidd and Castano's (2013) results. (PsycINFO Database Record

  11. 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...

  12. 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...

  13. 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.

  14. Integrating prior knowledge and structure from motion

    DEFF Research Database (Denmark)

    Guilbert, Nicolas; Aanæs, Henrik; Larsen, Rasmus

    2001-01-01

    A new approach for formulating prior knowledge in structure form motion is presented, where the structure is viewed as a 3D stochastic variable, hereby priors are more naturally expressed. It is demonstrated that this formulation is efficient for regularizing structure reconstruction via prior...... knowledge. Specifically algorithms for imposing priors in the proposed formulation are presented....

  15. Efficient β-cell regeneration by a combination of neogenesis and replication following β-cell ablation and reversal of pancreatic duct ligation.

    Science.gov (United States)

    Hao, Ergeng; Lee, Seung-Hee; Levine, Fred

    2013-11-01

    Achieving efficient β-cell regeneration is a major goal of diabetes research. Previously, we found that a combination of β-cell ablation and pancreatic duct ligation led to β-cell regeneration by direct conversion from α-cells. Here, we studied the effect of surgical reversal of the duct ligation, finding that there was a wave of β-cell replication following reversal. The combination of β-cell neogenesis prior to reversal of the duct ligation and β-cell replication following reversal resulted in efficient β-cell regeneration and eventual recovery of function. This provides an important proof of principle that efficient β-cell regeneration is possible, even from a starting point of profound β-cell ablation. This has important implications for efforts to promote β-cell regeneration.

  16. 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.

  17. Reference priors of nuisance parameters in Bayesian sequential population analysis

    CERN Document Server

    Bousquet, Nicolas

    2010-01-01

    Prior distributions elicited for modelling the natural fluctuations or the uncertainty on parameters of Bayesian fishery population models, can be chosen among a vast range of statistical laws. Since the statistical framework is defined by observational processes, observational parameters enter into the estimation and must be considered random, similarly to parameters or states of interest like population levels or real catches. The former are thus perceived as nuisance parameters whose values are intrinsically linked to the considered experiment, which also require noninformative priors. In fishery research Jeffreys methodology has been presented by Millar (2002) as a practical way to elicit such priors. However they can present wrong properties in multiparameter contexts. Therefore we suggest to use the elicitation method proposed by Berger and Bernardo to avoid paradoxical results raised by Jeffreys priors. These benchmark priors are derived here in the framework of sequential population analysis.

  18. DBR1 siRNA inhibition of HIV-1 replication

    Directory of Open Access Journals (Sweden)

    Naidu Yathi

    2005-10-01

    Full Text Available Abstract Background HIV-1 and all retroviruses are related to retroelements of simpler organisms such as the yeast Ty elements. Recent work has suggested that the yeast retroelement Ty1 replicates via an unexpected RNA lariat intermediate in cDNA synthesis. The putative genomic RNA lariat intermediate is formed by a 2'-5' phosphodiester bond, like that found in pre-mRNA intron lariats and it facilitates the minus-strand template switch during cDNA synthesis. We hypothesized that HIV-1 might also form a genomic RNA lariat and therefore that siRNA-mediated inhibition of expression of the human RNA lariat de-branching enzyme (DBR1 expression would specifically inhibit HIV-1 replication. Results We designed three short interfering RNA (siRNA molecules targeting DBR1, which were capable of reducing DBR1 mRNA expression by 80% and did not significantly affect cell viability. We assessed HIV-1 replication in the presence of DBR1 siRNA and found that DBR1 knockdown led to decreases in viral cDNA and protein production. These effects could be reversed by cotransfection of a DBR1 cDNA indicating that the inhibition of HIV-1 replication was a specific effect of DBR1 underexpression. Conclusion These data suggest that DBR1 function may be needed to debranch a putative HIV-1 genomic RNA lariat prior to completion of reverse transcription.

  19. Replication of Psycholinguistic Experiments and the Resolution of Inconsistencies.

    Science.gov (United States)

    Rákosi, Csilla

    2017-05-05

    Non-exact replications are regarded as effective tools of problem solving in psycholinguistic research because they lead to more plausible experimental results; however, they are also ineffective tools of problem solving because they trigger cumulative contradictions among different replications of an experiment. This paper intends to resolve this paradox by putting forward a metatheoretical model that clarifies the criteria with the help of which various aspects of the effectiveness of the problem solving process can be differentiated and evaluated. The key point is the reconstruction of the relationship between original experiments and their non-exact replications by introducing the concept of 'experimental complex' and analysing the problem solving strategies that the researchers apply. The workability of the proposed metatheoretical model is illustrated with the help of three case studies.

  20. 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.

  1. Learning to read words in a new language shapes the neural organization of the prior languages.

    Science.gov (United States)

    Mei, Leilei; Xue, Gui; Lu, Zhong-Lin; Chen, Chuansheng; Zhang, Mingxia; He, Qinghua; Wei, Miao; Dong, Qi

    2014-12-01

    Learning a new language entails interactions with one׳s prior language(s). Much research has shown how native language affects the cognitive and neural mechanisms of a new language, but little is known about whether and how learning a new language shapes the neural mechanisms of prior language(s). In two experiments in the current study, we used an artificial language training paradigm in combination with an fMRI to examine (1) the effects of different linguistic components (phonology and semantics) of a new language on the neural process of prior languages (i.e., native and second languages), and (2) whether such effects were modulated by the proficiency level in the new language. Results of Experiment 1 showed that when the training in a new language involved semantics (as opposed to only visual forms and phonology), neural activity during word reading in the native language (Chinese) was reduced in several reading-related regions, including the left pars opercularis, pars triangularis, bilateral inferior temporal gyrus, fusiform gyrus, and inferior occipital gyrus. Results of Experiment 2 replicated the results of Experiment 1 and further found that semantic training also affected neural activity during word reading in the subjects׳ second language (English). Furthermore, we found that the effects of the new language were modulated by the subjects׳ proficiency level in the new language. These results provide critical imaging evidence for the influence of learning to read words in a new language on word reading in native and second languages. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. 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...

  3. Genome-wide alterations of the DNA replication program during tumor progression

    Science.gov (United States)

    Arneodo, A.; Goldar, A.; Argoul, F.; Hyrien, O.; Audit, B.

    2016-08-01

    Oncogenic stress is a major driving force in the early stages of cancer development. Recent experimental findings reveal that, in precancerous lesions and cancers, activated oncogenes may induce stalling and dissociation of DNA replication forks resulting in DNA damage. Replication timing is emerging as an important epigenetic feature that recapitulates several genomic, epigenetic and functional specificities of even closely related cell types. There is increasing evidence that chromosome rearrangements, the hallmark of many cancer genomes, are intimately associated with the DNA replication program and that epigenetic replication timing changes often precede chromosomic rearrangements. The recent development of a novel methodology to map replication fork polarity using deep sequencing of Okazaki fragments has provided new and complementary genome-wide replication profiling data. We review the results of a wavelet-based multi-scale analysis of genomic and epigenetic data including replication profiles along human chromosomes. These results provide new insight into the spatio-temporal replication program and its dynamics during differentiation. Here our goal is to bring to cancer research, the experimental protocols and computational methodologies for replication program profiling, and also the modeling of the spatio-temporal replication program. To illustrate our purpose, we report very preliminary results obtained for the chronic myelogeneous leukemia, the archetype model of cancer. Finally, we discuss promising perspectives on using genome-wide DNA replication profiling as a novel efficient tool for cancer diagnosis, prognosis and personalized treatment.

  4. Assessment of unskilled adults’ prior learning – fair to whom?

    DEFF Research Database (Denmark)

    Aarkrog, Vibe

    2014-01-01

    As in many other countries, Danish adult education policy focuses on how to encourage adults for education; the most important and challenging group of adults being those with few or no formal qualifications. Assessment of prior learning (APL) is perceived as an important tool for motivating adults...... for education and training. The most important part of the adults’ prior learning has been obtained outside the formal school system, typically consisting of their work experiences. This paper discusses research that examined the meeting between on the one hand the adults’ prior learning and on the other...

  5. INFLUENCE OF PRIORS OVER MULTITYPED OBJECT IN EVOLUTIONARY CLUSTERING

    Directory of Open Access Journals (Sweden)

    L.Visalatchi

    2013-02-01

    Full Text Available In recent years, Evolutionary clustering is an evolving research area in data mining. The evolution diagnosis of any homogeneous as well as heterogeneous network will provide an overall view about the network. Applications of evolutionary clustering includes, analyzing, the social networks, information networks, about their structure, properties and behaviors. In this paper, the authors study the problem of influence of priors over multi-typed object in evolutionary clustering. Priors are defined for each type of object in a heterogeneous information network and experimental results were produced to show how consistency and quality of cluster changes according to the priors.

  6. 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.

  7. 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...

  8. 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.

  9. FANCM interacts with PCNA to promote replication traverse of DNA interstrand crosslinks.

    Science.gov (United States)

    Rohleder, Florian; Huang, Jing; Xue, Yutong; Kuper, Jochen; Round, Adam; Seidman, Michael; Wang, Weidong; Kisker, Caroline

    2016-04-20

    FANCM is a highly conserved DNA remodeling enzyme that promotes the activation of the Fanconi anemia DNA repair pathway and facilitates replication traverse of DNA interstrand crosslinks. However, how FANCM interacts with the replication machinery to promote traverse remains unclear. Here, we show that FANCM and its archaeal homolog Hef from Thermoplasma acidophilum interact with proliferating cell nuclear antigen (PCNA), an essential co-factor for DNA polymerases in both replication and repair. The interaction is mediated through a conserved PIP-box; and in human FANCM, it is strongly stimulated by replication stress. A FANCM variant carrying a mutation in the PIP-box is defective in promoting replication traverse of interstrand crosslinks and is also inefficient in promoting FANCD2 monoubiquitination, a key step of the Fanconi anemia pathway. Our data reveal a conserved interaction mode between FANCM and PCNA during replication stress, and suggest that this interaction is essential for FANCM to aid replication machines to traverse DNA interstrand crosslinks prior to post-replication repair.

  10. 24 hours prior to curtain.

    Science.gov (United States)

    Mishra, S; Rosen, C A; Murry, T

    2000-03-01

    A retrospective review was conducted of 40 singers presenting with acute voice problems prior to performance. The purpose of this study was to determine the reasons for seeking emergent voice treatment, the types of acute voice disorders, and the performance outcome. The patients were assessed by age, singing style, years of experience, chief complaint, laryngovideostroboscopic findings, and treatment regimens. The outcomes were classified as full, restricted, or no performance. The majority of patients were classical singers. Laryngovideostroboscopy frequently revealed a pattern of early glottic contact at the mid-portion of the membranous vocal fold in patients with acute laryngitis. Experienced singers uniformly sought treatment many days before their performance compared with inexperienced singers who presented closer in time to performance. Six patients initially withheld information, which had a bearing on their acute management. The results of this study suggest that there is a need to accurately diagnose and treat the singer's emergent problem and educate singers regarding early evaluation of medical problems. With modern evaluation techniques and multi-modality treatment, 85% of the singers proceeded to full performance without negative sequelae.

  11. Can Coloring Mandalas Reduce Anxiety? A Replication Study

    Science.gov (United States)

    van der Vennet, Renee; Serice, Susan

    2012-01-01

    This experimental study replicated Curry and Kasser's (2005) research that tested whether coloring a mandala would reduce anxiety. After inducing an anxious mood via a writing activity, participants were randomly assigned to three groups that colored either on a mandala design, on a plaid design, or on a blank paper. Anxiety level was measured…

  12. Reproducible and replicable CFD: it's harder than you think

    CERN Document Server

    Mesnard, Olivier

    2016-01-01

    Completing a full replication study of our previously published findings on bluff-body aerodynamics was harder than we thought. Despite the fact that we have good reproducible-research practices, sharing our code and data openly. Here's what we learned from three years, four CFD codes and hundreds of runs.

  13. Can Coloring Mandalas Reduce Anxiety? A Replication Study

    Science.gov (United States)

    van der Vennet, Renee; Serice, Susan

    2012-01-01

    This experimental study replicated Curry and Kasser's (2005) research that tested whether coloring a mandala would reduce anxiety. After inducing an anxious mood via a writing activity, participants were randomly assigned to three groups that colored either on a mandala design, on a plaid design, or on a blank paper. Anxiety level was measured…

  14. DNA breaks early in replication in B cell cancers

    Science.gov (United States)

    Research by scientists at the NCI has identified a new class of DNA sites in cells that break early in the replication process. They found that these break sites correlate with damage often seen in B cell cancers, such as diffuse large B cell lymphoma.

  15. 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....

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. The dual frontier: Patented inventions and prior scientific advance.

    Science.gov (United States)

    Ahmadpoor, Mohammad; Jones, Benjamin F

    2017-08-11

    The extent to which scientific advances support marketplace inventions is largely unknown. We study 4.8 million U.S. patents and 32 million research articles to determine the minimum citation distance between patented inventions and prior scientific advances. We find that most cited research articles (80%) link forward to a future patent. Similarly, most patents (61%) link backward to a prior research article. Linked papers and patents typically stand 2 to 4 degrees distant from the other domain. Yet, advances directly along the patent-paper boundary are notably more impactful within their own domains. The distance metric further provides a typology of the fields, institutions, and individuals involved in science-to-technology linkages. Overall, the findings are consistent with theories that emphasize substantial and fruitful connections between patenting and prior scientific inquiry. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  1. Novice and expert teachers' conceptions of learners' prior knowledge

    Science.gov (United States)

    Meyer, Helen

    2004-11-01

    This study presents comparative case studies of preservice and first-year teachers' and expert teachers' conceptions of the concept of prior knowledge. Kelly's (The Psychology of Personal Construct, New York: W.W. Norton, 1955) theory of personal constructs as discussed by Akerson, Flick, and Lederman (Journal of Research in Science Teaching, 2000, 37, 363-385) in relationship to prior knowledge underpins the study. Six teachers were selected to participate in the case studies based upon their level experience teaching science and their willingness to take part. The comparative case studies of the novice and expert teachers provide insights into (a) how novice and expert teachers understand the concept of prior knowledge and (b) how they use this knowledge to make instructional decisions. Data collection consisted of interviews, classroom observations, and document analysis. Findings suggest that novice teachers hold insufficient conceptions of prior knowledge and its role in instruction to effectively implement constructivist teaching practices. While expert teachers hold a complex conception of prior knowledge and make use of their students' prior knowledge in significant ways during instruction. A second finding was an apparent mismatch between the novice teachers' beliefs about their urban students' life experiences and prior knowledge and the wealth of knowledge the expert teachers found to draw upon.

  2. 34 CFR 642.32 - Prior experience.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false Prior experience. 642.32 Section 642.32 Education....32 Prior experience. (a)(1) The Secretary gives priority to each applicant that has conducted a... points to be awarded each eligible applicant, the Secretary considers the applicant's prior experience of...

  3. Iterated random walks with shape prior

    DEFF Research Database (Denmark)

    Pujadas, Esmeralda Ruiz; Kjer, Hans Martin; Piella, Gemma;

    2016-01-01

    We propose a new framework for image segmentation using random walks where a distance shape prior is combined with a region term. The shape prior is weighted by a confidence map to reduce the influence of the prior in high gradient areas and the region term is computed with k-means to estimate th...

  4. Research on the simulation of prior upsetting for heavy disk forgings%大型饼类锻件预镦粗工序的数值模拟研究

    Institute of Scientific and Technical Information of China (English)

    丁燕青; 高锦张; 王兴中; 马武江

    2016-01-01

    In order to solve the deformation defect, prior upsetting is split into upsetting of frustum anvil and sur-face flattening of flat anvil, and the forging process is modeled and simulated by DEFORM-3D finite element software.Based on the simulation result of stress and strain field in forging, it shows the detail about upsetting and surface flattening such as the parameters of frustum degree, reduction ratio, rotation mode of flat anvil and the down anvil shape.It obtains the rational forging parameters, provides the theoretical basis for the process de-sign of heavy disk forgings.%为了解决镦粗变形缺陷,将饼类锻件的预镦粗工序分为锥台砧镦粗和平砧端面整平两个阶段,利用DEFORM-3D计算平台建立锻造过程的有限元模型并进行仿真分析;分别从锻件内部的应力场和应变场等方面研究了锥台砧锥角和压下率对镦粗过程的影响,平砧旋转锻造方式和下砧砧形对端面整平过程的影响,以获得合理的预镦粗锻造工艺参数,指导实际生产过程.

  5. SUSPENSION OF THE PRIOR DISCIPLINARY INVESTIGATION ACCORDING TO LABOR LAW

    Directory of Open Access Journals (Sweden)

    Nicolae, GRADINARU

    2014-11-01

    Full Text Available In order to conduct the prior disciplinary investigation, the employee shall be convoked in writing by the person authorized by the employer to carry out the research, specifying the subject, date, time and place of the meeting. For this purpose the employer shall appoint a committee charged with conducting the prior disciplinary investigation. Prior disciplinary research cannot be done without the possibility of the accused person to defend himself. It would be an abuse of the employer to violate these provisions. Since the employee is entitled to formulate and sustain defence in proving innocence or lesser degree of guilt than imputed, it needs between the moment were disclosed to the employee and the one of performing the prior disciplinary investigation to be a reasonable term for the employee to be able to prepare a defence in this regard. The employee's failure to present at the convocation, without an objective reason entitles the employer to dispose the sanctioning without making the prior disciplinary investigation. The objective reason which makes the employee, that is subject to prior disciplinary investigation, unable to present to the preliminary disciplinary investigation, should be at the time of the investigation in question.

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

    Directory of Open Access Journals (Sweden)

    Chengcheng eSong

    2015-09-01

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

  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. 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.

  9. 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.

  10. 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…

  11. 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

  12. The power prior: theory and applications.

    Science.gov (United States)

    Ibrahim, Joseph G; Chen, Ming-Hui; Gwon, Yeongjin; Chen, Fang

    2015-12-10

    The power prior has been widely used in many applications covering a large number of disciplines. The power prior is intended to be an informative prior constructed from historical data. It has been used in clinical trials, genetics, health care, psychology, environmental health, engineering, economics, and business. It has also been applied for a wide variety of models and settings, both in the experimental design and analysis contexts. In this review article, we give an A-to-Z exposition of the power prior and its applications to date. We review its theoretical properties, variations in its formulation, statistical contexts for which it has been used, applications, and its advantages over other informative priors. We review models for which it has been used, including generalized linear models, survival models, and random effects models. Statistical areas where the power prior has been used include model selection, experimental design, hierarchical modeling, and conjugate priors. Frequentist properties of power priors in posterior inference are established, and a simulation study is conducted to further examine the empirical performance of the posterior estimates with power priors. Real data analyses are given illustrating the power prior as well as the use of the power prior in the Bayesian design of clinical trials.

  13. Reliability of single-item ratings of quality in higher education: a replication.

    Science.gov (United States)

    Ginns, Paul; Barrie, Simon

    2004-12-01

    Single-item ratings of the quality of instructors or subjects are widely used by higher education institutions, yet such ratings are commonly assumed to have inadequate psychometric properties. Recent research has demonstrated that reliability of such ratings can indeed be estimated, using either the correction for attenuation formula or factor analytic methods. This study replicates prior research on the reliability of single-item ratings of quality of instruction, using a different, more student-focussed approach to teaching and learning evaluation than used by previous researchers. Class average data from 1,097 classes, representing responses from 59,815 students, were analysed. At the "class" level of analysis, both methods of estimation suggested the single item of quality had high reliability: .96 using the correction for attenuation formula, and .94 using the factor analytic method. An alternative method of calculating reliability, which takes into account the hierarchical nature of the data, likewise suggested high estimated reliability (.92) of the single-item rating. These results indicate the suitability of the overall class rating for quality improvement in higher education, with a large sample.

  14. Lack of association between digit ratio (2D:4D) and assertiveness: replication in a large sample.

    Science.gov (United States)

    Voracek, Martin

    2009-12-01

    Findings regarding within-sex associations of digit ratio (2D:4D), a putative pointer to long-lasting effects of prenatal androgen action, and sexually differentiated personality traits have generally been inconsistent or unreplicable, suggesting that effects in this domain, if any, are likely small. In contrast to evidence from Wilson's important 1983 study, a forerunner of modern 2D:4D research, two recent studies in 2005 and 2008 by Freeman, et al. and Hampson, et al. showed assertiveness, a presumably male-typed personality trait, was not associated with 2D:4D; however, these studies were clearly statistically underpowered. Hence this study examined this question anew, based on a large sample of 491 men and 627 women. Assertiveness was only modestly sexually differentiated, favoring men, and a positive correlate of age and education and a negative correlate of weight and Body Mass Index among women, but not men. Replicating the two prior studies, 2D:4D was throughout unrelated to assertiveness scores. This null finding was preserved with controls for correlates of assertiveness, also in nonparametric analysis and with tests for curvilinear relations. Discussed are implications of this specific null finding, now replicated in a large sample, for studies of 2D:4D and personality in general and novel research approaches to proceed in this field.

  15. Inhibition and recovery of the replication of depurinated parvovirus DNA in mouse fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Vos, J.M.; Avalosse, B.; Su, Z.Z.; Rommelaere, J.

    1984-01-01

    Apurinic sites were introduced in the single-stranded DNA of parvovirus minute-virus-of-mice (MVM) and their effect on viral DNA synthesis was measured in mouse fibroblasts. Approximately one apurinic site per viral genome, is sufficient to block its replication in untreated cells. The exposure of host cells to a sublethal dose of UV-light 15 hours prior to virus infection, enhances their ability to support the replication of depurinated MVM. Cell preirradiation induces the apparent overcome of 10-15% of viral DNA replication blocks. These results indicate that apurinic sites prevent mammalian cells from replicating single-stranded DNA unless a recovery process is activated by cell UV-irradiation.

  16. Evidence for an asthma risk locus on chromosome Xp: a replication linkage study

    DEFF Research Database (Denmark)

    Brasch-Andersen, C; Møller, M U; Haagerup, A;

    2008-01-01

    BACKGROUND: Asthma is a complex genetic disorder characterized by chronic inflammation in the airways. Identification of genetic risk factors for asthma has been complicated due to genetic heterogeneity and influence from environmental risk factors. Despite the fact that multiple genetic linkage...... studies have been carried out the results are still conflicting and call for replication experiments. A Danish genome-wide scan has prior reported evidence for candidate regions for asthma susceptibility genes on chromosomes 1p, 5q, 6p, 12q and Xp. Linkage to chromosome 12q was later confirmed in the same...... replication sample as used in the present study. The aim of the study was to replicate linkage to candidate regions for asthma in an independent Danish sample. METHODS: We performed a replication study investigating linkage to candidate regions for asthma on chromosomes 1p36.31-p36.21, 5q15-q23.2, 6p24.3-p22...

  17. 46 CFR 195.07-90 - Vessels contracted for prior to March 1, 1968.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Vessels contracted for prior to March 1, 1968. 195.07-90 Section 195.07-90 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH... Vessels contracted for prior to March 1, 1968. (a) Vessels contracted for prior to March 1, 1968,...

  18. The Effects of Activating Prior Topic and Metacognitive Knowledge on Text Comprehension Scores

    Science.gov (United States)

    Kostons, Danny; van der Werf, Greetje

    2015-01-01

    Background: Research on prior knowledge activation has consistently shown that activating learners' prior knowledge has beneficial effects on learning. If learners activate their prior knowledge, this activated knowledge serves as a framework for establishing relationships between the knowledge they already possess and new information provided to…

  19. "Dare I Ask?": Eliciting Prior Knowledge and Its Implications for Teaching and Learning

    Science.gov (United States)

    Dávila, Liv Thorstensson

    2015-01-01

    This article examines high school teachers' engagement of newcomer English learner students' prior knowledge. Three central research questions guided this study: 1) To what extent do teachers function as mediators of their students' prior knowledge? 2) What goes into teachers' thinking about how and when to elicit prior knowledge? and 3) How do…

  20. Dengue virus replicates and accumulates in Aedes aegypti salivary glands.

    Science.gov (United States)

    Raquin, Vincent; Lambrechts, Louis

    2017-07-01

    Dengue virus (DENV) is an RNA virus transmitted among humans by mosquito vectors, mainly Aedes aegypti. DENV transmission requires viral dissemination from the mosquito midgut to the salivary glands. During this process the virus undergoes several population bottlenecks, which are stochastic reductions in population size that restrict intra-host viral genetic diversity and limit the efficiency of natural selection. Despite the implications for virus transmission and evolution, DENV replication in salivary glands has not been directly demonstrated. Here, we used a strand-specific quantitative RT-PCR assay to demonstrate that negative-strand DENV RNA is produced in Ae. aegypti salivary glands, providing conclusive evidence that viral replication occurs in this tissue. Furthermore, we showed that the concentration of DENV genomic RNA in salivary glands increases significantly over time, indicating that active replication likely replenishes DENV genetic diversity prior to transmission. These findings improve our understanding of the biological determinants of DENV fitness and evolution. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Initiation of chromosomal replication in predatory bacterium Bdellovibrio bacteriovorus

    Directory of Open Access Journals (Sweden)

    Lukasz Makowski

    2016-11-01

    Full Text Available Bdellovibrio bacteriovorus is a small Gram-negative predatory bacterium that attacks other Gram-negative bacteria, including many animal, human, and plant pathogens. This bacterium exhibits a peculiar biphasic life cycle during which two different types of cells are produced: non-replicating highly motile cells (the free-living phase and replicating cells (the intracellular-growth phase. The process of chromosomal replication in B. bacteriovorus must therefore be temporally and spatially regulated to ensure that it is coordinated with cell differentiation and cell cycle progression. Recently, B. bacteriovorus has received considerable research interest due to its intriguing life cycle and great potential as a prospective antimicrobial agent. Although we know that chromosomal replication in bacteria is mainly regulated at the initiation step, no data exists about this process in B. bacteriovorus. We report the first characterization of key elements of initiation of chromosomal replication – DnaA protein and oriC region from the predatory bacterium, B. bacteriovorus. In vitro studies using different approaches demonstrate that the B. bacteriovorus oriC (BdoriC is specifically bound and unwound by the DnaA protein. Sequence comparison of the DnaA-binding sites enabled us to propose a consensus sequence for the B. bacteriovorus DnaA box (5’-NN(A/TTCCACA-3’. Surprisingly, in vitro analysis revealed that BdoriC is also bound and unwound by the host DnaA proteins (relatively distantly related from B. bacteriovorus. We compared the architecture of the DnaA–oriC complexes (orisomes in homologous (oriC and DnaA from B. bacteriovorus and heterologous (BdoriC and DnaA from prey, E. coli or P. aeruginosa systems. This work provides important new entry points toward improving our understanding of the initiation of chromosomal replication in this predatory bacterium.

  7. A Structure Learning Algorithm for Bayesian Network Using Prior Knowledge

    Institute of Scientific and Technical Information of China (English)

    徐俊刚; 赵越; 陈健; 韩超

    2015-01-01

    Learning structure from data is one of the most important fundamental tasks of Bayesian network research. Particularly, learning optional structure of Bayesian network is a non-deterministic polynomial-time (NP) hard problem. To solve this problem, many heuristic algorithms have been proposed, and some of them learn Bayesian network structure with the help of different types of prior knowledge. However, the existing algorithms have some restrictions on the prior knowledge, such as quality restriction and use restriction. This makes it difficult to use the prior knowledge well in these algorithms. In this paper, we introduce the prior knowledge into the Markov chain Monte Carlo (MCMC) algorithm and propose an algorithm called Constrained MCMC (C-MCMC) algorithm to learn the structure of the Bayesian network. Three types of prior knowledge are defined: existence of parent node, absence of parent node, and distribution knowledge including the conditional probability distribution (CPD) of edges and the probability distribution (PD) of nodes. All of these types of prior knowledge are easily used in this algorithm. We conduct extensive experiments to demonstrate the feasibility and effectiveness of the proposed method C-MCMC.

  8. Functional uniform priors for nonlinear modeling.

    Science.gov (United States)

    Bornkamp, Björn

    2012-09-01

    This article considers the topic of finding prior distributions when a major component of the statistical model depends on a nonlinear function. Using results on how to construct uniform distributions in general metric spaces, we propose a prior distribution that is uniform in the space of functional shapes of the underlying nonlinear function and then back-transform to obtain a prior distribution for the original model parameters. The primary application considered in this article is nonlinear regression, but the idea might be of interest beyond this case. For nonlinear regression the so constructed priors have the advantage that they are parametrization invariant and do not violate the likelihood principle, as opposed to uniform distributions on the parameters or the Jeffrey's prior, respectively. The utility of the proposed priors is demonstrated in the context of design and analysis of nonlinear regression modeling in clinical dose-finding trials, through a real data example and simulation.

  9. 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.

  10. Bayesian variable selection with spherically symmetric priors

    OpenAIRE

    De Kock, M. B.; Eggers, H. C.

    2014-01-01

    We propose that Bayesian variable selection for linear parametrisations with Gaussian iid likelihoods be based on the spherical symmetry of the diagonalised parameter space. Our r-prior results in closed forms for the evidence for four examples, including the hyper-g prior and the Zellner-Siow prior, which are shown to be special cases. Scenarios of a single variable dispersion parameter and of fixed dispersion are studied, and asymptotic forms comparable to the traditional information criter...

  11. Imprinted chromosomal domains revealed by allele-specific replication timing of the GABRB3 and GABRA5 genes

    Energy Technology Data Exchange (ETDEWEB)

    LaSalle, J.; Flint, A.; Lalande, M. [Harvard Medical School, Boston, MA (United States)] [and others

    1994-09-01

    The GABRB3 and GABRA5 genes are organized as a cluster in chromosome 15q11-q13. The genes are separated by around 100 kb and arranged in opposite transcriptional orientations. The GABA{sub A} receptor cluster lies near the Angelman and Prader-Willi loci and displays asynchronous DNA replication, suggesting that this region is subject to parental imprinting. In order to further study the association between DNA replication and imprinting, allele-specific replication was assayed by fluorescence in situ hybridization with {lambda}-phage probes from the GABRB3/A5 region and a D15Z1 satellite probe to identify the parental origin of each chromosome. The replication kinetics of each allele was determined by using a flow sorter to fractionate mitogen-stimulated lymphocytes on the basis of cell cycle progression prior to FISH analysis. These kinetic studies reveal a 50-150 kb chromosomal domain extending from the middle of the GABRB3/A5 intergenic region into the GABRA5 5{prime}-UTR which displays maternal replication in early S with paternal replication delayed until the end of S. In contrast, genomic regions on either side of this maternal early replication domain exhibit the opposite pattern with paternal before maternal replication and both alleles replicating in the latter half of S. These results indicate that the GABRB3/A5 region is divided into domains in which replication timing is determined by parental origin. In addition to a loss of asynchronous replication, organization into replication timing domains is also lost in lymphocytes from maternal and paternal uniparental disomy 15 patients suggesting that a chromosome contribution from both parents is required for the establishment of the imprinted replication domains.

  12. Prior Experiences Shaping Family Science Conversations at a Nature Center

    Science.gov (United States)

    McClain, Lucy R.; Zimmerman, Heather Toomey

    2014-01-01

    Using families as the analytical focus, this study informs the field of informal science education with a focus on the role of prior experiences in family science conversations during nature walks at an outdoor-based nature center. Through video-based research, the team analyzed 16 families during walks at a nature center. Each family's prior…

  13. Penalised Complexity Priors for Stationary Autoregressive Processes

    KAUST Repository

    Sørbye, Sigrunn Holbek

    2017-05-25

    The autoregressive (AR) process of order p(AR(p)) is a central model in time series analysis. A Bayesian approach requires the user to define a prior distribution for the coefficients of the AR(p) model. Although it is easy to write down some prior, it is not at all obvious how to understand and interpret the prior distribution, to ensure that it behaves according to the users\\' prior knowledge. In this article, we approach this problem using the recently developed ideas of penalised complexity (PC) priors. These prior have important properties like robustness and invariance to reparameterisations, as well as a clear interpretation. A PC prior is computed based on specific principles, where model component complexity is penalised in terms of deviation from simple base model formulations. In the AR(1) case, we discuss two natural base model choices, corresponding to either independence in time or no change in time. The latter case is illustrated in a survival model with possible time-dependent frailty. For higher-order processes, we propose a sequential approach, where the base model for AR(p) is the corresponding AR(p-1) model expressed using the partial autocorrelations. The properties of the new prior distribution are compared with the reference prior in a simulation study.

  14. 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...

  15. 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.

  16. How frog embryos replicate their DNA reliably

    Science.gov (United States)

    Bechhoefer, John; Marshall, Brandon

    2007-03-01

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

  17. Just War Theory and Presidential Discourse Prior to Conflict

    Science.gov (United States)

    2014-12-04

    addresses prior to US intervention and War. The method used in this monograph is a structured focused comparison utilizing seven research questions...method used in this monograph is a structured focused comparison utilizing seven research questions applied to five case studies from 1983 to 2013 and...Fisher’s work and not enter the debate over the Middle Age, Modern, or Theological interpretations of whether or not war, or aggression, is itself a

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  19. 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.

  20. Research

    African Journals Online (AJOL)

    raoul

    2012-04-11

    Apr 11, 2012 ... Physical measurements were ... confounders including fever, glycosuria, hematuria, urinary tract infection, and exercise prior to test. .... Parving HH, Hommel E. High blood pressure is a major factor in progression of diabetic ...

  1. Research

    African Journals Online (AJOL)

    abp

    2015-02-10

    Feb 10, 2015 ... screening blood/blood products prior to transfusion include ... assay (ELISA) and nucleic acid test (NAT) or polymerase chain reaction (PCR) ... transported in cold boxes to Komfo Anokye Teaching Hospital and stored at -20 ...

  2. Seismicity prior to the 2016 Kumamoto earthquakes

    CERN Document Server

    Nanjo, K Z; Orihara, Y; Furuse, N; Togo, S; Nitta, H; Okada, T; Tanaka, R; Kamogawa, M; Nagao, T

    2016-01-01

    The 2016 Kumamoto earthquakes occurred under circumstance that seismicity remains high in all parts of Japan since the 2011 Tohoku-Oki earthquake. Identifying what happened before this incident is one starting point for promote earthquake forecast research to prepare for subsequent large earthquakes in the near future in Japan. Here we report precursory seismic patterns prior to the Kumamoto earthquakes, measured by four different methods based on seismicity changes that can be used for earthquake forecasting: b-value method, two kinds of seismic quiescence evaluation methods, and a method of detailed foreshock evaluation. The spatial extent of precursory patterns differs from one method to the other and ranges from local scales (typically asperity size), to regional scales (e.g., 2{\\deg} x 3{\\deg} around the source zone). The earthquakes are preceded by periods of pronounced anomalies, which lasted decade scales (e.g., 20 years or longer) to yearly scales (e.g., 1~2 years). We demonstrate that combination of...

  3. Relationship between Prior Knowledge and Reading Comprehension

    Science.gov (United States)

    Abdelaal, Noureldin Mohamed; Sase, Amal Saleh

    2014-01-01

    This study investigates the relationship between prior knowledge and reading comprehension in second language among postgraduate students in UPM. Participants in the study were 20 students who have the same level in English as a second language from several faculties. On the basis of a prior-knowledge questionnaire and test, students were…

  4. Signaling Without Common Prior : An Experiment

    NARCIS (Netherlands)

    Drouvelis, M.; Müller, W.; Possajennikov, A.

    2009-01-01

    The common prior assumption is pervasive in game-theoretic models with incomplete information. This paper investigates experimentally the importance of inducing a common prior in a two-person signaling game. For a specific probability distribution of the sender’s type, the long-run behavior without

  5. Signaling Without Common Prior : An Experiment

    NARCIS (Netherlands)

    Drouvelis, M.; Müller, W.; Possajennikov, A.

    2009-01-01

    The common prior assumption is pervasive in game-theoretic models with incomplete information. This paper investigates experimentally the importance of inducing a common prior in a two-person signaling game. For a specific probability distribution of the sender’s type, the long-run behavior without

  6. Improving Open Access through Prior Learning Assessment

    Science.gov (United States)

    Yin, Shuangxu; Kawachi, Paul

    2013-01-01

    This paper explores and presents new data on how to improve open access in distance education through using prior learning assessments. Broadly there are three types of prior learning assessment (PLAR): Type-1 for prospective students to be allowed to register for a course; Type-2 for current students to avoid duplicating work-load to gain…

  7. On Node Replication Attack in Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    Mumtaz Qabulio

    2016-04-01

    Full Text Available WSNs (Wireless Sensor Networks comprise a large number of small, inexpensive, low power and memory constrained sensing devices (called sensor nodes that are densely deployed to measure a given physical phenomenon. Since WSNs are commonly deployed in a hostile and unattended environment, it is easy for an adversary to physically capture one or more legitimate sensor nodes, re-program and redeploy them in the network. As a result, the adversary becomes able to deploy several identical copies of physically captured nodes in the network in order to perform illegitimate activities. This type of attack is referred to as Node Replication Attack or Clone Node Attack. By launching node replication attack, an adversary can easily get control on the network which consequently is the biggest threat to confidentiality, integrity and availability of data and services. Thus, detection and prevention of node replication attack in WSNs has become an active area of research and to date more than two dozen schemes have been proposed, which address this issue. In this paper, we present a comprehensive review, classification and comparative analysis of twenty five of these schemes which help to detect and/or prevent node replication attack in WSNs

  8. Replicated Risk Nicotinic Cholinergic Receptor Genes for Nicotine Dependence

    Directory of Open Access Journals (Sweden)

    Lingjun Zuo

    2016-11-01

    Full Text Available It has been hypothesized that the nicotinic acetylcholine receptors (nAChRs play important roles in nicotine dependence (ND and influence the number of cigarettes smoked per day (CPD in smokers. We compiled the associations between nicotinic cholinergic receptor genes (CHRNs and ND/CPD that were replicated across different studies, reviewed the expression of these risk genes in human/mouse brains, and verified their expression using independent samples of both human and mouse brains. The potential functions of the replicated risk variants were examined using cis-eQTL analysis or predicted using a series of bioinformatics analyses. We found replicated and significant associations for ND/CPD at 19 SNPs in six genes in three genomic regions (CHRNB3-A6, CHRNA5-A3-B4 and CHRNA4. These six risk genes are expressed in at least 18 distinct areas of the human/mouse brain, with verification in our independent human and mouse brain samples. The risk variants might influence the transcription, expression and splicing of the risk genes, alter RNA secondary or protein structure. We conclude that the replicated associations between CHRNB3-A6, CHRNA5-A3-B4, CHRNA4 and ND/CPD are very robust. More research is needed to examine how these genetic variants contribute to the risk for ND/CPD.

  9. Replicated Risk Nicotinic Cholinergic Receptor Genes for Nicotine Dependence

    Science.gov (United States)

    Zuo, Lingjun; Garcia-Milian, Rolando; Guo, Xiaoyun; Zhong, Chunlong; Tan, Yunlong; Wang, Zhiren; Wang, Jijun; Wang, Xiaoping; Kang, Longli; Lu, Lu; Chen, Xiangning; Li, Chiang-Shan R.; Luo, Xingguang

    2016-01-01

    It has been hypothesized that the nicotinic acetylcholine receptors (nAChRs) play important roles in nicotine dependence (ND) and influence the number of cigarettes smoked per day (CPD) in smokers. We compiled the associations between nicotinic cholinergic receptor genes (CHRNs) and ND/CPD that were replicated across different studies, reviewed the expression of these risk genes in human/mouse brains, and verified their expression using independent samples of both human and mouse brains. The potential functions of the replicated risk variants were examined using cis-eQTL analysis or predicted using a series of bioinformatics analyses. We found replicated and significant associations for ND/CPD at 19 SNPs in six genes in three genomic regions (CHRNB3-A6, CHRNA5-A3-B4 and CHRNA4). These six risk genes are expressed in at least 18 distinct areas of the human/mouse brain, with verification in our independent human and mouse brain samples. The risk variants might influence the transcription, expression and splicing of the risk genes, alter RNA secondary or protein structure. We conclude that the replicated associations between CHRNB3-A6, CHRNA5-A3-B4, CHRNA4 and ND/CPD are very robust. More research is needed to examine how these genetic variants contribute to the risk for ND/CPD. PMID:27827986

  10. 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.

  11. Replicated Risk Nicotinic Cholinergic Receptor Genes for Nicotine Dependence.

    Science.gov (United States)

    Zuo, Lingjun; Garcia-Milian, Rolando; Guo, Xiaoyun; Zhong, Chunlong; Tan, Yunlong; Wang, Zhiren; Wang, Jijun; Wang, Xiaoping; Kang, Longli; Lu, Lu; Chen, Xiangning; Li, Chiang-Shan R; Luo, Xingguang

    2016-11-07

    It has been hypothesized that the nicotinic acetylcholine receptors (nAChRs) play important roles in nicotine dependence (ND) and influence the number of cigarettes smoked per day (CPD) in smokers. We compiled the associations between nicotinic cholinergic receptor genes (CHRNs) and ND/CPD that were replicated across different studies, reviewed the expression of these risk genes in human/mouse brains, and verified their expression using independent samples of both human and mouse brains. The potential functions of the replicated risk variants were examined using cis-eQTL analysis or predicted using a series of bioinformatics analyses. We found replicated and significant associations for ND/CPD at 19 SNPs in six genes in three genomic regions (CHRNB3-A6, CHRNA5-A3-B4 and CHRNA4). These six risk genes are expressed in at least 18 distinct areas of the human/mouse brain, with verification in our independent human and mouse brain samples. The risk variants might influence the transcription, expression and splicing of the risk genes, alter RNA secondary or protein structure. We conclude that the replicated associations between CHRNB3-A6, CHRNA5-A3-B4,CHRNA4 and ND/CPD are very robust. More research is needed to examine how these genetic variants contribute to the risk for ND/CPD.

  12. Professional nursing burnout and irrational thinking: a replication study.

    Science.gov (United States)

    Balevre, Park S; Cassells, Julie; Buzaianu, Elena

    2012-01-01

    This expanded (n = 648) replication study examines job-related burnout in practicing nurses in relation to five maladaptive thinking patterns at eight northeast Florida hospitals. Data supported the hypothesis that maladaptive thinking patterns may be related to nurses' burnout thoughts and behaviors. The focus of this research spotlights the individual nurse's thoughts, emotions, and actions and suggests that these burnout tendencies can be mitigated if not changed.

  13. Vaccine-Induced Enhancement of EIAV Replication and Disease

    Science.gov (United States)

    1994-01-14

    including dengue virus, respiratory syncytial virus, and feline infectious peritonitis virus (Porterfield 1986). In many of these cases, the enhancement...funding was to initiate the expansion of ongoing research in which the equine infectious anemia virus (EIAV)/Shetland pony animal lentivirus system is...enhancement of EIAV replication and disease. 14. SUBJECT TERMS 15. NUMBER OF PAGES AIDS vaccines, equine infectious anemia virus, 16. PRICE CODE

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. Nucleosome occupancy as a novel chromatin parameter for replication origin functions

    Science.gov (United States)

    Rodriguez, Jairo; Lee, Laura; Lynch, Bryony; Tsukiyama, Toshio

    2017-01-01

    Eukaryotic DNA replication initiates from multiple discrete sites in the genome, termed origins of replication (origins). Prior to S phase, multiple origins are poised to initiate replication by recruitment of the pre-replicative complex (pre-RC). For proper replication to occur, origin activation must be tightly regulated. At the population level, each origin has a distinct firing time and frequency of activation within S phase. Many studies have shown that chromatin can strongly influence initiation of DNA replication. However, the chromatin parameters that affect properties of origins have not been thoroughly established. We found that nucleosome occupancy in G1 varies greatly around origins across the S. cerevisiae genome, and nucleosome occupancy around origins significantly correlates with the activation time and efficiency of origins, as well as pre-RC formation. We further demonstrate that nucleosome occupancy around origins in G1 is established during transition from G2/M to G1 in a pre-RC-dependent manner. Importantly, the diminished cell-cycle changes in nucleosome occupancy around origins in the orc1-161 mutant are associated with an abnormal global origin usage profile, suggesting that proper establishment of nucleosome occupancy around origins is a critical step for regulation of global origin activities. Our work thus establishes nucleosome occupancy as a novel and key chromatin parameter for proper origin regulation. PMID:27895110

  19. 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.

  20. Bayesian generalized linear mixed modeling of Tuberculosis using informative priors.

    Science.gov (United States)

    Ojo, Oluwatobi Blessing; Lougue, Siaka; Woldegerima, Woldegebriel Assefa

    2017-01-01

    TB is rated as one of the world's deadliest diseases and South Africa ranks 9th out of the 22 countries with hardest hit of TB. Although many pieces of research have been carried out on this subject, this paper steps further by inculcating past knowledge into the model, using Bayesian approach with informative prior. Bayesian statistics approach is getting popular in data analyses. But, most applications of Bayesian inference technique are limited to situations of non-informative prior, where there is no solid external information about the distribution of the parameter of interest. The main aim of this study is to profile people living with TB in South Africa. In this paper, identical regression models are fitted for classical and Bayesian approach both with non-informative and informative prior, using South Africa General Household Survey (GHS) data for the year 2014. For the Bayesian model with informative prior, South Africa General Household Survey dataset for the year 2011 to 2013 are used to set up priors for the model 2014.

  1. Colorization by classifying the prior knowledge

    Institute of Scientific and Technical Information of China (English)

    DU Weiwei

    2011-01-01

    When a one-dimensional luminance scalar is replaced by a vector of a colorful multi-dimension for every pixel of a monochrome image,the process is called colorization.However,colorization is under-constrained.Therefore,the prior knowledge is considered and given to the monochrome image.Colorization using optimization algorithm is an effective algorithm for the above problem.However,it cannot effectively do with some images well without repeating experiments for confirming the place of scribbles.In this paper,a colorization algorithm is proposed,which can automatically generate the prior knowledge.The idea is that firstly,the prior knowledge crystallizes into some points of the prior knowledge which is automatically extracted by downsampling and upsampling method.And then some points of the prior knowledge are classified and given with corresponding colors.Lastly,the color image can be obtained by the color points of the prior knowledge.It is demonstrated that the proposal can not only effectively generate the prior knowledge but also colorize the monochrome image according to requirements of user with some experiments.

  2. Study on the micro-replication of shark skin

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

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

  3. 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

  4. A 4-study replication of the moderating effects of greed on socioeconomic status and unethical behaviour.

    Science.gov (United States)

    Balakrishnan, Anjana; Palma, Paolo A; Patenaude, Joshua; Campbell, Lorne

    2017-01-31

    Four replications of Piff and colleagues' study examined the moderating effects of greed attitudes on the relationship between socio-economic status (SES) and unethical behaviour (Study 7). In the original study, the researchers found that both greed and SES predicted increased propensity to engage in unethical behavior. Furthermore, this association was moderated such that the effects of SES on unethical behaviour were no longer present in the greed prime condition versus the neutral condition. In replication 1 of the original study main effects of greed attitudes and SES were found, but no interaction was found. Main effects for greed emerged in replications 3 and 4. However no main effects for SES or interactions emerged for replications 2-4. A meta-analysis was conducted with all replications and the original study, and found no moderating effect of greed on the relationship between SES and unethical behavior.

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

    Directory of Open Access Journals (Sweden)

    Koonin Eugene V

    2006-12-01

    help of the archaeal system, and viruses with the bacterial system never took off. I further suggest that the two other systems of DNA replication, the rolling circle mechanism and the protein-primed mechanism, which are represented in diverse selfish elements, also evolved prior to the emergence of the bacterial replication system. This hypothesis is compatible with the distinct structural affinities of PolB, which has the palm-domain fold shared with reverse transcriptases and RNA-dependent RNA polymerases, and PolC that has a distinct, unrelated nucleotidyltransferase fold. I propose that PolB is a descendant of polymerases that were involved in the replication of genetic elements in the RNA-protein world, prior to the emergence of DNA replication. By contrast, PolC might have evolved from an ancient non-templated polymerase, e.g., polyA polymerase. The proposed temporal succession of the evolving DNA replication systems does not depend on the specific scenario adopted for the evolution of cells and viruses, i.e., whether viruses are derived from cells or virus-like elements are thought to originate from a primordial gene pool. However, arguments are presented in favor of the latter scenario as the most parsimonious explanation of the evolution of DNA replication systems. Conclusion Comparative analysis of the diversity of genomic strategies and organizations of viruses and cellular life forms has the potential to open windows into the deep past of life's evolution, especially, with the regard to the origin of genome replication systems. When complemented with information on the evolution of the relevant protein folds, this comparative approach can yield credible scenarios for very early steps of evolution that otherwise appear to be out of reach. Reviewers Eric Bapteste, Patrick Forterre, and Mark Ragan.

  6. A Simulation of Pell Grant Awards and Costs Using Prior-Prior Year Financial Data

    Science.gov (United States)

    Kelchen, Robert; Jones, Gigi

    2015-01-01

    We examine the likely implications of switching from a prior year (PY) financial aid system, the current practice in which students file the Free Application for Federal Student Aid (FAFSA) using income data from the previous tax year, to prior-prior year (PPY), in which data from two years before enrollment is used. While PPY allows students to…

  7. 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.

  8. The pathological consequences of impaired genome integrity in humans; disorders of the DNA replication machinery.

    Science.gov (United States)

    O'Driscoll, Mark

    2017-01-01

    Accurate and efficient replication of the human genome occurs in the context of an array of constitutional barriers, including regional topological constraints imposed by chromatin architecture and processes such as transcription, catenation of the helical polymer and spontaneously generated DNA lesions, including base modifications and strand breaks. DNA replication is fundamentally important for tissue development and homeostasis; differentiation programmes are intimately linked with stem cell division. Unsurprisingly, impairments of the DNA replication machinery can have catastrophic consequences for genome stability and cell division. Functional impacts on DNA replication and genome stability have long been known to play roles in malignant transformation through a variety of complex mechanisms, and significant further insights have been gained from studying model organisms in this context. Congenital hypomorphic defects in components of the DNA replication machinery have been and continue to be identified in humans. These disorders present with a wide range of clinical features. Indeed, in some instances, different mutations in the same gene underlie different clinical presentations. Understanding the origin and molecular basis of these features opens a window onto the range of developmental impacts of suboptimal DNA replication and genome instability in humans. Here, I will briefly overview the basic steps involved in DNA replication and the key concepts that have emerged from this area of research, before switching emphasis to the pathological consequences of defects within the DNA replication network; the human disorders. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  9. DNA replication restart and cellular dynamics of Hef helicase/nuclease protein in Haloferax volcanii.

    Science.gov (United States)

    Lestini, Roxane; Delpech, Floriane; Myllykallio, Hannu

    2015-11-01

    Understanding how frequently spontaneous replication arrests occur and how archaea deal with these arrests are very interesting and challenging research topics. Here we will described how genetic and imaging studies have revealed the central role of the archaeal helicase/nuclease Hef belonging to the XPF/MUS81/FANCM family of endonucleases in repair of arrested replication forks. Special focus will be on description of a recently developed combination of genetic and imaging tools to study the dynamic localization of a functional Hef::GFP (Green Fluorescent Protein) fusion protein in the living cells of halophilic archaea Haloferax volcanii. As Archaea provide an excellent and unique model for understanding how DNA replication is regulated to allow replication of a circular DNA molecule either from single or multiple replication origins, we will also summarize recent studies that have revealed peculiar features regarding DNA replication, particularly in halophilic archaea. We strongly believe that fundamental knowledge of our on-going studies will shed light on the evolutionary history of the DNA replication machinery and will help to establish general rules concerning replication restart and the key role of recombination proteins not only in bacteria, yeast and higher eukaryotes but also in archaea.

  10. Open chromatin encoded in DNA sequence is the signature of 'master' replication origins in human cells.

    Science.gov (United States)

    Audit, Benjamin; Zaghloul, Lamia; Vaillant, Cédric; Chevereau, Guillaume; d'Aubenton-Carafa, Yves; Thermes, Claude; Arneodo, Alain

    2009-10-01

    For years, progress in elucidating the mechanisms underlying replication initiation and its coupling to transcriptional activities and to local chromatin structure has been hampered by the small number (approximately 30) of well-established origins in the human genome and more generally in mammalian genomes. Recent in silico studies of compositional strand asymmetries revealed a high level of organization of human genes around 1000 putative replication origins. Here, by comparing with recently experimentally identified replication origins, we provide further support that these putative origins are active in vivo. We show that regions approximately 300-kb wide surrounding most of these putative replication origins that replicate early in the S phase are hypersensitive to DNase I cleavage, hypomethylated and present a significant enrichment in genomic energy barriers that impair nucleosome formation (nucleosome-free regions). This suggests that these putative replication origins are specified by an open chromatin structure favored by the DNA sequence. We discuss how this distinctive attribute makes these origins, further qualified as 'master' replication origins, priviledged loci for future research to decipher the human spatio-temporal replication program. Finally, we argue that these 'master' origins are likely to play a key role in genome dynamics during evolution and in pathological situations.

  11. 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.

  12. 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.

  13. Prior Authorization of PMDs Demonstration - Status Update

    Data.gov (United States)

    U.S. Department of Health & Human Services — CMS implemented a Prior Authorization process for scooters and power wheelchairs for people with Fee-For-Service Medicare who reside in seven states with high...

  14. Modeling and validating Bayesian accrual models on clinical data and simulations using adaptive priors.

    Science.gov (United States)

    Jiang, Yu; Simon, Steve; Mayo, Matthew S; Gajewski, Byron J

    2015-02-20

    Slow recruitment in clinical trials leads to increased costs and resource utilization, which includes both the clinic staff and patient volunteers. Careful planning and monitoring of the accrual process can prevent the unnecessary loss of these resources. We propose two hierarchical extensions to the existing Bayesian constant accrual model: the accelerated prior and the hedging prior. The new proposed priors are able to adaptively utilize the researcher's previous experience and current accrual data to produce the estimation of trial completion time. The performance of these models, including prediction precision, coverage probability, and correct decision-making ability, is evaluated using actual studies from our cancer center and simulation. The results showed that a constant accrual model with strongly informative priors is very accurate when accrual is on target or slightly off, producing smaller mean squared error, high percentage of coverage, and a high number of correct decisions as to whether or not continue the trial, but it is strongly biased when off target. Flat or weakly informative priors provide protection against an off target prior but are less efficient when the accrual is on target. The accelerated prior performs similar to a strong prior. The hedging prior performs much like the weak priors when the accrual is extremely off target but closer to the strong priors when the accrual is on target or only slightly off target. We suggest improvements in these models and propose new models for future research. Copyright © 2014 John Wiley & Sons, Ltd.

  15. 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...

  16. 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.

  17. 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.

  18. 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...

  19. 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...

  20. Inference with the Median of a Prior

    Directory of Open Access Journals (Sweden)

    Ali Mohammad-Djafari

    2006-06-01

    Full Text Available We consider the problem of inference on one of the two parameters of a probability distribution when we have some prior information on a nuisance parameter. When a prior probability distribution on this nuisance parameter is given, the marginal distribution is the classical tool to account for it. If the prior distribution is not given, but we have partial knowledge such as a fixed number of moments, we can use the maximum entropy principle to assign a prior law and thus go back to the previous case. In this work, we consider the case where we only know the median of the prior and propose a new tool for this case. This new inference tool looks like a marginal distribution. It is obtained by first remarking that the marginal distribution can be considered as the mean value of the original distribution with respect to the prior probability law of the nuisance parameter, and then, by using the median in place of the mean.

  1. Transferring visual prior for online object tracking.

    Science.gov (United States)

    Wang, Qing; Chen, Feng; Yang, Jimei; Xu, Wenli; Yang, Ming-Hsuan

    2012-07-01

    Visual prior from generic real-world images can be learned and transferred for representing objects in a scene. Motivated by this, we propose an algorithm that transfers visual prior learned offline for online object tracking. From a collection of real-world images, we learn an overcomplete dictionary to represent visual prior. The prior knowledge of objects is generic, and the training image set does not necessarily contain any observation of the target object. During the tracking process, the learned visual prior is transferred to construct an object representation by sparse coding and multiscale max pooling. With this representation, a linear classifier is learned online to distinguish the target from the background and to account for the target and background appearance variations over time. Tracking is then carried out within a Bayesian inference framework, in which the learned classifier is used to construct the observation model and a particle filter is used to estimate the tracking result sequentially. Experiments on a variety of challenging sequences with comparisons to several state-of-the-art methods demonstrate that more robust object tracking can be achieved by transferring visual prior.

  2. Varying prior information in Bayesian inversion

    Science.gov (United States)

    Walker, Matthew; Curtis, Andrew

    2014-06-01

    Bayes' rule is used to combine likelihood and prior probability distributions. The former represents knowledge derived from new data, the latter represents pre-existing knowledge; the Bayesian combination is the so-called posterior distribution, representing the resultant new state of knowledge. While varying the likelihood due to differing data observations is common, there are also situations where the prior distribution must be changed or replaced repeatedly. For example, in mixture density neural network (MDN) inversion, using current methods the neural network employed for inversion needs to be retrained every time prior information changes. We develop a method of prior replacement to vary the prior without re-training the network. Thus the efficiency of MDN inversions can be increased, typically by orders of magnitude when applied to geophysical problems. We demonstrate this for the inversion of seismic attributes in a synthetic subsurface geological reservoir model. We also present results which suggest that prior replacement can be used to control the statistical properties (such as variance) of the final estimate of the posterior in more general (e.g., Monte Carlo based) inverse problem solutions.

  3. AcMNPV As A Model for Baculovirus DNA Replication

    Institute of Scientific and Technical Information of China (English)

    Eric B. Carstens

    2009-01-01

    Baculoviruses were first identified as insect-specific pathogens, and it was this specificity that lead to their use as safe, target specific biological pesticides. For the past 30 years, AcMNPV has served as the subject of intense basic molecular research into the baculovirus infectious cycle including the interaction of the virus with a continuous insect cell line derived from Spodoptera frugiperda. The studies on baculoviruese have led to an in-depth understanding of the physical organization of the viral genomes including many complete genomic sequences, the time course of gene expression, and the application of this basic research to the use of baculoviruses not only as insecticides, but also as a universal eukaryotic protein expression system, and a potential vector in gene therapy. A great deal has also been discovered about the viral genes required for the replication of the baculovirus genome, while much remains to be learned about the mechanism of viral DNA replication. This report outlines the current knowledge of the factors involved in baculovirus DNA replication, using data on AcMNPV as a model for most members of the Baculoviridae.

  4. 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.

  5. 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

  6. 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

  7. 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...

  8. 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.

  9. Porcine Epidemic Diarrhea Virus Induces Autophagy to Benefit Its Replication

    Directory of Open Access Journals (Sweden)

    Xiaozhen Guo

    2017-03-01

    Full Text Available The new porcine epidemic diarrhea (PED has caused devastating economic losses to the swine industry worldwide. Despite extensive research on the relationship between autophagy and virus infection, the concrete role of autophagy in porcine epidemic diarrhea virus (PEDV infection has not been reported. In this study, autophagy was demonstrated to be triggered by the effective replication of PEDV through transmission electron microscopy, confocal microscopy, and Western blot analysis. Moreover, autophagy was confirmed to benefit PEDV replication by using autophagy regulators and RNA interference. Furthermore, autophagy might be associated with the expression of inflammatory cytokines and have a positive feedback loop with the NF-κB signaling pathway during PEDV infection. This work is the first attempt to explore the complex interplay between autophagy and PEDV infection. Our findings might accelerate our understanding of the pathogenesis of PEDV infection and provide new insights into the development of effective therapeutic strategies.

  10. Inhibition of HIV-1 replication by balsamin, a ribosome inactivating protein of Momordica balsamina.

    Science.gov (United States)

    Kaur, Inderdeep; Puri, Munish; Ahmed, Zahra; Blanchet, Fabien P; Mangeat, Bastien; Piguet, Vincent

    2013-01-01

    Ribosome-inactivating proteins (RIPs) are endowed with several medicinal properties, including antiviral activity. We demonstrate here that the recently identified type I RIP from Momordica balsamina also possesses antiviral activity, as determined by viral growth curve assays and single-round infection experiments. Importantly, this activity is at play even as doses where the RIP has no cytotoxic effect. In addition, balsamin inhibits HIV-1 replication not only in T cell lines but also in human primary CD4(+) T cells. This antiviral compound exerts its activity at a viral replicative step occurring later than reverse-transcription, most likely on viral protein translation, prior to viral budding and release. Finally, we demonstrate that balsamin antiviral activity is broad since it also impedes influenza virus replication. Altogether our results demonstrate that type I RIP can exert a potent anti-HIV-1 activity which paves the way for new therapeutic avenues for the treatment of viral infections.

  11. Behavioral Momentum in Sports: A Partial Replication with Women's Basketball

    Science.gov (United States)

    Roane, Henry S.; Kelley, Michael E.; Trosclair, Nicole M.; Hauer, Lindsay S.

    2004-01-01

    Previous research has applied the behavioral momentum metaphor to men's college basketball. In the current investigation, the relative rate of reinforcement prior to and following adversities (e.g., turnovers, fouls) and periods of time-out were examined in a subset of women's college basketball games.

  12. Coinfection of tick cell lines has variable effects on replication of intracellular bacterial and viral pathogens

    Science.gov (United States)

    Moniuszko, Anna; Rückert, Claudia; Alberdi, M. Pilar; Barry, Gerald; Stevenson, Brian; Fazakerley, John K.; Kohl, Alain; Bell-Sakyi, Lesley

    2014-01-01

    Ticks transmit various human and animal microbial pathogens and may harbour more than one pathogen simultaneously. Both viruses and bacteria can trigger, and may subsequently suppress, vertebrate host and arthropod vector anti-microbial responses. Microbial coinfection of ticks could lead to an advantage or disadvantage for one or more of the microorganisms. In this preliminary study, cell lines derived from the ticks Ixodes scapularis and Ixodes ricinus were infected sequentially with 2 arthropod-borne pathogens, Borrelia burgdorferi s.s., Ehrlichia ruminantium, or Semliki Forest virus (SFV), and the effect of coinfection on the replication of these pathogens was measured. Prior infection of tick cell cultures with the spirochaete B. burgdorferi enhanced subsequent replication of the rickettsial pathogen E. ruminantium whereas addition of spirochaetes to cells infected with E. ruminantium had no effect on growth of the latter. Both prior and subsequent presence of B. burgdorferi also had a positive effect on SFV replication. Presence of E. ruminantium or SFV had no measurable effect on B. burgdorferi growth. In tick cells infected first with E. ruminantium and then with SFV, virus replication was significantly higher across all time points measured (24, 48, 72 h post infection), while presence of the virus had no detectable effect on bacterial growth. When cells were infected first with SFV and then with E. ruminantium, there was no effect on replication of either pathogen. The results of this preliminary study indicate that interplay does occur between different pathogens during infection of tick cells. Further study is needed to determine if this results from direct pathogen–pathogen interaction or from effects on host cell defences, and to determine if these observations also apply in vivo in ticks. If presence of one pathogen in the tick vector results in increased replication of another, this could have implications for disease transmission and incidence

  13. Coinfection of tick cell lines has variable effects on replication of intracellular bacterial and viral pathogens.

    Science.gov (United States)

    Moniuszko, Anna; Rückert, Claudia; Alberdi, M Pilar; Barry, Gerald; Stevenson, Brian; Fazakerley, John K; Kohl, Alain; Bell-Sakyi, Lesley

    2014-06-01

    Ticks transmit various human and animal microbial pathogens and may harbour more than one pathogen simultaneously. Both viruses and bacteria can trigger, and may subsequently suppress, vertebrate host and arthropod vector anti-microbial responses. Microbial coinfection of ticks could lead to an advantage or disadvantage for one or more of the microorganisms. In this preliminary study, cell lines derived from the ticks Ixodes scapularis and Ixodes ricinus were infected sequentially with 2 arthropod-borne pathogens, Borrelia burgdorferi s.s., Ehrlichia ruminantium, or Semliki Forest virus (SFV), and the effect of coinfection on the replication of these pathogens was measured. Prior infection of tick cell cultures with the spirochaete B. burgdorferi enhanced subsequent replication of the rickettsial pathogen E. ruminantium whereas addition of spirochaetes to cells infected with E. ruminantium had no effect on growth of the latter. Both prior and subsequent presence of B. burgdorferi also had a positive effect on SFV replication. Presence of E. ruminantium or SFV had no measurable effect on B. burgdorferi growth. In tick cells infected first with E. ruminantium and then with SFV, virus replication was significantly higher across all time points measured (24, 48, 72h post infection), while presence of the virus had no detectable effect on bacterial growth. When cells were infected first with SFV and then with E. ruminantium, there was no effect on replication of either pathogen. The results of this preliminary study indicate that interplay does occur between different pathogens during infection of tick cells. Further study is needed to determine if this results from direct pathogen-pathogen interaction or from effects on host cell defences, and to determine if these observations also apply in vivo in ticks. If presence of one pathogen in the tick vector results in increased replication of another, this could have implications for disease transmission and incidence.

  14. 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.

  15. A replication and methodological critique of the study "Evaluating drug trafficking on the Tor Network"

    DEFF Research Database (Denmark)

    Munksgaard, Rasmus; Demant, Jakob Johan; Branwen, Gwern

    2016-01-01

    by evaluating drug trafficking on one of the most well-known cryptomarkets, Silk Road 2.0. The research on cryptomarkets in general—particularly in Dolliver's article—poses a number of new questions for methodologies. This commentary is structured around a replication of Dolliver's original study....... The replication study is not based on Dolliver's original dataset, but on a second dataset collected applying the same methodology. We have found that the results produced by Dolliver differ greatly from our replicated study. While a margin of error is to be expected, the inconsistencies we found are too great...

  16. Specification guidelines for surface preparation of concrete prior to repair

    OpenAIRE

    Courard, Luc; Bissonnette, Benoît; Garbacz, Andrzej

    2017-01-01

    The repair of concrete requests specific preparation operations needed for guaranteeing compatibility between substrate and new materials as well as the development of adhesion properties. These specification guidelines contain design and construction recommendations for surface preparation of concrete for repair and overlay. The paper summarizes current knowledge, best practices and results of the research concerning the surface preparation of concrete prior to application of repair/overlay ...

  17. Tuning your priors to the world.

    Science.gov (United States)

    Feldman, Jacob

    2013-01-01

    The idea that perceptual and cognitive systems must incorporate knowledge about the structure of the environment has become a central dogma of cognitive theory. In a Bayesian context, this idea is often realized in terms of "tuning the prior"-widely assumed to mean adjusting prior probabilities so that they match the frequencies of events in the world. This kind of "ecological" tuning has often been held up as an ideal of inference, in fact defining an "ideal observer." But widespread as this viewpoint is, it directly contradicts Bayesian philosophy of probability, which views probabilities as degrees of belief rather than relative frequencies, and explicitly denies that they are objective characteristics of the world. Moreover, tuning the prior to observed environmental frequencies is subject to overfitting, meaning in this context overtuning to the environment, which leads (ironically) to poor performance in future encounters with the same environment. Whenever there is uncertainty about the environment-which there almost always is-an agent's prior should be biased away from ecological relative frequencies and toward simpler and more entropic priors.

  18. Generative supervised classification using Dirichlet process priors.

    Science.gov (United States)

    Davy, Manuel; Tourneret, Jean-Yves

    2010-10-01

    Choosing the appropriate parameter prior distributions associated to a given bayesian model is a challenging problem. Conjugate priors can be selected for simplicity motivations. However, conjugate priors can be too restrictive to accurately model the available prior information. This paper studies a new generative supervised classifier which assumes that the parameter prior distributions conditioned on each class are mixtures of Dirichlet processes. The motivations for using mixtures of Dirichlet processes is their known ability to model accurately a large class of probability distributions. A Monte Carlo method allowing one to sample according to the resulting class-conditional posterior distributions is then studied. The parameters appearing in the class-conditional densities can then be estimated using these generated samples (following bayesian learning). The proposed supervised classifier is applied to the classification of altimetric waveforms backscattered from different surfaces (oceans, ices, forests, and deserts). This classification is a first step before developing tools allowing for the extraction of useful geophysical information from altimetric waveforms backscattered from nonoceanic surfaces.

  19. Physical warmth and perceptual focus: A replication of IJzerman and Semin (2009)

    OpenAIRE

    Janneke D Schilder; Hans IJzerman; Jaap J. A. Denissen

    2014-01-01

    With the changing of modal research practices in psychology, the grounded cognition perspective (sometimes categorized under the more popular term of "social priming") has become heavily criticized. Specifically, LeBel and Campbell (2013) reported a failed replication of a study involving what some would call "social priming." We sought to replicate a study from our own lab (IJzerman & Semin, 2009), to investigate the reproducibility of the reported effect that physical warmth leads to a grea...

  20. Exogenous IFN-alpha administration reduces influenza A virus replication in the lower respiratory tract of rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Shannon R Matzinger

    Full Text Available To determine the role of innate immune responses in controlling influenza A virus replication, rhesus macaques (RM were administered pegylated IFN-alpha prior to virus challenge. Systemic and mucosal pegylated IFN-alpha administration induced expression of the interferon-stimulated genes (ISG MxA and OAS in the airways. RM treated with IFN-alpha 24 hours prior to influenza virus challenge had significantly lower peak vRNA levels in the trachea compared to untreated animals. In addition to blunting viral replication, IFN-alpha treatment minimized the weight loss and spike in body temperature after influenza infection of RM. These results confirm the importance of IFN-alpha induced innate immune responses in the rapid control of influenza A virus replication in primates.

  1. Low pathogenic avian influenza isolates from wild birds replicate and transmit via contact in ferrets without prior adaptation.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Driskell

    Full Text Available Direct transmission of avian influenza viruses to mammals has become an increasingly investigated topic during the past decade; however, isolates that have been primarily investigated are typically ones originating from human or poultry outbreaks. Currently there is minimal comparative information on the behavior of the innumerable viruses that exist in the natural wild bird host. We have previously demonstrated the capacity of numerous North American avian influenza viruses isolated from wild birds to infect and induce lesions in the respiratory tract of mice. In this study, two isolates from shorebirds that were previously examined in mice (H1N9 and H6N1 subtypes are further examined through experimental inoculations in the ferret with analysis of viral shedding, histopathology, and antigen localization via immunohistochemistry to elucidate pathogenicity and transmission of these viruses. Using sequence analysis and glycan binding analysis, we show that these avian viruses have the typical avian influenza binding pattern, with affinity for cell glycoproteins/glycolipids having terminal sialic acid (SA residues with α 2,3 linkage [Neu5Ac(α2,3Gal]. Despite the lack of α2,6 linked SA binding, these AIVs productively infected both the upper and lower respiratory tract of ferrets, resulting in nasal viral shedding and pulmonary lesions with minimal morbidity. Moreover, we show that one of the viruses is able to transmit to ferrets via direct contact, despite its binding affinity for α 2,3 linked SA residues. These results demonstrate that avian influenza viruses, which are endemic in aquatic birds, can potentially infect humans and other mammals without adaptation. Finally this work highlights the need for additional study of the wild bird subset of influenza viruses in regard to surveillance, transmission, and potential for reassortment, as they have zoonotic potential.

  2. 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.

  3. 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

  4. Structured sparse priors for image classification.

    Science.gov (United States)

    Srinivas, Umamahesh; Suo, Yuanming; Dao, Minh; Monga, Vishal; Tran, Trac D

    2015-06-01

    Model-based compressive sensing (CS) exploits the structure inherent in sparse signals for the design of better signal recovery algorithms. This information about structure is often captured in the form of a prior on the sparse coefficients, with the Laplacian being the most common such choice (leading to l1 -norm minimization). Recent work has exploited the discriminative capability of sparse representations for image classification by employing class-specific dictionaries in the CS framework. Our contribution is a logical extension of these ideas into structured sparsity for classification. We introduce the notion of discriminative class-specific priors in conjunction with class specific dictionaries, specifically the spike-and-slab prior widely applied in Bayesian sparse regression. Significantly, the proposed framework takes the burden off the demand for abundant training image samples necessary for the success of sparsity-based classification schemes. We demonstrate this practical benefit of our approach in important applications, such as face recognition and object categorization.

  5. Commissioning of the PRIOR proton microscope

    CERN Document Server

    Varentsov, D; Bakhmutova, A; Barnes, C W; Bogdanov, A; Danly, C R; Efimov, S; Endres, M; Fertman, A; Golubev, A A; Hoffmann, D H H; Ionita, B; Kantsyrev, A; Krasik, Ya E; Lang, P M; Lomonosov, I; Mariam, F G; Markov, N; Merrill, F E; Mintsev, V B; Nikolaev, D; Panyushkin, V; Rodionova, M; Schanz, M; Schoenberg, K; Semennikov, A; Shestov, L; Skachkov, V S; Turtikov, V; Udrea, S; Vasylyev, O; Weyrich, K; Wilde, C; Zubareva, A

    2015-01-01

    Recently a new high energy proton microscopy facility PRIOR (Proton Microscope for FAIR) has been designed, constructed and successfully commissioned at GSI Helmholtzzentrum f\\"ur Schwerionenforschung (Darmstadt, Germany). As a result of the experiments with 3.5-4.5 GeV proton beams delivered by the heavy ion synchrotron SIS-18 of GSI, 30 um spatial and 10 ns temporal resolutions of the proton microscope have been demostrated. A new pulsed power setup for studying properties of matter under extremes has been developed for the dynamic commissioning of the PRIOR facility. This paper describes the PRIOR setup as well as the results of the first static and dynamic proton radiography experiments performed at GSI.

  6. Entropic Priors and Bayesian Model Selection

    CERN Document Server

    Brewer, Brendon J

    2009-01-01

    We demonstrate that the principle of maximum relative entropy (ME), used judiciously, can ease the specification of priors in model selection problems. The resulting effect is that models that make sharp predictions are disfavoured, weakening the usual Bayesian "Occam's Razor". This is illustrated with a simple example involving what Jaynes called a "sure thing" hypothesis. Jaynes' resolution of the situation involved introducing a large number of alternative "sure thing" hypotheses that were possible before we observed the data. However, in more complex situations, it may not be possible to explicitly enumerate large numbers of alternatives. The entropic priors formalism produces the desired result without modifying the hypothesis space or requiring explicit enumeration of alternatives; all that is required is a good model for the prior predictive distribution for the data. This idea is illustrated with a simple rigged-lottery example, and we outline how this idea may help to resolve a recent debate amongst ...

  7. Generative Prior Knowledge for Discriminative Classification

    CERN Document Server

    DeJong, G; 10.1613/jair.1934

    2011-01-01

    We present a novel framework for integrating prior knowledge into discriminative classifiers. Our framework allows discriminative classifiers such as Support Vector Machines (SVMs) to utilize prior knowledge specified in the generative setting. The dual objective of fitting the data and respecting prior knowledge is formulated as a bilevel program, which is solved (approximately) via iterative application of second-order cone programming. To test our approach, we consider the problem of using WordNet (a semantic database of English language) to improve low-sample classification accuracy of newsgroup categorization. WordNet is viewed as an approximate, but readily available source of background knowledge, and our framework is capable of utilizing it in a flexible way.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. Maintenance of Genome Integrity: How Mammalian Cells Orchestrate Genome Duplication by Coordinating Replicative and Specialized DNA Polymerases.

    Science.gov (United States)

    Barnes, Ryan; Eckert, Kristin

    2017-01-06

    Precise duplication of the human genome is challenging due to both its size and sequence complexity. DNA polymerase errors made during replication, repair or recombination are central to creating mutations that drive cancer and aging. Here, we address the regulation of human DNA polymerases, specifically how human cells orchestrate DNA polymerases in the face of stress to complete replication and maintain genome stability. DNA polymerases of the B-family are uniquely adept at accurate genome replication, but there are numerous situations in which one or more additional DNA polymerases are required to complete genome replication. Polymerases of the Y-family have been extensively studied in the bypass of DNA lesions; however, recent research has revealed that these polymerases play important roles in normal human physiology. Replication stress is widely cited as contributing to genome instability, and is caused by conditions leading to slowed or stalled DNA replication. Common Fragile Sites epitomize "difficult to replicate" genome regions that are particularly vulnerable to replication stress, and are associated with DNA breakage and structural variation. In this review, we summarize the roles of both the replicative and Y-family polymerases in human cells, and focus on how these activities are regulated during normal and perturbed genome replication.

  13. Genome position specific priors for genomic prediction

    DEFF Research Database (Denmark)

    Brøndum, Rasmus Froberg; Su, Guosheng; Lund, Mogens Sandø

    2012-01-01

    population when using a prior derived from the Nordic Holstein population compared to using no prior information. These improvements were significant (PHotelling Williams t-test for protein- and fat yield Conclusion For some traits the method might be advantageous compared to pooling...... to estimate SNP effects, except in the case of fat yield. The small size of the Jersey validation set meant that these improvements in accuracy were not significant using a Hotelling-Williams t-test at the 5% level. An increase in accuracy of 1-2% for all traits was observed in the Australian Holstein...

  14. Numbers and prior knowledge in sentence comprehension

    Directory of Open Access Journals (Sweden)

    Pedro Macizo

    2013-01-01

    Full Text Available We evaluated whether the comprehension of sentences that contained numerical information could benefit from presenting numbers in Arabic format and from using prior knowledge. Participants read sentences including numbers (Arabic digits or number words while the comprehension accuracy was evaluated. In addition, the sentences were biased or unbiased by people's prior knowledge about quantities. The results showed better comprehension for sentences that contained Arabic digits as compared to number words. Moreover, biased sentences were understood more accurately than unbiased sentences. These results indicate that information about magnitude in sentence context is comprehended better when quantities are presented in Arabic format and when they are associated with participants' world knowledge.

  15. 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.

  16. Increased Replicative Fitness Can Lead to Decreased Drug Sensitivity of Hepatitis C Virus

    Science.gov (United States)

    Sheldon, Julie; Beach, Nathan M.; Moreno, Elena; Gallego, Isabel; Piñeiro, David; Martínez-Salas, Encarnación; Gregori, Josep; Quer, Josep; Esteban, Juan Ignacio; Rice, Charles M.

    2014-01-01

    ABSTRACT Passage of hepatitis C virus (HCV) in human hepatoma cells resulted in populations that displayed partial resistance to alpha interferon (IFN-α), telaprevir, daclatasvir, cyclosporine, and ribavirin, despite no prior exposure to these drugs. Mutant spectrum analyses and kinetics of virus production in the absence and presence of drugs indicate that resistance is not due to the presence of drug resistance mutations in the mutant spectrum of the initial or passaged populations but to increased replicative fitness acquired during passage. Fitness increases did not alter host factors that lead to shutoff of general host cell protein synthesis and preferential translation of HCV RNA. The results imply that viral replicative fitness is a mechanism of multidrug resistance in HCV. IMPORTANCE Viral drug resistance is usually attributed to the presence of amino acid substitutions in the protein targeted by the drug. In the present study with HCV, we show that high viral replicative fitness can confer a general drug resistance phenotype to the virus. The results exclude the possibility that genomes with drug resistance mutations are responsible for the observed phenotype. The fact that replicative fitness can be a determinant of multidrug resistance may explain why the virus is less sensitive to drug treatments in prolonged chronic HCV infections that favor increases in replicative fitness. PMID:25122776

  17. 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 ...

  18. 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 ...

  19. 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.

  20. 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

  1. Synchronization of DNA array replication kinetics

    Science.gov (United States)

    Manturov, Alexey O.; Grigoryev, Anton V.

    2016-04-01

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

  2. 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.

  3. Legionella pneumophila-Derived Outer Membrane Vesicles Promote Bacterial Replication in Macrophages.

    Directory of Open Access Journals (Sweden)

    Anna Lena Jung

    2016-04-01

    Full Text Available The formation and release of outer membrane vesicles (OMVs is a phenomenon of Gram-negative bacteria. This includes Legionella pneumophila (L. pneumophila, a causative agent of severe pneumonia. Upon its transmission into the lung, L. pneumophila primarily infects and replicates within macrophages. Here, we analyzed the influence of L. pneumophila OMVs on macrophages. To this end, differentiated THP-1 cells were incubated with increasing doses of Legionella OMVs, leading to a TLR2-dependent classical activation of macrophages with the release of pro-inflammatory cytokines. Inhibition of TLR2 and NF-κB signaling reduced the induction of pro-inflammatory cytokines. Furthermore, treatment of THP-1 cells with OMVs prior to infection reduced replication of L. pneumophila in THP-1 cells. Blocking of TLR2 activation or heat denaturation of OMVs restored bacterial replication in the first 24 h of infection. With prolonged infection-time, OMV pre-treated macrophages became more permissive for bacterial replication than untreated cells and showed increased numbers of Legionella-containing vacuoles and reduced pro-inflammatory cytokine induction. Additionally, miRNA-146a was found to be transcriptionally induced by OMVs and to facilitate bacterial replication. Accordingly, IRAK-1, one of miRNA-146a's targets, showed prolonged activation-dependent degradation, which rendered THP-1 cells more permissive for Legionella replication. In conclusion, L. pneumophila OMVs are initially potent pro-inflammatory stimulators of macrophages, acting via TLR2, IRAK-1, and NF-κB, while at later time points, OMVs facilitate L. pneumophila replication by miR-146a-dependent IRAK-1 suppression. OMVs might thereby promote spreading of L. pneumophila in the host.

  4. Alterations in the expression of DEAD-box and other RNA binding proteins during HIV-1 replication

    Directory of Open Access Journals (Sweden)

    Zeichner Steven L

    2004-12-01

    Full Text Available Abstract Recent results showed that certain DEAD box protein RNA helicases, DDX3 and DDX1, play an important role in the HIV infection cycle by facilitating the export of long, singly spliced or unspliced HIV RNAs from the nucleus via the CRM1-Rev pathway. Close examination of an extensive microarray expression profiling dataset obtained from cells latently infected with HIV induced to undergo lytic viral replication indicated that additional DEAD box proteins, beyond DDX3 and DDX1, exhibit differential expression during lytic HIV replication, and in latently infected cells prior to induction into active replication. This finding provides additional evidence that the involvement of DEAD box proteins and other RNA-binding proteins may play roles in active HIV replication and in the control of viral latency. Agents targeting these functions may offer new approaches to antiretroviral therapy and the therapeutic manipulation of HIV latency.

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

    Directory of Open Access Journals (Sweden)

    Chong ePeng

    2015-02-01

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

  6. Do Highly Test Anxious Students Respond Differentially to Fear Appeals Made Prior to a Test?

    Science.gov (United States)

    Putwain, David W.; Best, Natalie

    2012-01-01

    Prior research has suggested that fear appeals used in the primary classroom prior to a test, messages emphasising the importance of the test and the consequences of failure, may have negative pupil outcomes by increasing anxiety and reducing test performance. This study aimed to examine whether this effect was stronger in those students who were…

  7. 46 CFR 190.20-90 - Vessels contracted for prior to March 1, 1968.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Vessels contracted for prior to March 1, 1968. 190.20-90 Section 190.20-90 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH...-90 Vessels contracted for prior to March 1, 1968. Existing structures, arrangements, materials,...

  8. 46 CFR 190.01-90 - Vessels contracted for prior to March 1, 1968.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Vessels contracted for prior to March 1, 1968. 190.01-90 Section 190.01-90 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS CONSTRUCTION AND ARRANGEMENT Hull Structure § 190.01-90 Vessels contracted for prior to March...

  9. 46 CFR 190.10-90 - Vessels contracted for prior to March 1, 1968.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Vessels contracted for prior to March 1, 1968. 190.10-90 Section 190.10-90 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS CONSTRUCTION AND ARRANGEMENT Means of Escape § 190.10-90 Vessels contracted for prior to March...

  10. 46 CFR 190.15-90 - Vessels contracted for prior to March 1, 1968.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Vessels contracted for prior to March 1, 1968. 190.15-90 Section 190.15-90 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS CONSTRUCTION AND ARRANGEMENT Ventilation § 190.15-90 Vessels contracted for prior to March 1,...

  11. Validity in assessment of prior learning

    DEFF Research Database (Denmark)

    Wahlgren, Bjarne; Aarkrog, Vibe

    2015-01-01

    The article deals with the results of a study of school-based assessment of adults who have enrolled as students at a vocational college in order to qualify for occupations as skilled workers. Based on examples of methods for assessing the students’ prior learning in a programme for hairdressers...

  12. Action priors for learning domain invariances

    CSIR Research Space (South Africa)

    Rosman, Benjamin S

    2015-04-01

    Full Text Available , defined as distributions over the action space, conditioned on environment state, and show how these can be learnt from a set of value functions. We apply action priors in the setting of reinforcement learning, to bias action selection during exploration...

  13. Recognition of Prior Learning: The Participants' Perspective

    Science.gov (United States)

    Miguel, Marta C.; Ornelas, José H.; Maroco, João P.

    2016-01-01

    The current narrative on lifelong learning goes beyond formal education and training, including learning at work, in the family and in the community. Recognition of prior learning is a process of evaluation of those skills and knowledge acquired through life experience, allowing them to be formally recognized by the qualification systems. It is a…

  14. Validity in assessment of prior learning

    DEFF Research Database (Denmark)

    Wahlgren, Bjarne; Aarkrog, Vibe

    2015-01-01

    The article deals with the results of a study of school-based assessment of adults who have enrolled as students at a vocational college in order to qualify for occupations as skilled workers. Based on examples of methods for assessing the students’ prior learning in a programme for hairdressers...

  15. The prior statistics of object colors

    NARCIS (Netherlands)

    Koenderink, J.J.

    2010-01-01

    The prior statistics of object colors is of much interest because extensive statistical investigations of reflectance spectra reveal highly non-uniform structure in color space common to several very different databases. This common structure is due to the visual system rather than to the statistics

  16. Models for Validation of Prior Learning (VPL)

    DEFF Research Database (Denmark)

    Ehlers, Søren

    would have been categorized as utopian can become realpolitik. Validation of Prior Learning (VPL) was in Europe mainly regarded as utopian while universities in the United States of America (USA) were developing ways to obtain credits to those students which was coming with experiences from working life....

  17. Offending prior to first psychiatric contact

    DEFF Research Database (Denmark)

    Stevens, H; Agerbo, E; Dean, K

    2012-01-01

    There is a well-established association between psychotic disorders and subsequent offending but the extent to which those who develop psychosis might have a prior history of offending is less clear. Little is known about whether the association between illness and offending exists in non-psychot...

  18. 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....

  19. 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...

  20. 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.

  1. Objective prior distribution of climate sensitivity

    Science.gov (United States)

    Pueyo, S.

    2012-04-01

    The problems posed by the choice of prior distribution constitute one of the most fundamental obstacles to assign probabilities to the possible values of climate sensitivity S. The prior is the probability distribution that we assume before introducing data. In the literature about climate sensitivity, the most frequently used prior is the uniform. On first inspection, this distribution would seem to represent absence of information, but, as is well known, this assumption leads to paradoxes. This observation has led to the widespread belief that priors are inherently subjective and should be decided by expert elicitation, even though this amounts to questioning the objective value of scientific results. In general, the climate science community is unaware of the "objective Bayesian" literature, which seeks objective criteria to determine non-informative prior distributions (or reference priors). In a recent paper (Pueyo 2011) I applied an objective Bayesian approach to climate sensitivity. I described three lines of evidence indicating that the distribution that really represents absence of information about S is log-uniform, i.e. it consists of a uniform distribution of log(S) instead of S: • In the case of S, only the log-uniform distribution satisfies Jaynes' invariant groups criterion, i.e. this distribution does not change when modifying assumptions that are not explicitly included in the enunciate of the problem (I only included the definition of S). • In terms of information theory, information about S can be identified with mutual information between changes in radiative forcing and in temperature. Absence of mutual information between these variables implies a log-uniform distribution of S. • The frequency distribution of sets of parameters formally comparable to climate sensitivity is approximately log-uniform for a broad range of values. A log-uniform distribution of S is intermediate between a uniform distribution of S and a uniform distribution

  2. 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.

  3. 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.

  4. Deepening Understanding of Prior Knowledge: What Diverse First-Generation College Students in the U.S. Can Teach Us

    Science.gov (United States)

    Castillo-Montoya, Milagros

    2017-01-01

    Educational research indicates that teachers revealing and utilizing students' prior knowledge supports students' academic learning. Yet, the variation in students' prior knowledge is not fully known. To better understand students' prior knowledge, I drew on sociocultural learning theories to examine racially and ethnically diverse college…

  5. Electronic Commerce Adoption in SME: The Trend of Prior Studies

    Directory of Open Access Journals (Sweden)

    Rosli Mohamad

    2009-08-01

    Full Text Available Emergence of Internet, particularly Electronic Commerce (EC application brings new landscape in conduct ing business . Apart of better ef ficiency, EC enables firm to diversify business strategy, to introduce newly accepted business model and to embrace globali za tion. Despite profound usage among large firms, EC is now getting attention of small medium - sized enterprises (SMEs. This is obvio usly raise s concern as small firms have long been recognized for limited resources and capabilities than larger firms . Consequently, the issue of EC in SMEs attracts considerable research works in this area . This conceptual paper reports on the extensive r eview of prior studies pertaining to the EC usage among small firms . This paper , however, limit s the review to s everal major aspects i.e. research themes , underpinning theories , research approaches, and the context/country of the stud y . T he last section th en outlines important findings of the previous studies and future research direction

  6. 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.

  7. 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.

  8. Optimization of in vitro HBV replication and HBsAg production in HuH7 cell line.

    Science.gov (United States)

    Cavallone, Daniela; Moriconi, Francesco; Colombatto, Piero; Oliveri, Filippo; Bonino, Ferruccio; Brunetto, Maurizia Rossana

    2013-04-01

    The Gunther's vector-free method (GM), using PCR-amplified full length HBV-DNA (fl-HBV-DNA), is currently the best in vitro HBV replication system despite the low intracellular HBV-DNA production. The replication efficiency and HBsAg secretion of 12 isolates from HBsAg/HBeAg positive sera by GM, Monomer-Linear-Sticky-Ends-DNA (MLSE) and Monomer-Circular-Closed (MCC) were compared in HuH7 cells. Eight of twelve genomes (67%) were replication competent by GM; however direct sequencing (DS) showed that more than 80% of input DNA was undigested in spite of SapI treatment. Replication Intermediates (RI) were detected earlier (24 vs. 48h) and in higher amounts (2.51±0.32 and 6.43±0.43 fold) by MCC than GM or MLSE. By MCC 10 of 12 genomes (83%) were replication competent and 7 produced high RI levels. RI and HBsAg kinetics correlated positively in MCC (R=0.696, p=0.017 overall; R=0.928, p=0.008), but not in GM (R=-0.437, p=0.179 overall; R=-0.395, p=0.439) in genotype D isolates. In conclusion, HBV-DNA circularization prior transfection improves in vitro viral replication and replication competent HBsAg production, mimicking better the in vivo conditions.

  9. 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.

  10. Diminished nocturnal penile tumescence in depression: a replication study.

    Science.gov (United States)

    Thase, M E; Reynolds, C F; Jennings, J R; Frank, E; Garamoni, G L; Nofzinger, E A; Fascizka, A L; Kupfer, D J

    1992-06-01

    A descriptive study was conducted in a new sample of 51 men with DSM-III-R research diagnostic criteria (RDC) major depression in order to replicate earlier observations that measures of nocturnal penile tumescence (NPT) and penile rigidity are disturbed in depressive states. When compared to both the age-equated patient (n = 34) and normal control (n = 28) groups reported in our 1988 study, the new sample manifested significant abnormalities of NPT and diminished penile rigidity. Such disturbances were not, however, significantly correlated with psychobiological indicators of severe or endogenous depression.

  11. 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...

  12. A novel nucleoid-associated protein coordinates chromosome replication and chromosome partition.

    Science.gov (United States)

    Taylor, James A; Panis, Gaël; Viollier, Patrick H; Marczynski, Gregory T

    2017-09-06

    We searched for regulators of chromosome replication in the cell cycle model Caulobacter crescentus and found a novel DNA-binding protein (GapR) that selectively aids the initiation of chromosome replication and the initial steps of chromosome partitioning. The protein binds the chromosome origin of replication (Cori) and has higher-affinity binding to mutated Cori-DNA that increases Cori-plasmid replication in vivo. gapR gene expression is essential for normal rapid growth and sufficient GapR levels are required for the correct timing of chromosome replication. Whole genome ChIP-seq identified dynamic DNA-binding distributions for GapR, with the strongest associations at the partitioning (parABS) locus near Cori. Using molecular-genetic and fluorescence microscopy experiments, we showed that GapR also promotes the first steps of chromosome partitioning, the initial separation of the duplicated parS loci following replication from Cori. This separation occurs before the parABS-dependent partitioning phase. Therefore, this early separation, whose mechanisms is not known, coincides with the poorly defined mechanism(s) that establishes chromosome asymmetry: C. crescentus chromosomes are partitioned to distinct cell-poles which develop into replicating and non-replicating cell-types. We propose that GapR coordinates chromosome replication with asymmetry-establishing chromosome separation, noting that both roles are consistent with the phylogenetic restriction of GapR to asymmetrically dividing bacteria. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  13. Research

    African Journals Online (AJOL)

    A possible strategy to influence students' understanding and perception ... researcher in higher education teaching and learning facilitated the data- ..... B. Qualitative content analysis in nursing research: Concepts, procedures and measures.

  14. Does Literacy Skill Level Predict Performance in Community College Courses: A Replication and Extension

    Science.gov (United States)

    Allen, Nancy J.; DeLauro, Kimberly A.; Perry, Julia K.; Carman, Carol A.

    2017-01-01

    Previous research has found a positive relationship between students who had completed a sequence of developmental reading and writing courses and success in a reading-intensive college-level course. This study replicates and expands upon the previous research of Goldstein and Perin (2008) by utilizing a differently diverse sample and an…

  15. Does Literacy Skill Level Predict Performance in Community College Courses: A Replication and Extension

    Science.gov (United States)

    Allen, Nancy J.; DeLauro, Kimberly A.; Perry, Julia K.; Carman, Carol A.

    2017-01-01

    Previous research has found a positive relationship between students who had completed a sequence of developmental reading and writing courses and success in a reading-intensive college-level course. This study replicates and expands upon the previous research of Goldstein and Perin (2008) by utilizing a differently diverse sample and an…

  16. 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.

  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. 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

  7. Prior Information in Inverse Boundary Problems

    DEFF Research Database (Denmark)

    Garde, Henrik

    This thesis gives a threefold perspective on the inverse problem of inclusion detection in electrical impedance tomography: depth dependence, monotonicitybased reconstruction, and sparsity-based reconstruction. The depth dependence is given in terms of explicit bounds on the datum norm, which shows...... into how much noise that can be allowed in the datum before an inclusion cannot be detected. The monotonicity method is a direct reconstruction method that utilizes a monotonicity property of the forward problem in order to characterize the inclusions. Here we rigorously prove that the method can...... of the method. Sparsity-based reconstruction is an iterative method, that through an optimization problem with a sparsity prior, approximates the inhomogeneities. Here we make use of prior information, that can cheaply be obtained from the monotonicity method, to improve both the contrast and resolution...

  8. Image Segmentation Using Weak Shape Priors

    CERN Document Server

    Xu, Robert Sheng; Salama, Magdy

    2010-01-01

    The problem of image segmentation is known to become particularly challenging in the case of partial occlusion of the object(s) of interest, background clutter, and the presence of strong noise. To overcome this problem, the present paper introduces a novel approach segmentation through the use of "weak" shape priors. Specifically, in the proposed method, an segmenting active contour is constrained to converge to a configuration at which its geometric parameters attain their empirical probability densities closely matching the corresponding model densities that are learned based on training samples. It is shown through numerical experiments that the proposed shape modeling can be regarded as "weak" in the sense that it minimally influences the segmentation, which is allowed to be dominated by data-related forces. On the other hand, the priors provide sufficient constraints to regularize the convergence of segmentation, while requiring substantially smaller training sets to yield less biased results as compare...

  9. The Effects of Prior Outcomes on Risky Choice: Evidence from the Stock Market

    Directory of Open Access Journals (Sweden)

    Fenghua Wen

    2014-01-01

    Full Text Available How do prior outcomes affect the risk choice? Research on this can help people to understand investors’ dynamic decisions in financial market. This paper puts forward a new value function. By analyzing the new value function, we find that the prior gains and losses have an impact on the form of value function and the current investors’ risk attitude. Then the paper takes the behavior of the whole stock market as the research object, adopts aggregative index number of 14 representative stocks around the world as samples, and establishes a TVRA-GARCH-M model to investigate the influences of prior gains and losses on the current risk attitude. The empirical study indicates that, at the whole market level, prior gains increase people’s current willingness to take risk assert; that is to say, the house money effect exists in the market, while people are more risk aversion following prior losses.

  10. Maintenance of Genome Integrity: How Mammalian Cells Orchestrate Genome Duplication by Coordinating Replicative and Specialized DNA Polymerases

    Directory of Open Access Journals (Sweden)

    Ryan Barnes

    2017-01-01

    Full Text Available Precise duplication of the human genome is challenging due to both its size and sequence complexity. DNA polymerase errors made during replication, repair or recombination are central to creating mutations that drive cancer and aging. Here, we address the regulation of human DNA polymerases, specifically how human cells orchestrate DNA polymerases in the face of stress to complete replication and maintain genome stability. DNA polymerases of the B-family are uniquely adept at accurate genome replication, but there are numerous situations in which one or more additional DNA polymerases are required to complete genome replication. Polymerases of the Y-family have been extensively studied in the bypass of DNA lesions; however, recent research has revealed that these polymerases play important roles in normal human physiology. Replication stress is widely cited as contributing to genome instability, and is caused by conditions leading to slowed or stalled DNA replication. Common Fragile Sites epitomize “difficult to replicate” genome regions that are particularly vulnerable to replication stress, and are associated with DNA breakage and structural variation. In this review, we summarize the roles of both the replicative and Y-family polymerases in human cells, and focus on how these activities are regulated during normal and perturbed genome replication.

  11. Prior image constrained image reconstruction in emerging computed tomography applications

    Science.gov (United States)

    Brunner, Stephen T.

    Advances have been made in computed tomography (CT), especially in the past five years, by incorporating prior images into the image reconstruction process. In this dissertation, we investigate prior image constrained image reconstruction in three emerging CT applications: dual-energy CT, multi-energy photon-counting CT, and cone-beam CT in image-guided radiation therapy. First, we investigate the application of Prior Image Constrained Compressed Sensing (PICCS) in dual-energy CT, which has been called "one of the hottest research areas in CT." Phantom and animal studies are conducted using a state-of-the-art 64-slice GE Discovery 750 HD CT scanner to investigate the extent to which PICCS can enable radiation dose reduction in material density and virtual monochromatic imaging. Second, we extend the application of PICCS from dual-energy CT to multi-energy photon-counting CT, which has been called "one of the 12 topics in CT to be critical in the next decade." Numerical simulations are conducted to generate multiple energy bin images for a photon-counting CT acquisition and to investigate the extent to which PICCS can enable radiation dose efficiency improvement. Third, we investigate the performance of a newly proposed prior image constrained scatter correction technique to correct scatter-induced shading artifacts in cone-beam CT, which, when used in image-guided radiation therapy procedures, can assist in patient localization, and potentially, dose verification and adaptive radiation therapy. Phantom studies are conducted using a Varian 2100 EX system with an on-board imager to investigate the extent to which the prior image constrained scatter correction technique can mitigate scatter-induced shading artifacts in cone-beam CT. Results show that these prior image constrained image reconstruction techniques can reduce radiation dose in dual-energy CT by 50% in phantom and animal studies in material density and virtual monochromatic imaging, can lead to radiation

  12. 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.

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

    Science.gov (United States)

    Herlihy, Anna E; de Bruin, Robertus A M

    2017-03-02

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

  14. 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.

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    Michelle Hawkins

    2013-11-01

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

  17. Intersection of the multivesicular body pathway and lipid homeostasis in RNA replication by a positive-strand RNA virus.

    Science.gov (United States)

    Wang, Xiaofeng; Diaz, Arturo; Hao, Linhui; Gancarz, Brandi; den Boon, Johan A; Ahlquist, Paul

    2011-06-01

    Like many positive-strand RNA viruses, brome mosaic virus (BMV) RNA replication occurs in membrane-invaginated vesicular compartments. BMV RNA replication compartments show parallels with membrane-enveloped, budding retrovirus virions, whose release depends on the cellular multivesicular body (MVB) sorting pathway. BMV RNA replication compartments are not released from their parent membranes, but might depend on MVB functions for membrane invagination. Prior results show that BMV RNA replication is severely inhibited by deletion of the crucial MVB gene DOA4 or BRO1. We report here that involvement of DOA4 and BRO1 in BMV RNA replication is not dependent on the MVB pathway's membrane-shaping functions but rather is due to their roles in recycling ubiquitin from MVB cargos. We show that deleting DOA4 or BRO1 inhibits the ubiquitination- and proteasome-dependent activation of homologous transcription factors Mga2p and Spt23p, which regulate many lipid metabolism genes, including the fatty acid desaturase gene OLE1, which is essential for BMV RNA replication. However, Mga2p processing and BMV RNA replication are restored by supplementing free ubiquitin, which is depleted in doa4Δ and bro1Δ cells. The results identify Mga2p and Spt23p processing and lipid regulation as sensitive targets of ubiquitin depletion and correctly predict multiple effects of modulating additional host genes RFU1, UBP6, and UFD3. Our results also show that BMV RNA replication depends on additional Mga2p-regulated genes likely involved in lipid metabolism beyond OLE1. Among other points, these findings show the potential for blocking viral RNA replication by modulating lipid synthesis at multiple levels.

  18. 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.

  19. 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

  20. 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.

  1. Difference-based clustering of short time-course microarray data with replicates

    Directory of Open Access Journals (Sweden)

    Kim Jihoon

    2007-07-01

    Full Text Available Abstract Background There are some limitations associated with conventional clustering methods for short time-course gene expression data. The current algorithms require prior domain knowledge and do not incorporate information from replicates. Moreover, the results are not always easy to interpret biologically. Results We propose a novel algorithm for identifying a subset of genes sharing a significant temporal expression pattern when replicates are used. Our algorithm requires no prior knowledge, instead relying on an observed statistic which is based on the first and second order differences between adjacent time-points. Here, a pattern is predefined as the sequence of symbols indicating direction and the rate of change between time-points, and each gene is assigned to a cluster whose members share a similar pattern. We evaluated the performance of our algorithm to those of K-means, Self-Organizing Map and the Short Time-series Expression Miner methods. Conclusions Assessments using simulated and real data show that our method outperformed aforementioned algorithms. Our approach is an appropriate solution for clustering short time-course microarray data with replicates.

  2. 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

  3. 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.

  4. Research

    African Journals Online (AJOL)

    A sequential mixed-methods research design was chosen. This research ... development of the questionnaire used in the second phase of the survey. Quantitative data ... Microsoft Office Excel 2010 spreadsheet, descriptive data analysis was applied .... undergraduate curriculum, and implementation and evaluation thereof,.

  5. Research

    African Journals Online (AJOL)

    ebutamanya

    2015-03-02

    Mar 2, 2015 ... Shared and mutually beneficial resources within international research ... organizations[1-9]. ... facilitate research career paths, but few career models exist in Africa ..... international and local resources to clinical studies locally. The ability of ... investigators were seen as an important asset for the transfer of.

  6. The role of prior knowledge in error correction for younger and older adults.

    Science.gov (United States)

    Sitzman, Danielle M; Rhodes, Matthew G; Tauber, Sarah K; Liceralde, Van Rynald T

    2015-01-01

    Previous work has demonstrated that, when given feedback, younger adults are more likely to correct high-confidence errors compared with low-confidence errors, a finding termed the hypercorrection effect. Research examining the hypercorrection effect in both older and younger adults has demonstrated that the relationship between confidence and error correction was stronger for younger adults compared with older adults. Their results demonstrated that the relationship between confidence and error correction was stronger for younger adults compared with older adults. However, recent work suggests that error correction is largely related to prior knowledge, while confidence may primarily serve as a proxy for prior knowledge. Prior knowledge generally remains stable or increases with age; thus, the current experiment explored how both confidence and prior knowledge contributed to error correction in younger and older adults. Participants answered general knowledge questions, rated how confident they were that their response was correct, received correct answer feedback, and rated their prior knowledge of the correct response. Overall, confidence was related to error correction for younger adults, but this relationship was much smaller for older adults. However, prior knowledge was strongly related to error correction for both younger and older adults. Confidence alone played little unique role in error correction after controlling for the role of prior knowledge. These data demonstrate that prior knowledge largely predicts error correction and suggests that both older and younger adults can use their prior knowledge to effectively correct errors in memory.

  7. Investigating different approaches to develop informative priors in hierarchical Bayesian safety performance functions.

    Science.gov (United States)

    Yu, Rongjie; Abdel-Aty, Mohamed

    2013-07-01

    The Bayesian inference method has been frequently adopted to develop safety performance functions. One advantage of the Bayesian inference is that prior information for the independent variables can be included in the inference procedures. However, there are few studies that discussed how to formulate informative priors for the independent variables and evaluated the effects of incorporating informative priors in developing safety performance functions. This paper addresses this deficiency by introducing four approaches of developing informative priors for the independent variables based on historical data and expert experience. Merits of these informative priors have been tested along with two types of Bayesian hierarchical models (Poisson-gamma and Poisson-lognormal models). Deviance information criterion (DIC), R-square values, and coefficients of variance for the estimations were utilized as evaluation measures to select the best model(s). Comparison across the models indicated that the Poisson-gamma model is superior with a better model fit and it is much more robust with the informative priors. Moreover, the two-stage Bayesian updating informative priors provided the best goodness-of-fit and coefficient estimation accuracies. Furthermore, informative priors for the inverse dispersion parameter have also been introduced and tested. Different types of informative priors' effects on the model estimations and goodness-of-fit have been compared and concluded. Finally, based on the results, recommendations for future research topics and study applications have been made.

  8. 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.

  9. 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...

  10. 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...

  11. 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.

  12. 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.

  13. 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.

  14. Tomato bushy stunt virus and DI RNAs as a model for studying mechanisms of RNA virus replication, pathogenicity and recombination. Final technical report for 1994--1997

    Energy Technology Data Exchange (ETDEWEB)

    Morris, T.J. [Univ. of Nebraska, Lincoln, NE (United States). School of Biological Sciences; Jackson, A.O. [Univ. of California, Berkeley, CA (United States). Dept. of Plant Biology

    1997-12-31

    Tomato bushy stunt virus (TBSV) is a small icosahedral virus with a very broad host-range. The symptoms of systemic infection range from mild mosaic to severe necrosis that often results in death. The genome of TBSV is composed of a single plus stranded RNA molecule with five genes. Two 5 inch genes are translated from the viral RNA, and the remaining three are translated from two subgenomic RNAs. Prior to the DOE supported studies, TBSV gene function had been assigned solely on the basis of sequence similarity with other virus genes of known function. The two 5 inch proximal genes (p33 and p92) were thought to be involved in viral replication, the middle gene encoded the capsid protein (p41), but no clear function was assigned to two nested 3 inch genes (p19 and p22), although it was suggested that at least one could be involved in movement. This research has determined the roles of each of the viral genes in the infection process, and the authors have obtained considerable genetic information pertinent to the contributions of the coat protein and the nested genes to the disease phenotypes observed in several host plants. They have also identified another genetic element with a short open reading frame in the 3 inch-noncoding region of the genome that provides a host-dependent replication function.

  15. [Registration of prehabilitation prior to surgery].

    Science.gov (United States)

    Tønnesen, Hanne; Duus, Benn R

    2008-04-21

    Four to eight week prehabilitation programs for smokers and harmful drinkers were included in the national guidelines in 2001. In October 2007 a guarantee for surgery within one month of waiting time came into effect in Denmark. The present Danish patient administration system already contains room for registration of prehabilitation prior to surgery. Using one specific code for prehabilitation at the surgical department and another for prehabilitation at other departments will enable correct registration. Thereby, it is possible to differentiate between ordinary waiting time before surgery and time for prehabilitation.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. RepExplore: addressing technical replicate variance in proteomics and metabolomics data analysis.

    Science.gov (United States)

    Glaab, Enrico; Schneider, Reinhard

    2015-07-01

    High-throughput omics datasets often contain technical replicates included to account for technical sources of noise in the measurement process. Although summarizing these replicate measurements by using robust averages may help to reduce the influence of noise on downstream data analysis, the information on the variance across the replicate measurements is lost in the averaging process and therefore typically disregarded in subsequent statistical analyses.We introduce RepExplore, a web-service dedicated to exploit the information captured in the technical replicate variance to provide more reliable and informative differential expression and abundance statistics for omics datasets. The software builds on previously published statistical methods, which have been applied successfully to biomedical omics data but are difficult to use without prior experience in programming or scripting. RepExplore facilitates the analysis by providing a fully automated data processing and interactive ranking tables, whisker plot, heat map and principal component analysis visualizations to interpret omics data and derived statistics. Freely available at http://www.repexplore.tk enrico.glaab@uni.lu Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press.

  3. PriC-mediated DNA replication restart requires PriC complex formation with the single-stranded DNA-binding protein.

    Science.gov (United States)

    Wessel, Sarah R; Marceau, Aimee H; Massoni, Shawn C; Zhou, Ruobo; Ha, Taekjip; Sandler, Steven J; Keck, James L

    2013-06-14

    Frequent collisions between cellular DNA replication complexes (replisomes) and obstacles such as damaged DNA or frozen protein complexes make DNA replication fork progression surprisingly sporadic. These collisions can lead to the ejection of replisomes prior to completion of replication, which, if left unrepaired, results in bacterial cell death. As such, bacteria have evolved DNA replication restart mechanisms that function to reload replisomes onto abandoned DNA replication forks. Here, we define a direct interaction between PriC, a key Escherichia coli DNA replication restart protein, and the single-stranded DNA-binding protein (SSB), a protein that is ubiquitously associated with DNA replication forks. PriC/SSB complex formation requires evolutionarily conserved residues from both proteins, including a pair of Arg residues from PriC and the C terminus of SSB. In vitro, disruption of the PriC/SSB interface by sequence changes in either protein blocks the first step of DNA replication restart, reloading of the replicative DnaB helicase onto an abandoned replication fork. Consistent with the critical role of PriC/SSB complex formation in DNA replication restart, PriC variants that cannot bind SSB are non-functional in vivo. Single-molecule experiments demonstrate that PriC binding to SSB alters SSB/DNA complexes, exposing single-stranded DNA and creating a platform for other proteins to bind. These data lead to a model in which PriC interaction with SSB remodels SSB/DNA structures at abandoned DNA replication forks to create a DNA structure that is competent for DnaB loading.

  4. Tensors, BICEP2, prior dependence, and dust

    CERN Document Server

    Cortês, Marina; Parkinson, David

    2014-01-01

    We investigate the prior dependence on the inferred spectrum of primordial tensor perturbations, in light of recent results from BICEP2 and taking into account a possible dust contribution to polarized anisotropies. We highlight an optimized parameterization of the tensor power spectrum, and adoption of a logarithmic prior on its amplitude $A_T$, leading to results that transform more evenly under change of pivot scale. In the absence of foregrounds the tension between the results of BICEP2 and Planck drives the tensor spectral index $n_T$ to be blue-tilted in a joint analysis, which would be in contradiction to the standard inflation prediction ($n_T<0$). When foregrounds are accounted for, the BICEP2 results no longer require non-standard inflationary parameter regions. We present limits on primordial $A_T$ and $n_T$, adopting foreground scenarios put forward by Mortonson & Seljak and motivated by Planck 353 GHz observations, and assess what dust contribution leaves a detectable cosmological signal. ...

  5. How prior expectations shape multisensory perception.

    Science.gov (United States)

    Gau, Remi; Noppeney, Uta

    2016-01-01

    The brain generates a representation of our environment by integrating signals from a common source, but segregating signals from different sources. This fMRI study investigated how the brain arbitrates between perceptual integration and segregation based on top-down congruency expectations and bottom-up stimulus-bound congruency cues. Participants were presented audiovisual movies of phonologically congruent, incongruent or McGurk syllables that can be integrated into an illusory percept (e.g. "ti" percept for visual «ki» with auditory /pi/). They reported the syllable they perceived. Critically, we manipulated participants' top-down congruency expectations by presenting McGurk stimuli embedded in blocks of congruent or incongruent syllables. Behaviorally, participants were more likely to fuse audiovisual signals into an illusory McGurk percept in congruent than incongruent contexts. At the neural level, the left inferior frontal sulcus (lIFS) showed increased activations for bottom-up incongruent relative to congruent inputs. Moreover, lIFS activations were increased for physically identical McGurk stimuli, when participants segregated the audiovisual signals and reported their auditory percept. Critically, this activation increase for perceptual segregation was amplified when participants expected audiovisually incongruent signals based on prior sensory experience. Collectively, our results demonstrate that the lIFS combines top-down prior (in)congruency expectations with bottom-up (in)congruency cues to arbitrate between multisensory integration and segregation.

  6. Depth image enhancement using perceptual texture priors

    Science.gov (United States)

    Bang, Duhyeon; Shim, Hyunjung

    2015-03-01

    A depth camera is widely used in various applications because it provides a depth image of the scene in real time. However, due to the limited power consumption, the depth camera presents severe noises, incapable of providing the high quality 3D data. Although the smoothness prior is often employed to subside the depth noise, it discards the geometric details so to degrade the distance resolution and hinder achieving the realism in 3D contents. In this paper, we propose a perceptual-based depth image enhancement technique that automatically recovers the depth details of various textures, using a statistical framework inspired by human mechanism of perceiving surface details by texture priors. We construct the database composed of the high quality normals. Based on the recent studies in human visual perception (HVP), we select the pattern density as a primary feature to classify textures. Upon the classification results, we match and substitute the noisy input normals with high quality normals in the database. As a result, our method provides the high quality depth image preserving the surface details. We expect that our work is effective to enhance the details of depth image from 3D sensors and to provide a high-fidelity virtual reality experience.

  7. Research

    African Journals Online (AJOL)

    raoul

    2012-02-17

    Feb 17, 2012 ... This is an Open Access article distributed under the terms of the Creative ..... However, this system has great potential to negatively affect access to ... Dr. Samuel Yaw Opoku: Defining the Concept and Research Design; ...

  8. Research

    African Journals Online (AJOL)

    abp

    2016-04-26

    Apr 26, 2016 ... Management of biomedical waste in two medical laboratories in Bangui, Central ... Research .... Central African Republic Ministry of Health and corresponding ethics ..... In CAR, the management of BW remains embryonic. It is.

  9. Research

    African Journals Online (AJOL)

    ebutamanya

    2015-08-28

    Aug 28, 2015 ... Ethiopia, 2Bahir Dar Regional Health Research Laboratory Center, Department ... of Public Health, 4Institute of Medical Microbiology and Epidemiology of Infectious .... active ingredient x 10,000 dilution rate of product): 0.1%.

  10. Research

    African Journals Online (AJOL)

    raoul

    2011-03-11

    Mar 11, 2011 ... ... to General Organization of Teaching Hospitals and Institutes, Egypt, 2Department of .... Ethiopia at Max-Burger Research Institute, Leipzig, Germany ... [22] than Croatia (50%), Australia (53%), Thailand (41%), Italy (32.6%), ...

  11. Research

    African Journals Online (AJOL)

    7, No. 1 AJHPE. Research. A comprehensive approach to curriculum evaluation is deemed ... While evaluators are guided by the experiences of using different methods, ..... provided a follow-up in-depth exploration of the quantitative results.

  12. Research

    African Journals Online (AJOL)

    ... community in the design, conduct and/or evaluation of these activities. ... During Phase I of the mixed-methods research design, data were collected by ... A questionnaire survey was administered to all students registered for ... Data analysis.

  13. Research

    African Journals Online (AJOL)

    ebutamanya

    2016-02-03

    Feb 3, 2016 ... Published in partnership with the African Field Epidemiology Network (AFENET). (www.afenet.net) .... What is known about this topic ... India Co-ordinated Research Project. Ministry .... African Journal of Biotechnology. 2005 ...

  14. Research

    African Journals Online (AJOL)

    raoul

    2011-12-06

    Dec 6, 2011 ... Asia indicate a high incidence of Kikuchi lymphadenitis [6]. However ... It is believed that information derived from this study will be of immense value to the attending physician and also form a baseline data for future research.

  15. Research

    African Journals Online (AJOL)

    judicious use of current best evidence in making decisions about the care of individual ... [5] This highlights that teaching research methodology is inclined ... to evidence-based practice in final-year undergraduate physiotherapy students.

  16. Research

    African Journals Online (AJOL)

    curricula to address health systems changes and challenges .... Likert scale questions were used, along with open-ended qualitative questions. ... Clear communicator: Able to communicate important aspects of theory, research findings clearly ...

  17. researchers

    African Journals Online (AJOL)

    levels who is fluent in only Afrikaans and English. Differences in race .... The lack of knowledge of a particular vernacular often places a researcher firmly as an ..... discourse of African American women', Black women in the academy. Promises.

  18. Research

    African Journals Online (AJOL)

    2014-05-06

    May 6, 2014 ... Methods. The researchers used an exploratory, sequential mixed-method design, ... This design is useful to explore a topic, using qualitative ... interview a Delphi questionnaire was used to gather additional quantitative.

  19. Research

    African Journals Online (AJOL)

    Research. Clinical teaching is a technique used in the education of nurses. It ... learnt in a contextualised learning environment, which should support them in their ..... development of continuing professional development strategies. This study ...

  20. Research

    African Journals Online (AJOL)

    ebutamanya

    2016-03-03

    Mar 3, 2016 ... radiation therapy [9, 10]. The signs of obstructive ... year's undergraduate medical student: socio-demographic including age (in years), sex. .... awareness and enhance further research in this domain. Conclusion. Patients ...

  1. Research

    Science.gov (United States)

    Mathematics Teaching, 1973

    1973-01-01

    Implications for teachers from Piagetian-oriented piagetian-oriented research on problem solving reported in an article by Eleanor Duckworth are presented. Edward de Bono's Children Solve Problems,'' a collection of examples, is also discussed. (MS)

  2. Research

    African Journals Online (AJOL)

    abp

    2016-04-29

    Apr 29, 2016 ... performance hence workplace training is tied to achieving organizational aims and objectives. .... Ethical consideration: Permission to conduct research was sought from the County ..... Everybody Business: Strengthening.

  3. Requirement of cellular DDX3 for hepatitis C virus replication is unrelated to its interaction with the viral core protein.

    Science.gov (United States)

    Angus, Allan G N; Dalrymple, David; Boulant, Steeve; McGivern, David R; Clayton, Reginald F; Scott, Martin J; Adair, Richard; Graham, Susan; Owsianka, Ania M; Targett-Adams, Paul; Li, Kui; Wakita, Takaji; McLauchlan, John; Lemon, Stanley M; Patel, Arvind H

    2010-01-01

    The cellular DEAD-box protein DDX3 was recently shown to be essential for hepatitis C virus (HCV) replication. Prior to that, we had reported that HCV core binds to DDX3 in yeast-two hybrid and transient transfection assays. Here, we confirm by co-immunoprecipitation that this interaction occurs in cells replicating the JFH1 virus. Consistent with this result, immunofluorescence staining of infected cells revealed a dramatic redistribution of cytoplasmic DDX3 by core protein to the virus assembly sites around lipid droplets. Given this close association of DDX3 with core and lipid droplets, and its involvement in virus replication, we investigated the importance of this host factor in the virus life cycle. Mutagenesis studies located a single amino acid in the N-terminal domain of JFH1 core that when changed to alanine significantly abrogated this interaction. Surprisingly, this mutation did not alter infectious virus production and RNA replication, indicating that the core-DDX3 interaction is dispensable in the HCV life cycle. Consistent with previous studies, siRNA-led knockdown of DDX3 lowered virus production and RNA replication levels of both WT JFH1 and the mutant virus unable to bind DDX3. Thus, our study shows for the first time that the requirement of DDX3 for HCV replication is unrelated to its interaction with the viral core protein.

  4. Recombination occurs within minutes of replication blockage by RTS1 producing restarted forks that are prone to collapse

    Science.gov (United States)

    Nguyen, Michael O; Jalan, Manisha; Morrow, Carl A; Osman, Fekret; Whitby, Matthew C

    2015-01-01

    The completion of genome duplication during the cell cycle is threatened by the presence of replication fork barriers (RFBs). Following collision with a RFB, replication proteins can dissociate from the stalled fork (fork collapse) rendering it incapable of further DNA synthesis unless recombination intervenes to restart replication. We use time-lapse microscopy and genetic assays to show that recombination is initiated within ∼10 min of replication fork blockage at a site-specific barrier in fission yeast, leading to a restarted fork within ∼60 min, which is only prevented/curtailed by the arrival of the opposing replication fork. The restarted fork is susceptible to further collapse causing hyper-recombination downstream of the barrier. Surprisingly, in our system fork restart is unnecessary for maintaining cell viability. Seemingly, the risk of failing to complete replication prior to mitosis is sufficient to warrant the induction of recombination even though it can cause deleterious genetic change. DOI: http://dx.doi.org/10.7554/eLife.04539.001 PMID:25806683

  5. 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.

  6. 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.

  7. Prior storm experience moderates water surge perception and risk.

    Directory of Open Access Journals (Sweden)

    Gregory D Webster

    Full Text Available BACKGROUND: How accurately do people perceive extreme water speeds and how does their perception affect perceived risk? Prior research has focused on the characteristics of moving water that can reduce human stability or balance. The current research presents the first experiment on people's perceptions of risk and moving water at different speeds and depths. METHODS: Using a randomized within-person 2 (water depth: 0.45, 0.90 m ×3 (water speed: 0.4, 0.8, 1.2 m/s experiment, we immersed 76 people in moving water and asked them to estimate water speed and the risk they felt. RESULTS: Multilevel modeling showed that people increasingly overestimated water speeds as actual water speeds increased or as water depth increased. Water speed perceptions mediated the direct positive relationship between actual water speeds and perceptions of risk; the faster the moving water, the greater the perceived risk. Participants' prior experience with rip currents and tropical cyclones moderated the strength of the actual-perceived water speed relationship; consequently, mediation was stronger for people who had experienced no rip currents or fewer storms. CONCLUSIONS: These findings provide a clearer understanding of water speed and risk perception, which may help communicate the risks associated with anticipated floods and tropical cyclones.

  8. EdU Incorporation for FACS and Microscopy Analysis of DNA Replication in Budding Yeast.

    Science.gov (United States)

    Talarek, Nicolas; Petit, Julie; Gueydon, Elisabeth; Schwob, Etienne

    2015-01-01

    DNA replication is a key determinant of chromosome segregation and stability in eukaryotes. The yeast Saccharomyces cerevisiae has been extensively used for cell cycle studies, yet simple but key parameters such as the fraction of cells in S phase in a population or the subnuclear localization of DNA synthesis have been difficult to gather for this organism. 5-ethynyl-2'-deoxyuridine (EdU) is a thymidine analogue that can be incorporated in vivo and later detected using copper-catalyzed azide alkyne cycloaddition (Click reaction) without prior DNA denaturation. This chapter describes a budding yeast strain and conditions that allow rapid EdU incorporation at moderate extracellular concentrations, followed by its efficient detection for the analysis of DNA replication in single cells by flow cytometry and fluorescence microscopy.

  9. 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.

  10. 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.

  11. 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...

  12. 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 ...

  13. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Kai, Mihoko; Wang, Teresa S.-F

    2003-11-27

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

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

    Directory of Open Access Journals (Sweden)

    Shlomit Farkash-Amar

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

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. 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...

  2. 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...

  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 g

  4. 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...

  5. 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.

  6. Effects of prior stimulus and prior perception on neural correlates of auditory stream segregation.

    Science.gov (United States)

    Snyder, Joel S; Holder, W Trent; Weintraub, David M; Carter, Olivia L; Alain, Claude

    2009-11-01

    We examined whether effects of prior experience are mediated by distinct brain processes from those processing current stimulus features. We recorded event-related potentials (ERPs) during an auditory stream segregation task that presented an adaptation sequence with a small, intermediate, or large frequency separation between low and high tones (Deltaf), followed by a test sequence with intermediate Deltaf. Perception of two streams during the test was facilitated by small prior Deltaf and by prior perception of two streams and was accompanied by more positive ERPs. The scalp topography of these perception-related changes in ERPs was different from that observed for ERP modulations due to increasing the current Deltaf. These results reveal complex interactions between stimulus-driven activity and temporal-context-based processes and suggest a complex set of brain areas involved in modulating perception based on current and previous experience.

  7. On the replication of genetic associations: timing can be everything!

    Science.gov (United States)

    Lasky-Su, Jessica; Lyon, Helen N; Emilsson, Valur; Heid, Iris M; Molony, Cliona; Raby, Benjamin A; Lazarus, Ross; Klanderman, Barbara; Soto-Quiros, Manuel E; Avila, Lydiana; Silverman, Edwin K; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Kronenberg, Florian; Vollmert, Caren; Illig, Thomas; Fox, Caroline S; Levy, Daniel; Laird, Nan; Ding, Xiao; McQueen, Matt B; Butler, Johannah; Ardlie, Kristin; Papoutsakis, Constantina; Dedoussis, George; O'Donnell, Christopher J; Wichmann, H-Erich; Celedón, Juan C; Schadt, Eric; Hirschhorn, Joel; Weiss, Scott T; Stefansson, Kari; Lange, Christoph

    2008-04-01

    The failure of researchers to replicate genetic-association findings is most commonly attributed to insufficient statistical power, population stratification, or various forms of between-study heterogeneity or environmental influences.(1) Here, we illustrate another potential cause for nonreplications that has so far not received much attention in the literature. We illustrate that the strength of a genetic effect can vary by age, causing "age-varying associations." If not taken into account during the design and the analysis of a study, age-varying genetic associations can cause nonreplication. By using the 100K SNP scan of the Framingham Heart Study, we identified an age-varying association between a SNP in ROBO1 and obesity and hypothesized an age-gene interaction. This finding was followed up in eight independent samples comprising 13,584 individuals. The association was replicated in five of the eight studies, showing an age-dependent relationship (one-sided combined p = 3.92 x 10(-9), combined p value from pediatric cohorts = 2.21 x 10(-8), combined p value from adult cohorts = 0.00422). Furthermore, this study illustrates that it is difficult for cross-sectional study designs to detect age-varying associations. If the specifics of age- or time-varying genetic effects are not considered in the selection of both the follow-up samples and in the statistical analysis, important genetic associations may be missed.

  8. 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.

  9. Improving semantic scene understanding using prior information

    Science.gov (United States)

    Laddha, Ankit; Hebert, Martial

    2016-05-01

    Perception for ground robot mobility requires automatic generation of descriptions of the robot's surroundings from sensor input (cameras, LADARs, etc.). Effective techniques for scene understanding have been developed, but they are generally purely bottom-up in that they rely entirely on classifying features from the input data based on learned models. In fact, perception systems for ground robots have a lot of information at their disposal from knowledge about the domain and the task. For example, a robot in urban environments might have access to approximate maps that can guide the scene interpretation process. In this paper, we explore practical ways to combine such prior information with state of the art scene understanding approaches.

  10. Theoretical Priors On Modified Growth Parametrisations

    CERN Document Server

    Song, Yong-Seon; Caldera-Cabral, Gabriela; Koyama, Kazuya

    2010-01-01

    Next generation surveys will observe the large-scale structure of the Universe with unprecedented accuracy. This will enable us to test the relationships between matter over-densities, the curvature perturbation and the Newtonian potential. Any large-distance modification of gravity or exotic nature of dark energy modifies these relationships as compared to those predicted in the standard smooth dark energy model based on General Relativity. In linear theory of structure growth such modifications are often parameterised by virtue of two functions of space and time that enter the relation of the curvature perturbation to, first, the matter over-density, and second, the Newtonian potential. We investigate the predictions for these functions in Brans-Dicke theory, clustering dark energy models and interacting dark energy models. We find that each theory has a distinct path in the parameter space of modified growth. Understanding these theoretical priors on the parameterisations of modified growth is essential to...

  11. Care for women with prior preterm birth

    Science.gov (United States)

    Iams, Jay D.; Berghella, Vincenzo

    2013-01-01

    Women who have delivered an infant between 16 and 36 weeks’ gestation have an increased risk of preterm birth in subsequent pregnancies. The risk increases with more than 1 preterm birth and is inversely proportional to the gestational age of the previous preterm birth. African American women have rates of recurrent preterm birth that are nearly twice that of women of other backgrounds. An approximate risk of recurrent preterm birth can be estimated by a comprehensive reproductive history, with emphasis on maternal race, the number and gestational age of prior births, and the sequence of events preceding the index preterm birth. Interventions including smoking cessation, eradication of asymptomatic bacteriuria, progestational agents, and cervical cerclage can reduce the risk of recurrent preterm birth when employed appropriately. PMID:20417491

  12. Sparse Multivariate Modeling: Priors and Applications

    DEFF Research Database (Denmark)

    Henao, Ricardo

    modeling, a model for peptide-protein/protein-protein interactions called latent protein tree, a framework for sparse Gaussian process classification based on active set selection and a linear multi-category sparse classifier specially targeted to gene expression data. The thesis is organized to provide......This thesis presents a collection of statistical models that attempt to take advantage of every piece of prior knowledge available to provide the models with as much structure as possible. The main motivation for introducing these models is interpretability since in practice we want to be able...... to use them as hypothesis generating tools. All of our models start from a family of structures, for instance factor models, directed acyclic graphs, classifiers, etc. Then we let them be selectively sparse as a way to provide them with structural fl exibility and interpretability. Finally, we complement...

  13. Care for women with prior preterm birth.

    Science.gov (United States)

    Iams, Jay D; Berghella, Vincenzo

    2010-08-01

    Women who have delivered an infant between 16 and 36 weeks' gestation have an increased risk of preterm birth in subsequent pregnancies. The risk increases with more than 1 preterm birth and is inversely proportional to the gestational age of the previous preterm birth. African American women have rates of recurrent preterm birth that are nearly twice that of women of other backgrounds. An approximate risk of recurrent preterm birth can be estimated by a comprehensive reproductive history, with emphasis on maternal race, the number and gestational age of prior births, and the sequence of events preceding the index preterm birth. Interventions including smoking cessation, eradication of asymptomatic bacteriuria, progestational agents, and cervical cerclage can reduce the risk of recurrent preterm birth when employed appropriately. Copyright (c) 2010 Mosby, Inc. All rights reserved.

  14. Early medical abortion without prior ultrasound.

    Science.gov (United States)

    Raymond, Elizabeth G; Bracken, Hillary

    2015-09-01

    To explore the potential for using last menstrual period (LMP) rather than ultrasound to establish gestational age (GA) eligibility for medical abortion. We used the results of a recently published systematic review to identify studies with data on the number of abortion patients with GA more than 63 or 70 days by ultrasound but less than those or other specific limits by LMP. We analyzed data from these studies to estimate the proportion of women with GAs greater than 63 or 70 days by ultrasound in various subgroups of women defined by LMP. We found three studies with relevant data. One enrolled 4257 medical abortion patients of whom 4% had GAs of >70 days by ultrasound. Of the 2681 who were certain that their LMPs began no more than 56 days prior, only 16 (0.6%) were >70 days by ultrasound. In a second much smaller study of surgical abortion patients, of whom 19% were >70 days by ultrasound, 90 women were certain that their LMPs started more than 56 days prior, and of those, 7 (7.8%) had GAs of >70 days by ultrasound. In the third study, which included surgical abortion patients with a mean GA of 61 days, at least 12% of the 138 patients with LMPs 70 days by ultrasound. The possibility that access to medical abortion can be enhanced for selected women by omitting the requirement for a screening ultrasound is promising and should be further investigated. Gestational dating using LMP rather than ultrasound may be reasonable for selected patients before medical abortion. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Research

    African Journals Online (AJOL)

    abp

    2013-02-25

    Feb 25, 2013 ... Of these 56 eyes, the visual acuity in 49 eyes (87.5%) improved with pinhole. Twenty seven pupils had ... (www.afenet.net). Research ... primary basic 1 to 6 and aged 5 to 15 years were included in the study. The United ...

  16. Research

    African Journals Online (AJOL)

    collaboration, but also in less tangible ways affecting quality of research.[5] ... Methods. A 40-hour workshop in biostatistical reasoning was conducted ... test median score was 68% (IQR 62 - 76%), with p<0.0001 for the overall comparison of pre- v. post-scores. ... limitations of a traditional lecture-based mode of instruction.

  17. Research

    African Journals Online (AJOL)

    abp

    2014-03-13

    Mar 13, 2014 ... &Corresponding author: Dr. Oliver Ezechi, Clinical Sciences Division, Nigerian Institute of Medical Research, ... with Hepatitis B and C Virus infection in pregnant HIV positive Nigerians. ... Whether or not HCV directly impacts HIV disease ..... natural history, fibrosis, and impact of antiretroviral treatment:.

  18. Research

    African Journals Online (AJOL)

    understood in the profession, evolved from therapeutic activity (within a medi- cal model ... facilitate students' ability to examine institutional systems that hinder ..... don't have connections with each other … we went to the schools and were told ... for change or conduct action research projects that deal with occupational.

  19. Research

    African Journals Online (AJOL)

    abp

    2015-12-11

    Dec 11, 2015 ... ... Dschang, Cameroon, 2Division of Health Operations Research, Ministry of Public ... This is an Open Access article distributed under the terms of the Creative Commons ... not yet been investigated but may can be explained by weakness of .... Cameroonian market and why not apply for surveillance of.

  20. Research

    African Journals Online (AJOL)

    by teaching them skills on how to acquire and appraise knowledge for a particular ... [3] Similarities have been noted in the roles of lecturers that facilitate learning rather than ..... Student feedback related to facilitators of and barriers to learning. Facilitators of ... 'Sometimes time (clinical, research, social, sport) was limited.'.

  1. Research

    African Journals Online (AJOL)

    raoul

    2011-08-25

    Aug 25, 2011 ... completely replaced animals with computer modeling, manikins and ... distribution, and reproduction in any medium, provided the original ... developed internal guidelines on the use of animals in research in 2004 [13]. ... Only one institution used human cell cultures as a replacement to live animal use.

  2. Research

    African Journals Online (AJOL)

    abp

    2013-08-05

    Aug 5, 2013 ... In 2007, The World Health Organization (WHO) recommended ... are taken nearer to the community through clinical outreach ... Sample size and Sampling procedure ... researchers shared and debated the way each of them understood .... this may involve selling off assets to get the money for transport.

  3. Research

    African Journals Online (AJOL)

    ebutamanya

    2016-04-20

    Apr 20, 2016 ... ... Journal - ISSN 1937-8688. This is an Open Access article distributed under the terms of the Creative ... diabetes mellitus, obesity, family history of premature CHD in a first ... was reviewed and approved by the Hospital's Research and Ethics .... apoptosis of peripheral adipocytes, decreased pre-adipocyte.

  4. Performing Inferential Statistics Prior to Data Collection

    Science.gov (United States)

    Trafimow, David; MacDonald, Justin A.

    2017-01-01

    Typically, in education and psychology research, the investigator collects data and subsequently performs descriptive and inferential statistics. For example, a researcher might compute group means and use the null hypothesis significance testing procedure to draw conclusions about the populations from which the groups were drawn. We propose an…

  5. 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

  6. 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.

  7. 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.

  8. 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)....

  9. 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....

  10. 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.

  11. 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.

  12. Influence of Injection-Molding Process Parameters on Part Replication of Microstructures with Additively-Manufactured Soft Tooling Inserts WCMNM 2017 No

    DEFF Research Database (Denmark)

    Mischkot, Michael; Zhang, Yang; Segebrecht Gøtje, Asger

    2017-01-01

    The objective of this research is to investigate the influence of injection molding parameters on the dimensional replication of microstructure surfaces in injection molding with additively manufactured soft tooling inserts in a photopolymer material. The replication degree of micropillars...... diameter and decreases the replication degree of the pillar height. A high melt temperature increases the pillar diameter independently from the pillar height. A higher injection speed affects both pillar diameter and height negatively. In addition, the study showed a significant difference...

  13. Effects of Interactions between Environmental and Genetic Factors on Health Aging:A Review on the Relevant Prior Research%环境与遗传因素交互作用对老龄健康的影响*--相关前期研究综述

    Institute of Scientific and Technical Information of China (English)

    曾毅; 程令国; 阮荣平; 陈华帅; 李建新; 张风雨; 陶伟; 顾军; 田小利

    2014-01-01

    综述了环境与遗传交互作用对老龄健康影响的文献和国际研究进展,概述三个相关前期研究案例:FOXO基因类型与高龄老人60岁左右和当前喝茶的交互作用显著影响高龄老人健康,携带FOXO基因者喝茶对认知功能改善作用比不携带 FOXO 基因者显著要大;ADRB2-rs1042718或 ADRB2-rs1042719基因类型与经常锻炼和参加社会休闲活动的交互作用对高龄老人认知功能和自评健康有显著改善;APOE4基因与生活重压交互作用会显著诱发老人自评健康差。根据研究分析结论,建议在保护个人隐私前提下,充分考虑环境因素与基因类型交互作用,实行有的放矢的健康干预方案,可能大大提高老龄健康干预效益。%This paper presents a summarized review of the literature and international research program progress about investigations of effects of interactions between environmental and genetic factors (GxE) on health aging .We also briefly review three of our prior researches in this field ,including :Interactions between carrying the FOXO genotypes and tea drinking around age 60 or at present were significantly associated with lower risk of cognitive disability at advanced ages ;Interactions between carrying the minor allele rs1042718 or rs1042719 of ADRB2 gene and regular exercise or social-leisure activities predicted significantly increased cognitive function and the likelihood of self-reporting good health at advanced ages ;Interactions between carrying the APOE4 genotype and the life stress factors significantly increased the risk of poor self-rated health among older adults .Our review and analysis imply that health promotion and intervention programs considering individuals’ genetic profiles as well as the GxE effects ,with appropriate protection of privacy/confidentiality , would yield increased benefits and reduced costs to the programs and their participants .

  14. 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.

  15. 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...

  16. Bacterial replication, transcription and translation : mechanistic insights from single-molecule biochemical studies

    NARCIS (Netherlands)

    Robinson, Andrew; van Oijen, Antoine M.

    2013-01-01

    Decades of research have resulted in a remarkably detailed understanding of the molecular mechanisms of bacterial DNA replication, transcription and translation. Our understanding of the kinetics and physical mechanisms that drive these processes forward has been expanded by the ability of single-mo

  17. Moderators of the Body Dissatisfaction-Eating Disorder Symptomatology Relationship: Replication and Extension

    Science.gov (United States)

    Brannan, Megan E.; Petrie, Trent A.

    2008-01-01

    In this study, research conducted by T. L. Tylka (2004) was replicated and extended by examining perfectionism (self-oriented and socially prescribed), ego goal orientation, body surveillance, and neuroticism as moderators of the relationship between body dissatisfaction and bulimic and anorexic symptomatology among female undergraduates (N =…

  18. Foreign Language Anxiety and Oral Exam Performance: A Replication of Phillips's "MLJ" Study

    Science.gov (United States)

    Hewitt, Elaine; Stephenson, Jean

    2012-01-01

    This article reports on a replication study of a substantial piece of research published in "The Modern Language Journal", carried out by Elaine Matties Phillips in 1992, and entitled "The Effects of Language Anxiety on Students' Oral Test Performance and Attitudes." The aim of both studies was to assess the influence of…

  19. Fidelity of DNA Replication in Normal and Malignant Human Breast Cells.

    Science.gov (United States)

    1997-08-01

    A vatit"Y Of DNA synthesis and the typt of DNA replica~tion Products " celular prca including DNA rsplicatlon. DNA repsair. R~NA formed in experiments...Sicrturn thlarida wsMi SocletylMai yland Division . cnd the University of Maryland rDesigntld FIG.4. 1w ffet o a angeof cmu;, tloideResearch

  20. The silent defense: Micro-RNA directed defense against HIV-1 replication

    Directory of Open Access Journals (Sweden)

    Kumar Ajit

    2007-04-01

    Full Text Available Abstract MicroRNAs play critical role in regulating gene expression. MicroRNA profile of particular cell type bears the signature of cell type specific gene expression. Given that viral pathogens replicate by evading host defenses, research is now focused on the miRNA-regulated genes that critically regulate HIV-1 propagation in human host cells.

  1. "Project ALERT's" Effects on Adolescents' Prodrug Beliefs: A Replication and Extension Study

    Science.gov (United States)

    Clark, Heddy Kovach; Ringwalt, Chris L.; Hanley, Sean; Shamblen, Stephen R.

    2010-01-01

    This article represents a replication and extension of previous studies of the effects of "Project ALERT", a school-based substance use prevention program, on the prodrug beliefs of adolescents. Specifically, the authors' research examined "Project ALERT's" effects on adolescents' intentions to use substances in the future, beliefs about substance…

  2. Practice Guidelines for School Social Workers: A Modified Replication and Extension of a Prototype

    Science.gov (United States)

    Staudt, Marlys M.; Cherry, Donna J.; Watson, Melanie

    2005-01-01

    Based on a review of intervention studies in 13 social work journals, one group of researchers organized the targets of interventions and the interventions tested in relation to them as a first step to develop practice guidelines for social workers. The authors replicated and extended that work to the specialty of school social work by reviewing…

  3. Bacterial replication, transcription and translation : mechanistic insights from single-molecule biochemical studies

    NARCIS (Netherlands)

    Robinson, Andrew; van Oijen, Antoine M.

    2013-01-01

    Decades of research have resulted in a remarkably detailed understanding of the molecular mechanisms of bacterial DNA replication, transcription and translation. Our understanding of the kinetics and physical mechanisms that drive these processes forward has been expanded by the ability of single-mo

  4. A Systematic Replication Comparing Interteaching and Lecture in the Community College Classroom

    Science.gov (United States)

    Felderman, Theresa A.

    2016-01-01

    Researchers demonstrated the effectiveness of interteaching relative to lecture in 4-year university classrooms, but exploration in other settings is deficient. This systematic replication examines the extent to which interteaching leads to increased exam scores compared to traditional lecture in the community college classroom. Participants in…

  5. Examining the Validity of Cyclothymic Disorder in a Youth Sample: Replication and Extension

    Science.gov (United States)

    Van Meter, Anna; Youngstrom, Eric A.; Demeter, Christine; Findling, Robert L.

    2013-01-01

    DSM-IV-TR defines four subtypes of bipolar disorder (BP): bipolar I, bipolar II, cyclothymic disorder and bipolar not otherwise specified (NOS). However, cyclothymic disorder in children is rarely researched, or often subsumed in an "NOS" category. The present study tests the replicability of findings from an earlier study, and expands on the…

  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. Foreign Language Anxiety and Oral Exam Performance: A Replication of Phillips's "MLJ" Study

    Science.gov (United States)

    Hewitt, Elaine; Stephenson, Jean

    2012-01-01

    This article reports on a replication study of a substantial piece of research published in "The Modern Language Journal", carried out by Elaine Matties Phillips in 1992, and entitled "The Effects of Language Anxiety on Students' Oral Test Performance and Attitudes." The aim of both studies was to assess the influence of…

  8. 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.

  9. 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.

  10. Reconstruction of methods of execution of the death penalty by shooting in the years 1949-1954 based on exhumation research of "prison fields" in Osobowicki Cemetery in Wroclaw. Part I--Historical outline and results of research conducted prior to exhumations performed in 2011.

    Science.gov (United States)

    Szleszkowski, Łukasz

    2012-01-01

    In the period between October and December 2011, a series of exhumation research of the so-called prison quarters dating back to 1949-1954 was conducted in Osobowicki Cemetery in Wrocław. Among the buried there were political prisoners executed by shooting--genuine or alleged members of post-war independence organizations. It was a unique opportunity to determine the method of execution of the death penalty in that period because, according to historical data and the results of two test exhumations, this method considerably differed from instructions on the use of a firing squad during execution of the death penalty.

  11. The Territorial Prior-Residence Effect and Children's Behavior in Social Dilemmas

    Science.gov (United States)

    Han, Ru; Li, Shu; Shi, Jian-Nong

    2009-01-01

    Research on territorial behavior has focused on animal populations, and relatively little has dealt with territoriality in humans, except in the area of human sports. This study was an investigation of the prior-residence effect on children's behavior in social dilemmas. The analysis was carried out by means of research designed for preschool…

  12. 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...

  13. 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...

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.