WorldWideScience

Sample records for replication previous studies

  1. 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...

  2. Three Conceptual Replication Studies in Group Theory

    Science.gov (United States)

    Melhuish, Kathleen

    2018-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

    Anderson, Samantha F; Maxwell, Scott E

    2017-01-01

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

  5. On the Tengiz petroleum deposit previous study

    International Nuclear Information System (INIS)

    Nysangaliev, A.N.; Kuspangaliev, T.K.

    1997-01-01

    Tengiz petroleum deposit previous study is described. Some consideration about structure of productive formation, specific characteristic properties of petroleum-bearing collectors are presented. Recommendation on their detail study and using of experience on exploration and development of petroleum deposit which have analogy on most important geological and industrial parameters are given. (author)

  6. Lack of replication of previous autism spectrum disorder GWAS hits in European populations

    NARCIS (Netherlands)

    Torrico, B.; Chiocchetti, A.G.; Bacchelli, E.; Trabetti, E.; Hervas, A.; Franke, B.; Buitelaar, J.K.; Rommelse, N.N.J.; Yousaf, A.; Duketis, E.; Freitag, C.M.; Caballero-Andaluz, R.; Martinez-Mir, A.; Scholl, F.G.; Ribases, M.; Battaglia, A.; Malerba, G.; Delorme, R.; Benabou, M.; Maestrini, E.; Bourgeron, T.; Cormand, B.; Toma, C.

    2017-01-01

    Common variants contribute significantly to the genetics of autism spectrum disorder (ASD), although the identification of individual risk polymorphisms remains still elusive due to their small effect sizes and limited sample sizes available for association studies. During the last decade several

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

    Science.gov (United States)

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

    2016-07-01

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

  8. 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.

  9. The AGIS metric and time of test: A replication study

    OpenAIRE

    Counsell, S; Swift, S; Tucker, A

    2016-01-01

    Visual Field (VF) tests and corresponding data are commonly used in clinical practices to manage glaucoma. The standard metric used to measure glaucoma severity is the Advanced Glaucoma Intervention Studies (AGIS) metric. We know that time of day when VF tests are applied can influence a patient’s AGIS metric value; a previous study showed that this was the case for a data set of 160 patients. In this paper, we replicate that study using data from 2468 patients obtained from Moorfields Eye Ho...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-05-01

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

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

    NARCIS (Netherlands)

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

    1974-01-01

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

  12. Bayesian evaluation of effect size after replicating an original study

    NARCIS (Netherlands)

    Van Aert, Robbie C M; Van Assen, Marcel A.L.M.

    2017-01-01

    The vast majority of published results in the literature is statistically significant, which raises concerns about their reliability. The Reproducibility Project Psychology (RPP) and Experimental Economics Replication Project (EE-RP) both replicated a large number of published studies in psychology

  13. Personality disorders in previously detained adolescent females: a prospective study

    NARCIS (Netherlands)

    Krabbendam, A.; Colins, O.F.; Doreleijers, T.A.H.; van der Molen, E.; Beekman, A.T.F.; Vermeiren, R.R.J.M.

    2015-01-01

    This longitudinal study investigated the predictive value of trauma and mental health problems for the development of antisocial personality disorder (ASPD) and borderline personality disorder (BPD) in previously detained women. The participants were 229 detained adolescent females who were assessed

  14. Is Implicit Theory of Mind a Real and Robust Phenomenon? Results From a Systematic Replication Study.

    Science.gov (United States)

    Kulke, Louisa; von Duhn, Britta; Schneider, Dana; Rakoczy, Hannes

    2018-06-01

    Recently, theory-of-mind research has been revolutionized by findings from novel implicit tasks suggesting that at least some aspects of false-belief reasoning develop earlier in ontogeny than previously assumed and operate automatically throughout adulthood. Although these findings are the empirical basis for far-reaching theories, systematic replications are still missing. This article reports a preregistered large-scale attempt to replicate four influential anticipatory-looking implicit theory-of-mind tasks using original stimuli and procedures. Results showed that only one of the four paradigms was reliably replicated. A second set of studies revealed, further, that this one paradigm was no longer replicated once confounds were removed, which calls its validity into question. There were also no correlations between paradigms, and thus, no evidence for their convergent validity. In conclusion, findings from anticipatory-looking false-belief paradigms seem less reliable and valid than previously assumed, thus limiting the conclusions that can be drawn from them.

  15. Is dopamine D1 receptor availability related to social behavior? A positron emission tomography replication study.

    Directory of Open Access Journals (Sweden)

    Pontus Plavén-Sigray

    Full Text Available Associations between dopamine receptor levels and pro- and antisocial behavior have previously been demonstrated in human subjects using positron emission tomography (PET and self-rated measures of personality traits. So far, only one study has focused on the dopamine D1-receptor (D1-R, finding a positive correlation with the trait social desirability, which is characterized by low dominant and high affiliative behavior, while physical aggression showed a negative correlation. The aim of the present study was to replicate these previous findings using a new independent sample of subjects.Twenty-six healthy males were examined with the radioligand [11C]SCH-23390, and completed the Swedish universities Scales of Personality (SSP which includes measures of social desirability and physical trait aggression. The simplified reference tissue model with cerebellum as reference region was used to calculate BPND values in the whole striatum and limbic striatum. The two regions were selected since they showed strong association between D1-R availability and personality scores in the previous study. Pearson's correlation coefficients and replication Bayes factors were then employed to assess the replicability and robustness of previous results.There were no significant correlations (all p values > 0.3 between regional BPND values and personality scale scores. Replication Bayes factors showed strong to moderate evidence in favor no relationship between D1-receptor availability and social desirability (striatum BF01 = 12.4; limbic striatum BF01 = 7.2 or physical aggression scale scores (limbic striatum BF01 = 3.3, compared to the original correlations.We could not replicate the previous findings of associations between D1-R availability and either pro- or antisocial behavior as measured using the SSP. Rather, there was evidence in favor of failed replications of associations between BPND and scale scores. Potential reasons for these results are restrictive

  16. Role of Importance and Distinctiveness of Semantic Features in People with Aphasia: A Replication Study

    Science.gov (United States)

    Mason-Baughman, Mary Beth; Wallace, Sarah E.

    2014-01-01

    Previous studies suggest that people with aphasia have incomplete lexical-semantic representations with decreased low-importance distinctive (LID) feature knowledge. In addition, decreased LID feature knowledge correlates with ability to discriminate among semantically related words. The current study seeks to replicate and extend previous…

  17. Optorsim: A Grid Simulator for Studying Dynamic Data Replication Strategies

    CERN Document Server

    Bell, William H; Millar, A Paul; Capozza, Luigi; Stockinger, Kurt; Zini, Floriano

    2003-01-01

    Computational grids process large, computationally intensive problems on small data sets. In contrast, data grids process large computational problems that in turn require evaluating, mining and producing large amounts of data. Replication, creating geographically disparate identical copies of data, is regarded as one of the major optimization techniques for reducing data access costs. In this paper, several replication algorithms are discussed. These algorithms were studied using the Grid simulator: OptorSim. OptorSim provides a modular framework within which optimization strategies can be studied under different Grid configurations. The goal is to explore the stability and transient behaviour of selected optimization techniques. We detail the design and implementation of OptorSim and analyze various replication algorithms based on different Grid workloads.

  18. A comprehensive family-based replication study of schizophrenia genes

    DEFF Research Database (Denmark)

    Aberg, Karolina A; Liu, Youfang; Bukszár, Jozsef

    2013-01-01

     768 control subjects from 6 databases and, after quality control 6298 individuals (including 3286 cases) from 1811 nuclear families. MAIN OUTCOMES AND MEASURES Case-control status for SCZ. RESULTS Replication results showed a highly significant enrichment of SNPs with small P values. Of the SNPs...... in an independent family-based replication study that, after quality control, consisted of 8107 SNPs. SETTING Linkage meta-analysis, brain transcriptome meta-analysis, candidate gene database, OMIM, relevant mouse studies, and expression quantitative trait locus databases. PATIENTS We included 11 185 cases and 10...

  19. Gambling, Risk-Taking, and Antisocial Behavior: A Replication Study Supporting the Generality of Deviance.

    Science.gov (United States)

    Mishra, Sandeep; Lalumière, Martin L; Williams, Robert J

    2017-03-01

    Research suggests that high frequency gambling is a component of the "generality of deviance", which describes the observation that various forms of risky and antisocial behavior tend to co-occur among individuals. Furthermore, risky and antisocial behaviors have been associated with such personality traits as low self-control, and impulsivity, and sensation-seeking. We conducted a replication (and extension) of two previous studies examining whether high frequency gambling is part of the generality of deviance using a large and diverse community sample (n = 328). This study was conducted as a response to calls for more replication studies in the behavioral and psychological sciences (recent systematic efforts suggest that a significant proportion of psychology studies do not replicate). The results of the present study largely replicate those previously found, and in many cases, we observed stronger associations among measures of gambling, risk-taking, and antisocial behavior in this diverse sample. Together, this study provides evidence for the generality of deviance inclusive of gambling (and, some evidence for the replicability of research relating to gambling and individual differences).

  20. Who Needs Replication?

    Science.gov (United States)

    Porte, Graeme

    2013-01-01

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

  1. The big five as tendencies in situations : A replication study

    NARCIS (Netherlands)

    Hendriks, AAJ

    1996-01-01

    Van Heck, Perugini, Caprara and Froger (1994) report the average generalizability coefficient reflecting the consistent ordering of persons across different situations and different trait markers (items) to be in the order of 0.70. We performed a replication study in which we improved on their

  2. Reproducibility and replicability of rodent phenotyping in preclinical studies

    NARCIS (Netherlands)

    Kafkafi, Neri; Agassi, Joseph; Chesler, Elissa J.; Crabbe, John C.; Crusio, Wim E.; Eilam, David; Gerlai, Robert; Golani, Ilan; Gomez-Marin, Alex; Heller, Ruth; Iraqi, Fuad; Jaljuli, Iman; Karp, Natasha A.; Morgan, Hugh; Nicholson, George; Pfaff, Donald W.; Richter, S. Helene; Stark, Philip B.; Stiedl, Oliver; Stodden, Victoria; Tarantino, Lisa M.; Tucci, Valter; Valdar, William; Williams, Robert W.; Würbel, Hanno; Benjamini, Yoav

    The scientific community is increasingly concerned with the proportion of published “discoveries” that are not replicated in subsequent studies. The field of rodent behavioral phenotyping was one of the first to raise this concern, and to relate it to other methodological issues: the complex

  3. 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…

  4. Radon anomalies prior to earthquakes (1). Review of previous studies

    International Nuclear Information System (INIS)

    Ishikawa, Tetsuo; Tokonami, Shinji; Yasuoka, Yumi; Shinogi, Masaki; Nagahama, Hiroyuki; Omori, Yasutaka; Kawada, Yusuke

    2008-01-01

    The relationship between radon anomalies and earthquakes has been studied for more than 30 years. However, most of the studies dealt with radon in soil gas or in groundwater. Before the 1995 Hyogoken-Nanbu earthquake, an anomalous increase of atmospheric radon was observed at Kobe Pharmaceutical University. The increase was well fitted with a mathematical model related to earthquake fault dynamics. This paper reports the significance of this observation, reviewing previous studies on radon anomaly before earthquakes. Groundwater/soil radon measurements for earthquake prediction began in 1970's in Japan as well as foreign countries. One of the most famous studies in Japan is groundwater radon anomaly before the 1978 Izu-Oshima-kinkai earthquake. We have recognized the significance of radon in earthquake prediction research, but recently its limitation was also pointed out. Some researchers are looking for a better indicator for precursors; simultaneous measurements of radon and other gases are new trials in recent studies. Contrary to soil/groundwater radon, we have not paid much attention to atmospheric radon before earthquakes. However, it might be possible to detect precursors in atmospheric radon before a large earthquake. In the next issues, we will discuss the details of the anomalous atmospheric radon data observed before the Hyogoken-Nanbu earthquake. (author)

  5. 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.

  6. Blinded with Science or Informed by Charts? A Replication Study

    OpenAIRE

    Dragicevic , Pierre; Jansen , Yvonne

    2018-01-01

    International audience; We provide a reappraisal of Tal and Wansink's study "Blinded with Science" , where seemingly trivial charts were shown to increase belief in drug efficacy, presumably because charts are associated with science. Through a series of four replications conducted on two crowdsourcing platforms, we investigate an alternative explanation, namely, that the charts allowed participants to better assess the drug's efficacy. Considered together, our experiments suggest that the ch...

  7. Trust, trolleys and social dilemmas: A replication study.

    Science.gov (United States)

    Bostyn, Dries H; Roets, Arne

    2017-05-01

    The present manuscript addresses how perceived trustworthiness of cooperative partners in a social dilemma context is influenced by the moral judgments those partners make on Trolley-type moral dilemmas; an issue recently investigated by Everett, Pizarro, and Crockett (2016). The present research comprises 2 studies that were conducted independently, simultaneously with, and incognizant of the Everett studies. Whereas the present studies aimed at investigating the same research hypothesis, a different and more elaborate methodology was used, as such providing a conceptual replication opportunity and extension to the Everett et al. Overall, the present studies clearly confirmed the main finding of Everett et al., that deontologists are more trusted than consequentialists in social dilemma games. Study 1 replicates Everett et al.'s effect in the context of trust games. Study 2 generalizes the effect to public goods games, thus demonstrating that it is not specific to the type of social dilemma game used in Everett et al. Finally, both studies build on these results by demonstrating that the increased trust in deontologists may sometimes, but not always, be warranted: deontologists displayed increased cooperation rates but only in the public goods game and not in trust games. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  8. Wine glass size and wine sales: a replication study in two bars.

    Science.gov (United States)

    Pechey, Rachel; Couturier, Dominique-Laurent; Hollands, Gareth J; Mantzari, Eleni; Zupan, Zorana; Marteau, Theresa M

    2017-08-01

    Wine glass size may influence perceived volume and subsequently purchasing and consumption. Using a larger glass to serve the same portions of wine was found to increase wine sales by 9.4% (95% CI 1.9, 17.5) in a recent study conducted in one bar. The current study aimed to replicate this previous work in two other bars using a wider range of glass sizes. To match the previous study, a repeated multiple treatment reversal design, during which wine was served in glasses of the same design but different sizes, was used. The study was conducted in two bars in Cambridge, England, using glass sizes of 300, 370, 510 ml (Bar 1) and 300 and 510 ml (Bar 2). Customers purchased their choice of a 750 ml bottle, or standard UK measures of 125, 175 or 250 ml of wine, each of which was served with the same glass. Bar 1 Daily wine volume (ml) purchased was 10.5% (95% CI 1.0, 20.9) higher when sold in 510 ml compared to 370 ml glasses; but sales were not significantly higher with 370 ml versus 300 ml glasses (6.5%, 95% CI -5.2, 19.6). Bar 2 Findings were inconclusive as to whether daily wine purchased differed when using 510 ml versus 300 ml glasses (-1.1%, 95% CI -12.6, 11.9). These results provide a partial replication of previous work showing that introducing larger glasses (without manipulating portion size) increases purchasing. Understanding the mechanisms by which wine glass size influences consumption may elucidate when the effect can be expected and when not. Trial registration This study is a replication study, based on the procedure set out in the trial registration for the study that it attempts to replicate (ISRCTN registry: ISRCTN12018175).

  9. Risk Factors as Major Determinants of Resilience: A Replication Study.

    Science.gov (United States)

    Eshel, Yohanan; Kimhi, Shaul; Lahad, Mooli; Leykin, Dmitry; Goroshit, Marina

    2018-03-16

    The present study was conducted in the context of current concerns about replication in psychological research. It claims that risk factors should be regarded as an integral part of the definition of individual resilience, which should be defined in terms of the balance between individual strength or protective factors, and individual vulnerability or risk factors (IND-SVR). Five independent samples, including 3457 Israeli participants, were employed to determine the effects of resilience promoting and resilience suppressing variables on the IND-SVR index of resilience, and on its two components: recovery from adversity, and distress symptoms. Five path analyses were employed for determining the role of distress symptoms as a measure of psychological resilience, as compared to other indices of this resilience. Results indicated the major role of risk factors (distress symptoms) as an integral component of resilience. This role was generally replicated in the five investigated samples. Risk factors are legitimate, valid, and useful parts of the definition of psychological resilience. Resilience research has shifted away from studying individual risk factors to investigating the process through which individuals overcome the hardships they experience. The present data seem to suggest that this shift should be reexamined.

  10. Adaptive scaling of reward in episodic memory: a replication study.

    Science.gov (United States)

    Mason, Alice; Ludwig, Casimir; Farrell, Simon

    2017-11-01

    Reward is thought to enhance episodic memory formation via dopaminergic consolidation. Bunzeck, Dayan, Dolan, and Duzel [(2010). A common mechanism for adaptive scaling of reward and novelty. Human Brain Mapping, 31, 1380-1394] provided functional magnetic resonance imaging (fMRI) and behavioural evidence that reward and episodic memory systems are sensitive to the contextual value of a reward-whether it is relatively higher or lower-as opposed to absolute value or prediction error. We carried out a direct replication of their behavioural study and did not replicate their finding that memory performance associated with reward follows this pattern of adaptive scaling. An effect of reward outcome was in the opposite direction to that in the original study, with lower reward outcomes leading to better memory than higher outcomes. There was a marginal effect of reward context, suggesting that expected value affected memory performance. We discuss the robustness of the reward memory relationship to variations in reward context, and whether other reward-related factors have a more reliable influence on episodic memory.

  11. Reproducibility and replicability of rodent phenotyping in preclinical studies.

    Science.gov (United States)

    Kafkafi, Neri; Agassi, Joseph; Chesler, Elissa J; Crabbe, John C; Crusio, Wim E; Eilam, David; Gerlai, Robert; Golani, Ilan; Gomez-Marin, Alex; Heller, Ruth; Iraqi, Fuad; Jaljuli, Iman; Karp, Natasha A; Morgan, Hugh; Nicholson, George; Pfaff, Donald W; Richter, S Helene; Stark, Philip B; Stiedl, Oliver; Stodden, Victoria; Tarantino, Lisa M; Tucci, Valter; Valdar, William; Williams, Robert W; Würbel, Hanno; Benjamini, Yoav

    2018-04-01

    The scientific community is increasingly concerned with the proportion of published "discoveries" that are not replicated in subsequent studies. The field of rodent behavioral phenotyping was one of the first to raise this concern, and to relate it to other methodological issues: the complex interaction between genotype and environment; the definitions of behavioral constructs; and the use of laboratory mice and rats as model species for investigating human health and disease mechanisms. In January 2015, researchers from various disciplines gathered at Tel Aviv University to discuss these issues. The general consensus was that the issue is prevalent and of concern, and should be addressed at the statistical, methodological and policy levels, but is not so severe as to call into question the validity and the usefulness of model organisms as a whole. Well-organized community efforts, coupled with improved data and metadata sharing, have a key role in identifying specific problems and promoting effective solutions. Replicability is closely related to validity, may affect generalizability and translation of findings, and has important ethical implications. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Sample preparation composite and replicate strategy case studies for assay of solid oral drug products.

    Science.gov (United States)

    Nickerson, Beverly; Harrington, Brent; Li, Fasheng; Guo, Michele Xuemei

    2017-11-30

    Drug product assay is one of several tests required for new drug products to ensure the quality of the product at release and throughout the life cycle of the product. Drug product assay testing is typically performed by preparing a composite sample of multiple dosage units to obtain an assay value representative of the batch. In some cases replicate composite samples may be prepared and the reportable assay value is the average value of all the replicates. In previously published work by Harrington et al. (2014) [5], a sample preparation composite and replicate strategy for assay was developed to provide a systematic approach which accounts for variability due to the analytical method and dosage form with a standard error of the potency assay criteria based on compendia and regulatory requirements. In this work, this sample preparation composite and replicate strategy for assay is applied to several case studies to demonstrate the utility of this approach and its application at various stages of pharmaceutical drug product development. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Poor replication validity of biomedical association studies reported by newspapers.

    Science.gov (United States)

    Dumas-Mallet, Estelle; Smith, Andy; Boraud, Thomas; Gonon, François

    2017-01-01

    To investigate the replication validity of biomedical association studies covered by newspapers. We used a database of 4723 primary studies included in 306 meta-analysis articles. These studies associated a risk factor with a disease in three biomedical domains, psychiatry, neurology and four somatic diseases. They were classified into a lifestyle category (e.g. smoking) and a non-lifestyle category (e.g. genetic risk). Using the database Dow Jones Factiva, we investigated the newspaper coverage of each study. Their replication validity was assessed using a comparison with their corresponding meta-analyses. Among the 5029 articles of our database, 156 primary studies (of which 63 were lifestyle studies) and 5 meta-analysis articles were reported in 1561 newspaper articles. The percentage of covered studies and the number of newspaper articles per study strongly increased with the impact factor of the journal that published each scientific study. Newspapers almost equally covered initial (5/39 12.8%) and subsequent (58/600 9.7%) lifestyle studies. In contrast, initial non-lifestyle studies were covered more often (48/366 13.1%) than subsequent ones (45/3718 1.2%). Newspapers never covered initial studies reporting null findings and rarely reported subsequent null observations. Only 48.7% of the 156 studies reported by newspapers were confirmed by the corresponding meta-analyses. Initial non-lifestyle studies were less often confirmed (16/48) than subsequent ones (29/45) and than lifestyle studies (31/63). Psychiatric studies covered by newspapers were less often confirmed (10/38) than the neurological (26/41) or somatic (40/77) ones. This is correlated to an even larger coverage of initial studies in psychiatry. Whereas 234 newspaper articles covered the 35 initial studies that were later disconfirmed, only four press articles covered a subsequent null finding and mentioned the refutation of an initial claim. Journalists preferentially cover initial findings

  14. Poor replication validity of biomedical association studies reported by newspapers.

    Directory of Open Access Journals (Sweden)

    Estelle Dumas-Mallet

    Full Text Available To investigate the replication validity of biomedical association studies covered by newspapers.We used a database of 4723 primary studies included in 306 meta-analysis articles. These studies associated a risk factor with a disease in three biomedical domains, psychiatry, neurology and four somatic diseases. They were classified into a lifestyle category (e.g. smoking and a non-lifestyle category (e.g. genetic risk. Using the database Dow Jones Factiva, we investigated the newspaper coverage of each study. Their replication validity was assessed using a comparison with their corresponding meta-analyses.Among the 5029 articles of our database, 156 primary studies (of which 63 were lifestyle studies and 5 meta-analysis articles were reported in 1561 newspaper articles. The percentage of covered studies and the number of newspaper articles per study strongly increased with the impact factor of the journal that published each scientific study. Newspapers almost equally covered initial (5/39 12.8% and subsequent (58/600 9.7% lifestyle studies. In contrast, initial non-lifestyle studies were covered more often (48/366 13.1% than subsequent ones (45/3718 1.2%. Newspapers never covered initial studies reporting null findings and rarely reported subsequent null observations. Only 48.7% of the 156 studies reported by newspapers were confirmed by the corresponding meta-analyses. Initial non-lifestyle studies were less often confirmed (16/48 than subsequent ones (29/45 and than lifestyle studies (31/63. Psychiatric studies covered by newspapers were less often confirmed (10/38 than the neurological (26/41 or somatic (40/77 ones. This is correlated to an even larger coverage of initial studies in psychiatry. Whereas 234 newspaper articles covered the 35 initial studies that were later disconfirmed, only four press articles covered a subsequent null finding and mentioned the refutation of an initial claim.Journalists preferentially cover initial findings

  15. Poor replication validity of biomedical association studies reported by newspapers

    Science.gov (United States)

    Smith, Andy; Boraud, Thomas; Gonon, François

    2017-01-01

    Objective To investigate the replication validity of biomedical association studies covered by newspapers. Methods We used a database of 4723 primary studies included in 306 meta-analysis articles. These studies associated a risk factor with a disease in three biomedical domains, psychiatry, neurology and four somatic diseases. They were classified into a lifestyle category (e.g. smoking) and a non-lifestyle category (e.g. genetic risk). Using the database Dow Jones Factiva, we investigated the newspaper coverage of each study. Their replication validity was assessed using a comparison with their corresponding meta-analyses. Results Among the 5029 articles of our database, 156 primary studies (of which 63 were lifestyle studies) and 5 meta-analysis articles were reported in 1561 newspaper articles. The percentage of covered studies and the number of newspaper articles per study strongly increased with the impact factor of the journal that published each scientific study. Newspapers almost equally covered initial (5/39 12.8%) and subsequent (58/600 9.7%) lifestyle studies. In contrast, initial non-lifestyle studies were covered more often (48/366 13.1%) than subsequent ones (45/3718 1.2%). Newspapers never covered initial studies reporting null findings and rarely reported subsequent null observations. Only 48.7% of the 156 studies reported by newspapers were confirmed by the corresponding meta-analyses. Initial non-lifestyle studies were less often confirmed (16/48) than subsequent ones (29/45) and than lifestyle studies (31/63). Psychiatric studies covered by newspapers were less often confirmed (10/38) than the neurological (26/41) or somatic (40/77) ones. This is correlated to an even larger coverage of initial studies in psychiatry. Whereas 234 newspaper articles covered the 35 initial studies that were later disconfirmed, only four press articles covered a subsequent null finding and mentioned the refutation of an initial claim. Conclusion Journalists

  16. Recovery from Proactive Semantic Interference and MRI Volume: A Replication and Extension Study.

    Science.gov (United States)

    Loewenstein, David A; Curiel, Rosie E; DeKosky, Steven; Rosselli, Monica; Bauer, Russell; Grieg-Custo, Maria; Penate, Ailyn; Li, Chunfei; Lizagarra, Gabriel; Golde, Todd; Adjouadi, Malek; Duara, Ranjan

    2017-01-01

    The rise in incidence of Alzheimer's disease (AD) has led to efforts to advance early detection of the disease during its preclinical stages. To achieve this, the field needs to develop more sensitive cognitive tests that relate to biological markers of disease pathology. Failure to recover from proactive interference (frPSI) is one such cognitive marker that is associated with volumetric reductions in the hippocampus, precuneus, and other AD-prone regions, and to amyloid load in the brain. The current study attempted to replicate and extend our previous findings that frPSI is a sensitive marker of early AD, and related to a unique pattern of volumetric loss in AD prone areas. Three different memory measures were examined relative to volumetric loss and cortical thickness among 45 participants with amnestic mild cognitive impairment. frPSI was uniquely associated with reduced volumes in the hippocampus (r = 0.50) precuneus (r = 0.41), and other AD prone regions, replicating previous findings. Strong associations between frPSI and lower entorhinal cortex volumes and cortical thickness (r≥0.60) and precuneus (r = 0.50) were also observed. Unique and strong associations between volumetric reductions and frPSI as observed by Loewenstein and colleagues were replicated. Together with cortical thickness findings, these results indicate that frPSI is worthy of further study as a sensitive and early cognitive marker of AD.

  17. Examining reproducibility in psychology : A hybrid method for combining a statistically significant original study and a replication

    NARCIS (Netherlands)

    Van Aert, R.C.M.; Van Assen, M.A.L.M.

    2018-01-01

    The unrealistically high rate of positive results within psychology has increased the attention to replication research. However, researchers who conduct a replication and want to statistically combine the results of their replication with a statistically significant original study encounter

  18. Vocal fold immobility and aspiration status: a direct replication study.

    Science.gov (United States)

    Leder, Steven B; Suiter, Debra M; Duffey, Dianne; Judson, Benjamin L

    2012-06-01

    The purpose of this direct replication study was to confirm the incidence of vocal fold immobility (VFI) and its relationship to pharyngeal dysphagia and aspiration. Using a single-group consecutively referred case series, a total of 2,650 participants underwent fiberoptic endoscopic evaluation of swallowing between August 2003 and December 2007. Main outcome measures included overall incidence of VFI and aspiration status, with specific emphasis on age, gender, etiology and pharyngeal phase bolus flow characteristics, and side of VFI (right, left, or bilateral). These data were compared to and then combined with the original study (n = 1,452) for a total of 4,102 participants. Results indicated that the incidence of VFI was 4.3% (112/2,650), i.e., 27% (31/112) unilateral right, 58% (65/112) unilateral left, and 14% (16/112) bilateral. Incidence of aspiration was 22% (580/2,650). Of those with VFI, 40% (45/112) aspirated, i.e., 42% (13/31) unilateral right, 37% (24/65) unilateral left, and 50% (8/16) bilateral. An individual with VFI had 2.50 times the odds of aspirating as someone without VFI (95% CI = 1.86-3.37). For liquid aspiration, the odds ratio (OR) = 2.41 (95% CI = 1.77-3.28), and for puree aspiration, OR = 2.08 (95% CI = 1.47-2.93). Left VFI occurred most frequently due to surgical trauma. Liquid was aspirated more often than a puree. Males exhibited VFI more often than females. Side of VFI and age were not factors that increased the incidence of aspiration significantly. It was confirmed that VFI is not an uncommon finding during dysphagia testing and, when present, increased the odds of aspiration compared to a population already being evaluated for dysphagia.

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

    Science.gov (United States)

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

    2017-10-03

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

  20. Antecedents and outcomes of satisfaction in buyer–supplier relationships in South Africa: A replication study

    Directory of Open Access Journals (Sweden)

    Mornay Roberts-Lombard

    2017-10-01

    Full Text Available Background: There is a clear difference of opinion amongst researchers on the interrelatedness of the variables trust, commitment, satisfaction, coordination, cooperation and continuity in a business-to-business (B2B environment. The reason is that in previous studies much emphasis has been placed on creating and testing new theories, and not on providing practical generalities. Aim: The aim of this study was to determine how the variable satisfaction is positioned in relation to trust and commitment, and how satisfaction relates to the variables coordination, cooperation and continuity in a South African B2B environment. Setting: This study replicates a similar study conducted in 2013 in a B2B environment in South Africa and hopes to validate the outcome of that study by determining the relationship between the constructs postulated in the current study. The relationships between the different constructs in the proposed model will, therefore, provide a longitudinal perspective which is unique in terms of B2B research in South Africa. Methods: Both the original and replication studies followed a quantitative approach and targeted large companies in South Africa. In the original study, data were collected from 500 large South African companies, while in the replication study data were collected from 250 large companies. Structural equation modelling was used to analyse the data. Results: The findings specifically point to the need for organisations to direct resources towards the establishment of relationships that are founded on trust and commitment. Doing so will help ensure increased satisfaction, which, in turn, will result in greater coordination and cooperation in B2B relationships as well as long-term continuation of the relationship. Conclusion: The foundation for strong B2B relationships is to secure customer satisfaction. Business managers ought to understand that when business customers are dissatisfied, it can result in the

  1. On Scalability and Replicability of Smart Grid Projects—A Case Study

    Directory of Open Access Journals (Sweden)

    Lukas Sigrist

    2016-03-01

    Full Text Available This paper studies the scalability and replicability of smart grid projects. Currently, most smart grid projects are still in the R&D or demonstration phases. The full roll-out of the tested solutions requires a suitable degree of scalability and replicability to prevent project demonstrators from remaining local experimental exercises. Scalability and replicability are the preliminary requisites to perform scaling-up and replication successfully; therefore, scalability and replicability allow for or at least reduce barriers for the growth and reuse of the results of project demonstrators. The paper proposes factors that influence and condition a project’s scalability and replicability. These factors involve technical, economic, regulatory and stakeholder acceptance related aspects, and they describe requirements for scalability and replicability. In order to assess and evaluate the identified scalability and replicability factors, data has been collected from European and national smart grid projects by means of a survey, reflecting the projects’ view and results. The evaluation of the factors allows quantifying the status quo of on-going projects with respect to the scalability and replicability, i.e., they provide a feedback on to what extent projects take into account these factors and on whether the projects’ results and solutions are actually scalable and replicable.

  2. Owner reports of attention, activity, and impulsivity in dogs: a replication study

    Directory of Open Access Journals (Sweden)

    Iosif Ana-Maria

    2010-01-01

    Full Text Available Abstract Background When developing behaviour measurement tools that use third party assessments, such as parent report, it is important to demonstrate reliability of resulting scales through replication using novel cohorts. The domestic dog has been suggested as a model to investigate normal variation in attention, hyperactivity, and impulsive behaviours impaired in Attention Deficit Hyperactive Disorder (ADHD. The human ADHD Rating Scale, modified for dogs and using owner-directed surveys, was applied in a European sample. We asked whether findings would be replicated utilizing an Internet survey in a novel sample, where unassisted survey completion, participant attitudes and breeds might affect previous findings. Methods Using a slightly modified version of the prior survey, we collected responses (n = 1030, 118 breeds representing 7 breed groups primarily in the United States and Canada. This study was conducted using an Internet survey mechanism. Results Reliability analyses confirmed two scales previously identified for dogs (inattention [IA], hyperactivity-impulsivity [HA-IM]. Models including age, training status, and breed group accounted for very little variance in subscales, with no effect of gender. Conclusions The factor invariance demonstrated in these findings confirms that owner report, using this modified human questionnaire, provides dog scores according to "inattention" and "hyperactivity-impulsivity" axes. Further characterization of naturally occurring variability of attention, activity, and impulsivity in domestic dogs may provide insight into genetic backgrounds underlying behaviours impaired in attention and associated disorders.

  3. 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.

  4. Testing the Efficacy of a Tier 2 Mathematics Intervention: A Conceptual Replication Study

    Science.gov (United States)

    Doabler, Christian T.; Clarke, Ben; Kosty, Derek B.; Kurtz-Nelson, Evangeline; Fien, Hank; Smolkowski, Keith; Baker, Scott K.

    2016-01-01

    The purpose of this closely aligned conceptual replication study was to investigate the efficacy of a Tier 2 kindergarten mathematics intervention. The replication study differed from the initial randomized controlled trial on three important elements: geographical region, timing of the intervention, and instructional context of the…

  5. Analysis of 60 reported glioma risk SNPs replicates published GWAS findings but fails to replicate associations from published candidate-gene studies.

    Science.gov (United States)

    Walsh, Kyle M; Anderson, Erik; Hansen, Helen M; Decker, Paul A; Kosel, Matt L; Kollmeyer, Thomas; Rice, Terri; Zheng, Shichun; Xiao, Yuanyuan; Chang, Jeffrey S; McCoy, Lucie S; Bracci, Paige M; Wiemels, Joe L; Pico, Alexander R; Smirnov, Ivan; Lachance, Daniel H; Sicotte, Hugues; Eckel-Passow, Jeanette E; Wiencke, John K; Jenkins, Robert B; Wrensch, Margaret R

    2013-02-01

    Genomewide association studies (GWAS) and candidate-gene studies have implicated single-nucleotide polymorphisms (SNPs) in at least 45 different genes as putative glioma risk factors. Attempts to validate these associations have yielded variable results and few genetic risk factors have been consistently replicated. We conducted a case-control study of Caucasian glioma cases and controls from the University of California San Francisco (810 cases, 512 controls) and the Mayo Clinic (852 cases, 789 controls) in an attempt to replicate previously reported genetic risk factors for glioma. Sixty SNPs selected from the literature (eight from GWAS and 52 from candidate-gene studies) were successfully genotyped on an Illumina custom genotyping panel. Eight SNPs in/near seven different genes (TERT, EGFR, CCDC26, CDKN2A, PHLDB1, RTEL1, TP53) were significantly associated with glioma risk in the combined dataset (P 0.05). Although several confirmed associations are located near genes long known to be involved in gliomagenesis (e.g., EGFR, CDKN2A, TP53), these associations were first discovered by the GWAS approach and are in noncoding regions. These results highlight that the deficiencies of the candidate-gene approach lay in selecting both appropriate genes and relevant SNPs within these genes. © 2012 WILEY PERIODICALS, INC.

  6. 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.

  7. Case-control study for colorectal cancer genetic susceptibility in EPICOLON: previously identified variants and mucins

    Directory of Open Access Journals (Sweden)

    Moreno Victor

    2011-08-01

    Full Text Available Abstract Background Colorectal cancer (CRC is the second leading cause of cancer death in developed countries. Familial aggregation in CRC is also important outside syndromic forms and, in this case, a polygenic model with several common low-penetrance alleles contributing to CRC genetic predisposition could be hypothesized. Mucins and GALNTs (N-acetylgalactosaminyltransferase are interesting candidates for CRC genetic susceptibility and have not been previously evaluated. We present results for ten genetic variants linked to CRC risk in previous studies (previously identified category and 18 selected variants from the mucin gene family in a case-control association study from the Spanish EPICOLON consortium. Methods CRC cases and matched controls were from EPICOLON, a prospective, multicenter, nationwide Spanish initiative, comprised of two independent stages. Stage 1 corresponded to 515 CRC cases and 515 controls, whereas stage 2 consisted of 901 CRC cases and 909 controls. Also, an independent cohort of 549 CRC cases and 599 controls outside EPICOLON was available for additional replication. Genotyping was performed for ten previously identified SNPs in ADH1C, APC, CCDN1, IL6, IL8, IRS1, MTHFR, PPARG, VDR and ARL11, and 18 selected variants in the mucin gene family. Results None of the 28 SNPs analyzed in our study was found to be associated with CRC risk. Although four SNPs were significant with a P-value ADH1C (OR = 1.63, 95% CI = 1.06-2.50, P-value = 0.02, recessive, rs1800795 in IL6 (OR = 1.62, 95% CI = 1.10-2.37, P-value = 0.01, recessive, rs3803185 in ARL11 (OR = 1.58, 95% CI = 1.17-2.15, P-value = 0.007, codominant, and rs2102302 in GALNTL2 (OR = 1.20, 95% CI = 1.00-1.44, P-value = 0.04, log-additive 0, 1, 2 alleles], only rs3803185 achieved statistical significance in EPICOLON stage 2 (OR = 1.34, 95% CI = 1.06-1.69, P-value = 0.01, recessive. In the joint analysis for both stages, results were only significant for rs3803185 (OR = 1

  8. Case-control study for colorectal cancer genetic susceptibility in EPICOLON: previously identified variants and mucins

    International Nuclear Information System (INIS)

    Abulí, Anna; Morillas, Juan D; Rigau, Joaquim; Latorre, Mercedes; Fernández-Bañares, Fernando; Peña, Elena; Riestra, Sabino; Payá, Artemio; Jover, Rodrigo; Xicola, Rosa M; Llor, Xavier; Fernández-Rozadilla, Ceres; Carvajal-Carmona, Luis; Villanueva, Cristina M; Moreno, Victor; Piqué, Josep M; Carracedo, Angel; Castells, Antoni; Andreu, Montserrat; Ruiz-Ponte, Clara; Castellví-Bel, Sergi; Alonso-Espinaco, Virginia; Muñoz, Jenifer; Gonzalo, Victoria; Bessa, Xavier; González, Dolors; Clofent, Joan; Cubiella, Joaquin

    2011-01-01

    Colorectal cancer (CRC) is the second leading cause of cancer death in developed countries. Familial aggregation in CRC is also important outside syndromic forms and, in this case, a polygenic model with several common low-penetrance alleles contributing to CRC genetic predisposition could be hypothesized. Mucins and GALNTs (N-acetylgalactosaminyltransferase) are interesting candidates for CRC genetic susceptibility and have not been previously evaluated. We present results for ten genetic variants linked to CRC risk in previous studies (previously identified category) and 18 selected variants from the mucin gene family in a case-control association study from the Spanish EPICOLON consortium. CRC cases and matched controls were from EPICOLON, a prospective, multicenter, nationwide Spanish initiative, comprised of two independent stages. Stage 1 corresponded to 515 CRC cases and 515 controls, whereas stage 2 consisted of 901 CRC cases and 909 controls. Also, an independent cohort of 549 CRC cases and 599 controls outside EPICOLON was available for additional replication. Genotyping was performed for ten previously identified SNPs in ADH1C, APC, CCDN1, IL6, IL8, IRS1, MTHFR, PPARG, VDR and ARL11, and 18 selected variants in the mucin gene family. None of the 28 SNPs analyzed in our study was found to be associated with CRC risk. Although four SNPs were significant with a P-value < 0.05 in EPICOLON stage 1 [rs698 in ADH1C (OR = 1.63, 95% CI = 1.06-2.50, P-value = 0.02, recessive), rs1800795 in IL6 (OR = 1.62, 95% CI = 1.10-2.37, P-value = 0.01, recessive), rs3803185 in ARL11 (OR = 1.58, 95% CI = 1.17-2.15, P-value = 0.007, codominant), and rs2102302 in GALNTL2 (OR = 1.20, 95% CI = 1.00-1.44, P-value = 0.04, log-additive 0, 1, 2 alleles], only rs3803185 achieved statistical significance in EPICOLON stage 2 (OR = 1.34, 95% CI = 1.06-1.69, P-value = 0.01, recessive). In the joint analysis for both stages, results were only significant for rs3803185 (OR = 1.12, 95% CI = 1

  9. New Methods to Address Old Challenges: The Use of Administrative Data for Longitudinal Replication Studies of Child Maltreatment.

    Science.gov (United States)

    Hurren, Emily; Stewart, Anna; Dennison, Susan

    2017-09-15

    Administrative data are crucial to the "big data" revolution of social science and have played an important role in the development of child maltreatment research. These data are also of value to administrators, policy makers, and clinicians. The focus of this paper is the use of administrative data to produce and replicate longitudinal studies of child maltreatment. Child protection administrative data have several advantages. They are often population-based, and allow longitudinal examination of child maltreatment and complex multi-level analyses. They also allow comparison across subgroups and minority groups, remove burden from individuals to disclose traumatic experiences, and can be less biased than retrospective recall. Finally, they can be linked to data from other agencies to explore comorbidity and outcomes, and are comparatively cost and time effective. The benefits and challenges associated with the use of administrative data for longitudinal child maltreatment research become magnified when these data are used to produce replications. Techniques to address challenges and support future replication efforts include developing a biographical understanding of the systems from which the data are drawn, using multiple data sources to contextualize the data and research results, recognizing and adopting various approaches to replication, and documenting all data coding and manipulation processes. These techniques are illustrated in this paper via a case study of previous replication work.

  10. Building Evidence in Early Childhood Special Education: A Systematic Review of Replication Intervention Studies

    Science.gov (United States)

    Banerjee, Rashida; Movahedazarhouligh, Sara; Millen, Kaitlyn; Luckner, John L.

    2018-01-01

    Valid and evidence-informed practices are critical to help young children with disabilities and their families with highly effective interventions and instruction to reach their potentials. Replication research is critical for appraising research and identifying evidence-based practices. The purpose of this study was to replicate the methods used…

  11. Effectiveness of strategies to increase the validity of findings from association studies: size vs. replication

    Directory of Open Access Journals (Sweden)

    Kallischnigg Gerd

    2010-05-01

    Full Text Available Abstract Background The capacity of multiple comparisons to produce false positive findings in genetic association studies is abundantly clear. To address this issue, the concept of false positive report probability (FPRP measures "the probability of no true association between a genetic variant and disease given a statistically significant finding". This concept involves the notion of prior probability of an association between a genetic variant and a disease, making it difficult to achieve acceptable levels for the FPRP when the prior probability is low. Increasing the sample size is of limited efficiency to improve the situation. Methods To further clarify this problem, the concept of true report probability (TRP is introduced by analogy to the positive predictive value (PPV of diagnostic testing. The approach is extended to consider the effects of replication studies. The formula for the TRP after k replication studies is mathematically derived and shown to be only dependent on prior probability, alpha, power, and number of replication studies. Results Case-control association studies are used to illustrate the TRP concept for replication strategies. Based on power considerations, a relationship is derived between TRP after k replication studies and sample size of each individual study. That relationship enables study designers optimization of study plans. Further, it is demonstrated that replication is efficient in increasing the TRP even in the case of low prior probability of an association and without requiring very large sample sizes for each individual study. Conclusions True report probability is a comprehensive and straightforward concept for assessing the validity of positive statistical testing results in association studies. By its extension to replication strategies it can be demonstrated in a transparent manner that replication is highly effective in distinguishing spurious from true associations. Based on the generalized TRP

  12. Tus-Ter as a tool to study site-specific DNA replication perturbation in eukaryotes

    DEFF Research Database (Denmark)

    Larsen, Nicolai B; Hickson, Ian D; Mankouri, Hocine W

    2014-01-01

    The high-affinity binding of the Tus protein to specific 21-bp sequences, called Ter, causes site-specific, and polar, DNA replication fork arrest in E coli. The Tus-Ter complex serves to coordinate DNA replication with chromosome segregation in this organism. A number of recent and ongoing studies...... have demonstrated that Tus-Ter can be used as a heterologous tool to generate site-specific perturbation of DNA replication when reconstituted in eukaryotes. Here, we review these recent findings and explore the molecular mechanism by which Tus-Ter mediates replication fork (RF) arrest in the budding...... yeast, S. cerevisiae. We propose that Tus-Ter is a versatile, genetically tractable, and regulatable RF blocking system that can be utilized for disrupting DNA replication in a diverse range of host cells....

  13. Tus-Ter as a tool to study site-specific DNA replication perturbation in eukaryotes.

    Science.gov (United States)

    Larsen, Nicolai B; Hickson, Ian D; Mankouri, Hocine W

    2014-01-01

    The high-affinity binding of the Tus protein to specific 21-bp sequences, called Ter, causes site-specific, and polar, DNA replication fork arrest in E coli. The Tus-Ter complex serves to coordinate DNA replication with chromosome segregation in this organism. A number of recent and ongoing studies have demonstrated that Tus-Ter can be used as a heterologous tool to generate site-specific perturbation of DNA replication when reconstituted in eukaryotes. Here, we review these recent findings and explore the molecular mechanism by which Tus-Ter mediates replication fork (RF) arrest in the budding yeast, S. cerevisiae. We propose that Tus-Ter is a versatile, genetically tractable, and regulatable RF blocking system that can be utilized for disrupting DNA replication in a diverse range of host cells.

  14. Short term memory for single surface features and bindings in ageing: A replication study.

    Science.gov (United States)

    Isella, Valeria; Molteni, Federica; Mapelli, Cristina; Ferrarese, Carlo

    2015-06-01

    In the present study we replicated a previous experiment investigating visuo-spatial short term memory binding in young and older healthy individuals, in the attempt to verify the pattern of impairment that can be observed in normal elderly for short term memory for single items vs short term memory for bindings. Assessing a larger sample size (25 young and 25 older subjects), using a more appropriate measure of accuracy for a change detection task (A'), and adding the evaluation of speed of performance, we confirmed that old normals show a decline in short term memory for bindings of shape and colour that is of comparable extent, and not major, to the decline in memory for single shapes and single colours. The absence of a specific deficit of short term memory for conjunctions of surface features seems to distinguish cognitive ageing from Alzheimer's Disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Vocabulary Development in European Portuguese: A Replication Study Using the Language Development Survey

    Science.gov (United States)

    Rescorla, Leslie; Nyame, Josephine; Dias, Pedro

    2016-01-01

    Purpose: Our objective was to replicate previous cross­linguistic findings by comparing Portuguese and U.S. children with respect to (a) effects of language, gender, and age on vocabulary size; (b) lexical composition; and (c) late talking. Method: We used the Language Development Survey (LDS; Rescorla, 1989) with children (18-35 months) learning…

  16. Replication Studies: Vocabulary Knowledge in Relation to Memory and Analysis--An Approximate Replication of Milton's (2007) Study on Lexical Profiles and Learning Style

    Science.gov (United States)

    Booth, Paul

    2013-01-01

    This paper presents an approximate replication of Milton's (2007) study on lexical profiles and learning style. Milton investigated the assumption that more frequent words are acquired before less frequent ones. Using a vocabulary recognition test ("X-Lex") to measure vocabulary size, Milton found that L2 English group profiles show…

  17. 40 CFR 152.93 - Citation of a previously submitted valid study.

    Science.gov (United States)

    2010-07-01

    ... Data Submitters' Rights § 152.93 Citation of a previously submitted valid study. An applicant may demonstrate compliance for a data requirement by citing a valid study previously submitted to the Agency. The... the original data submitter, the applicant may cite the study only in accordance with paragraphs (b...

  18. Fowl plague virus replication in mammalian cell-avian erythrocyte heterokaryons: studies concerning the actinomycin D and ultra-violet lig sensitive phase in influenza virus replication

    International Nuclear Information System (INIS)

    Kelly, D.C.; Dimmock, N.J.

    1974-01-01

    The replication of fowl plague virus in BHK and L cells specifically blocked prior to infection with inhibitors of influenza virus replication (actinomycin D and ultraviolet light irradiation) has been studied by the introduction of a metabolically dormant avian erythrocyte nucleus. This permits the synthesis of just the influenza virus nucleoprotein in actinomycin D (but not ultraviolet light) blocked cells. The NP antigen is first detected in the avian erythrocyte nucleus and subsequently in the heterokaryon cytoplasm

  19. Common variant of ALPK1 is not associated with gout: a replication study.

    Science.gov (United States)

    Chiba, Toshinori; Matsuo, Hirotaka; Sakiyama, Masayuki; Nakayama, Akiyoshi; Shimizu, Seiko; Wakai, Kenji; Suma, Shino; Nakashima, Hiroshi; Sakurai, Yutaka; Shimizu, Toru; Ichida, Kimiyoshi; Shinomiya, Nariyoshi

    2015-01-01

    Gout is one of the most kinds of common inflammatory arthritis as a consequence of hyperuricemia. Alpha-protein kinase 1 (ALPK1) gene locates in a gout-susceptibility locus on chromosome 4q21-31, and encodes ALPK1 protein which plays a pivotal role in the phosphorylation of myosin 1. In the previous genetic study of Taiwanese populations, 3 single nucleotide polymorphisms (SNPs), rs11726117, rs231247 and rs231253, in ALPK1 gene were reported to have a significant association with gout. However, no replication study has been performed to confirm this association. Therefore, we first conducted a replication study with clinically defined gout patients in a different population. Linkage disequilibrium (LD) analyzes of the 3 SNPs in ALPK1 revealed that these SNPs are in strong LD in a Japanese population. Among the 3 SNPs of ALPK1, rs11726117 (M861T) is the only missense SNP. Therefore, rs11726117 was genotyped in a Japanese population of 903 clinically defined gout cases and 1,302 controls, and was evaluated for a possible association with gout. The minor allele frequencies of rs11726117 were 0.26 and 0.25 in the case and control groups, respectively. The association analysis has not detected a significant association between rs11726117 and gout susceptibility in a Japanese population (p = 0.44). Because ABCG2, a major causative gene for gout, also locates in the gout-susceptibility locus on chromosome 4q, these findings suggest that among genes in a gout-susceptibility locus, not ALPK1 but ABCG2 could be important as a gout-susceptible gene.

  20. Autoradiographic studies of chromosome replication during the cell cycle of Streptococcus faecium

    International Nuclear Information System (INIS)

    Higgins, M.L.; Koch, A.L.; Dicker, D.T.; Daneo-Moore, L.

    1986-01-01

    Analysis of the distribution of autoradiographic grains around cells of Streptococcus faecium which had been either continuously or pulse-labeled with tritiated thymidine (mass doubling time, 90 min) showed a non-Poisson distribution even when the distribution of cell sizes in the populations studied was taken into account. These non-Poisson distributions of grains were assumed to reflect the discontinuous nature of chromosome replication. To study this discontinuous process further, an equation was fitted to the grain distribution observed for the pulse-labeled cells that assumed that in any population of cells there were subpopulations in which there were zero, one, or two replicating chromosomes. This analysis predicted an average time for chromosome replication and for the period between completion of rounds of chromosome replication and division of 55 and 43 min, respectively, which were in excellent agreement with estimates made by other techniques. The present investigation extended past studies in indicating that the initiation and completion of rounds of chromosome replication are poorly phased with increases in cell volume and that the amount of chromosome replication may be different in different cell halves

  1. Synthesizing Results from Replication Studies Using Robust Variance Estimation: Corrections When the Number of Studies Is Small

    Science.gov (United States)

    Tipton, Elizabeth

    2014-01-01

    Replication studies allow for making comparisons and generalizations regarding the effectiveness of an intervention across different populations, versions of a treatment, settings and contexts, and outcomes. One method for making these comparisons across many replication studies is through the use of meta-analysis. A recent innovation in…

  2. Summary of Previous Chamber or Controlled Anthrax Studies and Recommendations for Possible Additional Studies

    Energy Technology Data Exchange (ETDEWEB)

    Piepel, Gregory F.; Amidan, Brett G.; Morrow, Jayne B.

    2010-12-29

    This report and an associated Excel file(a) summarizes the investigations and results of previous chamber and controlled studies(b) to characterize the performance of methods for collecting, storing and/or transporting, extracting, and analyzing samples from surfaces contaminated by Bacillus anthracis (BA) or related simulants. This report and the Excel are the joint work of the Pacific Northwest National Laboratory (PNNL) and the National Institute of Standards and Technology (NIST) for the Department of Homeland Security, Science and Technology Directorate. The report was originally released as PNNL-SA-69338, Rev. 0 in November 2009 with limited distribution, but was subsequently cleared for release with unlimited distribution in this Rev. 1. Only minor changes were made to Rev. 0 to yield Rev. 1. A more substantial update (including summarizing data from other studies and more condensed summary tables of data) is underway

  3. 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

    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...... 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.......3, and Xp22.31-p11.4 using additional markers in an independent set of 136 Danish asthmatic sib pair families. RESULTS: Nonparametric multipoint linkage analyses yielded suggestive evidence for linkage to asthma to chromosome Xp21.2 (MLS 2.92) but failed to replicate linkage to chromosomes 1p36.31-p36.21, 5...

  4. Matched cohort study of external cephalic version in women with previous cesarean delivery.

    Science.gov (United States)

    Keepanasseril, Anish; Anand, Keerthana; Soundara Raghavan, Subrahmanian

    2017-07-01

    To evaluate the efficacy and safety of external cephalic version (ECV) among women with previous cesarean delivery. A retrospective study was conducted using data for women with previous cesarean delivery and breech presentation who underwent ECV at or after 36 weeks of pregnancy during 2011-2016. For every case, two multiparous women without previous cesarean delivery who underwent ECV and were matched for age and pregnancy duration were included. Characteristics and outcomes were compared between groups. ECV was successful for 32 (84.2%) of 38 women with previous cesarean delivery and 62 (81.6%) in the control group (P=0.728). Multivariate regression analysis confirmed that previous cesarean was not associated with ECV success (odds ratio 1.89, 95% confidence interval 0.19-18.47; P=0.244). Successful vaginal delivery after successful ECV was reported for 19 (59.4%) women in the previous cesarean delivery group and 52 (83.9%) in the control group (P<0.001). No ECV-associated complications occurred in women with previous cesarean delivery. To avoid a repeat cesarean delivery, ECV can be offered to women with breech presentation and previous cesarean delivery who are otherwise eligible for a trial of labor. © 2017 International Federation of Gynecology and Obstetrics.

  5. One for all and all for One: Improving replication of genetic studies through network diffusion.

    Directory of Open Access Journals (Sweden)

    Daniel Lancour

    2018-04-01

    Full Text Available Improving accuracy in genetic studies would greatly accelerate understanding the genetic basis of complex diseases. One approach to achieve such an improvement for risk variants identified by the genome wide association study (GWAS approach is to incorporate previously known biology when screening variants across the genome. We developed a simple approach for improving the prioritization of candidate disease genes that incorporates a network diffusion of scores from known disease genes using a protein network and a novel integration with GWAS risk scores, and tested this approach on a large Alzheimer disease (AD GWAS dataset. Using a statistical bootstrap approach, we cross-validated the method and for the first time showed that a network approach improves the expected replication rates in GWAS studies. Several novel AD genes were predicted including CR2, SHARPIN, and PTPN2. Our re-prioritized results are enriched for established known AD-associated biological pathways including inflammation, immune response, and metabolism, whereas standard non-prioritized results were not. Our findings support a strategy of considering network information when investigating genetic risk factors.

  6. Career in mental health still an unlikely career choice for nursing graduates: a replicated longitudinal study.

    Science.gov (United States)

    Stevens, John; Browne, Graeme; Graham, Iain

    2013-06-01

    The lack of qualified mental health nurses is at critical level with the problem likely to worsen as the aging mental health nursing workforce retires. This study investigates the career preferences of undergraduate nursing students by comparing preferences at the start, middle, and end of the Bachelor of Nursing program. The comparison of the cohorts gave an indication of the change in preferences over the intervening years. It replicates research completed in 1992, 1997, and 2001, and develops a profile of nursing career preferences and the rationale underpinning those preferences in a cohort of students (n = 150) who began their Bachelor of Nursing studies in 2007 and completed in 2009. The main findings included that, like the previous studies, mental health nursing is one of the least desirable career choices for most nurses at the start of their course and remains so as they approach graduation. The reasons change but the outcome remains the same. The current system of using the Bachelor of Nursing award to produce mental health nurses in Australia does not encourage nurses to consider a career in mental health nursing. Which begs the question: where will mental health nurses in the future come from? © 2012 The Authors. International Journal of Mental Health Nursing © 2012 Australian College of Mental Health Nurses Inc.

  7. Directional selection in temporally replicated studies is remarkably consistent.

    Science.gov (United States)

    Morrissey, Michael B; Hadfield, Jarrod D

    2012-02-01

    Temporal variation in selection is a fundamental determinant of evolutionary outcomes. A recent paper presented a synthetic analysis of temporal variation in selection in natural populations. The authors concluded that there is substantial variation in the strength and direction of selection over time, but acknowledged that sampling error would result in estimates of selection that were more variable than the true values. We reanalyze their dataset using techniques that account for the necessary effect of sampling error to inflate apparent levels of variation and show that directional selection is remarkably constant over time, both in magnitude and direction. Thus we cannot claim that the available data support the existence of substantial temporal heterogeneity in selection. Nonetheless, we conject that temporal variation in selection could be important, but that there are good reasons why it may not appear in the available data. These new analyses highlight the importance of applying techniques that estimate parameters of the distribution of selection, rather than parameters of the distribution of estimated selection (which will reflect both sampling error and "real" variation in selection); indeed, despite availability of methods for the former, focus on the latter has been common in synthetic reviews of the aspects of selection in nature, and can lead to serious misinterpretations. © 2011 The Author(s). Evolution© 2011 The Society for the Study of Evolution.

  8. The structure of psychopathology in adolescence : Replication of a general psychopathology factor in the TRAILS study

    NARCIS (Netherlands)

    Laceulle, O.M.; Vollebergh, W.A.M.; Ormel, J.

    2015-01-01

    This study aimed to replicate a study by Caspi and colleagues, which proposed that the structure of psychopathology is characterized by a general psychopathology factor, in addition to smaller internalizing and externalizing factors. Our study expanded the approach of the original by using

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

    Directory of Open Access Journals (Sweden)

    Cameron Palmer

    2017-07-01

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

  10. Replication Validity of Initial Association Studies: A Comparison between Psychiatry, Neurology and Four Somatic Diseases

    Science.gov (United States)

    Dumas-Mallet, Estelle; Button, Katherine; Boraud, Thomas; Munafo, Marcus; Gonon, François

    2016-01-01

    Context There are growing concerns about effect size inflation and replication validity of association studies, but few observational investigations have explored the extent of these problems. Objective Using meta-analyses to measure the reliability of initial studies and explore whether this varies across biomedical domains and study types (cognitive/behavioral, brain imaging, genetic and “others”). Methods We analyzed 663 meta-analyses describing associations between markers or risk factors and 12 pathologies within three biomedical domains (psychiatry, neurology and four somatic diseases). We collected the effect size, sample size, publication year and Impact Factor of initial studies, largest studies (i.e., with the largest sample size) and the corresponding meta-analyses. Initial studies were considered as replicated if they were in nominal agreement with meta-analyses and if their effect size inflation was below 100%. Results Nominal agreement between initial studies and meta-analyses regarding the presence of a significant effect was not better than chance in psychiatry, whereas it was somewhat better in neurology and somatic diseases. Whereas effect sizes reported by largest studies and meta-analyses were similar, most of those reported by initial studies were inflated. Among the 256 initial studies reporting a significant effect (p<0.05) and paired with significant meta-analyses, 97 effect sizes were inflated by more than 100%. Nominal agreement and effect size inflation varied with the biomedical domain and study type. Indeed, the replication rate of initial studies reporting a significant effect ranged from 6.3% for genetic studies in psychiatry to 86.4% for cognitive/behavioral studies. Comparison between eight subgroups shows that replication rate decreases with sample size and “true” effect size. We observed no evidence of association between replication rate and publication year or Impact Factor. Conclusion The differences in reliability

  11. Susceptibility loci for sporadic brain arteriovenous malformation; a replication study and meta-analysis

    NARCIS (Netherlands)

    Kremer, P.H.; Koeleman, B.P.C.; Rinkel, G.J.; Diekstra, F.P.; Berg, L.H. van den; Veldink, J.H.; Klijn, C.J.M.

    2016-01-01

    BACKGROUND: Case-control studies have reported multiple genetic loci to be associated with sporadic brain arteriovenous malformations (AVMs) but most of these have not been replicated in independent populations. The aim of this study was to find additional evidence for these reported associations

  12. Replication protocol analysis: a method for the study of real-world design thinking

    DEFF Research Database (Denmark)

    Galle, Per; Kovacs, L. B.

    1996-01-01

    ’ is refined into a method called ‘replication protocol analysis’ (RPA), and discussed from a methodological perspective of design research. It is argued that for the study of real-world design thinking this method offers distinct advantages over traditional ‘design protocol analysis’, which seeks to capture......Given the brief of an architectural competition on site planning, and the design awarded the first prize, the first author (trained as an architect but not a participant in the competition) produced a line of reasoning that might have led from brief to design. In the paper, such ‘design replication...... the designer’s authentic line of reasoning. To illustrate how RPA can be used, the site planning case is briefly presented, and part of the replicated line of reasoning analysed. One result of the analysis is a glimpse of a ‘logic of design’; another is an insight which sheds new light on Darke’s classical...

  13. Replication protocol analysis: a method for the study of real-world design thinking

    DEFF Research Database (Denmark)

    Galle, Per; Kovacs, L. B.

    1996-01-01

    Given the brief of an architectural competition on site planning, and the design awarded the first prize, the first author (trained as an architect but not a participant in the competition) produced a line of reasoning that might have led from brief to design. In the paper, such ‘design replication......’ is refined into a method called ‘replication protocol analysis’ (RPA), and discussed from a methodological perspective of design research. It is argued that for the study of real-world design thinking this method offers distinct advantages over traditional ‘design protocol analysis’, which seeks to capture...

  14. Uncertain Context Factors in ERP Project Estimation are an Asset: Insights from a Semi-Replication Case Study in a Financial Services Firm

    NARCIS (Netherlands)

    Daneva, Maia

    This paper reports on the findings of a case study in a company in the financial services sector in which we replicated the use of a previously published approach to systematically balance the contextual uncertainties in the estimation of Enterprise Resource Planning (ERP) projects. The approach is

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

    Science.gov (United States)

    Munksgaard, Rasmus; Demant, Jakob; Branwen, Gwern

    2016-09-01

    The development of cryptomarkets has gained increasing attention from academics, including growing scientific literature on the distribution of illegal goods using cryptomarkets. Dolliver's 2015 article "Evaluating drug trafficking on the Tor Network: Silk Road 2, the Sequel" addresses this theme 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 to attribute to anything other than methodological issues. The analysis and conclusions drawn from studies using these methods are promising and insightful. However, based on the replication of Dolliver's study, we suggest that researchers using these methodologies consider and that datasets be made available for other researchers, and that methodology and dataset metrics (e.g. number of downloaded pages, error logs) are described thoroughly in the context of web-o-metrics and web crawling. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. When and Why Replication Studies Should Be Published: Guidelines for Mathematics Education Journals

    Science.gov (United States)

    Star, Jon R.

    2018-01-01

    The present issue of "JRME" features three articles--Melhuish (2018; see EJ1167195); Jamil, Larsen, and Hamres (2018; see EJ1167178); and Thanheiser (2018; see EJ1167179)--that involve, at least to some degree, replication of prior published studies. In each of these articles, the authors provide a clear rationale for the importance of…

  17. A Replication Study on the Multi-Dimensionality of Online Social Presence

    Science.gov (United States)

    Mykota, David B.

    2015-01-01

    The purpose of the present study is to conduct an external replication into the multi-dimensionality of social presence as measured by the Computer-Mediated Communication Questionnaire (Tu, 2005). Online social presence is one of the more important constructs for determining the level of interaction and effectiveness of learning in an online…

  18. Human CD46-transgenic mice in studies involving replication-incompetent adenoviral type 35 vectors

    NARCIS (Netherlands)

    Verhaagh, S.; Jong, E. de; Goudsmit, J.; Lecollinet, S.; Gillissen, G.; Vries, M. de; Leuven, K. van; Que, I.; Ouwehand, K.; Mintardjo, R.; Weverling, G.J.; Radošević, K.; Richardson, J.; Eloit, M.; Lowik, C.; Quax, P.; Havenga, M.

    2006-01-01

    Wild-type strains of mice do not express CD46, a high-affinity receptor for human group B adenoviruses including type 35. Therefore, studies performed to date in mice using replication-incompetent Ad35 (rAd35) vaccine carriers may underestimate potency or result in altered vector distribution. Here,

  19. Study of some physical aspects previous to design of an exponential experiment

    International Nuclear Information System (INIS)

    Caro, R.; Francisco, J. L. de

    1961-01-01

    This report presents the theoretical study of some physical aspects previous to the design of an exponential facility. The are: Fast and slow flux distribution in the multiplicative medium and in the thermal column, slowing down in the thermal column, geometrical distribution and minimum needed intensity of sources access channels and perturbations produced by possible variations in its position and intensity. (Author) 4 refs

  20. Survival after a psychoeducational intervention for patients with cutaneous malignant melanoma: a replication study

    DEFF Research Database (Denmark)

    Boesen, Ellen H; Boesen, Sidsel H; Frederiksen, Kirsten

    2007-01-01

    The results of a randomized, intervention study done in 1993 of psychoeducation for patients with early-stage malignant melanoma showed a beneficial effect on recurrence and survival 6 years after the intervention. In the present study, we replicated the study with 258 Danish patients with malign...... with malignant melanoma. We also compared recurrence and survival among the participants in the randomized study with 137 patients who refused to participate....

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

    Directory of Open Access Journals (Sweden)

    Ana Paula Carneiro Salgado

    2013-08-01

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

  2. Study of functional-performance deficits in athletes with previous ankle sprains

    Directory of Open Access Journals (Sweden)

    hamid Babaee

    2008-04-01

    Full Text Available Abstract Background: Despite the importance of functional-performance deficits in athletes with history of ankle sprain few, studies have been carried out in this area. The aim of this research was to study relationship between previous ankle sprains and functional-performance deficits in athletes. Materials and methods: The subjects were 40 professional athletes selected through random sampling among volunteer participants in soccer, basketball, volleyball and handball teams of Lorestan province. The subjects were divided into 2 groups: Injured group (athletes with previous ankle sprains and healthy group (athletes without previous ankle sprains. In this descriptive study we used Functional-performance tests (figure 8 hop test and side hop test to determine ankle deficits and limitations. They participated in figure 8 hop test including hopping in 8 shape course with the length of 5 meters and side hop test including 10 side hop repetitions in course with the length of 30 centimeters. Time were recorded via stopwatch. Results: After data gathering and assessing information distributions, Pearson correlation was used to assess relationships, and independent T test to assess differences between variables. Finally the results showed that there is a significant relationship between previous ankle sprains and functional-performance deficits in the athletes. Conclusion: The athletes who had previous ankle sprains indicated functional-performance deficits more than healthy athletes in completion of mentioned functional-performance tests. The functional-performance tests (figure 8 hop test and side hop test are sensitive and suitable to assess and detect functional-performance deficits in athletes. Therefore we can use the figure 8 hop and side hop tests for goals such as prevention, assessment and rehabilitation of ankle sprains without spending too much money and time.

  3. Implications of “too good to be true” for replication, theoretical claims, and experimental design: An example using prominent studies of racial bias

    Directory of Open Access Journals (Sweden)

    Greg Francis

    2016-09-01

    Full Text Available In response to concerns about the validity of empirical findings in psychology, some scientists use replication studies as a way to validate good science and to identify poor science. Such efforts are resource intensive and are sometimes controversial (with accusations of researcher incompetence when a replication fails to show a previous result. An alternative approach is to examine the statistical properties of the reported literature to identify some cases of poor science. This review discusses some details of this process for prominent findings about racial bias, where a set of studies seems too good to be true. This kind of analysis is based on the original studies, so it avoids criticism from the original authors about the validity of replication studies. The analysis is also much easier to perform than a new empirical study. A variation of the analysis can also be used to explore whether it makes sense to run a replication study. As demonstrated here, there are situations where the existing data suggest that a direct replication of a set of studies is not worth the effort. Such a conclusion should motivate scientists to generate alternative experimental designs that better test theoretical ideas.

  4. Risk/protective factors among addicted mothers' offspring: a replication study.

    Science.gov (United States)

    Weissman, M M; McAvay, G; Goldstein, R B; Nunes, E V; Verdeli, H; Wickramaratne, P J

    1999-11-01

    There are few systematic studies of the school-aged offspring of drug-dependent patients, although this information is useful for planning evidence-based prevention programs. We have completed such a study, which we compare to a similar study independently conducted in 1998. In both studies, both the parent and offspring were assessed blindly and independently by direct diagnostic interviews, and parental assessment of offspring was also obtained. The similarity in design and methods between studies provided an opportunity for replication by reanalysis of data. The major findings are a replication in two independently conducted studies of school-aged offspring of opiate- and/or cocaine-addicted mothers of the high rates of any psychiatric disorder (60% in both studies), major depression (20%, 26%), oppositional defiant disorder (ODD) (18%, 23%), conduct disorder (17%, 9%), attention-deficit/hyperactivity disorder (ADHD) (13%, 8%), and substance abuse (5%, 10%) among offspring. Both studies also found high rates of comorbid alcohol abuse, depression, and multiple drugs of abuse in the mothers. We conclude that efforts to replicate findings by analyses of independently conducted studies are an inexpensive way to test the sturdiness of findings that can provide the empirical basis for preventive efforts. Clinically, the data in both studies suggest that both drug dependence and associated psychopathology should be assessed and treated in opiate addicts with young offspring, and the offspring should be monitored for the development of conduct and mood disorders and substance use.

  5. Replication of endometriosis-associated single-nucleotide polymorphisms from genome-wide association studies in a Caucasian population.

    Science.gov (United States)

    Sundqvist, J; Xu, H; Vodolazkaia, A; Fassbender, A; Kyama, C; Bokor, A; Gemzell-Danielsson, K; D'Hooghe, T M; Falconer, H

    2013-03-01

    Is it possible to replicate the previously identified genetic association of four single-nucleotide polymorphisms (SNPs), rs12700667, rs7798431, rs1250248 and rs7521902, with endometriosis in a Caucasian population? A borderline association was observed for rs1250248 and endometriosis (P = 0.049). However, we could not replicate the other previously identified endometriosis-associated SNPs (rs12700667, rs7798431 and rs7521902) in the same population. Endometriosis is considered a complex disease, influenced by several genetic and environmental factors, as well as interactions between them. Previous studies have found genetic associations with endometriosis for SNPs at the 7p15 and 2q35 loci in a Caucasian population. Allele frequencies of SNPs were investigated in patients with endometriosis and controls. Blood samples and peritoneal biopsies were taken from a Caucasian female population consisting of 1129 patients with endometriosis and 831 controls. DNA was extracted for genotyping. The study was performed at a University hospital and research laboratories. A weak association with endometriosis (all stages) was observed for rs1250248 (P = 0.049). No significant associations were observed for the SNPs rs12700667, rs7798431 and rs7521902. A non-significant trend towards the association of rs1250248 with moderate/severe endometriosis was observed (odds ratio 1.18, 95% confidence interval 0.97-1.44). The inability to confirm all previous findings may result from differences between populations and type II errors. Our result demonstrates the difficulty of identifying common genetic variants in complex diseases. This study was supported by grants from the Karolinska Institutet and Stockholm City County/Karolinska Institutet (ALF), Stockholm, Sweden, Swedish Medical Research Council (K2007-54X-14212-06-3, K2010-54X-14212-09-3), Stockholm, Sweden, Leuven University Research Council (Onderzoeksraad KU Leuven), the Leuven University Hospitals Clinical Research Foundation

  6. Replicating a study of collaborative use of mobile phones for photo sharing in a different cultural context

    DEFF Research Database (Denmark)

    Sandoval, Carolina; Montero, Camila; Jokela, Tero

    2014-01-01

    In this paper, we replicate a study of collaborative mobile phone use to share personal photos in groups of collocated people. The replication study was conducted in a different cultural context to check the generalizability of the findings from the original study in terms of the proposed...

  7. Implementing three evidence-based program models: early lessons from the Teen Pregnancy Prevention Replication Study.

    Science.gov (United States)

    Kelsey, Meredith; Layzer, Jean

    2014-03-01

    This article describes some of the early implementation challenges faced by nine grantees participating in the Teen Pregnancy Prevention Replication Study and their response to them. The article draws on information collected as part of a comprehensive implementation study. Sources include site and program documents; program officer reports; notes from site investigation, selection and negotiation; ongoing communications with grantees as part of putting the study into place; and semi-structured interviews with program staff. The issues faced by grantees in implementing evidence-based programs designed to prevent teen pregnancy varied by program model. Grantees implementing a classroom-based curriculum faced challenges in delivering the curriculum within the constraints of school schedules and calendars (program length and size of class). Grantees implementing a culturally tailored curriculum faced a series of challenges, including implementing the intervention as part of the regular school curriculum in schools with diverse populations; low attendance when delivered as an after-school program; and resistance on the part of schools to specific curriculum content. The third set of grantees, implementing a program in clinics, faced challenges in identifying and recruiting young women into the program and in retaining young women once they were in the program. The experiences of these grantees reflect some of the complexities that should be carefully considered when choosing to replicate evidence-based programs. The Teen Pregnancy Prevention replication study will provide important context for assessing the effectiveness of some of the more widely replicated evidence-based programs. Copyright © 2014 Society for Adolescent Health and Medicine. All rights reserved.

  8. Data from studies of previous radioactive waste disposal in Massachusetts Bay

    International Nuclear Information System (INIS)

    Curtis, W.R.; Mardis, H.M.

    1984-12-01

    This report presents the results of studies conducted in Massachusetts Bay during 1981 and 1982. Included are data from: (1) a side scan sonar survey of disposal areas in the Bay that was carried out by the National Oceanic and Atmospheric Administration (NOAA) for EPA; (2) Collections of sediment and biota by NOAA for radiochemical analysis by EPA; (3) collections of marketplace seafood samples by the Food and Drug Administration (FDA) for radioanalysis by both FDA and EPA; and (4) a radiological monitoring survey of LLW disposal areas by EPA to determine whether there should be any concern for public health resulting from previous LLW disposals in the Bay

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

    NARCIS (Netherlands)

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

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

  10. 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

  11. Can concurrent memory load reduce distraction? A replication study and beyond.

    Science.gov (United States)

    Gil-Gómez de Liaño, Beatriz; Stablum, Franca; Umiltà, Carlo

    2016-01-01

    The effects of concurrent working memory load in attentional processes have been 1 of the most puzzling issues in cognitive psychology. Studies have shown detrimental effects, no effects, and even beneficial effects of working memory load in different attentional tasks. In the present study we attempted to replicate Kim, Kim, and Chun's (2005, Experiment 3b) findings of beneficial effects of concurrent working memory load in a spatial Stroop-like task. In 3 experiments in which our sample was 3 times larger than that in the original Kim et al. study, we could not replicate their findings. The results are discussed in terms of what may have produced the conflicting results, trying to shed light on how working memory load affects attentional tasks. Also, we emphasize the importance of using adequately large samples in cognitive research. Although we acknowledge the relevance of meta-analyses to analyze conflicting results, in the present article we stress (perhaps more important) the power of an essential trademark in science for research development: replicability. (c) 2015 APA, all rights reserved).

  12. Theoretical study of magnetic pattern replication by He+ ion irradiation through stencil masks

    International Nuclear Information System (INIS)

    Devolder, T.; Chappert, C.; Bernas, H.

    2002-01-01

    We have developed an irradiation technique that allows us to tune the magnetic properties of Co/Pt multilayers without affecting their roughness. The planarity and the ability to independently control nanostructure size and coercivity make our technique very appealing for magnetic recording. We study the irradiation-induced 1:1 replication of features drilled in a stencil mask. Both the 'gap' G between the magnetic film and the mask, and the aspect ratio (AR) of the mask features are analyzed, in view of the ion straggling in the mask resulting in collateral damages. Optimal gap is such that D<< G<< D/tan(α) (typically 0.1<< G<<25 μm), where the D is the feature size. The replication quality is best for AR≥3. Since the allowed gap interval is wide, we anticipate that mask fast positioning will be possible for the applications to magnetic recording

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

    Directory of Open Access Journals (Sweden)

    Eric-Jan eWagenmakers

    2015-04-01

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

  14. A Study on Generic Representation of Skeletal Remains Replication of Prehistoric Burial

    Directory of Open Access Journals (Sweden)

    C.-W. Shao

    2015-08-01

    Full Text Available Generic representation of skeletal remains from burials consists of three dimensions which include physical anthropologists, replication technicians, and promotional educators. For the reason that archaeological excavation is irreversible and disruptive, detail documentation and replication technologies are surely needed for many purposes. Unearthed bones during the process of 3D digital scanning need to go through reverse procedure, 3D scanning, digital model superimposition, rapid prototyping, mould making, and the integrated errors generated from the presentation of colours and textures are important issues for the presentation of replicate skeleton remains among professional decisions conducted by physical anthropologists, subjective determination of makers, and the expectations of viewers. This study presents several cases and examines current issues on display and replication technologies for human skeletal remains of prehistoric burials. This study documented detail colour changes of human skeleton over time for the reference of reproduction. The tolerance errors of quantification and required technical qualification is acquired according to the precision of 3D scanning, the specification requirement of rapid prototyping machine, and the mould making process should following the professional requirement for physical anthropological study. Additionally, the colorimeter is adopted to record and analyse the “colour change” of the human skeletal remains from wet to dry condition. Then, the “colure change” is used to evaluate the “real” surface texture and colour presentation of human skeletal remains, and to limit the artistic presentation among the human skeletal remains reproduction. The“Lingdao man No.1”, is a well preserved burial of early Neolithic period (8300 B.P. excavated from Liangdao-Daowei site, Matsu, Taiwan , as the replicating object for this study. In this study, we examined the reproduction procedures step by

  15. Genomics and structure/function studies of Rhabdoviridae proteins involved in replication and transcription.

    Science.gov (United States)

    Assenberg, R; Delmas, O; Morin, B; Graham, S C; De Lamballerie, X; Laubert, C; Coutard, B; Grimes, J M; Neyts, J; Owens, R J; Brandt, B W; Gorbalenya, A; Tucker, P; Stuart, D I; Canard, B; Bourhy, H

    2010-08-01

    Some mammalian rhabdoviruses may infect humans, and also infect invertebrates, dogs, and bats, which may act as vectors transmitting viruses among different host species. The VIZIER programme, an EU-funded FP6 program, has characterized viruses that belong to the Vesiculovirus, Ephemerovirus and Lyssavirus genera of the Rhabdoviridae family to perform ground-breaking research on the identification of potential new drug targets against these RNA viruses through comprehensive structural characterization of the replicative machinery. The contribution of VIZIER programme was of several orders. First, it contributed substantially to research aimed at understanding the origin, evolution and diversity of rhabdoviruses. This diversity was then used to obtain further structural information on the proteins involved in replication. Two strategies were used to produce recombinant proteins by expression of both full length or domain constructs in either E. coli or insect cells, using the baculovirus system. In both cases, parallel cloning and expression screening at small-scale of multiple constructs based on different viruses including the addition of fusion tags, was key to the rapid generation of expression data. As a result, some progress has been made in the VIZIER programme towards dissecting the multi-functional L protein into components suitable for structural and functional studies. However, the phosphoprotein polymerase co-factor and the structural matrix protein, which play a number of roles during viral replication and drives viral assembly, have both proved much more amenable to structural biology. Applying the multi-construct/multi-virus approach central to protein production processes in VIZIER has yielded new structural information which may ultimately be exploitable in the derivation of novel ways of intervening in viral replication. Copyright 2010 Elsevier B.V. All rights reserved.

  16. Large-scale replication study reveals a limit on probabilistic prediction in language comprehension.

    Science.gov (United States)

    Nieuwland, Mante S; Politzer-Ahles, Stephen; Heyselaar, Evelien; Segaert, Katrien; Darley, Emily; Kazanina, Nina; Von Grebmer Zu Wolfsthurn, Sarah; Bartolozzi, Federica; Kogan, Vita; Ito, Aine; Mézière, Diane; Barr, Dale J; Rousselet, Guillaume A; Ferguson, Heather J; Busch-Moreno, Simon; Fu, Xiao; Tuomainen, Jyrki; Kulakova, Eugenia; Husband, E Matthew; Donaldson, David I; Kohút, Zdenko; Rueschemeyer, Shirley-Ann; Huettig, Falk

    2018-04-03

    Do people routinely pre-activate the meaning and even the phonological form of upcoming words? The most acclaimed evidence for phonological prediction comes from a 2005 Nature Neuroscience publication by DeLong, Urbach and Kutas, who observed a graded modulation of electrical brain potentials (N400) to nouns and preceding articles by the probability that people use a word to continue the sentence fragment ('cloze'). In our direct replication study spanning 9 laboratories ( N =334), pre-registered replication-analyses and exploratory Bayes factor analyses successfully replicated the noun-results but, crucially, not the article-results. Pre-registered single-trial analyses also yielded a statistically significant effect for the nouns but not the articles. Exploratory Bayesian single-trial analyses showed that the article-effect may be non-zero but is likely far smaller than originally reported and too small to observe without very large sample sizes. Our results do not support the view that readers routinely pre-activate the phonological form of predictable words. © 2018, Nieuwland et al.

  17. A longitudinal study of plasma insulin and glucagon in women with previous gestational diabetes

    DEFF Research Database (Denmark)

    Damm, P; Kühl, C; Hornnes, P

    1995-01-01

    OBJECTIVE: To investigate whether plasma insulin or glucagon predicts later development of diabetes in women with gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: The subjects studied were 91 women with diet-treated GDM and 33 healthy women. Plasma insulin and glucagon during a 50...... at follow-up (2 had insulin-dependent diabetes mellitus, 13 had non-insulin-dependent diabetes mellitus, and 12 had impaired glucose tolerance). Compared with the control subjects, women with previous GDM had relatively impaired insulin secretion (decreased insulinogenic index and delayed peak insulin...... for subsequent development of overt diabetes (logistic regression analysis). CONCLUSIONS: Women who develop GDM have a relative insulin secretion deficiency, the severity of which is predictive for later development of diabetes. Furthermore, our data indicate that their relatively reduced beta-cell function may...

  18. Distributional Replication

    OpenAIRE

    Beare, Brendan K.

    2009-01-01

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

  19. A maize root tip system to study DNA replication programmes in somatic and endocycling nuclei during plant development.

    Science.gov (United States)

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

    2014-06-01

    The progress of nuclear DNA replication is complex in both time and space, and may reflect several levels of chromatin structure and 3-dimensional organization within the nucleus. To understand the relationship between DNA replication and developmental programmes, it is important to examine replication and nuclear substructure in different developmental contexts including natural cell-cycle progressions in situ. Plant meristems offer an ideal opportunity to analyse such processes in the context of normal growth of an organism. Our current understanding of large-scale chromosomal DNA replication has been limited by the lack of appropriate tools to visualize DNA replication with high resolution at defined points within S phase. In this perspective, we discuss a promising new system that can be used to visualize DNA replication in isolated maize (Zea mays L.) root tip nuclei after in planta pulse labelling with the thymidine analogue, 5-ethynyl-2'-deoxyuridine (EdU). Mixed populations of EdU-labelled nuclei are then separated by flow cytometry into sequential stages of S phase and examined directly using 3-dimensional deconvolution microscopy to characterize spatial patterns of plant DNA replication. Combining spatiotemporal analyses with studies of replication and epigenetic inheritance at the molecular level enables an integrated experimental approach to problems of mitotic inheritance and cellular differentiation. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  20. Yeast as a model host to study replication and recombination of defective interfering RNA of Tomato bushy stunt virus

    International Nuclear Information System (INIS)

    Panavas, Tadas; Nagy, Peter D.

    2003-01-01

    Defective interfering (DI) RNA associated with Tomato bushy stunt virus (TBSV), which is a plus-strand RNA virus, requires p33 and p92 proteins of TBSV or the related Cucumber necrosis virus (CNV), for replication in plants. To test if DI RNA can replicate in a model host, we coexpressed TBSV DI RNA and p33/p92 of CNV in yeast. We show evidence for replication of DI RNA in yeast, including (i) dependence on p33 and p92 for DI replication; (ii) presence of active CNV RNA-dependent RNA polymerase in isolated membrane-containing preparations; (iii) increasing amount of DI RNA(+) over time; (iv) accumulation of (-)stranded DI RNA; (v) presence of correct 5' and 3' ends in DI RNA; (vi) inhibition of replication by mutations in the replication enhancer; and (vii) evolution of DI RNA over time, as shown by sequence heterogeneity. We also produced evidence supporting the occurrence of DI RNA recombinants in yeast. In summary, development of yeast as a host for replication of TBSV DI RNA will facilitate studies on the roles of viral and host proteins in replication/recombination

  1. The Reliability and Validity of the Outcome Rating Scale: A Replication Study of a Brief Clinical Measure

    National Research Council Canada - National Science Library

    Bringhurst, David L; Watson, Curtis W; Miller, Scott D; Duncan, Barry L

    2004-01-01

    ... (Miller, Duncan, Brown, Sparks, AND Claud, 2003). This article reports the findings of an independent replication study evaluating the reliability and concurrent validity of the ORS as studied in a non-clinical sample...

  2. A study about the interest and previous contact of high school students with Astronomy

    Science.gov (United States)

    Carvalho, C. L.; Zanitti, M. H. R.; Felicidade, B. L.; Gomes, A. D. T.; Dias, E. W.; Coelho, F. O.

    2016-04-01

    The currently problems in Astronomy teaching in Brazilian Basic Education contrast with the space, and the popularity that astronomical themes have in various media in the country. In this work, we present the results of a study about the interest, and previous contact of high school students from a public school in the city of "São João del-Rei"/MG with topics related to Astronomy. The study and the pedagogical intervention were carried out by students of the PIBID/CAPES/UFSJ. The intervention was performed through an oral exposition with the students' participation, followed by the use of the Stellarium program. The results suggest the majority of students surveyed are interested in Astronomy, and have had some contact with the area. However, some inconsistencies in their responses were identified and examined. The implications for research and for Astronomy Education are discussed. We also make some considerations about relationship between the lack of specific knowledge and the misinformation as one possible reason for the little interest of students in various areas of Science.

  3. Association of STAT4 with rheumatoid arthritis - A replication study in three European populations : a replication study in three European populations

    NARCIS (Netherlands)

    Orozco, Gisela; Alizadeh, Behrooz Z.; Delgado-Vega, Angelica M.; Gonzalez-Gay, Miguel A.; Balsa, Alejandro; Pascual-Salcedo, Dora; Fernandez-Gutierrez, Benjamin; Gonzalez-Escribano, Maria F.; Petersson, Ingemar F.; van Riel, Piet L. C. M.; Barrera, Pilar; Coenen, Marieke J. H.; Radstake, Timothy R. D. J.; van Leeuwen, Miek A.; Wijmenga, Cisca; Koeleman, Bobby P. C.; Alarcon-Riquelme, Marta; Martin, Javier

    Objective. This study was undertaken to investigate the previously reported association of the STAT4 polymorphism rs7574865 with rheumatoid arthritis (RA) in 3 different European populations from Spain, Sweden, and The Netherlands, comprising a total of 2,072 patients and 2,474 controls. Methods.

  4. 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

    The development of cryptomarkets has gained increasing attention from academics, including growing scientific literature on the distribution of illegal goods using cryptomarkets. Dolliver's 2015 article “Evaluating drug trafficking on the Tor Network: Silk Road 2, the Sequel” addresses this theme...... 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...

  5. Fire Risk Scoping Study: Investigation of nuclear power plant fire risk, including previously unaddressed issues

    International Nuclear Information System (INIS)

    Lambright, J.A.; Nowlen, S.P.; Nicolette, V.F.; Bohn, M.P.

    1989-01-01

    An investigation of nuclear power plant fire risk issues raised as a result of the USNRC sponsored Fire Protection Research Program at Sandia National Laboratories has been performed. The specific objectives of this study were (1) to review and requantify fire risk scenarios from four fire probabilistic risk assessments (PRAs) in light of updated data bases made available as a result of USNRC sponsored Fire Protection Research Program and updated computer fire modeling capabilities, (2) to identify potentially significant fire risk issues that have not been previously addressed in a fire risk context and to quantify the potential impact of those identified fire risk issues where possible, and (3) to review current fire regulations and plant implementation practices for relevance to the identified unaddressed fire risk issues. In performance of the fire risk scenario requantifications several important insights were gained. It was found that utilization of a more extensive operational experience base resulted in both fire occurrence frequencies and fire duration times (i.e., time required for fire suppression) increasing significantly over those assumed in the original works. Additionally, some thermal damage threshold limits assumed in the original works were identified as being nonconservative based on more recent experimental data. Finally, application of the COMPBRN III fire growth model resulted in calculation of considerably longer fire damage times than those calculated in the original works using COMPBRN I. 14 refs., 2 figs., 16 tabs

  6. Replication Catastrophe

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  7. No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study

    Science.gov (United States)

    Bjelland, Douglas W.; Howrigan, Daniel P.; Abdellaoui, Abdel; Breen, Gerome; Borglum, Anders; Cichon, Sven; Degenhardt, Franziska; Forstner, Andreas J.; Genovese, Giulio; Heilmann-Heimbach, Stefanie; Hoffman, Per; Maier, Wolfgang; Mattheisen, Manuel; Morris, Derek; Mowry, Bryan; Müller-Mhysok, Betram; Neale, Benjamin; Nenadic, Igor; Nöthen, Markus M.; O’Dushlaine, Colm; Rietschel, Marcella; Ruderfer, Douglas M.; Rujescu, Dan; Schulze, Thomas G.; Simonson, Matthew A.; Stahl, Eli; Strohmaier, Jana; Sullivan, Patrick F.; Keller, Matthew C.

    2016-01-01

    It is well known that inbreeding increases the risk of recessive monogenic diseases, but it is less certain whether it contributes to the etiology of complex diseases such as schizophrenia. One way to estimate the effects of inbreeding is to examine the association between disease diagnosis and genome-wide autozygosity estimated using runs of homozygosity (ROH) in genome-wide single nucleotide polymorphism arrays. Using data for schizophrenia from the Psychiatric Genomics Consortium (n = 21,868), Keller et al. (2012) estimated that the odds of developing schizophrenia increased by approximately 17% for every additional percent of the genome that is autozygous (β = 16.1, CI(β) = [6.93, 25.7], Z = 3.44, p = 0.0006). Here we describe replication results from 22 independent schizophrenia case-control datasets from the Psychiatric Genomics Consortium (n = 39,830). Using the same ROH calling thresholds and procedures as Keller et al. (2012), we were unable to replicate the significant association between ROH burden and schizophrenia in the independent PGC phase II data, although the effect was in the predicted direction, and the combined (original + replication) dataset yielded an attenuated but significant relationship between Froh and schizophrenia (β = 4.86,CI(β) = [0.90,8.83],Z = 2.40,p = 0.02). Since Keller et al. (2012), several studies reported inconsistent association of ROH burden with complex traits, particularly in case-control data. These conflicting results might suggest that the effects of autozygosity are confounded by various factors, such as socioeconomic status, education, urbanicity, and religiosity, which may be associated with both real inbreeding and the outcome measures of interest. PMID:27792727

  8. Analytical strategies for discovery and replication of genetic effects in pharmacogenomic studies

    Directory of Open Access Journals (Sweden)

    Kohler JR

    2014-08-01

    Full Text Available Jared R Kohler, Tobias Guennel, Scott L MarshallBioStat Solutions, Inc., Frederick, MD, USAAbstract: In the past decade, the pharmaceutical industry and biomedical research sector have devoted considerable resources to pharmacogenomics (PGx with the hope that understanding genetic variation in patients would deliver on the promise of personalized medicine. With the advent of new technologies and the improved collection of DNA samples, the roadblock to advancements in PGx discovery is no longer the lack of high-density genetic information captured on patient populations, but rather the development, adaptation, and tailoring of analytical strategies to effectively harness this wealth of information. The current analytical paradigm in PGx considers the single-nucleotide polymorphism (SNP as the genomic feature of interest and performs single SNP association tests to discover PGx effects – ie, genetic effects impacting drug response. While it can be straightforward to process single SNP results and to consider how this information may be extended for use in downstream patient stratification, the rate of replication for single SNP associations has been low and the desired success of producing clinically and commercially viable biomarkers has not been realized. This may be due to the fact that single SNP association testing is suboptimal given the complexities of PGx discovery in the clinical trial setting, including: 1 relatively small sample sizes; 2 diverse clinical cohorts within and across trials due to genetic ancestry (potentially impacting the ability to replicate findings; and 3 the potential polygenic nature of a drug response. Subsequently, a shift in the current paradigm is proposed: to consider the gene as the genomic feature of interest in PGx discovery. The proof-of-concept study presented in this manuscript demonstrates that genomic region-based association testing has the potential to improve the power of detecting single SNP or

  9. Being a good nurse and doing the right thing: a replication study.

    Science.gov (United States)

    Catlett, Shelia; Lovan, Sherry R

    2011-01-01

    This qualitative research study, a replication of a study published in 2002, investigated the qualities of a good nurse and the role ethics plays in decision making. After reviewing the limitations of the published work, the current study implemented modifications related to the research questions, sample selection, data collection, and use of software for data analysis. The original study identified seven categories that related to being a good nurse and doing the right thing. In the present study, the use of relational analysis led to the recognition of four categories: (1) personal traits and attributes; (2) technical skills and management of care; (3) work environment and co-workers; and (4) caring and caring behaviors. To understand what it means to be a good nurse and do the right thing is a complex task; however, this research adds to the small amount of empirical data that exists to describe those characteristics.

  10. 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…

  11. An Epidemiologic Study on Ageing and Dysphagia in the Acute Care Geriatric-Hospitalized Population: A Replication and Continuation Study.

    Science.gov (United States)

    Leder, Steven B; Suiter, Debra M; Agogo, George O; Cooney, Leo M

    2016-10-01

    United States census data project dramatic increases in the geriatric population ageing demographics by 2060 with concomitant health-care consequences. The purpose of this replication and continuation study was to collect new 2014 demographic data relative to ageing, swallow evaluation referral rates, and oral feeding status in geriatric-hospitalized patients for comparison with published data from 2000 to 2007. This was a planned data acquisition study of consecutive hospitalized patients referred for swallow assessments. Swallow evaluation referral rates for 2014 were described according to inpatient discharges, age range 60-105 years grouped by decade, gender, admitting diagnostic category, results of swallow evaluations, and oral feeding status. Determination of aspiration risk status was made with the Yale Swallow Protocol and diagnosis of dysphagia made with fiberoptic endoscopic evaluation of swallowing (FEES). There were 1348 referrals and 961 patients ≥60 years of age participated. Overall swallow evaluation referral rates increased an average of 63 % between the comparison years 2007 and 2014 with consistent increases corresponding to the decades, i.e., 60-69 (46 %), 70-79 (68 %), 80-89 (53 %), and 90+ (222 %). A total of 75 % of participants resumed oral alimentation and oral medications. Swallow evaluation referral rates increased by 63 % for 60-90+ year-old acute care geriatric-hospitalized participants despite only a 23 % increase in inpatient discharges for the years 2007 versus 2014. This corroborated previously reported increases for individual years from 2000 to 2007. For timely, safe, and successful initiation of oral alimentation, it is important to perform a reliable swallow screen for aspiration risk assessment with the Yale Swallow Protocol and, if failed, instrumental testing with FEES. More dysphagia specialists are needed through 2060 and beyond due to projections of continued population ageing resulting in ever increasing

  12. Replication study of STAT4 rs7574865 G/T polymorphism and risk of rheumatoid arthritis in a Chinese population.

    Science.gov (United States)

    Shen, Li; Liu, Ruiping; Zhang, Hui; Huang, Yong; Sun, Rongbin; Tang, Peifu

    2013-09-10

    Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are common systemic autoimmune diseases with genetic and environmental predisposing factors. Signal transducer and activator of transcription 4 (STAT4) transmits signals induced by interleukin-12, interleukin-23 and interferon-γ, which are key cytokines and play important roles in the development of autoimmune diseases. Previous studies confirmed the STAT4 rs7574865 G/T locus to be associated with RA. Thus we conducted a replication study to investigate STAT4 rs7574865 G/T polymorphism and RA/AS susceptibility in a Chinese population. We studied STAT4 rs7574865 G/T gene polymorphism in 520 patients with RA, 100 AS patients and 520 controls in a Chinese population. Genotyping was done using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). When the STAT4 rs7574865 GG homozygote genotype was used as the reference group, the GT or GT/TT genotypes were associated with the risk for RA. After stratification analyses, a significantly increased risk for RA associated with the STAT4 rs7574865 GT genotype was evident among the rheumatoid factor (RF)-positive patients, patients with higher erythrocyte sedimentation rate (ESR) level and patients with higher RA disease activity score (DAS28) compared with the STAT4 rs7574865 GG genotype. A significantly increased risk for RA associated with the STAT4 rs7574865 TT genotype was evident among older patients and RF-negative patients compared with the STAT4 rs7574865 GG genotype. STAT4 rs7574865 G/T was not associated with susceptibility to AS. This replication study confirmed that STAT4 rs7574865 G/T polymorphism was associated with the risk of RA. STAT4 polymorphisms are associated with rheumatoid arthritis risk. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. The biomechanics of running in athletes with previous hamstring injury: A case-control study.

    Science.gov (United States)

    Daly, C; Persson, U McCarthy; Twycross-Lewis, R; Woledge, R C; Morrissey, D

    2016-04-01

    Hamstring injury is prevalent with persistently high reinjury rates. We aim to inform hamstring rehabilitation by exploring the electromyographic and kinematic characteristics of running in athletes with previous hamstring injury. Nine elite male Gaelic games athletes who had returned to sport after hamstring injury and eight closely matched controls sprinted while lower limb kinematics and muscle activity of the previously injured biceps femoris, bilateral gluteus maximus, lumbar erector spinae, rectus femoris, and external oblique were recorded. Intergroup comparisons of muscle activation ratios and kinematics were performed. Previously injured athletes demonstrated significantly reduced biceps femoris muscle activation ratios with respect to ipsilateral gluteus maximus (maximum difference -12.5%, P = 0.03), ipsilateral erector spinae (maximum difference -12.5%, P = 0.01), ipsilateral external oblique (maximum difference -23%, P = 0.01), and contralateral rectus femoris (maximum difference -22%, P = 0.02) in the late swing phase. We also detected sagittal asymmetry in hip flexion (maximum 8°, P = 0.01), pelvic tilt (maximum 4°, P = 0.02), and medial rotation of the knee (maximum 6°, P = 0.03) effectively putting the hamstrings in a lengthened position just before heel strike. Previous hamstring injury is associated with altered biceps femoris associated muscle activity and potentially injurious kinematics. These deficits should be considered and addressed during rehabilitation. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Statistical Analysis of Microarray Data with Replicated Spots: A Case Study with Synechococcus WH8102

    Directory of Open Access Journals (Sweden)

    E. V. Thomas

    2009-01-01

    Full Text Available Until recently microarray experiments often involved relatively few arrays with only a single representation of each gene on each array. A complete genome microarray with multiple spots per gene (spread out spatially across the array was developed in order to compare the gene expression of a marine cyanobacterium and a knockout mutant strain in a defined artificial seawater medium. Statistical methods were developed for analysis in the special situation of this case study where there is gene replication within an array and where relatively few arrays are used, which can be the case with current array technology. Due in part to the replication within an array, it was possible to detect very small changes in the levels of expression between the wild type and mutant strains. One interesting biological outcome of this experiment is the indication of the extent to which the phosphorus regulatory system of this cyanobacterium affects the expression of multiple genes beyond those strictly involved in phosphorus acquisition.

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

    OpenAIRE

    Stuckey, Ruth

    2014-01-01

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

  16. Age at onset in Huntington's disease: replication study on the association of HAP1.

    Science.gov (United States)

    Karadima, Georgia; Dimovasili, Christina; Koutsis, Georgios; Vassilopoulos, Demetris; Panas, Marios

    2012-11-01

    In recent years two association studies investigating the HAP1 T441M (rs4523977) polymorphism as a potential modifying factor of the age at onset (AAO) of Huntington's disease (HD), have been reported. Initially evidence for association was found between the M441 risk allele and the AAO. Subsequently, a second study, although failing to replicate these findings, found evidence for association between the same risk allele and AAO of motor symptoms (mAAO). In the present study, the role of the HAP1 T441M polymorphism as a modifier of the AAO in HD was investigated in a cohort of 298 Greek HD patients. In this cohort the CAG repeat number accounted for 55% of the variance in AAO. No association was found between the HAP1 T441M polymorphism and the AAO of HD. © 2012 Elsevier Ltd. All rights reserved.

  17. Rancidity inhibition study in frozen whole mackerel (scomber scombrus by a previous plant extract treatment.

    Directory of Open Access Journals (Sweden)

    Aubourg, Santiago P.

    2005-09-01

    Full Text Available The effect of flaxseeds (Linum usitatissimum on rancidity development in frozen whole mackerel (Scomber scombrus was studied. For it, fresh mackerel were dipped in flaxseeds aqueous extract during 60 min, frozen at –80 ºC during 24 hours and kept frozen (–20 ºC up to 12 months. Sampling was carried out on the initial material and at months 1, 3, 5, 7, 9 and 12 of frozen storage at –20 ºC. A parallel experiment with non treated fish was carried out in the same conditions. Rancidity development was measured by several biochemical indices (free fatty acids, peroxides, conjugated dienes and trienes, secondary oxidation products and lipoxygenase activity and complemented by the sensory analysis (skin, flesh odour, consistency and flesh appearance. As a result of the previous antioxidant treatment, peroxides showed to breakdown faster (pSe ha estudiado el efecto del lino (Linum usitatissimum en el desarrollo de rancidez en caballa entera congelada (Scomber scombrus. Para ello, caballas frescas fueron sumergidas en extractos acuosos de semillas de lino durante 60 min, congeladas a -80 ºC durante 24 h y mantenidas congeladas ( -20 ºC durante 12 meses. Se tomaron muestras del material inicial y tras 1, 3, 5, 7, 9 y 12 meses de congelación a -20 ºC . Un experimento paralelo con pescado no tratado fue llevado acabo en las mismas condiciones. El desarrollo de la rancidez fue medido por varios índices bioquímicos (ácidos grasos libres, peróxidos, dienos y trienos conjugados, productos secundarios de oxidación y actividad lipoxigenasa y completado con análisis sensorial (piel, olor de la carne, consistencia y apariencia de la carne. Como resultado del tratamiento antioxidante, los peróxidos se degradaron más rápidos (p < 0.05 después del mes 7, y por tanto, contenidos mayores (p < 0.05 de dienos y trienos conjugados pudieron ser detectados en el pescado tratado. El tratamiento antioxidante también condujo a un

  18. Polymorphisms in RYBP and AOAH genes are associated with chronic rhinosinusitis in a Chinese population: a replication study.

    Directory of Open Access Journals (Sweden)

    Yuan Zhang

    Full Text Available BACKGROUND: The development of CRS is believed to be the result of combined interactions between the genetic background of the affected subject and environmental factors. OBJECTIVES: To replicate and extend our recent findings from genetic association studies in chronic rhinosinusitis (CRS performed in a Canadian Caucasian population in a Chinese population. METHODS: In a case-control replication study, DNA samples were obtained from CRS with (n  = 306; CRSwNP and without (n = 332; CRSsNP nasal polyps, and controls (n = 315 in a Chinese population. A total of forty-nine single nucleotide polymorphisms (SNPs selected from previous identified SNPs associated with CRS in Canadian population, and SNPs from the CHB HapMap dataset were individually genotyped. RESULTS: We identified two SNPs respectively in RYBP (rs4532099, p = 2.15E-06, OR = 2.59 and AOAH (rs4504543, p = 0.0001152, OR = 0.58 significantly associated with whole CRS cohort. Subgroup analysis for the presence of nasal polyps (CRSwNP and CRSsNP displayed significant association in CRSwNP cohorts regarding to one SNP in RYBP (P = 3.24(E-006, OR = 2.76. Evidence of association in the CRSsNP groups in terms of 2 SNPs (AOAH_rs4504543 and RYBP_rs4532099 was detected as well. Stratifying analysis by gender demonstrated that none of the selected SNPs were associated with CRSwNP as well as CRSsNP. Meanwhile 3 SNPs (IL1A_rs17561, P = 0.005778; IL1A_rs1800587, P = 0.009561; IRAK4_rs4251513, P = 0.03837 were associated with serum total IgE level. CONCLUSIONS: These genes are biologically plausible, with roles in regulation of transcription (RYBP and inflammatory response (AOAH. The present data suggests the potential common genetic basis in the development of CRS in Chinese and Caucasian population.

  19. One-year prospective replication study of an untreated sample of community dysthymia subjects.

    Science.gov (United States)

    McCullough, J P; McCune, K J; Kaye, A L; Braith, J A; Friend, R; Roberts, W C; Belyea-Caldwell, S; Norris, S L; Hampton, C

    1994-07-01

    This study replicates an earlier naturalistic-prospective investigation of nontreatment, community DSM-III-R dysthymia subjects. Major goals were to determine spontaneous remission rates and monitor the stability of psychosocial functioning levels over time. Twenty-four dysthymia subjects were followed for 1 year. Three remissions (13%) were diagnosed at the final interview. At a 4-year diagnostic follow-up contact with the remitters only, one remitter had relapsed and two remained in remission. Subjects were monitored for depressive symptom intensity, personality functioning, general medical distress, cognitive functioning, coping stylistics, interpersonal functioning, quality of their social support resources, and general family functioning. Stable levels of psychosocial functioning were maintained across all measures over the 1-year period. Current psychometric findings confirm the conclusions of the earlier nontreatment prospective study that dysthymia is a chronic mood disorder with stable psychosocial features and is unlikely to remit spontaneously over time.

  20. Assessment of heterogeneity between European Populations: a Baltic and Danish replication case-control study of SNPs from a recent European ulcerative colitis genome wide association study.

    Science.gov (United States)

    Andersen, Vibeke; Ernst, Anja; Sventoraityte, Jurgita; Kupcinskas, Limas; Jacobsen, Bent A; Krarup, Henrik B; Vogel, Ulla; Jonaitis, Laimas; Denapiene, Goda; Kiudelis, Gediminas; Balschun, Tobias; Franke, Andre

    2011-10-13

    Differences in the genetic architecture of inflammatory bowel disease between different European countries and ethnicities have previously been reported. In the present study, we wanted to assess the role of 11 newly identified UC risk variants, derived from a recent European UC genome wide association study (GWAS) (Franke et al., 2010), for 1) association with UC in the Nordic countries, 2) for population heterogeneity between the Nordic countries and the rest of Europe, and, 3) eventually, to drive some of the previous findings towards overall genome-wide significance. Eleven SNPs were replicated in a Danish sample consisting of 560 UC patients and 796 controls and nine missing SNPs of the German GWAS study were successfully genotyped in the Baltic sample comprising 441 UC cases and 1156 controls. The independent replication data was then jointly analysed with the original data and systematic comparisons of the findings between ethnicities were made. Pearson's χ2, Breslow-Day (BD) and Cochran-Mantel-Haenszel (CMH) tests were used for association analyses and heterogeneity testing. The rs5771069 (IL17REL) SNP was not associated with UC in the Danish panel. The rs5771069 (IL17REL) SNP was significantly associated with UC in the combined Baltic, Danish and Norwegian UC study sample driven by the Norwegian panel (OR = 0.89, 95% CI: 0.79-0.98, P = 0.02). No association was found between rs7809799 (SMURF1/KPNA7) and UC (OR = 1.20, 95% CI: 0.95-1.52, P = 0.10) or between UC and all other remaining SNPs. We had 94% chance of detecting an association for rs7809799 (SMURF1/KPNA7) in the combined replication sample, whereas the power were 55% or lower for the remaining SNPs.Statistically significant PBD was found for OR heterogeneity between the combined Baltic, Danish, and Norwegian panel versus the combined German, British, Belgian, and Greek panel (rs7520292 (P = 0.001), rs12518307 (P = 0.007), and rs2395609 (TCP11) (P = 0.01), respectively).No SNP reached genome

  1. Assessment of heterogeneity between European Populations: a Baltic and Danish replication case-control study of SNPs from a recent European ulcerative colitis genome wide association study

    Directory of Open Access Journals (Sweden)

    Jonaitis Laimas

    2011-10-01

    Full Text Available Abstract Background Differences in the genetic architecture of inflammatory bowel disease between different European countries and ethnicities have previously been reported. In the present study, we wanted to assess the role of 11 newly identified UC risk variants, derived from a recent European UC genome wide association study (GWAS (Franke et al., 2010, for 1 association with UC in the Nordic countries, 2 for population heterogeneity between the Nordic countries and the rest of Europe, and, 3 eventually, to drive some of the previous findings towards overall genome-wide significance. Methods Eleven SNPs were replicated in a Danish sample consisting of 560 UC patients and 796 controls and nine missing SNPs of the German GWAS study were successfully genotyped in the Baltic sample comprising 441 UC cases and 1156 controls. The independent replication data was then jointly analysed with the original data and systematic comparisons of the findings between ethnicities were made. Pearson's χ2, Breslow-Day (BD and Cochran-Mantel-Haenszel (CMH tests were used for association analyses and heterogeneity testing. Results The rs5771069 (IL17REL SNP was not associated with UC in the Danish panel. The rs5771069 (IL17REL SNP was significantly associated with UC in the combined Baltic, Danish and Norwegian UC study sample driven by the Norwegian panel (OR = 0.89, 95% CI: 0.79-0.98, P = 0.02. No association was found between rs7809799 (SMURF1/KPNA7 and UC (OR = 1.20, 95% CI: 0.95-1.52, P = 0.10 or between UC and all other remaining SNPs. We had 94% chance of detecting an association for rs7809799 (SMURF1/KPNA7 in the combined replication sample, whereas the power were 55% or lower for the remaining SNPs. Statistically significant PBD was found for OR heterogeneity between the combined Baltic, Danish, and Norwegian panel versus the combined German, British, Belgian, and Greek panel (rs7520292 (P = 0.001, rs12518307 (P = 0.007, and rs2395609 (TCP11 (P = 0

  2. 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

  3. Effect of Previous Irradiation on Vascular Thrombosis of Microsurgical Anastomosis: A Preclinical Study in Rats

    Science.gov (United States)

    Gallardo-Calero, Irene; López-Fernández, Alba; Romagosa, Cleofe; Vergés, Ramona; Aguirre-Canyadell, Marius; Soldado, Francisco; Velez, Roberto

    2016-01-01

    Background: The objective of the present investigation was to compare the effect of neoadjuvant irradiation on the microvascular anastomosis in cervical bundle using an experimental model in rats. Methods: One hundred forty male Sprague–Dawley rats were allocated into 4 groups: group I, control, arterial microanastomosis; group II, control, venous microanastomosis; group III, arterial microanastomosis with previous irradiation (20 Gy); and group IV, venous microanastomosis with previous irradiation (20 Gy). Clinical parameters, technical values of anastomosis, patency, and histopathological parameters were evaluated. Results: Irradiated groups (III and IV) and vein anastomosis groups (II and IV) showed significantly increased technical difficulties. Group IV showed significantly reduced patency rates (7/35) when compared with the control group (0/35). Radiotherapy significantly decreased the patency rates of the vein (7/35) when compared with the artery (1/35). Groups III and IV showed significantly reduced number of endothelial cells and also showed the presence of intimal thickening and adventitial fibrosis as compared with the control group. Conclusion: Neoadjuvant radiotherapy reduces the viability of the venous anastomosis in a preclinical rat model with a significant increase in the incidence of vein thrombosis. PMID:27975009

  4. TNFA-863 polymorphism is associated with a reduced risk of Chronic Obstructive Pulmonary Disease: A replication study

    Directory of Open Access Journals (Sweden)

    Medina-Coello Chaxiraxi

    2011-10-01

    Full Text Available Background TNF-α mediated inflammation is thought to play a key role in the respiratory and systemic features of Chronic Obstructive Pulmonary Disease. The aim of the present study was to replicate and extend recent findings in Taiwanese and Caucasian populations of associations between COPD susceptibility and variants of the TNFA gene in a Spanish cohort. Methods The 3 reported SNPs were complemented with nine tag single nucleotide polymorphisms (SNP of the TNFA and LTA genes and genotyped in 724 individuals (202 COPD patients, 90 smokers without COPD and 432 healthy controls. Pulmonary function parameters and serum inflammatory markers were also measured in COPD patients. Results The TNFA rs1800630 (-863C/A SNP was associated with a lower COPD susceptibility (ORadj = 0.50, 95% CI = 0.33-0.77, p = 0.001. The -863A allele was also associated with less severe forms of the disease (GOLD stages I and II (ORadj = 0.303, 95%CI = 0.14-0.65, p = 0.014 and with lower scores of the BODE index (1 percent predicted (p = 0.004 and a lower BODE index (p = 0.003 over a 2 yrs follow-up period. None of the TNFA or LTA gene variants correlated with the serum inflammatory markers in COPD patients (p > 0.05. Conclusions We replicated the previously reported association between the TNFA -863 SNP and COPD. TNFA -863A allele may confer a protective effect to the susceptibility to the disease in the Spanish population.

  5. 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,…

  6. A large replication study and meta-analysis in European samples provides further support for association of AHI1 markers with schizophrenia

    DEFF Research Database (Denmark)

    Ingason, Andrés; Giegling, Ina; Cichon, Sven

    2010-01-01

    The Abelson helper integration site 1 (AHI1) gene locus on chromosome 6q23 is among a group of candidate loci for schizophrenia susceptibility that were initially identified by linkage followed by linkage disequilibrium mapping, and subsequent replication of the association in an independent sample....... Here, we present results of a replication study of AHI1 locus markers, previously implicated in schizophrenia, in a large European sample (in total 3907 affected and 7429 controls). Furthermore, we perform a meta-analysis of the implicated markers in 4496 affected and 18,920 controls. Both...... as the neighbouring phosphodiesterase 7B (PDE7B)-may be considered candidates for involvement in the genetic aetiology of schizophrenia....

  7. 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.

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

    Science.gov (United States)

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

    2015-01-01

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

  9. Late preterm birth and previous cesarean section: a population-based cohort study.

    Science.gov (United States)

    Yasseen Iii, Abdool S; Bassil, Kate; Sprague, Ann; Urquia, Marcelo; Maguire, Jonathon L

    2018-02-21

    Late preterm birth (LPB) is increasingly common and associated with higher morbidity and mortality than term birth. Yet, little is known about the influence of previous cesarean section (PCS) and the occurrence of LPB in subsequent pregnancies. We aim to evaluate this association along with the potential mediation by cesarean sections in the current pregnancy. We use population-based birth registry data (2005-2012) to establish a cohort of live born singleton infants born between 34 and 41 gestational weeks to multiparous mothers. PCS was the primary exposure, LPB (34-36 weeks) was the primary outcome, and an unplanned or emergency cesarean section in the current pregnancy was the potential mediator. Associations were quantified using propensity weighted multivariable Poisson regression, and mediating associations were explored using the Baron-Kenny approach. The cohort included 481,531 births, 21,893 (4.5%) were LPB, and 119,983 (24.9%) were predated by at least one PCS. Among mothers with at least one PCS, 6307 (5.26%) were LPB. There was increased risk of LPB among women with at least one PCS (adjusted Relative Risk (aRR): 1.20 (95%CI [1.16, 1.23]). Unplanned or emergency cesarean section in the current pregnancy was identified as a strong mediator to this relationship (mediation ratio = 97%). PCS was associated with higher risk of LPB in subsequent pregnancies. This may be due to an increased risk of subsequent unplanned or emergency preterm cesarean sections. Efforts to minimize index cesarean sections may reduce the risk of LPB in subsequent pregnancies.

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

    Science.gov (United States)

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

    2013-01-01

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

  11. The value of repeating studies and multiple controls: replicated 28-day growth studies of rainbow trout exposed to clofibric acid.

    Science.gov (United States)

    Owen, Stewart F; Huggett, Duane B; Hutchinson, Thomas H; Hetheridge, Malcolm J; McCormack, Paul; Kinter, Lewis B; Ericson, Jon F; Constantine, Lisa A; Sumpter, John P

    2010-12-01

    Two studies to examine the effect of waterborne clofibric acid (CA) on growth-rate and condition of rainbow trout were conducted using accepted regulatory tests (Organisation for Economic Co-operation and Development [OECD] 215). The first study (in 2005) showed significant reductions after 21 d of exposure (21-d growth lowest-observed-effect concentration [LOEC] = 0.1 µg/L, 21-d condition LOEC = 0.1 µg/L) that continued to 28 d. Growth rate was reduced by approximately 50% (from 5.27 to 2.67% per day), while the condition of the fish reduced in a concentration-dependant manner. Additionally, in a concentration-dependent manner, significant changes in relative liver size were observed, such that increasing concentrations of CA resulted in smaller livers after 28-d exposure. A no-observed-effect concentration (NOEC) was not achieved in the 2005 study. An expanded second study (in 2006) that included a robust bridge to the 2005 study, with four replicate tanks of eight individual fish per concentration, did not repeat the 2005 findings. In the 2006 study, no significant effect on growth rate, condition, or liver biometry was observed after 21 or 28 d (28-d growth NOEC = 10 µg/L, 28-d condition NOEC = 10 µg/L), contrary to the 2005 findings. We do not dismiss either of these findings and suggest both are relevant and stand for comparison. However, the larger 2006 study carries more statistical power and multiple-tank replication, so probably produced the more robust findings. Despite sufficient statistical power in each study, interpretation of these and similar studies should be conducted with caution, because much significance is placed on the role of limited numbers of individual and tank replicates and the influence of control animals. Copyright © 2010 SETAC.

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

    Science.gov (United States)

    Xu, Kai; Nagy, Peter D

    2017-04-01

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

  13. Phase III Study of Cabozantinib in Previously Treated Metastatic Castration-Resistant Prostate Cancer: COMET-1.

    Science.gov (United States)

    Smith, Matthew; De Bono, Johann; Sternberg, Cora; Le Moulec, Sylvestre; Oudard, Stéphane; De Giorgi, Ugo; Krainer, Michael; Bergman, Andries; Hoelzer, Wolfgang; De Wit, Ronald; Bögemann, Martin; Saad, Fred; Cruciani, Giorgio; Thiery-Vuillemin, Antoine; Feyerabend, Susan; Miller, Kurt; Houédé, Nadine; Hussain, Syed; Lam, Elaine; Polikoff, Jonathan; Stenzl, Arnulf; Mainwaring, Paul; Ramies, David; Hessel, Colin; Weitzman, Aaron; Fizazi, Karim

    2016-09-01

    Cabozantinib is an inhibitor of kinases, including MET and vascular endothelial growth factor receptors, and has shown activity in men with previously treated metastatic castration-resistant prostate cancer (mCRPC). This blinded phase III trial compared cabozantinib with prednisone in patients with mCRPC. Men with progressive mCRPC after docetaxel and abiraterone and/or enzalutamide were randomly assigned at a two-to-one ratio to cabozantinib 60 mg once per day or prednisone 5 mg twice per day. The primary end point was overall survival (OS). Bone scan response (BSR) at week 12 as assessed by independent review committee was the secondary end point; radiographic progression-free survival (rPFS) and effects on circulating tumor cells (CTCs), bone biomarkers, serum prostate-specific antigen (PSA), and symptomatic skeletal events (SSEs) were exploratory assessments. A total of 1,028 patients were randomly assigned to cabozantinib (n = 682) or prednisone (n = 346). Median OS was 11.0 months with cabozantinib and 9.8 months with prednisone (hazard ratio, 0.90; 95% CI, 0.76 to 1.06; stratified log-rank P = .213). BSR at week 12 favored cabozantinib (42% v 3%; stratified Cochran-Mantel-Haenszel P < .001). rPFS was improved in the cabozantinib group (median, 5.6 v 2.8 months; hazard ratio, 0.48; 95% CI, 0.40 to 0.57; stratified log-rank P < .001). Cabozantinib was associated with improvements in CTC conversion, bone biomarkers, and post-random assignment incidence of SSEs but not PSA outcomes. Grade 3 to 4 adverse events and discontinuations because of adverse events were higher with cabozantinib than with prednisone (71% v 56% and 33% v 12%, respectively). Cabozantinib did not significantly improve OS compared with prednisone in heavily treated patients with mCRPC and progressive disease after docetaxel and abiraterone and/or enzalutamide. Cabozantinib had some activity in improving BSR, rPFS, SSEs, CTC conversions, and bone biomarkers but not PSA outcomes. © 2016 by

  14. Structural studies demonstrating a bacteriophage-like replication cycle of the eukaryote-infecting Paramecium bursaria chlorella virus-1.

    Directory of Open Access Journals (Sweden)

    Elad Milrot

    2017-08-01

    Full Text Available A fundamental stage in viral infection is the internalization of viral genomes in host cells. Although extensively studied, the mechanisms and factors responsible for the genome internalization process remain poorly understood. Here we report our observations, derived from diverse imaging methods on genome internalization of the large dsDNA Paramecium bursaria chlorella virus-1 (PBCV-1. Our studies reveal that early infection stages of this eukaryotic-infecting virus occurs by a bacteriophage-like pathway, whereby PBCV-1 generates a hole in the host cell wall and ejects its dsDNA genome in a linear, base-pair-by-base-pair process, through a membrane tunnel generated by the fusion of the virus internal membrane with the host membrane. Furthermore, our results imply that PBCV-1 DNA condensation that occurs shortly after infection probably plays a role in genome internalization, as hypothesized for the infection of some bacteriophages. The subsequent perforation of the host photosynthetic membranes presumably enables trafficking of viral genomes towards host nuclei. Previous studies established that at late infection stages PBCV-1 generates cytoplasmic organelles, termed viral factories, where viral assembly takes place, a feature characteristic of many large dsDNA viruses that infect eukaryotic organisms. PBCV-1 thus appears to combine a bacteriophage-like mechanism during early infection stages with a eukaryotic-like infection pathway in its late replication cycle.

  15. Radon diffusion coefficients for soils. Previous studies and their application to uranium-bearing wastes

    International Nuclear Information System (INIS)

    Sasaki, Tomozo; Gunji, Yasuyoshi; Iida, Takao

    2008-01-01

    Radon diffusion in soils has been studied over the years by many researchers. The application of such studies to the evaluation of radiation exposure caused by radon from uranium-bearing wastes disposed in a shallow land site is very important. The present paper surveyed closely relevant studies and elucidated the inherent nature of radon diffusion in terms of the definition of radon diffusion coefficients. Then, basic features of measurement methods for determining radon diffusion coefficients in soils were explained. Furthermore, theoretical aspects of radon diffusion in soils were discussed in terms of microscopic radon diffusion in soils and large-scale radon diffusion through cover soil defects for uranium mill tailings. Finally, in order to apply the radon diffusion studies to uranium-bearing waste disposal in shallow land sites, new challenges were presented: elucidation of radon diffusion in uranium-bearing wastes and cover-soil cracks, and demonstration of the validity of applying only radon diffusion in the evaluation of radiation exposure caused by radon, which would come through Japanese cover soils for uranium-bearing waste disposal. (author)

  16. Interbirth interval and history of previous preeclampsia: a case–control study among multiparous women

    OpenAIRE

    Harutyunyan, Arusyak; Armenian, Haroutune; Petrosyan, Varduhi

    2013-01-01

    Abstract Background Preeclampsia is a disorder with a reported incidence of 2%-8% among all pregnancies, accounting for more than 50,000 deaths worldwide each year. In low- and middle- income countries maternal/perinatal morbidity and mortality associated with preeclampsia are high due to the lack of proper prenatal and hospital care and limited access to neonatal intensive care. The objectives of our study were to determine the association of long in...

  17. A Review of Previous Studies on Information Processing in Career Decision Making among University Students

    OpenAIRE

    池田, 智子; Satoko, Ikeda

    2018-01-01

    This review of the researches of career choice of Japanese university students focused the studies on decision-making theory conducted in Japan. The present review suggested the necessity of examination of the effect of self-efficacy about career information search on the process of career choice. It is also needed to examine the relationship between specific self-efficacy about career information search and career decision-making self-efficacy, moreover, general self-efficacy.

  18. A Comment Upon Previous Studies on 3-D Boundary Layer Transition

    OpenAIRE

    ÇARPINLIOĞLU, Melda Özdinç

    2014-01-01

    The common feature of the experimental studies upon 3-D boundary layer development on swept flat plates cited in the available literature is the application of streamwise and/or spanwise pressure gradients. In fact; presence of the pressure gradients was suggested to be vital for having crossflow effective in 3-D boundary layer transition. In the presented paper here, this idea is questioned evaluating the results of an experimental investigation conducted on swept flat plates under the ab...

  19. Neuropsychiatric and cardiometabolic comorbidities in patients with previously diagnosed Cushing's disease: a longitudinal observational study

    OpenAIRE

    Dimopoulou, C; Geraedts, V; Stalla, G K; Sievers, C

    2015-01-01

    INTRODUCTION: Only few studies have systematically investigated neuropsychiatric aspects in patients with Cushing's disease (CD). Pain syndromes have been described in patients with pituitary adenomas, but so far no systematical investigation has been conducted in patients with CD. Additionally, CD has an association with cardiometabolic comorbidities which ultimately leads to increased morbidity and mortality. Long-term treatment of the hypercortisolic state cannot prevent the persistence of...

  20. A New Zealand based cohort study of anaesthetic trainees' career outcomes compared with previously expressed intentions.

    Science.gov (United States)

    Moran, E M L; French, R A; Kennedy, R R

    2011-09-01

    Predicting workforce requirements is a difficult but necessary part of health resource planning. A 'snapshot' workforce survey undertaken in 2002 examined issues that New Zealand anaesthesia trainees expected would influence their choice of future workplace. We have restudied the same cohort to see if that workforce survey was a good predictor of outcome. Seventy (51%) of 138 surveys were completed in 2009 compared with 100 (80%) of 138 in the 2002 survey. Eighty percent of the 2002 respondents planned consultant positions in New Zealand. We found 64% of respondents were working in New Zealand (P New Zealand based respondents but only 40% of those living outside New Zealand agreed or strongly agreed with this statement (P New Zealand but was important for only 2% of those resident in New Zealand (P New Zealand were predominantly between NZ$150,000 and $200,000 while those overseas received between NZ$300,000 and $400,000. Of those that are resident in New Zealand, 84% had studied in a New Zealand medical school compared with 52% of those currently working overseas (P < 0.01). Our study shows that stated career intentions in a group do not predict the actual group outcomes. We suggest that 'snapshot' studies examining workforce intentions are of little value for workforce planning. However we believe an ongoing program matching career aspirations against career outcomes would be a useful tool in workforce planning.

  1. [Transparency and replicability of nursing intervention studies in long-term care: A selective literature review].

    Science.gov (United States)

    Gspörer, Irene; Schrems, Berta M

    2018-05-01

    The development and evaluation of interventions in long-term care is time-consuming and expensive due to their complexity. To ensure reproducibility and successful implementation, these interventions must be described and published in a comprehensible and qualitative manner. The aim of this study is to analyze intervention studies from the inpatient long-term care setting with regard to their completeness, reporting quality, transparency and thus reproducibility. The completeness and the reporting quality of the interventions described in the publications were examined in the context of a selective literature review by means of intervention studies from the long-term care setting (n=22). To this end, the Template for Intervention Description and Replication (TIDieR) checklist and the Criteria for Reporting the Development and Evaluation of Complex Interventions in Healthcare 2 (CReDECI2-DE) list were used. Transparency criteria included study registration and access to study protocols. The TIDieR checklist examination revealed that only three studies contained all the information necessary; the CReDECI2 test provided a complete description for only one study. Frequent shortcomings were observed concerning the information on modifications and titrations for the study participants and the location. Protocols were available for eight studies, 14 studies were registered. In terms of science, this means that the reproducibility of scientific findings is limited, which is why they cannot provide secure knowledge. As a result, the practical benefit to be derived from published studies that are accessible to decision-makers is limited as well. As far as publishers are concerned they should pay more attention to the completeness, registration and availability of materials. Copyright © 2018. Published by Elsevier GmbH.

  2. Deficit of entropy modulation of the EEG in schizophrenia associated to cognitive performance and symptoms. A replication study.

    Science.gov (United States)

    Molina, Vicente; Bachiller, Alejandro; Gomez-Pilar, Javier; Lubeiro, Alba; Hornero, Roberto; Cea-Cañas, Benjamín; Valcárcel, César; Haidar, Mahmoun-Karim; Poza, Jesús

    2017-09-05

    Spectral entropy (SE) is a measurement from information theory field that provides an estimation of EEG regularity and may be useful as a summary of its spectral properties. Previous studies using small samples reported a deficit of EEG entropy modulation in schizophrenia during cognitive activity. The present study is aimed at replicating this finding in a larger sample, to explore its cognitive and clinical correlates and to discard antipsychotic treatment as the main source of that deficit. We included 64 schizophrenia patients (21 first episodes, FE) and 65 healthy controls. We computed SE during performance of an odd-ball paradigm, at the windows prior (-300 to 0ms) and following (150 to 450ms) stimulus presentation. Modulation of SE was defined as the difference between post- and pre-stimulus windows. In comparison to controls, patients showed a deficit of SE modulation over frontal and central regions, also shown by FE patients. Baseline SE did not differ between patients and controls. Modulation deficit was directly associated with cognitive deficits and negative symptoms, and inversely with positive symptoms. SE modulation was not related to antipsychotic doses. Patients also showed a smaller change of median frequency (i.e., smaller slowing of oscillatory activity) of the EEG from pre- to post-stimulus windows. These results support that a deficit of fast modulation contributes to cognitive deficits and symptoms in schizophrenia patients. Copyright © 2017. Published by Elsevier B.V.

  3. The Utility of EEG in Attention Deficit Hyperactivity Disorder: A Replication Study.

    Science.gov (United States)

    Swatzyna, Ronald J; Tarnow, Jay D; Roark, Alexandra; Mardick, Jacob

    2017-07-01

    The routine use of stimulants in pediatrics has increased dramatically over the past 3 decades and the long-term consequences have yet to be fully studied. Since 1978 there have been 7 articles identifying electroencephalogram (EEG) abnormalities, particularly epileptiform discharges in children with attention deficit hyperactivity disorder (ADHD). Many have studied the prevalence of these discharges in this population with varying results. An article published in 2011 suggests that EEG technology should be considered prior to prescribing stimulants to children diagnosed with ADHD due to a high prevalence of epileptiform discharges. The 2011 study found a higher prevalence (26%) of epileptiform discharges when using 23-hour and sleep-deprived EEGs in comparison with other methods of activation (hyperventilation or photostimulation) and conventional EEG. We sought to replicate the 2011 results using conventional EEG with the added qEEG technologies of automatic spike detection and low-resolution electromagnetic tomography analysis (LORETA) brain mapping. Our results showed 32% prevalence of epileptiform discharges, which suggests that an EEG should be considered prior to prescribing stimulant medications.

  4. Life cycle impact assessment of ammonia production in Algeria: A comparison with previous studies

    Energy Technology Data Exchange (ETDEWEB)

    Makhlouf, Ali, E-mail: almakhsme@gmail.com; Serradj, Tayeb; Cheniti, Hamza

    2015-01-15

    In this paper, a Life Cycle Analysis (LCA) from “cradle to gate” of one anhydrous ton of ammonia with a purity of 99% was achieved. Particularly, the energy and environmental performance of the product (ammonia) were evaluated. The eco-profile of the product and the share of each stage of the Life Cycle on the whole environmental impacts have been evaluated. The flows of material and energy for each phase of the life cycle were counted and the associated environmental problems were identified. Evaluation of the impact was achieved using GEMIS 4.7 software. The primary data collection was executed at the production installations located in Algeria (Annaba locality). The analysis was conducted according to the LCA standards ISO 14040 series. The results show that Cumulative Energy Requirement (CER) is of 51.945 × 10{sup 3} MJ/t of ammonia, which is higher than the global average. Global Warming Potential (GWP) is of 1.44 t CO{sub 2} eq/t of ammonia; this value is lower than the world average. Tropospheric ozone precursor and Acidification are also studied in this article, their values are: 549.3 × 10{sup −6} t NMVOC eq and 259.3 × 10{sup −6} t SO{sub 2} eq respectively.

  5. Life cycle impact assessment of ammonia production in Algeria: A comparison with previous studies

    International Nuclear Information System (INIS)

    Makhlouf, Ali; Serradj, Tayeb; Cheniti, Hamza

    2015-01-01

    In this paper, a Life Cycle Analysis (LCA) from “cradle to gate” of one anhydrous ton of ammonia with a purity of 99% was achieved. Particularly, the energy and environmental performance of the product (ammonia) were evaluated. The eco-profile of the product and the share of each stage of the Life Cycle on the whole environmental impacts have been evaluated. The flows of material and energy for each phase of the life cycle were counted and the associated environmental problems were identified. Evaluation of the impact was achieved using GEMIS 4.7 software. The primary data collection was executed at the production installations located in Algeria (Annaba locality). The analysis was conducted according to the LCA standards ISO 14040 series. The results show that Cumulative Energy Requirement (CER) is of 51.945 × 10 3 MJ/t of ammonia, which is higher than the global average. Global Warming Potential (GWP) is of 1.44 t CO 2 eq/t of ammonia; this value is lower than the world average. Tropospheric ozone precursor and Acidification are also studied in this article, their values are: 549.3 × 10 −6 t NMVOC eq and 259.3 × 10 −6 t SO 2 eq respectively

  6. Design, characterization and use of replicate human upper airways for radon dosimetry studies

    International Nuclear Information System (INIS)

    Swift, D.L.; Cheng, Y.S.; Su, Y.F.; Yeh, H.C.

    1992-01-01

    The size distribution of inhaled radon progeny aerosols is a significant factor in dosimetry. The role of the airways above the trachea is an important determinant of the respiratory distribution of both attached and unattached progeny aerosols. In order to provide information on the effect of particle size and breathing conditions on the overall and local deposition, we have developed a method to produce a replicate airway model from an in vivo magnetic resonance imaging coronal scan. The model consists of a sandwich of methacrylate elements, each element having the thickness of the scan interval. The transition between successive scan outlines traced on the front and back surfaces of each element is handsculpted in the plastic. The hollow model of the nasal passages thus produced has been characterized both morphologically and fluid-mechanically and has a flow resistance typical of a normal adult. The model has several distinct advantages for studies of radon progeny aerosol deposition. After exposure to a radioaerosol (or to an aerosol of an otherwise measurable substance) the individual elements can be separated to determine local deposition. The dimensions of specific upper-airway regions can be changed by replacing a small number of elements. The model has been incorporated in an exposure system for determining overall nandregional deposition of aerosols whose median diameter is approximately 1.7 nm. Measurements at several flow rates are presented to demonstrate use of the model in radon dosimetry. The model should also be useful for determining the airway deposition of other environmental aerosols

  7. Replicable personality types in childhood and adolescence: A Slovenian cross-sectional study

    Directory of Open Access Journals (Sweden)

    Maja Zupančič

    2006-12-01

    Full Text Available The present study explored individual constellations of five personality dimensions (personality types and their internal replicability with a sample of 4- to 14-year-olds (N = 1341. Employing an age- and culture-decentered assessment tool the target participants were rated by their mothers and the procedure by Asendorpf et al. (2001 was followed to derive personality types. Several cluster solutions were investigated with the one representing four personality types appearing the most interpretable. The average type included individuals (26% expressing mean levels of conscientiousness, extraversion, openness/intellect, and neuroticism, and a relatively high level of agreeableness. The reserved children/adolescents (35 % scored below-average in openess/intellect, relatively low in conscientiousness and extraversion, and they were rated relatively high for neuroticism. The wilful participants (30 % were high in openness/intelect and within the average range they appeared relatively extraverted and disagreeable. The resilient type turned out to be the least capacious as it captured extremly conscientious, extraverted, open, emotionally stable and relatively high agreeable individuals. More girls than boys were classified as average and the boys were, in comparison to the girls, more often assigned to the wilful and to the reserved personality types. The wilful type was the most common in early childhood, the reserved type memberhip was the most frequent in middle and late childhood, and early adolesscents were the most frequently classified to the average type.

  8. Replicated mesocosm study on the role of natural ultraviolet radiation in high CDOM, shallow lakes.

    Science.gov (United States)

    Pérez, A Patricia; Diaz, Mónica M; Ferraro, Marcela A; Cusminsky, Gabriela C; Zagarese, Horacio E

    2003-02-01

    The role of ultraviolet radiation on shallow, high CDOM (colored dissolved organic matter) lakes was investigated during two consecutive summers (1999 and 2000) in replicated mesocosms (rectangular fiberglass tanks). Each tank (volume: 300 L; depth: 40 cm) was covered with a layer (approximately 3 cm) of sediment from lake El Toro (40 degrees 14' S; 70 degrees 22' W) and filled with filtered water. The experimental design consisted of two treatments: full natural radiation (UV-exposed) and natural radiation without ultraviolet radiation (UV-shielded). UV-exposed and UV-shielded treatments differed in most studied variables as revealed by repeated measures ANOVA. UV-exposed tanks displayed lower CDOM levels (dissolved absorbance) of lower average molecular size (absorbance ratio between 250 and 365 nm), higher bacterial biomass, and lower chlorophyll a concentration. The effect on consumers (rotifers and crustaceans) was less noticeable. The results are consistent with UV stimulation of bacteria production mediated by higher rates of CDOM photobleaching, and the photoinhibition of planktonic algae. Thus, a major effect of UVR in shallow, high CDOM ecosystems appears to be the stimulation of heterotrophic pathways and a simultaneous inhibition of photoautotrophs.

  9. The Internal Consistency and Validity of the Vaccination Attitudes Examination Scale: A Replication Study.

    Science.gov (United States)

    Wood, Louise; Smith, Michael; Miller, Christopher B; O'Carroll, Ronan E

    2018-06-19

    Vaccinations are important preventative health behaviors. The recently developed Vaccination Attitudes Examination (VAX) Scale aims to measure the reasons behind refusal/hesitancy regarding vaccinations. The aim of this replication study is to conduct an independent test of the newly developed VAX Scale in the UK. We tested (a) internal consistency (Cronbach's α); (b) convergent validity by assessing its relationships with beliefs about medication, medical mistrust, and perceived sensitivity to medicines; and (c) construct validity by testing how well the VAX Scale discriminated between vaccinators and nonvaccinators. A sample of 243 UK adults completed the VAX Scale, the Beliefs About Medicines Questionnaire, the Perceived Sensitivity to Medicines Scale, and the Medical Mistrust Index, in addition to demographics of age, gender, education levels, and social deprivation. Participants were asked (a) whether they received an influenza vaccination in the past year and (b) if they had a young child, whether they had vaccinated the young child against influenza in the past year. The VAX (a) demonstrated high internal consistency (α = .92); (b) was positively correlated with medical mistrust and beliefs about medicines, and less strongly correlated with perceived sensitivity to medicines; and (c) successfully differentiated parental influenza vaccinators from nonvaccinators. The VAX demonstrated good internal consistency, convergent validity, and construct validity in an independent UK sample. It appears to be a useful measure to help us understand the health beliefs that promote or deter vaccination behavior.

  10. Negative Emotional Reactions to Challenging Behaviour and Staff Burnout: Two Replication Studies

    Science.gov (United States)

    Rose, David; Horne, Sharon; Rose, John L.; Hastings, Richard P.

    2004-01-01

    Background: Hastings, R. P. ["American Journal on Mental Retardation" (2002) Vol. 107, pp. 455-467] hypothesized that staff negative emotional reactions to challenging behaviour might accumulate over time to affect staff well-being. Only one previous study (Mitchell, G.& Hastings, R. P. ["American Journal on Mental…

  11. Association of STAT4 with rheumatoid arthritis: a replication study in three European populations.

    NARCIS (Netherlands)

    Orozco, G.; Alizadeh, B.Z.; Delgado-Vega, A.M.; Gonzalez-Gay, M.A.; Balsa, A.; Pascual-Salcedo, D.; Fernandez-Gutierrez, B.; Gonzalez-Escribano, M.F.; Petersson, I.F.; Riel, P.L.C.M. van; Barrera, P.; Coenen, M.J.H.; Radstake, T.R.D.J.; Leeuwen, M.A. van; Wijmenga, C.; Koeleman, B.P.; Alarcon-Riquelme, M.E.; Martin, J.

    2008-01-01

    OBJECTIVE: This study was undertaken to investigate the previously reported association of the STAT4 polymorphism rs7574865 with rheumatoid arthritis (RA) in 3 different European populations from Spain, Sweden, and The Netherlands, comprising a total of 2,072 patients and 2,474 controls. METHODS:

  12. Genetic influences on hand osteoarthritis in Finnish women--a replication study of candidate genes.

    Directory of Open Access Journals (Sweden)

    Satu Hämäläinen

    Full Text Available OBJECTIVES: Our aims were to replicate some previously reported associations of single nucleotide polymorphisms (SNPs in five genes (A2BP1, COG5, GDF5, HFE, ESR1 with hand osteoarthritis (OA, and to examine whether genes (BCAP29, DIO2, DUS4L, DVWA, HLA, PTGS2, PARD3B, TGFB1 and TRIB1 associated with OA at other joint sites were associated with hand OA among Finnish women. DESIGN: We examined the bilateral hand radiographs of 542 occupationally active Finnish female dentists and teachers aged 45 to 63 and classified them according to the presence of OA by using reference images. Data regarding finger joint pain and other risk factors were collected using a questionnaire. We defined two hand OA phenotypes: radiographic OA in at least three joints (ROA and symptomatic DIP OA. The genotypes were determined by PCR-based methods. In statistical analysis, we used SNPStats software, the chi-square test and logistic regression. RESULTS: Of the SNPs, rs716508 in A2BP1 was associated with ROA (OR = 0.7, 95% CI 0.5-0.9 and rs1800470 in TGFB1 with symptomatic DIP OA (1.8, 1.2-2.9. We found an interaction between ESR1 (rs9340799 and occupation: teachers with the minor allele were at an increased risk of symptomatic DIP OA (2.8, 1.3-6.5. We saw no association among the dentists. We also found that the carriage of the COG5 rs3757713 C allele increased the risk of ROA only among women with the BCAP29 rs10953541 CC genotype (2.6; 1.1-6.1. There was also a suggestive interaction between the HFE rs179945 and the ESR1 rs9340799, and the carriage of the minor allele of either of these SNPs was associated with an increased risk of symptomatic DIP OA (2.1, 1.3-2.5. CONCLUSIONS: Our results support the earlier findings of A2BP1 and TBGF1 being OA susceptibility genes and provide evidence of a possible gene-gene interaction in the genetic influence on hand OA predisposition.

  13. Registered Replication Report

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  14. Genetic Moderation of Stability in Attachment Security from Early Childhood to Age 18 Years: A Replication Study

    Science.gov (United States)

    Raby, K. Lee; Roisman, Glenn I.; Booth-LaForce, Cathryn

    2015-01-01

    A longstanding question for attachment theory and research is whether genetically based characteristics of the child influence the development of attachment security and its stability over time. This study attempted to replicate and extend recent findings indicating that the developmental stability of attachment security is moderated by oxytocin…

  15. Verbal Self-Guidance as a Treatment Approach for Children with Developmental Coordination Disorder: A Systematic Replication Study.

    Science.gov (United States)

    Martini, Rose; Polatajko, Helene J.

    1998-01-01

    Replicating a 1994 study, four children with developmental coordination disorder (DCD) were taught a verbal self-guidance strategy (Goal, Plan, Do, Check) by an occupational therapist. All four improved performance in attaining their occupational goals, supporting the possible use of a cognitive strategy with children with DCD. (SK)

  16. Ifosfamide in previously untreated disseminated neuroblastoma. Results of Study 3A of the European Neuroblastoma Study Group.

    Science.gov (United States)

    Kellie, S J; De Kraker, J; Lilleyman, J S; Bowman, A; Pritchard, J

    1988-05-01

    A prospective study of the effectiveness of ifosfamide as a single agent in the management of previously untreated patients with Evans stage IV neuroblastoma was undertaken. Eighteen children aged more than 1 year were treated with ifosfamide (IFX) 3 g/m2 daily for 2 days immediately after diagnosis and 3 weeks later. Treatment was continued with combination chemotherapy using vincristine, cyclophosphamide, cisplatinum and etoposide (OPEC) or a variant. Mesna (2-mercaptoethane sulphonate) was given to all patients during IFX treatment to prevent urotoxicity. Eight of the 18 patients (44%) responded to IFX. Nine had greater than 66% reduction in baseline tumor volume. Of 15 evaluable patients with raised pre-treatment urinary catecholamine excretion, six (40%) achieved greater than 50% reduction in pretreatment levels. Two of 10 patients evaluable for bone marrow response had complete clearance. Toxicity was mild in all patients. Upon completing 'first line' therapy, only four patients (22%) achieved a good partial remission (GPR) or complete response (CR). Median survival was 11 months. There was a lower rate of attaining GPR and shortened median survival in patients receiving phase II IFX before OPEC or variant, compared to patients with similar pre-treatment characteristics treated with OPEC from diagnosis in an earlier study.

  17. Studies on the mechanism of replication of adenovirus DNA. IV. Discontinuous DNA chain propagation

    NARCIS (Netherlands)

    Vlak, J.M.; Rozijn, Th.H.; Sussenbach, J.S.

    The replication of adenovirus type 5 DNA occurs by discontinuous chain propagation via short pieces of DNA. These pieces accumulate if the infected cells are treated with hydroxyurea. They have a sedimentation coefficient of 11 S corresponding to a molecular weight of about 700,000, and they contain

  18. Non-replication study of a genome-wide association study for hypertension and blood pressure in African Americans

    Directory of Open Access Journals (Sweden)

    Kidambi Srividya

    2012-04-01

    Full Text Available Abstract Background A recent genome wide association study in 1017 African Americans identified several single nucleotide polymorphisms that reached genome-wide significance for systolic blood pressure. We attempted to replicate these findings in an independent sample of 2474 unrelated African Americans in the Milwaukee metropolitan area; 53% were women and 47% were hypertensives. Methods We evaluated sixteen top associated SNPs from the above genome wide association study for hypertension as a binary trait or blood pressure as a continuous trait. In addition, we evaluated eight single nucleotide polymorphisms located in two genes (STK-39 and CDH-13 found to be associated with systolic and diastolic blood pressures by other genome wide association studies in European and Amish populations. TaqMan MGB-based chemistry with fluorescent probes was used for genotyping. We had an adequate sample size (80% power to detect an effect size of 1.2-2.0 for all the single nucleotide polymorphisms for hypertension as a binary trait, and 1% variance in blood pressure as a continuous trait. Quantitative trait analyses were performed both by excluding and also by including subjects on anti-hypertensive therapy (after adjustments were made for anti-hypertensive medications. Results For all 24 SNPs, no statistically significant differences were noted in the minor allele frequencies between cases and controls. One SNP (rs2146204 showed borderline association (p = 0.006 with hypertension status using recessive model and systolic blood pressure (p = 0.02, but was not significant after adjusting for multiple comparisons. In quantitative trait analyses, among normotensives only, rs12748299 was associated with SBP (p = 0.002. In addition, several nominally significant associations were noted with SBP and DBP among normotensives but none were statistically significant. Conclusions This study highlights the importance of replication to confirm the validity of genome wide

  19. Understanding Conditionals in the East: A Replication Study of Politzer et al. (2010 With Easterners

    Directory of Open Access Journals (Sweden)

    Hiroko Nakamura

    2018-04-01

    Full Text Available The new probabilistic approaches to the natural language conditional imply that there is a parallel relation between indicative conditionals (ICs “if s then b” and conditional bets (CBs “I bet $1 that if s then b” in two aspects. First, the probability of an IC and the probability of winning a CB are both the conditional probability, P(s|b. Second, both an IC and a CB have a third value “void” (neither true nor false, neither wins nor loses when the antecedent is false (¬s. These aspects of the parallel relation have been found in Western participants. In the present study, we investigated whether this parallel is also present in Eastern participants. We replicated the study of Politzer et al. (2010 with Chinese and Japanese participants and made two predictions. First, Eastern participants will tend to engage in more holistic cognition and take all possible cases, including ¬s, into account when they judge the probability of conditional: Easterners may assess the probability of antecedent s out of all possible cases, P(s, and then may focus on consequent b out of s, P(b|s. Consequently, Easterners may judge the probability of the conditional, and of winning the bet, to be P(s ∗ P(b|s = P(s & b, and false/losing the bet as P(s ∗ P(¬b|s = P(s & ¬b. Second, Eastern participants will tend to be strongly affected by context, and they may not show parallel relationships between ICs and CBs. The results indicate no cultural differences in judging the false antecedent cases: Eastern participants judged false antecedent cases as not making the IC true nor false and as not being winning or losing outcomes. However, there were cultural differences when asked about the probability of a conditional. Consistent with our hypothesis, Eastern participants had a greater tendency to take all possible cases into account, especially in CBs. We discuss whether these results can be explained by a hypothesized tendency for Eastern people to think

  20. Estimating the effect of current, previous and never use of drugs in studies based on prescription registries

    DEFF Research Database (Denmark)

    Nielsen, Lars Hougaard; Løkkegaard, Ellen; Andreasen, Anne Helms

    2009-01-01

    of this misclassification for analysing the risk of breast cancer. MATERIALS AND METHODS: Prescription data were obtained from Danish Registry of Medicinal Products Statistics and we applied various methods to approximate treatment episodes. We analysed the duration of HT episodes to study the ability to identify......PURPOSE: Many studies which investigate the effect of drugs categorize the exposure variable into never, current, and previous use of the study drug. When prescription registries are used to make this categorization, the exposure variable possibly gets misclassified since the registries do...... not carry any information on the time of discontinuation of treatment.In this study, we investigated the amount of misclassification of exposure (never, current, previous use) to hormone therapy (HT) when the exposure variable was based on prescription data. Furthermore, we evaluated the significance...

  1. Eukaryotic DNA Replication Fork.

    Science.gov (United States)

    Burgers, Peter M J; Kunkel, Thomas A

    2017-06-20

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

  2. An fMRI study of neuronal activation in schizophrenia patients with and without previous cannabis use

    Directory of Open Access Journals (Sweden)

    Else-Marie eLøberg

    2012-10-01

    Full Text Available Previous studies have mostly shown positive effects of cannabis use on cognition in patients with schizophrenia, which could reflect lower neurocognitive vulnerability. There are however no studies comparing whether such cognitive differences have neuronal correlates. Thus, the aim of the present study was to compare whether patients with previous cannabis use differ in brain activation from patients who has never used cannabis. The patients groups were compared on the ability to up-regulate an effort mode network during a cognitive task and down-regulate activation in the same network during a task-absent condition. Task-present and task-absent brain activation was measured by functional magnetic resonance neuroimaging (fMRI. Twenty-six patients with a DSM-IV and ICD-10 diagnosis of schizophrenia were grouped into a previous cannabis user group and a no-cannabis group. An auditory dichotic listening task with instructions of attention focus on either the right or left ear stimulus was used to tap verbal processing, attention and cognitive control, calculated as an aggregate score. When comparing the two groups, there were remaining activations in the task-present condition for the cannabis group, not seen in the no-cannabis group, while there was remaining activation in the task-absent condition for the no-cannabis group, not seen in the cannabis group. Thus, the patients with previous cannabis use showed increased activation in an effort mode network and decreased activation in the default mode network as compared to the no-cannabis group. It is concluded that the present study show some differences in brain activation to a cognitively challenging task between previous cannabis and no-cannabis schizophrenia patients.

  3. Common variant of ALPK1 is not associated with gout: a replication study

    OpenAIRE

    Chiba, Toshinori; Matsuo, Hirotaka; Sakiyama, Masayuki; Nakayama, Akiyoshi; Shimizu, Seiko; Wakai, Kenji; Suma, Shino; Nakashima, Hiroshi; Sakurai, Yutaka; Shimizu, Toru; Ichida, Kimiyoshi; Shinomiya, Nariyoshi

    2014-01-01

    Gout is one of the most kinds of common inflammatory arthritis as a consequence of hyperuricemia. Alpha-protein kinase 1 (ALPK1) gene locates in a gout-susceptibility locus on chromosome 4q21?31, and encodes ALPK1 protein which plays a pivotal role in the phosphorylation of myosin 1. In the previous genetic study of Taiwanese populations, 3 single nucleotide polymorphisms (SNPs), rs11726117, rs231247 and rs231253, in ALPK1 gene were reported to have a significant association with gout. Howeve...

  4. Individual and Contextual Factors Influencing Engagement in Learning Activities after Errors at Work: A Replication Study in a German Retail Bank

    Science.gov (United States)

    Leicher, Veronika; Mulder, Regina H.

    2016-01-01

    Purpose: The purpose of this replication study is to identify relevant individual and contextual factors influencing learning from errors at work and to determine if the predictors for learning activities are the same for the domains of nursing and retail banking. Design/methodology/approach: A cross-sectional replication study was carried out in…

  5. Adolescent Loneliness and the Interaction between the Serotonin Transporter Gene (5-HTTLPR and Parental Support: A Replication Study.

    Directory of Open Access Journals (Sweden)

    Annette W M Spithoven

    Full Text Available Gene-by-environment interaction (GxEs studies have gained popularity over the last decade, but the robustness of such observed interactions has been questioned. The current study contributes to this debate by replicating the only study on the interaction between the serotonin transporter gene (5-HTTLPR and perceived parental support on adolescents' peer-related loneliness. A total of 1,111 adolescents (51% boys with an average age of 13.70 years (SD = 0.93 participated and three annual waves of data were collected. At baseline, adolescent-reported parental support and peer-related loneliness were assessed and genetic information was collected. Assessment of peer-related loneliness was repeated at Waves 2 and 3. Using a cohort-sequential design, a Latent Growth Curve Model was estimated. Overall, a slight increase of loneliness over time was found. However, the development of loneliness over time was found to be different for boys and girls: girls' levels of loneliness increased over time, whereas boys' levels of loneliness decreased. Parental support was inversely related to baseline levels of loneliness, but unrelated to change of loneliness over time. We were unable to replicate the main effect of 5-HTTLPR or the 5-HTTLPR x Support interaction effect. In the Discussion, we examine the implications of our non-replication.

  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. Epigenetic Studies Point to DNA Replication/Repair Genes as a Basis for the Heritable Nature of Long Term Complications in Diabetes

    Directory of Open Access Journals (Sweden)

    Alexey A. Leontovich

    2016-01-01

    Full Text Available Metabolic memory (MM is defined as the persistence of diabetic (DM complications even after glycemic control is pharmacologically achieved. Using a zebrafish diabetic model that induces a MM state, we previously reported that, in this model, tissue dysfunction was of a heritable nature based on cell proliferation studies in limb tissue and this correlated with epigenetic DNA methylation changes that paralleled alterations in gene expression. In the current study, control, DM, and MM excised fin tissues were further analyzed by MeDIP sequencing and microarray techniques. Bioinformatics analysis of the data found that genes of the DNA replication/DNA metabolism process group (with upregulation of the apex1, mcm2, mcm4, orc3, lig1, and dnmt1 genes were altered in the DM state and these molecular changes continued into MM. Interestingly, DNA methylation changes could be found as far as 6–13 kb upstream of the transcription start site for these genes suggesting potential higher levels of epigenetic control. In conclusion, DNA methylation changes in members of the DNA replication/repair process group best explain the heritable nature of cell proliferation impairment found in the zebrafish DM/MM model. These results are consistent with human diabetic epigenetic studies and provide one explanation for the persistence of long term tissue complications as seen in diabetes.

  8. Dexamethasone intravitreal implant in previously treated patients with diabetic macular edema : Subgroup analysis of the MEAD study

    OpenAIRE

    Augustin, A.J.; Kuppermann, B.D.; Lanzetta, P.; Loewenstein, A.; Li, X.; Cui, H.; Hashad, Y.; Whitcup, S.M.; Abujamra, S.; Acton, J.; Ali, F.; Antoszyk, A.; Awh, C.C.; Barak, A.; Bartz-Schmidt, K.U.

    2015-01-01

    Background Dexamethasone intravitreal implant 0.7?mg (DEX 0.7) was approved for treatment of diabetic macular edema (DME) after demonstration of its efficacy and safety in the MEAD registration trials. We performed subgroup analysis of MEAD study results to evaluate the efficacy and safety of DEX 0.7 treatment in patients with previously treated DME. Methods Three-year, randomized, sham-controlled phase 3 study in patients with DME, best-corrected visual acuity (BCVA) of 34?68 Early Treatment...

  9. Psychological essentialism among Korean children and adults: a modified replication study.

    Science.gov (United States)

    Kim, Geunyoung

    2013-01-01

    Developmental psychologists have shown interest in the development of psychological essentialism among children; that is, a belief that certain psychological characteristics (such as personality) are relatively stable and unchanging. Although previous studies have shown that children are essentialistic about human traits, and the coherence among various essentialism dimensions increases with age, moderating cultural factors in the development of essentialism, especially among Asian children, have received little attention. Using the methodologies of Gelman, Heyman, and Legare (2007), levels of psychological essentialism among Korean children and adults were measured, and compared with the original US data. Results demonstrated cross-cultural similarity in the development of coherence in essentialistic thought, and difference in the level of essentialism among adult participants. The present findings imply that different cultural values between Asians and Westerners can play a role in the developmental trajectory of psychological essentialism.

  10. A Critical Review of Theory in Social Work Journals: A Replication Study

    Directory of Open Access Journals (Sweden)

    Carolyn S. Gentle-Genitty

    2007-05-01

    Full Text Available The purpose of this paper is multifold.Key aspects discussed include exploring the extent of theory discussion and progression in social work journals for the year 2004; discussing the necessity of theory in social work research and practice; reviewing previous research literature regarding evaluation of theory discussion and progression; proposing criteria for defining theory in social work journals; and presenting findings from the current study concerning theory discussion and progression in social work journals. Results: Of the 1,168 articles reviewed from 37 journals, 71 (approximately 6% met the criteria for theory development with empirical base. Thus, a minimal number of articles (3 out of 71 or 4.2% evaluated, based on the criteria in the theory quality scale (Table 1, received high quality ratings. Conclusion: Based on the results yielded by the analysis, we assert that social workers need to make a conscious effort to include theory in practice decisions.

  11. Association of STAT4 with rheumatoid arthritis: a replication study in three European populations.

    Science.gov (United States)

    Orozco, Gisela; Alizadeh, Behrooz Z; Delgado-Vega, Angélica M; González-Gay, Miguel A; Balsa, Alejandro; Pascual-Salcedo, Dora; Fernández-Gutierrez, Benjamín; González-Escribano, María F; Petersson, Ingemar F; van Riel, Piet L C M; Barrera, Pilar; Coenen, Marieke J H; Radstake, Timothy R D J; van Leeuwen, Miek A; Wijmenga, Cisca; Koeleman, Bobby P C; Alarcón-Riquelme, Marta; Martín, Javier

    2008-07-01

    This study was undertaken to investigate the previously reported association of the STAT4 polymorphism rs7574865 with rheumatoid arthritis (RA) in 3 different European populations from Spain, Sweden, and The Netherlands, comprising a total of 2,072 patients and 2,474 controls. Three different cohorts were included in the study: 923 RA patients and 1,296 healthy controls from Spain, 273 RA patients and 285 healthy controls from Sweden, and 876 RA patients and 893 healthy controls from The Netherlands. DNA from patients and controls was obtained from peripheral blood. Samples were genotyped for the STAT4 single-nucleotide polymorphism rs7574865 using a TaqMan 5'-allele discrimination assay. The chi-square test was performed to compare allele and genotype distributions. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. We observed a significantly increased frequency of the minor T allele in RA patients compared with healthy controls in the Spanish population (24.8% versus 20.8%; P = 0.001, OR 1.26 [95% CI 1.09-1.45]). This association was confirmed in both the Swedish population (P = 0.03, OR 1.35 [95% CI 1.03-1.77]) and the Dutch population (P = 0.03, OR 1.45 [95% CI 1.21-1.73]). The overall P value for all 3 populations was 9.79 x 10(-6) (OR 1.25 [95% CI 1.13-1.37]). No association between rs7574865 and the presence of rheumatoid factor or anti-cyclic citrullinated peptide autoantibodies was observed. A meta-analysis of all published STAT4 associations revealed an OR of 1.25 (95% CI 1.19-1.33) (P = 1 x 10(-5)). Our findings indicate an association between the STAT4 polymorphism rs7574865 and RA in 3 different populations, from Spain, Sweden, and The Netherlands, thereby confirming previous data.

  12. Genetic moderation of effects of maternal sensitivity on girl's age of menarche: Replication of the Manuck et al. study.

    Science.gov (United States)

    Hartman, Sarah; Widaman, Keith F; Belsky, Jay

    2015-08-01

    Manuck, Craig, Flory, Halder, and Ferrell (2011) reported that a theoretically anticipated effect of family rearing on girls' menarcheal age was genetically moderated by two single nucleotide polymorphisms (SNPs) of the estrogen receptor-α gene. We sought to replicate and extend these findings, studying 210 White females followed from birth. The replication was general because a different measure of the rearing environment was used in this inquiry (i.e., maternal sensitivity) than in the prior one (i.e., family cohesion). Extensions of the work included prospective rather than retrospective measurements of the rearing environment, reports of first menstruation within a year of its occurrence rather than decades later, accounting for some heritability of menarcheal age by controlling for maternal age of menarche, and using a new model-fitting approach to competitively compare diathesis-stress versus differential-susceptibility models of Gene × Environment interaction. The replication/extension effort proved successful in the case of both estrogen receptor-α SNPs, with the Gene × Environment interactions principally reflecting diathesis-stress: lower levels of maternal sensitivity predicted earlier age of menarche for girls homozygous for the minor alleles of either SNP but not for girls carrying other genotypes. Results are discussed in light of the new analytic methods adopted.

  13. The functional subdivision of the visual brain: Is there a real illusion effect on action? A multi-lab replication study.

    Science.gov (United States)

    Kopiske, Karl K; Bruno, Nicola; Hesse, Constanze; Schenk, Thomas; Franz, Volker H

    2016-06-01

    It has often been suggested that visual illusions affect perception but not actions such as grasping, as predicted by the "two-visual-systems" hypothesis of Milner and Goodale (1995, The Visual Brain in Action, Oxford University press). However, at least for the Ebbinghaus illusion, relevant studies seem to reveal a consistent illusion effect on grasping (Franz & Gegenfurtner, 2008. Grasping visual illusions: consistent data and no dissociation. Cognitive Neuropsychology). Two interpretations are possible: either grasping is not immune to illusions (arguing against dissociable processing mechanisms for vision-for-perception and vision-for-action), or some other factors modulate grasping in ways that mimic a vision-for perception effect in actions. It has been suggested that one such factor may be obstacle avoidance (Haffenden Schiff & Goodale, 2001. The dissociation between perception and action in the Ebbinghaus illusion: nonillusory effects of pictorial cues on grasp. Current Biology, 11, 177-181). In four different labs (total N = 144), we conducted an exact replication of previous studies suggesting obstacle avoidance mechanisms, implementing conditions that tested grasping as well as multiple perceptual tasks. This replication was supplemented by additional conditions to obtain more conclusive results. Our results confirm that grasping is affected by the Ebbinghaus illusion and demonstrate that this effect cannot be explained by obstacle avoidance. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Replication stress-induced chromosome breakage is correlated with replication fork progression and is preceded by single-stranded DNA formation.

    Science.gov (United States)

    Feng, Wenyi; Di Rienzi, Sara C; Raghuraman, M K; Brewer, Bonita J

    2011-10-01

    Chromosome breakage as a result of replication stress has been hypothesized to be the direct consequence of defective replication fork progression, or "collapsed" replication forks. However, direct and genome-wide evidence that collapsed replication forks give rise to chromosome breakage is still lacking. Previously we showed that a yeast replication checkpoint mutant mec1-1, after transient exposure to replication impediment imposed by hydroxyurea (HU), failed to complete DNA replication, accumulated single-stranded DNA (ssDNA) at the replication forks, and fragmented its chromosomes. In this study, by following replication fork progression genome-wide via ssDNA detection and by direct mapping of chromosome breakage after HU exposure, we have tested the hypothesis that the chromosome breakage in mec1 cells occurs at collapsed replication forks. We demonstrate that sites of chromosome breakage indeed correlate with replication fork locations. Moreover, ssDNA can be detected prior to chromosome breakage, suggesting that ssDNA accumulation is the common precursor to double strand breaks at collapsed replication forks.

  15. Youth suicide: an insight into previous hospitalisation for injury and sociodemographic conditions from a nationwide cohort study.

    Science.gov (United States)

    Zambon, Francesco; Laflamme, Lucie; Spolaore, Paolo; Visentin, Cristiana; Hasselberg, Marie

    2011-06-01

    This study investigates the degree to which a previous hospitalisation for injury of any intent is a risk of subsequent youth suicide and whether this association is influenced by family socioeconomic status or economic stress. A nationwide register-based cohort study was conducted covering all Swedish subjects born between January 1977 and December 1991 (N=1,616,342, male/female ratio=1.05). The cohort subjects were followed-up from January 1998 to December 2003, when aged 7-26 years. Poisson regression and the likelihood ratio test (95% CI) were used to assess the age-adjusted effect of hospitalisation for injuries of various intent on youth suicide and its effect once adjusted for family sociodemographic and social circumstances. Each set of exposures was associated independently and significantly with suicide mortality. Being hospitalised for self-inflicted injuries or injuries of undetermined intent was associated with a risk of suicide 36 to 47 times, respectively, that of subjects never hospitalised in the period under study (95% CI 28.36 to 45.58 and 26.67 to 83.87 for self-inflicted injuries and for events of undetermined intent, respectively; overall psuicide (RR 3.08; 95% CI 2.26 to 4.19). These effects were solid and not substantially altered after adjustment for family demographic and socioeconomic circumstances. A strong association exists between previous hospitalisation for injury of any intent and youth suicide. The association is robust and unaltered by family socioeconomic circumstances.

  16. Looking Is Not Seeing and Listening Is Not Hearing: A Replication Study With Accelerated BSN Students.

    Science.gov (United States)

    Honan, Linda; Shealy, Sarah; Fennie, Kristopher; Duffy, Thomas C; Friedlaender, Linda; Del Vecchio, Megan

    2016-01-01

    Development of perceptual aptitude is a critical yet complex skill that requires the effective organization and interpretation of data using visual and auditory clinical observation. Educators face challenges in creating pedagogy that consistently demonstrates reliability and validity in fostering clinical skills. We have dependably used the arts as a means to improve students' auditory and visual skills, and this article will describe replication of our work with accelerated nursing students in a bachelor's program in their last semester of nursing school (n=23). Our results reveal that auscultative and observational abilities of soon-to-be registered nurses are in need of improvement. The use of art in a museum improves observational and assessment abilities, and music training increases auscultative interpretive skills significantly. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Previous Fractures at Multiple Sites Increase the Risk for Subsequent Fractures: The Global Longitudinal Study of Osteoporosis in Women

    Science.gov (United States)

    Gehlbach, Stephen; Saag, Kenneth G.; Adachi, Jonathan D.; Hooven, Fred H.; Flahive, Julie; Boonen, Steven; Chapurlat, Roland D.; Compston, Juliet E.; Cooper, Cyrus; Díez-Perez, Adolfo; Greenspan, Susan L.; LaCroix, Andrea Z.; Netelenbos, J. Coen; Pfeilschifter, Johannes; Rossini, Maurizio; Roux, Christian; Sambrook, Philip N.; Silverman, Stuart; Siris, Ethel S.; Watts, Nelson B.; Lindsay, Robert

    2016-01-01

    Previous fractures of the hip, spine, or wrist are well-recognized predictors of future fracture, but the role of other fracture sites is less clear. We sought to assess the relationship between prior fracture at 10 skeletal locations and incident fracture. The Global Longitudinal Study of Osteoporosis in Women (GLOW) is an observational cohort study being conducted in 17 physician practices in 10 countries. Women ≥ 55 years answered questionnaires at baseline and at 1 and/or 2 years (fractures in previous year). Of 60,393 women enrolled, follow-up data were available for 51,762. Of these, 17.6%, 4.0%, and 1.6% had suffered 1, 2, or ≥3 fractures since age 45. During the first 2 years of follow-up, 3149 women suffered 3683 incident fractures. Compared with women with no prior fractures, women with 1, 2, or ≥ 3 prior fractures were 1.8-, 3.0-, and 4.8-fold more likely to have any incident fracture; those with ≥3 prior fractures were 9.1-fold more likely to sustain a new vertebral fracture. Nine of 10 prior fracture locations were associated with an incident fracture. The strongest predictors of incident spine and hip fractures were prior spine fracture (hazard ratio 7.3) and hip (hazard ratio 3.5). Prior rib fractures were associated with a 2.3-fold risk of subsequent vertebral fracture, previous upper leg fracture predicted a 2.2-fold increased risk of hip fracture; women with a history of ankle fracture were at 1.8-fold risk of future fracture of a weight-bearing bone. Our findings suggest that a broad range of prior fracture sites are associated with an increased risk of incident fractures, with important implications for clinical assessments and risk model development. PMID:22113888

  18. Previous experiences and emotional baggage as barriers to lifestyle change - a qualitative study of Norwegian Healthy Life Centre participants.

    Science.gov (United States)

    Følling, Ingrid S; Solbjør, Marit; Helvik, Anne-S

    2015-06-23

    Changing lifestyle is challenging and difficult. The Norwegian Directorate of Health recommends that all municipalities establish Healthy Life Centres targeted to people with lifestyle issues. Little is known about the background, experiences and reflections of participants. More information is needed about participants to shape effective lifestyle interventions with lasting effect. This study explores how participants in a lifestyle intervention programme describe previous life experiences in relation to changing lifestyle. Semi-structured qualitative in-depth interviews were performed with 23 participants (16 women and 7 men) aged 18 - 70 years. The data were analysed using systematic text condensation searching for issues describing participants' responses, and looking for the essence, aiming to share the basis of life-world experiences as valid knowledge. Participants identified two main themes: being stuck in old habits, and being burdened with emotional baggage from their previous negative experiences. Participants expressed a wish to change their lifestyles, but were unable to act in accordance with the health knowledge they possessed. Previous experiences with lifestyle change kept them from initiating attempts without professional assistance. Participants also described being burdened by an emotional baggage with problems from childhood and/or with family, work and social life issues. Respondents said that they felt that emotional baggage was an important explanation for why they were stuck in old habits and that conversely, being stuck in old habits added load to their already emotional baggage and made it heavier. Behavioural change can be hard to perform as psychological distress from life baggage can influence the ability to change. The study participants' experience of being stuck in old habits and having substantial emotional baggage raises questions as to whether or not Healthy Life Centres are able to help participants who need to make a lifestyle

  19. Everolimus for Previously Treated Advanced Gastric Cancer: Results of the Randomized, Double-Blind, Phase III GRANITE-1 Study

    Science.gov (United States)

    Ohtsu, Atsushi; Ajani, Jaffer A.; Bai, Yu-Xian; Bang, Yung-Jue; Chung, Hyun-Cheol; Pan, Hong-Ming; Sahmoud, Tarek; Shen, Lin; Yeh, Kun-Huei; Chin, Keisho; Muro, Kei; Kim, Yeul Hong; Ferry, David; Tebbutt, Niall C.; Al-Batran, Salah-Eddin; Smith, Heind; Costantini, Chiara; Rizvi, Syed; Lebwohl, David; Van Cutsem, Eric

    2013-01-01

    Purpose The oral mammalian target of rapamycin inhibitor everolimus demonstrated promising efficacy in a phase II study of pretreated advanced gastric cancer. This international, double-blind, phase III study compared everolimus efficacy and safety with that of best supportive care (BSC) in previously treated advanced gastric cancer. Patients and Methods Patients with advanced gastric cancer that progressed after one or two lines of systemic chemotherapy were randomly assigned to everolimus 10 mg/d (assignment schedule: 2:1) or matching placebo, both given with BSC. Randomization was stratified by previous chemotherapy lines (one v two) and region (Asia v rest of the world [ROW]). Treatment continued until disease progression or intolerable toxicity. Primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), overall response rate, and safety. Results Six hundred fifty-six patients (median age, 62.0 years; 73.6% male) were enrolled. Median OS was 5.4 months with everolimus and 4.3 months with placebo (hazard ratio, 0.90; 95% CI, 0.75 to 1.08; P = .124). Median PFS was 1.7 months and 1.4 months in the everolimus and placebo arms, respectively (hazard ratio, 0.66; 95% CI, 0.56 to 0.78). Common grade 3/4 adverse events included anemia, decreased appetite, and fatigue. The safety profile was similar in patients enrolled in Asia versus ROW. Conclusion Compared with BSC, everolimus did not significantly improve overall survival for advanced gastric cancer that progressed after one or two lines of previous systemic chemotherapy. The safety profile observed for everolimus was consistent with that observed for everolimus in other cancers. PMID:24043745

  20. How many bootstrap replicates are necessary?

    Science.gov (United States)

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

    2010-03-01

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

  1. 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…

  2. Doxorubicin and ifosfamide combination chemotherapy in previously treated acute leukemia in adults: a Southwest Oncology Group pilot study.

    Science.gov (United States)

    Ryan, D H; Bickers, J N; Vial, R H; Hussein, K; Bottomley, R; Hewlett, J S; Wilson, H E; Stuckey, W J

    1980-01-01

    The Southwest Oncology Group did a limited institutional pilot study of the combination of doxorubicin and ifosfamide in the treatment of previously treated adult patients with acute leukemia. Thirty-four patients received one or two courses of the combination. All patients had received prior chemotherapy and 32 had received prior anthracycline chemotherapy. Three patients died before their responses could be fully evaluated. Fourteen patients achieved complete remission (41%) and one patient achieved partial remission. The complete remission rate was 27% for patients with acute myeloblastic leukemia (myelomonoblastic leukemia, monoblastic leukemia, and erythroleukemia) and 89% for patients with acute lymphocytic and undifferentiated leukemia (ALL). Toxic effects included severe hematologic reactions in 33 of 34 patients, hematuria in six patients, altered sensorium in one patient, and congestive heart failure in one patient. The safety of the combination was established and toxic side effects of this therapy were tolerable. The 89% complete remission rate for previously treated patients with ALL suggests that the combination of doxorubicin and ifosfamide may be particularly effective in ALL.

  3. The Impact of Teacher Study Groups in Vocabulary on Teaching Practice, Teacher Knowledge, and Student Vocabulary Knowledge: A Large-Scale Replication Study

    Science.gov (United States)

    Jayanthi, Madhavi; Dimino, Joseph; Gersten, Russell; Taylor, Mary Jo; Haymond, Kelly; Smolkowski, Keith; Newman-Gonchar, Rebecca

    2018-01-01

    The purpose of this replication study was to examine the impact of the Teacher Study Group (TSG) professional development in vocabulary on first-grade teachers' knowledge of vocabulary instruction and observed teaching practice, and on students' vocabulary knowledge. Sixty-two schools from 16 districts in four states were randomly assigned to…

  4. McCoy cell line as a possible model containing CD4+ receptors for the study of HIV-1 replication

    Directory of Open Access Journals (Sweden)

    Nogueira Yeda L.

    2003-01-01

    Full Text Available Several studies have recently shown the use of recombinant rabies virus as potential vector-viral vaccine for HIV-1. The sequence homology between gp 120 and rabies virus glycoprotein has been reported. The McCoy cell line has therefore been used to show CD4+ or CD4+ like receptors. Samples of HIV-1 were isolated, when plasma of HIV-1 positive patients was inoculated in the McCoy cell line. The virus infection was then studied during successive virus passages. The proteins released in the extra cellular medium were checked for protein activity, by exposure to SDS Electrophoresis and blotting to nitro-cellulose filter, then reacting with sera of HIV positive and negative patients. Successive passages were performed, and showed viral replication, membrane permeabilization, the syncytium formation, and the cellular lysis (cytopathic effect. Flow cytometry analysis shows clear evidence that CD4+ receptors are present in this cell line, which enhances the likelihood of easy isolation and replication of HIV. The results observed allow the use of this cell line as a possible model for isolating HIV, as well as for carrying out studies of the dynamics of viral infection in several situations, including exposure to drugs in pharmacological studies, and possibly studies and analyses of the immune response in vaccine therapies.

  5. The suitability of XRF analysis for compositional classification of archaeological ceramic fabric: A comparison with a previous NAA study

    International Nuclear Information System (INIS)

    Padilla, R.; Espen, P. van; Torres, P.P. Godo

    2006-01-01

    The main drawbacks of EDXRF techniques, restricting its more frequent use for the specific purpose of compositional analysis of archaeological ceramic fabric, have been the insufficient sensitivity to determine some important elements (like Cr, REE, among others), a somewhat worse precision and the inability to perform standard-less quantitative procedures in the absence of suitable certified reference materials (CRM) for ceramic fabric. This paper presents the advantages of combining two energy dispersive X-ray fluorescence methods for fast and non-destructive analysis of ceramic fabric with increased sensitivity. Selective polarized excitation using secondary targets (EDPXRF) and radioisotope excitation (R-XRF) using a 241 Am source. The analytical performance of the methods was evaluated by analyzing several CRM of sediment type, and the fitness for the purpose of compositional classification was compared with that obtained by using Instrumental Neutron Activation Analysis in a previous study of Cuban aborigine pottery

  6. The suitability of XRF analysis for compositional classification of archaeological ceramic fabric: A comparison with a previous NAA study

    Energy Technology Data Exchange (ETDEWEB)

    Padilla, R. [Centro de Aplicaciones Tecnologicas y Desarrollo Nuclear (CEADEN), Laboratorio de Analisis Quimico, Calle 30 no. 502, Playa, Ciudad Habana (Cuba)]. E-mail: roman.padilla@infomed.sld.cu; Espen, P. van [University of Antwerp (Belgium); Torres, P.P. Godo [Centro de Antropologia, Havana (Cuba)

    2006-02-03

    The main drawbacks of EDXRF techniques, restricting its more frequent use for the specific purpose of compositional analysis of archaeological ceramic fabric, have been the insufficient sensitivity to determine some important elements (like Cr, REE, among others), a somewhat worse precision and the inability to perform standard-less quantitative procedures in the absence of suitable certified reference materials (CRM) for ceramic fabric. This paper presents the advantages of combining two energy dispersive X-ray fluorescence methods for fast and non-destructive analysis of ceramic fabric with increased sensitivity. Selective polarized excitation using secondary targets (EDPXRF) and radioisotope excitation (R-XRF) using a {sup 241}Am source. The analytical performance of the methods was evaluated by analyzing several CRM of sediment type, and the fitness for the purpose of compositional classification was compared with that obtained by using Instrumental Neutron Activation Analysis in a previous study of Cuban aborigine pottery.

  7. Treatment satisfaction with paliperidone extended-release tablets: open-label study in schizophrenia patients dissatisfied with previous antipsychotic medication

    Directory of Open Access Journals (Sweden)

    Yang FD

    2017-04-01

    Full Text Available Fu De Yang,1 Juan Li,1 Yun Long Tan,1 Wei Ye Liang,1 Rongzhen Zhang,1 Ning Wang,1 Wei Feng,1 Shangli Cai,2 Jian Min Zhuo,2 Li Li Zhang2 1Beijing Hui-Long-Guan Hospital, 2Department of Medical Affairs, Xian Janssen Pharmaceutical Ltd, Beijing, People’s Republic of China Objective: The aim of this study was to evaluate the changes in treatment satisfaction after switching to paliperidone extended-release (ER in Chinese schizophrenia patients dissatisfied with their previous antipsychotic treatment.Methods: In this 8-week, open-label, single-arm, multicenter, prospective study, 1,693 patients dissatisfied with previous antipsychotic medication were enrolled and switched to paliperidone ER tablets (3–12 mg/d based on clinical judgment. The primary efficacy end point was change in Medication Satisfaction Questionnaire (MSQ score from baseline to week 8. The secondary end points included percentage of patients with MSQ score ≥4, as well as changes in Clinical Global Improvement-Severity (CGI-S and Personal and Social Performance (PSP scores.Results: MSQ scores increased significantly from baseline (mean [standard deviation {SD}]: 2.48 [0.55] to week 8 (5.47 [0.89], P<0.0001; primary end point, full analysis set. The percentage of patients with MSQ score ≥4 was 95.9% at week 8, indicating that most of the patients were satisfied with their treatment. Significant (P<0.0001 improvements from baseline to week 8 were noted in CGI-S score (2.37 [1.20] and PSP score (25.5 [15.0]. A total of 174 (10.28% patients experienced adverse events (AEs. The most common (>10 patients events were extrapyramidal disorder (n=84, 4.96%, poor quality sleep (n=18, 1.06% and akathisia (n=13, 0.77%. The majority of AEs were mild to moderate in severity. No deaths occurred.Conclusion: Treatment satisfaction improved after switching to paliperidone ER from the previous antipsychotic in Chinese patients with schizophrenia. Keywords: atypical antipsychotics, open label

  8. Replication Improves Sorting-Task Results Analyzed by DISTATIS in a Consumer Study of American Bourbon and Rye Whiskeys.

    Science.gov (United States)

    Lahne, Jacob; Collins, Thomas S; Heymann, Hildegarde

    2016-05-01

    In consumer food-sensory studies, sorting and closely related methods (for example, projective mapping) have often been applied to large product sets which are complex and fatiguing for panelists. Analysis of sorting by Multi-Dimensional Scaling (MDS) is common, but this method discards relevant individual decisions; analysis by DISTATIS, which accounts for individual differences, is gaining acceptance. This research posits that replication can improve DISTATIS analysis by stabilizing consumer sensory maps, which are often extremely unstable. As a case study a fatiguing product set was sorted: 10 American whiskeys-5 bourbons and 5 ryes-were sorted into groups by 21 consumers over 2 replications. These products were chosen because American whiskeys are some of the most important distilled beverages in today's market; in particular, "bourbon" (mashbill more than 50% corn) and "rye" (more than 50% rye) whiskeys are important and assumed to be products with distinct sensory attributes. However, there is almost no scientific information about their sensory properties. Data were analyzed using standard and aggregated DISTATIS and MDS. No significant relationship between mashbill and consumer categorization in whiskeys was found; instead, there was evidence of producer and aging effects. aggregated DISTATIS was found to provide more stable results than without replication, and DISTATIS results provided a number of benefits over MDS, including bootstrapped confidence intervals for product separation. In addition, this is the first published evidence that mashbill does not determine sensory properties of American whiskey: bourbons and ryes, while legally distinct, were not separated by consumers. © 2016 Institute of Food Technologists®

  9. Value and reliability of findings from previous epidemiologic studies in the assessment of radiation-related cancer risks. Pt. 3

    International Nuclear Information System (INIS)

    Frasch, G.; Martignoni, K.

    1990-01-01

    The theories put forward here are predominantly based on pooled data from previous studies in a number of cohorts made up by mostly non-average individuals. These studies were carried out by various researchers and differed in procedures and aims. Factors of major importance to the validity and reliability of the conclusions drawn from this study are pointed out. In one chapter some light is thrown on factors known to bear a relation to the incidence of radiation-induced cancer of the breast, even though at present this can only very vaguely be described on a quantitative basis. These factors include fractionated dose regimens, pregnancies and parturitions, menarche, menopause, synergisms as well as secondary cancer of the breast. The available body of evidence suggests that exposure of each of 1 million women to a dose of 10 mGy (rad) can be linked with approx. 3 additional cases of mammary cancer reported on an average per year after the latency period. The fact that there is some statistical scatter around this value is chiefly attributable to age-related causes at the beginning of exposure. Differences in ethnic and cultural characteristics between the populations investigated appeared to be less important here. (orig./MG) [de

  10. Barriers to postpartum screening for type 2 diabetes: a qualitative study of women with previous gestational diabetes.

    Science.gov (United States)

    Rafii, Forough; Rahimparvar, Seyedeh Fatemeh Vasegh; Mehrdad, Neda; Keramat, Afsaneh

    2017-01-01

    Risk of developing type 2 diabetes is increased in women with previous gestational diabetes mellitus (GDM). Postpartum glycemic screening is recommended in women with recent GDM. But this screening rate is low and the reasons are unclear. The aim of this study was to explore the experiences of Iranian women with recent GDM on barriers of postpartum screening for diabetes. This qualitative study was conducted in Tehran, Iran in 2016. Semi-structured interview was used for data collection. 22 women with recent GDM were interviewed. These women gave birth in Tehran hospitals at a minimum of 6 months before interview. The missed screening defined as not attending to laboratory for Fasting Blood Sugar and/or Oral Glucose Tolerance Test, 6 week to 6 month after their child birthing. The data was analyzed by content analysis method. Themes and sub-themes that illustrated the barriers to postpartum diabetes screening were: inadequate education (about developing diabetes in the future, implementation of the screening, and glucometer validity in diagnosis of diabetes), perceiving the screening as difficult (feeling comfortable with the glucometer, poor laboratory conditions, issues related to the baby/babies, and financial problems), improper attitudes toward the screening (unwilling to get diagnosed, not giving priority to oneself, having false beliefs) and procrastination (gap to intention and action, self-deception and self-regulation failure). Women with recent GDM reported several barriers for postpartum diabetes screening. This study help to develop the evidence-based interventions for improving this screening rate.

  11. A Flexible-Dose Study of Paliperidone ER in Patients With Nonacute Schizophrenia Previously Treated Unsuccessfully With Oral Olanzapine.

    Science.gov (United States)

    Kotler, Moshe; Dilbaz, Nesrin; Rosa, Fernanda; Paterakis, Periklis; Milanova, Vihra; Smulevich, Anatoly B; Lahaye, Marjolein; Schreiner, Andreas

    2016-01-01

    The goal of this study was to explore the tolerability, safety, and treatment response of switching from oral olanzapine to paliperidone extended release (ER). Adult patients with nonacute schizophrenia who had been treated unsuccessfully with oral olanzapine were switched to flexible doses of paliperidone ER (3 to 12 mg/d). The primary efficacy outcome was a ≥ 20% improvement in Positive and Negative Syndrome Scale (PANSS) total scores from baseline to endpoint for patients who switched medications because of lack of efficacy with olanzapine and noninferiority versus previous olanzapine treatment (mean endpoint change in PANSS total scores vs. baseline of ≤ 5 points) for patients who switched for reasons other than lack of efficacy. Safety and tolerability were assessed by monitoring adverse events, extrapyramidal symptoms, and weight change. Of 396 patients, 65.2% were men, mean age was 40.0 ± 12.0 years, and 75.5% had paranoid schizophrenia. Among the patients whose main reason for switching was lack of efficacy, an improvement in the PANSS total score of ≥ 20% occurred in 57.4% of patients. Noninferiority was confirmed for each subgroup of patients whose main reason for switching was something other than lack of efficacy. Paliperidone ER was generally well tolerated. Extrapyramidal symptoms as measured by total Extrapyramidal Symptom Rating Scale scores showed statistically significant and clinically relevant improvements at endpoint, the average weight decreased by 0.8 ± 5.2 kg at endpoint, and a clinically relevant weight gain of ≥ 7% occurred in 8.0% of patients. Paliperidone ER flexibly-dosed over 6 months was well tolerated and associated with a meaningful clinical response in patients with nonacute schizophrenia who had previously been unsuccessfully treated with oral olanzapine.

  12. Grey Matter Abnormalities in Social Anxiety Disorder: Primary, Replication, and Specificity Studies

    Science.gov (United States)

    Talati, Ardesheer; Pantazatos, Spiro P.; Schneier, Franklin R.; Weissman, Myrna M; Hirsch, Joy

    2012-01-01

    Background Despite increasing evidence that neuroanatomical abnormalities underlie pathological anxiety, social anxiety disorder (SAD), although among the most common of anxiety disorders, has received little attention. Using Magnetic Resonance Imaging, we (1) examined grey matter (GM) differences between generalized SAD and healthy control groups; (2) retested the findings in an independent clinical sample; and (3) tested for specificity by contrasting the SAD group to a separate group of panic disorder (PD) subjects. Methods The primary SAD group (N=16) was required to meet DSM-IV criteria for SAD, with onset by age 30; controls (N=20) had no lifetime history of anxiety. The replication sample included 17 generalized SAD and 17 control subjects. The PD comparison group (N=16) was required to have no lifetime SAD. Images were acquired on a 1.5Tesla GE Signa MRI scanner using a 3D T1-weighted spoiled gradient recalled pulse sequence. Morphological differences were determined using voxel based morphometry, in SPM8. Results After adjusting for age, gender, and total intracranial volume, SAD (as compared to control) subjects had greater GM in the left parahippocampal and middle occipital, and bilateral supramarginal and angular cortices, and left cerebellum; and lower GM in bilateral temporal poles and left lateral orbitofrontal cortex. Cerebellar, parahippocampal, and temporal pole differences were observed in both samples, survived whole brain corrections, and were not observed in the PD group, pointing to relative specificity to SAD. Conclusions These findings parallel the functional literature on SAD, and suggest structural abnormalities underlying the functional disturbances. PMID:22748614

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

    Science.gov (United States)

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

    2007-12-19

    In budding yeast, the replication checkpoint slows progress through S phase by inhibiting replication origin firing. In mammals, the replication checkpoint inhibits both origin firing and replication fork movement. To find out which strategy is employed in the fission yeast, Schizosaccharomyces pombe, we used microarrays to investigate the use of origins by wild-type and checkpoint-mutant strains in the presence of hydroxyurea (HU), which limits the pool of deoxyribonucleoside triphosphates (dNTPs) and activates the replication checkpoint. The checkpoint-mutant cells carried deletions either of rad3 (which encodes the fission yeast homologue of ATR) or cds1 (which encodes the fission yeast homologue of Chk2). Our microarray results proved to be largely consistent with those independently obtained and recently published by three other laboratories. However, we were able to reconcile differences between the previous studies regarding the extent to which fission yeast replication origins are affected by the replication checkpoint. We found (consistent with the three previous studies after appropriate interpretation) that, in surprising contrast to budding yeast, most fission yeast origins, including both early- and late-firing origins, are not significantly affected by checkpoint mutations during replication in the presence of HU. A few origins (approximately 3%) behaved like those in budding yeast: they replicated earlier in the checkpoint mutants than in wild type. These were located primarily in the heterochromatic subtelomeric regions of chromosomes 1 and 2. Indeed, the subtelomeric regions defined by the strongest checkpoint restraint correspond precisely to previously mapped subtelomeric heterochromatin. This observation implies that subtelomeric heterochromatin in fission yeast differs from heterochromatin at centromeres, in the mating type region, and in ribosomal DNA, since these regions replicated at least as efficiently in wild-type cells as in checkpoint

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

    Science.gov (United States)

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

    2007-01-01

    Background In budding yeast, the replication checkpoint slows progress through S phase by inhibiting replication origin firing. In mammals, the replication checkpoint inhibits both origin firing and replication fork movement. To find out which strategy is employed in the fission yeast, Schizosaccharomyces pombe, we used microarrays to investigate the use of origins by wild-type and checkpoint-mutant strains in the presence of hydroxyurea (HU), which limits the pool of deoxyribonucleoside triphosphates (dNTPs) and activates the replication checkpoint. The checkpoint-mutant cells carried deletions either of rad3 (which encodes the fission yeast homologue of ATR) or cds1 (which encodes the fission yeast homologue of Chk2). Results Our microarray results proved to be largely consistent with those independently obtained and recently published by three other laboratories. However, we were able to reconcile differences between the previous studies regarding the extent to which fission yeast replication origins are affected by the replication checkpoint. We found (consistent with the three previous studies after appropriate interpretation) that, in surprising contrast to budding yeast, most fission yeast origins, including both early- and late-firing origins, are not significantly affected by checkpoint mutations during replication in the presence of HU. A few origins (~3%) behaved like those in budding yeast: they replicated earlier in the checkpoint mutants than in wild type. These were located primarily in the heterochromatic subtelomeric regions of chromosomes 1 and 2. Indeed, the subtelomeric regions defined by the strongest checkpoint restraint correspond precisely to previously mapped subtelomeric heterochromatin. This observation implies that subtelomeric heterochromatin in fission yeast differs from heterochromatin at centromeres, in the mating type region, and in ribosomal DNA, since these regions replicated at least as efficiently in wild-type cells as in

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

    Directory of Open Access Journals (Sweden)

    Scott Donna

    2007-12-01

    Full Text Available Abstract Background In budding yeast, the replication checkpoint slows progress through S phase by inhibiting replication origin firing. In mammals, the replication checkpoint inhibits both origin firing and replication fork movement. To find out which strategy is employed in the fission yeast, Schizosaccharomyces pombe, we used microarrays to investigate the use of origins by wild-type and checkpoint-mutant strains in the presence of hydroxyurea (HU, which limits the pool of deoxyribonucleoside triphosphates (dNTPs and activates the replication checkpoint. The checkpoint-mutant cells carried deletions either of rad3 (which encodes the fission yeast homologue of ATR or cds1 (which encodes the fission yeast homologue of Chk2. Results Our microarray results proved to be largely consistent with those independently obtained and recently published by three other laboratories. However, we were able to reconcile differences between the previous studies regarding the extent to which fission yeast replication origins are affected by the replication checkpoint. We found (consistent with the three previous studies after appropriate interpretation that, in surprising contrast to budding yeast, most fission yeast origins, including both early- and late-firing origins, are not significantly affected by checkpoint mutations during replication in the presence of HU. A few origins (~3% behaved like those in budding yeast: they replicated earlier in the checkpoint mutants than in wild type. These were located primarily in the heterochromatic subtelomeric regions of chromosomes 1 and 2. Indeed, the subtelomeric regions defined by the strongest checkpoint restraint correspond precisely to previously mapped subtelomeric heterochromatin. This observation implies that subtelomeric heterochromatin in fission yeast differs from heterochromatin at centromeres, in the mating type region, and in ribosomal DNA, since these regions replicated at least as efficiently in wild

  16. Reproducibility discrepancies following reanalysis of raw data for a previously published study on diisononyl phthalate (DINP in rats

    Directory of Open Access Journals (Sweden)

    Min Chen

    2017-08-01

    Full Text Available A 2011 publication by Boberg et al. entitled “Reproductive and behavioral effects of diisononyl phthalate (DINP in perinatally exposed rats” [1] reported statistically significant changes in sperm parameters, testicular histopathology, anogenital distance and retained nipples in developing males. Using the statistical methods as reported by Boberg et al. (2011 [1], we reanalyzed the publically available raw data ([dataset] US EPA (United States Environmental Protection Agency, 2016 [2]. The output of our reanalysis and the discordances with the data as published in Boberg et al. (2011 [1] are highlighted herein. Further discussion of the basis for the replication discordances and the insufficiency of the Boberg et al. (2011 [1] response to address them can be found in a companion letter of correspondence (doi: 10.1016/j.reprotox.2017.03.013.; (Morfeld et al., 2011 [3].

  17. In vivo study on the replicative model validity of sister chromatid exchanges production

    International Nuclear Information System (INIS)

    Cruz V, V.L.

    1996-01-01

    The sister chromatid exchanges (SCE) frequency determination has been used as index of damage to DNA, however the biological meaning of this event is still ignored. Different models in order to explain the mechanism of their formation have been proposed and they could be contained in two categories: a) those that consider that the SCE is produced by means of discreet lesions to the DNA and that they occur in the place of the lesion, and b) those that propose that the SCE is caused by a group of lesions and that therefore the place in which they occur could not be associated with a lesion in particular. The model of Painter (1980) belongs to this last group. It suggests that the region of the DNA where the clusters are united, is the only place in which the exchange of double chain could happen during the synthesis of the DNA and makes the prediction that since the x rays retard the beginning of the duplication, the pretreatment with ionizing radiation would reduce the frequency of SCE induced by agents capable to block the lengthening of the chain of DNA, that are the most efficient SCE inducers. The objective of the present work was to establish the validity of this replicative model for the SCE formation, based in its prediction. The effect of the unilateral preexposition of mouse to gamma radiation was determined on the SCE induction by Mitomycin C (MMC), in cells of the femoral bone marrow In vivo. This strategy allows to determine the effect of the pretreatment in the same organism, minimizing the variability of the response between individuals. There was not a significant variability between the frequencies of SCE, basal and induced by gamma radiation or MMC in the same organism. The animals that received the gamma radiation pretreatment, showed a reduction of approximately the 30 % in the frequency of SCE, assuming an additive effect of the radiation with the MMC. These results coincide with the prediction of the model of Painter, however it is not

  18. USP7/HAUSP: A SUMO deubiquitinase at the heart of DNA replication.

    Science.gov (United States)

    Smits, Veronique A J; Freire, Raimundo

    2016-09-01

    DNA replication is both highly conserved and controlled. Problematic DNA replication can lead to genomic instability and therefore carcinogenesis. Numerous mechanisms work together to achieve this tight control and increasing evidence suggests that post-translational modifications (phosphorylation, ubiquitination, SUMOylation) of DNA replication proteins play a pivotal role in this process. Here we discuss such modifications in the light of a recent article that describes a novel role for the deubiquitinase (DUB) USP7/HAUSP in the control of DNA replication. USP7 achieves this function by an unusual and novel mechanism, namely deubiquitination of SUMOylated proteins at the replication fork, making USP7 also a SUMO DUB (SDUB). This work extends previous observations of increased levels of SUMO and low levels of ubiquitin at the on-going replication fork. Here, we discuss this novel study, its contribution to the DNA replication and genomic stability field and what questions arise from this work. © 2016 WILEY Periodicals, Inc.

  19. Database Replication Prototype

    OpenAIRE

    Vandewall, R.

    2000-01-01

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

  20. Pilot Study of an Individualised Early Postpartum Intervention to Increase Physical Activity in Women with Previous Gestational Diabetes

    Directory of Open Access Journals (Sweden)

    Harold David McIntyre

    2012-01-01

    Full Text Available Optimal strategies to prevent progression towards overt diabetes in women with recent gestational diabetes remain ill defined. We report a pilot study of a convenient, home based exercise program with telephone support, suited to the early post-partum period. Twenty eight women with recent gestational diabetes were enrolled at six weeks post-partum into a 12 week randomised controlled trial of Usual Care (n=13 versus Supported Care (individualised exercise program with regular telephone support; n=15. Baseline characteristics (Mean ± SD were: Age  33±4  years; Weight 80 ± 20 kg and Body Mass Index (BMI 30.0±9.7 kg/m2. The primary outcome, planned physical activity {Median (Range}, increased by 60 (0–540 mins/week in the SC group versus 0 (0–580 mins/week in the UC group (P=0.234. Walking was the predominant physical activity. Body weight, BMI, waist circumference, % body fat, fasting glucose and insulin did not change significantly over time in either group. This intervention designed to increase physical activity in post-partum women with previous gestational diabetes proved feasible. However, no measurable improvement in metabolic or biometric parameters was observed over a three month period.

  1. Patterns and Determinants of Treatment Seeking among Previously Untreated Psychotic Patients in Aceh Province, Indonesia: A Qualitative Study

    Directory of Open Access Journals (Sweden)

    Marthoenis Marthoenis

    2016-01-01

    Full Text Available Immediate treatment of first-episode psychosis is essential in order to achieve a positive outcome. However, Indonesian psychiatric patients often delay accessing health services, the reason for which is not yet fully understood. The current study aimed to understand patterns of treatment seeking and to reveal determinants of the delay in accessing psychiatric care among first-time user psychotic patients. Qualitative interviews were conducted with sixteen family members who accompanied the patients to a psychiatric hospital. Many families expressed beliefs that mental illness appertains to village sickness and not hospital sickness; therefore, they usually take the patients to traditional or religious healers before taking them to a health professional. They also identified various factors that potentially delay accessing psychiatric treatment: low literacy and beliefs about the cause of the illness, stigmatisation, the role of extended family, financial problems, and long distance to the psychiatric hospital. On the other hand, the family mentioned various factors related to timely help seeking, including being a well-educated family, living closer to health facilities, previous experience of successful psychotic therapy, and having more positive symptoms of psychosis. The findings call for mental health awareness campaigns in the community.

  2. A replication of the relationship between elderly suicides rates and elderly dependency ratios: a cross-national study.

    Science.gov (United States)

    Shah, Ajit

    2010-01-01

    A positive correlation between elderly dependency ratios and elderly suicide rates has been observed using one-year cross-sectional data on elderly suicide rates. A cross-national study designed to replicate this positive correlation between elderly dependency ratios and elderly suicide rates was undertaken by: (i) using one-year average of five years data on suicide rates; and (ii) using more recent data on both elderly suicide rates and elderly dependency ratios. Data on elderly suicide rates, and the total number of elderly and young people was ascertained from the World Health Organization website. The main findings were of significant positive correlations between elderly dependency ratios and suicide rates in both sexes in both the elderly age-bands (65-74 years and 75+ years). The replication of the positive correlations between elderly dependency ratios and elderly suicide rates by using one-year average of five years data on suicide rates suggests that this relationship is robust and accurate. ‎

  3. A replication of the relationship between elderly suicides rates and elderly dependency ratios: cross-national study

    Science.gov (United States)

    Shah, Ajit

    2010-01-01

    Abstract: Background: A positive correlation between elderly dependency ratios and elderly suicide rates has been observed using one-year cross-sectional data on elderly suicide rates. Methods: A cross-national study designed to replicate this positive correlation between elderly dependency ratios and elderly suicide rates was undertaken by: (i) using one-year average of five years data on suicide rates; and (ii) using more recent data on both elderly suicide rates and elderly dependency ratios. Data on elderly suicide rates, and the total number of elderly and young people was ascertained from the World Health Organization website. Results: The main findings were of significant positive correlations between elderly dependency ratios and suicide rates in both sexes in both the elderly age-bands (65-74 years and 75+ years). Conclusions: The replication of the positive correlations between elderly dependency ratios and elderly suicide rates by using one-year average of five years data on suicide rates suggests that this relationship is robust and accurate. PMID:21483194

  4. A Questionnaire Study on the Attitudes and Previous Experience of Croatian Family Physicians toward their Preparedness for Disaster Management.

    Science.gov (United States)

    Pekez-Pavliško, Tanja; Račić, Maja; Jurišić, Dinka

    2018-04-01

    To explore family physicians' attitudes, previous experience and self-assessed preparedness to respond or to assist in mass casualty incidents in Croatia. The cross-sectional survey was carried out during January 2017. Study participants were recruited through a Facebook group that brings together family physicians from Croatia. They were asked to complete the questionnaire, which was distributed via google.docs. Knowledge and attitudes toward disaster preparedness were evaluated by 18 questions. Analysis of variance, Student t test and Kruskal-Wallis test t were used for statistical analysis. Risk awareness of disasters was high among respondents (M = 4.89, SD=0.450). Only 16.4 of respondents have participated in the management of disaster at the scene. The majority (73.8%) of physicians have not been participating in any educational activity dealing with disaster over the past two years. Family physicians believed they are not well prepared to participate in national (M = 3.02, SD=0.856) and local community emergency response system for disaster (M = 3.16, SD=1.119). Male physicians scored higher preparedness to participate in national emergency response system for disaster ( p =0.012), to carry out accepted triage principles used in the disaster situation ( p =0.003) and recognize differences in health assessments indicating potential exposure to specific agents ( p =0,001) compared to their female colleagues. Croatian primary healthcare system attracts many young physicians, who can be an important part of disaster and emergency management. However, the lack of experience despite a high motivation indicates a need for inclusion of disaster medicine training during undergraduate studies and annual educational activities.

  5. Previous injuries and some training characteristics predict running-related injuries in recreational runners: a prospective cohort study.

    Science.gov (United States)

    Hespanhol Junior, Luiz Carlos; Pena Costa, Leonardo Oliveira; Lopes, Alexandre Dias

    2013-12-01

    What is the incidence of running-related injuries (RRIs) in recreational runners? Which personal and training characteristics predict RRIs in recreational runners? Prospective cohort study. A total of 200 recreational runners answered a fortnightly online survey containing questions about their running routine, races, and presence of RRI. These runners were followed-up for a period of 12 weeks. The primary outcome of this study was running-related injury. The incidence of injuries was calculated taking into account the exposure to running and was expressed by RRI/1000 hours. The association between potential predictive factors and RRIs was estimated using generalised estimating equation models. A total of 84 RRIs were registered in 60 (31%) of the 191 recreational runners who completed all follow-up surveys. Of the injured runners 30% (n=18/60) developed two or more RRIs, with 5/18 (28%) being recurrences. The incidence of RRI was 10 RRI/1000 hours of running exposure. The main type of RRI observed was muscle injuries (30%, n=25/84). The knee was the most commonly affected anatomical region (19%, n=16/84). The variables associated with RRI were: previous RRI (OR 1.88, 95% CI 1.01 to 3.51), duration of training although the effect was very small (OR 1.01, 95% CI 1.00 to 1.02), speed training (OR 1.46, 95% CI 1.02 to 2.10), and interval training (OR 0.61, 95% CI 0.43 to 0.88). Physiotherapists should be aware and advise runners that past RRI and speed training are associated with increased risk of further RRI, while interval training is associated with lower risk, although these associations may not be causative. Copyright © 2013 Australian Physiotherapy Association. Published by Elsevier B.V. All rights reserved.

  6. Radiation-induced cross-link DNA damages: synthesis, measurement and insertion into oligonucleotides for replication and enzymatic repair studies

    International Nuclear Information System (INIS)

    Bellon, Sophie

    2003-01-01

    This research thesis addresses the synthesis, measurement and study of the biological impact of radio-induced DNA double damages. In the first part, the author reports the study of the reactivity and fate of the 5-(2'-desoxy-uridilyl)methyl radical which is one of the intermediates formed by oxidizing photo-sensitisation of thymine. The next part reports results of the formation and measurement of double damages of isolated and cellular DNA, notably in the case of γ irradiation. The third part reports the study of in vitro replication of one of the double damages. The behaviour of different polymerases with respect to the damage is reported. Finally, the modified oligonucleotide has been used as a substrate to highlight possible activities of enzymatic repair for this type of cross-link damages by purified proteins or proteins present within cellular extracts [fr

  7. Replication of bacteriophage lambda DNA

    International Nuclear Information System (INIS)

    Tsurimoto, T.; Matsubara, K.

    1983-01-01

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

  8. Blood donations from previously transfused or pregnant donors: a multicenter study to determine the frequency of alloexposure.

    Science.gov (United States)

    Rios, Jorge A; Schlumpf, Karen S; Kakaiya, Ram M; Triulzi, Darrell J; Roback, John D; Kleinman, Steve H; Murphy, Edward L; Gottschall, Jerome L; Carey, Patricia M

    2011-06-01

    Transfusion-related acute lung injury (TRALI) mitigation strategies include the deferral of female donors from apheresis platelet (PLT) donations and the distribution of plasma for transfusion from male donors only. We studied the implications of these policies in terms of component loss at six blood centers in the United States. We collected data from allogeneic blood donors making whole blood and blood component donations during calendar years 2006 through 2008. We analyzed the distribution of donations in terms of the sex, transfusion and pregnancy histories, and blood type. A TRALI mitigation policy that would not allow plasma from female whole blood donors to be prepared into transfusable plasma components would result in nearly a 50% reduction in the units of whole blood available for plasma manufacturing and would decrease the number of type AB plasma units that could be made from whole blood donations by the same amount. Deferral of all female apheresis PLT donors, all female apheresis PLT donors with histories of prior pregnancies, or all female apheresis PLT donors with histories of prior pregnancies and positive screening test results for antibodies to human leukocyte antigens (HLAs) will result in a loss of 37.1, 22.5, and 5.4% of all apheresis PLT donations, respectively. A TRALI mitigation policy that only defers female apheresis PLT donors with previous pregnancies and HLAs would result in an approximately 5% decrease in the inventory of apheresis PLTs, but would eliminate a large proportion of components that are associated with TRALI. © 2010 American Association of Blood Banks.

  9. PCNL - a comparative study in nonoperated and in previously operated (open nephrolithotomy/pyelolithotomy patients - a single-surgeon experience

    Directory of Open Access Journals (Sweden)

    Rahul Gupta

    2011-12-01

    Full Text Available PURPOSE: Re-procedure in patients with history of open stone surgery is usually challenging due to the alteration in the retroperitoneal anatomy. The aim of this study was to determine the possible impact of open renal surgery on the efficacy and morbidity of subsequent percutaneous nephrolithotomy (PCNL. MATERIALS AND METHODS: From March 2009 until September 2010, 120 patients underwent PCNL. Of these, 20 patients were excluded (tubeless or bilateral simultaneous PCNL. Of the remaining 100, 55 primary patients were categorized as Group 1 and the remaining (previous open nephrolithotomy as Group 2. Standard preoperative evaluation was carried out prior to intervention, Statistical analysis was performed using SPSS v. 11 with the chi-square test, independent samples t-test, and Mann-Whitney U test. A p-value < 0.05 was taken as statistically significant. RESULTS: Both groups were similar in demographic profile and stone burden. Attempts to access the PCS was less in Group 1 compared to Group 2 (1.2 + 1 2 vs 3 + 1.3 respectively and this was statistically significant (p < 0.04. However, the mean operative time between the two groups was not statistically significant (p = 0.44. Blood transfusion rate was comparable in the two groups (p = 0.24. One patient in Group 2 developed hemothorax following a supra-11th puncture. Remaining complications were comparable in both groups. CONCLUSION: Patients with past history of renal stone surgery may need more attempts to access the pelvicaliceal system and have difficulty in tract dilation secondary to retroperitoneal scarring. But overall morbidity and efficacy is same in both groups.

  10. Genes and sequences involved in the replication of cowpea mosaic virus RNAs

    NARCIS (Netherlands)

    Eggen, R.

    1989-01-01

    The aim of the studies described in this thesis was to gain more insight in the complex molecular mechanisms underlying the RNA replication of the cowpea mosaic virus genome. Previously the replication of CPMV RNA has been examined extensively with crude membrane fractions prepared from

  11. Sunburn and sun-protective behaviors among adults with and without previous nonmelanoma skin cancer: a population-based study

    Science.gov (United States)

    Fischer, Alexander H.; Wang, Timothy S.; Yenokyan, Gayane; Kang, Sewon; Chien, Anna L.

    2016-01-01

    Background Individuals with previous nonmelanoma skin cancer (NMSC) are at increased risk for subsequent skin cancer, and should therefore limit UV exposure. Objective To determine whether individuals with previous NMSC engage in better sun protection than those with no skin cancer history. Methods We pooled self-reported data (2005 and 2010 National Health Interview Surveys) from US non-Hispanic white adults (758 with and 34,161 without previous NMSC). We calculated adjusted prevalence odds ratios (aPOR) and 95% confidence intervals (95% CI), taking into account the complex survey design. Results Individuals with previous NMSC versus no history of NMSC had higher rates of frequent use of shade (44.3% versus 27.0%; aPOR=1.41; 1.16–1.71), long sleeves (20.5% versus 7.7%; aPOR=1.55; 1.21–1.98), a wide-brimmed hat (26.1% versus 10.5%; aPOR=1.52; 1.24–1.87), and sunscreen (53.7% versus 33.1%; aPOR=2.11; 95% CI=1.73–2.59), but did not have significantly lower odds of recent sunburn (29.7% versus 40.7%; aPOR=0.95; 0.77–1.17). Among subjects with previous NMSC, recent sunburn was inversely associated with age, sun avoidance, and shade but not sunscreen. Limitations Self-reported cross-sectional data and unavailable information quantifying regular sun exposure. Conclusion Physicians should emphasize sunburn prevention when counseling patients with previous NMSC, especially younger adults, focusing on shade and sun avoidance over sunscreen. PMID:27198078

  12. GWA study data mining and independent replication identify cardiomyopathy-associated 5 (CMYA5) as a risk gene for schizophrenia.

    LENUS (Irish Health Repository)

    Chen, X

    2011-11-01

    We conducted data-mining analyses using the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and molecular genetics of schizophrenia genome-wide association study supported by the genetic association information network (MGS-GAIN) schizophrenia data sets and performed bioinformatic prioritization for all the markers with P-values ≤0.05 in both data sets. In this process, we found that in the CMYA5 gene, there were two non-synonymous markers, rs3828611 and rs10043986, showing nominal significance in both the CATIE and MGS-GAIN samples. In a combined analysis of both the CATIE and MGS-GAIN samples, rs4704591 was identified as the most significant marker in the gene. Linkage disequilibrium analyses indicated that these markers were in low LD (3 828 611-rs10043986, r(2)=0.008; rs10043986-rs4704591, r(2)=0.204). In addition, CMYA5 was reported to be physically interacting with the DTNBP1 gene, a promising candidate for schizophrenia, suggesting that CMYA5 may be involved in the same biological pathway and process. On the basis of this information, we performed replication studies for these three single-nucleotide polymorphisms. The rs3828611 was found to have conflicting results in our Irish samples and was dropped out without further investigation. The other two markers were verified in 23 other independent data sets. In a meta-analysis of all 23 replication samples (family samples, 912 families with 4160 subjects; case-control samples, 11 380 cases and 15 021 controls), we found that both markers are significantly associated with schizophrenia (rs10043986, odds ratio (OR)=1.11, 95% confidence interval (CI)=1.04-1.18, P=8.2 × 10(-4) and rs4704591, OR=1.07, 95% CI=1.03-1.11, P=3.0 × 10(-4)). The results were also significant for the 22 Caucasian replication samples (rs10043986, OR=1.11, 95% CI=1.03-1.17, P=0.0026 and rs4704591, OR=1.07, 95% CI=1.02-1.11, P=0.0015). Furthermore, haplotype conditioned analyses indicated that the association

  13. Laparoscopy After Previous Laparotomy

    Directory of Open Access Journals (Sweden)

    Zulfo Godinjak

    2006-11-01

    Full Text Available Following the abdominal surgery, extensive adhesions often occur and they can cause difficulties during laparoscopic operations. However, previous laparotomy is not considered to be a contraindication for laparoscopy. The aim of this study is to present that an insertion of Veres needle in the region of umbilicus is a safe method for creating a pneumoperitoneum for laparoscopic operations after previous laparotomy. In the last three years, we have performed 144 laparoscopic operations in patients that previously underwent one or two laparotomies. Pathology of digestive system, genital organs, Cesarean Section or abdominal war injuries were the most common causes of previouslaparotomy. During those operations or during entering into abdominal cavity we have not experienced any complications, while in 7 patients we performed conversion to laparotomy following the diagnostic laparoscopy. In all patients an insertion of Veres needle and trocar insertion in the umbilical region was performed, namely a technique of closed laparoscopy. Not even in one patient adhesions in the region of umbilicus were found, and no abdominal organs were injured.

  14. GWA study data mining and independent replication identify cardiomyopathy-associated 5 (CMYA5) as a risk gene for schizophrenia

    DEFF Research Database (Denmark)

    Chen, X; Lee, G; Maher, B S

    2011-01-01

    We conducted data-mining analyses using the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and molecular genetics of schizophrenia genome-wide association study supported by the genetic association information network (MGS-GAIN) schizophrenia data sets and performed...... bioinformatic prioritization for all the markers with P-values ¿0.05 in both data sets. In this process, we found that in the CMYA5 gene, there were two non-synonymous markers, rs3828611 and rs10043986, showing nominal significance in both the CATIE and MGS-GAIN samples. In a combined analysis of both the CATIE...... in our Irish samples and was dropped out without further investigation. The other two markers were verified in 23 other independent data sets. In a meta-analysis of all 23 replication samples (family samples, 912 families with 4160 subjects; case-control samples, 11¿380 cases and 15¿021 controls), we...

  15. A replicated field intervention study evaluating the impact of a highly adjustable chair and office ergonomics training on visual symptoms☆

    Science.gov (United States)

    Menéndez, Cammie Chaumont; Amick, Benjamin C.; Robertson, Michelle; Bazzani, Lianna; DeRango, Kelly; Rooney, Ted; Moore, Anne

    2016-01-01

    Objective Examine the effects of two office ergonomics interventions in reducing visual symptoms at a private sector worksite. Methods A quasi-experimental study design evaluated the effects of a highly adjustable chair with office ergonomics training intervention (CWT group) and the training only (TO group) compared with no intervention (CO group). Data collection occurred 2 and 1 month(s) pre-intervention and 2, 6 and 12 months post-intervention. During each data collection period, a work environment and health questionnaire (covariates) and daily health diary (outcomes) were completed. Multilevel statistical models tested hypotheses. Results Both the training only intervention (p office ergonomics training alone and coupled with a highly adjustable chair reduced visual symptoms. In replicating results from a public sector worksite at a private sector worksite the external validity of the interventions is strengthened, thus broadening its generalizability. PMID:22030069

  16. A replicated field intervention study evaluating the impact of a highly adjustable chair and office ergonomics training on visual symptoms.

    Science.gov (United States)

    Menéndez, Cammie Chaumont; Amick, Benjamin C; Robertson, Michelle; Bazzani, Lianna; DeRango, Kelly; Rooney, Ted; Moore, Anne

    2012-07-01

    Examine the effects of two office ergonomics interventions in reducing visual symptoms at a private sector worksite. A quasi-experimental study design evaluated the effects of a highly adjustable chair with office ergonomics training intervention (CWT group) and the training only (TO group) compared with no intervention (CO group). Data collection occurred 2 and 1 month(s) pre-intervention and 2, 6 and 12 months post-intervention. During each data collection period, a work environment and health questionnaire (covariates) and daily health diary (outcomes) were completed. Multilevel statistical models tested hypotheses. Both the training only intervention (poffice ergonomics training alone and coupled with a highly adjustable chair reduced visual symptoms. In replicating results from a public sector worksite at a private sector worksite the external validity of the interventions is strengthened, thus broadening its generalizability. Published by Elsevier Ltd.

  17. Students classified as LD who received course substitutions for the college foreign language requirement: a replication study.

    Science.gov (United States)

    Sparks, Richard L; Philips, Lois G; Javorsky, James

    2002-01-01

    This replication study examined whether 158 college students classified as learning disabled (LD) who were granted course substitutions for the foreign language (FL) requirement would display significant cognitive and academic achievement differences when grouped by levels of IQ-achievement and achievement-achievement discrepancy and by level of performance on an FL aptitude test (Modern Language Aptitude Test; MLAT), phonological/orthographic processing measures, and in FL courses. The results showed that there were few differences among groups with differing levels of IQ-achievement or achievement-achievement discrepancy (i.e., 1.50 SD) on MLAT and American College Testing (ACT) scores, graduating grade point average (GPA), or college FL GPA. The results also showed that between groups who scored at or above versus below the 15th percentile (i.e., or = 1.0 SD) for classification as LD. These findings suggest that many traditional assumptions about LD and FL learning are likely to be false.

  18. Replicative phenotyping adds value to genotypic resistance testing in heavily pre-treated HIV-infected individuals - the Swiss HIV Cohort Study

    Directory of Open Access Journals (Sweden)

    Martinetti Gladys

    2011-01-01

    Full Text Available Abstract Background Replicative phenotypic HIV resistance testing (rPRT uses recombinant infectious virus to measure viral replication in the presence of antiretroviral drugs. Due to its high sensitivity of detection of viral minorities and its dissecting power for complex viral resistance patterns and mixed virus populations rPRT might help to improve HIV resistance diagnostics, particularly for patients with multiple drug failures. The aim was to investigate whether the addition of rPRT to genotypic resistance testing (GRT compared to GRT alone is beneficial for obtaining a virological response in heavily pre-treated HIV-infected patients. Methods Patients with resistance tests between 2002 and 2006 were followed within the Swiss HIV Cohort Study (SHCS. We assessed patients' virological success after their antiretroviral therapy was switched following resistance testing. Multilevel logistic regression models with SHCS centre as a random effect were used to investigate the association between the type of resistance test and virological response (HIV-1 RNA Results Of 1158 individuals with resistance tests 221 with GRT+rPRT and 937 with GRT were eligible for analysis. Overall virological response rates were 85.1% for GRT+rPRT and 81.4% for GRT. In the subgroup of patients with >2 previous failures, the odds ratio (OR for virological response of GRT+rPRT compared to GRT was 1.45 (95% CI 1.00-2.09. Multivariate analyses indicate a significant improvement with GRT+rPRT compared to GRT alone (OR 1.68, 95% CI 1.31-2.15. Conclusions In heavily pre-treated patients rPRT-based resistance information adds benefit, contributing to a higher rate of treatment success.

  19. A Crystallographic Study of the Role of Sequence Context in Thymine Glycol Bypass by a Replicative DNA Polymerase Serendipitously Sheds Light on the Exonuclease Complex

    Energy Technology Data Exchange (ETDEWEB)

    Aller, Pierre; Duclos, Stéphanie; Wallace, Susan S.; Doublié, Sylvie (Vermont)

    2012-06-27

    Thymine glycol (Tg) is the most common oxidation product of thymine and is known to be a strong block to replicative DNA polymerases. A previously solved structure of the bacteriophage RB69 DNA polymerase (RB69 gp43) in complex with Tg in the sequence context 5'-G-Tg-G shed light on how Tg blocks primer elongation: The protruding methyl group of the oxidized thymine displaces the adjacent 5'-G, which can no longer serve as a template for primer elongation [Aller, P., Rould, M. A., Hogg, M, Wallace, S. S. and Doublie S. (2007). A structural rationale for stalling of a replicative DNA polymerase at the most common oxidative thymine lesion, thymine glycol. Proc. Natl. Acad. Sci. USA, 104, 814-818.]. Several studies showed that in the sequence context 5'-C-Tg-purine, Tg is more likely to be bypassed by Klenow fragment, an A-family DNA polymerase. We set out to investigate the role of sequence context in Tg bypass in a B-family polymerase and to solve the crystal structures of the bacteriophage RB69 DNA polymerase in complex with Tg-containing DNA in the three remaining sequence contexts: 5'-A-Tg-G, 5'-T-Tg-G, and 5'-C-Tg-G. A combination of several factors - including the associated exonuclease activity, the nature of the 3' and 5' bases surrounding Tg, and the cis-trans interconversion of Tg - influences Tg bypass. We also visualized for the first time the structure of a well-ordered exonuclease complex, allowing us to identify and confirm the role of key residues (Phe123, Met256, and Tyr257) in strand separation and in the stabilization of the primer strand in the exonuclease site.

  20. A genome-wide association study of bipolar disorder with comorbid eating disorder replicates the SOX2-OT region.

    Science.gov (United States)

    Liu, Xiaohua; Kelsoe, John R; Greenwood, Tiffany A

    2016-01-01

    Bipolar disorder is a heterogeneous mood disorder associated with several important clinical comorbidities, such as eating disorders. This clinical heterogeneity complicates the identification of genetic variants contributing to bipolar susceptibility. Here we investigate comorbidity of eating disorders as a subphenotype of bipolar disorder to identify genetic variation that is common and unique to both disorders. We performed a genome-wide association analysis contrasting 184 bipolar subjects with eating disorder comorbidity against both 1370 controls and 2006 subjects with bipolar disorder only from the Bipolar Genome Study (BiGS). The most significant genome-wide finding was observed bipolar with comorbid eating disorder vs. controls within SOX2-OT (p=8.9×10(-8) for rs4854912) with a secondary peak in the adjacent FXR1 gene (p=1.2×10(-6) for rs1805576) on chromosome 3q26.33. This region was also the most prominent finding in the case-only analysis (p=3.5×10(-7) and 4.3×10(-6), respectively). Several regions of interest containing genes involved in neurodevelopment and neuroprotection processes were also identified. While our primary finding did not quite reach genome-wide significance, likely due to the relatively limited sample size, these results can be viewed as a replication of a recent study of eating disorders in a large cohort. These findings replicate the prior association of SOX2-OT with eating disorders and broadly support the involvement of neurodevelopmental/neuroprotective mechanisms in the pathophysiology of both disorders. They further suggest that different clinical manifestations of bipolar disorder may reflect differential genetic contributions and argue for the utility of clinical subphenotypes in identifying additional molecular pathways leading to illness. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Prelife catalysts and replicators

    OpenAIRE

    Ohtsuki, Hisashi; Nowak, Martin A.

    2009-01-01

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

  2. Career Services at Colleges and Universities: A 30-Year Replication Study

    Science.gov (United States)

    Vinson, Bonita M.; Reardon, Robert C.; Bertoch, Sara C.

    2014-01-01

    This study examines career planning programs and career services offices at colleges and universities in the United States as viewed by senior student affairs officers (SSAOs). Findings from a 1979 study of career services offices (CSOs) were compared to the current findings. Additionally, new areas of research were examined in order to provide…

  3. Radioimmunotherapy with Y-90-epratuzumab in patients with previously treated B-cell lymphoma. A fractionated dose-escalation study

    International Nuclear Information System (INIS)

    Linden, O.; Cavallin-Stahl, E.; Tennvall, J.; Hindorf, C.; Olsson, T.; Strand, S.E.; Stenberg, L.; Wingardh, K.

    2002-01-01

    Aim: Fractionated RIT may improve outcome by decreasing heterogeneity in absorbed dose and by increasing therapeutic window. The humanised anti-CD22 antibody, Epratuzumab, (Immunomedics, Inc., Morris Plains, NJ) can be given repeatedly with minimal risk of neutralising Ab (HAHA), making fractionated treatment with 90 Y-labelled epratuzumab possible. Materials and Methods: Patients with previously treated B-cell lymphoma received increasing number (2-4) of weekly infusions of 90 Y-epratuzumab. Patients received either 185 MBq/m 2 per infusion (group A), or, if they had a history of high-dose chemotherapy with stem-cell rescue, 92.5 MBq/m 2 per infusion (group B). The first infusion included 150 MBq of 111 Indium for scintigraphic verification of tumour targeting and dosimetry. 1.5 mg/kg epratuzumab was administered with each infusion. The treatment could be repeated once after 3 m. Results: Of 23 patients, 16 in group A and 6 in group B were evaluable for response. The RR in group A was 62% objective response (OR) and 25% CR/CRu. One patient in group B showed OR. OR was seen in aggressive and indolent lymphoma. Response was also long-lasting and event-free survival of patients showing CR/CRu was 14 to 25+ months. In group A all seven patient, receiving three infusions, showed less than grade 3 platelet and neutrophil toxicity, except for two patients suffering grade 3 neutropenia. Of five patients with 4 weekly infusions there were two patients with dose-limiting haematological toxicity (DLT), both recently treated with high dose cytosar before RIT. With criteria used the maximal tolerated dose was three infusions 185 MBq/m 2 . In group B no patient suffered DLT and one patient exhibited OR. Seven patients were retreated after 3 months with minor toxicity, but improvement in OR in two cases. No patient has developed HAHA. CD22 expression on tumour cells, as assessed by flow cytometry, is available in 18 of 22 patients. In group A, seven of eight patients with

  4. Inhibition of DNA replication by ultraviolet light

    International Nuclear Information System (INIS)

    Edenberg, H.J.

    1976-01-01

    DNA replication in ultraviolet-irradiated HeLa cells was studied by two different techniques: measurements of the kinetics of semiconservative DNA synthesis, and DNA fiber autoradiography. In examining the kinetics of semiconservative DNA synthesis, density label was used to avoid measuring the incorporation due to repair replication. The extent of inhibition varied with time. After doses of less than 10 J/m 2 the rate was initially depressed but later showed some recovery. After higher doses, a constant, low rate of synthesis was seen for at least the initial 6 h. An analysis of these data indicated that the inhibition of DNA synthesis could be explained by replication forks halting at pyrimidine dimers. DNA fiber autoradiography was used to further characterize replication after ultraviolet irradiation. The average length of labeled segments in irradiated cells increased in the time immediately after irradiation, and then leveled off. This is the predicted pattern if DNA synthesis in each replicon continued at its previous rate until a lesion is reached, and then halted. The frequency of lesions that block synthesis is approximately the same as the frequency of pyrimidine dimers

  5. On the Prevalence of Multiple-Account Cheating in Massive Open Online Learning : A replicant study

    NARCIS (Netherlands)

    Bao, Yingying; Chen, G.; Hauff, C.; Hu, X.; Barnes, T.; Hershkovitz, A.; Paquette, L.

    2017-01-01

    Massive Open Online Courses (MOOCs) are a promising form of online education. However, the occurrence of academic dishonesty has been threatening MOOC certificates’ effectiveness as a serious tool for recruiters and employers. Recently, a large-scale study on the log traces from more than one

  6. Validation of reported genetic risk factors for periodontitis in a large-scale replication study

    NARCIS (Netherlands)

    Schaefer, A.S.; Bochenek, G.; Manke, T.; Nothnagel, M.; Graetz, C.; Thien, A.; Jockel-Schneider, Y.; Harks, I.; Staufenbiel, I.; Wijmenga, C.; Eberhard, J.; Guzeldemir-Akcakanat, E.; Cine, N.; Folwaczny, M.; Noack, B.; Meyle, J.; Eickholz, P.; Trombelli, L.; Scapoli, C.; Nohutcu, R.; Bruckmann, C.; Doerfer, C.; Jepsen, S.; Loos, B.G.; Schreiber, S.

    2013-01-01

    Aim Many studies investigated the role of genetic variants in periodontitis, but few were established as risk factors. We aimed to validate the associations of recent candidate genes in aggressive periodontitis (AgP). Material and Methods We analysed 23 genes in 600 German AgP patients and 1441

  7. Validation of reported genetic risk factors for periodontitis in a large-scale replication study

    NARCIS (Netherlands)

    Schaefer, Arne S.; Bochenek, Gregor; Manke, Thomas; Nothnagel, Michael; Graetz, Christian; Thien, Anneke; Jockel-Schneider, Yvonne; Harks, Inga; Staufenbiel, Ingmar; Wijmenga, Cisca; Eberhard, Joerg; Guzeldemir-Akcakanat, Esra; Cine, Naci; Folwaczny, Mathias; Noack, Barbara; Meyle, Joerg; Eickholz, Peter; Trombelli, Leonardo; Scapoli, Chiara; Nohutcu, Rahime; Bruckmann, Corinna; Doerfer, Christof; Jepsen, Soren; Loos, Bruno G.; Schreiber, Stefan

    Aim Many studies investigated the role of genetic variants in periodontitis, but few were established as risk factors. We aimed to validate the associations of recent candidate genes in aggressive periodontitis (AgP). Material and Methods We analysed 23 genes in 600 German AgP patients and 1441

  8. Teaching of the International Component in the Introductory Marketing Course: A Replication Study

    Science.gov (United States)

    Zimmer, Robert; Koernig, Stephen K.; Greene, Scott

    2004-01-01

    For almost three decades, the AACSB and business leaders have sought increased emphasis on internationalizing students' perspectives. Recent studies demonstrate mixed results in the extent to which business schools have globalized their curricula. With decreasing student interest in the marketing major, Introductory Marketing emerges as a critical…

  9. Association of SNCA with Parkinson: replication in the Harvard NeuroDiscovery Center Biomarker Study

    Science.gov (United States)

    Ding, Hongliu; Sarokhan, Alison K.; Roderick, Sarah S.; Bakshi, Rachit; Maher, Nancy E.; Ashourian, Paymon; Kan, Caroline G.; Chang, Sunny; Santarlasci, Andrea; Swords, Kyleen E.; Ravina, Bernard M.; Hayes, Michael T.; Sohur, U. Shivraj; Wills, Anne-Marie; Flaherty, Alice W.; Unni, Vivek K.; Hung, Albert Y.; Selkoe, Dennis J.; Schwarzschild, Michael A.; Schlossmacher, Michael G.; Sudarsky, Lewis R.; Growdon, John H.; Ivinson, Adrian J.; Hyman, Bradley T.; Scherzer, Clemens R.

    2011-01-01

    Background Mutations in the α-synuclein gene (SNCA) cause autosomal dominant forms of Parkinson’s disease, but the substantial risk conferred by this locus to the common sporadic disease has only recently emerged from genome-wide association studies. Methods Here we genotyped a prioritized non-coding variant in SNCA intron-4 in 344 patients with Parkinson’s and 275 controls from the longitudinal Harvard NeuroDiscovery Center Biomarker Study. Results The common minor allele of rs2736990 was associated with elevated disease susceptibility (odds ratio = 1.40, P value = 0.0032). Conclusions This result increases confidence in the notion that in many clinically well-characterized patients genetic variation in SNCA contributes to “sporadic” disease. PMID:21953863

  10. Replication of genome wide association studies on hepatocellular carcinoma susceptibility loci in a Chinese population.

    Directory of Open Access Journals (Sweden)

    Kangmei Chen

    Full Text Available BACKGROUND: Genome-wide association studies (GWAS have identified three loci (rs17401966 in KIF1B, rs7574865 in STAT4, rs9275319 in HLA-DQ as being associated with hepatitis B virus-related hepatocellular carcinoma (HBV-related HCC in a Chinese population, two loci (rs2596542 in MICA, rs9275572 located between HLA-DQA and HLA-DQB with hepatitis C virus-related HCC (HCV-related HCC in a Japanese population. In the present study, we sought to determine whether these SNPs are predictive for HBV-related HCC development in other Chinese population as well. METHOD AND FINDINGS: We genotyped 4 SNPs, rs2596542, rs9275572, rs17401966, rs7574865, in 506 HBV-related HCC patients and 772 chronic hepatitis B (CHB patients in Han Chinese by TaqMan methods. Odds ratio(ORand 95% confidence interval (CI were calculated by logistic regression. In our case-control study, significant association between rs9275572 and HCC were observed (P = 0.02, OR = 0.73, 95% CI = 0.56-0.95. In the further haplotype analysis between rs2596542 at 6p21.33 and rs9275572 at 6p21.3, G-A showed a protective effect on HBV-related HCC occurrence (P<0.001, OR = 0.66, 95% CI = 0.52-0.84. CONCLUSION: These findings provided convincing evidence that rs9275572 significantly associated with HBV-related HCC.

  11. Replication of genome wide association studies on hepatocellular carcinoma susceptibility loci in a Chinese population.

    Science.gov (United States)

    Chen, Kangmei; Shi, Weimei; Xin, Zhenhui; Wang, Huifen; Zhu, Xilin; Wu, Xiaopan; Li, Zhuo; Li, Hui; Liu, Ying

    2013-01-01

    Genome-wide association studies (GWAS) have identified three loci (rs17401966 in KIF1B, rs7574865 in STAT4, rs9275319 in HLA-DQ) as being associated with hepatitis B virus-related hepatocellular carcinoma (HBV-related HCC) in a Chinese population, two loci (rs2596542 in MICA, rs9275572 located between HLA-DQA and HLA-DQB) with hepatitis C virus-related HCC (HCV-related HCC) in a Japanese population. In the present study, we sought to determine whether these SNPs are predictive for HBV-related HCC development in other Chinese population as well. We genotyped 4 SNPs, rs2596542, rs9275572, rs17401966, rs7574865, in 506 HBV-related HCC patients and 772 chronic hepatitis B (CHB) patients in Han Chinese by TaqMan methods. Odds ratio(OR)and 95% confidence interval (CI) were calculated by logistic regression. In our case-control study, significant association between rs9275572 and HCC were observed (P = 0.02, OR = 0.73, 95% CI = 0.56-0.95). In the further haplotype analysis between rs2596542 at 6p21.33 and rs9275572 at 6p21.3, G-A showed a protective effect on HBV-related HCC occurrence (P<0.001, OR = 0.66, 95% CI = 0.52-0.84). These findings provided convincing evidence that rs9275572 significantly associated with HBV-related HCC.

  12. The role of IREB2 and transforming growth factor beta-1 genetic variants in COPD: a replication case-control study

    LENUS (Irish Health Repository)

    Chappell, Sally L

    2011-02-14

    Abstract Background Genetic factors are known to contribute to COPD susceptibility and these factors are not fully understood. Conflicting results have been reported for many genetic studies of candidate genes based on their role in the disease. Genome-wide association studies in combination with expression profiling have identified a number of new candidates including IREB2. A meta-analysis has implicated transforming growth factor beta-1 (TGFbeta1) as a contributor to disease susceptibility. Methods We have examined previously reported associations in both genes in a collection of 1017 white COPD patients and 912 non-diseased smoking controls. Genotype information was obtained for seven SNPs in the IREB2 gene, and for four SNPs in the TGFbeta1 gene. Allele and genotype frequencies were compared between COPD cases and controls, and odds ratios were calculated. The analysis was adjusted for age, sex, smoking and centre, including interactions of age, sex and smoking with centre. Results Our data replicate the association of IREB2 SNPs in association with COPD for SNP rs2568494, rs2656069 and rs12593229 with respective adjusted p-values of 0.0018, 0.0039 and 0.0053. No significant associations were identified for TGFbeta1. Conclusions These studies have therefore confirmed that the IREB2 locus is a contributor to COPD susceptibility and suggests a new pathway in COPD pathogenesis invoking iron homeostasis.

  13. Replication study confirms link between TSPAN18 mutation and schizophrenia in Han Chinese.

    Directory of Open Access Journals (Sweden)

    Jianmin Yuan

    Full Text Available Schizophrenia (SCZ is a severe psychiatric disorder associated with many different risk factors, both genetic and environmental. A recent genome-wide association study (GWAS of Han Chinese identified three single-nucleotide polymorphisms (SNPs rs11038167, rs11038172, and rs835784 in the tetraspanins gene TSPAN18 as possible susceptibility loci for schizophrenia. Hoping to validate these findings, we conducted a case-control study of Han Chinese with 1093 schizophrenia cases and 1022 healthy controls. Using the LDR-PCR method to genotype polymorphisms in TSPAN18, we found no significant differences (P>0.05 between patients and controls in either the allele or genotype frequency of the SNPs rs11038167 and rs11038172. We did find, however, that the frequency of the 'A' allele of SNP rs835784 is significantly higher in patients than in controls. We further observed a significant association (OR= 1.197, 95%CI= 1.047-1.369 between risk for SCZ and this 'A' allele. These results confirm the significant association, in Han Chinese populations, of increased SCZ risk and the variant of the TSPAN18 gene containing the 'A' allele of SNP rs835784.

  14. PET studies of phonetic processing of speech: review, replication, and reanalysis

    DEFF Research Database (Denmark)

    Zatorre, R J; Meyer, E; Gjedde, A

    1996-01-01

    Positron emission tomography was used to investigate cerebral blood flow (CBF) changes associated with the processing of speech. In a first experiment, normal right-handed volunteers were scanned under two conditions that required phonetic processing (discrimination of final consonants and phoneme...... monitoring), and one baseline condition of passive listening. Analysis was carried out by paired-image subtraction, with MRI overlay for anatomical localization. Comparison of each phonetic condition with the baseline condition revealed increased CBF in the left frontal lobe, close to the border between...... Broca's area and the motor cortex, and in a left parietal region. A second experiment showed that this area was not activated by a semantic judgement task. Reanalysis of data from an earlier study, in which various baseline conditions were used, confirmed that this region of left frontal cortex...

  15. On the social nature of global self-esteem: a replication study.

    Science.gov (United States)

    Stephan, Yannick; Maiano, Christophe

    2007-10-01

    Few researchers have considered the relationship between global self-esteem and the reflected appraisal of others in one's life, or how reflected appraisals and global self-esteem may change as a result of interpersonal feedback. In this study, the authors collected data from 110 undergraduate students on (a) their global self-esteem and the reflected appraisals of multiple others in their lives and (b) how these dimensions changed in hypothetical interpersonal-feedback situations. Results showed that participants' global self-esteem was related to the reflected appraisals of their fathers, teachers, and friends. The results also indicated that others' reflected appraisals and the individual's global self-esteem fluctuated according to the nature (i.e., positive vs. negative) of the hypothetical interpersonal feedback. Overall, the findings emphasize the social nature and regulation of global self-esteem.

  16. On the Relationship between Brain Laterality and Language Proficiency in L2: A Replication Study

    Directory of Open Access Journals (Sweden)

    Nima Shakouri

    2016-06-01

    Full Text Available The present paper attempted to investigate whether there is any significant relationship between participants' brain laterality and L2 proficiency level. To carry out the experiment, 30 participants administered in the present study. Fifteen of them did not have any English language learning experience and were at the start of language learning, while the rest had attended L2 learning classes for about 2 years in a popular English language center, located in Bandar-e Anzali, Iran. Finally, the researchers concluded that the activity of the right hemisphere went up by the increase in language proficiency among bilinguals. Thereupon, the result of the paper was at variance with Albert and Obler's (1978 early work on hemispheric differentiation, which indicated that bilinguals were less hemispheric dominant than monolinguals.

  17. A Cell Internalizing Antibody Targeting Capsid Protein (p24 Inhibits the Replication of HIV-1 in T Cells Lines and PBMCs: A Proof of Concept Study.

    Directory of Open Access Journals (Sweden)

    Syed A Ali

    Full Text Available There remains a need for newer therapeutic approaches to combat HIV/AIDS. Viral capsid protein p24 plays important roles in HIV pathogenesis. Peptides and small molecule inhibitors targeting p24 have shown to inhibit virus replication in treated cell. High specificity and biological stability of monoclonal antibodies (mAbs make them an attractive contender for in vivo treatments. However, mAbs do not enter into cells, thus are restricted to target surface molecules. This also makes targeting intracellular HIV-1 p24 a challenge. A mAb specific to p24 that can internalize into the HIV-infected cells is hypothesized to inhibit the virus replication. We selected a mAb that has previously shown to inhibit p24 polymerization in an in vitro assay and chemically conjugated it with cell penetrating peptides (CPP to generate cell internalizing anti-p24 mAbs. Out of 8 CPPs tested, κFGF-MTS -conjugated mAbs internalized T cells most efficiently. At nontoxic concentration, the κFGF-MTS-anti-p24-mAbs reduced the HIV-1 replication up to 73 and 49% in T-lymphocyte and PBMCs respectively. Marked inhibition of HIV-1 replication in relevant cells by κFGF-MTS-anti-p24-mAbs represents a viable strategy to target HIV proteins present inside the cells.

  18. Replication Study of Polymorphisms Associated With Brain Arteriovenous Malformation in a Population From South of Brazil.

    Science.gov (United States)

    Franciscatto, André Cerutti; Ludwig, Fernanda S; Matte, Ursula S; Mota, Simone; Stefani, Marco A

    2016-02-24

    The aim of this study was to reproducibly determine if any of the polymorphisms were associated with the susceptibility to brain arteriovenous malformations (BAVM) or the risk of intracranial hemorrhage (ICH) presentation. We recruited 63 BAVM patients and 96 controls. The polymorphisms selected for evaluation were apolipoprotein E (APOE), tumor necrosis factor alpha (TNF 238G>A - rs361525), interleukin 1 beta (IL1B 511C>T - rs16944 and IL1B -31T>C - rs1143627), activin-like kinase 1 (ACVRL1 IVS3-35A>G - rs2071219), endoglin (ENG 207G>A - rs11545664), and interleukin 6 (IL6 174G>C - rs1800795). In the single analysis, we observed statistically significant differences in the allele distributions for IL1B -31T>C (rs1143627) between the BAVM patients and control subjects (P = 0.02). There was a trend toward significance for the association between the IL1B 511C>T (rs16944) allele and BAVM risk (P = 0.07). In further logistic regression analysis, no polymorphism was significantly associated with the risk of BAVM. No polymorphisms were associated with hemorrhage presentation according to both single and multivariable analyses. In our sample from a south Brazil population, we found no association between the risks of BAVM and ICH presentation with any of the selected polymorphisms.

  19. Replication of prostate cancer risk loci in a Japanese case-control association study.

    Science.gov (United States)

    Yamada, Hiroki; Penney, Kathryn L; Takahashi, Hiroyuki; Katoh, Takahiko; Yamano, Yuko; Yamakado, Minoru; Kimura, Takahiro; Kuruma, Hidetoshi; Kamata, Yuko; Egawa, Shin; Freedman, Matthew L

    2009-10-07

    Two prostate cancer genome-wide scans in populations of European ancestry identified several genetic variants that are strongly associated with prostate cancer risk. The effect of these risk variants and their cumulative effect in other populations are unknown. We evaluated the association of 23 risk single-nucleotide polymorphisms (SNPs) with prostate cancer risk and clinical covariates (Gleason score, tumor aggressiveness, and age at diagnosis) in men of Japanese ancestry (311 case subjects and 1035 control subjects) using unconditional logistic regression. We also used logistic regression to test the association between increasing numbers of independently associated risk alleles and the risk of prostate cancer, prostate cancer aggressiveness, and age at diagnosis. All statistical tests were two-sided. Seven of the 23 SNPs (five independent loci) were associated with prostate cancer risk (P values ranged from .0084 to 2.3 x 10(-8) and effect sizes [estimated as odds ratios, ORs] ranged from 1.35 to 1.82). None of the seven SNPs was associated with Gleason score or aggressive disease. rs6983561 and rs4430796 were associated with age at diagnosis (Ps = .0188 and .0339, respectively). Men with six or more risk alleles (27% of case patients and 11% of control subjects) had a higher risk of prostate cancer than men with two or fewer risk alleles (7% of case patients and 20% of control subjects) (OR = 6.22, P = 1.5 x 10(-12)). These results highlight the critical importance of considering ancestry in understanding how risk alleles influence disease and suggest that risk estimates and variants differ across populations. It is important to perform studies in multiple ancestral populations so that the composite genetic architecture of prostate cancer can be rigorously addressed.

  20. General, crystallized and fluid intelligence are not associated with functional global network efficiency: A replication study with the human connectome project 1200 data set.

    Science.gov (United States)

    Kruschwitz, J D; Waller, L; Daedelow, L S; Walter, H; Veer, I M

    2018-05-01

    One hallmark example of a link between global topological network properties of complex functional brain connectivity and cognitive performance is the finding that general intelligence may depend on the efficiency of the brain's intrinsic functional network architecture. However, although this association has been featured prominently over the course of the last decade, the empirical basis for this broad association of general intelligence and global functional network efficiency is quite limited. In the current study, we set out to replicate the previously reported association between general intelligence and global functional network efficiency using the large sample size and high quality data of the Human Connectome Project, and extended the original study by testing for separate association of crystallized and fluid intelligence with global efficiency, characteristic path length, and global clustering coefficient. We were unable to provide evidence for the proposed association between general intelligence and functional brain network efficiency, as was demonstrated by van den Heuvel et al. (2009), or for any other association with the global network measures employed. More specifically, across multiple network definition schemes, ranging from voxel-level networks to networks of only 100 nodes, no robust associations and only very weak non-significant effects with a maximal R 2 of 0.01 could be observed. Notably, the strongest (non-significant) effects were observed in voxel-level networks. We discuss the possibility that the low power of previous studies and publication bias may have led to false positive results fostering the widely accepted notion of general intelligence being associated to functional global network efficiency. Copyright © 2018 Elsevier Inc. All rights reserved.

  1. 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...

  2. Loss of maintenance DNA methylation results in abnormal DNA origin firing during DNA replication.

    Science.gov (United States)

    Haruta, Mayumi; Shimada, Midori; Nishiyama, Atsuya; Johmura, Yoshikazu; Le Tallec, Benoît; Debatisse, Michelle; Nakanishi, Makoto

    2016-01-22

    The mammalian maintenance methyltransferase DNMT1 [DNA (cytosine-5-)-methyltransferase 1] mediates the inheritance of the DNA methylation pattern during replication. Previous studies have shown that depletion of DNMT1 causes a severe growth defect and apoptosis in differentiated cells. However, the detailed mechanisms behind this phenomenon remain poorly understood. Here we show that conditional ablation of Dnmt1 in murine embryonic fibroblasts (MEFs) resulted in an aberrant DNA replication program showing an accumulation of late-S phase replication and causing severely defective growth. Furthermore, we found that the catalytic activity and replication focus targeting sequence of DNMT1 are required for a proper DNA replication program. Taken together, our findings suggest that the maintenance of DNA methylation by DNMT1 plays a critical role in proper regulation of DNA replication in mammalian cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. A case study of IMRT planning (Plan B) subsequent to a previously treated IMRT plan (Plan A)

    International Nuclear Information System (INIS)

    2Department of Radiation Oncology, Fraser Valley Centre, BC Cancer Agency, Surrey, British Columbia (Canada))" data-affiliation=" (Department of Medical Physics and 2Department of Radiation Oncology, Fraser Valley Centre, BC Cancer Agency, Surrey, British Columbia (Canada))" >Cao, F; 2Department of Radiation Oncology, Fraser Valley Centre, BC Cancer Agency, Surrey, British Columbia (Canada))" data-affiliation=" (Department of Medical Physics and 2Department of Radiation Oncology, Fraser Valley Centre, BC Cancer Agency, Surrey, British Columbia (Canada))" >Leong, C; 2Department of Radiation Oncology, Fraser Valley Centre, BC Cancer Agency, Surrey, British Columbia (Canada))" data-affiliation=" (Department of Medical Physics and 2Department of Radiation Oncology, Fraser Valley Centre, BC Cancer Agency, Surrey, British Columbia (Canada))" >Schroeder, J; 2Department of Radiation Oncology, Fraser Valley Centre, BC Cancer Agency, Surrey, British Columbia (Canada))" data-affiliation=" (Department of Medical Physics and 2Department of Radiation Oncology, Fraser Valley Centre, BC Cancer Agency, Surrey, British Columbia (Canada))" >Lee, B

    2014-01-01

    Background and purpose: Treatment of the contralateral neck after previous ipsilateral intensity modulated radiation therapy (IMRT) for head and neck cancer is a challenging problem. We have developed a technique that limits the cumulative dose to the spinal cord and brainstem while maximizing coverage of a planning target volume (PTV) in the contralateral neck. Our case involves a patient with right tonsil carcinoma who was given ipsilateral IMRT with 70Gy in 35 fractions (Plan A). A left neck recurrence was detected 14 months later. The patient underwent a neck dissection followed by postoperative left neck radiation to a dose of 66 Gy in 33 fractions (Plan B). Materials and Methods: The spinal cord-brainstem margin (SCBM) was defined as the spinal cord and brainstem with a 1.0 cm margin. Plan A was recalculated on the postoperative CT scan but the fluence outside of SCBM was deleted. A further modification of Plan A resulted in a base plan that was summed with Plan B to evaluate the cumulative dose received by the spinal cord and brainstem. Plan B alone was used to evaluate for coverage of the contralateral neck PTV. Results: The maximum cumulative doses to the spinal cord with 0.5cm margin and brainstem with 0.5cm margin were 51.96 Gy and 45.60 Gy respectively. For Plan B, 100% of the prescribed dose covered 95% of PTVb1. Conclusion: The use of a modified ipsilateral IMRT plan as a base plan is an effective way to limit the cumulative dose to the spinal cord and brainstem while enabling coverage of a PTV in the contralateral neck.

  4. Evaluation of a rapid dipstick (Crystal VC for the diagnosis of cholera in Zanzibar and a comparison with previous studies.

    Directory of Open Access Journals (Sweden)

    Benedikt Ley

    Full Text Available The gold standard for the diagnosis of cholera is stool culture, but this requires laboratory facilities and takes at least 24 hours. A rapid diagnostic test (RDT that can be used by minimally trained staff at treatment centers could potentially improve the reporting and management of cholera outbreaks.We evaluated the Crystal VC™ RDT under field conditions in Zanzibar in 2009. Patients presenting to treatment centers with watery diarrhea provided a stool sample for rapid diagnostic testing. Results were compared to stool culture performed in a reference laboratory. We assessed the overall performance of the RDT and evaluated whether previous intake of antibiotics, intravenous fluids, location of testing, and skill level of the technician affected the RDT results.We included stool samples from 624 patients. Compared to culture, the overall sensitivity of the RDT was 93.1% (95%CI: 88.7 to 96.2%, specificity was 49.2% (95%CI: 44.3 to 54.1%, the positive predictive value was 47.0% (95%CI: 42.1 to 52.0% and the negative predictive value was 93.6% (95%CI: 89.6 to 96.5%. The overall false positivity rate was 50.8% (213/419; fieldworkers frequently misread very faint test lines as positive.The observed sensitivity of the Crystal VC RDT evaluated was similar compared to earlier versions, while specificity was poorer. The current version of the RDT could potentially be used as a screening tool in the field. Because of the high proportion of false positive results when field workers test stool specimens, positive results will need to be confirmed with stool culture.

  5. Internet delivered transdiagnostic treatment with telephone support for pain patients with emotional comorbidity: a replicated single case study

    Directory of Open Access Journals (Sweden)

    Matilda Wurm

    2017-12-01

    Full Text Available In pain patients, comorbid emotional problems have been linked to negative outcomes, including suboptimal treatment gains. Developing parsimonious and accessible treatment options is therefore important. The overarching aim of this study was to test an internet delivered therapist guided transdiagnostic treatment with telephone support. An adapted version of the Unified Protocol for Transdiagnostic Treatments of Emotional Disorders was used as an intervention for pain patients with residual pain problems and comorbid emotional problems after having received a multimodal pain rehabilitation. The study used a replicated AB single case experimental design (N = 5; 3 females. Outcome measures were depressive and general anxiety symptoms, pain intensity, pain coping problems, and diagnostic status. Feasibility measures (completion and compliance and patient satisfaction were also assessed. Scores on Nonoverlap of All Pairs (NAP indicate a decrease of anxiety for three participants and a decrease of depression for four participants. Decreases were small and did not always reach statistical significance. Also, Tau-U scores could only confirm a reliable trend for one participant. Two out of four patients who were diagnosed with psychiatric disorders before treatment did no longer fulfill diagnostic criteria posttreatment. No improvements could be seen on pain problems. The treatment was feasible and patient satisfaction was high. Hence, while an internet delivered transdiagnostic treatment with telephone support may be a feasible and accepted secondary intervention for pain patients with comorbid emotional problems, the effects are unclear. The gap between high patient satisfaction and small changes in symptomatology should be explored further.

  6. A quick behavioral dichotic word test is prognostic for clinical response to cognitive therapy for depression: A replication study.

    Science.gov (United States)

    Bruder, Gerard E; Haggerty, Agnes; Siegle, Greg J

    2017-02-01

    There are no commonly used clinical indicators of whether an individual will benefit from cognitive therapy (CT) for depression. A prior study found right ear (left hemisphere) advantage for perceiving dichotic words predicted CT response. This study replicates this finding at a different research center in clinical trials that included clinically representative samples and community therapists. Right-handed individuals with unipolar major depressive disorder who subsequently received 12-14 weeks of CT at the University of Pittsburgh were tested on dichotic fused words and complex tones tests. Responders to CT showed twice the mean right ear advantage in dichotic fused words performance than non-responders. Patients with a right ear advantage greater than the mean for healthy controls had an 81% response rate to CT, whereas those with performance lower than the mean for controls had a 46% response rate. Individuals with a right ear advantage, indicative of strong left hemisphere language dominance, may be better at utilizing cognitive processes and left frontotemporal cortical regions critical for success of CT for depression. Findings at two clinical research centers suggest that verbal dichotic listening may be a clinically disseminative brief, inexpensive and easily automated test prognostic for response to CT across diverse clinical settings. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Exploring cultural differences in feedback processes and perceived instructiveness during clerkships: replicating a Dutch study in Indonesia.

    Science.gov (United States)

    Suhoyo, Yoyo; van Hell, Elisabeth A; Prihatiningsih, Titi S; Kuks, Jan B M; Cohen-Schotanus, Janke

    2014-03-01

    Cultural differences between countries may entail differences in feedback processes. By replicating a Dutch study in Indonesia, we analysed whether differences in processes influenced the perceived instructiveness of feedback. Over a two-week period, Indonesian students (n = 215) recorded feedback moments during clerkships, noting who provided the feedback, whether the feedback was based on observations, who initiated the feedback, and its perceived instructiveness. Data were compared with the earlier Dutch study and analysed with χ(2) tests, t-tests and multilevel techniques. Cultural differences were explored using Hofstede's Model, with Indonesia and the Netherlands differing on "power distance" and "individualism." Perceived instructiveness of feedback did not differ significantly between both countries. However, significant differences were found in feedback provider, observation and initiative. Indonesian students perceived feedback as more instructive if provided by specialists and initiated jointly by the supervisor and student (βresidents = -0.201, p culture. Further research is necessary to unravel other possible influences of culture in implementing feedback procedures in different countries.

  8. An ADAM33 polymorphism associates with progression of preschool wheeze into childhood asthma: a prospective case-control study with replication in a birth cohort study.

    Directory of Open Access Journals (Sweden)

    Ester M M Klaassen

    Full Text Available The influence of asthma candidate genes on the development from wheeze to asthma in young children still needs to be defined.To link genetic variants in asthma candidate genes to progression of wheeze to persistent wheeze into childhood asthma.In a prospective study, children with recurrent wheeze from the ADEM (Asthma DEtection and Monitoring study were followed until the age of six. At that age a classification (transient wheeze or asthma was based on symptoms, lung function and medication use. In 198 children the relationship between this classification and 30 polymorphisms in 16 asthma candidate genes was assessed by logistic regression. In case of an association based on a p<0.10, replication analysis was performed in an independent birth cohort study (KOALA study, n = 248 included for the present analysis.In the ADEM study, the minor alleles of ADAM33 rs511898 and rs528557 and the ORMDL3/GSDMB rs7216389 polymorphisms were negatively associated, whereas the minor alleles of IL4 rs2243250 and rs2070874 polymorphisms were positively associated with childhood asthma. When replicated in the KOALA study, ADAM33 rs528557 showed a negative association of the CG/GG-genotype with progression of recurrent wheeze into childhood asthma (0.50 (0.26-0.97 p = 0.04 and no association with preschool wheeze.Polymorphisms in ADAM33, ORMDL3/GSDMB and IL4 were associated with childhood asthma in a group of children with recurrent wheeze. The replication of the negative association of the CG/GG-genotype of rs528557 ADAM33 with childhood asthma in an independent birth cohort study confirms that a compromised ADAM33 gene may be implicated in the progression of wheeze into childhood asthma.

  9. Testing causal models of job characteristics and employee well-being : a replication study using cross-lagged structural equation modelling

    NARCIS (Netherlands)

    Doest, ter L.; Jonge, de J.

    2006-01-01

    This study re-evaluated causal relationships between job characteristics (demands, autonomy, social support) and employee well-being (job satisfaction, emotional exhaustion) in a methodological replication of De Jonge et al.'s (2001) two-wave panel study. The principal difference was the 2-year time

  10. Alzheimer's Disease Sequencing Project discovery and replication criteria for cases and controls: Data from a community-based prospective cohort study with autopsy follow-up.

    Science.gov (United States)

    Crane, Paul K; Foroud, Tatiana; Montine, Thomas J; Larson, Eric B

    2017-12-01

    The Alzheimer's Disease Sequencing Project (ADSP) used different criteria for assigning case and control status from the discovery and replication phases of the project. We considered data from a community-based prospective cohort study with autopsy follow-up where participants could be categorized as case, control, or neither by both definitions and compared the two sets of criteria. We used data from the Adult Changes in Thought (ACT) study including Diagnostic and Statistical Manual-IV criteria for dementia status, McKhann et al. criteria for clinical Alzheimer's disease, and Braak and Consortium to Establish a Registry for AD findings on neurofibrillary tangles and neuritic plaques to categorize the 621 ACT participants of European ancestry who died and came to autopsy. We applied ADSP discovery and replication definitions to identify controls, cases, and people who were neither controls nor cases. There was some agreement between the discovery and replication definitions. Major areas of discrepancy included the finding that only 40% of the discovery sample controls had sufficiently low levels of neurofibrillary tangles and neuritic plaques to be considered controls by the replication criteria and the finding that 16% of the replication phase cases were diagnosed with non-AD dementia during life and thus were excluded as cases for the discovery phase. These findings should inform interpretation of genetic association findings from the ADSP. Differences in genetic association findings between the two phases of the study may reflect these different phenotype definitions from the discovery and replication phase of the ADSP. Copyright © 2017 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  11. Violent offending promotes appetitive aggression rather than posttraumatic stress - a replication study with Burundian ex-combatants

    Directory of Open Access Journals (Sweden)

    Anke eKöbach

    2015-12-01

    Full Text Available Research has identified appetitive aggression, i.e., the perception of committed, violent acts as appealing, exciting and fascinating, as a common phenomenon within populations living in precarious and violent circumstances. Investigating demobilized soldiers in the Democratic Republic of Congo demonstrated that violent offending is associated with appetitive aggression but not necessarily with symptoms of posttraumatic stress. In the present study we sought to replicate these results in an independent and larger sample of demobilized soldiers from Burundi. As with the Congolese ex-combatants, random forest regression revealed that the number of lifetime perpetrated violent acts is the most important predictor of appetitive aggression and the number of lifetime experienced traumatic events is the main predictor for posttraumatic stress. Perpetrated violent acts with salient cues of hunting (pursuing the victim, the sight of blood, etc. were most predictive for perceiving violent cues appealingly after demobilization. Moreover, the association of violent acts and appetitive aggression as well as traumatic events and posttraumatic stress remains strong even years after demobilization. Patterns of traumatic events and perpetrated acts as predictors for posttraumatic stress and appetitive aggression seem to be robust among different samples of ex-combatants who fought in civil wars. Psychotherapeutic interventions that address these complementary facets of combat-related disorders -- namely, posttraumatic stress and appetitive aggression -- are indispensable for a successful reintegration of those who fought in armed conflicts and to achieve a successful transition to peace.

  12. Is Comfort Food Really Good for the Soul? A Replication of Troisi and Gabriel’s (2011 Study 2

    Directory of Open Access Journals (Sweden)

    Lay See eOng

    2015-04-01

    Full Text Available We report the results of three high-powered replications of Troisi and Gabriel’s (2011 idea that writing about comfort food reduces feelings of loneliness amongst securely attached individuals after a belongingness threat. We conducted our studies amongst a large group of participants (Total N = 649 amongst American (MTurk, Dutch (Tilburg University; TiU, and Singaporean (Singapore Management University; SMU samples. Participants first completed an attachment style scale, followed by writing two essays for manipulating a sense of belongingness and salience of comfort food, and then reporting their loneliness levels. We did not confirm the overall effect over all three countries. However, exploratory results provide the preliminary suggestion that 1 the comfort food explanation likely holds amongst the American samples (including Troisi & Gabriel’s, but not amongst the TiU and SMU samples, and potentially that 2 the TiU and SMU participants self-regulate through warmer (vs. colder temperature foods. Both of these should be regarded with great caution as these analyses were exploratory, and because the Ns for the different temperature foods were small. We suspect we have uncovered first cross-cultural differences in self-regulation through food, but further confirmatory work is required to understand the cultural significance of comfort food for self-regulation.

  13. A pilot study on interaction between donkey tetherin and EIAV stains with different virulent and replication characteristics.

    Science.gov (United States)

    Yao, Qiucheng; Ma, Jian; Wang, Xuefeng; Guo, Miaomiao; Li, Yanfei; Wang, Xiaojun

    2017-05-01

    Tetherin (BST-2) is an important host restriction factor that can inhibit the release of a diverse array of enveloped viruses from infected cells. Conversely, to facilitate their release and spread, many viruses have evolved various strategies to overcome the antiviral effect of tetherin in a species-specific manner. During the development of an attenuated equine infectious anemia virus (EIAV) vaccine in our laboratory, we found that serial passage of a field-isolated virulent EIAV strains in horse and donkey as well as the cultivated donkey cells, produces several typical EIAV strains, including EIAV DV , EIAV DLV , and EIAV FDDV , which exhibit distinct virulence and replication features in vivo and in vitro. However, the role of host restriction factors in EIAV evolution during the serial passage is not well understood. This study aimed to evaluate whether these newly generated strains adapt differently to donkey tetherin (do-tetherin) based on their virulence. We found that do-tetherin exerts an inhibition on the release of the viral particles produced by all three strains, albeit with varying intensity: EIAV DV   EIAV DLV  > EIAV FDDV . These results indicate that donkey tetherin is involved in shaping of EIAV evolution during serial passage. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Productively infected murine Kaposi's sarcoma-like tumors define new animal models for studying and targeting KSHV oncogenesis and replication.

    Directory of Open Access Journals (Sweden)

    Brittany M Ashlock

    Full Text Available Kaposi's sarcoma (KS is an AIDS-defining cancer caused by the KS-associated herpesvirus (KSHV. KS tumors are composed of KSHV-infected spindle cells of vascular origin with aberrant neovascularization and erythrocyte extravasation. KSHV genes expressed during both latent and lytic replicative cycles play important roles in viral oncogenesis. Animal models able to recapitulate both viral and host biological characteristics of KS are needed to elucidate oncogenic mechanisms, for developing targeted therapies, and to trace cellular components of KS ontogeny. Herein, we describe two new murine models of Kaposi's sarcoma. We found that murine bone marrow-derived cells, whether established in culture or isolated from fresh murine bone marrow, were infectable with rKSHV.219, formed KS-like tumors in immunocompromised mice and produced mature herpesvirus-like virions in vivo. Further, we show in vivo that the histone deacetylase (HDAC inhibitor suberoylanilide hydroxamic acid (SAHA/Vorinostat enhanced viral lytic reactivation. We propose that these novel models are ideal for studying both viral and host contributions to KSHV-induced oncogenesis as well as for testing virally-targeted antitumor strategies for the treatment of Kaposi's sarcoma. Furthermore, our isolation of bone marrow-derived cell populations containing a cell type that, when infected with KSHV, renders a tumorigenic KS-like spindle cell, should facilitate systematic identification of KS progenitor cells.

  15. Studies in iodine metabolism: 33 year summary, 1948-1979 (as previously submitted) with appendix, 1979-1982

    International Nuclear Information System (INIS)

    Middlesworth, L.V.

    1982-01-01

    The results of research into iodine metabolism from 1948 to 1982 are summarized. Study areas included the monitoring of iodine 131 from fallout in the thyroid glands of cattle and humans, the biological functions and metabolism of thyroid hormones, and methods to reduce the retention of radioiodine in the thyroid

  16. CHRONOVAC VOYAGEUR: A study of the immune response to yellow fever vaccine among infants previously immunized against measles.

    Science.gov (United States)

    Goujon, Catherine; Gougeon, Marie-Lise; Tondeur, Laura; Poirier, Béatrice; Seffer, Valérie; Desprès, Philippe; Consigny, Paul-Henri; Vray, Muriel

    2017-10-27

    For administration of multiple live attenuated vaccines, the Advisory Committee on Immunization Practices recommends either simultaneous immunization or period of at least 28days between vaccines, due to a possible reduction in the immune response to either vaccine. The main objective of this study was to compare the immune response to measles (alone or combined with mumps and rubella) and yellow fever vaccines among infants aged 6-24months living in a yellow fever non-endemic country who had receivedmeasles and yellow fever vaccines before travelling to a yellow fever endemic area. A retrospective, multicenter case-control study was carried out in 7 travel clinics in the Paris area from February 1st 2011 to march 31, 2015. Cases were defined as infants immunized with the yellow fever vaccine and with the measles vaccine, either alone or in combination with mumps and rubella vaccine, with a period of 1-27days between each immunization. For each case, two controls were matched based on sex and age: a first control group (control 1) was defined as infants having received the measles vaccine and the yellow fever vaccine simultaneously; a second control group (control 2) was defined as infants who had a period of more than 27days between receiving the measles vaccine and yellow fever vaccine. The primary endpoint of the study was the percentage of infants with protective immunity against yellow fever, measured by the titer of neutralizing antibodies in a venous blood sample. One hundred and thirty-one infants were included in the study (62 cases, 50 infants in control 1 and 19 infants in control 2). Of these, 127 (96%) were shown to have a protective titer of yellow fever antibodies. All 4 infants without a protective titer of yellow fever antibodies were part of control group 1. The measles vaccine, alone or combined with mumps and rubella vaccines, appears to have no influence on humoral immune response to the yellow fever vaccine when administered between 1 and 27

  17. Structural Study and Evaluation of Previous Restoration Work of Mohammad 'Ali Pasha Mosque at the Citadel in Cairo

    Directory of Open Access Journals (Sweden)

    dr.Yaser Yehya Amin Abdel-Aty

    2011-01-01

    Full Text Available Mohammad 'Ali Pasha Mosque at the Citadel in Cairo is considered one of the main landmarks in Egypt. It majestically stands at a northwestern bend of the Citadel and it is visible from numerous locations in Cairo. It has become the symbol of the Citadel, to the point that its name is given to the whole complex in the colloquial Egyptian parlance. This paper studies analytically the static and dynamic structural behavior of this great mosque using computer numerical modeling techniques, to reach the main reasons for past cracking and failures in its domed-roof and other structural elements, which occurred by the end of 19th Century. A number of 3D-models are analyzed to study the mosque, in both original and after restoration conditions, under static (i.e. dead and live loads and dynamic (i.e. Eigenvector modal analysis, response-spectrum and time-history cases of loading. Besides, structural evaluation of major restoration project, in 1930s, is conducted to determine the current structural safety status of the mosque

  18. Genome-wide association study identifies single nucleotide polymorphism in DYRK1A associated with replication of HIV-1 in monocyte-derived macrophages.

    Directory of Open Access Journals (Sweden)

    Sebastiaan M Bol

    2011-02-01

    Full Text Available HIV-1 infected macrophages play an important role in rendering resting T cells permissive for infection, in spreading HIV-1 to T cells, and in the pathogenesis of AIDS dementia. During highly active anti-retroviral treatment (HAART, macrophages keep producing virus because tissue penetration of antiretrovirals is suboptimal and the efficacy of some is reduced. Thus, to cure HIV-1 infection with antiretrovirals we will also need to efficiently inhibit viral replication in macrophages. The majority of the current drugs block the action of viral enzymes, whereas there is an abundance of yet unidentified host factors that could be targeted. We here present results from a genome-wide association study identifying novel genetic polymorphisms that affect in vitro HIV-1 replication in macrophages.Monocyte-derived macrophages from 393 blood donors were infected with HIV-1 and viral replication was determined using Gag p24 antigen levels. Genomic DNA from individuals with macrophages that had relatively low (n = 96 or high (n = 96 p24 production was used for SNP genotyping with the Illumina 610 Quad beadchip. A total of 494,656 SNPs that passed quality control were tested for association with HIV-1 replication in macrophages, using linear regression. We found a strong association between in vitro HIV-1 replication in monocyte-derived macrophages and SNP rs12483205 in DYRK1A (p = 2.16 × 10(-5. While the association was not genome-wide significant (p<1 × 10(-7, we could replicate this association using monocyte-derived macrophages from an independent group of 31 individuals (p = 0.0034. Combined analysis of the initial and replication cohort increased the strength of the association (p = 4.84 × 10(-6. In addition, we found this SNP to be associated with HIV-1 disease progression in vivo in two independent cohort studies (p = 0.035 and p = 0.0048.These findings suggest that the kinase DYRK1A is involved in the replication of HIV-1, in vitro in macrophages

  19. Genome-Wide Association Study Identifies Single Nucleotide Polymorphism in DYRK1A Associated with Replication of HIV-1 in Monocyte-Derived Macrophages

    Science.gov (United States)

    Bol, Sebastiaan M.; Moerland, Perry D.; Limou, Sophie; van Remmerden, Yvonne; Coulonges, Cédric; van Manen, Daniëlle; Herbeck, Joshua T.; Fellay, Jacques; Sieberer, Margit; Sietzema, Jantine G.; van 't Slot, Ruben; Martinson, Jeremy; Zagury, Jean-François; Schuitemaker, Hanneke; van 't Wout, Angélique B.

    2011-01-01

    Background HIV-1 infected macrophages play an important role in rendering resting T cells permissive for infection, in spreading HIV-1 to T cells, and in the pathogenesis of AIDS dementia. During highly active anti-retroviral treatment (HAART), macrophages keep producing virus because tissue penetration of antiretrovirals is suboptimal and the efficacy of some is reduced. Thus, to cure HIV-1 infection with antiretrovirals we will also need to efficiently inhibit viral replication in macrophages. The majority of the current drugs block the action of viral enzymes, whereas there is an abundance of yet unidentified host factors that could be targeted. We here present results from a genome-wide association study identifying novel genetic polymorphisms that affect in vitro HIV-1 replication in macrophages. Methodology/Principal Findings Monocyte-derived macrophages from 393 blood donors were infected with HIV-1 and viral replication was determined using Gag p24 antigen levels. Genomic DNA from individuals with macrophages that had relatively low (n = 96) or high (n = 96) p24 production was used for SNP genotyping with the Illumina 610 Quad beadchip. A total of 494,656 SNPs that passed quality control were tested for association with HIV-1 replication in macrophages, using linear regression. We found a strong association between in vitro HIV-1 replication in monocyte-derived macrophages and SNP rs12483205 in DYRK1A (p = 2.16×10−5). While the association was not genome-wide significant (p<1×10−7), we could replicate this association using monocyte-derived macrophages from an independent group of 31 individuals (p = 0.0034). Combined analysis of the initial and replication cohort increased the strength of the association (p = 4.84×10−6). In addition, we found this SNP to be associated with HIV-1 disease progression in vivo in two independent cohort studies (p = 0.035 and p = 0.0048). Conclusions/Significance These findings suggest that

  20. Effect of Tools for Getting along on Student Risk for Emotional and Behavioral Problems in Upper Elementary Classrooms: A Replication Study

    Science.gov (United States)

    Smith, Stephen W.; Daunic, Ann P.; Aydin, Burak; Van Loan, Christopher L.; Barber, Brian R.; Taylor, Gregory G.

    2016-01-01

    Social-emotional learning curricula to prevent student problematic behaviors should play a prominent role in public school instruction. While social-emotional curricula have been shown to be effective, there are few replication studies that substantiate their capacity to improve outcomes for students who exhibit problem behaviors. Thus, we…

  1. Politics Perceptions as Moderator of the Political Skill-Job Performance Relationship: A Two-Study, Cross-National, Constructive Replication

    Science.gov (United States)

    Kapoutsis, Ilias; Papalexandris, Alexandros; Nikolopoulos, Andreas; Hochwarter, Wayne A.; Ferris, Gerald R.

    2011-01-01

    We developed a two-study, cross-national, constructive replication to examine the role of organizational politics perceptions as a contextual moderator of the political skill-job performance relationship. Specifically, we hypothesized that high levels of political skill would demonstrate its strongest positive effects on job performance when…

  2. Replicating Health Economic Models: Firm Foundations or a House of Cards?

    Science.gov (United States)

    Bermejo, Inigo; Tappenden, Paul; Youn, Ji-Hee

    2017-11-01

    Health economic evaluation is a framework for the comparative analysis of the incremental health gains and costs associated with competing decision alternatives. The process of developing health economic models is usually complex, financially expensive and time-consuming. For these reasons, model development is sometimes based on previous model-based analyses; this endeavour is usually referred to as model replication. Such model replication activity may involve the comprehensive reproduction of an existing model or 'borrowing' all or part of a previously developed model structure. Generally speaking, the replication of an existing model may require substantially less effort than developing a new de novo model by bypassing, or undertaking in only a perfunctory manner, certain aspects of model development such as the development of a complete conceptual model and/or comprehensive literature searching for model parameters. A further motivation for model replication may be to draw on the credibility or prestige of previous analyses that have been published and/or used to inform decision making. The acceptability and appropriateness of replicating models depends on the decision-making context: there exists a trade-off between the 'savings' afforded by model replication and the potential 'costs' associated with reduced model credibility due to the omission of certain stages of model development. This paper provides an overview of the different levels of, and motivations for, replicating health economic models, and discusses the advantages, disadvantages and caveats associated with this type of modelling activity. Irrespective of whether replicated models should be considered appropriate or not, complete replicability is generally accepted as a desirable property of health economic models, as reflected in critical appraisal checklists and good practice guidelines. To this end, the feasibility of comprehensive model replication is explored empirically across a small

  3. Comparative study of a novel application of automated HR HPV assay and stability in a previously untested Preservative media.

    Science.gov (United States)

    Morel, Mike E; McBride, Simon E; Gomez, Maria P

    2017-12-01

    The suitability and stability of cervical cells in Novaprep media (NHQ) for certain HPV assays is unknown. We evaluated the accuracy of an automated HPV assay (Abbott RealTime HR HPV) for cervical cells prepared in NHQ and NHQ with a pre-treatment to mimic a worst case clinical use, compared to the assay manufacturers media; repeatability and reproducibility of HPV results and the stability of detectable HPV in NHQ over time compared to CE marked liquid based cytology preservatives. Cell lines were used to simulate patient samples. Cells stored in NHQ produced accurate, repeatable and reproducible results. Stability in NHQ was comparable to the best performing LBC, with at least 7 months' stability at 18-25°C, 2-8°C, -20°C and -80°C; and at least 3 months' stability at 40°C. Similar results were obtained for pre-treated NHQ except only 3.5 months' stability at 18-25°C. Cell line samples in all media and concentrations tested were detected appropriately by the assay. Based on this first stage validation analytical study, cervical cells stored in NHQ are suitable for the Realtime HPV assay. There should be no reservations for inclusion of NHQ in any further validation and clinical performance evaluation of this assay. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  4. Comparative study of a novel application of automated HR HPV assay and stability in a previously untested Preservative media

    Directory of Open Access Journals (Sweden)

    Mike E. Morel

    2017-12-01

    Full Text Available Background: The suitability and stability of cervical cells in Novaprep media (NHQ for certain HPV assays is unknown. Methods: We evaluated the accuracy of an automated HPV assay (Abbott RealTime HR HPV for cervical cells prepared in NHQ and NHQ with a pre-treatment to mimic a worst case clinical use, compared to the assay manufacturers media; repeatability and reproducibility of HPV results and the stability of detectable HPV in NHQ over time compared to CE marked liquid based cytology preservatives. Cell lines were used to simulate patient samples. Results: Cells stored in NHQ produced accurate, repeatable and reproducible results. Stability in NHQ was comparable to the best performing LBC, with at least 7 months’ stability at 18–25 °C, 2–8 °C, −20 °C and −80 °C; and at least 3 months’ stability at 40 °C. Similar results were obtained for pre-treated NHQ except only 3.5 months’ stability at 18–25 °C. Cell line samples in all media and concentrations tested were detected appropriately by the assay. Conclusions: Based on this first stage validation analytical study, cervical cells stored in NHQ are suitable for the Realtime HPV assay. There should be no reservations for inclusion of NHQ in any further validation and clinical performance evaluation of this assay. Keywords: HPV, Preservative, Sample stability, Automated HR HPV assay

  5. An ADAM33 polymorphism associates with progression of preschool wheeze into childhood asthma: a prospective case-control study with replication in a birth cohort study.

    Science.gov (United States)

    Klaassen, Ester M M; Penders, John; Jöbsis, Quirijn; van de Kant, Kim D G; Thijs, Carel; Mommers, Monique; van Schayck, Constant P; van Eys, Guillaume; Koppelman, Gerard H; Dompeling, Edward

    2015-01-01

    The influence of asthma candidate genes on the development from wheeze to asthma in young children still needs to be defined. To link genetic variants in asthma candidate genes to progression of wheeze to persistent wheeze into childhood asthma. In a prospective study, children with recurrent wheeze from the ADEM (Asthma DEtection and Monitoring) study were followed until the age of six. At that age a classification (transient wheeze or asthma) was based on symptoms, lung function and medication use. In 198 children the relationship between this classification and 30 polymorphisms in 16 asthma candidate genes was assessed by logistic regression. In case of an association based on a pchildhood asthma. When replicated in the KOALA study, ADAM33 rs528557 showed a negative association of the CG/GG-genotype with progression of recurrent wheeze into childhood asthma (0.50 (0.26-0.97) p = 0.04) and no association with preschool wheeze. Polymorphisms in ADAM33, ORMDL3/GSDMB and IL4 were associated with childhood asthma in a group of children with recurrent wheeze. The replication of the negative association of the CG/GG-genotype of rs528557 ADAM33 with childhood asthma in an independent birth cohort study confirms that a compromised ADAM33 gene may be implicated in the progression of wheeze into childhood asthma.

  6. Docosahexaenoic acid for reading, working memory and behavior in UK children aged 7-9: A randomized controlled trial for replication (the DOLAB II study).

    Science.gov (United States)

    Montgomery, Paul; Spreckelsen, Thees F; Burton, Alice; Burton, Jennifer R; Richardson, Alexandra J

    2018-01-01

    Omega-3 fatty acids are central to brain-development of children. Evidence from clinical trials and systematic reviews demonstrates the potential of long-chain Omega-3 supplementation for learning and behavior. However, findings are inconclusive and in need of robust replication studies since such work is lacking. Replication of the 2012 DOLAB 1 study findings that a dietary supplementation with the long-chain omega-3 docosahexaenoic acid (DHA) had beneficial effects on the reading, working memory, and behavior of healthy schoolchildren. Parallel group, fixed-dose, randomized (minimization, 30% random element), double-blind, placebo-controlled trial (RCT). Mainstream primary schools (n = 84) from five counties in the UK in 2012-2015. Healthy children aged 7-9 underperforming in reading (reading, working memory, and behavior, parent-rated and as secondary outcome teacher-rated. 376 children were randomized. Reading, working memory, and behavior change scores showed no consistent differences between intervention and placebo group. Some behavioral subscales showed minor group differences. This RCT did not replicate results of the earlier DOLAB 1 study on the effectiveness of nutritional supplementation with DHA for learning and behavior. Possible reasons are discussed, particularly regarding the replication of complex interventions. www.controlled-trials.com (ISRCTN48803273) and protocols.io (https://dx.doi.org/10.17504/protocols.io.k8kczuw).

  7. Identification of valid reference genes for microRNA expression studies in a hepatitis B virus replicating liver cell line

    DEFF Research Database (Denmark)

    Jacobsen, Kari Stougaard; Nielsen, Kirstine Overgaard; Nordmann Winther, Thilde

    2016-01-01

    expressed microRNAs with liver-specific target genes in plasma from children with chronic hepatitis B. To further understand the biological role of these microRNAs in the pathogenesis of chronic hepatitis B, we have used the human liver cell line HepG2, with and without HBV replication, after transfection...

  8. COMT Val158Met genotype is associated with reward learning: A replication study and meta-analysis

    Science.gov (United States)

    Corral-Frías, Nadia S.; Pizzagalli, Diego A.; Carré, Justin; Michalski, Lindsay J; Nikolova, Yuliya S.; Perlis, Roy H.; Fagerness, Jesen; Lee, Mary R.; Conley, Emily Drabant; Lancaster, Thomas M.; Haddad, Stephen; Wolf, Aaron; Smoller, Jordan W.; Hariri, Ahmad R.; Bogdan, Ryan

    2016-01-01

    Identifying mechanisms through which individual differences in reward learning emerge offers an opportunity to understand both a fundamental form of adaptive responding as well as etiological pathways through which aberrant reward learning may contribute to maladaptive behaviors and psychopathology. One candidate mechanism through which individual differences in reward learning may emerge is variability in dopaminergic reinforcement signaling. A common functional polymorphism within the catechol-O-methyl transferase gene (COMT; rs4680, Val158Met) has been linked to reward learning where homozygosity for the Met allele (associated with heightened prefrontal dopamine function and decreased dopamine synthesis in the midbrain) has been associated with relatively increased reward learning. Here, we used a probabilistic reward learning task to asses response bias, a behavioral form of reward learning, across 3 separate samples that were combined for analyses (age: 21.80 ± 3.95; n=392; 268 female; European-American, n=208). We replicate prior reports that COMT rs4680 Met allele homozygosity is associated with increased reward learning in European-American participants (β=0.20, t= 2.75, p< 0.01; ΔR2= 0.04). Moreover, a meta-analysis of 4 studies, including the current one, confirmed the association between COMT rs4680 genotype and reward learning (95% CI −0.11 to −0.03; z=3.2; p<0.01). These results suggest that variability in dopamine signaling associated with COMT rs4680 influences individual differences in reward which may potentially contribute to psychopathology characterized by reward dysfunction. PMID:27138112

  9. Aldehyde levels in e-cigarette aerosol: Findings from a replication study and from use of a new-generation device.

    Science.gov (United States)

    Farsalinos, Konstantinos E; Kistler, Kurt A; Pennington, Alexander; Spyrou, Alketa; Kouretas, Dimitris; Gillman, Gene

    2018-01-01

    A recent study identified high aldehyde emissions from e-cigarettes (ECs), that when converted to reasonable daily human EC liquid consumption, 5 g/day, gave formaldehyde exposure equivalent to 604-3257 tobacco cigarettes. We replicated this study and also tested a new-generation atomizer under verified realistic (no dry puff) conditions. CE4v2 atomizers were tested at 3.8 V and 4.8 V, and a Nautilus Mini atomizer was tested at 9.0 W and 13.5 W. All measurements were performed in a laboratory ISO-accredited for EC aerosol collection and aldehyde measurements. CE4v2 generated dry puffs at both voltage settings. Formaldehyde levels were >10-fold lower, acetaldehyde 6-9-fold lower and acrolein 16-26-fold lower than reported in the previous study. Nautilus Mini did not generate dry puffs, and minimal aldehydes were emitted despite >100% higher aerosol production per puff compared to CE4v2 (formaldehyde: 16.7 and 16.5 μg/g; acetaldehyde: 9.6 and 10.3 μg/g; acrolein: 8.6 and 11.7 μg/g at 9.0 W and 13.5 W, respectively). EC liquid consumption of 5 g/day reduces aldehyde exposure by 94.4-99.8% compared to smoking 20 tobacco cigarettes. Checking for dry puffs is essential for EC emission testing. Under realistic conditions, new-generation ECs emit minimal aldehydes/g liquid at both low and high power. Validated methods should be used when analyzing EC aerosol. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2016-01-01

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

  11. Non-replication of genome-wide based associations between common variants in INSIG2 and PFKP and obesity in studies of 18,014 Danes

    DEFF Research Database (Denmark)

    Sandholt, Camilla Helene; Mogensen, Mette S; Borch-Johnsen, Knut

    2008-01-01

    The INSIG2 rs7566605 and PFKP rs6602024 polymorphisms have been identified as obesity gene variants in genome-wide association (GWA) studies. However, replication has been contradictory for both variants. The aims of this study were to validate these obesity-associations through case-control stud......The INSIG2 rs7566605 and PFKP rs6602024 polymorphisms have been identified as obesity gene variants in genome-wide association (GWA) studies. However, replication has been contradictory for both variants. The aims of this study were to validate these obesity-associations through case......-control studies and analyses of obesity-related quantitative traits. Moreover, since environmental and genetic factors may modulate the impact of a genetic variant, we wanted to perform such interaction analyses. We focused on physical activity as an environmental risk factor, and on the GWA identified obesity...

  12. A numerical study of one-dimensional replicating patterns in reaction-diffusion systems with non-linear diffusion coefficients

    International Nuclear Information System (INIS)

    Ferreri, J. C.; Carmen, A. del

    1998-01-01

    A numerical study of the dynamics of pattern evolution in reaction-diffusion systems is performed, although limited to one spatial dimension. The diffusion coefficients are nonlinear, based on powers of the scalar variables. The system keeps the dynamics of previous studies in the literature, but the presence of nonlinear diffusion generates a field of strong nonlinear interactions due to the presence of receding travelling waves. This field is limited by the plane of symmetry of the space domain and the last born outgoing travelling wave. These effects are discussed. (author). 10 refs., 7 figs

  13. Mothers in methadone treatment and their involvement with the child protection system: a replication and extension study.

    Science.gov (United States)

    Taplin, Stephanie; Mattick, Richard P

    2013-08-01

    Although a high level of involvement with the child protection system has been identified in families where parental substance use is a feature, not all such parents abuse or neglect their children or have contact with the child protection system. Identifying parents with substance-use histories who are able to care for their children without intervention by the child protection system, and being able to target interventions to the families who need them the most is important. This study interviewed a relatively large sample of mothers about their histories, their children and their involvement with the child protection system. We hypothesized that mothers in opioid pharmacological treatment who are involved with child protection services are different in characteristics to those mothers who are not involved. One hundred and seventy-one women, with at least one child aged under 16 years, were interviewed at nine treatment clinics providing pharmacological treatment for opioid dependence across Sydney, Australia. Just over one-third of the women were involved with child protection services at the time of interview, mostly with children in out-of-home care. Logistic regression analyses revealed that factors which significantly increased the likelihood of the mother being involved with the child protection system were: (1) having a greater number of children, (2) being on psychiatric medication, and (3) having less than daily contact with her own parents. This study replicates and extends the work of Grella, Hser, and Huang (2006) and the limited literature published to date examining the factors which contribute to some substance-using mothers becoming involved with the child protection system while others do not. The finding that mental health problems and parental supports (along with the number of children) were significantly associated with child protection system involvement in this study, indicates a need for improved interventions and the provision of

  14. Computational system to create an entry file for replicating I-125 seeds simulating brachytherapy case studies using the MCNPX code

    Directory of Open Access Journals (Sweden)

    Leonardo da Silva Boia

    2014-03-01

    decline for short distances.------------------------------Cite this article as: Boia LS, Junior J, Menezes AF, Silva AX. Computational system to create an entry file for replicating I-125 seeds simulating brachytherapy case studies using the MCNPX code. Int J Cancer Ther Oncol 2014; 2(2:02023.DOI: http://dx.doi.org/10.14319/ijcto.0202.3

  15. 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....

  16. Loss of maintenance DNA methylation results in abnormal DNA origin firing during DNA replication

    Energy Technology Data Exchange (ETDEWEB)

    Haruta, Mayumi [Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Shimada, Midori, E-mail: midorism@med.nagoya-cu.ac.jp [Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Nishiyama, Atsuya; Johmura, Yoshikazu [Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Le Tallec, Benoît; Debatisse, Michelle [Institut Curie, Centre de Recherche, 26 rue d’Ulm, CNRS UMR 3244, 75248 ParisCedex 05 (France); Nakanishi, Makoto, E-mail: mkt-naka@med.nagoya-cu.ac.jp [Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan)

    2016-01-22

    The mammalian maintenance methyltransferase DNMT1 [DNA (cytosine-5-)-methyltransferase 1] mediates the inheritance of the DNA methylation pattern during replication. Previous studies have shown that depletion of DNMT1 causes a severe growth defect and apoptosis in differentiated cells. However, the detailed mechanisms behind this phenomenon remain poorly understood. Here we show that conditional ablation of Dnmt1 in murine embryonic fibroblasts (MEFs) resulted in an aberrant DNA replication program showing an accumulation of late-S phase replication and causing severely defective growth. Furthermore, we found that the catalytic activity and replication focus targeting sequence of DNMT1 are required for a proper DNA replication program. Taken together, our findings suggest that the maintenance of DNA methylation by DNMT1 plays a critical role in proper regulation of DNA replication in mammalian cells. - Highlights: • DNMT1 depletion results in an abnormal DNA replication program. • Aberrant DNA replication is independent of the DNA damage checkpoint in DNMT1cKO. • DNMT1 catalytic activity and RFT domain are required for proper DNA replication. • DNMT1 catalytic activity and RFT domain are required for cell proliferation.

  17. Loss of maintenance DNA methylation results in abnormal DNA origin firing during DNA replication

    International Nuclear Information System (INIS)

    Haruta, Mayumi; Shimada, Midori; Nishiyama, Atsuya; Johmura, Yoshikazu; Le Tallec, Benoît; Debatisse, Michelle; Nakanishi, Makoto

    2016-01-01

    The mammalian maintenance methyltransferase DNMT1 [DNA (cytosine-5-)-methyltransferase 1] mediates the inheritance of the DNA methylation pattern during replication. Previous studies have shown that depletion of DNMT1 causes a severe growth defect and apoptosis in differentiated cells. However, the detailed mechanisms behind this phenomenon remain poorly understood. Here we show that conditional ablation of Dnmt1 in murine embryonic fibroblasts (MEFs) resulted in an aberrant DNA replication program showing an accumulation of late-S phase replication and causing severely defective growth. Furthermore, we found that the catalytic activity and replication focus targeting sequence of DNMT1 are required for a proper DNA replication program. Taken together, our findings suggest that the maintenance of DNA methylation by DNMT1 plays a critical role in proper regulation of DNA replication in mammalian cells. - Highlights: • DNMT1 depletion results in an abnormal DNA replication program. • Aberrant DNA replication is independent of the DNA damage checkpoint in DNMT1cKO. • DNMT1 catalytic activity and RFT domain are required for proper DNA replication. • DNMT1 catalytic activity and RFT domain are required for cell proliferation.

  18. Synthesis of modified oligonucleotides for repair and replication studies of single and double radio-induced DNA lesions

    International Nuclear Information System (INIS)

    Muller, E.

    2002-01-01

    Several oxidative processes induce the formation of DNA lesions. In order to evaluate the biological and structural significance of such damage, several DNA lesions were inserted into synthetic oligonucleotides at defined sites. The research work aimed at describing the preparation of oligonucleotides t hat contained DNA damage and the evaluation of the biological properties of the lesions. A first part described the incorporation of radiation-induced lesions, namely (5'S,6S)-5',6-cyclo-5,6-dihydro-2'-deoxyuridine and (5'S,5S,6S)-5',6-cyclo-5-hydroxy-5,6-dihydro-2'-desoxyuridine into oligonucleotides. The modified DNA fragments were characterised by several spectroscopic and biochemical analyses including ESI MS, MALDI-TOF MS, CLHP and enzymatic digestions. During in vitro DNA synthesis by Taq DNA polymerase and Klenow exo fragment, the pyrimidine cyclo-nucleosides were found to block the progression of the enzymes. Then, repair studies by ADN N glycosylases, operating in the base excision repair pathway, have shown that the anhydro-nucleoside lesions were not recognised nor excised by Fpg, endo III, endo VIII, yNtg1 yNtg2 and yOgg1. Interestingly, the Latococcus lactis Fpg protein recognises (formation of a non covalent complex) but do not excise the damage. The incorporation into oligonucleotides of the (5R*) and (5S*) diastereoisomers of 1-[2-deoxy-β-D-erythro-pentofuranosyl]-5-hydroxy-hydantoin, generated by several oxidative processes was then described. In vitro DNA replication assays using modified oligonucleotides matrix showed a lethal potential of the latter base damage. Repair studies by ADN N-glycosylases showed that the damage was substrate for Fpg, endo III, endo VIII, Ntg1, Ntg2 and Fpg-L1. The rates of excision as inferred from the determination of the Michaelis kinetics constants were found to be affected by the presence of the damage. MALDI-TOF MS was used in order to gain insights into mechanistic aspects of oligonucleotides cleavage by the

  19. A coral Sr/Ca calibration and replication study of two massive corals from the Gulf of Mexico

    Science.gov (United States)

    DeLong, Kristine L.; Flannery, Jennifer A.; Maupin, Christopher R.; Poore, Richard Z.; Quinn, Terrence M.

    2011-01-01

    This study examined the variations in the ratio of strontium-to-calcium (Sr/Ca) for two Atlantic corals (Montastraea faveolata and Siderastrea siderea) from the Dry Tortugas National Park (centered on 24.7°N, 82.8°W) in the Gulf of Mexico. Cores from coral colonies in close proximity (10s of meters) and with the same environmental conditions (i.e., depth and water chemistry) were micro-sampled with approximately monthly resolution and the resulting Sr/Ca variations were calibrated with local sea surface temperature (SST) records. Replication tests for coral Sr/Ca variations found high agreement between intra-colony variations and between individual colonies of S. siderea (a single M. faveolata colony was sampled). Regression analysis of monthly variations in coral Sr/Ca and local SST revealed significant correlation on monthly and inter-annual timescales. Verification of the calibration on different timescales found coral Sr/Ca–SST reconstructions in S. siderea were more accurate than those from M. faveolata, especially on inter-annual timescales. Sr/Ca–SST calibration equations for the two species are significantly different (cf., Sr/Ca = -0.042 SST + 10.070, S. siderea; Sr/Ca = -0.027 SST + 9.893, M. faveolata). Mean linear extension for M. faveolata is approximately twice that of S. siderea (4.63, 4.31, and 8.31 mm year−1, A1, F1, and B3, respectively); however, seasonal Sr/Ca variability in M. faveolata is less than S. siderea (0.323, 0.353, and 0.254 mmol mol−1, A1, F1, and B3, respectively). The reduced slope for M. faveolata is attributed to physical sampling issues associated with complex time-skeletal structure of M. faveolata, i.e., a sampling effect, and not a growth effect since the faster growing M. faveolata has the reduced Sr/Ca variability.

  20. 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...

  1. 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.

  2. Polychlorinated biphenyl exposure, diabetes and endogenous hormones: a cross-sectional study in men previously employed at a capacitor manufacturing plant.

    Science.gov (United States)

    Persky, Victoria; Piorkowski, Julie; Turyk, Mary; Freels, Sally; Chatterton, Robert; Dimos, John; Bradlow, H Leon; Chary, Lin Kaatz; Burse, Virlyn; Unterman, Terry; Sepkovic, Daniel W; McCann, Kenneth

    2012-08-29

    Studies have shown associations of diabetes and endogenous hormones with exposure to a wide variety of organochlorines. We have previously reported positive associations of polychlorinated biphenyls (PCBs) and inverse associations of selected steroid hormones with diabetes in postmenopausal women previously employed in a capacitor manufacturing plant. This paper examines associations of PCBs with diabetes and endogenous hormones in 63 men previously employed at the same plant who in 1996 underwent surveys of their exposure and medical history and collection of bloods and urine for measurements of PCBs, lipids, liver function, hematologic markers and endogenous hormones. PCB exposure was positively associated with diabetes and age and inversely associated with thyroid stimulating hormone and triiodothyronine-uptake. History of diabetes was significantly related to total PCBs and all PCB functional groupings, but not to quarters worked and job score, after control for potential confounders. None of the exposures were related to insulin resistance (HOMA-IR) in non-diabetic men. Associations of PCBs with specific endogenous hormones differ in some respects from previous findings in postmenopausal women employed at the capacitor plant. Results from this study, however, do confirm previous reports relating PCB exposure to diabetes and suggest that these associations are not mediated by measured endogenous hormones.

  3. Docosahexaenoic acid for reading, working memory and behavior in UK children aged 7-9: A randomized controlled trial for replication (the DOLAB II study.

    Directory of Open Access Journals (Sweden)

    Paul Montgomery

    Full Text Available Omega-3 fatty acids are central to brain-development of children. Evidence from clinical trials and systematic reviews demonstrates the potential of long-chain Omega-3 supplementation for learning and behavior. However, findings are inconclusive and in need of robust replication studies since such work is lacking.Replication of the 2012 DOLAB 1 study findings that a dietary supplementation with the long-chain omega-3 docosahexaenoic acid (DHA had beneficial effects on the reading, working memory, and behavior of healthy schoolchildren.Parallel group, fixed-dose, randomized (minimization, 30% random element, double-blind, placebo-controlled trial (RCT.Mainstream primary schools (n = 84 from five counties in the UK in 2012-2015.Healthy children aged 7-9 underperforming in reading (<20th centile. 1230 invited, 376 met study criteria.600 mg/day DHA (from algal oil, placebo: taste/color matched corn/soybean oil; for 16 weeks.Age-standardized measures of reading, working memory, and behavior, parent-rated and as secondary outcome teacher-rated.376 children were randomized. Reading, working memory, and behavior change scores showed no consistent differences between intervention and placebo group. Some behavioral subscales showed minor group differences.This RCT did not replicate results of the earlier DOLAB 1 study on the effectiveness of nutritional supplementation with DHA for learning and behavior. Possible reasons are discussed, particularly regarding the replication of complex interventions.www.controlled-trials.com (ISRCTN48803273 and protocols.io (https://dx.doi.org/10.17504/protocols.io.k8kczuw.

  4. Quantifying the influence of previously burned areas on suppression effectiveness and avoided exposure: A case study of the Las Conchas Fire

    Science.gov (United States)

    Matthew P. Thompson; Patrick Freeborn; Jon D. Rieck; Dave Calkin; Julie W. Gilbertson-Day; Mark A. Cochrane; Michael S. Hand

    2016-01-01

    We present a case study of the Las Conchas Fire (2011) to explore the role of previously burned areas (wildfires and prescribed fires) on suppression effectiveness and avoided exposure. Methodological innovations include characterisation of the joint dynamics of fire growth and suppression activities, development of a fire line effectiveness framework, and...

  5. Study of some physical aspects previous to design of an exponential experiment; Estudio de algunos aspectos fisicos previos al diseno de una experiencia exponencial

    Energy Technology Data Exchange (ETDEWEB)

    Caro, R; Francisco, J L. de

    1961-07-01

    This report presents the theoretical study of some physical aspects previous to the design of an exponential facility. The are: Fast and slow flux distribution in the multiplicative medium and in the thermal column, slowing down in the thermal column, geometrical distribution and minimum needed intensity of sources access channels and perturbations produced by possible variations in its position and intensity. (Author) 4 refs.

  6. Use of two-part regression calibration model to correct for measurement error in episodically consumed foods in a single-replicate study design: EPIC case study.

    Science.gov (United States)

    Agogo, George O; van der Voet, Hilko; van't Veer, Pieter; Ferrari, Pietro; Leenders, Max; Muller, David C; Sánchez-Cantalejo, Emilio; Bamia, Christina; Braaten, Tonje; Knüppel, Sven; Johansson, Ingegerd; van Eeuwijk, Fred A; Boshuizen, Hendriek

    2014-01-01

    In epidemiologic studies, measurement error in dietary variables often attenuates association between dietary intake and disease occurrence. To adjust for the attenuation caused by error in dietary intake, regression calibration is commonly used. To apply regression calibration, unbiased reference measurements are required. Short-term reference measurements for foods that are not consumed daily contain excess zeroes that pose challenges in the calibration model. We adapted two-part regression calibration model, initially developed for multiple replicates of reference measurements per individual to a single-replicate setting. We showed how to handle excess zero reference measurements by two-step modeling approach, how to explore heteroscedasticity in the consumed amount with variance-mean graph, how to explore nonlinearity with the generalized additive modeling (GAM) and the empirical logit approaches, and how to select covariates in the calibration model. The performance of two-part calibration model was compared with the one-part counterpart. We used vegetable intake and mortality data from European Prospective Investigation on Cancer and Nutrition (EPIC) study. In the EPIC, reference measurements were taken with 24-hour recalls. For each of the three vegetable subgroups assessed separately, correcting for error with an appropriately specified two-part calibration model resulted in about three fold increase in the strength of association with all-cause mortality, as measured by the log hazard ratio. Further found is that the standard way of including covariates in the calibration model can lead to over fitting the two-part calibration model. Moreover, the extent of adjusting for error is influenced by the number and forms of covariates in the calibration model. For episodically consumed foods, we advise researchers to pay special attention to response distribution, nonlinearity, and covariate inclusion in specifying the calibration model.

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

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

    Science.gov (United States)

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

    2017-05-05

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

  9. A cross-sectional study of tuberculosis drug resistance among previously treated patients in a tertiary hospital in Accra, Ghana: public health implications of standardized regimens.

    Science.gov (United States)

    Forson, Audrey; Kwara, Awewura; Kudzawu, Samuel; Omari, Michael; Otu, Jacob; Gehre, Florian; de Jong, Bouke; Antonio, Martin

    2018-04-02

    Mycobacterium tuberculosis drug resistance is a major challenge to the use of standardized regimens for tuberculosis (TB) therapy, especially among previously treated patients. We aimed to investigate the frequency and pattern of drug resistance among previously treated patients with smear-positive pulmonary tuberculosis at the Korle-Bu Teaching Hospital Chest Clinic, Accra. This was a cross-sectional survey of mycobacterial isolates from previously treated patients referred to the Chest Clinic Laboratory between October 2010 and October 2013. The Bactec MGIT 960 system for mycobactrerial culture and drug sensitivity testing (DST) was used for sputum culture of AFB smear-positive patients with relapse, treatment failure, failure of smear conversion, or default. Descriptive statistics were used to summarize patient characteristics, and frequency and patterns of drug resistance. A total of 112 isolates were studied out of 155 from previously treated patients. Twenty contaminated (12.9%) and 23 non-viable isolates (14.8%) were excluded. Of the 112 studied isolates, 53 (47.3%) were pan-sensitive to all first-line drugs tested Any resistance (mono and poly resistance) to isoniazid was found in 44 isolates (39.3%) and any resistance to streptomycin in 43 (38.4%). Thirty-one (27.7%) were MDR-TB. Eleven (35.5%) out of 31 MDR-TB isolates were pre-XDR. MDR-TB isolates were more likely than non-MDR isolates to have streptomycin and ethambutol resistance. The main findings of this study were the high prevalence of MDR-TB and streptomycin resistance among previously treated TB patients, as well as a high prevalence of pre-XDR-TB among the MDR-TB patients, which suggest that first-line and second-line DST is essential to aid the design of effective regimens for these groups of patients in Ghana.

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

    Directory of Open Access Journals (Sweden)

    Richard A. Klein

    2014-04-01

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

  11. Construction and Cloning of Reporter-Tagged Replicon cDNA for an In Vitro Replication Study of Murine Norovirus-1 (MNV-1).

    Science.gov (United States)

    Ahmad, Muhammad Khairi; Tabana, Yasser M; Ahmed, Mowaffaq Adam; Sandai, Doblin Anak; Mohamed, Rafeezul; Ismail, Ida Shazrina; Zulkiflie, Nurulisa; Yunus, Muhammad Amir

    2017-12-01

    A norovirus maintains its viability, infectivity and virulence by its ability to replicate. However, the biological mechanisms of the process remain to be explored. In this work, the NanoLuc™ Luciferase gene was used to develop a reporter-tagged replicon system to study norovirus replication. The NanoLuc™ Luciferase reporter protein was engineered to be expressed as a fusion protein for MNV-1 minor capsid protein, VP2. The foot-and-mouth disease virus 2A (FMDV2A) sequence was inserted between the 3'end of the reporter gene and the VP2 start sequence to allow co-translational 'cleavage' of fusion proteins during intracellular transcript expression. Amplification of the fusion gene was performed using a series of standard and overlapping polymerase chain reactions. The resulting amplicon was then cloned into three readily available backbones of MNV-1 cDNA clones. Restriction enzyme analysis indicated that the NanoLucTM Luciferase gene was successfully inserted into the parental MNV-1 cDNA clone. The insertion was further confirmed by using DNA sequencing. NanoLuc™ Luciferase-tagged MNV-1 cDNA clones were successfully engineered. Such clones can be exploited to develop robust experimental assays for in vitro assessments of viral RNA replication.

  12. 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)

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

    OpenAIRE

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

    2009-01-01

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

  14. Intermolecular RNA Recombination Occurs at Different Frequencies in Alternate Forms of Brome Mosaic Virus RNA Replication Compartments

    Directory of Open Access Journals (Sweden)

    Hernan Garcia-Ruiz

    2018-03-01

    Full Text Available Positive-strand RNA viruses replicate their genomes in membrane-bound replication compartments. Brome mosaic virus (BMV replicates in vesicular invaginations of the endoplasmic reticulum membrane. BMV has served as a productive model system to study processes like virus-host interactions, RNA replication and recombination. Here we present multiple lines of evidence showing that the structure of the viral RNA replication compartments plays a fundamental role and that recruitment of parental RNAs to a common replication compartment is a limiting step in intermolecular RNA recombination. We show that a previously defined requirement for an RNA recruitment element on both parental RNAs is not to function as a preferred crossover site, but in order for individual RNAs to be recruited into the replication compartments. Moreover, modulating the form of the replication compartments from spherular vesicles (spherules to more expansive membrane layers increased intermolecular RNA recombination frequency by 200- to 1000-fold. We propose that intermolecular RNA recombination requires parental RNAs to be recruited into replication compartments as monomers, and that recruitment of multiple RNAs into a contiguous space is much more common for layers than for spherules. These results could explain differences in recombination frequencies between viruses that replicate in association with smaller spherules versus larger double-membrane vesicles and convoluted membranes.

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

    Directory of Open Access Journals (Sweden)

    Molly L. Bristol

    2016-06-01

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

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

    Science.gov (United States)

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

    2016-06-22

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

  17. Is email a reliable means of contacting authors of previously published papers? A study of the Emergency Medicine Journal for 2001.

    Science.gov (United States)

    O'Leary, F

    2003-07-01

    To determine whether it is possible to contact authors of previously published papers via email. A cross sectional study of the Emergency Medicine Journal for 2001. 118 articles were included in the study. The response rate from those with valid email addresses was 73%. There was no statistical difference between the type of email address used and the address being invalid (p=0.392) or between the type of article and the likelihood of a reply (p=0.197). More responses were obtained from work addresses when compared with Hotmail addresses (86% v 57%, p=0.02). Email is a valid means of contacting authors of previously published articles, particularly within the emergency medicine specialty. A work based email address may be a more valid means of contact than a Hotmail address.

  18. The Policy Impact of Social Movements: A Replication Through Qualitative Comparative Analysis

    OpenAIRE

    Giugni, Marco; Yamasaki, Sakura

    2009-01-01

    This article reanalyzes the data of a previous study on the policy impact of antinuclear, ecology, and peace movements in three countries with the aim of replicating its findings. Our goal is to see whether using a different analytical technique will yield similar results. The previous study used a regression approach to time-series analysis. Here, we use qualitative comparative analysis (QCA) to analyze the previous study’s data. Specifically, we test the two main hypotheses based on the joi...

  19. Previous dropout from diabetic care as a predictor of patients' willingness to use mobile applications for self-management: A cross-sectional study.

    Science.gov (United States)

    Yamaguchi, Satoko; Waki, Kayo; Tomizawa, Nobuko; Waki, Hironori; Nannya, Yasuhito; Nangaku, Masaomi; Kadowaki, Takashi; Ohe, Kazuhiko

    2017-07-01

    Preventing dropout is crucial in managing diabetes. Accordingly, we investigated whether patients who had dropped out of diabetic care are suitable candidates for the use of mobile technologies - such as smartphone applications - to support self-management (mHealth), which might help prevent dropout. We carried out a cross-sectional study in Tokyo, Japan. Patients aged 20 years or older who were clinically diagnosed as diabetic and who regularly visited the outpatient unit at the University of Tokyo Hospital were recruited between August 2014 and March 2015. Data were collected through face-to-face structured interviews, physical measurements and medical records. Participants were asked whether they were willing to use mHealth after being shown DialBetics - an mHealth application for diabetics - as an example, and about their history of dropout and previous mHealth experience. Data were analyzed by multivariate logistic regression models. Of 307 patients with type 1 and type 2 diabetes, 34 (11.1%) had previously dropped out from diabetic care. Multivariate analysis identified previous mHealth experience as a negative predictor of dropout (odds ratio 0.211, P = 0.023). Of those 34 patients, 27 (79.4%) expressed willingness to use mHealth, a significantly higher percentage than for those who had never dropped out (51.5%, P = 0.002). After adjusting for confounders, history of dropout remained a strong predictor of willingness (odds ratio 3.870, P = 0.004). Patients who previously dropped out of diabetic care are suitable candidates for mHealth. Future studies must evaluate whether mHealth is effective for preventing repeated dropout and improving glycemic control among this population. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

  20. STAT4 gene influences genetic predisposition to ulcerative colitis but not Crohn's disease in the Spanish population: a replication study.

    Science.gov (United States)

    Diaz-Gallo, Lina Marcela; Palomino-Morales, Rogelio J; Gómez-García, María; Cardeña, Carlos; Rodrigo, Luis; Nieto, Antonio; Alcain, Guillermo; Cueto, Ignacio; López-Nevot, Miguel A; Martin, Javier

    2010-05-01

    Recently, the signal transducer and activator of transcription 4 (STAT4) gene has been associated with multiple autoimmune diseases. Interestingly, a recent work showed that the T allele of the rs7574865 STAT4 SNP was associated with inflammatory bowel disease (IBD) in a Spanish population. The aim of the present study was to reevaluate the role of the STAT4 rs7574865 polymorphism on IBD. The present case-control study included 498 Crohn's disease (CD) patients, 402 ulcerative colitis (UC) patients, and 1296 healthy matched controls. Genotyping was performed using a PCR system with a pre-developed TaqMan allelic discrimination assay for the rs7574865 STAT4 SNP. Moreover, a meta-analysis was performed with the previous work in a Spanish population and the current study, including a final sample size of 1574 IBD patients (820 with CD and 754 with UC) and 2012 healthy controls. No evidence of association was found for the current case-control study (CD: p = 0.23, OR = 0.9, 95% CI = 0.75-1.1; UC: p = 0.17, OR = 1.14, 95% CI = 0.95-1.38). However, the meta-analysis showed that the STAT4 rs7574865 T allele was significantly associated with susceptibility to UC (p = 0.012 pooled; OR = 1.20, 95% CI = 1.04-1.39) but not CD (p = 0.71 pooled; OR = 0.93, 95% CI = 0.65-1.34). Our data suggest that the rs7574865 STAT4 SNP is a genetic susceptibility variant for UC but not CD in the Spanish population. Copyright 2010 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  1. Mortality and cardiovascular risk associated with different insulin secretagogues compared with metformin in type 2 diabetes, with or without a previous myocardial infarction: a nationwide study

    DEFF Research Database (Denmark)

    Schramm, Tina Ken; Gislason, Gunnar Hilmar; Vaag, Allan

    2011-01-01

    Aims The impact of insulin secretagogues (ISs) on long-term major clinical outcomes in type 2 diabetes remains unclear. We examined mortality and cardiovascular risk associated with all available ISs compared with metformin in a nationwide study. Methods and results All Danish residents >20 years......, initiating single-agent ISs or metformin between 1997 and 2006 were followed for up to 9 years (median 3.3 years) by individual-level linkage of nationwide registers. All-cause mortality, cardiovascular mortality, and the composite of myocardial infarction (MI), stroke, and cardiovascular mortality...... associated with individual ISs were investigated in patients with or without previous MI by multivariable Cox proportional-hazard analyses including propensity analyses. A total of 107 806 subjects were included, of whom 9607 had previous MI. Compared with metformin, glimepiride (hazard ratios and 95...

  2. Challenging previous conceptions of vegetarianism and eating disorders.

    Science.gov (United States)

    Fisak, B; Peterson, R D; Tantleff-Dunn, S; Molnar, J M

    2006-12-01

    The purpose of this study was to replicate and expand upon previous research that has examined the potential association between vegetarianism and disordered eating. Limitations of previous research studies are addressed, including possible low reliability of measures of eating pathology within vegetarian samples, use of only a few dietary restraint measures, and a paucity of research examining potential differences in body image and food choice motives of vegetarians versus nonvegetarians. Two hundred and fifty-six college students completed a number of measures of eating pathology and body image, and a food choice motives questionnaire. Interestingly, no significant differences were found between vegetarians and nonvegetarians in measures of eating pathology or body image. However, significant differences in food choice motives were found. Implications for both researchers and clinicians are discussed.

  3. Replication of kinetoplast minicircle DNA

    International Nuclear Information System (INIS)

    Sheline, C.T.

    1989-01-01

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

  4. 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

  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. Activation of human herpesvirus replication by apoptosis.

    Science.gov (United States)

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

    2013-10-01

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

  7. Acceleration and Orientation Jumping Performance Differences Among Elite Professional Male Handball Players With or Without Previous ACL Reconstruction: An Inertial Sensor Unit-Based Study.

    Science.gov (United States)

    Setuain, Igor; González-Izal, Miriam; Alfaro, Jesús; Gorostiaga, Esteban; Izquierdo, Mikel

    2015-12-01

    Handball is one of the most challenging sports for the knee joint. Persistent biomechanical and jumping capacity alterations can be observed in athletes with an anterior cruciate ligament (ACL) injury. Commonly identified jumping biomechanical alterations have been described by the use of laboratory technologies. However, portable and easy-to-handle technologies that enable an evaluation of jumping biomechanics at the training field are lacking. To analyze unilateral/bilateral acceleration and orientation jumping performance differences among elite male handball athletes with or without previous ACL reconstruction via a single inertial sensor unit device. Case control descriptive study. At the athletes' usual training court. Twenty-two elite male (6 ACL-reconstructed and 16 uninjured control players) handball players were evaluated. The participants performed a vertical jump test battery that included a 50-cm vertical bilateral drop jump, a 20-cm vertical unilateral drop jump, and vertical unilateral countermovement jump maneuvers. Peak 3-dimensional (X, Y, Z) acceleration (m·s(-2)), jump phase duration and 3-dimensional orientation values (°) were obtained from the inertial sensor unit device. Two-tailed t-tests and a one-way analysis of variance were performed to compare means. The P value cut-off for significance was set at P handball athletes with previous ACL reconstruction demonstrated a jumping biomechanical profile similar to control players, including similar jumping performance values in both bilateral and unilateral jumping maneuvers, several years after ACL reconstruction. These findings are in agreement with previous research showing full functional restoration of abilities in top-level male athletes after ACL reconstruction, rehabilitation and subsequent return to sports at the previous level. Copyright © 2015 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  8. 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.

  9. Selected single-nucleotide polymorphisms in FOXE1, SERPINA5, FTO, EVPL, TICAM1 and SCARB1 are associated with papillary and follicular thyroid cancer risk: replication study in a German population.

    Science.gov (United States)

    Sigurdson, Alice J; Brenner, Alina V; Roach, James A; Goudeva, Lilia; Müller, Jörg A; Nerlich, Kai; Reiners, Christoph; Schwab, Robert; Pfeiffer, Liliane; Waldenberger, Melanie; Braganza, Melissa; Xu, Li; Sturgis, Erich M; Yeager, Meredith; Chanock, Stephen J; Pfeiffer, Ruth M; Abend, Michael; Port, Matthias

    2016-07-01

    Several single-nucleotide polymorphisms (SNPs) have been associated with papillary and follicular thyroid cancer (PTC and FTC, respectively) risk, but few have replicated. After analyzing 17525 tag SNPs in 1129 candidate genes, we found associations with PTC risk in SERPINA5, FTO, HEMGN (near FOXE1) and other genes. Here, we report results from a replication effort in a large independent PTC/FTC case-control study conducted in Germany. We evaluated the best tagging SNPs from our previous PTC study and additionally included SNPs in or near FOXE1 and NKX2-1 genes, known susceptibility loci for thyroid cancer. We genotyped 422 PTC and 130 FTC cases and 752 controls recruited from three German clinical centers. We used polytomous logistic regression to simultaneously estimate PTC and FTC associations for 79 SNPs based on log-additive models. We assessed effect modification by body mass index (BMI), gender and age for all SNPs, and selected SNP by SNP interactions. We confirmed associations with PTC and SNPs in FOXE1/HEMGN, SERPINA5 (rs2069974), FTO (rs8047395), EVPL (rs2071194), TICAM1 (rs8120) and SCARB1 (rs11057820) genes. We found associations with SNPs in FOXE1, SERPINA5, FTO, TICAM1 and HSPA6 and FTC. We found two significant interactions between FTO (rs8047395) and BMI (P = 0.0321) and between TICAM1 (rs8120) and FOXE1 (rs10984377) (P = 0.0006). Besides the known associations with FOXE1 SNPs, we confirmed additional PTC SNP associations reported previously. We also found several new associations with FTC risk and noteworthy interactions. We conclude that multiple variants and host factors might interact in complex ways to increase risk of PTC and FTC. Published by Oxford University Press 2016.

  10. Replicating a self-affirmation intervention to address gender differences: Successes and challenges

    Science.gov (United States)

    Kost-Smith, Lauren E.; Pollock, Steven J.; Finkelstein, Noah D.; Cohen, Geoffrey L.; Ito, Tiffany A.; Miyake, Akira

    2012-02-01

    We previously reported on the success of a psychological intervention implemented to reduce gender differences in achievement in an introductory college physics course. In this prior study, we found that the gender gap on exams and the FMCE among students who completed two 15-minute self-affirmation writing exercises was significantly reduced compared to the gender gap among students who completed neutral writing exercises. In a follow-up study we replicated the self-affirmation intervention in a later semester of the same course, with the same instructor. In this paper, we report the details and preliminary results of the replication study, where we find similar patterns along exams and course grades, but do not observe these patterns along the FMCE. We begin to investigate the critical features of replicating educational interventions, finding that replicating educational interventions is challenging, complex, and involves potentially subtle factors, some of which we explore and others that require further research.

  11. De novo adamantinomatous craniopharyngioma presenting anew in an elderly patient with previous normal CT and MRI studies: A case report and implications on pathogenesis

    Directory of Open Access Journals (Sweden)

    Amy Walker, B.S.

    2015-09-01

    Full Text Available Adamantinomatous craniopharyngiomas are histologically benign epithelial tumors which arise from embryonic remnants of the craniopharyngeal duct and Rathke’s pouch. They are thought to have a congenital origin and are histologically unique from papillary craniopharyngioma. We describe the case of an elderly male who presented with symptoms related to a large craniopharyngioma with previously normal brain magnetic resonance and computed tomography imaging studies. These findings dispute the embryogenic theory that craniopharyngiomas observed in adults develop from the persistent slow growth of embryonic remnants.

  12. Inspirations on Virus Replication and Cell-to-Cell Movement from Studies Examining the Cytopathology Induced by Lettuce infectious yellows virus in Plant Cells

    Directory of Open Access Journals (Sweden)

    Wenjie Qiao

    2017-09-01

    Full Text Available Lettuce infectious yellows virus (LIYV is the type member of the genus Crinivirus in the family Closteroviridae. Like many other positive-strand RNA viruses, LIYV infections induce a number of cytopathic changes in plant cells, of which the two most characteristic are: Beet yellows virus-type inclusion bodies composed of vesicles derived from cytoplasmic membranes; and conical plasmalemma deposits (PLDs located at the plasmalemma over plasmodesmata pit fields. The former are not only found in various closterovirus infections, but similar structures are known as ‘viral factories’ or viroplasms in cells infected with diverse types of animal and plant viruses. These are generally sites of virus replication, virion assembly and in some cases are involved in cell-to-cell transport. By contrast, PLDs induced by the LIYV-encoded P26 non-virion protein are not involved in replication but are speculated to have roles in virus intercellular movement. These deposits often harbor LIYV virions arranged to be perpendicular to the plasma membrane over plasmodesmata, and our recent studies show that P26 is required for LIYV systemic plant infection. The functional mechanism of how LIYV P26 facilitates intercellular movement remains unclear, however, research on other plant viruses provides some insights on the possible ways of viral intercellular movement through targeting and modifying plasmodesmata via interactions between plant cellular components and viral-encoded factors. In summary, beginning with LIYV, we review the studies that have uncovered the biological determinants giving rise to these cytopathological effects and their importance in viral replication, virion assembly and intercellular movement during the plant infection by closteroviruses, and compare these findings with those for other positive-strand RNA viruses.

  13. Impact of Availability and Use of ART/PMTCT Services on Fertility Desires of Previously Pregnant Women in Rakai, Uganda: A Retrospective Cohort Study.

    Science.gov (United States)

    Litwin, Lindsay E; Makumbi, Frederick E; Gray, Ronald; Wawer, Maria; Kigozi, Godfrey; Kagaayi, Joseph; Nakigozi, Gertrude; Lutalo, Tom; Serwada, David; Brahmbhatt, Heena

    2015-07-01

    To assess fertility desires by availability and use of antiretroviral therapy and prevention of mother-to-child transmission (ART/PMTCT) services in Rakai, Uganda. Retrospective analyses of longitudinal data from the Rakai Community Cohort Study. Study participants were retrospectively identified and categorized by HIV status. Availability of ART/PMTCT services in Rakai was defined in three periods: (1) pre-ART/PMTCT (ART/PMTCT rollout (2005-2006), and (3) universal ART/PMTCT (>2006); and use of ART/PMTCT was coded as yes if the woman received services. Trends in fertility desires were assessed by χ. "Modified" Poisson regression was performed using generalized linear models with a log link and Poisson family to estimate prevalence rate ratios (PRRs) and 95% confidence intervals (CIs) of desire for another child among previously and currently pregnant women; PRRs were adjusted for demographic and behavioral factors. A total of 4227 sexually active women in Rakai, including 436 HIV+ women, contributed 13,970 observations over 5 survey rounds. Fertility desires increased in the population in the ART/PMTCT rollout [adjusted (adj.) PRR: 1.08, 95% CI: 1.04 to 1.13] and the universal availability periods (adj. PRR: 1.11, 95% CI: 1.08 to 1.14) compared with pre-ART/PMTCT period. A total of 862 woman observations used ART/PMTCT services. Fertility desires were similar among ART/PMTCT service users and nonusers in cross-sectional analysis (adj. PRR: 0.84, 95% CI: 0.62 to 1.14) and 1 year after ART/PMTCT use (adj. PRR: 1.27, 95% CI: 0.83 to 1.94). Availability of ART/PMTCT may increase fertility desires of previously pregnant women in Rakai, Uganda. Use of ART/PMTCT services was not correlated with fertility desires of previously or current pregnant women.

  14. Outcome of secondary high-grade glioma in children previously treated for a malignant condition: A study of the Canadian Pediatric Brain Tumour Consortium

    International Nuclear Information System (INIS)

    Carret, Anne-Sophie; Tabori, Uri; Crooks, Bruce; Hukin, Juliette; Odame, Isaac; Johnston, Donna L.; Keene, Daniel L.; Freeman, Carolyn; Bouffet, Eric

    2006-01-01

    Background and purpose: Reports of secondary high-grade glioma (HGG) in survivors of childhood cancer are scarce. The aim of this study was to review the pattern of diagnosis, the treatment, and outcome of secondary pediatric HGG. Patients and methods: We performed a multi-center retrospective study among the 17 paediatric institutions participating in the Canadian Pediatric Brain Tumour Consortium (CPBTC). Results: We report on 18 patients (14 males, 4 females) treated in childhood for a primary cancer, who subsequently developed a HGG as a second malignancy. All patients had previously received radiation therapy +/- chemotherapy for either acute lymphoblastic leukaemia (n = 9) or solid tumour (n = 9). All HGG occurred within the previous radiation fields. At the last follow-up, 17 patients have died and the median survival time is 9.75 months. Conclusion: Although aggressive treatment seems to provide sustained remissions in some patients, the optimal management is still to be defined. Further documentation of such cases is necessary in order to better understand the pathogenesis, the natural history and the prevention of these tumours

  15. Surface microstructure replication in injection molding

    DEFF Research Database (Denmark)

    Theilade, Uffe Arlø; Hansen, Hans Nørgaard

    2006-01-01

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

  16. Suppression of Poxvirus Replication by Resveratrol.

    Science.gov (United States)

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

    2017-01-01

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

  17. Suppression of Poxvirus Replication by Resveratrol

    Directory of Open Access Journals (Sweden)

    Shuai Cao

    2017-11-01

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

  18. The yeast replicative aging model.

    Science.gov (United States)

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

    2018-03-08

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

  19. Vitamin D deficiency in medical patients at a central hospital in Malawi: a comparison with TB patients from a previous study.

    Directory of Open Access Journals (Sweden)

    Yamikani Mastala

    Full Text Available OBJECTIVES: To determine the prevalence of vitamin D deficiency (VDD in adult medical, non-tuberculous (non-TB patients. To investigate associations with VDD. To compare the results with a similar study in TB patients at the same hospital. DESIGN: Cross-sectional sample. SETTING: Central hospital in Malawi. PARTICIPANTS: Adult non-TB patients (n = 157, inpatients and outpatients. OUTCOME MEASURES: The primary outcome was the prevalence of VDD. Potentially causal associations sought included nutritional status, in/outpatient status, HIV status, anti-retroviral therapy (ART and, by comparison with a previous study, a diagnosis of tuberculosis (TB. RESULTS: Hypovitaminosis D (≤75 nmol/L occurred in 47.8% (75/157 of patients, 16.6% (26/157 of whom had VDD (≤50 nmol/L. None had severe VDD (≤25 nmol/L. VDD was found in 22.8% (23/101 of in-patients and 5.4% (3/56 of out-patients. In univariable analysis in-patient status, ART use and low dietary vitamin D were significant predictors of VDD. VDD was less prevalent than in previously studied TB patients in the same hospital (68/161 = 42%. In multivariate analysis of the combined data set from both studies, having TB (OR 3.61, 95%CI 2.02-6.43 and being an in-patient (OR 2.70, 95%CI 1.46-5.01 were significant independent predictors of VDD. CONCLUSIONS: About half of adult medical patients without TB have suboptimal vitamin D status, which is more common in in-patients. VDD is much more common in TB patients than non-TB patients, even when other variables are controlled for, suggesting that vitamin D deficiency is associated with TB.

  20. Mutant analysis of Cdt1's function in suppressing nascent strand elongation during DNA replication in Xenopus egg extracts.

    Science.gov (United States)

    Nakazaki, Yuta; Tsuyama, Takashi; Azuma, Yutaro; Takahashi, Mikiko; Tada, Shusuke

    2017-09-02

    The initiation of DNA replication is strictly regulated by multiple mechanisms to ensure precise duplication of chromosomes. In higher eukaryotes, activity of the Cdt1 protein is temporally regulated during the cell cycle, and deregulation of Cdt1 induces DNA re-replication. In previous studies, we showed that excess Cdt1 inhibits DNA replication by suppressing progression of replication forks in Xenopus egg extracts. Here, we investigated the functional regions of Cdt1 that are required for the inhibition of DNA replication. We constructed a series of N-terminally or C-terminally deleted mutants of Cdt1 and examined their inhibitory effects on DNA replication in Xenopus egg extracts. Our results showed that the region spanning amino acids (a. a.) 255-620 is required for efficient inhibition of DNA replication, and that, within this region, a. a. 255-289 have a critical role in inhibition. Moreover, one of the Cdt1 mutants, Cdt1 R285A, was compromised with respect to the licensing activity but still inhibited DNA replication. This result suggests that Cdt1 has an unforeseen function in the negative regulation of DNA replication, and that this function is located within a molecular region that is distinct from those required for the licensing activity. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Evolution of Replication Machines

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    1979-08-01

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

  4. Women's Stereotypic Roles: A Replication and Standardization of the AWS and PAQ for Selected Ethnic Groups.

    Science.gov (United States)

    Wheeler, Edwin E.; And Others

    A replication of two previous studies, this study examined the effect of both sex and ethnicity on attitudes toward women, self-reported masculinity-femininity, and masculine-feminine stereotypic attitudes. The Attitudes Toward Women Scale (AWS) and the Personal Attributes Questionnaire (PAQ) were administered to 367 college students (112 Anglos,…

  5. Rhythmic Engagement with Music in Early Childhood: A Replication and Extension

    Science.gov (United States)

    Ilari, Beatriz

    2015-01-01

    The purpose of this study was to replicate and extend previous findings on spontaneous movement and rhythmic engagement with music in infancy. Using the identical stimuli and procedures from the original study, I investigated spontaneous rhythmic movements in response to music, infant-directed speech, and contrasting rhythmic patterns in 30…

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

    Science.gov (United States)

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

    2017-01-01

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

  7. Plantar pressure in diabetic peripheral neuropathy patients with active foot ulceration, previous ulceration and no history of ulceration: a meta-analysis of observational studies.

    Science.gov (United States)

    Fernando, Malindu Eranga; Crowther, Robert George; Pappas, Elise; Lazzarini, Peter Anthony; Cunningham, Margaret; Sangla, Kunwarjit Singh; Buttner, Petra; Golledge, Jonathan

    2014-01-01

    Elevated dynamic plantar pressures are a consistent finding in diabetes patients with peripheral neuropathy with implications for plantar foot ulceration. This meta-analysis aimed to compare the plantar pressures of diabetes patients that had peripheral neuropathy and those with neuropathy with active or previous foot ulcers. Published articles were identified from Medline via OVID, CINAHL, SCOPUS, INFORMIT, Cochrane Central EMBASE via OVID and Web of Science via ISI Web of Knowledge bibliographic databases. Observational studies reporting barefoot dynamic plantar pressure in adults with diabetic peripheral neuropathy, where at least one group had a history of plantar foot ulcers were included. Interventional studies, shod plantar pressure studies and studies not published in English were excluded. Overall mean peak plantar pressure (MPP) and pressure time integral (PTI) were primary outcomes. The six secondary outcomes were MPP and PTI at the rear foot, mid foot and fore foot. The protocol of the meta-analysis was published with PROPSERO, (registration number CRD42013004310). Eight observational studies were included. Overall MPP and PTI were greater in diabetic peripheral neuropathy patients with foot ulceration compared to those without ulceration (standardised mean difference 0.551, 95% CI 0.290-0.811, pdiabetic peripheral neuropathy with a history of foot ulceration compared to those with diabetic neuropathy without a history of ulceration. More homogenous data is needed to confirm these findings.

  8. Nonequilibrium Entropic Bounds for Darwinian Replicators

    Directory of Open Access Journals (Sweden)

    Jordi Piñero

    2018-01-01

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

  9. Partial Purification of a Megadalton DNA Replication Complex by Free Flow Electrophoresis.

    Directory of Open Access Journals (Sweden)

    Caroline M Li

    Full Text Available We describe a gentle and rapid method to purify the intact multiprotein DNA replication complex using free flow electrophoresis (FFE. In particular, we applied FFE to purify the human cell DNA synthesome, which is a multiprotein complex that is fully competent to carry-out all phases of the DNA replication process in vitro using a plasmid containing the simian virus 40 (SV40 origin of DNA replication and the viral large tumor antigen (T-antigen protein. The isolated native DNA synthesome can be of use in studying the mechanism by which mammalian DNA replication is carried-out and how anti-cancer drugs disrupt the DNA replication or repair process. Partially purified extracts from HeLa cells were fractionated in a native, liquid based separation by FFE. Dot blot analysis showed co-elution of many proteins identified as part of the DNA synthesome, including proliferating cell nuclear antigen (PCNA, DNA topoisomerase I (topo I, DNA polymerase δ (Pol δ, DNA polymerase ɛ (Pol ɛ, replication protein A (RPA and replication factor C (RFC. Previously identified DNA synthesome proteins co-eluted with T-antigen dependent and SV40 origin-specific DNA polymerase activity at the same FFE fractions. Native gels show a multiprotein PCNA containing complex migrating with an apparent relative mobility in the megadalton range. When PCNA containing bands were excised from the native gel, mass spectrometric sequencing analysis identified 23 known DNA synthesome associated proteins or protein subunits.

  10. Partial Purification of a Megadalton DNA Replication Complex by Free Flow Electrophoresis.

    Science.gov (United States)

    Li, Caroline M; Miao, Yunan; Lingeman, Robert G; Hickey, Robert J; Malkas, Linda H

    2016-01-01

    We describe a gentle and rapid method to purify the intact multiprotein DNA replication complex using free flow electrophoresis (FFE). In particular, we applied FFE to purify the human cell DNA synthesome, which is a multiprotein complex that is fully competent to carry-out all phases of the DNA replication process in vitro using a plasmid containing the simian virus 40 (SV40) origin of DNA replication and the viral large tumor antigen (T-antigen) protein. The isolated native DNA synthesome can be of use in studying the mechanism by which mammalian DNA replication is carried-out and how anti-cancer drugs disrupt the DNA replication or repair process. Partially purified extracts from HeLa cells were fractionated in a native, liquid based separation by FFE. Dot blot analysis showed co-elution of many proteins identified as part of the DNA synthesome, including proliferating cell nuclear antigen (PCNA), DNA topoisomerase I (topo I), DNA polymerase δ (Pol δ), DNA polymerase ɛ (Pol ɛ), replication protein A (RPA) and replication factor C (RFC). Previously identified DNA synthesome proteins co-eluted with T-antigen dependent and SV40 origin-specific DNA polymerase activity at the same FFE fractions. Native gels show a multiprotein PCNA containing complex migrating with an apparent relative mobility in the megadalton range. When PCNA containing bands were excised from the native gel, mass spectrometric sequencing analysis identified 23 known DNA synthesome associated proteins or protein subunits.

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

    Science.gov (United States)

    Dewar, James M; Walter, Johannes C

    2013-03-04

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

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

    National Research Council Canada - National Science Library

    Firshein, William

    1998-01-01

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

  13. Phase II study of a 3-day schedule with topotecan and cisplatin in patients with previously untreated small cell lung cancer and extensive disease

    DEFF Research Database (Denmark)

    Sorensen, M.; Lassen, Ulrik Niels; Jensen, Peter Buhl

    2008-01-01

    INTRODUCTION: Treatment with a topoisomerase I inhibitor in combination with a platinum results in superior or equal survival compared with etoposide-based treatment in extensive disease small cell lung cancer (SCLC). Five-day topotecan is inconvenient and therefore shorter schedules of topotecan...... and cisplatin are needed. The aim of this phase II study was to establish the response rate and response duration in chemo-naive patients with SCLC receiving a 3-day topotecan and cisplatin schedule. METHODS: Simons optimal two-stage design was used. Patients with previously untreated extensive disease SCLC...... age was 59 (range 44-74), 79% had performance status 0 or 1. Thirty-one patients completed all six cycles. Grade 3/4 anemia, neutrocytopenia, and thrombocytopenia were recorded in 9.5%, 66.7%, and 21.4% of patients, respectively. Fourteen percent of patients experienced neutropenic fever. No episodes...

  14. Lack of replication of thirteen single-nucleotide polymorphisms implicated in Parkinson’s disease: a large-scale international study

    Science.gov (United States)

    Elbaz, Alexis; Nelson, Lorene M; Payami, Haydeh; Ioannidis, John P A; Fiske, Brian K; Annesi, Grazia; Belin, Andrea Carmine; Factor, Stewart A; Ferrarese, Carlo; Hadjigeorgiou, Georgios M; Higgins, Donald S; Kawakami, Hideshi; Krüger, Rejko; Marder, Karen S; Mayeux, Richard P; Mellick, George D; Nutt, John G; Ritz, Beate; Samii, Ali; Tanner, Caroline M; Van Broeckhoven, Christine; Van Den Eeden, Stephen K; Wirdefeldt, Karin; Zabetian, Cyrus P; Dehem, Marie; Montimurro, Jennifer S; Southwick, Audrey; Myers, Richard M; Trikalinos, Thomas A

    2013-01-01

    Summary Background A genome-wide association study identified 13 single-nucleotide polymorphisms (SNPs) significantly associated with Parkinson’s disease. Small-scale replication studies were largely non-confirmatory, but a meta-analysis that included data from the original study could not exclude all SNP associations, leaving relevance of several markers uncertain. Methods Investigators from three Michael J Fox Foundation for Parkinson’s Research-funded genetics consortia—comprising 14 teams—contributed DNA samples from 5526 patients with Parkinson’s disease and 6682 controls, which were genotyped for the 13 SNPs. Most (88%) participants were of white, non-Hispanic descent. We assessed log-additive genetic effects using fixed and random effects models stratified by team and ethnic origin, and tested for heterogeneity across strata. A meta-analysis was undertaken that incorporated data from the original genome-wide study as well as subsequent replication studies. Findings In fixed and random-effects models no associations with any of the 13 SNPs were identified (odds ratios 0·89 to 1·09). Heterogeneity between studies and between ethnic groups was low for all SNPs. Subgroup analyses by age at study entry, ethnic origin, sex, and family history did not show any consistent associations. In our meta-analysis, no SNP showed significant association (summary odds ratios 0·95 to 1.08); there was little heterogeneity except for SNP rs7520966. Interpretation Our results do not lend support to the finding that the 13 SNPs reported in the original genome-wide association study are genetic susceptibility factors for Parkinson’s disease. PMID:17052658

  15. Assessment of heterogeneity between European Populations: a Baltic and Danish replication case-control study of SNPs from a recent European ulcerative colitis genome wide association study

    DEFF Research Database (Denmark)

    Andersen, Vibeke; Ernst, Anja; Sventoraityte, Jurgita

    2011-01-01

    the combined Baltic, Danish, and Norwegian panel versus the combined German, British, Belgian, and Greek panel (rs7520292 (P = 0.001), rs12518307 (P = 0.007), and rs2395609 (TCP11) (P = 0.01), respectively). No SNP reached genome-wide significance in the combined analyses of all the panels. Conclusions......Background: Differences in the genetic architecture of inflammatory bowel disease between different European countries and ethnicities have previously been reported. In the present study, we wanted to assess the role of 11 newly identified UC risk variants, derived from a recent European UC genome...... wide association study (GWAS) (Franke et al., 2010), for 1) association with UC in the Nordic countries, 2) for population heterogeneity between the Nordic countries and the rest of Europe, and, 3) eventually, to drive some of the previous findings towards overall genome-wide significance. Methods...

  16. Quantitative live imaging of endogenous DNA replication in mammalian cells.

    Directory of Open Access Journals (Sweden)

    Andrew Burgess

    Full Text Available Historically, the analysis of DNA replication in mammalian tissue culture cells has been limited to static time points, and the use of nucleoside analogues to pulse-label replicating DNA. Here we characterize for the first time a novel Chromobody cell line that specifically labels endogenous PCNA. By combining this with high-resolution confocal time-lapse microscopy, and with a simplified analysis workflow, we were able to produce highly detailed, reproducible, quantitative 4D data on endogenous DNA replication. The increased resolution allowed accurate classification and segregation of S phase into early-, mid-, and late-stages based on the unique subcellular localization of endogenous PCNA. Surprisingly, this localization was slightly but significantly different from previous studies, which utilized over-expressed GFP tagged forms of PCNA. Finally, low dose exposure to Hydroxyurea caused the loss of mid- and late-S phase localization patterns of endogenous PCNA, despite cells eventually completing S phase. Taken together, these results indicate that this simplified method can be used to accurately identify and quantify DNA replication under multiple and various experimental conditions.

  17. 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.

  18. Replication-Competent Influenza A and B Viruses Expressing a Fluorescent Dynamic Timer Protein for In Vitro and In Vivo Studies.

    Directory of Open Access Journals (Sweden)

    Michael Breen

    Full Text Available Influenza A and B viruses (IAV and IBV, respectively cause annual seasonal human respiratory disease epidemics. In addition, IAVs have been implicated in occasional pandemics with inordinate health and economic consequences. Studying influenza viruses in vitro or in vivo requires the use of laborious secondary methodologies to identify infected cells. To circumvent this requirement, replication-competent infectious influenza viruses expressing an easily traceable fluorescent reporter protein can be used. Timer is a fluorescent protein that undergoes a time-dependent color emission conversion from green to red. The rate of spectral change is independent of Timer protein concentration and can be used to chronologically measure the duration of its expression. Here, we describe the generation of replication-competent IAV and IBV where the viral non-structural protein 1 (NS1 was fused to the fluorescent dynamic Timer protein. Timer-expressing IAV and IBV displayed similar plaque phenotypes and growth kinetics to wild-type viruses in tissue culture. Within infected cells, Timer's spectral shift can be used to measure the rate and cell-to-cell spread of infection using fluorescent microscopy, plate readers, or flow cytometry. The progression of Timer-expressing IAV infection was also evaluated in a mouse model, demonstrating the feasibility to characterize IAV cell-to-cell infections in vivo. By providing the ability to chronologically track viral spread, Timer-expressing influenza viruses are an excellent option to evaluate the in vitro and in vivo dynamics of viral infection.

  19. Replication of an Experimental Study Investigating the Efficacy of a Multisyllabic Word Reading Intervention With and Without Motivational Beliefs Training for Struggling Readers.

    Science.gov (United States)

    Toste, Jessica R; Capin, Philip; Williams, Kelly J; Cho, Eunsoo; Vaughn, Sharon

    2018-05-01

    This randomized control trial examined the efficacy of an intervention aimed at improving multisyllabic word reading (MWR) skills among fourth- and fifth-grade struggling readers ( n = 109, 48.6% male), as well as the relative effects of an embedded motivational beliefs training component. This study was a closely aligned replication of our earlier work. The intervention was replicated with a three-condition design: MWR only, MWR with a motivational beliefs component, and business-as-usual control. Students were tutored in small groups for 40 lessons (four 40-min lessons each week). When we combined performance of students in both MWR conditions, intervention students significantly outperformed controls on proximal measures of affix reading and MWR, as well as standardized measures of decoding, spelling, and text comprehension. Furthermore, there was a noted interaction between English learner status and treatment on spelling performance. There were no statistically significant main effects between the MWR groups on proximal or standardized measures of interest. Findings are discussed in terms of their relevance to MWR instruction for students with persistent reading difficulties and considerations for future research related to the malleability of motivation.

  20. EXPERIMENTAL CHALLENGE STUDY OF FV3-LIKE RANAVIRUS INFECTION IN PREVIOUSLY FV3-LIKE RANAVIRUS INFECTED EASTERN BOX TURTLES (TERRAPENE CAROLINA CAROLINA) TO ASSESS INFECTION AND SURVIVAL.

    Science.gov (United States)

    Hausmann, Jennifer C; Wack, Allison N; Allender, Matthew C; Cranfield, Mike R; Murphy, Kevin J; Barrett, Kevin; Romero, Jennell L; Wellehan, James F X; Blum, Stella A; Zink, M Christine; Bronson, Ellen

    2015-12-01

    The Maryland Zoo in Baltimore experienced an outbreak of Frog virus-3 (FV3)-like ranavirus during the summer of 2011, during which 14 of 27 (52%) of its captive eastern box turtles (Terrapene carolina carolina) survived. To assess survival, immunity, and viral shedding, an experimental challenge study was performed in which the surviving, previously infected turtles were reinfected with the outbreak strain of FV3-like ranavirus. Seven turtles were inoculated with virus intramuscularly and four control turtles received saline intramuscularly. The turtles were monitored for 8 wk with blood and oral swabs collected for quantitative polymerase chain reaction (qPCR). During that time, one of seven (14%) inoculated turtles and none of the controls (0%) died; there was no significant difference in survival. Clinical signs of the inoculated turtles, except for the turtle that died, were mild compared to the original outbreak. Quantitative PCR for FV3-like ranavirus on blood and oral swabs was positive for all inoculated turtles and negative for all controls. The turtle that died had intracytoplasmic inclusion bodies in multiple organs. Three inoculated and two control turtles were euthanized at the end of the study. No inclusion bodies were present in any of the organs. Quantitative PCR detected FV3-like ranavirus in the spleen of a control turtle, which suggested persistence of the virus. The surviving five turtles were qPCR-negative for FV3-like ranavirus from blood and oral swabs after brumation. Quantitative PCR for Terrapene herpesvirus 1 found no association between ranavirus infection and herpesvirus loads. In conclusion, previously infected eastern box turtles can be reinfected with the same strain of FV3-like ranavirus and show mild to no clinical signs but can shed the virus from the oral cavity.

  1. Trial of labour and vaginal birth after previous caesarean section: A population based study of Eastern African immigrants in Victoria, Australia.

    Science.gov (United States)

    Belihu, Fetene B; Small, Rhonda; Davey, Mary-Ann

    2017-03-01

    Variations in caesarean section (CS) between some immigrant groups and receiving country populations have been widely reported. Often, African immigrant women are at higher risk of CS than the receiving population in developed countries. However, evidence about subsequent mode of birth following CS for African women post-migration is lacking. The objective of this study was to examine differences in attempted and successful vaginal birth after previous caesarean (VBAC) for Eastern African immigrants (Eritrea, Ethiopia, Somalia and Sudan) compared with Australian-born women. A population-based observational study was conducted using the Victorian Perinatal Data Collection. Pearson's chi-square test and logistic regression analysis were performed to generate adjusted odds ratios for attempted and successful VBAC. Victoria, Australia. 554 Eastern African immigrants and 24,587 Australian-born eligible women with previous CS having singleton births in public care. 41.5% of Eastern African immigrant women and 26.1% Australian-born women attempted a VBAC with 50.9% of Eastern African immigrants and 60.5% of Australian-born women being successful. After adjusting for maternal demographic characteristics and available clinical confounding factors, Eastern African immigrants were more likely to attempt (OR adj 1.94, 95% CI 1.57-2.47) but less likely to succeed (OR adj 0.54 95% CI 0.41-0.71) in having a VBAC. There are disparities in attempted and successful VBAC between Eastern African origin and Australian-born women. Unsuccessful VBAC attempt is more common among Eastern African immigrants, suggesting the need for improved strategies to select and support potential candidates for vaginal birth among these immigrants to enhance success and reduce potential complications associated with failed VBAC attempt. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  2. Biomarker-driven trial in metastatic pancreas cancer: feasibility in a multicenter study of saracatinib, an oral Src inhibitor, in previously treated pancreatic cancer

    International Nuclear Information System (INIS)

    Arcaroli, John; Quackenbush, Kevin; Dasari, Arvind; Powell, Rebecca; McManus, Martine; Tan, Aik-Choon; Foster, Nathan R; Picus, Joel; Wright, John; Nallapareddy, Sujatha; Erlichman, Charles; Hidalgo, Manuel; Messersmith, Wells A

    2012-01-01

    Src tyrosine kinases are overexpressed in pancreatic cancers, and the oral Src inhibitor saracatinib has shown antitumor activity in preclinical models of pancreas cancer. We performed a CTEP-sponsored Phase II clinical trial of saracatinib in previously treated pancreas cancer patients, with a primary endpoint of 6-month survival. A Simon MinMax two-stage phase II design was used. Saracatinib (175 mg/day) was administered orally continuously in 28-day cycles. In the unselected portion of the study, 18 patients were evaluable. Only two (11%) patients survived for at least 6 months, and three 6-month survivors were required to move to second stage of study as originally designed. The study was amended as a biomarker-driven trial (leucine rich repeat containing protein 19 [LRRC19] > insulin-like growth factor-binding protein 2 [IGFBP2] “top scoring pairs” polymerase chain reaction [PCR] assay, and PIK3CA mutant) based on preclinical data in a human pancreas tumor explant model. In the biomarker study, archival tumor tissue or fresh tumor biopsies were tested. Biomarker-positive patients were eligible for the study. Only one patient was PIK3CA mutant in a 3′ untranslated region (UTR) portion of the gene. This patient was enrolled in the study and failed to meet the 6-month survival endpoint. As the frequency of biomarker-positive patients was very low (<3%), the study was closed. Although we were unable to conclude whether enriching for a subset of second/third line pancreatic cancer patients treated with a Src inhibitor based on a biomarker would improve 6-month survival, we demonstrate that testing pancreatic tumor samples for a biomarker-driven, multicenter study in metastatic pancreas cancer is feasible

  3. Factors influencing microinjection molding replication quality

    Science.gov (United States)

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

    2018-01-01

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

  4. Women's decision-making processes and the influences on their mode of birth following a previous caesarean section in Taiwan: a qualitative study.

    Science.gov (United States)

    Chen, Shu-Wen; Hutchinson, Alison M; Nagle, Cate; Bucknall, Tracey K

    2018-01-17

    Vaginal birth after caesarean (VBAC) is an alternative option for women who have had a previous caesarean section (CS); however, uptake is limited because of concern about the risks of uterine rupture. The aim of this study was to explore women's decision-making processes and the influences on their mode of birth following a previous CS. A qualitative approach was used. The research comprised three stages. Stage I consisted of naturalistic observation at 33-34 weeks' gestation. Stage II involved interviews with pregnant women at 35-37 weeks' gestation. Stage III consisted of interviews with the same women who were interviewed postnatally, 1 month after birth. The research was conducted in a private medical centre in northern Taiwan. Using a purposive sampling, 21 women and 9 obstetricians were recruited. Data collection involved in-depth interviews, observation and field notes. Constant comparative analysis was employed for data analysis. Ensuring the safety of mother and baby was the focus of women's decisions. Women's decisions-making influences included previous birth experience, concern about the risks of vaginal birth, evaluation of mode of birth, current pregnancy situation, information resources and health insurance. In communicating with obstetricians, some women complied with obstetricians' recommendations for repeat caesarean section (RCS) without being informed of alternatives. Others used four step decision-making processes that included searching for information, listening to obstetricians' professional judgement, evaluating alternatives, and making a decision regarding mode of birth. After birth, women reflected on their decisions in three aspects: reflection on birth choices; reflection on factors influencing decisions; and reflection on outcomes of decisions. The health and wellbeing of mother and baby were the major concerns for women. In response to the decision-making influences, women's interactions with obstetricians regarding birth choices

  5. The Development of Replicated Optical Integral Field Spectrographs and their Application to the Study of Lyman-alpha Emission at Moderate Redshifts

    Science.gov (United States)

    Chonis, Taylor Steven

    In the upcoming era of extremely large ground-based astronomical telescopes, the design of wide-field spectroscopic survey instrumentation has become increasingly complex due to the linear growth of instrument pupil size with telescope diameter for a constant spectral resolving power. The upcoming Visible Integral field Replicable Unit Spectrograph (VIRUS), a baseline array of 150 copies of a simple integral field spectrograph that will be fed by 3:36 x 104 optical fibers on the upgraded Hobby-Eberly Telescope (HET) at McDonald Observatory, represents one of the first uses of large-scale replication to break the relationship between instrument pupil size and telescope diameter. By dividing the telescope's field of view between a large number of smaller and more manageable instruments, the total information grasp of a traditional monolithic survey spectrograph can be achieved at a fraction of the cost and engineering complexity. To highlight the power of this method, VIRUS will execute the HET Dark Energy Experiment (HETDEX) and survey & 420 degrees2 of sky to an emission line flux limit of ˜ 10-17 erg s-1 cm -2 to detect ˜ 106 Lyman-alpha emitting galaxies (LAEs) as probes of large-scale structure at redshifts of 1:9 production of the suite of volume phase holographic (VPH) diffraction gratings for VIRUS is presented, which highlights the challenge and success associated with producing of a very large number of highly customized optical elements whose performance is crucial to meeting the efficiency requirements of the spectrograph system. To accommodate VIRUS, the HET is undergoing a substantial wide-field upgrade to increase its field of view to 22' in diameter. The previous HET facility Low Resolution Spectrograph (LRS), which was directly fed by the telescope's previous spherical aberration corrector, must be removed from the prime focus instrument package as a result of the telescope upgrades and instead be fiber-coupled to the telescope focal plane. For a

  6. Four Forensic Entomology Case Studies: Records and Behavioral Observations on Seldom Reported Cadaver Fauna With Notes on Relevant Previous Occurrences and Ecology.

    Science.gov (United States)

    Lindgren, Natalie K; Sisson, Melissa S; Archambeault, Alan D; Rahlwes, Brent C; Willett, James R; Bucheli, Sibyl R

    2015-03-01

    A yearlong survey of insect taxa associated with human decomposition was conducted at the Southeast Texas Applied Forensic Science (STAFS) facility located in the Center for Biological Field Studies of Sam Houston State University in Huntsville, TX. During this study, four insect-cadaver interactions were observed that represent previously poorly documented yet forensically significant interactions: Syrphidae maggots colonized a corpse in an aquatic situation; Psychodidae adults mated and oviposited on an algal film that was present on a corpse that had been recently removed from water; several Panorpidae were the first insects to feed upon a freshly placed corpse in the autumn; and a noctuid caterpillar was found chewing and ingesting dried human skin. Baseline knowledge of insect-cadaver interactions is the foundation of forensic entomology, and unique observations have the potential to expand our understanding of decomposition ecology. © The Author 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  7. Comparative study between Federer and Gomez method for number of replication in complete randomized design using simulation: study of Areca Palm (Areca catechu) as organic waste for producing handicraft paper

    Science.gov (United States)

    Ihwah, A.; Deoranto, P.; Wijana, S.; Dewi, I. A.

    2018-03-01

    The part of Areca Palm (Areca catechu) that economical is the seed. It is commercially available in dried, cured and fresh forms, while the fibre is usually thrown away. Cellulose fibers from agricultural waste can be utilized as raw material for handicraft paper. Laboratory research showed that Areca palm fibre contained 70.2% of cellulose, 10.92% of water, and 6.02% of ash. This indicated that Areca palm fibre is very potential to be processed as handicraft paper. Handicraft paper is made of wastepaper or plants which cointain celluloce to produce rough-textured paper. In order to obtain preferred sensory quality of handicraft paper such as color, fiber appearance and texture as well as good physical quantity such as tensile strength, tear resistance and grammage, the addition of wastepaper to provide secondary fibre and sometimes adhesive are needed in making handicraft paper. Handicraft paper making was one alternative to treat the solid waste and to reduce the use of wood fiber as paper raw material. The aim of this study is to compare the two most famous method, i.e. Federer and Gomez Method, for calculate the number of replications. This study is preliminary research before do the research in order to get the best treatment to produce handicraft paper. The Gomez method calculates fewer replications than the Federer method. Based on data simulation the error generated using 3 replicates of 0.0876 while using 2 replicates of 0.1032.

  8. Late tamoxifen in patients previously operated for breast cancer without postoperative tamoxifen: 5-year results of a single institution randomised study

    International Nuclear Information System (INIS)

    Veronesi, Andrea; Miolo, GianMaria; Magri, Maria D; Crivellari, Diana; Scalone, Simona; Bidoli, Ettore; Lombardi, Davide

    2010-01-01

    A population of breast cancer patients exists who, for various reasons, never received adjuvant post-operative tamoxifen (TAM). This study was aimed to evaluate the role of late TAM in these patients. From 1997 to 2003, patients aged 35 to 75 years, operated more than 2 years previously for monolateral breast cancer without adjuvant TAM, with no signs of metastases and no contraindication to TAM were randomized to TAM 20 mg/day orally for 2 years or follow-up alone. Events were categorized as locoregional relapse, distant metastases, metachronous breast cancer, tumours other than breast cancer and death from any causes, whichever occurred first. The sample size (197 patients per arm, plus 10% allowance) was based on the assumption of a 30% decrease in the number of events occurring at a rate of 5% annually in the 10 years following randomization. Four hundred and thirty-three patients were randomized in the study (TAM 217, follow-up 216). Patients characteristics (TAM/follow-up) included: median age 55/55 years, median time from surgery 25/25 months (range, 25-288/25-294), in situ carcinoma 18/24, oestrogen receptor (ER) positive in 75/68, negative in 70/57, unknown in 72/91 patients. Previous adjuvant treatment included chemotherapy in 131/120 and an LHRH analogue in 11/13 patients. Thirty-six patients prematurely discontinued TAM after a median of 1 month, mostly because of subjective intolerance. Eighty-three events (TAM 39, follow-up 44) occurred: locoregional relapse in 10/8, distant metastases in 14/16, metachronous breast cancer in 4/10, other tumours in 11/10 patients. Less ER-positive secondary breast cancers occurred in the TAM treated patients than in follow-up patients (1 vs 10, p = 0.005). Event-free survival was similar in both groups of patients. This 5-year analysis revealed significantly less metachronous ER-positive breast cancers in the TAM treated patients. No other statistically significant differences have emerged thus far

  9. Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Prevented Weight Regain in Obese Women with Polycystic Ovary Syndrome Previously Treated with Liraglutide: A Pilot Randomized Study.

    Science.gov (United States)

    Ferjan, Simona; Janez, Andrej; Jensterle, Mojca

    2017-12-01

    Weight loss is often nonsustainable after liraglutide cessation. The present study is the first insight into the potential prevention of weight regain in obese subjects who have been withdrawn from liraglutide. We evaluated whether dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin in adjunct to metformin prevents body weight regain more effectively than metformin alone in obese polycystic ovary syndrome (PCOS) previously treated with liraglutide. A 12-week prospective randomized open-label study was conducted with 24 obese women with PCOS who had been pretreated with liraglutide 3.0 mg due to antiobesity management (aged 34.3 ± 6.8 years, body mass index [BMI] 36.3 ± 5.2 kg/m 2 , mean ± standard deviation). They were randomized to combined treatment (COMBO) with sitagliptin 100 mg per day (QD) and metformin (MET) 1000 mg twice daily (BID) (n = 12) or MET 1000 mg BID (n = 12). Lifestyle intervention was promoted in both groups. The primary outcome was change in anthropometric measures of obesity. Women treated with MET regain 4.7 ± 2.7 kg (P = 0.002) compared with a 0.9 ± 2.5 kg in COMBO (P = 0.147). BMI increased for 1.7 ± 0.9 kg/m 2 in MET (P = 0.002) compared with 0.3 ± 0.8 kg/m 2 increase in COMBO (P = 0.136). MET group regain 4.5% ± 2.5% of body weight as opposed to 0.8% ± 2.6% in COMBO. The between-treatment differences were significant for weight change (P weight change (P weight regain in obese women with PCOS previously treated with liraglutide.

  10. Cathepsin B & L are not required for ebola virus replication.

    Science.gov (United States)

    Marzi, Andrea; Reinheckel, Thomas; Feldmann, Heinz

    2012-01-01

    Ebola virus (EBOV), family Filoviridae, emerged in 1976 on the African continent. Since then it caused several outbreaks of viral hemorrhagic fever in humans with case fatality rates up to 90% and remains a serious Public Health concern and biothreat pathogen. The most pathogenic and best-studied species is Zaire ebolavirus (ZEBOV). EBOV encodes one viral surface glycoprotein (GP), which is essential for replication, a determinant of pathogenicity and an important immunogen. GP mediates viral entry through interaction with cellular surface molecules, which results in the uptake of virus particles via macropinocytosis. Later in this pathway endosomal acidification activates the cysteine proteases Cathepsin B and L (CatB, CatL), which have been shown to cleave ZEBOV-GP leading to subsequent exposure of the putative receptor-binding and fusion domain and productive infection. We studied the effect of CatB and CatL on in vitro and in vivo replication of EBOV. Similar to previous findings, our results show an effect of CatB, but not CatL, on ZEBOV entry into cultured cells. Interestingly, cell entry by other EBOV species (Bundibugyo, Côte d'Ivoire, Reston and Sudan ebolavirus) was independent of CatB or CatL as was EBOV replication in general. To investigate whether CatB and CatL have a role in vivo during infection, we utilized the mouse model for ZEBOV. Wild-type (control), catB(-/-) and catL(-/-) mice were equally susceptible to lethal challenge with mouse-adapted ZEBOV with no difference in virus replication and time to death. In conclusion, our results show that CatB and CatL activity is not required for EBOV replication. Furthermore, EBOV glycoprotein cleavage seems to be mediated by an array of proteases making targeted therapeutic approaches difficult.

  11. Cathepsin B & L are not required for ebola virus replication.

    Directory of Open Access Journals (Sweden)

    Andrea Marzi

    Full Text Available Ebola virus (EBOV, family Filoviridae, emerged in 1976 on the African continent. Since then it caused several outbreaks of viral hemorrhagic fever in humans with case fatality rates up to 90% and remains a serious Public Health concern and biothreat pathogen. The most pathogenic and best-studied species is Zaire ebolavirus (ZEBOV. EBOV encodes one viral surface glycoprotein (GP, which is essential for replication, a determinant of pathogenicity and an important immunogen. GP mediates viral entry through interaction with cellular surface molecules, which results in the uptake of virus particles via macropinocytosis. Later in this pathway endosomal acidification activates the cysteine proteases Cathepsin B and L (CatB, CatL, which have been shown to cleave ZEBOV-GP leading to subsequent exposure of the putative receptor-binding and fusion domain and productive infection. We studied the effect of CatB and CatL on in vitro and in vivo replication of EBOV. Similar to previous findings, our results show an effect of CatB, but not CatL, on ZEBOV entry into cultured cells. Interestingly, cell entry by other EBOV species (Bundibugyo, Côte d'Ivoire, Reston and Sudan ebolavirus was independent of CatB or CatL as was EBOV replication in general. To investigate whether CatB and CatL have a role in vivo during infection, we utilized the mouse model for ZEBOV. Wild-type (control, catB(-/- and catL(-/- mice were equally susceptible to lethal challenge with mouse-adapted ZEBOV with no difference in virus replication and time to death. In conclusion, our results show that CatB and CatL activity is not required for EBOV replication. Furthermore, EBOV glycoprotein cleavage seems to be mediated by an array of proteases making targeted therapeutic approaches difficult.

  12. 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.

  13. The TGFB1 gene is associated with curve severity but not with the development of adolescent idiopathic scoliosis: a replication study in the Chinese population.

    Science.gov (United States)

    Xu, Leilei; Sun, Weixiang; Qin, Xiaodong; Qiu, Yong; Zhu, Zezhang

    2016-01-13

    The transforming growth factor beta-1 (TGFB1) gene was recently reported to be a new susceptible gene of adolescent idiopathic scoliosis (AIS) in Russian population. This study aimed to replicate the relationship between the TGFB1 gene and the susceptibility of AIS in a Chinese population, and to further describe its association with the curve severity. A total of 1251 female AIS patients and 994 age-matched healthy controls were included in this study. The rs1800469 of TGFB1 gene was genotyped for all participants using the PCR-based Invader assay. The differences of genotype and allele distributions between AIS patients and healthy controls were assessed using the Chi-square test. One-way ANOVA test was used to compare the mean Cobb angles among patients with different genotypes. There was no significant difference in terms of the genotype and the allele frequency between the patients and the controls. The mean Cobb angle was 34.7 ± 11.9° (range 25-61°). Case-only analysis showed that rs1800469 was significantly associated with the curve severity. Patients with genotype TT had remarkably higher curve magnitude (39.1 ± 12.8°) than those with genotype CT (34.8 ± 11.1°) or CC (32.1 ± 10.6°). The TGFB1 gene may not be a predisposition gene of AIS in the Chinese population. However, it can play a role in the curve progression of AIS. Replication studies in other ethnic groups are warranted to understand the implication of TGFB1 gene in AIS.

  14. In vitro evaluation of oestrogenic/androgenic activity of the serum organochlorine pesticide mixtures previously described in a breast cancer case–control study

    International Nuclear Information System (INIS)

    Rivero, Javier; Luzardo, Octavio P.; Henríquez-Hernández, Luis A.; Machín, Rubén P.; Pestano, José; Zumbado, Manuel; Boada, Luis D.; Camacho, María; Valerón, Pilar F.

    2015-01-01

    Some organochlorine pesticides (OCs) have been individually linked to breast cancer (BC) because they exert oestrogenic effects on mammary cells. However, humans are environmentally exposed to more or less complex mixtures of these organochlorines, and the biological effects of these mixtures must be elucidated. In this work we evaluated the in vitro effects exerted on human BC cells by the OC mixtures that were most frequently detected in two groups of women who participated in a BC case–control study developed in Spain: healthy women and women diagnosed with BC. The cytotoxicity, oestrogenicity, and androgenicity of the most prevalent OC mixtures found in healthy women (H-mixture) and in BC patients (BC-mixture) were tested at concentrations that resembled those found in the serum of the evaluated women. Our results showed that both OC mixtures presented a similar oestrogenic activity and effect on cell viability, but BC-mixture showed an additional anti-androgenic effect. These results indicate that although the proliferative effect exerted by these mixtures on human breast cells seems to depend mainly on their oestrogenic action, the BC-mixture might additionally induce cell proliferation due to its anti-androgenic activity, therefore increasing the carcinogenic potential of this mixture. The findings of this study demonstrate that subtle variations in the composition of a mixture may induce relevant changes in its biological action. - Highlights: • E-screen and A-screen of two mixtures of organochlorine pesticides (OCP) • Assay concentrations based on a previous breast cancer case–control study • Only non-cytotoxic concentrations assayed • Both OCP mixtures induce proliferation mediated by oestrogen receptor. • OCP mixture of breast cancer patients exhibits additional androgenic activity.

  15. In vitro evaluation of oestrogenic/androgenic activity of the serum organochlorine pesticide mixtures previously described in a breast cancer case–control study

    Energy Technology Data Exchange (ETDEWEB)

    Rivero, Javier; Luzardo, Octavio P., E-mail: octavio.perez@ulpgc.es; Henríquez-Hernández, Luis A.; Machín, Rubén P.; Pestano, José; Zumbado, Manuel; Boada, Luis D.; Camacho, María; Valerón, Pilar F.

    2015-12-15

    Some organochlorine pesticides (OCs) have been individually linked to breast cancer (BC) because they exert oestrogenic effects on mammary cells. However, humans are environmentally exposed to more or less complex mixtures of these organochlorines, and the biological effects of these mixtures must be elucidated. In this work we evaluated the in vitro effects exerted on human BC cells by the OC mixtures that were most frequently detected in two groups of women who participated in a BC case–control study developed in Spain: healthy women and women diagnosed with BC. The cytotoxicity, oestrogenicity, and androgenicity of the most prevalent OC mixtures found in healthy women (H-mixture) and in BC patients (BC-mixture) were tested at concentrations that resembled those found in the serum of the evaluated women. Our results showed that both OC mixtures presented a similar oestrogenic activity and effect on cell viability, but BC-mixture showed an additional anti-androgenic effect. These results indicate that although the proliferative effect exerted by these mixtures on human breast cells seems to depend mainly on their oestrogenic action, the BC-mixture might additionally induce cell proliferation due to its anti-androgenic activity, therefore increasing the carcinogenic potential of this mixture. The findings of this study demonstrate that subtle variations in the composition of a mixture may induce relevant changes in its biological action. - Highlights: • E-screen and A-screen of two mixtures of organochlorine pesticides (OCP) • Assay concentrations based on a previous breast cancer case–control study • Only non-cytotoxic concentrations assayed • Both OCP mixtures induce proliferation mediated by oestrogen receptor. • OCP mixture of breast cancer patients exhibits additional androgenic activity.

  16. The role of avoidant and obsessive-compulsive personality disorder traits in matching patients with major depression to cognitive behavioral and psychodynamic therapy: A replication study.

    Science.gov (United States)

    Kikkert, Martijn J; Driessen, Ellen; Peen, Jaap; Barber, Jacques P; Bockting, Claudi; Schalkwijk, Frans; Dekker, Jeff; Dekker, Jack J M

    2016-11-15

    Barber and Muenz (1996) reported that cognitive behavior therapy (CBT) was more effective than interpersonal therapy (IPT) for depressed patients with elevated levels of avoidant personality disorder, while IPT was more effective than CBT in patients with elevated levels of obsessive-compulsive personality disorder. These findings may have important clinical implications, but have not yet been replicated. We conducted a study using data from a randomized clinical trial comparing the efficacy of CBT and short-term psychodynamic supportive psychotherapy in the outpatient treatment of depression. We found no evidence indicating that avoidant patients may benefit more from CBT compared to short-term psychodynamic supportive therapy (SPSP). Our results indicate that treatment effect does not depend on the level of avoidance, or obsessive-compulsiveness personality disorders further examine the influence of personality disorders on the effectiveness of CBT or psychodynamic therapy in the treatment of depression. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Evaluation of the Widal tube agglutination test for the diagnosis of typhoid fever among children admitted to a rural hdospital in Tanzania and a comparison with previous studies

    Directory of Open Access Journals (Sweden)

    Malahiyo Rajabu

    2010-06-01

    Full Text Available Abstract Background The diagnosis of typhoid fever is confirmed by culture of Salmonella enterica serotype Typhi (S. typhi. However, a more rapid, simpler, and cheaper diagnostic method would be very useful especially in developing countries. The Widal test is widely used in Africa but little information exists about its reliability. Methods We assessed the performance of the Widal tube agglutination test among febrile hospitalized Tanzanian children. We calculated the sensitivity, specificity, positive predictive value (PPV, and negative predictive value (NPV of various anti-TH and -TO titers using culture-confirmed typhoid fever cases as the "true positives" and all other febrile children with blood culture negative for S. typhi as the "true negatives." Results We found that 16 (1% of 1,680 children had culture-proven typhoid fever. A single anti-TH titer of 1:80 and higher was the optimal indicator of typhoid fever. This had a sensitivity of 75%, specificity of 98%, NPV of 100%, but PPV was only 26%. We compared our main findings with those from previous studies. Conclusion Among febrile hospitalized Tanzanian children with a low prevalence of typhoid fever, a Widal titer of ≥ 1:80 performed well in terms of sensitivity, specificity, and NPV. However a test with improved PPV that is similarly easy to apply and cost-efficient is desirable.

  18. Caring for women wanting a vaginal birth after previous caesarean section: A qualitative study of the experiences of midwives and obstetricians.

    Science.gov (United States)

    Foureur, Maralyn; Turkmani, Sabera; Clack, Danielle C; Davis, Deborah L; Mollart, Lyndall; Leiser, Bernadette; Homer, Caroline S E

    2017-02-01

    One of the greatest contributors to the overall caesarean section rate is elective repeat caesarean section. Decisions around mode of birth are often complex for women and influenced by the views of the doctors and midwives who care for and counsel women. Women may be more likely to choose a repeat elective caesarean section (CS) if their health care providers lack skills and confidence in supporting vaginal birth after caesarean section (VBAC). To explore the views and experiences of providers in caring for women considering VBAC, in particular the decision-making processes and the communication of risk and safety to women. A descriptive interpretive method was utilised. Four focus groups with doctors and midwives were conducted. The central themes were: 'developing trust', 'navigating the system' and 'optimising support'. The impact of past professional experiences; the critical importance of continuity of carer and positive relationships; the ability to weigh up risks versus benefits; and the language used were all important elements. The role of policy and guidelines on providing standardised care for women who had a previous CS was also highlighted. Midwives and doctors in this study were positively oriented towards assisting and supporting women to attempt a VBAC. Care providers considered that women who have experienced a prior CS need access to midwifery continuity of care with a focus on support, information-sharing and effective communication. Copyright © 2016 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

  19. Gefitinib plus cisplatin and radiotherapy in previously untreated head and neck squamous cell carcinoma: A phase II, randomized, double-blind, placebo-controlled study

    International Nuclear Information System (INIS)

    Gregoire, Vincent; Hamoir, Marc; Chen Changhu; Kane, Madeleine; Kawecki, Andrzej; Julka, Pramod K.; Wang, Hung-Ming; Prasad, Srihari; D'Cruz, Anil K.; Radosevic-Jelic, Ljiljana; Kumar, Rejnish R.; Korzeniowski, Stanislaw; Fijuth, Jacek; Machiels, Jean-Pascal; Sellers, Mark V.; Tchakov, Ilian; Raben, David

    2011-01-01

    Background and purpose: To assess the efficacy and safety of gefitinib given concomitantly and/or as maintenance therapy to standard cisplatin/radiotherapy for previously untreated, unresected, stage III/IV non-metastatic SCCHN. Materials and methods: In this phase II, double-blind, study, 226 patients were randomized to gefitinib 250 mg/day, 500 mg/day or placebo in two phases: a concomitant phase (gefitinib or placebo with chemoradiotherapy), followed by a maintenance phase (gefitinib or placebo alone). Primary endpoint was local disease control rate (LDCR) at 2 years; secondary endpoints were LDCR at 1 year, objective response rate, progression-free survival, overall survival, and safety and tolerability. Results: Gefitinib (250 and 500 mg/day) did not improve 2-year LDCR compared with placebo either when given concomitantly with chemoradiotherapy (32.7% vs. 33.6%, respectively; OR 0.921, 95% CI 0.508, 1.670 [1-sided p = 0.607]) or as maintenance therapy (28.8% vs. 37.4%, respectively; OR 0.684, 95% CI 0.377, 1.241 [1-sided p = 0.894]). Secondary efficacy outcomes were broadly consistent with the 2-year LDCR results. In both doses, gefitinib was well-tolerated and did not adversely affect the safety and tolerability of concomitant chemoradiotherapy. Conclusion: Gefitinib was well-tolerated, but did not improve efficacy compared with placebo when given concomitantly with chemoradiotherapy, or as maintenance therapy alone.

  20. Mechanisms of DNA replication termination.

    Science.gov (United States)

    Dewar, James M; Walter, Johannes C

    2017-08-01

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

  1. Prevalence of pain in the head, back and feet in refugees previously exposed to torture: a ten-year follow-up study

    DEFF Research Database (Denmark)

    Olsen, Dorthe Reff; Montgomery, Edith; Bøjholm, Søren

    2007-01-01

    AIM: To estimate change over 10 years concerning the prevalence of pain in the head, back and feet, among previously tortured refugees settled in Denmark, and to compare associations between methods of torture and prevalent pain at baseline and at 10-year follow-up. METHODS: 139 refugees previous...... associated with the type and bodily focus of the torture. This presents a considerable challenge to future evidence-based development of effective treatment programs....

  2. Mapping replication origins in yeast chromosomes.

    Science.gov (United States)

    Brewer, B J; Fangman, W L

    1991-07-01

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

  3. Chromatin replication and epigenome maintenance

    DEFF Research Database (Denmark)

    Alabert, Constance; Groth, Anja

    2012-01-01

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

  4. Immunogenicity and safety of tetravalent dengue vaccine in 2-11 year-olds previously vaccinated against yellow fever: randomized, controlled, phase II study in Piura, Peru.

    Science.gov (United States)

    Lanata, Claudio F; Andrade, Teresa; Gil, Ana I; Terrones, Cynthia; Valladolid, Omar; Zambrano, Betzana; Saville, Melanie; Crevat, Denis

    2012-09-07

    In a randomized, placebo-controlled, monocenter, observer blinded study conducted in an area where dengue is endemic, we assessed the safety and immunogenicity of a recombinant, live, attenuated, tetravalent dengue vaccine candidate (CYD-TDV) in 2-11 year-olds with varying levels of pre-existing yellow-fever immunity due to vaccination 1-7 years previously. 199 children received 3 injections of CYD-TDV (months 0, 6 and 12) and 99 received placebo (months 0 and 6) or pneumococcal polysaccharide vaccine (month 12). One month after the third dengue vaccination, serotype specific neutralizing antibody GMTs were in the range of 178-190 (1/dil) (versus 16.7-38.1 in the control group), a 10-20 fold-increase from baseline, and 94% of vaccines were seropositive to all four serotypes (versus 39% in the control group). There were no vaccine-related SAEs. The observed reactogenicity profile was consistent with phase I studies, with severity grade 1-2 injection site pain, headache, malaise and fever most frequently reported and no increase after subsequent vaccinations. Virologically confirmed dengue cases were seen after completion of the 3 doses: 1 in the CYD-TDV group (N=199), and 3 in the control group (N=99). A 3-dose regimen of CYD-TDV had a good safety profile in 2-11 year olds with a history of YF vaccination and elicited robust antibody responses that were balanced against the four serotypes. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. A phase II study of VP-16-ifosfamide-cisplatin combination chemotherapy plus early concurrent thoracic irradiation for previously untreated limited small cell lung cancer

    International Nuclear Information System (INIS)

    Woo, In Sook; Park, Young Suk; Kwon, Sung Hee

    2000-01-01

    At present the addition of thoracic irradiation to combination chemotherapy is a standard treatment for limited staged small cell ling cancer. However, there is still controversy about the optimum timing of chest irradiation. We conducted a phase II study of etoposide (VP-16)-ifosfamide-cisplatin (VIP) combination chemotherapy plus early concurrent thoracic irradiation for the patients with previously untreated limited small cell lung cancer in order to assess if the treatment modality could improve the response rate and the toxicity. Forty-four patients with limited small cell lung cancer were treated with etoposide-ifosfamide-cisplatin and concurrent thoracic irradiation. Combination chemotherapy consisted of etoposide 100 mg/m 2 (on day 1-3), ifosfamide 1000 mg/m 2 (on days 1 and 2) and cisplatin 100 mg/m 2 (on day 1). Concurrent thoracic irradiation consisted of a total of 4000 cGy over 4 weeks starting on the first day of the first chemotherapy. All patients who showed a complete response were given prophylactic cranial irradiation for 2.5 weeks. Forty-four of the 49 patients who entered the study from May 1994 to August 1998 were evaluable. The median age was 59 years and 40 patients had a performance status of 0 or 1. The median survival time was 22.5 months. Twenty-eight patients (62%) showed a complete response and 16 (38%) a partial response. Twenty-four patients (54%) developed grade 3 or 4 neutropenia; there was a 9% RTOG score 3 or 4 esophagitis. VIP combination chemotherapy and early concurrent thoracic irradiation for patients with limited stage small cell lung cancer revealed excellent antitumor response with tolerable toxicity. (author)

  6. Hypnotism as a Function of Trance State Effects, Expectancy, and Suggestibility: An Italian Replication.

    Science.gov (United States)

    Pekala, Ronald J; Baglio, Francesca; Cabinio, Monia; Lipari, Susanna; Baglio, Gisella; Mendozzi, Laura; Cecconi, Pietro; Pugnetti, Luigi; Sciaky, Riccardo

    2017-01-01

    Previous research using stepwise regression analyses found self-reported hypnotic depth (srHD) to be a function of suggestibility, trance state effects, and expectancy. This study sought to replicate and expand that research using a general state measure of hypnotic responsivity, the Phenomenology of Consciousness Inventory: Hypnotic Assessment Procedure (PCI-HAP). Ninety-five participants completed an Italian translation of the PCI-HAP, with srHD scores predicted from the PCI-HAP assessment items. The regression analysis replicated the previous research results. Additionally, stepwise regression analyses were able to predict the srHD score equally well using only the PCI dimension scores. These results not only replicated prior research but suggest how this methodology to assess hypnotic responsivity, when combined with more traditional neurophysiological and cognitive-behavioral methodologies, may allow for a more comprehensive understanding of that enigma called hypnosis.

  7. Surface Micro Topography Replication in Injection Moulding

    DEFF Research Database (Denmark)

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

    2005-01-01

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

  8. Replication of genome wide association studies on hepatocellular carcinoma susceptibility loci of STAT4 and HLA-DQ in a Korean population.

    Science.gov (United States)

    Kim, Lyoung Hyo; Cheong, Hyun Sub; Namgoong, Suhg; Kim, Ji On; Kim, Jeong-Hyun; Park, Byung Lae; Cho, Sung Won; Park, Neung Hwa; Cheong, Jae Youn; Koh, InSong; Shin, Hyoung Doo; Kim, Yoon-Jun

    2015-07-01

    A recent genome-wide association study (GWAS) for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) identified two loci (rs7574865 in STAT4 and rs9275319 in HLA-DQ) in a Chinese population. We attempted to replicate the associations between the two SNP loci and the risk of HCC in a Korean population. The rs7574865 in STAT4 and rs9275319 in HLA-DQ were genotyped in a total of 3838 Korean subjects composed of 287 HBV-related hepatocellular carcinoma patients, 671 chronic hepatitis B virus (CHB) patients, and 2880 population controls using TaqMan genotyping assay. Gene expression was measured by microarray. A logistic regression analysis revealed that rs7574865 in STAT4 and rs9275319 in HLA-DQ were associated with the risk of CHB (OR = 1.25, P = 0.0002 and OR = 1.57, P= 1.44 × 10(-10), respectively). However, these loci were no association with the risk of HBV-related HCC among CHB patients. In the gene expression analyses, although no significant differences in mRNA expression of nearby genes according to genotypes were detected, a significantly decreased mRNA expression in HCC subjects was observed in STAT4, HLA-DQA1, and HLA-DQB1. Although the genetic effects of two HCC susceptibility loci were not replicated, the two loci were found to exert susceptibility effects on the risk of CHB in a Korean population. In addition, the decreased mRNA expression of STAT4, HLA-DQA1, and HLA-DQB1 in HCC tissue might provide a clue to understanding their role in the progression to HCC. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. GWA study data mining and independent replication identify cardiomyopathy-associated 5 (CMYA5) as a risk gene for schizophrenia

    NARCIS (Netherlands)

    Chen, X.; Lee, G.; Maher, B. S.; Fanous, A. H.; Chen, J.; Zhao, Z.; Guo, A.; van den Oord, E.; Sullivan, P. F.; Shi, J.; Levinson, D. F.; Gejman, P. V.; Sanders, A.; Duan, J.; Owen, M. J.; Craddock, N. J.; O'Donovan, M. C.; Blackman, J.; Lewis, D.; Kirov, G. K.; Qin, W.; Schwab, S.; Wildenauer, D.; Chowdari, K.; Nimgaonkar, V.; Straub, R. E.; Weinberger, D. R.; O'Neill, F. A.; Walsh, D.; Bronstein, M.; Darvasi, A.; Lencz, T.; Malhotra, A. K.; Rujescu, D.; Giegling, I.; Werge, T.; Hansen, T.; Ingason, A.; Nöethen, M. M.; Rietschel, M.; Cichon, S.; Djurovic, S.; Andreassen, O. A.; Cantor, R. M.; Ophoff, R.; Corvin, A.; Morris, D. W.; Gill, M.; Pato, C. N.; Pato, M. T.; Macedo, A.; Gurling, H. M. D.; McQuillin, A.; Pimm, J.; Hultman, C.; Lichtenstein, P.; Sklar, P.; Purcell, S. M.; Scolnick, E.; St Clair, D.; Blackwood, D. H. R.; Kendler, K. S.; Kahn, René S.; Linszen, Don H.; van Os, Jim; Wiersma, Durk; Bruggeman, Richard; Cahn, Wiepke; de Haan, Lieuwe; Krabbendam, Lydia; Myin-Germeys, Inez; O'Donovan, Michael C.; Kirov, George K.; Craddock, Nick J.; Holmans, Peter A.; Williams, Nigel M.; Georgieva, Lyudmila; Nikolov, Ivan; Norton, N.; Williams, H.; Toncheva, Draga; Milanova, Vihra; Owen, Michael J.; Hultman, Christina M.; Lichtenstein, Paul; Thelander, Emma F.; Sullivan, Patrick; Morris, Derek W.; O'Dushlaine, Colm T.; Kenny, Elaine; Quinn, Emma M.; Gill, Michael; Corvin, Aiden; McQuillin, Andrew; Choudhury, Khalid; Datta, Susmita; Pimm, Jonathan; Thirumalai, Srinivasa; Puri, Vinay; Krasucki, Robert; Lawrence, Jacob; Quested, Digby; Bass, Nicholas; Gurling, Hugh; Crombie, Caroline; Fraser, Gillian; Kuan, Soh Leh; Walker, Nicholas; St Clair, David; Blackwood, Douglas H. R.; Muir, Walter J.; McGhee, Kevin A.; Pickard, Ben; Malloy, Pat; Maclean, Alan W.; van Beck, Margaret; Wray, Naomi R.; Macgregor, Stuart; Visscher, Peter M.; Pato, Michele T.; Medeiros, Helena; Middleton, Frank; Carvalho, Celia; Morley, Christopher; Fanous, Ayman; Conti, David; Knowles, James A.; Ferreira, Carlos Paz; Macedo, Antonio; Azevedo, M. Helena; Pato, Carlos N.; Stone, Jennifer L.; Ruderfer, Douglas M.; Kirby, Andrew N.; Ferreira, Manuel A. R.; Daly, Mark J.; Purcell, Shaun M.; Sklar, Pamela; Chambert, Kimberly; Kuruvilla, Finny; Gabriel, Stacey B.; Ardlie, Kristin; Moran, Jennifer L.; Scolnick, Edward M.

    2011-01-01

    We conducted data-mining analyses using the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and molecular genetics of schizophrenia genome-wide association study supported by the genetic association information network (MGS-GAIN) schizophrenia data sets and performed

  10. Spacetime replication of continuous variable quantum information

    International Nuclear Information System (INIS)

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

    2016-01-01

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

  11. Progerin sequestration of PCNA promotes replication fork collapse and mislocalization of XPA in laminopathy-related progeroid syndromes.

    Science.gov (United States)

    Hilton, Benjamin A; Liu, Ji; Cartwright, Brian M; Liu, Yiyong; Breitman, Maya; Wang, Youjie; Jones, Rowdy; Tang, Hui; Rusinol, Antonio; Musich, Phillip R; Zou, Yue

    2017-09-01

    Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder that is caused by a point mutation in the LMNA gene, resulting in production of a truncated farnesylated-prelamin A protein (progerin). We previously reported that XPA mislocalized to the progerin-induced DNA double-strand break (DSB) sites, blocking DSB repair, which led to DSB accumulation, DNA damage responses, and early replication arrest in HGPS. In this study, the XPA mislocalization to DSBs occurred at stalled or collapsed replication forks, concurrent with a significant loss of PCNA at the forks, whereas PCNA efficiently bound to progerin. This PCNA sequestration likely exposed ds-ssDNA junctions at replication forks for XPA binding. Depletion of XPA or progerin each significantly restored PCNA at replication forks. Our results suggest that although PCNA is much more competitive than XPA in binding replication forks, PCNA sequestration by progerin may shift the equilibrium to favor XPA binding. Furthermore, we demonstrated that progerin-induced apoptosis could be rescued by XPA, suggesting that XPA-replication fork binding may prevent apoptosis in HGPS cells. Our results propose a mechanism for progerin-induced genome instability and accelerated replicative senescence in HGPS.-Hilton, B. A., Liu, J., Cartwright, B. M., Liu, Y., Breitman, M., Wang, Y., Jones, R., Tang, H., Rusinol, A., Musich, P. R., Zou, Y. Progerin sequestration of PCNA promotes replication fork collapse and mislocalization of XPA in laminopathy-related progeroid syndromes. © FASEB.

  12. Food and Drug Administration criteria for the diagnosis of drug-induced valvular heart disease in patients previously exposed to benfluorex: a prospective multicentre study.

    Science.gov (United States)

    Maréchaux, Sylvestre; Rusinaru, Dan; Jobic, Yannick; Ederhy, Stéphane; Donal, Erwan; Réant, Patricia; Arnalsteen, Elise; Boulanger, Jacques; Garban, Thierry; Ennezat, Pierre-Vladimir; Jeu, Antoine; Szymanski, Catherine; Tribouilloy, Christophe

    2015-02-01

    The Food and Drug Administration (FDA) criteria for diagnosis of drug-induced valvular heart disease (DIVHD) are only based on the observation of aortic regurgitation ≥ mild and/or mitral regurgitation ≥ moderate. We sought to evaluate the diagnostic value of FDA criteria in a cohort of control patients and in a cohort of patients exposed to a drug (benfluorex) known to induce VHD. This prospective, multicentre study included 376 diabetic control patients not exposed to valvulopathic drugs and 1000 subjects previously exposed to benfluorex. Diagnosis of mitral or aortic DIVHD was based on a combined functional and morphological echocardiographic analysis of cardiac valves. Patients were classified according to the FDA criteria [mitral or aortic-FDA(+) and mitral or aortic-FDA(-)]. Among the 376 control patients, 2 were wrongly classified as mitral-FDA(+) and 17 as aortic-FDA(+) (0.53 and 4.5% of false positives, respectively). Of those exposed to benfluorex, 48 of 58 with a diagnosis of mitral DIVHD (83%) were classified as mitral-FDA(-), and 901 of the 910 patients (99%) without a diagnosis of the mitral DIVHD group were classified as mitral-FDA(-). All 40 patients with a diagnosis of aortic DIVHD were classified as aortic-FDA(+), and 105 of the 910 patients without a diagnosis of aortic DIVHD (12%) were classified aortic-FDA(+). Older age and lower BMI were independent predictors of disagreement between FDA criteria and the diagnosis of DIVHD in patients exposed to benfluorex (both P ≤ 0.001). FDA criteria solely based on the Doppler detection of cardiac valve regurgitation underestimate for the mitral valve and overestimate for the aortic valve the frequency of DIVHD. Therefore, the diagnosis of DIVHD must be based on a combined echocardiographic and Doppler morphological and functional analysis of cardiac valves. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

  13. SAFETY AND ACTIVITY OF TEMSIROLIMUS AND BEVACIZUMAB IN PATIENTS WITH ADVANCED RENAL CELL CARCINOMA PREVIOUSLY TREATED WITH TYROSINE KINASE INHIBITORS: A PHASE 2 CONSORTIUM STUDY

    Science.gov (United States)

    Merchan, Jaime R.; Qin, Rui; Pitot, Henry; Picus, Joel; Liu, Glenn; Fitch, Tom; Maples, William J.; Flynn, Patrick J.; Fruth, Briant F.; Erlichman, Charles

    2015-01-01

    Purpose Bevacizumab or Temsirolimus regimens have clinical activity in the first line treatment of advanced renal cell carcinoma (RCC). This phase I/II trial was conducted to determine the safety of combining both agents and its efficacy in RCC patients who progressed on at least one prior anti-VEGF receptor tyrosine kinase inhibitor (RTKI) agent. Methods In the phase I portion, eligible patients were treated with Temsirolimus (25 mg IV weekly) and escalating doses of IV Bevacizumab (level 1=5mg/kg; level 2=10 mg/kg) every other week. The primary endpoint for the phase II portion (RTKI resistant patients) was the 6-month progression free rate. Secondary endpoints were response rate, toxicity evaluation, PFS and OS. Results MTD was not reached at the maximum dose administered in 12 phase I patients. Forty evaluable patients were treated with the phase II recommended dose (Temsirolimus 25 mg IV weekly and Bevacizumab 10 mg/kg IV every two weeks). The 6-month progression free rate was 40% (16/40 pts). Median PFS was 5.9 (4-7.8) months, and median OS was 20.6 (11.5-23.7) months. Partial response/stable/progressive disease were seen in 23%/63%/14% of patients. Most common grade 3-4 AEs included fatigue (17.8%), hypertriglyceridemia (11.1%), stomatitis (8.9%), proteinuria (8.9%), abdominal pain (6.7%), and anemia (6.7%). Baseline levels of serum sFLT-1 and VEGF-A were inversely correlated with PFS and OS, respectively. Conclusions Temsirolimus and Bevacizumab is a feasible combination in patients with advanced RCC previously exposed to oral anti-VEGF agents. The safety and efficacy results warrant further confirmatory studies in this patient population. PMID:25556030

  14. Low-calorie energy drink improves physiological response to exercise in previously sedentary men: a placebo-controlled efficacy and safety study.

    Science.gov (United States)

    Lockwood, Christopher M; Moon, Jordan R; Smith, Abbie E; Tobkin, Sarah E; Kendall, Kristina L; Graef, Jennifer L; Cramer, Joel T; Stout, Jeffrey R

    2010-08-01

    Energy drink use has grown despite limited research to support efficacy or safety and amid concerns when combined with exercise. The purpose of this study was to assess the effects of 10 weeks of once-daily energy drink consumption or energy drink consumption with exercise on measures of body composition, cardiorespiratory fitness, strength, mood, and safety in previously sedentary males. Thirty-eight males were randomly assigned to energy drink + exercise (EX-A), energy drink (NEX-A), placebo + exercise (EX-B), or placebo (NEX-B). All participants consumed 1 drink per day for 10 weeks; EX-A and EX-B participated in 10 weeks of resistance and endurance exercise. Testing was performed before (PRE) and after (POST) the 10-week intervention. No significant (p > 0.05) changes were observed for body composition, fitness, or strength in NEX-A; however, significantly greater decreases in fat mass and percentage body fat and increases in VO2peak were observed in EX-A versus EX-B. Ventilatory threshold (VT), minute ventilation, VO2 at VT, and power output at VT improved significantly PRE to POST in EX-A but not in EX-B or nonexercising groups. Clinical markers for hepatic, renal, cardiovascular, and immune function, as determined by PRE and POST blood work revealed no adverse effects in response to the energy drink. Mood was not affected by energy drink use. Absent energy restriction or other dietary controls, chronic ingestion of a once-daily low-calorie energy drink appears ineffective at improving body composition, cardiorespiratory fitness, or strength in sedentary males. However, when combined with exercise, preworkout energy drink consumption may significantly improve some physiological adaptations to combined aerobic and resistance training.

  15. Phase I/II study of gefitinib (Iressa(®)) and vorinostat (IVORI) in previously treated patients with advanced non-small cell lung cancer.

    Science.gov (United States)

    Han, Ji-Youn; Lee, Soo Hyun; Lee, Geon Kook; Yun, Tak; Lee, Young Joo; Hwang, Kum Hui; Kim, Jin Young; Kim, Heung Tae

    2015-03-01

    Vorinostat has been shown to overcome resistance to gefitinib. We performed a phase I/II study combining gefitinib with vorinostat in previously treated non-small cell lung cancer (NSCLC). A 3 + 3 dose-escalation design was used to determine maximum tolerated dose (MTD) and recommended phase II dose (RP2D). Three dose levels were tested: 250 mg/day gefitinib on days 1-28 and 200, 300 or 400 mg/day vorinostat on days 1-7, and 15-21 out of every 28 days. The primary endpoint was median progression-free survival (PFS). Fifty-two patients were enrolled and treated (43 in phase II). The median age was 59 years, 28 patients were male, 44 had adenocarcinoma, 29 had never smoked, and 36 had undergone one prior treatment. Twenty-two patients exhibited sensitive EGFR mutations. Planned dose escalation was completed without reaching the MTD. The RP2D was 250 mg gefitinib and 400 mg vorinostat. In 43 assessable patients in phase II, the median PFS was 3.2 months; the overall survival (OS) was 19.0 months. There were 16 partial responses and six cases of stable disease. In EGFR-mutant NSCLC, response rate was 77 %, median PFS was 9.1 months, and median OS was 24.1 months. The most common adverse events were anorexia and diarrhea. Treatment with 250 mg gefitinib daily with biweekly 400 mg/day vorinostat was feasible and well tolerated. In an unselected patient population, this combination dose did not improve PFS. However, this combination showed a potential for improving efficacy of gefitinib in EGFR-mutant NSCLC (NCT01027676).

  16. Effect of donepezil in patients with Alzheimer's disease previously untreated or treated with memantine or nootropic agents in Germany: an observational study.

    Science.gov (United States)

    Klinger, Tatjana; Ibach, Bernd; Schoenknecht, Peter; Kamleiter, Martin; Silver, Gabrielle; Schroeder, Johannes; Mielke, Ruediger

    2005-05-01

    This open-label, prospective, observational, Post-Marketing Surveillance (PMS) study assessed the efficacy and safety of donepezil in patients who had been switched from therapies currently used in Germany to treat Alzheimer's disease (AD), such as memantine and nootropics, due to insufficient efficacy or poor tolerability. A treatment-naive population was included as a comparator. Patients with AD were treated with donepezil and observed for a period of approximately 3 months. A cognitive assessment was made using the Mini-Mental State Examination (MMSE). Quality of life (QoL) was assessed by the investigators who answered the question 'How did therapy with donepezil influence the QoL of the patient and/or his family over the observation period?' and was graded using three ratings: improved/unchanged/worsened. Adverse events (AEs) were also monitored. A total of 913 patients entered the study (mean +/- SD MMSE score 18.03 +/- 5.34). Efficacy assessments were analyzed for three groups: an overall group of patients who had received any form of prior AD drug therapy (N+ group; n = 709); a subgroup of patients from the N+ group who had received prior memantine therapy only (M+ group; n = 111) and patients who were drug treatment naive (N- group; n = 204). In the evaluable population donepezil improved MMSE scores by 2.21 +/- 3.47 points on average, with similar improvements observed in all three groups. QoL was judged to be improved in at least 70% of patients, again with similar results obtained for all three groups. Donepezil was well tolerated, with 85 of 913 (9.3%) patients reporting AEs. The most common AEs were those typically seen with cholinergic therapies (i.e., diarrhoea, vomiting and nausea). In this observational PMS study, donepezil was shown to be efficacious and well tolerated in patients who were being insufficiently treated with memantine or nootropic therapy. The magnitude of response was similar to that observed in patients who were previously

  17. Replication of TCF4 through association and linkage studies in late-onset Fuchs endothelial corneal dystrophy.

    Directory of Open Access Journals (Sweden)

    Yi-Ju Li

    Full Text Available Fuchs endothelial corneal dystrophy (FECD is a common, late-onset disorder of the corneal endothelium. Although progress has been made in understanding the genetic basis of FECD by studying large families in which the phenotype is transmitted in an autosomal dominant fashion, a recently reported genome-wide association study identified common alleles at a locus on chromosome 18 near TCF4 which confer susceptibility to FECD. Here, we report the findings of our independent validation study for TCF4 using the largest FECD dataset to date (450 FECD cases and 340 normal controls. Logistic regression with sex as a covariate was performed for three genetic models: dominant (DOM, additive (ADD, and recessive (REC. We found significant association with rs613872, the target marker reported by Baratz et al.(2010, for all three genetic models (DOM: P = 9.33×10(-35; ADD: P = 7.48×10(-30; REC: P = 5.27×10(-6. To strengthen the association study, we also conducted a genome-wide linkage scan on 64 multiplex families, composed primarily of affected sibling pairs (ASPs, using both parametric and non-parametric two-point and multipoint analyses. The most significant linkage region localizes to chromosome 18 from 69.94cM to 85.29cM, with a peak multipoint HLOD = 2.5 at rs1145315 (75.58cM under the DOM model, mapping 1.5 Mb proximal to rs613872. In summary, our study presents evidence to support the role of the intronic TCF4 single nucleotide polymorphism rs613872 in late-onset FECD through both association and linkage studies.

  18. The role of age in the perceptions of politics--job performance relationship: a three-study constructive replication.

    Science.gov (United States)

    Treadway, Darren C; Ferris, Gerald R; Hochwarter, Wayne; Perrewé, Pamela; Witt, L A; Goodman, Joseph M

    2005-09-01

    This research examined the interaction of organizational politics perceptions and employee age on job performance in 3 studies. On the basis of conservation of resources theory, the authors predicted that perceptions of politics would demonstrate their most detrimental effects on job performance for older workers. Results across the 3 studies provided strong support for the hypothesis that increases in politics perceptions are associated with decreases in job performance for older employees and that perceptions of politics do not affect younger employees' performance. Implications of these results, strengths and limitations, and directions for future research are discussed. Copyright 2005 APA, all rights reserved.

  19. Sunburn and sun-protective behaviors among adults with and without previous nonmelanoma skin cancer (NMSC): A population-based study.

    Science.gov (United States)

    Fischer, Alexander H; Wang, Timothy S; Yenokyan, Gayane; Kang, Sewon; Chien, Anna L

    2016-08-01

    Individuals with previous nonmelanoma skin cancer (NMSC) are at increased risk for subsequent skin cancer, and should therefore limit ultraviolet exposure. We sought to determine whether individuals with previous NMSC engage in better sun protection than those with no skin cancer history. We pooled self-reported data (2005 and 2010 National Health Interview Surveys) from US non-Hispanic white adults (758 with and 34,161 without previous NMSC). We calculated adjusted prevalence odds ratios (aPOR) and 95% confidence intervals (CI), taking into account the complex survey design. Individuals with previous NMSC versus no history of NMSC had higher rates of frequent use of shade (44.3% vs 27.0%; aPOR 1.41; 95% CI 1.16-1.71), long sleeves (20.5% vs 7.7%; aPOR 1.55; 95% CI 1.21-1.98), a wide-brimmed hat (26.1% vs 10.5%; aPOR 1.52; 95% CI 1.24-1.87), and sunscreen (53.7% vs 33.1%; aPOR 2.11; 95% CI 1.73-2.59), but did not have significantly lower odds of recent sunburn (29.7% vs 40.7%; aPOR 0.95; 95% CI 0.77-1.17). Among those with previous NMSC, recent sunburn was inversely associated with age, sun avoidance, and shade but not sunscreen. Self-reported cross-sectional data and unavailable information quantifying regular sun exposure are limitations. Physicians should emphasize sunburn prevention when counseling patients with previous NMSC, especially younger adults, focusing on shade and sun avoidance over sunscreen. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  20. The association between short periods of everyday life activities and affective states: a replication study using ambulatory assessment

    Directory of Open Access Journals (Sweden)

    Thomas eBossmann

    2013-04-01

    Full Text Available Regularly conducted exercise programs effectively influence affective states. Studies suggest that this is also true for short bouts of physical activity of ten minutes or less. Accordingly, everyday life activities of short duration might be used to regulate affective states. However, this association has rarely been studied in reference to unstructured activities in ongoing real-life situations. The current study examined the influence of various everyday life activities on three dimensions of mood (valence, calmness, energetic arousal in a predominantly inactive sample. Ambulatory Assessment (AA was used to investigate the association between actual physical activity (aPA and affective states during the course of one day. Seventy-seven students ages 19 - 30 participated in the study. aPA was assessed with accelerometers, and affective state assessments were conducted hourly using an e-diary with a six-item mood scale that was specially designed for AA. Multilevel analyses indicated that the mood dimensions energetic arousal (p = .001 and valence (p = .005 were positively influenced by the intensity of the activity carried out in the ten minutes prior to the assessment. As their activity increased, the participants’ positive feelings and energetic arousal increased. However, the students’ calmness was not affected by their activity levels. The findings highlight the importance of integrating short activity intervals of 10 minutes or less into everyday life routines to improve affective states.

  1. Replication of genome wide association studies of alcohol dependence: support for association with variation in ADH1C.

    Directory of Open Access Journals (Sweden)

    Joanna M Biernacka

    Full Text Available Genome-wide association studies (GWAS have revealed many single nucleotide polymorphisms (SNPs associated with complex traits. Although these studies frequently fail to identify statistically significant associations, the top association signals from GWAS may be enriched for true associations. We therefore investigated the association of alcohol dependence with 43 SNPs selected from association signals in the first two published GWAS of alcoholism. Our analysis of 808 alcohol-dependent cases and 1,248 controls provided evidence of association of alcohol dependence with SNP rs1614972 in the ADH1C gene (unadjusted p = 0.0017. Because the GWAS study that originally reported association of alcohol dependence with this SNP [1] included only men, we also performed analyses in sex-specific strata. The results suggest that this SNP has a similar effect in both sexes (men: OR (95%CI = 0.80 (0.66, 0.95; women: OR (95%CI = 0.83 (0.66, 1.03. We also observed marginal evidence of association of the rs1614972 minor allele with lower alcohol consumption in the non-alcoholic controls (p = 0.081, and independently in the alcohol-dependent cases (p = 0.046. Despite a number of potential differences between the samples investigated by the prior GWAS and the current study, data presented here provide additional support for the association of SNP rs1614972 in ADH1C with alcohol dependence and extend this finding by demonstrating association with consumption levels in both non-alcoholic and alcohol-dependent populations. Further studies should investigate the association of other polymorphisms in this gene with alcohol dependence and related alcohol-use phenotypes.

  2. Mcm2 phosphorylation and the response to replicative stress

    Directory of Open Access Journals (Sweden)

    Stead Brent E

    2012-05-01

    Full Text Available Abstract Background The replicative helicase in eukaryotic cells is comprised of minichromosome maintenance (Mcm proteins 2 through 7 (Mcm2-7 and is a key target for regulation of cell proliferation. In addition, it is regulated in response to replicative stress. One of the protein kinases that targets Mcm2-7 is the Dbf4-dependent kinase Cdc7 (DDK. In a previous study, we showed that alanine mutations of the DDK phosphorylation sites at S164 and S170 in Saccharomyces cerevisiae Mcm2 result in sensitivity to caffeine and methyl methanesulfonate (MMS leading us to suggest that DDK phosphorylation of Mcm2 is required in response to replicative stress. Results We show here that a strain with the mcm2 allele lacking DDK phosphorylation sites (mcm2AA is also sensitive to the ribonucleotide reductase inhibitor, hydroxyurea (HU and to the base analogue 5-fluorouracil (5-FU but not the radiomimetic drug, phleomycin. We screened the budding yeast non-essential deletion collection for synthetic lethal interactions with mcm2AA and isolated deletions that include genes involved in the control of genome integrity and oxidative stress. In addition, the spontaneous mutation rate, as measured by mutations in CAN1, was increased in the mcm2AA strain compared to wild type, whereas with a phosphomimetic allele (mcm2EE the mutation rate was decreased. These results led to the idea that the mcm2AA strain is unable to respond properly to DNA damage. We examined this by screening the deletion collection for suppressors of the caffeine sensitivity of mcm2AA. Deletions that decrease spontaneous DNA damage, increase homologous recombination or slow replication forks were isolated. Many of the suppressors of caffeine sensitivity suppressed other phenotypes of mcm2AA including sensitivity to genotoxic drugs, the increased frequency of cells with RPA foci and the increased mutation rate. Conclusions Together these observations point to a role for DDK-mediated phosphorylation

  3. Self-Esteem, Relationship Threat, and Dependency Regulation: Independent Replication of Murray, Rose, Bellavia, Holmes, and Kusche (2002) Study 3

    OpenAIRE

    Stanton, Sarah; Moroz, Sarah; Balzarini, Rhonda; Dobson, Kiersten; Hahn, Christian; Kohut, Taylor; Campbell, Lorne

    2017-01-01

    Across three studies, Murray et al. (2002) found that low self-esteem individuals responded in a negative manner compared to those high in self-esteem in the face of relationship threat, perceiving their partners and relationships less positively. This was the first empirical support for the hypothesized dynamics of a dependency regulation perspective, and has had a significant impact on the field of relationship science. In the present research, we sought to reproduce the methods and procedu...

  4. EPA Lean Government Initiative: How to Replicate Lean Successes

    Science.gov (United States)

    This Lean Replication Primer describes how EPA Offices and Regions can identify and adapt successful practices from previous Lean projects to “replicate” their successes and generate further improvements.

  5. Replication and robustness in developmental research.

    Science.gov (United States)

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

    2014-11-01

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

  6. International Expansion through Flexible Replication

    DEFF Research Database (Denmark)

    Jonsson, Anna; Foss, Nicolai Juul

    2011-01-01

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

  7. “Climb!” – A Composition Case Study. Actualising and Replicating Virtual Spaces in Classical Music Composition and Performance

    DEFF Research Database (Denmark)

    Kallionpaa, Maria; Gasselseder, Hans-Peter

    2018-01-01

    , for example, the acoustics of the concert hall, the instrumentation, the qualities of the concert instrument, or the technologies used. Today´s electroacoustic repertoires frequently contain manipulation of (either physical or virtual) space or acoustic qualities, which sets new requirements...... to the capabilities of the performers. This leads to a question what these requirements may be and how can the performers and composers best deal with them? Can the space itself form part of the structure of a composition and/or performance? This chapter explores the topic through a composition case study “Climb...

  8. Body Image and Anti-Fat Attitudes: An Experimental Study Using a Haptic Virtual Reality Environment to Replicate Human Touch.

    Science.gov (United States)

    Tremblay, Line; Roy-Vaillancourt, Mélina; Chebbi, Brahim; Bouchard, Stéphane; Daoust, Michael; Dénommée, Jessica; Thorpe, Moriah

    2016-02-01

    It is well documented that anti-fat attitudes influence the interactions individuals have with overweight people. However, testing attitudes through self-report measures is challenging. In the present study, we explore the use of a haptic virtual reality environment to physically interact with overweight virtual human (VH). We verify the hypothesis that duration and strength of virtual touch vary according to the characteristics of VH in ways similar to those encountered from interaction with real people in anti-fat attitude studies. A group of 61 participants were randomly assigned to one of the experimental conditions involving giving a virtual hug to a female or a male VH of either normal or overweight. We found significant associations between body image satisfaction and anti-fat attitudes and sex differences on these measures. We also found a significant interaction effect of the sex of the participants, sex of the VH, and the body size of the VH. Female participants hugged longer the overweight female VH than overweight male VH. Male participants hugged longer the normal-weight VH than the overweight VH. We conclude that virtual touch is a promising method of measuring attitudes, emotion and social interactions.

  9. A comparative study of mixed exponential and Weibull distributions in a stochastic model replicating a tropical rainfall process

    Science.gov (United States)

    Abas, Norzaida; Daud, Zalina M.; Yusof, Fadhilah

    2014-11-01

    A stochastic rainfall model is presented for the generation of hourly rainfall data in an urban area in Malaysia. In view of the high temporal and spatial variability of rainfall within the tropical rain belt, the Spatial-Temporal Neyman-Scott Rectangular Pulse model was used. The model, which is governed by the Neyman-Scott process, employs a reasonable number of parameters to represent the physical attributes of rainfall. A common approach is to attach each attribute to a mathematical distribution. With respect to rain cell intensity, this study proposes the use of a mixed exponential distribution. The performance of the proposed model was compared to a model that employs the Weibull distribution. Hourly and daily rainfall data from four stations in the Damansara River basin in Malaysia were used as input to the models, and simulations of hourly series were performed for an independent site within the basin. The performance of the models was assessed based on how closely the statistical characteristics of the simulated series resembled the statistics of the observed series. The findings obtained based on graphical representation revealed that the statistical characteristics of the simulated series for both models compared reasonably well with the observed series. However, a further assessment using the AIC, BIC and RMSE showed that the proposed model yields better results. The results of this study indicate that for tropical climates, the proposed model, using a mixed exponential distribution, is the best choice for generation of synthetic data for ungauged sites or for sites with insufficient data within the limit of the fitted region.

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

    International Nuclear Information System (INIS)

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

    1979-01-01

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

  11. Sp100 colocalizes with HPV replication foci and restricts the productive stage of the infectious cycle.

    Directory of Open Access Journals (Sweden)

    Wesley H Stepp

    2017-10-01

    Full Text Available We have shown previously that Sp100 (a component of the ND10 nuclear body represses transcription, replication and establishment of incoming human papillomavirus (HPV DNA in the early stages of infection. In this follow up study, we show that Sp100 does not substantially regulate viral infection in the maintenance phase, however at late stages of infection Sp100 interacts with amplifying viral genomes to repress viral processes. We find that Sp100 localizes to HPV16 replication foci generated in primary keratinocytes, to HPV31 replication foci that form in differentiated cells, and to HPV16 replication foci in CIN 1 cervical biopsies. To analyze this further, Sp100 was down regulated by siRNA treatment of differentiating HPV31 containing cells and levels of viral transcription and replication were assessed. This revealed that Sp100 represses viral transcription and replication in differentiated cells. Analysis of Sp100 binding to viral chromatin showed that Sp100 bound across the viral genome, and that binding increased at late stages of infection. Therefore, Sp100 represses the HPV life cycle at both early and late stages of infection.

  12. The Impact of Sexual Assault Nurse Examiner Programs on Criminal Justice Case Outcomes: A Multisite Replication Study.

    Science.gov (United States)

    Campbell, Rebecca; Bybee, Deborah; Townsend, Stephanie M; Shaw, Jessica; Karim, Nidal; Markowitz, Jenifer

    2014-05-01

    To address the underreporting and underprosecution of adult sexual assaults, communities throughout the United States have implemented multidisciplinary interventions to improve postassault care for victims and the criminal justice system response. One such model is the Sexual Assault Nurse Examiner (SANE) Program, whereby specially trained nurses provide comprehensive psychological, medical, and forensic services for sexual assault. In this study, we conducted a multisite evaluation of six SANE programs (two rural programs, two serving midsized communities, two urban) to assess how implementation of SANE programs affects adult sexual assault prosecution rates. At each site, most sexual assaults reported to law enforcement were never referred by police to prosecutors or were not charged by the prosecutor's office (80%-89%). Individually, none of the sites had a statistically significant increase in prosecution rates pre-SANE to post-SANE. However, when the data were aggregated across sites, thereby increasing statistical power, there was a significant effect such that cases were more likely to be prosecuted post-SANE as compared with pre-SANE. These findings suggest that the SANE intervention model does have a positive impact on sexual assault case progression in the criminal justice system. Nevertheless, there is still a pressing need for improvement as the vast majority of both pre-SANE and post-SANE resulted in nonreferral/no charges filed. © The Author(s) 2014.

  13. A tale of two cities: replication of a study on the acculturation and adaptation of immigrant adolescents from the former Soviet Union in a different community context.

    Science.gov (United States)

    Birman, Dina; Trickett, Edison; Buchanan, Rebecca M

    2005-03-01

    While a great deal of research has been conducted to understand acculturation and its relationship to adaptation in the new country, surprisingly little attention has been paid to the ways in which the characteristics of the local community impact these processes. The present study addresses this gap in the literature by exploring the potential role of community differences in the acculturation and adaptation processes of 269 refugee and immigrant adolescents from the former Soviet Union who resettled in two different community contexts. Specifically, a prior study on acculturation and adjustment among high school students (D. Birman, E. J. Trickett, & A. Vinokurov, 2002) was replicated with the same émigré population in a contrasting community within the same state. The contrast between these communities allowed us to test hypotheses emerging from an ecological perspective concerning (1) patterns of acculturation, (2) levels of discrimination and its effect on acculturative outcomes, and (3) community differences in the relationship between acculturation and outcomes. In addition to the focus on community differences, the study also employs a multidimensional measure of acculturation and assesses acculturation to both American and Russian culture. Furthermore, adaptation is assessed across different life domains; including peer relationships, family relationships, school adaptation, and psychological adaptation. Findings support the general ecological perspective, suggesting the importance of studying acculturation and adaptation as a reflexive process in which culture and context are very much intertwined.

  14. 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.

  15. 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.

  16. A cross-sectional study of 'yaws' in districts of Ghana which have previously undertaken azithromycin mass drug administration for trachoma control.

    Directory of Open Access Journals (Sweden)

    Rosanna Ghinai

    2015-01-01

    Full Text Available Yaws, caused by Treponema pallidum ssp. pertenue, is reportedly endemic in Ghana. Mass distribution of azithromycin is now the cornerstone of the WHO yaws eradication campaign. Mass distribution of azithromycin at a lower target dose was previously undertaken in two regions of Ghana for the control of trachoma. Ongoing reporting of yaws raises the possibility that resistance may have emerged in T. pallidum pertenue, or that alternative infections may be responsible for some of the reported cases. We conducted a cross-sectional survey in thirty communities in two districts of Ghana where MDA for trachoma had previously been conducted. Children aged 5-17 years with ulcerative lesions compatible with yaws were enrolled. Samples for treponemal serology and lesion PCR were collected from all children. 90 children with 98 lesions were enrolled. Syphilis serology was negative in all of them. PCR for T. pallidum ssp pertenue was negative in all children, but Haemophilus ducreyi DNA was detected in 9 lesions. In these communities, previously treated for trachoma, we found no evidence of ongoing transmission of yaws. H. ducreyi was associated with a proportion of skin lesions, but the majority of lesions remain unexplained. Integration of diagnostic testing into both pre and post-MDA surveillance systems is required to better inform yaws control programmes.

  17. Replication study for the association of 9 East Asian GWAS-derived loci with susceptibility to type 2 diabetes in a Japanese population.

    Directory of Open Access Journals (Sweden)

    Kensuke Sakai

    Full Text Available AIMS: East Asian genome-wide association studies (GWAS for type 2 diabetes identified 8 loci with genome-wide significance, and 2 loci with a borderline association. However, the associations of these loci except MAEA locus with type 2 diabetes have not been evaluated in independent East Asian cohorts. We performed a replication study to investigate the association of these susceptibility loci with type 2 diabetes in an independent Japanese population. METHODS: We genotyped 7,379 Japanese participants (5,315 type 2 diabetes and 2,064 controls for each of the 9 single nucleotide polymorphisms (SNPs, rs7041847 in GLIS3, rs6017317 in FITM2-R3HDML-HNF4A, rs6467136 near GCCI-PAX4, rs831571 near PSMD6, rs9470794 in ZFAND3, rs3786897 in PEPD, rs1535500 in KCNK16, rs16955379 in CMIP, and rs17797882 near WWOX. Because the sample size in this study was not sufficient to replicate single SNP associations, we constructed a genetic risk score (GRS by summing a number of risk alleles of the 9 SNPs, and examined the association of the GRS with type 2 diabetes using logistic regression analysis. RESULTS: With the exception of rs1535500 in KCNK16, all SNPs had the same direction of effect (odds ratio [OR]>1.0 as in the original reports. The GRS constructed from the 9 SNPs was significantly associated with type 2 diabetes in the Japanese population (p = 4.0 × 10(-4, OR = 1.05, 95% confidence interval: 1.02-1.09. In quantitative trait analyses, rs16955379 in CMIP was nominally associated with a decreased homeostasis model assessment of β-cell function and with increased fasting plasma glucose, but neither the individual SNPs nor the GRS showed a significant association with the glycemic traits. CONCLUSIONS: These results indicate that 9 loci that were identified in the East Asian GWAS meta-analysis have a significant effect on the susceptibility to type 2 diabetes in the Japanese population.

  18. Lipoprotein(a) levels, genotype, and incident aortic valve stenosis: a prospective mendelian randomization study and replication in a case-control cohort

    NARCIS (Netherlands)

    Arsenault, Benoit J.; Boekholdt, S. Matthijs; Dubé, Marie-Pierre; Rhéaume, Eric; Wareham, Nicholas J.; Khaw, Kay-Tee; Sandhu, Manjinder S.; Tardif, Jean-Claude

    2014-01-01

    Although a previous study has suggested that a genetic variant in the LPA region was associated with the presence of aortic valve stenosis (AVS), no prospective study has suggested a role for lipoprotein(a) levels in the pathophysiology of AVS. Our objective was to determine whether lipoprotein(a)

  19. 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.

  20. DNA replication is an integral part of the mouse oocyte's reprogramming machinery.

    Directory of Open Access Journals (Sweden)

    Bingyuan Wang

    Full Text Available Many of the structural and mechanistic requirements of oocyte-mediated nuclear reprogramming remain elusive. Previous accounts that transcriptional reprogramming of somatic nuclei in mouse zygotes may be complete in 24-36 hours, far more rapidly than in other reprogramming systems, raise the question of whether the mere exposure to the activated mouse ooplasm is sufficient to enact reprogramming in a nucleus. We therefore prevented DNA replication and cytokinesis, which ensue after nuclear transfer, in order to assess their requirement for transcriptional reprogramming of the key pluripotency genes Oct4 (Pou5f1 and Nanog in cloned mouse embryos. Using transcriptome and allele-specific analysis, we observed that hundreds of mRNAs, but not Oct4 and Nanog, became elevated in nucleus-transplanted oocytes without DNA replication. Progression through the first round of DNA replication was essential but not sufficient for transcriptional reprogramming of Oct4 and Nanog, whereas cytokinesis and thereby cell-cell interactions were dispensable for transcriptional reprogramming. Responses similar to clones also were observed in embryos produced by fertilization in vitro. Our results link the occurrence of reprogramming to a previously unappreciated requirement of oocyte-mediated nuclear reprogramming, namely DNA replication. Nuclear transfer alone affords no immediate transition from a somatic to a pluripotent gene expression pattern unless DNA replication is also in place. This study is therefore a resource to appreciate that the quest for always faster reprogramming methods may collide with a limit that is dictated by the cell cycle.

  1. Hypoxia training: symptom replication in experienced military aircrew.

    Science.gov (United States)

    Johnston, Ben J; Iremonger, Gareth S; Hunt, Sheena; Beattie, Elizabeth

    2012-10-01

    Military aircrew are trained to recognize the signs and symptoms of hypoxia in a safe environment using a variety of methods to simulate altitude. In order to investigate the effectiveness of hypoxia training, this study compared the recall of hypoxia symptoms in military aircrew between two consecutive hypobaric chamber hypoxia training sessions conducted, on average, 4.5 yr apart. Previously trained subjects completed a questionnaire immediately before and after they underwent refresher hypoxia training and recorded the occurrence, order, and severity of symptoms experienced. Responses from refresher training were compared with their recall of symptoms experienced during previous training. There was no difference in the recall of most hypoxia symptoms between training sessions. Slurred speech was recalled more frequently from previous training compared to refresher training (14 vs. 4 subjects), whereas hot/cold flushes were recalled less frequently from previous training compared to refresher training (5 vs. 17 subjects). There was a statistically significant difference in overall hypoxia score (10.3 vs. 8.3), suggesting that from memory subjects may underestimate the level of hypoxia experienced in previous training. A high level of similarity between the recall of previously experienced hypoxia symptoms and recent experience supports the effectiveness of hypoxia training. These results replicate the finding of a 'hypoxia signature' reported by a previous study. Small differences in the recall of some symptoms and in overall hypoxia score highlight the importance of drawing attention to the more subtle symptoms of early hypoxia, and of using training techniques which optimize aircrew recall.

  2. Regulatory cross-talk links Vibrio cholerae chromosome II replication and segregation.

    Directory of Open Access Journals (Sweden)

    Yoshiharu Yamaichi

    2011-07-01

    Full Text Available There is little knowledge of factors and mechanisms for coordinating bacterial chromosome replication and segregation. Previous studies have revealed that genes (and their products that surround the origin of replication (oriCII of Vibrio cholerae chromosome II (chrII are critical for controlling the replication and segregation of this chromosome. rctB, which flanks one side of oriCII, encodes a protein that initiates chrII replication; rctA, which flanks the other side of oriCII, inhibits rctB activity. The chrII parAB2 operon, which is essential for chrII partitioning, is located immediately downstream of rctA. Here, we explored how rctA exerts negative control over chrII replication. Our observations suggest that RctB has at least two DNA binding domains--one for binding to oriCII and initiating replication and the other for binding to rctA and thereby inhibiting RctB's ability to initiate replication. Notably, the inhibitory effect of rctA could be alleviated by binding of ParB2 to a centromere-like parS site within rctA. Furthermore, by binding to rctA, ParB2 and RctB inversely regulate expression of the parAB2 genes. Together, our findings suggest that fluctuations in binding of the partitioning protein ParB2 and the chrII initiator RctB to rctA underlie a regulatory network controlling both oriCII firing and the production of the essential chrII partitioning proteins. Thus, by binding both RctB and ParB2, rctA serves as a nexus for regulatory cross-talk coordinating chrII replication and segregation.

  3. A Novel System for Identification of Inhibitors of Rift Valley Fever Virus Replication

    Directory of Open Access Journals (Sweden)

    Mary E. Piper

    2010-03-01

    Full Text Available Rift Valley fever virus (RVFV is a human and livestock pathogen endemic to sub-Saharan Africa. We have developed a T7-dependent system for the efficient production of RVFV-like particles (RVF-VLPs based on the virulent ZH-501 strain of RVFV. The RVF-VLPs are capable of performing a single round of infection, allowing for the study of viral replication, assembly, and infectivity. We demonstrate that these RVF-VLPs are antigenically indistinguishable from authentic RVFV and respond similarly to a wide array of known and previously unknown chemical inhibitors. This system should be useful for screening for small molecule inhibitors of RVFV replication.

  4. A novel system for identification of inhibitors of rift valley Fever virus replication.

    Science.gov (United States)

    Piper, Mary E; Gerrard, Sonja R

    2010-03-01

    Rift Valley fever virus (RVFV) is a human and livestock pathogen endemic to sub-Saharan Africa. We have developed a T7-dependent system for the efficient production of RVFV-like particles (RVF-VLPs) based on the virulent ZH-501 strain of RVFV. The RVF-VLPs are capable of performing a single round of infection, allowing for the study of viral replication, assembly, and infectivity. We demonstrate that these RVF-VLPs are antigenically indistinguishable from authentic RVFV and respond similarly to a wide array of known and previously unknown chemical inhibitors. This system should be useful for screening for small molecule inhibitors of RVFV replication.

  5. DNA Replication Profiling Using Deep Sequencing.

    Science.gov (United States)

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

    2018-01-01

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

  6. Inferential misconceptions and replication crisis

    Directory of Open Access Journals (Sweden)

    Norbert Hirschauer

    2016-12-01

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

  7. Discussing the Need of Experimental Replication with 5th Grade Students Conducting a Mealworm Experiment

    Science.gov (United States)

    Asshoff, Roman

    2017-01-01

    Scientific inquiry requires the replication of results in experimental studies. Recent studies draw a severe picture on the need of replication and the difficulties in replicating already published studies. As replicated confirmation of results is the basis of scientific and medical research, there may be a need to introduce the topic of…

  8. Hydroxyurea-Induced Replication Stress

    Directory of Open Access Journals (Sweden)

    Kenza Lahkim Bennani-Belhaj

    2010-01-01

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

  9. DATABASE REPLICATION IN HETEROGENOUS PLATFORM

    OpenAIRE

    Hendro Nindito; Evaristus Didik Madyatmadja; Albert Verasius Dian Sano

    2014-01-01

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

  10. The N-Terminal of Aquareovirus NS80 Is Required for Interacting with Viral Proteins and Viral Replication.

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    Jie Zhang

    Full Text Available Reovirus replication and assembly occurs within viral inclusion bodies that formed in specific intracellular compartments of cytoplasm in infected cells. Previous study indicated that aquareovirus NS80 is able to form inclusion bodies, and also can retain viral proteins within its inclusions. To better understand how NS80 performed in viral replication and assembly, the functional regions of NS80 associated with other viral proteins in aquareovirus replication were investigated in this study. Deletion mutational analysis and rotavirus NSP5-based protein association platform were used to detect association regions. Immunofluorescence images indicated that different N-terminal regions of NS80 could associate with viral proteins VP1, VP4, VP6 and NS38. Further co-immunoprecipitation analysis confirmed the interaction between VP1, VP4, VP6 or NS38 with different regions covering the N-terminal amino acid (aa, 1-471 of NS80, respectively. Moreover, removal of NS80 N-terminal sequences required for interaction with proteins VP1, VP4, VP6 or NS38 not only prevented the capacity of NS80 to support viral replication in NS80 shRNA-based replication complementation assays, but also inhibited the expression of aquareovirus proteins, suggesting that N-terminal regions of NS80 are necessary for viral replication. These results provided a foundational basis for further understanding the role of NS80 in viral replication and assembly during aquareovirus infection.

  11. The effect of technical replicate (repeats) on Nix Pro Color Sensor™ measurement precision for meat: A case-study on aged beef colour stability.

    Science.gov (United States)

    Holman, Benjamin W B; Collins, Damian; Kilgannon, Ashleigh K; Hopkins, David L

    2018-01-01

    The Nix Pro Colour Sensor™ (NIX) can be potentially used to measure meat colour, but procedural guidelines that assure measurement reproducibility and repeatability (precision) must first be established. Technical replicate number (r) will minimise response variation, measureable as standard error of predicted mean (SEM), and contribute to improved precision. Consequently, we aimed to explore the effects of r on NIX precision when measuring aged beef colour (colorimetrics; L*, a*, b*, hue and chroma values). Each colorimetric SEM declined with increasing r to indicate improved precision and followed a diminishing rate of improvement that allowed us to recommend r=7 for meat colour studies using the NIX. This definition was based on practical limitations and a* variability, as additional r would be required if other colorimetrics or advanced levels of precision are necessary. Beef ageing and display period, holding temperature, loin and sampled portion were also found to contribute to colorimetric variation, but were incorporated within our definition of r. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  12. Treatment of advanced, recurrent, resistant to previous treatments basal and squamous cell skin carcinomas with a synergistic formulation of interferons. Open, prospective study

    Directory of Open Access Journals (Sweden)

    Lopez-Saura Pedro

    2009-07-01

    Full Text Available Abstract Background Aggressive non-melanoma skin cancer (deeply infiltrating, recurrent, and morphea form lesions are therapeutically challenging because they require considerable tissue loss and may demand radical disfiguring surgery. Interferons (IFN may provide a non-surgical approach to the management of these tumors. The aim of this work was to evaluate the effect of a formulation containing IFNs-α and -γ in synergistic proportions on patients with recurrent, advanced basal cell (BCC or squamous cell skin carcinomas (SCSC. Methods Patients with extensive, recurrent, resistant to other procedures BCC or SCSC received the IFN formulation peri- and intralesionally, three times per week for 3 weeks. They had been previously treated with surgery and/or radiotherapy or chemotherapy. Thirteen weeks after the end of treatment, the original lesion sites were examined for histological evidence of remaining tumor. Results Sixteen elder (median 70 years-old patients were included. They beared 12 BCC and 4 SCSC ranging from 1.5 to 12.5 cm in the longest dimension. At the end of treatment 47% CR (complete tumor elimination, 40% PR (>30% tumor reduction, and 13% stable disease were obtained. None of the patients relapsed during the treatment period. The median duration of the response was 38 months. Only one patient with complete response had relapsed until today. Principal adverse reactions were influenza-like symptoms well known to occur with interferon therapy, which were well tolerated. Conclusion The peri- and intralesional combination of IFNs-α and -γ was safe and showed effect for the treatment of advanced, recurrent and resistant to previous treatments of BCC and SCSC in elder patients. This is the first report of such treatment in patients with advance non-melanoma skin cancer. The encouraging result justifies further confirmatory trials. Trial registration Current Controlled Trials RPCEC00000052.

  13. Treatment of advanced, recurrent, resistant to previous treatments basal and squamous cell skin carcinomas with a synergistic formulation of interferons. Open, prospective study

    International Nuclear Information System (INIS)

    Anasagasti-Angulo, Lorenzo; Garcia-Vega, Yanelda; Barcelona-Perez, Silvia; Lopez-Saura, Pedro; Bello-Rivero, Iraldo

    2009-01-01

    Aggressive non-melanoma skin cancer (deeply infiltrating, recurrent, and morphea form lesions) are therapeutically challenging because they require considerable tissue loss and may demand radical disfiguring surgery. Interferons (IFN) may provide a non-surgical approach to the management of these tumors. The aim of this work was to evaluate the effect of a formulation containing IFNs-α and -γ in synergistic proportions on patients with recurrent, advanced basal cell (BCC) or squamous cell skin carcinomas (SCSC). Patients with extensive, recurrent, resistant to other procedures BCC or SCSC received the IFN formulation peri- and intralesionally, three times per week for 3 weeks. They had been previously treated with surgery and/or radiotherapy or chemotherapy. Thirteen weeks after the end of treatment, the original lesion sites were examined for histological evidence of remaining tumor. Sixteen elder (median 70 years-old) patients were included. They beared 12 BCC and 4 SCSC ranging from 1.5 to 12.5 cm in the longest dimension. At the end of treatment 47% CR (complete tumor elimination), 40% PR (>30% tumor reduction), and 13% stable disease were obtained. None of the patients relapsed during the treatment period. The median duration of the response was 38 months. Only one patient with complete response had relapsed until today. Principal adverse reactions were influenza-like symptoms well known to occur with interferon therapy, which were well tolerated. The peri- and intralesional combination of IFNs-α and -γ was safe and showed effect for the treatment of advanced, recurrent and resistant to previous treatments of BCC and SCSC in elder patients. This is the first report of such treatment in patients with advance non-melanoma skin cancer. The encouraging result justifies further confirmatory trials. Current Controlled Trials RPCEC00000052

  14. The evolutionary ecology of molecular replicators.

    Science.gov (United States)

    Nee, Sean

    2016-08-01

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

  15. Prognostic factors in multiple myeloma: definition of risk groups in 410 previously untreated patients: a Grupo Argentino de Tratamiento de la Leucemia Aguda study.

    Science.gov (United States)

    Corrado, C; Santarelli, M T; Pavlovsky, S; Pizzolato, M

    1989-12-01

    Four hundred ten previously untreated multiple myeloma patients entered onto two consecutive Grupo Argentino de Tratamiento de la Leucemia Aguda (GATLA) protocols were analyzed to identify significant prognostic factors influencing survival. The univariate analysis selected the following variables: performance status, renal function, percentage of bone marrow plasma cells at diagnosis, hemoglobin, and age. A multivariate analysis showed that performance status, renal function, percentage of bone marrow plasma cells, hemoglobin, and age were the best predictive variables for survival. A score was assigned to each patient according to these variables, which led to their classification in three groups: good, intermediate, and poor risk, with a probability of survival of 26% and 10% at 96 months, and 5% at 56 months, and median survival of 60, 37, and 14 months, respectively (P = .0000). In our patient population, this model proved to be superior to the Durie-Salmon staging system in defining prognostic risk groups, and separating patients with significantly different risks within each Durie-Salmon stage.

  16. Implementation of an electronic medical record system in previously computer-naïve primary care centres: a pilot study from Cyprus.

    Science.gov (United States)

    Samoutis, George; Soteriades, Elpidoforos S; Kounalakis, Dimitris K; Zachariadou, Theodora; Philalithis, Anastasios; Lionis, Christos

    2007-01-01

    The computer-based electronic medical record (EMR) is an essential new technology in health care, contributing to high-quality patient care and efficient patient management. The majority of southern European countries, however, have not yet implemented universal EMR systems and many efforts are still ongoing. We describe the development of an EMR system and its pilot implementation and evaluation in two previously computer-naïve public primary care centres in Cyprus. One urban and one rural primary care centre along with their personnel (physicians and nurses) were selected to participate. Both qualitative and quantitative evaluation tools were used during the implementation phase. Qualitative data analysis was based on the framework approach, whereas quantitative assessment was based on a nine-item questionnaire and EMR usage parameters. Two public primary care centres participated, and a total often health professionals served as EMR system evaluators. Physicians and nurses rated EMR relatively highly, while patients were the most enthusiastic supporters for the new information system. Major implementation impediments were the physicians' perceptions that EMR usage negatively affected their workflow, physicians' legal concerns, lack of incentives, system breakdowns, software design problems, transition difficulties and lack of familiarity with electronic equipment. The importance of combining qualitative and quantitative evaluation tools is highlighted. More efforts are needed for the universal adoption and routine use of EMR in the primary care system of Cyprus as several barriers to adoption exist; however, none is insurmountable. Computerised systems could improve efficiency and quality of care in Cyprus, benefiting the entire population.

  17. Replication and Relevance of Multiple Susceptibility Loci Discovered from Genome Wide Association Studies for Type 2 Diabetes in an Indian Population.

    Directory of Open Access Journals (Sweden)

    Nagaraja M Phani

    Full Text Available Several genetic variants for type 2 diabetes (T2D have been identified through genome wide association studies (GWAS from Caucasian population; however replication studies were not consistent across various ethnicities. Objective of the current study is to examine the possible correlation of 9 most significant GWAS single nucleotide polymorphisms (SNPs for T2D susceptibility as well as the interactive effect of these variants on the risk of T2D in an Indian population.Case-control cohorts of 1156 individuals were genotyped for 9 SNPs from an Indian population. Association analyses were performed using logistic regression after adjusting for covariates. Multifactor dimensionality reduction (MDR analysis was adopted to determine gene-gene interactions and discriminatory power of combined SNP effect was assessed by grouping individuals based on the number of risk alleles and by calculating area under the receiver-operator characteristic curve (AUC.We confirm the association of TCF7L2 (rs7903146 and SLC30A8 (rs13266634 with T2D. MDR analysis showed statistically significant interactions among four SNPs of SLC30A8 (rs13266634, IGF2BP2 (rs4402960, HHEX (rs1111875 and CDKN2A (rs10811661 genes. Cumulative analysis showed an increase in odds ratio against the baseline group of individuals carrying 5 to 6 risk alleles and discriminatory power of genetic test based on 9 variants showed higher AUC value when analyzed along with body mass index (BMI.These results provide a strong evidence for independent association between T2D and SNPs for in TCF7L2 and SLC30A8. MDR analysis demonstrates that independently non-significant variants may interact with one another resulting in increased disease susceptibility in the population tested.

  18. Selective recruitment of nuclear factors to productively replicating herpes simplex virus genomes.

    Science.gov (United States)

    Dembowski, Jill A; DeLuca, Neal A

    2015-05-01

    Much of the HSV-1 life cycle is carried out in the cell nucleus, including the expression, replication, repair, and packaging of viral genomes. Viral proteins, as well as cellular factors, play essential roles in these processes. Isolation of proteins on nascent DNA (iPOND) was developed to label and purify cellular replication forks. We adapted aspects of this method to label viral genomes to both image, and purify replicating HSV-1 genomes for the identification of associated proteins. Many viral and cellular factors were enriched on viral genomes, including factors that mediate DNA replication, repair, chromatin remodeling, transcription, and RNA processing. As infection proceeded, packaging and structural components were enriched to a greater extent. Among the more abundant proteins that copurified with genomes were the viral transcription factor ICP4 and the replication protein ICP8. Furthermore, all seven viral replication proteins were enriched on viral genomes, along with cellular PCNA and topoisomerases, while other cellular replication proteins were not detected. The chromatin-remodeling complexes present on viral genomes included the INO80, SWI/SNF, NURD, and FACT complexes, which may prevent chromatinization of the genome. Consistent with this conclusion, histones were not readily recovered with purified viral genomes, and imaging studies revealed an underrepresentation of histones on viral genomes. RNA polymerase II, the mediator complex, TFIID, TFIIH, and several other transcriptional activators and repressors were also affinity purified with viral DNA. The presence of INO80, NURD, SWI/SNF, mediator, TFIID, and TFIIH components is consistent with previous studies in which these complexes copurified with ICP4. Therefore, ICP4 is likely involved in the recruitment of these key cellular chromatin remodeling and transcription factors to viral genomes. Taken together, iPOND is a valuable method for the study of viral genome dynamics during infection and

  19. Selective recruitment of nuclear factors to productively replicating herpes simplex virus genomes.

    Directory of Open Access Journals (Sweden)

    Jill A Dembowski

    2015-05-01

    Full Text Available Much of the HSV-1 life cycle is carried out in the cell nucleus, including the expression, replication, repair, and packaging of viral genomes. Viral proteins, as well as cellular factors, play essential roles in these processes. Isolation of proteins on nascent DNA (iPOND was developed to label and purify cellular replication forks. We adapted aspects of this method to label viral genomes to both image, and purify replicating HSV-1 genomes for the identification of associated proteins. Many viral and cellular factors were enriched on viral genomes, including factors that mediate DNA replication, repair, chromatin remodeling, transcription, and RNA processing. As infection proceeded, packaging and structural components were enriched to a greater extent. Among the more abundant proteins that copurified with genomes were the viral transcription factor ICP4 and the replication protein ICP8. Furthermore, all seven viral replication proteins were enriched on viral genomes, along with cellular PCNA and topoisomerases, while other cellular replication proteins were not detected. The chromatin-remodeling complexes present on viral genomes included the INO80, SWI/SNF, NURD, and FACT complexes, which may prevent chromatinization of the genome. Consistent with this conclusion, histones were not readily recovered with purified viral genomes, and imaging studies revealed an underrepresentation of histones on viral genomes. RNA polymerase II, the mediator complex, TFIID, TFIIH, and several other transcriptional activators and repressors were also affinity purified with viral DNA. The presence of INO80, NURD, SWI/SNF, mediator, TFIID, and TFIIH components is consistent with previous studies in which these complexes copurified with ICP4. Therefore, ICP4 is likely involved in the recruitment of these key cellular chromatin remodeling and transcription factors to viral genomes. Taken together, iPOND is a valuable method for the study of viral genome dynamics

  20. rMATS: robust and flexible detection of differential alternative splicing from replicate RNA-Seq data.

    Science.gov (United States)

    Shen, Shihao; Park, Juw Won; Lu, Zhi-xiang; Lin, Lan; Henry, Michael D; Wu, Ying Nian; Zhou, Qing; Xing, Yi

    2014-12-23

    Ultra-deep RNA sequencing (RNA-Seq) has become a powerful approach for genome-wide analysis of pre-mRNA alternative splicing. We previously developed multivariate analysis of transcript splicing (MATS), a statistical method for detecting differential alternative splicing between two RNA-Seq samples. Here we describe a new statistical model and computer program, replicate MATS (rMATS), designed for detection of differential alternative splicing from replicate RNA-Seq data. rMATS uses a hierarchical model to simultaneously account for sampling uncertainty in individual replicates and variability among replicates. In addition to the analysis of unpaired replicates, rMATS also includes a model specifically designed for paired replicates between sample groups. The hypothesis-testing framework of rMATS is flexible and can assess the statistical significance over any user-defined magnitude of splicing change. The performance of rMATS is evaluated by the analysis of simulated and real RNA-Seq data. rMATS outperformed two existing methods for replicate RNA-Seq data in all simulation settings, and RT-PCR yielded a high validation rate (94%) in an RNA-Seq dataset of prostate cancer cell lines. Our data also provide guiding principles for designing RNA-Seq studies of alternative splicing. We demonstrate that it is essential to incorporate biological replicates in the study design. Of note, pooling RNAs or merging RNA-Seq data from multiple replicates is not an effective approach to account for variability, and the result is particularly sensitive to outliers. The rMATS source code is freely available at rnaseq-mats.sourceforge.net/. As the popularity of RNA-Seq continues to grow, we expect rMATS will be useful for studies of alternative splicing in diverse RNA-Seq projects.

  1. Pattern replication by confined dewetting

    NARCIS (Netherlands)

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

    2003-01-01

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

  2. 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…

  3. USP7 is a SUMO deubiquitinase essential for DNA replication

    DEFF Research Database (Denmark)

    Lecona, Emilio; Rodriguez-Acebes, Sara; Specks, Julia

    2016-01-01

    Post-translational modification of proteins by ubiquitin (Ub) and Ub-like modifiers regulates DNA replication. We have previously shown that chromatin around replisomes is rich in SUMO and poor in Ub, whereas mature chromatin exhibits an opposite pattern. How this SUMO-rich, Ub-poor environment...... is maintained at sites of DNA replication in mammalian cells remains unexplored. Here we identify USP7 as a replisome-enriched SUMO deubiquitinase that is essential for DNA replication. By acting on SUMO and SUMOylated proteins, USP7 counteracts their ubiquitination. Inhibition or genetic deletion of USP7 leads...... to the accumulation of Ub on SUMOylated proteins, which are displaced away from replisomes. Our findings provide a model explaining the differential accumulation of SUMO and Ub at replication forks and identify an essential role of USP7 in DNA replication that should be considered in the development of USP7...

  4. Prospective monitoring and self-report of previous falls among older women at high risk of falls and fractures: a study of comparison and agreement.

    Science.gov (United States)

    Garcia, Patrícia A; Dias, João M D; Silva, Silvia L A; Dias, Rosângela C

    2015-01-01

    The identification of the occurrence of falls is an important step for screening and for rehabilitation processes for the elderly. The methods of monitoring these events are susceptible to recording biases, and the choice of the most accurate method remains challenging. (i) To investigate the agreement between retrospective self-reporting and prospective monitoring of methods of recording falls, and (ii) to compare the retrospective self-reporting of falls and the prospective monitoring of falls and recurrent falls over a 12-month period among older women at high risk of falls and fractures. A total of 118 community-dwelling older women with low bone density were recruited. The incidence of falls was monitored prospectively in 116 older women (2 losses) via monthly phone calls over the course of a year. At the end of this monitoring period, the older women were asked about their recall of falls in the same 12-month period. The agreement between the two methods was analyzed, and the sensitivity and specificity of self-reported previous falls in relation to the prospective monitoring were calculated. There was moderate agreement between the prospective monitoring and the retrospective self-reporting of falls in classifying fallers (Kappa = 0.595) and recurrent fallers (Kappa = 0.589). The limits of agreement were 0.35 ± 1.66 falls. The self-reporting of prior falls had a 67.2% sensitivity and a 94.2% specificity in classifying fallers among older women and a 50% sensitivity and a 98.9% specificity in classifying recurrent fallers. Self-reporting of falls over a 12-month period underestimated 32.8% of falls and 50% of recurrent falls. The findings recommend caution if one is considering replacing monthly monitoring with annual retrospective questioning.

  5. The importance of continued exercise participation in quality of life and psychological well-being in previously inactive postmenopausal women: a pilot study.

    Science.gov (United States)

    Asbury, Elizabeth A; Chandrruangphen, Pornpat; Collins, Peter

    2006-01-01

    Exercise and physical activity provide a wide range of health benefits for postmenopausal women, although the impact of maintained exercise participation on psychological well-being is unclear. An exploration of continued exercise participation in psychological well-being after a moderate-intensity exercise program in previously inactive postmenopausal women was therefore undertaken. : Twenty-three healthy sedentary postmenopausal women (age 56 +/- 4 years) were randomly assigned to two groups. All participants completed the Short Form-36, Hospital Anxiety and Depression Scale (HADS), and Health Anxiety Questionnaire (HAQ) and then began a 6-week walking program at 50% heart rate reserve defined by (.-)V(O(2)) treadmill testing. Post-intervention, all participants underwent (.-)V(O(2)) treadmill testing and questionnaires. Group 1 was then instructed to continue exercising, whereas group 2 was instructed to desist for an additional 6-week period. On completion of the 6-week follow-up, participants completed a final set of questionnaires. Participants performed 97% of the prescribed 15-hour (900 minute) exercise program (875.1 +/- 177.4 minutes) in an average of 26 +/- 5 sessions. Total HAQ (P = 0.001), health worry (P = 0.001), fear of illness (P = 0.037), reassurance seeking behavior (P = 0.037), SF-36 well-being (P = 0.037), total HADS (P = 0.019), and HADS depression (P = 0.015) improved significantly following the exercise program. At follow-up, group 1 had lower HADS anxiety (P = 0.013), total HADS (P = 0.02), total HAQ (P = 0.03), and HAQ interference with life (P = 0.03) and significantly higher SF-36 energy (P = 0.01) than group 2. Healthy postmenopausal women gain significant psychological benefit from moderate-intensity exercise. However, exercise participation must continue to maintain improvements in psychological well-being and quality of life.

  6. A role for the weak DnaA binding sites in bacterial replication origins

    DEFF Research Database (Denmark)

    Charbon, Godefroid; Løbner-Olesen, Anders

    2011-01-01

    DnaA initiates the chromosomal DNA replication in nearly all bacteria, and replication origins are characterized by binding sites for the DnaA protein (DnaA-boxes) along with an ‘AT-rich’ region. However, great variation in number, spatial organization and specificity of DnaA-boxes is observed...... between species. In the study by Taylor et al. (2011), new and unexpectedly weak DnaA-boxes were identified within the Caulobacter crescentus origin of replication (Cori). The position of weak and stronger DnaA-boxes follows a pattern seen in Escherichia coli oriC. This raises the possibility...... that bacterial origins might be more alike than previously thought....

  7. LHCb experience with LFC replication

    International Nuclear Information System (INIS)

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

    2008-01-01

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

  8. 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.

  9. 3D Spatially Resolved Models of the Intracellular Dynamics of the Hepatitis C Genome Replication Cycle

    KAUST Repository

    Knodel, Markus

    2017-10-02

    Mathematical models of virus dynamics have not previously acknowledged spatial resolution at the intracellular level despite substantial arguments that favor the consideration of intracellular spatial dependence. The replication of the hepatitis C virus (HCV) viral RNA (vRNA) occurs within special replication complexes formed from membranes derived from endoplasmatic reticulum (ER). These regions, termed membranous webs, are generated primarily through specific interactions between nonstructural virus-encoded proteins (NSPs) and host cellular factors. The NSPs are responsible for the replication of the vRNA and their movement is restricted to the ER surface. Therefore, in this study we developed fully spatio-temporal resolved models of the vRNA replication cycle of HCV. Our simulations are performed upon realistic reconstructed cell structures-namely the ER surface and the membranous webs-based on data derived from immunostained cells replicating HCV vRNA. We visualized 3D simulations that reproduced dynamics resulting from interplay of the different components of our models (vRNA, NSPs, and a host factor), and we present an evaluation of the concentrations for the components within different regions of the cell. Thus far, our model is restricted to an internal portion of a hepatocyte and is qualitative more than quantitative. For a quantitative adaption to complete cells, various additional parameters will have to be determined through further in vitro cell biology experiments, which can be stimulated by the results deccribed in the present study.

  10. Sensitivity to Audiovisual Temporal Asynchrony in Children with a History of Specific Language Impairment and Their Peers with Typical Development: A Replication and Follow-Up Study

    Science.gov (United States)

    Kaganovich, Natalya

    2017-01-01

    Purpose: Earlier, my colleagues and I showed that children with a history of specific language impairment (H-SLI) are significantly less able to detect audiovisual asynchrony compared with children with typical development (TD; Kaganovich & Schumaker, 2014). Here, I first replicate this finding in a new group of children with H-SLI and TD and…

  11. 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

  12. The influence of mortality and socioeconomic status on risk and delayed rewards: a replication with British participants

    Directory of Open Access Journals (Sweden)

    Gillian V. Pepper

    2017-07-01

    Full Text Available Here, we report three attempts to replicate a finding from an influential psychological study (Griskevicius et al., 2011b. The original study found interactions between childhood SES and experimental mortality-priming condition in predicting risk acceptance and delay discounting outcomes. The original study used US student samples. We used British university students (replication 1 and British online samples (replications 2 and 3 with a modified version of the original priming material, which was tailored to make it more credible to a British audience. We did not replicate the interaction between childhood SES and mortality-priming condition in any of our three experiments. The only consistent trend of note was an interaction between sex and priming condition for delay discounting. We note that psychological priming effects are considered fragile and often fail to replicate. Our failure to replicate the original finding could be due to demographic differences in study participants, alterations made to the prime, or other study limitations. However, it is also possible that the previously reported interaction is not a robust or generalizable finding.

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

    Science.gov (United States)

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

    2015-12-01

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

  14. DNA replication stress and cancer chemotherapy.

    Science.gov (United States)

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

    2018-02-01

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

  15. 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.

  16. Two non-synonymous markers in PTPN21, identified by genome-wide association study data-mining and replication, are associated with schizophrenia.

    LENUS (Irish Health Repository)

    Chen, Jingchun

    2011-09-01

    We conducted data-mining analyses of genome wide association (GWA) studies of the CATIE and MGS-GAIN datasets, and found 13 markers in the two physically linked genes, PTPN21 and EML5, showing nominally significant association with schizophrenia. Linkage disequilibrium (LD) analysis indicated that all 7 markers from PTPN21 shared high LD (r(2)>0.8), including rs2274736 and rs2401751, the two non-synonymous markers with the most significant association signals (rs2401751, P=1.10 × 10(-3) and rs2274736, P=1.21 × 10(-3)). In a meta-analysis of all 13 replication datasets with a total of 13,940 subjects, we found that the two non-synonymous markers are significantly associated with schizophrenia (rs2274736, OR=0.92, 95% CI: 0.86-0.97, P=5.45 × 10(-3) and rs2401751, OR=0.92, 95% CI: 0.86-0.97, P=5.29 × 10(-3)). One SNP (rs7147796) in EML5 is also significantly associated with the disease (OR=1.08, 95% CI: 1.02-1.14, P=6.43 × 10(-3)). These 3 markers remain significant after Bonferroni correction. Furthermore, haplotype conditioned analyses indicated that the association signals observed between rs2274736\\/rs2401751 and rs7147796 are statistically independent. Given the results that 2 non-synonymous markers in PTPN21 are associated with schizophrenia, further investigation of this locus is warranted.

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

    Science.gov (United States)

    O'Neill, Paul

    2010-01-01

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

  18. Iterated function systems for DNA replication

    Science.gov (United States)

    Gaspard, Pierre

    2017-10-01

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

  19. The possibility of previous epidemiological data to serve as baseline for future national oral health surveys--a study in Vietnam.

    NARCIS (Netherlands)

    Palenstein Helderman, W.H. van; Truin, G.J.; Can, N.; Khanh, N.D.

    2001-01-01

    AIM: The purpose of this paper is to review the most recent epidemiological data (1985-2000) on dental caries and periodontal diseases in Vietnam in an attempt to obtain a 'baseline' for future national oral health surveys. METHODS: Studies on periodontal diseases and caries were included when CPITN

  20. Dynamics of picornavirus RNA replication within infected cells

    DEFF Research Database (Denmark)

    Belsham, Graham; Normann, Preben

    2008-01-01

    Replication of many picornaviruses is inhibited by low concentrations of guanidine. Guanidine-resistant mutants are readily isolated and the mutations map to the coding region for the 2C protein. Using in vitro replication assays it has been determined previously that guanidine blocks the initiat......Replication of many picornaviruses is inhibited by low concentrations of guanidine. Guanidine-resistant mutants are readily isolated and the mutations map to the coding region for the 2C protein. Using in vitro replication assays it has been determined previously that guanidine blocks...... the initiation of negative-strand synthesis. We have now examined the dynamics of RNA replication, measured by quantitative RT-PCR, within cells infected with either swine vesicular disease virus (an enterovirus) or foot-and-mouth disease virus as regulated by the presence or absence of guanidine. Following...... the removal of guanidine from the infected cells, RNA replication occurs after a significant lag phase. This restoration of RNA synthesis requires de novo protein synthesis. Viral RNA can be maintained for at least 72 h within cells in the absence of apparent replication but guanidine-resistant virus can...

  1. Alfalfa (Medicago sativa L.) is tolerant to higher levels of salinity than previous guidelines indicated: Implications of field and greenhouse studies

    Science.gov (United States)

    Putnam, Daniel H.; Benes, Sharon; Galdi, Giuliano; Hutmacher, Bob; Grattan, Steve

    2017-04-01

    Alfalfa (Medicago sativa L.) is the most widely grown leguminous forage crop in North America and is valued for high productivity, quality, economic value, and for dairy productivity. Alfalfa has historically been classified as moderately sensitive to saline conditions, with yield declines predicted at >2 dS/m in the saturated soil paste extract. However, greenhouse, sand tank, and field studies over the past five years have confirmed that alfalfa can be grown with limited negative effects at much higher salinity levels. A broad collection of alfalfa varieties has exhibited a range of resistance at irrigation water salinities >5 dS/m ECw in greenhouse trials, with significant variation due to variety. USDA-ARS sand tank studies indicated similar or greater tolerances closer to 8 dS/m in the soil water, in addition to confirmation of significant varietal differences. A three-year field study on clay loam soil with applications of 5-7 dS/m ECw irrigation water indicated normal yields and excellent stand survivability. A second field study in the same soil type with levels from 8-10 dS/m ECw showed yield reductions of 10-15% but economic yields were still achieved at those levels. Field and greenhouse studies were conducted with mixed salt saline sodic waters typical of the San Joaquin Valley of California. Field evaluation of variety performance was subject to greater variation due to secondary salinity-soil interactions including water infiltration and crusting problems, not only salinity per-se. Thus, adequate irrigation water availability to the crop may be as important as salinity in impacting yields under field conditions. Once established, the deep-rooted characteristics of alfalfa enable utilization of deeper subsurface moisture, even at moderate to high salinity levels, as documented by USDA lysimeter studies. Significant advantages to salinity-tolerant varieties have been observed. It will be important to consider specific management factors which may enable

  2. Effect of benzalkonium chloride?free travoprost on intraocular pressure and ocular surface symptoms in patients with glaucoma previously on latanoprost: an open-label study

    OpenAIRE

    Lopes, Joao F.; Hubatsch, Douglas A.; Amaris, Patricia

    2015-01-01

    Background Prostaglandin analogs reduce intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension; however, these medications may affect the ocular surface and elicit ocular discomfort when preserved with benzalkonium chloride (BAK). Methods This was an open-label, single-arm study conducted in Latin America from February 2012 to May 2013. Patients with open-angle glaucoma or ocular hypertension who were intolerant of latanoprost 0.005?% were transitioned to recei...

  3. Effect of benzalkonium chloride-free travoprost on intraocular pressure and ocular surface symptoms in patients with glaucoma previously on latanoprost: an open-label study.

    Science.gov (United States)

    Lopes, Joao F; Hubatsch, Douglas A; Amaris, Patricia

    2015-11-12

    Prostaglandin analogs reduce intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension; however, these medications may affect the ocular surface and elicit ocular discomfort when preserved with benzalkonium chloride (BAK). This was an open-label, single-arm study conducted in Latin America from February 2012 to May 2013. Patients with open-angle glaucoma or ocular hypertension who were intolerant of latanoprost 0.005 % were transitioned to receive once-daily BAK-free travoprost 0.004 % containing polyquaternium-1 (Travatan® preserved with POLYQUAD® [PQ], Alcon Laboratories, Inc; Fort Worth, TX) for 12 weeks. Mean change in IOP from baseline (primary efficacy endpoint) and the percentage of patients who achieved a target IOP of ≤18 mmHg were evaluated at all on-therapy visits. Ocular hyperemia, patient preference, and self-projected adherence were assessed at week 12. Adverse events (AEs) were monitored throughout the study. All enrolled patients were included in the analysis (n = 191); the majority of patients (90.6 %, n = 173/191) completed the study. Mean (SD) patient age was 67.5 (11.3) years, and mean baseline IOP was 14.8 mmHg. Mean IOP was reduced by 0.94 mmHg at week 6 and by 1.09 mmHg at week 12 (P glaucoma or ocular hypertension who were intolerant of latanoprost. BAK-free travoprost 0.004 % is a viable alternative for patients who require switching their IOP-lowering medications because of tolerability issues. ClinicalTrials.gov identifier, NCT01510145.

  4. Rev1, Rev3, or Rev7 siRNA Abolishes Ultraviolet Light-Induced Translesion Replication in HeLa Cells: A Comprehensive Study Using Alkaline Sucrose Density Gradient Sedimentation

    Directory of Open Access Journals (Sweden)

    Jun Takezawa

    2010-01-01

    Full Text Available When a replicative DNA polymerase stalls upon encountering a lesion on the template strand, it is relieved by other low-processivity polymerase(s, which insert nucleotide(s opposite the lesion, extend by a few nucleotides, and dissociate from the 3′-OH. The replicative polymerase then resumes DNA synthesis. This process, termed translesion replication (TLS or replicative bypass, may involve at least five different polymerases in mammals, although the participating polymerases and their roles have not been entirely characterized. Using siRNAs originally designed and an alkaline sucrose density gradient sedimentation technique, we verified the involvement of several polymerases in ultraviolet (UV light-induced TLS in HeLa cells. First, siRNAs to Rev3 or Rev7 largely abolished UV-TLS, suggesting that these 2 gene products, which comprise Polζ, play a main role in mutagenic TLS. Second, Rev1-targeted siRNA also abrogated UV-TLS, indicating that Rev1 is also indispensable to mutagenic TLS. Third, Polη-targeted siRNA also prevented TLS to a greater extent than our expectations. Forth, although siRNA to Polι had no detectable effect, that to Polκ delayed UV-TLS. To our knowledge, this is the first study reporting apparent evidence for the participation of Polκ in UV-TLS.

  5. Does hyperbaric oxygen treatment have the potential to increase salivary flow rate and reduce xerostomia in previously irradiated head and neck cancer patients? A pilot study

    DEFF Research Database (Denmark)

    Forner, Lone; Hansen, Ole Hyldegaard; von Brockdorff, Annet Schack

    2011-01-01

    in irradiated head and neck cancer patients. Eighty patients eligible for HBO treatment on the indication of prevention/treatment of osteoradionecrosis or soft tissue radiation injury were consecutively sampled, of whom 45 had hyposalivation (i.e. unstimulated whole saliva (UWS) flow rate......Irradiated head and neck cancer survivors treated in the Hyperbaric Oxygen (HBO) Unit, Copenhagen University Hospital, spontaneously reported improvement of radiation-induced dry mouth feeling. The aim of this pilot study was to evaluate salivary flow rate and xerostomia before and after HBO...

  6. Previous study for the setting up and optimization of detection of ZnS(Ag) scintillation applied to the measure of alpha radioactivity index

    International Nuclear Information System (INIS)

    Pujol, L.; Suarez-Navarro, J.A.; Montero, M.

    1998-01-01

    The determination of radiological water quality is useful for a wide range of environmental studies. In these cases, the gross alpha activity is one of the parameters to determine. This parameter permits to decide if further radiological analyses are necessary in order to identify and quantify the presence of alpha emitters in water. The usual method for monitoring the gross alpha activity includes sample evaporation to dryness on a disk and counting using ZnS(Ag) scintillation detector. Detector electronics is provided with two components which are adjustable by the user the high-voltage applied to the photomultiplier tubes and the low level discriminator that is used to eliminate the electronic noise. The high-voltage and low level discriminator optimization are convenient in order to reach the best counting conditions. This paper is a preliminary study of the procedure followed for the setting up and optimization of the detector electronics in the laboratories of CEDEX for the measurement of gross alpha activity. (Author)

  7. [Mutations of resistance of HIV-1 in previously untreated patients at penitentiary centers of the Autonomous Community of Valencia, Spain. REPRICOVA study].

    Science.gov (United States)

    García-Guerrero, Julio; Herrero, Agustín; Vera, Enrique; Almenara, José M; Araújo, Rosa; Saurí, Vicente V; Castellano, Juan C; Fernández-Clemente, Luis; Bedia, Miguel; Llorente, María I; González-Morán, Francisco

    2002-03-02

    Our purpose was to determine the prevalence of mutations of resistance to nucleoside inhibitors of reverse transcriptase (NIRT) and protease inhibitors (PI) in the HIV-1 genotype of naïve infected subjects in the prisons of the Autonomous Community of Valencia, Spain. Multicentric, descriptive, cross-sectional study of prevalence including a systematic stratified and randomised sampling by centres. Demographic, clinical, virological and immunological data were collected. The HIV gene of protease and transcriptase was studied in peripheral blood plasma samples by means of double PCR amplification and subsequent automatic sequence. Reference: wild strain HXB2. Plasma was obtained from 133 individuals (119 men and 14 women). 117 samples were selected and the rest did not have enough copies for transcription. With regard to NIRT, 7 samples (5.2% of total) showed some mutation of resistance: M41L, D67N, L210W and K219Q, all them secondary to and associated with resistance to zidovudine, abacavir as well as group B multinucleoside-resistance. With regard to PI, only one sample showed a primary mutation, M46I, which was associated with resistance to indinavir. Moreover, a further 41 samples were found to express some secondary mutation. In our series, there was a low number of primary mutations of resistance. These results allow us to exclude the systematic use of resistance tests before an initiation antiretroviral therapy.

  8. Responses of Multi-Aged Music Students to Mid-20th-Century Art Music: A Replication and Extension

    Science.gov (United States)

    Madsen, Clifford K.; Geringer, John M.

    2015-01-01

    This investigation replicates previous research into K-12 students' responses to mid-20th-century art music. The study extends that research to include undergraduates and graduates as well as an additional group of graduate students who had taken a 20th-century music class. Children's responses showed remarkable consistency and indicated that…

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

    Science.gov (United States)

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

    2018-01-20

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

  10. Peretinoin, an Acyclic Retinoid, Inhibits Hepatitis B Virus Replication by Suppressing Sphingosine Metabolic Pathway In Vitro

    Directory of Open Access Journals (Sweden)

    Kazuhisa Murai

    2018-01-01

    Full Text Available Hepatocellular carcinoma (HCC frequently develops from hepatitis C virus (HCV and hepatitis B virus (HBV infection. We previously reported that peretinoin, an acyclic retinoid, inhibits HCV replication. This study aimed to examine the influence of peretinoin on the HBV lifecycle. HBV-DNA and covalently closed circular DNA (cccDNA were evaluated by a qPCR method in HepG2.2.15 cells. Peretinoin significantly reduced the levels of intracellular HBV-DNA, nuclear cccDNA, and HBV transcript at a concentration that did not induce cytotoxicity. Conversely, other retinoids, such as 9-cis, 13-cis retinoic acid (RA, and all-trans-retinoic acid (ATRA, had no effect or rather increased HBV replication. Mechanistically, although peretinoin increased the expression of HBV-related transcription factors, as observed for other retinoids, peretinoin enhanced the binding of histone deacetylase 1 (HDAC1 to cccDNA in the nucleus and negatively regulated HBV transcription. Moreover, peretinoin significantly inhibited the expression of SPHK1, a potential inhibitor of HDAC activity, and might be involved in hepatic inflammation, fibrosis, and HCC. SPHK1 overexpression in cells cancelled the inhibition of HBV replication induced by peretinoin. This indicates that peretinoin activates HDAC1 and thereby suppresses HBV replication by inhibiting the sphingosine metabolic pathway. Therefore, peretinoin may be a novel therapeutic agent for HBV replication and chemoprevention against HCC.

  11. Enhanced replication of attenuated HSV-1 in irradiated human glioma xenografts

    International Nuclear Information System (INIS)

    Advani, Sunil J.; Kataoka, Yasushi; Sibley, Greg S.; Song, Paul Y.; Hallahan, Dennis E.; Roizman, Bernard; Weichselbaum, Ralph R.

    1997-01-01

    Purpose: Previously we had shown that combining ionizing radiation (IR) with attenuated replication competent HSV-1 (R3616) significantly increased glioma xenograft eradication compared to IR or virus alone. One hypothesis is that IR induces cell factors that contribute to augment viral replication thereby increasing the efficacy of attenuated HSV-1. The purpose of this study was to examine if IR altered viral replication of attenuated HSV-1 in glioma xenografts Material and Methods: Human U-87MG glioma cells were grown in the hindlimb of athymic mice and grown to >200 mm 3 . Tumors were infected with 2x10 7 plaque forming units (pfu) of R3616 ( γ1 34.5 - ) or R7020 (multimutated, γ1 34.5 + ) on day 0 and irradiated with 20 Gy on day 1 and 25 Gy on day 2. Tumors were harvested 3, 5, 7, and 14 days after viral injection. Tumors were homogenized and sonnicated. Serial dilutions of tumor extract were overlaid on Vero cells to determine the number of pfu. In addition, in-situ hybridization to HSV-1 DNA was performed on tumors harvested at day 7. Results: In-situ hybridization revealed larger numbers of glial cells infected with HSV along with a greater distribution in the irradiated tumors compared to non-irradiated tumors. We next quantified viral particles in infected tumors +/- IR: Conclusion: Herein we demonstrate radiation enhanced viral replication as one of the interactive effects of combining IR and attenuated HSV in treating glioma xenografts and a potential therapeutic motif in the treatment of gliomas. To reduce normal tissue toxicity of HSV in glioma therapy, viruses must be attenuated. However, attenuating the virus compromises its replication and thus its potential efficacy. Our results indicate that IR augments the amount of virus recovered from human glioma xenografts for up to 3 days post IR. The results do not appear to be related to a specific mutation in the herpes genome but rather to herpes viruses in general. Yields of R7020 were greater than R

  12. Rv0004 is a new essential member of the mycobacterial DNA replication machinery.

    Science.gov (United States)

    Mann, Katherine M; Huang, Deborah L; Hooppaw, Anna J; Logsdon, Michelle M; Richardson, Kirill; Lee, Hark Joon; Kimmey, Jacqueline M; Aldridge, Bree B; Stallings, Christina L

    2017-11-01

    DNA replication is fundamental for life, yet a detailed understanding of bacterial DNA replication is limited outside the organisms Escherichia coli and Bacillus subtilis. Many bacteria, including mycobacteria, encode no identified homologs of helicase loaders or regulators of the initiator protein DnaA, despite these factors being essential for DNA replication in E. coli and B. subtilis. In this study we discover that a previously uncharacterized protein, Rv0004, from the human pathogen Mycobacterium tuberculosis is essential for bacterial viability and that depletion of Rv0004 leads to a block in cell cycle progression. Using a combination of genetic and biochemical approaches, we found that Rv0004 has a role in DNA replication, interacts with DNA and the replicative helicase DnaB, and affects DnaB-DnaA complex formation. We also identify a conserved domain in Rv0004 that is predicted to structurally resemble the N-terminal protein-protein interaction domain of DnaA. Mutation of a single conserved tryptophan within Rv0004's DnaA N-terminal-like domain leads to phenotypes similar to those observed upon Rv0004 depletion and can affect the association of Rv0004 with DnaB. In addition, using live cell imaging during depletion of Rv0004, we have uncovered a previously unappreciated role for DNA replication in coordinating mycobacterial cell division and cell size. Together, our data support that Rv0004 encodes a homolog of the recently identified DciA family of proteins found in most bacteria that lack the DnaC-DnaI helicase loaders in E. coli and B. subtilis. Therefore, the mechanisms of Rv0004 elucidated here likely apply to other DciA homologs and reveal insight into the diversity of bacterial strategies in even the most conserved biological processes.

  13. In Vitro Fertilization Outcomes After Placement of Essure Microinserts in Patients With Hydrosalpinges Who Previously Failed In Vitro Fertilization Treatment: A Multicenter Study.

    Science.gov (United States)

    Cohen, Shlomo B; Bouaziz, Jerome; Schiff, Eyal; Simon, Alexander; Nadjary, Michel; Goldenberg, Mordechai; Orvieto, Raoul; Revel, Ariel

    2016-01-01

    To investigate whether hysteroscopic proximal tubal occlusion with Essure microinserts (Conceptus Inc.; Bayer, AG, North Rhine-Westphalia, Germany) can improve pregnancy rates in patients with hydrosalpinges who had failed in vitro fertilization (IVF) treatment. A prospective cohort study. University-affiliated tertiary centers. Twenty-four consecutive women with hydrosalpinges who had failed IVF treatment were included. Hysteroscopic placement of Essure microinserts for hydrosalpinx blockage followed by IVF treatment. Ongoing pregnancy and live birth rates were recorded. Of the 24 patients undergoing a total of 42 IVF cycles after Essure insertion, 18 (75% of patients and 42.8% of IVF cycle attempts) conceived and 16 delivered live births (66.6% of patients and 38.1% of IVF cycle attempts). Hysteroscopic proximal occlusion of hydrosalpinges with Essure microinserts is a valuable alternative to laparoscopic salpingectomy, resulting in reasonable pregnancy rates. Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.

  14. Kansas City Cardiomyopathy Questionnaire Score Is Associated With Incident Heart Failure Hospitalization in Patients With Chronic Kidney Disease Without Previously Diagnosed Heart Failure: Chronic Renal Insufficiency Cohort Study.

    Science.gov (United States)

    Mishra, Rakesh K; Yang, Wei; Roy, Jason; Anderson, Amanda H; Bansal, Nisha; Chen, Jing; DeFilippi, Christopher; Delafontaine, Patrice; Feldman, Harold I; Kallem, Radhakrishna; Kusek, John W; Lora, Claudia M; Rosas, Sylvia E; Go, Alan S; Shlipak, Michael G

    2015-07-01

    Chronic kidney disease is a risk factor for heart failure (HF). Patients with chronic kidney disease without diagnosed HF have an increased burden of symptoms characteristic of HF. It is not known whether these symptoms are associated with occurrence of new onset HF. We studied the association of a modified Kansas City Cardiomyopathy Questionnaire with newly identified cases of hospitalized HF among 3093 participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study who did not report HF at baseline. The annually updated Kansas City Cardiomyopathy Questionnaire score was categorized into quartiles (Q1-4) with the lower scores representing the worse symptoms. Multivariable-adjusted repeated measure logistic regression models were adjusted for demographic characteristics, clinical risk factors for HF, N-terminal probrain natriuretic peptide level and left ventricular hypertrophy, left ventricular systolic and diastolic dysfunction. Over a mean (±SD) follow-up period of 4.3±1.6 years, there were 211 new cases of HF hospitalizations. The risk of HF hospitalization increased with increasing symptom quartiles; 2.62, 1.85, 1.14, and 0.74 events per 100 person-years, respectively. The median number of annual Kansas City Cardiomyopathy Questionnaire assessments per participant was 5 (interquartile range, 3-6). The annually updated Kansas City Cardiomyopathy Questionnaire score was independently associated with higher risk of incident HF hospitalization in multivariable-adjusted models (odds ratio, 3.30 [1.66-6.52]; P=0.001 for Q1 compared with Q4). Symptoms characteristic of HF are common in patients with chronic kidney disease and are associated with higher short-term risk for new hospitalization for HF, independent of level of kidney function, and other known HF risk factors. © 2015 American Heart Association, Inc.

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

    Science.gov (United States)

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

    2016-10-21

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

  16. RapidArc, intensity modulated photon and proton techniques for recurrent prostate cancer in previously irradiated patients: a treatment planning comparison study

    International Nuclear Information System (INIS)

    Weber, Damien C; Miralbell, Raymond; Wang, Hui; Cozzi, Luca; Dipasquale, Giovanna; Khan, Haleem G; Ratib, Osman; Rouzaud, Michel; Vees, Hansjoerg; Zaidi, Habib

    2009-01-01

    A study was performed comparing volumetric modulated arcs (RA) and intensity modulation (with photons, IMRT, or protons, IMPT) radiation therapy (RT) for patients with recurrent prostate cancer after RT. Plans for RA, IMRT and IMPT were optimized for 7 patients. Prescribed dose was 56 Gy in 14 fractions. The recurrent gross tumor volume (GTV) was defined on 18 F-fluorocholine PET/CT scans. Plans aimed to cover at least 95% of the planning target volume with a dose > 50.4 Gy. A maximum dose (D Max ) of 61.6 Gy was allowed to 5% of the GTV. For the urethra, D Max was constrained to 37 Gy. Rectal D Median was < 17 Gy. Results were analyzed using Dose-Volume Histogram and conformity index (CI 90 ) parameters. Tumor coverage (GTV and PTV) was improved with RA (V 95% 92.6 ± 7.9 and 83.7 ± 3.3%), when compared to IMRT (V 95% 88.6 ± 10.8 and 77.2 ± 2.2%). The corresponding values for IMPT were intermediate for the GTV (V 95% 88.9 ± 10.5%) and better for the PTV (V 95% 85.6 ± 5.0%). The percentages of rectal and urethral volumes receiving intermediate doses (35 Gy) were significantly decreased with RA (5.1 ± 3.0 and 38.0 ± 25.3%) and IMPT (3.9 ± 2.7 and 25.1 ± 21.1%), when compared to IMRT (9.8 ± 5.3 and 60.7 ± 41.7%). CI 90 was 1.3 ± 0.1 for photons and 1.6 ± 0.2 for protons. Integral Dose was 1.1 ± 0.5 Gy*cm 3 *10 5 for IMPT and about a factor three higher for all photon's techniques. RA and IMPT showed improvements in conformal avoidance relative to fixed beam IMRT for 7 patients with recurrent prostate cancer. IMPT showed further sparing of organs at risk

  17. Phase 2 study of tabalumab, a human anti-B-cell activating factor antibody, with bortezomib and dexamethasone in patients with previously treated multiple myeloma.

    Science.gov (United States)

    Raje, Noopur S; Moreau, Philippe; Terpos, Evangelos; Benboubker, Lotfi; Grząśko, Norbert; Holstein, Sarah A; Oriol, Albert; Huang, Shang-Yi; Beksac, Meral; Kuliczkowski, Kazimierz; Tai, Datchen F; Wooldridge, James E; Conti, Ilaria; Kaiser, Christopher J; Nguyen, Tuan S; Cronier, Damien M; Palumbo, Antonio

    2017-03-01

    In this double-blind, Phase 2 study, 220 patients with relapsed/refractory multiple myeloma were randomly assigned 1:1:1 to receive placebo (N = 72), tabalumab 100 mg (N = 74), or tabalumab 300 mg (N = 74), each in combination with dexamethasone 20 mg and subcutaneous bortezomib 1·3 mg/m 2 on a 21-day cycle. No significant intergroup differences were observed among primary (median progression-free survival [mPFS]) or secondary efficacy outcomes. The mPFS was 6·6, 7·5 and 7·6 months for the tabalumab 100, 300 mg and placebo groups, respectively (tabalumab 100 mg vs. placebo Hazard ratio (HR) [95% confidence interval (CI)] = 1·13 [0·80-1·59], P = 0·480; tabalumab 300 mg vs. placebo HR [95% CI] = 1·03 [0·72-1·45], P = 0·884). The most commonly-reported treatment-emergent adverse events were thrombocytopenia (37%), fatigue (37%), diarrhoea (35%) and constipation (32%). Across treatments, patients with low baseline BAFF (also termed TNFSF13B) expression (n = 162) had significantly longer mPFS than those with high BAFF expression (n = 55), using the 75th percentile cut-off point (mPFS [95% CI] = 8·3 [7·0-9·3] months vs. 5·8 [3·7-6·6] months; HR [95% CI] = 1·59 [1·11-2·29], P = 0·015). Although generally well tolerated, PFS was not improved during treatment with tabalumab compared to placebo. A higher dose of 300 mg tabalumab did not improve efficacy compared to the 100 mg dose. Nonetheless, BAFF appears to have some prognostic value in patients with multiple myeloma. © 2016 John Wiley & Sons Ltd.

  18. Replication of associations between LRP5 and ESRRA variants and bone density in premenopausal women.

    Science.gov (United States)

    Giroux, S; Elfassihi, L; Cole, D E C; Rousseau, F

    2008-12-01

    Replication is a critical step to validate positive genetic associations. In this study, we tested two previously reported positive associations. The low density lipoprotein receptor-related protein 5 (LRP5) Val667Met and lumbar spine bone density are replicated. This result is in line with results from large consortiums such as Genomos. However, the estrogen-related receptor alpha (ESRRA) repeat in the promoter is not replicated although the polymorphism studied was functional and could have been a causative variant. We sought to validate associations previously reported between LRP5 V667M polymorphism and lumbar spine (LS, p = 0.013) and femoral neck (FN, p = 0.0002) bone mineral density (BMD), and between ESRRA 23 base pair repeat polymorphism and LS BMD (p = 0.0036) in a sample of premenopausal Caucasian women using an independent sample. For the replication sample, we recruited 673 premenopausal women from the Toronto metropolitan area. All women were Caucasian and had BMD measured. LRP5 V667M was genotyped by allele-specific PCR and ESRRA repeats by sizing of PCR products on agarose gels. We reproduced the same association as we reported previously between LRP5 V667M and LS BMD (p = 0.015) but not with FN BMD (p = 0.254). The combined data from the two populations indicate an effect size of 0.28SD for LS BMD (p = 0.00048) and an effect size of 0.26 SD for FN BMD (p = 0.00037). In contrast, the association we reported earlier between ESRRA repeats and LS BMD was not replicated in the sample from Toronto (p = 0.645). The association between LRP5 V667M and LS BMD is confirmed but not that between ESRRA repeats and LS BMD. This result indicates that it is imperative to validate any positive association in an independent sample.

  19. Structure of replicating intermediates of human herpesvirus type 6

    International Nuclear Information System (INIS)

    Severini, Alberto; Sevenhuysen, Claire; Garbutt, Michael; Tipples, Graham A.

    2003-01-01

    We have studied the structure of the replicative intermediates of human herpesvirus 6 (HHV-6) using pulsed-field gel electrophoresis, partial digestion, two-dimensional gel electrophoresis, and sedimentation centrifugation. The results show that DNA replication of HHV-6 produces head-to-tail concatemeric intermediates as well as approximately equal amounts of circular monomers or oligomers. Unlike the situation in herpes simplex virus, the intermediates of human herpesvirus 6 replication are not highly branched, suggesting a difference in the mechanism of replication or a lower frequency of homologous recombination in human herpesvirus 6 compared to herpes simplex virus

  20. Previously unknown species of Aspergillus.

    Science.gov (United States)

    Gautier, M; Normand, A-C; Ranque, S

    2016-08-01

    The use of multi-locus DNA sequence analysis has led to the description of previously unknown 'cryptic' Aspergillus species, whereas classical morphology-based identification of Aspergillus remains limited to the section or species-complex level. The current literature highlights two main features concerning these 'cryptic' Aspergillus species. First, the prevalence of such species in clinical samples is relatively high compared with emergent filamentous fungal taxa such as Mucorales, Scedosporium or Fusarium. Second, it is clearly important to identify these species in the clinical laboratory because of the high frequency of antifungal drug-resistant isolates of such Aspergillus species. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) has recently been shown to enable the identification of filamentous fungi with an accuracy similar to that of DNA sequence-based methods. As MALDI-TOF MS is well suited to the routine clinical laboratory workflow, it facilitates the identification of these 'cryptic' Aspergillus species at the routine mycology bench. The rapid establishment of enhanced filamentous fungi identification facilities will lead to a better understanding of the epidemiology and clinical importance of these emerging Aspergillus species. Based on routine MALDI-TOF MS-based identification results, we provide original insights into the key interpretation issues of a positive Aspergillus culture from a clinical sample. Which ubiquitous species that are frequently isolated from air samples are rarely involved in human invasive disease? Can both the species and the type of biological sample indicate Aspergillus carriage, colonization or infection in a patient? Highly accurate routine filamentous fungi identification is central to enhance the understanding of these previously unknown Aspergillus species, with a vital impact on further improved patient care. Copyright © 2016 European Society of Clinical Microbiology and

  1. Development and application of a quantitative PCR assay to study equine herpesvirus 5 invasion and replication in equine tissues in vitro and in vivo.

    Science.gov (United States)

    Zarski, Lila M; High, Emily A; Nelli, Rahul K; Bolin, Steven R; Williams, Kurt J; Hussey, Gisela

    2017-10-01

    Equine herpesvirus 5 (EHV-5) infection is associated with pulmonary fibrosis in horses, but further studies on EHV-5 persistence in equine cells are needed to fully understand viral and host contributions to disease pathogenesis. Our aim was to develop a quantitative PCR (qPCR) assay to measure EHV-5 viral copy number in equine cell cultures, blood lymphocytes, and nasal swabs of horses. Furthermore, we used a recently developed equine primary respiratory cell culture system to study EHV-5 pathogenesis at the respiratory tract. PCR primers and a probe were designed to target gene E11 of the EHV-5 genome. Sensitivity and repeatability were established, and specificity was verified by testing multiple isolates of EHV-5, as well as DNA from other equine herpesviruses. Four-week old fully differentiated (mature), newly seeded (immature) primary equine respiratory epithelial cell (ERECs), and equine dermal cell cultures were inoculated with EHV-5 and the cells and supernatants collected daily for 14days. Blood lymphocytes and nasal swabs were collected from horses experimentally infected with equine herpesvirus 1 (EHV-1). The qPCR assay detected EHV-5 at stable concentrations throughout 14days in inoculated mature EREC and equine dermal cell cultures (peaking at 202 and 5861 viral genomes per 10 6 cellular β actin, respectively). EHV-5 copies detected in the immature EREC cultures increased over 14days and reached levels greater than 10,000 viral genomes per 10 6 cellular β actin. Moreover, EHV-5 was detected in the lymphocytes of 76% of horses and in the nasal swabs of 84% of horses experimentally infected with EHV-1 pre-inoculation with EHV-1. Post-inoculation with EHV-1, EHV-5 was detected in lymphocytes of 52% of horses while EHV-5 levels in nasal swabs were not significantly different from pre-inoculation levels. In conclusion, qPCR was a reliable technique to investigate viral load in in vivo and in vitro samples, and EHV-5 replication in equine epithelial cells

  2. The Alleged Crisis and the Illusion of Exact Replication

    NARCIS (Netherlands)

    Stroebe, Wolfgang; Strack, Fritz

    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

  3. Infection and Replication of Influenza Virus at the Ocular Surface.

    Science.gov (United States)

    Creager, Hannah M; Kumar, Amrita; Zeng, Hui; Maines, Taronna R; Tumpey, Terrence M; Belser, Jessica A

    2018-04-01

    Although influenza viruses typically cause respiratory tract disease, some viruses, particularly those with an H7 hemagglutinin, have been isolated from the eyes of conjunctivitis cases. Previous work has shown that isolates of multiple subtypes from both ocular and respiratory infections are capable of replication in human ex vivo ocular tissues and corneal or conjunctival cell monolayers, leaving the determinants of ocular tropism unclear. Here, we evaluated the effect of several variables on tropism for ocular cells cultured in vitro and examined the potential effect of the tear film on viral infectivity. All viruses tested were able to replicate in primary human corneal epithelial cell monolayers subjected to aerosol inoculation. The temperature at which cells were cultured postinoculation minimally affected infectivity. Replication efficiency, in contrast, was reduced at 33°C relative to that at 37°C, and this effect was slightly greater for the conjunctivitis isolates than for the respiratory ones. With the exception of a seasonal H3N2 virus, the subset of viruses studied in multilayer corneal tissue constructs also replicated productively after either aerosol or liquid inoculation. Human tears significantly inhibited the hemagglutination of both ocular and nonocular isolates, but the effect on viral infectivity was more variable, with tears reducing the infectivity of nonocular isolates more than ocular isolates. These data suggest that most influenza viruses may be capable of establishing infection if they reach the surface of ocular cells but that this is more likely for ocular-tropic viruses, as they are better able to maintain their infectivity during passage through the tear film. IMPORTANCE The potential spread of zoonotic influenza viruses to humans represents an important threat to public health. Unfortunately, despite the importance of cellular and tissue tropism to pathogenesis, determinants of influenza virus tropism have yet to be fully

  4. Review of previous geophysical and geological studies

    Digital Repository Service at National Institute of Oceanography (India)

    Levchenko, O.V.; Neprochnov, Y.P; Rao, D.G; Subrahmanyam, C.; Murthy, K.S

    stream_size 5 stream_content_type text/plain stream_name Mem_Geol_Soc_India_39_5.pdf.txt stream_source_info Mem_Geol_Soc_India_39_5.pdf.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 ...

  5. Myopic loss aversion: Potential causes of replication failures

    Directory of Open Access Journals (Sweden)

    Alexander Klos

    2013-09-01

    Full Text Available This paper presents two studies on narrow bracketing and myopic loss aversion. The first study shows that the tendency to segregate multiple gambles is eliminated if subjects face a certainty equivalent or a probability equivalent task instead of a binary choice. The second study argues that the behavioral differences previously attributed entirely to myopic loss aversion are partly because long-term return properties are simply easier to grasp if the return information is already provided in the form of long-term returns rather than one-year returns. Both results may be related to recent failures to replicate myopic loss aversion. When the choice situation is structured in such a way that it draws respondents' attention to the final outcome distribution and/or if severe misestimations of long-term returns based on short-term return information are unlikely, behavioral differences consistent with myopic loss aversion are less likely to be observed.

  6. Chaotic interactions of self-replicating RNA.

    Science.gov (United States)

    Forst, C V

    1996-03-01

    A general system of high-order differential equations describing complex dynamics of replicating biomolecules is given. Symmetry relations and coordinate transformations of general replication systems leading to topologically equivalent systems are derived. Three chaotic attractors observed in Lotka-Volterra equations of dimension n = 3 are shown to represent three cross-sections of one and the same chaotic regime. Also a fractal torus in a generalized three-dimensional Lotka-Volterra Model has been linked to one of the chaotic attractors. The strange attractors are studied in the equivalent four-dimensional catalytic replicator network. The fractal torus has been examined in adapted Lotka-Volterra equations. Analytic expressions are derived for the Lyapunov exponents of the flow in the replicator system. Lyapunov spectra for different pathways into chaos has been calculated. In the generalized Lotka-Volterra system a second inner rest point--coexisting with (quasi)-periodic orbits--can be observed; with an abundance of different bifurcations. Pathways from chaotic tori, via quasi-periodic tori, via limit cycles, via multi-periodic orbits--emerging out of periodic doubling bifurcations--to "simple" chaotic attractors can be found.

  7. Gene organization inside replication domains in mammalian genomes

    Science.gov (United States)

    Zaghloul, Lamia; Baker, Antoine; Audit, Benjamin; Arneodo, Alain

    2012-11-01

    We investigate the large-scale organization of human genes with respect to "master" replication origins that were previously identified as bordering nucleotide compositional skew domains. We separate genes in two categories depending on their CpG enrichment at the promoter which can be considered as a marker of germline DNA methylation. Using expression data in mouse, we confirm that CpG-rich genes are highly expressed in germline whereas CpG-poor genes are in a silent state. We further show that, whether tissue-specific or broadly expressed (housekeeping genes), the CpG-rich genes are over-represented close to the replication skew domain borders suggesting some coordination of replication and transcription. We also reveal that the transcription of the longest CpG-rich genes is co-oriented with replication fork progression so that the promoter of these transcriptionally active genes be located into the accessible open chromatin environment surrounding the master replication origins that border the replication skew domains. The observation of a similar gene organization in the mouse genome confirms the interplay of replication, transcription and chromatin structure as the cornerstone of mammalian genome architecture.

  8. Preoperative screening: value of previous tests.

    Science.gov (United States)

    Macpherson, D S; Snow, R; Lofgren, R P

    1990-12-15

    To determine the frequency of tests done in the year before elective surgery that might substitute for preoperative screening tests and to determine the frequency of test results that change from a normal value to a value likely to alter perioperative management. Retrospective cohort analysis of computerized laboratory data (complete blood count, sodium, potassium, and creatinine levels, prothrombin time, and partial thromboplastin time). Urban tertiary care Veterans Affairs Hospital. Consecutive sample of 1109 patients who had elective surgery in 1988. At admission, 7549 preoperative tests were done, 47% of which duplicated tests performed in the previous year. Of 3096 previous results that were normal as defined by hospital reference range and done closest to the time of but before admission (median interval, 2 months), 13 (0.4%; 95% CI, 0.2% to 0.7%), repeat values were outside a range considered acceptable for surgery. Most of the abnormalities were predictable from the patient's history, and most were not noted in the medical record. Of 461 previous tests that were abnormal, 78 (17%; CI, 13% to 20%) repeat values at admission were outside a range considered acceptable for surgery (P less than 0.001, frequency of clinically important abnormalities of patients with normal previous results with those with abnormal previous results). Physicians evaluating patients preoperatively could safely substitute the previous test results analyzed in this study for preoperative screening tests if the previous tests are normal and no obvious indication for retesting is present.

  9. REPLICATION TOOL AND METHOD OF PROVIDING A REPLICATION TOOL

    DEFF Research Database (Denmark)

    2016-01-01

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

  10. CRISPR-mediated control of the bacterial initiation of replication

    NARCIS (Netherlands)

    Wiktor, J.M.; Lesterlin, Christian; Sherratt, David J.; Dekker, C.

    2016-01-01

    Programmable control of the cell cycle has been shown to be a powerful tool in cell-biology studies. Here, we develop a novel system for controlling the bacterial cell cycle, based on binding of CRISPR/dCas9 to the origin-of-replication locus. Initiation of replication of bacterial chromosomes is

  11. 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…

  12. Oblique roughness replication in strained SiGe/Si multilayers

    NARCIS (Netherlands)

    Holy, V.; Darhuber, A.A.; Stangl, J.; Bauer, G.; Nützel, J.-F.; Abstreiter, G.

    1998-01-01

    The replication of the interface roughness in SiGe/Si multilayers grown on miscut Si(001) substrates has been studied by means of x-ray reflectivity reciprocal space mapping. The interface profiles were found to be highly correlated and the direction of the maximal replication was inclined with

  13. Do gender and personality traits (BFI-10) influence trust? A replication

    DEFF Research Database (Denmark)

    Sudzina, Frantisek

    2016-01-01

    of this article is to investigate if gender and personality traits influence rating of these two statement. And if so, if it is possible to account for these factors and to create a robust trust indicator from these two statements after all. Big Five Inventory-10 is used to measure personality traits. Findings...... with adding personality traits into the equation. This article is a replication of a previous study. This study uses 1-5 Likert scales while the previous used 1-7 Likert scales, while all the questions/statements stayed the same. The difference is that both measures (not only the first measure) of trust were...

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

    Directory of Open Access Journals (Sweden)

    Anthony Lane

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

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

    Directory of Open Access Journals (Sweden)

    Bittner Alexandra

    2004-12-01

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

  16. Golimumab in patients with active rheumatoid arthritis who have previous experience with tumour necrosis factor inhibitors: results of a long-term extension of the randomised, double-blind, placebo-controlled GO-AFTER study through week 160

    NARCIS (Netherlands)

    Smolen, Josef S.; Kay, Jonathan; Landewé, Robert B. M.; Matteson, Eric L.; Gaylis, Norman; Wollenhaupt, Jurgen; Murphy, Frederick T.; Zhou, Yiying; Hsia, Elizabeth C.; Doyle, Mittie K.

    2012-01-01

    The aim of this study was to assess long-term golimumab therapy in patients with rheumatoid arthritis (RA) who discontinued previous tumour necrosis factor alpha (TNFα) inhibitor(s) for any reason. Results through week 24 of this multicentre, randomised, double-blind, placebo-controlled study of

  17. ATR prohibits replication catastrophe by preventing global exhaustion of RPA.

    Science.gov (United States)

    Toledo, Luis Ignacio; Altmeyer, Matthias; Rask, Maj-Britt; Lukas, Claudia; Larsen, Dorthe Helena; Povlsen, Lou Klitgaard; Bekker-Jensen, Simon; Mailand, Niels; Bartek, Jiri; Lukas, Jiri

    2013-11-21

    ATR, activated by replication stress, protects replication forks locally and suppresses origin firing globally. Here, we show that these functions of ATR are mechanistically coupled. Although initially stable, stalled forks in ATR-deficient cells undergo nucleus-wide breakage after unscheduled origin firing generates an excess of single-stranded DNA that exhausts the nuclear pool of RPA. Partial reduction of RPA accelerated fork breakage, and forced elevation of RPA was sufficient to delay such "replication catastrophe" even in the absence of ATR activity. Conversely, unscheduled origin firing induced breakage of stalled forks even in cells with active ATR. Thus, ATR-mediated suppression of dormant origins shields active forks against irreversible breakage via preventing exhaustion of nuclear RPA. This study elucidates how replicating genomes avoid destabilizing DNA damage. Because cancer cells commonly feature intrinsically high replication stress, this study also provides a molecular rationale for their hypersensitivity to ATR inhibitors. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Biomarkers of replicative senescence revisited

    DEFF Research Database (Denmark)

    Nehlin, Jan

    2016-01-01

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

  19. A rolling circle replication mechanism produces multimeric lariats of mitochondrial DNA in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Samantha C Lewis

    2015-02-01

    Full Text Available Mitochondrial DNA (mtDNA encodes respiratory complex subunits essential to almost all eukaryotes; hence respiratory competence requires faithful duplication of this molecule. However, the mechanism(s of its synthesis remain hotly debated. Here we have developed Caenorhabditis elegans as a convenient animal model for the study of metazoan mtDNA synthesis. We demonstrate that C. elegans mtDNA replicates exclusively by a phage-like mechanism, in which multimeric molecules are synthesized from a circular template. In contrast to previous mammalian studies, we found that mtDNA synthesis in the C. elegans gonad produces branched-circular lariat structures with multimeric DNA tails; we were able to detect multimers up to four mtDNA genome unit lengths. Further, we did not detect elongation from a displacement-loop or analogue of 7S DNA, suggesting a clear difference from human mtDNA in regard to the site(s of replication initiation. We also identified cruciform mtDNA species that are sensitive to cleavage by the resolvase RusA; we suggest these four-way junctions may have a role in concatemer-to-monomer resolution. Overall these results indicate that mtDNA synthesis in C. elegans does not conform to any previously documented metazoan mtDNA replication mechanism, but instead are strongly suggestive of rolling circle replication, as employed by bacteriophages. As several components of the metazoan mitochondrial DNA replisome are likely phage-derived, these findings raise the possibility that the rolling circle mtDNA replication mechanism may be ancestral among metazoans.

  20. Pyrimidine Pool Disequilibrium Induced by a Cytidine Deaminase Deficiency Inhibits PARP-1 Activity, Leading to the Under Replication of DNA.

    Directory of Open Access Journals (Sweden)

    Simon Gemble

    2015-07-01

    Full Text Available Genome stability is jeopardized by imbalances of the dNTP pool; such imbalances affect the rate of fork progression. For example, cytidine deaminase (CDA deficiency leads to an excess of dCTP, slowing the replication fork. We describe here a novel mechanism by which pyrimidine pool disequilibrium compromises the completion of replication and chromosome segregation: the intracellular accumulation of dCTP inhibits PARP-1 activity. CDA deficiency results in incomplete DNA replication when cells enter mitosis, leading to the formation of ultrafine anaphase bridges between sister-chromatids at "difficult-to-replicate" sites such as centromeres and fragile sites. Using molecular combing, electron microscopy and a sensitive assay involving cell imaging to quantify steady-state PAR levels, we found that DNA replication was unsuccessful due to the partial inhibition of basal PARP-1 activity, rather than slower fork speed. The stimulation of PARP-1 activity in CDA-deficient cells restores replication and, thus, chromosome segregation. Moreover, increasing intracellular dCTP levels generates under-replication-induced sister-chromatid bridges as efficiently as PARP-1 knockdown. These results have direct implications for Bloom syndrome (BS, a rare genetic disease combining susceptibility to cancer and genomic instability. BS results from mutation of the BLM gene, encoding BLM, a RecQ 3'-5' DNA helicase, a deficiency of which leads to CDA downregulation. BS cells thus have a CDA defect, resulting in a high frequency of ultrafine anaphase bridges due entirely to dCTP-dependent PARP-1 inhibition and independent of BLM status. Our study describes previously unknown pathological consequences of the distortion of dNTP pools and reveals an unexpected role for PARP-1 in preventing DNA under-replication and chromosome segregation defects.

  1. SARS-coronavirus replication is supported by a reticulovesicular network of modified endoplasmic reticulum.

    Directory of Open Access Journals (Sweden)

    Kèvin Knoops

    2008-09-01

    Full Text Available Positive-strand RNA viruses, a large group including human pathogens such as SARS-coronavirus (SARS-CoV, replicate in the cytoplasm of infected host cells. Their replication complexes are commonly associated with modified host cell membranes. Membrane structures supporting viral RNA synthesis range from distinct spherular membrane invaginations to more elaborate webs of packed membranes and vesicles. Generally, their ultrastructure, morphogenesis, and exact role in viral replication remain to be defined. Poorly characterized double-membrane vesicles (DMVs were previously implicated in SARS-CoV RNA synthesis. We have now applied electron tomography of cryofixed infected cells for the three-dimensional imaging of coronavirus-induced membrane alterations at high resolution. Our analysis defines a unique reticulovesicular network of modified endoplasmic reticulum that integrates convoluted membranes, numerous interconnected DMVs (diameter 200-300 nm, and "vesicle packets" apparently arising from DMV merger. The convoluted membranes were most abundantly immunolabeled for viral replicase subunits. However, double-stranded RNA, presumably revealing the site of viral RNA synthesis, mainly localized to the DMV interior. Since we could not discern a connection between DMV interior and cytosol, our analysis raises several questions about the mechanism of DMV formation and the actual site of SARS-CoV RNA synthesis. Our data document the extensive virus-induced reorganization of host cell membranes into a network that is used to organize viral replication and possibly hide replicating RNA from antiviral defense mechanisms. Together with biochemical studies of the viral enzyme complex, our ultrastructural description of this "replication network" will aid to further dissect the early stages of the coronavirus life cycle and its virus-host interactions.

  2. Contextual mediation of perceptions during hauntings and poltergeist-like experiences: a replication and extension.

    Science.gov (United States)

    Harte, T M

    2000-10-01

    This study is a replication of the experiment by Lange, Houran, Harte, and Havens (1996 on contextual variables, in which hallucinations appear to be affected by the environmental context. These contextual variables are influential in the reporting of haunting and poltergeist-like episodes. This study extended the previous study by adding new factors of time of day, climactic conditions, and emotional feelings. These were analyzed for a different sample, looking for further congruency between experiential content and the context. The sample (N=8431 were reports found on the Internet and in one book. The Lange, et al. study was replicated in that contextual variables were identified in 99.2% of the reports, the content of the reports was judged to be consistent with the nature of the contextual variables in 58.8% of the reports, and contextual variables were related to the percipients' state of arousal and the modalities of experience.

  3. Replication in hydroxyurea: it's a matter of time.

    Science.gov (United States)

    Alvino, Gina M; Collingwood, David; Murphy, John M; Delrow, Jeffrey; Brewer, Bonita J; Raghuraman, M K

    2007-09-01

    Hydroxyurea (HU) is a DNA replication inhibitor that negatively affects both the elongation and initiation phases of replication and triggers the "intra-S phase checkpoint." Previous work with budding yeast has shown that, during a short exposure to HU, MEC1/RAD53 prevent initiation at some late S phase origins. In this study, we have performed microarray experiments to follow the fate of all origins over an extended exposure to HU. We show that the genome-wide progression of DNA synthesis, including origin activation, follows the same pattern in the presence of HU as in its absence, although the time frames are very different. We find no evidence for a specific effect that excludes initiation from late origins. Rather, HU causes S phase to proceed in slow motion; all temporal classes of origins are affected, but the order in which they become active is maintained. We propose a revised model for the checkpoint response to HU that accounts for the continued but slowed pace of the temporal program of origin activation.

  4. Cytoplasmic ATR Activation Promotes Vaccinia Virus Genome Replication

    Directory of Open Access Journals (Sweden)

    Antonio Postigo

    2017-05-01

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

  5. Successive Research: A Strategy for Building on Previous Research.

    Science.gov (United States)

    Noble, Mary Anne

    1979-01-01

    Describes an approach to clinical research used by the author in teaching graduate nursing students, involving replication and expansion of a primary study of hospital intensive care units. This approach provided valuable experience as well as validated data about clinical pra