WorldWideScience

Sample records for replication previous studies

  1. Convergence in the Bilingual Lexicon: A Pre-registered Replication of Previous Studies

    Science.gov (United States)

    White, Anne; Malt, Barbara C.; Storms, Gert

    2017-01-01

    Naming patterns of bilinguals have been found to converge and form a new intermediate language system from elements of both the bilinguals’ languages. This converged naming pattern differs from the monolingual naming patterns of both a bilingual’s languages. We conducted a pre-registered replication study of experiments addressing the question whether there is a convergence between a bilingual’s both lexicons. The replication used an enlarged set of stimuli of common household containers, providing generalizability, and more reliable representations of the semantic domain. Both an analysis at the group-level and at the individual level of the correlations between naming patterns reject the two-pattern hypothesis that poses that bilinguals use two monolingual-like naming patterns, one for each of their two languages. However, the results of the original study and the replication comply with the one-pattern hypothesis, which poses that bilinguals converge the naming patterns of their two languages and form a compromise. Since this convergence is only partial the naming pattern in bilinguals corresponds to a moderate version of the one-pattern hypothesis. These findings are further confirmed by a representation of the semantic domain in a multidimensional space and the finding of shorter distances between bilingual category centers than monolingual category centers in this multidimensional space both in the original and in the replication study. PMID:28167921

  2. Effective Teaching and Learning Environments and Principal Self-Efficacy in Oklahoma: Replication of a Previous Study

    Science.gov (United States)

    Berry, Kathryn

    2013-01-01

    The purpose of this study was to replicate a previous study by Smith et al. (2006) that explored principal self-efficacy beliefs for facilitating effective instructional environments at their schools. There has been limited research conducted on principal's self-efficacy, and the studies that have been completed on the topic have not been…

  3. 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...

  4. The pre-engagement cohabitation effect: a replication and extension of previous findings.

    Science.gov (United States)

    Rhoades, Galena K; Stanley, Scott M; Markman, Howard J

    2009-02-01

    Using a random telephone survey of men and women married within the past 10 years (N = 1,050), the current study replicated previous findings regarding the timing of engagement and the premarital cohabitation effect (see Kline et al., 2004). Those who cohabited before engagement (43.1%) reported lower marital satisfaction, dedication, and confidence as well as more negative communication and greater potential for divorce than those who cohabited only after engagement (16.4%) or not at all until marriage (40.5%). These differences were generally small, but could not be accounted for by length of marriage or by variables often associated with selection into cohabitation (i.e., age, income, education, and religiousness). Similar results were found in a subsample of individuals who cohabited only with the current spouse. There were no significant differences between those who cohabited after engagement and not at all before marriage, supporting a pre-engagement, but not a premarital cohabitation effect.

  5. Abnormal Parietal Brain Function in ADHD: Replication and Extension of Previous EEG Beta Asymmetry Findings

    Directory of Open Access Journals (Sweden)

    T. Sigi eHale

    2014-07-01

    Full Text Available Background: Abundant work indicates ADHD abnormal posterior brain structure and function, including abnormal structural and functional asymmetries and reduced corpus callosum size. However, this literature has attracted considerably less research interest than fronto-striatal findings. Objective: To help address this imbalance, the current study replicates and extends our previous work showing abnormal parietal brain function in ADHD adults during the Conner’s continuous performance test (CPT. Method: Our previous study found that ADHD adults had increased rightward EEG beta (16-21 Hz asymmetry in inferior parietal brain regions during the CPT (p=.00001, and that this metric exhibited a lack of normal correlation (i.e., observed in controls with beta asymmetry at temporal-parietal regions. We re-tested these effects in a new ADHD sample, and with both new and old samples combined. We additionally examined: a EEG asymmetry in multiple frequency bands, b unilateral effects for all asymmetry findings, and c the association between EEG asymmetry and a battery of cognitive tests. Results: We replicated our original findings, again demonstrating abnormal rightward inferior parietal beta asymmetry in adults with ADHD during the CPT, and again this metric exhibited abnormal reduced correlation to temporal-parietal beta asymmetry. Novel analyses also demonstrated a broader pattern of rightward beta and theta asymmetry across inferior, superior, and temporal-parietal brain regions, and showed that rightward parietal asymmetry in ADHD was atypically associated with multiple cognitive tests. Conclusion: Abnormal increased rightward parietal EEG beta asymmetry is an important feature of ADHD. We speculate that this phenotype may occur with any form of impaired capacity for top-down task-directed control over sensory encoding functions, and that it may reflect associated increases of attentional shifting and compensatory sustained/selective attention.

  6. Two-stage replication of previous genome-wide association studies of AS3MT-CNNM2-NT5C2 gene cluster region in a large schizophrenia case-control sample from Han Chinese population.

    Science.gov (United States)

    Guan, Fanglin; Zhang, Tianxiao; Li, Lu; Fu, Dongke; Lin, Huali; Chen, Gang; Chen, Teng

    2016-10-01

    Schizophrenia is a devastating psychiatric condition with high heritability. Replicating the specific genetic variants that increase susceptibility to schizophrenia in different populations is critical to better understand schizophrenia. CNNM2 and NT5C2 are genes recently identified as susceptibility genes for schizophrenia in Europeans, but the exact mechanism by which these genes confer risk for schizophrenia remains unknown. In this study, we examined the potential for genetic susceptibility to schizophrenia of a three-gene cluster region, AS3MT-CNNM2-NT5C2. We implemented a two-stage strategy to conduct association analyses of the targeted regions with schizophrenia. A total of 8218 individuals were recruited, and 45 pre-selected single nucleotide polymorphisms (SNPs) were genotyped. Both single-marker and haplotype-based analyses were conducted in addition to imputation analysis to increase the coverage of our genetic markers. Two SNPs, rs11191419 (OR=1.24, P=7.28×10(-5)) and rs11191514 (OR=1.24, P=0.0003), with significant independent effects were identified. These results were supported by the data from both the discovery and validation stages. Further haplotype and imputation analyses also validated these results, and bioinformatics analyses indicated that CALHM1, which is located approximately 630kb away from CNNM2, might be a susceptible gene for schizophrenia. Our results provide further support that AS3MT, CNNM2 and CALHM1 are involved with the etiology and pathogenesis of schizophrenia, suggesting these genes are potential targets of interest for the improvement of disease management and the development of novel pharmacological strategies.

  7. Previous infection with virulent strains of Newcastle disease virus reduces highly pathogenic avian influenza virus replication, disease, and mortality in chickens.

    Science.gov (United States)

    Costa-Hurtado, Mar; Afonso, Claudio L; Miller, Patti J; Shepherd, Eric; Cha, Ra Mi; Smith, Diane; Spackman, Erica; Kapczynski, Darrell R; Suarez, David L; Swayne, David E; Pantin-Jackwood, Mary J

    2015-09-23

    Highly pathogenic avian influenza virus (HPAIV) and Newcastle disease virus (NDV) are two of the most important viruses affecting poultry worldwide and produce co-infections especially in areas of the world where both viruses are endemic; but little is known about the interactions between these two viruses. The objective of this study was to determine if co-infection with NDV affects HPAIV replication in chickens. Only infections with virulent NDV strains (mesogenic Pigeon/1984 or velogenic CA/2002), and not a lentogenic NDV strain (LaSota), interfered with the replication of HPAIV A/chicken/Queretaro/14588-19/95 (H5N2) when the H5N2 was given at a high dose (10(6.9) EID50) two days after the NDV inoculation, but despite this interference, mortality was still observed. However, chickens infected with the less virulent mesogenic NDV Pigeon/1984 strain three days prior to being infected with a lower dose (10(5.3-5.5) EID50) of the same or a different HPAIV, A/chicken/Jalisco/CPA-12283-12/2012 (H7N3), had reduced HPAIV replication and increased survival rates. In conclusion, previous infection of chickens with virulent NDV strains can reduce HPAIV replication, and consequently disease and mortality. This interference depends on the titer of the viruses used, the virulence of the NDV, and the timing of the infections. The information obtained from these studies helps to understand the possible interactions and outcomes of infection (disease and virus shedding) when HPAIV and NDV co-infect chickens in the field.

  8. Simulation Studies in Data Replication Strategies

    Institute of Scientific and Technical Information of China (English)

    HarveyB.Newman; IosifC.Legrand

    2001-01-01

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

  9. 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.

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

    Science.gov (United States)

    Davies, M S

    1996-01-01

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

  12. Hypotension and Environmental Noise: A Replication Study

    Science.gov (United States)

    Lercher, Peter; Widmann, Ulrich; Thudium, Jürg

    2014-01-01

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

  13. Hypotension and Environmental Noise: A Replication Study

    Directory of Open Access Journals (Sweden)

    Peter Lercher

    2014-08-01

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

  14. Optimal Allocation of Replicates for Measurement Evaluation Studies

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

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

    Science.gov (United States)

    Radke, Sina; de Bruijn, Ellen R A

    2015-10-01

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

  16. Previous studies underestimate BMAA concentrations in cycad flour.

    Science.gov (United States)

    Cheng, Ran; Banack, Sandra Anne

    2009-01-01

    The traditional diet of the Chamorro people of Guam has high concentrations of the neurotoxin BMAA, beta-methyl-amino-L-alanine, in cycad tortillas and from animals that feed on cycad seeds. We measured BMAA concentration in washed cycad flour and compared different extraction methods used by previous researchers in order to determine how much BMAA may have been unaccounted for in prior research. Samples were analyzed with AQC precolumn derivatization using HPLC-FD detection and verified with UPLC-UV, UPLC-MS, and triple quadrupole LC/MS/MS. Although previous workers had studied only the free amino acid component of BMAA in washed cycad flour, we detected significant levels of protein-associated BMAA in washed cycad flour. These data support a link between ALS/PDC and exposure to BMAA.

  17. SNP CHARACTERISTICS PREDICT REPLICATION SUCCESS IN ASSOCIATION STUDIES

    Science.gov (United States)

    Gorlov, Ivan P.; Moore, Jason H.; Peng, Bo; Jin, Jennifer L.; Gorlova, Olga Y.; Amos, Christopher I.

    2014-01-01

    Successful independent replication is the most direct approach for distinguishing real genotype-disease associations from false discoveries in Genome Wide Association Studies (GWAS). Selecting SNPs for replication has been primarily based on p-values from the discovery stage, although additional characteristics of SNPs may be used to improve replication success. We used disease-associated SNPs from more than 2,000 published GWASs to identify predictors of SNP reproducibility. SNP reproducibility was defined as a proportion of successful replications among all replication attempts. The study reporting association for the first time was considered to be discovery and all consequent studies targeting the same phenotype replications. We found that −Log(P), where P is a p-value from the discovery study, is the strongest predictor of the SNP reproducibility. Other significant predictors include type of the SNP (e.g. missense vs intronic SNPs) and minor allele frequency. Features of the genes linked to the disease-associated SNP also predict SNP reproducibility. Based on empirically defined rules, we developed a reproducibility score (RS) to predict SNP reproducibility independently of −Log(P). We used data from two lung cancer GWAS studies as well as recently reported disease-associated SNPs to validate RS. Minus Log(P) outperforms RS when the very top SNPs are selected, while RS works better with relaxed selection criteria. In conclusion, we propose an empirical model to predict SNP reproducibility, which can be used to select SNPs for validation and prioritization. PMID:25273843

  18. Hemisphere Susceptibility and Personality: a Replication Study

    Science.gov (United States)

    Dimond, Stuart; Beaumont, Graham

    1974-01-01

    Author studied the capacity of the normal brain to carry out a paired-associate learning task by projecting the stimulus material to either the right or left hemisphere in order to establish if there was a lateral specialization for this type of learning in the normal brain. (Author/RK)

  19. 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.

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

    Science.gov (United States)

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

    2010-01-01

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

  1. Study of cystic artery by arteriography. Importance of previous cholecystography

    Energy Technology Data Exchange (ETDEWEB)

    Machado, G.O.

    An oral cholecystography previously to celiac and mesenteric arteriography is performed, in order to identify the cystic artery, in 42 patients with pancreatitis, according Seldinger technique. The cystic artery was identified in all the cases, the pattern being the outlet of the cystic artery from the right hepatic artery. Infusion pump and seriography were not used.

  2. 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…

  3. 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 selec

  4. 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…

  5. Study on the micro-replication of shark skin

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

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

  6. New study reveals twice as many asteroids as previously believed

    Science.gov (United States)

    2002-05-01

    The ISO satellite Credits: ESA ISO An artist's impression of the ISO spacecraft. The ISO Deep Asteroid Search indicates that there are between 1.1 million and 1.9 million 'space rocks' larger than 1 kilometre in diameter in the so-called 'main asteroid belt', about twice as many as previously believed. However, astronomers think it is premature to revise current assessments of the risk of the Earth being hit by an asteroid. Despite being in our own Solar System, asteroids can be more difficult to study than very distant galaxies. With sizes of up to one thousand kilometres in diameter, the brightness of these rocky objects may vary considerably in just a few minutes. They move very quickly with respect to the stars - they have been dubbed 'vermin of the sky' because they often appear as trails on long exposure images. This elusiveness explains why their actual number and size distribution remains uncertain. Most of the almost 40,000 asteroids catalogued so far (1) orbit the Sun forming the 'main asteroid belt', between Mars and Jupiter, too far to pose any threat to Earth. However, space-watchers do keep a closer eye on another category of asteroids, the 'Near Earth Asteroids' or 'NEAs', which are those whose orbits cross, or are likely to cross, that of our planet. The ISO Deep Asteroid Search (IDAS), the first systematic search for these objects performed in infrared light, focused on main belt asteroids. Because it is impossible to simply point the telescope at the whole main belt and count, astronomers choose selected regions of the belt and then use a theoretical model to extrapolate the data to the whole belt. Edward Tedesco (TerraSystems, Inc., New Hampshire, United States) and François-Xavier Desert (Observatoire de Grenoble, France) observed their main belt selected areas in 1996 and 1997 with ESA's ISO. They found that in the middle region of the belt the density of asteroids was 160 asteroids larger than 1 kilometre per square degree - an area of the

  7. Replication of Prostate Cancer Risk Variants in a Danish Case-Control Association Study

    DEFF Research Database (Denmark)

    Bentzon, Diem Nguyen; Nyegaard, Mette; Børglum, Anders

    2012-01-01

    assays and associations between SNPs, prostate cancer risk, and clinico-pathological variables were assessed. Results: Seventeen SNPs were successfully replicated in our case-control study and the association estimates were consistent with previous reports. Four markers were excluded from further...... (P = 0.045). In addition, variants rs6983267 (GG) and rs5759167 (GG/GT) were significantly associated with negative family history (P = 0.04 and P = 0.02, respectively). Conclusion: We replicated 17 previously identified prostate cancer-associated risk SNPs in a Danish case-control study and found...... developed to predict prostate cancer risk. The association between genetic markers and clinico-pathological tumor variables has, however, been inconsistent. Methods and Materials: A total of 32 previously identified prostate cancer-associated risk SNPs were genotyped in 648 prostate cancer cases and 526 age...

  8. Replication study of 34 common SNPs associated with prostate cancer in the Romanian population.

    Science.gov (United States)

    Jinga, Viorel; Csiki, Irma Eva; Manolescu, Andrei; Iordache, Paul; Mates, Ioan Nicolae; Radavoi, Daniel; Rascu, Stefan; Badescu, Daniel; Badea, Paula; Mates, Dana

    2016-04-01

    Prostate cancer is the third-most common form of cancer in men in Romania. The Romanian unscreened population represents a good sample to study common genetic risk variants. However, a comprehensive analysis has not been conducted yet. Here, we report our replication efforts in a Romanian population of 979 cases and 1027 controls, for potential association of 34 literature-reported single nucleotide polymorphisms (SNPs) with prostate cancer. We also examined whether any SNP was differentially associated with tumour grade or stage at diagnosis, with disease aggressiveness, and with the levels of PSA (prostate specific antigen). In the allelic analysis, we replicated the previously reported risk for 19 loci on 4q24, 6q25.3, 7p15.2, 8q24.21, 10q11.23, 10q26.13, 11p15.5, 11q13.2, 11q13.3. Statistically significant associations were replicated for other six SNPs only with a particular disease phenotype: low-grade tumour and low PSA levels (rs1512268), high PSA levels (rs401681 and rs11649743), less aggressive cancers (rs1465618, rs721048, rs17021918). The strongest association of our tested SNP's with PSA in controls was for rs2735839, with 29% increase for each copy of the major allele G, consistent with previous results. Our results suggest that rs4962416, previously associated only with prostate cancer, is also associated with PSA levels, with 12% increase for each copy of the minor allele C. The study enabled the replication of the effect for the majority of previously reported genetic variants in a set of clinically relevant prostate cancers. This is the first replication study on these loci, known to associate with prostate cancer, in a Romanian population.

  9. A Comprehensive Family-Based Replication Study of Schizophrenia Genes

    Science.gov (United States)

    Aberg, Karolina A.; Liu, Youfang; Bukszár, Jozsef; McClay, Joseph L.; Khachane, Amit N.; Andreassen, Ole A.; Blackwood, Douglas; Corvin, Aiden; Djurovic, Srdjan; Gurling, Hugh; Ophoff, Roel; Pato, Carlos N.; Pato, Michele T.; Riley, Brien; Webb, Todd; Kendler, Kenneth; O’Donovan, Mick; Craddock, Nick; Kirov, George; Owen, Mike; Rujescu, Dan; St Clair, David; Werge, Thomas; Hultman, Christina M.; Delisi, Lynn E.; Sullivan, Patrick; van den Oord, Edwin J.

    2017-01-01

    Importance Schizophrenia (SCZ) is a devastating psychiatric condition. Identifying the specific genetic variants and pathways that increase susceptibility to SCZ is critical to improve disease understanding and address the urgent need for new drug targets. Objective To identify SCZ susceptibility genes. Design We integrated results from a meta-analysis of 18 genome-wide association studies (GWAS) involving 1 085 772 single-nucleotide polymorphisms (SNPs) and 6 databases that showed significant informativeness for SCZ. The 9380 most promising SNPs were then specifically genotyped 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 10 768 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 with replication values of P<.01, the proportion of SNPs that had the same direction of effects as in the GWAS meta-analysis was 89% in the combined ancestry group (sign test, P<2.20×10−16) and 93% in subjects of European ancestry only (P<2.20×10−16). Our results supported the major histocompatibility complex region showing a 3.7-fold overall enrichment of replication values of P<.01 in subjects from European ancestry. We replicated SNPs in TCF4 (P=2.53×10−10) and NOTCH4 (P=3.16×10−7) that are among the most robust SCZ findings. More novel findings included POM121L2 (P=3.51×10−7), AS3MT (P=9.01×10−7), CNNM2 (P=6.07×10−7), and NT5C2 (P=4.09×10−7). To explore the many small effects, we performed pathway analyses. The most significant pathways involved neuronal function

  10. 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.

  11. Ultrastructural study of Mayaro virus replication in BHK-21 cells.

    Science.gov (United States)

    Mezencio, J M; de Souza, W; Fonseca, M E; Rebello, M A

    1990-01-01

    The replication of Mayaro virus in BHK-21 cells was studied by electron microscopy. The infected cells show an intense vacuolization and proliferation of membranous structures. At 5 h post-infection, precursor virus particles were seen in the cytoplasm of infected cells. Later, mature virus particles were found outside the cells and budding from the plasma membrane. Enveloped virus particles were also observed inside the vesicles and budding across their membrane. The release of virus particles into the extracellular space by exocytosis was also observed. In a later stage of the infection, inclusion bodies were sometimes present in the cytoplasm of infected cells. We conclude that in BHK-21 cells, budding from the plasma membrane is the main process of Mayaro virus maturation, and in this kind of cell replication differs significantly from that observed in Aedes albopictus cells.

  12. Study on the micro-replication of shark skin

    Institute of Scientific and Technical Information of China (English)

    HAN Xin; ZHANG DeYuan

    2008-01-01

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

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

    Science.gov (United States)

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

    1992-06-01

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

  14. Residuals and outliers in replicate design crossover studies.

    Science.gov (United States)

    Schall, Robert; Endrenyi, Laszlo; Ring, Arne

    2010-07-01

    Outliers in bioequivalence trials may arise through various mechanisms, requiring different interpretation and handling of such data points. For example, regulatory authorities might permit exclusion from analysis of outliers caused by product or process failure, while exclusion of outliers caused by subject-by-treatment interaction generally is not acceptable. In standard 2 x 2 crossover studies it is not possible to distinguish between relevant types of outliers based on statistical criteria alone. However, in replicate design (2-treatment, 4-period) crossover studies three types of outliers can be distinguished: (i) Subject outliers are usually unproblematic, at least regarding the analysis of bioequivalence, and may require no further action; (ii) Subject-by-formulation outliers may affect the outcome of the bioequivalence test but generally cannot simply be removed from analysis; and (iii) Removal of single-data-point outliers from analysis may be justified in certain cases. As a very simple but effective diagnostic tool for the identification and classification of outliers in replicate design crossover studies we propose to calculate and plot three types of residual corresponding to the three different types of outliers that can be distinguished. The residuals are obtained from four mutually orthogonal linear contrasts of the four data points associated with each subject. If preferred, outlier tests can be applied to the resulting sets of residuals after suitable standardization.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1974-01-01

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

  16. 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

    2017-08-16

    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. Published by Elsevier B.V.

  17. 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

  18. Association between HTR2C gene polymorphisms and the metabolic syndrome in patients using antipsychotics : a replication study

    NARCIS (Netherlands)

    Risselada, A. J.; Vehof, J.; Bruggeman, R.; Wilffert, B.; Cohen, D.; Al Hadithy, A. F.; Arends, J.; Mulder, H.

    2012-01-01

    In two previous studies we found an association between HTR2C polymorphisms and the prevalence of the metabolic syndrome in patients using antipsychotics. In this study, we set out to replicate our findings in a third separate sample of patients. Data for this cross-sectional study came from the ong

  19. Association between HTR2C gene polymorphisms and the metabolic syndrome in patients using antipsychotics : a replication study

    NARCIS (Netherlands)

    Risselada, A. J.; Vehof, J.; Bruggeman, R.; Wilffert, B.; Cohen, D.; Al Hadithy, A. F.; Arends, J.; Mulder, H.

    In two previous studies we found an association between HTR2C polymorphisms and the prevalence of the metabolic syndrome in patients using antipsychotics. In this study, we set out to replicate our findings in a third separate sample of patients. Data for this cross-sectional study came from the

  20. 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

  1. Genome-wide studies highlight indirect links between human replication origins and gene regulation.

    Science.gov (United States)

    Cadoret, Jean-Charles; Meisch, Françoise; Hassan-Zadeh, Vahideh; Luyten, Isabelle; Guillet, Claire; Duret, Laurent; Quesneville, Hadi; Prioleau, Marie-Noëlle

    2008-10-14

    To get insights into the regulation of replication initiation, we systematically mapped replication origins along 1% of the human genome in HeLa cells. We identified 283 origins, 10 times more than previously known. Origin density is strongly correlated with genomic landscapes, with clusters of closely spaced origins in GC-rich regions and no origins in large GC-poor regions. Origin sequences are evolutionarily conserved, and half of them map within or near CpG islands. Most of the origins overlap transcriptional regulatory elements, providing further evidence of a connection with gene regulation. Moreover, we identify c-JUN and c-FOS as important regulators of origin selection. Half of the identified replication initiation sites do not have an open chromatin configuration, showing the absence of a direct link with gene regulation. Replication timing analyses coupled with our origin mapping suggest that a relatively strict origin-timing program regulates the replication of the human genome.

  2. 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.

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

    Science.gov (United States)

    Rescorla, Leslie; Nyame, Josephine; Dias, Pedro

    2016-12-01

    Our objective was to replicate previous cross-linguistic 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. We used the Language Development Survey (LDS; Rescorla, 1989) with children (18-35 months) learning European Portuguese (n = 181) and English (n = 206). In both languages, girls had higher vocabulary scores than boys and vocabulary scores increased with age. Portuguese LDS scores were significantly lower than English scores, but the effect size was small. Cross-linguistic concordance of percentage use scores yielded a Q correlation of .50, with 64 of the "top 100" words being exact matches. Cross-linguistic concordance was highest for the youngest age group. In both languages, vocabulary composition in late talkers (children ≥ 24 months with < 50 words) was highly correlated with composition in vocabulary size-matched younger children. Results replicated previous Greek, Korean, and Italian LDS studies. The early lexicons of typical talkers and late talkers contained many of the same words, indicating considerable universality and suggesting good targets for clinical intervention.

  4. 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.

  5. 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.

  6. Replication of association between ELAVL4 and Parkinson disease: the GenePD study

    Science.gov (United States)

    DeStefano, Anita L.; Latourelle, Jeanne; Lew, Mark F.; Suchowersky, Oksana; Klein, Christine; Golbe, Lawrence I.; Mark, Margery H.; Growdon, John H.; Wooten, G. Fredrick; Watts, Ray; Guttman, Mark; Racette, Brad A.; Perlmutter, Joel S.; Marlor, Lynn; Shill, Holly A.; Singer, Carlos; Goldwurm, Stefano; Pezzoli, Gianni; Saint-Hilaire, Marie H.; Hendricks, Audrey E.; Gower, Adam; Williamson, Sally; Nagle, Michael W.; Wilk, Jemma B.; Massood, Tiffany; Huskey, Karen W.; Baker, Kenneth B.; Itin, Ilia; Litvan, Irene; Nicholson, Garth; Corbett, Alastair; Nance, Martha; Drasby, Edward; Isaacson, Stuart; Burn, David J.; Chinnery, Patrick F.; Pramstaller, Peter P.; Al-hinti, Jomana; Moller, Anette T.; Ostergaard, Karen; Sherman, Scott J.; Roxburgh, Richard; Snow, Barry; Slevin, John T.; Cambi, Franca; Gusella, James F.; Myers, Richard H.

    2009-01-01

    Genetic variants in embryonic lethal, abnormal vision, Drosophila-like 4 (ELAVL4) have been reported to be associated with onset age of Parkinson disease (PD) or risk for PD affection in Caucasian populations. In the current study we genotyped three single nucleotide polymorphisms in ELAVL4 in a Caucasian study sample consisting of 712 PD patients and 312 unrelated controls from the GenePD study. The minor allele of rs967582 was associated with increased risk of PD (odds ratio = 1.46, nominal P value = 0.011) in the GenePD population. The minor allele of rs967582 was also the risk allele for PD affection or earlier onset age in the previously studied populations. This replication of association with rs967582 in a third cohort further implicates ELAVL4 as a PD susceptibility gene. PMID:18587682

  7. 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.

  8. 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.

  9. 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

  10. Replication of genetic association studies in aortic stenosis in adults.

    Science.gov (United States)

    Gaudreault, Nathalie; Ducharme, Valérie; Lamontagne, Maxime; Guauque-Olarte, Sandra; Mathieu, Patrick; Pibarot, Philippe; Bossé, Yohan

    2011-11-01

    Only a handful of studies have attempted to unravel the genetic architecture of calcific aortic valve stenosis (AS). The goal of this study was to validate genes previously associated with AS. Seven genes were assessed: APOB, APOE, CTGF, IL10, PTH, TGFB1, and VDR. Each gene was tested for a comprehensive set of single-nucleotide polymorphisms (SNPs). SNPs were genotyped in 457 patients who underwent surgical aortic valve replacement, and allele frequencies were compared to 3,294 controls. A missense mutation in the APOB gene was significantly associated with AS (rs1042031, E4181K, p = 0.00001). A second SNP located 5.6 kilobases downstream of the APOB stop codon was also associated with the disease (rs6725189, p = 0.000013). Six SNPs surrounding the IL10 locus were strongly associated with AS (0.02 > p > 6.2 × 10⁻¹¹). The most compelling association for IL10 was found with a promoter polymorphism (rs1800872) well known to regulate the production of the encoded anti-inflammatory cytokine. The frequency of the low-producing allele was greater in cases compared to controls (30% vs 20%, p = 6.2 × 10⁻¹¹). SNPs in PTH, TGFB1, and VDR had nominal p values <0.05 but did not resist Bonferroni correction. In conclusion, this study suggests that subjects carrying specific polymorphisms in the IL10 and APOB genes are at higher risk for developing AS.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    (P = 9.01 × 10-7), CNNM2 (P = 6.07 × 10-7), and NT5C2 (P = 4.09 × 10-7). To explore the many small effects, we performed pathway analyses. The most significant pathways involved neuronal function (axonal guidance, neuronal systems, and L1 cell adhesion molecule interaction) and the immune system......IMPORTANCE Schizophrenia (SCZ) is a devastating psychiatric condition. Identifying the specific genetic variants and pathways that increase susceptibility to SCZ is critical to improve disease understanding and address the urgent need for new drug targets. OBJECTIVE To identify SCZ susceptibility...... (antigen processing, cell adhesion molecules relevant to T cells, and translocation to immunological synapse). CONCLUSIONS AND RELEVANCE We replicated novel SCZ disease genes and pathogenic pathways. Better understanding the molecular and biological mechanisms involved with schizophrenia may improve...

  12. Studies on the replication of Escherichia coli phage lambda DNA. I. The kinetics of DNA replication and requirements for the generation of rolling circles.

    Science.gov (United States)

    Better, M; Freifelder, D

    1983-04-15

    Escherichia coli phage lambda DNA has been isolated from infected bacteria using a new technique by which virtually all phage DNA is recovered. Isolated DNA is examined by electron microscopy. Addition of phi X174 RF1 molecules as a counting standard enables us to determine the average number of lambda DNA molecules present in an infected cell. In this study, we have followed the kinetics of lambda DNA replication and examined rolling circle replication. The most important findings are the following: (1) Rolling circle replication is initiated at roughly the same time as is theta replication, indicating that the rolling circle is not solely a late-replicating form. (2) theta replication stops at about 16 min after infection. (3) Early in infection the number of DNA molecules per cell doubles every 2-3 min until theta replication stops, at which point most DNA synthesis consists of growth of the tails of about three rolling circles per cell. (4) Neither the timing of rolling circle replication nor the number of molecules is affected by the activity of the lambda red genes. (5). The red genes are responsible for the production of oligomeric circles late in infection.

  13. 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....

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  16. HLA alleles associated with the adaptive immune response to smallpox vaccine: a replication study.

    Science.gov (United States)

    Ovsyannikova, Inna G; Pankratz, V Shane; Salk, Hannah M; Kennedy, Richard B; Poland, Gregory A

    2014-09-01

    We previously reported HLA allelic associations with vaccinia virus (VACV)-induced adaptive immune responses in a cohort of healthy individuals (n = 1,071 subjects) after a single dose of the licensed smallpox (Dryvax) vaccine. This study demonstrated that specific HLA alleles were significantly associated with VACV-induced neutralizing antibody (NA) titers (HLA-B*13:02, *38:02, *44:03, *48:01, and HLA-DQB1*03:02, *06:04) and cytokine (HLA-DRB1*01:03, *03:01, *10:01, *13:01, *15:01) immune responses. We undertook an independent study of 1,053 healthy individuals and examined associations between HLA alleles and measures of adaptive immunity after a single dose of Dryvax-derived ACAM2000 vaccine to evaluate previously discovered HLA allelic associations from the Dryvax study and determine if these associations are replicated with ACAM2000. Females had significantly higher NA titers than male subjects in both study cohorts [median ID50 discovery cohort 159 (93, 256) vs. 125 (75, 186), p smallpox vaccine-induced adaptive immune responses are significantly influenced by HLA gene polymorphisms. These data provide information for functional studies and design of novel candidate smallpox vaccines.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  18. The impact of previous traumatic brain injury on health and functioning: a TRACK-TBI study.

    Science.gov (United States)

    Dams-O'Connor, Kristen; Spielman, Lisa; Singh, Ayushi; Gordon, Wayne A; Lingsma, Hester F; Maas, Andrew I R; Manley, Geoffrey T; Mukherjee, Pratik; Okonkwo, David O; Puccio, Ava M; Schnyer, David M; Valadka, Alex B; Yue, John K; Yuh, Esther L

    2013-12-15

    The idea that multiple traumatic brain injury (TBI) can have a cumulative detrimental effect on functioning is widely accepted. Most research supporting this idea comes from athlete samples, and it is not known whether remote history of previous TBI affects functioning after subsequent TBI in community-based samples. This study investigates whether a previous history of TBI with loss of consciousness (LOC) is associated with worse health and functioning in a sample of individuals who require emergency department care for current TBI. Twenty-three percent of the 586 individuals with current TBI in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury study reported having sustained a previous TBI with LOC. Individuals with previous TBI were more likely to be unemployed (χ(2)=17.86; p=0.000), report a variety of chronic medical and psychiatric conditions (4.75≤χ(2)≥24.16; pTBI history. Those with a previous TBI had less-severe acute injuries, but experienced worse outcomes at 6-month follow-up. Results of a series of regression analyses controlling for demographics and acute injury severity indicated that individuals with previous TBI reported more mood symptoms, more postconcussive symptoms, lower life satisfaction, and had slower processing speed and poorer verbal learning, compared to those with no previous TBI history. These findings suggest that history of TBI with LOC may have important implications for health and psychological functioning after TBI in community-based samples.

  19. 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 (Pcesarean 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.

  20. Archaeal DNA replication.

    Science.gov (United States)

    Kelman, Lori M; Kelman, Zvi

    2014-01-01

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

  1. Developing Reading Comprehension through Metacognitive Strategies: A Review of Previous Studies

    Science.gov (United States)

    Channa, Mansoor Ahmed; Nordin, Zaimuariffudin Shukri; Siming, Insaf Ali; Chandio, Ali Asgher; Koondher, Mansoor Ali

    2015-01-01

    This paper has reviewed the previous studies on metacognitive strategies based on planning, monitoring, and evaluating in order to develop reading comprehension. The main purpose of this review in metacognition, and reading domain is to help readers to enhance their capabilities and power reading through these strategies. The researchers reviewed…

  2. 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?

  3. Nurses' knowledge, attitudes about HIV, AIDS. A replication study.

    Science.gov (United States)

    Reeder, J M; Hamblet, J L; Killen, A R; King, C A; Uruburu, A

    1994-02-01

    The AIDS epidemic is now in its second decade and shows no sign of relenting. Unfortunately, however, the AORN study shows that perioperative nurses' knowledge regarding HIV and AIDS is not adequate to enable them to provide patient care while maintaining safe practices. Focused educational programs should be made available to perioperative nurses to help them apply universal precautions and OSHA standards to everyday practice. Perioperative nurses must become knowledgeable about the disease and sensitive to the needs of patients who have this illness. All nurses have a special obligation to care for all patients; education and management strategies that enable exploration of values, fears, and prejudices will help nurses understand their own beliefs and those of other individuals. Recommendations from this study may be viewed as a starting point for this perioperative education.

  4. 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...

  5. 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

  6. Sourcing quality-of-life weights obtained from previous studies: theory and reality in Korea.

    Science.gov (United States)

    Bae, SeungJin; Bae, Eun Young; Lim, Sang Hee

    2014-01-01

    The quality-of-life weights obtained in previous studies are frequently used in cost-utility analyses. The purpose of this study is to describe how the values obtained in previous studies are incorporated into the industry submissions requesting listing at the Korean National Health Insurance (NHI), focusing on the issues discussed in theoretical studies and national guidelines. The industry submissions requesting listing at the Korean NHI from January 2007 until December 2009 were evaluated by two independent researchers at the Health Insurance Review and Assessment Service (HIRA). Specifically, we observed the methods that were used to pool, predict joint health state utilities, and retain consistency within submissions in terms of the issues discussed in methodological research papers and recommendations from national guidelines. More than half of the submissions used QALY as an outcome measure, and most of these submissions were sourced from prior studies. Heterogeneous methodologies were frequently used within a submission, with the inconsistent use of upper and lower anchors being prevalent. Assumptions behind measuring joint health state utilities or pooling multiple values for single health states were omitted in all submissions. Most national guidelines were rather vague regarding how to predict joint health states, how to select the best available value, how to maintain consistency within a submission, and how to generalize values obtained from prior studies. Previously-generated values were commonly sourced, but this practice was frequently related to inconsistencies within and among submissions. Attention should be paid to the consistency and transparency of the value, especially if the value is sourced from prior studies.

  7. 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.

  8. 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

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

    Science.gov (United States)

    Hewitt, Elaine; Stephenson, Jean

    2012-01-01

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

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

    Science.gov (United States)

    Hewitt, Elaine; Stephenson, Jean

    2012-01-01

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

  11. Mechanistic studies on a peptide-based self-replicating system

    NARCIS (Netherlands)

    Colomb-Delsuc, Mathieu

    2015-01-01

    Dit proefschrift beschrijft de werkzaamheden uitgevoerd op een zelfassemblerende en self-replicating systeem. Het werk is opgedeeld in verschillende studies, waarbij een eerste studie gedaan die een demonstratie en een beschrijving van de exponentiële zelfreplicerende aard van het systeem. Mechanist

  12. 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

  13. 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

    2011-01-01

    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

  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, Maya

    2011-01-01

    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. Vibrations of twisted cantilevered plates - Summary of previous and current studies

    Science.gov (United States)

    Leissa, A. W.; Macbain, J. C.; Kielb, R. E.

    1984-01-01

    This work summarizes a comprehensive study made of the free vibrations of twisted, cantilevered plates of rectangular planform. Numerous theoretical and experimental investigations previously made by others have resulted in frequency results which disagree considerably. To clarify the problem a joint industry/government/university research effort was initiated to obtain comprehensive theoretical and experimental results for models having useful ranges of aspect ratios, thickness ratios and twist angles. Theoretical data came from 19 independent computer analyses, including finite element, shell theory and beam theory idealizations. Two independent sets of experimental data were also obtained. The theoretical and experimental results are summarized and compared.

  16. 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...

  17. NMDA receptor gene variations as modifiers in Huntington disease: a replication study

    OpenAIRE

    2011-01-01

    Several candidate modifier genes which, in addition to the pathogenic CAG repeat expansion, influence the age at onset (AO) in Huntington disease (HD) have already been described. The aim of this study was to replicate association of variations in the N-methyl D-aspartate receptor subtype genes GRIN2A and GRIN2B in the “REGISTRY” cohort from the European Huntington Disease Network (EHDN). The analyses did replicate the association reported between the GRIN2A rs2650427 variation and AO in the ...

  18. 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.

  19. 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…

  20. Study of the Regulation of Telomere Replication by Characterizing the Cdc-13p Pathway in Yeast

    Science.gov (United States)

    2001-01-01

    binding protein Cdcl3p appears to play a key regulatory role in telomere replication. Identifying Cdcl3p interacting proteins could yield important...telomerase and Pol a. Other Cdcl3p interacting proteins were also identified. Further studies are in progress.

  1. Learned Attention in Adult Language Acquisition: A Replication and Generalization Study and Meta-Analysis

    Science.gov (United States)

    Ellis, Nick C.; Sagarra, Nuria

    2011-01-01

    This study investigates associative learning explanations of the limited attainment of adult compared to child language acquisition in terms of learned attention to cues. It replicates and extends Ellis and Sagarra (2010) in demonstrating short- and long-term learned attention in the acquisition of temporal reference in Latin. In Experiment 1,…

  2. NMDA receptor gene variations as modifiers in Huntington disease : a replication study

    NARCIS (Netherlands)

    Saft, Carsten; Epplen, Jörg T; Wieczorek, Stefan; Landwehrmeyer, G Bernhard; Roos, Raymund A C; de Yebenes, Justo Garcia; Dose, Matthias; Tabrizi, Sarah J; Craufurd, David; Arning, Larissa; Kremer, Berry

    2011-01-01

    Several candidate modifier genes which, in addition to the pathogenic CAG repeat expansion, influence the age at onset (AO) in Huntington disease (HD) have already been described. The aim of this study was to replicate association of variations in the N-methyl D-aspartate receptor subtype genes GRIN

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

    Science.gov (United States)

    Shao, C.-W.; Chiu, H.-L.; Chang, S.-K.

    2015-08-01

    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 step for ensuring the surface

  4. STUDY OF OBSTETRIC AND FETAL OUTCOME OF PREGNANCY IN PREVIOUS CAESAREAN SECTION

    Directory of Open Access Journals (Sweden)

    Gurpreet Kaur

    2015-09-01

    Full Text Available Previous caesarean section sparks an area of controversy in Obstetrics. The management of women with previous caesarean section regarding the mode of delivery whether to opt for repeat caesarean section or vaginal delivery, is an area of debate. Very often the decision on management is not made on Principle of sound reasoning and many who choose the elective repeat caesarean section do so to circumvent the anxious moment that arise during conduct ion of labour. AIMS AND OBJECTIVE: To determine the maternal and fetal outcome in relation to type of delivery . MATERIALS AND METHOD S: A 18 month prospective observational study was conducted where in 150 patients who had a term pregnancy with a history of prior LSCS were included after obtaining their consent for participation. The obstetric and fetal outcomes of these patients in the present pregnancy were analyzed by Z test. RESULTS: Out of the 150 subjects 78 ( 52% were in age group of 26 - 30 years, 106 ( 70.67% patients belonged to the urban population, 116 ( 77.33% were booked patie nts, 107 ( 71.33% were housewives, 122 ( 81.33% belonged to middle class and 22 ( 14.67% were from high socio economic status. 67 ( 44.67% were second gravid, 112 ( 74.67% were para 1. Out of total 134 patients 29 ( 21.64% had elective caesarean section and 5 ( 3 .73% patients came as emergency admission and underwent caesarean section. Out of 134 patients, with one previous caesarean section. 32 had spontaneous onset of labour. Out of which 20 ( 68.97% had vaginal delivery and 9 ( 31.03% had repeat caesarean section. 13 patients had augmentation, 11 ( 84.62% had vaginal delivery and 2 ( 15.38% had caesarean section. In 58 patients labour was induced 29 ( 50% had section. 14 patients out of 50 who had previous 2 caesarean section only 1 ( 7.69% patient had spontane ous onset of labour and had caesarean section. 3 ( 92.86% patients had elective caesarean section. There were only 2 patients with previous 3 caesarean

  5. 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......-g oral glucose tolerance test (OGTT) were measured during pregnancy, postpartum, and at follow-up 5-11 years later. At follow-up, the women were also examined with a 75-g OGTT or an intravenous glucagon test. RESULTS: Twenty-seven (30%) of the women with previous GDM had abnormal glucose tolerance...... response) at all time points investigated; this was also found when only nonobese glucose-tolerant women were examined. Low insulin secretion during pregnancy together with a high fasting plasma glucose level at the diagnostic OGTT in pregnancy and hyperglycemia during the postpartum OGTT were predictive...

  6. 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.

  7. 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.

  8. Fe and Cu do not differ in Parkinson's disease: a replication study plus meta-analysis.

    Science.gov (United States)

    Mariani, Stefania; Ventriglia, Mariacarla; Simonelli, Ilaria; Donno, Silvia; Bucossi, Serena; Vernieri, Fabrizio; Melgari, Jean-Marc; Pasqualetti, Patrizio; Rossini, Paolo M; Squitti, Rosanna

    2013-02-01

    To evaluate whether iron and copper levels in serum, plasma, and cerebrospinal fluid are disarranged in Parkinson's disease (PD), we performed meta-analyses of 33 studies on the topic published from 1987 to 2011 and contextually carried out a replication study in serum by ourselves as well. We found no variation in metals between PD patients and healthy controls, according to our replication study. The metaregression for sex revealed that serum copper differences found in some studies could be referred to the different percentage of women in the PD sample. Transferrin and transferrin saturation levels found increased in PD subjects underline the concept to extend the iron study in PD to iron master proteins.

  9. 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.

  10. Religious Identity in Iranian Society: A Systematic Review of Previous Studies (2001-2013

    Directory of Open Access Journals (Sweden)

    2015-06-01

    literature on identity, evidence suggests that the role of religion in shaping individuals' and group's identity is widely ignored. However, a growing number of studies have begun to take into consideration the key role of religion (Arweck & Nesbitt 2010, King and Boyatzis 2004, Peek 2005. This article has attempted to review systematically previous research and conceptualizations on the religious identity based on national studies and surveys and academic dissertations.     Materials and Methods   As mentioned, the purpose of this study was to review the results of some influential researches in the field of religious identity. To get this purpose, one of the best known methods for reviewing previous studies, a systematic review, was applied. Systematic review deals with establishing and synthesizing of researches and evidences with focus on a specific question. This occurs through the organized, transparent, formal, clear and flexible procedures and processes. A systematic review of research is not limited to review the history and this overview and review can be used in different levels, fields and goals. During the first phase of the study, terms of "religious identity", "Islamic identity", "Iranian identity" and "religious identity" was searched at libraries and research centers and in databases such as Center for Scientific Information Database (SID, a database of Iranian journals and magazines (Magiran, Noor specialized journals database, and Science and Information Technology Institute (IrnaDoc. After reviewing the gathered documents and specifying its relationship with the object and purpose of the study, a total of 47 documents were selected. Documents based on the five major parameter were summarized and reviewed: 1-general information, 2-goals and research questions, 3-research methodology, 4-variables, 5-findings     Discussion of Results and Conclusion   Findings show that in the highest percentage (38.2% of researches, religious identity has been

  11. Phase II study of pegylated liposomal doxorubicin plus vinorelbine in breast cancer with previous anthracycline exposure.

    Science.gov (United States)

    Martin, Miguel; García-Donas, Jesus; Casado, Antonio; de la Gándara, Isabel; Pérez-Segura, Pedro; García-Saenz, Jose-Angel; Ibáñez, Gabriel; Loboff, Belen; García-Ledo, Gemma; Moreno, Fernando; Grande, Enrique; Diaz-Rubio, Eduardo

    2004-12-01

    Thirty-five patients with metastatic breast cancer (MBC) entered a phase II study of pegylated liposomal doxorubicin 35 mg/m2 intravenously (i.v.) on day 1 plus vinorelbine 30 mg/m2 i.v. on day 1 every 4 weeks. Patients were required to have measurable disease, previous chemotherapy with an anthracycline-containing regimen, and a normal left ventricular ejection fraction (LVEF). Thirty-four patients were assessable for response and toxicity. The overall response rate (on an intent-to-treat basis) was 35% (12 of 34; 95% CI, 20%-54%). One complete response and 11 partial responses were noted. In addition, 14 patients (41%) had stable disease of > 4 months duration, and 7 patients (20.5%) had disease progression. The response rates to the combination when it was used as first- and second-line chemotherapy were 31% (4 of 13) and 38% (8 of 21), respectively. Median time to disease progression was 7 months (range, 1-35 months) and median overall survival was 13 months (range, 2 to > 62 months). Neutropenia was the most frequent toxicity (grade 4 in 44% of patients and 19% of cycles), but neutropenic fever was seen in only 3 cases. No septic deaths occurred. Nonhematologic grade 3 side effects included skin toxicity (palmar-plantar erythrodysesthesia syndrome, 6%) and mucositis (15%). Late alopecia was seen in 53% of patients (grade 1 in 41%, and grade 2 in 12%). The median LVEFs were 64% (range, 50%-81%) at baseline and 62% (range, 37%-70%) after treatment. Three patients presented an LVEF decrease to < 50%; however, no clinical heart failure was noted, and 2 of these patients recovered normal values after cessation of therapy. The combination of pegylated liposomal doxorubicin and vinorelbine can be safely administered to patients with anthracycline-pretreated MBC and is active in this population.

  12. Replication of genome-wide association study (GWAS) susceptibility loci in a Latino bipolar disorder cohort.

    Science.gov (United States)

    Gonzalez, Suzanne; Gupta, Jayanta; Villa, Erika; Mallawaarachchi, Indika; Rodriguez, Marco; Ramirez, Mercedes; Zavala, Juan; Armas, Regina; Dassori, Albana; Contreras, Javier; Flores, Deborah; Jerez, Alvaro; Ontiveros, Alfonso; Nicolini, Humberto; Escamilla, Michael

    2016-09-01

    Recent genome-wide association studies (GWASs) have identified numerous putative genetic polymorphisms associated with bipolar disorder (BD) and/or schizophrenia (SC). We hypothesized that a portion of these polymorphisms would also be associated with BD in the Latino American population. To identify such regions, we tested previously identified genetic variants associated with BD and/or SC and ancestral haploblocks containing these single nucleotide polymorphisms (SNPs) in a sample of Latino subjects with BD. A total of 2254 Latino individuals were genotyped for 91 SNPs identified in previous BD and/or SC GWASs, along with selected SNPs in strong linkage disequilibrium with these markers. Family-based single marker and haplotype association testing was performed using the PBAT software package. Empirical P-values were derived from 10 000 permutations. Associations of eight a priori GWAS SNPs with BD were replicated with nominal (P≤.05) levels of significance. These included SNPs within nuclear factor I A (NFIA), serologically defined colon cancer antigen 8 (SDCCAG8), lysosomal associated membrane protein 3 (LAMP3), nuclear factor kappa B subunit 1 (NFKB1), major histocompatibility complex, class I, B (HLA-B) and 5'-nucleotidase, cytosolic II (NT5C2) and SNPs within intragenic regions microRNA 6828 (MIR6828)-solute carrier family 7 member 14 (SLC7A14) and sonic hedgehog (SHH)-long intergenic non-protein coding RNA 1006 (LINC01006). Of the 76 ancestral haploblocks that were tested for associations with BD, our top associated haploblock was located in LAMP3; however, the association did not meet statistical thresholds of significance following Bonferroni correction. These results indicate that some of the gene variants found to be associated with BD or SC in other populations are also associated with BD risk in Latinos. Variants in six genes and two intragenic regions were associated with BD in our Latino sample and provide additional evidence for overlap in

  13. The Replication Recipe: What makes for a convincing replication?

    NARCIS (Netherlands)

    Brandt, M.J.; IJzerman, H.; Dijksterhuis, A.J.; Farach, F.J.; Geller, J.; Giner-Sorolla, R.; Grange, J.A.; Perugini, M.; Spies, J.R.; Veer, A. van 't

    2014-01-01

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

  14. 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

    BACKGROUND: MicroRNAs are regulatory molecules and suggested as non-invasive biomarkers for molecular diagnostics and prognostics. Altered expression levels of specific microRNAs are associated with hepatitis B virus infection and hepatocellular carcinoma. We previously identified differentially...... of hepatitis B virus expression vectors. RT-qPCR is the preferred method for microRNA studies, and a careful normalisation strategy, verifying the optimal set of reference genes, is decisive for correctly evaluating microRNA expression levels. The aim of this study was to provide valid reference genes...... identified miR-24-3p, miR-151a-5p, and miR-425-5p as the most valid combination of reference genes for microRNA RT-qPCR studies in our hepatitis B virus replicating HepG2 cell model....

  15. An investigation of genome-wide studies reported susceptibility loci for ulcerative colitis shows limited replication in north Indians.

    Directory of Open Access Journals (Sweden)

    Garima Juyal

    Full Text Available Genome-Wide Association studies (GWAS of both Crohn's Disease (CD and Ulcerative Colitis (UC have unearthed over 40 risk conferring variants. Recently, a meta-analysis on UC revealed several loci, most of which were either previously associated with UC or CD susceptibility in populations of European origin. In this study, we attempted to replicate these findings in an ethnically distinct north Indian UC cohort. 648 UC cases and 850 controls were genotyped using Infinium Human 660W-quad. Out of 59 meta-analysis index SNPs, six were not in the SNP array used in the study. Of the remaining 53 SNPs, four were found monomorphic. Association (p<0.05 at 25 SNPs was observed, of which 15 were CD specific. Only five SNPs namely rs2395185 (HLA-DRA, rs3024505 (IL10, rs6426833 (RNF186, rs3763313 (BTNL2 and rs2066843 (NOD2 retained significance after Bonferroni correction. These results (i reveal limited replication of Caucasian based meta-analysis results; (ii reiterate overlapping molecular mechanism(s in UC and CD; (iii indicate differences in genetic architecture between populations; and (iv suggest that resources such as HapMap need to be extended to cover diverse ethnic populations. They also suggest a systematic GWAS in this terrain may be insightful for identifying population specific IBD risk conferring loci and thus enable cross-ethnicity fine mapping of disease loci.

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

    Science.gov (United States)

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

    2015-01-01

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

  17. 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.

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

    DEFF Research Database (Denmark)

    Johnson, Emma C; Bjelland, Douglas W; Howrigan, Daniel P

    2016-01-01

    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....

  19. 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.

  20. 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

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

    Science.gov (United States)

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

    2016-11-01

    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. 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. 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. Neoadjuvant radiotherapy reduces the viability of the venous anastomosis in a preclinical rat model with a significant increase in the incidence of vein thrombosis.

  2. 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.

  3. APOBEC3G-Augmented Stem Cell Therapy to Modulate HIV Replication: A Computational Study.

    Directory of Open Access Journals (Sweden)

    Iraj Hosseini

    Full Text Available The interplay between the innate immune system restriction factor APOBEC3G and the HIV protein Vif is a key host-retrovirus interaction. APOBEC3G can counteract HIV infection in at least two ways: by inducing lethal mutations on the viral cDNA; and by blocking steps in reverse transcription and viral integration into the host genome. HIV-Vif blocks these antiviral functions of APOBEC3G by impeding its encapsulation. Nonetheless, it has been shown that overexpression of APOBEC3G, or interfering with APOBEC3G-Vif binding, can efficiently block in vitro HIV replication. Some clinical studies have also suggested that high levels of APOBEC3G expression in HIV patients are correlated with increased CD4+ T cell count and low levels of viral load; however, other studies have reported contradictory results and challenged this observation. Stem cell therapy to replace a patient's immune cells with cells that are more HIV-resistant is a promising approach. Pre-implantation gene transfection of these stem cells can augment the HIV-resistance of progeny CD4+ T cells. As a protein, APOBEC3G has the advantage that it can be genetically encoded, while small molecules cannot. We have developed a mathematical model to quantitatively study the effects on in vivo HIV replication of therapeutic delivery of CD34+ stem cells transfected to overexpress APOBEC3G. Our model suggests that stem cell therapy resulting in a high fraction of APOBEC3G-overexpressing CD4+ T cells can effectively inhibit in vivo HIV replication. We extended our model to simulate the combination of APOBEC3G therapy with other biological activities, to estimate the likelihood of improved outcomes.

  4. 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.

  5. 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

    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. Th

  6. Recent advances in the study of Kaposi’s sarcoma-associated herpesvirus replication and pathogenesis

    Institute of Scientific and Technical Information of China (English)

    Denis; Avey; Brittany; Brewers; Fanxiu; Zhu

    2015-01-01

    It has now been over twenty years since a novel herpesviral genome was identified in Kaposi’s sarcoma biopsies. Since then, the cumulative research effort by molecular biologists, virologists, clinicians, and epidemiologists alike has led to the extensive characterization of this tumor virus, Kaposi’s sarcoma-associated herpesvirus(KSHV; also known as human herpesvirus 8(HHV-8)), and its associated diseases. Here we review the current knowledge of KSHV biology and pathogenesis, with a particular emphasis on new and exciting advances in the field of epigenetics. We also discuss the development and practicality of various cell culture and animal model systems to study KSHV replication and pathogenesis.

  7. Keratinocytes derived from chicken embryonic stem cells support Marek's disease virus infection: a highly differentiated cell model to study viral replication and morphogenesis.

    Science.gov (United States)

    Couteaudier, Mathilde; Courvoisier, Katia; Trapp-Fragnet, Laetitia; Denesvre, Caroline; Vautherot, Jean-François

    2016-01-07

    Marek's disease is a virus disease with worldwide distribution that causes major losses to poultry production. Vaccines against Marek's disease virus, an oncogenic alphaherpesvirus, reduce tumour formation but have no effect on virus shedding. Successful horizontal virus transmission is linked to the active viral replication in feather follicle epithelial cells of infected chickens, from which infectious viral particles are shed into the environment. The feather follicle epithelium is the sole tissue in which those infectious particles are produced and no in vitro cell-systems can support this highly efficient morphogenesis. We previously characterized embryonic stem-cell-derived keratinocytes, showing they display a marker-gene profile similar to skin keratinocytes, and therefore we tested their susceptibility to Marek's disease virus infection. We show herein that keratinocytes derived from chicken embryonic stem-cells are fully permissive to the replication of either non-pathogenic or pathogenic Marek's disease viruses. All viruses replicated on all three keratinocyte lines and kinetics of viral production as well as viral loads were similar to those obtained on primary cells. Morphogenesis studies were conducted on infected keratinocytes and on corneocytes, showing that all types of capsids/virions were present inside the cells, but extracellular viruses were absent. The keratinocyte lines are the first epithelial cell-line showing ectodermal specific markers supporting Marek's disease virus replication. In this in vitro model the replication lead to the production of cell-associated viral progeny. Further work will be devoted to the study of relationship between 3D differentiation of keratinocytes and Marek's disease virus replication.

  8. Quantifying the reliability of image replication studies: the image intraclass correlation coefficient (I2C2).

    Science.gov (United States)

    Shou, H; Eloyan, A; Lee, S; Zipunnikov, V; Crainiceanu, A N; Nebel, N B; Caffo, B; Lindquist, M A; Crainiceanu, C M

    2013-12-01

    This article proposes the image intraclass correlation (I2C2) coefficient as a global measure of reliability for imaging studies. The I2C2 generalizes the classic intraclass correlation (ICC) coefficient to the case when the data of interest are images, thereby providing a measure that is both intuitive and convenient. Drawing a connection with classical measurement error models for replication experiments, the I2C2 can be computed quickly, even in high-dimensional imaging studies. A nonparametric bootstrap procedure is introduced to quantify the variability of the I2C2 estimator. Furthermore, a Monte Carlo permutation is utilized to test reproducibility versus a zero I2C2, representing complete lack of reproducibility. Methodologies are applied to three replication studies arising from different brain imaging modalities and settings: regional analysis of volumes in normalized space imaging for characterizing brain morphology, seed-voxel brain activation maps based on resting-state functional magnetic resonance imaging (fMRI), and fractional anisotropy in an area surrounding the corpus callosum via diffusion tensor imaging. Notably, resting-state fMRI brain activation maps are found to have low reliability, ranging from .2 to .4. Software and data are available to provide easy access to the proposed methods.

  9. 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

  10. Effect of temperature on cystic fibrosis lung disease and infections: a replicated cohort study.

    Directory of Open Access Journals (Sweden)

    Joseph M Collaco

    Full Text Available BACKGROUND: Progressive lung disease accounts for the majority of morbidity and mortality observed in cystic fibrosis (CF. Beyond secondhand smoke exposure and socio-economic status, the effect of specific environmental factors on CF lung function is largely unknown. METHODS: Multivariate regression was used to assess correlation between specific environmental factors, the presence of pulmonary pathogens, and variation in lung function using subjects enrolled in the U.S. CF Twin and Sibling Study (CFTSS: n = 1378. Significant associations were tested for replication in the U.S. CF Foundation Patient Registry (CFF: n = 16439, the Australian CF Data Registry (ACFDR: n = 1801, and prospectively ascertained subjects from Australia/New Zealand (ACFBAL: n = 167. RESULTS: In CFTSS subjects, the presence of Pseudomonas aeruginosa (OR = 1.06 per °F; p<0.001 was associated with warmer annual ambient temperatures. This finding was independently replicated in the CFF (1.02; p<0.001, ACFDR (1.05; p = 0.002, and ACFBAL (1.09; p = 0.003 subjects. Warmer temperatures (-0.34 points per °F; p = 0.005 and public insurance (-6.43 points; p<0.001 were associated with lower lung function in the CFTSS subjects. These findings were replicated in the CFF subjects (temperature: -0.31; p<0.001; insurance: -9.11; p<0.001 and similar in the ACFDR subjects (temperature: -0.23; p = 0.057. The association between temperature and lung function was minimally influenced by P. aeruginosa. Similarly, the association between temperature and P. aeruginosa was largely independent of lung function. CONCLUSIONS: Ambient temperature is associated with prevalence of P. aeruginosa and lung function in four independent samples of CF patients from two continents.

  11. 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

  12. 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…

  13. 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…

  14. Randomized phase 2 study of obinutuzumab monotherapy in symptomatic, previously untreated chronic lymphocytic leukemia.

    Science.gov (United States)

    Byrd, John C; Flynn, Joseph M; Kipps, Thomas J; Boxer, Michael; Kolibaba, Kathryn S; Carlile, David J; Fingerle-Rowson, Guenter; Tyson, Nicola; Hirata, Jamie; Sharman, Jeff P

    2016-01-07

    Obinutuzumab is a glycoengineered, type 2 anti-CD20 humanized antibody with single-agent activity in relapsed chronic lymphocytic leukemia (CLL). With other CD20 antibodies, a dose-response relationship has been shown. We therefore performed a randomized phase 2 study in symptomatic, untreated CLL patients to evaluate if an obinutuzumab dose response exists. Obinutuzumab was given at a dose of 1000 mg (100 mg IV day 1, 900 mg day 2, 1000 mg day 8 and day 15 of cycle 1; 1000 mg day 1 of cycles 2-8) or 2000 mg (100 mg IV day 1, 900 mg day 2, 1000 mg day 3, 2000 mg day 8 and day 15 of cycle 1; 2000 mg day 1 of cycles 2-8). The primary end point was overall response rate (ORR). Eighty patients were enrolled with similar demographics: median age 67 years, 41% high-risk Rai disease, and 10% del(17p)(13.1). ORR (67% vs 49%, P = .08) and complete response (CR) or CR with incomplete cytopenia response (20% vs 5%) favored 2000 mg obinutuzumab. Overall, therapy was well tolerated, and infusion events were manageable. This study demonstrates significant efficacy of obinutuzumab monotherapy, for 1000 mg as well as for 2000 mg, in untreated CLL patients with acceptable toxicity. Although exploratory, a dose-response relationship may exist, but its relevance to improving progression-free survival is uncertain and will require further follow-up. This trial was registered at www.clinicaltrials.gov as #NCT01414205.

  15. A STUDY OF THE OUTCOME OF SUBSEQUENT PREGNANCY FOLLOWING PREVIOUS C ESAREAN SECTION

    Directory of Open Access Journals (Sweden)

    Suman

    2014-02-01

    Full Text Available With the world - wide rising trend of caesarean delivery (CD, modern obstetric practice deals with a new group of mothers carrying reproductive performance upon a scarred uterus with obvious risk in feto - maternal outcome. AIMS: (1 To analyse the maternal & neonatal outcome in post - caesarean pregnancy. (2 To evaluate the factors influencing outcome in such cases. Design : Observational analytical study. MATERIALS & METHODS: The present study was carried out over two years (2010 - 11 taking consecutive 100 p ost - caesarean cases as admitted on my admission days & delivered in BR Singh Hospital. Data collection was done by interview technique along with hospital records. ANALYSIS USED: Percentage analysis was most often done. Categorical variables were compared with chi - square test; P value was calculated with 2012 Graphpad Software. Relative risk (RR & Odd ratio (OR were calculated with 1993 - 2012 Medcalc Software bvba (Version 12.3.0. All statistical tests were evaluated at the 0.05 significance level. RESULT S: Post - caesarean pregnancy rate was 26.02%. Vaginal birth after caesarean (VBAC incidence was 22% whereas VBAC success on trial of labour was 55%. VBAC gave best morbidity outcome (18.18% & 27.27%. But failed VBAC cases result more significant maternal morbidity (RR=3.97, P=0.0037 & NICU admission was also found highest in failed VBAC cases (38.89%. Maternal and neonatal morbidity were significantly high when scar integrity was lost; also significantly co - related with elderly mothers (>35 yrs., un - boo ked cases & non - admitted cases undergone repeat CD. CONCLUSIONS: Post - caesarean cases need meticulous antenatal check - up & mandatory institutional delivery with proper selection of mode of confinement to have a better maternal & neonatal outcome

  16. Serum Iron, Zinc, and Copper Levels in Patients with Alzheimer's Disease: A Replication Study and Meta-Analyses.

    Science.gov (United States)

    Wang, Zi-Xuan; Tan, Lan; Wang, Hui-Fu; Ma, Jing; Liu, Jinyuan; Tan, Meng-Shan; Sun, Jia-Hao; Zhu, Xi-Chen; Jiang, Teng; Yu, Jin-Tai

    2015-01-01

    To evaluate whether iron, zinc, and copper levels in serum are disarranged in Alzheimer's disease (AD), we performed meta-analyses of all studies on the topic published from 1984 to 2014 and contextually carried out a replication study in serum as well. Our meta-analysis results showed that serum zinc was significantly lower in AD patients. Our replication and meta-analysis results showed that serum copper was significantly higher in AD patients than in healthy controls, so our findings were consistent with the conclusions of four previously published copper meta-analyses. Even if a possible role of iron in the pathophysiology of the disease could not be ruled out, the results of our meta-analysis showed no change of serum iron levels in AD patients, but this conclusion was not robust and requires further investigation. The meta-regression analyses revealed that in some studies, differences in serum iron levels could be due to the different mean ages, while differences in zinc levels appeared to be due to the different sex ratios. However, the effect of sex ratio on serum zinc levels in our meta-analysis is subtle and needs further confirmation. Also, diverse demographic terms and methodological approaches appeared not to explain the high heterogeneity of our copper meta-analysis. Therefore, when investigating trace elements, covariants such as age and sex have to be taken into account in the analyses. In the light of these findings, we suggest that the possible alteration of serum zinc and copper levels are involved in the pathogenesis of AD.

  17. Genome-wide association study and meta-analysis in Northern European populations replicate multiple colorectal cancer risk loci.

    Science.gov (United States)

    Tanskanen, Tomas; van den Berg, Linda; Välimäki, Niko; Aavikko, Mervi; Ness-Jensen, Eivind; Hveem, Kristian; Wettergren, Yvonne; Bexe Lindskog, Elinor; Tõnisson, Neeme; Metspalu, Andres; Silander, Kaisa; Orlando, Giulia; Law, Philip J; Tuupanen, Sari; Gylfe, Alexandra E; Hänninen, Ulrika A; Cajuso, Tatiana; Kondelin, Johanna; Sarin, Antti-Pekka; Pukkala, Eero; Jousilahti, Pekka; Salomaa, Veikko; Ripatti, Samuli; Palotie, Aarno; Järvinen, Heikki; Renkonen-Sinisalo, Laura; Lepistö, Anna; Böhm, Jan; Mecklin, Jukka-Pekka; Al-Tassan, Nada A; Palles, Claire; Martin, Lynn; Barclay, Ella; Tenesa, Albert; Farrington, Susan; Timofeeva, Maria N; Meyer, Brian F; Wakil, Salma M; Campbell, Harry; Smith, Christopher G; Idziaszczyk, Shelley; Maughan, Tim S; Kaplan, Richard; Kerr, Rachel; Kerr, David; Buchanan, Daniel D; Win, Aung K; Hopper, John; Jenkins, Mark; Newcomb, Polly A; Gallinger, Steve; Conti, David; Schumacher, Fredrick R; Casey, Graham; Cheadle, Jeremy P; Dunlop, Malcolm G; Tomlinson, Ian P; Houlston, Richard S; Palin, Kimmo; Aaltonen, Lauri A

    2017-09-28

    Genome-wide association studies have been successful in elucidating the genetic basis of colorectal cancer, but there remains unexplained variability in genetic risk. To identify new risk variants and to confirm reported associations, we conducted a genome-wide association study in 1,701 colorectal cancer cases and 14,082 cancer-free controls from the Finnish population. A total of 9,068,015 genetic variants were imputed and tested, and 30 promising variants were studied in additional 11,647 cases and 12,356 controls of European ancestry. The previously reported association between the single-nucleotide polymorphism rs992157 (2q35) and colorectal cancer was independently replicated (p=2.08x10(-4) ; OR, 1.14; 95% CI, 1.06-1.23), and it was genome-wide significant in combined analysis (p=1.50x10(-9) ; OR, 1.12; 95% CI, 1.08-1.16). Variants at 2q35, 6p21.2, 8q23.3, 8q24.21, 10q22.3, 10q24.2, 11q13.4, 11q23.1, 14q22.2, 15q13.3, 18q21.1, 20p12.3, and 20q13.33 were associated with colorectal cancer in the Finnish population (false discovery rate <0.1), but new risk loci were not found. These results replicate the effects of multiple loci on the risk of colorectal cancer and identify shared risk alleles between the Finnish population isolate and outbred populations. This article is protected by copyright. All rights reserved. © 2017 UICC.

  18. 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.

  19. Studying the replication history of human B lymphocytes by real-time quantitative (RQ)-PCR.

    Science.gov (United States)

    van Zelm, Menno C; Berkowska, Magdalena A; van Dongen, Jacques J M

    2013-01-01

    The cells of the adaptive immune system, B and T lymphocytes, each generate a unique antigen receptor through V(D)J recombination of their immunoglobulin (Ig) and T cell receptor (TCR) loci, respectively. Such rearrangements join coding elements to form a coding joint and delete the intervening DNA as circular excision products containing the signal joint. These excision circles are stable structures that cannot replicate and have no function in the cell. Since the coding joint in the genome is replicated with each cell division, the ratio between coding joints and signal joints in a population of B cells can be used as a measure for proliferation. This chapter describes a real-time quantitative (RQ-)PCR-based approach to quantify proliferation through calculating the ratio between coding joints and signal joints of the frequently occurring intronRSS-Kde rearrangements in the IGK light chain locus. The approach is useful to study basic B-cell biology as well as abnormal proliferation in human diseases.

  20. 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.

  1. Experimental bluetongue virus infection of sheep; effect of previous vaccination: clinical and immunologic studies.

    Science.gov (United States)

    Mahrt, C R; Osburn, B I

    1986-06-01

    Clinical and immunologic responses of sheep to vaccination and subsequent bluetongue virus (BTV) challenge exposure were studied and compared with those of non-vaccinated sheep. Sheep were vaccinated with inactivated BTV administered with aluminum hydroxide and cimetidine or levamisole. After sheep were vaccinated, precipitating group-specific antibodies to BTV were detected, but serotype-specific neutralizing antibodies were not detected. Cellular immune responses (lymphocyte blastogenesis) to BTV were not detected. After virulent BTV challenge exposure, vaccinated and nonvaccinated sheep developed acute clinical disease of similar severity. Clinical signs included hyperemia and petechiae of oral mucosa and coronary bands of the feet, excess salivation, nasal discharge with crusting, ulceration of the muzzle, and edema of lips and intermandibular space. Marked increases in serum creatine kinase activity were associated with stiff gait, reluctance to move, and vomiting. Fever and leukopenia were detected in most of the challenge-exposed sheep. Viremia and neutralizing antibodies were detected in vaccinated and nonvaccinated sheep after challenge exposure. Bluetongue virus-specific reaginic antibodies were not detected in sera from any of the sheep when the passive cutaneous anaphylaxis test was used.

  2. Phase III Randomized Study of Bendamustine Compared With Chlorambucil in Previously Untreated Patients With Chronic Lymphocytic Leukemia

    National Research Council Canada - National Science Library

    Wolfgang U. Knauf; Toshko Lissichkov; Ali Aldaoud; Anna Liberati; Javier Loscertales; Raoul Herbrecht; Gunnar Juliusson; Gerhard Postner; Liana Gercheva; Stefan Goranov; Martin Becker; Hans-Joerg Fricke; Francoise Huguet; Ilaria Del Giudice; Peter Klein; Lothar Tremmel; Karlheinz Merkle; Marco Montillo

    2009-01-01

    This randomized, open-label, parallel-group, multicenter study was designed to compare the efficacy and safety of bendamustine and chlorambucil in previously untreated patients with advanced (Binet stage B or C...

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

    OpenAIRE

    Stuckey, Ruth

    2014-01-01

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

  4. 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, ...

  5. Consistency of HLA associations between two independent measles vaccine cohorts: a replication study.

    Science.gov (United States)

    Ovsyannikova, Inna G; Pankratz, V Shane; Vierkant, Robert A; Jacobson, Robert M; Poland, Gregory A

    2012-03-09

    Associations between HLA genotypes and measles vaccine humoral and cellular immune responses were examined to better understand immunogenetic drivers of vaccine response. Two independent study cohorts of healthy schoolchildren were examined: cohort one, 346 children between 12 and 18 years of age; and cohort two, 388 children between 11 and 19 years of age. All received two age-appropriate doses of measles-containing vaccine. The purpose of this study was to identify and replicate associations between HLA genes and immune responses following measles vaccination found in our first cohort. Associations of comparable magnitudes and with similar p-values were observed between B*3503 (1st cohort p=0.01; 2nd cohort p=0.07), DQA1*0201 (1st cohort p=0.03; 2nd cohort p=0.03), DQB1*0303 (1st cohort p=0.10; 2 cohort p=0.02), DQB1*0602 (1st cohort p=0.07; 2nd cohort p=0.10), and DRB1*0701 (1st cohort p=0.03; 2nd cohort p=0.07) alleles and measles-specific antibody levels. Suggestive, yet consistent, associations were observed between the B7 (1st cohort p=0.01; 2nd cohort p=0.08) supertype and higher measles antibody levels in both cohorts. Also, in both cohorts, the B*0801 and DRB1*0301 alleles, C*0802 and DPA1*0202 alleles, and DRB1*1303 alleles displayed consistent associations with variations in IFN-γ, IL-2 and IL-10 secretion, respectively. This study emphasizes the importance of replicating HLA associations with measles vaccine-induced humoral and cellular immune responses and increases confidence in the results. These data will inform strategies for functional studies and novel vaccine development, including epitope-based measles vaccines. This is the first HLA association replication study with measles vaccine-specific immune responses to date.

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

    Energy Technology Data Exchange (ETDEWEB)

    Krysan, P.J.

    1993-01-01

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

  7. 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.

  8. Replicating the violence risk appraisal guide: a total forensic cohort study.

    Directory of Open Access Journals (Sweden)

    Astrid Rossegger

    Full Text Available INTRODUCTION: The performance of violence risk assessment instruments can be primarily investigated by analysing two psychometric properties: discrimination and calibration. Although many studies have examined the discrimination capacity of the Violence Risk Appraisal Guide (VRAG and other actuarial risk assessment tools, few have evaluated how well calibrated these instruments are. The aim of the present investigation was to replicate the development study of the VRAG in Europe including measurements of discrimination and calibration. METHOD: Using a prospective study design, we assessed a total cohort of violent offenders in the Zurich Canton of Switzerland using the VRAG prior to discharge from prisons, secure facilities, and outpatient clinics. Assessors adhered strictly to the assessment protocol set out in the instrument's manual. After controlling for attrition, 206 offenders were followed in the community for a fixed period of 7 years. We used charges and convictions for subsequent violent offenses as the outcomes. Receiver operating characteristic analysis was conducted to measure discrimination, and Sanders' decomposition of the Brier score as well as Bayesian credible intervals were calculated to measure calibration. RESULTS: The discrimination of the VRAG's risk bins was modest (area under the curve = 0.72, 95% CI = 0.63-0.81, p<0.05. However, the calibration of the tool was poor, with Sanders' calibration score suggesting an average assessment error of 21% in the probabilistic estimates associated with each bin. The Bayesian credible intervals revealed that in five out of nine risk bins the intervals did not contain the expected risk rates. DISCUSSION: Measurement of the calibration validity of risk assessment instruments needs to be improved, as has been done with respect to discrimination. Additional replication studies that focus on the calibration of actuarial risk assessment instruments are needed. Meanwhile, we recommend

  9. 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,…

  10. The Study of Detecting Replicate Documents Using MD5 Hash Function

    Directory of Open Access Journals (Sweden)

    Pushpendra Singh Tomar

    2011-12-01

    Full Text Available A great deal of the Web is replicate or near- replicate content. Documents may be served in different formats: HTML, PDF, and Text for different audiences. Documents may get mirrored to avoid delays or to provide fault tolerance. Algorithms for detecting replicate documents are critical in applications where data is obtained from multiple sources. The removal of replicate documents is necessary, not only to reduce runtime, but also to improve search accuracy. Today, search engine crawlers are retrieving billions of unique URL’s, of which hundreds of millions are replicates of some form. Thus, quickly identifying replicate detection expedites indexing and searching. One vendor’s analysis of 1.2 billion URL’s resulted in 400 million exact replicates found with a MD5 hash. Reducing the collection sizes by tens of percentage point’s results in great savings in indexing time and a reduction in the amount of hardware required to support the system. Last and probably more significant, users benefit by eliminating replicate results. By efficiently presenting only unique documents, user satisfaction is likely to increase.

  11. The Study of Detecting Replicate Documents Using MD5 Hash Functio

    Directory of Open Access Journals (Sweden)

    Mr. Pushpendra Singh Tomar

    2011-09-01

    Full Text Available A great deal of the Web is replicate or near- replicate content. Documents may be served in different formats: HTML, PDF, and Text for different audiences. Documents may get mirrored to avoid delays or to provide fault tolerance. Algorithms for detecting replicate documents are critical in applications where data is obtained from multiple sources. The removal of replicate documents is necessary, not only to reduce runtime, but also to improve search accuracy. Today, search engine crawlers are retrieving billions of unique URL’s, of which hundreds of millions are replicates of some form. Thus, quickly identifying replicate detection expedites indexing and searching. One vendor’s analysis of 1.2 billion URL’s resulted in 400 million exact replicates found with a MD5 hash. Reducing the collection sizes by tens of percentage point’s results in great savings in indexing time and a reduction in the amount of hardware required to support the system. Last and probably more significant, users benefit by eliminating replicate results. By efficiently presenting only unique documents, user satisfaction is likely to increase.

  12. Expression and replication studies to identify new candidate genes involved in normal hearing function.

    Science.gov (United States)

    Girotto, Giorgia; Vuckovic, Dragana; Buniello, Annalisa; Lorente-Cánovas, Beatriz; Lewis, Morag; Gasparini, Paolo; Steel, Karen P

    2014-01-01

    Considerable progress has been made in identifying deafness genes, but still little is known about the genetic basis of normal variation in hearing function. We recently carried out a Genome Wide Association Study (GWAS) of quantitative hearing traits in southern European populations and found several SNPs with suggestive but none with significant association. In the current study, we followed up these SNPs to investigate which of them might show a genuine association with auditory function using alternative approaches. Firstly, we generated a shortlist of 19 genes from the published GWAS results. Secondly, we carried out immunocytochemistry to examine expression of these 19 genes in the mouse inner ear. Twelve of them showed distinctive cochlear expression patterns. Four showed expression restricted to sensory hair cells (Csmd1, Arsg, Slc16a6 and Gabrg3), one only in marginal cells of the stria vascularis (Dclk1) while the others (Ptprd, Grm8, GlyBP, Evi5, Rimbp2, Ank2, Cdh13) in multiple cochlear cell types. In the third step, we tested these 12 genes for replication of association in an independent set of samples from the Caucasus and Central Asia. Nine out of them showed nominally significant association (pgene-based test. Finally, to look for genotype-phenotype relationship, the audiometric profiles of the three genotypes of the most strongly associated gene variants were analyzed. Seven out of the 9 replicated genes (CDH13, GRM8, ANK2, SLC16A6, ARSG, RIMBP2 and DCLK1) showed an audiometric pattern with differences between different genotypes further supporting their role in hearing function. These data demonstrate the usefulness of this multistep approach in providing new insights into the molecular basis of hearing and may suggest new targets for treatment and prevention of hearing impairment.

  13. 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

  14. A replication of the study ‘Adverse effects of spinal manipulation: a systematic review’

    Directory of Open Access Journals (Sweden)

    Tuchin Peter

    2012-09-01

    Full Text Available Abstract Objective To assess the significance of adverse events after spinal manipulation therapy (SMT by replicating and critically reviewing a paper commonly cited when reviewing adverse events of SMT as reported by Ernst (J Roy Soc Med 100:330–338, 2007. Method Replication of a 2007 Ernst paper to compare the details recorded in this paper to the original source material. Specific items that were assessed included the time lapse between treatment and the adverse event, and the recording of other significant risk factors such as diabetes, hyperhomocysteinemia, use of oral contraceptive pill, any history of hypertension, atherosclerosis and migraine. Results The review of the 32 papers discussed by Ernst found numerous errors or inconsistencies from the original case reports and case series. These errors included alteration of the age or sex of the patient, and omission or misrepresentation of the long term response of the patient to the adverse event. Other errors included incorrectly assigning spinal manipulation therapy (SMT as chiropractic treatment when it had been reported in the original paper as delivered by a non-chiropractic provider (e.g. Physician. The original case reports often omitted to record the time lapse between treatment and the adverse event, and other significant clinical or risk factors. The country of origin of the original paper was also overlooked, which is significant as chiropractic is not legislated in many countries. In 21 of the cases reported by Ernst to be chiropractic treatment, 11 were from countries where chiropractic is not legislated. Conclusion The number of errors or omissions in the 2007 Ernst paper, reduce the validity of the study and the reported conclusions. The omissions of potential risk factors and the timeline between the adverse event and SMT could be significant confounding factors. Greater care is also needed to distinguish between chiropractors and other health practitioners when reviewing

  15. A replication of the study 'Adverse effects of spinal manipulation: a systematic review'.

    Science.gov (United States)

    Tuchin, Peter

    2012-09-21

    To assess the significance of adverse events after spinal manipulation therapy (SMT) by replicating and critically reviewing a paper commonly cited when reviewing adverse events of SMT as reported by Ernst (J Roy Soc Med 100:330-338, 2007). Replication of a 2007 Ernst paper to compare the details recorded in this paper to the original source material. Specific items that were assessed included the time lapse between treatment and the adverse event, and the recording of other significant risk factors such as diabetes, hyperhomocysteinemia, use of oral contraceptive pill, any history of hypertension, atherosclerosis and migraine. The review of the 32 papers discussed by Ernst found numerous errors or inconsistencies from the original case reports and case series. These errors included alteration of the age or sex of the patient, and omission or misrepresentation of the long term response of the patient to the adverse event. Other errors included incorrectly assigning spinal manipulation therapy (SMT) as chiropractic treatment when it had been reported in the original paper as delivered by a non-chiropractic provider (e.g. Physician).The original case reports often omitted to record the time lapse between treatment and the adverse event, and other significant clinical or risk factors. The country of origin of the original paper was also overlooked, which is significant as chiropractic is not legislated in many countries. In 21 of the cases reported by Ernst to be chiropractic treatment, 11 were from countries where chiropractic is not legislated. The number of errors or omissions in the 2007 Ernst paper, reduce the validity of the study and the reported conclusions. The omissions of potential risk factors and the timeline between the adverse event and SMT could be significant confounding factors. Greater care is also needed to distinguish between chiropractors and other health practitioners when reviewing the application of SMT and related adverse effects.

  16. 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...... interaction techniques, current photo sharing practices, and privacy. Our results confirm and expand the original findings. We report our main findings by comparing them to the key findings of the original study. Finally, we discuss possible reasons for some variance in the results....

  17. Maternal and perinatal outcomes of delivery after a previous Cesarean section in Enugu, Southeast Nigeria: a prospective observational study.

    Science.gov (United States)

    Ugwu, George O; Iyoke, Chukwuemeka A; Onah, Hyacinth E; Egwuatu, Vincent E; Ezugwu, Frank O

    2014-01-01

    Obstetricians in developing countries appear generally reluctant to conduct vaginal delivery in women with a previous Cesarean because of lack of adequate facilities for optimal fetomaternal monitoring. To describe delivery outcomes among women with one previous Cesarean section at a tertiary hospital in Southeast Nigeria. This was a prospective observational study to determine maternal and perinatal outcomes of attempted vaginal birth after Cesarean sections (VBAC) following one previous Cesarean section. Analysis was done with SPSS statistical software version 17.0 for Windows using descriptive and inferential statistics at 95% level of confidence. Two thousand six hundred and ten women delivered in the center during the study period, of whom 395 had one previous Cesarean section. A total of 370 women with one previous Cesarean section had nonrecurrent indications, of whom 355 consenting pregnant women with one previous Cesarean section were studied. A majority of the women (320/355, 90.1%) preferred to have vaginal delivery despite the one previous Cesarean section. However, only approximately 54% (190/355) were found suitable for trial of VBAC, out of whom 50% (95/190 had successful VBAC. Ninety-five women (50.0%) had failed attempt at VBAC and were delivered by emergency Cesarean section while 35 women (9.8%) had emergency Cesarean section for other obstetric indications (apart from failed VBAC). There was no case of uterine rupture or neonatal and maternal deaths recorded in any group. Apgar scores of less than 7 in the first minute were significantly more frequent amongst women who had vaginal delivery when compared to those who had elective repeat Cesarean section (P=0.03). Most women who had one previous Cesarean delivery chose to undergo trial of VBAC, although only about half were considered suitable for VBAC. The maternal and fetal outcomes of trial of VBAC in selected women with one previous Cesarean delivery for non-recurrent indications were good

  18. 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.

  19. Predicting Psychiatric Rehabilitation Outcome Using Demographic Characteristics: A Replication

    Science.gov (United States)

    Anthony, William A.; Buell, Gregory J.

    1974-01-01

    Replication was undertaken of a recent study conducted by Buell and Anthony which had found that recidivism and posthospital employment could be predicted by a single demographic variable, number of previous hospitalizations and employment history, respectively. Results of the replication were consistent for posthospital employment but not for…

  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

    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 ca...... with Hazard Ratios ranging from 1.68 to 1.78 for current use compared to never use. CONCLUSIONS: The findings suggest that it is possible to estimate the effect of never, current and previous use of HT on breast cancer using prescription data.......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. Animal models for the study of hepatitis C virus infection and replication

    Institute of Scientific and Technical Information of China (English)

    Kristin L MacArthur; Catherine H Wu; George Y Wu

    2012-01-01

    Hepatitis C virus (HCV) hepatitis,initially termed non-A,non-B hepatitis,has become one of the leading causes of cirrhosis and hepatocellular carcinoma worldwide.With the help of animal models,our understanding of the virus has grown substantially from the time of initial discovery.There is a paucity of available animal models for the study of HCV,mainly because of the selective susceptibility limited to humans and primates.Recent work has focused modification of animals to permit HCV entry,replication and transmission.In this review,we highlight the currently available models for the study of HCV including chimpanzees,tupaia,mouse and rat models.Discussion will include methods of model design as well as the advantages and disadvantages of each model.Particular focus is dedicated to knowledge of pathophysiologic mechanisms of HCV infection that have been elucidated through animal studies.Research within animal models is critically important to establish a complete understanding of HCV infection,which will ultimately form the basis for future treatments and prevention of disease.

  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. Reaching Diverse Participants Utilizing a Diverse Delivery Infrastructure: A Replication Study

    Directory of Open Access Journals (Sweden)

    Matthew Lee eSmith

    2015-04-01

    Full Text Available This replication study examines participant recruitment and program adoption aspects of disease self-management programs by delivery site types. Data were analyzed from 58,526 adults collected during a national dissemination of the Stanford suite of Chronic Disease Self-Management Education (CDSME programs spanning 45 states, the District of Columbia, and Puerto Rico. Participant data were analyzed using multinomial logistic regression to generate profiles by delivery site type. Profiles were created for the five leading delivery site types, which included senior centers or Area Agencies on Aging (AAA, residential facilities, healthcare organizations, community or multi-purpose centers, and faith-based organizations. Significant variation in neighborhood characteristics (e.g., rurality, median household income, percent of the population age 65 years and older, percent of the population that is non-Hispanic white and participant characteristics (e.g., age, sex, ethnicity, race, rurality were observed by delivery site type. Study findings confirm that these evidence-based programs are capable of reaching large numbers of diverse participants through the aging services network. Given the importance of participant reach and program adoption to the success of translational research dissemination initiatives, these findings can assist program deliverers to create strategic plans to engage community partners to diversify their participant base.

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

    Science.gov (United States)

    DeSoto, K. Andrew; Schweinsberg, Martin

    2017-01-01

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

  5. 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.; Radstake, T.R.D.J.; Leeuwen, M.A. van; Wijmenga, C.; Koeleman, B.P.; Alarcon-Riquelme, M.; 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:

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

    NARCIS (Netherlands)

    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

    2008-01-01

    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: Th

  7. 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.; Radstake, T.R.D.J.; Leeuwen, M.A. van; Wijmenga, C.; Koeleman, B.P.; Alarcon-Riquelme, M.; 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: Th

  8. Replication Study: Coadministration of a tumor-penetrating peptide enhances the efficacy of cancer drugs

    Science.gov (United States)

    Mantis, Christine; Kandela, Irawati; Aird, Fraser

    2017-01-01

    In 2015, as part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Kandela et al., 2015) that described how we intended to replicate selected experiments from the paper “Coadministration of a tumor-penetrating peptide enhances the efficacy of cancer drugs“ (Sugahara et al., 2010). Here we report the results of those experiments. We found that coadministration with iRGD peptide did not have an impact on permeability of the chemotherapeutic agent doxorubicin (DOX) in a xenograft model of prostate cancer, whereas the original study reported that it increased the penetrance of this cancer drug (Figure 2B; Sugahara et al., 2010). Further, in mice bearing orthotopic 22Rv1 human prostate tumors, we did not find a statistically significant difference in tumor weight for mice treated with DOX and iRGD compared to DOX alone, whereas the original study reported a decrease in tumor weight when DOX was coadministered with iRGD (Figure 2C; Sugahara et al., 2010). In addition, we did not find a statistically significant difference in TUNEL staining in tumor tissue between mice treated with DOX and iRGD compared to DOX alone, while the original study reported an increase in TUNEL positive staining with iRGD coadministration (Figure 2D; Sugahara et al., 2010). Similar to the original study (Supplemental Figure 9A; Sugahara et al., 2010), we did not observe an impact on mouse body weight with DOX and iRGD treatment. Finally, we report meta-analyses for each result. DOI: http://dx.doi.org/10.7554/eLife.17584.001 PMID:28100395

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

    NARCIS (Netherlands)

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

    2014-01-01

    Context: Cultural differences between countries may entail differences in feedback processes. Aims: By replicating a Dutch study in Indonesia, we analysed whether differences in processes influenced the perceived instructiveness of feedback. Methods: Over a two-week period, Indonesian students (n =

  10. Scientific Evidence as Content Knowledge: A Replication Study with English and Turkish Pre-Service Primary Teachers

    Science.gov (United States)

    Roberts, Ros; Sahin-Pekmez, Esin

    2012-01-01

    Pre-service teachers around the world need to develop their content knowledge of scientific evidence to meet the requirements of recent school curriculum developments which prepare pupils to be scientifically literate. This research reports a replication study in Turkey of an intervention originally carried out with pre-service primary teachers in…

  11. Children's Toleration of Real-Life Aggression after Exposure to Media Violence: A Replication of the Drabman and Thomas Studies.

    Science.gov (United States)

    Molitor, Fred; Hirsch, Kenneth William

    1994-01-01

    Results of four mid-1970s experiments continue to be used as evidence that exposure to media violence desensitizes children to real-life aggression. This study replicated procedures from those experiments using contemporary video materials, and results confirmed original findings that children tend to tolerate more the aggressive behaviors of…

  12. Factors Associated with Unfavorable Treatment Outcomes in New and Previously Treated TB Patients in Uzbekistan: A Five Year Countrywide Study.

    Directory of Open Access Journals (Sweden)

    Jamshid Gadoev

    Full Text Available TB is one of the main health priorities in Uzbekistan and relatively high rates of unfavorable treatment outcomes have recently been reported. This requires closer analysis to explain the reasons and recommend interventions to improve the situation. Thus, by using countrywide data this study sought to determine trends in unfavorable outcomes (lost-to-follow-ups, deaths and treatment failures and describe their associations with socio-demographic and clinical factors.A countrywide retrospective cohort study of all new and previously treated TB patients registered in the National Tuberculosis programme between January 2006 and December 2010.Among 107,380 registered patients, 67% were adults, with smaller proportions of children (10%, adolescents (4% and elderly patients (19%. Sixty per cent were male, 66% lived in rural areas, 1% were HIV-infected and 1% had a history of imprisonment. Pulmonary TB (PTB was present in 77%, of which 43% were smear-positive and 53% were smear-negative. Overall, 83% of patients were successfully treated, 6% died, 6% were lost-to-follow-up, 3% failed treatment and 2% transferred out. Factors associated with death included being above 55 years of age, HIV-positive, sputum smear positive, previously treated, jobless and living in certain provinces. Factors associated with lost-to-follow-up were being male, previously treated, jobless, living in an urban area, and living in certain provinces. Having smear-positive PTB, being an adolescent, being urban population, being HIV-negative, previously treated, jobless and residing in particular provinces were associated with treatment failure.Overall, 83% treatment success rate was achieved. However, our study findings highlight the need to improve TB services for certain vulnerable groups and in specific areas of the country. They also emphasize the need to develop unified monitoring and evaluation tools for drug-susceptible and drug-resistant TB, and call for better TB

  13. Clinical value of the VMI supplemental tests: a modified replication study.

    Science.gov (United States)

    Avi-Itzhak, Tamara; Obler, Doris Richard

    2008-10-01

    To carry out a modified replication of the study performed by Kulp and Sortor evaluating the clinical value of the information provided by Beery's visual-motor supplemental tests of Visual Perception (VP) and Motor Coordination (MC) in normally developed children. The objectives were to (a) estimate the correlations among the three tests scores; (b) assess the predictive power of the VP and MC scores in explaining the variance in Visual-Motor Integration (VMI) scores; and (c) examine whether poor performance on the VMI is related to poor performance on VP or MC. METHODS.: A convenience sample of 71 children ages 4 and 5 years (M = 4.62 +/- 0.43) participated in the study. The supplemental tests significantly (F = 9.59; dF = 2; p VMI performance. Only VP was significantly related to VMI (beta = 0.39; T = 3.49) accounting for the total amount of explained variance. Using the study population norms, 11 children (16% of total sample) did poorly on the VMI; of those 11, 73% did poorly on the VP, and none did poorly on the MC. None of these 11 did poorly on both the VP and MC. Nine percent of total sample who did poorly on the VP performed within the norm on the VMI. Thirteen percent who performed poorly on the MC performed within the norm on the VMI. Using the VMI published norms, 14 children (20% of total sample) who did poorly on the VP performed within the norm on the VMI. Forty-eight percent who did poorly on MC performed within the norm on the VMI. Findings supported Kulp and Sortor's conclusions that each area should be individually evaluated during visual-perceptual assessment of children regardless of performance on the VMI.

  14. Assessment of empathy in first-episode psychosis and meta-analytic comparison with previous studies in schizophrenia.

    Science.gov (United States)

    Achim, Amelie M; Ouellet, Rosalie; Roy, Marc-André; Jackson, Philip L

    2011-11-30

    Empathy is a multidimensional construct that relies on affective and cognitive component processes. A few studies have reported impairments of both cognitive and affective empathy components in patients with schizophrenia. It is, however, not known whether these difficulties are already present at psychosis onset. The affective and cognitive components of empathy were thus assessed in 31 patients with first-episode psychosis (FEP) and 31 matched healthy controls using the Interpersonal Reactivity Index (IRI). Our results were then compared to previous studies of empathy in patients with more chronic schizophrenia via a meta-analysis. In addition, we also assessed the relationship between empathy ratings, Mentalizing performance and clinical symptoms. Contrary to what has been reported in people with more chronic schizophrenia, the IRI ratings did not significantly differ between FEP and controls in our study, though a trend was observed for the Personal distress scale. For the Perspective taking scale, our meta-analysis revealed a significantly lower effect size in this study with FEP patients relative to previous schizophrenia studies. In the FEP group, the IRI ratings were not related to positive, negative or general psychopathology symptoms, but a significant relationship emerged between the Liebowitz Social Anxiety Scale and Perspective taking (negative correlation). In addition, a significant positive correlation was observed between the Empathic concern subscale and our theory of mind task. This study supports the idea that the cognitive component of empathy is less affected in patients with first-episode psychosis relative to patients with more chronic schizophrenia, and the impairments reported in previous reports with more chronic populations should be interpreted in light of a possible deterioration of this cognitive skill. The findings also provide some insight into the relationship between empathy and clinical symptoms such as social anxiety.

  15. Psychotic illness in first-time mothers with no previous psychiatric hospitalizations: a population-based study.

    Directory of Open Access Journals (Sweden)

    Unnur Valdimarsdóttir

    2009-02-01

    Full Text Available BACKGROUND: Psychotic illness following childbirth is a relatively rare but severe condition with unexplained etiology. The aim of this study was to investigate the impact of maternal background characteristics and obstetric factors on the risk of postpartum psychosis, specifically among mothers with no previous psychiatric hospitalizations. METHODS AND FINDINGS: We investigated incidence rates and potential maternal and obstetric risk factors of psychoses after childbirth in a national cohort of women who were first-time mothers from 1983 through 2000 (n = 745,596. Proportional hazard regression models were used to estimate relative risks of psychoses during and after the first 90 d postpartum, among mothers without any previous psychiatric hospitalization and among all mothers. Within 90 d after delivery, 892 women (1.2 per 1,000 births; 4.84 per 1,000 person-years were hospitalized due to psychoses and 436 of these (0.6 per 1,000 births; 2.38 per 1,000 person-years had not previously been hospitalized for any psychiatric disorder. During follow-up after the 90 d postpartum period, the corresponding incidence rates per 1,000 person-years were reduced to 0.65 for all women and 0.49 for women not previously hospitalized. During (but not after the first 90 d postpartum the risk of psychoses among women without any previous psychiatric hospitalization was independently affected by: maternal age (35 y or older versus 19 y or younger; hazard ratio 2.4, 95% confidence interval [CI] 1.2 to 4.7; high birth weight (> or = 4,500 g; hazard ratio 0.3, 95% CI 0.1 to 1.0; and diabetes (hazard ratio 0. CONCLUSIONS: The incidence of psychotic illness peaks immediately following a first childbirth, and almost 50% of the cases are women without any previous psychiatric hospitalization. High maternal age increases the risk while diabetes and high birth weight are associated with reduced risk of first-onset psychoses, distinctly during the postpartum period.

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

    NARCIS (Netherlands)

    Robinson, Andrew; van Oijen, Antoine M.

    2013-01-01

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

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

    NARCIS (Netherlands)

    E.-J. Wagenmakers; T.F. Beek; M. Rotteveel; A. Gierholz; D. Matzke; H. Steingroever; A. Ly; J. Verhagen; R. Selker; A. Sasiadek; Q.F. Gronau; J. Love; Y. Pinto

    2015-01-01

    In a series of four experiments, Topolinski and Sparenberg (2012) found support for the conjecture that clockwise movements induce psychological states of temporal progression and an orientation toward the future and novelty. Here we report the results of a preregistered replication attempt of Exper

  18. Replication of recently identified systemic lupus erythematosus genetic associations : a case-control study

    NARCIS (Netherlands)

    Suarez-Gestal, Marian; Calaza, Manuel; Endreffy, Emoeke; Pullmann, Rudolf; Ordi-Ros, Josep; Sebastiani, Gian Domenico; Ruzickova, Sarka; Santos, Maria Jose; Papasteriades, Chryssa; Marchini, Maurizio; Skopouli, Fotini N.; Suarez, Ana; Blanco, Francisco J.; D'Alfonso, Sandra; Bijl, Marc; Carreira, Patricia; Witte, Torsten; Migliaresi, Sergio; Gomez-Reino, Juan J.; Gonzalez, Antonio

    2009-01-01

    Introduction We aimed to replicate association of newly identified systemic lupus erythematosus (SLE) loci. Methods We selected the most associated SNP in 10 SLE loci. These 10 SNPs were analysed in 1,579 patients with SLE and 1,726 controls of European origin by single-base extension. Comparison of

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

    NARCIS (Netherlands)

    Robinson, Andrew; van Oijen, Antoine M.

    2013-01-01

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

  20. Abiotic self-replication.

    Science.gov (United States)

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

    2012-12-18

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

  1. Replication of genome‐wide association study (GWAS) susceptibility loci in a Latino bipolar disorder cohort

    OpenAIRE

    Gonzalez, Suzanne; Gupta, Jayanta; Villa, Erika; Mallawaarachchi, Indika; Rodriguez, Marco; Ramirez, Mercedes; Zavala, Juan; Armas, Regina; Dassori, Albana; Contreras, Javier; Flores, Deborah; Jerez, Alvaro; Ontiveros, Alfonso; Nicolini, Humberto; Escamilla, Michael

    2016-01-01

    Objectives Recent genome‐wide association studies (GWASs) have identified numerous putative genetic polymorphisms associated with bipolar disorder (BD) and/or schizophrenia (SC). We hypothesized that a portion of these polymorphisms would also be associated with BD in the Latino American population. To identify such regions, we tested previously identified genetic variants associated with BD and/or SC and ancestral haploblocks containing these single nucleotide polymorphisms (SNPs) in a sampl...

  2. 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

  3. Initiation of adenovirus DNA replication.

    OpenAIRE

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

    1980-01-01

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

  4. A multicenter phase II study of irinotecan in patients with advanced colorectal cancer previously treated with 5-fluorouracil.

    Science.gov (United States)

    Méndez, Miguel; Salut, Antonieta; García-Girón, Carlos; Navalon, Marta; Diz, Pilar; García López, Maria José; España, Pilar; de la Torre, Ascensión; Martínez del Prado, Purificación; Duarte, Isabel; Pujol, Eduardo; Arizcun, Alberto; Cruz, Juan Jesús

    2003-11-01

    This multicenter, open-label, phase II study was performed to assess the efficacy and toxicity of irinotecan 350 mg/m2 intravenously every 3 weeks in patients with advanced colorectal cancer (CRC) previously treated with 5-fluorouracil (5-FU). The study enrolled 115 patients and a total of 558 cycles (median, 6 per patient) were administered. The overall objective response rate on an intent-to-treat basis was 18% (with 1 complete response and 20 partial responses), whereas 42 patients (37%) showed stable disease. Median time to progression was 4.8 months and median survival was 13.6 months. Grade 3/4 toxicities included delayed diarrhea (19.1%), nausea/vomiting (10.4%), and neutropenia (8.7%). There were 2 toxic deaths, 1 from delayed diarrhea and 1 from hemorrhage and grade 4 mucositis. In conclusion, the present study confirms the antitumor efficacy of irinotecan monotherapy in patients with CRC pretreated with 5-FU.

  5. Outcomes of induction of labour in women with previous caesarean delivery: a retrospective cohort study using a population database.

    Directory of Open Access Journals (Sweden)

    Sarah J Stock

    Full Text Available BACKGROUND: There is evidence that induction of labour (IOL around term reduces perinatal mortality and caesarean delivery rates when compared to expectant management of pregnancy (allowing the pregnancy to continue to await spontaneous labour or definitive indication for delivery. However, it is not clear whether IOL in women with a previous caesarean section confers the same benefits. The aim of this study was to describe outcomes of IOL at 39-41 weeks in women with one previous caesarean delivery and to compare outcomes of IOL or planned caesarean delivery to those of expectant management. METHODS AND FINDINGS: We performed a population-based retrospective cohort study of singleton births greater than 39 weeks gestation, in women with one previous caesarean delivery, in Scotland, UK 1981-2007 (n = 46,176. Outcomes included mode of delivery, perinatal mortality, neonatal unit admission, postpartum hemorrhage and uterine rupture. 40.1% (2,969/7,401 of women who underwent IOL 39-41 weeks were ultimately delivered by caesarean. When compared to expectant management IOL was associated with lower odds of caesarean delivery (adjusted odds ratio [AOR] after IOL at 39 weeks of 0.81 [95% CI 0.71-0.91]. There was no significant effect on the odds of perinatal mortality but greater odds of neonatal unit admission (AOR after IOL at 39 weeks of 1.29 [95% CI 1.08-1.55]. In contrast, when compared with expectant management, elective repeat caesarean delivery was associated with lower perinatal mortality (AOR after planned caesarean at 39 weeks of 0.23 [95% CI 0.07-0.75] and, depending on gestation, the same or lower neonatal unit admission (AOR after planned caesarean at 39 weeks of 0.98 [0.90-1.07] at 40 weeks of 1.08 [0.94-1.23] and at 41 weeks of 0.77 [0.60-1.00]. CONCLUSIONS: A more liberal policy of IOL in women with previous caesarean delivery may reduce repeat caesarean delivery, but increases the risks of neonatal complications.

  6. Birth outcome in women with previously treated breast cancer--a population-based cohort study from Sweden.

    Directory of Open Access Journals (Sweden)

    Kristina Dalberg

    2006-09-01

    Full Text Available BACKGROUND: Data on birth outcome and offspring health after the appearance of breast cancer are limited. The aim of this study was to assess the risk of adverse birth outcomes in women previously treated for invasive breast cancer compared with the general population of mothers. METHODS AND FINDINGS: Of all 2,870,932 singleton births registered in the Swedish Medical Birth Registry during 1973-2002, 331 first births following breast cancer surgery--with a mean time to pregnancy of 37 mo (range 7-163--were identified using linkage with the Swedish Cancer Registry. Logistic regression analysis was used. The estimates were adjusted for maternal age, parity, and year of delivery. Odds ratios (ORs and 95% confidence intervals (CIs were used to estimate infant health and mortality, delivery complications, the risk of preterm birth, and the rates of instrumental delivery and cesarean section. The large majority of births from women previously treated for breast cancer had no adverse events. However, births by women exposed to breast cancer were associated with an increased risk of delivery complications (OR 1.5, 95% CI 1.2-1.9, cesarean section (OR 1.3, 95% CI 1.0-1.7, very preterm birth (<32 wk (OR 3.2, 95% CI 1.7-6.0, and low birth weight (<1500 g (OR 2.9, 95% CI 1.4-5.8. A tendency towards an increased risk of malformations among the infants was seen especially in the later time period (1988-2002 (OR 2.1, 95% CI 1.2-3.7. CONCLUSIONS: It is reassuring that births overall were without adverse events, but our findings indicate that pregnancies in previously treated breast cancer patients should possibly be regarded as higher risk pregnancies, with consequences for their surveillance and management.

  7. Does the previous diagnosis of arterial hypertension affect one´s daily life? Pró-Saúde Study

    Directory of Open Access Journals (Sweden)

    Gilberto Senechal de Goffredo Filho

    2013-12-01

    Full Text Available In addition to damaging several target organs, arterial hypertension may negatively impact patients' activities of daily living. Biological and behavioral mechanisms underlying such limitations have yet to be clarified. The objectives of this study were to investigate whether having been previously told of a hypertension diagnosis is associated with the frequency and duration of temporary limitations in activities of daily living, and whether these relationships differ by gender, age, or socioeconomic position. We analyzed sectional data from 2,666 participants (56% women; 55% with high school or lower schooling at the baseline phase (1999 - 2001 of a longitudinal investigation of university employees in Rio de Janeiro, Brazil (Pró-Saúde Study, asking participants whether they had ever been diagnosed with hypertension by a health professional, if they had been unable to perform any activities of daily living due to a health problem in the previous 2 weeks, and for how many days that had occurred. Multinomial logistic regression models were fitted for the overall study population and for age, gender, educational level, and per capita household income strata. Associations between hypertension diagnosis and temporary limitations were not observed in the overall study population and in gender, education and income strata. However, there were higher odds of temporary limitations among participants aged 55 years old or more with hypertension diagnosis (adjusted OR = 9.5; 95%CI 1.5 - 58.6, regardless of blood pressure levels and use of antihypertensive medication. Elderly people may keep an attitude of higher vigilance regarding conditions or events potentially worsening their health status.

  8. Adenovirus DNA Replication

    OpenAIRE

    Hoeben, Rob C.; Uil, Taco G.

    2013-01-01

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

  9. Predicting DUI recidivism of male drunken driving: a prospective study of the impact of alcohol markers and previous drunken driving.

    Science.gov (United States)

    Portman, M; Penttilä, A; Haukka, J; Eriksson, P; Alho, H; Kuoppasalmi, K

    2010-01-15

    The aim of the present study was to determine whether the alcohol biomarkers CDT, GGT, the biomarker gamma-CDT index and previous drunken driving contributed significantly to the prediction of DUI recidivism. The subjects consisted of two different samples of drivers, viz. drivers who were found to have a positive breath alcohol concentration during random breath testing surveys (n=237), and drunken drivers who were apprehended during ordinary police work (n=193). The drunken driving events were monitored using a data-base both retrospectively and prospectively. It was found that the biomarker index, gamma-CDT, emerged as a notable predictor of recidivism in the group of random breath tested drivers. Measurement of gamma-CDT and its impact on DUI recidivism has not to our knowledge been applied to random breath tested drivers before. The apprehended drunken drivers, on the other hand, did not show a significant relationship between gamma-CDT and DUI recidivism. However, in both groups of drivers it was found that a previous conviction for drunken driving strongly predicted DUI recidivism. More attention should be paid by both physicians and the police to the high risk of recidivism among those convicted of drunken driving.

  10. Replicating Cardiovascular Condition-Birth Month Associations

    Science.gov (United States)

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

    2016-01-01

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

  11. 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.

  12. 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.

  13. Evaluation of questionnaire-based information on previous physical work loads. Stockholm MUSIC 1 Study Group. Musculoskeletal Intervention Center.

    Science.gov (United States)

    Torgén, M; Winkel, J; Alfredsson, L; Kilbom, A

    1999-06-01

    The principal aim of the present study was to evaluate questionnaire-based information on past physical work loads (6-year recall). Effects of memory difficulties on reproducibility were evaluated for 82 subjects by comparing previously reported results on current work loads (test-retest procedure) with the same items recalled 6 years later. Validity was assessed by comparing self-reports in 1995, regarding work loads in 1989, with worksite measurements performed in 1989. Six-year reproducibility, calculated as weighted kappa coefficients (k(w)), varied between 0.36 and 0.86, with the highest values for proportion of the workday spent sitting and for perceived general exertion and the lowest values for trunk and neck flexion. The six-year reproducibility results were similar to previously reported test-retest results for these items; this finding indicates that memory difficulties was a minor problem. The validity of the questionnaire responses, expressed as rank correlations (r(s)) between the questionnaire responses and workplace measurements, varied between -0.16 and 0.78. The highest values were obtained for the items sitting and repetitive work, and the lowest and "unacceptable" values were for head rotation and neck flexion. Misclassification of exposure did not appear to be differential with regard to musculoskeletal symptom status, as judged by the calculated risk estimates. The validity of some of these self-administered questionnaire items appears sufficient for a crude assessment of physical work loads in the past in epidemiologic studies of the general population with predominantly low levels of exposure.

  14. 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.

  15. Alemtuzumab as rescue therapy in a cohort of 16 aggressive multiple sclerosis patients previously treated by Mitoxantrone: an observational study.

    Science.gov (United States)

    Le Page, Emmanuelle; Deburghgraeve, Véronique; Lester, Marie-Antoinette; Cardiet, Isabelle; Leray, Emmanuelle; Edan, Gilles

    2015-01-01

    Our study aimed to describe safety and neurological impact of alemtuzumab as last-line rescue therapy in aggressive multiple sclerosis (MS) patients, previously treated by Mitoxantrone (MITOX). Between June 2004 and October 2013, 13 patients received alemtuzumab at 20 mg/day and 3 at 12 mg/day for 5 days. EDSS, relapses, secondary progression were prospectively assessed 12 and 6 months before treatment, at baseline and every 3 months. Mean follow-up was 6.2 years [1-10]. Mean age at alemtuzumab start was 40 years [26-49] for 8 Secondary Progressive (SP) and 30 years [26-35] for 8 Relapsing-Remitting (RR) patients. MS duration was 13.7 (± 3) and 8.3 (± 4) years, respectively. During the 12 months before alemtuzumab, annual relapse rate was 0.75 and 3.14, respectively and the 16 patients accumulated 2-30 new gadolinium enhancing lesions. 4 patients (suboptimal responders) received alemtuzumab during MITOX and 12 patients 1-7.8 years after MITOX. Out of 8 SPMS, 2 were disease free up to last visit (4.7 and 8 years), 5 improved or stabilized but only transiently and 1 worsened. Out of 8 RRMS, 1 remained stable up to last visit (8.7 years) despite 1 relapse and active MRI at 18 months and 7 improved (1-4 point EDSS): 4 remained disease free up to last visit (12, 24, 38 months and 7 years), 2 were successfully retreated at 25 and 33 months and 1 worsened progressively 24 months after alemtuzumab. 2 patients developed Grave's disease and 1 hypothyroidism. Alemtuzumab controls aggressive RRMS despite previous use of MITOX.

  16. 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

  17. Dynamics of Escherichia coli Chromosome Segregation during Multifork Replication

    DEFF Research Database (Denmark)

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

    2007-01-01

    Slowly growing Escherichia coli cells have a simple cell cycle, with replication and progressive segregation of the chromosome completed before cell division. In rapidly growing cells, initiation of replication occurs before the previous replication rounds are complete. At cell division...

  18. 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.

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

    Science.gov (United States)

    Leontovich, Alexey A.; Intine, Robert V.; Sarras, Michael P.

    2016-01-01

    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. PMID:26981540

  20. Studies on the replication of Mayaro virus grown in interferon treated cells.

    Science.gov (United States)

    Rebello, M C; Fonseca, M E; Marinho, J O; Rebello, M A

    1994-01-01

    Mayaro virus grown in interferon treated infected cells has been characterized with regard to its ability to replicate in vertebrate (TC7) and invertebrate (Aedes albopictus) cells. Virus purified from interferon treated TC7 cells adsorbs and penetrates to the same extent as the control virus. During infection, these virus particles caused inhibition of host protein synthesis and synthesized the same spectrum of viral proteins as normal virus. This population however, was apparently more sensitive to interferon treatment. Electron microscopy of TC7 cells showed the presence of numerous aberrant virus particles budding from the plasma membrane.

  1. Studies on the replication of Mayaro virus grown in interferon treated cells

    Directory of Open Access Journals (Sweden)

    M. C. S. Rebello

    1994-12-01

    Full Text Available Mayaro virus grown in interferon treated infected cells has been characterized with regard to its ability to replicate in vertebrate (TC7 and invertebrate (Aedes albopictus cells. Virus purified from interferon treated TC7 cells adsorbs and penetrates to the same extent as the control virus. During infection, these virus particles caused inhibition of host protein synthesis and synthesized the same spectrum of viral proteins as normal virus. This population however, was apparently more sensitive to interferon treatment. Electron microscopy of TC7 cells showed the presence of numerous aberrant virus particles budding from the plasma membrane.

  2. 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].

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

    Science.gov (United States)

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

    2016-09-01

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

  4. A phase I study of imatinib mesylate in combination with chlorambucil in previously treated chronic lymphocytic leukemia patients.

    Science.gov (United States)

    Hebb, Jonathan; Assouline, Sarit; Rousseau, Caroline; Desjardins, Pierre; Caplan, Stephen; Egorin, Merrill J; Amrein, Lilian; Aloyz, Raquel; Panasci, Lawrence

    2011-09-01

    The tyrosine kinase inhibitor, imatinib, has the potential to indirectly inhibit DNA repair. This mechanism of action has been shown to mediate sensitization to chlorambucil in chronic lymphocytic leukemia (CLL). To evaluate this effect in vivo, we performed a phase I study of chlorambucil combined with imatinib in relapsed CLL patients. The three dose levels studied included imatinib at 300, 400, or 600 mg/day. Imatinib was given on days 1-10, and chlorambucil (8 mg/m(2) daily) was given on days 3-7 of a 28-day cycle (up to 6 cycles). Eleven patients participated in this study. Low-grade gastrointestinal toxicities were observed in a dose-dependent manner. Forty-five percent of patients responded (two unconfirmed CRs and three PRs). Two responding patients were fludarabine refractory. The in vitro IC(50) of chlorambucil alone or in the presence of 5 μM imatinib in CLL lymphocytes correlated with the decrease in lymphocyte counts on day 15. Imatinib plasma concentrations achieved in patients were in the range of those effective in in vitro sensitization studies. The combination of chlorambucil and imatinib in patients with previously treated CLL was well tolerated and showed evidence of clinical efficacy. Based on our results, we recommend the 400 mg daily dose of imatinib on days 1-10 with 8 mg/m(3) chlorambucil on days 3-7 every 28 days as the phase II dose. This represents the first clinical trial examining the potential synergy between a tyrosine kinase inhibitor and a conventional alkylating agent for the treatment of CLL.

  5. 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.

  6. Early Intervention with a Parent-Delivered Massage Protocol Directed at Tactile Abnormalities Decreases Severity of Autism and Improves Child-to-Parent Interactions: A Replication Study

    Directory of Open Access Journals (Sweden)

    Louisa M. T. Silva

    2015-01-01

    Full Text Available Tactile abnormalities are severe and universal in preschool children with autism. They respond well to treatment with a daily massage protocol directed at tactile abnormalities (QST massage for autism. Treatment is based on a model for autism proposing that tactile impairment poses a barrier to development. Two previous randomized controlled trials evaluating five months of massage treatment reported improvement of behavior, social/communication skills, and tactile and other sensory symptoms. This is the first report from a two-year replication study evaluating the protocol in 103 preschool children with autism. Parents gave daily treatment; trained staff gave weekly treatment and parent support. Five-month outcomes replicated earlier studies and showed normalization of receptive language (18%, P=.03, autistic behavior (32%, P=.006, total sensory abnormalities (38%, P=.0000005, tactile abnormalities (49%, P=.0002, and decreased autism severity (medium to large effect size, P=.008. In addition, parents reported improved child-to-parent interactions, bonding, and decreased parenting stress (44%, P=.00008. Early childhood special education programs are tasked with addressing sensory abnormalities and engaging parents in effective home programs. Until now, they have lacked research-based methods to do so. This program fulfills the need. It is recommended to parents and ECSE programs (ages 3–5 at autism diagnosis.

  7. 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.

  8. Phase III randomized study of bendamustine compared with chlorambucil in previously untreated patients with chronic lymphocytic leukemia.

    Science.gov (United States)

    Knauf, Wolfgang U; Lissichkov, Toshko; Aldaoud, Ali; Liberati, Anna; Loscertales, Javier; Herbrecht, Raoul; Juliusson, Gunnar; Postner, Gerhard; Gercheva, Liana; Goranov, Stefan; Becker, Martin; Fricke, Hans-Joerg; Huguet, Francoise; Del Giudice, Ilaria; Klein, Peter; Tremmel, Lothar; Merkle, Karlheinz; Montillo, Marco

    2009-09-10

    This randomized, open-label, parallel-group, multicenter study was designed to compare the efficacy and safety of bendamustine and chlorambucil in previously untreated patients with advanced (Binet stage B or C) chronic lymphocytic leukemia (CLL). Patients (chlorambucil 0.8 mg/kg (Broca's normal weight) orally on days 1 and 15; treatment cycles were repeated every 4 weeks for a maximum of six cycles. The response to treatment was assessed according to National Cancer Institute Working Group criteria, and the final determination of response was made by a blinded independent review committee. A total of 319 patients were randomly assigned (162 bendamustine, 157 chlorambucil). Complete or partial responses were achieved in 110 (68%) of 162 bendamustine-treated and 48 (31%) of 157 chlorambucil-treated patients (P chlorambucil (31% v 2%). Median progression-free survival was 21.6 months with bendamustine and 8.3 months with chlorambucil (P chlorambucil (median, 21.8 v 8.0 months). Hematologic National Cancer Institute Common Toxicity Criteria grade 3 to 4 adverse events were more common with bendamustine than with chlorambucil (occurring in 40% v 19% of patients). Severe infections (grade 3 to 4) occurred in 8% of bendamustine-treated patients and 3% of chlorambucil-treated patients. Bendamustine offers significantly greater efficacy than chlorambucil, and a manageable toxicity profile, when used as first-line therapy in patients with advanced CLL.

  9. Integrating Sonography Training Into Undergraduate Medical Education: A Study of the Previous Exposure of One Institution's Incoming Residents.

    Science.gov (United States)

    Day, James; Davis, Joshua; Riesenberg, Lee Ann; Heil, Daniel; Berg, Katherine; Davis, Robyn; Berg, Dale

    2015-07-01

    Sonography is a crucial and versatile tool within the field of medicine. Recent advancements in technology have led to increased use of point-of-care sonography. We designed a survey to assess prior point-of-care sonography training among incoming interns at an academic teaching hospital. In 2012 and 2013, we surveyed incoming interns (n = 154 and 145, respectively) regarding point-of-care sonography training received during medical school. The survey questions included formal didactic sessions, bedside instruction, and the use of simulation technology. One-fourth (26.3% in 2012 and 23.4% in 2013) of responding interns reported having never done an ultrasound scan at the bedside. In 2012 and 2013, 55.0% and 55.6% of respondents reported never having done an ultrasound scan in a simulation center, respectively. Interns agreed that sonography education should be provided during medical school. On average, interns disagreed with the statement that sonography should be taught in residency only. There was no significant difference in the sex or general previous experience with sonography across both intern classes. Point-of-care sonography is inconsistently taught in medical school. The interns in our study also thought that sonography education should begin in medical school, and sonography should be taught by using simulation and at the bedside. © 2015 by the American Institute of Ultrasound in Medicine.

  10. 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.

  11. Risk factors and therapeutic coverage at 6 years in patients with previous myocardial infarction: the CASTUO study

    Science.gov (United States)

    Félix-Redondo, Francisco Javier; Lozano Mera, Luis; Consuegra-Sánchez, Luciano; Giménez Sáez, Fernando; Garcipérez de Vargas, Francisco Javier; Castellano Vázquez, José María; Fernández-Bergés, Daniel

    2016-01-01

    Objectives To determine the degree of risk factor control, the clinical symptoms and the therapeutic management of patients with a history of previous myocardial infarction. Methods Cross-sectional study at 6 years of a first episode of acute myocardial infarction between 2000 and 2009, admitted at a hospital in the region of Extremadura (Spain). Of 2177 patients with this diagnosis, 1365 remained alive and therefore were included in the study. Results We conducted a person-to-person survey in 666 (48.8%) individuals and telephone survey in 437 (31.9%) individuals. The former are analysed. 130 were female (19.5%). The mean age was 67.4 years and the median time since the event was 5.8 (IQR 3.6–8.2) years. Active smokers made up 13.8%, low-density lipoprotein (LDL) cholesterol was ≥70 mg/dL: 82%, blood pressure ≥140/90 mm Hg (≥140/85 in diabetics): 49.8%, fasting glucose ≥126 mg/dL: 26%, heart rate 50–59 bpm: 60.7%, and obesity: 45.9%. Patients reported presenting angina comprised 22.4% and those with dyspnoea, 29.3%. Drug coverage was: 88.0% antiplatelet drugs, 86.5% statins, 75.6% β-blockers and 65.8% blockers of the renin-angiotensin system. Patients receiving all four types of drugs made up 41.9%, with only 3.0% having jointly controlled cholesterol, blood pressure, heart rate and glycaemia. Conclusions LDL cholesterol, heart rate and blood pressure were risk factors with less control. More than 1/5 of patients had angina and more than 1/4, dyspnoea. Risk factor control and the clinical condition were far from optimal, as was drug coverage, although to a lesser degree. PMID:27127637

  12. Aquareovirus NS80 Initiates Efficient Viral Replication by Retaining Core Proteins within Replication-Associated Viral Inclusion Bodies

    OpenAIRE

    Liming Yan; Jie Zhang; Hong Guo; Shicui Yan; Qingxiu Chen; Fuxian Zhang; Qin Fang

    2015-01-01

    Viral inclusion bodies (VIBs) are specific intracellular compartments for reoviruses replication and assembly. Aquareovirus nonstructural protein NS80 has been identified to be the major constituent for forming globular VIBs in our previous study. In this study, we investigated the role of NS80 in viral structural proteins expression and viral replication. Immunofluorescence assays showed that NS80 could retain five core proteins or inner-capsid proteins (VP1-VP4 and VP6), but not outer-capsi...

  13. Organic Compounds Detected in Deciduous Teeth: A Replication Study from Children with Autism in Two Samples

    Directory of Open Access Journals (Sweden)

    Raymond F. Palmer

    2015-01-01

    Full Text Available Biological samples are an important part of investigating toxic exposures and disease outcomes. However, blood, urine, saliva, or hair can only reflect relatively recent exposures. Alternatively, deciduous teeth have served as a biomarker of early developmental exposure to heavy metals, but little has been done to assess organic toxic exposures such as pesticides, plastics, or medications. The purpose of our study was to determine if organic chemicals previously detected in a sample of typically developing children could be detected in teeth from a sample of children with autism. Eighty-three deciduous teeth from children with autism spectrum disorders (ASD were chosen from our tooth repository. Organic compounds were assessed using liquid chromatography tandem mass spectrometry and gas chromatography methods. Consistent with a prior report from Camann et al., (2013, we have demonstrated that specific semivolatile organic chemicals relevant to autism etiology can be detected in deciduous teeth. This report provides evidence that teeth can be useful biomarkers of early life exposure for use in epidemiologic case-control studies seeking to identify differential unbiased exposures during development between those with and without specific disorders such as autism.

  14. Laterality, frequency and replication of rTMS treatment for chronic tinnitus: pilot studies and a review of maintenance treatment

    Science.gov (United States)

    Mennemeier, M.; Munn, T.; Allensworth, M.; Lenow, J.K.; Brown, G.; Allen, S.; Dornhoffer, J.; Williams, D.K.

    2012-01-01

    This manuscript reports on findings of three open label, pilot studies and it reviews studies using rTMS as a maintenance treatment for any disorder. The first pilot study examined whether a patient’s original treatment response to 1 Hz rTMS over temporal cortex could be replicated by stimulating a homologous region of the opposite hemisphere. The second study examined whether a patient’s response to 1Hz rTMS could be replicated by applying 10 Hz rTMS over the same treatment site. The third study applied a 3-day course of maintenance rTMS, either at 1 or 10 Hz, when subjects indicated that the benefit of their last course of treatment was waning. Patients with bilateral subjective tinnitus of at least 6 months duration were recruited from a prior, sham controlled study with treatment crossover that applied 1Hz rTMS over temporal cortex. Both treatment responders and non-responders were recruited. Results indicated, first, that the original treatment response, both positive and negative, is replicated after stimulating a homologous region of the opposite hemisphere; second, patients respond similarly to 1 and 10 Hz stimulation of the same treatment site (an exception was one patient who initially failed 1 Hz stimulation but responded positively to 10 Hz stimulation); and, third, maintenance rTMS had a sustained and additive benefit for tinnitus among treatment responders. Conclusions are that rTMS-induced effects on tinnitus are neither hemisphere specific nor frequency dependent; although, different frequencies of rTMS may have greater potency for a given subject. Maintenance treatment is a well tolerated approach with demonstrated feasibility for managing chronic tinnitus in persons who respond positively to an initial course of treatment. PMID:22486989

  15. Persistence of cardiovascular risk factors in women with previous preeclampsia: a long-term follow-up study.

    Science.gov (United States)

    Aykas, Fatma; Solak, Yalcin; Erden, Abdulsamet; Bulut, Kadir; Dogan, Selcuk; Sarli, Bahadr; Acmaz, Gokhan; Afsar, Baris; Siriopol, Dimitrie; Covic, Adrian; Sharma, Shailendra; Johnson, Richard J; Kanbay, Mehmet

    2015-04-01

    Preeclampsia is a cardiovascular (CV) disease risk factor, and lifestyle modifications are recommended. It was suggested that preeclampsia may increase the prevalence of various CV disease risk factors such as metabolic syndrome, hypertension, insulin resistance, microalbuminuria, and endothelial dysfunction, among others. Here, we investigate the role of serum uric acid in preeclampsia in the development of CV complications. This was an observational case-control study that compared women with history of preeclampsia (n = 25) with age-matched controls with uncomplicated pregnancies (n = 20) who were followed for at least 5 years. Measurements included clinical and ambulatory blood pressure monitoring, ultrasound-measured flow-mediated dilatation (FMD), microalbuminuria, carotid intima-media thickness (CIMT) and serum uric acid, as well as clinical and demographic features. Cardiovascular disease risk factors were compared in women with and without previous preeclampsia. At the time of index gestation, preeclamptic women had higher serum uric acid values (4.36 ± 0.61 vs 2.27 ± 0.38 mg/dL, P preeclampsia were more likely to have hypertension and had higher serum uric acid levels, higher microalbuminuria and CIMT levels, and lower FMD values than did the patients who did not have preeclampsia. The 2 groups were similar with regard to various ambulatory blood pressure parameters. Univariate associates of FMD were history of preeclampsia and the current hypertension status. Microalbuminuria correlated with gestational uric acid levels (coefficient of correlation of 0.40, P = 0.01 for FMD and coefficient of correlation of 0.37, P = 0.01 for CIMT, respectively). Preeclampsia might be a risk factor for the development of cardiovascular risk factors at least 5 years after index pregnancy. Serum uric acid and microalbuminuria may be mechanistic mediators of heightened risk, along with impaired endothelial function in preeclampsia.

  16. Sitagliptin added to previously taken antidiabetic agents on insulin resistance and lipid profile: a 2-year study evaluation.

    Science.gov (United States)

    Derosa, Giuseppe; Ragonesi, Pietro Dario; Fogari, Elena; Cicero, Arrigo Francesco Giuseppe; Bianchi, Lucio; Bonaventura, Aldo; Romano, Davide; Maffioli, Pamela

    2014-04-01

    The aim of this study was to evaluate whether the positive effects of sitagliptin on glycemic control and insulin resistance were maintained also after 2 years of therapy and whether sitagliptin could be effective also in improving lipid profile. In this randomized, double-blind, placebo-controlled trial, 205 patients with type 2 diabetes in therapy with different antidiabetic drugs were randomized to add sitagliptin 100 mg once a day or placebo to their current therapy. We evaluated at the baseline and after 6, 12, 18, and 24 months the following parameters: body mass index, glycated hemoglobin (HbA1c ), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (Tg). Sitagliptin, added to previously taken antidiabetic agents, proved to be effective in improving glycemic profile, reducing HbA1c by -17.5%, FPG by -12.7%, PPG by -20.5%. Regarding insulin resistance, sitagliptin decreased FPI by -8.3% and HOMA-IR by -20.0%, confirming that what have been already reported in short-term studies can be applied also after 2 years of treatment. Sitagliptin also reduced body weight by -4.3%. Our study also showed the positive effect of sitagliptin on lipid profile; in particular, sitagliptin decreased TC by -13.3%, LDL-C by -20.4%, and Tg by -32.3%, and also increased HDL-C by + 13.6%. Sitagliptin proved to be effective on glycemic profile and insulin resistance even after 2 years of therapy and to be effective in improving body weight and lipid profile. © 2012 The Authors Fundamental and Clinical Pharmacology © 2012 Société Française de Pharmacologie et de Thérapeutique.

  17. The SNP rs402710 in 5p15.33 is associated with lung cancer risk: a replication study in Chinese population and a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Xuzai Lu

    Full Text Available BACKGROUND: Lung cancer is the most commonly diagnosed cancer and leading cause of cancer mortality in the world. A single nucleotide polymorphism (SNP, rs402710, located in 5p15.33, was firstly identified to be associated with the lung cancer risk in a genome-wide association study. However, some following replication studies yielded inconsistent results. METHODOLOGY AND FINDINGS: A case-control study of 611 cases and 1062 controls in a Chinese population was conducted, and then a meta-analysis integrating the current and previously published studies with a total 31811 cases and 36333 controls was performed to explore the real effect of rs402710 on lung cancer susceptibility. Significant associations between the SNP rs402710 and lung cancer risk were observed in both case-control study and meta-analysis, with ORs equal to 0.77 (95%CI = 0.63-0.95 and 0.83 (95%CI = 0.81-0.86 in dominant model, respectively. By stratified analysis of our case-control study, the associations were also observed in never smoker group and non-small cell lung cancer(NSCLC group with ORs equal to 0.71 (95%CI = 0.53-0.95 and 0.69 (95%CI = 0.55-0.87, which was remarkable that larger effect of the minor allele T was seen in the two groups than that in overall lung cancer. Besides, the sensitive and cumulative analysis indicated the robust stability of the current results of meta-analysis. CONCLUSION: The results from our replication study and the meta-analysis provided firm evidence that rs402710 T allele significantly contributed to decreased lung cancer risk, and the case-control study implied that the variant may yield stronger effect on NSCLC and never smokers. However, the mechanism underlying the polymorphism conferring susceptibility to lung cancer is warranted to clarify in the follow-up studies.

  18. Central Arctic atmospheric summer conditions during the Arctic Summer Cloud Ocean Study (ASCOS: contrasting to previous expeditions

    Directory of Open Access Journals (Sweden)

    M. Tjernström

    2012-02-01

    Full Text Available Understanding the rapidly changing climate in the Arctic is limited by a lack of understanding of underlying strong feedback mechanisms that are specific to the Arctic. Progress in this field can only be obtained by process-level observations; this is the motivation for intensive ice-breaker-based campaigns such as that described in this paper: the Arctic Summer Cloud-Ocean Study (ASCOS. However, detailed field observations also have to be put in the context of the larger-scale meteorology, and short field campaigns have to be analysed within the context of the underlying climate state and temporal anomalies from this.

    To aid in the analysis of other parameters or processes observed during this campaign, this paper provides an overview of the synoptic-scale meteorology and its climatic anomaly during the ASCOS field deployment. It also provides a statistical analysis of key features during the campaign, such as some key meteorological variables, the vertical structure of the lower troposphere and clouds, and energy fluxes at the surface. In order to assess the representativity of the ASCOS results, we also compare these features to similar observations obtained during three earlier summer experiments in the Arctic Ocean, the AOE-96, SHEBA and AOE-2001 expeditions.

    We find that these expeditions share many key features of the summertime lower troposphere. Taking ASCOS and the previous expeditions together, a common picture emerges with a large amount of low-level cloud in a well-mixed shallow boundary layer, capped by a weak to moderately strong inversion where moisture, and sometimes also cloud top, penetrate into the lower parts of the inversion. Much of the boundary-layer mixing is due to cloud-top cooling and subsequent buoyant overturning of the cloud. The cloud layer may, or may not, be connected with surface processes depending on the depths of the cloud and surface-based boundary layers and on the relative strengths of

  19. Personality and Academic Motivation: Replication, Extension, and Replication

    Science.gov (United States)

    Jones, Martin H.; McMichael, Stephanie N.

    2015-01-01

    Previous work examines the relationships between personality traits and intrinsic/extrinsic motivation. We replicate and extend previous work to examine how personality may relate to achievement goals, efficacious beliefs, and mindset about intelligence. Approximately 200 undergraduates responded to the survey with a 150 participants replicating…

  20. A Replication Study for Association of LBX1 locus with Adolescent Idiopathic Scoliosis in French-Canadian Population.

    Science.gov (United States)

    Nada, Dina; Julien, Cédric; Samuels, Mark E; Moreau, Alain

    2017-06-09

    A case-control association study. To investigate the relationship between LBX1 polymorphisms and Adolescent Idiopathic Scoliosis (AIS) in French-Canadian population. It is widely accepted that genetic factors contribute to AIS. Although the LBX1 locus is so far the most successfully replicated locus in different AIS cohorts, these associations were replicated mainly in Asian populations, with few studies in Caucasian populations of European descent. We recruited 1568 participants (667 AIS patients and 901 healthy controls) in the French-Canadian population. Genomic data was generated using the Illumina Human Omni 2.5 M BeadChip. An additional 121 AIS cases and 51 controls were genotyped for specific SNPs by multiplex PCR using standard procedures. BEAGLE 3 was used to impute the following markers: rs7893223, rs11190878 and rs678741 against the 1000-genomes European cohort phased genotypes given that they were absent in our GWAS panel. Resulting genotypes were combined then used for single marker and haplotyped-based association. Four markers showed association with AIS in our cohort at this locus; rs11190870 the most studied marker, rs7893223, rs594791, and rs11190878. When we restricted the analysis to severe cases only, four additional SNPs showed associations: rs11598177, rs1322331, rs670206 and rs678741. In addition, we analyzed the associations of the observed haplotypes and dihaplotypes formed by these SNPs. The haplotype TTAAGAAA and its homozygous dihaplotype showed the highest association with our severe group and was the highest risk haplotype. The haplotype CCGCAGGG was significantly more associated with the control group, and its homozygous or heterozygous dihaplotype was less frequent in the severe group compared to the control group, suggesting that CCGCAGGG may represent a protective haplotype. We have replicated the association of the LBX1 locus with AIS in French-Canadian population, a novel European descent cohort, which is known for its unique

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

    Science.gov (United States)

    Sirrine, Nicole K.; McCarthy, Shauna K.

    2008-05-01

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

  2. Structure-activity relationship study of arbidol derivatives as inhibitors of chikungunya virus replication.

    Science.gov (United States)

    Di Mola, Antonia; Peduto, Antonella; La Gatta, Annalisa; Delang, Leen; Pastorino, Boris; Neyts, Johan; Leyssen, Pieter; de Rosa, Mario; Filosa, Rosanna

    2014-11-01

    Chikungunya virus (CHIKV), a mosquito-borne arthrogenic Alphavirus, causes an acute febrile illness in humans, that is, accompanied by severe joint pains. In many cases, the infection leads to persistent arthralgia, which may last for weeks to several years. The re-emergence of this infection in the early 2000s was exemplified by numerous outbreaks in the eastern hemisphere. Since then, the virus is rapidly spreading. Currently, no drugs have been approved or are in development for the treatment of CHIKV, which makes this viral infection particularly interesting for academic medicinal chemistry efforts. Several molecules have already been identified that inhibit CHIKV replication in phenotypic virus-cell-based assays. One of these is arbidol, a molecule that already has been licensed for the treatment of influenza A and B virus infections. For structural optimization, a dedicated libraries of 43 indole-based derivatives were evaluated leading to more potent analogues (IIIe and IIIf) with anti-chikungunya virus (CHIKV) activities higher than those of the other derivatives, including the lead compound, and with a selective index of inhibition 13.2 and 14.6, respectively, higher than that of ARB (4.6).

  3. Replication pauses of the wild-type and mutant mitochondrial DNA polymerase gamma: a simulation study.

    Directory of Open Access Journals (Sweden)

    Zhuo Song

    2011-11-01

    Full Text Available The activity of polymerase γ is complicated, involving both correct and incorrect DNA polymerization events, exonuclease activity, and the disassociation of the polymerase:DNA complex. Pausing of pol-γ might increase the chance of deletion and depletion of mitochondrial DNA. We have developed a stochastic simulation of pol-γ that models its activities on the level of individual nucleotides for the replication of mtDNA. This method gives us insights into the pausing of two pol-γ variants: the A467T substitution that causes PEO and Alpers syndrome, and the exonuclease deficient pol-γ (exo(- in premature aging mouse models. To measure the pausing, we analyzed simulation results for the longest time for the polymerase to move forward one nucleotide along the DNA strand. Our model of the exo(- polymerase had extremely long pauses, with a 30 to 300-fold increase in the time required for the longest single forward step compared to the wild-type, while the naturally occurring A467T variant showed at most a doubling in the length of the pauses compared to the wild-type. We identified the cause of these differences in the polymerase pausing time to be the number of disassociations occurring in each forward step of the polymerase.

  4. Replication pauses of the wild-type and mutant mitochondrial DNA polymerase gamma: a simulation study.

    Science.gov (United States)

    Song, Zhuo; Cao, Yang; Samuels, David C

    2011-11-01

    The activity of polymerase γ is complicated, involving both correct and incorrect DNA polymerization events, exonuclease activity, and the disassociation of the polymerase:DNA complex. Pausing of pol-γ might increase the chance of deletion and depletion of mitochondrial DNA. We have developed a stochastic simulation of pol-γ that models its activities on the level of individual nucleotides for the replication of mtDNA. This method gives us insights into the pausing of two pol-γ variants: the A467T substitution that causes PEO and Alpers syndrome, and the exonuclease deficient pol-γ (exo(-)) in premature aging mouse models. To measure the pausing, we analyzed simulation results for the longest time for the polymerase to move forward one nucleotide along the DNA strand. Our model of the exo(-) polymerase had extremely long pauses, with a 30 to 300-fold increase in the time required for the longest single forward step compared to the wild-type, while the naturally occurring A467T variant showed at most a doubling in the length of the pauses compared to the wild-type. We identified the cause of these differences in the polymerase pausing time to be the number of disassociations occurring in each forward step of the polymerase.

  5. Discussion on further studies to measure and evaluate fitness and motor performance for preschool children; summary and previous studies in Japan and future consideratin

    OpenAIRE

    Murase, Tomohiko; Demura, Shinichi

    2005-01-01

    This article discusses and summarizes previous studies dealing with fitness and motor performance in preschool children from the viewpoint of measurement and evaluation, and determines topics for further studies. The studies reviewed in this article were mainly published in the “Japan Journal of Physical Education, Health and Sport Sciences” (edited by the Japan Society of Physical Education, Health and Sport Sciences), and the “Japanese Journal of Physical Fitness and Sports Medicine” (edite...

  6. Replication of the Wellcome Trust genome-wide association study of essential hypertension: the Family Blood Pressure Program.

    Science.gov (United States)

    Ehret, Georg B; Morrison, Alanna C; O'Connor, Ashley A; Grove, Megan L; Baird, Lisa; Schwander, Karen; Weder, Alan; Cooper, Richard S; Rao, D C; Hunt, Steven C; Boerwinkle, Eric; Chakravarti, Aravinda

    2008-12-01

    Essential hypertension is a principal cardiovascular risk factor whose origin remains unknown. Classical genetic studies have shown that blood pressure is at least partially heritable, opening a window to understanding the pathophysiology of essential hypertension in the human using modern genetic tools. The Wellcome Trust Case Control Consortium has recently published the results of screening the genomes of 2000 essential hypertension cases and 3000 controls using 500 000 genome-wide single nucleotide polymorphisms (SNPs). None of the variants proved to be genome-wide significant after correction for multiple tests but the most significantly associated SNPs (PFamily Blood Pressure Program comprising 11 433 individuals recruited by hypertensive families. The results suggest that only one of the six SNPs might be associated with essential hypertension in Americans of European origin. This SNP shows a significant but opposite effect in Americans of Hispanic origin and no association in African Americans. The significance of the opposing effect estimates is unclear. No replication could be shown for hypertension status, but there are differences in study design. This attempted replication highlights that essential hypertension studies will require more comprehensive and larger genetic screens.

  7. Single molecule analysis of replicated DNA reveals the usage of multiple KSHV genome regions for latent replication.

    Directory of Open Access Journals (Sweden)

    Subhash C Verma

    2011-11-01

    Full Text Available Kaposi's sarcoma associated herpesvirus (KSHV, an etiologic agent of Kaposi's sarcoma, Body Cavity Based Lymphoma and Multicentric Castleman's Disease, establishes lifelong latency in infected cells. The KSHV genome tethers to the host chromosome with the help of a latency associated nuclear antigen (LANA. Additionally, LANA supports replication of the latent origins within the terminal repeats by recruiting cellular factors. Our previous studies identified and characterized another latent origin, which supported the replication of plasmids ex-vivo without LANA expression in trans. Therefore identification of an additional origin site prompted us to analyze the entire KSHV genome for replication initiation sites using single molecule analysis of replicated DNA (SMARD. Our results showed that replication of DNA can initiate throughout the KSHV genome and the usage of these regions is not conserved in two different KSHV strains investigated. SMARD also showed that the utilization of multiple replication initiation sites occurs across large regions of the genome rather than a specified sequence. The replication origin of the terminal repeats showed only a slight preference for their usage indicating that LANA dependent origin at the terminal repeats (TR plays only a limited role in genome duplication. Furthermore, we performed chromatin immunoprecipitation for ORC2 and MCM3, which are part of the pre-replication initiation complex to determine the genomic sites where these proteins accumulate, to provide further characterization of potential replication initiation sites on the KSHV genome. The ChIP data confirmed accumulation of these pre-RC proteins at multiple genomic sites in a cell cycle dependent manner. Our data also show that both the frequency and the sites of replication initiation vary within the two KSHV genomes studied here, suggesting that initiation of replication is likely to be affected by the genomic context rather than the DNA

  8. Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma.

    Science.gov (United States)

    Kumar, Shaji; Flinn, Ian; Richardson, Paul G; Hari, Parameswaran; Callander, Natalie; Noga, Stephen J; Stewart, A Keith; Turturro, Francesco; Rifkin, Robert; Wolf, Jeffrey; Estevam, Jose; Mulligan, George; Shi, Hongliang; Webb, Iain J; Rajkumar, S Vincent

    2012-05-10

    Combinations of bortezomib (V) and dexamethasone (D) with either lenalidomide (R) or cyclophosphamide (C) have shown significant efficacy. This randomized phase 2 trial evaluated VDC, VDR, and VDCR in previously untreated multiple myeloma (MM). Patients received V 1.3 mg/m2 (days 1, 4, 8, 11) and D 40 mg (days 1, 8, 15), with either C 500 mg/m2 (days 1, 8) and R 15 mg (days 1-14; VDCR), R 25 mg (days 1-14; VDR), C 500 mg/m2 (days 1, 8; VDC) or C 500 mg/m2 (days 1, 8, 15; VDC-mod) in 3-week cycles (maximum 8 cycles), followed by maintenance with V 1.3 mg/m2 (days 1, 8, 15, 22) for four 6-week cycles (all arms)≥very good partial response was seen in 58%, 51%, 41%, and 53% (complete response rate of 25%, 24%, 22%, and 47%) of patients (VDCR, VDR, VCD, and VCD-mod, respectively); the corresponding 1-year progression-free survival was 86%, 83%, 93%, and 100%, respectively. Common adverse events included hematologic toxicities, peripheral neuropathy, fatigue, and gastrointestinal disturbances. All regimens were highly active and well tolerated in previously untreated MM, and, based on this trial, VDR and VCD-mod are preferred for clinical practice and further comparative testing. No substantial advantage was noted with VDCR over the 3-drug combinations. This trial is registered at www.clinicaltrials.gov (NCT00507442).

  9. 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.

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

    Science.gov (United States)

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

    2017-01-01

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

  11. Regulation of Replication Recovery and Genome Integrity

    DEFF Research Database (Denmark)

    Colding, Camilla Skettrup

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

  12. 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 CP

  13. 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 CPMV inf

  14. Patient acceptance and clinical impact of Bravo monitoring in patients with previous failed catheter-based studies.

    Science.gov (United States)

    Sweis, R; Fox, M; Anggiansah, R; Anggiansah, A; Basavaraju, K; Canavan, R; Wong, T

    2009-03-15

    Standard pH monitoring is performed over 24 h with a naso-oesophageal catheter (C-pH). Limitations include naso-pharyngeal discomfort, nausea and social embarrassment resulting in reduced reflux-provoking activities. Recently a catheter-free pH-monitoring technique has become available. The tolerability and diagnostic yield of this system in patients who failed standard monitoring remain unknown. To examine the tolerability and diagnostic outcome of catheter-free pH-monitoring technique in patients who failed standard monitoring. Patients referred for C-pH and catheter-free pH monitoring completed a tolerability questionnaire. Acid exposure in the distal oesophagus and symptom index (SI) were reviewed. Over 4 years, 883/1751 (50%) of patients with typical reflux symptoms referred for C-pH were diagnosed with gastro-oesophageal reflux disease (GERD) based on a pathological percentage time acid exposure (%time pH patients failed C-pH and, of these, 129 successfully completed 2-day catheter-free pH monitoring. Ninety-eight (76%) of these patients had a pathological percentage pH patients (P patients who had previously failed C-pH; catheter-free pH monitoring assists the definitive diagnosis of GERD in this group.

  15. Association of CD247 polymorphisms with rheumatoid arthritis: a replication study and a meta-analysis.

    Directory of Open Access Journals (Sweden)

    María Teruel

    Full Text Available Given the role of CD247 in the response of the T cells, its entailment in autoimmune diseases and in order to better clarify the role of this gene in RA susceptibility, we aimed to analyze CD247 gene variants previously associated with other autoimmune diseases (rs1052237, rs2056626 and rs864537 in a large independent European Caucasian population. However, no evidence of association was found for the analyzed CD247 single-nucleotide polymorphisms (SNPs with RA and with the presence/absence of anti-cyclic citrullinated polypeptide. We performed a meta-analysis including previously published GWAS data from the rs864537 variant, revealing an overall genome-wide significant association between this CD247 SNP and RA with anti-CCP (OR = 0.90, CI 95% = 0.87-0.93, Poverall = 2.1×10(-10. Our results show for first time a GWAS-level association between this CD247 polymorphism and RA risk.

  16. A Combined Computational and Experimental Study on the Structure-Regulation Relationships of Putative Mammalian DNA Replication Initiator GINS

    Institute of Scientific and Technical Information of China (English)

    Reiko Hayashi; Takako Arauchi; Moe Tategu; Yuya Goto; Kenichi Yoshida

    2006-01-01

    GINS, a heterotetramer of SLD5, PSF1, PSF2, and PSF3 proteins, is an emerging chromatin factor recognized to be involved in the initiation and elongation step of DNA replication. Although the yeast and Xenopus GINS genes are well documented, their orthologous genes in higher eukaryotes are not fully characterized.In this study, we report the genomic structure and transcriptional regulation of mammalian GINS genes. Serum stimulation increased the GINS Mrna levels in human cells. Reporter gene assay using putative GINS promoter sequences revealed that the expression of mammalian GINS is regulated by 17β-Estradiolstimulated estrogen receptor α, and human PSF3 acts as a gene responsive to transcription factor E2F1. The goal of this study is to present the current data so as to encourage further work in the field of GINS gene regulation and functions in mammalian cells.

  17. A Study of the Relationship between Previous Exposure to Education and Practice-Teaching Performance at the University of Ife.

    Science.gov (United States)

    Olatunji, S. A.

    1976-01-01

    A study to identify relationships between the amount of exposure students have to education (as a discipline) and their student teaching performances is reported. Students attending the University of Ife from 1973-1976 were studied. A positive relationship was discovered, but other factors need to be researched further. (MLW)

  18. Marine fouling community in the Eastern harbour of Alexandria, Egypt compared with four decades of previous studies

    Directory of Open Access Journals (Sweden)

    SH.E. RAMADAN

    2006-12-01

    Full Text Available The aim of the present study is to compare the fouling communities between the years 1960 and 1999 in the Eastern harbour of Alexandria, Egypt and to study the main factors that may be controlling these communities. This comparison is based on monthly durations of panel immersion. By using roughened white polystyrene test panels (12.5x12.5 cm, monthly samples of marine fouling were collected from the harbour from October 1998 through September 1999. It is clear that a remarkable variation in number and diversity of fouling communities throughout the last four decades is evident. The minimum diversities were recorded during the studies of 1960 and 1970 (19 and 20 species respectively, while the maximum diversity (35 species was achieved during the 1991 study. Moreover, a small shift among the four dominant groups (Polychaeta, Cirripedia, Bryozoa and Amphipoda was noted during the four decades of the studies. The present comparison indicated that many factors may contribute to this variation, of which nutrient enrichment is the most important and the nature of the applied test panel is lees so.

  19. 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

  20. 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.

  1. 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...

  2. A cross-sectional study of personality traits in women previously treated or untreated for alcohol use disorders

    Directory of Open Access Journals (Sweden)

    Sundh Valter

    2007-08-01

    Full Text Available Abstract Background A better understanding of the relationship between treatment-seeking for alcohol problems and personality traits could give useful insight in factors promoting or hindering treatment for alcohol use disorders (AUD. The aim of this study was to analyze the associations between treatment-seeking for AUD, personality traits, and psychiatric co-morbidity in women. The study was based on pooled cross-sectional data from three population based samples and one clinical sample (n = 1,339. Comparisons were made between treated and untreated women with AUD, and between those with resolved and unresolved AUD. Results A stepwise logistic regression model showed that treatment-seeking for AUD was not associated with personality traits. Among women with lifetime AUD (n = 217, those who had been treated (n = 42 had significantly higher scores than untreated women (n = 175 on three personality traits of the Karolinska Scales of Personality (KSP; somatic anxiety, muscular tension, and guilt. Women with resolved AUD, who had received treatment (n = 23 had significantly higher scores on scales measuring somatic anxiety, psychic anxiety, muscular tension, irritability, and guilt than untreated women with resolved AUD. The latter group resembled women without AUD on most personality traits. There were no differences in occurrence of lifetime psychiatric disorders between the treated and the untreated women, whereas treated women with current AUD had increased risk of lifetime anxiety (OR: 3.1, 95% CI: 1.1–8.7. Conclusion Treatment-seeking was not associated with personality traits in this study. Still, it can be concluded that women with resolved AUD who had received treatment had high scores on the KSP-scales measuring psychic and somatic anxiety, tension, irritability, and feelings of guilt. This suggests that personality assessment might be a useful tool in tailoring individual treatment programs for women with AUD. Future studies need to

  3. Chemical Processes with Supercritical CO2 in Engineered Geologic Systems: Significance, Previous Study, and Path Forward (Invited)

    Science.gov (United States)

    Xu, T.; Pruess, K.

    2009-12-01

    Chemical reactions with dissolved CO2 in the aqueous phase have long been considered in fundamental geosciences and practical applications. Recently, studies on geologic carbon sequestration and enhanced geothermal systems using CO2 as heat transmission fluid have brought new interests in chemical reaction processes directly with supercritical CO2 (scCO2, or gas phase). In the vicinity of a CO2 injection well, the aqueous fluid initially present in a geological formation would be quickly removed by dissolution (evaporation) into the flowing gas stream and by immiscible displacement by the scCO2, creating a gas phase dominant zone. In this zone, the water evaporation could cause formation dry-out and precipitation of salt near the injection well, reducing formation porosity, permeability, and injectivity. The scCO2 may directly attack well construction materials such as cement. Over time, the gas phase will tend to migrate upwards towards the caprock because the density of the scCO2 is lower than that of the aqueous phase. In the upper portions of the reservoir, the scCO2 will directly react with caprock minerals and alter the hydrological properties and mechanical strength. On the other hand, the scCO2 phase will maintain the dissolution into the aqueous phase, lowering pH, inducing mineral dissolution, complexing with dissolved cations, increasing CO2 solubility, increasing the density of the aqueous phase, and promoting “convective mixing”. Chemical processes are quite different in the scCO2 dominant geologic systems. The absence of an aqueous phase poses unique questions, as little is presently known about the chemistry of non-aqueous systems. Additional issues arise from the reactivity of water that is dissolved in the ScCO2 phase. In this presentation, the author will discuss the importance, state of the studies performed, and future research directions.

  4. A Replication Study for the Association of rs726252 in PAPPA2 with Developmental Dysplasia of the Hip in Chinese Han Population

    Science.gov (United States)

    Shi, Dongquan; Xu, Xingquan; Hao, Zheng; Dai, Jin; Xu, Zhihong; Chen, Dongyang; Teng, Huajian; Jiang, Qing

    2014-01-01

    Developmental dysplasia of the hip (DDH) is a common developmental hip disorder, which ranges from mild acetabulum malformation to irreducible hip dislocation. A previous study suggested a significant association of pregnancy-associated plasma protein-A2 (PAPPA2) with DDH susceptibility in Chinese Han population. But with the consideration of the sample size, the association was still debatable. To confirm the association of the reported single nucleotide polymorphism (SNP) in PAPPA2, rs726252 with DDH, we conducted a case-control study in a larger number of subjects. We genotyped rs726252 in 697 DDH subjects and 707 control subjects by TaqMan assay. The association between this SNP and DDH was evaluated statistically. No significant difference was found in any comparison of genotype distribution nor allele frequency between cases and controls. Our replication study indicated that the association between rs726252 and DDH in Chinese Han population was debatable. The association between PAPPA2 and DDH should be evaluated by additional studies. PMID:24672801

  5. Warfarin dosing after bariatric surgery: a retrospective study of 10 patients previously stable on chronic warfarin therapy.

    Science.gov (United States)

    Schullo-Feulner, A M; Stoecker, Z; Brown, G A; Schneider, J; Jones, T A; Burnett, B

    2014-04-01

    Many changes associated with bariatric surgery have the potential to affect warfarin dosing; yet current literature includes little data describing this phenomenon. Investigating this relationship may allow for determination of post-bariatric surgery warfarin dosing using stable pre-operative dosing levels. A retrospective chart review was completed for 10 patients stabilized on chronic warfarin therapy who underwent bariatric surgery. Data collection consisted of the following: warfarin requirement in mg/week, time in target range (TTR), creatinine, liver function, diarrhoea, medication changes, diet, and signs of bleeding and/or thrombosis. Three study patients underwent laparoscopic adjustable gastric banding procedures and seven patients underwent Roux-en-Y gastric bypass. The average (standard deviation) weekly warfarin dose required in the immediate post-operative interval was 64% (25%) of baseline dosing, corresponding to a TTR of 48%. At 6 months, patients required 85% (19%) of baseline weekly dosing, with TTR of 53.4%. At 1 year, dosing was 90% (16%) of baseline with TTR of 63.5%. Patients underwent medication changes as well as transient bouts of diarrhoea. Two patients suffered unspecified haemorrhages of the gastrointestinal tract (international normalized ratio [INR] = 2.3 and 9.8). This patient set demonstrated an initial drop in warfarin requirement, followed by escalating dosing trends that became more predictable as patients were farther out from procedure.

  6. 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…

  7. Learning from Television and Books: A Dutch Replication Study Based on Salomon's Model.

    Science.gov (United States)

    Beentjes, Johannes W. J.

    1989-01-01

    Discussion of the amount of mental effort children invest in television viewing versus book reading focuses on a Dutch study based on Salomon's model and his studies with children in Israel and the United States. The depth of information processed is discussed, and differences in results are examined. (18 references) (LRW)

  8. "Fear of Success" Revisited: A Replication of Matina Horner's Study 30 Years Later.

    Science.gov (United States)

    Engle, Jennifer

    This study updated and extended the classic "fear of success" study conducted by Matina Horner more than 30 years ago. Horner (1970) asked college students to respond to a scenario in which "Anne" or "John" is at the top of her/his medical school class. Based on the negative responses of students to "Anne,"…

  9. THE INTEGRATION OF ENGINEERED AND INSTITUTIONAL CONTROLS: A CASE STUDY APPROACH WITH LESSONS LEARNED FROM PREVIOUSLY CLOSED SITES

    Energy Technology Data Exchange (ETDEWEB)

    Kevin M. Kostelnik; James H. Clarke; Jerry L. Harbour

    2005-02-01

    Environmental remediation efforts that are underway at hundreds of contaminated sites in the United States will not be able to remediate large portions of those sites to conditions that would permit unrestricted access. Rather, large volumes of waste materials, contaminated soils and cleanup residuals will have to be isolated either in place or in new, often on-site, disposal cells with long term monitoring, maintenance and institutional control needs. The challenge continues to be to provide engineering systems and controls that can ensure the protection of public health and the environment over very long time horizons (hundreds to perhaps thousands of years) with minimal intervention. Effective long term management of legacy hazardous and nuclear waste requires an integrated approach that addresses both the engineered containment and control system itself and the institutional controls and other responsibilities that are needed. Decisions concerning system design, monitoring and maintenance, and the institutional controls that will be employed are best done through a "risk-nformed, performance-based" approach. Such an approach should incorporate an analysis of potential "failure" modes and consequences for all important system features, together with lessons learned from experience with systems already in place. The authors will present the preliminary results of a case study approach that included several sites where contamination isolation systems including institutional controls have been implemented. The results are being used together with failure trees and logic diagrams that have been developed for both the engineered barriers and the institutional controls. The use of these analytical tools to evaluate the potential for different levels of failure and associated consequences will be discussed. Of special interest is the robustness of different approaches to providing long-term protection through redundancy and defense in depth.

  10. Variations of the accessory nerve: anatomical study including previously undocumented findings-expanding our misunderstanding of this nerve.

    Science.gov (United States)

    Tubbs, R Shane; Ajayi, Olaide O; Fries, Fabian N; Spinner, Robert J; Oskouian, Rod J

    2017-02-01

    The anatomy of the accessory nerve has been well described but continued new clinical and anatomical findings exemplify our lack of a full understanding of the course of this nerve. Therefore, this study aimed to expand on our knowledge of the course of the 11th cranial nerve via anatomical dissections. Fifty-six cadavers (112 sides) underwent dissection of the accessory nerve from its cranial and spinal origins to its emergence into the posterior cervical triangle. Immunohistochemistry was performed when appropriate. Our findings included two cases (1.8%) where the nerve was duplicated, one intracranially and one extracranially. One accessory nerve (0.9%) was found to enter its own dural compartment within the jugular foramen. The majority of sides (80%) were found to have a cranial root of the accessory nerve. Thirty-one sides (28%) had connections to cervical dorsal roots medially and three sides (2.7%) laterally. Medial connections were most common with the C1 nerve. Medial components of these dorsal root connections were all sensory in nature. However, lateral components were motor on two sides (1.8%). Nerves traveled anterior to the internal jugular vein on 88% of sides. One (0.9%) left side nerve joined an interneural anastomosis between the dorsal rootlets. Macroganglia were found on the spinal part of the intracranial nerve on 13% of sides. The lesser occipital nerve arose directly from the accessory nerve on two sides (1.8%) and communicated with the accessory nerve on 5.4% of sides. One side (0.9%) was found to communicate with the facial nerve with both nerves innervating the sternocleidomastoid muscle. Additional anatomical knowledge of the variants of the accessory nerve may benefit patient care when this nerve is pathologically involved.

  11. The replication of Rocio virus in brain tissue of suckling mice. Study by electron microscopy.

    Science.gov (United States)

    Tanaka, H; Weigl, D R; de Souza Lopes, O

    1983-01-01

    By electron microscopy studies, Rocio virus particles were about 43 nm and spherically shaped. They were found within the cisternae of the endoplasmic reticulum and Golgi complex of infected neurons. No precursor particles were detected nor virus budding was evident.

  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. The Strange Stories test--a replication study of children and adolescents with Asperger syndrome.

    Science.gov (United States)

    Kaland, Nils; Møller-Nielsen, Annette; Smith, Lars; Mortensen, Erik Lykke; Callesen, Kirsten; Gottlieb, Dorte

    2005-03-01

    The aim of the present study was to assess the ability of 21 children and adolescents with Asperger syndrome (AS) of normal intelligence to infer mental states in a story context using Happe's Strange Stories test. The participants in the AS group were compared with an age-matched control group (N=20) of normally developing children and adolescents on a test of social understanding. The test material comprised social communication such as Pretence, Joke, Lie, White Lie, Figure of Speech, Misunderstanding, Persuasion, Irony, Double Bluff and Contrary Emotions, Appearance/Reality and Forgetting. As compared to the controls, the participants in the AS group performed less well on these tasks, and answered fewer correct mental state inferences, but performed well on a physical state control task. This study supports the main finding of earlier studies, showing that even individuals with AS of normal intelligence have problems in using mental state terms context-appropriately when tested on the Strange Stories test.

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

    DEFF Research Database (Denmark)

    Johnson, Emma C; Bjelland, Douglas W; Howrigan, Daniel P

    2016-01-01

    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...

  15. Cognitive Development, Personality and Drawing: Their Interrelationships in a Replicated Longitudinal Study.

    Science.gov (United States)

    Lewis, Hilda P.; Livson, Norman

    1980-01-01

    Studied 72 children for whom the following data were available: IQ score on a conventional test (WISC or Stanford-Binet); Goodenough-Harris drawing test IQ score; and behavior description by the test administrator. Personality traits of children who performed better on either the graphic or conventional IQ test were assessed. (SJL)

  16. 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

    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...

  17. Barriers to Implementing Individualized Substance Abuse Treatment: Qualitative Findings from the CASPAR Replication Studies.

    Science.gov (United States)

    Mericle, Amy A; Casaletto, Kathryn; Knoblach, Dan; Brooks, Adam C; Carise, Deni

    2010-10-01

    Problem-to-services matching is critical to patient-centered care. Further, the extent to which substance abuse treatment is individualized to meet specific client needs is a key predictor of success and represents "best practice" in substance abuse treatment. The CASPAR Resource Guide, an electronic database of local free and low-cost services, is an evidence-based tool designed to help counselors easily and quickly provide offsite referrals to services not available in most community treatment programs to increase problem-to-service matching. This paper examines system-level barriers to using the CASPAR Resource Guide among 30 counselors and 21 site directors across 16 sites in two different studies. Results from qualitative implementation analyses found that key program components needed to support the implementation of this evidence-based practice (e.g., individualized treatment planning, individual treatment sessions, and individual counselor supervision) were lacking, which jeopardized successful adoption of the CASPAR research interventions and prompted a redesign of the studies in order to enhance each program's ability to support individualized care.

  18. Replication of a Genome-Wide Association Study of Birth Weight in Preterm Neonates

    Science.gov (United States)

    Ryckman, Kelli K; Feenstra, Bjarke; Shaffer, John R.; Bream, Elise NA; Geller, Frank; Feingold, Eleanor; Weeks, Daniel E; Gadow, Enrique; Cosentino, Viviana; Saleme, Cesar; Simhan, Hyagriv N; Merrill, David; Fong, Chin-To; Busch, Tamara; Berends, Susan K; Comas, Belen; Camelo, Jorge L; Boyd, Heather; Laurie, Cathy; Crosslin, David; Zhang, Qi; Doheny, Kim F; Pugh, Elizabeth; Melbye, Mads; Marazita, Mary L; Dagle, John M; Murray, Jeffrey C

    2011-01-01

    Objective To examine associations in a preterm population between rs9883204 in ADCY5 and rs900400 near LEKR1 and CCNL1 with birth weight. Both markers were associated with birth weight in a term population in a recent genome-wide association (GWA) study by Freathy et al. Study design A meta-analysis of mother and infant samples was performed for associations of rs900400 and rs9883204 with birth weight in 393 families from the U.S., 265 families from Argentina and 735 mother-infant pairs from Denmark. Z scores adjusted for infant sex and gestational age were generated for each population separately and regressed on allele counts. Association evidence was combined across sites by inverse-variance weighted meta-analysis. Results Each additional C allele of rs900400 (LEKR1/CCNL1) in infants was marginally associated with a 0.069 standard deviation (SD) lower birth weight (95% CI = −0.159 – 0.022, P = 0.068). This result was slightly more pronounced after adjusting for smoking (P = 0.036). There were no significant associations identified with rs9883204 or in maternal samples. Conclusions These results indicate the potential importance of this marker on birth weight irrespective of gestational age. PMID:21885063

  19. Nursing students' experiences with and strategic approaches to case-based instruction: a replication and comparison study between two disciplines.

    Science.gov (United States)

    Demarco, Rosanna; Hayward, Lorna; Lynch, Marcia

    2002-04-01

    In the classroom and in clinical areas, knowing how to learn, reason, reflect, think creatively, generate and evaluate ideas, make decisions, and solve problems have been identified as key elements of critical thinking. However, to be successful in the current health care arena, caregivers cannot be satisfied with possessing the ability to solve problems and simply meet preestablished "outcomes" (Alfaro-LeFevre, 1998). It is necessary to improve knowledge and practice applications and to explore the best ways to do things within a work group. This qualitative study evaluated the experiences of senior-level nursing students using case-based instruction in a course titled, Leading and Managing in Nursing. It is a replication and extension (Phase II) of an original case-based instruction study, completed with senior physical therapy students (Phase I). Phase III of this study trajectory is the creation of an interdisciplinary case-based course that addresses either or both clinical collaborative care issues or leadership and management issues for health care profession students. From this Phase II study, six thematic groupings emerged as distinct student experiences in case-based instruction-motivation, real world, learning, knowledge development, emerging from within, and group dynamic issues.

  20. A post-GWAS replication study confirming the PTK2 gene associated with milk production traits in Chinese Holstein.

    Science.gov (United States)

    Wang, Haifei; Jiang, Li; Liu, Xuan; Yang, Jie; Wei, Julong; Xu, Jingen; Zhang, Qin; Liu, Jian-Feng

    2013-01-01

    Our initial genome-wide association study (GWAS) demonstrated that two SNPs (ARS-BFGL-NGS-33248, UA-IFASA-9288) within the protein tyrosine kinase 2 (PTK2) gene were significantly associated with milk production traits in Chinese Holstein dairy cattle. To further validate if the statistical evidence provided in GWAS were true-positive findings, a replication study was performed herein through genotype-phenotype associations. The two tested SNPs were found to show significant associations with milk production traits, which confirmed the associations observed in the original study. Specifically, SNPs lying in the PTK2 gene were also detected by sequencing 14 unrelated sires in Chinese Holsteins and a total of thirty-three novel SNPs were identified. Thirteen out of these identified SNPs were genotyped and tested for association with milk production traits in an independent resource population. After Bonferroni correction for multiple testing, twelve SNPs were statistically significant for more than two milk production traits. Analyses of pairwise D' measures of linkage disequilibrium (LD) between all SNPs were also explored. Two haplotype blocks were inferred and the association study at haplotype level revealed similar effects on milk production traits. In addition, the RNA expression analyses revealed that a non-synonymous coding SNP (g.4061098T>G) was involved in the regulation of gene expression. Thus the findings presented here provide strong evidence for associations of PTK2 variants with dairy production traits and may be applied in Chinese Holstein breeding program.

  1. 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.

  2. Disclosing the Firing Protocol of Athenian Pottery Production: A Raman and Colorimetric Study of Replicates and Original Samples

    Science.gov (United States)

    Cianchetta, I.; Trentelman, K.; Maish, J.; Walton, M.

    2014-06-01

    The work presented here examines the technological foundations of Athenian pottery production through the replication of the firing technology. Raman spectroscopy and colorimetry were used to investigate composition and color of ceramics slips.

  3. PTK2 rs7460 and rs7843014 Polymorphisms and Exceptional Longevity: A Functional Replication Study

    Science.gov (United States)

    Fuku, Noriyuki; He, Zi-hong; Tian, Ye; Arai, Yasumichi; Abe, Yukiko; Murakami, Haruka; Miyachi, Motohiko; Yvert, Thomas; Venturini, Letizia; Santiago, Catalina; Santos-Lozano, Alejandro; Rodríguez, Gabriel; Ricevuti, Giovanni; Pareja-Galeano, Helios; Sanchis-Gomar, Fabian; Emanuele, Enzo; Hirose, Nobuyoshi; Lucia, Alejandro

    2014-01-01

    Abstract Focal adhesion is critical for cell survival. The focal adhesion kinase (FAK, or PTK2) is an important component of the human interactome and thus is a potential longevity-related protein. Here we studied the association between two PTK2 gene single-nucleotide polymorphisms (SNPs) (rs7843014, rs7460) and exceptional longevity (EL). In addition to gaining insight into their functionality by determining luciferase gene reporter activity, we studied the genotype/allele frequency of these two SNPs among three different cohorts: (1) Spanish centenarians (n=175, 100–111 years, 144 women) and healthy controls (n=355, 20–50 years, 284 women); (2) Italian centenarians (n=79, 100–104 years, 40 women) and controls (n=316, 29–50 years, 156 women); and (3) Japanese centenarians (n=742, 100–116 years, 623 women) and healthy controls (n=499, 23–59 years, 356 women). Both SNPs had functional significance, with the A allele up-regulating luciferase activity compared to the other allele (rs7460 T allele and rs7843014 C allele, respectively). The A allele of both SNPs was negatively associated with EL in the Spanish cohort (rs7460, odds ratio [OR] adjusted by sex=0.40, 95% confidence intervals [CI] 0.3, 0.6, p<0.001); rs7843014, OR=0.37, 95% CI 0.3, 0.5, p<0.001). The OR of being a centenarian if having the rs7460-TT genotype was 6.68 (95% CI 4.1, 10.8, p<0.001). The rs7843014 CC genotype was also positively associated with EL (OR=7.58, 95% CI 4.6, 12.3, p<0.001]. No association was, however, found for the Italian or Japanese cohorts. Thus, two genotypes of the FAK gene, rs7460 TT and rs7843014 CC, are possibly associated with lower gene expression and might favor the likelihood of reaching EL in the Spanish population. Further research is needed to unveil the mechanisms by which FAK expression could perhaps influence the rate of aging. PMID:24930376

  4. Association between HTR2C gene polymorphisms and the metabolic syndrome in patients Using Antipsychotics: A Replication Study

    NARCIS (Netherlands)

    Risselada, Arne; Vehof, Jelle; Bruggeman, Richard; Wilffert, Bob; Cohen, Dan; Al Hadithy, Asmar; Arends, Johan; Mulder, Hans

    2010-01-01

    Background: In two previous studies we investigated the association between the rs1414334 C/G and 759 C/T polymorphisms in the HTR2C gene, coding for the 5HT2c-receptor, and prevalence of the metabolic syndrome in a schizophrenic population. In both studies we found an association between the varian

  5. Association between HTR2C polymorphisms and the metabolic syndrome in patients using antipsychotics : a replication study

    NARCIS (Netherlands)

    Risselada, A.; Vehof, J.; Bruggeman, R.; Wilffert, B.; Cohen, D.; Al Hadithy, A. F.; Arends, J.; Mulder, H.

    2010-01-01

    Background: In two previous studies we investigated the possible association between the rs1414334 C/G and 759 C/T polymorphisms in the gene that encodes the 5HT2c receptor (HTR2c) and prevalence of the metabolic syndrome in a schizophrenic population [1,2]. In both studies we found an association b

  6. Association between HTR2C polymorphisms and the metabolic syndrome in patients using antipsychotics: A replication study

    NARCIS (Netherlands)

    Risselada, A.; Vehof, J.; Bruggeman, R.; Wilffert, B.; Cohen, D.; Al Hadithy, A.F.; Arends, J.; Mulder, H.

    2010-01-01

    Background: In two previous studies we investigated the possible association between the rs1414334 C/G and 759 C/T polymorphisms in the gene that encodes the 5HT2c receptor (HTR2c) and prevalence of the metabolic syndrome in a schizophrenic population [1,2]. In both studies we found an association b

  7. Association between HTR2C polymorphisms and the metabolic syndrome in patients using antipsychotics : a replication study

    NARCIS (Netherlands)

    Risselada, A.; Vehof, J.; Bruggeman, R.; Wilffert, B.; Cohen, D.; Al Hadithy, A. F.; Arends, J.; Mulder, H.

    2010-01-01

    Background: In two previous studies we investigated the possible association between the rs1414334 C/G and 759 C/T polymorphisms in the gene that encodes the 5HT2c receptor (HTR2c) and prevalence of the metabolic syndrome in a schizophrenic population [1,2]. In both studies we found an association b

  8. Association between HTR2C polymorphisms and the metabolic syndrome in patients using antipsychotics: A replication study

    NARCIS (Netherlands)

    Risselada, A.; Vehof, J.; Bruggeman, R.; Wilffert, B.; Cohen, D.; Al Hadithy, A.F.; Arends, J.; Mulder, H.

    2010-01-01

    Background: In two previous studies we investigated the possible association between the rs1414334 C/G and 759 C/T polymorphisms in the gene that encodes the 5HT2c receptor (HTR2c) and prevalence of the metabolic syndrome in a schizophrenic population [1,2]. In both studies we found an association b

  9. Association between HTR2C gene polymorphisms and the metabolic syndrome in patients Using Antipsychotics: A Replication Study

    NARCIS (Netherlands)

    Risselada, Arne; Vehof, Jelle; Bruggeman, Richard; Wilffert, Bob; Cohen, Dan; Al Hadithy, Asmar; Arends, Johan; Mulder, Hans

    2010-01-01

    Background: In two previous studies we investigated the association between the rs1414334 C/G and 759 C/T polymorphisms in the HTR2C gene, coding for the 5HT2c-receptor, and prevalence of the metabolic syndrome in a schizophrenic population. In both studies we found an association between the varian

  10. 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.

  11. Evaluating replicability of laboratory experiments in economics.

    Science.gov (United States)

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

    2016-03-25

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

  12. A review study on the effect of Iranian herbal medicines against in vitro replication of herpes simplex virus

    Directory of Open Access Journals (Sweden)

    Mohammad-Taghi Moradi

    2016-08-01

    Full Text Available Objective: There are a number of published data indicating in vitro anti-HSV activity of some of Iranian herbal extracts with no systematic review to discuss these results. Therefore, this article was aimed to review and discuss the methods carried out and the phytochemistry and bioactivity of the extracts used and also conclusions provided in these publications. Materials and Methods: Published articles both in English (from Medline, Science Direct, EMBASE, Scopus, Pro Quest, Google scholar, Cochrane Library and in Persian (from SID, Iran Medex and Magiran databases, from 1966 to October 2014 were incorporated in this review. The in vitro studies that lacked CC50, IC50, were excluded. Results: Only 42 published reports were found to examine Iranian herbs against HSV replication in vitro. Seventeen out of 42 studies in which 23 kinds of medicinal plants were subjected to crude extraction were included. The review of data showed that some of the herbal extracts including Hyssopus officinalis methanolic extract, Melissa officinalis aqueous extract, Quercus persica L. hydroalcoholic extract and Securigeras ecuridaca methanolic extract with selective index (SI of 234, 877, >778 and 250, respectively were highly effective against HSV in vitro. Conclusion: More comprehensive studies using more advanced methods are needed to be done to achieve promising anti-HSV agents from the bioactive compounds isolated from these herbs.

  13. A review study on the effect of Iranian herbal medicines against in vitro replication of herpes simplex virus

    Science.gov (United States)

    Moradi, Mohammad-Taghi; Rafieian-Kopaei, Mahmoud; Karimi, Ali

    2016-01-01

    Objective: There are a number of published data indicating in vitro anti-HSV activity of some of Iranian herbal extracts with no systematic review to discuss these results. Therefore, this article was aimed to review and discuss the methods carried out and the phytochemistry and bioactivity of the extracts used and also conclusions provided in these publications. Materials and Methods: Published articles both in English (from Medline, Science Direct, EMBASE, Scopus, Pro Quest, Google scholar, Cochrane Library) and in Persian (from SID, Iran Medex and Magiran) databases, from 1966 to October 2014 were incorporated in this review. The in vitro studies that lacked CC50, IC50, were excluded. Results: Only 42 published reports were found to examine Iranian herbs against HSV replication in vitro. Seventeen out of 42 studies in which 23 kinds of medicinal plants were subjected to crude extraction were included. The review of data showed that some of the herbal extracts including Hyssopus officinalis methanolic extract, Melissa officinalis aqueous extract, Quercus persica L. hydroalcoholic extract and Securigeras ecuridaca methanolic extract with selective index (SI) of 234, 877, >778 and 250, respectively were highly effective against HSV in vitro. Conclusion: More comprehensive studies using more advanced methods are needed to be done to achieve promising anti-HSV agents from the bioactive compounds isolated from these herbs.

  14. A review study on the effect of Iranian herbal medicines against in vitro replication of herpes simplex virus.

    Science.gov (United States)

    Moradi, Mohammad-Taghi; Rafieian-Kopaei, Mahmoud; Karimi, Ali

    2016-01-01

    There are a number of published data indicating in vitro anti-HSV activity of some of Iranian herbal extracts with no systematic review to discuss these results. Therefore, this article was aimed to review and discuss the methods carried out and the phytochemistry and bioactivity of the extracts used and also conclusions provided in these publications. Published articles both in English (from Medline, Science Direct, EMBASE, Scopus, Pro Quest, Google scholar, Cochrane Library) and in Persian (from SID, Iran Medex and Magiran) databases, from 1966 to October 2014 were incorporated in this review. The in vitro studies that lacked CC50, IC50, were excluded. Only 42 published reports were found to examine Iranian herbs against HSV replication in vitro. Seventeen out of 42 studies in which 23 kinds of medicinal plants were subjected to crude extraction were included. The review of data showed that some of the herbal extracts including Hyssopus officinalis methanolic extract, Melissa officinalis aqueous extract, Quercus persica L. hydroalcoholic extract and Securigeras ecuridaca methanolic extract with selective index (SI) of 234, 877, >778 and 250, respectively were highly effective against HSV in vitro. More comprehensive studies using more advanced methods are needed to be done to achieve promising anti-HSV agents from the bioactive compounds isolated from these herbs.

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

    CERN Document Server

    Mesnard, Olivier

    2016-01-01

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

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

    Science.gov (United States)

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

    2007-12-01

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

  17. 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.

  18. A replication study of GWAS-derived lipid genes in Asian Indians: the chromosomal region 11q23.3 harbors loci contributing to triglycerides.

    Directory of Open Access Journals (Sweden)

    Timothy R Braun

    Full Text Available Recent genome-wide association scans (GWAS and meta-analysis studies on European populations have identified many genes previously implicated in lipid regulation. Validation of these loci on different global populations is important in determining their clinical relevance, particularly for development of novel drug targets for treating and preventing diabetic dyslipidemia and coronary artery disease (CAD. In an attempt to replicate GWAS findings on a non-European sample, we examined the role of six of these loci (CELSR2-PSRC1-SORT1 rs599839; CDKN2A-2B rs1333049; BUD13-ZNF259 rs964184; ZNF259 rs12286037; CETP rs3764261; APOE-C1-C4-C2 rs4420638 in our Asian Indian cohort from the Sikh Diabetes Study (SDS comprising 3,781 individuals (2,902 from Punjab and 879 from the US. Two of the six SNPs examined showed convincing replication in these populations of Asian Indian origin. Our study confirmed a strong association of CETP rs3764261 with high-density lipoprotein cholesterol (HDL-C (p = 2.03×10(-26. Our results also showed significant associations of two GWAS SNPs (rs964184 and rs12286037 from BUD13-ZNF259 near the APOA5-A4-C3-A1 genes with triglyceride (TG levels in this Asian Indian cohort (rs964184: p = 1.74×10(-17; rs12286037: p = 1.58×10(-2. We further explored 45 SNPs in a ∼195 kb region within the chromosomal region 11q23.3 (encompassing the BUD13-ZNF259, APOA5-A4-C3-A1, and SIK3 genes in 8,530 Asian Indians from the London Life Sciences Population (LOLIPOP (UK and SDS cohorts. Five more SNPs revealed significant associations with TG in both cohorts individually as well as in a joint meta-analysis. However, the strongest signal for TG remained with BUD13-ZNF259 (rs964184: p = 1.06×10(-39. Future targeted deep sequencing and functional studies should enhance our understanding of the clinical relevance of these genes in dyslipidemia and hypertriglyceridemia (HTG and, consequently, diabetes and CAD.

  19. International Expansion through Flexible Replication

    DEFF Research Database (Denmark)

    Jonsson, Anna; Foss, Nicolai Juul

    2011-01-01

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

  20. 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...

  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

    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......: This replication study supports an important role for the studied rs5771069 (IL17REL) SNP, but not for rs7809799 (SMURF1/KPNA7), in UC etiology in the Danish, Baltic, and Norwegian populations. Significant genetic heterogeneity was suggested for rs7520292, rs12518307, and rs2395609 (TCP11) in UC etiology between...

  2. Identification of IRF8, TMEM39A, and IKZF3-ZPBP2 as Susceptibility Loci for Systemic Lupus Erythematosus in a Large-Scale Multiracial Replication Study

    Science.gov (United States)

    Lessard, Christopher J.; Adrianto, Indra; Ice, John A.; Wiley, Graham B.; Kelly, Jennifer A.; Glenn, Stuart B.; Adler, Adam J.; Li, He; Rasmussen, Astrid; Williams, Adrienne H.; Ziegler, Julie; Comeau, Mary E.; Marion, Miranda; Wakeland, Benjamin E.; Liang, Chaoying; Ramos, Paula S.; Grundahl, Kiely M.; Gallant, Caroline J.; Alarcón, Graciela S.; Anaya, Juan-Manuel; Bae, Sang-Cheol; Boackle, Susan A.; Brown, Elizabeth E.; Chang, Deh-Ming; Cho, Soo-Kyung; Criswell, Lindsey A.; Edberg, Jeffrey C.; Freedman, Barry I.; Gilkeson, Gary S.; Jacob, Chaim O.; James, Judith A.; Kamen, Diane L.; Kimberly, Robert P.; Kim, Jae-Hoon; Martin, Javier; Merrill, Joan T.; Niewold, Timothy B.; Park, So-Yeon; Petri, Michelle A.; Pons-Estel, Bernardo A.; Ramsey-Goldman, Rosalind; Reveille, John D.; Scofield, R. Hal; Song, Yeong Wook; Stevens, Anne M.; Tsao, Betty P.; Vila, Luis M.; Vyse, Timothy J.; Yu, Chack-Yung; Guthridge, Joel M.; Kaufman, Kenneth M.; Harley, John B.; Wakeland, Edward K.; Langefeld, Carl D.; Gaffney, Patrick M.; Montgomery, Courtney G.; Moser, Kathy L.

    2012-01-01

    Systemic lupus erythematosus (SLE) is a chronic heterogeneous autoimmune disorder characterized by the loss of tolerance to self-antigens and dysregulated interferon responses. The etiology of SLE is complex, involving both heritable and environmental factors. Candidate-gene studies and genome-wide association (GWA) scans have been successful in identifying new loci that contribute to disease susceptibility; however, much of the heritable risk has yet to be identified. In this study, we sought to replicate 1,580 variants showing suggestive association with SLE in a previously published GWA scan of European Americans; we tested a multiethnic population consisting of 7,998 SLE cases and 7,492 controls of European, African American, Asian, Hispanic, Gullah, and Amerindian ancestry to find association with the disease. Several genes relevant to immunological pathways showed association with SLE. Three loci exceeded the genome-wide significance threshold: interferon regulatory factor 8 (IRF8; rs11644034; pmeta-Euro = 2.08 × 10−10), transmembrane protein 39A (TMEM39A; rs1132200; pmeta-all = 8.62 × 10−9), and 17q21 (rs1453560; pmeta-all = 3.48 × 10−10) between IKAROS family of zinc finger 3 (AIOLOS; IKZF3) and zona pellucida binding protein 2 (ZPBP2). Fine mapping, resequencing, imputation, and haplotype analysis of IRF8 indicated that three independent effects tagged by rs8046526, rs450443, and rs4843869, respectively, were required for risk in individuals of European ancestry. Eleven additional replicated effects (5 × 10−8 < pmeta-Euro < 9.99 × 10−5) were observed with CFHR1, CADM2, LOC730109/IL12A, LPP, LOC63920, SLU7, ADAMTSL1, C10orf64, OR8D4, FAM19A2, and STXBP6. The results of this study increase the number of confirmed SLE risk loci and identify others warranting further investigation. PMID:22464253

  3. 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.

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

    Science.gov (United States)

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

    2016-11-15

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

  5. 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

    Full Text Available 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 the kinase

  6. 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…

  7. Replication Restart in Bacteria.

    Science.gov (United States)

    Michel, Bénédicte; Sandler, Steven J

    2017-07-01

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

  8. Missing osteoconductive effect of a resorbable PEO/PBT copolymer in human bone defects: a clinically relevant pilot study with contrary results to previous animal studies.

    Science.gov (United States)

    Roessler, M; Wilke, A; Griss, P; Kienapfel, H

    2000-01-01

    PEO/PBT 70/30 (POLYACTIVE(R) 70/30), a degradable porous copolymer with elastic properties, was found to be osteoconductive in many animal studies. The aim of this study was to determine the osteoconductive effect in a human paired control iliac defect model. In seven patients undergoing anterior spinal interbody fusion surgery, two bicortical iliac defects for autograft harvesting were created. The defect size was identical for both defects measuring about 40 x 15 mm (group I). One defect was filled with the degradable implants, whereas the remaining one was left untreated as a control. The defect site for treatment was chosen randomly. In three further patients, only one defect measuring about 40 x 35 mm was created (group II). All patients were examined clinically and radiologically by spiral-CT after 1, 6, 12, 24, and 52 weeks. Three-dimensional reconstructions as well as CT-volumetric measurements using 1 mm sections were used as evaluation methods. In group I, a two-tailed paired t-test showed that the treated defects had significantly less formation of new bone than the untreated ones (p < 0.05 after 12 weeks, p < 0.01 after 52 weeks). Also, in group II, not much bone ingrowth could be observed. The histological evaluation of one patient in group I revealed no bone within the pores, and a fibrous layer between bone and implant was always present. Therefore, PEO/PBT 70/30 cannot be recommended as a bone substitute for clinical use. Differences in bone regeneration between humans and certain animal species as well as inapplicable defect models in previous animal studies are discussed as possible reasons for the failure.

  9. A new light on DNA replication from the inactive X chromosome.

    Science.gov (United States)

    Aladjem, Mirit I; Fu, Haiqing

    2014-06-01

    While large portions of the mammalian genome are known to replicate sequentially in a distinct, tissue-specific order, recent studies suggest that the inactive X chromosome is duplicated rapidly via random, synchronous DNA synthesis at numerous adjacent regions. The rapid duplication of the inactive X chromosome was observed in high-resolution studies visualizing DNA replication patterns in the nucleus, and by allele-specific DNA sequencing studies measuring the extent of DNA synthesis. These studies conclude that inactive X chromosomes complete replication earlier than previously thought and suggest that the strict order of DNA replication detected in the majority of genomic regions is not preserved in non-transcribed, "silent" chromatin. These observations alter current concepts about the regulation of DNA replication in non-transcribed portions of the genome in general and in the inactive X-chromosome in particular.

  10. 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...

  11. 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.

  12. Phase II study of reintroduction of oxaliplatin for advanced colorectal cancer in patients previously treated with oxaliplatin and irinotecan: RE-OPEN study

    Directory of Open Access Journals (Sweden)

    Suenaga M

    2015-06-01

    Full Text Available Mitsukuni Suenaga,1 Nobuyuki Mizunuma,1 Satoshi Matsusaka,1 Eiji Shinozaki,1 Masato Ozaka,1 Mariko Ogura,1 Toshiharu Yamaguchi21Department of Gastroenterology, 2Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, JapanBackground: The effectiveness of reintroducing oxaliplatin in patients with metastatic colorectal cancer refractory to standard chemotherapy has not been verified. We performed a single-arm, open-label, Phase II study to evaluate the safety and efficacy of reintroducing oxaliplatin. Methods: Eligible patients had received prior chemotherapy including oxaliplatin and irinotecan that achieved a response or stable disease followed by confirmed disease progression ≥6 months previously during prior oxaliplatin-based therapy. The primary endpoint was the disease control rate (DCR after 12 weeks of treatment starting. The DCR was defined as the sum of patients with complete response, partial response, and stable disease. Results: Thirty-three patients were enrolled. The median age was 62 (range: 35–77 years and the male/female ratio was 19/14. Eastern Cooperative Oncology Group performance status was 0 in 84.8%. Fourteen primary tumors were in the colon and 19 were in the rectum. All patients received modified FOLFOX6 as the protocol treatment. After 12 weeks of treatment starting, the DCR was 39.4% (95% confidence interval 21.8–57.0 and the response rate (complete response and partial response was 6.1%. The median number of chemotherapy cycles was five and the median total dose of oxaliplatin was 425 mg/m2. Median progression-free survival time was 98 days and median overall survival was 300 days. The incidence of grade ≥1 and grade ≥3 allergic reactions was 28.1% and 3.1%, respectively. The incidence of grade ≥1 and grade ≥3 peripheral sensory neuropathy was 53.1% and 0%, respectively. There were no other severe adverse events and no treatment

  13. Replication of prions in differentiated muscle cells.

    Science.gov (United States)

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

    2014-01-01

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

  14. Confirmation of TNIP1 but not RHOB and PSORS1C1 as systemic sclerosis risk factors in a large independent replication study

    Science.gov (United States)

    Bossini-Castillo, Lara; Martin, Jose Ezequiel; Broen, Jasper; Simeon, Carmen P; Beretta, Lorenzo; Gorlova, Olga Y; Vonk, Madelon C; Ortego-Centeno, Norberto; Espinosa, Gerard; Carreira, Patricia; García de la Peña, Paloma; Oreiro, Natividad; Román-Ivorra, José Andrés; Castillo, María Jesús; González-Gay, Miguel A; Sáez-Comet, Luis; Castellví, Ivan; Schuerwegh, Annemie J; Voskuyl, Alexandre E; Hoffmann-Vold, Anna-Maria; Hesselstrand, Roger; Nordin, Annika; Lunardi, Claudio; Scorza, Raffaella; van Laar, Jacob M; Shiels, Paul G; Herrick, Ariane; Worthington, Jane; Fonseca, Carmen; Denton, Christopher; Tan, Filemon K; Arnett, Frank C; Assassi, Shervin; Koeleman, Bobby P; Mayes, Maureen D; Radstake, Timothy R D J; Martin, Javier

    2013-01-01

    Introduction A recent genome-wide association study in European systemic sclerosis (SSc) patients identified three loci (PSORS1C1, TNIP1 and RHOB) as novel genetic risk factors for the disease. The aim of this study was to replicate the previously mentioned findings in a large multicentre independent SSc cohort of Caucasian ancestry. Methods 4389 SSc patients and 7611 healthy controls from different European countries and the USA were included in the study. Six single nucleotide polymorphisms (SNP): rs342070, rs13021401 (RHOB), rs2233287, rs4958881, rs3792783 (TNIP1) and rs3130573 (PSORS1C1) were analysed. Overall significance was calculated by pooled analysis of all the cohorts. Haplotype analyses and conditional logistic regression analyses were carried out to explore further the genetic structure of the tested loci. Results Pooled analyses of all the analysed SNPs in TNIP1 revealed significant association with the whole disease (rs2233287 pMH=1.94×10−4, OR 1.19; rs4958881 pMH=3.26×10−5, OR 1.19; rs3792783 pMH=2.16×10−4, OR 1.19). These associations were maintained in all the subgroups considered. PSORS1C1 comparison showed association with the complete set of patients and all the subsets except for the anti-centromere-positive patients. However, the association was dependent on different HLA class II alleles. The variants in the RHOB gene were not associated with SSc or any of its subsets. Conclusions These data confirmed the influence of TNIP1 on an increased susceptibility to SSc and reinforced this locus as a common autoimmunity risk factor. PMID:22896740

  15. E-cigarettes emit very high formaldehyde levels only in conditions that are aversive to users: A replication study under verified realistic use conditions.

    Science.gov (United States)

    Farsalinos, Konstantinos E; Voudris, Vassilis; Spyrou, Alketa; Poulas, Konstantinos

    2017-08-31

    In 2015, a study identified 5-15-fold higher levels of formaldehyde emissions from an old-generation e-cigarette tested at 5.0 V compared to tobacco cigarettes. We set to replicate this study using the same e-cigarette equipment and e-liquid, while checking for the generation of dry puffs. Experienced e-cigarette users (n = 26) took 4 s puffs at different voltage settings and were asked to report the generation of dry puffs. Formaldehyde emissions were measured at both realistic and dry puff conditions. Dry puffs were detected at ≤4.2 V by 88% of participants; thus, 4.0 V was defined as the upper limit of realistic use. Levels ranged from 3.4 (SE = 2.2) μg/10 puffs at 3.3 V to 718.2 (SE = 58.2) μg/10 puffs at 5.0 V. The levels detected at 4.0 V were 19.8 (SE = 5.6) μg/10 puffs. At 4.0 V, the daily exposure to formaldehyde from consuming 3 g of liquid with the device tested would be 32% lower compared to smoking 20 tobacco cigarettes. The high levels of formaldehyde emissions that were reported in a previous study were caused by unrealistic use conditions that create the unpleasant taste of dry puffs to e-cigarette users and are thus avoided. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Studies in Historical Replication in Psychology VII: The Relative Utility of "Ancestor Analysis" from Scientific and Educational Vantages

    Science.gov (United States)

    Ranney, Michael Andrew

    2008-01-01

    This article discusses, from various vantages, Ryan Tweney's (this issue) pedagogical technique of employing historical replications of psychological experiments with graduate students in psychology. A "prima facie" perspective suggests great promise for this sort of academic "ancestor analysis," particularly given the enthusiasm and skill…

  17. Dissection of the beta-globin replication-initiation region reveals specific requirements for replicator elements during gene amplification.

    Directory of Open Access Journals (Sweden)

    Naoya Okada

    Full Text Available Gene amplification plays a pivotal role in malignant transformation of human cells. A plasmid with both a mammalian replication-initiation region (IR/origin/replicator and a nuclear matrix-attachment region (MAR is spontaneously amplified in transfected cells by a mechanism that involves amplification at the extrachromosomal site, followed by amplification at the chromosomal arm, ultimately generating a long homogeneously staining region (HSR. Several observations suggest that replication initiation from IR sequences might mediate amplification. To test this idea, we previously dissected c-myc and DHFR IRs to identify the minimum sequence required to support amplification. In this study, we applied an improved analysis that discriminates between two amplification steps to the ß-globin RepP IR, which contains separate elements already known to be essential for initiation on the chromosome arm. The IR sequence was required at least for the extrachromosomal amplification step. In addition to the vector-encoded MAR, amplification also required an AT-rich region and a MAR-like element, consistent with the results regarding replicator activity on the chromosome. However, amplification did not require the AG-rich tract necessary for replicator activity, but instead required a novel sequence containing another AG-rich tract. The differential sequence requirement might be a consequence of extrachromosomal replication.

  18. Replication-Uncoupled Histone Deposition during Adenovirus DNA Replication

    OpenAIRE

    Komatsu, Tetsuro; Nagata, Kyosuke

    2012-01-01

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

  19. A replication study of priorities and attitudes of two nursing programs' communities of interest: an appreciative inquiry.

    Science.gov (United States)

    Farrell, Marie; Wallis, Nancy C; Evans, Marci Tyler

    2007-01-01

    American universities and nursing faculties, caught between the imperatives of community demand and university financial constraints, need to analyze their communities of interests' shared priorities for nursing education. This replication study's objective was to compare the priorities and attitudes of two nursing programs' communities of interest using appreciative inquiry (AI). The researchers used AI to conduct a qualitative, comparative analysis of data from two nursing programs. They used one-on-one and focus group interviews to examine stakeholders' views of the best of the nursing program's past, their vision and approaches to realizing the vision, and their roles in contributing to the vision they created. The researchers analyzed the qualitative data using a standardized codebook and content analysis. Respondents' priorities for both academic programs were similar, with the western respondents emphasizing nursing's contribution to quality care and the southern respondents emphasizing its leadership and commitment to diversity. Both identified the role of legislators and the community in partnering with nursing to secure funds for expansion. Both programs' respondents viewed nursing as a major part of the university and considered their role as supporters of the university's academic and financial goals. The two nursing programs appeared to harness external and internal support in their respective communities. While some priorities differed between the two nursing programs, respondents were aware of the ripple effect of decreased funding for nursing education on the delivery of nursing services to the community. Differences among the undergraduate and graduate students, which reflect a nursing program's student mix, underscore the priorities that nursing programs must emphasize.

  20. Sources of synchronized induced Gamma-Band responses during a simple object recognition task: a replication study in human MEG.

    Science.gov (United States)

    Gruber, T; Maess, B; Trujillo-Barreto, N J; Müller, M M

    2008-02-27

    Natural stimuli are compiled of numerous features, which are cortically represented in dispersed structures. Synchronized oscillations in the Gamma-Band (>30 Hz; induced Gamma-Band Responses, iGBRs), are regarded as a plausible mechanism to re-integrate these regions into a meaningful cortical object representation. Using electroencephalography (EEG) it was demonstrated that the generators of iGBRs can be localized to temporal, parietal, posterior, and frontal areas. The present magnetoencephalogram (MEG) study intended to replicate these findings in order contribute to the ongoing debate regarding the possible functional difference of high-frequency signals as measured by both techniques. During a standard object recognition task we found an augmentation of the iGBR after the presentation of meaningful as opposed to meaningless stimuli at approximately 160-440 ms after stimulus onset. This peak was localized to inferior temporal gyri, superior parietal lobules and the right middle frontal gyrus. Importantly, most of these brain structures were significantly phase-locked to each other. The implications of these results are twofold: (1) they present further evidence for the view that iGBRs signify neuronal activity in a broadly distributed network during object recognition. (2) MEG is well suited to detect induced high-frequency oscillations with a very similar morphology as revealed by EEG recordings, thereby eliminating known problems with electroencephalographical methods (e.g. reference confounds). In contrast to the iGBR, the localization of event-related fields (ERFs) and evoked Gamma-Band Response (eGBRs) revealed generators in focal visual areas, and thus, seem to mirror early sensory processing.

  1. ATLANTIC-DIP: prevalence of metabolic syndrome and insulin resistance in women with previous gestational diabetes mellitus by International Association of Diabetes in Pregnancy Study Groups criteria.

    Science.gov (United States)

    Noctor, Eoin; Crowe, Catherine; Carmody, Louise A; Kirwan, Breda; O'Dea, Angela; Glynn, Liam G; McGuire, Brian E; O'Shea, Paula M; Dunne, Fidelma P

    2015-02-01

    Women with previous gestational diabetes (GDM) are a high-risk group for future development of diabetes, metabolic syndrome, and cardiovascular disease. The new International Association of Diabetes in Pregnancy Study Groups (IADPSG) criteria significantly increase the number of women diagnosed with GDM. The long-term metabolic outcome in these women is unknown. We set out to determine the prevalence of metabolic syndrome, using adult treatment panel-III criteria; and insulin resistance, using HOMA2-IR, in white European women with previous GDM. Using a cohort design, we invited women meeting IADPSG GDM criteria across four Irish antenatal centres between 2007 and 2010 to participate. Two hundred and sixty-five women with previous values meeting IADPSG criteria for GDM participated (44 % of the population eligible for participation). Mean age was 36.7 years (SD 5.0). These women were compared with a randomly selected control group of 378 women (mean age 37.6 years, SD 5.1) known to have normal glucose tolerance (NGT) in pregnancy during the same period. A total of 25.3 % of women with previous IADPSG-defined GDM met metabolic syndrome criteria, compared to 6.6 % of women with NGT [at 2.6 (SD 1.0) vs. 3.3 years (SD 0.7) post-partum]. The prevalence of HOMA2-IR >1.8 was higher in women with previous IADPSG-defined GDM (33.6 vs. 9.1 % with NGT, p Women with previous GDM by IADPSG criteria demonstrate a greater than threefold prevalence of metabolic syndrome compared to women with NGT in pregnancy. Efforts to prevent projected long-term consequences of this should focus on interventions both in the preconception and post-partum periods.

  2. Nucleotide Metabolism and DNA Replication.

    Science.gov (United States)

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

    2014-10-01

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

  3. Do gender and personality traits (BFI-10) influence trust? A replication

    DEFF Research Database (Denmark)

    Sudzina, Frantisek

    2016-01-01

    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...

  4. Effectiveness of Peer-Led Eating Disorders Prevention: A Replication Trial

    Science.gov (United States)

    Becker, Carolyn Black; Bull, Stephanie; Schaumberg, Katherine; Cauble, Adele; Franco, Amanda

    2008-01-01

    The aim of this study was to replicate and extend results of a previous trial that investigated the effectiveness of 2 peer-led eating disorders prevention interventions in reducing eating disorder risk factors in undergraduate women (C. B. Becker, L. M. Smith, & A. C. Ciao, 2006). To extend findings from the previous study by allowing for…

  5. Replication of association study between type 2 diabetes mellitus and IGF2BP2 in Han Chinese population

    Institute of Scientific and Technical Information of China (English)

    ZHANG Si-min; XIAO Jian-zhong; REN Qian; HAN Xue-yao; TANG Yong; YANG Wen-ying; JI Li-nong

    2013-01-01

    Background The association between IGF2BP2 and type 2 diabetes mellitus (T2DM) has been repeatedly confirmed among different ethnic populations.However,in several genome-wide association studies (GWAS) from the Chinese Han population,the gene IGF2BP2 has not been replicated.The results of relevant studies for the association between IGF2BP2 and T2DM showed controversy in Chinese Han population.It is necessary to systematically evaluate the contribution of common variants in IGF2BP2 to T2DM in Chinese Han population.Methods Two single-nucleotide polymorphisms (SNPs,rs4402960 and rs1470579) in IGF2BP2 were genotyped in Chinese Han population (3807 controls/4531 T2DM cases) by Illumina GoldenGate Indexing assay.The association between SNPs and T2DM was evaluated by multiple Logistic Regression analysis.A meta-analysis was used to estimate the effects of IGF2BP2 in 20854 Chinese Han individuals.Results rs1470579 and rs4402960 were confirmed to have strong association with T2DM in the Chinese Han population (rs1470579 P=-1.80x10-7,OR (95% CI)=1.22 (1.14-1.32),rs4402960 P=7.46x10-9,OR (95% CI)=1.26 (1.17-1.37),respectively).Moreover,11 studies for rs4402960 were included in the meta-analysis and 7 studies for rs1470579.The meta-analysis also showed the association between T2DM and IGF2BP2 (rs1470579 OR of 1.15 (95% CI=1.10-1.19),P <0.0001 under an additive model and rs4402960 OR of 1.14 (95% CI=1.10-1.18),P <0.0001 under an additive model).Conclusion IGF2BP2 was strongly associated with the risk of T2DM in Chinese Han population.

  6. Prevention and health promotion in undergraduate medical education: Preferences, attitudes and previous knowledge of medical students - a cross-sectional study

    OpenAIRE

    Klement, Andreas; Bretschneider, Kristin; Lautenschläger, Christine; Stang, Andreas; Herrmann, Markus; Haerting, Johannes

    2011-01-01

    Objective: The interdisciplinary topic "prevention and health promotion" (Q10) was introduced into the medical training in Germany by the new medical licensing regulations in 2004. For the conception of an effective curriculum, it is helpful to know student preferences concerning teaching-formats, attitudes and self-estimated previous knowledge. Little is known concerning student perception of “prevention and health promotion” in Germany. Thus, this explorative cross-sectional study aims to p...

  7. Continous controversy about radiation oncologists' choice of treatment regimens for bone metatases: should we blame doctors, canser-related features, or design of previous clinical studies

    OpenAIRE

    Nieder, Carsten; Pawinski, Adam; Dalhaug, Astrid

    2013-01-01

    Recent studies from Italy, Japan and Norway have confirmed previous reports, which found that a large variety of palliative radiotherapy regimens are used for painful bone metastases. Routine use of single fraction treatment might or might not be the preferred institutional approach. It is not entirely clear why inter-physician and inter-institution differences continue to persist despite numerous randomized trials, meta-analyses and guidelines, which recommend against more costly and inconve...

  8. 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.

  9. Unscheduled DNA replication origin activation at inserted HPV 18 sequences in a HPV-18/MYC amplicon.

    Science.gov (United States)

    Conti, Chiara; Herrick, John; Bensimon, Aaron

    2007-08-01

    Oncogene amplification is a critical step leading to tumorigenesis, but the underlying mechanisms are still poorly understood. Despite data suggesting that DNA replication is a major source of genomic instability, little is known about replication origin usage and replication fork progression in rearranged regions. Using a single DNA molecule approach, we provide here the first study of replication kinetics on a previously characterized MYC/papillomavirus (HPV18) amplicon in a cervical cancer. Using this amplicon as a model, we investigated the role DNA replication control plays in generating amplifications in human cancers. The data reveal severely perturbed DNA replication kinetics in the amplified region when compared with other regions of the same genome. It was found that DNA replication is initiated from both genomic and viral sequences, resulting in a higher median frequency of origin firings. In addition, it was found that the higher initiation frequency was associated with an equivalent increase in the number of stalled replication forks. These observations raise the intriguing possibility that unscheduled replication origin activation at inserted HPV-18 viral DNA sequences triggers DNA amplification in this cancer cell line and the subsequent overexpression of the MYC oncogene.

  10. 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

  11. The impact of smoking and previous periodontal disease on peri-implant microbiota and health: a retrospective study up to 7-year follow-up.

    Science.gov (United States)

    Quaranta, Alessandro; Assenza, Bartolomeo; D'Isidoro, Orlando; Profili, Fabia; Polimeni, Antonella; Vozza, Iole

    2015-01-01

    To evaluate the impact of smoking and previous periodontal disease on peri-implant microbiota and health in medium to long-term maintained patients. A retrospective evaluation of partial edentulous patients restored with dental implants and enrolled in a regular supportive therapy was performed. Inclusion criteria were: medium to long-term periodontal and implant maintenance (at least 5 years), a minimum of 2 implants placed in each patient, absence of systemic diseases that may affect osseointegration. 30 implants in 15 patients were included in the study. Subjects were divided in smokers or non-smokers and between patients previously affected by periodontal disease and periodontally healthy. Peri-implant and periodontal parameters were assessed (PD,BoP, mPI). Microbiological samples were collected around implant and an adjacent tooth. Real- Time Polymerase Chain Reaction (RT-PCR) analysis was performed. In all the three groups no differences in bacterial counts between dental and implant sites were observed. Non smoker, healthy patients: healthy clinical parameters, significant counts of spirochetes in isolated patients. Non smokers with previous periodontal disease: occasional positive BoP values, significant high counts of pathogenic bacteria. Smokers with previous periodontal disease: clinical signs of inflammation including deep pockets and slight bone resorption, significant counts of pathogenic bacteria. Over a follow-up of 5 to 7 years, it is possible to state that the absence of smoking habit and previous periodontal disease positively influences the peri-implant microbiological and clinical conditions in partial edentulous patients restored with dental implants and enrolled in a strict regular supportive therapy.

  12. Role of previous hospitalization in clinically-significant MRSA infection among HIV-infected inpatients: results of a case-control study

    Directory of Open Access Journals (Sweden)

    Festa Anna

    2007-04-01

    Full Text Available Abstract Background HIV-infected subjects have high incidence rates of Staphylococcus aureus infections, with both methicillin-susceptible and methicillin-resistant (MRSA strains. Possible explanations could include the high burden of colonization, the behavioral risk factors, and the frequent exposures to health care facilities of HIV-infected patients. The purpose of the study was to assess the risk factors for clinically- significant methicillin-resistant Staphylococcus aureus (CS-MRSA infections in HIV-infected patients admitted to Infectious Diseases Units. Methods From January 1, 2002 to December 31, 2005, we conducted a retrospective case-control (1:2 study. We identified all the cases of CS-MRSA infections in HIV-infected patients admitted to the National Institute for Infectious Diseases (INMI "Lazzaro Spallanzani" in the 4-year study period. A conditional logistic regression model was used to identify risk factors for CS-MRSA infection. Results We found 27 CS-MRSA infections, i.e. 0.9 CS-MRSA infections per 100 HIV-infected individuals cared for in our Institute. At multivariate analysis, independent predictors of CS-MRSA infection were cumulative hospital stay, invasive procedures in the previous year, and low CD4 cell count. Particularly, the risk for CS-MRSA increased by 14% per an increase of 5 days hospitalization in the previous year. Finally, we identified a low frequency of community-acquired MRSA infections (only 1 of 27; 3.7% among HIV-infected patients. Conclusion Clinicians should be aware of the risk for CS-MRSA infection in the clinical management of HIV-infected patients, especially in those patients with a low CD4 cell count, longer previous hospital stay, and previous invasive procedures.

  13. Role of previous hospitalization in clinically-significant MRSA infection among HIV-infected inpatients: results of a case-control study

    Science.gov (United States)

    Drapeau, Cecilia MJ; Angeletti, Claudio; Festa, Anna; Petrosillo, Nicola

    2007-01-01

    Background HIV-infected subjects have high incidence rates of Staphylococcus aureus infections, with both methicillin-susceptible and methicillin-resistant (MRSA) strains. Possible explanations could include the high burden of colonization, the behavioral risk factors, and the frequent exposures to health care facilities of HIV-infected patients. The purpose of the study was to assess the risk factors for clinically- significant methicillin-resistant Staphylococcus aureus (CS-MRSA) infections in HIV-infected patients admitted to Infectious Diseases Units. Methods From January 1, 2002 to December 31, 2005, we conducted a retrospective case-control (1:2) study. We identified all the cases of CS-MRSA infections in HIV-infected patients admitted to the National Institute for Infectious Diseases (INMI) "Lazzaro Spallanzani" in the 4-year study period. A conditional logistic regression model was used to identify risk factors for CS-MRSA infection. Results We found 27 CS-MRSA infections, i.e. 0.9 CS-MRSA infections per 100 HIV-infected individuals cared for in our Institute. At multivariate analysis, independent predictors of CS-MRSA infection were cumulative hospital stay, invasive procedures in the previous year, and low CD4 cell count. Particularly, the risk for CS-MRSA increased by 14% per an increase of 5 days hospitalization in the previous year. Finally, we identified a low frequency of community-acquired MRSA infections (only 1 of 27; 3.7%) among HIV-infected patients. Conclusion Clinicians should be aware of the risk for CS-MRSA infection in the clinical management of HIV-infected patients, especially in those patients with a low CD4 cell count, longer previous hospital stay, and previous invasive procedures. PMID:17470274

  14. Replication of 6 obesity genes in a meta-analysis of genome-wide association studies from diverse ancestries.

    Directory of Open Access Journals (Sweden)

    Li-Jun Tan

    Full Text Available Obesity is a major public health problem with a significant genetic component. Multiple DNA polymorphisms/genes have been shown to be strongly associated with obesity, typically in populations of European descent. The aim of this study was to verify the extent to which 6 confirmed obesity genes (FTO, CTNNBL1, ADRB2, LEPR, PPARG and UCP2 genes could be replicated in 8 different samples (n = 11,161 and to explore whether the same genes contribute to obesity-susceptibility in populations of different ancestries (five Caucasian, one Chinese, one African-American and one Hispanic population. GWAS-based data sets with 1000 G imputed variants were tested for association with obesity phenotypes individually in each population, and subsequently combined in a meta-analysis. Multiple variants at the FTO locus showed significant associations with BMI, fat mass (FM and percentage of body fat (PBF in meta-analysis. The strongest association was detected at rs7185735 (P-value = 1.01×10(-7 for BMI, 1.80×10(-6 for FM, and 5.29×10(-4 for PBF. Variants at the CTNNBL1, LEPR and PPARG loci demonstrated nominal association with obesity phenotypes (meta-analysis P-values ranging from 1.15×10(-3 to 4.94×10(-2. There was no evidence of association with variants at ADRB2 and UCP2 genes. When stratified by sex and ethnicity, FTO variants showed sex-specific and ethnic-specific effects on obesity traits. Thus, it is likely that FTO has an important role in the sex- and ethnic-specific risk of obesity. Our data confirmed the role of FTO, CTNNBL1, LEPR and PPARG in obesity predisposition. These findings enhanced our knowledge of genetic associations between these genes and obesity-related phenotypes, and provided further justification for pursuing functional studies of these genes in the pathophysiology of obesity. Sex and ethnic differences in genetic susceptibility across populations of diverse ancestries may contribute to a more targeted prevention and

  15. Replication of 6 Obesity Genes in a Meta-Analysis of Genome-Wide Association Studies from Diverse Ancestries

    Science.gov (United States)

    Tan, Li-Jun; Zhu, Hu; He, Hao; Wu, Ke-Hao; Li, Jian; Chen, Xiang-Ding; Zhang, Ji-Gang; Shen, Hui; Tian, Qing; Krousel-Wood, Marie; Papasian, Christopher J.; Bouchard, Claude; Pérusse, Louis; Deng, Hong-Wen

    2014-01-01

    Obesity is a major public health problem with a significant genetic component. Multiple DNA polymorphisms/genes have been shown to be strongly associated with obesity, typically in populations of European descent. The aim of this study was to verify the extent to which 6 confirmed obesity genes (FTO, CTNNBL1, ADRB2, LEPR, PPARG and UCP2 genes) could be replicated in 8 different samples (n = 11,161) and to explore whether the same genes contribute to obesity-susceptibility in populations of different ancestries (five Caucasian, one Chinese, one African-American and one Hispanic population). GWAS-based data sets with 1000 G imputed variants were tested for association with obesity phenotypes individually in each population, and subsequently combined in a meta-analysis. Multiple variants at the FTO locus showed significant associations with BMI, fat mass (FM) and percentage of body fat (PBF) in meta-analysis. The strongest association was detected at rs7185735 (P-value = 1.01×10−7 for BMI, 1.80×10−6 for FM, and 5.29×10−4 for PBF). Variants at the CTNNBL1, LEPR and PPARG loci demonstrated nominal association with obesity phenotypes (meta-analysis P-values ranging from 1.15×10−3 to 4.94×10−2). There was no evidence of association with variants at ADRB2 and UCP2 genes. When stratified by sex and ethnicity, FTO variants showed sex-specific and ethnic-specific effects on obesity traits. Thus, it is likely that FTO has an important role in the sex- and ethnic-specific risk of obesity. Our data confirmed the role of FTO, CTNNBL1, LEPR and PPARG in obesity predisposition. These findings enhanced our knowledge of genetic associations between these genes and obesity-related phenotypes, and provided further justification for pursuing functional studies of these genes in the pathophysiology of obesity. Sex and ethnic differences in genetic susceptibility across populations of diverse ancestries may contribute to a more targeted prevention and customized

  16. Replication of 6 obesity genes in a meta-analysis of genome-wide association studies from diverse ancestries.

    Science.gov (United States)

    Tan, Li-Jun; Zhu, Hu; He, Hao; Wu, Ke-Hao; Li, Jian; Chen, Xiang-Ding; Zhang, Ji-Gang; Shen, Hui; Tian, Qing; Krousel-Wood, Marie; Papasian, Christopher J; Bouchard, Claude; Pérusse, Louis; Deng, Hong-Wen

    2014-01-01

    Obesity is a major public health problem with a significant genetic component. Multiple DNA polymorphisms/genes have been shown to be strongly associated with obesity, typically in populations of European descent. The aim of this study was to verify the extent to which 6 confirmed obesity genes (FTO, CTNNBL1, ADRB2, LEPR, PPARG and UCP2 genes) could be replicated in 8 different samples (n = 11,161) and to explore whether the same genes contribute to obesity-susceptibility in populations of different ancestries (five Caucasian, one Chinese, one African-American and one Hispanic population). GWAS-based data sets with 1000 G imputed variants were tested for association with obesity phenotypes individually in each population, and subsequently combined in a meta-analysis. Multiple variants at the FTO locus showed significant associations with BMI, fat mass (FM) and percentage of body fat (PBF) in meta-analysis. The strongest association was detected at rs7185735 (P-value = 1.01×10(-7) for BMI, 1.80×10(-6) for FM, and 5.29×10(-4) for PBF). Variants at the CTNNBL1, LEPR and PPARG loci demonstrated nominal association with obesity phenotypes (meta-analysis P-values ranging from 1.15×10(-3) to 4.94×10(-2)). There was no evidence of association with variants at ADRB2 and UCP2 genes. When stratified by sex and ethnicity, FTO variants showed sex-specific and ethnic-specific effects on obesity traits. Thus, it is likely that FTO has an important role in the sex- and ethnic-specific risk of obesity. Our data confirmed the role of FTO, CTNNBL1, LEPR and PPARG in obesity predisposition. These findings enhanced our knowledge of genetic associations between these genes and obesity-related phenotypes, and provided further justification for pursuing functional studies of these genes in the pathophysiology of obesity. Sex and ethnic differences in genetic susceptibility across populations of diverse ancestries may contribute to a more targeted prevention and customized

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

    Science.gov (United States)

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

    2015-03-11

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

  18. Use of electrospray ionization mass spectrometry to study binding interactions between a replication terminator protein and DNA

    OpenAIRE

    Kapur, Amit; Beck, Jennifer L.; Brown, Susan E.; Dixon, Nicholas E.; Sheil, Margaret M.

    2002-01-01

    Tus protein binds tightly to specific DNA sequences (Ter) on the Escherichia coli chromosome halting replication. We report here conditions for detecting the 1 : 1 Tus–Ter complex by electrospray ionization mass spectrometry (ESI-MS). ESI mass spectra of a mixture of Tus and nonspecific DNA showed ions predominantly from uncomplexed Tus protein, indicating that the Tus–Ter complex observed in the gas phase was the result of a specific interaction rather than nonspecific associations in the io...

  19. Rif1 regulates initiation timing of late replication origins throughout the S. cerevisiae genome.

    Directory of Open Access Journals (Sweden)

    Jared M Peace

    Full Text Available Chromosomal DNA replication involves the coordinated activity of hundreds to thousands of replication origins. Individual replication origins are subject to epigenetic regulation of their activity during S-phase, resulting in differential efficiencies and timings of replication initiation during S-phase. This regulation is thought to involve chromatin structure and organization into timing domains with differential ability to recruit limiting replication factors. Rif1 has recently been identified as a genome-wide regulator of replication timing in fission yeast and in mammalian cells. However, previous studies in budding yeast have suggested that Rif1's role in controlling replication timing may be limited to subtelomeric domains and derives from its established role in telomere length regulation. We have analyzed replication timing by analyzing BrdU incorporation genome-wide, and report that Rif1 regulates the timing of late/dormant replication origins throughout the S. cerevisiae genome. Analysis of pfa4Δ cells, which are defective in palmitoylation and membrane association of Rif1, suggests that replication timing regulation by Rif1 is independent of its role in localizing telomeres to the nuclear periphery. Intra-S checkpoint signaling is intact in rif1Δ cells, and checkpoint-defective mec1Δ cells do not comparably deregulate replication timing, together indicating that Rif1 regulates replication timing through a mechanism independent of this checkpoint. Our results indicate that the Rif1 mechanism regulates origin timing irrespective of proximity to a chromosome end, and suggest instead that telomere sequences merely provide abundant binding sites for proteins that recruit Rif1. Still, the abundance of Rif1 binding in telomeric domains may facilitate Rif1-mediated repression of non-telomeric origins that are more distal from centromeres.

  20. Excess Cdt1 inhibits nascent strand elongation by repressing the progression of replication forks in Xenopus egg extracts.

    Science.gov (United States)

    Nakazaki, Yuta; Tsuyama, Takashi; Seki, Masayuki; Takahashi, Mikiko; Enomoto, Takemi; Tada, Shusuke

    2016-02-01

    Cdt1 is a protein essential for initiation of DNA replication; it recruits MCM helicase, a core component of the replicative DNA helicase, onto replication origins. In our previous study, we showed that addition of excess Cdt1 inhibits nascent strand elongation during DNA replication in Xenopus egg extracts. In the present study, we investigated the mechanism behind the inhibitory effect of Cdt1. We found that addition of recombinant Cdt1 inhibited nascent DNA synthesis in a reinitiation-independent manner. To identify the mechanism by which Cdt1 inhibits nascent strand elongation, the effect of Cdt1 on loading of Mcm4 and Rpa70 onto chromatin was examined. The results showed that Cdt1 suppressed the excessive Rpa70 binding caused by extensive, aphidicolin-induced DNA unwinding; this unwinding occurs between stalled DNA polymerases and advancing replication forks. These findings suggested that excess Cdt1 suppressed the progression of replication forks.

  1. 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....

  2. Role of Ribonucleic Acid Synthesis in Replication of Deoxyribonucleic Acid

    Science.gov (United States)

    Pato, Martin L.

    1975-01-01

    An experiment previously interpreted to show a ribonucleic acid requirement for propagation of deoxyribonucleic replication is reexamined and the earlier interpretation is shown to be incorrect. PMID:1090599

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

    Science.gov (United States)

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

    2016-01-01

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

  4. Internal RNA Replication Elements are Prevalent in Tombusviridae

    Directory of Open Access Journals (Sweden)

    Beth L Nicholson

    2012-08-01

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

  5. Phase II study of capecitabine as palliative treatment for patients with recurrent and metastatic squamous head and neck cancer after previous platinum-based treatment

    Science.gov (United States)

    Martinez-Trufero, J; Isla, D; Adansa, J C; Irigoyen, A; Hitt, R; Gil-Arnaiz, I; Lambea, J; Lecumberri, M J; Cruz, J J

    2010-01-01

    Background: Platinum-based therapy (PBT) is the standard therapy for recurrent and/or metastatic head and neck cancer (HNC), but the incidence of recurrence remains high. This study evaluates the efficacy and tolerability of capecitabine as palliative monotherapy for recurrent HNC previously treated with PBT. Methods: Patients aged 18–75 years, with Eastern Cooperative Oncology Group performance status 0–2, squamous HNC with locoregional and/or metastatic recurrence previously treated with PBT and adequate organ functions, were included. Capecitabine (1.250 mg m−2 BID) was administered on days 1–14 every 21 days for at least two cycles. Results: A total of 40 male patients with a median age of 58 years were analysed. All patients received a median number of four cycles of capecitabine (range: 1–9) and the median relative dose intensity was 91%. Seven patients were not evaluable for response. Overall response rate was 24.2%. Median time to progression and overall survival were 4.8 and 7.3 months, respectively. Haematological adverse events (AEs) grade 3/4 were reported in six patients. Most common grade 3/4 non-haematological AEs were asthenia (12.5%), palmar-plantar eritrodisestesia (10%), mucositis (10%), dysphagia (10%) and diarrhoea (7.5%). Conclusions: Capecitabine seems to be an active, feasible and well-tolerated mode of palliative treatment for advanced HNC patients who have previously received PBT schedules. PMID:20485287

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

  8. Risk for High Depressive Symptoms in Diagnosed and Previously Undetected Diabetes: 5-Year Follow-Up Results of the Heinz Nixdorf Recall Study

    Science.gov (United States)

    Icks, Andrea; Albers, Bernd; Haastert, Burkhard; Pechlivanis, Sonali; Pundt, Noreen; Slomiany, Uta; Erbel, Raimund; Jöckel, Karl-Heinz; Kruse, Johannes; Kulzer, Bernd; Nowotny, Bettina; Herder, Christian; Giani, Guido; Moebus, Susanne

    2013-01-01

    Objective The objective of this study was to determine the risk for the development of high depressive symptoms in study participants with diagnosed and previously undetected diabetes mellitus compared to those without diabetes in a prospective population-based cohort study in Germany. Methods We estimated the 5-year cumulative incidence of high depressive symptoms in participants without high depressive symptoms at baseline (n = 3,633, 51.4% men, mean age (SD) 59.1 (7.6) years, 7.0% diagnosed diabetes, 5.3% previously undetected diabetes) from the population-based Heinz Nixdorf Recall study. Diabetes was assessed by self-report, medication, and blood glucose. High depressive symptoms were assessed using CES-D. We calculated odds ratios and their corresponding 95% confidence interval, using multiple logistic regression analyses. Result Cumulative 5-year incidences (95% CI) of high depressive symptoms in participants with diagnosed, undetected, and without diabetes were 7.1 (4.2–10.9), 4.1 (1.8–8.0), and 6.5 (5.6–7.4), respectively. The age-sex-adjusted OR for developing high depressive symptoms was 1.22 (0.74–2.03) in participants with diagnosed compared to those without diabetes, and 1.00 (0.59–1.68) after adjustment for BMI, physical activity, education, stroke, and myocardial infarction. The age-sex adjusted OR for developing high depressive symptoms in participants with previously undetected diabetes compared to those without diabetes was 0.72; 0.35–1.48; and fully adjusted 0.62; 0.30–1.30. Conclusion We found no significant associations, maybe due to low power. However, our results are in line with a recent meta-analysis suggesting that risk of developing high depressive symptoms in patients with diagnosed diabetes may be moderately higher than in those without diabetes, and that comorbidity may explain in part this association. In participants with previously undetected diabetes, this first longitudinal study indicates that the risk is not

  9. Risk for high depressive symptoms in diagnosed and previously undetected diabetes: 5-year follow-up results of the Heinz Nixdorf Recall study.

    Directory of Open Access Journals (Sweden)

    Andrea Icks

    Full Text Available OBJECTIVE: The objective of this study was to determine the risk for the development of high depressive symptoms in study participants with diagnosed and previously undetected diabetes mellitus compared to those without diabetes in a prospective population-based cohort study in Germany. METHODS: We estimated the 5-year cumulative incidence of high depressive symptoms in participants without high depressive symptoms at baseline (n = 3,633, 51.4% men, mean age (SD 59.1 (7.6 years, 7.0% diagnosed diabetes, 5.3% previously undetected diabetes from the population-based Heinz Nixdorf Recall study. Diabetes was assessed by self-report, medication, and blood glucose. High depressive symptoms were assessed using CES-D. We calculated odds ratios and their corresponding 95% confidence interval, using multiple logistic regression analyses. RESULT: Cumulative 5-year incidences (95% CI of high depressive symptoms in participants with diagnosed, undetected, and without diabetes were 7.1 (4.2-10.9, 4.1 (1.8-8.0, and 6.5 (5.6-7.4, respectively. The age-sex-adjusted OR for developing high depressive symptoms was 1.22 (0.74-2.03 in participants with diagnosed compared to those without diabetes, and 1.00 (0.59-1.68 after adjustment for BMI, physical activity, education, stroke, and myocardial infarction. The age-sex adjusted OR for developing high depressive symptoms in participants with previously undetected diabetes compared to those without diabetes was 0.72; 0.35-1.48; and fully adjusted 0.62; 0.30-1.30. CONCLUSION: We found no significant associations, maybe due to low power. However, our results are in line with a recent meta-analysis suggesting that risk of developing high depressive symptoms in patients with diagnosed diabetes may be moderately higher than in those without diabetes, and that comorbidity may explain in part this association. In participants with previously undetected diabetes, this first longitudinal study indicates that the risk is not

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

    Science.gov (United States)

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

    1996-03-01

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

  11. 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...

  12. 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.

    Directory of Open Access Journals (Sweden)

    George O Agogo

    Full Text Available 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.

  13. The organotypic multicellular spheroid is a relevant three-dimensional model to study adenovirus replication and penetration in human tumors in vitro.

    Science.gov (United States)

    Grill, Jacques; Lamfers, Martine L M; van Beusechem, Victor W; Dirven, Clemens M; Pherai, D Shareen; Kater, Mathijs; Van der Valk, Paul; Vogels, Ronald; Vandertop, W Peter; Pinedo, Herbert M; Curiel, David T; Gerritsen, Winald R

    2002-11-01

    The use of adenoviruses for gene transfer and as oncolytic agents is currently receiving widespread attention. As specific constraints to adenovirus distribution and spread cannot be studied in cell cultures, there is a need for an in vitro three-dimensional (3D) model mimicking the in vivo biology of tumors. We studied the interactions between tumor and adenoviruses using multicellular spheroids grown from primary brain tumor material. Using beta-galactosidase and luciferase reporter genes expressed by replication-defective adenoviruses, we showed that infection was restricted to the first layer of cells. Using a replication-competent adenovirus expressing the luciferase gene, we showed that transgene expression in the spheroid was considerably enhanced and that viral spreading deep into the 3D structure took place. In addition, a tetrazolium salt-based metabolic assay could be used to compare the oncolytic activity of different concentrations of replication-competent adenoviruses. We can conclude that organotypic spheroids offer a versatile in vitro system for studying distribution, spread, and oncolysis by adenoviruses in a clinically relevant model.

  14. Shallow landslide susceptibility model for the Oria river basin, Gipuzkoa province (North of Spain). Application of the logistic regression and comparison with previous studies.

    Science.gov (United States)

    Bornaetxea, Txomin; Antigüedad, Iñaki; Ormaetxea, Orbange

    2016-04-01

    In the Oria river basin (885 km2) shallow landslides are very frequent and they produce several roadblocks and damage in the infrastructure and properties, causing big economic loss every year. Considering that the zonification of the territory in different landslide susceptibility levels provides a useful tool for the territorial planning and natural risk management, this study has the objective of identifying the most prone landslide places applying an objective and reproducible methodology. To do so, a quantitative multivariate methodology, the logistic regression, has been used. Fieldwork landslide points and randomly selected stable points have been used along with Lithology, Land Use, Distance to the transport infrastructure, Altitude, Senoidal Slope and Normalized Difference Vegetation Index (NDVI) independent variables to carry out a landslide susceptibility map. The model has been validated by the prediction and success rate curves and their corresponding area under the curve (AUC). In addition, the result has been compared to those from two landslide susceptibility models, covering the study area previously applied in different scales, such as ELSUS1000 version 1 (2013) and Landslide Susceptibility Map of Gipuzkoa (2007). Validation results show an excellent prediction capacity of the proposed model (AUC 0,962), and comparisons highlight big differences with previous studies.

  15. Food intake during the previous 24 h as a percentage of usual intake: a marker of hypoxia in infants with bronchiolitis: an observational, prospective, multicenter study

    Directory of Open Access Journals (Sweden)

    Corrard François

    2013-01-01

    Full Text Available Abstract Background Hypoxia associated with bronchiolitis is not always easy to assess on clinical grounds alone. The aim of this study was to determine the value of food intake during the previous 24 hours (bottle and spoon feeding, as a percentage of usual intake (24h FI, as a marker of hypoxia, and to compare its diagnostic value with that of usual clinical signs. Methods In this observational, prospective, multicenter study, 18 community pediatricians, enrolled 171 infants, aged from 0 to 6 months, with bronchiolitis (rhinorrhea + dyspnea + cough + expiratory sounds. Infants with risk factors (history of prematurity, chronic heart or lung disorders, breast-fed infants, and infants having previously been treated for bronchial disorders were excluded. The 24h FI, subcostal, intercostal, supracostal retractions, nasal flaring, respiratory rate, pauses, cyanosis, rectal temperature and respiratory syncytial virus test results were noted. The highest stable value of transcutaneous oxygen saturation (SpO2 was recorded. Hypoxia was noted if SpO2 was below 95% and verified. Results 24h FI ≥ 50% was associated with a 96% likelihood of SpO2 ≥ 95% [95% CI, 91–99]. In univariate analysis, 24h FI  Conclusion In practice, the measure of 24 h FI may be useful in identifying hypoxia and deserves further study.

  16. 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.

  17. Involvement of the skin during bluetongue virus infection and replication in the ruminant host.

    Science.gov (United States)

    Darpel, Karin E; Monaghan, Paul; Simpson, Jennifer; Anthony, Simon J; Veronesi, Eva; Brooks, Harriet W; Elliott, Heather; Brownlie, Joe; Takamatsu, Haru-Hisa; Mellor, Philip S; Mertens, Peter Pc

    2012-04-30

    Bluetongue virus (BTV) is a double stranded (ds) RNA virus (genus Orbivirus; family Reoviridae), which is considered capable of infecting all species of domestic and wild ruminants, although clinical signs are seen mostly in sheep. BTV is arthropod-borne ("arbovirus") and able to productively infect and replicate in many different cell types of both insects and mammalian hosts. Although the organ and cellular tropism of BTV in ruminants has been the subject of several studies, many aspects of its pathogenesis are still poorly understood, partly because of inherent problems in distinguishing between "virus replication" and "virus presence".BTV replication and organ tropism were studied in a wide range of infected sheep tissues, by immuno-fluorescence-labeling of non-structural or structural proteins (NS2 or VP7 and core proteins, respectively) using confocal microscopy to distinguish between virus presence and replication. These results are compared to gross and microscopic pathological findings in selected organs from infected sheep. Replication was demonstrated in two major cell types: vascular endothelial cells, and agranular leukocytes which morphologically resemble lymphocytes, monocytes/macrophages and/or dendritic cells. Two organs (the skin and tonsils) were shown to support relatively high levels of BTV replication, although they have not previously been proposed as important replication sites during BTV infection. The high level of BTV replication in the skin is thought to be of major significance for the pathogenesis and transmission of BTV (via biting insects) and a refinement of our current model of BTV pathogenesis is discussed.

  18. 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.

  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. 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.

  1. Myocardial adaptation to high-intensity (interval) training in previously untrained men with a longitudinal cardiovascular magnetic resonance imaging study (Running Study and Heart Trial).

    Science.gov (United States)

    Scharf, Michael; Schmid, Axel; Kemmler, Wolfgang; von Stengel, Simon; May, Matthias S; Wuest, Wolfgang; Achenbach, Stephan; Uder, Michael; Lell, Michael M

    2015-04-01

    To prospectively evaluate whether short-term high-intensity (interval) training (HI(I)T) induces detectable morphological cardiac changes in previously untrained men in cardiovascular magnetic resonance imaging. Eighty-four untrained volunteers were randomly assigned to a HI(I)T group (n=42; 44.1±4.7 years) or an inactive control group (n=42; 42.3±5.6 years). HI(I)T focused on interval runs (intensity: 95%-105% of individually calculated heart rate at the anaerobic threshold). Before and after 16 weeks, all subjects underwent physiological examination, stepwise treadmill test with blood lactate analysis, and contrast-enhanced cardiovascular magnetic resonance imaging (cine, tagging, and delayed enhancement). Indexed left ventricular (LV) and right ventricular (RV) volume (LV, 77.1±8.5-83.9±8.6; RV, 80.5±8.5-86.6±8.1) and mass (LV, 58.2±6.4-63.4±8.1; RV, 14.8±1.7-16.1±2.1) significantly increased with HI(I)T. Changes in LV and RV morphological parameters with HI(I)T were highly correlated with an increase in maximal aerobic capacity (VO2max) and a decrease in blood lactate concentration at the anaerobic threshold. Mean LV and RV remodeling index of HI(I)T group did not alter with training (0.76 ±0.09 and 0.24±0.10 g/mL, respectively [P=0.97 and P=0.72]), indicating balanced cardiac adaptation. Myocardial circumferential strain decreased after HI(I)T within all 6 basal segments (anteroseptal, P=0.01 and anterolateral, PHeart Association, Inc.

  2. Evaluation of canonical siRNA and Dicer substrate RNA for inhibition of hepatitis C virus genome replication--a comparative study.

    Directory of Open Access Journals (Sweden)

    Bruno Carneiro

    Full Text Available Hepatitis C virus (HCV frequently establishes persistent infections in the liver, leading to the development of chronic hepatitis and, potentially, to liver cirrhosis and hepatocellular carcinoma at later stages. The objective of this study was to test the ability of five Dicer substrate siRNAs (DsiRNA to inhibit HCV replication and to compare these molecules to canonical 21 nt siRNA. DsiRNA molecules were designed to target five distinct regions of the HCV genome - the 5' UTR and the coding regions for NS3, NS4B, NS5A or NS5B. These molecules were transfected into Huh7.5 cells that stably harboured an HCV subgenomic replicon expressing a firefly luciferase/neoR reporter (SGR-Feo-JFH-1 and were also tested on HCVcc-infected cells. All of the DsiRNAs inhibited HCV replication in both the subgenomic system and HCVcc-infected cells. When DsiRNAs were transfected prior to infection with HCVcc, the inhibition levels reached 99.5%. When directly compared, canonical siRNA and DsiRNA exhibited similar potency of virus inhibition. Furthermore, both types of molecules exhibited similar dynamics of inhibition and frequencies of resistant mutants after 21 days of treatment. Thus, DsiRNA molecules are as potent as 21 nt siRNAs for the inhibition of HCV replication and may provide future approaches for HCV therapy if the emergence of resistant mutants can be addressed.

  3. 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.

  4. Biomechanical jumping differences among elite female handball players with and without previous anterior cruciate ligament reconstruction: a novel inertial sensor unit study.

    Science.gov (United States)

    Setuain, Igor; Millor, Nora; González-Izal, Miriam; Gorostiaga, Esteban M; Gómez, Marisol; Alfaro-Adrián, Jesús; Maffiuletti, Nicola A; Izquierdo, Mikel

    2015-09-01

    Persistent biomechanical and jumping capacity alterations have been observed among female athletes who have sustained anterior cruciate ligament (ACL) injuries. The purpose of this study was to examine if biomechanical jumping differences persist among a cohort of elite female handball players with previous ACL reconstruction several years after return to top-level competition. In order to achieve this goal, a direct mechanics simplified analysis by using a single Inertial Sensor Unit (IU) was used. Twenty-one elite female (6 anterior cruciate ligament reconstructed and 15 uninjured control players) handball players were recruited and evaluated 6.0 ± 3.5 years after surgical anterior cruciate ligament reconstruction. Bilateral and unilateral vertical jumps were performed to evaluate the functional performance and a single inertial sensor unit was employed in order to collect 3D acceleration and 3D orientation data. Previously ACL-reconstructed analysed athletes demonstrated significant (p reconstruction. Identification of the encountered deficits through the use of an IU devise could provide clinicians with a new reliable tool for movement analysis in a clinical setting.

  5. A longitudinal study of relationships between previous academic achievement, emotional intelligence and personality traits with psychological health of medical students during stressful periods.

    Science.gov (United States)

    Yusoff, Muhamad Saiful Bahri; Esa, Ab Rahman; Mat Pa, Mohamad Najib; Mey, See Ching; Aziz, Rosniza Abdul; Abdul Rahim, Ahmad Fuad

    2013-01-01

    There is considerable evidence that emotional intelligence, previous academic achievement (i.e. cumulative grade point average (GPA)) and personality are associated with success in various occupational settings. This study evaluated the relationships of these variables with psychological health of first year medical students during stressful periods. A 1-year prospective study was done with students accepted into the School of Medical Sciences, Universiti Sains Malaysia. Information on emotional intelligence, GPA and personality traits were obtained prior to admission. The validated Universiti Sains Malaysia Emotional Quotient Inventory and Universiti Sains Malaysia Personality Inventory were used to measure emotional intelligence and personality traits, respectively. Stress, anxiety and depression were measured by the 21-item Depression Anxiety Stress Scale during the end-of-course (time 1) and final (time 2) examinations. At the less stressful period (time 1), stress level was associated with agreeableness and the final GPA, anxiety level was associated with emotional control and emotional conscientiousness and depression level was associated with the final GPA and extraversion. At the more stressful period (time 2), neuroticism associated with stress level, anxiety level was associated with neuroticism and emotional expression, and depression level was associated with neuroticism. This study found that neuroticism was the strongest associated factor of psychological health of medical students during their most stressful testing period. Various personality traits, emotional intelligence and previous academic performance were associated factors of psychological health during a less stressful period. These data suggest that early identification of medical students who are vulnerable to the stressful environment of medical schools might help them maintain psychological well-being during medical training.

  6. Covert Reinforcement: A Partial Replication.

    Science.gov (United States)

    Ripstra, Constance C.; And Others

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

  7. 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

    -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...... variants in FTO (rs9939609) and near MC4R (rs17782313) as genetic risk factors.......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...

  8. Study on the Properties of TiN Coatings on Previously Ion-Implanted Pure Magnesium Surface by MEVVA Ion Implantation

    Institute of Scientific and Technical Information of China (English)

    ZHOU Hai; CHEN Fei; WANG Jian-ping

    2007-01-01

    A metal vapor vacuum arc (MEVVA) is used in ion implantation for substrate preparation before the deposition process which would ensure the improvement of mechanical properties of the coating.Ti ion is implanted into pure magnesium surface by MEVVA implanter operated with a modified cathode.Implanting energy is kept at 45 keV and dose is set at 3×1017 cm-2.TiN coatings are deposited by magnetically filtered vacuum-arc plasma source on unimplanted and previously implanted substrates.Microstructure and phase composition are analysed using scanning electron microscopy (SEM) and X-ray diffraction (XRD).The property of corrosion resistance of TiN coatings was studied by CS300P electrochemistry-corrosion workstation,and the main impact factor of the corrosion resistance was also analyzed.

  9. 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

    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......, adequate organ functions and performance status less than 3 were eligible. Topotecan (2.0 mg/m, intravenously) was administered on days 1 to 3 with cisplatin (50 mg/m, intravenously) on day 3 every 3 weeks for a total of six cycles. RESULTS: Forty-three patients received 219 cycles of chemotherapy. Median.......3-7.7), respectively. CONCLUSION: Three-day topotecan with cisplatin on day 3 is active and safe in extensive disease SCLC. An ongoing phase III randomized trial compares this combination to standard treatment Udgivelsesdato: 2008/8...

  10. 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.

  11. Investigation of previously implicated genetic variants in chronic tic disorders

    DEFF Research Database (Denmark)

    Abdulkadir, Mohamed; Londono, Douglas; Gordon, Derek

    2017-01-01

    Genetic studies in Tourette syndrome (TS) are characterized by scattered and poorly replicated findings. We aimed to replicate findings from candidate gene and genome-wide association studies (GWAS). Our cohort included 465 probands with chronic tic disorder (93% TS) and both parents from 412 fam...

  12. Clinical evaluation of balloon occlusion of the lower abdominal aorta in patients with placenta previa and previous cesarean section: A retrospective study on 43 cases.

    Science.gov (United States)

    Chen, Manru; Xie, Lan

    2016-10-01

    This study investigated the efficacy of balloon occlusion of the lower abdominal aorta in cesarean section surgery for the patients with placenta previa and previous cesarean section. The patients who had placenta previa and underwent cesarean section (CS) were evaluated. The patients treated with CS to terminate the pregnancy were used as control group (23 cases); the patients treated with the preset abdominal aorta balloon before CS was taken as study group (20 cases). The investigated indicators included the intraoperative blood loss, blood loss within postoperative 24 h, the transfusion amount of red cell suspension (RCS), hospital stay, incidence rate of disseminated intravascular coagulation (DIC), the asphyxia, premature delivery and the mortality of the newborns. The two groups are comparable. The intraoperative blood loss, blood loss within postoperative 24 h, the transfusion amount of RCS and the percentage of uterus resection in the study group were significantly lower (P < 0.05) than that in the control group. The percentage of uterine cavity filling with ribbon gauze in the study group was higher than the control group (P < 0.05). The balloon occlusion of lower abdominal aorta seems effective in reducing postpartum hemorrhage and the blood transfusion and decreasing the risk of hysterectomy without harming the newborns. Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

  13. The Dual Nature of Nek9 in Adenovirus Replication

    OpenAIRE

    Jung, Richard; Radko, Sandi; Pelka, Peter

    2016-01-01

    To successfully replicate in an infected host cell, a virus must overcome sophisticated host defense mechanisms. Viruses, therefore, have evolved a multitude of devices designed to circumvent cellular defenses that would lead to abortive infection. Previous studies have identified Nek9, a cellular kinase, as a binding partner of adenovirus E1A, but the biology behind this association remains a mystery. Here we show that Nek9 is a transcriptional repressor that functions together with E1A to s...

  14. Study report on tissue organ regeneration and replication in situ%组织器官的原位再生复制研究报告

    Institute of Scientific and Technical Information of China (English)

    徐荣祥

    2003-01-01

    果对人类生命科学的一大贡献.%In this report ,we mainly covered the following aspects of "Tissue organ regeneration and replication in situ":1)Procedures of tissue organd regeneration and replication and replication in clnical practice;2)The discover and existence of Potentiald Regenerative Cell(PRC);3)The proliferation ,differentiation and regeneration law of Potential law of Potential Regenerative Cells;4)Study procedure on tissue organ regeneration and replication from PRCs in vitro based on the model of full skin organ regeneration in situ after extensive in vitro,set up the method and technology of searching life regenerative substance required in tissue organ regeneration and replication in situ.In this study,first ,the whole human body is divided into 206 function units,which are the "Tissue Organ"in regeneration study.Then the histology foundation of tissue organ regeneration and replication in situ is set up.In ordre to prove the existence of the Potential Regenerative Cells and their potential baility and function ,we established clinical tracking rechnique of skin organ regeneration in situ;meanwhile,several tissue organ regeneration and replication in vitro models which represent different kinds of runctions were sucessfully set up,With all these techniques and models ,we confirmed:1)the existence ,function and ability of Pptemtoa Regenerative Cells;2)the importance of life regenerative substance;3)the feasibility of tissue organ regeneration and replication in situ;4)the big value of tissue organ regeneration and replication in situ in life science and medicine progerss.We also showed the possible foreground of capture cancer with this method and technologh.In this report,nearly 200 photographs of several tissue organ regeneration and replication in situ or in vitro demonstrated the whole process of tissue organ and big organ entities regeneration and replication from cells .The results of tissue organ regeneration and replication in situ

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

    Science.gov (United States)

    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

    2012-10-01

    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 (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.

  16. 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)

  17. A Phase III Study of Durvalumab (MEDI4736) With or Without Tremelimumab for Previously Treated Patients With Advanced NSCLC: Rationale and Protocol Design of the ARCTIC Study.

    Science.gov (United States)

    Planchard, David; Yokoi, Takashi; McCleod, Michael J; Fischer, Jürgen R; Kim, Young-Chul; Ballas, Marc; Shi, Kelvin; Soria, Jean-Charles

    2016-05-01

    Anti-programmed cell death-1 and anti-programmed cell death ligand-1 (PD-L1) monotherapies have shown promising clinical activity in advanced, refractory non-small-cell lung cancer (NSCLC), but antitumor activity appears to be greater in patients with PD-L1(+) tumors compared with patients harboring PD-L1(-) tumors. Combining the anti-PD-L1 antibody durvalumab and the anti-cytotoxic T-lymphocyte antigen 4 antibody tremelimumab offers the potential for antitumor activity in patients with advanced NSCLC, regardless of PD-L1 tumor status. ARCTIC (NCT02352948) is a global, phase III, randomized, open-label multicenter study in patients with advanced NSCLC assessing the safety and clinical activity of durvalumab versus standard of care (SoC; erlotinib, gemcitabine, or vinorelbine) in patients with PD-L1(+) tumors (≥25% of tumor cells with membrane staining using VENTANA PD-L1 [SP263] CDx Assay) (Sub-study A) and the combination of durvalumab + tremelimumab or either agent as monotherapy versus SoC in patients with PD-L1(-) tumors (Sub-study B). Eligible patients are those with locally advanced or metastatic NSCLC (Stage IIIB/IV), without epidermal growth factor receptor tyrosine kinase activating mutations or anaplastic lymphoma kinase rearrangements, who have received at least 2 prior systemic regimens, including 1 platinum-based chemotherapy regimen. Co-primary endpoints are progression-free survival and overall survival. Secondary endpoints include the proportion of patients alive at 12 months, objective response rate, duration of response, progression-free survival at 6 and 12 months, safety and tolerability, pharmacokinetics, immunogenicity, and quality of life. The exploratory endpoints will assess potential biomarkers of treatment response. Recruitment started in January 2015 and is ongoing.

  18. Phase III study of 5FU, etoposide and leucovorin (FELV) compared to epirubicin, cisplatin and 5FU (ECF) in previously untreated patients with advanced biliary cancer.

    Science.gov (United States)

    Rao, S; Cunningham, D; Hawkins, R E; Hill, M E; Smith, D; Daniel, F; Ross, P J; Oates, J; Norman, A R

    2005-05-09

    The purpose of this study was to determine whether epirubicin, cisplatin and infused 5FU (ECF) improves overall survival (OS) compared to 5FU, etoposide and leucovorin (FELV) in patients with previously untreated advanced biliary cancer in a prospective randomised study. Patients were randomly assigned to receive epirubicin, cisplatin and infused 5FU ECF or bolus 5FU etoposide and leucovorin (FELV). The primary end point was OS with secondary end points of objective response rate (ORR), failure-free survival (FFS), quality of life (QOL) and toxicity. In all, 54 patients were recruited with 27 randomly assigned to each arm. The median OS for ECF was 9.02 months (95% confidence interval (CI): 6.46-11.51) and FELV 12.03 months (95% CI: 9.3-14.7), P=0.2059. Objective response rates were similar for both arms: ECF 19.2% (95% CI: 6.55-39.3); FELV 15% (95% CI: 3.2-37.9), P=0.72. There was significantly increased grade 3/4 neutropenia with FELV vs ECF (53.8 vs 29.5%, respectively, P=0.020). Symptom resolution was impressive for both regimens. This is the largest reported randomised study to date in this setting. ECF did not improve OS compared to FELV, but was associated with less acute toxicity. These data suggest that chemotherapy can prolong OS and achieve good symptomatic relief in advanced biliary cancer.

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

    Directory of Open Access Journals (Sweden)

    Malindu Eranga Fernando

    Full Text Available AIMS: 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. METHODS: 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. RESULTS: 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, p<0.001; and 0.762, 95% CI 0.303-1.221, p = 0.001, respectively. Sub-group analyses demonstrated no significant difference in MPP for those with neuropathy with active ulceration compared to those without ulcers. A significant difference in MPP was found for those with neuropathy with a past history of ulceration compared to those without ulcers; (0.467, 95% CI 0.181- 0.753, p = 0.001. Statistical heterogeneity between studies was moderate. CONCLUSIONS: Plantar pressures appear to be significantly higher in patients with diabetic peripheral neuropathy with a history of foot ulceration compared to those with diabetic

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

    Science.gov (United States)

    Tannenbaum, Emmanuel

    2008-01-01

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

  1. The influence of previous infections and antichlamydia pneumoniae seropositivity on functional outcome in ischemic stroke patients: results from the IN2 study.

    Science.gov (United States)

    Consoli, Domenico; Vidale, Simone; Aguglia, Umberto; Bassi, Pietro; Cavallini, Anna; Consoli, Arturo; Galati, Franco; Guidetti, Donata; Micieli, Giuseppe; Neri, Giuseppe; Rasura, Maurizia; Sterzi, Roberto; Toni, Danilo; Inzitari, Domenico

    2015-05-01

    Although a growing attention is being paid to acute ischemic stroke patients, the correlation between clinical outcome and infectious events in this population has been poorly investigated. 749 ischemic stroke (mean age 71 years old, males 56%) patients were enrolled in this prospective case-control study by 11 Italian Stroke Units. Demographic data, vascular risk factors, previous infections and post-stroke infections (PSIs) were recorded. Blood samples were collected and the enzyme-linked immunoassay was chosen to measure Chlamydia pneumoniae IgG and IgA plasma antibodies (antibody titers were classified with specific cut-off levels: IgA > 1:16 and IgG > 1:64). Early poor outcome was defined as mRS score >2 at discharge, while poor outcome at 6-month follow-up. Univariate and multivariate analyses were performed. Median NIHSS was 7, IgA and IgG antichlamydia pneumoniae seropositivities were observed in 308 (37.1%) and 207 (23.6%) patients, respectively. Multivariate analyses showed significant correlations between PSIs and NIHSS (RR: 1.06; 95% CI 1.02-1.09; p < 0.001) and PSIs and IgA antichlamydia pneumoniae seropositivity (RR: 3.84; 95% CI 2.53-5.84; p < 0.001). Significant disability was associated with baseline NIHSS (RR: 1.32; 95% CI 1.16-1.50; p < 0.001), IgA (RR: 2.67; 95% CI 1.06-6.70; p = 0.035) and IgG antichlamydia (RR: 5.75; 95% CI 1.83-18.03; p = 0.003) seropositivity and atrial fibrillation (RR: 2.58; 95% CI 1.81-3.67; p < 0.001). While previous infections were not associated with functional outcome, antichlamydia antibodies play a negative role in ischemic stroke patients. Preventive strategies may reduce the stroke burden and improve the clinical outcome.

  2. Replication of a chronic hepatitis B virus genotype F1b construct.

    Science.gov (United States)

    Hernández, Sergio; Jiménez, Gustavo; Alarcón, Valentina; Prieto, Cristian; Muñoz, Francisca; Riquelme, Constanza; Venegas, Mauricio; Brahm, Javier; Loyola, Alejandra; Villanueva, Rodrigo A

    2016-03-01

    Genotype F is one of the less-studied genotypes of human hepatitis B virus, although it is widely distributed in regions of Central and South American. Our previous studies have shown that HBV genotype F is prevalent in Chile, and phylogenetic analysis of its full-length sequence amplified from the sera of chronically infected patients identified it as HBV subgenotype F1b. We have previously reported the full-length sequence of a HBV molecular clone obtained from a patient chronically infected with genotype F1b. In this report, we established a system to study HBV replication based on hepatoma cell lines transfected with full-length monomers of the HBV genome. Culture supernatants were analyzed after transfection and found to contain both HBsAg and HBeAg viral antigens. Consistently, fractionated cell extracts revealed the presence of viral replication, with both cytoplasmic and nuclear DNA intermediates. Analysis of HBV-transfected cells by indirect immunofluorescence or immunoelectron microscopy revealed the expression of viral antigens and cytoplasmic viral particles, respectively. To test the functionality of the ongoing viral replication further at the level of chromatinized cccDNA, transfected cells were treated with a histone deacetylase inhibitor, and this resulted in increased viral replication. This correlated with changes posttranslational modifications of histones at viral promoters. Thus, the development of this viral replication system for HBV genotype F will facilitate studies on the regulation of viral replication and the identification of new antiviral drugs.

  3. A Retrospective Case-Control Study Evaluating the Role of Mifepristone for Induction of Labor in Women with Previous Cesarean Section.

    Science.gov (United States)

    Sharma, Chanderdeep; Soni, Anjali; Soni, Pawan K; Verma, Suresh; Verma, Ashok; Gupta, Amit

    2016-10-01

    To investigate the role of "mifepristone" for induction of labor (IOL) in pregnant women with prior cesarean section (CS). In this retrospective study, all pregnant women with prior CS who received oral mifepristone (400 mg) for IOL (as per clear obstetric indications) [group 1] were compared with pregnant women with prior CS who had spontaneous onset of labor (SOL) [group 2], with respect to incidence of vaginal delivery, CS, duration of labor, and various maternal and fetal outcomes. During the study period, 72 women received mifepristone (group 1) for IOL and 346 had SOL (group 2). In group 1 after mifepristone administration, 40 (55.6 %) women had labor onset, and 24 (33.3 %) women had cervical ripening (Bishop Score ≥ 8) within 48 h. There were no statistically significant differences with respect to duration of labor (p value: 0.681), mode of delivery (i.e., normal delivery or CS-p value: 0.076 or 0.120, respectively), or maternal (blood loss or scar dehiscence/rupture uterus), or fetal outcomes (NICU admission) compared to women with previous CS with SOL (group 2). However, the need of oxytocin (p value 0.020) and dose of oxytocin requirement (p value 0.008) were more statistically significant in group 1. Mifepristone may be considered as an agent for IOL in women with prior CS.

  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.

  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. ACTG-HIV symptoms changes in patients switched to RPV/FTC/TDF due to previous intolerance to CART. Interim analysis of the PRO-STR study

    Directory of Open Access Journals (Sweden)

    Daniel Podzamczer

    2014-11-01

    Full Text Available Introduction: Tolerability and convenience are crucial aspects for the long-term success of combined antiretroviral therapy (cART. The aim of this study was to investigate the impact in routine clinical practice of switching to the single tablet regimen (STR RPV/FTC/TDF in patients with intolerance to previous cART, in terms of patients’ well-being, assessed by several validated measures. Methods: Prospective, multicenter study. Adult HIV-infected patients with viral load under 1.000 copies/mL while receiving a stable ART for at least the last three months and switched to RPV/FTC/TDF due to intolerance of previous regimen, were included. Analyses were performed by ITT. Presence/magnitude of symptoms (ACTG-HIV Symptom Index, quality of life (EQ-5D, EUROQoL & MOS-HIV, adherence (SMAQ, preference of treatment and perceived ease of medication (ESTAR through 48 weeks were performed. Results: Interim analysis of 125 patients with 16 weeks of follow up was performed. 100 (80% were male, mean age 46 years. Mean CD4 at baseline was 629.5±307.29 and 123 (98.4% had viral load <50 copies/mL; 15% were HCV co-infected. Ninety two (73.6% patients switched from a NNRTI (84.8% from EFV/FTC/TDF and 33 (26.4% from a PI/r. The most frequent reasons for switching were psychiatric disorders (51.2%, CNS adverse events (40.8%, gastrointestinal (19.2% and metabolic disorders (19.2%. At the time of this analysis (week 16, four patients (3.2% discontinued treatment: one due to adverse events, two virologic failures and one with no data. A total of 104 patients (83.2% were virologically suppressed (<50 copies/mL. The average degree of discomfort in the ACTG-HIV Symptom Index significantly decreased from baseline (21±15.55 to week 4 (10.89±12.36 & week 16 (10.81±12.62, p<0.001. In all the patients, quality of life tools showed a significant benefit in well-being of the patients (Table 1. Adherence to therapy significantly and progressively increased (SMAQ from

  7. Perturbation of lipids and glucose metabolism associated with previous 2,4-D exposure: a cross-sectional study of NHANES III data, 1988-1994

    Directory of Open Access Journals (Sweden)

    Schreinemachers Dina M

    2010-02-01

    Full Text Available Abstract Background Results from previous population studies showed that mortality rates from acute myocardial infarction and type-2 diabetes during the 1980s and 1990s in rural, agricultural counties of Minnesota, Montana, North and South Dakota, were higher in counties with a higher level of spring wheat farming than in counties with lower levels of this crop. Spring wheat, one of the major field crops in these four states, was treated for 85% or more of its acreage with chlorophenoxy herbicides. In the current study NHANES III data were reviewed for associations of 2,4-dichlorophenoxy acetic acid (2,4-D exposure, one of the most frequently used chlorophenoxy herbicides, with risk factors that are linked to the pathogenesis of acute myocardial infarction and type-2 diabetes, such as dyslipidemia and impaired glucose metabolism. Methods To investigate the toxicity pattern of chlorophenoxy herbicides, effects of a previous 2,4-D exposure were assessed by comparing levels of lipids, glucose metabolism, and thyroid stimulating hormone in healthy adult NHANES III subjects with urinary 2,4-D above and below the level of detection, using linear regression analysis. The analyses were conducted for all available subjects and for two susceptible subpopulations characterized by high glycosylated hemoglobin (upper 50th percentile and low thyroxine (lower 50th percentile. Results Presence of urinary 2,4-D was associated with a decrease of HDL levels: 8.6% in the unadjusted data (p-value = 0.006, 4.8% in the adjusted data (p-value = 0.08, and 9% in the adjusted data for the susceptible subpopulation with low thyroxine (p-value = 0.02. An effect modification of the inverse triglycerides-HDL relation was observed in association with 2,4-D. Among subjects with low HDL, urinary 2,4-D was associated with increased levels of triglycerides, insulin, C-peptide, and thyroid stimulating hormone, especially in the susceptible subpopulations. In contrast, subjects with

  8. Late tamoxifen in patients previously operated for breast cancer without postoperative tamoxifen: 5-year results of a single institution randomised study

    Directory of Open Access Journals (Sweden)

    Bidoli Ettore

    2010-05-01

    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusions This 5-year analysis revealed significantly less metachronous ER-positive breast cancers in the TAM treated patients. No other statistically

  9. 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

  10. Educational needs of inpatients with severe & persistent mental illness: a partial replication.

    Science.gov (United States)

    Burlingame, Gary M; Ridge, Nathanael; Matsuno, Joyce; Hwang, Anthony D; Earnshaw, Dallas

    2006-05-01

    Although a great deal has been written about the importance of patient education, few replications of past research have been conducted to increase clinicians' confidence in the conclusions of previous studies. This is especially true of studies conducted in clinical settings where findings may or may not be generalizable to other institutions. This partial replication study tested whether previous findings about patient education in an outpatient setting were applicable to an inpatient setting using a modified version of the instrument. A 1998 study published in this journal suggested that differences may exist between the perceived health education needs of outpatients and their health care providers. In this partial replication, we examined the differences between the educational needs of inpatients and those perceived by their attending nurses. As in the original study, we found discrepancies between patients' actual needs and nurses' perceptions of those needs, supporting the importance of assessing patients' health educational needs in the treatment planning process.

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

    Science.gov (United States)

    Krude, T; Knippers, R

    1994-08-19

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

  12. 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.

  13. 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.

  14. 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.

  15. Effects of testosterone replacement therapy on nocturia and quality of life in men with hypogonadism: a subanalysis of a previous prospective randomized controlled study in Japan.

    Science.gov (United States)

    Shigehara, Kazuyoshi; Konaka, Hiroyuki; Koh, Eitetsu; Izumi, Koji; Kitagawa, Yasuhide; Mizokami, Atsushi; Nakashima, Takao; Shimamura, Masayoshi; Iwamoto, Teruaki; Namiki, Mikio

    2015-01-01

    We investigated the effects of testosterone replacement therapy (TRT) on nocturia and general health among men with hypogonadism and nocturia. From our previous EARTH study population, 64 patients with a clinical diagnosis of nocturia (two or more times per one night) and hypogonadism, comprising the TRT group (n = 31) and controls (n = 33), were included in this analysis. The TRT group was administered 250 mg of testosterone enanthate as an intramuscular injection every 4 weeks for 6 months. All patients responded to the following questionnaires: International Prostatic Symptoms Score (IPSS), Aging Male Symptoms (AMS) score and Short Form-36 health survey at baseline and 6-month visit. These categories were compared based on changes from baseline to the 6-month visit between TRT and control groups. At the 6-month visit, the TRT group had a significant decrease in IPSS question no. 7 and AMS question no. 4, whereas no significant changes were observed in the control group. Additionally, role limitation because of health program, vitality and mental health domains were significantly improved in the TRT group. Six-month TRT may improve nocturia, sleep conditions and quality of life among men with hypogonadism and nocturia.

  16. Efficacy of confrontational counselling for smoking cessation in smokers with previously undiagnosed mild to moderate airflow limitation: study protocol of a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Huibers Marcus JH

    2007-11-01

    Full Text Available Abstract Background The use of spirometry for early detection of chronic obstructive pulmonary disease (COPD is still an issue of debate, particularly because of a lack of convincing evidence that spirometry has an added positive effect on smoking cessation. We hypothesise that early detection of COPD and confrontation with spirometry for smoking cessation may be effective when applying an approach we have termed "confrontational counselling"; a patient-centred approach which involves specific communication skills and elements of cognitive therapy. An important aspect is to confront the smoker with his/her airflow limitation during the counselling sessions. The primary objective of this study is to test the efficacy of confrontational counselling in comparison to regular health education and promotion for smoking cessation delivered by specialized respiratory nurses in current smokers with previously undiagnosed mild to moderate airflow limitation. Methods/Design The study design is a randomized controlled trial comparing confrontational counselling delivered by a respiratory nurse combined with nortriptyline for smoking cessation (experimental group, health education and promotion delivered by a respiratory nurse combined with nortriptyline for smoking cessation (control group 1, and "care as usual" delivered by the GP (control group 2. Early detection of smokers with mild to moderate airflow limitation is achieved by means of a telephone interview in combination with spirometry. Due to a comparable baseline risk of airflow limitation and motivation to quit smoking, and because of the standardization of number, duration, and scheduling of counselling sessions between the experimental group and control group 1, the study enables to assess the "net" effect of confrontational counselling. The study has been ethically approved and registered. Discussion Ethical as well as methodological considerations of the study are discussed in this protocol. A

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  18. Hepatitis B virus replication

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

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

  19. Ground-water quality in Geauga County, Ohio; review of previous studies, status in 1999, and comparison of 1986 and 1999 data

    Science.gov (United States)

    Jagucki, Martha L.; Darner, Robert A.

    2001-01-01

    Most residents in Geauga County, Ohio, rely on ground water as their primary source of drinking water. With population growing at a steady rate, the possibility that human activity will affect ground-water quality becomes considerable. This report presents the results of a study by the U.S. Geological Survey (USGS), in cooperation with the Geauga County Planning Commission and Board of County Commissioners, to provide a brief synopsis of work previously done within the county, to assess the present (1999) ground-water quality, and to determine any changes in ground-water quality between 1986 and 1999. Previous studies of ground-water quality in the county have consistently reported that manganese and iron concentrations in ground water in Geauga County often exceed the U.S. Environmental Protection Agency (USEPA) Secondary Maximum Contaminant Level (SMCL). Road salt and, less commonly, oil-field brines and volatile organic compounds (VOCs) have been found in ground water at isolated locations. Nitrate has not been detected above the USEPA Maximum Contaminant Level (MCL) of 10 milligrams per liter as N; however, nitrate has been found in some locations at levels that may indicate the effects of fertilizer application or effluent from septic systems. Between June 7 and July 1, 1999, USGS personnel collected a total of 31 water-quality samples from wells completed in glacial deposits, the Pottsville Formation, the Cuyahoga Group, and the Berea Sandstone. All samples were analyzed for VOCs, sulfide, dissolved organic carbon, major ions, trace elements, alkalinity, total coliforms, and Escherichia coli bacteria. Fourteen of the samples also were analyzed for tritium. Water-quality data were used to determine (1) suitability of water for drinking, (2) age of ground water, (3) stratigraphic variation in water quality, (4) controls on water quality, and (5) temporal variation in water quality. Water from 16 of the 31 samples exceeded the Geauga County General Health

  20. Distribution of interferon lambda-3 gene polymorphisms in Australian patients with previously untreated genotype 1 chronic hepatitis C: Analysis from the PREDICT and CHARIOT studies.

    Science.gov (United States)

    Roberts, Stuart K; Mitchell, Joanne; Leung, Reynold; Booth, David; Bollipo, Steven; Ostapowicz, George; Sloss, Andrew; McCaughan, Geoffrey W; Dore, Gregory J; Thompson, Alexander; Crawford, Darrell Hg; Sievert, William; Weltman, Martin; Cheng, Wendy; George, Jacob

    2014-01-01

    The aim of this study was to examine the distribution of interferon lambda-3 (IFN-λ3) gene polymorphisms in previously untreated Australian patients with genotype 1 (Gt1) chronic hepatitis C (CHC) and to compare the IFN-λ3 genotype frequency among the different ethnic populations. This was a prospective, multicenter, observational study undertaken by the Australian Liver Association Clinical Research Network. Eligible subjects had Gt1 CHC and were being considered for and/or undergoing treatment. IFN-λ3 single nucleotide polymorphisms were genotyped by the Applied Biosystems's Taqman single nucleotide polymorphism genotyping assay. Between May 2012 and June 2012, 1132 patients were recruited from 38 treatment clinics across Australia. Also, 561 subjects from the CHARIOT (collaborative group hepatitis C study using high dose Pegasys RBV Induction dose in genotype one) study of high-dose interferon who had baseline serum available were retrospectively tested. The overall frequency of IFN-λ3 rs12979860 CC/CT/TT genotypes was 36%, 52%, and 12%, and that of rs8099917 TT/TG/GG genotypes was 54%, 41%, and 5%, respectively. The prevalence of the favorable IFN-λ3 rs12979860 CC and rs8099917 TT genotypes in Causcasians, Asians, Aboriginals, Maori/Pacific Islanders, and Mediterraneans was 32% and 52%, 80% and 86%, 33% and 63%, 77% and 88%, and 19% and 29%, respectively. Compared with Caucasians, the frequency of IFN-λ3 CC was significantly higher among Asians (P < 0.0001) and Maori/Pacific Islander subjects (P < 0.0001). The distribution of IFN-λ3 polymorphisms among untreated patients with Gt1 CHC in Australia appears similar to that reported from North America. The frequency of the favorable response alleles varies considerably according to ethnicity, being more common in self-reported Asians and Maori/Pacific Islanders than Caucasians, Aboriginals, and Mediterraneans. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty

  1. Epistatic interaction of ERAP1 and HLA-B in Behcet disease: a replication study in the Spanish population.

    Directory of Open Access Journals (Sweden)

    Marta Conde-Jaldón

    Full Text Available Behçet's disease (BD is a multifactorial disorder associated with the HLA region. Recently, the ERAP1 gene has been proposed as a susceptibility locus with a recessive model and with epistatic interaction with HLA-B51. ERAP1 trims peptides in the endoplasmic reticulum to optimize their length for MHC-I binding. Polymorphisms in this gene have been related with the susceptibility to other immune-mediated diseases associated to HLA class I. Our aim was, the replication in the Spanish population of the association described in the Turkish population between ERAP1 (rs17482078 and BD. Additionally, in order to improve the understanding of this association we analyzed four additional SNPs (rs27044, rs10050860, rs30187 and rs2287987 associated with other diseases related to HLA class I and the haplotype blocks in this gene region. According to our results, frequencies of the homozygous genotypes for the minor alleles of all the SNPs were increased among patients and the OR values were higher in the subgroup of patients with the HLA-B risk factors, although differences were not statistically significant. Moreover, the presence of the same mutation in both chromosomes increased the OR values from 4.51 to 10.72 in individuals carrying the HLA-B risk factors. Therefore, although they were not statistically significant, our data were consistent with an association between ERAP1 and BD as well as with an epistatic interaction between ERAP1 and HLA-B in the Spanish population.

  2. Psychology, replication & beyond.

    Science.gov (United States)

    Laws, Keith R

    2016-06-01

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

  3. 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,…

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

    Science.gov (United States)

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

    2015-05-27

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

  5. Replication banding and molecular studies of a mosaic, unbalanced dic(X;15)(Xpter {yields} Xq26.1::15p11 {yields} 15qter)

    Energy Technology Data Exchange (ETDEWEB)

    Scheuerle, A.; Ledbetter, D.H.; Greenberg, F. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1995-05-08

    We present a patient with a chromosomal mosaicism involving the X chromosome. One cell line is 45,X and the other has a de novo paternally derived dicentric X;15 translocation. Her karyotype is therefore 45,X/45,X,dic(X;15)(Xpter {yields} Xq26.1::15p11 {yields} 15qter) based on G-banding. The presence of 2 centromeres on the derivative X was confirmed by fluorescence in situ hybridization (FISH) and a deletion of Xq26.1 {yields} qter was confirmed by polymerase chain reaction (PCR) using DXS52 and DXYS154. Replication banding studies indicate that the derivative X is late replicating. Based on these studies, it is unclear whether inactivation has spread to proximal 15q. The patient has a unique phenotype distinct from Ullrich-Turner or Prader-Willi syndromes, but includes ataxia and language delay which are commonly seen in Angelman syndrome. These findings are contrary to those anticipated since deficiency of paternal genes at 15q12 typically leads to Prader-Willi syndrome. Molecular analysis of PCR-based polymorphisms of chromosomes 15 and X indicates that uniparental disomy is not present for the X chromosome or chromosome 15 in either cell line. It is hypothesized that her phenotype results from the interaction of the 2 abnormal genotypes. Each abnormality may be diluted by the mosaicism and, in the derivative X line, by the possible variation among cells of inactivation spreading to chromosome 15. 18 refs., 6 figs., 1 tab.

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

    Science.gov (United States)

    Wu, LiHong; Liu, Yang; Kong, DaoChun

    2014-05-01

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

  7. 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. PMID:28036377

  8. 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.

  9. 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

  10. Geographic differences in genetic susceptibility to IgA nephropathy: GWAS replication study and geospatial risk analysis.

    Directory of Open Access Journals (Sweden)

    Krzysztof Kiryluk

    Full Text Available IgA nephropathy (IgAN, major cause of kidney failure worldwide, is common in Asians, moderately prevalent in Europeans, and rare in Africans. It is not known if these differences represent variation in genes, environment, or ascertainment. In a recent GWAS, we localized five IgAN susceptibility loci on Chr.6p21 (HLA-DQB1/DRB1, PSMB9/TAP1, and DPA1/DPB2 loci, Chr.1q32 (CFHR3/R1 locus, and Chr.22q12 (HORMAD2 locus. These IgAN loci are associated with risk of other immune-mediated disorders such as type I diabetes, multiple sclerosis, or inflammatory bowel disease. We tested association of these loci in eight new independent cohorts of Asian, European, and African-American ancestry (N = 4,789, followed by meta-analysis with risk-score modeling in 12 cohorts (N = 10,755 and geospatial analysis in 85 world populations. Four susceptibility loci robustly replicated and all five loci were genome-wide significant in the combined cohort (P = 5×10⁻³²-3×10⁻¹⁰, with heterogeneity detected only at the PSMB9/TAP1 locus (I² = 0.60. Conditional analyses identified two new independent risk alleles within the HLA-DQB1/DRB1 locus, defining multiple risk and protective haplotypes within this interval. We also detected a significant genetic interaction, whereby the odds ratio for the HORMAD2 protective allele was reversed in homozygotes for a CFHR3/R1 deletion (P = 2.5×10⁻⁴. A seven-SNP genetic risk score, which explained 4.7% of overall IgAN risk, increased sharply with Eastward and Northward distance from Africa (r = 0.30, P = 3×10⁻¹²⁸. This model paralleled the known East-West gradient in disease risk. Moreover, the prediction of a South-North axis was confirmed by registry data showing that the prevalence of IgAN-attributable kidney failure is increased in Northern Europe, similar to multiple sclerosis and type I diabetes. Variation at IgAN susceptibility loci correlates with differences in disease prevalence

  11. The influence of previous and concomitant leflunomide on the efficacy and safety of infliximab therapy in patients with rheumatoid arthritis; a longitudinal observational study.

    NARCIS (Netherlands)

    Flendrie, M.; Creemers, M.C.W.; Welsing, P.M.J.; Riel, P.L.C.M. van

    2005-01-01

    OBJECTIVE: To investigate the influence of previous and concomitant leflunomide on the efficacy and safety of infliximab therapy in rheumatoid arthritis (RA) and to compare it to infliximab in combination with other disease-modifying anti-rheumatic drugs. METHODS: RA patients starting infliximab the

  12. Erlotinib dosing-to-rash: A phase II intrapatient dose escalation and pharmacologic study of erlotinib in previously treated advanced non-small cell lung cancer

    NARCIS (Netherlands)

    A. mita (Alain); K. Papadopoulos (K.); M.J.A. de Jonge (Maja); G. Schwartz (G.); J. Verweij (Jaap); A. Ricart (A.); Q.S.C. Chu (Q. S C); A.W. Tolcher (A. W.); L. Wood (Lori); S.W. McCarthy (Stanley); M. Hamilton; K.K. Iwata (Kenneth); B. Wacker; K. de Witte (Karel); E.K. Rowinsky (Eric Keith)

    2011-01-01

    textabstractBackground: To evaluate the anticancer activity of erlotinib in patients with previously treated, advanced non-small cell lung cancer (NSCLC) whose dose is increased to that associated with a maximal level of tolerable skin toxicity (i.e., target rash (TR)); to characterise the pharmacok

  13. Phase I study of cisplatin, hyperthermia, and lapatinib in patients with recurrent carcinoma of the uterine cervix in a previously irradiated area

    NARCIS (Netherlands)

    E.V. Meerten (Esther Van); M. Franckena (Martine); E.A.C. Wiemer (Erik); L.V. Doorn (Lena Van); J. Kraan (Jaco); A.M. Westermann (Anneke); S. Sleijfer (Stefan)

    2015-01-01

    textabstractBackground. Patients with recurrent cervical cancer in a previously irradiated area might benefit from cisplatin combined with hyperthermia. Lapatinib inhibits the intracellular tyrosine kinase domain of the epidermal growth factor receptor (EGFR) and HER2. Overexpression of EGFR and

  14. Impact of previous percutaneous transluminal coronary angioplasty and/or stenting revascularization on outcomes after surgical revascularization : insights from the imagine study

    NARCIS (Netherlands)

    Chocron, Sidney; Baillot, Richard; Rouleau, Jean Lucien; Warnica, Wayne J.; Block, Pierre; Johnstone, David; Myers, Martin G.; Calciu, Cristina Dana; Nozza, Anna; Martineau, Pierre; van Gilst, Wiek H.

    2008-01-01

    Aim To determine the impact of previous coronary artery revascularization by percutaneous transluminal coronary angioplasty and/or stenting (PCI) on outcome after subsequent coronary artery bypass grafting (CABG). Methods and results The ischaemia management with Accupril post-bypass Graft via Inhib

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

    Science.gov (United States)

    Brassinga, A K; Marczynski, G T

    2001-11-01

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

  16. 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.

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

    Science.gov (United States)

    Breen, Michael; Nogales, Aitor; Baker, Steven F; Perez, Daniel R; Martínez-Sobrido, Luis

    2016-01-01

    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.

  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. Effects of DNA replication on mRNA noise.

    Science.gov (United States)

    Peterson, Joseph R; Cole, John A; Fei, Jingyi; Ha, Taekjip; Luthey-Schulten, Zaida A

    2015-12-29

    There are several sources of fluctuations in gene expression. Here we study the effects of time-dependent DNA replication, itself a tightly controlled process, on noise in mRNA levels. Stochastic simulations of constitutive and regulated gene expression are used to analyze the time-averaged mean and variation in each case. The simulations demonstrate that to capture mRNA distributions correctly, chromosome replication must be realistically modeled. Slow relaxation of mRNA from the low copy number steady state before gene replication to the high steady state after replication is set by the transcript's half-life and contributes significantly to the shape of the mRNA distribution. Consequently both the intrinsic kinetics and the gene location play an important role in accounting for the mRNA average and variance. Exact analytic expressions for moments of the mRNA distributions that depend on the DNA copy number, gene location, cell doubling time, and the rates of transcription and degradation are derived for the case of constitutive expression and subsequently extended to provide approximate corrections for regulated expression and RNA polymerase variability. Comparisons of the simulated models and analytical expressions to experimentally measured mRNA distributions show that they better capture the physics of the system than previous theories.

  20. DNA replication origins in archaea

    OpenAIRE

    Zhenfang eWu; Jingfang eLiu; Haibo eYang; Hua eXiang

    2014-01-01

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

  1. Clinical evaluation of recombinant factor VIII preparation (Kogenate) in previously treated patients with hemophilia A: descriptive meta-analysis of post-marketing study data.

    Science.gov (United States)

    Yoshioka, A; Fukutake, K; Takamatsu, J; Shirahata, A

    2006-08-01

    The safety and efficacy of Kogenate, a recombinant factor VIII (rFVIII) preparation for the treatment of bleeding episodes, were studied in a 123-patient meta-analysis population of previously treated patients (PTPs), including 15 enrolled in the registration Phase III trial (PTP-I group), 93 from the post-marketing special investigation (PTP-II group), and 15 from short-term special investigations in surgery or tooth extraction (SI group). These patients (82 severe, 31 moderate, 9 mild, and 1 unknown), aged 11 months to 72 years, were enrolled in 28 centers in Japan. Blood samples taken at the baseline and at 3, 6, 9, 12, 18, and 24 months after the introduction of Kogenate were evaluated for FVIII inhibitor antibodies, antibodies formed against trace proteins derived from the rFVIII production process, and for general changes in laboratory test results. Mean exposure to Kogenate was 1103 days in PTP-I, 86 days in PTP-II, 27 days in patients in surgery, and 2 days in patients with tooth extraction. Assessment of FVIII inhibitor activity was conducted in 115 of the 123 patients by means of the Bethesda assay. Twelve patients were found to have a low titer of FVIII inhibitor (0.5-3.0 BU/mL) prior to any administration of Kogenate, and 103 were inhibitor-negative at the baseline. Among this latter group, 3 patients (2.9%) tested inhibitor-positive, with titers ranging from 1.2 to 2.1 BU/mL, with 4 patients below 1.0 BU/mL. One patient in the 11 PTPs investigated (PTP-I) developed antibodies against baby hamster kidney protein and mouse immunoglobulin G, but these findings were transient and asymptomatic. Hemostasis was achieved (markedly effective or effective) in 3666 of the 3855 bleeding episodes (95.1%) observed in 108 patients. Only 1 infusion was necessary in 3790 (98.3%) of these episodes. These data indicate that Kogenate is safe and very effective for the treatment of bleeding in PTPs with hemophilia A.

  2. Replication-Fork Dynamics

    NARCIS (Netherlands)

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

    2014-01-01

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

  3. Coronavirus Attachment and Replication

    Science.gov (United States)

    1988-03-28

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

  4. Flow cytometric analysis of the inhibition of human basophil activation by histamine high dilutions – a replication study

    Directory of Open Access Journals (Sweden)

    Chantal Wälchli

    2012-09-01

    Full Text Available Background: Inhibition of human basophil activation by highly diluted histamine was reported to be a reliable experimental model to examine biological effects of high dilutions. However, independent replications did not always yield concordant results. Aims: We aimed at performing an independent replication of a former study [1] using rigorously controlled experimental conditions to minimise confounding factors. Materials and Methods: In 20 independent experiments, human basophils were treated with highly diluted histamine (15cH, 16cH, corresponding to 10-30-10-32 M prior to activation by fMLP (formyl-methionyl-leucyl-phenylalanine peptide. Controls were treated with analogously diluted water (15cH, 16cH. The dilutions were prepared freshly for each experiment in deionised water by successive steps of centesimal dilution and agitation (10 s vortex at high speed. Highly diluted samples were blinded and randomised. All samples were set in triplicates. Activated basophils were determined by flow cytometry using anti-CD203c. 20 independent systematic negative control (SNC experiments were carried out to investigate possible systematic errors. Results: No difference in basophil activation was observed between the highly diluted histamine samples and the highly diluted water controls. There was no evidence for a blood donor specificity of the results. The SNC experiments demonstrated the stability of the test system. Experimental variability within and between experiments was slightly reduced for the highly diluted histamine samples. Discussion: This study was designed as an independent reproduction of a former study [1]. Though we strictly adopted the experimental procedure described in [1], our results do not confirm the large inhibitory effects observed for histamine 15cH and 16cH. This lack of reproducibility might be due to minor differences in the experimental design, such as blinding and randomising of the samples, which we chose to

  5. Role of preterminal protein processing in adenovirus replication.

    Science.gov (United States)

    Webster, A; Leith, I R; Nicholson, J; Hounsell, J; Hay, R T

    1997-09-01

    Preterminal protein (pTP), the protein primer for adenovirus DNA replication, is processed at two sites by the virus-encoded protease to yield mature terminal protein (TP). Here we demonstrate that processing to TP, via an intermediate (iTP), is conserved in all serotypes sequenced to date; and in determining the sites cleaved in Ad4 pTP, we extend the previously published substrate specificity of human adenovirus proteases to include a glutamine residue at P4. Furthermore, using monoclonal antibodies raised against pTP, we show that processing to iTP and TP are temporally separated in the infectious cycle, with processing to iTP taking place outside the virus particles. In vitro and in vivo studies of viral DNA replication reveal that iTP can act as a template for initiation and elongation and argue against a role for virus-encoded protease in switching off DNA replication. Virus DNA with TP attached to its 5' end (TP-DNA) has been studied extensively in in vitro DNA replication assays. Given that in vivo pTP-DNA, not TP-DNA, is the template for all but the first round of replication, the two templates were compared in vitro and shown to have different properties. Immunofluorescence studies suggest that a region spanning the TP cleavage site is involved in defining the subnuclear localization of pTP. Therefore, a likely role for the processing of pTP-DNA is to create a distinct template for early transcription (TP-DNA), while the terminal protein moiety, be it TP or pTP, serves to guide the template to the appropriate subcellular location through the course of infection.

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

    Directory of Open Access Journals (Sweden)

    Camilla H Andreasen

    Full Text Available BACKGROUND: 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 variants in FTO (rs9939609 and near MC4R (rs17782313 as genetic risk factors. MATERIALS AND METHODS: The four variants were genotyped in a combined study sample comprising a total of 18,014 subject ascertained from, the population-based Inter99 cohort (n = 6,514, the ADDITION screening cohort (n = 8,662, a population-based study sample (n = 680 and a type 2 diabetic patient group (n = 2,158 from Steno Diabetes Center. RESULTS: No association with overweight, obesity or obesity-related measures was shown for either the INSIG2 rs7566605 or the PFKP rs6602024 variants. However, an interaction between the INSIG2 rs7566605 variant and the level of self-reported physical activity (p(Int = 0.004 was observed. A BMI difference of 0.53 (SE 0.42 kg/m(2 was found when comparing physically passive homozygous C-allele carriers with physically passive G-allele carriers. No interactions between the two variants and FTO rs9939609 and MC4R rs17782313 were observed. CONCLUSIONS: The INSIG2 rs7566605 and PFKP rs6602024 polymorphisms play no apparent role in the development of common forms of obesity in the Danish population. However, if replicated, the INSIG2 rs7566605 may influence the level of BMI in combination with the level of physical activity.

  7. 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.

  8. A cross-sectional study of 'yaws' in districts of Ghana which have previously undertaken azithromycin mass drug administration for trachoma control.

    Science.gov (United States)

    Ghinai, Rosanna; El-Duah, Philip; Chi, Kai-Hua; Pillay, Allan; Solomon, Anthony W; Bailey, Robin L; Agana, Nsiire; Mabey, David C W; Chen, Cheng-Yen; Adu-Sarkodie, Yaw; Marks, Michael

    2015-01-01

    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.

  9. 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

    % confidence intervals): 1.32 (1.24-1.40), glibenclamide: 1.19 (1.11-1.28), glipizide: 1.27 (1.17-1.38), and tolbutamide: 1.28 (1.17-1.39) were associated with increased all-cause mortality in patients without previous MI. The corresponding results for patients with previous MI were as follows: glimepiride: 1.......30 (1.11-1.44), glibenclamide: 1.47 (1.22-1.76), glipizide: 1.53 (1.23-1.89), and tolbutamide: 1.47 (1.17-1.84). Results for gliclazide [1.05 (0.94-1.16) and 0.90 (0.68-1.20)] and repaglinide and [0.97 (0.81-1.15) and 1.29 (0.86-1.94)] were not statistically different from metformin in both patients...... without and with previous MI, respectively. Results were similar for cardiovascular mortality and for the composite endpoint. Conclusion Monotherapy with the most used ISs, including glimepiride, glibenclamide, glipizide, and tolbutamide, seems to be associated with increased mortality and cardiovascular...

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

    Science.gov (United States)

    Nakagawa, Shinichi; Parker, Timothy H

    2015-10-28

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

  11. Nicotinic acetylcholine receptor subunit variants are associated with blood pressure; findings in the Old Order Amish and replication in the Framingham Heart Study

    Directory of Open Access Journals (Sweden)

    Ott Sandy

    2008-07-01

    Full Text Available Abstract Background Systemic blood pressure, influenced by both genetic and environmental factors, is regulated via sympathetic nerve activity. We assessed the role of genetic variation in three subunits of the neuromuscular nicotinic acetylcholine receptor positioned on chromosome 2q, a region showing replicated evidence of linkage to blood pressure. Methods We sequenced CHRNA1, CHRND and CHRNG in 24 Amish subjects from the Amish Family Diabetes Study (AFDS and identified 20 variants. We then performed association analysis of non-redundant variants (n = 12 in the complete AFDS cohort of 1,189 individuals, and followed by genotyping blood pressure-associated variants (n = 5 in a replication sample of 1,759 individuals from the Framingham Heart Study (FHS. Results The minor allele of a synonymous coding SNP, rs2099489 in CHRNG, was associated with higher systolic blood pressure in both the Amish (p = 0.0009 and FHS populations (p = 0.009 (minor allele frequency = 0.20 in both populations. Conclusion CHRNG is currently thought to be expressed only during fetal development. These findings support the Barker hypothesis, that fetal genotype and intra-uterine environment influence susceptibility to chronic diseases later in life. Additional studies of this variant in other populations, as well as the effect of this variant on acetylcholine receptor expression and function, are needed to further elucidate its potential role in the regulation of blood pressure. This study suggests for the first time in humans, a possible role for genetic variation in the neuromuscular nicotinic acetylcholine receptor, particularly the gamma subunit, in systolic blood pressure regulation.

  12. Multifork chromosome replication in slow-growing bacteria

    Science.gov (United States)

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

    2017-01-01

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

  13. Replication of a rare protective allele in the noradrenaline transporter gene and ADHD

    NARCIS (Netherlands)

    Xu, X.; Hawi, Z.; Brookes, K.J.; Anney, R.; Bellgrove, M.; Franke, B.; Barry, E.; Chen, W.; Kuntsi, J.; Banaschewski, T.; Buitelaar, J.K.; Ebstein, R.; Fitzgerald, M.; Miranda, A.; Oades, R.D.; Roeyers, H.; Rothenberger, A.; Sergeant, J.A.; Sonuga-Barke, E.; Steinhausen, H.C.; Faraone, S.V.; Gill, M.; Asherson, P.

    2008-01-01

    Replication is a key to resolving whether a reported genetic association represents a false positive finding or an actual genetic risk factor. In a previous study screening 51 candidate genes for association with ADHD in a multi-centre European sample (the IMAGE project), two single nucleotide polym

  14. The Item Parameter Replication Method for Detecting Differential Functioning in the Polytomous DFIT Framework

    Science.gov (United States)

    Raju, Nambury S.; Fortmann-Johnson, Kristen A.; Kim, Wonsuk; Morris, Scott B.; Nering, Michael L.; Oshima, T. C.

    2009-01-01

    The recent study of Oshima, Raju, and Nanda proposes the item parameter replication (IPR) method for assessing statistical significance of the noncompensatory differential item functioning (NCDIF) index within the differential functioning of items and tests (DFIT) framework. Previous Monte Carlo simulations have found that the appropriate cutoff…

  15. Reversible Switching of Cooperating Replicators

    Science.gov (United States)

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

    2017-02-01

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

  16. Targeting DNA Replication Stress for Cancer Therapy

    Science.gov (United States)

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

    2016-01-01

    The human cellular genome is under constant stress from extrinsic and intrinsic factors, which can lead to DNA damage and defective replication. In normal cells, DNA damage response (DDR) mediated by various checkpoints will either activate the DNA repair system or induce cellular apoptosis/senescence, therefore maintaining overall genomic integrity. Cancer cells, however, due to constitutive growth signaling and defective DDR, may exhibit “replication stress” —a phenomenon unique to cancer cells that is described as the perturbation of error-free DNA replication and slow-down of DNA synthesis. Although replication stress has been proven to induce genomic instability and tumorigenesis, recent studies have counterintuitively shown that enhancing replicative stress through further loosening of the remaining checkpoints in cancer cells to induce their catastrophic failure of proliferation may provide an alternative therapeutic approach. In this review, we discuss the rationale to enhance replicative stress in cancer cells, past approaches using traditional radiation and chemotherapy, and emerging approaches targeting the signaling cascades induced by DNA damage. We also summarize current clinical trials exploring these strategies and propose future research directions including the use of combination therapies, and the identification of potential new targets and biomarkers to track and predict treatment responses to targeting DNA replication stress. PMID:27548226

  17. 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.

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

    Directory of Open Access Journals (Sweden)

    Nathan Donley

    2015-01-01

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

  19. 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.

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

    Science.gov (United States)

    Stroebe, Wolfgang; Strack, Fritz

    2014-01-01

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

  1. Chromatin replication and epigenome maintenance

    DEFF Research Database (Denmark)

    Alabert, Constance; Groth, Anja

    2012-01-01

    initiates, whereas the replication process itself disrupts chromatin and challenges established patterns of genome regulation. Specialized replication-coupled mechanisms assemble new DNA into chromatin, but epigenome maintenance is a continuous process taking place throughout the cell cycle. If DNA...

  2. Chromatin replication and epigenome maintenance

    DEFF Research Database (Denmark)

    Alabert, Constance; Groth, Anja

    2012-01-01

    initiates, whereas the replication process itself disrupts chromatin and challenges established patterns of genome regulation. Specialized replication-coupled mechanisms assemble new DNA into chromatin, but epigenome maintenance is a continuous process taking place throughout the cell cycle. If DNA...

  3. Type A-B scores and insomnia among college students: a replication and extension of earlier studies.

    Science.gov (United States)

    Hayer, C A; Hicks, R A

    1993-12-01

    In an attempt to rationalize conflicting sets of data from earlier studies, groups of Type A- and Type B-classified university students were asked to respond to a sleep habits questionnaire that included the items of the Coren Insomnia Scale. As was the case in two earlier studies, we found significant but weak evidence from the Coren scale only that Type A-scoring students experience more sleep problems than Type B scorers. We also found, as in a recent study, a sharp increase in sleep problems among all the students sampled from the frequencies reported by similar groups in 1982.

  4. Replicator-dynamics models of sexual conflict.

    Science.gov (United States)

    Kimura, Mariko; Ihara, Yasuo

    2009-09-07

    Evolutionary conflict between the sexes has been studied in various taxa and in various contexts. When the sexes are in conflict over mating rates, natural selection favors both males that induce higher mating rates and females that are more successful at resisting mating attempts. Such sexual conflict may result in an escalating coevolutionary arms race between males and females. In this article, we develop simple replicator-dynamics models of sexual conflict in order to investigate its evolutionary dynamics. Two specific models of the dependence of a female's fitness on her number of matings are considered: in model 1, female fitness decreases linearly with increasing number of matings and in model 2, there is an optimal number of matings that maximizes female fitness. For each of these models, we obtain the conditions for a coevolutionary process to establish costly male and female traits and examine under what circumstances polymorphism is maintained at equilibrium. Then we discuss how assumptions in previous models of sexual conflict are translated to fit to our model framework and compare our results with those of the previous studies. The simplicity of our models allows us to consider sexual conflict in various contexts within a single framework. In addition, we find that our model 2 shows more complicated evolutionary dynamics than model 1. In particular, the population exhibits bistability, where the evolutionary outcome depends on the initial state, only in model 2.

  5. On the association between loneliness and bathing habits: nine replications of Bargh and Shalev (2012) Study 1.

    Science.gov (United States)

    Donnellan, M Brent; Lucas, Richard E; Cesario, Joseph

    2015-02-01

    Bargh and Shalev (2012) hypothesized that people use warm showers and baths to compensate for a lack of social warmth. As support for this idea, they reported results from two studies that found an association between trait loneliness and bathing habits. Given the potential practical and theoretical importance of this association, we conducted nine additional studies on this topic. Using our own bathing or showering measures and the most current version of the UCLA Loneliness Scale (Russell, 1996), we found no evidence for an association between trait loneliness and a composite index of showering or bathing habits in a combined sample of 1,153 participants from four studies. Likewise, the aggregated effect size estimate was not statistically significant using the same measures as the original studies in a combined sample of 1,920 participants from five studies. A local meta-analysis including the original studies yielded an effect size estimate for the composite that included zero in the 95% confidence interval. The current results therefore cast doubt on the idea of a strong connection between trait loneliness and personal bathing habits related to warmth.

  6. 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...

  7. A RAPD based study revealing a previously unreported wide range of mesophilic and thermophilic spore formers associated with milk powders in China.

    Science.gov (United States)

    Sadiq, Faizan A; Li, Yun; Liu, TongJie; Flint, Steve; Zhang, Guohua; He, GuoQing

    2016-01-18

    Aerobic spore forming bacteria are potential milk powder contaminants and are viewed as indicators of poor quality. A total of 738 bacteria, including both mesophilic and thermophilic, isolated from twenty-five powdered milk samples representative of three types of milk powders in China were analyzed based on the random amplified polymorphic DNA (RAPD) protocol to provide insight into species diversity. Bacillus licheniformis was found to be the most prevalent bacterium with greatest diversity (~43% of the total isolates) followed by Geobacillus stearothermophilus (~21% of the total isolates). Anoxybacillus flavithermus represented only 8.5% of the total profiles. Interestingly, actinomycetes represented a major group of the isolates with the predominance of Laceyella sacchari followed by Thermoactinomyces vulgaris, altogether comprising of 7.3% of the total isolates. Out of the nineteen separate bacterial species (except five unidentified groups) recovered and identified from milk powders, twelve proved to belong to novel or previously unreported species in milk powders. Assessment and characterization of the harmful effects caused by this particular micro-flora on the quality and safety of milk powders will be worth doing in the future.

  8. Update of the pompe disease mutation database with 60 novel GAA sequence variants and additional studies on the functional effect of 34 previously reported variants.

    Science.gov (United States)

    Kroos, Marian; Hoogeveen-Westerveld, Marianne; Michelakakis, Helen; Pomponio, Robert; Van der Ploeg, Ans; Halley, Dicky; Reuser, Arnold

    2012-08-01

    Pompe disease is an autosomal recessive lysosomal glycogen storage disorder, characterized by progressive muscle weakness. Deficiency of acid α-glucosidase (EC; 3.2.1.20/3) can be caused by numerous pathogenic variants in the GAA gene. The Pompe Disease Mutation Database at http://www.pompecenter.nl aims to list all variants and their effect. This update reports on 94 variants. We examined 35 novel and 34 known mutations by site-directed mutagenesis and transient expression in COS-7 cells or HEK293T cells. Each of these mutations was given a severity rating using a previously published system, based on the level of acid α-glucosidase activity in medium and transfected cells and on the quantity and quality of the different molecular mass species in the posttranslational modification and transport of acid α-glucosidase. This approach enabled to classify 55 missense mutations as pathogenic and 13 as likely nonpathogenic. Based on their nature and the use of in silico analysis (Alamut® software), 12 of the additional 25 novel mutations were predicted to be pathogenic including 4 splicing mutations, 6 mutations leading to frameshift, and 2 point mutations causing stop codons. Seven of the additional mutations were considered nonpathogenic (4 silent and 3 occurring in intron regions), and 6 are still under investigation.

  9. 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.

  10. No Previous Public Services Required

    Science.gov (United States)

    Taylor, Kelley R.

    2009-01-01

    In 2007, the Supreme Court heard a case that involved the question of whether a school district could be required to reimburse parents who unilaterally placed their child in private school when the child had not previously received special education and related services in a public institution ("Board of Education v. Tom F."). The…

  11. Spacetime replication of continuous variable quantum information

    Science.gov (United States)

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

    2016-08-01

    The theory of relativity requires that no information travel faster than light, whereas the unitarity of quantum mechanics ensures that quantum information cannot be cloned. These conditions provide the basic constraints that appear in information replication tasks, which formalize aspects of the behavior of information in relativistic quantum mechanics. In this article, we provide continuous variable (CV) strategies for spacetime quantum information replication that are directly amenable to optical or mechanical implementation. We use a new class of homologically constructed CV quantum error correcting codes to provide efficient solutions for the general case of information replication. As compared to schemes encoding qubits, our CV solution requires half as many shares per encoded system. We also provide an optimized five-mode strategy for replicating quantum information in a particular configuration of four spacetime regions designed not to be reducible to previously performed experiments. For this optimized strategy, we provide detailed encoding and decoding procedures using standard optical apparatus and calculate the recovery fidelity when finite squeezing is used. As such we provide a scheme for experimentally realizing quantum information replication using quantum optics.

  12. 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

  13. Abstract or Concrete Examples in Learning Mathematics? A Replication and Elaboration of Kaminski, Sloutsky, and Heckler's Study

    Science.gov (United States)

    De Bock, Dirk; Deprez, Johan; Van Dooren, Wim; Roelens, Michel; Verschaffel, Lieven

    2011-01-01

    Kaminski, Sloutsky, and Heckler (2008a) published in "Science" a study on "The advantage of abstract examples in learning math," in which they claim that students may benefit more from learning mathematics through a single abstract, symbolic representation than from multiple concrete examples. This publication elicited both enthusiastic and…

  14. 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.

  15. The Association between Short Periods of Everyday Life Activities and Affective States: A Replication Study Using Ambulatory Assessment.

    Science.gov (United States)

    Bossmann, Thomas; Kanning, Martina; Koudela-Hamila, Susanne; Hey, Stefan; Ebner-Priemer, Ulrich

    2013-01-01

    Regularly conducted exercise programs effectively influence affective states. Studies suggest that this is also true for short bouts of physical activity (PA) of 10 min 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 PA and affective states during the course of 1 day. Seventy-seven students ages 19-30 participated in the study. PA 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 = 0.001) and valence (p = 0.005) were positively influenced by the intensity of the activity carried out in the 10-min 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 min or less into everyday life routines to improve affective states.

  16. Providing Visions of a Different Life: Self-study Narrative Inquiry as an Instrument for Seeing Ourselves in Previously-Unimagined Places

    Directory of Open Access Journals (Sweden)

    Carmen Shields

    2011-01-01

    Full Text Available In this paper, we share stories of coming to narrative self-study research in graduate studies, and the impact this choice has had on personal and professional directions in ways we could not have imagined when graduate studies were initially embarked upon. Central to self-study narrative inquiry is a focus on life experience as a tool for connection with our own storied pasts. There we find the roots of our present-day perspectives and actions that we can incorporate into our everyday meaning-making, using our emergent understanding to choose present and future possibilities in our relationships.

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

    Science.gov (United States)

    Hang, Lisa; Zhao, Xiaolan

    2016-07-03

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

  18. Control of chromosome replication in caulobacter crescentus.

    Science.gov (United States)

    Marczynski, Gregory T; Shapiro, Lucy

    2002-01-01

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

  19. Within- and between-session replicability of cognitive brain processes: An MEG study with an N-back task.

    Science.gov (United States)

    Ahonen, L; Huotilainen, M; Brattico, E

    2016-05-01

    In the vast majority of electrophysiological studies on cognition, participants are only measured once during a single experimental session. The dearth of studies on test-retest reliability in magnetoencephalography (MEG) within and across experimental sessions is a preventing factor for longitudinal designs, imaging genetics studies, and clinical applications. From the recorded signals, it is not straightforward to draw robust and steady indices of brain activity that could directly be used in exploring behavioral effects or genetic associations. To study the variations in markers associated with cognitive functions, we extracted three event-related field (ERF) features from time-locked global field power (GFP) epochs using MEG while participants were performing a numerical N-back task in four consecutive measurements conducted during two different days separated by two weeks. We demonstrate that the latency of the M170, a neural correlate associated with cognitive functions such as working memory, was a stable parameter and did not show significant variations over time. In addition, the M170 peak amplitude and the mean amplitude of late positive component (LPP) also expressed moderate-to-strong reliability across multiple measures over time over many sensor spaces and between participants. The M170 amplitude varied more significantly between the measurements in some conditions but showed consistency over the participants over time. In addition we demonstrated significant correlation with the M170 and LPP parameters and cognitive load. The results are in line with the literature showing less within-subject fluctuation for the latency parameters and more consistency in between-subject comparisons for amplitude based features. The within-subject consistency was apparent also with longer delays between the measurements. We suggest that with a few limitations the ERF features show sufficient reliability and stability for longitudinal research designs and clinical

  20. HIV-1 Vpr increases HCV replication through VprBP in cell culture.

    Science.gov (United States)

    Yan, Yanling; Huang, Fang; Yuan, Ting; Sun, Binlian; Yang, Rongge

    2016-09-02

    Coinfection of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) occurs at a high frequency, in which HIV shows a promotion of HCV-derived liver diseases. However, the mechanism of how this occurs is not well understood. Our previous work has demonstrated that the HIV-1 accessory protein Vpr enhances HCV RNA replication in cell culture. Because Vpr performs most of its functions through host protein VprBP (DCAF1), the role of VprBP in the regulation of HCV by Vpr was investigated in this study. We found that the Vpr mutant Q65R, which is deficient in VprBP binding, could not enhance HCV replication. Furthermore, Vpr-mediated enhancement of HCV replication was severely diminished in VprBP knockdown cells. In addition, an inhibitor of Cullin RING E3 ligases, MLN4924, impaired the function of Vpr during HCV replication. Together, these results suggest that Vpr promotes HCV replication in a VprBP-dependent manner, and that the activity of Cullin RING E3 ligases is essential to this process. In conclusion, our findings demonstrate that HIV-1 Vpr makes the cellular environment more suitable for HCV replication, which might relate with the host ubiquitination system.

  1. Insights into the Determination of the Templating Nucleotide at the Initiation of φ29 DNA Replication.

    Science.gov (United States)

    del Prado, Alicia; Lázaro, José M; Longás, Elisa; Villar, Laurentino; de Vega, Miguel; Salas, Margarita

    2015-11-06

    Bacteriophage φ29 from Bacillus subtilis starts replication of its terminal protein (TP)-DNA by a protein-priming mechanism. To start replication, the DNA polymerase forms a heterodimer with a free TP that recognizes the replication origins, placed at both 5' ends of the linear chromosome, and initiates replication using as primer the OH-group of Ser-232 of the TP. The initiation of φ29 TP-DNA replication mainly occurs opposite the second nucleotide at the 3' end of the template. Earlier analyses of the template position that directs the initiation reaction were performed using single-stranded and double-stranded oligonucleotides containing the replication origin sequence without the parental TP. Here, we show that the parental TP has no influence in the determination of the nucleotide used as template in the initiation reaction. Previous studies showed that the priming domain of the primer TP determines the template position used for initiation. The results obtained here using mutant TPs at the priming loop where Ser-232 is located indicate that the aromatic residue Phe-230 is one of the determinants that allows the positioning of the penultimate nucleotide at the polymerization active site to direct insertion of the initiator dAMP during the initiation reaction. The role of Phe-230 in limiting the internalization of the template strand in the polymerization active site is discussed.

  2. The change in motivating factors influencing commencement, adherence and retention to a supervised resistance training programme in previously sedentary post-menopausal women: a prospective cohort study.

    Science.gov (United States)

    Viljoen, Janet Erica; Christie, Candice Jo-Anne

    2015-03-12

    Understanding motivators for exercise participation in post-menopausal women may impact retention to exercise programmes and inform intervention trial designs. The purpose of this investigation was to assess self-reported motivational factors influencing adherence and retention to a 24-week progressive resistance training programme. Post-menopausal females (n = 34) were passively recruited to undertake a 24-week progressive resistance training protocol, in small-group sessions, on three non-consecutive days of the week. Attendance was recorded by the researcher. Qualitative reports were sourced from the sample for four phases of the study: pre-study (prior to week 1), recruitment (week 1), during study (weeks 2 - 24), and post-intervention (beyond week 24). Responses were categorised according to ten descriptors: specific health index improvement, education, flexibility of time, social contact, conscience (loyalty to the researcher), wellness, weight management, organisation parameters (pertaining to the study programme) and enjoyment of the exercises. Of the initial sample, 76.5% (n = 26) met the specified ≥80% attendance criterion. The primary findings were that motivation to volunteer for the study was driven by a perceived need for a structured exercise programme (50% of respondents). A commitment to the researcher was the primary motivator for continued adherence to the study for 50% of participants. Social contact with other participants was cited by 60% of the sample as the primary reason for adherence for the full duration of 24 weeks. A desire to maintain the "wellness" derived from the programme was cited by 60% as a reason for continuing an exercise routine post-study. This study identified that routine and supervision initially attract women to exercise programmes, while social cohesion of the group setting contributes to retention over time. Understanding the changing nature of motivating factors may contribute to better overall adherence

  3. 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.

  4. Previous heat shock treatment inhibits Mayaro virus replication in human lung adenocarcinoma (A549) cells.

    Science.gov (United States)

    Virgilio, P L; Godinho-Netto, M C; Carvalho Mda, G

    1997-01-01

    Human lung adenocarcinoma cells (A549) were submitted to mild or severe heat shock (42 degrees C or 44 degrees C) for 1 h, while another group of cells was double-heat-shocked (submitted to 42 degrees C for 1 h, returned to 37 degrees C for 3 h, then exposed to 44 degrees C for 1 h). After each heat treatment, the cells were infected with Mayaro virus for 24 h and incubated at 37 degrees C. The results showed that the double-heat-shocked thermotolerant cells exhibited a 10(4)-fold virus titre inhibition, despite the recovery of protein synthesis and original morphology 24 h post-infection. In contrast, cells submitted to mild or severe heat shock exhibited weaker inhibition of Mayaro virus titre (10(2)-fold). The mildly heat-shocked cells also presented a full recovery in protein synthesis, which was not observed in severely heat-shocked cells. These results indicate that exposure of A549 cells to a mild or to a double heat shock treatment before Mayaro virus infection induces an antiviral state.

  5. Training Cognitive Functioning in the Elderly--Inability to Replicate Previous Findings.

    Science.gov (United States)

    Papalia-Finlay, Diane; And Others

    1980-01-01

    Elderly women volunteers were given a pretest battery of conservation tasks. Conservation scores were the highest yet recorded by elderly participants; consequently, training was not implemented. Results suggest that advanced chronological age does not guarantee poor conservation performance. (Author)

  6. Anatomy of Mammalian Replication Domains

    Science.gov (United States)

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

    2017-01-01

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

  7. Replication of biotinylated human immunodeficiency viruses.

    Science.gov (United States)

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

    2011-01-01

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

  8. Marek's disease virus infection in the eye: chronological study of the lesions, virus replication, and vaccine-induced protection.

    Science.gov (United States)

    Pandiri, Arun K R; Cortes, Aneg L; Lee, Lucy F; Gimeno, I M

    2008-12-01

    Marek's disease virus (MDV) infection in the eye was studied chronologically after inoculating 1-day-old chickens with a very virulent MDV strain, Md5. The ocular lesions could be classified as early lesions (6-11 days postinoculation [dpi]) and late lesions (26 and 56 dpi), based upon the location and severity of the lesions. The early lesions involved iris, ciliary body, and choroid layer, and were characterized by endothelial cell hypertrophy, vasculitis, and infiltration of lymphocytes (mainly CD8+), plasma cells, macrophages, and heterophils. Expression of early MDV-antigen pp38 in the cells infiltrating choroid layer was detected as early as 11 dpi. Late lesions consisted of severe lymphohistiocytic uveitis, keratitis, pectenitis, vitreitis, retinitis, and segmental to diffuse retinal necrosis. Cell infiltration included macrophages, granulocytes, plasma cells, and both CD4+ and CD8+ cells of various sizes. Expression of early MDV-antigen pp38 was readily found within the retina, uveal tract, and corneal epithelium. No expression of late-antigen gB or oncoprotein meq was detected in any of the eyes examined. A second experiment was conducted to study the effect of vaccination on the development of ocular lesions. Both HVT and CVI988 were able to protect against the development of early ocular lesions in chickens infected with very virulent plus strain MDV 648A. However, only CVI988 conferred complete protection against the development of late ocular lesions. HVT conferred partial protection, as it reduced the frequency and severity of the late ocular lesions. These results enhance our understanding of the nature and pattern of MDV infection in the eye.

  9. Structure of viroid replicative intermediates: physico-chemical studies on SP6 transcripts of cloned oligomeric potato spindle tuber viroid.

    Science.gov (United States)

    Steger, G; Tabler, M; Brüggemann, W; Colpan, M; Klotz, G; Sänger, H L; Riesner, D

    1986-12-22

    The structure and structural transitions of transcripts of cloned oligomeric viroid were studied in physico-chemical experiments and stability calculations. Transcripts of (+) and (-) polarity, from unit up to sixfold length, were synthesized from DNA clones of the potato spindle tuber viroid (PSTV) with the SP6 transcription system. Their structural properties were investigated by optical denaturation curves, high performance liquid chromatography (HPLC), electron microscopy, sedimentation-diffusion equilibrium and velocity sedimentation. Secondary structures of the RNAs and theoretical denaturation curves were calculated using an energy optimization program. The secondary structure of lowest free energy for unit length and oligomeric transcripts is a rod-like structure similar to that of the mature circular viroids. When this structure is used as a model for calculations, there is a large degree of agreement between the theoretical and the experimental denaturation curves. At high temperatures, however, (+) strand transcripts exhibited a transition which was more stable than expected from the calculations or than was known from curves of mature viroids. This transition arises from a rearrangement of the central conserved region of viroids to a helical region of 28 stable base pairs either intermolecularly leading to bimolecular complexes, or intramolecularly giving rise to a branched secondary structure. The rearrangement could be detected by electron microscopy, HPLC, and analytical ultracentrifugation. The helical region serves to divide up the oligomeric (+) strand into structural units which may be recognized by cleavage and ligation enzymes which process the oligomeric intermediates to circular mature viroids.

  10. 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.

  11. A brief review of the estimated economic burden of sexually transmitted diseases in the United States: inflation-adjusted updates of previously published cost studies.

    Science.gov (United States)

    Chesson, Harrell W; Gift, Thomas L; Owusu-Edusei, Kwame; Tao, Guoyu; Johnson, Ana P; Kent, Charlotte K

    2011-10-01

    We conducted a literature review of studies of the economic burden of sexually transmitted diseases in the United States. The annual direct medical cost of sexually transmitted diseases (including human immunodeficiency virus) has been estimated to be $16.9 billion (range: $13.9-$23.0 billion) in 2010 US dollars.

  12. 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

    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...

  13. The safety and effectiveness of once daily detemir in patients with type 2 diabetes previously failing oral agents:the Chinese cohort from SOL-VETM observational study

    Institute of Scientific and Technical Information of China (English)

    潘长玉

    2013-01-01

    Objective To evaluate the safety and effectiveness of initiating once-daily insulin detemir(Levemir) as add-on therapy in patients with type 2 diabetes mellitus(T2DM) who failed treatment of oral anti-diabetic drugs(OAD).Methods The present study was derived from the data of

  14. 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

  15. Common Chemical Inductors of Replication Stress:  Focus on Cell‐Based Studies

    Directory of Open Access Journals (Sweden)

    Eva Vesela

    2017-02-01

    Full Text Available DNA replication is a highly demanding process regarding the energy and material supply and must be precisely regulated, involving multiple cellular feedbacks. The slowing down or stalling of DNA synthesis and/or replication forks is referred to as replication stress (RS. Owing to the complexity and requirements of replication, a plethora of factors may interfere and challenge the genome stability, cell survival or affect the whole organism. This review outlines chemical compounds that are known inducers of RS and commonly used in laboratory research. These compounds act on replication by direct interaction with DNA causing DNA crosslinks and bulky lesions (cisplatin, chemical interference with the metabolism of deoxyribonucleotide triphosphates (hydroxyurea, direct inhibition of the activity of replicative DNA polymerases (aphidicolin and interference with enzymes dealing with topological DNA stress (camptothecin, etoposide. As a variety of mechanisms can induce RS, the responses of mammalian cells also vary. Here, we review the activity and mechanism of action of these compounds based on recent knowledge, accompanied by examples of induced phenotypes, cellular readouts and commonly used doses.

  16. Role of micronized progesterone in prevention of preterm labour in women with previous history of one or more preterm births: a research study at a tertiary care hospital

    Directory of Open Access Journals (Sweden)

    Rashmi Ahuja

    2015-08-01

    Conclusions: The study concluded that progesterone use was associated with 64.2% reduction in the incidence of preterm delivery (p=0.029.Antenatal administration of progesterone reduces the risk of preterm birth before 37 weeks and 34 weeks as well as the risk of a newborn being born with a birth weight of less than 2500 gms. [Int J Reprod Contracept Obstet Gynecol 2015; 4(4.000: 1176-1180

  17. 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.

  18. Mycobacterium tuberculosis replicates within necrotic human macrophages

    Science.gov (United States)

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

    2017-01-01

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

  19. A Retrospective Study of Capecitabine/Temozolomide (CAPTEM Regimen in the Treatment of Metastatic Pancreatic Neuroendocrine Tumors (pNETs after Failing Previous Therapy

    Directory of Open Access Journals (Sweden)

    Muhammad Wasif Saif

    2013-09-01

    Full Text Available Context Pancreatic neuroendocrine tumors (pNETs are notoriously resistant to currently available chemotherapy agents.Preclinical data has suggested synergy between temozolomide and capecitabine. Objective To report a retrospective data on the efficacy and safety of capecitabine and temozolomide (CAPTEM regimen in patients with metastatic pancreaticneuroendocrine tumors (pNETs who have failed prior therapies. Methods We reviewed the medical records of 7 patientswith metastatic pNETs who had had progressive cancer prior to treatment despite therapy, including long-acting releaseoctreotide (60 mg/month, chemotherapy and hepatic chemoembolization. Capecitabine was administered at a flat dose of1,000 mg orally twice daily on days 1-14 and temozolomide 200 mg/m2 was given in two divided doses daily on days 10-14of a 28-day cycle. Tumor assessments were repeated every two cycles and serum tumor markers were measured every cycle. Response to treatment was assessed using Response Evaluation Criteria in Solid Tumors (RECIST parameters, and toxicity was graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE, version 3.0. Results Among 7 patients treated, three patients achieved a partial response, and two patients had stable disease. Totalresponse rate was 43%, and clinical benefit (responders and stable disease was 71%. Median duration of response was 8months (range: 4-12 months. Grade 3 and 4 toxicities included grade 3 thrombocytopenia in one patient and grade 3 fatigue in one patient. The most common toxicities were grade 1 and 2 neutropenia, grade 1 fatigue, grade 1 and 2 hand-foot syndrome. Conclusions Our retrospective study showed that modified CAPTEM regimen was well-tolerated and produced comparable response to historical data in neuroendocrine tumors, including pNETs. Our study is unique as it only included patients with pNETs. Further prospective studies are warranted to evaluate the combination of

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    Arach Goldar

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

  2. Regulatory cross-talk links Vibrio cholerae chromosome II replication and segregation.

    Science.gov (United States)

    Yamaichi, Yoshiharu; Gerding, Matthew A; Davis, Brigid M; Waldor, Matthew K

    2011-07-01

    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 gender-medicine post hoc analysis (MetaGeM project to test sex differences in previous observational studies in different diseases: methodology

    Directory of Open Access Journals (Sweden)

    Colombo D

    2014-10-01

    Full Text Available Delia Colombo,1 Gilberto Bellia,1 Donatella Vassellatti,1 Emanuela Zagni,1 Simona Sgarbi,2 Sara Rizzoli21Novartis Farma, Origgio, 2MediData, Modena, ltaly Abstract: Only recently has medical research begun to understand the importance of taking sex into account, recognizing that symptoms and responses to medical treatment may be very different between males and females. However, the analyses provided by the pharmaceutical industry to regulatory authorities often do not present safety and efficacy data by sex. Novartis has started a gender-medicine project called MetaGeM, which includes nine observational studies sponsored by Novartis Farma, Italy; conducted in Italy between 2002 and 2013 in a range of different clinical areas. The MetaGeM project aims to analyze and describe by means of post hoc analyses and meta-analyses, clinical outcomes, therapeutic approaches, and safety data of these studies, by sex: PSYCHAE; GENDER ATTENTION in psoriasis; Synergy in psoriatic arthritis; ICEBERG in HBsAg carriers; SURF and CETRA in liver- and renal transplanted patients, respectively; DEEP in Parkinson's disease; and EVOLUTION and AXEPT in Alzheimer's disease. The present paper describes the methodology of the MetaGeM project.Keywords: gender-medicine, MetaGeM project, methodology

  4. Predicting Behavior Assessment System for Children-Second Edition Self-Report of Personality Child Form Results Using the Behavioral and Emotional Screening System Student Form: A Replication Study with an Urban, Predominantly Latino/a Sample

    Science.gov (United States)

    Kiperman, Sarah; Black, Mary S.; McGill, Tia M.; Harrell-Williams, Leigh M.; Kamphaus, Randy W.

    2014-01-01

    This study assesses the ability of a brief screening form, the Behavioral and Emotional Screening System-Student Form (BESS-SF), to predict scores on the much longer form from which it was derived: the Behavior Assessment System for Children-Second Edition Self-Report of Personality-Child Form (BASC-2-SRP-C). The present study replicates a former…

  5. A study of the presence of B. burgdorferi, Anaplasma (previously Ehrlichia) phagocytophilum, Rickettsia, and Babesia in Ixodes ricinus collected within the territory of Belluno, Italy.

    Science.gov (United States)

    Piccolin, G; Benedetti, G; Doglioni, C; Lorenzato, C; Mancuso, S; Papa, N; Pitton, L; Ramon, M C; Zasio, C; Bertiato, G

    2006-01-01

    In the years 2000 and 2001, we sampled ticks in order to establish the distribution of Ixodes ricinus in the province of Belluno; 5987 tick samples from 244 sites throughout the province were gathered, by dragging for a 5-min period. In 40 sites, seasonal variations and cycle stages of the parasites were studied at monthly intervals from March to September. A polymerase chain reaction (PCR) technique was used to identify the tick-infected sites. Of 1931 individual ticks, 8.23% were positive for Borrelia burgdorferi, 4.4% were positive for Ehrlichia, 1.6% were positive for Rickettsia, and 1.6% were positive for Babesia. The co-presence of Borrelia and Ehrlichia (1.2%) and Babesia (0.5%), Borrelia, Ehrlichia and Rickettsia (0.1%) was also found.

  6. Performance of the new 2012 EULAR/ACR classification criteria for polymyalgia rheumatica: comparison with the previous criteria in a single-centre study.

    Science.gov (United States)

    Macchioni, Pierluigi; Boiardi, Luigi; Catanoso, Mariagrazia; Pazzola, Giulia; Salvarani, Carlo

    2014-06-01

    To compare the performance of published classification/diagnostic criteria for polymyalgia rheumatica (PMR), including the new 2012 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) criteria, in a single-centre study. We studied all consecutive patients with new-onset PMR seen in our centre over 6 years, whose diagnosis was confirmed during a prospective 12-month follow-up period. Subjects were classified by each of the seven different criteria. Sensitivity and specificity were compared. Control population consisted of all consecutive patients aged ≥50 years seen in a 4-year period in our early arthritis clinic who had a 12-month confirmation of a diagnosis of rheumatoid arthritis (RA) or other inflammatory articular diseases. Data were collected from 136 cases and 149 controls, including 94 patients with RA. The most sensitive criteria were the new 2012 EULAR/ACR classification criteria (92.6%). Adding ultrasound (US) specificity increased from 81.5% to 91.3% in total cases and from 79.7% to 89.9% in RA. Bird criteria had a sensitivity of 89.2% but the lowest specificity (40.2% in total cases and 72.5% in RA). Jones and Nobunaga criteria were the most specific criteria (96.7% and 97.8% in total cases and 98.6% and 99.5% in RA) but the less sensitive (63.1% and 58.2%) ones. Overall, discriminatory ability, as reflected by the area under the receiver operating characteristic curve, was better for the 2012 US EULAR/ACR criteria (0.920 in total cases and 0.910 in RA). The new EULAR/ACR criteria in new-onset PMR patients perform best in discriminating PMR from RA and other inflammatory articular diseases. Ultrasound further increases the specificity of the criteria.

  7. Acyl coenzyme A synthetase long-chain 1 (ACSL1 gene polymorphism (rs6552828 and elite endurance athletic status: a replication study.

    Directory of Open Access Journals (Sweden)

    Thomas Yvert

    Full Text Available The aim of this study was to determine the association between the rs6552828 polymorphism in acyl coenzyme A synthetase (ACSL1 and elite endurance athletic status. We studied 82 Caucasian (Spanish World/Olympic-class endurance male athletes, and a group of sex and ethnically matched healthy young adults (controls, n=197. The analyses were replicated in a cohort of a different ethnic origin (Chinese of the Han ethnic group, composed of elite endurance athletes (runners [cases, n=241 (128 male] and healthy sedentary adults [controls, n=504 (267 male]. In the Spanish cohort, genotype (P=0.591 and minor allele (A frequencies were similar in cases and controls (P=0.978. In the Chinese cohort, genotype (P=0.973 and minor allele (G frequencies were comparable in female endurance athletes and sedentary controls (P=0.881, whereas in males the frequency of the G allele was higher in endurance athletes (0.40 compared with their controls (0.32, P=0.040. The odds ratio (95%CI for an elite endurance Chinese athlete to carry the G allele compared with ethnically matched controls was 1.381 (1.015-1.880 (P-value=0.04. Our findings suggest that the ACSL1 gene polymorphism rs6552828 is not associated with elite endurance athletic status in Caucasians, yet a marginal association seems to exist for the Chinese (Han male population.

  8. Phase II Study of Bortezomib as a Single Agent in Patients with Previously Untreated or Relapsed/Refractory Acute Myeloid Leukemia Ineligible for Intensive Therapy

    Directory of Open Access Journals (Sweden)

    Chiara Sarlo

    2013-01-01

    Full Text Available We explored the safety and efficacy of bortezomib given as single agent in patients with untreated or relapsed/refractory acute myeloid leukemia (AML, unfit for conventional chemotherapy. Fourteen patients were treated with bortezomib 1.5 mg/m2 administered twice weekly for two weeks, every 3 weeks. Median age was 70 years (range 60–81 and the median number of cycles delivered was 2 (range 1–4. Of 13 evaluable patients, in 8 (61%, the administration of bortezomib resulted in an antileukemic effect as demonstrated by peripheral blood and/or bone marrow blast reduction. In 4 (50% of these 8, a decrease by 37% of transfusion requirement was also observed . Overall median survival was 4 months (range 0.25–10. Neurotoxicity was the most frequent adverse event with 7 of 13 (54% patients experiencing grades 3-4 peripheral neuropathy. Neurotoxicity led to treatment discontinuation in 4 (57% of 7. In conclusion, the observed anti-leukemic activity of bortezomib indicates that there is room for designing additional studies in which combination with other chemotherapeutic agents should be considered. Clinical registration no.: EUDRACT 2006-006923-38.

  9. Can a Repeated Sprint Ability Test Help Clear a Previously Injured Soccer Player for Fully Functional Return to Activity? A Pilot Study.

    Science.gov (United States)

    Padulo, Johnny; Attene, Giuseppe; Ardigò, Luca P; Bragazzi, Nicola L; Maffulli, Nicola; Zagatto, Alessandro M; Dello Iacono, Antonio

    2017-07-01

    To investigate the effects of fatigue induced by a repeated sprint ability (RSA) test on the neuromuscular responses of soccer players with a recent history of lower limb injuries (CH) and a matched control group in good fitness condition (GH). This was a case-control study. Nine CH and 9 GH. Allocation to CH or GH. Each player was assessed for blood lactate concentration and jumping performance [squat jump (SJ) and countermovement jump (CMJ)] before/after RSA. Post-RSA rate of perceived exertion (RPE) was obtained. Receiver operating characteristic analysis was performed to calculate RSA sensitivity and specificity in distinguishing between CH and GH. Intraclass correlation coefficient was used to assess reliability. No baseline differences were found for any variable. ΔSJ before/after RSA was -14 ± 2% and -5 ± 2% in CH and GH, respectively (P Repeated sprint ability is a simple, low-cost field test potentially able to assist in clinical decision making for return to sport.

  10. 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

    exposed to torture in their home country were interviewed at a Danish rehabilitation clinic on average 8 years after their final release from confinement and re-interviewed 10 years later. Interviews focused on history of exposure to physical and mental torture and on pain in the head, back and feet...... prevalent at study. RESULTS: The mean number of times imprisoned was 2.5 and the mean cumulative duration of imprisonment 19.4 months. The most frequent physical torture method reported was beating (95.0%) and the main mental torture method deprivation (88.5%). Pain reported at follow-up was strongly...... associated with pain reported at baseline, and the prevalence of pain increased considerably (pain in the head, 47.5% at baseline and 58.3% at follow-up; back, 48.2% and 75.5%; feet, 23.7% and 63.3%). Predictor patterns at baseline and at follow-up had common traits, so that pain in the head and pain...

  11. The N-Terminal of Aquareovirus NS80 Is Required for Interacting with Viral Proteins and Viral Replication.

    Directory of Open Access Journals (Sweden)

    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.

  12. Effects of dopaminergic replacement therapy on motor speech disorders in Parkinson's disease: longitudinal follow-up study on previously untreated patients.

    Science.gov (United States)

    Rusz, Jan; Tykalová, Tereza; Klempíř, Jiří; Čmejla, Roman; Růžička, Evžen

    2016-04-01

    Although speech disorders represent an early and common manifestation of Parkinson's disease (PD), little is known about their progression and relationship to dopaminergic replacement therapy. The aim of the current study was to examine longitudinal motor speech changes after the initiation of pharmacotherapy in PD. Fifteen newly-diagnosed, untreated PD patients and ten healthy controls of comparable age were investigated. PD patients were tested before the introduction of antiparkinsonian therapy and then twice within the following 6 years. Quantitative acoustic analyses of seven key speech dimensions of hypokinetic dysarthria were performed. At baseline, PD patients showed significantly altered speech including imprecise consonants, monopitch, inappropriate silences, decreased quality of voice, slow alternating motion rates, imprecise vowels and monoloudness. At follow-up assessment, preservation or slight improvement of speech performance was objectively observed in two-thirds of PD patients within the first 3-6 years of dopaminergic treatment, primarily associated with the improvement of stop consonant articulation. The extent of speech improvement correlated with L-dopa equivalent dose (r = 0.66, p = 0.008) as well as with reduction in principal motor manifestations based on the Unified Parkinson's Disease Rating Scale (r = -0.61, p = 0.02), particularly reflecting treatment-related changes in bradykinesia but not in rigidity, tremor, or axial motor manifestations. While speech disorders are frequently present in drug-naive PD patients, they tend to improve or remain relatively stable after the initiation of dopaminergic treatment and appear to be related to the dopaminergic responsiveness of bradykinesia.

  13. Comparative study of Hg xCd 1-xTe films grown on CdTe thin films previously deposited from two different techniques

    Science.gov (United States)

    Ali, A.; Abbas Shah, N.; Maqsood, A.

    2009-04-01

    High quality cadmium telluride (CdTe) thin films were grown on glass substrates with two different techniques, two evaporation source (TES) and closed space sublimation (CSS). Further to the above mercury telluride (HgTe) was then deposited by using single source on both CdTe thin films for obtaining Hg xCd 1-xTe samples. The crystalline structure of the Hg xCd 1-xTe sample grown from CSS-CdTe showed the preferential (1 1 1) orientation with smoother and larger grain size than those of TES-CdTe. The optical transmission for TES-CdTe sample was above 90% in the 1000-1500 nm range whereas it was significantly below 80% for CSS-CdTe sample. The optical transmission for TES-Hg xCd 1-xTe and CSS-Hg xCd 1-xTe was ˜60%. The resistivity at room temperature of TES-CdTe and CSS-CdTe was ˜3.33×10 9 Ω cm and ˜2.20×10 8 Ω cm, respectively, while the resistivity of TES-Hg xCd 1-xTe and CSS-Hg xCd 1-xTe samples was ˜1.73 Ω cm and ˜5.34×10 5 Ω cm, respectively. The comparative study of ternary compound prepared with the above techniques has been carried out for the first time.

  14. Eukaryotic Mismatch Repair in Relation to DNA Replication.

    Science.gov (United States)

    Kunkel, Thomas A; Erie, Dorothy A

    2015-01-01

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

  15. 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.

  16. Intravenous C.E.R.A. maintains stable haemoglobin levels in patients on dialysis previously treated with darbepoetin alfa: results from STRIATA, a randomized phase III study

    Science.gov (United States)

    Canaud, Bernard; Mingardi, Giulio; Braun, Johann; Aljama, Pedro; Kerr, Peter G.; Locatelli, Francesco; Villa, Giuseppe; Van Vlem, Bruno; McMahon, Alan W.; Kerloëguen, Cécile; Beyer, Ulrich

    2008-01-01

    Background. Extending the administration interval of erythropoiesis-stimulating agents (ESAs) represents an opportunity to improve the efficiency of anaemia management in patients with chronic kidney disease (CKD). However, effective haemoglobin (Hb) maintenance can be challenging with epoetin alfa and epoetin beta administered at extended intervals. C.E.R.A., a continuous erythropoietin receptor activator, has a unique pharmacologic profile and long half-life (∼130 h), allowing administration at extended intervals. Phase III results have demonstrated that C.E.R.A. administered once every 4 weeks effectively maintains stable Hb levels in patients with CKD on dialysis. Methods. STRIATA (Stabilizing haemoglobin TaRgets in dialysis following IV C.E.R.A. Treatment for Anaemia) was a multicentre, open-label randomized phase III study to evaluate the efficacy and safety of intravenous C.E.R.A. administered once every 2 weeks (Q2W) for Hb maintenance following direct conversion from darbepoetin alfa (DA). Adult patients on dialysis receiving stable intravenous DA once weekly (QW) or Q2W were randomized (1:1) to continue their current DA regimen (n = 156) or receive intravenous C.E.R.A. Q2W (n = 157) for 52 weeks. Doses were adjusted to maintain Hb levels within ± 1.0 g/dl of baseline and between 10.0 and 13.5 g/dl. The primary endpoint was the mean Hb change between baseline and the evaluation period (weeks 29–36). Results. Most patients (>80%) received DA QW before randomization. The mean (95% CI) difference between C.E.R.A. and DA in the primary endpoint was 0.18 g/dl (−0.05, 0.41), within a pre-defined non-inferiority limit. C.E.R.A. was clinically non-inferior to DA (P < 0.0001) in maintaining Hb levels. Both treatments were well tolerated. Conclusions. Stable Hb levels were successfully maintained in patients on haemodialysis directly converted to Q2W intravenous C.E.R.A. from DA. PMID:18586762

  17. RapidArc, intensity modulated photon and proton techniques for recurrent prostate cancer in previously irradiated patients: a treatment planning comparison study

    Directory of Open Access Journals (Sweden)

    Ratib Osman

    2009-09-01

    Full Text Available Abstract Background 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. Methods 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 18F-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 (DMax of 61.6 Gy was allowed to 5% of the GTV. For the urethra, DMax was constrained to 37 Gy. Rectal DMedian was 90 parameters. Results Tumor coverage (GTV and PTV was improved with RA (V95% 92.6 ± 7.9 and 83.7 ± 3.3%, when compared to IMRT (V95% 88.6 ± 10.8 and 77.2 ± 2.2%. The corresponding values for IMPT were intermediate for the GTV (V95% 88.9 ± 10.5% and better for the PTV (V95%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%. CI90 was 1.3 ± 0.1 for photons and 1.6 ± 0.2 for protons. Integral Dose was 1.1 ± 0.5 Gy*cm3 *105 for IMPT and about a factor three higher for all photon's techniques. Conclusion 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.

  18. Cross-centre replication of suppressed burrowing behaviour as an ethologically relevant pain outcome measure in the rat: a prospective multicentre study

    Science.gov (United States)

    Wodarski, Rachel; Delaney, Ada; Ultenius, Camilla; Morland, Rosie; Andrews, Nick; Baastrup, Catherine; Bryden, Luke A.; Caspani, Ombretta; Christoph, Thomas; Gardiner, Natalie J.; Huang, Wenlong; Kennedy, Jeffrey D.; Koyama, Suguru; Li, Dominic; Ligocki, Marcin; Lindsten, Annika; Machin, Ian; Pekcec, Anton; Robens, Angela; Rotariu, Sanziana M.; Voß, Sabrina; Segerdahl, Marta; Stenfors, Carina; Svensson, Camilla I.; Treede, Rolf-Detlef; Uto, Katsuhiro; Yamamoto, Kazumi; Rutten, Kris; Rice, Andrew S.C.

    2016-01-01

    Abstract Burrowing, an ethologically relevant rodent behaviour, has been proposed as a novel outcome measure to assess the global impact of pain in rats. In a prospective multicentre study using male rats (Wistar, Sprague-Dawley), replication of suppressed burrowing behaviour in the complete Freund adjuvant (CFA)-induced model of inflammatory pain (unilateral, 1 mg/mL in 100 µL) was evaluated in 11 studies across 8 centres. Following a standard protocol, data from participating centres were collected centrally and analysed with a restricted maximum likelihood-based mixed model for repeated measures. The total population (TP—all animals allocated to treatment; n = 249) and a selected population (SP—TP animals burrowing over 500 g at baseline; n = 200) were analysed separately, assessing the effect of excluding “poor” burrowers. Mean baseline burrowing across studies was 1113 g (95% confidence interval: 1041-1185 g) for TP and 1329 g (1271-1387 g) for SP. Burrowing was significantly suppressed in the majority of studies 24 hours (7 studies/population) and 48 hours (7 TP, 6 SP) after CFA injections. Across all centres, significantly suppressed burrowing peaked 24 hours after CFA injections, with a burrowing deficit of −374 g (−479 to −269 g) for TP and −498 g (−609 to −386 g) for SP. This unique multicentre approach first provided high-quality evidence evaluating suppressed burrowing as robust and reproducible, supporting its use as tool to infer the global effect of pain on rodents. Second, our approach provided important informative value for the use of multicentre studies in the future. PMID:27643836

  19. Inhibition of herpes simplex virus type 1 replication by adeno-associated virus rep proteins depends on their combined DNA-binding and ATPase/helicase activities.

    Science.gov (United States)

    Glauser, Daniel L; Seyffert, Michael; Strasser, Regina; Franchini, Marco; Laimbacher, Andrea S; Dresch, Christiane; de Oliveira, Anna Paula; Vogel, Rebecca; Büning, Hildegard; Salvetti, Anna; Ackermann, Mathias; Fraefel, Cornel

    2010-04-01

    Adeno-associated virus (AAV) has previously been shown to inhibit the replication of its helper virus herpes simplex virus type 1 (HSV-1), and the inhibitory activity has been attributed to the expression of the AAV Rep proteins. In the present study, we assessed the Rep activities required for inhibition of HSV-1 replication using a panel of wild-type and mutant Rep proteins lacking defined domains and activities. We found that the inhibition of HSV-1 replication required Rep DNA-binding and ATPase/helicase activities but not endonuclease activity. The Rep activities required for inhibition of HSV-1 replication precisely coincided with the activities that were responsible for induction of cellular DNA damage and apoptosis, suggesting that these three processes are closely linked. Notably, the presence of Rep induced the hyperphosphorylation of a DNA damage marker, replication protein A (RPA), which has been reported not to be normally hyperphosphorylated during HSV-1 infection and to be sequestered away from HSV-1 replication compartments during infection. Finally, we demonstrate that the execution of apoptosis is not required for inhibition of HSV-1 replication and that the hyperphosphorylation of RPA per se is not inhibitory for HSV-1 replication, suggesting that these two processes are not directly responsible for the inhibition of HSV-1 replication by Rep.

  20. In vitro replication of plasmids containing human ribosomal gene sequences: origin localization and dependence on an aprotinin-binding cytosolic protein.

    Science.gov (United States)

    Coffman, F D; Georgoff, I; Fresa, K L; Sylvester, J; Gonzalez, I; Cohen, S

    1993-11-01

    We previously investigated the role of an aprotinin-binding protein (ADR) in the initiation of DNA replication in isolated quiescent nuclei. In the present study, we have used a cell-free DNA replication system to test the ability of plasmid vectors which contain sequences from the human ribosomal RNA gene to serve as replicative templates in vitro when exposed to ADR-containing preparations. Significant dTTP incorporation was seen using DNA from either a 7-kb sequence in the 5' spacer region (CHE) or a 7-kb sequence which begins near the end of the 28S coding region and extends into the 3' spacer region (ADBB), while sequences from other regions of the rRNA gene mediated little or no dTTP incorporation. The characteristics of plasmid-directed dTTP incorporation indicate that most incorporation is due to DNA replication and not repair or damage-initiated processes. To conclusively demonstrate origin-dependent replication in the plasmid system and to further map replication origins, an approach was developed using ddGTP to restrict the length of daughter strands followed by hybridization of these replication products to restriction fragments spanning the putative origin region. This approach allowed us to identify replication origin activity apart from parent strand repair or synthesis initiated at random damaged sites. One of the origins was localized to a 1375-bp fragment within the 5' spacer region, and this fragment contains sequences homologous to those found in other replication origins.

  1. Replicated Spectrographs in Astronomy

    CERN Document Server

    Hill, Gary J

    2014-01-01

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

  2. 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.

  3. The Effect of Root, Shoot and Seed Extracts of The Iranian Thymus L. (Family: Lamiaceae) Species on HIV-1 Replication and CD4 Expression

    OpenAIRE

    Maryam Soleimani Farsani; Mandana Behbahani; Hamid Zarkesh Isfahani

    2016-01-01

    Objective The genus Thymus L. is a cushion plant that was previously used for the treatment of bronchitis and rheumatism. The present investigation was carried out to study the effects of root, shoot, leaf and seed extracts of five Thymus species and subspecies on peripheral blood mononuclear cells (PBMCs) toxicity and HIV-1 replication. Materials and Methods In this experimental study, the activity of the Thymus extracts on HIV-1 replication and lymphocytes population were examin...

  4. A genome-wide linkage study of bipolar disorder and co-morbid migraine: replication of migraine linkage on chromosome 4q24, and suggestion of an overlapping susceptibility region for both disorders on chromosome 20p11.

    Science.gov (United States)

    Oedegaard, K J; Greenwood, T A; Lunde, A; Fasmer, O B; Akiskal, H S; Kelsoe, J R

    2010-04-01

    Migraine and Bipolar Disorder (BPAD) are clinically heterogeneous disorders of the brain with a significant, but complex, genetic component. Epidemiological and clinical studies have demonstrated a high degree of co-morbidity between migraine and BPAD. Several genome-wide linkage studies in BPAD and migraine have shown overlapping regions of linkage on chromosomes, and two functionally similar voltage-dependent calcium channels CACNA1A and CACNA1C have been identified in familial hemiplegic migraine and recently implicated in two whole genome BPAD association studies, respectively. We hypothesized that using migraine co-morbidity to look at subsets of BPAD families in a genetic linkage analysis would prove useful in identifying genetic susceptibility regions in both of these disorders. We used BPAD with co-morbid migraine as an alternative phenotype definition in a re-analysis of the NIMH Bipolar Genetics Initiative wave 4 data set. In this analysis we selected only those families in which at least two members were diagnosed with migraine by a doctor according to patients' reports. Nonparametric linkage analysis performed on 31 families segregating both BPAD and migraine identified a linkage signal on chromosome 4q24 for migraine (but not BPAD) with a peak LOD of 2.26. This region has previously been implicated in two independent migraine linkage studies. In addition we identified a locus on chromosome 20p11 with overlapping elevated LOD scores for both migraine (LOD=1.95) and BPAD (LOD=1.67) phenotypes. This region has previously been implicated in two BPAD linkage studies, and, interestingly, it harbors a known potassium dependant sodium/calcium exchanger gene, SLC24A3, that plays a critical role in neuronal calcium homeostasis. Our findings replicate a previously identified migraine linkage locus on chromosome 4 (not co-segregating with BPAD) in a sample of BPAD families with co-morbid migraine, and suggest a susceptibility locus on chromosome 20, harboring a

  5. 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

    2017-09-04

    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.

  6. Replicate study design in bioequivalency assessment, pros and cons: bioavailabilities of the antidiabetic drugs pioglitazone and glimepiride present in a fixed-dose combination formulation.

    Science.gov (United States)

    Karim, Aziz; Zhao, Zhen; Slater, Margaret; Bradford, Dawn; Schuster, Jennifer; Laurent, Aziz

    2007-07-01

    An open-label, randomized, 2-sequence, 4-period crossover (7-day washout period between treatment), replicate design study was conducted in 37 healthy subjects to assess intersubject and intrasubject variabilities in the peak (Cmax) and total (AUC) exposures to 2 oral antidiabetic drugs, pioglitazone and glimepiride, after single doses of 30 mg pioglitazone and 4 mg glimepiride, given under fasted state, as commercial tablets coadministered or as a single fixed-dose combination tablet. Variabilities for AUC(infinity) for coadministered and fixed-dose combination treatments were similar: 16% to 19% (intra) and 23% to 25% (inter) for pioglitazone and 18% to 19% (intra) and 29% to 30% for glimepiride (inter, excluding 1 poor metabolizer). Fixed-dose combination/coadministered least squares mean ratios of >or=0.86 and the 90% confidence intervals of these ratios for pioglitazone and glimepiride of between 0.80 and 1.25 for Cmax, AUC(lqc), and AUC(infinity) met the bioequivalency standards. Gender analysis showed that women showed mean of 16% and 30% higher exposure than men for glimepiride (excluding 1 poor metabolizer) and pioglitazone, respectively. There was considerable overlapping in the AUC(infinity) values, making gender-dependent dosing unnecessary. Patients taking pioglitazone and glimepiride as cotherapy may replace their medication with a single fixed-dose combination tablet containing these 2 oral antidiabetic drugs.

  7. Studies on the role of the 2'-5'-oligoadenylate synthetase-RNase L pathway in beta interferon-mediated inhibition of encephalomyocarditis virus replication.

    Science.gov (United States)

    Kumar, R; Choubey, D; Lengyel, P; Sen, G C

    1988-01-01

    Interferons inhibit the replication of vesicular stomatitis virus (VSV), but not of encephalomyocarditis virus (EMCV), in mouse JLSV-11 cells. We report the isolation of clonal derivatives from this cell line in which the replication of both viruses is impaired by interferons. These clones were selected from the parental line by virtue of their rescue by interferon treatment from the cytopathic effects of EMCV infection. In one such clone, RK8, the replication of VSV and EMCV and the production of resident murine leukemia virus were inhibited by interferon. On the other hand, in clone RK6, which was isolated without any selection, the replication of VSV, but not of EMCV, was impaired by interferons. The levels of 2'-5'-oligoadenylate synthetase mRNA and enzyme activity were similarly elevated upon interferon treatment in the two clones. However, the level of RNase L, as determined by binding and cross-linking of a radiolabeled 2'-5'-oligoadenylate derivative, was much lower in RK6 cells than in RK8 cells. In accord with this observation, the introduction of 2'-5'-oligoadenylates into cells inhibited protein synthesis much less strongly in RK6 cells than in RK8 cells. These results are consistent with the notion that the 2'-5'-oligoadenylate-dependent RNase L may be a mediator of the inhibition of EMCV replication by interferons. Images PMID:2841470

  8. Review of previous geophysical and geological studies

    Digital Repository Service at National Institute of Oceanography (India)

    Levchenko, O.V; Neprochnov, Y.P.; Rao, D; Subrahmanyam, C; Murthy, K.S.R

    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 ...

  9. A replicate designed bioequivalence study to compare two fixed-dose combination products of artesunate and amodiaquine in healthy chinese volunteers.

    Science.gov (United States)

    Liu, Yun; Hu, Chaoying; Liu, Gangyi; Jia, Jingying; Yu, Chen; Zhu, Jianmin; Zheng, Qingsi; Zhang, Kanyin E

    2014-10-01

    Artesun-Plus is a fixed-dose combination antimalarial agent containing artesunate and amodiaquine. The current study was conducted to compare the pharmacokinetic and safety profiles of Artesun-Plus and the WHO-designated comparator product Artesunate Amodiaquine Winthrop. To overcome the high intrasubject variability of artesunate, the study applied a two-sequence and four-period crossover (2 by 4), replicate study design to assess bioequivalence between the two products in 31 healthy male Chinese volunteers under fasting conditions. The results showed that the values of the geometric mean ratios of maximum concentration of drug in plasma (Cmax) and area under the concentration-time curve from time zero to the last blood sample collection (AUC0-last) for the artesunate component in the test and reference products were 95.9% and 93.9%, respectively, and that the corresponding 90% confidence intervals were 84.5% to 108.7% and 87.2% to 101.1%, while the geometric mean ratios for the amodiaquine component in the test and reference products were 95.0% and 100.0%, respectively, and the corresponding 90% confidence intervals were 86.7% to 104.1% and 93.5% to 107.0%. In conclusion, bioequivalence between the two artesunate and amodiaquine fixed-dose combination products was demonstrated for both components. The study also confirmed high intrasubject variability, especially for artesunate: the coefficients of variation (CV) of Cmax values for the test and reference products were 39.2% and 43.7%, respectively, while those for amodiaquine were 30.6% and 30.2%, respectively.

  10. Efficient usage of Adabas replication

    CERN Document Server

    Storr, Dieter W

    2011-01-01

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

  11. Solving the Telomere Replication Problem

    Science.gov (United States)

    Maestroni, Laetitia; Matmati, Samah; Coulon, Stéphane

    2017-01-01

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

  12. 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.

  13. Replication and Relevance of Multiple Susceptibility Loci Discovered from Genome Wide Association Studies for Type 2 Diabetes in an Indian Population.

    Science.gov (United States)

    Phani, Nagaraja M; Adhikari, Prabha; Nagri, Shivashankara K; D'Souza, Sydney C; Satyamoorthy, Kapaettu; Rai, Padmalatha S

    2016-01-01

    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.

  14. Cellular peptidyl-prolyl cis/trans isomerase Pin1 facilitates replication of feline coronavirus.

    Science.gov (United States)

    Tanaka, Yoshikazu; Amano, Arisa; Morisaki, Masateru; Sato, Yuka; Sasaki, Takashi

    2016-02-01

    Although feline coronavirus (FCoV) causes feline infectious peritonitis (FIP), which is a fatal infectious disease, there are no effective therapeutic medicines or vaccines. Previously, in vitro studies have shown that cyclosporin (CsA) and FK506 inhibit virus replication in diverse coronaviruses. CsA and FK506 are targets of clinically relevant immunosuppressive drugs and bind to cellular cyclophilins (Cyps) or FK506 binding proteins (FKBPs), respectively. Both Cyp and FKBP have peptidyl-prolyl cis-trans isomerase (PPIase) activity. However, protein interacting with NIMA (Pin1), a member of the parvulin subfamily of PPIases that differs from Cyps and FKBPs, is essential for various signaling pathways. Here we demonstrated that genetic silencing or knockout of Pin1 resulted in decreased FCoV replication in vitro. Dipentamethylene thiuram monosulfide, a specific inhibitor of Pin1, inhibited FCoV replication. These data indicate that Pin1 modulates FCoV propagation.

  15. PAR-4/LKB1 regulates DNA replication during asynchronous division of the early C. elegans embryo

    Science.gov (United States)

    Descoteaux, Catherine; Chartier, Nicolas T.; Pintard, Lionel; Labbé, Jean-Claude

    2014-01-01

    Regulation of cell cycle duration is critical during development, yet the underlying molecular mechanisms are still poorly understood. The two-cell stage Caenorhabditis elegans embryo divides asynchronously and thus provides a powerful context in which to study regulation of cell cycle timing during development. Using genetic analysis and high-resolution imaging, we found that deoxyribonucleic acid (DNA) replication is asymmetrically regulated in the two-cell stage embryo and that the PAR-4 and PAR-1 polarity proteins dampen DNA replication dynamics specifically in the posterior blastomere, independently of regulators previously implicated in the control of cell cycle timing. Our results demonstrate that accurate control of DNA replication is crucial during C. elegans early embryonic development and further provide a novel mechanism by which PAR proteins control cell cycle progression during asynchronous cell division. PMID:24841566

  16. Towards an Open-Source Social Science: The Replication Study in Quantitative Social Analysis%走向开源的社会学 定量分析中的复制性研究

    Institute of Scientific and Technical Information of China (English)

    陈云松; 吴晓刚

    2012-01-01

    社会科学定量分析亟待建立一个透明和开源的学术机制,让研究数据和模型公开共享,使研究成果可以得到他人的验证和进一步拓展。这个学术机制的核心就是倡导"复制性研究"。本文结合近年来西方社会科学界围绕复制性研究的实践和讨论,提出了复制性研究对于社会科学特别是中国社会学定量分析的重要意义、操作可能性以及可能存在的争议。在此基础上,本文通过两个实证定量分析的例子,为如何进行复制性研究提供了简明的范本。最后,结合中国实际提出了就复制性研究所应达成的共识和建议。本文所论及的复制性研究,对社会科学定量分析其他领域也同样具有参考价值。%The development of quantitative analysis in social science calls for the establishment of an open and transparent mechanism to allow research data and models to be shared to the community, and the research findings to be verify and elaborated by others. The core in this practice is replication studies in social sciences. In this essay, we review the discussion and practices of replication studies in western social sciences and highlight its significance in promoting quantitative social science research in China. Why is the replication study necessary? First, the collectivity of social science research suggests the research process should be transparent; Second, the principle of parsimony in quantitative social analysis requires the verification of research process~ Third, the issue of endogeneity calls for extension of the past quantitative social analysis~ Four, as a matter of fact, the rate of successful verification in published social science literature is low. Fifth, replication study is important to the teaching and training of quantitative social science~ and finally, replication study can facilitate the professionalization of quantitative sociology and make us of late-development advantages. Why is

  17. 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...

  18. USP7 is a SUMO deubiquitinase essential for DNA replication.

    Science.gov (United States)

    Lecona, Emilio; Rodriguez-Acebes, Sara; Specks, Julia; Lopez-Contreras, Andres J; Ruppen, Isabel; Murga, Matilde; Muñoz, Javier; Mendez, Juan; Fernandez-Capetillo, Oscar

    2016-04-01

    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 inhibitors as anticancer agents.

  19. 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.

  20. Genetic heritability of ischemic stroke and the contribution of previously reported candidate gene and genomewide associations.

    Science.gov (United States)

    Bevan, Steve; Traylor, Matthew; Adib-Samii, Poneh; Malik, Rainer; Paul, Nicola L M; Jackson, Caroline; Farrall, Martin; Rothwell, Peter M; Sudlow, Cathie; Dichgans, Martin; Markus, Hugh S

    2012-12-01

    The contribution of genetics to stroke risk, and whether this differs for different stroke subtypes, remainsuncertain. Genomewide complex trait analysis allows heritability to be assessed from genomewide association study (GWAS) data. Previous candidate gene studies have identified many associations with stoke but whether these are important requires replication in large independent data sets. GWAS data sets provide a powerful resource to perform replication studies. We applied genomewide complex trait analysis to a GWAS data set of 3752 ischemic strokes and 5972 controls and determined heritability for all ischemic stroke and the most common subtypes: large-vessel disease, small-vessel disease, and cardioembolic stroke. By systematic review we identified previous candidate gene and GWAS associations with stroke and previous GWAS associations with related cardiovascular phenotypes (myocardial infarction, atrial fibrillation, and carotid intima-media thickness). Fifty associations were identified. For all ischemic stroke, heritability was 37.9%. Heritability varied markedly by stroke subtype being 40.3% for large-vessel disease and 32.6% for cardioembolic but lower for small-vessel disease (16.1%). No previously reported candidate gene was significant after rigorous correction for multiple testing. In contrast, 3 loci from related cardiovascular GWAS studies were significant: PHACTR1 in large-vessel disease (P=2.63e(-6)), PITX2 in cardioembolic stroke (P=4.78e(-8)), and ZFHX3 in cardioembolic stroke (P=5.50e(-7)). There is substantial heritability for ischemic stroke, but this varies for different stroke subtypes. Previous candidate gene associations contribute little to this heritability, but GWAS studies in related cardiovascular phenotypes are identifying robust associations. The heritability data, and data from GWAS, suggest detecting additional associations will depend on careful stroke subtyping.

  1. Meier-Gorlin syndrome genotype-phenotype studies: 35 individuals with pre-replication complex gene mutations and 10 without molecular diagnosis.

    NARCIS (Netherlands)

    Munnik, S.A. de; Bicknell, L.S.; Aftimos, S.; Al-Aama, J.Y.; Bever, Y. Van; Bober, M.B.; Clayton-Smith, J.; Edrees, A.Y.; Feingold, M.; Fryer, A.; Hagen, J.M. van; Hennekam, R.C.M.; Jansweijer, M.C.E.; Johnson, D.; Kant, S.G.; Opitz, J.M.; Ramadevi, A.R.; Reardon, W.; Ross, A.; Sarda, P.; Schrander-Stumpel, C.T.R.M.; Schoots, J.; Temple, I.K.; Terhal, P.A.; Toutain, A.; Wise, C.A.; Wright, M.; Skidmore, D.L.; Samuels, M.E.; Hoefsloot, L.H.; Knoers, N.V.A.M.; Brunner, H.G.; Jackson, A.P.; Bongers, M.H.F.

    2012-01-01

    Meier-Gorlin syndrome (MGS) is an autosomal recessive disorder characterized by microtia, patellar aplasia/hypoplasia, and short stature. Recently, mutations in five genes from the pre-replication complex (ORC1, ORC4, ORC6, CDT1, and CDC6), crucial in cell-cycle progression and growth, were

  2. Meier-Gorlin syndrome genotype-phenotype studies: 35 individuals with pre-replication complex gene mutations and 10 without molecular diagnosis.

    NARCIS (Netherlands)

    Munnik, S.A. de; Bicknell, L.S.; Aftimos, S.; Al-Aama, J.Y.; Bever, Y. Van; Bober, M.B.; Clayton-Smith, J.; Edrees, A.Y.; Feingold, M.; Fryer, A.; Hagen, J.M. van; Hennekam, R.C.M.; Jansweijer, M.C.E.; Johnson, D.; Kant, S.G.; Opitz, J.M.; Ramadevi, A.R.; Reardon, W.; Ross, A.; Sarda, P.; Schrander-Stumpel, C.T.R.M.; Schoots, J.; Temple, I.K.; Terhal, P.A.; Toutain, A.; Wise, C.A.; Wright, M.; Skidmore, D.L.; Samuels, M.E.; Hoefsloot, L.H.; Knoers, N.V.A.M.; Brunner, H.G.; Jackson, A.P.; Bongers, M.H.F.

    2012-01-01

    Meier-Gorlin syndrome (MGS) is an autosomal recessive disorder characterized by microtia, patellar aplasia/hypoplasia, and short stature. Recently, mutations in five genes from the pre-replication complex (ORC1, ORC4, ORC6, CDT1, and CDC6), crucial in cell-cycle progression and growth, were identifi

  3. Self-replication with magnetic dipolar colloids.

    Science.gov (United States)

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

    2015-10-01

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

  4. 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…

  5. A replication study for genome-wide gene expression levels in two layer lines elucidates differentially expressed genes of pathways involved in bone remodeling and immune responsiveness.

    Directory of Open Access Journals (Sweden)

    Christin Habig

    Full Text Available The current replication study confirmed significant differences in gene expression profiles of the cerebrum among the two commercial layer lines Lohmann Selected Leghorn (LSL and Lohmann Brown (LB. Microarray analyses were performed for 30 LSL and another 30 LB laying hens kept in the small group housing system Eurovent German. A total of 14,103 microarray probe sets using customized Affymetrix ChiGene-1_0-st Arrays with 20,399 probe sets were differentially expressed among the two layer lines LSL and LB (FDR adjusted P-value <0.05. An at least 2-fold change in expression levels could be observed for 388 of these probe sets. In LSL, 214 of the 388 probe sets were down- and 174 were up-regulated and vice versa for the LB layer line. Among the 174 up-regulated probe sets in LSL, we identified 51 significantly enriched Gene ontology (GO terms of the biological process category. A total of 63 enriched GO-terms could be identified for the 214 down-regulated probe sets of the layer line LSL. We identified nine genes significantly differentially expressed between the two layer lines in both microarray experiments. These genes play a crucial role in protection of neuronal cells from oxidative stress, bone mineral density and immune response among the two layer lines LSL and LB. Thus, the different regulation of these genes may significantly contribute to phenotypic trait differences among these layer lines. In conclusion, these novel findings provide a basis for further research to improve animal welfare in laying hens and these layer lines may be of general interest as an animal model.

  6. Conditioned blocking and schizophrenia: a replication and study of the role of symptoms, age, onset-age of psychosis and illness-duration.

    Science.gov (United States)

    Bender, S; Müller, B; Oades, R D; Sartory, G

    2001-04-15

    Measures of selective attention processing like latent inhibition (LI) and conditioned blocking (CB) are disturbed in some patients with schizophrenia. [LI is the delay in learning about the associations of a stimulus that has been associated with no event (versus de novo learning); CB is the delay in learning the associations of a stimulus-component when the other component has already started to acquire these associations.] We proposed: (1) to replicate the reported decreases of CB in patients without paranoid-hallucinatory symptoms; (2) to see if CB depends on the age of illness-onset and its duration, as reported for LI. We studied 101 young and old, acute and chronically ill patients with schizophrenia, of whom 62 learned a modified 'mouse-in-house' CB task, and compared them with 62 healthy controls matched for age, education and socio-economic background. CB was more evident in patients with a diagnosis of paranoid schizophrenia than other subtypes. An unusual persistence of high CB scores through testing was associated with productive symptoms (including positive thought disorder). Reduced CB related to the expression of (a) Schneider's first rank symptoms of ideas-of-reference and (b) to negative symptoms like poor rapport and poor attention. CB was less evident in the older patients and those with an earlier illness-onset. In contrast to the similar LI test of selective attention, CB is found in patients with paranoid schizophrenia and its expression is not related closely to illness duration. This implies that the two tests reflect the activity of different underlying processes. We suggest that reduced CB on initial test-trials in nonparanoid schizophrenia reflects the unusual persistence of controlled information processing strategies that would normally become automatic during conditioning. In contrast, continued CB during testing reflects an unusual persistence of automatic processing strategies.

  7. 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.

  8. 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.

  9. 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.

  10. DATABASE REPLICATION IN HETEROGENOUS PLATFORM

    Directory of Open Access Journals (Sweden)

    Hendro Nindito

    2014-01-01

    Full Text Available The application of diverse database technologies in enterprises today is increasingly a common practice. To provide high availability and survavibality of real-time information, a database replication technology that has capability to replicate databases under heterogenous platforms is required. The purpose of this research is to find the technology with such capability. In this research, the data source is stored in MSSQL database server running on Windows. The data will be replicated to MySQL running on Linux as the destination. The method applied in this research is prototyping in which the processes of development and testing can be done interactively and repeatedly. The key result of this research is that the replication technology applied, which is called Oracle GoldenGate, can successfully manage to do its task in replicating data in real-time and heterogeneous platforms.