WorldWideScience

Sample records for replicate earlier studies

  1. 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.

  2. A primary care Web-based Intervention Modeling Experiment replicated behavior changes seen in earlier paper-based experiment

    OpenAIRE

    Treweek, S.; Francis, JJ; Bonetti, D; Barnett, K; Eccles, MP; Hudson, J.; Jones, C.; Pitts, NB; Ricketts, IW; Sullivan, F; Weal, M; MacLennan, G.

    2016-01-01

    OBJECTIVES: Intervention Modeling Experiments (IMEs) are a way of developing and testing behavior change interventions before a trial. We aimed to test this methodology in a Web-based IME that replicated the trial component of an earlier, paper-based IME. STUDY DESIGN AND SETTING: Three-arm, Web-based randomized evaluation of two interventions (persuasive communication and action plan) and a "no intervention" comparator. The interventions were designed to reduce the number of antibiotic p...

  3. A primary care Web-based Intervention Modeling Experiment replicated behavior changes seen in earlier paper-based experiment.

    Science.gov (United States)

    Treweek, Shaun; Francis, Jill J; Bonetti, Debbie; Barnett, Karen; Eccles, Martin P; Hudson, Jemma; Jones, Claire; Pitts, Nigel B; Ricketts, Ian W; Sullivan, Frank; Weal, Mark; MacLennan, Graeme

    2016-12-01

    Intervention Modeling Experiments (IMEs) are a way of developing and testing behavior change interventions before a trial. We aimed to test this methodology in a Web-based IME that replicated the trial component of an earlier, paper-based IME. Three-arm, Web-based randomized evaluation of two interventions (persuasive communication and action plan) and a "no intervention" comparator. The interventions were designed to reduce the number of antibiotic prescriptions in the management of uncomplicated upper respiratory tract infection. General practitioners (GPs) were invited to complete an online questionnaire and eight clinical scenarios where an antibiotic might be considered. One hundred twenty-nine GPs completed the questionnaire. GPs receiving the persuasive communication did not prescribe an antibiotic in 0.70 more scenarios (95% confidence interval [CI] = 0.17-1.24) than those in the control arm. For the action plan, GPs did not prescribe an antibiotic in 0.63 (95% CI = 0.11-1.15) more scenarios than those in the control arm. Unlike the earlier IME, behavioral intention was unaffected by the interventions; this may be due to a smaller sample size than intended. A Web-based IME largely replicated the findings of an earlier paper-based study, providing some grounds for confidence in the IME methodology. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. 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...

  5. Childhood Hair Product Use and Earlier Age at Menarche in a Racially Diverse Study Population: A Pilot Study

    Science.gov (United States)

    James-Todd, Tamarra; Terry, Mary Beth; Rich-Edwards, Janet; Deierlein, Andrea; Senie, Ruby

    2013-01-01

    Purpose Previous studies suggest that hair products containing endocrine disrupting chemicals could alter puberty. We evaluated the association between childhood hair product use and age at menarche in a racially diverse study population. Methods We recruited 300 African-American, African-Caribbean, Hispanic, and white women from the New York City metropolitan area who were between 18 and 77 years of age. Data were collected retrospectively on hair oil, lotion, leave-in conditioner, perm, and other types of hair products used prior to age 13. Recalled age at menarche ranged from 8 to 19 years. We used multivariable binomial regression to evaluate the association between hair product use and age at menarche (=12), adjusting for potential confounders. Results African-Americans were more likely to use hair products and reached menarche earlier than other racial/ethnic groups. Women reporting childhood hair oil use had a risk ratio of 1.4 (95% CI: 1.1-1.9) for earlier menarche, adjusting for race/ethnicity and year of birth. Hair perm users had an increased risk for earlier menarche (adjusted risk ratio: 1.4, 95% CI: 1.1-1.8). Other types of hair products assessed in this study were not associated with earlier menarche. Conclusions Childhood hair oil and perm use were associated with earlier menarche. If replicated, these results suggest that hair product use may be important to measure in evaluating earlier age at menarche. PMID:21421329

  6. 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.

  7. Does menopause start earlier in smokers? Evidence from the Pro-Saude Study

    Directory of Open Access Journals (Sweden)

    Paula de Holanda Mendes

    2013-12-01

    Full Text Available OBJECTIVES: cigarette smoking has been the modifiable risk factor most consistently associated with earlier menopause. This preliminary study based on cross-sectional data aimed to analyze the association between smoking status and age of onset of menopause in a Brazilian population. METHODS: a cross-sectional study was carried out with 1,222 female employees of Rio de Janeiro university campuses aged over 35 years who were at risk of natural menopause. A Cox proportional hazards model was used to investigate the association between smoking status and age at the onset of menopause, adjusting for education, parity and alcohol consumption. RESULTS: current smokers showed a 56% increase in the risk of menopause, being 1.8 years younger at menopause onset compared with women who had never smoked. However, no differences were observed between former smokers and women who had never smoked. The adjusted median age at menopause was 49.5 years for current smokers and 51.3 years for women who had never smoked (p<0.05. CONCLUSIONS: the results suggest a deleterious but potentially reversible effect of smoking on the age of onset of menopause, which should receive greater attention in tobacco control efforts. Longitudinal analyses of this association will be carried out in the future in a follow-up study of this population.

  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. High hunting pressure selects for earlier birth date: Wild boar as a case study

    Science.gov (United States)

    Gamelon, M.; Besnard, A.; Gaillard, J.-M.; Servanty, S.; Baubet, E.; Brandt, S.; Gimenez, O.

    2011-01-01

    Exploitation by humans affects the size and structure of populations. This has evolutionary and demographic consequences that have typically being studied independent of one another. We here applied a framework recently developed applying quantitative tools from population ecology and selection gradient analysis to quantify the selection on a quantitative trait-birth date-through its association with multiple fitness components. From the long-term monitoring (22 years) of a wild boar (Sus scrofa scrofa) population subject to markedly increasing hunting pressure, we found that birth dates have advanced by up to 12 days throughout the study period. During the period of low hunting pressure, there was no detectable selection. However, during the period of high hunting pressure, the selection gradient linking breeding probability in the first year of life to birth date was negative, supporting current life-history theory predicting selection for early births to reproduce within the first year of life with increasing adult mortality. ?? 2011 The Author(s). Evolution?? 2011 The Society for the Study of Evolution..

  11. 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

  12. 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

  13. 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.

  14. 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

  15. Learning for interprofessional and inter-agency practice in the new social work curriculum: evidence from an earlier research study.

    Science.gov (United States)

    Whittington, C; Bell, L

    2001-05-01

    The UK Government's consultation document, A Quality Strategy for Social Care (2000) seeks consistency and excellence in care services and enhanced service partnerships. It states that this requires improved training for social workers and raises the prospect of a new social work curriculum in which learning for interprofessional and inter-agency practice will be strengthened. The document stresses the importance of evidence in decision-making in social care and this principle applies equally to training but there are few recent research findings on interprofessional and inter-agency learning in the social work curriculum. There are, however, findings from an earlier study which contributed to the mid-1990s review of the Diploma in Social Work but which have not previously been published in the mainstream media. These findings are reported and show: the kinds of organisations and professions with whom social work practitioners were in close contact in their jobs; the importance attached by social workers to defined skills in working with them; the perceived usefulness of training in developing relevant knowledge and skills; perceptions of shared training; and marked differences of learning experience reported by practitioners who had taken different training courses. Each set of findings is described and used as the basis of questions for the new social work curriculum.

  16. 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)

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

    CERN Document Server

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

    2003-01-01

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

  18. 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…

  19. 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

  20. 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…

  1. 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.

  2. 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

  3. The Fischa-Dagnitz spring, Southern Vienna Basin: a multi tracer time series study re-assessing earlier conceptual assumptions.

    Science.gov (United States)

    Suckow, Axel; Gerber, Christoph; Kralik, Martin; Sültenfuss, Jürgen; Purtschert, Roland

    2013-04-01

    The gravel aquifer of the Southern Vienna Basin is a very important backup drinking water resource for the city of Vienna. A discharge location, the Fischa-Dagnitz spring in the Southern Vienna Basin, Austria, was re-investigated in 2011, five years after the gas exchange tracer test published in (Stolp et al., 2010), and sampled for stable isotopes 18O/2H, tritium, 3He, SF6 and 85Kr (Gerber et al., 2012). Additionally, new tritium time series data (Davis et al., 1967), previously not considered in Stolp et al. (2010), were included. These show a higher and earlier tritium peak of >300 TU in 1965 in the discharge of the Fischa-Dagnitz spring as compared to 221 TU in 1972 considered in Stolp et al. (2010). The new 3He, SF6 and 85Kr gas tracer data from 2011 confirm the earlier finding for 3He of Stolp et al. (2010) and indicate a more recent equilibration with the atmosphere than the water bound tracers 18O, 2H and tritium. A new modelling attempt using the Lumpy code (Suckow, 2012) confirmed the discrepancy between the tritium data and the gaseous tracers 3He, SF6 and 85Kr. No steady-state combination of local recharge (represented by an exponential model) and Schwarza river infiltration flowing through the gravel aquifer (represented by a parallel dispersion model) can equally well explain both the tritium time series and the gas tracer results. A revised conceptual model proposes that a pinching of the aquifer at unconformities in the gravel body or a fault zone known in the gravel body forces groundwater along the flow path closer to the surface and exposes it to the atmosphere. This would tend to reset the "dating" clock for the gaseous tracers 3He, SF6 and 85Kr, which can equilibrate quickly with the atmosphere, but not for tritium, which marks the transport behaviour of the water itself. These findings are of importance also for other multi-tracer assessments of groundwater movement in phreatic aquifer systems. References: Davis, G.H., Payne, B.R., Dincer, T

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. Wean Earlier and Automatically with New technology (the WEAN study: a protocol of a multicentre, pilot randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Lessard Martin R

    2009-09-01

    Full Text Available Abstract Background Weaning is the process during which mechanical ventilation is withdrawn and the work of breathing is transferred from the ventilator back to the patient. Prolonged weaning is associated with development of ventilator-related complications and longer stays in the Intensive Care Unit (ICU. Computerized or Automated Weaning is a novel weaning strategy that continuously measures and adapts ventilator support (by frequently measuring and averaging three breathing parameters and automatically conducts Spontaneous Breathing Trials to ascertain whether patients can resume autonomous breathing. Automated Weaning holds promise as a strategy to reduce the time spent on the ventilator, decrease ICU length of stay, and improve clinically important outcomes. Methods/Design A pilot weaning randomized controlled trial (RCT is underway in the ICUs of 8 Canadian hospitals. We will randomize 90 critically ill adults requiring invasive ventilation for at least 24 hours and identified at an early stage of the weaning process to either Automated Weaning (SmartCare™ or Protocolized Weaning. The results of a National Weaning Survey informed the design of the Protocolized Weaning arm. Both weaning protocols are operationalized in Pressure Support mode, include opportunities for Spontaneous Breathing Trials, and share a common sedation protocol, oxygen titration parameters, and extubation and reintubation criteria. The primary outcome of the WEAN study is to evaluate compliance with the proposed weaning and sedation protocols. A key secondary outcome of the pilot RCT is to evaluate clinician acceptance of the weaning and sedation protocols. Prior to initiating the WEAN Study, we conducted a run-in phase, involving two patients per centre (randomizing the first participant to either weaning strategy and assigning the second patient to the alternate strategy to ensure that participating centres could implement the weaning and sedation protocols and

  9. Toward earlier identification and preventative intervention in schizophrenia: evidence from the London Child Health and Development Study.

    Science.gov (United States)

    Laurens, Kristin R; Cullen, Alexis E

    2016-04-01

    The London Child Health and Development Study (CHADS) is a prospective, longitudinal investigation of children, sampled from the general community aged 9-11 years and assessed biennially, who present premorbid risk markers for schizophrenia. The study aims to characterise developmental trajectories of psychological, cognitive, and biological functioning in at-risk children and identify potential targets for early preventative intervention. This review summarises CHADS findings, discusses these in the context of recent theory regarding aetiology and prevention of schizophrenia, and highlights challenges to be addressed with future research. We review (1) epidemiological information on the prevalence and correlates of developmental antecedents of schizophrenia in the general child population, (2) evidence of psychosocial, cognitive, and biological dysfunctions in at-risk children presenting multiple antecedents of schizophrenia and at-risk children with a family history of schizophrenia, and (3) related findings from an associated sample of help-seeking children receiving intervention. Community-based screening of 9-11-year olds identified ~9 % with a triad of antecedents of schizophrenia [including psychotic-like experiences (PLEs)] who are putatively at-risk of psychosis; these children reported greater exposure and responsivity to stressors, impairments in general intelligence and specific cognitive functions, brain structure and function abnormalities, and neuromotor dysfunction. Preliminary evidence suggests distressing PLEs are a viable target for cognitive-behavioural intervention in at-risk children. Intervention in early, premorbid phases of illness might alleviate current difficulties and avert future schizophrenia using benign treatments. The CHADS programme has identified several markers that may index early pathophysiology and constitute potential targets for preventative intervention.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. Interplay between filter-feeding zoobenthos and hydrodynamics in the shallow Odense Fjord (Denmark) - Earlier and recent studies, perspectives and modelling

    Science.gov (United States)

    Riisgård, H. U.; Lassen, J.; Kortegaard, M.; Møller, L. F.; Friedrichs, M.; Jensen, M. H.; Larsen, P. S.

    2007-11-01

    The shallow Odense Fjord (Denmark) is characterized by a large biomass of filter-feeding polychaetes ( Nereis diversicolor), clams ( Mya arenaria), cockles ( Cerastoderma glaucum), and amphipods ( Corophium volutator). The present paper summarizes studies on zoobenthic filter-feeding in Odense Fjord from the last 10 years. The general principles discovered are extracted and compared to available tools for modelling of the primary characteristics of interplay between benthic filter-feeders and hydrodynamics. Earlier works have been supplemented with data from a recent field study conducted in the shallow inner part of the fjord. Based on data from this study site, the reduction in phytoplankton for fully mixed and incompletely mixed flows has been modelled. It was found that fully mixed flow results in a potential half-life for phytoplankton of only 1.3 h, whereas for the incompletely mixed water the half-life is 2.7 times longer. The field measurements clearly demonstrate the presence of a strong interplay between filter-feeders and hydrodynamics, but although a certain grazing impact is evident from vertical chlorophyll a profiles with often strongly reduced near-bottom concentrations it is not straightforward to identify and model even the main bio-physical processes that prevent the dense populations of filter-feeders to completely control the phytoplankton biomass in Odense Fjord.

  17. 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.

  18. 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...

  19. 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.

  20. 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....

  1. 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...

  2. 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...

  3. Heart Disease Kicks in Earlier for Obese People

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_164003.html Heart Disease Kicks in Earlier for Obese People Study found ... News) -- Overweight and obese people tend to develop heart disease at an earlier age, living with chronic illness ...

  4. 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.

  5. 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.

  6. 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.

  7. 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...

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  9. Euthanasia: why people want to die earlier.

    Science.gov (United States)

    Seale, C; Addington-Hall, J

    1994-09-01

    The results from two surveys in England of relatives and others who knew people in samples drawn from death certificates are reported. The main focus is on a sample of 3696 people dying in 1990 in 20 health authorities, with supporting analysis from an earlier national sample of 639 people dying in 1987. The incidence of people saying they wanted to die sooner, and of requests for euthanasia are reported. Excluding a proportion who did not wish to express a view, or did not know the answer, about a quarter of both respondents and the people who died expressed the view that an earlier death would be, or would have been, preferable. 3.6% of people in the 1990 study were said to have asked for euthanasia at some point in the last year of life. The extent to which such views were determined by the experience of pain, other distressing symptoms, dependency and social and cultural factors such as religious belief and social class is explored. The finding that dependency was important in causing the feeling that an earlier death would have been better, as well as requests for euthanasia, is related to the public debate about euthanasia, which often contains the assertion that fear of pain is a dominant factor. Pain was found to be a significant factor in death from cancer, but not as important for other causes of death. Social class, place of residence of the deceased, and strength and type of religious faith were found to be largely insignificant in influencing feelings about an earlier death and requests for euthanasia.

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

    Directory of Open Access Journals (Sweden)

    Cameron Palmer

    2017-07-01

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

  11. 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

  12. 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…

  13. 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…

  14. 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

  15. Alzheimer's and Dementia Testing for Earlier Diagnosis

    Science.gov (United States)

    ... Today Major Milestones Treatment Horizon Earlier Diagnosis Prevention Alzheimer’s and Dementia Testing for Earlier Diagnosis What if we could diagnose Alzheimer's before symptoms started? The hope is, future treatments ...

  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. "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…

  3. 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

  4. 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

  5. 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

  6. Premarital Cohabitation vs. Traditional Courtship and Subsequent Marital Adjustment: A Replication and Follow-up.

    Science.gov (United States)

    Watson, Roy E. L.; DeMeo, Peter W.

    1987-01-01

    Replicated earlier study of couples in first year of marriage. Conducted follow-up study of couples in fourth year of marriage who had participated in original or replication studies. Concludes that premarital relationships of the couples, whether cohabitation or traditional courtship, does not appear to have had long-term effect on marital…

  7. 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.

  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. 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.

  10. 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.

  11. Epidemiological study of sun exposure and visual field damage in children in Primorsko-Goranska County--the risk factors of earlier development of macular degeneration.

    Science.gov (United States)

    Vojniković, Bozo; Synek, Svatopluk; Mićović, Vladimir; Telezar, Mirna; Linsak, Zeljko

    2010-04-01

    The aim of this study was to examine the possible harmful effects of solar exposure on visual field damage in children living in Primorsko-Goranska County. Our previous work has shown noxious influence on visual field in children with anamnesis long term exposure to sunlight. This is an extended study, including children in Novi Vinodolski and Gorski kotar. We measured possible defect in isopteric visual field and macular-meridian thresholds. In the area of island of Rab these changes were the biggest, subsequently is Novi Vinodolski and at least Gorski kotar with the smallest range of eye complicates according to exposure to sunlight. These damages correlate with the areas of great solar emission. Damages in periphery isopters of visual field have shown the characteristics of periphery defect invagination, while increased macular thresholds in complete visual field was from 5 to 15Asb. We can conclude that there is direct connection between increased sunlight and long-term exposure to sunlight on one side, and on the other side, damages of retinal perception. Increased sun exposure may represent very important factors in early occurrence and develop of Age-Related Macular Degeneration (AMD). It is recommended the children protection in summer months, as well as taking derivates of vitamin A and antioxidants. Nowadays, AMD is one of the most important causes of damaged visual field, pretend to be national problem if we don't use the adequate prevention. World Health Organization has to begin with prevention of AMD, including these risk factors.

  12. Cognitive function in a middle aged cohort is related to higher quality dietary pattern 5 and 25 years earlier: the CARDIA study.

    Science.gov (United States)

    Zhu, N; Jacobs, D R; Meyer, K A; He, K; Launer, L; Reis, J P; Yaffe, K; Sidney, S; Whitmer, R A; Steffen, L M

    2015-01-01

    Preserving cognitive function is an important public health issue. We investigated whether dietary pattern associates with cognitive function in middle-age. We studied 2435 participants in the community-based Coronary Artery Risk Development in Young Adults (CARDIA) study of black and white men and women aged 18-30 in 1985-86 (year 0, Y0). We hypothesized that a higher A Priori Diet Quality Score, measured at Y0 and Y20, is associated with better cognitive function measured at Y25. The diet score incorporated 46 food groups (each in servings/day) as the sum of quintile ranks of food groups rated beneficial, 0 for food groups rated neutral, and reversed quintile ranks for food groups rated adverse; higher score indicated better diet quality. Y25 cognitive testing included verbal memory (Rey Auditory-Verbal Learning Test (RAVLT)), psychomotor speed (Digit Symbol Substitution Test (DSST)) and executive function (Stroop). Per 10-unit higher diet score at Y20, the RAVLT was 0.32 words recalled higher, the DSST was 1.76 digits higher, and the Stroop was 1.00 seconds+errors lower (better performance) after adjusting for race, sex, age, clinic, and energy intake. Further adjustment for physical activity, smoking, education, and body mass index attenuated the association slightly. Diet score at Y0 and increase in diet score over 20 years were also positively associated with each cognitive test. A higher quality dietary pattern was associated with better cognitive function 5 years and even 25 years later in apparently healthy middle-aged adults.

  13. 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...

  14. 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

  15. 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.

  16. 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.

  17. 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....

  18. Leadership Orientation as a Function of Interpersonal Need Structure: A Replication with Negative Results.

    Science.gov (United States)

    Tucker, Jeffrey H.

    1983-01-01

    To replicate the Kuehl et al. (1975) study, 151 graduate students completed the Leadership Opinion Questionnaire, Least Preferred Co-Worker (LPC) Questionnaire, FIRO-B (Functional Interpersonal Relations Orientation-Behavior), and F-Scale. Data failed to replicate earlier significant correlations between interpersonal needs as measured by the LPC…

  19. Leadership Orientation as a Function of Interpersonal Need Structure: A Replication with Negative Results.

    Science.gov (United States)

    Tucker, Jeffrey H.

    1983-01-01

    To replicate the Kuehl et al. (1975) study, 151 graduate students completed the Leadership Opinion Questionnaire, Least Preferred Co-Worker (LPC) Questionnaire, FIRO-B (Functional Interpersonal Relations Orientation-Behavior), and F-Scale. Data failed to replicate earlier significant correlations between interpersonal needs as measured by the LPC…

  20. Can Breath Test Detect Stomach Cancers Earlier?

    Science.gov (United States)

    ... news/fullstory_163342.html Can Breath Test Detect Stomach Cancers Earlier? New technology may also spot esophageal cancers ... the only way to diagnose esophageal cancer or stomach cancer is with endoscopy. This method is expensive, invasive ...

  1. Can prion disease suspicion be supported earlier?

    Science.gov (United States)

    Medina, Zaira; Balaguer, Rainier Rodriguez; Calleja, Jesus Higuera

    2011-01-01

    The subacute spongiform encephalopathies are prion diseases characterized by acute and rapid neurodegeneration that lead to the death of the patient within months to a few years. The epidemiology of CJD is complicated and the frequency in Mexico is unknown. We aim to describe the cases of prion disease in Mexico. Consecutive patients who met the diagnostic criteria by the WHO were enrolled. We describe 26 patients with clinical manifestations, imaging and laboratory studies compatible with prion disease. The mean age at onset was 52 years old. The main clinical manifestations were cognitive alterations (69%) followed by extrapyramidal movements (50%), abnormal cerebellar function (46%), behavioral alterations (46%), myoclonus (46%) and mood depression (23%), among other features. Half of the patients progressed rapidly to a state of akinetic mutism (53%). Only 2 (7.6%) patients had a family history of a similar disease. Time interval between onset and diagnosis varied between 71 days to 24 months, with a median of 6 months. The classical bilateral basal ganglia hyperintensities were present in the very early stage of the disease. Protein 14-3-3 immuneassay in the CSF was positive in all measured cases. Bilateral basal ganglia hyperintensities was the most important early finding, while protein 14-3-3 was a late finding and the results were usually obtained after the patient was discharged. Around 1.5 cases of CJD cases per year are reported in our country. When suspected, MRI can support the diagnosis earlier than other studies. PMID:21869605

  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. 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.

  5. 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.

  6. 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...

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

    Science.gov (United States)

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

    2016-01-01

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

  8. 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.

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  10. The Persuasiveness of Metaphor: A Replication and Extension.

    Science.gov (United States)

    Siltanen, Susan A.

    A study was conducted to replicate and extend an earlier investigation of the persuasive effects of extended, intense concluding sex and death metaphors by using a more controlled design and by mixing metaphors. Fifty-eight high school students completed pretests assessing their attitudes toward a speech topic (legalization of marijuana). Two…

  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. 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.

  13. 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.

  14. 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.

  15. 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.

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

    OpenAIRE

    Stuckey, Ruth

    2014-01-01

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

  17. 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, ...

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. 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.

  10. 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....

  11. 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.

  12. 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.

  13. 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

  14. 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…

  15. 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

  16. 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.

  17. 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?

  18. 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.

  19. 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

  20. 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.

  1. 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

  2. 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 =

  3. 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…

  4. 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…

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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 ...

  12. Replication of Mu prophages lacking the central strong gyrase site.

    Science.gov (United States)

    Pato, Martin L

    2004-09-01

    Replication of Mu prophages lacking the central strong gyrase site (SGS) is severely slowed. To study details of the replication of these prophages, an assay was developed for determining the rate and extent of introduction of nicks at the 3'-ends of a Mu prophage, an early step in Mu replicative transposition. The maximal level of end-nicking of a prophage with the SGS, about 70-90% depending upon the host strain, was achieved within about 15 min after induction, whereas at that time less than 5% nicking was observed with a prophage lacking the SGS. The amount of nicking at the end of the SGS(-) prophage increased with time, and approx. 30% nicking of the SGS(-) prophage was achieved by 60 min post-induction. Nicking kinetics were identical at each end of the prophages, and no nicking was observed at the 5'-ends of the prophages, verifying in vivo the earlier results with in vitro systems. To determine if prophage location affects the kinetics of replication, we examined prophages at numerous chromosomal locations. SGS(+) prophages at different chromosomal locations showed essentially identical replication kinetics. SGS(-) prophages showed a range of delays in replication and host lysis. A gradient of delays was apparent, with prophages further from the chromosomal origin of replication, oriC, showing longer delays than ones nearer to oriC. However, there were also exceptions to this overall gradient. Possible explanations for the differences in the delays observed with SGS(-) prophages are discussed.

  13. 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...

  14. 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.

  15. 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

  16. Eukaryotic DNA Replication Fork.

    Science.gov (United States)

    Burgers, Peter M J; Kunkel, Thomas A

    2017-06-20

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

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

    Science.gov (United States)

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

    2013-01-01

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

  18. Earlier Debridement and Antibiotic Administration Decrease Infection

    Science.gov (United States)

    2010-01-01

    10.68 g). Using aseptic technique , a longitudinal incision was made over the left anterolateral femur, and the entire femoral shaft was exposed using... inoculated with Staphylococcus aureus. At 2, 6, or 24 hours following contamination, defects were irrigated and debrided then directly closed or...surgical techniques across clinicians. Animal studies may help to elucidate the issue. The aim of this study was to determine in a contami- nated critical

  19. 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.

  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. Accreting Binary Populations in the Earlier Universe

    Science.gov (United States)

    Hornschemeier, Ann

    2010-01-01

    It is now understood that X-ray binaries dominate the hard X-ray emission from normal star-forming galaxies. Thanks to the deepest (2-4 Ms) Chandra surveys, such galaxies are now being studied in X-rays out to z approximates 4. Interesting X-ray stacking results (based on 30+ galaxies per redshift bin) suggest that the mean rest-frame 2-10 keV luminosity from z=3-4 Lyman break galaxies (LBGs), is comparable to the most powerful starburst galaxies in the local Universe. This result possibly indicates a similar production mechanism for accreting binaries over large cosmological timescales. To understand and constrain better the production of X-ray binaries in high-redshift LBGs, we have utilized XMM-Newton observations of a small sample of z approximates 0.1 GALEX-selected Ultraviolet-Luminous Galaxies (UVLGs); local analogs to high-redshift LBGs. Our observations enable us to study the X-ray emission from LBG-like galaxies on an individual basis, thus allowing us to constrain object-to-object variances in this population. We supplement these results with X-ray stacking constraints using the new 3.2 Ms Chandra Deep Field-South (completed spring 2010) and LBG candidates selected from HST, Swift UVOT, and ground-based data. These measurements provide new X-ray constraints that sample well the entire z=0-4 baseline

  3. Study on the Earlier Public Security Work to Solve the Group Events%基于群体性事件的公安工作前置研究

    Institute of Scientific and Technical Information of China (English)

    陈小华

    2015-01-01

    How to deal with group events concerns the image of government and public security agency and re-flects their social governance capacity. Development of group events and the idea of ruling the country according to law advocated by Central Government set new demands on public security agency about how to deal with group e-vents, and the earlier public security work can be seen as an effective measure to meet the demands. Assisted by the laws that how the group events happens and develops, the public security can provide the earlier community ser-vice, set up local police stations on network, keep its indiscriminate service as long as 24 hours and establish joint control with jurisdiction units on network through making full use of high and new technology and continuously inno-vating service mode. Only in this way can the public security do some earlier work to reduce the factors leading to group events, to solve contradictions timely and to stop the group events from happening or worsening.%群体性事件的处置关乎政府和公安机关的形象,体现了他们的社会治理能力。我国群体性事件发展态势和中央倡导的依法治国理念,对公安机关处置群体性事件提出了新要求,公安工作前置便是实现这一要求的有效手段。公安机关根据群体性事件发生、演变的规律,充分利用高新技术,不断创新服务方式,通过社区服务前置、建立网络派出所、提供全天候、无差别服务、以及辖区单位建立治安联控网络等措施,就能较好地将公安工作前置付诸实践,减少引发群体性事件的因素,适时化解相关方面的矛盾,降低事件发生或恶化的概率。

  4. 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.

  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

    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 : 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

  7. 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.

  8. 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

  9. 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

  10. 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?

  11. 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).

  12. 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.

  13. 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.

  14. 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.

  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. 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...

  17. 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.

  18. Trend of earlier spring in central Europe continued

    Science.gov (United States)

    Ungersböck, Markus; Jurkovic, Anita; Koch, Elisabeth; Lipa, Wolfgang; Scheifinger, Helfried; Zach-Hermann, Susanne

    2013-04-01

    Modern phenology is the study of the timing of recurring biological events in the animal and plant world, the causes of their timing with regard to biotic and abiotic forces, and the interrelation among phases of the same or different species. The relationship between phenology and climate explains the importance of plant phenology for Climate Change studies. Plants require light, water, oxygen mineral nutrients and suitable temperature to grow. In temperate zones the seasonal life cycle of plants is primarily controlled by temperature and day length. Higher spring air temperatures are resulting in an earlier onset of the phenological spring in temperate and cool climate. On the other hand changes in phenology due to climate change do have impact on the climate system itself. Vegetation is a dynamic factor in the earth - climate system and has positive and negative feedback mechanisms to the biogeochemical and biogeophysical fluxes to the atmosphere Since the mid of the 1980s spring springs earlier in Europe and autumn is shifting back to the end of the year resulting in a longer vegetation period. The advancement of spring can be clearly attributed to temperature increase in the months prior to leaf unfolding and flowering, the timing of autumn is more complex and cannot easily be attributed to one or some few parameters. To demonstrate that the observed advancement of spring since the mid of 1980s is pro-longed in 2001 to 2010 and the delay of fall and the lengthening of the growing season is confirmed in the last decade we picked out several indicator plants from the PEP725 database www.pep725.eu. The PEP725 database collects data from different European network operators and thus offers a unique compilation of phenological observations; the database is regularly updated. The data follow the same classification scheme, the so called BBCH coding system so they can be compared. Lilac Syringa vulgaris, birch Betula pendula, beech Fagus and horse chestnut Aesculus

  19. 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....

  20. Replication program of active and inactive multigene families in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Hatton, K.S.; Dhar, V.; Brown, E.H.; Iqbal, M.A.; Stuart, S.; Didamo, V.T.; Schildkraut, C.L.

    1988-05-01

    In a comprehensive study, the temporal replication of tissue-specific genes and flanking sequences was compared in nine cells lines exhibiting different tissue-specific functions. Some of the rules the authors determined for the replication of these tissue specific genes include the following. (i) Actively transcribed genes usually replicate during the first quarter of the S phase. (ii) Some immunoglobulin genes replicate during the first half of S phase even when no transcriptional activity is detected but appear to replicate even earlier in cell lines where they are transcribed. (iii) Nontranscribed genes can replicate during any interval of S phase. (iv) Multigene families arranged in clusters of 250 kilobases or less define a temporal compartment comprising approximately one-quarter of S phase. While these rules, and others that are discussed, apply to the tissue-specific genes studied here, all tissue-specific genes may not follow this pattern. In addition, housekeeping genes did not follow some of these rules. These results provide the first molecular evidence that the coordinate timing of replication of contiguous sequences within a multigene family is a general property of the mammalian genome. The relationship between replication very early during S phase and the transcriptional activity within a chromosomal domain is discussed.

  1. Scientific Knowledge Suppresses but Does Not Supplant Earlier Intuitions

    Science.gov (United States)

    Shtulman, Andrew; Valcarcel, Joshua

    2012-01-01

    When students learn scientific theories that conflict with their earlier, naive theories, what happens to the earlier theories? Are they overwritten or merely suppressed? We investigated this question by devising and implementing a novel speeded-reasoning task. Adults with many years of science education verified two types of statements as quickly…

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. Pre-admission clinical course of meningococcal disease and opportunities for the earlier start of appropriate intervention: a prospective epidemiological study on 752 patients in the Netherlands, 2003-2005.

    NARCIS (Netherlands)

    Greeff, SC de; Melker, HE de; Schouls, L.M.; Spanjaard, L.; Deuren, M. van

    2008-01-01

    To improve the timeliness of health care delivery to patients with meningococcal disease, the early disease evolution and clinical manifestation at admission were studied in all 752 patients with invasive meningococcal disease in the Netherlands in 2003-2005. Eighty-eight percent (88%) had serogroup

  7. Mismatch repair balances leading and lagging strand DNA replication fidelity.

    Directory of Open Access Journals (Sweden)

    Scott A Lujan

    Full Text Available The two DNA strands of the nuclear genome are replicated asymmetrically using three DNA polymerases, α, δ, and ε. Current evidence suggests that DNA polymerase ε (Pol ε is the primary leading strand replicase, whereas Pols α and δ primarily perform lagging strand replication. The fact that these polymerases differ in fidelity and error specificity is interesting in light of the fact that the stability of the nuclear genome depends in part on the ability of mismatch repair (MMR to correct different mismatches generated in different contexts during replication. Here we provide the first comparison, to our knowledge, of the efficiency of MMR of leading and lagging strand replication errors. We first use the strand-biased ribonucleotide incorporation propensity of a Pol ε mutator variant to confirm that Pol ε is the primary leading strand replicase in Saccharomyces cerevisiae. We then use polymerase-specific error signatures to show that MMR efficiency in vivo strongly depends on the polymerase, the mismatch composition, and the location of the mismatch. An extreme case of variation by location is a T-T mismatch that is refractory to MMR. This mismatch is flanked by an AT-rich triplet repeat sequence that, when interrupted, restores MMR to > 95% efficiency. Thus this natural DNA sequence suppresses MMR, placing a nearby base pair at high risk of mutation due to leading strand replication infidelity. We find that, overall, MMR most efficiently corrects the most potentially deleterious errors (indels and then the most common substitution mismatches. In combination with earlier studies, the results suggest that significant differences exist in the generation and repair of Pol α, δ, and ε replication errors, but in a generally complementary manner that results in high-fidelity replication of both DNA strands of the yeast nuclear genome.

  8. 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...

  9. 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.

  10. 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.

  11. 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…

  12. 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)

  13. "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,"…

  14. FDA Facilitates Research on Earlier Stages of Alzheimer's Disease

    Science.gov (United States)

    ... Updates FDA Facilitates Research on Earlier Stages of Alzheimer's Disease Share Tweet Linkedin Pin it More sharing ... disease.” back to top New Paths for New Alzheimer’s Drugs FDA’s draft guidance aims to encourage research ...

  15. Family History of Colon Cancer Calls for Earlier Screening

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_164202.html Family History of Colon Cancer Calls for Earlier Screening ... 2017 (HealthDay News) -- If you've got a family history of colon or rectal cancers, you probably ...

  16. This contribution follows an earlier attempt to show that many ...

    African Journals Online (AJOL)

    spamer

    of longevity in large squid should be revised upwards. * Fisheries Centre, 2204 .... can be assumed to trigger reproduction in squid as well (see text) ..... and the ageing bias mentioned earlier), the second phase, however, is ... and senescence ...

  17. 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.

  18. 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:

  19. 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

  20. 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

  1. 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...

  2. 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)

  3. Earlier speech exposure does not accelerate speech acquisition.

    Science.gov (United States)

    Peña, Marcela; Werker, Janet F; Dehaene-Lambertz, Ghislaine

    2012-08-15

    Critical periods in language acquisition have been discussed primarily with reference to studies of people who are deaf or bilingual. Here, we provide evidence on the opening of sensitivity to the linguistic environment by studying the response to a change of phoneme at a native and nonnative phonetic boundary in full-term and preterm human infants using event-related potentials. Full-term infants show a decline in their discrimination of nonnative phonetic contrasts between 9 and 12 months of age. Because the womb is a high-frequency filter, many phonemes are strongly degraded in utero. Preterm infants thus benefit from earlier and richer exposure to broadcast speech. We find that preterms do not take advantage of this enriched linguistic environment: the decrease in amplitude of the mismatch response to a nonnative change of phoneme at the end of the first year of life was dependent on maturational age and not on the duration of exposure to broadcast speech. The shaping of phonological representations by the environment is thus strongly constrained by brain maturation factors.

  4. 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...

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Identification of the Sex of Earlier Embryos from Generic Hybrids of Chicken-Quail by Wpkci

    Institute of Scientific and Technical Information of China (English)

    QIAO Ai-jun; MA Wen-xia; LI Da-quan; MENG Qing-mei

    2008-01-01

    In this study,a protocol was deveolped the sex of earlier embryos of chicken(♂)-quail(♀)hybrids and successfully tested the sex proportion of each period (66-120 h). We acquired cross bred eggs by artificial insemination, hatched them in the same batch according to the standard hatching condition of chicken, and collected earlier living embryos at 66,72,78, 84,90,96,102,108,114, and 120 h randomly. We adopted RT-PCR protocol and multiple PCR, made the known sex quail as the external control, employed β-actin as the internal control, and used primers that were designed according to conservative area of gene Wpkci of quail to identify the sex of earlier hybrid embryos. The results indicated that the primer of Wpkci can be used to identify the sex of hybrid embryos accurately; there were more male than female in earlier embryos, the sex proportion of earlier embryos compared with academic numerical value was significantly different (P0.05). In the present study, we concluded that a simple, fast, credible and stable protocol to identify the sex of earlier hybrids embryos had been established by using primer of Wpkci; in earlier embryos, the death rate of female was higher than that of male and there was no fluctuant peak.

  20. International Expansion through Flexible Replication

    DEFF Research Database (Denmark)

    Jonsson, Anna; Foss, Nicolai Juul

    2011-01-01

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

  1. Adenovirus sequences required for replication in vivo.

    OpenAIRE

    Wang, K.; Pearson, G D

    1985-01-01

    We have studied the in vivo replication properties of plasmids carrying deletion mutations within cloned adenovirus terminal sequences. Deletion mapping located the adenovirus DNA replication origin entirely within the first 67 bp of the adenovirus inverted terminal repeat. This region could be further subdivided into two functional domains: a minimal replication origin and an adjacent auxillary region which boosted the efficiency of replication by more than 100-fold. The minimal origin occup...

  2. Mapping vaccinia virus DNA replication origins at nucleotide level by deep sequencing.

    Science.gov (United States)

    Senkevich, Tatiana G; Bruno, Daniel; Martens, Craig; Porcella, Stephen F; Wolf, Yuri I; Moss, Bernard

    2015-09-01

    Poxviruses reproduce in the host cytoplasm and encode most or all of the enzymes and factors needed for expression and synthesis of their double-stranded DNA genomes. Nevertheless, the mode of poxvirus DNA replication and the nature and location of the replication origins remain unknown. A current but unsubstantiated model posits only leading strand synthesis starting at a nick near one covalently closed end of the genome and continuing around the other end to generate a concatemer that is subsequently resolved into unit genomes. The existence of specific origins has been questioned because any plasmid can replicate in cells infected by vaccinia virus (VACV), the prototype poxvirus. We applied directional deep sequencing of short single-stranded DNA fragments enriched for RNA-primed nascent strands isolated from the cytoplasm of VACV-infected cells to pinpoint replication origins. The origins were identified as the switching points of the fragment directions, which correspond to the transition from continuous to discontinuous DNA synthesis. Origins containing a prominent initiation point mapped to a sequence within the hairpin loop at one end of the VACV genome and to the same sequence within the concatemeric junction of replication intermediates. These findings support a model for poxvirus genome replication that involves leading and lagging strand synthesis and is consistent with the requirements for primase and ligase activities as well as earlier electron microscopic and biochemical studies implicating a replication origin at the end of the VACV genome.

  3. 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...

  4. 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.

  5. 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.

  6. Modern human settlement in East Asia earlier than thought

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    @@ Tracing through human migration history with the help of genes, Dr. SU Bing and coworkers from the CAS Kunming Institute of Zoology (KIZ) lately revealed the evidence of a much earlier modem human settlement in East Asia than people previously thought.

  7. Hemodynamic parameters change earlier than tissue oxygen tension in hemorrhage.

    Science.gov (United States)

    Pestel, Gunther J; Fukui, Kimiko; Kimberger, Oliver; Hager, Helmut; Kurz, Andrea; Hiltebrand, Luzius B

    2010-05-15

    Untreated hypovolemia results in impaired outcome. This study tests our hypothesis whether general hemodynamic parameters detect acute blood loss earlier than monitoring parameters of regional tissue beds. Eight pigs (23-25 kg) were anesthetized and mechanically ventilated. A pulmonary artery catheter and an arterial catheter were inserted. Tissue oxygen tension was measured with Clark-type electrodes in the jejunal and colonic wall, in the liver, and subcutaneously. Jejunal microcirculation was assessed by laser Doppler flowmetry (LDF). Intravascular volume was optimized using difference in pulse pressure (dPP) to keep dPP below 13%. Sixty minutes after preparation, baseline measurements were taken. At first, 5% of total blood volume was withdrawn, followed by another 5% increment, and then in 10% increments until death. After withdrawal of 5% of estimated blood volume, dPP increased from 6.1% +/- 3.0% to 20.8% +/- 2.7% (P < 0.01). Mean arterial pressure (MAP), mean pulmonary artery pressure (PAP) and pulmonary artery occlusion pressure (PAOP) decreased with a blood loss of 10% (P < 0.01). Cardiac output (CO) changed after a blood loss of 20% (P < 0.05). Tissue oxygen tension in central organs, and blood flow in the jejunal muscularis decreased (P < 0.05) after a blood loss of 20%. Tissue oxygen tension in the skin, and jejunal mucosa blood flow decreased (P < 0.05) after a blood loss of 40% and 50%, respectively. In this hemorrhagic pig model systemic hemodynamic parameters were more sensitive to detect acute hypovolemia than tissue oxygen tension measurements or jejunal LDF measurements. Acute blood loss was detected first by dPP. Copyright (c) 2010 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2001-01-20

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

  9. 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

  10. 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

  11. 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

  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

    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

  13. 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…

  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. Replication Restart in Bacteria.

    Science.gov (United States)

    Michel, Bénédicte; Sandler, Steven J

    2017-07-01

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

  16. 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. 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.

  18. 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.

  19. Nucleotide Metabolism and DNA Replication.

    Science.gov (United States)

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

    2014-10-01

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

  20. 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.

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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.

  6. 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...

  7. 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....

  8. Earlier vegetation green-up has reduced spring dust storms.

    Science.gov (United States)

    Fan, Bihang; Guo, Li; Li, Ning; Chen, Jin; Lin, Henry; Zhang, Xiaoyang; Shen, Miaogen; Rao, Yuhan; Wang, Cong; Ma, Lei

    2014-01-01

    The observed decline of spring dust storms in Northeast Asia since the 1950s has been attributed to surface wind stilling. However, spring vegetation growth could also restrain dust storms through accumulating aboveground biomass and increasing surface roughness. To investigate the impacts of vegetation spring growth on dust storms, we examine the relationships between recorded spring dust storm outbreaks and satellite-derived vegetation green-up date in Inner Mongolia, Northern China from 1982 to 2008. We find a significant dampening effect of advanced vegetation growth on spring dust storms (r = 0.49, p = 0.01), with a one-day earlier green-up date corresponding to a decrease in annual spring dust storm outbreaks by 3%. Moreover, the higher correlation (r = 0.55, p green-up date and dust storm outbreak ratio (the ratio of dust storm outbreaks to times of strong wind events) indicates that such effect is independent of changes in surface wind. Spatially, a negative correlation is detected between areas with advanced green-up dates and regional annual spring dust storms (r = -0.49, p = 0.01). This new insight is valuable for understanding dust storms dynamics under the changing climate. Our findings suggest that dust storms in Inner Mongolia will be further mitigated by the projected earlier vegetation green-up in the warming world.

  9. Glycemic management in ESRD and earlier stages of CKD.

    Science.gov (United States)

    Williams, Mark E; Garg, Rajesh

    2014-02-01

    The management of hyperglycemia in patients with kidney failure is complex, and the goals and methods regarding glycemic control in chronic kidney disease (CKD) are not clearly defined. Although aggressive glycemic control seems to be advantageous in early diabetic nephropathy, outcome data supporting tight glycemic control in patients with advanced CKD (including end-stage renal disease [ESRD]) are lacking. Challenges in the management of such patients include therapeutic inertia, monitoring difficulties, and the complexity of available treatments. In this article, we review the alterations in glucose homeostasis that occur in kidney failure, current views on the value of glycemic control and issues with its determination, and more recent approaches to monitor or measure glycemic control. Hypoglycemia and treatment options for patients with diabetes and ESRD or earlier stages of CKD also are addressed, discussing the insulin and noninsulin agents that currently are available, along with their indications and contraindications. The article provides information to help clinicians in decision making in order to provide individualized glycemic goals and appropriate therapy for patients with ESRD or earlier stages of CKD.

  10. 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...

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

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

    DEFF Research Database (Denmark)

    Jensen, Rasmus Bugge

    2006-01-01

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

  17. 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…

  18. 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...

  19. Do BRCA1/2 mutation carriers have an earlier onset of natural menopause?

    NARCIS (Netherlands)

    Tilborg, T.C. van; Broekmans, F.J.; Pijpe, A.; Schrijver, L.H.; Mooij, T.M.; Oosterwijk, J.C; Verhoef, S.; Gomez Garcia, E.B.; Zelst-Stams, W.A.G. van; Adank, M.A.; Asperen, C.J. van; Doorn, H.C. van; Os, T.A. van; Bos, A.M.; Rookus, M.A.; Ausems, M.G.

    2016-01-01

    OBJECTIVE: It has been hypothesized that BRCA1/2 mutation carriers have an earlier age at natural menopause (ANM), although to date findings are inconclusive. This study assessed the influence of BRCA mutation status on ANM, and aimed to explore the reasons of inconsistency in the literature. METHOD

  20. Do BRCA1/2 mutation carriers have an earlier onset of natural menopause?

    NARCIS (Netherlands)

    van Tilborg, Theodora C.; Broekmans, Frank J.; Pijpe, Anouk; Schrijver, Lieske H.; Mooij, Thea M.; Oosterwijk, Jan C.; Verhoef, Senno; Garcia, Encarna B. Gomez; van Zelst-Stams, Wendy A.; Adank, Muriel A.; van Asperen, Christi J.; van Doorn, Helena C.; van Os, Theo A.; Bos, Anna M.; Rookus, Matti A.; Ausems, Margreet G.

    2016-01-01

    Objective: It has been hypothesized that BRCA1/2 mutation carriers have an earlier age at natural menopause (ANM), although to date findings are inconclusive. This study assessed the influence of BRCA mutation status on ANM, and aimed to explore the reasons of inconsistency in the literature. Method

  1. Later endogenous circadian temperature nadir relative to an earlier wake time in older people

    Science.gov (United States)

    Duffy, J. F.; Dijk, D. J.; Klerman, E. B.; Czeisler, C. A.

    1998-01-01

    The contribution of the circadian timing system to the age-related advance of sleep-wake timing was investigated in two experiments. In a constant routine protocol, we found that the average wake time and endogenous circadian phase of 44 older subjects were earlier than that of 101 young men. However, the earlier circadian phase of the older subjects actually occurred later relative to their habitual wake time than it did in young men. These results indicate that an age-related advance of circadian phase cannot fully account for the high prevalence of early morning awakening in healthy older people. In a second study, 13 older subjects and 10 young men were scheduled to a 28-h day, such that they were scheduled to sleep at many circadian phases. Self-reported awakening from scheduled sleep episodes and cognitive throughput during the second half of the wake episode varied markedly as a function of circadian phase in both groups. The rising phase of both rhythms was advanced in the older subjects, suggesting an age-related change in the circadian regulation of sleep-wake propensity. We hypothesize that under entrained conditions, these age-related changes in the relationship between circadian phase and wake time are likely associated with self-selected light exposure at an earlier circadian phase. This earlier exposure to light could account for the earlier clock hour to which the endogenous circadian pacemaker is entrained in older people and thereby further increase their propensity to awaken at an even earlier time.

  2. Poorest countries experience earlier anthropogenic emergence of daily temperature extremes

    Science.gov (United States)

    Harrington, Luke J.; Frame, David J.; Fischer, Erich M.; Hawkins, Ed; Joshi, Manoj; Jones, Chris D.

    2016-05-01

    Understanding how the emergence of the anthropogenic warming signal from the noise of internal variability translates to changes in extreme event occurrence is of crucial societal importance. By utilising simulations of cumulative carbon dioxide (CO2) emissions and temperature changes from eleven earth system models, we demonstrate that the inherently lower internal variability found at tropical latitudes results in large increases in the frequency of extreme daily temperatures (exceedances of the 99.9th percentile derived from pre-industrial climate simulations) occurring much earlier than for mid-to-high latitude regions. Most of the world’s poorest people live at low latitudes, when considering 2010 GDP-PPP per capita; conversely the wealthiest population quintile disproportionately inhabit more variable mid-latitude climates. Consequently, the fraction of the global population in the lowest socio-economic quintile is exposed to substantially more frequent daily temperature extremes after much lower increases in both mean global warming and cumulative CO2 emissions.

  3. 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

  4. 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)

  5. 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

  6. 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.

  7. 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…

  8. 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

  9. 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.

  10. Patient- and system-related barriers for the earlier diagnosis of colorectal cancer

    OpenAIRE

    2009-01-01

    Abstract Background A cohort of colorectal cancer (CRC) patients represents an opportunity to study missed opportunities for earlier diagnosis. Primary objective: To study the epidemiology of diagnostic delays and failures to offer/complete CRC screening. Secondary objective: To identify system- and patient-related factors that may contribute to diagnostic delays or failures to offer/complete CRC screening. Methods Setting: Rural Veterans Administration (VA) Healthcare system. Participants: C...

  11. 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.

  12. 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.

  13. 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.

  14. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Krysan, P.J.

    1993-01-01

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

  16. 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.

  17. 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.

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

    Science.gov (United States)

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

    2015-05-27

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

  19. 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.

  20. 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.

  1. Compulsive buying: Earlier illicit drug use, impulse buying, depression, and adult ADHD symptoms.

    Science.gov (United States)

    Brook, Judith S; Zhang, Chenshu; Brook, David W; Leukefeld, Carl G

    2015-08-30

    This longitudinal study examined the association between psychosocial antecedents, including illicit drug use, and adult compulsive buying (CB) across a 29-year time period from mean age 14 to mean age 43. Participants originally came from a community-based random sample of residents in two upstate New York counties. Multivariate linear regression analysis was used to study the relationship between the participant's earlier psychosocial antecedents and adult CB in the fifth decade of life. The results of the multivariate linear regression analyses showed that gender (female), earlier adult impulse buying (IB), depressive mood, illicit drug use, and concurrent ADHD symptoms were all significantly associated with adult CB at mean age 43. It is important that clinicians treating CB in adults should consider the role of drug use, symptoms of ADHD, IB, depression, and family factors in CB. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. 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.

  3. 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.

  4. In-utero cigarette smoke exposure and the risk of earlier menopause.

    Science.gov (United States)

    Honorato, Talita C; Haadsma, Maaike L; Land, Jolande A; Boezen, Marike H; Hoek, Annemieke; Groen, Henk

    2017-08-28

    Cigarette smoking is a risk factor for earlier menopause. Animal studies show that in-utero smoke exposure is toxic to developing ovaries. Our aim was to evaluate whether in-utero smoke exposed women reach menopause earlier compared with nonexposed women. This is a cohort study within the Avon Longitudinal Study of Parents and Children. Participants included in this study were followed from 1991/1992 until 2010. Participant characteristics for the current analysis were obtained from obstetric records and from annual follow-up questionnaires. When not available, age at natural menopause was estimated by age at filling in the questionnaire minus 1 year. Cox proportional hazards modeling was used to estimate hazard ratios of menopause for in-utero exposed and nonexposed women. There were 695/2,852 postmenopausal women, of whom 466 had natural menopause, 117 had hormonal therapy, and 112 had surgical menopause. Age at natural menopause was 50.6 ± 3.7 years. Of all participants, 20.2% (577/2,852) were exposed to smoke in-utero. Participants who were in-utero exposed but were not smokers did not have higher hazards of menopause (adjusted hazard ratio [HR] 0.92, 95% CI 0.72-1.18), whereas participants who were ever smokers (current or previous) and were in-utero exposed (adjusted HR 1.41, 95% CI 1.01-1.95) or were ever smokers but not exposed (adjusted HR 1.24, 95% CI 1.00-1.53) did have higher hazards of earlier menopause. In-utero smoke exposure was not associated with earlier menopause, but the effect of in-utero smoke exposure was modified by the smoking habits of the participants themselves increasing the risk for smokers who were in-utero exposed.

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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 ...

  11. Replication-Fork Dynamics

    NARCIS (Netherlands)

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

    2014-01-01

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

  12. Coronavirus Attachment and Replication

    Science.gov (United States)

    1988-03-28

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

  13. Contain of Material and Freedom of Spiritual: Study on the Salary of University Teachers in the Earlier Stage of the Republic of China%物质牵制与精神自由:民国前期大学教师薪酬研究

    Institute of Scientific and Technical Information of China (English)

    李海萍; 上官剑

    2012-01-01

    Marxist historical materialism points out that a person' s social Existence determines his social Different salary at different times is not only as a social condition for intellectuals to produce creative spirit, which is also an important symbol that reflects intellectuals' social impact and historical destiny. Based on the study of university teachers' salary in the Earlier Stage of the Republic of China, this paper outlines the salary system of university teachers in this period and gives a comparative analysis with the other classes of society, exploring during this period how university teachers sur- pass the fetters of power and money with the economic autonomy, and realize the reality of "independent personality" and "freedom of thought. "%人的社会存在决定人的社会意识。不同时期知识分子的不同薪酬,不仅是作为他们创造性精神生产赖以实现的社会条件,同时也是反映其社会影响及历史命运的重要标志。本文主要以民国前期的大学教师薪酬为研究对象,概述了这一时期大学教师的薪酬制度,并与其他社会阶层进行了比较与分析,探讨了这一时期的大学教师如何以经济自主超越“权”的羁绊和“钱”的束缚,从而真正实现“独立之人格”和“自由之思想”。

  14. Is Earlier Better? Mastery of Reading Fluency in Early Schooling

    Science.gov (United States)

    Park, Yonghan; Chaparro, Erin A.; Preciado, Jorge; Cummings, Kelli D.

    2015-01-01

    Research Findings: The goal of the present study was to provide empirical evidence for the importance of mastering reading fluency in early schooling. Study participants were 1,322 students in 3rd grade in 42 schools in a northwestern state. These students were assessed using a battery of reading skill tests as well as comprehensive tests of more…

  15. A vantage from space can detect earlier drought onset: an approach using relative humidity.

    Science.gov (United States)

    Farahmand, Alireza; AghaKouchak, Amir; Teixeira, Joao

    2015-02-25

    Each year, droughts cause significant economic and agricultural losses across the world. The early warning and onset detection of drought is of particular importance for effective agriculture and water resource management. Previous studies show that the Standard Precipitation Index (SPI), a measure of precipitation deficit, detects drought onset earlier than other indicators. Here we show that satellite-based near surface air relative humidity data can further improve drought onset detection and early warning. This paper introduces the Standardized Relative Humidity Index (SRHI) based on the NASA Atmospheric Infrared Sounder (AIRS) observations. The results indicate that the SRHI typically detects the drought onset earlier than the SPI. While the AIRS mission was not originally designed for drought monitoring, we show that its relative humidity data offers a new and unique avenue for drought monitoring and early warning. We conclude that the early warning aspects of SRHI may have merit for integration into current drought monitoring systems.

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

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    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

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

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    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.

  18. 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.

  19. 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.

  20. New Evidence: Data Documenting Parental Support for Earlier Sexuality Education

    Science.gov (United States)

    Barr, Elissa M.; Moore, Michele J.; Johnson, Tammie; Forrest, Jamie; Jordan, Melissa

    2014-01-01

    Background: Numerous studies document support for sexuality education to be taught in high school, and often, in middle school. However, little research has been conducted addressing support for sexuality education in elementary schools. Methods: As part of the state Behavioral Risk Factor Surveillance System (BRFSS) Survey administration, the…

  1. An evidence-based approach to earlier initiation of dialysis.

    Science.gov (United States)

    Churchill, D N

    1997-12-01

    The objective was to review evidence addressing the optimal time to initiate dialysis treatment. The database was derived from an evidence-based review of the medical literature and from the Canada-United States peritoneal dialysis study. The publications were divided into (1) those addressing the clinical impact of early versus late referral to a dialysis program; (2) those evaluating the association between residual renal function at initiation of dialysis and the concurrent nutritional status; (3) those evaluating the association between residual renal function at initiation of dialysis and subsequent clinical outcomes, including patient survival. There were five studies evaluating early versus late referral, three cohort design and two case-control design. Late referrals had worse outcomes than early referrals. The former had more serious comorbidity and many had been noncompliant with follow-up. The latter were more likely to have hereditary renal disease. Renal function was slightly worse at initiation among those referred late. Three studies addressed the association between renal function at initiation of dialysis and concurrent nutritional status. Two showed decreased protein intake with diminished glomerular filtration rate (GFR). Poor nutritional status is associated with decreased patient survival among both incident and prevalent dialysis patients. The third study reported excellent patient survival among patients with late initiation of dialysis. These patients had received a supplemented low-protein diet and were not malnourished at initiation of dialysis. Three groups have studied the association between GFR at initiation of dialysis and clinical outcomes. Decreased GFR at initiation of dialysis is associated with a increased probability of hospitalization and death. None of these studies has used the rigorous randomized clinical trial design, and they are therefore subject to bias. Referral time bias, comorbidity, patient compliance, and starting

  2. A review of quality of life after predictive testing for and earlier identification of neurodegenerative diseases.

    Science.gov (United States)

    Paulsen, Jane S; Nance, Martha; Kim, Ji-In; Carlozzi, Noelle E; Panegyres, Peter K; Erwin, Cheryl; Goh, Anita; McCusker, Elizabeth; Williams, Janet K

    2013-11-01

    The past decade has witnessed an explosion of evidence suggesting that many neurodegenerative diseases can be detected years, if not decades, earlier than previously thought. To date, these scientific advances have not provoked any parallel translational or clinical improvements. There is an urgency to capitalize on this momentum so earlier detection of disease can be more readily translated into improved health-related quality of life for families at risk for, or suffering with, neurodegenerative diseases. In this review, we discuss health-related quality of life (HRQOL) measurement in neurodegenerative diseases and the importance of these "patient reported outcomes" for all clinical research. Next, we address HRQOL following early identification or predictive genetic testing in some neurodegenerative diseases: Huntington disease, Alzheimer's disease, Parkinson's disease, Dementia with Lewy bodies, frontotemporal dementia, amyotrophic lateral sclerosis, prion diseases, hereditary ataxias, Dentatorubral-pallidoluysian atrophy and Wilson's disease. After a brief report of available direct-to-consumer genetic tests, we address the juxtaposition of earlier disease identification with assumed reluctance toward predictive genetic testing. Forty-one studies examining health-related outcomes following predictive genetic testing for neurodegenerative disease suggested that (a) extreme or catastrophic outcomes are rare; (b) consequences commonly include transiently increased anxiety and/or depression; (c) most participants report no regret; (d) many persons report extensive benefits to receiving genetic information; and (e) stigmatization and discrimination for genetic diseases are poorly understood and policy and laws are needed. Caution is appropriate for earlier identification of neurodegenerative diseases but findings suggest further progress is safe, feasible and likely to advance clinical care.

  3. A Review of Quality of Life after Predictive Testing for and Earlier Identification of Neurodegenerative Diseases

    Science.gov (United States)

    Paulsen, Jane S.; Nance, Martha; Kim, Ji-In; Carlozzi, Noelle E.; Panegyres, Peter K.; Erwin, Cheryl; Goh, Anita; McCusker, Elizabeth; Williams, Janet K.

    2013-01-01

    The past decade has witnessed an explosion of evidence suggesting that many neurodegenerative diseases can be detected years, if not decades, earlier than previously thought. To date, these scientific advances have not provoked any parallel translational or clinical improvements. There is an urgency to capitalize on this momentum so earlier detection of disease can be more readily translated into improved health-related quality of life for families at risk for, or suffering with, neurodegenerative diseases. In this review, we discuss health-related quality of life (HRQOL) measurement in neurodegenerative diseases and the importance of these “patient reported outcomes” for all clinical research. Next, we address HRQOL following early identification or predictive genetic testing in some neurodegenerative diseases: Huntington disease, Alzheimer's disease, Parkinson's disease, Dementia with Lewy bodies, frontotemporal dementia, amyotrophic lateral sclerosis, prion diseases, hereditary ataxias, Dentatorubral-pallidoluysian atrophy and Wilson's disease. After a brief report of available direct-to-consumer genetic tests, we address the juxtaposition of earlier disease identification with assumed reluctance towards predictive genetic testing. Forty-one studies examining health related outcomes following predictive genetic testing for neurodegenerative disease suggested that (a) extreme or catastrophic outcomes are rare; (b) consequences commonly include transiently increased anxiety and/or depression; (c) most participants report no regret; (d) many persons report extensive benefits to receiving genetic information; and (e) stigmatization and discrimination for genetic diseases are poorly understood and policy and laws are needed. Caution is appropriate for earlier identification of neurodegenerative diseases but findings suggest further progress is safe, feasible and likely to advance clinical care. PMID:24036231

  4. Replication of an empirical approach to delineate the heterogeneity of chronic unexplained fatigue

    Directory of Open Access Journals (Sweden)

    White Peter D

    2009-10-01

    Full Text Available Abstract Background Chronic fatigue syndrome (CFS is defined by self-reported symptoms. There are no diagnostic signs or laboratory markers, and the pathophysiology remains inchoate. In part, difficulties identifying and replicating biomarkers and elucidating the pathophysiology reflect the heterogeneous nature of the syndromic illness CFS. We conducted this analysis of people from defined metropolitan, urban, and rural populations to replicate our earlier empirical delineation of medically unexplained chronic fatigue and CFS into discrete endophenotypes. Both the earlier and current analyses utilized quantitative measures of functional impairment and symptoms as well as laboratory data. This study and the earlier one enrolled participants from defined populations and measured the internal milieu, which differentiates them from studies of clinic referrals that examine only clinical phenotypes. Methods This analysis evaluated 386 women identified in a population-based survey of chronic fatigue and unwellness in metropolitan, urban, and rural populations of the state of Georgia, USA. We used variables previously demonstrated to effectively delineate endophenotypes in an attempt to replicate identification of these endophenotypes. Latent class analyses were used to derive the classes, and these were compared and contrasted to those described in the previous study based in Wichita, Kansas. Results We identified five classes in the best fit analysis. Participants in Class 1 (25% were polysymptomatic, with sleep problems and depressed mood. Class 2 (24% was also polysymptomatic, with insomnia and depression, but participants were also obese with associated metabolic strain. Class 3 (20% had more selective symptoms but was equally obese with metabolic strain. Class 4 (20% and Class 5 (11% consisted of nonfatigued, less symptomatic individuals, Class 4 being older and Class 5 younger. The classes were generally validated by independent variables. People

  5. 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.

  6. 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

  7. 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.

  8. Earlier development of analytical than holistic object recognition in adolescence.

    Directory of Open Access Journals (Sweden)

    Elley Wakui

    Full Text Available BACKGROUND: Previous research has shown that object recognition may develop well into late childhood and adolescence. The present study extends that research and reveals novel differences in holistic and analytic recognition performance in 7-12 year olds compared to that seen in adults. We interpret our data within a hybrid model of object recognition that proposes two parallel routes for recognition (analytic vs. holistic modulated by attention. METHODOLOGY/PRINCIPAL FINDINGS: Using a repetition-priming paradigm, we found in Experiment 1 that children showed no holistic priming, but only analytic priming. Given that holistic priming might be thought to be more 'primitive', we confirmed in Experiment 2 that our surprising finding was not because children's analytic recognition was merely a result of name repetition. CONCLUSIONS/SIGNIFICANCE: Our results suggest a developmental primacy of analytic object recognition. By contrast, holistic object recognition skills appear to emerge with a much more protracted trajectory extending into late adolescence.

  9. Antisense oligonucleotide inhibition of hepatitis C virus genotype 4 replication in HepG2 cells

    Directory of Open Access Journals (Sweden)

    Omran Moataza H

    2006-06-01

    Full Text Available Abstract Background Hepatitis C (HCV viral infection is a serious medical problem in Egypt and it has a devastating impact on the Egyptian economy. It is estimated that over 15% of Egyptians are infected by the virus and thus finding a cure for this disease is of utmost importance. Current therapies for hepatitis C virus (HCV genotype 4 with interferon/ribavirin have not been successful and thus the development of alternative therapy for this genotype is disparately needed. Results Although previous studies utilizing viral subgenomic or full cDNA fragments linked to reporter genes transfected into adhered cells or in a cell free system showed promise, demonstration of efficient viral replication was lacking. Thus, we utilized HepG2 cells infected with native HCV RNA genomes in a replication competent system and used antisense phosphorothioate Oligonucleotides (S-ODN against stem loop IIId and the AUG translation start site of the viral polyprotein precursor to monitor viral replication. We were able to show complete arrest of intracellular replication of HCV-4 at 1 uM S-ODN, thus providing a proof of concept for the potential antiviral activity of S-ODN on native genomic replication of HCV genotype 4. Conclusion We have successfully demonstrated that by using two S-ODNs [(S-ODN1 (nt 326–348 and S-ODN-2 (nt 264–282], we were able to completely inhibit viral replication in culture, thus confirming earlier reports on subgenomic constructs and suggesting a potential therapeutic value in HCV type 4.

  10. 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.

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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.

  18. 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...

  19. 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...

  20. 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.

  1. 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...

  2. Replication Research and Special Education

    Science.gov (United States)

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

    2016-01-01

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

  3. Replication Research and Special Education

    Science.gov (United States)

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

    2016-01-01

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

  4. 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…

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. Factors associated with late diagnosis of HIV infection and missed opportunities for earlier testing.

    Science.gov (United States)

    Gullón, Alejandra; Verdejo, José; de Miguel, Rosa; Gómez, Ana; Sanz, Jesús

    2016-10-01

    Late diagnosis (LD) of human immunodeficiency virus (HIV) infection continues to be a significant problem that increases disease burden both for patients and for the public health system. Guidelines have been updated in order to facilitate earlier HIV diagnosis, introducing "indicator condition-guided HIV testing". In this study, we analysed the frequency of LD and associated risk factors. We retrospectively identified those cases that could be considered missed opportunities for an earlier diagnosis. All patients newly diagnosed with HIV infection who attended Hospital La Princesa, Madrid (Spain) between 2007 and 2014 were analysed. We collected epidemiological, clinical and immunological data. We also reviewed electronic medical records from the year before the HIV diagnosis to search for medical consultations due to clinical indicators. HIV infection was diagnosed in 354 patients. The median CD4 count at presentation was 352 cells/mm(3). Overall, 158 patients (50%) met the definition of LD, and 97 (30.7%) the diagnosis of advanced disease. LD was associated with older age and was more frequent amongst immigrants. Heterosexual relations and injection drug use were more likely to be the reasons for LD than relations between men who have sex with men. During the year preceding the diagnosis, 46.6% of the patients had sought medical advice owing to the presence of clinical indicators that should have led to HIV testing. Of those, 24 cases (14.5%) were classified as missed opportunities for earlier HIV diagnosis because testing was not performed. According to these results, all health workers should pursue early HIV diagnosis through the proper implementation of HIV testing guidelines. Such an approach would prove directly beneficial to the patient and indirectly beneficial to the general population through the reduction in the risk of transmission.

  1. 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.

  2. 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

  3. 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…

  4. 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.

  5. 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.

  6. 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

  7. 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...

  8. 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.

  9. Audio-Visual Perception of Gender by Infants Emerges Earlier for Adult-Directed Speech

    Science.gov (United States)

    Richoz, Anne-Raphaëlle; Quinn, Paul C.; Hillairet de Boisferon, Anne; Berger, Carole; Loevenbruck, Hélène; Lewkowicz, David J.; Lee, Kang; Dole, Marjorie; Caldara, Roberto; Pascalis, Olivier

    2017-01-01

    Early multisensory perceptual experiences shape the abilities of infants to perform socially-relevant visual categorization, such as the extraction of gender, age, and emotion from faces. Here, we investigated whether multisensory perception of gender is influenced by infant-directed (IDS) or adult-directed (ADS) speech. Six-, 9-, and 12-month-old infants saw side-by-side silent video-clips of talking faces (a male and a female) and heard either a soundtrack of a female or a male voice telling a story in IDS or ADS. Infants participated in only one condition, either IDS or ADS. Consistent with earlier work, infants displayed advantages in matching female relative to male faces and voices. Moreover, the new finding that emerged in the current study was that extraction of gender from face and voice was stronger at 6 months with ADS than with IDS, whereas at 9 and 12 months, matching did not differ for IDS versus ADS. The results indicate that the ability to perceive gender in audiovisual speech is influenced by speech manner. Our data suggest that infants may extract multisensory gender information developmentally earlier when looking at adults engaged in conversation with other adults (i.e., ADS) than when adults are directly talking to them (i.e., IDS). Overall, our findings imply that the circumstances of social interaction may shape early multisensory abilities to perceive gender. PMID:28060872

  10. Light pollution is associated with earlier tree budburst across the United Kingdom.

    Science.gov (United States)

    Ffrench-Constant, Richard H; Somers-Yeates, Robin; Bennie, Jonathan; Economou, Theodoros; Hodgson, David; Spalding, Adrian; McGregor, Peter K

    2016-06-29

    The ecological impact of night-time lighting is of concern because of its well-demonstrated effects on animal behaviour. However, the potential of light pollution to change plant phenology and its corresponding knock-on effects on associated herbivores are less clear. Here, we test if artificial lighting can advance the timing of budburst in trees. We took a UK-wide 13 year dataset of spatially referenced budburst data from four deciduous tree species and matched it with both satellite imagery of night-time lighting and average spring temperature. We find that budburst occurs up to 7.5 days earlier in brighter areas, with the relationship being more pronounced for later-budding species. Excluding large urban areas from the analysis showed an even more pronounced advance of budburst, confirming that the urban 'heat-island' effect is not the sole cause of earlier urban budburst. Similarly, the advance in budburst across all sites is too large to be explained by increases in temperature alone. This dramatic advance of budburst illustrates the need for further experimental investigation into the impact of artificial night-time lighting on plant phenology and subsequent species interactions. As light pollution is a growing global phenomenon, the findings of this study are likely to be applicable to a wide range of species interactions across the world.

  11. Association of Family History of Epilepsy with Earlier Age Onset of Juvenile Myoclonic Epilepsy

    Science.gov (United States)

    NAJAFI, Mohammad Reza; NAJAFI, Mohammad Amin; SAFAEI, Ali

    2016-01-01

    Objective Juvenile myoclonic epilepsy (JME) is supposedly the most frequent subtype of idiopathic generalized epilepsies (IGE). The aim of this study was to determine the prevalence of JME and comparison of patients’ demographics as well as timeline of the disease between positive family history epileptic patients (PFHE) and negative family history epileptic patients (NFHE) among sample of Iranian epileptic patients. Materials & Methods From Feb. 2006 to Oct. 2009, 1915 definite epileptic patients (873 females) referred to epilepsy clinics in Isfahan, central Iran, were surveyed and among them, 194 JME patients were diagnosed. JME was diagnosed by its specific clinical and EEG criteria. Patients were divided into two groups as PFHE and NFHE and data were compared between them. Results JME was responsible for 10% (194 patients) of all types of epilepsies. Of JME patients, 53% were female. In terms of family history of epilepsy, 40% were positive. No significant differences was found between PFHE and NFHE groups as for gender (P>0.05). Age of epilepsy onset was significantly earlier in PFHE patients (15 vs. 22 yr, P<0.001). Occurrence of JME before 18 yr old among PFHE patients was significantly higher (OR=2.356, P=0.007). Conclusion A family history of epilepsy might be associated with an earlier age of onset in patients with JME. PMID:27247579

  12. Higher Sensitivity and Earlier Identification of Celiac Disease Autoimmunity by a Nonradioactive Assay for Transglutaminase Autoantibodies

    Directory of Open Access Journals (Sweden)

    Zhiyuan Zhao

    2016-01-01

    Full Text Available Higher sensitive transglutaminase autoantibody (TGA assay will detect the onset of celiac disease (CD autoimmunity earlier. In developing a nonradioactive assay for TGA, we utilized electrochemiluminescence (ECL technology and compared it to a high-performance radioimmunoassay (RIA currently being used to screen patients with type 1 diabetes (T1D and genetically at-risk individuals for CD. We selected 183 T1D patients with 60 patients having received biopsy and analyzed 396 sequential samples from 73 young children longitudinally followed up with TGA seroconversion, with 27 undergoing biopsy. In addition, 112 age-matched healthy control subjects were included in the study. With the 99th percentile of specificity, the ECL assay detected significantly more TGA positivity among patients with T1D (133/183 than RIA (114/183 and more of the sequential samples (34% from 73 children than RIA (18%. The TGA assay performed by ECL was positive in all 59 subjects with villous atrophy. Among 73 longitudinally followed up children, ECL assay had earlier detection of TGA on 34 children by a mean of 2.5 years. In conclusion, the new TGA assay by ECL has a higher sensitivity than the current RIA assay and may better predict the onset of CD.

  13. Association of Family History of Epilepsy with Earlier Age Onset of Juvenile Myoclonic Epilepsy.

    Science.gov (United States)

    Najafi, Mohammad Reza; Najafi, Mohammad Amin; Safaei, Ali

    2016-01-01

    Juvenile myoclonic epilepsy (JME) is supposedly the most frequent subtype of idiopathic generalized epilepsies (IGE). The aim of this study was to determine the prevalence of JME and comparison of patients' demographics as well as timeline of the disease between positive family history epileptic patients (PFHE) and negative family history epileptic patients (NFHE) among sample of Iranian epileptic patients. From Feb. 2006 to Oct. 2009, 1915 definite epileptic patients (873 females) referred to epilepsy clinics in Isfahan, central Iran, were surveyed and among them, 194 JME patients were diagnosed. JME was diagnosed by its specific clinical and EEG criteria. Patients were divided into two groups as PFHE and NFHE and data were compared between them. JME was responsible for 10% (194 patients) of all types of epilepsies. Of JME patients, 53% were female. In terms of family history of epilepsy, 40% were positive. No significant differences was found between PFHE and NFHE groups as for gender (P>0.05). Age of epilepsy onset was significantly earlier in PFHE patients (15 vs. 22 yr, P<0.001). Occurrence of JME before 18 yr old among PFHE patients was significantly higher (OR=2.356, P=0.007). A family history of epilepsy might be associated with an earlier age of onset in patients with JME.

  14. 精神分裂症白质损害与发病年龄的弥散张量成像研究%Disrupted white matter integrity is associated with earlier onset age in schizophrenia:A diffusion tensor imaging study

    Institute of Scientific and Technical Information of China (English)

    蔡丽伟; 赵强; 袁慧书; 张岱; 阎浩; 田霖; 刘琦; 闫俊; 孙伟; 卢天兰; 阮燕燕; 王力芳; 岳伟华

    2012-01-01

    Objective: To investigate the abnormal changes in white matter in patients with schizophrenia, and to explore the correlations between the fractional anisotropy (FA) alterations and the onset age. Methods: Twenty-seven patients with schizophrenia and 29 gender, age and education matched healthy volunteers underwent a diffusion tensor imaging (DTI) scan. According to the onset age of schizophrenia, the patients group were divided into early onset schizophrenia (EOS, < 18 years old) and adult onset schizophrenia (AOS, ≥18 years old). Voxel-based analysis of FA value was performed to investigate the difference of white matter integrity between patients and con- trols and between EOS patients and AOS patients as well. In addition, the association between FA value and the onset age of schizophrenic patients was assessed. Results: Compared with the healthy controls, the FA values were significantly decreased in right superior longitudinal fasciculus and right superior corona radiate in schizophrenic patients. Though no significant difference of FA value was found between EOS and AOS, the significantly positive correlation was found between onset age and FA values in right anterior corona radiate and right genu of corpus cal-losum (r=0.70,0.65; Ps <0.01). Conclusion: It indicates that the white matter abnormalities exist in the right superior longitudinal fasciculus and right superior corona radiate in patients with schizophrenia. The schizophrenic patients with earlier onset age show more severe deficit in white matter integrity in the right anterior corona radiate and right genu of corpus callosum. This study demonstrated that brain white matter abnormalities in schizophrenia may depend on developmental stage at onset time of the illness. The findings moreover support clues for the future studies on pathophysiological abnormalities in schizophrenia.%目的:应用弥散张量成像(DTI)比较精神分裂症患者脑白质与正常人群间的差异,并探究各向异

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. Earlier spring snowmelt in northern Alaska as an indicator of climate change

    Science.gov (United States)

    Stone, Robert S.; Dutton, Ellsworth G.; Harris, Joyce M.; Longenecker, David

    2002-05-01

    Predictions of global circulation models (GCMs) that account for increasing concentrations of greenhouse gases and aerosols in the atmosphere show that warming in the Arctic will be amplified in response to the melting of sea ice and snow cover. There is now conclusive evidence that much of the Arctic has warmed in recent decades. Northern Alaska is one region where significant warming has occurred, especially during winter and spring. We investigate how the changing climate of northern Alaska has influenced the annual cycle of snow cover there and in turn, how changes in snow cover perturb the region's surface radiation budget and temperature regime. The focus is on Barrow, Alaska, for which comprehensive data sets exist. A review of earlier studies that documented a trend toward an earlier disappearance of snow in spring is given. Detection and monitoring activities at Barrow are described, and records of snow disappearance from other sites in the Alaskan Arctic are compared. Correlated variations and trends in the date of final snowmelt (melt date) are found by examining several independent time series. Since the mid-1960s the melt date in northern Alaska has advanced by ~8 days. The advance appears to be a consequence of decreased snowfall in winter, followed by warmer spring conditions. These changes in snowfall and temperature are attributed to variations in regional circulation patterns. In recent decades, there has been a higher frequency of northerly airflow during winter that tends to diminish snowfall over northern Alaska. During spring, however, intrusions of warm moist air from the North Pacific have become more common, and these tend to accelerate the ablation of snow on the North Slope of Alaska. One result of an earlier melt date is an increase in the net surface radiation budget. At Barrow, net radiative forcing can exceed 150 W m-2 on a daily basis immediately following the last day of snowmelt, and as a result of an 8-day advance in this event

  20. Mouse T-cells restrict replication of human immunodeficiency virus at the level of integration

    Directory of Open Access Journals (Sweden)

    Goffinet Christine

    2008-07-01

    Full Text Available Abstract Background The development of an immunocompetent, genetically modified mouse model to study HIV-1 pathogenesis and to test antiviral strategies has been hampered by the fact that cells from native mice do not or only inefficiently support several steps of the HIV-1 replication cycle. Upon HIV-1 infection, mouse T-cell lines fail to express viral proteins, but the underlying replication barrier has thus far not been unambiguously identified. Here, we performed a kinetic and quantitative assessment of consecutive steps in the early phase of the HIV-1 replication cycle in T-cells from mice and humans. Results Both T-cell lines and primary T-cells from mice harbor a severe post-entry defect that is independent of potential species-specTR transactivation. Reverse transcription occurred efficiently following VSV-G-mediated entry of virions into mouse T-cells, and abundant levels of 2-LTR circles indicated successful nuclear import of the pre-integration complex. To probe the next step in the retroviral replication cycle, i.e. the integration of HIV-1 into the host cell genome, we established and validated a nested real-time PCR to specifically quantify HIV-1 integrants exploiting highly repetitive mouse B1 elements. Importantly, we demonstrate that the frequency of integrant formation is diminished 18- to > 305-fold in mouse T-cell lines compared to a human counterpart, resulting in a largely abortive infection. Moreover, differences in transgene expression from residual vector integrants, the transcription off which is cyclin T1-independent, provided evidence for an additional, peri-integrational deficit in certain mouse T-cell lines. Conclusion In contrast to earlier reports, we find that mouse T-cells efficiently support early replication steps up to and including nuclear import, but restrict HIV-1 at the level of chromosomal integration.

  1. 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.

  2. Earlier Detection of Breast Cancer with Ultrasound Molecular Imaging in a Transgenic Mouse Model

    Science.gov (United States)

    Bachawal, Sunitha V.; Jensen, Kristin C.; Lutz, Amelie M.; Gambhir, Sanjiv S.; Tranquart, Francois; Tian, Lu; Willmann, Jürgen K.

    2013-01-01

    While there is an increasing role of ultrasound for breast cancer screening in patients with dense breast, conventional anatomical-ultrasound lacks sensitivity and specificity for early breast cancer detection. In this study we assessed the potential of molecular-ultrasound imaging, using clinically-translatable vascular endothelial growth factor receptor (VEGFR2)-targeted microbubbles (MBVEGFR2), to improve the diagnostic accuracy of ultrasound in earlier detection of breast cancer and ductal carcinoma in situ (DCIS) in a transgenic mouse model (FVB/N-Tg(MMTV-PyMT)634Mul). In vivo binding specificity studies (n=26 tumors) showed that ultrasound imaging signal was significantly higher (P95% of cases and highly agreed between each other (ICC=0.98; 95% CI, 97, 99). These results suggest that VEGFR2-targeted ultrasound molecular imaging allows highly accurate detection of DCIS and breast cancer in transgenic mice and may be a promising approach for early breast cancer detection in women. PMID:23328585

  3. 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

  4. Solving the Telomere Replication Problem

    Science.gov (United States)

    Maestroni, Laetitia; Matmati, Samah; Coulon, Stéphane

    2017-01-01

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

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. Earlier age of smoking initiation may not predict heavier cigarette consumption in later adolescence.

    Science.gov (United States)

    Morrell, Holly E R; Song, Anna V; Halpern-Felsher, Bonnie L

    2011-09-01

    Previous studies suggest that earlier cigarette smoking initiation in adolescence predicts greater cigarette consumption later in adolescence or adulthood. Results from these studies have been used to inform interventions for adolescent smoking. However, previous studies suffer from several important methodological limitations. The objective of the present study was to address these limitations by longitudinally and prospectively examining whether and how age of initiation of smoking among adolescents predicts cigarette consumption by age 16 or 17. Participants completed an in-class survey every 6 months for 2-3 school years. Participants included 395 adolescents (Mean age=14 years at baseline; 53.2% female) from two public high schools in Northern California (Schools A and B) who completed self-report measures of smoking initiation, number of friends who smoke, and number of whole cigarettes smoked by the final survey time point. Adolescents who were older when they first smoked one whole cigarette were 5.3 to 14.6 times more likely in School A and 2.9 to 4.3 times more likely in School B to have smoked a greater number of cigarettes by age 16 or 17. Results suggested that earlier smoking initiation may not lead to heavier cigarette consumption later in time, as has been previously shown. There may be a period of heightened vulnerability in mid- or late adolescence where smoking experimentation is more likely to lead to greater cigarette consumption. Targeting prevention efforts to adolescents aged 14 to 17 years may further reduce smoking initiation among youth, thus limiting subsequent smoking-related morbidity and mortality in adulthood.

  10. Patient- and system-related barriers for the earlier diagnosis of colorectal cancer

    Science.gov (United States)

    Wahls, Terry L; Peleg, Ika

    2009-01-01

    Background A cohort of colorectal cancer (CRC) patients represents an opportunity to study missed opportunities for earlier diagnosis. Primary objective: To study the epidemiology of diagnostic delays and failures to offer/complete CRC screening. Secondary objective: To identify system- and patient-related factors that may contribute to diagnostic delays or failures to offer/complete CRC screening. Methods Setting: Rural Veterans Administration (VA) Healthcare system. Participants: CRC cases diagnosed within the VA between 1/1/2000 and 3/1/2007. Data sources: progress notes, orders, and pathology, laboratory, and imaging results obtained between 1/1/1995 and 12/31/2007. Completed CRC screening was defined as a fecal occult blood test or flexible sigmoidoscopy (both within five years), or colonoscopy (within 10 years); delayed diagnosis was defined as a gap of more than six months between an abnormal test result and evidence of clinician response. A summary abstract of the antecedent clinical care for each patient was created by a certified gastroenterologist (GI), who jointly reviewed and coded the abstracts with a general internist (TW). Results The study population consisted of 150 CRC cases that met the inclusion criteria. The mean age was 69.04 (range 35-91); 99 (66%) were diagnosed due to symptoms; 61 cases (46%) had delays associated with system factors; of them, 57 (38% of the total) had delayed responses to abnormal findings. Fifteen of the cases (10%) had prompt symptom evaluations but received no CRC screening; no patient factors were identified as potentially contributing to the failure to screen/offer to screen. In total, 97 (65%) of the cases had missed opportunities for early diagnosis and 57 (38%) had patient factors that likely contributed to the diagnostic delay or apparent failure to screen/offer to screen. Conclusion Missed opportunities for earlier CRC diagnosis were frequent. Additional studies of clinical data management, focusing on following

  11. Patient- and system-related barriers for the earlier diagnosis of colorectal cancer

    Directory of Open Access Journals (Sweden)

    Wahls Terry L

    2009-09-01

    Full Text Available Abstract Background A cohort of colorectal cancer (CRC patients represents an opportunity to study missed opportunities for earlier diagnosis. Primary objective: To study the epidemiology of diagnostic delays and failures to offer/complete CRC screening. Secondary objective: To identify system- and patient-related factors that may contribute to diagnostic delays or failures to offer/complete CRC screening. Methods Setting: Rural Veterans Administration (VA Healthcare system. Participants: CRC cases diagnosed within the VA between 1/1/2000 and 3/1/2007. Data sources: progress notes, orders, and pathology, laboratory, and imaging results obtained between 1/1/1995 and 12/31/2007. Completed CRC screening was defined as a fecal occult blood test or flexible sigmoidoscopy (both within five years, or colonoscopy (within 10 years; delayed diagnosis was defined as a gap of more than six months between an abnormal test result and evidence of clinician response. A summary abstract of the antecedent clinical care for each patient was created by a certified gastroenterologist (GI, who jointly reviewed and coded the abstracts with a general internist (TW. Results The study population consisted of 150 CRC cases that met the inclusion criteria. The mean age was 69.04 (range 35-91; 99 (66% were diagnosed due to symptoms; 61 cases (46% had delays associated with system factors; of them, 57 (38% of the total had delayed responses to abnormal findings. Fifteen of the cases (10% had prompt symptom evaluations but received no CRC screening; no patient factors were identified as potentially contributing to the failure to screen/offer to screen. In total, 97 (65% of the cases had missed opportunities for early diagnosis and 57 (38% had patient factors that likely contributed to the diagnostic delay or apparent failure to screen/offer to screen. Conclusion Missed opportunities for earlier CRC diagnosis were frequent. Additional studies of clinical data management

  12. 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

  13. Decreasing the required lumbar extensor moment induces earlier onset of flexion relaxation.

    Science.gov (United States)

    Zwambag, Derek P; De Carvalho, Diana E; Brown, Stephen H M

    2016-10-01

    Flexion relaxation (FR) is characterized by the lumbar erector spinae (LES) becoming myoelectrically silent near full trunk flexion. This study was designed to: (1) determine if decreasing the lumbar moment during flexion would induce FR to occur earlier; (2) characterize thoracic and abdominal muscle activity during FR. Ten male participants performed four trunk flexion/extension movement conditions; lumbar moment was altered by attaching 0, 5, 10, or 15lb counterweights to the torso. Electromyography (EMG) was recorded from eight trunk muscles. Lumbar moment, lumbar flexion and trunk inclination angles were calculated at the critical point of LES inactivation (CPLES). Results demonstrated that counterweights decreased the lumbar moment and lumbar flexion angle at CPLES (pactive throughout flexion. Abdominal muscles activated at the same instant as CPLES, except in the 15lb condition where abdominal muscles activated before CPLES resulting in a period of increased co-contraction. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. 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

  15. 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

  16. Identified research directions for using manufacturing knowledge earlier in the product lifecycle.

    Science.gov (United States)

    Hedberg, Thomas D; Hartman, Nathan W; Rosche, Phil; Fischer, Kevin

    2017-01-01

    Design for Manufacturing (DFM), especially the use of manufacturing knowledge to support design decisions, has received attention in the academic domain. However, industry practice has not been studied enough to provide solutions that are mature for industry. The current state of the art for DFM is often rule-based functionality within Computer-Aided Design (CAD) systems that enforce specific design requirements. That rule-based functionality may or may not dynamically affect geometry definition. And, if rule-based functionality exists in the CAD system, it is typically a customization on a case-by-case basis. Manufacturing knowledge is a phrase with vast meanings, which may include knowledge on the effects of material properties decisions, machine and process capabilities, or understanding the unintended consequences of design decisions on manufacturing. One of the DFM questions to answer is how can manufacturing knowledge, depending on its definition, be used earlier in the product lifecycle to enable a more collaborative development environment? This paper will discuss the results of a workshop on manufacturing knowledge that highlights several research questions needing more study. This paper proposes recommendations for investigating the relationship of manufacturing knowledge with shape, behavior, and context characteristics of product to produce a better understanding of what knowledge is most important. In addition, the proposal includes recommendations for investigating the system-level barriers to reusing manufacturing knowledge and how model-based manufacturing may ease the burden of knowledge sharing. Lastly, the proposal addresses the direction of future research for holistic solutions of using manufacturing knowledge earlier in the product lifecycle.

  17. 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.

  18. 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…

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. LHCb experience with LFC replication

    CERN Document Server

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

    2007-01-01

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

  5. Unperturbed posttranscriptional regulatory Rev protein function and HIV-1 replication in astrocytes.

    Directory of Open Access Journals (Sweden)

    Ashok Chauhan

    Full Text Available Astrocytes protect neurons, but also evoke proinflammatory responses to injury and viral infections, including HIV. There is a prevailing notion that HIV-1 Rev protein function in astrocytes is perturbed, leading to restricted viral replication. In earlier studies, our finding of restricted viral entry into astrocytes led us to investigate whether there are any intracellular restrictions, including crippled Rev function, in astrocytes. Despite barely detectable levels of DDX3 (Rev-supporting RNA helicase and TRBP (anti-PKR in primary astrocytes compared to astrocytic cells, Rev function was unperturbed in wild-type, but not DDX3-ablated astrocytes. As in permissive cells, after HIV-1 entry bypass in astrocytes, viral-encoded Tat and Rev proteins had robust regulatory activities, leading to efficient viral replication. Productive HIV-1 infection in astrocytes persisted for several weeks. Our findings on HIV-1 entry bypass in astrocytes demonstrated that the intracellular environment is conducive to viral replication and that Tat and Rev functions are unperturbed.

  6. Optical tweezers reveal how proteins alter replication

    Science.gov (United States)

    Chaurasiya, Kathy

    Single molecule force spectroscopy is a powerful method that explores the DNA interaction properties of proteins involved in a wide range of fundamental biological processes such as DNA replication, transcription, and repair. We use optical tweezers to capture and stretch a single DNA molecule in the presence of proteins that bind DNA and alter its mechanical properties. We quantitatively characterize the DNA binding mechanisms of proteins in order to provide a detailed understanding of their function. In this work, we focus on proteins involved in replication of Escherichia coli (E. coli ), endogenous eukaryotic retrotransposons Ty3 and LINE-1, and human immunodeficiency virus (HIV). DNA polymerases replicate the entire genome of the cell, and bind both double-stranded DNA (dsDNA) and single-stranded DNA (ssDNA) during DNA replication. The replicative DNA polymerase in the widely-studied model system E. coli is the DNA polymerase III subunit alpha (DNA pol III alpha). We use optical tweezers to determine that UmuD, a protein that regulates bacterial mutagenesis through its interactions with DNA polymerases, specifically disrupts alpha binding to ssDNA. This suggests that UmuD removes alpha from its ssDNA template to allow DNA repair proteins access to the damaged DNA, and to facilitate exchange of the replicative polymerase for an error-prone translesion synthesis (TLS) polymerase that inserts nucleotides opposite the lesions, so that bacterial DNA replication may proceed. This work demonstrates a biophysical mechanism by which E. coli cells tolerate DNA damage. Retroviruses and retrotransposons reproduce by copying their RNA genome into the nuclear DNA of their eukaryotic hosts. Retroelements encode proteins called nucleic acid chaperones, which rearrange nucleic acid secondary structure and are therefore required for successful replication. The chaperone activity of these proteins requires strong binding affinity for both single- and double-stranded nucleic

  7. Efficacy and safety of olodaterol once daily delivered via Respimat® in patients with GOLD 2–4 COPD: results from two replicate 48-week studies

    Directory of Open Access Journals (Sweden)

    Ferguson GT

    2014-06-01

    Full Text Available Gary T Ferguson,1 Gregory J Feldman,2 Peter Hofbauer,3 Alan Hamilton,4 Lisa Allen,5 Lawrence Korducki,5 Paul Sachs6 1Pulmonary Research Institute of Southeast Michigan, Livonia, MI, 2S Carolina Pharmaceutical Research, Spartanburg, SC, USA; 3Pneumologie, Weinheim, Germany; 4Boehringer Ingelheim, Burlington, ON, Canada; 5Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, 6Pulmonary Associates of Stamford, Stamford, CT, USA Background: Olodaterol is a long-acting β2-agonist with a 24-hour bronchodilator profile. Two replicate, randomized, double-blind, placebo-controlled, parallel-group, Phase III trials were performed as part of a comprehensive clinical program to investigate the long-term safety and efficacy of olodaterol in patients with moderate to very severe chronic obstructive pulmonary disease (COPD receiving usual-care background therapy. Methods: Patients received olodaterol 5 µg or 10 µg or placebo once daily for 48 weeks. Coprimary end points were forced expiratory volume in 1 second (FEV1 area under the curve from 0 to 3 hours (AUC0–3 response (change from baseline, and trough FEV1 response at 12 weeks. Secondary end points included additional lung function assessments, use of rescue medications, FEV1 AUC response from 0 to 12 hours, and Patient Global Rating over 48 weeks. Results: Overall, 624 and 642 patients were evaluated in studies 1222.11 and 1222.12, respectively. In both studies, olodaterol 5 µg and 10 µg significantly improved the FEV1 AUC0–3 response (P<0.0001 and trough FEV1 (study 1222.11, P<0.0001; study 1222.12, P<0.05, post hoc at week 12, with an incidence of adverse events comparable with that of placebo. Secondary end points supported the efficacy of olodaterol. Conclusion: These studies demonstrate the long-term efficacy and safety of once-daily olodaterol 5 µg and 10 µg in patients with moderate to very severe COPD continuing with usual-care maintenance therapy. Keywords: chronic obstructive

  8. Content replication and placement in mobile networks

    CERN Document Server

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

    2011-01-01

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

  9. Synchronization of DNA array replication kinetics

    Science.gov (United States)

    Manturov, Alexey O.; Grigoryev, Anton V.

    2016-04-01

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

  10. GFLV replication in electroporated grapevine protoplasts.

    Science.gov (United States)

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

    2000-06-29

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

  11. Rev1, Rev3, or Rev7 siRNA Abolishes Ultraviolet Light-Induced Translesion Replication in HeLa Cells: A Comprehensive Study Using Alkaline Sucrose Density Gradient Sedimentation

    Directory of Open Access Journals (Sweden)

    Jun Takezawa

    2010-01-01

    Full Text Available When a replicative DNA polymerase stalls upon encountering a lesion on the template strand, it is relieved by other low-processivity polymerase(s, which insert nucleotide(s opposite the lesion, extend by a few nucleotides, and dissociate from the 3′-OH. The replicative polymerase then resumes DNA synthesis. This process, termed translesion replication (TLS or replicative bypass, may involve at least five different polymerases in mammals, although the participating polymerases and their roles have not been entirely characterized. Using siRNAs originally designed and an alkaline sucrose density gradient sedimentation technique, we verified the involvement of several polymerases in ultraviolet (UV light-induced TLS in HeLa cells. First, siRNAs to Rev3 or Rev7 largely abolished UV-TLS, suggesting that these 2 gene products, which comprise Polζ, play a main role in mutagenic TLS. Second, Rev1-targeted siRNA also abrogated UV-TLS, indicating that Rev1 is also indispensable to mutagenic TLS. Third, Polη-targeted siRNA also prevented TLS to a greater extent than our expectations. Forth, although siRNA to Polι had no detectable effect, that to Polκ delayed UV-TLS. To our knowledge, this is the first study reporting apparent evidence for the participation of Polκ in UV-TLS.

  12. The replication of expansive production knowledge

    DEFF Research Database (Denmark)

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

    2012-01-01

    . Design/methodology/approach – Two case studies are introduced. Empirical data were collected over a period of two years based on interviews and participating observations. Findings – The findings show that (1) knowledge transfer within the replication of a production line is a stepwise expansive process......Purpose – With the aim to support offshore production line replication, this paper specifically aims to explore the use of templates and principles to transfer expansive productive knowledge embedded in a production line and understand the contingencies that influence the mix of these approaches...... and principles to transfer productive knowledge in a specific context, which, in this paper, is a production line....

  13. NACSA Charter School Replication Guide: The Spectrum of Replication Options. Authorizing Matters. Replication Brief 1

    Science.gov (United States)

    O'Neill, Paul

    2010-01-01

    One of the most important and high-profile issues in public education reform today is the replication of successful public charter school programs. With more than 5,000 failing public schools in the United States, there is a tremendous need for strong alternatives for parents and students. Replicating successful charter school models is an…

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

    Science.gov (United States)

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

    2011-12-01

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

  15. 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

  16. Surface Micro Topography Replication in Injection Moulding

    DEFF Research Database (Denmark)

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

    2005-01-01

    The surface micro topography of injection moulded plastic parts can be important for aesthetical and technical reasons. The quality of replication of mould surface topography onto the plastic surface depends among other factors on the process conditions. A study of this relationship has been...

  17. Multiseason occupancy models for correlated replicate surveys

    Science.gov (United States)

    Hines, James; Nichols, James; Collazo, Jaime

    2014-01-01

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

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

    Science.gov (United States)

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

    2012-12-01

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

  19. The Alleged Crisis and the Illusion of Exact Replication

    NARCIS (Netherlands)

    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 r

  20. 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,…

  1. The Alleged Crisis and the Illusion of Exact Replication

    NARCIS (Netherlands)

    Stroebe, Wolfgang; Strack, Fritz

    There has been increasing criticism of the way psychologists conduct and analyze studies. These critiques as well as failures to replicate several high-profile studies have been used as justification to proclaim a replication crisis in psychology. Psychologists are encouraged to conduct more exact

  2. Conditioned blocking and schizophrenia: a replication and study of the role of symptoms, age, onset-age of psychosis and illness-duration

    OpenAIRE

    Bender,; Müller; Oades,; Sartory,

    2001-01-01

    Introduction: 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 [vs. 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, - a) to replicate the reported decre...

  3. The Psychology of Replication and Replication in Psychology.

    Science.gov (United States)

    Francis, Gregory

    2012-11-01

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

  4. Regulation of Replication Recovery and Genome Integrity

    DEFF Research Database (Denmark)

    Colding, Camilla Skettrup

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

  5. Association between HIV replication and serum leptin levels: an observational study of a cohort of HIV-1-infected South African women

    Directory of Open Access Journals (Sweden)

    Azzoni Livio

    2010-09-01

    Full Text Available Abstract Background Advanced HIV infection can result in lipoatrophy and wasting, even in the absence of ongoing opportunistic infections, suggesting that HIV may directly affect adipose tissue amount and distribution. Methods We assessed the relationship of fat (measured using anthropometry, DEXA, MRI scans or markers related to glucose and lipid metabolism with viral load in a cross-sectional sample of 83 antiretroviral-naïve HIV-1-infected South African women. A multivariable linear model was fitted to log10VL to assess the combined effect of these variables. Results In addition to higher T cell activation, women with viral load greater than the population median had lower waist circumference, body mass index and subcutaneous abdominal fat, as well as lower serum leptin. We demonstrate that leptin serum levels are inversely associated with viral replication, independent of the amount of adipose tissue. This association is maintained after adjusting for multiple variables associated with disease progression (i.e., cellular activation and innate immunity effector levels. Conclusions Our results demonstrate that serum leptin levels are inversely associated with viral replication, independent of disease progression: we postulate that leptin may affect viral replication.

  6. "Replicable effects of primes on human behavior": Correction to Payne et al. (2016).

    Science.gov (United States)

    2016-12-01

    Reports an error in "Replicable effects of primes on human behavior" by B. Keith Payne, Jazmin L. Brown-Iannuzzi and Chris Loersch (Journal of Experimental Psychology: General, 2016[Oct], Vol 145[10], 1269-1279). In the article, the graph in Figure 5 did not contain the asterisk mentioned in the figure caption, which was intended to indicate a statistically significant difference between bet and pass prime. The online version of this article has been corrected. (The following abstract of the original article appeared in record 2016-46925-002.) The effect of primes (i.e., incidental cues) on human behavior has become controversial. Early studies reported counterintuitive findings, suggesting that primes can shape a wide range of human behaviors. Recently, several studies failed to replicate some earlier priming results, raising doubts about the reliability of those effects. We present a within-subjects procedure for priming behavior, in which participants decide whether to bet or pass on each trial of a gambling game. We report 6 replications (N = 988) showing that primes consistently affected gambling decisions when the decision was uncertain. Decisions were influenced by primes presented visibly, with a warning to ignore the primes (Experiments 1 through 3) and with subliminally presented masked primes (Experiment 4). Using a process dissociation procedure, we found evidence that primes influenced responses through both automatic and controlled processes (Experiments 5 and 6). Results provide evidence that primes can reliably affect behavior, under at least some conditions, without intention. The findings suggest that the psychological question of whether behavior priming effects are real should be separated from methodological issues affecting how easily particular experimental designs will replicate. (PsycINFO Database Record

  7. Angiopoietin-Like-4, a Potential Target of Tacrolimus, Predicts Earlier Podocyte Injury in Minimal Change Disease.

    Science.gov (United States)

    Li, Jian-Si; Chen, Xiao; Peng, Lei; Wei, Shi-Yao; Zhao, Shi-Lei; Diao, Tian-Tian; He, Yi-Xin; Liu, Fang; Wei, Qiu-Ju; Zhang, Qing-Fang; Li, Bing

    2015-01-01

    Podocyte injury plays central roles in proteinuria and kidney dysfunction, therefore, identifying specific biomarker to evaluate earlier podocyte injury is highly desirable. Podocyte-secreted angiopoietin-like-4 (Angptl4) mediates proteinuria in different types of podocytopathy. In the present study, we established an experimental minimal change disease (MCD) rat model, induced by adriamycin (ADR) and resulted in definite podocyte injury, to identify the dynamic changes in Angptl4 expression. We also investigated the direct effects of tacrolimus on Angptl4 and podocyte repair. We determined that the glomerular Angptl4 expression was rapidly upregulated and reached a peak earlier than desmin, an injured podocyte marker, in the ADR rats. Furthermore, this upregulation occurred prior to heavy proteinuria and was accompanied by increased urinary Angptl4. We observed that the Angptl4 upregulation occurred only when podocyte was mainly damaged since we didn't observe little Angptl4 upregulation in MsPGN patients. In addition, we observed the glomerular Angptl4 mainly located in injured podocytes rather than normal podocytes. Moreover, we found that tacrolimus treatment significantly promoted podocyte repair and reduced glomerular and urinary Angptl4 expression at an earlier stage with a significant serum Angptl4 upregulation. And similar results were confirmed in MCD patients. In conclusion, this study represents the first investigation to demonstrate that Angptl4 can predict podocyte injury at earlier stages in MCD and the identification of earlier podocyte injury biomarkers could facilitate the prompt diagnosis and treatment of patients with podocytopathy, as well as determination of the prognosis and treatment efficacy in these diseases.

  8. Arctic lakes show strong decadal trend in earlier spring ice-out

    Science.gov (United States)

    Šmejkalová, Tereza; Edwards, Mary E.; Dash, Jadunandan

    2016-12-01

    The timing of the seasonal freeze-thaw cycle of arctic lakes affects ecological processes and land-atmosphere energy fluxes. We carried out detailed ice-phenology mapping of arctic lakes, based on daily surface-reflectance time series for 2000-2013 from MODIS at 250 m spatial resolution. We used over 13,300 lakes, area >1 km2, in five study areas distributed evenly across the circumpolar Arctic — the first such phenological dataset. All areas showed significant trends towards an earlier break-up, stronger than previously reported. The mean shift in break-up start ranged from -0.10 days/year (Northern Europe) to -1.05 days/year (central Siberia); the shift in break-up end was between -0.14 and -0.72 days/year. Finally, we explored the effect of temperature on break-up timing and compared results among study areas. The 0 °C isotherm shows the strongest relationship (r = 0.56-0.81) in all study areas. If the trend in early break-up continues, rapidly changing ice phenology will likely generate significant, arctic-wide impacts.

  9. Biomarkers of replicative senescence revisited

    DEFF Research Database (Denmark)

    Nehlin, Jan

    2016-01-01

    Biomarkers of replicative senescence can be defined as those ultrastructural and physiological variations as well as molecules whose changes in expression, activity or function correlate with aging, as a result of the gradual exhaustion of replicative potential and a state of permanent cell cycle...... with their chronological age and present health status, help define their current rate of aging and contribute to establish personalized therapy plans to reduce, counteract or even avoid the appearance of aging biomarkers....

  10. Microarray profiles on age-related genes in the earlier postnatal rat visual cortex

    Institute of Scientific and Technical Information of China (English)

    YANG Liu; NIE Yu-hong; ZHOU Li-hua; LIN Shao-chun; WU Kai-li

    2011-01-01

    Background Accumulating evidence indicates that both innate and adaptive mechanisms are responsible for the postnatal development of the mammalian visual cortex. Most of the studies, including gene expression analysis, were performed on the visual cortex during the critical period; few efforts were made to elucidate the molecular changes in the visual cortex during much earlier postnatal stages. The current study aimed to gain a general insight into the molecular mechanisms in the developmental process of the rat visual cortex using microarray to display the gene expression profiles of the visual cortex on postnatal days.Methods All age-matched Sprague-Dawley rats in various groups including postnatal day 0 (PO, n=20), day 10 (P10,n=15), day 20 (P20, n=15) and day 45 (P45, n=10) were sacrificed respectively. Fresh visual cortex from the binocular area (Area 17) was dissected for extraction of total RNA for microarray analyses. Taking advantage of annotation information from the gene ontology and pathway database, the gene expression profiles were systematically and globally analyzed.Results Of the 31 042 gene sequences represented on the rat expression microarray, more than 4000 of the transcripts significantly altered at days 45,20 or 10 compared to day 0. The most obvious alteration of gene expression occurred in the first ten days of the postnatal period and the genomic activities of the visual cortex maintained a high level from birth to day 45. Compared to the gene expression at birth, there were 2630 changed transcripts that shared in three postnatal periods.The up-regulated genes in most signaling pathways were more than those of the down-regulated genes.Conclusions Analyzing gene expression patterns, we provide a detailed insight into the molecular organization of the developing visual cortex in the earlier postnatal rat. The most obvious alteration of gene expression in visual cortex occurred in the first ten days. Our data were a basis to identify new

  11. Spatial and Temporal Variation in Primary Productivity (NDVI) of Coastal Alaskan Tundra: Decreased Vegetation Growth Following Earlier Snowmelt

    Science.gov (United States)

    Gamon, John A.; Huemmrich, K. Fred; Stone, Robert S.; Tweedie, Craig E.

    2015-01-01

    In the Arctic, earlier snowmelt and longer growing seasons due to warming have been hypothesized to increase vegetation productivity. Using the Normalized Difference Vegetation Index (NDVI) from both field and satellite measurements as an indicator of vegetation phenology and productivity, we monitored spatial and temporal patterns of vegetation growth for a coastal wet sedge tundra site near Barrow, Alaska over three growing seasons (2000-2002). Contrary to expectation, earlier snowmelt did not lead to increased productivity. Instead, productivity was associated primarily with precipitation and soil moisture, and secondarily with growing degree days, which, during this period, led to reduced growth in years with earlier snowmelt. Additional moisture effects on productivity and species distribution, operating over a longer time scale, were evident in spatial NDVI patterns associated with microtopography. Lower, wetter regions dominated by graminoids were more productive than higher, drier locations having a higher percentage of lichens and mosses, despite the earlier snowmelt at the more elevated sites. These results call into question the oft-stated hypothesis that earlier arctic growing seasons will lead to greater vegetation productivity. Rather, they agree with an emerging body of evidence from recent field studies indicating that early-season, local environmental conditions, notably moisture and temperature, are primary factors determining arctic vegetation productivity. For this coastal arctic site, early growing season conditions are strongly influenced by microtopography, hydrology, and regional sea ice dynamics, and may not be easily predicted from snowmelt date or seasonal average air temperatures alone. Our comparison of field to satellite NDVI also highlights the value of in-situ monitoring of actual vegetation responses using field optical sampling to obtain detailed information on surface conditions not possible from satellite observations alone.

  12. Plasmid Rolling-Circle Replication.

    Science.gov (United States)

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

    2015-02-01

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

  13. Focus Article: Replication in Second Language Writing Research

    Science.gov (United States)

    Porte, Graeme; Richards, Keith

    2012-01-01

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

  14. 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…

  15. Focus Article: Replication in Second Language Writing Research

    Science.gov (United States)

    Porte, Graeme; Richards, Keith

    2012-01-01

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

  16. Identification of the replication origins from Cyanothece ATCC 51142 and their interactions with the DnaA protein: from in silico to in vitro studies

    Directory of Open Access Journals (Sweden)

    He eHuang

    2015-12-01

    Full Text Available Based on the complete genome of Cyanothece ATCC 51142, the oriCs of both the circular and linear chromosomes in Cyanothece ATCC 51142 have been predicted by utilizing a web-based system Ori-Finder. Here, we provide the experimental supports for the results of Ori-Finder to identify the origins of replication of Cyanothece ATCC 51142 and their interactions with initiator protein DnaA . The two replication origins are both composed of three characteristically arranged DnaA boxes, and an AT-rich stretch, and the oriC in circular chromosome is followed by the dnaN gene. The dnaA gene is located downstream of the origin of circular chromosome and expresses a typical DnaA protein that follows the division into four domains (I, II, III, IV, as with other members of the DnaA protein family. Here, we report the purification of DnaA (IV and characterize the interaction of the purified protein with the replication origins, in order to offer experimental supports for the prediction. Combined with experimental validation, we identified the oriCs of Cyanothece ATCC 51142. The results of EMSA and DNase I footprint assay demonstrate that the C-terminal domain of Cyanothece ATCC 51142 DnaA protein specifically binds the oriCs of both the circular and linear chromosomes, and DNase I footprint assay demonstrates that DnaA (IV has a hypersensitive affinity interaction with DnaA boxes in both oriCs. The results also confirm the results predicted by Ori-Finder.

  17. Apple pomace, a by-product from the asturian cider industry, inhibits herpes simplex virus types 1 and 2 in vitro replication: study of its mechanisms of action.

    Science.gov (United States)

    Alvarez, Angel L; Melón, Santiago; Dalton, Kevin P; Nicieza, Inés; Roque, Annele; Suárez, Belén; Parra, Francisco

    2012-06-01

    The anti-herpes simplex virus type 1 and anti-herpes simplex virus type 2 effects of apple pomace, a by-product from the cider-processing industry, were investigated. The mechanisms of antiviral action were assessed using a battery of experiments targeting sequential steps in the viral replication cycle. The anti-herpetic mechanisms of apple pomaces included the inhibition of virus attachment to the cell surface and the arrest of virus entry and uncoating. Quercitrin and procyanidin B2 were found to play a crucial role in the antiviral activity.

  18. Apple Pomace, a By-Product from the Asturian Cider Industry, Inhibits Herpes Simplex Virus Types 1 and 2 In Vitro Replication: Study of Its Mechanisms of Action

    Science.gov (United States)

    Melón, Santiago; Dalton, Kevin P.; Nicieza, Inés; Roque, Annele; Suárez, Belén; Parra, Francisco

    2012-01-01

    Abstract The anti–herpes simplex virus type 1 and anti–herpes simplex virus type 2 effects of apple pomace, a by-product from the cider-processing industry, were investigated. The mechanisms of antiviral action were assessed using a battery of experiments targeting sequential steps in the viral replication cycle. The anti-herpetic mechanisms of apple pomaces included the inhibition of virus attachment to the cell surface and the arrest of virus entry and uncoating. Quercitrin and procyanidin B2 were found to play a crucial role in the antiviral activity. PMID:22424460

  19. Change in the cortical complexity of spinocerebellar ataxia type 3 appears earlier than clinical symptoms.

    Science.gov (United States)

    Wang, Tzu-Yun; Jao, Chii-Wen; Soong, Bing-Wen; Wu, Hsiu-Mei; Shyu, Kuo-Kai; Wang, Po-Shan; Wu, Yu-Te

    2015-01-01

    Patients with spinocerebellar ataxia type 3 (SCA3) have exhibited cerebral cortical involvement and various mental deficits in previous studies. Clinically, conventional measurements, such as the Mini-Mental State Examination (MMSE) and electroencephalography (EEG), are insensitive to cerebral cortical involvement and mental deficits associated with SCA3, particularly at the early stage of the disease. We applied a three-dimensional fractal dimension (3D-FD) method, which can be used to quantify the shape complexity of cortical folding, in assessing cortical degeneration. We evaluated 48 genetically confirmed SCA3 patients by employing clinical scales and magnetic resonance imaging and using 50 healthy participants as a control group. According to the Scale for the Assessment and Rating of Ataxia (SARA), the SCA3 patients were diagnosed with cortical dysfunction in the cerebellar cortex; however, no significant difference in the cerebral cortex was observed according to the patients' MMSE ratings. Using the 3D-FD method, we determined that cortical involvement was more extensive than involvement of traditional olivopontocerebellar regions and the corticocerebellar system. Moreover, the significant correlation between decreased 3D-FD values and disease duration may indicate atrophy of the cerebellar cortex and cerebral cortex in SCA3 patients. The change of the cerebral complexity in the SCA3 patients can be detected throughout the disease duration, especially it becomes substantial at the late stage of the disease. Furthermore, we determined that atrophy of the cerebral cortex may occur earlier than changes in MMSE scores and EEG signals.

  20. Change in the cortical complexity of spinocerebellar ataxia type 3 appears earlier than clinical symptoms.

    Directory of Open Access Journals (Sweden)

    Tzu-Yun Wang

    Full Text Available Patients with spinocerebellar ataxia type 3 (SCA3 have exhibited cerebral cortical involvement and various mental deficits in previous studies. Clinically, conventional measurements, such as the Mini-Mental State Examination (MMSE and electroencephalography (EEG, are insensitive to cerebral cortical involvement and mental deficits associated with SCA3, particularly at the early stage of the disease. We applied a three-dimensional fractal dimension (3D-FD method, which can be used to quantify the shape complexity of cortical folding, in assessing cortical degeneration. We evaluated 48 genetically confirmed SCA3 patients by employing clinical scales and magnetic resonance imaging and using 50 healthy participants as a control group. According to the Scale for the Assessment and Rating of Ataxia (SARA, the SCA3 patients were diagnosed with cortical dysfunction in the cerebellar cortex; however, no significant difference in the cerebral cortex was observed according to the patients' MMSE ratings. Using the 3D-FD method, we determined that cortical involvement was more extensive than involvement of traditional olivopontocerebellar regions and the corticocerebellar system. Moreover, the significant correlation between decreased 3D-FD values and disease duration may indicate atrophy of the cerebellar cortex and cerebral cortex in SCA3 patients. The change of the cerebral complexity in the SCA3 patients can be detected throughout the disease duration, especially it becomes substantial at the late stage of the disease. Furthermore, we determined that atrophy of the cerebral cortex may occur earlier than changes in MMSE scores and EEG signals.

  1. Falling through the cracks? Missed opportunities for earlier HIV diagnosis in a New York City Hospital.

    Science.gov (United States)

    Nakao, Jolene H; Wiener, Dan E; Newman, David H; Sharp, Victoria L; Egan, Daniel J

    2014-10-01

    Summary Newly diagnosed HIV-positive patients have frequent health care encounters prior to diagnosis representing missed opportunities for diagnosis. This study determines the proportion of patients with new HIV diagnoses with encounters in the 3 years prior to diagnosis. We describe the characteristics of newly diagnosed patients and of "late testers" (CD4 diagnosis). We identified all newly diagnosed with HIV in emergency department, inpatient, and outpatient settings between May 1, 2006, and December 31, 2009. Data abstractors searched hospital records to identify all emergency department, inpatient, and outpatient visits for the 3 years prior to diagnosis. In all, 23,271 HIV tests were performed and 253 persons were newly diagnosed (1.1%); 152 new positives (60.1%) made at least one prior visit. Of patients with CD4 counts available, 104/175 (59.4%) had CD4 HIV-positive patients had multiple encounters prior to diagnosis. Many of these patients presented with CD4 counts below 200 cells/mm(3), indicating true missed opportunities for earlier diagnosis.

  2. Stress responses and replication of plasmids in bacterial cells

    Directory of Open Access Journals (Sweden)

    Wegrzyn Alicja

    2002-05-01

    Full Text Available Abstract Plasmids, DNA (or rarely RNA molecules which replicate in cells autonomously (independently of chromosomes as non-essential genetic elements, play important roles for microbes grown under specific environmental conditions as well as in scientific laboratories and in biotechnology. For example, bacterial plasmids are excellent models in studies on regulation of DNA replication, and their derivatives are the most commonly used vectors in genetic engineering. Detailed mechanisms of replication initiation, which is the crucial process for efficient maintenance of plasmids in cells, have been elucidated for several plasmids. However, to understand plasmid biology, it is necessary to understand regulation of plasmid DNA replication in response to different environmental conditions in which host cells exist. Knowledge of such regulatory processes is also very important for those who use plasmids as expression vectors to produce large amounts of recombinant proteins. Variable conditions in large-scale fermentations must influence replication of plasmid DNA in cells, thus affecting the efficiency of recombinant gene expression significantly. Contrary to extensively investigated biochemistry of plasmid replication, molecular mechanisms of regulation of plasmid DNA replication in response to various environmental stress conditions are relatively poorly understood. There are, however, recently published studies that add significant data to our knowledge on relations between cellular stress responses and control of plasmid DNA replication. In this review we focus on plasmids derived from bacteriophage λ that are among the best investigated replicons. Nevertheless, recent results of studies on other plasmids are also discussed shortly.

  3. Murine leukemia virus (MLV replication monitored with fluorescent proteins

    Directory of Open Access Journals (Sweden)

    Bittner Alexandra

    2004-12-01

    Full Text Available Abstract Background Cancer gene therapy will benefit from vectors that are able to replicate in tumor tissue and cause a bystander effect. Replication-competent murine leukemia virus (MLV has been described to have potential as cancer therapeutics, however, MLV infection does not cause a cytopathic effect in the infected cell and viral replication can only be studied by immunostaining or measurement of reverse transcriptase activity. Results We inserted the coding sequences for green fluorescent protein (GFP into the proline-rich region (PRR of the ecotropic envelope protein (Env and were able to fluorescently label MLV. This allowed us to directly monitor viral replication and attachment to target cells by flow cytometry. We used this method to study viral replication of recombinant MLVs and split viral genomes, which were generated by replacement of the MLV env gene with the red fluorescent protein (RFP and separately cloning GFP-Env into a retroviral vector. Co-transfection of both plasmids into target cells resulted in the generation of semi-replicative vectors, and the two color labeling allowed to determine the distribution of the individual genomes in the target cells and was indicative for the occurrence of recombination events. Conclusions Fluorescently labeled MLVs are excellent tools for the study of factors that influence viral replication and can be used to optimize MLV-based replication-competent viruses or vectors for gene therapy.

  4. 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

    NARCIS (Netherlands)

    Agogo, G.O.; Voet, van der H.; Veer, van 't P.; Ferrari, P.; Leenders, M.; Muller, D.C.; Sánchez-Cantalejo, E.; Bamia, C.; Braaten, T.; Knüppel, S.; Johansson, I.; Eeuwijk, van F.A.; Boshuizen, H.C.

    2014-01-01

    In epidemiologic studies, measurement error in dietary variables often attenuates association between dietary intake and disease occurrence. To adjust for the attenuation caused by error in dietary intake, regression calibration is commonly used. To apply regression calibration, unbiased reference m

  5. 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

    NARCIS (Netherlands)

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

    2014-01-01

    In epidemiologic studies, measurement error in dietary variables often attenuates association between dietary intake and disease occurrence. To adjust for the attenuation caused by error in dietary intake, regression calibration is commonly used. To apply regression calibration, unbiased reference m

  6. The Development of Replicated Optical Integral Field Spectrographs and their Application to the Study of Lyman-alpha Emission at Moderate Redshifts

    Science.gov (United States)

    Chonis, Taylor Steven

    In the upcoming era of extremely large ground-based astronomical telescopes, the design of wide-field spectroscopic survey instrumentation has become increasingly complex due to the linear growth of instrument pupil size with telescope diameter for a constant spectral resolving power. The upcoming Visible Integral field Replicable Unit Spectrograph (VIRUS), a baseline array of 150 copies of a simple integral field spectrograph that will be fed by 3:36 x 104 optical fibers on the upgraded Hobby-Eberly Telescope (HET) at McDonald Observatory, represents one of the first uses of large-scale replication to break the relationship between instrument pupil size and telescope diameter. By dividing the telescope's field of view between a large number of smaller and more manageable instruments, the total information grasp of a traditional monolithic survey spectrograph can be achieved at a fraction of the cost and engineering complexity. To highlight the power of this method, VIRUS will execute the HET Dark Energy Experiment (HETDEX) and survey & 420 degrees2 of sky to an emission line flux limit of ˜ 10-17 erg s-1 cm -2 to detect ˜ 106 Lyman-alpha emitting galaxies (LAEs) as probes of large-scale structure at redshifts of 1:9 ProQuest.).

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

    Science.gov (United States)

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

    2015-01-01

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

  8. 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

  9. In vitro replication of cyanobacterial plasmids from Synechocystis PCC 6803.

    Science.gov (United States)

    Yang, X; Daniell, H; McFadden, B

    1994-09-01

    Little knowledge of DNA replication in cyanobacteria is available. In this study, we report the development and characterization of an in vitro system for studies of replication of the endogenous plasmids from the unicellular cyanobacterium Synechocystis 6803. This system (fraction III) was isolated at high salt concentrations and partially purified on a heparin-agarose column. DNA polymerases in Synechocystis 6803 appeared to be associated with membranes and could be released by the addition of ammonium sulfate to 20% saturation. DNA synthesis in fraction III was dependent on the addition of cyanobacterial plasmids isolated from the same strain. The in vitro replication products consist mostly of the supercoiled form of the plasmids. Unlike replication of many Escherichia coli plasmids, replication of cyanobacterial plasmids did not require added ATP, was not inhibited by omission of the ribonucleotides, and was insensitive to the RNA polymerase inhibitor rifampicin and the gyrase inhibitor novobiocin, but was inhibited by ethidium bromide. These data suggest that RNA may not be involved in the initiation of replication of cyanobacterial plasmids from Synechocystis 6803. In addition, intermediates of replication have been detected by two-dimensional gel electrophoresis. Density labeling experiments also indicate that cyanobacterial plasmid synthesis in vitro occurs by a semiconservative replication.

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

    Directory of Open Access Journals (Sweden)

    Shlomit Farkash-Amar

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

  11. Selection for earlier flowering crop associated with climatic variations in the Sahel.

    Directory of Open Access Journals (Sweden)

    Yves Vigouroux

    Full Text Available Climate changes will have an impact on food production and will require costly adaptive responses. Adapting to a changing environment will be particularly challenging in sub-Saharan Africa where climate change is expected to have a major impact. However, one important phenomenon that is often overlooked and is poorly documented is the ability of agro-systems to rapidly adapt to environmental variations. Such an adaptation could proceed by the adoption of new varieties or by the adaptation of varieties to a changing environment. In this study, we analyzed these two processes in one of the driest agro-ecosystems in Africa, the Sahel. We performed a detailed study in Niger where pearl millet is the main crop and covers 65% of the cultivated area. To assess how the agro-system is responding to recent recurrent drought, we analyzed samples of pearl millet landraces collected in the same villages in 1976 and 2003 throughout the entire cultivated area of Niger. We studied phenological and morphological differences in the 1976 and 2003 collections by comparing them over three cropping seasons in a common garden experiment. We found no major changes in the main cultivated varieties or in their genetic diversity. However, we observed a significant shift in adaptive traits. Compared to the 1976 samples, samples collected in 2003 displayed a shorter lifecycle, and a reduction in plant and spike size. We also found that an early flowering allele at the PHYC locus increased in frequency between 1976 and 2003. The increase exceeded the effect of drift and sampling, suggesting a direct effect of selection for earliness on this gene. We conclude that recurrent drought can lead to selection for earlier flowering in a major Sahelian crop. Surprisingly, these results suggest that diffusion of crop varieties is not the main driver of short term adaptation to climatic variation.

  12. Earlier Right Ventricular Pacing in Cardiac Resynchronization Therapy for a Patient with Right Axis Deviation.

    Science.gov (United States)

    Hattori, Yusuke; Ishibashi, Kohei; Noda, Takashi; Okamura, Hideo; Kanzaki, Hideaki; Anzai, Toshihisa; Yasuda, Satoshi; Kusano, Kengo

    2017-09-01

    We describe the case of a 37-year-old woman who presented with complete right bundle branch block and right axis deviation. She was admitted to our hospital due to severe heart failure and was dependent on inotropic agents. Cardiac resynchronization therapy was initiated but did not improve her condition. After the optimization of the pacing timing, we performed earlier right ventricular pacing, which led to an improvement of her heart failure. Earlier right ventricular pacing should be considered in patients with complete right bundle branch block and right axis deviation when cardiac resynchronization therapy is not effective.

  13. Defects of mitochondrial DNA replication.

    Science.gov (United States)

    Copeland, William C

    2014-09-01

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

  14. Shell Separation for Mirror Replication

    Science.gov (United States)

    1999-01-01

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

  15. A two-substrate Michaelis-Menten model for the growth of self-replicating polymers.

    Science.gov (United States)

    Ferreira, R

    1987-10-07

    A two-substrate Michaelis-Menten model is proposed for the growth of autocatalytic self-replicating polymers. Selective growth depends on the existence of two complementary pairs of monomers. Discrimination among sequences results from different products of binding constants, KCGnKAUm. The results support an earlier renormalization group treatment (Ferreira & Tsallis, 1985).

  16. Liposomal pegylated doxorubicin and oxaliplatin as salvage chemotherapy in patients with metastatic gastric cancer treated earlier.

    Science.gov (United States)

    Recchia, Francesco; Candeloro, Giampiero; Guerriero, Gabriele; Piazze, Juan; Desideri, Giovambattista; Necozione, Stefano; Rea, Silvio

    2010-06-01

    The aim of this study was to evaluate the activity and safety of pegylated liposomal doxorubicin (PLD) and oxaliplatin (LOHP) as salvage chemotherapy in patients with metastatic gastric cancer (MGC) who had earlier been treated with docetaxel, capecitabine, 5-fluorouracil, and leucovorin. Treatment consisted of PLD (40 mg/m(2)) and LOHP (120 mg/m(2)) administered over 2 days, every 3 weeks. Response to therapy was assessed using the Response Evaluation Criteria In Solid Tumors; toxicity was evaluated by the National Cancer Institute common toxicity criteria (version 2.0). Thirty-six patients with pretreated MGC and a mean age of 66 years were recruited for the study. After a median follow-up of 11 months and 202 courses of chemotherapy administered (median, five courses per patient), the overall response rate in the 36 evaluable patients was estimated to be 28%. Grades 3 and 4 hematological toxicities were neutropenia in 44% of patients, grade 2-3 diarrhea in 14% of patients, and grade 2 neuropathy in 12 patients. Median progression-free survival and overall survival were 5.8 and 9.2 months, respectively, with 1-year survival rate of 36%, [95% confidence interval (CI): 21-54%]. Median survival time from the diagnosis of metastatic disease was 31.5 months. Seventy-two percent of patients (n=26) (95% CI: 58-88%) obtained a clinical benefit from this chemotherapy regimen. PLD and LOHP is an active regimen, able to give palliation in a substantial percentage of MCG patients who have been pretreated with taxanes.

  17. NPH Log: Validation of a New Assessment Tool Leading to Earlier Diagnosis of Normal Pressure Hydrocephalus.

    Science.gov (United States)

    Jusué-Torres, Ignacio; Lu, Jennifer; Robison, Jamie; Hoffberger, Jamie B; Hulbert, Alicia; Sanyal, Abanti; Wemmer, Jan; Elder, Benjamin D; Rigamonti, Daniele

    2016-06-27

    Early treatment of normal pressure hydrocephalus (NPH) yields better postoperative outcomes. Our current tests often fail to detect significant changes at early stages. We developed a new scoring system (LP log score) to determine if this tool is more sensitive in detecting clinical differences than current tests. Sixty-two consecutive new patients with suspected idiopathic NPH were studied. Secondary, previously treated and obstructive cases were not included. We collected age, pre- and post-lumbar puncture (LP) Tinetti, Timed Up and Go (TUG) Test, European NPH scale, and LP log scores. The LP log score is recorded at baseline and for seven consecutive days after removing 40 cc of cerebrospinal fluid (CSF) via LP. We studied the diagnostic accuracy of the tests for surgical indication. The post-LP log showed improvement in 90% of people with good baseline gait tests and in 93% of people who did not show any pre-LP and post-LP change in gait tests. Sensitivity, specificity, and accuracy to detect intention to treat when positive post-LP improvements were 4%, 100%, and 24%, respectively, for TUG, 21%, 86%, and 34%, respectively, for the Tinetti Mobility Test, 66%, 29%, and 58%, respectively, for Medical College of Virginia (MCV) grade, and 98%, 33%, and 85%, respectively, for LP log score. Pre-LP and post-LP TUG improvement and pre-LP and post-LP Tinetti improvement were not associated with a surgical indication (p > 0.05). LP log improvement was associated with surgical indication odds ratio (OR): 24.5 95% CI (2.4-248.12) (p = 0.007). LP log showed better sensitivity, diagnostic accuracy, and association with surgical indication than the current diagnostic approach. An LP log may be useful detecting NPH patients at earlier stages and, therefore, yield better surgical outcomes.

  18. NPH Log: Validation of a New Assessment Tool Leading to Earlier Diagnosis of Normal Pressure Hydrocephalus

    Science.gov (United States)

    Lu, Jennifer; Robison, Jamie; Hoffberger, Jamie B; Hulbert, Alicia; Sanyal, Abanti; Wemmer, Jan; Elder, Benjamin D; Rigamonti, Daniele

    2016-01-01

    Introduction: Early treatment of normal pressure hydrocephalus (NPH) yields better postoperative outcomes. Our current tests often fail to detect significant changes at early stages. We developed a new scoring system (LP log score) to determine if this tool is more sensitive in detecting clinical differences than current tests. Material and Methods: Sixty-two consecutive new patients with suspected idiopathic NPH were studied. Secondary, previously treated and obstructive cases were not included. We collected age, pre- and post-lumbar puncture (LP) Tinetti, Timed Up and Go (TUG) Test, European NPH scale, and LP log scores. The LP log score is recorded at baseline and for seven consecutive days after removing 40 cc of cerebrospinal fluid (CSF) via LP. We studied the diagnostic accuracy of the tests for surgical indication. Results: The post-LP log showed improvement in 90% of people with good baseline gait tests and in 93% of people who did not show any pre-LP and post-LP change in gait tests. Sensitivity, specificity, and accuracy to detect intention to treat when positive post-LP improvements were 4%, 100%, and 24%, respectively, for TUG, 21%, 86%, and 34%, respectively, for the Tinetti Mobility Test, 66%, 29%, and 58%, respectively, for Medical College of Virginia (MCV) grade, and 98%, 33%, and 85%, respectively, for LP log score. Pre-LP and post-LP TUG improvement and pre-LP and post-LP Tinetti improvement were not associated with a surgical indication (p > 0.05). LP log improvement was associated with surgical indication odds ratio (OR): 24.5 95% CI (2.4-248.12) (p = 0.007). Conclusions: LP log showed better sensitivity, diagnostic accuracy, and association with surgical indication than the current diagnostic approach. An LP log may be useful detecting NPH patients at earlier stages and, therefore, yield better surgical outcomes. PMID:27489752

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

    Science.gov (United States)

    Francis, Gregory

    2012-12-01

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

  20. 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…

  1. Initiation and regulation of paramyxovirus transcription and replication.

    Science.gov (United States)

    Noton, Sarah L; Fearns, Rachel

    2015-05-01

    The paramyxovirus family has a genome consisting of a single strand of negative sense RNA. This genome acts as a template for two distinct processes: transcription to generate subgenomic, capped and polyadenylated mRNAs, and genome replication. These viruses only encode one polymerase. Thus, an intriguing question is, how does the viral polymerase initiate and become committed to either transcription or replication? By answering this we can begin to understand how these two processes are regulated. In this review article, we present recent findings from studies on the paramyxovirus, respiratory syncytial virus, which show how its polymerase is able to initiate transcription and replication from a single promoter. We discuss how these findings apply to other paramyxoviruses. Then, we examine how trans-acting proteins and promoter secondary structure might serve to regulate transcription and replication during different phases of the paramyxovirus replication cycle.

  2. NCOA4 transcriptional coactivator inhibits activation of DNA replication origins.

    Science.gov (United States)

    Bellelli, Roberto; Castellone, Maria Domenica; Guida, Teresa; Limongello, Roberto; Dathan, Nina Alayne; Merolla, Francesco; Cirafici, Anna Maria; Affuso, Andrea; Masai, Hisao; Costanzo, Vincenzo; Grieco, Domenico; Fusco, Alfredo; Santoro, Massimo; Carlomagno, Francesca

    2014-07-01

    NCOA4 is a transcriptional coactivator of nuclear hormone receptors that undergoes gene rearrangement in human cancer. By combining studies in Xenopus laevis egg extracts and mouse embryonic fibroblasts (MEFs), we show here that NCOA4 is a minichromosome maintenance 7 (MCM7)-interacting protein that is able to control DNA replication. Depletion-reconstitution experiments in Xenopus laevis egg extracts indicate that NCOA4 acts as an inhibitor of DNA replication origin activation by regulating CMG (CDC45/MCM2-7/GINS) helicase. NCOA4(-/-) MEFs display unscheduled origin activation and reduced interorigin distance; this results in replication stress, as shown by the presence of fork stalling, reduction of fork speed, and premature senescence. Together, our findings indicate that NCOA4 acts as a regulator of DNA replication origins that helps prevent inappropriate DNA synthesis and replication stress.

  3. Jnk2 effects on tumor development, genetic instability and replicative stress in an oncogene-driven mouse mammary tumor model.

    Directory of Open Access Journals (Sweden)

    Peila Chen

    Full Text Available Oncogenes induce cell proliferation leading to replicative stress, DNA damage and genomic instability. A wide variety of cellular stresses activate c-Jun N-terminal kinase (JNK proteins, but few studies have directly addressed the roles of JNK isoforms in tumor development. Herein, we show that jnk2 knockout mice expressing the Polyoma Middle T Antigen transgene developed mammary tumors earlier and experienced higher tumor multiplicity compared to jnk2 wildtype mice. Lack of jnk2 expression was associated with higher tumor aneuploidy and reduced DNA damage response, as marked by fewer pH2AX and 53BP1 nuclear foci. Comparative genomic hybridization further confirmed increased genomic instability in PyV MT/jnk2-/- tumors. In vitro, PyV MT/jnk2-/- cells underwent replicative stress and cell death as evidenced by lower BrdU incorporation, and sustained chromatin licensing and DNA replication factor 1 (CDT1 and p21(Waf1 protein expression, and phosphorylation of Chk1 after serum stimulation, but this response was not associated with phosphorylation of p53 Ser15. Adenoviral overexpression of CDT1 led to similar differences between jnk2 wildtype and knockout cells. In normal mammary cells undergoing UV induced single stranded DNA breaks, JNK2 localized to RPA (Replication Protein A coated strands indicating that JNK2 responds early to single stranded DNA damage and is critical for subsequent recruitment of DNA repair proteins. Together, these data support that JNK2 prevents replicative stress by coordinating cell cycle progression and DNA damage repair mechanisms.

  4. The lexical approach to the study of personality structure: toward the identification of cross-culturally replicable dimensions of personality variation.

    Science.gov (United States)

    Ashton, Michael C; Lee, Kibeom

    2005-06-01

    The structure of personality variation is discussed from the perspective of the lexical approach, which is based on the examination of relations among personality-descriptive adjectives that are indigenous to various languages. The results of this approach--which reveal a cross-culturally replicated set of six dimensions--are described. Specifically, the obtained structure corresponds rather closely to the Five-Factor Model, but differs from that model in the nature of the Agreeableness and Emotionality/Neuroticism factors and also in the existence of a sixth factor known as Honesty-Humility. It is suggested that the emergence of this structure provides support for attempts to establish a cross-culturally generalizable structural model that could summarize normal and abnormal personality variation.

  5. 75 FR 47316 - National Science Board; Sunshine Act Meetings; Notice (Subject Matter Revised From Earlier Notice)

    Science.gov (United States)

    2010-08-05

    ... National Science Board; Sunshine Act Meetings; Notice (Subject Matter Revised From Earlier Notice) The... National Science Board business and other matters specified, as follows: Date and Time: August 12, 2010, at 3 p.m. EDT. Subject Matter: Review and Discussion of Current Mid-Scale Research Funding Support...

  6. Use of metformin earlier in pregnancy predicts supplemental insulin therapy in women with gestational diabetes.

    Science.gov (United States)

    McGrath, Rachel T; Glastras, Sarah J; Hocking, Samantha; Fulcher, Gregory R

    2016-06-01

    The use of metformin in gestational diabetes is safe and effective, yet some women require additional insulin therapy to achieve glycaemic targets. We found a significant association between earlier gestational age at initiation of metformin therapy and the necessity for supplemental insulin in women treated with metformin during pregnancy.

  7. The impact of newborn screening and earlier intervention on the clinical course of cystic fibrosis

    NARCIS (Netherlands)

    Dijk, F. Nicole; Fitzgerald, Dominic A.

    2012-01-01

    Cystic fibrosis is a life-limiting condition which is readily diagnosed in the vast majority of cases on newborn screening [NBS]. A diagnosis made on newborn screening translates into earlier initiation of therapies, improved growth, better lung function into the adult years and culminates in better

  8. Analysis of radioactive corrosion test specimens by means of ICP-MS. Comparison with earlier methods

    Energy Technology Data Exchange (ETDEWEB)

    Forsyth, Roy [Forsyth Consulting, Nykoeping (Sweden)

    1997-07-01

    In June 1992, an ICP-MS instrument (Inductively Coupled Plasma-Mass Spectrometry) was commissioned for use with radioactive sample solutions at Studsvik Nuclear`s Hot Cell Laboratory. For conventional environmental samples the instrument permits the simultaneous analysis of many trace elements, but the software used in evaluation of the mass spectra is based on a library of isotopic compositions relevant only for elements in the lithosphere. Fission products and actinides, however, have isotopic compositions which are significantly different from the natural elements, and which also vary with the burnup of the nuclear fuel specimen. Consequently, a spread-sheet had to be developed which could evaluate the mass spectra with these isotopic compositions. Following these preparations, a large number of samples (about 200) from SKB`s experimental programme for the study of spent fuel corrosion have been analyzed by the ICP-MS technique. Many of these samples were archive solutions of samples which had been taken earlier in the programme. This report presents a comparison of the analytical results for uranium, plutonium, cesium, strontium and technetium by both the ICP-MS technique, and the previously used analytical methods. For three products, a satisfactory agreement between the results from the various methods was obtained, but for uranium and plutonium the ICP-MS method gave results which were 10-20% higher than the conventional methods. The comparison programme has also shown, not unexpectedly, that significant losses of plutonium from solution had occurred, by precipitation and/or absorption, in the archive solutions during storage. It can be expected that such losses also occur for the other actinides, and consequently, all the analytical results for actinides in older archive solutions must be treated with great caution. 9 refs.

  9. Effect of Functional Nano Channel Structures Different Widths on Injection Molding and Compression Molding Replication Capabilities

    DEFF Research Database (Denmark)

    Calaon, M.; Tosello, G.; Garnaes, J.

    The present study investigates the capabilities of the two employed processes, injection molding (IM) and injection compression molding (ICM) on replicating different channel cross sections. Statistical design of experiment was adopted to optimize replication quality of produced polymer parts wit...

  10. Earlier reperfusion in patients with ST-elevation Myocardial infarction by use of helicopter

    Directory of Open Access Journals (Sweden)

    Knudsen Lars

    2012-10-01

    Full Text Available Abstract Background In patients with ST-elevation myocardial infarction (STEMI reperfusion therapy should be initiated as soon as possible. This study evaluated whether use of a helicopter for transportation of patients is associated with earlier initiation of reperfusion therapy. Material and methods A prospective study was conducted, including patients with STEMI and symptom duration less than 12 hours, who had primary percutaneous coronary intervention (PPCI performed at Aarhus University Hospital in Skejby. Patients with a health care system delay (time from emergency call to first coronary intervention of more than 360 minutes were excluded. The study period ran from 1.1.2011 until 31.12.2011. A Western Denmark Helicopter Emergency Medical Service (HEMS project was initiated 1.6.2011 for transportation of patients with time-critical illnesses, including STEMI. Results The study population comprised 398 patients, of whom 376 were transported by ambulance Emergency Medical Service (EMS and 22 by HEMS. Field-triage directly to the PCI-center was used in 338 of patients. The median system delay was 94 minutes among those field-triaged, and 168 minutes among those initially admitted to a local hospital. Patients transported by EMS and field-triaged were stratified into four groups according to transport distance from the scene of event to the PCI-center: ≤25 km., 26–50 km., 51–75 km. and > 75 km. For these groups, the median system delay was 78, 89, 99, and 141 minutes. Among patients transported by HEMS and field-triaged the estimated median transport distance by ground transportation was 115 km, and the observed system delay was 107 minutes. Based on second order polynomial regression, it was estimated that patients with a transport distance of >60 km to the PCI-center may benefit from helicopter transportation, and that transportation by helicopter is associated with a system delay of less than 120 minutes even at a transport

  11. Continuously Cumulating Meta-Analysis and Replicability.

    Science.gov (United States)

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

    2014-05-01

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

  12. Hyperthermia stimulates HIV-1 replication.

    Directory of Open Access Journals (Sweden)

    Ferdinand Roesch

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

  13. Hyperthermia stimulates HIV-1 replication.

    Science.gov (United States)

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

    2012-01-01

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

  14. Cellular Responses to Replication Problems

    NARCIS (Netherlands)

    M. Budzowska (Magdalena)

    2008-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Tunin Karen

    2002-01-01

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

  16. Nanostructured surfaces yield earlier: Molecular dynamics study of nanoindentation into adatom islands

    Science.gov (United States)

    Ziegenhain, Gerolf; Urbassek, Herbert M.

    2010-04-01

    Using molecular-dynamics simulation we investigate nanoindentation into an fcc metal surface covered by an adatom island. Small islands are pushed into the solid and transported away by prismatic dislocation loops, and no defects remain under the indenter; thereafter indentation proceeds as for a flat surface. For large islands, the island boundaries do not influence indentation. Most interesting is the intermediate case, where the island size is comparable to the contact radius of the indenter at the onset of plasticity. Here plasticity starts immediately at the surface under the weakest step edges bounding the island. The dislocations are pinned to the step edges and dislocation activity remains localized under the island. For this intermediate case, the surface is weakest and yields earliest.

  17. Competition and cooperation in dynamic replication networks.

    Science.gov (United States)

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

    2015-01-07

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

  18. Proteasome-dependent degradation of replisome components regulates faithful DNA replication.

    Science.gov (United States)

    Roseaulin, Laura C; Noguchi, Chiaki; Noguchi, Eishi

    2013-08-15

    The replication machinery, or the replisome, collides with a variety of obstacles during the normal process of DNA replication. In addition to damaged template DNA, numerous chromosome regions are considered to be difficult to replicate owing to the presence of DNA secondary structures and DNA-binding proteins. Under these conditions, the replication fork stalls, generating replication stress. Stalled forks are prone to collapse, posing serious threats to genomic integrity. It is generally thought that the replication checkpoint functions to stabilize the replisome and replication fork structure upon replication stress. This is important in order to allow DNA replication to resume once the problem is solved. However, our recent studies demonstrated that some replisome components undergo proteasome-dependent degradation during DNA replication in the fission yeast Schizosaccharomyces pombe. Our investigation has revealed the involvement of the SCF(Pof3) (Skp1-Cullin/Cdc53-F-box) ubiquitin ligase in replisome regulation. We also demonstrated that forced accumulation of the replisome components leads to abnormal DNA replication upon replication stress. Here we review these findings and present additional data indicating the importance of replisome degradation for DNA replication. Our studies suggest that cells activate an alternative pathway to degrade replisome components in order to preserve genomic integrity.

  19. On the association between loneliness and physical warmth-seeking through bathing: Reply to Donnellan et al. (2014) and three further replications of Bargh and Shalev (2012) study 1: Correction to Shalev and Bargh (2014).

    Science.gov (United States)

    2015-02-01

    Reports an error in "On the Association Between Loneliness and Physical Warmth-Seeking Through Bathing: Reply to Donnellan et al. (2014) and Three Further Replications of Bargh and Shalev (2012) Study 1" by Idit Shalev and John Bargh (Emotion, Advanced Online Publication, Sep 8, 2014, np). In the article, there was an error in the abstract. The name of author Donnellan was misspelled as Donellan. (The following abstract of the original article appeared in record 2014-37463-001.) [Correction Notice: An Erratum for this article was reported in Vol 15(1) of Emotion (see record 2015-05076-004). In the article, the wrong supplemental file was originally posted. The correct file has now been posted.] As Tversky and Kahneman (1971) noted, effect sizes in smaller samples are inherently unstable. Donellan et al. (2014) in a large sample show that the relation between trait loneliness and warmth extraction through bathing activities is much smaller than in our initial smaller samples. We report further replications of our original findings in samples from India, Israel, and North America, again showing significant correlations between loneliness and physical warmth extraction from bathing and showering; the overall effect being reliable across all three samples, although, consistent with Donellan et al.'s conclusions, smaller than in our original studies. We also respond to criticisms of the original data analyses, noting that removal of the problematic 'bathing frequency' item from the warmth index did not substantially change the results and thus our conclusions from them. We also note that in their 2 studies in which Donellan et al. attempted to most closely follow our original procedure, they did replicate our original results, but not in the other 7 studies in which considerable procedural changes were made. As our new replications reveal variability in bathing and showering preferences and habits around the world, we recommend the inclusion of a wider sample of

  20. On the association between loneliness and physical warmth-seeking through bathing: Reply to Donnellan et al. (2014) and three further replications of Bargh and Shalev (2012) study 1: Correction to Shalev and Bargh (2014).

    Science.gov (United States)

    2015-02-01

    Reports an error in "On the Association Between Loneliness and Physical Warmth-Seeking Through Bathing: Reply to Donnellan et al. (2014) and Three Further Replications of Bargh and Shalev (2012) Study 1" by Idit Shalev and John Bargh (Emotion, Advanced Online Publication, Sep 8, 2014, np). In the article, the wrong supplemental file was originally posted. The correct file has now been posted. (The following abstract of the original article appeared in record 2014-37463-001.) As Tversky and Kahneman (1971) noted, effect sizes in smaller samples are inherently unstable. Donellan et al. (2014) in a large sample show that the relation between trait loneliness and warmth extraction through bathing activities is much smaller than in our initial smaller samples. We report further replications of our original findings in samples from India, Israel, and North America, again showing significant correlations between loneliness and physical warmth extraction from bathing and showering; the overall effect being reliable across all three samples, although, consistent with Donellan et al.'s conclusions, smaller than in our original studies. We also respond to criticisms of the original data analyses, noting that removal of the problematic 'bathing frequency' item from the warmth index did not substantially change the results and thus our conclusions from them. We also note that in their 2 studies in which Donellan et al. attempted to most closely follow our original procedure, they did replicate our original results, but not in the other 7 studies in which considerable procedural changes were made. As our new replications reveal variability in bathing and showering preferences and habits around the world, we recommend the inclusion of a wider sample of cultures beyond North American in future research. This research should also focus not only on the narrower question of how loneliness relates to bathing activities but on the broader relation between feelings of social coldness (e

  1. 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...

  2. REPLICATION TOOL AND METHOD OF PROVIDING A REPLICATION TOOL

    DEFF Research Database (Denmark)

    2016-01-01

    structured master surface (3a, 3b, 3c, 3d) having a lateral master pattern and a vertical master profile. The microscale structured master surface (3a, 3b, 3c, 3d) has been provided by localized pulsed laser treatment to generate microscale phase explosions. A method for producing a part with microscale......The invention relates to a replication tool (1, 1a, 1b) for producing a part (4) with a microscale textured replica surface (5a, 5b, 5c, 5d). The replication tool (1, 1a, 1b) comprises a tool surface (2a, 2b) defining a general shape of the item. The tool surface (2a, 2b) comprises a microscale...... energy directors on flange portions thereof uses the replication tool (1, 1a, 1b) to form an item (4) with a general shape as defined by the tool surface (2a, 2b). The formed item (4) comprises a microscale textured replica surface (5a, 5b, 5c, 5d) with a lateral arrangement of polydisperse microscale...

  3. Approximating the maximum weight clique using replicator dynamics.

    Science.gov (United States)

    Bomze, I R; Pelillo, M; Stix, V

    2000-01-01

    Given an undirected graph with weights on the vertices, the maximum weight clique problem (MWCP) is to find a subset of mutually adjacent vertices (i.e., a clique) having the largest total weight. This is a generalization of the classical problem of finding the maximum cardinality clique of an unweighted graph, which arises as a special case of the MWCP when all the weights associated to the vertices are equal. The problem is known to be NP-hard for arbitrary graphs and, according to recent theoretical results, so is the problem of approximating it within a constant factor. Although there has recently been much interest around neural-network algorithms for the unweighted maximum clique problem, no effort has been directed so far toward its weighted counterpart. In this paper, we present a parallel, distributed heuristic for approximating the MWCP based on dynamics principles developed and studied in various branches of mathematical biology. The proposed framework centers around a recently introduced continuous characterization of the MWCP which generalizes an earlier remarkable result by Motzkin and Straus. This allows us to formulate the MWCP (a purely combinatorial problem) in terms of a continuous quadratic programming problem. One drawback associated with this formulation, however, is the presence of "spurious" solutions, and we present characterizations of these solutions. To avoid them we introduce a new regularized continuous formulation of the MWCP inspired by previous works on the unweighted problem, and show how this approach completely solves the problem. The continuous formulation of the MWCP naturally maps onto a parallel, distributed computational network whose dynamical behavior is governed by the so-called replicator equations. These are dynamical systems introduced in evolutionary game theory and population genetics to model evolutionary processes on a macroscopic scale.We present theoretical results which guarantee that the solutions provided by

  4. Earlier detection can help avoid many serious complications of peripartum cardiomyopathy.

    Science.gov (United States)

    Fett, James D

    2013-11-01

    Peripartum cardiomyopathy (PPCM) has a remarkable potential for recovery. It may be within our capability to help almost all women with PPCM not only to survive, but also to completely recover heart function. Time-of-diagnosis left ventricular ejection fraction (LVEF) ≥0.35 is associated with better survival rates and higher full recovery rates. Increased mortality, chronic cardiomyopathy, thromboembolic complications and serious ventricular tachyarrhythmias are associated with diagnostic LVEF <0.30. Delays in diagnosis may result in lower LVEF at diagnosis and subsequent lower recovery rates. Greater awareness of the possibility of heart failure developing in previously healthy young women, with no history of heart disease, will contribute to earlier diagnosis, with potentially better preserved heart function. Women of African descent may be at higher risk for poorer outcomes. Recent investigations suggest newer biomarkers may help with earlier detection of PPCM.

  5. Optimal HIV testing and earlier care: the way forward in Europe

    DEFF Research Database (Denmark)

    Coenen, T; Lundgren, J; Lazarus, Jeff;

    2008-01-01

    representing advocacy, clinical and policy areas of the HIV field, was convened in an effort to gain a common understanding on the role of HIV testing and counselling in optimizing diagnosis and the need for earlier care. Key topics discussed at the conference and described in the following articles include......The articles in this supplement were developed from a recent pan-European conference entitled 'HIV in Europe 2007: Working together for optimal testing and earlier care', which took place on 26-27 November in Brussels, Belgium. The conference, organized by a multidisciplinary group of experts......: current barriers to HIV testing across Europe, trends in the epidemiology of HIV in the region, problems associated with undiagnosed infection and the psychosocial barriers impacting on testing. The supplement also provides a summary of the World Health Organization's recommendations for HIV testing...

  6. The molecular biology of Bluetongue virus replication.

    Science.gov (United States)

    Patel, Avnish; Roy, Polly

    2014-03-01

    The members of Orbivirus genus within the Reoviridae family are arthropod-borne viruses which are responsible for high morbidity and mortality in ruminants. Bluetongue virus (BTV) which causes disease in livestock (sheep, goat, cattle) has been in the forefront of molecular studies for the last three decades and now represents the best understood orbivirus at a molecular and structural level. The complex nature of the virion structure has been well characterised at high resolution along with the definition of the virus encoded enzymes required for RNA replication; the ordered assembly of the capsid shell as well as the protein and genome sequestration required for it; and the role of host proteins in virus entry and virus release. More recent developments of Reverse Genetics and Cell-Free Assembly systems have allowed integration of the accumulated structural and molecular knowledge to be tested at meticulous level, yielding higher insight into basic molecular virology, from which the rational design of safe efficacious vaccines has been possible. This article is centred on the molecular dissection of BTV with a view to understanding the role of each protein in the virus replication cycle. These areas are important in themselves for BTV replication but they also indicate the pathways that related viruses, which includes viruses that are pathogenic to man and animals, might also use providing an informed starting point for intervention or prevention.

  7. Mutation at Expanding Front of Self-Replicating Colloidal Clusters

    CERN Document Server

    Tanaka, Hidenori; Brenner, Michael P

    2016-01-01

    We construct a scheme for self-replicating square clusters of particles in two spatial dimensions, and validate it with computer simulations in a finite-temperature heat bath. We find that the self-replication reactions propagate through the bath in the form of Fisher waves. Our model reflects existing colloidal systems, but is simple enough to allow simulation of many generations and thereby the first study of evolutionary dynamics in an artificial system. By introducing spatially localized mutations in the replication rules, we show that the mutated cluster population can survive and spread with the expanding front in circular sectors of the colony.

  8. Culture in the cockpit: do Hofstede's dimensions replicate?

    Science.gov (United States)

    Merritt, A.; Helmreich, R. L. (Principal Investigator)

    2000-01-01

    Survey data collected from 9,400 male commercial airline pilots in 19 countries were used in a replication study of Hofstede's indexes of national culture. The analysis that removed the constraint of item equivalence proved superior, both conceptually and empirically, to the analysis using Hofstede's items and formulae as prescribed, and rendered significant replication correlations for all indexes (Individualism-Collectivism .96, Power Distance .87, Masculinity-Femininity .75, and Uncertainty Avoidance .68). The successful replication confirms that national culture exerts an influence on cockpit behavior over and above the professional culture of pilots, and that "one size fits all" training is inappropriate.

  9. Mutation at Expanding Front of Self-Replicating Colloidal Clusters

    Science.gov (United States)

    Tanaka, Hidenori; Zeravcic, Zorana; Brenner, Michael P.

    2016-12-01

    We construct a scheme for self-replicating square clusters of particles in two spatial dimensions, and validate it with computer simulations in a finite-temperature heat bath. We find that the self-replication reactions propagate through the bath in the form of Fisher waves. Our model reflects existing colloidal systems, but is simple enough to allow simulation of many generations and thereby the first study of evolutionary dynamics in an artificial system. By introducing spatially localized mutations in the replication rules, we show that the mutated cluster population can survive and spread with the expanding front in circular sectors of the colony.

  10. Application of hepatitis B virus replication mouse model

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To evaluate the value of the hepatitis B virus(HBV) replication mouse model with regard to several aspects of the study of HBV biology.METHODS:To evaluate the HBV replication mouse model in detecting the efficacy of anti-HBV agents,the interferon inducer polyinosinic-polytidylin acid(polyIC) and nucleotide analogues adefovir and entecavir were administered to mice injected with wild type pHBV4.1,and the inhibiting effect of these agents on HBV DNA replication was evaluated.To identify the model's value ...

  11. Identification of a New Ribonucleoside Inhibitor of Ebola Virus Replication

    Directory of Open Access Journals (Sweden)

    Olivier Reynard

    2015-12-01

    Full Text Available The current outbreak of Ebola virus (EBOV in West Africa has claimed the lives of more than 15,000 people and highlights an urgent need for therapeutics capable of preventing virus replication. In this study we screened known nucleoside analogues for their ability to interfere with EBOV replication. Among them, the cytidine analogue β-d-N4-hydroxycytidine (NHC demonstrated potent inhibitory activities against EBOV replication and spread at non-cytotoxic concentrations. Thus, NHC constitutes an interesting candidate for the development of a suitable drug treatment against EBOV.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1989-01-01

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

  13. Receptor tyrosine kinase signaling regulates replication of the peste des petits ruminants virus.

    Science.gov (United States)

    Chaudhary, K; Chaubey, K K; Singh, S V; Kumar, N

    2015-03-01

    In this study, we found out that blocking the receptor tyrosine kinase (RTK) signaling in Vero cells by tryphostin AG879 impairs the in vitro replication of the peste des petits ruminants virus (PPRV). A reduced virus replication in Trk1-knockdown (siRNA) Vero cells confirmed the essential role of RTK in the virus replication, in particular a specific regulation of viral RNA synthesis. These data represent the first evidence that the RTK signaling regulates replication of a morbillivirus.

  14. The bimodal lifestyle of intracellular Salmonella in epithelial cells: replication in the cytosol obscures defects in vacuolar replication.

    Directory of Open Access Journals (Sweden)

    Preeti Malik-Kale

    Full Text Available Salmonella enterica serovar Typhimurium invades and proliferates within epithelial cells. Intracellular bacteria replicate within a membrane bound vacuole known as the Salmonella containing vacuole. However, this bacterium can also replicate efficiently in the cytosol of epithelial cells and net intracellular growth is a product of both vacuolar and cytosolic replication. Here we have used semi-quantitative single-cell analyses to investigate the contribution of each of these replicative niches to intracellular proliferation in cultured epithelial cells. We show that cytosolic replication can account for the majority of net replication even though it occurs in less than 20% of infected cells. Consequently, assays for net growth in a population of infected cells, for example by recovery of colony forming units, are not good indicators of vacuolar proliferation. We also show that the Salmonella Type III Secretion System 2, which is required for SCV biogenesis, is not required for cytosolic replication. Altogether this study illustrates the value of single cell analyses when studying intracellular pathogens.

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

    Science.gov (United States)

    Adams, R. C.

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

  16. SMARCAL1 maintains telomere integrity during DNA replication.

    Science.gov (United States)

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

    2015-12-01

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

  17. Replicator dynamics in value chains

    DEFF Research Database (Denmark)

    Cantner, Uwe; Savin, Ivan; Vannuccini, Simone

    2016-01-01

    The pure model of replicator dynamics though providing important insights in the evolution of markets has not found much of empirical support. This paper extends the model to the case of firms vertically integrated in value chains. We show that i) by taking value chains into account, the replicator...... dynamics may revert its effect. In these regressive developments of market selection, firms with low fitness expand because of being integrated with highly fit partners, and the other way around; ii) allowing partner's switching within a value chain illustrates that periods of instability in the early...... stage of industry life-cycle may be the result of an 'optimization' of partners within a value chain providing a novel and simple explanation to the evidence discussed by Mazzucato (1998); iii) there are distinct differences in the contribution to market selection between the layers of a value chain...

  18. Therapeutic targeting of replicative immortality

    OpenAIRE

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

    2015-01-01

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

  19. Alphavirus polymerase and RNA replication.

    Science.gov (United States)

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

    2017-01-16

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

  20. Earlier timbre processing of instrumental tones compared to equally complex spectrally rotated sounds as revealed by the mismatch negativity.

    Science.gov (United States)

    Christmann, Corinna A; Lachmann, Thomas; Berti, Stefan

    2014-10-03

    Harmonically rich sounds have been shown to be processed more efficiently by the human brain compared to single sinusoidal tones. To control for stimulus complexity as a potentially confounding factor, tones and equally complex spectrally rotated sounds, have been used in the present study to investigate the role of the overtone series in sensory auditory processing in non-musicians. Timbre differences in instrumental tones with equal pitch elicited a MMN which was earlier compared to that elicited by the spectrally rotated sounds, indicating that harmonically rich tones are processed faster compared to non-musical sounds without an overtone series, even when pitch is not the relevant information.

  1. Dynamic replication of Web contents

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

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

  2. Temporal replication of the Pullman strain of Aleutian disease virus in royal pastel mink.

    Science.gov (United States)

    Hadlow, W J; Race, R E; Kennedy, R C

    1985-09-01

    Information was sought on the temporal replication of Aleutian disease virus in 27 royal pastel mink. Groups of three were examined 8 to 126 days after they were inoculated subcutaneously with 10(3) 50% lethal doses of the Pullman strain. Much individual variation was noted in the onset of infection, occurrence of viremia, and extent of virus replication in the tissues. Thus, virus was detected in lymph nodes regional to the site of inoculation in only some mink during the first 14 days after inoculation. During this period, virus was often present as well in the mesenteric lymph node and spleen. First detected on day 10, viremia was present in all mink examined on day 28 but occurred irregularly thereafter, even when virus was widespread in the tissues. Except in five mink succumbing to the disease, the tissue distribution of virus after day 28 tended to be more limited, and the titers were generally lower than they had been earlier. Even though present in the lymph nodes and spleen, virus was often absent from the kidney, liver, and intestine after day 28. Specific antibody was detected on day 28 and was present in all mink thereafter, ostensibly without any adverse effect on virus replication. In most mink, the infection was considered subclinical, for it was usually not accompanied by a rise in serum gamma globulin or by morphologic evidence of the disease. The virologic findings in this study have a bearing on the relationship of subclinical infections to both horizontal and vertical transmission of the virus.

  3. Deciphering DNA replication dynamics in eukaryotic cell populations in relation with their averaged chromatin conformations

    Science.gov (United States)

    Goldar, A.; Arneodo, A.; Audit, B.; Argoul, F.; Rappailles, A.; Guilbaud, G.; Petryk, N.; Kahli, M.; Hyrien, O.

    2016-03-01

    We propose a non-local model of DNA replication that takes into account the observed uncertainty on the position and time of replication initiation in eukaryote cell populations. By picturing replication initiation as a two-state system and considering all possible transition configurations, and by taking into account the chromatin’s fractal dimension, we derive an analytical expression for the rate of replication initiation. This model predicts with no free parameter the temporal profiles of initiation rate, replication fork density and fraction of replicated DNA, in quantitative agreement with corresponding experimental data from both S. cerevisiae and human cells and provides a quantitative estimate of initiation site redundancy. This study shows that, to a large extent, the program that regulates the dynamics of eukaryotic DNA replication is a collective phenomenon that emerges from the stochastic nature of replication origins initiation.

  4. Epistatic Interaction of ERAP1 and HLA-B in Behçet Disease: A Replication Study in the Spanish Population

    Science.gov (United States)

    Conde-Jaldón, Marta; Montes-Cano, Marco Antonio; García-Lozano, José Raul; Ortiz-Fernández, Lourdes; Ortego-Centeno, Norberto; González-León, Rocío; Espinosa, Gerard; Graña-Gil, Genaro; Sánchez-Bursón, Juan; González-Gay, Miguel Angel; Barnosi-Marín, Ana Celia; Solans, Roser; Fanlo, Patricia; Carballeira, Mónica Rodríguez; Camps, Teresa; Castañeda, Santos; Martín, Javier; González-Escribano, María Francisca

    2014-01-01

    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. PMID:25019531

  5. 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...

  6. Tumor promoters alter the temporal program of adenovirus replication in human cells.

    Science.gov (United States)

    Fisher, P B; Young, C S; Weinstein, I B; Carter, T H

    1981-04-01

    In this study we evaluated the effect of phorbol ester tumor promoters on the kinetics of adenovirus type 5 (Ad5) replication in human cells. When added at the time of infection, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) accelerated the appearance of an early virus antigen (72,000-molecular-weight [72K] deoxyribonucleic acid-binding protein), the onset of viral deoxyribonucleic acid synthesis, and the production of infectious virus. The appearance of an Ad5-specific cytopathic effect (CPE) was also accelerated in infected cultures exposed to TPA, whereas phorbol, 4 alpha-phorbol-12,13-didecanoate and 4-OmeTPA, which are inactive as tumor promoters, were ineffective in inducing this morphological change. The acceleration of the CPE seen in TPA-treated Ad5-infected cells was not caused by TPA induction of the protease plasminogen activator, since the protease inhibitors leupeptin and antipain do not inhibit the earlier onset of this CPE and, in contrast, epidermal growth factor, which induces plasminogen activator in HeLa cells, does not induce an earlier CPE. Evidence for a direct effect of TPA on viral gene expression was obtained by analyzing viral messenger ribonucleic acid (mRNA) synthesis. TPA accelerated the appearance of mRNA from all major early regions of Ad5, transiently stimulated the accumulation of region III mRNA, and accelerated the appearance of late Ad5 mRNA. Thus, TPA altered the temporal program of Ad5 mRNA production and accelerated the appearance of at least some Ad5-specific polypeptides during lytic infection of human cells. These effects presumably explain the earlier onset of the Ad5-specific CPE in TPA-treated cells and may have relevance to the effects of TPA on viral gene expression in nonpermissive cells carrying integrated viral deoxyribonucleic acid sequences.

  7. A Blm-Recql5 partnership in replication stress response

    Institute of Scientific and Technical Information of China (English)

    Xincheng Lu; Hua Lou; Guangbin Luo

    2011-01-01

    Deficiencies in DNA damage response and repair not only can result in genome instability and cancer predisposition, but also can render the cancer cells intrinsically more vulnerable to certain types of DNA damage insults. Particularly, replication stress is both a hallmark of human cancers and a common instigator for genome instability and cell death. Here, we review our work based on the genetic knockout studies on Blm and Recql5, two members of the mammalian RecQ helicase family. These studies have uncovered a unique partnership between these two helicases in the implementation of proper mitigation strategies under different circumstances to promote DNA replication and cell survival and suppress genome instability and cancer. In particular, current studies have revealed the presence of a novel Recql5/RECQL5-dependent mechanism for suppressing replication fork collapse in response to global replication fork stalling following exposure to camptothecin (CPT), a topoisomerase I inhibitor, and a potent inhibitor of DNA replication. The unique partnership between Blm and Recql5 in coping with the challenge imposed by replication stress is discussed. In addition, given that irinotecan and topotecan, two CPT derivatives, are currently used in clinic for treating human cancer patients with very promising results, the potential implication of the new findings from these studies in anticancer treatments is also discussed.

  8. Impact of replicate types on proteomic expression analysis.

    Science.gov (United States)

    Karp, Natasha A; Spencer, Matthew; Lindsay, Helen; O'Dell, Kevin; Lilley, Kathryn S

    2005-01-01

    In expression proteomics, the samples utilized within an experimental design may include technical, biological, or pooled replicates. This manuscript discusses various experimental designs and the conclusions that can be drawn from them. Specifically, it addresses the impact of mixing replicate types on the statistical analysis which can be performed. This study focuses on difference gel electrophoresis (DiGE), but the issues are equally applicable to all quantitative methodologies assessing relative changes in protein expression.

  9. Earlier Pulmonary Valve Replacement in Down Syndrome Patients Following Tetralogy of Fallot Repair.

    Science.gov (United States)

    Sullivan, Rachel T; Frommelt, Peter C; Hill, Garick D

    2017-08-01

    The association between Down syndrome and pulmonary hypertension could contribute to more severe pulmonary regurgitation after tetralogy of Fallot repair and possibly earlier pulmonary valve replacement. We compared cardiac magnetic resonance measures of pulmonary regurgitation and right ventricular dilation as well as timing of pulmonary valve replacement between those with and without Down syndrome after tetralogy of Fallot repair. Review of our surgical database from 2000 to 2015 identified patients with tetralogy of Fallot with pulmonary stenosis. Those with Down syndrome were compared to those without. The primary outcome of interest was time from repair to pulmonary valve replacement. Secondary outcomes included pulmonary regurgitation and indexed right ventricular volume on cardiac magnetic resonance imaging. The cohort of 284 patients included 35 (12%) with Down syndrome. Transannular patch repair was performed in 210 (74%). Down syndrome showed greater degree of pulmonary regurgitation (55 ± 14 vs. 37 ± 16%, p = 0.01) without a significantly greater rate of right ventricular dilation (p = 0.09). In multivariable analysis, Down syndrome (HR 2.3, 95% CI 1.2-4.5, p = 0.02) and transannular patch repair (HR 5.5, 95% CI 1.7-17.6, p = 0.004) were significant risk factors for valve replacement. Those with Down syndrome had significantly lower freedom from valve replacement (p = 0.03). Down syndrome is associated with an increased degree of pulmonary regurgitation and earlier pulmonary valve replacement after tetralogy of Fallot repair. These patients require earlier assessment by cardiac magnetic resonance imaging to determine timing of pulmonary valve replacement and evaluation for and treatment of preventable causes of pulmonary hypertension.

  10. Replication of micro-sized pillars in polypropylene using the extrusion coating process

    DEFF Research Database (Denmark)

    Okulova, Nastasia; Johansen, Peter; Christensen, Lars

    2017-01-01

    A recent advancement in nano-pattern replication using roll-to-roll extrusion coating (R2R-EC) shows potential for many biomimetic applications. For further development of the technique a study of the micro-replication regime is carried out. In this study a full and partial replication in polypro......A recent advancement in nano-pattern replication using roll-to-roll extrusion coating (R2R-EC) shows potential for many biomimetic applications. For further development of the technique a study of the micro-replication regime is carried out. In this study a full and partial replication...... in polypropylene (PP) of micro-sized pillars has been demonstrated using the extrusion coating process. The replication fidelity of the pillars is investigated in a systematic variation of different process parameters: the line-speed of the rolls, the extruder output, the cooling roll temperature and the pressure...

  11. Family history of atrial fibrillation is associated with earlier-onset and more symptomatic atrial fibrillation

    DEFF Research Database (Denmark)

    Gundlund, Anna; Fosbøl, Emil Loldrup; Kim, Sunghee

    2016-01-01

    BACKGROUND: We addressed whether patients with a family history of atrial fibrillation (AF) were diagnosed as having AF earlier in life, were more symptomatic, and had worse outcomes compared with those without a family history of AF. METHODS: Using the ORBIT-AF, we compared symptoms and disease ......, and had more severe AF-related symptoms. No differences were found between the 2 groups in the risk of AF progression (adjusted hazard ratio [HR] 0.98, 95% CI 0.85-1.14), stroke, non-central nervous system embolism, or transient ischemic attack (adjusted HR 0.95, 95% CI 0.67-1.34), all...

  12. Inhibiting NAD+-dependent DNA ligase activity with 2-(cyclopentyloxy)-5'-deoxyadenosine (CPOdA) offers a new tool for DNA replication and repair studies in the model archaeon Haloferax volcanii.

    Science.gov (United States)

    Giroux, Xavier; MacNeill, Stuart A

    2015-11-01

    DNA ligases play an essential role in many aspects of DNA metabolism in all three domains of life. The haloarchaeal organism Haloferax volcanii encodes both ATP- and NAD(+)-dependent DNA ligase enzymes designated LigA and LigN, respectively. Neither LigA nor LigN alone is required for cell viability but they share an essential function, most likely the ligation of Okazaki fragments during chromosome replication. Here we show that 2-(cyclopentyloxy)-5'-deoxyadenosine (referred to as CPOdA), originally developed as a inhibitor of bacterial NAD(+)-dependent DNA ligases, is a potent inhibitor of the growth of Hfx. volcanii cells expressing LigN alone, causing chromosome fragmentation and cell death, while cells expressing LigA are unaffected. Growth inhibition occurs at significantly lower CPOdA concentrations (MIC ≤ 50 ng ml(-1)) than those required for inhibition of bacterial growth (≥2 μg ml(-1)). CPOdA has the potential to become a vital tool in DNA replication and repair studies in this important model organism.

  13. Replication Origin Specification Gets a Push.

    Science.gov (United States)

    Plosky, Brian S

    2015-12-03

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

  14. Exploiting replicative stress to treat cancer

    DEFF Research Database (Denmark)

    Dobbelstein, Matthias; Sørensen, Claus Storgaard

    2015-01-01

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

  15. A Validity Study of the Pain Apperception Test

    Science.gov (United States)

    Haase, Richard F.; And Others

    1975-01-01

    This study assessed the validity of the Pain Apperception Test (PAT) against an accepted and validated predictive measure of pain tolerance, a Kinesthetic After Effects Task (KAE). As well, it replicated an earlier finding by Petrovich that suggested that scores derived from the PAT are related significantly to neuroticism. (Author/RK)

  16. On rethinking the psychology of tyranny: the BBC prison study.

    Science.gov (United States)

    Zimbardo, Philip G

    2006-03-01

    This commentary offers a critical evaluation of the scientific legitimacy of research generated by television programming interests. It challenges the validity of claims advanced by these researchers regarding the Stanford Prison Experiment (SPE) and highlights the biases, fallacies and distortions in this study conducted for BBC-TV that attempted a partial replication of my earlier experiment.

  17. Earlier Metabolizable Energy Intake Level Influences Heat Production during a Following 3-Day Fast in Laying Hens.

    Science.gov (United States)

    Ning, D; Guo, Y M; Wang, Y W; Peng, Y Z

    2013-04-01

    The present study was conducted to estimate energy requirements for maintenance in laying hens by using indirect calorimetry and energy balance. A total of 576 28-wk-old Nongda-3 laying hens with dwarf gene were randomly allocated into four ME intake levels (86.57, 124.45, 166.63 and 197.20 kcal/kg body weight (BW)(0.75) per d) with four replicates each. After a 4 d adaptation period, 36 hens from one replicate were maintained in one of the two respiration chambers to measure the heat production (HP) for 3 d during the feeding period and subsequent 3 d fast. Metabolizable energy (ME) intake was partitioned between heat increment (HI), HP associated with activity, fasting HP (FHP) and retained energy (RE). The equilibrium FHP may provide an estimate of NE requirements for maintenance (NEm). Results showed that HP, HI and RE in the fed state increased with ME intake level (phens to changes in ME intake level should be properly established when using indirect calorimetry technique to estimate dietary NE content, MEm and NEm for laying hens.

  18. Accounting for PDMS shrinkage when replicating structures

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  19. Replication of micro and nano surface geometries

    DEFF Research Database (Denmark)

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

    2011-01-01

    : manufacture of net-shape micro/nano surfaces, tooling (i.e. master making), and surface quality control (metrology, inspection). Replication processes and methods as well as the metrology of surfaces to determine the degree of replication are presented and classified. Examples from various application areas...... are given including replication for surface texture measurements, surface roughness standards, manufacture of micro and nano structured functional surfaces, replicated surfaces for optical applications (e.g. optical gratings), and process chains based on combinations of repeated surface replication steps....

  20. On the association between loneliness and physical warmth-seeking through bathing: reply to Donnellan et al. (2014) and three further replications of Bargh and Shalev (2012) study 1.

    Science.gov (United States)

    Shalev, Idit; Bargh, John

    2015-02-01

    [Correction Notice: An Erratum for this article was reported in Vol 15(1) of Emotion (see record 2015-05076-005). In the article, there was an error in the abstract. The name of author Donnellan was misspelled as Donellan.] [Correction Notice: An Erratum for this article was reported in Vol 15(1) of Emotion (see record 2015-05076-004). In the article, the wrong supplemental file was originally posted. The correct file has now been posted.] As Tversky and Kahneman (1971) noted, effect sizes in smaller samples are inherently unstable. Donnellan [corrected] et al. (2014) in a large sample show that the relation between trait loneliness and warmth extraction through bathing activities is much smaller than in our initial smaller samples. We report further replications of our original findings in samples from India, Israel, and North America, again showing significant correlations between loneliness and physical warmth extraction from bathing and showering; the overall effect being reliable across all three samples, although, consistent with Donnellan [corrected] et al.'s conclusions, smaller than in our original studies. We also respond to criticisms of the original data analyses, noting that removal of the problematic 'bathing frequency' item from the warmth index did not substantially change the results and thus our conclusions from them. We also note that in their 2 studies in which Donnellan [corrected] et al. attempted to most closely follow our original procedure, they did replicate our original results, but not in the other 7 studies in which considerable procedural changes were made. As our new replications reveal variability in bathing and showering preferences and habits around the world, we recommend the inclusion of a wider sample of cultures beyond North American in future research. This research should also focus not only on the narrower question of how loneliness relates to bathing activities but on the broader relation between feelings of social coldness

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

    Science.gov (United States)

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

    2014-11-15

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

  2. Replication Stress: A Lifetime of Epigenetic Change

    Directory of Open Access Journals (Sweden)

    Simran Khurana

    2015-09-01

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

  3. Human ribonuclease H1 resolves R-loops and thereby enables progression of the DNA replication fork.

    Science.gov (United States)

    Parajuli, Shankar; Teasley, Daniel C; Murali, Bhavna; Jackson, Jessica; Vindigni, Alessandro; Stewart, Sheila A

    2017-09-15

    Faithful DNA replication is essential for genome stability. To ensure accurate replication, numerous complex and redundant replication and repair mechanisms function in tandem with the core replication proteins to ensure DNA replication continues even when replication challenges are present that could impede progression of the replication fork. A unique topological challenge to the replication machinery is posed by RNA-DNA hybrids, commonly referred to as R-loops. Although R-loops play important roles in gene expression and recombination at immunoglobulin sites, their persistence is thought to interfere with DNA replication by slowing or impeding replication fork progression. Therefore, it is of interest to identify DNA-associated enzymes that help resolve replication-impeding R-loops. Here, using DNA fiber analysis, we demonstrate that human ribonuclease H1 (RNH1) plays an important role in replication fork movement in the mammalian nucleus by resolving R-loops. We found that RNH1 depletion results in accumulation of RNA-DNA hybrids, slowing of replication forks, and increased DNA damage. Our data uncovered a role for RNH1 in global DNA replication in the mammalian nucleus. Because accumulation of RNA-DNA hybrids is linked to various human cancers and neurodegenerative disorders, our study raises the possibility that replication fork progression might be impeded, adding to increased genomic instability and contributing to disease. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Luciferase imaging for evaluation of oncolytic adenovirus replication in vivo.

    Science.gov (United States)

    Guse, K; Dias, J D; Bauerschmitz, G J; Hakkarainen, T; Aavik, E; Ranki, T; Pisto, T; Särkioja, M; Desmond, R A; Kanerva, A; Hemminki, A

    2007-06-01

    Oncolytic viruses kill cancer cells by tumor-selective replication. Clinical data have established the safety of the approach but also the need of improvements in potency. Efficacy of oncolysis is linked to effective infection of target cells and subsequent productive replication. Other variables include intratumoral barriers, access to target cells, uptake by non-target organs and immune response. Each of these aspects relates to the location and degree of virus replication. Unfortunately, detection of in vivo replication has been difficult, labor intensive and costly and therefore not much studied. We hypothesized that by coinfection of a luciferase expressing E1-deleted virus with an oncolytic virus, both viruses would replicate when present in the same cell. Photon emission due to conversion of D-Luciferin is sensitive and penetrates tissues well. Importantly, killing of animals is not required and each animal can be imaged repeatedly. Two different murine xenograft models were used and intratumoral coinjections of luciferase encoding virus were performed with eight different oncolytic adenoviruses. In both models, we found significant correlation between photon emission and infectious virus production. This suggests that the system can be used for non-invasive quantitation of the amplitude, persistence and dynamics of oncolytic virus replication in vivo, which could be helpful for the development of more effective and safe agents.

  5. The View of Teachers of First Graders Regarding Scheduling the Age of Starting School to an Earlier Time

    Directory of Open Access Journals (Sweden)

    Huseyin Anilan

    2015-01-01

    Full Text Available The aim of the study is to present the reflections of scheduling the age of starting school to an earlier time related to the experiences inside and outside the classroom, students, problems and solutions experienced in teaching-learning process according to the view of teachers of first graders. The study is a collective case study. Work group was determined according to measurement sampling among purposive sampling methods in qualitative research approaches. 14 primary school teachers working at public primary schools in spring term in 2012-2013 educational term around Turkey attended the research. The data of the study were collected via interview and observation forms developed by the researchers. Descriptive analysis technique was used for the analysis of the data. When analyzing the data, Elo and Kyngas’s (2007 preparation, organization and reporting phases were taken into consideration. To validate the study, the findings were presented detachedly and quotations were taken directly from attendants’ statements. In order to provide the reliability of the research, we followed the way Stemler (2001 called repeatability or single coder reliability. In this research, the reliability was provided by considering the percentage of both single coder and two coders. In the research, we gained such findings that teachers disapprove of scheduling the age of starting school to an earlier time; they think that this affect teaching-learning process negatively; students 69-month-old or younger cannot discharge self-care skills because of their physical inability; and this hampers conduction of Phoneme Based Sentence Method.

  6. Earlier testing for HIV--how do we prevent late presentation?

    DEFF Research Database (Denmark)

    Yazdanpanah, Yazdan; Lange, Joep; Gerstoft, Jan

    2010-01-01

    of late-presenting patients by reviewing strategies that might be considered. Such strategies could include routine provider-initiated HIV testing of at-risk groups in settings such as sexually transmitted infection clinics, drug dependency programmes or antenatal care. Healthcare providers might also......HIV testing policies and practices vary widely across Europe. It is clear that there are individuals who might present late for HIV diagnosis and care within all risk groups, and potentially in any healthcare setting. This article explores the need to ensure earlier identification and treatment...... consider routine HIV testing in all healthcare facilities, in settings including emergency and primary care, where local HIV prevalence is above a threshold that should be further evaluated. They should also take advantage of rapid testing technologies and be aware of barriers to HIV testing among specific...

  7. Earlier testing for HIV--how do we prevent late presentation?

    DEFF Research Database (Denmark)

    Yazdanpanah, Yazdan; Lange, Joep; Gerstoft, Jan;

    2010-01-01

    HIV testing policies and practices vary widely across Europe. It is clear that there are individuals who might present late for HIV diagnosis and care within all risk groups, and potentially in any healthcare setting. This article explores the need to ensure earlier identification and treatment...... of late-presenting patients by reviewing strategies that might be considered. Such strategies could include routine provider-initiated HIV testing of at-risk groups in settings such as sexually transmitted infection clinics, drug dependency programmes or antenatal care. Healthcare providers might also...... consider routine HIV testing in all healthcare facilities, in settings including emergency and primary care, where local HIV prevalence is above a threshold that should be further evaluated. They should also take advantage of rapid testing technologies and be aware of barriers to HIV testing among specific...

  8. Spinal Epidural Abscess: A Review with Special Emphasis on Earlier Diagnosis.

    Science.gov (United States)

    Bond, Allison; Manian, Farrin A

    2016-01-01

    Spinal epidural abscess (SEA) is an uncommon but serious condition with significant morbidity and mortality. The prognosis of SEA is highly dependent on the timeliness of its diagnosis before neurological deficits develop. Unfortunately, often due to its nonspecific presentation, such as back pain, the diagnosis of SEA may be delayed in up to 75% of cases. Although many risk factors for SEA can be found in the published literature, their utility is limited by their frequent lack of objective evidence, numerousness, and absence in a significant proportion of cases. In this review, we call for a more discriminate evidence-based use of the term "risk factor" when discussing SEA and explore several approaches to its earlier diagnosis, including a simple algorithm based on its pathophysiology and serum C-reactive protein or erythrocyte sedimentation rate.

  9. Spinal Epidural Abscess: A Review with Special Emphasis on Earlier Diagnosis

    Directory of Open Access Journals (Sweden)

    Allison Bond

    2016-01-01

    Full Text Available Spinal epidural abscess (SEA is an uncommon but serious condition with significant morbidity and mortality. The prognosis of SEA is highly dependent on the timeliness of its diagnosis before neurological deficits develop. Unfortunately, often due to its nonspecific presentation, such as back pain, the diagnosis of SEA may be delayed in up to 75% of cases. Although many risk factors for SEA can be found in the published literature, their utility is limited by their frequent lack of objective evidence, numerousness, and absence in a significant proportion of cases. In this review, we call for a more discriminate evidence-based use of the term “risk factor” when discussing SEA and explore several approaches to its earlier diagnosis, including a simple algorithm based on its pathophysiology and serum C-reactive protein or erythrocyte sedimentation rate.

  10. Effects of Rumen Protected Methionine on Milk Yield and Milk Composition in Earlier Lactating Cow

    Institute of Scientific and Technical Information of China (English)

    SUN Manji; SHAN Anshan

    2008-01-01

    A total of 12 mature healthy Holstein dairy cows of the nearly body weight (580±30) kg, milk yield (22.5±2.8) kg in the early stages of lactation were selected in this experiment. The cows were randomly divided into 2 groups, every group had 6 cows, every group had 6 repeats, and every repeat had I cow. Added 20 g protected methionine in earlier lactating cow food every day. The results showed that protected methionine increased milk yield by 10.83%, testing group milk yield was significantly different than that of control (P<0.05);protected methionine increased milk fat by 5.98%, testing group milk fat was significantly different than that of control (P<0.05);Milk protein increased by 2.15%, but had insignificantly different (P>0.05);dry matter of milk had the tendency of decrease, but had insignificant difference (P>0.05).

  11. Warming and earlier spring increase Western U.S. forest wildfire activity

    Science.gov (United States)

    Westerling, A.L.; Hidalgo, H.G.; Cayan, D.R.; Swetnam, T.W.

    2006-01-01

    Western United States forest wildfire activity is widely thought to have increased in recent decades, yet neither the extent of recent changes nor the degree to which climate may be driving regional changes in wildfire has been systematically documented. Much of the public and scientific discussion of changes in western United States wildfire has focused instead on the effects of 19th- and 20th-century land-use history. We compiled a comprehensive database of large wildfires in western United States forests since 1970 and compared it with hydroclimatic and land-surface data. Here, we show that large wildfire activity increased suddenly and markedly in the mid-1980s, with higher large-wildfire frequency, longer wildfire durations, and longer wildfire seasons. The greatest increases occurred in mid-elevation, Northern Rockies forests, where land-use histories have relatively little effect on fire risks and are strongly associated with increased spring and summer temperatures and an earlier spring snowmelt.

  12. A Numerical Analysis Research on Earlier Behavior of Molten Droplet Covered with Vapor Film at the Stage of Triggering and Propagation in Steam Explosion

    Directory of Open Access Journals (Sweden)

    Mingjun Zhong

    2014-01-01

    Full Text Available When the molten fuel with high temperature falls into the cavity water, it will be dispersed into droplets which are covered with vapor films due to the rapid heat transfer with phase transition. This situation cannot be simply described by liquid-liquid or gas-liquid systems. And there are no sufficient experimental studies on the behavior of droplet covered with vapor film because of the rapid reaction and the difficulty in capture of the film configuration. In this paper, a multiphase code with the volume of fluid (VOF method is used to simulate the earlier behavior of droplet when vapor film exits. The earlier behavior is defined as behavior of the droplet before its disintegration. Thermal effect and pure hydrodynamic effect are, respectively, considered. The simulation results indicate that the film thickness and material density have significant effect on the earlier behavior of droplet. The situation assumed in Ciccarelli and Frost’s model (1994 is observed in current simulation of earlier thermal droplet behavior. The effect of triggering pressure pulse on earlier hydrodynamic behavior is also discussed and it indicates that vapor film has little effect on the hydrodynamic droplet deformation when the intensity of the pressure pulse is very high.

  13. Earlier migration timing, decreasing phenotypic variation, and biocomplexity in multiple salmonid species.

    Directory of Open Access Journals (Sweden)

    Ryan P Kovach

    Full Text Available Climate-induced phenological shifts can influence population, evolutionary, and ecological dynamics, but our understanding of these phenomena is hampered by a lack of long-term demographic data. We use a multi-decade census of 5 salmonid species representing 14 life histories in a warming Alaskan stream to address the following key questions about climate change and phenology: How consistent are temporal patterns and drivers of phenology for similar species and alternative life histories? Are shifts in phenology associated with changes in phenotypic variation? How do phenological changes influence the availability of resource subsidies? For most salmonid species, life stages, and life histories, freshwater temperature influences migration timing--migration events are occurring earlier in time (mean = 1.7 days earlier per decade over the 3-5 decades, and the number of days over which migration events occur is decreasing (mean = 1.5 days per decade. Temporal trends in migration timing were not correlated with changes in intra-annual phenotypic variation, suggesting that these components of the phenotypic distribution have responded to environmental change independently. Despite commonalities across species and life histories, there was important biocomplexity in the form of disparate shifts in migration timing and variation in the environmental factors influencing migration timing for alternative life history strategies in the same population. Overall, adult populations have been stable during these phenotypic and environmental changes (λ ≈ 1.0, but the temporal availability of salmon as a resource in freshwater has decreased by nearly 30 days since 1971 due to changes in the median date of migration timing and decreases in intra-annual variation in migration timing. These novel observations advance our understanding of phenological change in response to climate warming, and indicate that climate change has influenced the ecology of

  14. Placental Isoferritin Action in Pathogenesis of Pre-eclampsia and/or Intrauterine Growth Retardation and Its Earlier Predictive Value

    Institute of Scientific and Technical Information of China (English)

    朱颖; 王泽华; 熊桂荣

    2003-01-01

    In order to investigate the role of placental isoferritin (PLF) in pathogenesis of preeclampsia and/or intrauterine growth retardation (IUGR) and its earlier predictive value, a prospective double-blinded study was performed. In 120 initial normal pregnant women at earlier third trimester (from 24 to 34 weeks), plasma placental isoferritin and nitric oxide (NO) metabolites (nitrite/nitrate) (NO2-/NO3-) were examined by using ELISA and Criess assay respectively. The outcome of pregnancies and birth weight of their infants were followed up. The receiver operating characteristic curves (ROC) and predictive values of PLF predicting the outcome of pregnancy with IUGR, pre-eclampsia were analyzed. Results showed that in 120 initial normal pregnant women, IUGR occurred in 15 pregnant women (IUGR group) and pre-eclampsia in 19 (pre-eclampsia group), and the remaining 86 had normal pregnancy (normal group). The levels of plasma placental isoferritin were significantly decreased in IUGR group (260. 01± 58. 95) μg/ml and pre-eclampsia group (285.31± 53.73) μg/ml as compared with those in normal group (775.62± 89.32) μg/ml at earlier third trimester (both P<0. 01). The levels of plasma NO were significantly increased in IUGR group (61.57±46.22) μmol/L and pre-eclampsia group (58. 37± 30. 52) μmol/L as compared with those in the normal group (35. 29±24.46) μmol/L (both P<0. 01). There was no significant difference in plasma placental isoferritin and NO levels between IUGR group and pre-eclampsic group (both P> 0. 05). The plasma placental isoferritin was negatively correlated with NO levels (r= 0. 329,P<0. 01). The areas under ROC of PLF predicting IUGR and pre-eclampsia were 0. 977 and 0. 905 respectively. At the cut point of 400 μg/ml PLF level, the sensitivity, specificity, positive predictive value, negative predictive value and Kappa index of PLF levels predicting the outcome of pregnancy with pre-eclampsia were 100 %, 85.15 %, 55.88 %, 100 % and 0

  15. 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.

  16. Self-replication of DNA rings

    Science.gov (United States)

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

    2015-06-01

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

  17. Replication of genetic associations as pseudoreplication due to shared genealogy.

    Science.gov (United States)

    Rosenberg, Noah A; Vanliere, Jenna M

    2009-09-01

    The genotypes of individuals in replicate genetic association studies have some level of correlation due to shared descent in the complete pedigree of all living humans. As a result of this genealogical sharing, replicate studies that search for genotype-phenotype associations using linkage disequilibrium between marker loci and disease-susceptibility loci can be considered as "pseudoreplicates" rather than true replicates. We examine the size of the pseudoreplication effect in association studies simulated from evolutionary models of the history of a population, evaluating the excess probability that both of a pair of studies detect a disease association compared to the probability expected under the assumption that the two studies are independent. Each of nine combinations of a demographic model and a penetrance model leads to a detectable pseudoreplication effect, suggesting that the degree of support that can be attributed to a replicated genetic association result is less than that which can be attributed to a replicated result in a context of true independence.

  18. Deciphering DNA replication dynamics in eukaryotic cell populations in relation with their averaged chromatin conformations

    DEFF Research Database (Denmark)

    Goldar, A.; Arneodo, A.; Audit, B.

    2016-01-01

    We propose a non-local model of DNA replication that takes into account the observed uncertainty on the position and time of replication initiation in eukaryote cell populations. By picturing replication initiation as a two-state system and considering all possible transition configurations......, and by taking into account the chromatin's fractal dimension, we derive an analytical expression for the rate of replication initiation. This model predicts with no free parameter the temporal profiles of initiation rate, replication fork density and fraction of replicated DNA, in quantitative agreement...... with corresponding experimental data from both S. cerevisiae and human cells and provides a quantitative estimate of initiation site redundancy. This study shows that, to a large extent, the program that regulates the dynamics of eukaryotic DNA replication is a collective phenomenon that emerges from the stochastic...

  19. Analysis of JC virus DNA replication using a quantitative and high-throughput assay.

    Science.gov (United States)

    Shin, Jong; Phelan, Paul J; Chhum, Panharith; Bashkenova, Nazym; Yim, Sung; Parker, Robert; Gagnon, David; Gjoerup, Ole; Archambault, Jacques; Bullock, Peter A

    2014-11-01

    Progressive Multifocal Leukoencephalopathy (PML) is caused by lytic replication of JC virus (JCV) in specific cells of the central nervous system. Like other polyomaviruses, JCV encodes a large T-antigen helicase needed for replication of the viral DNA. Here, we report the development of a luciferase-based, quantitative and high-throughput assay of JCV DNA replication in C33A cells, which, unlike the glial cell lines Hs 683 and U87, accumulate high levels of nuclear T-ag needed for robust replication. Using this assay, we investigated the requirement for different domains of T-ag, and for specific sequences within and flanking the viral origin, in JCV DNA replication. Beyond providing validation of the assay, these studies revealed an important stimulatory role of the transcription factor NF1 in JCV DNA replication. Finally, we show that the assay can be used for inhibitor testing, highlighting its value for the identification of antiviral drugs targeting JCV DNA replication.

  20. 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.