Electronic bidirectional valve circuit prevents crossover distortion and threshold effect

NASA Technical Reports Server (NTRS)

Kernick, A.

1966-01-01

Four-terminal network forms a bidirectional valve which will switch or alternate an ac signal without crossover distortion or threshold effect. In this network, an isolated control signal is sufficient for circuit turn-on.

Effect of Crossover in Oncology Clinical Trials on Evidence Levels in Early Benefit Assessment in Germany.

PubMed

Isbary, Georg; Staab, Thomas R; Amelung, Volker E; Dintsios, Charalabos-Markos; Iking-Konert, Christof; Nesurini, Sonja Mariotti; Walter, Miriam; Ruof, Jörg

2018-06-01

In oncology clinical trials, crossover is used frequently but may lead to uncertainties regarding treatment effects. To investigate the handling of evidence from crossover trials by the European Medicines Agency (EMA) and the German Federal Joint Committee (G-BA). For oncology medicines with early benefit assessments before January 2015, presence of crossover, clinical data, EMA requests for additional data, and G-BA benefit ratings/evidence levels were analyzed from manufacturers' dossiers, G-BA appraisals, European Public Assessment Reports, and original publications. Eleven of 21 benefit assessments included crossover trials. Significant intergroup differences (P < 0.05) in overall survival (OS) were noted in 7 of 11 trials with and 7 of 10 without crossover. For 6 of 11 medicines with crossover, these were demonstrated before crossover. Treatment effects generally worsened with increasing proportions of crossover. The EMA requested additional data more frequently if crossover was performed, particularly if no OS data were available before crossover. The G-BA granted a considerable benefit to 73% of medicines with crossover and 40% of those without. Evidence levels were intermediate for 50% and 75%, respectively. None of the medicines received the highest evidence level. In G-BA appraisals, oncology medicines with crossover received better additional benefit ratings, but were assigned lower evidence levels, than those without. The five medicines with crossover after progression were assigned lower evidence levels than the six medicines with crossover after demonstration of superior OS, indicating that the way in which crossover is implemented may be one factor influencing the assignment of evidence levels by the G-BA. Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Magnetic field tuning of an excitonic insulator between the weak and strong coupling regimes in quantum limit graphite [Tunable excitonic insulator in quantum limit graphite

DOE PAGES

Zhu, Zengwei; McDonald, R. D.; Shekhter, A.; ...

2017-05-04

Here, the excitonic insulator phase has long been predicted to form in proximity to a band gap opening in the underlying band structure. The character of the pairing is conjectured to crossover from weak (BCS-like) to strong coupling (BEC-like) as the underlying band structure is tuned from the metallic to the insulating side of the gap opening. Here we report the high-magnetic field phase diagram of graphite to exhibit just such a crossover. By way of comprehensive angle-resolved magnetoresistance measurements, we demonstrate that the underlying band gap opening occurs inside the magnetic field-induced phase, paving the way for a systematicmore » study of the BCS-BEC-like crossover by means of conventional condensed matter probes.« less

Magnetic field tuning of an excitonic insulator between the weak and strong coupling regimes in quantum limit graphite [Tunable excitonic insulator in quantum limit graphite

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, Zengwei; McDonald, R. D.; Shekhter, A.

Here, the excitonic insulator phase has long been predicted to form in proximity to a band gap opening in the underlying band structure. The character of the pairing is conjectured to crossover from weak (BCS-like) to strong coupling (BEC-like) as the underlying band structure is tuned from the metallic to the insulating side of the gap opening. Here we report the high-magnetic field phase diagram of graphite to exhibit just such a crossover. By way of comprehensive angle-resolved magnetoresistance measurements, we demonstrate that the underlying band gap opening occurs inside the magnetic field-induced phase, paving the way for a systematicmore » study of the BCS-BEC-like crossover by means of conventional condensed matter probes.« less

A crossover-crossback prospective study of dibutyl-phthalate exposure from mesalamine medications and semen quality in men with inflammatory bowel disease.

PubMed

Nassan, Feiby L; Coull, Brent A; Skakkebaek, Niels E; Williams, Michelle A; Dadd, Ramace; Mínguez-Alarcón, Lidia; Krawetz, Stephen A; Hait, Elizabeth J; Korzenik, Joshua R; Moss, Alan C; Ford, Jennifer B; Hauser, Russ

2016-10-01

Phthalates are widely used chemicals with ubiquitous exposure. Dibutyl-phthalate (DBP), a male reproductive toxicant in animals, is understudied in humans. Some mesalamine medications used to treat inflammatory bowel disease (IBD) have DBP in their coating, whereas other mesalamine formulations do not. Taking advantage of differences in mesalamine formulations, we investigated whether high-DBP exposure from mesalamine medications was associated with decreased semen parameters. 73 men with IBD taking mesalamine participated in a crossover-crossback prospective study. Men taking non-DBP containing mesalamine at baseline i.e., background exposure, crossed-over for four months to high-DBP mesalamine and then crossed-back for four months to their non-DBP mesalamine (B1HB2-arm;Background1-High-Background2) and vice versa for men taking high-DBP mesalamine at baseline (H1BH2-arm;High1-Background-High2). Men provided up to six semen samples (2: baseline, 2: crossover and 2: crossback). We estimated crossover, crossback and carryover effects using linear mixed models adjusted for abstinence time, age, season and duration on high-DBP mesalamine at baseline. Semen parameters in B1HB2-arm (26 men, 133 samples) decreased after high-DBP mesalamine exposure (crossover versus baseline), especially motility parameters, and continued to decrease further even after crossback to non-DBP mesalamine (crossback versus crossover). The cumulative carryover effect of high-DBP (crossback versus baseline) was a decrease of % total sperm motility by 7.61(CI:-13.1, -2.15), % progressive sperm motility by 4.23(CI:-8.05, -0.4) and motile sperm count by 26.0% (CI:-46.2%, 1.7%). However, H1BH2-arm (47 men, 199 samples) had no significant change during crossover or crossback. Men newly exposed to high-DBP mesalamine for four months had a cumulative reduction in several semen parameters, primarily sperm motility, that was more pronounced and statistically significant even after exposure ended for four months. Copyright © 2016 Elsevier Ltd. All rights reserved.

Viewpoint: observations on scaled average bioequivalence.

PubMed

Patterson, Scott D; Jones, Byron

2012-01-01

The two one-sided test procedure (TOST) has been used for average bioequivalence testing since 1992 and is required when marketing new formulations of an approved drug. TOST is known to require comparatively large numbers of subjects to demonstrate bioequivalence for highly variable drugs, defined as those drugs having intra-subject coefficients of variation greater than 30%. However, TOST has been shown to protect public health when multiple generic formulations enter the marketplace following patent expiration. Recently, scaled average bioequivalence (SABE) has been proposed as an alternative statistical analysis procedure for such products by multiple regulatory agencies. SABE testing requires that a three-period partial replicate cross-over or full replicate cross-over design be used. Following a brief summary of SABE analysis methods applied to existing data, we will consider three statistical ramifications of the proposed additional decision rules and the potential impact of implementation of scaled average bioequivalence in the marketplace using simulation. It is found that a constraint being applied is biased, that bias may also result from the common problem of missing data and that the SABE methods allow for much greater changes in exposure when generic-generic switching occurs in the marketplace. Copyright © 2011 John Wiley & Sons, Ltd.

Viscosity minima in binary mixtures of ionic liquids + molecular solvents.

PubMed

Tariq, M; Shimizu, K; Esperança, J M S S; Canongia Lopes, J N; Rebelo, L P N

2015-05-28

The viscosity (η) of four binary mixtures (ionic liquids plus molecular solvents, ILs+MSs) was measured in the 283.15 < T/K < 363.15 temperature range. Different IL/MS combinations were selected in such a way that the corresponding η(T) functions exhibit crossover temperatures at which both pure components present identical viscosity values. Consequently, most of the obtained mixture isotherms, η(x), exhibit clear viscosity minima in the studied T-x range. The results are interpreted using auxiliary molecular dynamics (MD) simulation data in order to correlate the observed η(T,x) trends with the interactions in each mixture, including the balance between electrostatic forces and hydrogen bonding.

Experimental investigation of cross-over jets in a rib-roughened trailing-edge cooling channel

NASA Astrophysics Data System (ADS)

Xue, Fei

Increasing the rotor inlet temperature can dramatically increase the efficiency and power output of the gas turbine engine. However, the melting point of turbine blade material limits the realistic upper bound of the rotor inlet temperature. As a result, the development of high temperature turbine blade material and advanced turbine blade cooling technology determines the future of turbine blade engine. Adding impingement jet holes and rib turbulators in the inner cooling channel of the gas turbine blades are two effective ways to enhance the cooling effects. The purpose of this study is to figure out the influence of different combinations of jet holes and rib turbulators on the heat transfer efficiency. A tabletop scale test model is used in the study to simulate the cooling cavity of trailing edge and its feed channel in a real gas turbine blade. The Dimensional Analysis Theory is used in the study to eliminate the influence of scaling. Two different crossover slots are tested with 5 different rib arrangements, and each of the test geometries is tested for 6 jet Reynolds numbers ranging from 10,000 to 36,000. The two different crossover slots are the crossover slots with 0 and 5 degree tilt angles. The four different rib arrangements are ribs with 0 degree, 45 degree, 90 degree and 135 degree angles of attack with respect to the flow direction. Furthermore, a smooth test section (no ribs) was also tested. The steady state liquid crystal thermography is used to quantify the heat transfer performance of the target areas. The variation of Nusselt number versus Reynolds number is plotted for each of the 10 geometries. Also, the variation of Nusselt number versus Reynolds number are compared for different rib angles of attack with the same crossover slot tilt angle, and between different crossover slots tilt angles with the same rib angle. The results show that, the area-weighted average Nusselt number increases monotonically with the Reynolds number; the target areas near the open end have a larger Nusselt number comparing with the ones near the close end; the 90 degree rib angle has the highest Nusselt number among the 4 rib angles of attack and the smooth wall channel; the crossover slots with 0 degree tilt angle produce higher convective heat transfer coefficients than the crossover slots with 5 degree tilt angle. Possible physical explanations for the result are offered by the author.

Genetic Algorithm for Traveling Salesman Problem with Modified Cycle Crossover Operator

PubMed Central

Mohamd Shoukry, Alaa; Gani, Showkat

2017-01-01

Genetic algorithms are evolutionary techniques used for optimization purposes according to survival of the fittest idea. These methods do not ensure optimal solutions; however, they give good approximation usually in time. The genetic algorithms are useful for NP-hard problems, especially the traveling salesman problem. The genetic algorithm depends on selection criteria, crossover, and mutation operators. To tackle the traveling salesman problem using genetic algorithms, there are various representations such as binary, path, adjacency, ordinal, and matrix representations. In this article, we propose a new crossover operator for traveling salesman problem to minimize the total distance. This approach has been linked with path representation, which is the most natural way to represent a legal tour. Computational results are also reported with some traditional path representation methods like partially mapped and order crossovers along with new cycle crossover operator for some benchmark TSPLIB instances and found improvements. PMID:29209364

Genetic Algorithm for Traveling Salesman Problem with Modified Cycle Crossover Operator.

PubMed

Hussain, Abid; Muhammad, Yousaf Shad; Nauman Sajid, M; Hussain, Ijaz; Mohamd Shoukry, Alaa; Gani, Showkat

2017-01-01

Genetic algorithms are evolutionary techniques used for optimization purposes according to survival of the fittest idea. These methods do not ensure optimal solutions; however, they give good approximation usually in time. The genetic algorithms are useful for NP-hard problems, especially the traveling salesman problem. The genetic algorithm depends on selection criteria, crossover, and mutation operators. To tackle the traveling salesman problem using genetic algorithms, there are various representations such as binary, path, adjacency, ordinal, and matrix representations. In this article, we propose a new crossover operator for traveling salesman problem to minimize the total distance. This approach has been linked with path representation, which is the most natural way to represent a legal tour. Computational results are also reported with some traditional path representation methods like partially mapped and order crossovers along with new cycle crossover operator for some benchmark TSPLIB instances and found improvements.

Technical Note: The Relationship Between Heart Rate and Energy Expenditure in Growing Crossbred Boer and Spanish Wethers

USDA-ARS?s Scientific Manuscript database

Eight Boer (75%) x Spanish (BS) and 8 Spanish (S) wethers (155 +/- 8 d of age and 19.2 +/- 2.3 kg BW, initial) were used in a replicated crossover design with a 2 x 2 factorial arrangement of treatments to determine effects of genotype, diet quality, and time of the day on energy expenditure (EE), r...

Background controlled QTL mapping in pure-line genetic populations derived from four-way crosses

PubMed Central

Zhang, S; Meng, L; Wang, J; Zhang, L

2017-01-01

Pure lines derived from multiple parents are becoming more important because of the increased genetic diversity, the possibility to conduct replicated phenotyping trials in multiple environments and potentially high mapping resolution of quantitative trait loci (QTL). In this study, we proposed a new mapping method for QTL detection in pure-line populations derived from four-way crosses, which is able to control the background genetic variation through a two-stage mapping strategy. First, orthogonal variables were created for each marker and used in an inclusive linear model, so as to completely absorb the genetic variation in the mapping population. Second, inclusive composite interval mapping approach was implemented for one-dimensional scanning, during which the inclusive linear model was employed to control the background variation. Simulation studies using different genetic models demonstrated that the new method is efficient when considering high detection power, low false discovery rate and high accuracy in estimating quantitative trait loci locations and effects. For illustration, the proposed method was applied in a reported wheat four-way recombinant inbred line population. PMID:28722705

Background controlled QTL mapping in pure-line genetic populations derived from four-way crosses.

PubMed

Zhang, S; Meng, L; Wang, J; Zhang, L

2017-10-01

Pure lines derived from multiple parents are becoming more important because of the increased genetic diversity, the possibility to conduct replicated phenotyping trials in multiple environments and potentially high mapping resolution of quantitative trait loci (QTL). In this study, we proposed a new mapping method for QTL detection in pure-line populations derived from four-way crosses, which is able to control the background genetic variation through a two-stage mapping strategy. First, orthogonal variables were created for each marker and used in an inclusive linear model, so as to completely absorb the genetic variation in the mapping population. Second, inclusive composite interval mapping approach was implemented for one-dimensional scanning, during which the inclusive linear model was employed to control the background variation. Simulation studies using different genetic models demonstrated that the new method is efficient when considering high detection power, low false discovery rate and high accuracy in estimating quantitative trait loci locations and effects. For illustration, the proposed method was applied in a reported wheat four-way recombinant inbred line population.

Mus81 and Yen1 promote reciprocal exchange during mitotic recombination to maintain genome integrity in budding yeast

PubMed Central

Ho, Chu Kwen; Mazón, Gerard; Lam, Alicia F.; Symington, Lorraine S.

2010-01-01

Holliday junction (HJ) resolution is required for segregation of chromosomes and for formation of crossovers during homologous recombination. The identity of the resolvase(s) that functions in vivo has yet to be established, although several proteins able to cut HJs in vitro have been identified as candidates in yeasts and mammals. Using an assay to detect unselected products of mitotic recombination we found a significant decrease in crossovers in the Saccharomyces cerevisiae mus81Δ mutant. Yen1 serves a back-up function responsible for resolving intermediates in mus81Δ mutants, or when conversion tracts are short. In the absence of both Mus81 and Yen1 intermediates are not channeled exclusively to non-crossover recombinants, but instead are processed by Pol32-dependent break-induced replication (BIR). The channeling of recombination from reciprocal exchange to BIR results in greatly increased spontaneous loss of heterozygosity (LOH) and chromosome mis-segregation in the mus81Δ yen1Δ mutant, typical of the genomic instability found in tumor cells. PMID:21172663

Meiosis and Maternal Aging: Insights from Aneuploid Oocytes and Trisomy Births

PubMed Central

Herbert, Mary; Kalleas, Dimitrios; Cooney, Daniel; Lamb, Mahdi; Lister, Lisa

2015-01-01

In most organisms, genome haploidization requires reciprocal DNA exchanges (crossovers) between replicated parental homologs to form bivalent chromosomes. These are resolved to their four constituent chromatids during two meiotic divisions. In female mammals, bivalents are formed during fetal life and remain intact until shortly before ovulation. Extending this period beyond ∼35 years greatly increases the risk of aneuploidy in human oocytes, resulting in a dramatic increase in infertility, miscarriage, and birth defects, most notably trisomy 21. Bivalent chromosomes are stabilized by cohesion between sister chromatids, which is mediated by the cohesin complex. In mouse oocytes, cohesin becomes depleted from chromosomes during female aging. Consistent with this, premature loss of centromeric cohesion is a major source of aneuploidy in oocytes from older women. Here, we propose a mechanistic framework to reconcile data from genetic studies on human trisomy and oocytes with recent advances in our understanding of the molecular mechanisms of chromosome segregation during meiosis in model organisms. PMID:25833844

Graded exposure in vivo in the treatment of pain-related fear: a replicated single-case experimental design in four patients with chronic low back pain.

PubMed

Vlaeyen, J W; de Jong, J; Geilen, M; Heuts, P H; van Breukelen, G

2001-02-01

The aim of this investigation was to examine the effectiveness of a graded exposure in vivo treatment with behavioural experiments as compared to usual graded activity in reducing pain-related fears, catastrophising and pain disability in chronic low back pain patients reporting substantial fear of movement/(re)injury. Included in the study were four consecutive CLBP patients who were referred for outpatient behavioural rehabilitation, and who reported substantial fear of movement/(re)injury (Tampa Scale for Kinesiophobia score>40). A replicated single-case cross-over design was used. After a no-treatment baseline measurement period, the patients were randomly assigned to one of two interventions. In intervention A, patients received the exposure first, followed by graded activity. In intervention B, the sequence of treatment modules was reversed. Sixty-three daily measures of pain-related cognitions and fears were recorded with visual analogue scales. Before and after the treatment, the following measures were taken: pain-related fear, pain catastrophising, pain control and pain disability. Using time series analysis on the daily measures of pain-related cognitions and fears, we found that improvements only occurred during the graded exposure in vivo, and not during the graded activity, irrespective of the treatment order. Analysis of the pre-post treatment differences also revealed that decreases in pain-related fear concurred with decreases in pain catastrophising and pain disability, and in half of the cases an increase in pain control. This study shows that the external validity of exposure in vivo also extends to the subgroup of chronic low back pain patients who report substantial fear of movement/(re)injury.

Between-Batch Pharmacokinetic Variability Inflates Type I Error Rate in Conventional Bioequivalence Trials: A Randomized Advair Diskus Clinical Trial.

PubMed

Burmeister Getz, E; Carroll, K J; Mielke, J; Benet, L Z; Jones, B

2017-03-01

We previously demonstrated pharmacokinetic differences among manufacturing batches of a US Food and Drug Administration (FDA)-approved dry powder inhalation product (Advair Diskus 100/50) large enough to establish between-batch bio-inequivalence. Here, we provide independent confirmation of pharmacokinetic bio-inequivalence among Advair Diskus 100/50 batches, and quantify residual and between-batch variance component magnitudes. These variance estimates are used to consider the type I error rate of the FDA's current two-way crossover design recommendation. When between-batch pharmacokinetic variability is substantial, the conventional two-way crossover design cannot accomplish the objectives of FDA's statistical bioequivalence test (i.e., cannot accurately estimate the test/reference ratio and associated confidence interval). The two-way crossover, which ignores between-batch pharmacokinetic variability, yields an artificially narrow confidence interval on the product comparison. The unavoidable consequence is type I error rate inflation, to ∼25%, when between-batch pharmacokinetic variability is nonzero. This risk of a false bioequivalence conclusion is substantially higher than asserted by regulators as acceptable consumer risk (5%). © 2016 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of The American Society for Clinical Pharmacology and Therapeutics.

High-Resolution Mapping of Two Types of Spontaneous Mitotic Gene Conversion Events in Saccharomyces cerevisiae

PubMed Central

Yim, Eunice; O’Connell, Karen E.; St. Charles, Jordan; Petes, Thomas D.

2014-01-01

Gene conversions and crossovers are related products of the repair of double-stranded DNA breaks by homologous recombination. Most previous studies of mitotic gene conversion events have been restricted to measuring conversion tracts that are <5 kb. Using a genetic assay in which the lengths of very long gene conversion tracts can be measured, we detected two types of conversions: those with a median size of ∼6 kb and those with a median size of >50 kb. The unusually long tracts are initiated at a naturally occurring recombination hotspot formed by two inverted Ty elements. We suggest that these long gene conversion events may be generated by a mechanism (break-induced replication or repair of a double-stranded DNA gap) different from the short conversion tracts that likely reflect heteroduplex formation followed by DNA mismatch repair. Both the short and long mitotic conversion tracts are considerably longer than those observed in meiosis. Since mitotic crossovers in a diploid can result in a heterozygous recessive deleterious mutation becoming homozygous, it has been suggested that the repair of DNA breaks by mitotic recombination involves gene conversion events that are unassociated with crossing over. In contrast to this prediction, we found that ∼40% of the conversion tracts are associated with crossovers. Spontaneous mitotic crossover events in yeast are frequent enough to be an important factor in genome evolution. PMID:24990991

Threshold Levels of Infant and Under-Five Mortality for Crossover between Life Expectancies at Ages Zero, One and Five in India: A Decomposition Analysis.

PubMed

Dubey, Manisha; Ram, Usha; Ram, Faujdar

2015-01-01

Under the prevailing conditions of imbalanced life table and historic gender discrimination in India, our study examines crossover between life expectancies at ages zero, one and five years for India and quantifies the relative share of infant and under-five mortality towards this crossover. We estimate threshold levels of infant and under-five mortality required for crossover using age specific death rates during 1981-2009 for 16 Indian states by sex (comprising of India's 90% population in 2011). Kitagawa decomposition equations were used to analyse relative share of infant and under-five mortality towards crossover. India experienced crossover between life expectancies at ages zero and five in 2004 for menand in 2009 for women; eleven and nine Indian states have experienced this crossover for men and women, respectively. Men usually experienced crossover four years earlier than the women. Improvements in mortality below ages five have mostly contributed towards this crossover. Life expectancy at age one exceeds that at age zero for both men and women in India except for Kerala (the only state to experience this crossover in 2000 for men and 1999 for women). For India, using life expectancy at age zero and under-five mortality rate together may be more meaningful to measure overall health of its people until the crossover. Delayed crossover for women, despite higher life expectancy at birth than for men reiterates that Indian women are still disadvantaged and hence use of life expectancies at ages zero, one and five become important for India. Greater programmatic efforts to control leading causes of death during the first month and 1-59 months in high child mortality areas can help India to attain this crossover early.

Bioequivalence evaluation of two brands of amoxicillin/clavulanic acid 250/125 mg combination tablets in healthy human volunteers: use of replicate design approach.

PubMed

Idkaidek, Nasir M; Al-Ghazawi, Ahmad; Najib, Naji M

2004-12-01

The purpose of this study was to apply a replicate design approach to a bioequivalence study of amoxicillin/clavulanic acid combination following a 250/125 mg oral dose to 23 subjects, and to compare the analysis of individual bioequivalence with average bioequivalence. This was conducted as a 2-treatment 2-sequence 4-period crossover study. Average bioequivalence was shown, while the results from the individual bioequivalence approach had no success in showing bioequivalence. In conclusion, the individual bioequivalence approach is a strong statistical tool to test for intra-subject variances and also subject-by-formulation interaction variance compared with the average bioequivalence approach. copyright (c) 2004 John Wiley & Sons, Ltd.

Interindividual Responses of Appetite to Acute Exercise: A Replicated Crossover Study.

PubMed

Goltz, Fernanda R; Thackray, Alice E; King, James A; Dorling, James L; Atkinson, Greg; Stensel, David J

2018-04-01

Acute exercise transiently suppresses appetite, which coincides with alterations in appetite-regulatory hormone concentrations. Individual variability in these responses is suspected, but replicated trials are needed to quantify them robustly. We examined the reproducibility of appetite and appetite-regulatory hormone responses to acute exercise and quantified the individual differences in responses. Fifteen healthy, recreationally active men completed two control (60-min resting) and two exercise (60-min fasted treadmill running at 70% peak oxygen uptake) conditions in randomized sequences. Perceived appetite and circulating concentrations of acylated ghrelin and total peptide YY (PYY) were measured immediately before and after the interventions. Interindividual differences were explored by correlating the two sets of response differences between exercise and control conditions. Within-participant covariate-adjusted linear mixed models were used to quantify participant-condition interactions. Compared with control, exercise suppressed mean acylated ghrelin concentrations and appetite perceptions (all ES = 0.62-1.47, P < 0.001) and elevated total PYY concentrations (ES = 1.49, P < 0.001). For all variables, the standard deviation of the change scores was substantially greater in the exercise versus control conditions. Moderate-to-large positive correlations were observed between the two sets of control-adjusted exercise responses for all variables (r = 0.54-0.82, P ≤ 0.036). After adjusting for baseline measurements, participant-condition interactions were present for all variables (P ≤ 0.053). Our replicated crossover study allowed, for the first time, the interaction between participant and acute exercise response in appetite parameters to be quantified. Even after adjustment for individual baseline measurements, participants demonstrated individual differences in perceived appetite and hormone responses to acute exercise bouts beyond any random within-subject variability over time.

In Vivo fitness associated with high virulence in a vertebrate virus is a complex trait regulated by host entry, replication, and shedding

USGS Publications Warehouse

Wargo, Andrew R.; Kurath, Gael

2011-01-01

The relationship between pathogen fitness and virulence is typically examined by quantifying only one or two pathogen fitness traits. More specifically, it is regularly assumed that within-host replication, as a precursor to transmission, is the driving force behind virulence. In reality, many traits contribute to pathogen fitness, and each trait could drive the evolution of virulence in different ways. Here, we independently quantified four viral infection cycle traits, namely, host entry, within-host replication, within-host coinfection fitness, and shedding, in vivo, in the vertebrate virus Infectious hematopoietic necrosis virus (IHNV). We examined how each of these stages of the viral infection cycle contributes to the fitness of IHNV genotypes that differ in virulence in rainbow trout. This enabled us to determine how infection cycle fitness traits are independently associated with virulence. We found that viral fitness was independently regulated by each of the traits examined, with the largest impact on fitness being provided by within-host replication. Furthermore, the more virulent of the two genotypes of IHNV we used had advantages in all of the traits quantified. Our results are thus congruent with the assumption that virulence and within-host replication are correlated but suggest that infection cycle fitness is complex and that replication is not the only trait associated with virulence.

X-Chromosome Control of Genome-Scale Recombination Rates in House Mice.

PubMed

Dumont, Beth L

2017-04-01

Sex differences in recombination are widespread in mammals, but the causes of this pattern are poorly understood. Previously, males from two interfertile subspecies of house mice, Mus musculus musculus and M. m. castaneus , were shown to exhibit a ∼30% difference in their global crossover frequencies. Much of this crossover rate divergence is explained by six autosomal loci and a large-effect locus on the X chromosome. Intriguingly, the allelic effects at this X-linked locus are transgressive, with the allele conferring increased crossover rate being transmitted by the low crossover rate M. m. castaneus parent. Despite the pronounced divergence between males, females from these subspecies exhibit similar crossover rates, raising the question of how recombination is genetically controlled in this sex. Here, I analyze publicly available genotype data from early generations of the Collaborative Cross, an eight-way panel of recombinant inbred strains, to estimate crossover frequencies in female mice with sex-chromosome genotypes of diverse subspecific origins. Consistent with the transgressive influence of the X chromosome in males, I show that females inheriting an M. m. castaneus X possess higher average crossover rates than females lacking the M. m. castaneus X chromosome. The differential inheritance of the X chromosome in males and females provides a simple genetic explanation for sex-limited evolution of this trait. Further, the presence of X-linked and autosomal crossover rate modifiers with antagonistic effects hints at an underlying genetic conflict fueled by selection for distinct crossover rate optima in males and females. Copyright © 2017 by the Genetics Society of America.

The CRH1 antagonist GSK561679 increases human fear but not anxiety as assessed by startle.

PubMed

Grillon, Christian; Hale, Elizabeth; Lieberman, Lynne; Davis, Andrew; Pine, Daniel S; Ernst, Monique

2015-03-13

Fear to predictable threat and anxiety to unpredictable threat reflect distinct processes mediated by different brain structures, the central nucleus of the amygdala and the bed nucleus of the stria terminalis (BNST), respectively. This study tested the hypothesis that the corticotropin-releasing factor (CRF1) antagonist GSK561679 differentially reduces anxiety but increases fear in humans. A total of 31 healthy females received each of four treatments: placebo, 50 mg GSK561679 (low-GSK), 400 mg GSK561679 (high-GSK), and 1 mg alprazolam in a crossover design. Participants were exposed to three conditions during each of the four treatments. The three conditions included one in which predictable aversive shocks were signaled by a cue, a second during which shocks were administered unpredictably, and a third condition without shock. Fear and anxiety were assessed using the acoustic startle reflex. High-GSK had no effect on startle potentiation during unpredictable threat (anxiety) but increased startle potentiation during the predictable condition (fear). Low-GSK did not affect startle potentiation across conditions. Consistent with previous findings, alprazolam reduced startle potentiation during unpredictable threat but not during predictable threat. The increased fear by high-GSK replicates animal findings and suggests a lift of the inhibitory effect of the BNST on the amygdala by the CRF1 antagonist.

Stochastic resonance training reduces musculoskeletal symptoms in metal manufacturing workers: a controlled preventive intervention study.

PubMed

Burger, Christian; Schade, Volker; Lindner, Christina; Radlinger, Lorenz; Elfering, Achim

2012-01-01

This study examined the effects of stochastic resonance whole-body vibration training on work-related musculoskeletal symptoms and accidents. Participants were white and blue-collar employees of a Swiss metal manufacturer (N=38), and participation was voluntary. The study was designed as a switching-replications longitudinal trial with randomized group allocation. The randomized controlled cross-over design consisted of two groups each given four weeks of exercise and no intervention during a second four-week period. Outcome was measured on a daily basis with questionnaires. Three components constituted musculoskeletal symptoms: musculoskeletal pain, related function limitations and musculoskeletal well-being. Accidents were assessed by ratings for balance and daily near-accidents. For statistical analysis, a mixed model was calculated. At the end of the training period musculoskeletal pain and related function limitation were significantly reduced, whereas musculoskeletal well-being had significantly increased. For function limitation and musculoskeletal well-being, change over time was linear. There was no effect on balance or near-accidents. Stochastic resonance whole-body vibration was found to be effective in the prevention of work-related musculoskeletal symptoms. It is well suited for the use in a work environment since it requires very little effort in terms of infrastructure, time and investment from participants.

Creating complex molecular topologies by configuring DNA four-way junctions

NASA Astrophysics Data System (ADS)

Liu, Di; Chen, Gang; Akhter, Usman; Cronin, Timothy M.; Weizmann, Yossi

2016-10-01

The realization of complex topologies at the molecular level represents a grand challenge in chemistry. This necessitates the manipulation of molecular interactions with high precision. Here we show that single-stranded DNA (ssDNA) knots and links can be created by utilizing the inherent topological properties that pertain to the DNA four-way junction, at which the two helical strands form a node and can be configured conveniently and connected for complex topological construction. Using this strategy, we produced series of ssDNA topoisomers with the same sequences. By finely designing the curvature and torsion, double-stranded DNA knots were accessed by hybridizing and ligating the complementary strands with the knotted ssDNA templates. Furthermore, we demonstrate the use of a constructed ssDNA knot both to probe the topological conversion catalysed by DNA topoisomerase and to study the DNA replication under topological constraint.

New and old ways to control meiotic recombination.

PubMed

Phadnis, Naina; Hyppa, Randy W; Smith, Gerald R

2011-10-01

The unique segregation of homologs, rather than sister chromatids, at the first meiotic division requires the formation of crossovers (COs) between homologs by meiotic recombination in most species. Crossovers do not form at random along chromosomes. Rather, their formation is carefully controlled, both at the stage of formation of DNA double-strand breaks (DSBs) that can initiate COs and during the repair of these DSBs. Here, we review control of DSB formation and two recently recognized controls of DSB repair: CO homeostasis and CO invariance. Crossover homeostasis maintains a constant number of COs per cell when the total number of DSBs in a cell is experimentally or stochastically reduced. Crossover invariance maintains a constant CO density (COs per kb of DNA) across much of the genome despite strong DSB hotspots in some intervals. These recently uncovered phenomena show that CO control is even more complex than previously suspected. Copyright © 2011 Elsevier Ltd. All rights reserved.

Homing by path integration when a locomotion trajectory crosses itself.

PubMed

Yamamoto, Naohide; Meléndez, Jayleen A; Menzies, Derek T

2014-01-01

Path integration is a process with which navigators derive their current position and orientation by integrating self-motion signals along a locomotion trajectory. It has been suggested that path integration becomes disproportionately erroneous when the trajectory crosses itself. However, there is a possibility that this previous finding was confounded by effects of the length of a traveled path and the amount of turns experienced along the path, two factors that are known to affect path integration performance. The present study was designed to investigate whether the crossover of a locomotion trajectory truly increases errors of path integration. In an experiment, blindfolded human navigators were guided along four paths that varied in their lengths and turns, and attempted to walk directly back to the beginning of the paths. Only one of the four paths contained a crossover. Results showed that errors yielded from the path containing the crossover were not always larger than those observed in other paths, and the errors were attributed solely to the effects of longer path lengths or greater degrees of turns. These results demonstrated that path crossover does not always cause significant disruption in path integration processes. Implications of the present findings for models of path integration are discussed.

Meiosis gene inventory of four ciliates reveals the prevalence of a synaptonemal complex-independent crossover pathway.

PubMed

Chi, Jingyun; Mahé, Frédéric; Loidl, Josef; Logsdon, John; Dunthorn, Micah

2014-03-01

To establish which meiosis genes are present in ciliates, and to look for clues as to which recombination pathways may be treaded by them, four genomes were inventoried for 11 meiosis-specific and 40 meiosis-related genes. We found that the set of meiosis genes shared by Tetrahymena thermophila, Paramecium tetraurelia, Ichthyophthirius multifiliis, and Oxytricha trifallax is consistent with the prevalence of a Mus81-dependent class II crossover pathway that is considered secondary in most model eukaryotes. There is little evidence for a canonical class I crossover pathway that requires the formation of a synaptonemal complex (SC). This gene inventory suggests that meiotic processes in ciliates largely depend on mitotic repair proteins for executing meiotic recombination. We propose that class I crossovers and SCs were reduced sometime during the evolution of ciliates. Consistent with this reduction, we provide microscopic evidence for the presence only of degenerate SCs in Stylonychia mytilus. In addition, lower nonsynonymous to synonymous mutation rates of some of the meiosis genes suggest that, in contrast to most other nuclear genes analyzed so far, meiosis genes in ciliates are largely evolving at a slower rate than those genes in fungi and animals.

Test equality in binary data for a 4 × 4 crossover trial under a Latin-square design.

PubMed

Lui, Kung-Jong; Chang, Kuang-Chao

2016-10-15

When there are four or more treatments under comparison, the use of a crossover design with a complete set of treatment-receipt sequences in binary data is of limited use because of too many treatment-receipt sequences. Thus, we may consider use of a 4 × 4 Latin square to reduce the number of treatment-receipt sequences when comparing three experimental treatments with a control treatment. Under a distribution-free random effects logistic regression model, we develop simple procedures for testing non-equality between any of the three experimental treatments and the control treatment in a crossover trial with dichotomous responses. We further derive interval estimators in closed forms for the relative effect between treatments. To evaluate the performance of these test procedures and interval estimators, we employ Monte Carlo simulation. We use the data taken from a crossover trial using a 4 × 4 Latin-square design for studying four-treatments to illustrate the use of test procedures and interval estimators developed here. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Correlation between Fragility and the Arrhenius Crossover Phenomenon in Metallic, Molecular, and Network Liquids.

PubMed

Jaiswal, Abhishek; Egami, Takeshi; Kelton, K F; Schweizer, Kenneth S; Zhang, Yang

2016-11-11

We report the observation of a distinct correlation between the kinetic fragility index m and the reduced Arrhenius crossover temperature θ_{A}=T_{A}/T_{g} in various glass-forming liquids, identifying three distinguishable groups. In particular, for 11 glass-forming metallic liquids, we universally observe a crossover in the mean diffusion coefficient from high-temperature Arrhenius to low-temperature super-Arrhenius behavior at approximately θ_{A}≈2 which is in the stable liquid phases. In contrast, for fragile molecular liquids, this crossover occurs at much lower θ_{A}≈1.4 and usually in their supercooled states. The θ_{A} values for strong network liquids spans a wide range higher than 2. Intriguingly, the high-temperature activation barrier E_{∞} is universally found to be ∼11k_{B}T_{g} and uncorrelated with the fragility or the reduced crossover temperature θ_{A} for metallic and molecular liquids. These observations provide a way to estimate the low-temperature glassy characteristics (T_{g} and m) from the high-temperature liquid quantities (E_{∞} and θ_{A}).

Correlation between Fragility and the Arrhenius Crossover Phenomenon in Metallic, Molecular, and Network Liquids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jaiswal, Abhishek; Egami, Takeshi; Kelton, K. F.

2016-11-10

In this paper, we report the observation of a distinct correlation between the kinetic fragility index m and the reduced Arrhenius crossover temperature θ A = T A/T g in various glass-forming liquids, identifying three distinguishable groups. In particular, for 11 glass-forming metallic liquids, we universally observe a crossover in the mean diffusion coefficient from high-temperature Arrhenius to low-temperature super-Arrhenius behavior at approximately θ A ≈ 2 which is in the stable liquid phases. In contrast, for fragile molecular liquids, this crossover occurs at much lower θ A ≈ 1.4 and usually in their supercooled states. The θ A valuesmore » for strong network liquids spans a wide range higher than 2. Intriguingly, the high-temperature activation barrier E ∞ is universally found to be ~11k BT g and uncorrelated with the fragility or the reduced crossover temperature θ A for metallic and molecular liquids. Finally, these observations provide a way to estimate the low-temperature glassy characteristics (T g and m) from the high-temperature liquid quantities (E ∞ and θ A).« less

Bioequivalence of generic alendronate sodium tablets (70 mg) to Fosamax® tablets (70 mg) in fasting, healthy volunteers: a randomized, open-label, three-way, reference-replicated crossover study

PubMed Central

Zhang, Yifan; Chen, Xiaoyan; Tang, Yunbiao; Lu, Youming; Guo, Lixia; Zhong, Dafang

2017-01-01

Purpose The aim of this study was to evaluate the bioequivalence of a generic product 70 mg alendronate sodium tablets with the reference product Fosamax® 70 mg tablet. Materials and methods A single-center, open-label, randomized, three-period, three-sequence, reference-replicated crossover study was performed in 36 healthy Chinese male volunteers under fasting conditions. In each study period, the volunteers received a single oral dose of the generic or reference product (70 mg). Blood samples were collected at pre-dose and up to 8 h after administration. The bioequivalence of the generic product to the reference product was assessed using the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) reference-scaled average bioequivalence (RSABE) methods. Results The average maximum concentrations (Cmax) of alendronic acid were 64.78±43.76, 56.62±31.95, and 60.15±37.12 ng/mL after the single dose of the generic product and the first and second doses of the reference product, respectively. The areas under the plasma concentration–time curves from time 0 to the last timepoint (AUC0–t) were 150.36±82.90, 148.15±85.97, and 167.11±110.87 h⋅ng/mL, respectively. Reference scaling was used because the within-subject standard deviations of the reference product (sWR) for Cmax and AUC0–t were all higher than the cutoff value of 0.294. The 95% upper confidence bounds were −0.16 and −0.17 for Cmax and AUC0–t, respectively, and the point estimates for the generic/reference product ratio were 1.08 and 1.00, which satisfied the RSABE acceptance criteria of the FDA. The 90% CIs for Cmax and AUC0–t were 90.35%–129.04% and 85.31%–117.15%, respectively, which were within the limits of the EMA for the bioequivalence of 69.84%–143.19% and 80.00%–125.00%. Conclusion The generic product was bioequivalent to the reference product in terms of the rate and extent of alendronate absorption after a single 70 mg oral dose under fasting conditions. PMID:28744102

The Fanconi anemia ortholog FANCM ensures ordered homologous recombination in both somatic and meiotic cells in Arabidopsis.

PubMed

Knoll, Alexander; Higgins, James D; Seeliger, Katharina; Reha, Sarah J; Dangel, Natalie J; Bauknecht, Markus; Schröpfer, Susan; Franklin, F Christopher H; Puchta, Holger

2012-04-01

The human hereditary disease Fanconi anemia leads to severe symptoms, including developmental defects and breakdown of the hematopoietic system. It is caused by single mutations in the FANC genes, one of which encodes the DNA translocase FANCM (for Fanconi anemia complementation group M), which is required for the repair of DNA interstrand cross-links to ensure replication progression. We identified a homolog of FANCM in Arabidopsis thaliana that is not directly involved in the repair of DNA lesions but suppresses spontaneous somatic homologous recombination via a RecQ helicase (At-RECQ4A)-independent pathway. In addition, it is required for double-strand break-induced homologous recombination. The fertility of At-fancm mutant plants is compromised. Evidence suggests that during meiosis At-FANCM acts as antirecombinase to suppress ectopic recombination-dependent chromosome interactions, but this activity is antagonized by the ZMM pathway to enable the formation of interference-sensitive crossovers and chromosome synapsis. Surprisingly, mutation of At-FANCM overcomes the sterility phenotype of an At-MutS homolog4 mutant by apparently rescuing a proportion of crossover-designated recombination intermediates via a route that is likely At-MMS and UV sensitive81 dependent. However, this is insufficient to ensure the formation of an obligate crossover. Thus, At-FANCM is not only a safeguard for genome stability in somatic cells but is an important factor in the control of meiotic crossover formation.

Threshold Levels of Infant and Under-Five Mortality for Crossover between Life Expectancies at Ages Zero, One and Five in India: A Decomposition Analysis

PubMed Central

Dubey, Manisha

2015-01-01

Objectives Under the prevailing conditions of imbalanced life table and historic gender discrimination in India, our study examines crossover between life expectancies at ages zero, one and five years for India and quantifies the relative share of infant and under-five mortality towards this crossover. Methods We estimate threshold levels of infant and under-five mortality required for crossover using age specific death rates during 1981–2009 for 16 Indian states by sex (comprising of India’s 90% population in 2011). Kitagawa decomposition equations were used to analyse relative share of infant and under-five mortality towards crossover. Findings India experienced crossover between life expectancies at ages zero and five in 2004 for menand in 2009 for women; eleven and nine Indian states have experienced this crossover for men and women, respectively. Men usually experienced crossover four years earlier than the women. Improvements in mortality below ages five have mostly contributed towards this crossover. Life expectancy at age one exceeds that at age zero for both men and women in India except for Kerala (the only state to experience this crossover in 2000 for men and 1999 for women). Conclusions For India, using life expectancy at age zero and under-five mortality rate together may be more meaningful to measure overall health of its people until the crossover. Delayed crossover for women, despite higher life expectancy at birth than for men reiterates that Indian women are still disadvantaged and hence use of life expectancies at ages zero, one and five become important for India. Greater programmatic efforts to control leading causes of death during the first month and 1–59 months in high child mortality areas can help India to attain this crossover early. PMID:26683617

Bioequivalence of two lansoprazole delayed release capsules 30 mg in healthy male volunteers under fasting, fed and fasting-applesauce conditions: a partial replicate crossover study design to estimate the pharmacokinetics of highly variable drugs.

PubMed

Thota, S; Khan, S M; Tippabhotla, S K; Battula, R; Gadiko, C; Vobalaboina, V

2013-11-01

An open-label, 2-treatment, 3-sequence, 3-period, single-dose, partial replicate crossover studies under fasting (n=48), fed (n=60) and fasting-applesauce (n=48) (sprinkled on one table spoonful of applesauce) modalities were conducted in healthy adult male volunteers to evaluate bioequivalence between 2 formulations of lansoprazole delayed release capsules 30 mg. In all the 3 studies, as per randomization, either test or reference formulations were administered in a crossover manner with a required washout period of at least 7 days. Blood samples were collected adequately (0-24 h) to determine lansoprazole plasma concentrations using a validated LC-MS/MS analytical method. To characterize the pharmacokinetic parameters (Cmax, AUC0-t, AUC0-∞, Tmax, Kel and T1/2) of lansoprazole, non-compartmental analysis and ANOVA was applied on ln-transformed values. The bioequivalence was tested based on within-subject variability of the reference formulation. In fasting and fed studies (within-subject variability>30%) bioequivalence was evaluated with scaled average bioequivalence, hence for the pharmacokinetic parameters Cmax, AUC0-t and AUC0-∞, the 95% upper confidence bound for (μT-μR)2-θσ2 WR was ≤0, and the point estimates (test-to-reference ratio) were within the regulatory acceptance limit 80.00-125.00%. In fasting-applesauce study (within-subject variability<30%) bioequivalence was evaluated with average bioequivalence, the 90% CI of ln-transformed data of Cmax, AUC0-t and AUC0-∞ were within the regulatory acceptance limit 80.00-125.00%. Based on these aforesaid statistical inferences, it was concluded that the test formulation is bioequivalent to reference formulation. © Georg Thieme Verlag KG Stuttgart · New York.

Challenging Fiction: Exploring Meaning-Making Processes in the Crossover between Social Media and Drama in Education

ERIC Educational Resources Information Center

Knudsen, Kristian Nødtvedt

2018-01-01

The aim of this study was to explore how meaning-making activity can be expressed and shaped in the crossover between drama in education and social media. This study concerns the use of empirical material from an educational drama project called #iLive, which was designed and implemented, on four different occasions with a total of 89 students…

Randomized controlled trial of the Valencia model of waking hypnosis plus CBT for pain, fatigue, and sleep management in patients with cancer and cancer survivors.

PubMed

Mendoza, M E; Capafons, A; Gralow, J R; Syrjala, K L; Suárez-Rodríguez, J M; Fann, J R; Jensen, M P

2017-11-01

This study evaluated the efficacy of an intervention combining the Valencia model of waking hypnosis with cognitive-behavioral therapy (VMWH-CBT) in managing cancer-related pain, fatigue, and sleep problems in individuals with active cancer or who were post-treatment survivors. We hypothesized that four sessions of VMWH-CBT would result in greater improvement in participants' symptoms than four sessions of an education control intervention. Additionally, we examined the effects on several secondary outcome domains that are associated with increases in these symptoms (depression, pain interference, pain catastrophizing, and cancer treatment distress). The study design was a randomized controlled crossover clinical trial comparing the VMWH-CBT intervention with education control. Participants (N = 44) received four sessions of both treatments, in a counterbalanced order (n = 22 per order condition). Participants were 89% female (N = 39) with mean age of 61 years (SD = 12.2). They reported significantly greater improvement after receiving the active treatment relative to the control condition in all the outcome measures. Treatment gains were maintained at 3-month follow-up. This study supports the beneficial effects of the VMWH-CBT intervention relative to a control condition and that treatment gains remain stable. VMWH-CBT-trained clinicians should be accessible for managing symptoms both during and after cancer treatment, though the findings need to be replicated in larger samples of cancer survivors. Copyright © 2016 John Wiley & Sons, Ltd.

Role of the hydrophilic channels of simian virus 40 T-antigen helicase in DNA replication.

PubMed

Wang, Weiping; Manna, David; Simmons, Daniel T

2007-05-01

The simian virus 40 (SV40) hexameric helicase consists of a central channel and six hydrophilic channels located between adjacent large tier domains within each hexamer. To study the function of the hydrophilic channels in SV40 DNA replication, a series of single-point substitutions were introduced at sites not directly involved in protein-protein contacts. The mutants were characterized biochemically in various ways. All mutants oligomerized normally in the absence of DNA. Interestingly, 8 of the 10 mutants failed to unwind an origin-containing DNA fragment and nine of them were totally unable to support SV40 DNA replication in vitro. The mutants fell into four classes based on their biochemical properties. Class A mutants bound DNA normally and had normal ATPase and helicase activities but failed to unwind origin DNA and support SV40 DNA replication. Class B mutants were compromised in single-stranded DNA and origin DNA binding at low protein concentrations. They were defective in helicase activity and unwinding of the origin and in supporting DNA replication. Class C and D mutants possessed higher-than-normal single-stranded DNA binding activity at low protein concentrations. The class C mutants failed to separate origin DNA and support DNA replication. The class D mutants unwound origin DNA normally but were compromised in their ability to support DNA replication. Taken together, these results suggest that the hydrophilic channels have an active role in the unwinding of SV40 DNA from the origin and the placement of the resulting single strands within the helicase.

Improvement and Optimization of Two Engineered Phage Resistance Mechanisms in Lactococcus lactis

PubMed Central

McGrath, Stephen; Fitzgerald, Gerald F.; van Sinderen, Douwe

2001-01-01

Homologous replication module genes were identified for four P335 type phages. DNA sequence analysis revealed that all four phages exhibited more than 90% DNA homology for at least two genes, designated rep2009 and orf17. One of these genes, rep2009, codes for a putative replisome organizer protein and contains an assumed origin of phage DNA replication (ori2009), which was identical for all four phages. DNA fragments representing the ori2009 sequence confer a phage-encoded resistance (Per) phenotype on lactococcal hosts when they are supplied on a high-copy-number vector. Furthermore, cloning multiple copies of the ori2009 sequence was found to increase the effectiveness of the Per phenotype conferred. A number of antisense plasmids targeting specific genes of the replication module were constructed. Two separate plasmids targeting rep2009 and orf17 were found to efficiently inhibit proliferation of all four phages by interfering with intracellular phage DNA replication. These results represent two highly effective strategies for inhibiting bacteriophage proliferation, and they also identify a novel gene, orf17, which appears to be important for phage DNA replication. Furthermore, these results indicate that although the actual mechanisms of DNA replication are very similar, if not identical, for all four phages, expression of the replication genes is significantly different in each case. PMID:11157223

Antigenic change in feline calicivirus during persistent infection.

PubMed Central

Johnson, R P

1992-01-01

To determine if antigenic variation occurred during persistent infection of cats with feline caliciviruses (FCV), nine persistent (progeny) isolates from nine different carrier cats were compared antigenically to the original infecting parent strain, FCV 255, by two-way cross-neutralization tests with rabbit antisera. Five of the nine progeny viruses isolated 35 to 169 days after initial infection were antigenically different from the parent strain. These five isolates represented four distinct antigenic phenotypes. The emergence of four distinctly different antigenic variants from a single parent strain indicates that FCV, like many other RNA viruses, exhibits considerable antigenic heterogeneity during replication in its natural host, and supports the hypothesis that antigenic variation contributes to chronic FCV infection. PMID:1335833

Case-crossover design and its implementation in R

PubMed Central

2016-01-01

Case-crossover design is a variation of case-control design that it employs persons’ history periods as controls. Case-crossover design can be viewed as the hybrid of case-control study and crossover design. Characteristic confounding that is constant within one person can be well controlled with this method. The relative risk and odds ratio, as well as their 95% confidence intervals (CIs), can be estimated using Cochran-Mantel-Haenszel method. R codes for the calculation are provided in the main text. Readers may adapt these codes to their own task. Conditional logistic regression model is another way to estimate odds ratio of the exposure. Furthermore, it allows for incorporation of other time-varying covariates that are not constant within subjects. The model fitting per se is not technically difficult because there is well developed statistical package. However, it is challenging to convert original dataset obtained from case report form to that suitable to be passed to clogit() function. R code for this task is provided and explained in the text. PMID:27761445

A six-month crossover chemoprevention clinical trial of tea in smokers and non-smokers: methodological issues in a feasibility study

PubMed Central

2012-01-01

Background Chemoprevention crossover trials of tea can be more efficient than parallel designs but the attrition and compliance rates with such trials are unknown. Methods Attrition (dropouts) and compliance with treatment were assessed in a 25-week randomized, placebo controlled, crossover, feasibility clinical trial of four tea treatments to investigate the effect of tea on oral cancer biomarkers. Each treatment lasted 4 weeks with 2 weeks of washout in between. Participants were 32 smokers and 33 non-smokers without any evidence of premalignant oral lesions. The interventions consisted of packets of green tea, black tea, caffeinated water, or placebo. Participants were assigned to each treatment for four weeks, and were instructed to drink five packets per day while on the treatment. Dropout from the trial and compliance (consumption of ≥ 85% of the prescribed treatment packets) are the main outcome measures reported. Results There was a high rate of dropout (51%) from the study, and the rates were significantly higher among smokers (64%) than non-smokers (36%). Among participants who completed the study the rate of compliance was 72%. The highest rates of dropouts occurred between the first and second treatment visits in both smokers (38% dropout) and non-smokers (18% dropout). Throughout the study smokers were more likely to dropout than non-smokers. Black tea treatment was associated with the highest rates of dropout among smokers (37%), but was associated with the lowest rate of dropout among non-smokers (4%). Conclusions In a study conducted to test the feasibility of a four-treatment crossover tea trial, a high rate of dropout among smokers and non-smokers was observed. Multi-arm crossover tea trials might pose a higher burden on participants and research is needed to improve adherence and treatment compliance in such trials. Trial registration number ISRCTN70410203 PMID:22800470

Ultrastable light sources in the crossover from superradiance to lasing

NASA Astrophysics Data System (ADS)

Xu, Minghui; Tieri, David; Holland, Murray

2013-05-01

We theoretically investigate the crossover from steady-state superradiance to optical lasing. An exact solution of the quantum master equation is difficult to obtain due to the exponential scaling of the Hilbert space dimension with system size. However, since Lindblad operators in the master equation are invariant under SU(4) transformations, we are able to reduce the exponential scaling of the problem to cubic by expanding the density matrix in terms of an SU(4) basis. In this way, we obtain exact quantum solutions of the superradiance-laser crossover. We use this theory to investigate the potential for ultrastable lasers in the millihertz linewidth regime, and find the behavior of important observables, such as intensity, linewidth, spin-correlation, and entanglement. This work was supported by the DARPA QUASAR program and NSF.

A novel artificial fish swarm algorithm for solving large-scale reliability-redundancy application problem.

PubMed

He, Qiang; Hu, Xiangtao; Ren, Hong; Zhang, Hongqi

2015-11-01

A novel artificial fish swarm algorithm (NAFSA) is proposed for solving large-scale reliability-redundancy allocation problem (RAP). In NAFSA, the social behaviors of fish swarm are classified in three ways: foraging behavior, reproductive behavior, and random behavior. The foraging behavior designs two position-updating strategies. And, the selection and crossover operators are applied to define the reproductive ability of an artificial fish. For the random behavior, which is essentially a mutation strategy, the basic cloud generator is used as the mutation operator. Finally, numerical results of four benchmark problems and a large-scale RAP are reported and compared. NAFSA shows good performance in terms of computational accuracy and computational efficiency for large scale RAP. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.

System-wide Analysis of SUMOylation Dynamics in Response to Replication Stress Reveals Novel Small Ubiquitin-like Modified Target Proteins and Acceptor Lysines Relevant for Genome Stability*

PubMed Central

Xiao, Zhenyu; Chang, Jer-Gung; Hendriks, Ivo A.; Sigurðsson, Jón Otti; Olsen, Jesper V.; Vertegaal, Alfred C.O.

2015-01-01

Genotoxic agents can cause replication fork stalling in dividing cells because of DNA lesions, eventually leading to replication fork collapse when the damage is not repaired. Small Ubiquitin-like Modifiers (SUMOs) are known to counteract replication stress, nevertheless, only a small number of relevant SUMO target proteins are known. To address this, we have purified and identified SUMO-2 target proteins regulated by replication stress in human cells. The developed methodology enabled single step purification of His10-SUMO-2 conjugates under denaturing conditions with high yield and high purity. Following statistical analysis on five biological replicates, a total of 566 SUMO-2 targets were identified. After 2 h of hydroxyurea treatment, 10 proteins were up-regulated for SUMOylation and two proteins were down-regulated for SUMOylation, whereas after 24 h, 35 proteins were up-regulated for SUMOylation, and 13 proteins were down-regulated for SUMOylation. A site-specific approach was used to map over 1000 SUMO-2 acceptor lysines in target proteins. The methodology is generic and is widely applicable in the ubiquitin field. A large subset of these identified proteins function in one network that consists of interacting replication factors, transcriptional regulators, DNA damage response factors including MDC1, ATR-interacting protein ATRIP, the Bloom syndrome protein and the BLM-binding partner RMI1, the crossover junction endonuclease EME1, BRCA1, and CHAF1A. Furthermore, centromeric proteins and signal transducers were dynamically regulated by SUMOylation upon replication stress. Our results uncover a comprehensive network of SUMO target proteins dealing with replication damage and provide a framework for detailed understanding of the role of SUMOylation to counteract replication stress. Ultimately, our study reveals how a post-translational modification is able to orchestrate a large variety of different proteins to integrate different nuclear processes with the aim of dealing with the induced DNA damage. PMID:25755297

Hysteretic Four-Step Spin Crossover within a Three-Dimensional Porous Hofmann-like Material

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clements, John E.; Price, Jason R.; Neville, Suzanne M.

Materials that display multiple stepped spin crossover (SCO) transitions with accompanying hysteresis present the opportunity for ternary, quaternary, and quinary electronic switching and data storage but are rare in existence. Herein, we present the first report of a four-step hysteretic SCO framework. Single-crystal structure analysis of a porous 3D Hofmann-like material showed long-range ordering of spin states: HS, HS 0.67LS 0.33, HS 0.5LS 0.5, HS 0.33LS 0.67, and LS. These detailed structural studies provide insight into how multistep SCO materials can be rationally designed through control of host–host and host–guest interactions.

The CRH1 Antagonist GSK561679 Increases Human Fear But Not Anxiety as Assessed by Startle

PubMed Central

Grillon, Christian; Hale, Elizabeth; Lieberman, Lynne; Davis, Andrew; Pine, Daniel S; Ernst, Monique

2015-01-01

Fear to predictable threat and anxiety to unpredictable threat reflect distinct processes mediated by different brain structures, the central nucleus of the amygdala and the bed nucleus of the stria terminalis (BNST), respectively. This study tested the hypothesis that the corticotropin-releasing factor (CRF1) antagonist GSK561679 differentially reduces anxiety but increases fear in humans. A total of 31 healthy females received each of four treatments: placebo, 50 mg GSK561679 (low-GSK), 400 mg GSK561679 (high-GSK), and 1 mg alprazolam in a crossover design. Participants were exposed to three conditions during each of the four treatments. The three conditions included one in which predictable aversive shocks were signaled by a cue, a second during which shocks were administered unpredictably, and a third condition without shock. Fear and anxiety were assessed using the acoustic startle reflex. High-GSK had no effect on startle potentiation during unpredictable threat (anxiety) but increased startle potentiation during the predictable condition (fear). Low-GSK did not affect startle potentiation across conditions. Consistent with previous findings, alprazolam reduced startle potentiation during unpredictable threat but not during predictable threat. The increased fear by high-GSK replicates animal findings and suggests a lift of the inhibitory effect of the BNST on the amygdala by the CRF1 antagonist. PMID:25430779

Gastric acid control with esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole: a five-way crossover study.

PubMed

Miner, Philip; Katz, Philip O; Chen, Yusong; Sostek, Mark

2003-12-01

Proton pump inhibitors owe their clinical efficacy to their ability to suppress gastric acid production. The objective of this study was to evaluate and compare intragastric pH following standard doses of esomeprazole, lansoprazole, omeprazole, pantoprazole and rabeprazole. This randomized, open-label, comparative five-way crossover study evaluated the 24-h intragastric pH profile of oral esomeprazole 40 mg, lansoprazole 30 mg, omeprazole 20 mg, pantoprazole 40 mg, and rabeprazole 20 mg once daily in 34 Helicobacter pylori-negative patients aged 18-60 yr with symptoms of gastroesophageal reflux disease. Patients were randomly assigned to one of five treatment sequences and study drug was taken on 5 consecutive mornings 30 minutes prior to a standardized breakfast. A washout period of at least 10 days separated each treatment phase. Thirty-four patients provided evaluable data for all five comparators. The mean number of hours of evaluable pH data was > or =23.75 hours. On day 5, intragastric pH was maintained above 4.0 for a mean of 14.0 h with esomeprazole, 12.1 h with rabeprazole, 11.8 h with omeprazole, 11.5 h with lansoprazole, and 10.1 h with pantoprazole (p < or = 0.001 for differences between esomeprazole and all other comparators). Esomeprazole also provided a significantly higher percentage of patients with an intragastric pH greater than 4.0 for more than 12 h relative to the other proton pump inhibitors (p < 0.05). The frequency of adverse events was similar between treatment groups. Esomeprazole at the standard dose of 40 mg once daily provided more effective control of gastric acid at steady state than standard doses of lansoprazole, omeprazole, pantoprazole, and rabeprazole in patients with symptoms of gastroesophageal reflux disease.

Laying a Solid Foundation: Strategies for Effective Program Replication

ERIC Educational Resources Information Center

Summerville, Geri

2009-01-01

The replication of proven social programs is a cost-effective and efficient way to achieve large-scale, positive social change. Yet there has been little guidance available about how to approach program replication and limited development of systems--at local, state or federal levels--to support replication efforts. "Laying a Solid Foundation:…

Mitochondrial RNA polymerase is an essential enzyme in erythrocytic stages of Plasmodium falciparum.

PubMed

Ke, Hangjun; Morrisey, Joanne M; Ganesan, Suresh M; Mather, Michael W; Vaidya, Akhil B

2012-09-01

We have shown that transgenic Plasmodium falciparum parasites expressing the yeast DHODH (dihydroorotate dehydrogenase) are independent of the mtETC (mitochondrial electron transport chain), suggesting that they might not need the mitochondrial genome (mtDNA), since it only encodes three protein subunits belonging to the mtETC and fragmentary ribosomal RNA molecules. Disrupting the mitochondrial RNA polymerase (mtRNAP), which is critical for mtDNA replication and transcription, might then cause the generation of a ρ(0) parasite line lacking mtDNA. We made multiple attempts to disrupt the mtRNAP gene by double crossover recombination methods in parasite lines expressing yDHODH either episomally or integrated in the genome, but were unable to produce the desired knockout. We verified that the mtRNAP gene was accessible to recombination by successfully integrating a triple HA tag at the 3' end via single cross-over recombination. These studies suggest that mtRNAP is essential even in mtETC-independent P. falciparum parasites. Copyright © 2012 Elsevier B.V. All rights reserved.

Minimum length of the adaptation and collection period in digestibility trials with sheep fed ad libitum only forage or forage plus concentrate.

PubMed

Farenzena, R; Kozloski, G V; Gindri, M; Stefanello, S

2017-10-01

Two in vivo digestibility trials with sheep were conducted to identify the minimum period length of feeding a new diet to obtain reproducible values of nutritional variables onward and the minimum length of collection period as to obtain maximal precision for each variable. Trial 1 was conducted with ten Polwarth male sheep (34 ± 5 kg body weight (BW)) throughout three 21-day periods, in a completely randomized two-way crossover design. The animals were divided into two groups (Group A and B, n = 5 per group) which were fed ad libitum with a sequence of the following diets throughout the periods: Group A: hay - hay plus concentrate - hay; Group B: hay plus concentrate - hay - hay plus concentrate. The concentrate was included in a proportion of 0.33 of the total diet. The intake, and the faecal and urinary excretion were measured daily throughout the experiment. For evaluating rumen fermentation variables, in Trial 2 four Santa Inês male sheep (65 ± 5 kg BW) fitted with ruminal cannula were used. The animals were randomly divided into two groups (n = 2 per group), and the trial was conducted through four 21 days experimental period, in a three-way crossover design, using experimental diets and feeding management similar to Trial 1. The results indicated that, even though no clear or consistent steady-state condition was identified for rumen fermentation or urinary excretion variables, the adaptation period for measuring OM digestibility in in vivo trials with sheep fed ad libitum where the diet shifts from one of only hay to another containing concentrate, or vice-versa, should be at least 12 days long. Moreover, although no precision improvement was obtained by increasing the collection period above 1 day for measuring OM digestibility, the minimal length of collection period should be 4 days for measuring faecal excretion variables and 7 days for measuring urinary excretion variables. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

Low-dose oxytocin delivered intranasally with Breath Powered device affects social-cognitive behavior: a randomized four-way crossover trial with nasal cavity dimension assessment

PubMed Central

Quintana, D S; Westlye, L T; Rustan, Ø G; Tesli, N; Poppy, C L; Smevik, H; Tesli, M; Røine, M; Mahmoud, R A; Smerud, K T; Djupesland, P G; Andreassen, O A

2015-01-01

Despite the promise of intranasal oxytocin (OT) for modulating social behavior, recent work has provided mixed results. This may relate to suboptimal drug deposition achieved with conventional nasal sprays, inter-individual differences in nasal physiology and a poor understanding of how intranasal OT is delivered to the brain in humans. Delivering OT using a novel ‘Breath Powered' nasal device previously shown to enhance deposition in intranasal sites targeted for nose-to-brain transport, we evaluated dose-dependent effects on social cognition, compared response with intravenous (IV) administration of OT, and assessed nasal cavity dimensions using acoustic rhinometry. We adopted a randomized, double-blind, double-dummy, crossover design, with 16 healthy male adults completing four single-dose treatments (intranasal 8 IU (international units) or 24 IU OT, 1 IU OT IV and placebo). The primary outcome was social cognition measured by emotional ratings of facial images. Secondary outcomes included the pharmacokinetics of OT, vasopressin and cortisol in blood and the association between nasal cavity dimensions and emotional ratings. Despite the fact that all the treatments produced similar plasma OT increases compared with placebo, there was a main effect of treatment on anger ratings of emotionally ambiguous faces. Pairwise comparisons revealed decreased ratings after 8 IU OT in comparison to both placebo and 24 IU OT. In addition, there was an inverse relationship between nasal valve dimensions and anger ratings of ambiguous faces after 8-IU OT treatment. These findings provide support for a direct nose-to-brain effect, independent of blood absorption, of low-dose OT delivered from a Breath Powered device. PMID:26171983

Low-dose oxytocin delivered intranasally with Breath Powered device affects social-cognitive behavior: a randomized four-way crossover trial with nasal cavity dimension assessment.

PubMed

Quintana, D S; Westlye, L T; Rustan, Ø G; Tesli, N; Poppy, C L; Smevik, H; Tesli, M; Røine, M; Mahmoud, R A; Smerud, K T; Djupesland, P G; Andreassen, O A

2015-07-14

Despite the promise of intranasal oxytocin (OT) for modulating social behavior, recent work has provided mixed results. This may relate to suboptimal drug deposition achieved with conventional nasal sprays, inter-individual differences in nasal physiology and a poor understanding of how intranasal OT is delivered to the brain in humans. Delivering OT using a novel 'Breath Powered' nasal device previously shown to enhance deposition in intranasal sites targeted for nose-to-brain transport, we evaluated dose-dependent effects on social cognition, compared response with intravenous (IV) administration of OT, and assessed nasal cavity dimensions using acoustic rhinometry. We adopted a randomized, double-blind, double-dummy, crossover design, with 16 healthy male adults completing four single-dose treatments (intranasal 8 IU (international units) or 24 IU OT, 1 IU OT IV and placebo). The primary outcome was social cognition measured by emotional ratings of facial images. Secondary outcomes included the pharmacokinetics of OT, vasopressin and cortisol in blood and the association between nasal cavity dimensions and emotional ratings. Despite the fact that all the treatments produced similar plasma OT increases compared with placebo, there was a main effect of treatment on anger ratings of emotionally ambiguous faces. Pairwise comparisons revealed decreased ratings after 8 IU OT in comparison to both placebo and 24 IU OT. In addition, there was an inverse relationship between nasal valve dimensions and anger ratings of ambiguous faces after 8-IU OT treatment. These findings provide support for a direct nose-to-brain effect, independent of blood absorption, of low-dose OT delivered from a Breath Powered device.

The Frenkel Line: a direct experimental evidence for the new thermodynamic boundary

DOE PAGES

Bolmatov, Dima; Zhernenkov, Mikhail; Zav’yalov, Dmitry; ...

2015-11-05

We report that supercritical fluids play a significant role in elucidating fundamental aspects of liquid matter under extreme conditions. They have been extensively studied at pressures and temperatures relevant to various industrial applications. However, much less is known about the structural behaviour of supercritical fluids and no structural crossovers have been observed in static compression experiments in any temperature and pressure ranges beyond the critical point. The structure of supercritical state is currently perceived to be uniform everywhere on the pressure-temperature phase diagram, and to change only in a monotonic way even moving around the critical point, not only alongmore » isotherms or isobars. Conversely, we observe structural crossovers for the first time in a deeply supercritical sample through diffraction measurements in a diamond anvil cell and discover a new thermodynamic boundary on the pressure-temperature diagram. We explain the existence of these crossovers in the framework of the phonon theory of liquids using molecular dynamics simulations. The obtained results are of prime importance since they imply a global reconsideration of the mere essence of the supercritical phase. Furthermore, this discovery may pave the way to new unexpected applications and to the exploration of exotic behaviour of confined fluids relevant to geo- and planetary sciences.« less

An Exploration and Analysis of the Modes of Rural School Consolidation in China

ERIC Educational Resources Information Center

Hongyong, Jia; Fenfen, Zhou

2013-01-01

Based on research involving 177 primary and secondary schools spread over thirty-eight counties in six provinces (including one autonomous region), this article explores and analyzes four modes used in rural school consolidation in China. These four modes are: complete amalgamation, annexation, crossover, and centralization-decentralization.

Emotion-Work Performance among Dual-Earner Couples: Testing Four Theoretical Perspectives

ERIC Educational Resources Information Center

Minnotte, Krista Lynn; Stevens, Daphne Pedersen; Minnotte, Michael C.; Kiger, Gary

2007-01-01

This study compares four theories of domestic labor in their ability to predict relative emotion-work performance among dual-earner couples. Specifically, the authors investigate the effects of gender ideology, time availability, relative resources, and crossover factors on the dependent variable of relative emotion-work performance using…

The dynamical crossover phenomenon in bulk water, confined water and protein hydration water.

PubMed

Mallamace, Francesco; Corsaro, Carmelo; Baglioni, Piero; Fratini, Emiliano; Chen, Sow-Hsin

2012-02-15

We discuss a phenomenon regarding water that was until recently a subject of scientific controversy, i.e. the dynamical crossover from fragile-to-strong glass-forming material, for both bulk and protein hydration water. Such a crossover is characterized by a temperature T(L) at which significant dynamical changes occur, such as violation of the Stokes-Einstein relation and changes of behaviour of homologous transport parameters such as the density relaxation time and the viscosity. In this respect we will consider carefully the dynamic properties of water-protein systems. More precisely, we will study proteins and their hydration water as far as bulk and confined water. In order to clarify the controversy we will discuss in a comparative way many previous and new experimental data that have emerged using different techniques and molecular dynamic simulation (MD). We point out the reasons for the different dynamical findings from the use of different experimental techniques.

CENTERLINE RUMBLE STRIPS SAFETY IMPACT EVALUATION—PHASE 2

DOT National Transportation Integrated Search

2018-02-02

Centerline rumble strips are used by various states as a low-cost countermeasure for mitigating cross-over crashes on two-way highways. This study performs a safety impact evaluation using an empirical Bayesian analysis. The researchers obtained a cr...

Crossover from capillary fingering to viscous fingering in a rough fracture

NASA Astrophysics Data System (ADS)

Hu, R.; Chen, Y.; Wu, D. S.

2017-12-01

Controlled by the competition between capillary and viscous forces, the displacement patterns of one fluid displacing another more viscous one exhibit capillary fingering, viscous fingering, and the crossover between the two. Although extensive studies have investigated viscous and capillary fingerings in porous and fractured media, a few studies focused on the crossover in rough fractures, and how viscous and capillary forces affect the crossover remains unclear. Using a transparent fracture visualization system, we studied how the competition impacts the crossover in a horizontal rough fracture. Drainage experiments of water displacing oil were conducted at seven flow rates (capillary number log10Ca ranging from -7.07 to -3.07) and four viscosity ratios (M = 1/1000, 1/500, 1/100 and 1/50). We consistently observed lower invading fluid saturations in the crossover zone. In addition, we proposed a phase diagram for the displacement patterns in a rough fracture that is consistent with similar studies in porous media. Based on real-time imaging and statistical analysis of the invasion morphology, we showed that the competition between the capillary and viscous forces is responsible for the saturation reduction in the crossover zone. In this zone, finger propagation toward the outlet (characteristic of viscous fingering) as well as void-filling in the transverse and backward directions (characteristic of capillary fingering), are both suppressed. Therefore, the invading fluid tends to occupy larger apertures with higher characteristic front velocity, promoting void-filling toward the outlet with thinner finger growth and resulting in a larger volume of defending fluid left behind.

Biofeedback and dance performance: a preliminary investigation.

PubMed

Raymond, Joshua; Sajid, Imran; Parkinson, Lesley A; Gruzelier, John H

2005-03-01

Alpha-theta neurofeedback has been shown to produce professionally significant performance improvements in music students. The present study aimed to extend this work to a different performing art and compare alpha-theta neurofeedback with another form of biofeedback: heart rate variability (HRV) biofeedback. Twenty-four ballroom and Latin dancers were randomly allocated to three groups, one receiving neurofeedback, one HRV biofeedback and one no intervention. Dance was assessed before and after training. Performance improvements were found in the biofeedback groups but not in the control group. Neurofeedback and HRV biofeedback benefited performance in different ways. A replication with larger sample sizes is required.

The role of similarity, sound and awareness in the appreciation of visual artwork via motor simulation.

PubMed

McLean, Christine; Want, Stephen C; Dyson, Benjamin J

2015-04-01

One way to increase art appreciation is to create congruency between the actions performed by the artist and the actions performed by the viewer. Leder, Bar, and Topolinski (2012) successfully created such a link by asking participants to make either stroking or stippling motions while viewing stroke-style and pointillist-style paintings. We carried out a direct replication of Leder et al. (2012) in Experiment 1 but failed to reproduce their results. In Experiment 2, we achieved the desired cross-over interaction between image and action but only when the relationship was made more transparent. Experiment 3 demonstrated that this effect requires a motor component and cannot be reproduced by simply hearing the sounds associated with drawing production. Experiment 4 investigated whether either an external manipulation or a self-report measure of awareness of the image-action match modulated the liking ratings, in addition to artwork familiarity and participants' own hypotheses regarding the direction of the image-action effect. Participants who predicted that congruent relationships between what they saw and what they did would increase liking showed enhanced congruency effects. The links between historical production and contemporary exposure to art may then be an overt rather than covert process. Copyright © 2015 Elsevier B.V. All rights reserved.

Development of a fescue toxicosis model using a fescue seed extract

USDA-ARS?s Scientific Manuscript database

This study was designed to examine the efficacy of a fescue seed extract for inducing fescue toxicosis in cattle. Four growing Holstein steers (BW = 309±36kg) surgically fitted with ruminal cannulas were utilized in a four phase crossover design experiment. The basal diet consisted of endophyte fr...

Spin Order and Phase Transitions in Chains of Polariton Condensates.

PubMed

Ohadi, H; Ramsay, A J; Sigurdsson, H; Del Valle-Inclan Redondo, Y; Tsintzos, S I; Hatzopoulos, Z; Liew, T C H; Shelykh, I A; Rubo, Y G; Savvidis, P G; Baumberg, J J

2017-08-11

We demonstrate that multiply coupled spinor polariton condensates can be optically tuned through a sequence of spin-ordered phases by changing the coupling strength between nearest neighbors. For closed four-condensate chains these phases span from ferromagnetic (FM) to antiferromagnetic (AFM), separated by an unexpected crossover phase. This crossover phase is composed of alternating FM-AFM bonds. For larger eight-condensate chains, we show the critical role of spatial inhomogeneities and demonstrate a scheme to overcome them and prepare any desired spin state. Our observations thus demonstrate a fully controllable nonequilibrium spin lattice.

Outdoor recreation trend research: making the possible probable

Treesearch

Geoffery Godbey

1980-01-01

Outdoor recreation research has largely ignored the fundamental requirement of science that findings be replicative. "The only way to establish replicability, of course, is to replicate." Because of this, we know practically nothing about outdoor recreation trends. "Trends, in statistics, (is) a steady change in a variable or set of related variables in...

Application of one-way ANOVA in completely randomized experiments

NASA Astrophysics Data System (ADS)

Wahid, Zaharah; Izwan Latiff, Ahmad; Ahmad, Kartini

2017-12-01

This paper describes an application of a statistical technique one-way ANOVA in completely randomized experiments with three replicates. This technique was employed to a single factor with four levels and multiple observations at each level. The aim of this study is to investigate the relationship between chemical oxygen demand index and location on-sites. Two different approaches are employed for the analyses; critical value and p-value. It also presents key assumptions of the technique to be satisfied by the data in order to obtain valid results. Pairwise comparisons by Turkey method are also considered and discussed to determine where the significant differences among the means is after the ANOVA has been performed. The results revealed that there are statistically significant relationship exist between the chemical oxygen demand index and the location on-sites.

Efficacy of Cognitive-Functional (Cog-Fun) Occupational Therapy Intervention Among Children With ADHD: An RCT.

PubMed

Hahn-Markowitz, Jeri; Berger, Itai; Manor, Iris; Maeir, Adina

2016-09-16

To examine the efficacy of a Cognitive-Functional (Cog-Fun) intervention for children with ADHD. Random allocation of 107 children to study or control groups preceded 10 parent-child weekly Cog-Fun sessions emphasizing executive strategy training in games and daily activities. Controls received treatment after crossover. Study participants were followed up 3 months post-treatment. Outcomes included parent/teacher ratings of executive functions, ADHD symptoms, and parent ratings of quality of life. Eight children withdrew prior to treatment. All children in both groups who began treatment completed it. Mixed effects ANOVA revealed significant Time × Group interaction effects on all parent-reported outcomes. Treatment effects were moderate to large, replicated after crossover in the control group and not moderated by medication. Parent-reported treatment gains in the study group were maintained at follow-up. No significant Time × Group interaction effects were found on teacher outcomes. Cog-Fun occupational therapy (OT) intervention shows positive context-specific effects on parent, but not teacher, ratings. © The Author(s) 2016.

Visualizing and quantifying the crossover from capillary fingering to viscous fingering in a rough fracture

NASA Astrophysics Data System (ADS)

Chen, Yi-Feng; Fang, Shu; Wu, Dong-Sheng; Hu, Ran

2017-09-01

Immiscible fluid-fluid displacement in permeable media is important in many subsurface processes, including enhanced oil recovery and geological CO2 sequestration. Controlled by capillary and viscous forces, displacement patterns of one fluid displacing another more viscous one exhibit capillary and viscous fingering, and crossover between the two. Although extensive studies investigated viscous and capillary fingering in porous media, a few studies focused on the crossover in rough fractures, and how viscous and capillary forces affect the crossover remains unclear. Using a transparent fracture-visualization system, we studied how the two forces impact the crossover in a horizontal rough fracture. Drainage experiments of water displacing oil were conducted at seven flow rates (capillary number log10Ca ranging from -7.07 to -3.07) and four viscosity ratios (M=1/1000,1/500,1/100 and 1/50). We consistently observed lower invading fluid saturations in the crossover zone. We also proposed a phase diagram for the displacement patterns in a rough fracture that is consistent with similar studies in porous media. Based on real-time imaging and statistical analysis of the invasion morphology, we showed that the competition between capillary and viscous forces is responsible for the saturation reduction in the crossover zone. In this zone, finger propagation toward the outlet (characteristic of viscous fingering) as well as void-filling in the transverse/backward directions (characteristic of capillary fingering), are both suppressed. Therefore, the invading fluid tends to occupy larger apertures with higher characteristic front velocity, promoting void-filling toward the outlet with thinner finger growth and resulting in a larger volume of defending fluid left behind.

Why people stereotype affects how they stereotype: the differential influence of comprehension goals and self-enhancement goals on stereotyping.

PubMed

van den Bos, Arne; Stapel, Diederik A

2009-01-01

In four studies, the authors examined the hypothesis that the way people stereotype is determined by the motives that instigate it. Study 1 measured and demonstrated the effectiveness of a commonly used priming technique to manipulate comprehension and self-enhancement goals. Study 2 demonstrated that why people stereotype determines how they stereotype: When a comprehension goal was salient, positive as well as negative stereotypes were applied, whereas a salient self-enhancement goal led to the application of negative but not positive stereotypes. Study 3 replicated these effects with different stereotypes. Study 4 replicated these effects and gave more insight in the consequences of goal fulfillment on stereotyping. Results indicated the fulfillment of a salient self-enhancement or comprehension goal led to the reduction of stereotyping. These effects were goal specific: Fulfillment of a self-enhancement goal decreased enhancement-driven but not comprehension-driven stereotyping; fulfillment of a comprehension goal decreased comprehension-driven but not enhancement-driven stereotyping.

Enzyme-Free Replication with Two or Four Bases.

PubMed

Richert, Clemens; Hänle, Elena

2018-05-20

All known forms of life encode their genetic information in a sequence of bases of a genetic polymer and produce copies of their genes via semiconservative replication. How this process started before polymerase enzymes had been evolved is unclear. Enzyme-free copying of short stretches of DNA or RNA sequence has been demonstrated, using activated nucleotides, but not replication. We have developed a methodology for replication. It involves extension with reversible termination, enzyme-free ligation, and strand capture and allowed us to monitor nucleotide incorporation for an entire helical turn of DNA, both during a first and a second round of copying. When tracking replication mass spectrometrically, we found that with all four bases (A/C/G/T) an 'error catastrophe' occurs, with the correct sequence being 'overwhelmed' by incorrect ones. When only C and G were used, approx. half of all daughter strands had the mass of the correct sequence after 20 nonenzymatic copying steps. We conclude that enzyme-free replication is more likely to be successful with the two strongly pairing bases, rather than all four bases of the genetic alphabet. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Design and evaluation of modified centerline rumble strips : final report.

DOT National Transportation Integrated Search

2017-03-08

A centerline rumble strip (CLRS) is primarily installed on the centerline of undivided two-lane and two-way roadways : to alert drivers that they are moving out of their intended travel lane. The main purpose of CLRSs is to reduce crossover : collisi...

Precise replication of antireflective nanostructures from biotemplates

NASA Astrophysics Data System (ADS)

Gao, Hongjun; Liu, Zhongfan; Zhang, Jin; Zhang, Guoming; Xie, Guoyong

2007-03-01

The authors report herein a new type of nanonipple structures on the cicada's eye and the direct structural replication of the complex micro- and nanostructures for potential functional emulation. A two-step direct molding process is developed to replicate these natural micro- and nanostructures using epoxy resin with high fidelity, which demonstrates a general way of fabricating functional nanostructures by direct replication of natural biotemplates via a suitable physicochemical process. Measurements of spectral reflectance showed that this kind of replicated nanostructure has remarkable antireflective property, suggestive of its potential applications to optical devices.

Automatic Combination of Operators in a Genetic Algorithm to Solve the Traveling Salesman Problem.

PubMed

Contreras-Bolton, Carlos; Parada, Victor

2015-01-01

Genetic algorithms are powerful search methods inspired by Darwinian evolution. To date, they have been applied to the solution of many optimization problems because of the easy use of their properties and their robustness in finding good solutions to difficult problems. The good operation of genetic algorithms is due in part to its two main variation operators, namely, crossover and mutation operators. Typically, in the literature, we find the use of a single crossover and mutation operator. However, there are studies that have shown that using multi-operators produces synergy and that the operators are mutually complementary. Using multi-operators is not a simple task because which operators to use and how to combine them must be determined, which in itself is an optimization problem. In this paper, it is proposed that the task of exploring the different combinations of the crossover and mutation operators can be carried out by evolutionary computing. The crossover and mutation operators used are those typically used for solving the traveling salesman problem. The process of searching for good combinations was effective, yielding appropriate and synergic combinations of the crossover and mutation operators. The numerical results show that the use of the combination of operators obtained by evolutionary computing is better than the use of a single operator and the use of multi-operators combined in the standard way. The results were also better than those of the last operators reported in the literature.

Automatic Combination of Operators in a Genetic Algorithm to Solve the Traveling Salesman Problem

PubMed Central

2015-01-01

Genetic algorithms are powerful search methods inspired by Darwinian evolution. To date, they have been applied to the solution of many optimization problems because of the easy use of their properties and their robustness in finding good solutions to difficult problems. The good operation of genetic algorithms is due in part to its two main variation operators, namely, crossover and mutation operators. Typically, in the literature, we find the use of a single crossover and mutation operator. However, there are studies that have shown that using multi-operators produces synergy and that the operators are mutually complementary. Using multi-operators is not a simple task because which operators to use and how to combine them must be determined, which in itself is an optimization problem. In this paper, it is proposed that the task of exploring the different combinations of the crossover and mutation operators can be carried out by evolutionary computing. The crossover and mutation operators used are those typically used for solving the traveling salesman problem. The process of searching for good combinations was effective, yielding appropriate and synergic combinations of the crossover and mutation operators. The numerical results show that the use of the combination of operators obtained by evolutionary computing is better than the use of a single operator and the use of multi-operators combined in the standard way. The results were also better than those of the last operators reported in the literature. PMID:26367182

Get on Board the Cost Effective Way: A Tech Prep Replication Process.

ERIC Educational Resources Information Center

Moore, Wayne A.; Szul, Linda F.; Rivosecchi, Karen

1997-01-01

The Northwestern Pennsylvania Tech Prep Consortium model for replicating tech prep programs includes these steps: fact finding, local industry analysis, curriculum development, detailed description, marketing strategies, implementation, and program evaluation. (SK)

Scaling in the aggregation dynamics of a magnetorheological fluid.

PubMed

Domínguez-García, P; Melle, Sonia; Pastor, J M; Rubio, M A

2007-11-01

We present experimental results on the aggregation dynamics of a magnetorheological fluid, namely, an aqueous suspension of micrometer-sized superparamagnetic particles, under the action of a constant uniaxial magnetic field using video microscopy and image analysis. We find a scaling behavior in several variables describing the aggregation kinetics. The data agree well with the Family-Vicsek scaling ansatz for diffusion-limited cluster-cluster aggregation. The kinetic exponents z and z' are obtained from the temporal evolution of the mean cluster size S(t) and the number of clusters N(t), respectively. The crossover exponent Delta is calculated in two ways: first, from the initial slope of the scaling function; second, from the evolution of the nonaggregated particles, n1(t). We report on results of Brownian two-dimensional dynamics simulations and compare the results with the experiments. Finally, we discuss the differences obtained between the kinetic exponents in terms of the variation in the crossover exponent and relate this behavior to the physical interpretation of the crossover exponent.

The Satiating Properties of Pork are not Affected by Cooking Methods, Sousvide Holding Time or Mincing in Healthy Men—A Randomized Cross-Over Meal Test Study

PubMed Central

Kehlet, Ursula; Mitra, Bhaskar; Aaslyng, Margit D.

2017-01-01

Low temperature long time (LTLT) sous-vide cooking may modify meat proteins in a way that could promote satiety. We investigated the effects of (1) cooking method (LTLT 58 °C vs. oven 160 °C), (2) LTLT holding time (17 h vs. 72 min), and (3) pork structure, LTLT 58 °C for 17 h (minced vs. roast) on appetite regulation and in vitro protein digestibility. In a cross-over study, 37 healthy men consumed four meals containing pork: LTLT-cooked roast, 58 °C, 72 min; LTLT-cooked roast, 58 °C, 17 h; and, oven-cooked roast, 160 °C to a core temperature of 58 °C and LTLT-cooked minced patties, 58 °C, 17 h. Ad libitum energy intake (EI) after three hours was the primary endpoint. Moreover, subjective appetite sensations were assessed. Protein digestibility was determined in an in vitro simulated digestion model. Ad libitum EI did not differ between the meals. Furthermore, appetite ratings were not clearly affected. LTLT cooking for 72 min increased the proteolytic rate in the early gastric phase during digestion as compared to LTLT cooking for 17 h or oven cooking. In conclusion, LTLT cooking, LTLT holding time, and pork structure did not affect ad libitum EI. However, LTLT cooking at 58 °C for 72 min seemed to enhance in vitro protein digestibility. PMID:28846600

The Satiating Properties of Pork are not Affected by Cooking Methods, Sousvide Holding Time or Mincing in Healthy Men-A Randomized Cross-Over Meal Test Study.

PubMed

Kehlet, Ursula; Mitra, Bhaskar; Ruiz Carrascal, Jorge; Raben, Anne; Aaslyng, Margit D

2017-08-26

Low temperature long time (LTLT) sous-vide cooking may modify meat proteins in a way that could promote satiety. We investigated the effects of (1) cooking method (LTLT 58 °C vs. oven 160 °C), (2) LTLT holding time (17 h vs. 72 min), and (3) pork structure, LTLT 58 °C for 17 h (minced vs. roast) on appetite regulation and in vitro protein digestibility. In a cross-over study, 37 healthy men consumed four meals containing pork: LTLT-cooked roast, 58 °C, 72 min; LTLT-cooked roast, 58 °C, 17 h; and, oven-cooked roast, 160 °C to a core temperature of 58 °C and LTLT-cooked minced patties, 58 °C, 17 h. Ad libitum energy intake (EI) after three hours was the primary endpoint. Moreover, subjective appetite sensations were assessed. Protein digestibility was determined in an in vitro simulated digestion model. Ad libitum EI did not differ between the meals. Furthermore, appetite ratings were not clearly affected. LTLT cooking for 72 min increased the proteolytic rate in the early gastric phase during digestion as compared to LTLT cooking for 17 h or oven cooking. In conclusion, LTLT cooking, LTLT holding time, and pork structure did not affect ad libitum EI. However, LTLT cooking at 58 °C for 72 min seemed to enhance in vitro protein digestibility.

Associations between Eating Competence and Cardiovascular Disease Biomarkers

ERIC Educational Resources Information Center

Psota, Tricia L.; Lohse, Barbara; West, Sheila G.

2007-01-01

Objective: Explore the relationship between eating competence (EC) and biomarkers of risk for cardiovascular disease (CVD). Design: Secondary analysis of data collected for a larger, 2-way crossover clinical trial. Setting: Outpatient clinical research center. Participants: Forty-eight hypercholesterolemic (LDL cholesterol [greater than or equal]…

Four Bad Habits of Modern Psychologists

PubMed Central

Grice, James; Cota, Lisa; Taylor, Zachery; Garner, Samantha; Medellin, Eliwid; Vest, Adam

2017-01-01

Four data sets from studies included in the Reproducibility Project were re-analyzed to demonstrate a number of flawed research practices (i.e., “bad habits”) of modern psychology. Three of the four studies were successfully replicated, but re-analysis showed that in one study most of the participants responded in a manner inconsistent with the researchers’ theoretical model. In the second study, the replicated effect was shown to be an experimental confound, and in the third study the replicated statistical effect was shown to be entirely trivial. The fourth study was an unsuccessful replication, yet re-analysis of the data showed that questioning the common assumptions of modern psychological measurement can lead to novel techniques of data analysis and potentially interesting findings missed by traditional methods of analysis. Considered together, these new analyses show that while it is true replication is a key feature of science, causal inference, modeling, and measurement are equally important and perhaps more fundamental to obtaining truly scientific knowledge of the natural world. It would therefore be prudent for psychologists to confront the limitations and flaws in their current analytical methods and research practices. PMID:28805739

Four Bad Habits of Modern Psychologists.

PubMed

Grice, James; Barrett, Paul; Cota, Lisa; Felix, Crystal; Taylor, Zachery; Garner, Samantha; Medellin, Eliwid; Vest, Adam

2017-08-14

Four data sets from studies included in the Reproducibility Project were re-analyzed to demonstrate a number of flawed research practices (i.e., "bad habits") of modern psychology. Three of the four studies were successfully replicated, but re-analysis showed that in one study most of the participants responded in a manner inconsistent with the researchers' theoretical model. In the second study, the replicated effect was shown to be an experimental confound, and in the third study the replicated statistical effect was shown to be entirely trivial. The fourth study was an unsuccessful replication, yet re-analysis of the data showed that questioning the common assumptions of modern psychological measurement can lead to novel techniques of data analysis and potentially interesting findings missed by traditional methods of analysis. Considered together, these new analyses show that while it is true replication is a key feature of science, causal inference, modeling, and measurement are equally important and perhaps more fundamental to obtaining truly scientific knowledge of the natural world. It would therefore be prudent for psychologists to confront the limitations and flaws in their current analytical methods and research practices.

Elementary excitations and crossover phenomenon in liquids.

PubMed

Iwashita, T; Nicholson, D M; Egami, T

2013-05-17

The elementary excitations of vibration in solids are phonons. But in liquids phonons are extremely short lived and marginalized. In this Letter through classical and ab initio molecular dynamics simulations of the liquid state of various metallic systems we show that different excitations, the local configurational excitations in the atomic connectivity network, are the elementary excitations in high temperature metallic liquids. We also demonstrate that the competition between the configurational excitations and phonons determines the so-called crossover phenomenon in liquids. These discoveries open the way to the explanation of various complex phenomena in liquids, such as fragility and the rapid increase in viscosity toward the glass transition, in terms of these excitations.

The Design of Finite State Machine for Asynchronous Replication Protocol

NASA Astrophysics Data System (ADS)

Wang, Yanlong; Li, Zhanhuai; Lin, Wei; Hei, Minglei; Hao, Jianhua

Data replication is a key way to design a disaster tolerance system and to achieve reliability and availability. It is difficult for a replication protocol to deal with the diverse and complex environment. This means that data is less well replicated than it ought to be. To reduce data loss and to optimize replication protocols, we (1) present a finite state machine, (2) run it to manage an asynchronous replication protocol and (3) report a simple evaluation of the asynchronous replication protocol based on our state machine. It's proved that our state machine is applicable to guarantee the asynchronous replication protocol running in the proper state to the largest extent in the event of various possible events. It also can helpful to build up replication-based disaster tolerance systems to ensure the business continuity.

Multiculturalism in Four Teacher Education Programs: For Replication or Transformation

ERIC Educational Resources Information Center

Ensign, Jacque

2009-01-01

This article describes four teacher education programs and their student teachers' responses to why some students in their classrooms were not doing well. The responses and programs fell into two categories: education for replication of inequities and education for transformation. If teacher education programs want their prospective teachers to be…

Modified many-body wave function for BCS-BEC crossover in Fermi gases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tan, Shina; Levin, K.

2006-10-15

We present a many-body formalism for BCS-BEC crossover, which represents a modification of the Bardeen-Cooper-Schrieffer-Leggett ground state to include four-fermion and higher correlations. In the Bose-Einstein condensate regime, we show how our approach contains the four-fermion behavior of Petrov et al. and associated scattering length a{sub dd} at short distances and, second, reduces to composite-boson Bogoliubov physics at long distances. It reproduces the Lee-Yang term, whose numerical value is also fixed by a{sub dd}. We have also examined the next term beyond the Lee-Yang correction in a phenomenological fashion, building on cloud size data and collective mode experiments, although onemore » has to view this phenomenological analysis with some caution since experiments are in a state of flux and are performed close to unitarity.« less

DNA Replication Origins and Fork Progression at Mammalian Telomeres

PubMed Central

Higa, Mitsunori; Fujita, Masatoshi; Yoshida, Kazumasa

2017-01-01

Telomeres are essential chromosomal regions that prevent critical shortening of linear chromosomes and genomic instability in eukaryotic cells. The bulk of telomeric DNA is replicated by semi-conservative DNA replication in the same way as the rest of the genome. However, recent findings revealed that replication of telomeric repeats is a potential cause of chromosomal instability, because DNA replication through telomeres is challenged by the repetitive telomeric sequences and specific structures that hamper the replication fork. In this review, we summarize current understanding of the mechanisms by which telomeres are faithfully and safely replicated in mammalian cells. Various telomere-associated proteins ensure efficient telomere replication at different steps, such as licensing of replication origins, passage of replication forks, proper fork restart after replication stress, and dissolution of post-replicative structures. In particular, shelterin proteins have central roles in the control of telomere replication. Through physical interactions, accessory proteins are recruited to maintain telomere integrity during DNA replication. Dormant replication origins and/or homology-directed repair may rescue inappropriate fork stalling or collapse that can cause defects in telomere structure and functions. PMID:28350373

Oral Health-Related Quality of Life in Edentulous Patients with Two- vs Four-Locator-Retained Mandibular Overdentures: A Prospective, Randomized, Crossover Study.

PubMed

Karbach, Julia; Hartmann, Sinsa; Jahn-Eimermacher, Antje; Wagner, Wilfried

2015-01-01

To compare the oral health-related quality of life (OHRQoL) in a prospective, randomized crossover trial in patients with mandibular overdentures retained with two or four locators. In 30 patients with edentulous mandibles, four implants (ICX-plus implants [Medentis Medical]) were placed in the intraforaminal area. Eight weeks after transgingival healing, patients were randomly assigned to have two or four implants incorporated in the prosthesis. After 3 months, the retention concepts were switched. The patients with a two-implant-supported overdenture had four implants incorporated, whereas patients with a four-implant-supported overdenture had two retention locators taken out. After 3 more months, all four implants were retained in the implant-supported overdenture in every patient. To measure OHRQoL of the patients, the Oral Health Impact Profile 14, German version (OHIP-14 G), was used. A considerable increase in OHRQoL could be seen in all patients after the prosthesis was placed on the implants. Also, a statistically significant difference of OHRQoL could be seen in the OHIP-14 G scores between two-implant and four-implant overdentures. Patients had a higher OHRQoL after incorporation of four implants in the overdenture compared with only two implants. Patients with implant-retained overdentures had better OHRQoL compared with those with conventional dentures. The number of incorporated implants in the locator-retained overdenture also influenced the increase in OHRQoL, with four implants having a statistically significant advantage over two implants.

Random-effects linear modeling and sample size tables for two special crossover designs of average bioequivalence studies: the four-period, two-sequence, two-formulation and six-period, three-sequence, three-formulation designs.

PubMed

Diaz, Francisco J; Berg, Michel J; Krebill, Ron; Welty, Timothy; Gidal, Barry E; Alloway, Rita; Privitera, Michael

2013-12-01

Due to concern and debate in the epilepsy medical community and to the current interest of the US Food and Drug Administration (FDA) in revising approaches to the approval of generic drugs, the FDA is currently supporting ongoing bioequivalence studies of antiepileptic drugs, the EQUIGEN studies. During the design of these crossover studies, the researchers could not find commercial or non-commercial statistical software that quickly allowed computation of sample sizes for their designs, particularly software implementing the FDA requirement of using random-effects linear models for the analyses of bioequivalence studies. This article presents tables for sample-size evaluations of average bioequivalence studies based on the two crossover designs used in the EQUIGEN studies: the four-period, two-sequence, two-formulation design, and the six-period, three-sequence, three-formulation design. Sample-size computations assume that random-effects linear models are used in bioequivalence analyses with crossover designs. Random-effects linear models have been traditionally viewed by many pharmacologists and clinical researchers as just mathematical devices to analyze repeated-measures data. In contrast, a modern view of these models attributes an important mathematical role in theoretical formulations in personalized medicine to them, because these models not only have parameters that represent average patients, but also have parameters that represent individual patients. Moreover, the notation and language of random-effects linear models have evolved over the years. Thus, another goal of this article is to provide a presentation of the statistical modeling of data from bioequivalence studies that highlights the modern view of these models, with special emphasis on power analyses and sample-size computations.

Effect of fungicides on anthracnose and grain mold of sorghum in Wharton County, Texas, 2016

USDA-ARS?s Scientific Manuscript database

The experiment was conducted in Wharton County, Texas using the hybrid BH 5566. There were four replicates per treatment arranged in a randomized, blocked factorial design. Each replicate consisted of four, 20.5-ft rows, with 38-in. row spacing and a plant spacing of 1.9 in. within rows. Three fu...

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

ERIC Educational Resources Information Center

Martini, Rose; Polatajko, Helene J.

1998-01-01

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

DNA replication depends on photosynthetic electron transport in cyanobacteria.

PubMed

Ohbayashi, Ryudo; Watanabe, Satoru; Kanesaki, Yu; Narikawa, Rei; Chibazakura, Taku; Ikeuchi, Masahiko; Yoshikawa, Hirofumi

2013-07-01

The freshwater cyanobacterium Synechococcus elongatus PCC 7942 exhibits light-dependent growth. Although it has been reported that DNA replication also depends on light irradiation in S. elongatus 7942, the involvement of the light in the regulation of DNA replication remains unclear. To elucidate the regulatory pathway of DNA replication by light, we studied the effect of several inhibitors, including two electron transport inhibitors, 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) and 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone (DBMIB), on DNA replication in S. elongatus 7942. DCMU inhibited only DNA replication initiation, whereas DBMIB blocked both the initiation and progression of DNA replication. These results suggest that DNA replication depends on the photosynthetic electron transport activity and initiation and progression of DNA replication are regulated in different ways. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

An efficient early phase 2 procedure to screen medications for efficacy in smoking cessation.

PubMed

Perkins, Kenneth A; Lerman, Caryn

2014-01-01

Initial screening of new medications for potential efficacy (i.e., Food and Drug Administration (FDA) early phase 2), such as in aiding smoking cessation, should be efficient in identifying which drugs do, or do not, warrant more extensive (and expensive) clinical testing. This focused review outlines our research on development, evaluation, and validation of an efficient crossover procedure for sensitivity in detecting medication efficacy for smoking cessation. First-line FDA-approved medications of nicotine patch, varenicline, and bupropion were tested as model drugs, in three separate placebo-controlled studies. We also tested specificity of our procedure in identifying a drug that lacks efficacy, using modafinil. This crossover procedure showed sensitivity (increased days of abstinence) during week-long "practice" quit attempts with each of the active cessation medications (positive controls) versus placebo, but not with modafinil (negative control) versus placebo, as hypothesized. Sensitivity to medication efficacy signal was observed only in smokers high in intrinsic quit motivation (i.e., already preparing to quit soon) and not smokers low in intrinsic quit motivation, even if monetarily reinforced for abstinence (i.e., given extrinsic motivation). A crossover procedure requiring less time and fewer subjects than formal trials may provide an efficient strategy for a go/no-go decision whether to advance to subsequent phase 2 randomized clinical trials with a novel drug. Future research is needed to replicate our results and evaluate this procedure with novel compounds, identify factors that may limit its utility, and evaluate its applicability to testing efficacy of compounds for treating other forms of addiction.

Using Replication Projects in Teaching Research Methods

ERIC Educational Resources Information Center

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…

Improving care coordination using organisational routines.

PubMed

Prætorius, Thim

2016-01-01

The purpose of this paper is to systematically apply theory of organisational routines to standardised care pathways. The explanatory power of routines is used to address open questions in the care pathway literature about their coordinating and organising role, the way they change and can be replicated, the way they are influenced by the organisation and the way they influence health care professionals. Theory of routines is systematically applied to care pathways in order to develop theoretically derived propositions. Care pathways mirror routines by being recurrent, collective and embedded and specific to an organisation. In particular, care pathways resemble standard operating procedures that can give rise to recurrent collective action patterns. In all, 11 propositions related to five categories are proposed by building on these insights: care pathways and coordination, change, replication, the organisation and health care professionals. Research limitations/implications - The paper is conceptual and uses care pathways as illustrative instances of hospital routines. The propositions provide a starting point for empirical research. The analysis highlights implications that health care professionals and managers have to consider in relation to coordination, change, replication, the way the organisation influences care pathways and the way care pathways influence health care professionals. Originality/value - Theory on organisational routines offers fundamental, yet unexplored, insights into hospital processes, including in particular care coordination.

The role of crossover operator in evolutionary-based approach to the problem of genetic code optimization.

PubMed

Błażej, Paweł; Wnȩtrzak, Małgorzata; Mackiewicz, Paweł

2016-12-01

One of theories explaining the present structure of canonical genetic code assumes that it was optimized to minimize harmful effects of amino acid replacements resulting from nucleotide substitutions and translational errors. A way to testify this concept is to find the optimal code under given criteria and compare it with the canonical genetic code. Unfortunately, the huge number of possible alternatives makes it impossible to find the optimal code using exhaustive methods in sensible time. Therefore, heuristic methods should be applied to search the space of possible solutions. Evolutionary algorithms (EA) seem to be ones of such promising approaches. This class of methods is founded both on mutation and crossover operators, which are responsible for creating and maintaining the diversity of candidate solutions. These operators possess dissimilar characteristics and consequently play different roles in the process of finding the best solutions under given criteria. Therefore, the effective searching for the potential solutions can be improved by applying both of them, especially when these operators are devised specifically for a given problem. To study this subject, we analyze the effectiveness of algorithms for various combinations of mutation and crossover probabilities under three models of the genetic code assuming different restrictions on its structure. To achieve that, we adapt the position based crossover operator for the most restricted model and develop a new type of crossover operator for the more general models. The applied fitness function describes costs of amino acid replacement regarding their polarity. Our results indicate that the usage of crossover operators can significantly improve the quality of the solutions. Moreover, the simulations with the crossover operator optimize the fitness function in the smaller number of generations than simulations without this operator. The optimal genetic codes without restrictions on their structure minimize the costs about 2.7 times better than the canonical genetic code. Interestingly, the optimal codes are dominated by amino acids characterized by polarity close to its average value for all amino acids. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Assessment of bioequivalence of rifampicin, isoniazid and pyrazinamide in a four drug fixed dose combination with separate formulations at the same dose levels.

PubMed

Agrawal, Shrutidevi; Kaur, Kanwal Jit; Singh, Inderjit; Bhade, Shantaram R; Kaul, Chaman Lal; Panchagnula, Ramesh

2002-02-21

Tuberculosis (TB) needs treatment with three to five different drugs simultaneously, depending on the patient category. These drugs can be given as single drug preparations or fixed dose combinations (FDCs) of two more drugs in a single formulation. World Health Organization and International Union against Tuberculosis and Lung Disease (IUATLD) recommend FDCs only of proven bioavailability. The relative bioavailability of rifampicin (RIF), isoniazid (INH) and pyrazinamide (PYZ) was assessed on a group of 13 healthy male subjects from a four drug FDC versus separate formulations at the same dose levels. The study was designed to be an open, crossover experiment. A total of nine blood samples each of 3 ml volume were collected over a period of 24-h. The concentrations of RIF, its main metabolite desacetyl RIF (DRIF), INH and PYZ in plasma were assessed by HPLC analysis. Pharmacokinetic parameters namely AUC(0-24), AUC(0-inf), C(max), T(max), were calculated and subjected to different statistical tests (Hauschke analysis, two way ANOVA, normal and log transformed confidence interval) at 90% confidence interval. In addition, elimination rate constant (K(el)) and absorption efficiencies for each drug were also calculated. It was concluded that four drugs FDC tablet is bioequivalent for RIF, INH and PYZ to separate formulation at the same dose levels.

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

PubMed Central

Earp, Brian D.; Trafimow, David

2015-01-01

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

Psychology, Science, and Knowledge Construction: Broadening Perspectives from the Replication Crisis.

PubMed

Shrout, Patrick E; Rodgers, Joseph L

2018-01-04

Psychology advances knowledge by testing statistical hypotheses using empirical observations and data. The expectation is that most statistically significant findings can be replicated in new data and in new laboratories, but in practice many findings have replicated less often than expected, leading to claims of a replication crisis. We review recent methodological literature on questionable research practices, meta-analysis, and power analysis to explain the apparently high rates of failure to replicate. Psychologists can improve research practices to advance knowledge in ways that improve replicability. We recommend that researchers adopt open science conventions of preregi-stration and full disclosure and that replication efforts be based on multiple studies rather than on a single replication attempt. We call for more sophisticated power analyses, careful consideration of the various influences on effect sizes, and more complete disclosure of nonsignificant as well as statistically significant findings.

Preliminary design, analysis, and costing of a dynamic scale model of the NASA space station

NASA Technical Reports Server (NTRS)

Gronet, M. J.; Pinson, E. D.; Voqui, H. L.; Crawley, E. F.; Everman, M. R.

1987-01-01

The difficulty of testing the next generation of large flexible space structures on the ground places an emphasis on other means for validating predicted on-orbit dynamic behavior. Scale model technology represents one way of verifying analytical predictions with ground test data. This study investigates the preliminary design, scaling and cost trades for a Space Station dynamic scale model. The scaling of nonlinear joint behavior is studied from theoretical and practical points of view. Suspension system interaction trades are conducted for the ISS Dual Keel Configuration and Build-Up Stages suspended in the proposed NASA/LaRC Large Spacecraft Laboratory. Key issues addressed are scaling laws, replication vs. simulation of components, manufacturing, suspension interactions, joint behavior, damping, articulation capability, and cost. These issues are the subject of parametric trades versus the scale model factor. The results of these detailed analyses are used to recommend scale factors for four different scale model options, each with varying degrees of replication. Potential problems in constructing and testing the scale model are identified, and recommendations for further study are outlined.

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

PubMed

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

2016-06-01

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

A Distinct Class of Genome Rearrangements Driven by Heterologous Recombination.

PubMed

León-Ortiz, Ana María; Panier, Stephanie; Sarek, Grzegorz; Vannier, Jean-Baptiste; Patel, Harshil; Campbell, Peter J; Boulton, Simon J

2018-01-18

Erroneous DNA repair by heterologous recombination (Ht-REC) is a potential threat to genome stability, but evidence supporting its prevalence is lacking. Here we demonstrate that recombination is possible between heterologous sequences and that it is a source of chromosomal alterations in mitotic and meiotic cells. Mechanistically, we find that the RTEL1 and HIM-6/BLM helicases and the BRCA1 homolog BRC-1 counteract Ht-REC in Caenorhabditis elegans, whereas mismatch repair does not. Instead, MSH-2/6 drives Ht-REC events in rtel-1 and brc-1 mutants and excessive crossovers in rtel-1 mutant meioses. Loss of vertebrate Rtel1 also causes a variety of unusually large and complex structural variations, including chromothripsis, breakage-fusion-bridge events, and tandem duplications with distant intra-chromosomal insertions, whose structure are consistent with a role for RTEL1 in preventing Ht-REC during break-induced replication. Our data establish Ht-REC as an unappreciated source of genome instability that underpins a novel class of complex genome rearrangements that likely arise during replication stress. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Workload and Marital Satisfaction over Time: Testing Lagged Spillover and Crossover Effects during the Newlywed Years.

PubMed

Lavner, Justin A; Clark, Malissa A

2017-08-01

Although many studies have found that higher workloads covary with lower levels of marital satisfaction, the question of whether workloads may also predict changes in marital satisfaction over time has been overlooked. To address this question, we investigated the lagged association between own and partner workload and marital satisfaction using eight waves of data collected every 6 months over the first four years of marriage from 172 heterosexual couples. Significant crossover, but not spillover, effects were found, indicating that partners of individuals with higher workloads at one time point experience greater declines in marital satisfaction by the following time point compared to the partners of individuals with lower workloads. These effects were not moderated by gender or parental status. These findings suggest that higher partner workloads can prove deleterious for relationship functioning over time and call for increased attention to the long-term effects of spillover and crossover from work to marital functioning.

Ocular hemodynamic effects of nitrovasodilators in healthy subjects.

PubMed

Schmidl, D; Polska, E; Kiss, B; Sacu, S; Garhofer, G; Schmetterer, L

2010-01-01

Nitric oxide (NO) plays a key role in the regulation of ocular blood flow and may be an interesting therapeutic target in ocular ischemic disease. In the present study, we hypothesized that NO-releasing drugs may increase blood flow to the head of the optic nerve and also in the choroid. The study employed a randomized, placebo-controlled, double blind, four-way crossover design. On separate study days, 12 healthy subjects received infusions of nitroglycerin, isosorbide dinitrate, sodium nitroprusside, or placebo. All three study drugs reduced the mean arterial pressure (MAP) and ocular perfusion pressure (OPP) (P < 0.001). None of the administered drugs increased the ocular hemodynamic variables. By contrast, vascular resistance decreased dose dependently during administration of the study drugs (P < 0.001). These results indicate that systemic administration of NO-donor drugs is associated with a decrease in vascular resistance in the ocular vasculature. However, because these drugs also reduce blood pressure, they do not improve perfusion to the posterior eye pole.

The Reputational Consequences of Failed Replications and Wrongness Admission among Scientists

PubMed Central

Fetterman, Adam K.; Sassenberg, Kai

2015-01-01

Scientists are dedicating more attention to replication efforts. While the scientific utility of replications is unquestionable, the impact of failed replication efforts and the discussions surrounding them deserve more attention. Specifically, the debates about failed replications on social media have led to worry, in some scientists, regarding reputation. In order to gain data-informed insights into these issues, we collected data from 281 published scientists. We assessed whether scientists overestimate the negative reputational effects of a failed replication in a scenario-based study. Second, we assessed the reputational consequences of admitting wrongness (versus not) as an original scientist of an effect that has failed to replicate. Our data suggests that scientists overestimate the negative reputational impact of a hypothetical failed replication effort. We also show that admitting wrongness about a non-replicated finding is less harmful to one’s reputation than not admitting. Finally, we discovered a hint of evidence that feelings about the replication movement can be affected by whether replication efforts are aimed one’s own work versus the work of another. Given these findings, we then present potential ways forward in these discussions. PMID:26650842

The Reputational Consequences of Failed Replications and Wrongness Admission among Scientists.

PubMed

Fetterman, Adam K; Sassenberg, Kai

2015-01-01

Scientists are dedicating more attention to replication efforts. While the scientific utility of replications is unquestionable, the impact of failed replication efforts and the discussions surrounding them deserve more attention. Specifically, the debates about failed replications on social media have led to worry, in some scientists, regarding reputation. In order to gain data-informed insights into these issues, we collected data from 281 published scientists. We assessed whether scientists overestimate the negative reputational effects of a failed replication in a scenario-based study. Second, we assessed the reputational consequences of admitting wrongness (versus not) as an original scientist of an effect that has failed to replicate. Our data suggests that scientists overestimate the negative reputational impact of a hypothetical failed replication effort. We also show that admitting wrongness about a non-replicated finding is less harmful to one's reputation than not admitting. Finally, we discovered a hint of evidence that feelings about the replication movement can be affected by whether replication efforts are aimed one's own work versus the work of another. Given these findings, we then present potential ways forward in these discussions.

Sample-interpolation timing: an optimized technique for the digital measurement of time of flight for γ rays and neutrons at relatively low sampling rates

NASA Astrophysics Data System (ADS)

Aspinall, M. D.; Joyce, M. J.; Mackin, R. O.; Jarrah, Z.; Boston, A. J.; Nolan, P. J.; Peyton, A. J.; Hawkes, N. P.

2009-01-01

A unique, digital time pick-off method, known as sample-interpolation timing (SIT) is described. This method demonstrates the possibility of improved timing resolution for the digital measurement of time of flight compared with digital replica-analogue time pick-off methods for signals sampled at relatively low rates. Three analogue timing methods have been replicated in the digital domain (leading-edge, crossover and constant-fraction timing) for pulse data sampled at 8 GSa s-1. Events arising from the 7Li(p, n)7Be reaction have been detected with an EJ-301 organic liquid scintillator and recorded with a fast digital sampling oscilloscope. Sample-interpolation timing was developed solely for the digital domain and thus performs more efficiently on digital signals compared with analogue time pick-off methods replicated digitally, especially for fast signals that are sampled at rates that current affordable and portable devices can achieve. Sample interpolation can be applied to any analogue timing method replicated digitally and thus also has the potential to exploit the generic capabilities of analogue techniques with the benefits of operating in the digital domain. A threshold in sampling rate with respect to the signal pulse width is observed beyond which further improvements in timing resolution are not attained. This advance is relevant to many applications in which time-of-flight measurement is essential.

Entropic stabilization of a deubiquitinase provides conformational plasticity and slow unfolding kinetics beneficial for functioning on the proteasome

PubMed Central

Lee, Yun-Tzai Cloud; Chang, Chia-Yun; Chen, Szu-Yu; Pan, Yun-Ru; Ho, Meng-Ru; Hsu, Shang-Te Danny

2017-01-01

Human ubiquitin C-terminal hydrolyase UCH-L5 is a topologically knotted deubiquitinase that is activated upon binding to the proteasome subunit Rpn13. The length of its intrinsically disordered cross-over loop is essential for substrate recognition. Here, we showed that the catalytic domain of UCH-L5 exhibits higher equilibrium folding stability with an unfolding rate on the scale of 10−8 s−1, over four orders of magnitudes slower than its paralogs, namely UCH-L1 and -L3, which have shorter cross-over loops. NMR relaxation dynamics analysis confirmed the intrinsic disorder of the cross-over loop. Hydrogen deuterium exchange analysis further revealed a positive correlation between the length of the cross-over loop and the degree of local fluctuations, despite UCH-L5 being thermodynamically and kinetically more stable than the shorter UCHs. Considering the role of UCH-L5 in removing K48-linked ubiquitin to prevent proteasomal degradation of ubiquitinated substrates, our findings offered mechanistic insights into the evolution of UCH-L5. Compared to its paralogs, it is entropically stabilized to withstand mechanical unfolding by the proteasome while maintaining structural plasticity. It can therefore accommodate a broad range of substrate geometries at the cost of unfavourable entropic loss. PMID:28338014

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

PubMed

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

2018-06-01

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

A Successful Test of Parallel Replication Teams in Teaching Research Methods

ERIC Educational Resources Information Center

Standing, Lionel G.; Astrologo, Lisa; Benbow, Felecia F.; Cyr-Gauthier, Chelsea S.; Williams, Charlotte A.

2016-01-01

This paper describes the novel use of parallel student teams from a research methods course to perform a replication study, and suggests that this approach offers pedagogical benefits for both students and teachers, as well as potentially contributing to a resolution of the replication crisis in psychology today. Four teams, of five undergraduates…

Replication and Reporting: A Commentary.

ERIC Educational Resources Information Center

Polio, Charlene; Gass, Susan

1997-01-01

Addresses the need for replication studies in the field of second-language acquisition and discusses the problems surrounding standards of reporting research. Notes a lack of uniform standards in reporting second-language learners' proficiency levels and proposes ways to achieve more thorough reporting of research that will allow others to engage…

Assessment of levothyroxine sodium bioavailability: recommendations for an improved methodology based on the pooled analysis of eight identically designed trials with 396 drug exposures.

PubMed

Walter-Sack, Ingeborg; Clanget, Christof; Ding, Reinhard; Goeggelmann, Christoph; Hinke, Vera; Lang, Matthias; Pfeilschifter, Johannes; Tayrouz, Yorki; Wegscheider, Karl

2004-01-01

Assessment of dosage form performance in delivering endogenous compounds, such as hormones, in vivo requires a specific approach. Assessment of relative bioavailability of levothyroxine sodium (L-T4) from eight solid preparations, compared with a liquid formulation, by using pharmacological doses, and critical evaluation of trial methodology based on the pooled analysis of individual data. Eight open-label, randomised, single-dose, crossover phase I studies using eight solid L-T4 dosage forms (25, 50, 75, 100, 125, 150, 175, 200 microg per tablet; administered total doses 600, 625 or 700 microg) and a liquid formulation; assessment of relative bioavailability by 90% confidence intervals for the relative area under the concentration-time curve (AUC) of total thyroxine (TT4), i.e. protein-bound plus free thyroxine, calculated by using the recommended log AUC four-way analysis of variance models for crossover designs. For the pooled analysis, general linear models were applied to assess the validity of model assumptions, to identify potential sources of effect modification, to discuss alternative modelling approaches with respect to endogenous hormone secretion and to give recommendations for future designs and sample sizes. One hundred and sixty-nine healthy males; 29 of these individuals participating in two studies. Single oral doses of L-T4 tablets and the liquid formulation administered after fasting, separated by at least 6 weeks; a total of 396 drug exposures. TT4 AUC from 0 to 48 hours and peak plasma concentration with and without baseline correction. Each study demonstrated equivalence of the tablets to the drinking solution, independent of the chosen analysis model. Sequence effects that could devalidate the chosen crossover approach were not found. Period effects with changing directions that could best be explained by seasonal variation were detected. While the pre-specified method of baseline correction of simply subtracting individual time-zero TT4 values was disadvantageous, the analysis of total AUC could be improved considerably by covariate adjustment for baseline TT4. With this approach, sample sizes could have been substantially reduced or, alternatively, the recommended equivalence ranges could be reduced to +/-6%. Using a single pharmacological dose of L-T4 in two-period crossover designs is a safe and reliable procedure to assess L-T4 dosage form performance. With an adequate statistical modelling approach, the design is efficient and allows general conclusions with moderate sample sizes.

Learning as a Machine: Crossovers between Humans and Machines

ERIC Educational Resources Information Center

Hildebrandt, Mireille

2017-01-01

This article is a revised version of the keynote presented at LAK '16 in Edinburgh. The article investigates some of the assumptions of learning analytics, notably those related to behaviourism. Building on the work of Ivan Pavlov, Herbert Simon, and James Gibson as ways of "learning as a machine," the article then develops two levels of…

Three of the Four Nucleocapsid Proteins of Marburg Virus, NP, VP35, and L, Are Sufficient To Mediate Replication and Transcription of Marburg Virus-Specific Monocistronic Minigenomes

PubMed Central

Mühlberger, Elke; Lötfering, Beate; Klenk, Hans-Dieter; Becker, Stephan

1998-01-01

This paper describes the first reconstituted replication system established for a member of the Filoviridae, Marburg virus (MBGV). MBGV minigenomes containing the leader and trailer regions of the MBGV genome and the chloramphenicol acetyltransferase (CAT) gene were constructed. In MBGV-infected cells, these minigenomes were replicated and encapsidated and could be passaged. Unlike most other members of the order Mononegavirales, filoviruses possess four proteins presumed to be components of the nucleocapsid (NP, VP35, VP30, and L). To determine the protein requirements for replication and transcription, a reverse genetic system was established for MBGV based on the vaccinia virus T7 expression system. Northern blot analysis of viral RNA revealed that three nucleocapsid proteins (NP, VP35, and L) were essential and sufficient for transcription as well as replication and encapsidation. These data indicate that VP35, rather than VP30, is the functional homologue of rhabdo- and paramyxovirus P proteins. The reconstituted replication system was profoundly affected by the NP-to-VP35 expression ratio. To investigate whether CAT gene expression was achieved entirely by mRNA or in part by full-length plus-strand minigenomes, a copy-back minireplicon containing the CAT gene but lacking MBGV-specific transcriptional start sites was employed in the artificial replication system. This construct was replicated without accompanying CAT activity. It was concluded that the CAT activity reflected MBGV-specific transcription and not replication. PMID:9765419

Size of Coarse Woody Debris 5 Years After Girdling and Removal Treatments in 50-Year-Old Loblolly Pine Plantations

Treesearch

M. Boyd Edwards

2004-01-01

In 1996, a study began at Savannah River Site to investigate large-scale replicated forest areas to control coarse woody debris for integrated biodiversity objectives. Research design was a randomized complete block with four treatments replicated in four blocks, resulting in 16 plots. The treatments applied to 50-year-old loblolly pine stands were (1) control, (2)...

Workaholism and relationship quality: a spillover-crossover perspective.

PubMed

Bakker, Arnold B; Demerouti, Evangelia; Burke, Ronald

2009-01-01

This study of 168 dual-earner couples examined the relationship between workaholism and relationship satisfaction. More specifically, on the basis of the literature, it was hypothesized that workaholism is positively related to work-family conflict. In addition, the authors predicted that workaholism is related to reduced support provided to the partner, through work-family conflict, and that individuals who receive considerable support from their partners are more satisfied with their relationship. Finally, the authors hypothesized direct crossover of relationship satisfaction between partners. The results of structural equation modeling analyses using the matched responses of both partners supported these hypotheses. Moreover, in line with predictions, the authors found that gender did not affect the strength of the relationships in the proposed model. The authors discuss workplace interventions as possible ways to help workaholics and their partners.

Quantum corrections crossover and ferromagnetism in magnetic topological insulators.

PubMed

Bao, Lihong; Wang, Weiyi; Meyer, Nicholas; Liu, Yanwen; Zhang, Cheng; Wang, Kai; Ai, Ping; Xiu, Faxian

2013-01-01

Revelation of emerging exotic states of topological insulators (TIs) for future quantum computing applications relies on breaking time-reversal symmetry and opening a surface energy gap. Here, we report on the transport response of Bi2Te3 TI thin films in the presence of varying Cr dopants. By tracking the magnetoconductance (MC) in a low doping regime we observed a progressive crossover from weak antilocalization (WAL) to weak localization (WL) as the Cr concentration increases. In a high doping regime, however, increasing Cr concentration yields a monotonically enhanced anomalous Hall effect (AHE) accompanied by an increasing carrier density. Our results demonstrate a possibility of manipulating bulk ferromagnetism and quantum transport in magnetic TI, thus providing an alternative way for experimentally realizing exotic quantum states required by spintronic applications.

Plaque triclosan concentration and antimicrobial efficacy of a new calcium carbonate toothpaste with 0.3% triclosan compared to a marketed 0.3% triclosan toothpaste.

PubMed

Srinivasan, Shashank; Chandrasekhar, Sembian; Shashikumar, K V; Payne, David; Maclure, Robert; Kapadiya, Bhavin; Schäfer, Fred; Adams, Suzi

2013-01-01

To compare the delivery and retention of triclosan in dental plaque, and to compare the antibacterial efficacy of a newly developed toothpaste to a marketed calcium carbonate toothpaste. Two clinical delivery/retention studies were carried out to determine the concentration of triclosan in plaque 10 minutes, and two and four hours after brushing with a new triclosan-containing toothpaste with magnesium aluminium silicate or a marketed triclosan-containing toothpaste. Both studies had a double-blind, randomized, complete cross-over design. Supragingival plaque samples (minimum 2 microg) were taken from smooth surfaces of all teeth (1-7) in all four quadrants for the 10-minute plaque measurements and in two randomly allocated quadrants at the two- and four-hour time points. Triclosan concentration was measured by HPLC. Antibacterial efficacy was evaluated in vitro using a biofilm formation approach. Three replicate experiments were carried out to check for repeatability and consistency of the assay. Toothpaste slurries were prepared by stirring one part by weight of each toothpaste with two parts by weight of deionized water. An overnight culture suspension of Streptococcus mutans (ATCC 25175) was prepared and then adjusted to give a bacterial count of approximately 10(7) CFU/ml. Sterile HAP discs were used as substrate and treated with the toothpaste slurry before inoculation with the standardized culture suspension of S. mutans. Following incubation in brain heart infusion (BHI) broth containing 2% sucrose for four hours, standard Total Viable Count (TVC) procedures were carried out and colonies counted (log10 values). Brushing with the new calcium carbonate/triclosan toothpaste resulted in a higher triclosan concentration in plaque after 10 minutes, and two and four hours compared to a marketed triclosan toothpaste. The increase ranged from 14% to 35% and was statistically significant (p < 0.05). The antibacterial efficacy of the new calcium carbonate/triclosan toothpaste, measured four hours after application, was greater than that of a marketed toothpaste with 0.3% triclosan. The difference was statistically significant (p < 0.05). The new calcium carbonate toothpaste with 0.3% triclosan and magnesium aluminium silicate demonstrated significantly greater efficacy four hours post-brushing both in terms of in vivo delivery and in vitro antibacterial action compared to a marketed calcium carbonate toothpaste with 0.3% triclosan.

Excess single-stranded DNA inhibits meiotic double-strand break repair.

PubMed

Johnson, Rebecca; Borde, Valérie; Neale, Matthew J; Bishop-Bailey, Anna; North, Matthew; Harris, Sheila; Nicolas, Alain; Goldman, Alastair S H

2007-11-01

During meiosis, self-inflicted DNA double-strand breaks (DSBs) are created by the protein Spo11 and repaired by homologous recombination leading to gene conversions and crossovers. Crossover formation is vital for the segregation of homologous chromosomes during the first meiotic division and requires the RecA orthologue, Dmc1. We analyzed repair during meiosis of site-specific DSBs created by another nuclease, VMA1-derived endonuclease (VDE), in cells lacking Dmc1 strand-exchange protein. Turnover and resection of the VDE-DSBs was assessed in two different reporter cassettes that can repair using flanking direct repeat sequences, thereby obviating the need for a Dmc1-dependent DNA strand invasion step. Access of the single-strand binding complex replication protein A, which is normally used in all modes of DSB repair, was checked in chromatin immunoprecipitation experiments, using antibody against Rfa1. Repair of the VDE-DSBs was severely inhibited in dmc1Delta cells, a defect that was associated with a reduction in the long tract resection required to initiate single-strand annealing between the flanking repeat sequences. Mutants that either reduce Spo11-DSB formation or abolish resection at Spo11-DSBs rescued the repair block. We also found that a replication protein A component, Rfa1, does not accumulate to expected levels at unrepaired single-stranded DNA (ssDNA) in dmc1Delta cells. The requirement of Dmc1 for VDE-DSB repair using flanking repeats appears to be caused by the accumulation of large quantities of ssDNA that accumulate at Spo11-DSBs when Dmc1 is absent. We propose that these resected DSBs sequester both resection machinery and ssDNA binding proteins, which in wild-type cells would normally be recycled as Spo11-DSBs repair. The implication is that repair proteins are in limited supply, and this could reflect an underlying mechanism for regulating DSB repair in wild-type cells, providing protection from potentially harmful effects of overabundant repair proteins.

Excess Single-Stranded DNA Inhibits Meiotic Double-Strand Break Repair

PubMed Central

Bishop-Bailey, Anna; North, Matthew; Harris, Sheila; Nicolas, Alain; Goldman, Alastair S. H

2007-01-01

During meiosis, self-inflicted DNA double-strand breaks (DSBs) are created by the protein Spo11 and repaired by homologous recombination leading to gene conversions and crossovers. Crossover formation is vital for the segregation of homologous chromosomes during the first meiotic division and requires the RecA orthologue, Dmc1.We analyzed repair during meiosis of site-specific DSBs created by another nuclease, VMA1-derived endonuclease (VDE), in cells lacking Dmc1 strand-exchange protein. Turnover and resection of the VDE-DSBs was assessed in two different reporter cassettes that can repair using flanking direct repeat sequences, thereby obviating the need for a Dmc1-dependent DNA strand invasion step. Access of the single-strand binding complex replication protein A, which is normally used in all modes of DSB repair, was checked in chromatin immunoprecipitation experiments, using antibody against Rfa1. Repair of the VDE-DSBs was severely inhibited in dmc1Δ cells, a defect that was associated with a reduction in the long tract resection required to initiate single-strand annealing between the flanking repeat sequences. Mutants that either reduce Spo11-DSB formation or abolish resection at Spo11-DSBs rescued the repair block. We also found that a replication protein A component, Rfa1, does not accumulate to expected levels at unrepaired single-stranded DNA (ssDNA) in dmc1Δ cells. The requirement of Dmc1 for VDE-DSB repair using flanking repeats appears to be caused by the accumulation of large quantities of ssDNA that accumulate at Spo11-DSBs when Dmc1 is absent. We propose that these resected DSBs sequester both resection machinery and ssDNA binding proteins, which in wild-type cells would normally be recycled as Spo11-DSBs repair. The implication is that repair proteins are in limited supply, and this could reflect an underlying mechanism for regulating DSB repair in wild-type cells, providing protection from potentially harmful effects of overabundant repair proteins. PMID:18081428

The Inherent Asymmetry of DNA Replication.

PubMed

Snedeker, Jonathan; Wooten, Matthew; Chen, Xin

2017-10-06

Semiconservative DNA replication has provided an elegant solution to the fundamental problem of how life is able to proliferate in a way that allows cells, organisms, and populations to survive and replicate many times over. Somewhat lost, however, in our admiration for this mechanism is an appreciation for the asymmetries that occur in the process of DNA replication. As we discuss in this review, these asymmetries arise as a consequence of the structure of the DNA molecule and the enzymatic mechanism of DNA synthesis. Increasing evidence suggests that asymmetries in DNA replication are able to play a central role in the processes of adaptation and evolution by shaping the mutagenic landscape of cells. Additionally, in eukaryotes, recent work has demonstrated that the inherent asymmetries in DNA replication may play an important role in the process of chromatin replication. As chromatin plays an essential role in defining cell identity, asymmetries generated during the process of DNA replication may play critical roles in cell fate decisions related to patterning and development.

The Alleged Crisis and the Illusion of Exact Replication.

PubMed

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. © The Author(s) 2013.

Back to the Origin

PubMed Central

Evertts, Adam G.

2012-01-01

In bacteria, replication is a carefully orchestrated event that unfolds the same way for each bacterium and each cell division. The process of DNA replication in bacteria optimizes cell growth and coordinates high levels of simultaneous replication and transcription. In metazoans, the organization of replication is more enigmatic. The lack of a specific sequence that defines origins of replication has, until recently, severely limited our ability to define the organizing principles of DNA replication. This question is of particular importance as emerging data suggest that replication stress is an important contributor to inherited genetic damage and the genomic instability in tumors. We consider here the replication program in several different organisms including recent genome-wide analyses of replication origins in humans. We review recent studies on the role of cytosine methylation in replication origins, the role of transcriptional looping and gene gating in DNA replication, and the role of chromatin’s 3-dimensional structure in DNA replication. We use these new findings to consider several questions surrounding DNA replication in metazoans: How are origins selected? What is the relationship between replication and transcription? How do checkpoints inhibit origin firing? Why are there early and late firing origins? We then discuss whether oncogenes promote cancer through a role in DNA replication and whether errors in DNA replication are important contributors to the genomic alterations and gene fusion events observed in cancer. We conclude with some important areas for future experimentation. PMID:23634256

Effects of Dietary Supplementation of Astaxanthin and Sesamin on Daily Fatigue: A Randomized, Double-Blind, Placebo-Controlled, Two-Way Crossover Study

PubMed Central

Imai, Ayano; Oda, Yuriko; Seki, Shinobu; Nakagawa, Kiyotaka; Miyazawa, Teruo; Ueda, Fumitaka

2018-01-01

Severe fatigue can negatively affect quality of life, and oxidative stress may play a role in its mechanism. The aim of this study was to evaluate the effect of dietary supplementation of astaxanthin and sesamin (AS), strong food-derived antioxidants, on fatigue. Twenty-four healthy volunteers were supplemented with AS and placebo, each for four weeks. After each supplementation period, participants underwent tasks inducing mental and physical fatigue (visual display terminal task and ergometer task, respectively). Subjective fatigue was evaluated using a visual analogue scale during and after the mental and physical tasks, and daily subjective fatigue was evaluated by the Chalder fatigue questionnaire. Secondary outcomes included other subjective feelings, work efficiency, autonomic nerve activity, levels of an oxidative stress marker (plasma phosphatidylcholine hydroperoxide (PCOOH)) and safety. AS supplementation was associated with significantly improved recovery from mental fatigue compared with placebo. Increased PCOOH levels during mental and physical tasks were attenuated by AS supplementation. No differences between AS and placebo were detected in secondary outcomes, and no adverse effects of AS supplementation were observed. In conclusion, AS supplementation may be a candidate to promote recovery from mental fatigue which is experienced by many healthy people. PMID:29495607

Human Genome Replication Proceeds through Four Chromatin States

PubMed Central

Julienne, Hanna; Zoufir, Azedine; Audit, Benjamin; Arneodo, Alain

2013-01-01

Advances in genomic studies have led to significant progress in understanding the epigenetically controlled interplay between chromatin structure and nuclear functions. Epigenetic modifications were shown to play a key role in transcription regulation and genome activity during development and differentiation or in response to the environment. Paradoxically, the molecular mechanisms that regulate the initiation and the maintenance of the spatio-temporal replication program in higher eukaryotes, and in particular their links to epigenetic modifications, still remain elusive. By integrative analysis of the genome-wide distributions of thirteen epigenetic marks in the human cell line K562, at the 100 kb resolution of corresponding mean replication timing (MRT) data, we identify four major groups of chromatin marks with shared features. These states have different MRT, namely from early to late replicating, replication proceeds though a transcriptionally active euchromatin state (C1), a repressive type of chromatin (C2) associated with polycomb complexes, a silent state (C3) not enriched in any available marks, and a gene poor HP1-associated heterochromatin state (C4). When mapping these chromatin states inside the megabase-sized U-domains (U-shaped MRT profile) covering about 50% of the human genome, we reveal that the associated replication fork polarity gradient corresponds to a directional path across the four chromatin states, from C1 at U-domains borders followed by C2, C3 and C4 at centers. Analysis of the other genome half is consistent with early and late replication loci occurring in separate compartments, the former correspond to gene-rich, high-GC domains of intermingled chromatin states C1 and C2, whereas the latter correspond to gene-poor, low-GC domains of alternating chromatin states C3 and C4 or long C4 domains. This new segmentation sheds a new light on the epigenetic regulation of the spatio-temporal replication program in human and provides a framework for further studies in different cell types, in both health and disease. PMID:24130466

A checkpoint control orchestrates the replication of the two chromosomes of Vibrio cholerae

PubMed Central

Val, Marie-Eve; Marbouty, Martial; de Lemos Martins, Francisco; Kennedy, Sean P.; Kemble, Harry; Bland, Michael J.; Possoz, Christophe; Koszul, Romain; Skovgaard, Ole; Mazel, Didier

2016-01-01

Bacteria with multiple chromosomes represent up to 10% of all bacterial species. Unlike eukaryotes, these bacteria use chromosome-specific initiators for their replication. In all cases investigated, the machineries for secondary chromosome replication initiation are of plasmid origin. One of the important differences between plasmids and chromosomes is that the latter replicate during a defined period of the cell cycle, ensuring a single round of replication per cell. Vibrio cholerae carries two circular chromosomes, Chr1 and Chr2, which are replicated in a well-orchestrated manner with the cell cycle and coordinated in such a way that replication termination occurs at the same time. However, the mechanism coordinating this synchrony remains speculative. We investigated this mechanism and revealed that initiation of Chr2 replication is triggered by the replication of a 150-bp locus positioned on Chr1, called crtS. This crtS replication–mediated Chr2 replication initiation mechanism explains how the two chromosomes communicate to coordinate their replication. Our study reveals a new checkpoint control mechanism in bacteria, and highlights possible functional interactions mediated by contacts between two chromosomes, an unprecedented observation in bacteria. PMID:27152358

Failure to replicate depletion of self-control.

PubMed

Xu, Xiaomeng; Demos, Kathryn E; Leahey, Tricia M; Hart, Chantelle N; Trautvetter, Jennifer; Coward, Pamela; Middleton, Kathryn R; Wing, Rena R

2014-01-01

The limited resource or strength model of self-control posits that the use of self-regulatory resources leads to depletion and poorer performance on subsequent self-control tasks. We conducted four studies (two with community samples, two with young adult samples) utilizing a frequently used depletion procedure (crossing out letters protocol) and the two most frequently used dependent measures of self-control (handgrip perseverance and modified Stroop). In each study, participants completed a baseline self-control measure, a depletion or control task (randomized), and then the same measure of self-control a second time. There was no evidence for significant depletion effects in any of these four studies. The null results obtained in four attempts to replicate using strong methodological approaches may indicate that depletion has more limited effects than implied by prior publications. We encourage further efforts to replicate depletion (particularly among community samples) with full disclosure of positive and negative results.

Combined Activity of DCL2 and DCL3 Is Crucial in the Defense against Potato Spindle Tuber Viroid

PubMed Central

Katsarou, Konstantina; Mavrothalassiti, Eleni; Dermauw, Wannes; Van Leeuwen, Thomas; Kalantidis, Kriton

2016-01-01

Viroids are self replicating non-coding RNAs capable of infecting a wide range of plant hosts. They do not encode any proteins, thus the mechanism by which they escape plant defenses remains unclear. RNAi silencing is a major defense mechanism against virus infections, with the four DCL proteins being principal components of the pathway. We have used Nicotiana benthamiana as a model to study Potato spindle tuber viroid infection. This viroid is a member of the Pospiviroidae family and replicates in the nucleus via an asymmetric rolling circle mechanism. We have created knock-down plants for all four DCL genes and their combinations. Previously, we showed that DCL4 has a positive effect on PSTVd infectivity since viroid levels drop when DCL4 is suppressed. Here, we show that PSTVd levels remain decreased throughout infection in DCL4 knockdown plants, and that simultaneous knockdown of DCL1, DCL2 or DCL3 together with DCL4 cannot reverse this effect. Through infection of plants suppressed for multiple DCLs we further show that a combined suppression of DCL2 and DCL3 has a major effect in succumbing plant antiviral defense. Based on our results, we further suggest that Pospoviroids may have evolved to be primarily processed by DCL4 as it seems to be a DCL protein with less detrimental effects on viroid infectivity. These findings pave the way to delineate the complexity of the relationship between viroids and plant RNA silencing response. PMID:27732664

Cognitive-Functional (Cog-Fun) Dyadic Intervention for Children with ADHD and Their Parents: Impact on Parenting Self-Efficacy.

PubMed

Hahn-Markowitz, Jeri; Berger, Itai; Manor, Iris; Maeir, Adina

2018-03-01

The family context of children with ADHD plays a role in intervention outcomes, especially when parents are involved in treatment. Parental participation in evidence-based treatment for ADHD may play a role in improving their own parenting self-efficacy (PSE) as well as child outcomes. This study examined the impact of Cognitive-Functional (Cog-Fun) intervention in occupational therapy (OT) for school-aged children with ADHD, on PSE. In this randomized controlled trial with crossover design, 107 children were allocated to intervention and waitlist control groups. Intervention participants (n = 50) received Cog-Fun after baseline assessment and waitlist controls (n = 49) received treatment 3 months later. Intervention participants received 3-month follow-up assessment. Treatment included 10 parent-child Cog-Fun weekly sessions. PSE was assessed with the Tool to measure Parenting Self-Efficacy (TOPSE). All children who began treatment completed it. Mixed ANOVA revealed significant Time x Group interaction effects on TOPSE scales of Play and Enjoyment, Control, Self-Acceptance, Knowledge and Learning and Total score, which showed significant improvement with moderate treatment effects for the intervention group. Results were replicated in the control group after crossover. The findings of this study suggest that Cog-Fun OT intervention may be effective for improving aspects of PSE among parents of children with ADHD.

The Kondo problem. II. Crossover from asymptotic freedom to infrared slavery

NASA Astrophysics Data System (ADS)

Schlottmann, P.

1982-04-01

In the preceding paper we transformed the s-d Hamiltonian onto a resonance level with a large perturbation and derived the scaling equations for the vertices, the invariant coupling, and the resonance width. The scaling equations are integrated under the assumption that the energy dependence of the resonance width can be neglected. The transcendental equation obtained in this way for the renormalized resonance width is solved in the relevant limits and allows a calculation of the static and dynamical susceptibility. At high temperatures the perturbation expansion for the relaxation rate and the susceptibility is reproduced up to third order in Jρ. At low temperatures the lifetime and χ0 remain finite and vary according to a Fermi-liquid theory. The approximation scheme interpolates in this way between the asymptotic freedom and the infrared slavery, yielding a smooth crossover. The present results are in quantitative agreement with previous ones obtained with the relaxation-kernel method by Götze and Schlottmann. The advantages and drawbacks of the method are discussed. The calculation of the dynamical susceptibility is extended to nonzero external magnetic fields. The quasielastic peak of χ''(ω)ω is suppressed at low temperatures and large magnetic fields and shoulders develop at ω=+/-B.

Enhanced bioavailability of EPA from emulsified fish oil preparations versus capsular triacylglycerol

USDA-ARS?s Scientific Manuscript database

Pre-emulsified fish oil supplements, an alternative to capsular triacylglycerol, may enhance the uptake of LCn3 fatty acids it contains. A randomized, Latin-square crossover design was used to compare the effects of four fish oil supplement preparations on phospholipid (PLFA) and chylomicron fatty ...

The histone codes for meiosis.

PubMed

Wang, Lina; Xu, Zhiliang; Khawar, Muhammad Babar; Liu, Chao; Li, Wei

2017-09-01

Meiosis is a specialized process that produces haploid gametes from diploid cells by a single round of DNA replication followed by two successive cell divisions. It contains many special events, such as programmed DNA double-strand break (DSB) formation, homologous recombination, crossover formation and resolution. These events are associated with dynamically regulated chromosomal structures, the dynamic transcriptional regulation and chromatin remodeling are mainly modulated by histone modifications, termed 'histone codes'. The purpose of this review is to summarize the histone codes that are required for meiosis during spermatogenesis and oogenesis, involving meiosis resumption, meiotic asymmetric division and other cellular processes. We not only systematically review the functional roles of histone codes in meiosis but also discuss future trends and perspectives in this field. © 2017 Society for Reproduction and Fertility.

Dynamical crossover in a stochastic model of cell fate decision

NASA Astrophysics Data System (ADS)

Yamaguchi, Hiroki; Kawaguchi, Kyogo; Sagawa, Takahiro

2017-07-01

We study the asymptotic behaviors of stochastic cell fate decision between proliferation and differentiation. We propose a model of a self-replicating Langevin system, where cells choose their fate (i.e., proliferation or differentiation) depending on local cell density. Based on this model, we propose a scenario for multicellular organisms to maintain the density of cells (i.e., homeostasis) through finite-ranged cell-cell interactions. Furthermore, we numerically show that the distribution of the number of descendant cells changes over time, thus unifying the previously proposed two models regarding homeostasis: the critical birth death process and the voter model. Our results provide a general platform for the study of stochastic cell fate decision in terms of nonequilibrium statistical mechanics.

The actin-like MreB cytoskeleton organizes viral DNA replication in bacteria.

PubMed

Muñoz-Espín, Daniel; Daniel, Richard; Kawai, Yoshikazu; Carballido-López, Rut; Castilla-Llorente, Virginia; Errington, Jeff; Meijer, Wilfried J J; Salas, Margarita

2009-08-11

Little is known about the organization or proteins involved in membrane-associated replication of prokaryotic genomes. Here we show that the actin-like MreB cytoskeleton of the distantly related bacteria Escherichia coli and Bacillus subtilis is required for efficient viral DNA replication. Detailed analyses of B. subtilis phage ϕ29 showed that the MreB cytoskeleton plays a crucial role in organizing phage DNA replication at the membrane. Thus, phage double-stranded DNA and components of the ϕ29 replication machinery localize in peripheral helix-like structures in a cytoskeleton-dependent way. Importantly, we show that MreB interacts directly with the ϕ29 membrane-protein p16.7, responsible for attaching viral DNA at the cell membrane. Altogether, the results reveal another function for the MreB cytoskeleton and describe a mechanism by which viral DNA replication is organized at the bacterial membrane.

Chromosome Duplication in Saccharomyces cerevisiae

PubMed Central

Bell, Stephen P.; Labib, Karim

2016-01-01

The accurate and complete replication of genomic DNA is essential for all life. In eukaryotic cells, the assembly of the multi-enzyme replisomes that perform replication is divided into stages that occur at distinct phases of the cell cycle. Replicative DNA helicases are loaded around origins of DNA replication exclusively during G1 phase. The loaded helicases are then activated during S phase and associate with the replicative DNA polymerases and other accessory proteins. The function of the resulting replisomes is monitored by checkpoint proteins that protect arrested replisomes and inhibit new initiation when replication is inhibited. The replisome also coordinates nucleosome disassembly, assembly, and the establishment of sister chromatid cohesion. Finally, when two replisomes converge they are disassembled. Studies in Saccharomyces cerevisiae have led the way in our understanding of these processes. Here, we review our increasingly molecular understanding of these events and their regulation. PMID:27384026

Symmetry of interactions rules in incompletely connected random replicator ecosystems.

PubMed

Kärenlampi, Petri P

2014-06-01

The evolution of an incompletely connected system of species with speciation and extinction is investigated in terms of random replicators. It is found that evolving random replicator systems with speciation do become large and complex, depending on speciation parameters. Antisymmetric interactions result in large systems, whereas systems with symmetric interactions remain small. A co-dominating feature is within-species interaction pressure: large within-species interaction increases species diversity. Average fitness evolves in all systems, however symmetry and connectivity evolve in small systems only. Newcomers get extinct almost immediately in symmetric systems. The distribution in species lifetimes is determined for antisymmetric systems. The replicator systems investigated do not show any sign of self-organized criticality. The generalized Lotka-Volterra system is shown to be a tedious way of implementing the replicator system.

Predictive display design for the vehicles with time delay in dynamic response

NASA Astrophysics Data System (ADS)

Efremov, A. V.; Tiaglik, M. S.; Irgaleev, I. H.; Efremov, E. V.

2018-02-01

The two ways for the improvement of flying qualities are considered: the predictive display (PD) and the predictive display integrated with the flight control system (FCS). The both ways allow to transforming the controlled element dynamics in the crossover frequency range, to improve the accuracy of tracking and to suppress the effect of time delay in the vehicle response too. The technique for optimization of the predictive law is applied to the landing task. The results of the mathematical modeling and experimental investigations carried out for this task are considered in the paper.

Aldosterone changes after consumption of a sodium-bicarbonated mineral water in humans. A four-way randomized controlled trial.

PubMed

Toxqui, Laura; Vaquero, M Pilar

2016-12-01

Abnormally high aldosterone levels are associated to hypertension and cardiovascular disease. A sodium-rich mineral water was previously shown to reduce several markers of cardiovascular risk and did not increase blood pressure in healthy adults. We aimed to study the effects of consuming the same mineral water compared to a control water on aldosterone levels, and if the effects vary due to the presence of meal in healthy adults. The design was a four-way randomized controlled crossover 120-min-postprandial trial. Twenty-one healthy men and women participated in the study. Exclusion criteria are diabetes, hypertension, and being a usual consumer of carbonic mineral water. Two different mineral waters, high-sodium and bicarbonate mineral water (BW, sodium, 1 g/L; bicarbonate, 2 g/L) and low-mineral content control water (CW), were consumed with or without a standard meal (500 mL per meal). Statistical analysis was performed by repeated measures ANOVA. The results are as follows: serum sodium did not vary, and serum potassium decreased throughout the assay (p = 0.01) without water influence. Consumption of BW significantly decreased aldosterone levels at 30 (p = 0.046), 60 (p = 0.009), and 120 (p = 0.025) min when consumed alone, and at 120 min (p = 0.019) when consumed with meal, compared to CW. Moreover, the effect of BW on aldosterone levels was significant in women but not in men. In conclusion, consumption of a sodium-bicarbonated mineral water, in presence or absence of meal, induces aldosterone inhibition in healthy women, which is suggested to be a physiological response that protects them against hypertension. This trial is registered at clinicaltrial.gov as NCT01334840.

Top 10 Replicated Findings from Behavioral Genetics

PubMed Central

Plomin, Robert; DeFries, John C.; Knopik, Valerie S.; Neiderhiser, Jenae M.

2015-01-01

In the context of current concerns about replication in psychological science, we describe 10 findings from behavioral genetic research that have robustly replicated. These are ‘big’ findings, both in terms of effect size and potential impact on psychological science, such as linearly increasing heritability of intelligence from infancy (20%) through adulthood (60%). Four of our top-10 findings involve the environment, discoveries that could only have been found using genetically sensitive research designs. We also consider reasons specific to behavioral genetics that might explain why these findings replicate. PMID:26817721

Clinical pharmacokinetics of Icotinib, an anti-cancer drug: evaluation of dose proportionality, food effect, and tolerability in healthy subjects.

PubMed

Liu, Dongyang; Jiang, Ji; Zhang, Li; Tan, Fenlai; Wang, Yingxiang; Zhang, Don; Hu, Pei

2014-04-01

Icotinib, an oral epidermal growth factor receptor tyrosine kinase inhibitor, has proved effectiveness in xenografted nude mice. Purpose of the present studies was to investigate tolerability and pharmacokinetics of Icotinib in healthy subjects for the first time, including dose proportionality, food effect, and tolerability. Two studies were conducted in total of 22 healthy subjects: a randomized, two-Latin-square crossover, dose proportional study (n = 12) and a randomized two-way crossover food-effect study (n = 10). Plasma concentration of Icotinib reached peak at a median Tmax of 0.75-3.5 h after single dose and then declined with a mean t1/2β of 6.02-7.83 h. Over the dose range of 100-600 mg, AUC values were proportional to dose and Cmax showed a slight saturation when dose increases. Only 0.2 % of the dose was excreted through kidney in unchanged Icotinib. After dosing 400 mg of Icotinib with high-fat and high-calorie meal, mean Cmax and AUC were significantly increased by 59 and 79 %, respectively. Three subjects experienced four adverse events (rash, increase in AST and ALT, and external injury). Rash and increased levels of AST and ALT were considered as drug-related. No serious adverse events were reported. The current work demonstrated that Icotinib was well tolerated in healthy male subjects (n = 22) over the dose range of 100-600 mg with or without food. Icotinib exposure, expressed in AUC, was proportionally increased with dose over the above dose range. Food intake significantly increased the absorption and exposure of Icotinib in healthy subjects.

The effect of food on the pharmacokinetics of oral ibrutinib in healthy participants and patients with chronic lymphocytic leukemia.

PubMed

de Jong, Jan; Sukbuntherng, Juthamas; Skee, Donna; Murphy, Joe; O'Brien, Susan; Byrd, John C; James, Danelle; Hellemans, Peter; Loury, David J; Jiao, Juhui; Chauhan, Vijay; Mannaert, Erik

2015-05-01

To assess ibrutinib pharmacokinetics under fasted and fed conditions, impact of food-intake timing, and the safety and tolerability. Three studies were analyzed. Study 1 was a randomized, open-label, single-dose, four-way crossover study in 44 healthy participants. Study 2 was a randomized, repeat-dose crossover study in 16 patients with previously treated chronic lymphocytic leukemia (CLL). Ibrutinib dose was 420 mg in both studies. Study 3 was an open-label, sequential study to assess the effect of a standard breakfast on ibrutinib 560 mg in eight healthy participants. Administration of single-dose ibrutinib under fasting conditions (study 1) resulted in approximately 60 % of exposure compared with drug intake either 30 min before, 30 min after (fed), or 2 h after a high-fat meal. Similar food effect was observed (study 3) when ibrutinib was given 30 min before meal. In CLL patients (study 2), the C max and AUC under fasting conditions were 43 and 61 %, respectively, relative to fed conditions. When administered once-daily in uncontrolled food-intake conditions (≥30 min before or 2 h after), exposures were slightly (≈30 %) lower than in fed condition. When corrected for repeated dosing, pharmacokinetic parameters in healthy participants and patients were comparable. Ibrutinib was generally well tolerated in all settings studied. Ibrutinib administered in fasted condition reduces exposure to approximately 60 % as compared with dosing in proximity to food-intake, regardless of timing/type of meal. Because repeated drug intake in fasted condition is unlikely, no food restrictions may be needed to administer ibrutinib.

Protein Phosphatase 4 Promotes Chromosome Pairing and Synapsis, and Contributes to Maintaining Crossover Competence with Increasing Age

PubMed Central

Sato-Carlton, Aya; Li, Xuan; Crawley, Oliver; Testori, Sarah; Martinez-Perez, Enrique; Sugimoto, Asako; Carlton, Peter M.

2014-01-01

Prior to the meiotic divisions, dynamic chromosome reorganizations including pairing, synapsis, and recombination of maternal and paternal chromosome pairs must occur in a highly regulated fashion during meiotic prophase. How chromosomes identify each other's homology and exclusively pair and synapse with their homologous partners, while rejecting illegitimate synapsis with non-homologous chromosomes, remains obscure. In addition, how the levels of recombination initiation and crossover formation are regulated so that sufficient, but not deleterious, levels of DNA breaks are made and processed into crossovers is not understood well. We show that in Caenorhabditis elegans, the highly conserved Serine/Threonine protein phosphatase PP4 homolog, PPH-4.1, is required independently to carry out four separate functions involving meiotic chromosome dynamics: (1) synapsis-independent chromosome pairing, (2) restriction of synapsis to homologous chromosomes, (3) programmed DNA double-strand break initiation, and (4) crossover formation. Using quantitative imaging of mutant strains, including super-resolution (3D-SIM) microscopy of chromosomes and the synaptonemal complex, we show that independently-arising defects in each of these processes in the absence of PPH-4.1 activity ultimately lead to meiotic nondisjunction and embryonic lethality. Interestingly, we find that defects in double-strand break initiation and crossover formation, but not pairing or synapsis, become even more severe in the germlines of older mutant animals, indicating an increased dependence on PPH-4.1 with increasing maternal age. Our results demonstrate that PPH-4.1 plays multiple, independent roles in meiotic prophase chromosome dynamics and maintaining meiotic competence in aging germlines. PP4's high degree of conservation suggests it may be a universal regulator of meiotic prophase chromosome dynamics. PMID:25340746

Dynamic and thermodynamic crossover scenarios in the Kob-Andersen mixture: Insights from multi-CPU and multi-GPU simulations.

PubMed

Coslovich, Daniele; Ozawa, Misaki; Kob, Walter

2018-05-17

The physical behavior of glass-forming liquids presents complex features of both dynamic and thermodynamic nature. Some studies indicate the presence of thermodynamic anomalies and of crossovers in the dynamic properties, but their origin and degree of universality is difficult to assess. Moreover, conventional simulations are barely able to cover the range of temperatures at which these crossovers usually occur. To address these issues, we simulate the Kob-Andersen Lennard-Jones mixture using efficient protocols based on multi-CPU and multi-GPU parallel tempering. Our setup enables us to probe the thermodynamics and dynamics of the liquid at equilibrium well below the critical temperature of the mode-coupling theory, [Formula: see text]. We find that below [Formula: see text] the analysis is hampered by partial crystallization of the metastable liquid, which nucleates extended regions populated by large particles arranged in an fcc structure. By filtering out crystalline samples, we reveal that the specific heat grows in a regular manner down to [Formula: see text] . Possible thermodynamic anomalies suggested by previous studies can thus occur only in a region of the phase diagram where the system is highly metastable. Using the equilibrium configurations obtained from the parallel tempering simulations, we perform molecular dynamics and Monte Carlo simulations to probe the equilibrium dynamics down to [Formula: see text]. A temperature-derivative analysis of the relaxation time and diffusion data allows us to assess different dynamic scenarios around [Formula: see text]. Hints of a dynamic crossover come from analysis of the four-point dynamic susceptibility. Finally, we discuss possible future numerical strategies to clarify the nature of crossover phenomena in glass-forming liquids.

Mechanisms of mutagenesis: DNA replication in the presence of DNA damage

PubMed Central

Liu, Binyan; Xue, Qizhen; Tang, Yong; Cao, Jia; Guengerich, F. Peter; Zhang, Huidong

2017-01-01

Environmental mutagens cause DNA damage that disturbs replication and produces mutations, leading to cancer and other diseases. We discuss mechanisms of mutagenesis resulting from DNA damage, from the level of DNA replication by a single polymerase to the complex DNA replisome of some typical model organisms (including bacteriophage T7, T4, Sulfolobus solfataricus, E. coli, yeast and human). For a single DNA polymerase, DNA damage can affect replication in three major ways: reducing replication fidelity, causing frameshift mutations, and blocking replication. For the DNA replisome, protein interactions and the functions of accessory proteins can yield rather different results even with a single DNA polymerase. The mechanism of mutation during replication performed by the DNA replisome is a long-standing question. Using new methods and techniques, the replisomes of certain organisms and human cell extracts can now be investigated with regard to the bypass of DNA damage. In this review, we consider the molecular mechanism of mutagenesis resulting from DNA damage in replication at the levels of single DNA polymerases and complex DNA replisomes, including translesion DNA synthesis. PMID:27234563

Mechanisms of mutagenesis: DNA replication in the presence of DNA damage.

PubMed

Liu, Binyan; Xue, Qizhen; Tang, Yong; Cao, Jia; Guengerich, F Peter; Zhang, Huidong

2016-01-01

Environmental mutagens cause DNA damage that disturbs replication and produces mutations, leading to cancer and other diseases. We discuss mechanisms of mutagenesis resulting from DNA damage, from the level of DNA replication by a single polymerase to the complex DNA replisome of some typical model organisms (including bacteriophage T7, T4, Sulfolobus solfataricus, Escherichia coli, yeast and human). For a single DNA polymerase, DNA damage can affect replication in three major ways: reducing replication fidelity, causing frameshift mutations, and blocking replication. For the DNA replisome, protein interactions and the functions of accessory proteins can yield rather different results even with a single DNA polymerase. The mechanism of mutation during replication performed by the DNA replisome is a long-standing question. Using new methods and techniques, the replisomes of certain organisms and human cell extracts can now be investigated with regard to the bypass of DNA damage. In this review, we consider the molecular mechanism of mutagenesis resulting from DNA damage in replication at the levels of single DNA polymerases and complex DNA replisomes, including translesion DNA synthesis. Copyright © 2016 Elsevier B.V. All rights reserved.

Whole-genome analysis of genetic recombination of hepatitis delta virus: molecular domain in delta antigen determining trans-activating efficiency.

PubMed

Chao, Mei; Lin, Chia-Chi; Lin, Feng-Ming; Li, Hsin-Pai; Iang, Shan-Bei

2015-12-01

Hepatitis delta virus (HDV) is the only animal RNA virus that has an unbranched rod-like genome with ribozyme activity and is replicated by host RNA polymerase. HDV RNA recombination was previously demonstrated in patients and in cultured cells by analysis of a region corresponding to the C terminus of the delta antigen (HDAg), the only viral-encoded protein. Here, a whole-genome recombination map of HDV was constructed using an experimental system in which two HDV-1 sequences were co-transfected into cultured cells and the recombinants were analysed by sequencing of cloned reverse transcription-PCR products. Fifty homologous recombinants with 60 crossovers mapping to 22 junctions were identified from 200 analysed clones. Small HDAg chimeras harbouring a junction newly detected in the recombination map were then constructed. The results further indicated that the genome-replication level of HDV was sensitive to the sixth amino acid within the N-terminal 22 aa of HDAg. Therefore, the recombination map established in this study provided a tool for not only understanding HDV RNA recombination, but also elucidating the related mechanisms, such as molecular elements responsible for the trans-activation levels of the small HDAg.

A Comparison of Intention and Pantomime Gesture Treatment for Noun Retrieval in People with Aphasia

ERIC Educational Resources Information Center

Ferguson, Neina F.; Evans, Kelli; Raymer, Anastasia M.

2012-01-01

Purpose: The effects of intention gesture treatment (IGT) and pantomime gesture treatment (PGT) on word retrieval were compared in people with aphasia. Method: Four individuals with aphasia and word retrieval impairments subsequent to left-hemisphere stroke participated in a single-participant crossover treatment design. Each participant viewed…

Enquire within: cultural evolution and cognitive science.

PubMed

Heyes, Cecilia

2018-04-05

Cultural evolution and cognitive science need each other. Cultural evolution needs cognitive science to find out whether the conditions necessary for Darwinian evolution are met in the cultural domain. Cognitive science needs cultural evolution to explain the origins of distinctively human cognitive processes. Focusing on the first question, I argue that cultural evolutionists can get empirical traction on third-way cultural selection by rooting the distinction between replication and reconstruction, two modes of cultural inheritance, in the distinction between System 1 and System 2 cognitive processes. This move suggests that cultural epidemiologists are right in thinking that replication has higher fidelity than reconstruction, and replication processes are not genetic adaptations for culture, but wrong to assume that replication is rare. If replication is not rare, an important requirement for third-way cultural selection, one-shot fidelity , is likely to be met. However, there are other requirements, overlooked by dual-inheritance theorists when they conflate strong (Darwinian) and weak (choice) senses of 'cultural selection', including dumb choices and recurrent fidelity In a second excursion into cognitive science, I argue that these requirements can be met by metacognitive social learning strategies , and trace the origins of these distinctively human cognitive processes to cultural evolution. Like other forms of cultural learning, they are not cognitive instincts but cognitive gadgets.This article is part of the theme issue 'Bridging cultural gaps: interdisciplinary studies in human cultural evolution'. © 2018 The Author(s).

Design and evaluation of an aerial spray trial with true replicates to test the efficacy of Bacillus thuringiensis insecticide in a boreal forest.

PubMed

Cadogan, Beresford L; Scharbach, Roger D

2003-04-01

A field trial using true replicates was conducted successfully in a boreal forest in 1996 to evaluate the efficacy of two aerially applied Bacillus thuringiensis formulations, ABG 6429 and ABG 6430. A complete randomized design with four replicates per treatment was chosen. Twelve to 15 balsam fir (Abies balsamea [L.] Mill.) per plot were randomly selected as sample trees. Interplot buffer zones, > or = 200 m wide, adequately prevented cross contamination from sprays that were atomized with four rotary atomizers (volume median diameters ranging from 64.6 to 139.4 microm) and released approximately 30 m above the ground. The B. thuringiensis formulations were not significantly different (P > 0.05) from each other in reducing spruce budworm (Choristoneura fumiferana [Clem.]) populations and protecting balsam trees from defoliation but both formulations were significantly more efficacious than the controls. The results suggest that true replicates are a feasible alternative to pseudoreplication in experimental forest aerial applications.

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

PubMed

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

2018-02-01

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

Roles of the first and second round of DNA replication in the regulation of zygotic gene activation in mice.

PubMed

Sonehara, Hiroki; Nagata, Masao; Aoki, Fugaku

2008-10-01

In the mouse embryo, expression of zygotic genes starts in the S/G2 phase of the 1-cell stage and greatly increases during the 2-cell stage. Although the timing of zygotic gene activation (ZGA) is thus established, the mechanism regulating ZGA is poorly understood. Previous studies using reporter genes have suggested that a transcriptionally repressive state is established during the 2-cell stage and that the first and second rounds of DNA replication are involved in this process. To further elucidate the respective roles of the two rounds of DNA replication in ZGA, we analyzed the expression of four ZGA genes (hsp70.1, eif-1a, muerv and zscan4d) in embryos whose DNA replication was inhibited by treatment with aphidicolin, an inhibitor of DNA polymerase. Inhibiting the first round increased the expression levels of hsp70.1, eif-1a and zscan4d but decreased that of muerv, while inhibiting the second round increased the expression levels of all four genes. These results suggest that the transcriptionally repressive state seems to be established after the second round of DNA replication.

Contributions of societal modernity to cognitive development: a comparison of four cultures.

PubMed

Gauvain, Mary; Munroe, Robert L

2009-01-01

This study examined how societal changes associated with modernization are related to cognitive development. Data were from 4 cultural communities that represented a broad range of traditional and modern elements: the Garifuna (Belize), Logoli (Kenya), Newars (Nepal), and Samoans (American Samoa). Naturalistic observations and the performances of 3-, 5-, 7-, and 9-year-old children (N = 192) on 7 cognitive measures were examined. Results replicated age-related improvement on all measures. Contributions of modernity were evident in children's play behaviors and cognitive performances, especially in skills related to schooling. Modernization and schooling independently predicted differences on most of the measures. Results are discussed in relation to the Flynn effect, the worldwide increase in cognitive scores across generations, and the ways in which societal modernization may contribute to cognitive development.

Adaptation to the Spanish population of the Substance Use Risk Profile Scale (SURPS) and psychometric properties.

PubMed

Fernández-Calderón, Fermín; Díaz-Batanero, Carmen; Rojas-Tejada, Antonio J; Castellanos-Ryan, Natalie; Lozano-Rojas, Óscar M

2017-07-14

The identification of different personality risk profiles for substance misuse is useful in preventing substance-related problems. This study aims to test the psychometric properties of a new version of the Substance Use Risk Profile Scale (SURPS) for Spanish college students. Cross-sectional study with 455 undergraduate students from four Spanish universities. A new version of the SURPS, adapted to the Spanish population, was administered with the Beck Hopelessness Scale, the UPPS-P Impulsive Behavior Scale, the State-Trait Anxiety Inventory (STAI) and the Alcohol Use Disorders Identification Test (AUDIT). Internal consistency reliability ranged between 0.652 and 0.806 for the four SURPS subscales, while reliability estimated by split-half coefficients varied from 0.686 to 0.829. The estimated test-retest reliability ranged between 0.733 and 0.868. The expected four-factor structure of the original scale was replicated. As evidence of convergent validity, we found that the SURPS subscales were significantly associated with other conceptually-relevant personality scales and significantly associated with alcohol use measures in theoretically-expected ways. This SURPS version may be a useful instrument for measuring personality traits related to vulnerability to substance use and misuse when targeting personality with preventive interventions.

Improved Balance Confidence and Stability for Elderly After 6 Weeks of a Multimodal Self-Administered Balance-Enhancing Exercise Program

PubMed Central

Hafström, Anna; Malmström, Eva-Maj; Terdèn, Josefine; Fransson, Per-Anders; Magnusson, Måns

2016-01-01

Objective: To develop and assess the efficacy of a multimodal balance-enhancing exercise program (BEEP) designed to be regularly self-administered by community-dwelling elderly. The program aims to promote sensory reweighting, facilitate motor control, improve gaze stabilization, and stimulate continuous improvement by being constantly challenging. Method: Forty participants aged 60 to 80 years performed 6 weeks of BEEP training, on average for 16 min four times weekly, in a randomized one-arm crossover design. Results: One-leg standing time improved 32% with eyes open (EO), 206% with eyes closed (EC) on solid surface, and 54% EO on compliant surface (p < .001). Posturography confirmed balance improvements when perturbed on solid and compliant surfaces with EO and EC (p ≤ .033). Walking, step stool, and Timed Up and Go speeds increased (p ≤ .001), as did scores in Berg Balance and balance confidence scales (p ≤ .018). Discussion: Multimodal balance exercises offer an efficient, cost-effective way to improve balance control and confidence in elderly. PMID:28138495

Do saw palmetto extracts block human alpha1-adrenoceptor subtypes in vivo?

PubMed

Goepel, M; Dinh, L; Mitchell, A; Schäfers, R F; Rübben, H; Michel, M C

2001-02-15

To test whether saw palmetto extracts, which act as alpha1-adrenoceptor antagonists in vitro, also do so in vivo in man. In a placebo-controlled, double-blind, four-way cross-over study 12 healthy young men were treated with three different saw palmetto extract preparations (320 mg o.d.) for 8 days each. On the last day, before and 2, 4 and 6 hr after drug intake blood pressure and heart rate were determined and blood samples obtained, which were used in an ex vivo radioreceptor assay with cloned human alpha1-adrenoceptor subtypes. Saw palmetto extract treatment did not result in alpha1-adrenoceptor subtype occupancy in the radioreceptor assay. Although the saw palmetto extracts caused minor reductions of supine blood pressure, they did not affect blood pressure during orthostatic stress testing and did not alter heart rate under either condition. Moreover, plasma catecholamines remained largely unaltered. Despite their alpha1-adrenoceptor antagonist effects in vitro, therapeutically used doses of saw palmetto extracts do not cause alpha1-adrenoceptor antagonism in man in vivo. Copyright 2001 Wiley-Liss, Inc.

Characteristics of the sequence effect in Parkinson's disease.

PubMed

Kang, Suk Yun; Wasaka, Toshiaki; Shamim, Ejaz A; Auh, Sungyoung; Ueki, Yoshino; Lopez, Grisel J; Kida, Tetsuo; Jin, Seung-Hyun; Dang, Nguyet; Hallett, Mark

2010-10-15

The sequence effect (SE) in Parkinson's disease (PD) is progressive slowing of sequential movements. It is a feature of bradykinesia, but is separate from a general slowness without deterioration over time. It is commonly seen in PD, but its physiology is unclear. We measured general slowness and the SE separately with a computer-based, modified Purdue pegboard in 11 patients with advanced PD. We conducted a placebo-controlled, four-way crossover study to learn whether levodopa and repetitive transcranial magnetic stimulation (rTMS) could improve general slowness or the SE. We also examined the correlation between the SE and clinical fatigue. Levodopa alone and rTMS alone improved general slowness, but rTMS showed no additive effect on levodopa. Levodopa alone, rTMS alone, and their combination did not alleviate the SE. There was no correlation between the SE and fatigue. This study suggests that dopaminergic dysfunction and abnormal motor cortex excitability are not the relevant mechanisms for the SE. Additionally, the SE is not a component of clinical fatigue. Further work is needed to establish the physiology and clinical relevance of the SE. © 2010 Movement Disorder Society.

Peer Assessment Enhances Student Learning: The Results of a Matched Randomized Crossover Experiment in a College Statistics Class.

PubMed

Sun, Dennis L; Harris, Naftali; Walther, Guenther; Baiocchi, Michael

2015-01-01

Feedback has a powerful influence on learning, but it is also expensive to provide. In large classes it may even be impossible for instructors to provide individualized feedback. Peer assessment is one way to provide personalized feedback that scales to large classes. Besides these obvious logistical benefits, it has been conjectured that students also learn from the practice of peer assessment. However, this has never been conclusively demonstrated. Using an online educational platform that we developed, we conducted an in-class matched-set, randomized crossover experiment with high power to detect small effects. We establish that peer assessment causes a small but significant gain in student achievement. Our study also demonstrates the potential of web-based platforms to facilitate the design of high-quality experiments to identify small effects that were previously not detectable.

ESR and PALS detection of the dynamic crossover in the supercooled liquid states of short and medium-sized n-alkanes

NASA Astrophysics Data System (ADS)

Bartoš, J.; Zgardzinska, B.; Švajdlenková, H.; Lukešová, M.; Zaleski, R.

2018-05-01

A joint study of the spin probe TEMPO dynamics by ESR and the annihilation rate of ortho-positronium by PALS in four short-and medium-sized n-alkanes is presented. In addition to the usually observed changes in both the reorientation dynamics and size of free volumes at the temperature of melting, Tm, and solid-solid phase transition, Tss, an additional coincidence between the characteristic ESR and PALS temperatures TX1fast ≅ Tb1sol < Tm, Tss was found. The phenomenological analysis of the viscosity data of n-alkanes using the power law equation indicates a presence of locally disordered regions in which the dynamic change occurs at the crossover temperature TX ≅ TX1fast ≅ Tb1sol.

Quantum fluctuations in the BCS-BEC crossover of two-dimensional Fermi gases

DOE Office of Scientific and Technical Information (OSTI.GOV)

He, Lianyi; Lu, Haifeng; Cao, Gaoqing

2015-08-14

We present a theoretical study of the ground state of the BCS-BEC crossover in dilute two-dimensional Fermi gases. While the mean-field theory provides a simple and analytical equation of state, the pressure is equal to that of a noninteracting Fermi gas in the entire BCS-BEC crossover, which is not consistent with the features of a weakly interacting Bose condensate in the BEC limit and a weakly interacting Fermi liquid in the BCS limit. The inadequacy of the two-dimensional mean-field theory indicates that the quantum fluctuations are much more pronounced than those in three dimensions. In this work, we show thatmore » the inclusion of the Gaussian quantum fluctuations naturally recovers the above features in both the BEC and the BCS limits. In the BEC limit, the missing logarithmic dependence on the boson chemical potential is recovered by the quantum fluctuations. Near the quantum phase transition from the vacuum to the BEC phase, we compare our equation of state with the known grand canonical equation of state of two-dimensional Bose gases and determine the ratio of the composite boson scattering length a B to the fermion scattering length a 2D. We find a B ≃ 0.56a 2D, in good agreement with the exact four-body calculation. As a result, we compare our equation of state in the BCS-BEC crossover with recent results from the quantum Monte Carlo simulations and the experimental measurements and find good agreements.« less

Performance and microbial ecology of air-cathode microbial fuel cells with layered electrode assemblies.

PubMed

Butler, Caitlyn S; Nerenberg, Robert

2010-05-01

Microbial fuel cells (MFCs) can be built with layered electrode assemblies, where the anode, proton exchange membrane (PEM), and cathode are pressed into a single unit. We studied the performance and microbial community structure of MFCs with layered assemblies, addressing the effect of materials and oxygen crossover on the community structure. Four MFCs with layered assemblies were constructed using Nafion or Ultrex PEMs and a plain carbon cloth electrode or a cathode with an oxygen-resistant polytetrafluoroethylene diffusion layer. The MFC with Nafion PEM and cathode diffusion layer achieved the highest power density, 381 mW/m(2) (20 W/m(3)). The rates of oxygen diffusion from cathode to anode were three times higher in the MFCs with plain cathodes compared to those with diffusion-layer cathodes. Microsensor studies revealed little accumulation of oxygen within the anode cloth. However, the abundance of bacteria known to use oxygen as an electron acceptor, but not known to have exoelectrogenic activity, was greater in MFCs with plain cathodes. The MFCs with diffusion-layer cathodes had high abundance of exoelectrogenic bacteria within the genus Geobacter. This work suggests that cathode materials can significantly influence oxygen crossover and the relative abundance of exoelectrogenic bacteria on the anode, while PEM materials have little influence on anode community structure. Our results show that oxygen crossover can significantly decrease the performance of air-cathode MFCs with layered assemblies, and therefore limiting crossover may be of particular importance for these types of MFCs.

Atomic-scale dynamics of a model glass-forming metallic liquid: Dynamical crossover, dynamical decoupling, and dynamical clustering

DOE PAGES

Jaiswal, Abhishek; Egami, Takeshi; Zhang, Yang

2015-04-01

The phase behavior of multi-component metallic liquids is exceedingly complex because of the convoluted many-body and many-elemental interactions. Herein, we present systematic studies of the dynamic aspects of such a model ternary metallic liquid Cu 40Zr 51Al 9 using molecular dynamics simulation with embedded atom method. We observed a dynamical crossover from Arrhenius to super-Arrhenius behavior in the transport properties (diffusion coefficient, relaxation times, and shear viscosity) bordered at T x ~1300K. Unlike in many molecular and macromolecular liquids, this crossover phenomenon occurs in the equilibrium liquid state well above the melting temperature of the system (T m ~ 900K),more » and the crossover temperature is roughly twice of the glass-transition temperature (T g). Below T x, we found the elemental dynamics decoupled and the Stokes-Einstein relation broke down, indicating the onset of heterogeneous spatially correlated dynamics in the system mediated by dynamic communications among local configurational excitations. To directly characterize and visualize the correlated dynamics, we employed a non-parametric, unsupervised machine learning technique and identified dynamical clusters of atoms with similar atomic mobility. The revealed average dynamical cluster size shows an accelerated increase below T x and mimics the trend observed in other ensemble averaged quantities that are commonly used to quantify the spatially heterogeneous dynamics such as the non-Gaussian parameter and the four-point correlation function.« less

Numerical Investigations of the Thermal, Pressure and Size Effects on 2D Spin Crossover Nanoparticles

NASA Astrophysics Data System (ADS)

Harlé, C.; Allal, S. E.; Sohier, D.; Dufaud, T.; Caballero, R.; de Zela, F.; Dahoo, P. R.; Boukheddaden, K.; Linares, J.

2017-12-01

In the framework of the Ising-like model, the thermal and pressure effects on the spin crossover systems are evaluated through two-states fictitious spin operators σ with eigenvalues 𝜎 = -1 and 𝜎 = +1 respectively associated with the low-spin (LS) and highspin (HS) states of each spin-crossover (SCO) molecule. Based on each configurational state, the macroscopic SCO system, is described by the following variables: m=Σ σi, s=Σ σi σj and c=Σ σk standing respectively for the total magnetization, the short-range correlations and surface magnetization. To solve this problem, we first determine the density of macrostates d[m][s][c], giving the number of microscopic configurations with the same m, s and c values. In this contribution, two different ways have been performed to calculate this important quantity: (i) the entropic sampling method, based on Monte Carlo simulations and (ii) a new algorithm based on specific dynamic programming. These two methods were tested on the 2D SCO nanoparticles for which, we calculated the average magnetization < σ> taking into account for short-, long-range interactions as well as for the interaction between surface molecules with their surrounding matrix. We monitored the effect of the pressure, temperature and size on the properties of the SCO nanoparticles.

Evolutionarily diverse determinants of meiotic DNA break and recombination landscapes across the genome

PubMed Central

Fowler, Kyle R.; Sasaki, Mariko; Milman, Neta

2014-01-01

Fission yeast Rec12 (Spo11 homolog) initiates meiotic recombination by forming developmentally programmed DNA double-strand breaks (DSBs). DSB distributions influence patterns of heredity and genome evolution, but the basis of the highly nonrandom choice of Rec12 cleavage sites is poorly understood, largely because available maps are of relatively low resolution and sensitivity. Here, we determined DSBs genome-wide at near-nucleotide resolution by sequencing the oligonucleotides attached to Rec12 following DNA cleavage. The single oligonucleotide size class allowed us to deeply sample all break events. We find strong evidence across the genome for differential DSB repair accounting for crossover invariance (constant cM/kb in spite of DSB hotspots). Surprisingly, about half of all crossovers occur in regions where DSBs occur at low frequency and are widely dispersed in location from cell to cell. These previously undetected, low-level DSBs thus play an outsized and crucial role in meiosis. We further find that the influence of underlying nucleotide sequence and chromosomal architecture differs in multiple ways from that in budding yeast. DSBs are not strongly restricted to nucleosome-depleted regions, as they are in budding yeast, but are nevertheless spatially influenced by chromatin structure. Our analyses demonstrate that evolutionarily fluid factors contribute to crossover initiation and regulation. PMID:25024163

The Effects of Preservice Elementary School Teachers' Accurate Self-Assessments in the Context of Whole Number

ERIC Educational Resources Information Center

Thanheiser, Eva

2018-01-01

Elementary prospective school teachers (PSTs) often struggle to understand why they need to relearn the mathematics that they think they already know. In this set of replication studies, I address this struggle in 3 ways: First, by increasing and varying the participant pool, I replicate Thanheiser's (2009) study, which shows that PSTs do not yet…

Genome-wide Control of Heterochromatin Replication by the Telomere Capping Protein TRF2.

PubMed

Mendez-Bermudez, Aaron; Lototska, Liudmyla; Bauwens, Serge; Giraud-Panis, Marie-Josèphe; Croce, Olivier; Jamet, Karine; Irizar, Agurtzane; Mowinckel, Macarena; Koundrioukoff, Stephane; Nottet, Nicolas; Almouzni, Genevieve; Teulade-Fichou, Mare-Paule; Schertzer, Michael; Perderiset, Mylène; Londoño-Vallejo, Arturo; Debatisse, Michelle; Gilson, Eric; Ye, Jing

2018-05-03

Hard-to-replicate regions of chromosomes (e.g., pericentromeres, centromeres, and telomeres) impede replication fork progression, eventually leading, in the event of replication stress, to chromosome fragility, aging, and cancer. Our knowledge of the mechanisms controlling the stability of these regions is essentially limited to telomeres, where fragility is counteracted by the shelterin proteins. Here we show that the shelterin subunit TRF2 ensures progression of the replication fork through pericentromeric heterochromatin, but not centromeric chromatin. In a process involving its N-terminal basic domain, TRF2 binds to pericentromeric Satellite III sequences during S phase, allowing the recruitment of the G-quadruplex-resolving helicase RTEL1 to facilitate fork progression. We also show that TRF2 is required for the stability of other heterochromatic regions localized throughout the genome, paving the way for future research on heterochromatic replication and its relationship with aging and cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

Lubiprostone decreases the small bowel transit time by capsule endoscopy: an exploratory, randomised, double-blind, placebo-controlled 3-way crossover study.

PubMed

Matsuura, Mizue; Inamori, Masahiko; Endo, Hiroki; Matsuura, Tetsuya; Kanoshima, Kenji; Inoh, Yumi; Fujita, Yuji; Umezawa, Shotaro; Fuyuki, Akiko; Uchiyama, Shiori; Higurashi, Takuma; Ohkubo, Hidenori; Sakai, Eiji; Iida, Hiroshi; Nonaka, Takashi; Futagami, Seiji; Kusakabe, Akihiko; Maeda, Shin; Nakajima, Atsushi

2014-01-01

The aim of this study was to investigate the usefulness of lubiprostone for bowel preparation and as a propulsive agent in small bowel endoscopy. Six healthy male volunteers participated in this randomized, 3-way crossover study. The subjects received a 24 μg tablet of lubiprostone 60 minutes prior to the capsule ingestion for capsule endoscopy (CE) and a placebo tablet 30 minutes before the capsule ingestion (L-P regimen), a placebo tablet 60 minutes prior to CE and a 24 μg tablet of lubiprostone 30 minutes prior to CE (P-L regimen), or a placebo tablet 60 minutes prior to r CE and a placebo tablet again 30 minutes prior to CE (P-P regimen). The quality of the capsule endoscopic images and the amount of water in the small bowel were assessed on 5-point scale. The median SBTT was 178.5 (117-407) minutes in the P-P regimen, 122.5 (27-282) minutes in the L-P regimen, and 110.5 (11-331) minutes in the P-L regimen (P = 0.042). This study showed that the use of lubiprostone significantly decreased the SBTT. We also confirmed that lubiprostone was effective for inducing water secretion into the small bowel during CE.

A randomized, open-label 3-way crossover study to investigate the relative bioavailability and bioequivalence of crushed sildenafil 20 mg tablets mixed with apple sauce, extemporaneously prepared suspension (EP), and intact sildenafil 20 mg tablets in healthy volunteers under fasting conditions.

PubMed

Gao, Xiang; Ndongo, Marie-Noella; Checchio, Tina M; Cook, Jack; Duncan, Barbara; LaBadie, Robert R

2015-01-01

The relative bioavailability and bioequivalence of 20-mg doses of a pediatric formulation of sildenafil extemporaneous preparation suspension (EP; 10 mg/mL), the sildenafil 20-mg intact tablet and the crushed sildenafil 20-mg tablet mixed with apple sauce were assessed in a single-dose, randomized, open-label, 3-way crossover study with 18 healthy adult volunteers. Blood samples were collected at predefined times and analyzed for sildenafil plasma concentrations. Natural log-transformed sildenafil pharmacokinetic parameters (Cmax , AUClast , and AUCinf ) were used to estimate relative bioavailability and construct 90% confidence intervals (CI) using a mixed-effects model. Bioequivalence was concluded among the three formulations with one exception, in which the EP suspension showed a 15% decrease in Cmax with a lower 90% CI of 76% compared with the intact tablet. The 15% decrease in sildenafil Cmax is not considered to be clinically relevant. Therefore, the EP suspension is considered to be an appropriate pediatric formulation. All 3 formulations were well tolerated in healthy adult volunteers. © 2014, The American College of Clinical Pharmacology.

Coupled replicator equations for the dynamics of learning in multiagent systems

NASA Astrophysics Data System (ADS)

Sato, Yuzuru; Crutchfield, James P.

2003-01-01

Starting with a group of reinforcement-learning agents we derive coupled replicator equations that describe the dynamics of collective learning in multiagent systems. We show that, although agents model their environment in a self-interested way without sharing knowledge, a game dynamics emerges naturally through environment-mediated interactions. An application to rock-scissors-paper game interactions shows that the collective learning dynamics exhibits a diversity of competitive and cooperative behaviors. These include quasiperiodicity, stable limit cycles, intermittency, and deterministic chaos—behaviors that should be expected in heterogeneous multiagent systems described by the general replicator equations we derive.

Signal replication in a DNA nanostructure

NASA Astrophysics Data System (ADS)

Mendoza, Oscar; Houmadi, Said; Aimé, Jean-Pierre; Elezgaray, Juan

2017-01-01

Logic circuits based on DNA strand displacement reaction are the basic building blocks of future nanorobotic systems. The circuits tethered to DNA origami platforms present several advantages over solution-phase versions where couplings are always diffusion-limited. Here we consider a possible implementation of one of the basic operations needed in the design of these circuits, namely, signal replication. We show that with an appropriate preparation of the initial state, signal replication performs in a reproducible way. We also show the existence of side effects concomitant to the high effective concentrations in tethered circuits, such as slow leaky reactions and cross-activation.

Capacities of template-type platforms in the Gulf of Mexico during hurricane Andrew

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bea, R.G.; Loch, K.J.; Young, P.L.

1997-02-01

This paper details results from nonlinear analyses of the ultimate limit state performance characteristics of four Gulf of Mexico (GOM) platforms subjected to intense loadings from hurricane Andrew. These four platforms were located to the east of the track of hurricane Andrew, and were thus in the most intense portion of the storm (Smith, 1993). The nonlinear analyses are able to replicate details of the observed behavior of the four structures. This replication is very dependent on realistic characterization of the performance characteristics of the pile foundations and on accurate information on the as is condition of the platforms beforemore » the storm.« less

Covert Modeling vs. Behavior Rehearsal in the Training and Generalization of Assertive Behaviors: A Crossover Design.

ERIC Educational Resources Information Center

Zielinski, Joseph J.; Williams, Leslie J.

1979-01-01

Twenty-four underassertive adults were randomly assigned to two treatment orders that included covert modeling and behavior rehearsal. No measurable difference in treatments was found, but participants preferred and had greater expectations of behavior rehearsal. Skill generalization to untrained situations occurred on 8 of 11 behavioral measures.…

Report from the BIT's 4th Annual World Congress of High-Tech Acupuncture and Integrative Medicine Held in Xi'an, China, 25-27 September 2017.

PubMed

Litscher, Gerhard; Mei, Xiaodan

2017-10-19

High-tech acupuncture is an example of a very successful cross-over between tradition and innovation. "The Annual World Congress of High-Tech Acupuncture and Integrative Medicine" was successfully organized on four occasions, and attracted more than 800 participants from 55 countries [...].

Prediction of Suicide: A Replication Study

ERIC Educational Resources Information Center

Farberow, Norman L.; MacKinnon, Douglas

1975-01-01

A replication study was conducted to retest the validity of the Neuropsychiatric Hospital Suicide Potential Scale. Fifty four patients who had committed suicide and fifty who had not were the population studied to test, if possible, the limits of prediction the scale can attain by judging the behavior of these patients. (DEP)

The Respond/Read/Replicate/Report System.

ERIC Educational Resources Information Center

Schwartz, Rhea

An effective teaching technique for a university extension course for rural special education teachers is the respond/read/replicate/report system. The four-step system was developed to stimulate tired, beleaguered teachers with differing experiences, knowledgeability, and teaching/learning styles who drove up to 60 miles on country roads to…

Ultrastructure of the replication sites of positive-strand RNA viruses

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

2015-05-15

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

A randomized placebo controlled trial to evaluate the effects of butamirate and dextromethorphan on capsaicin induced cough in healthy volunteers

PubMed Central

Faruqi, Shoaib; Wright, Caroline; Thompson, Rachel; Morice, Alyn H

2014-01-01

Aims The examination of cough reflex sensitivity through inhalational challenge can be utilized to demonstrate pharmacological end points. Here we compare the effect of butamirate, dextromethorphan and placebo on capsaicin-induced cough in healthy volunteers. Methods In this randomized, placebo-controlled, six way crossover study the effect of dextromethrophan 30 mg, four doses of butamirate and placebo was evaluated on incremental capsaicin challenges performed at baseline and 2, 4, 6, 8, 12 and 24 h following dosing. The primary end point was the area under the curve (AUC(0,12h)) of log10 C5 from pre-dose to 12 h after dosing. Plasma butamirate metabolites were analyzed to evaluate pharmacokinetic and pharmacodynamic relationships. Results Thirty-four subjects (13 males, median age 25 years) completed the study. Cough sensitivity decreased from baseline in all arms of the study. Dextromethorphan was superior to placebo (P = 0.01) but butamirate failed to show significant activity with maximum attenuation at the 45 mg dose. There was no apparent relationship between pharmacokinetic and pharmacodynamic parameters for butamirate. Conclusions We have demonstrated for the first time that dextromethorphan attenuates capsaicin challenge confirming its broad activity on the cough reflex. The lack of efficacy of butamirate could be due to formulation issues at higher doses. PMID:24995954

A randomized placebo controlled trial to evaluate the effects of butamirate and dextromethorphan on capsaicin induced cough in healthy volunteers.

PubMed

Faruqi, Shoaib; Wright, Caroline; Thompson, Rachel; Morice, Alyn H

2014-12-01

The examination of cough reflex sensitivity through inhalational challenge can be utilized to demonstrate pharmacological end points. Here we compare the effect of butamirate, dextromethorphan and placebo on capsaicin-induced cough in healthy volunteers. In this randomized, placebo-controlled, six way crossover study the effect of dextromethrophan 30 mg, four doses of butamirate and placebo was evaluated on incremental capsaicin challenges performed at baseline and 2, 4, 6, 8, 12 and 24 h following dosing. The primary end point was the area under the curve (AUC(0,12h)) of log10 C5 from pre-dose to 12 h after dosing. Plasma butamirate metabolites were analyzed to evaluate pharmacokinetic and pharmacodynamic relationships. Thirty-four subjects (13 males, median age 25 years) completed the study. Cough sensitivity decreased from baseline in all arms of the study. Dextromethorphan was superior to placebo (P = 0.01) but butamirate failed to show significant activity with maximum attenuation at the 45 mg dose. There was no apparent relationship between pharmacokinetic and pharmacodynamic parameters for butamirate. We have demonstrated for the first time that dextromethorphan attenuates capsaicin challenge confirming its broad activity on the cough reflex. The lack of efficacy of butamirate could be due to formulation issues at higher doses. © 2014 The British Pharmacological Society.

Novel method to assess gastric emptying in humans: the Pellet Gastric Emptying Test

NASA Technical Reports Server (NTRS)

Choe, S. Y.; Neudeck, B. L.; Welage, L. S.; Amidon, G. E.; Barnett, J. L.; Amidon, G. L.

2001-01-01

To further validate the Pellet Gastric Emptying Test (PGET) as a marker of gastric emptying, a randomized, four-way crossover study was conducted with 12 healthy subjects. The study consisted of oral co-administration of enteric coated caffeine (CAFF) and acetaminophen (APAP) pellets in four treatment phases: Same Size (100 kcal), Fasted, Small Liquid Meal (100 kcal), and Standard Meal (847 kcal). The time of first appearance of measurable drug marker in plasma, t(initial), was taken as the emptying time for the markers. Co-administration of same size enteric coated pellets of CAFF and APAP (0.7 mm in diameter) revealed no statistically significant differences in t(initial) values indicating that emptying was dependent only on size and not on chemical make-up of the pellets. Co-administration of different size pellets indicated that the smaller 0.7-mm diameter (CAFF) pellets were emptied and absorbed significantly earlier than the larger 3.6-mm diameter (APAP) pellets with both the Small Liquid Meal (by 35 min) and the Standard Meal (by 33 min) (P<0.05). The differences in emptying of the pellets were not significant in the Fasted Phase. The results suggest that the pellet gastric emptying test could prove useful in monitoring changes in transit times in the fasted and fed states and their impact on drug absorption.

Interdependency in Multimodel Climate Projections: Component Replication and Result Similarity

NASA Astrophysics Data System (ADS)

Boé, Julien

2018-03-01

Multimodel ensembles are the main way to deal with model uncertainties in climate projections. However, the interdependencies between models that often share entire components make it difficult to combine their results in a satisfactory way. In this study, how the replication of components (atmosphere, ocean, land, and sea ice) between climate models impacts the proximity of their results is quantified precisely, in terms of climatological means and future changes. A clear relationship exists between the number of components shared by climate models and the proximity of their results. Even the impact of a single shared component is generally visible. These conclusions are true at both the global and regional scales. Given available data, it cannot be robustly concluded that some components are more important than others. Those results provide ways to estimate model interdependencies a priori rather than a posteriori based on their results, in order to define independence weights.

A randomized, double-blind, crossover study comparing two- and four-dose hydrocortisone regimen with regard to quality of life, cortisol and ACTH profiles in patients with primary adrenal insufficiency.

PubMed

Ekman, Bertil; Bachrach-Lindström, Margareta; Lindström, Torbjörn; Wahlberg, Jeanette; Blomgren, Johan; Arnqvist, Hans J

2012-07-01

Current guidelines on how to divide the daily cortisol substitution dose in patients with primary adrenal insufficiency (PAI) are controversial and mainly based on empirical data. To assess how an equal dose of hydrocortisone (HC) given either four times daily or twice daily influence diurnal profiles of cortisol and ACTH, patient preferences and health-related quality of life (HRQoL). Double blind, crossover. Fifteen patients with PAI (six women) were included. Capsules of HC or placebo were given at 07:00, 12:00, 16:00 and 22:00 h in 4-week treatment periods: either one period with four doses (10 + 10 + 5 + 5 mg) or one period with two doses (20 + 0 + 10 + 0 mg). Diurnal profiles of cortisol and ACTH were collected, and area under the curve (AUC) was calculated. Questionnaires were used to evaluate patient preferences and HRQoL. The four-dose regimen gave a higher serum cortisol before tablet intake in the morning (P = 0·027) and a higher 24-h cortisol(AUC) (P < 0·0001) compared with the two-dose period. In contrast, a lower median plasma ACTH in the morning before tablet intake (P = 0·003) and a lower 24-h ln(ACTH(AUC) ) were found during the four-dose period. The patients preferred the four-dose regimen (P = 0·03), and the HRQoL scores tended to be higher (high score indicates better HRQoL) for the four-dose period. In summary, a four-dose regimen gives increased availability of cortisol and an enhanced effect with a less elevated ACTH in the morning in comparison with a two-dose regimen but the effect on HRQoL remains inconclusive. © 2012 Blackwell Publishing Ltd.

Quantum-interference transport through surface layers of indium-doped ZnO nanowires

NASA Astrophysics Data System (ADS)

Chiu, Shao-Pin; Lu, Jia Grace; Lin, Juhn-Jong

2013-06-01

We have fabricated indium-doped ZnO (IZO) nanowires (NWs) and carried out four-probe electrical-transport measurements on two individual NWs with geometric diameters of ≈70 and ≈90 nm in a wide temperature T interval of 1-70 K. The NWs reveal overall charge conduction behavior characteristic of disordered metals. In addition to the T dependence of resistance R, we have measured the magnetoresistance (MR) in magnetic fields applied either perpendicular or parallel to the NW axis. Our R(T) and MR data in different T intervals are consistent with the theoretical predictions of the one- (1D), two- (2D) or three-dimensional (3D) weak-localization (WL) and the electron-electron interaction (EEI) effects. In particular, a few dimensionality crossovers in the two effects are observed. These crossover phenomena are consistent with the model of a ‘core-shell-like structure’ in individual IZO NWs, where an outer shell of thickness t (≃15-17 nm) is responsible for the quantum-interference transport. In the WL effect, as the electron dephasing length Lφ gradually decreases with increasing T from the lowest measurement temperatures, a 1D-to-2D dimensionality crossover takes place around a characteristic temperature where Lφ approximately equals d, an effective NW diameter which is slightly smaller than the geometric diameter. As T further increases, a 2D-to-3D dimensionality crossover occurs around another characteristic temperature where Lφ approximately equals t (

Quantum-interference transport through surface layers of indium-doped ZnO nanowires.

PubMed

Chiu, Shao-Pin; Lu, Jia Grace; Lin, Juhn-Jong

2013-06-21

We have fabricated indium-doped ZnO (IZO) nanowires (NWs) and carried out four-probe electrical-transport measurements on two individual NWs with geometric diameters of ≈70 and ≈90 nm in a wide temperature T interval of 1-70 K. The NWs reveal overall charge conduction behavior characteristic of disordered metals. In addition to the T dependence of resistance R, we have measured the magnetoresistance (MR) in magnetic fields applied either perpendicular or parallel to the NW axis. Our R(T) and MR data in different T intervals are consistent with the theoretical predictions of the one- (1D), two- (2D) or three-dimensional (3D) weak-localization (WL) and the electron-electron interaction (EEI) effects. In particular, a few dimensionality crossovers in the two effects are observed. These crossover phenomena are consistent with the model of a 'core-shell-like structure' in individual IZO NWs, where an outer shell of thickness t (~15-17 nm) is responsible for the quantum-interference transport. In the WL effect, as the electron dephasing length Lφ gradually decreases with increasing T from the lowest measurement temperatures, a 1D-to-2D dimensionality crossover takes place around a characteristic temperature where Lφ approximately equals d, an effective NW diameter which is slightly smaller than the geometric diameter. As T further increases, a 2D-to-3D dimensionality crossover occurs around another characteristic temperature where Lφ approximately equals t (

The influence of transcutaneous electrical nerve stimulation parameters on the level of pain perceived by participants with painful diabetic neuropathy: A crossover study.

PubMed

Upton, Gabrielle A; Tinley, Paul; Al-Aubaidy, Hayder; Crawford, Rachel

This pilot study aimed to investigate and compare the perceived pain relief effectiveness of two different modes of TENS in people with painful diabetic neuropathy (PDN). A cross-over study was conducted at Charles Sturt University, Orange. Five participants with PDN were assessed with a McGill Pain Questionnaire before and after each of the two TENS treatments. Participants were randomly allocated to Traditional TENS (80Hz, 200ms) or Acupuncture-like TENS (2Hz, 200ms) and the treatments were applied daily for 30min over ten days. Following a seven day washout period, the alternate mode of TENS was carried out using the same method. Wilcoxon Signed Rank tests were used to statistically analyse the results. All five participants reported personally meaningful pain relief during one or both of the TENS treatments. The Wilcoxon signed rank testing showed no statistical significance, p=1, likely due to the small sample size. Acupuncture-like TENS had a large effect size (z=-1.625, r=0.514), whilst Traditional TENS produced a medium effect size (z=-1.214, r=0.384). No adverse effects were reported. Acupuncture-like TENS may be more effective for PDN than traditional TENS. A larger scale replication of this pilot study is warranted. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Meiosis.

PubMed

Hillers, Kenneth J; Jantsch, Verena; Martinez-Perez, Enrique; Yanowitz, Judith L

2017-05-04

Sexual reproduction requires the production of haploid gametes (sperm and egg) with only one copy of each chromosome; fertilization then restores the diploid chromosome content in the next generation. This reduction in genetic content is accomplished during a specialized cell division called meiosis, in which two rounds of chromosome segregation follow a single round of DNA replication. In preparation for the first meiotic division, homologous chromosomes pair and synapse, creating a context that promotes formation of crossover recombination events. These crossovers, in conjunction with sister chromatid cohesion, serve to connect the two homologs and facilitate their segregation to opposite poles during the first meiotic division. During the second meiotic division, which is similar to mitosis, sister chromatids separate; the resultant products are haploid cells that become gametes. In Caenorhabditis elegans (and most other eukaryotes) homologous pairing and recombination are required for proper chromosome inheritance during meiosis; accordingly, the events of meiosis are tightly coordinated to ensure the proper execution of these events. In this chapter, we review the seminal events of meiosis: pairing of homologous chromosomes, the changes in chromosome structure that chromosomes undergo during meiosis, the events of meiotic recombination, the differentiation of homologous chromosome pairs into structures optimized for proper chromosome segregation at Meiosis I, and the ultimate segregation of chromosomes during the meiotic divisions. We also review the regulatory processes that ensure the coordinated execution of these meiotic events during prophase I.

Patient profiling can identify patients with adult spinal deformity (ASD) at risk for conversion from nonoperative to surgical treatment: initial steps to reduce ineffective ASD management.

PubMed

Passias, Peter G; Jalai, Cyrus M; Line, Breton G; Poorman, Gregory W; Scheer, Justin K; Smith, Justin S; Shaffrey, Christopher I; Burton, Douglas C; Fu, Kai-Ming G; Klineberg, Eric O; Hart, Robert A; Schwab, Frank; Lafage, Virginie; Bess, Shay

2018-02-01

Non-operative management is a common initial treatment for patients with adult spinal deformity (ASD) despite reported superiority of surgery with regard to outcomes. Ineffective medical care is a large source of resource drain on the health system. Characterization of patients with ASD likely to elect for operative treatment from non-operative management may allow for more efficient patient counseling and cost savings. This study aimed to identify deformity and disability characteristics of patients with ASD who ultimately convert to operative treatment compared with those who remain non-operative and those who initially choose surgery. A retrospective review was carried out. A total of 510 patients with ASD (189 non-operative, 321 operative) with minimum 2-year follow-up comprised the patient sample. Oswestry Disability Index (ODI), Short-Form 36 Health Assessment (SF-36), Scoliosis Research Society questionnaire (SRS-22r), and spinopelvic radiographic alignment were the outcome measures. Demographic, radiographic, and patient-reported outcome measures (PROMs) from a cohort of patients with ASD prospectively enrolled into a multicenter database were evaluated. Patients were divided into three treatment cohorts: Non-operative (NON=initial non-operative treatment and remained non-operative), Operative (OP=initial operative treatment), and Crossover (CROSS=initial non-operative treatment with subsequent conversion to operative treatment). NON and OP groups were propensity score-matched (PSM) to CROSS for baseline demographics (age, body mass index, Charlson Comorbidity Index). Time to crossover was divided into early (<1 year) and late (>1 year). Outcome measures were compared across and within treatment groups at four time points (baseline, 6 weeks, 1 year, and 2 years). Following PSM, 118 patients were included (NON=39, OP=38, CROSS=41). Crossover rate was 21.7% (41/189). Mean time to crossover was 394 days. All groups had similar baseline sagittal alignment, but CROSS had larger pelvic incidence and lumbar lordosis (PI-LL) mismatch than NON (11.9° vs. 3.1°, p=.032). CROSS and OP had similar baseline PROM scores; however, CROSS had worse baseline ODI, PCS, SRS-22r (p<.05). At time of crossover, CROSS had worse ODI (35.7 vs. 27.8) and SRS Satisfaction (2.6 vs. 3.3) compared with NON (p<.05). Alignment remained similar for CROSS from baseline to conversion; however, PROMs (ODI, PCS, SRS Activity/Pain/Total) worsened (p<.05). Early and late crossover evaluation demonstrated CROSS-early (n=25) had worsening ODI, SRS Activity/Pain at time of crossover (p<.05). From time of crossover to 2-year follow-up, CROSS-early had less SRS Appearance/Mental improvement compared with OP. Both CROSS-early/late had worse baseline, but greater improvements, in ODI, PCS, SRS Pain/Total compared with NON (p<.05). Baseline alignment and disability parameters increased crossover odds-Non with Schwab T/L/D curves and ODI≥40 (odds ratio [OR]: 3.05, p=.031), and Non with high PI-LL modifier grades ("+"/'++') and ODI≥40 (OR: 5.57, p=.007) were at increased crossover risk. High baseline and increasing disability over time drives conversion from non-operative to operative ASD care. CROSS patients had similar spinal deformity but worse PROMs than NON. CROSS achieved similar 2-year outcome scores as OP. Profiling at first visit for patients at risk of crossover may optimize physician counseling and cost savings. Copyright © 2017. Published by Elsevier Inc.

Quasi-One-Dimensional Ultracold Fermi Gases

NASA Astrophysics Data System (ADS)

Revelle, Melissa C.

Ultracold atoms have become an essential tool in studying condensed matter phenomena. The advantage of atomic physics experiments is that they provide an easily tunable system. This experiment uses the lowest two ground state hyperfine levels of fermionic lithium. Having two different states creates a pseudo-spin- 1/2 system and allows us to emulate electronic systems, such as superconductors and crystal lattices. In our experiment, we can control the ratio between these two states resulting in either a spin-balanced or a spin-imbalanced gas. Imposing an imbalance is analogous to applying a magnetic field to a superconductor which causes the electrons in the material to align to the field (thus breaking the electron pairs which cause superconductivity). This motivates us to understand the phases created when a spin-imbalance is created and the effect of changing the atomic interactions. In a 3D system, we find where superfluidity is suppressed throughout the BEC to BCS crossover. Using phase separation as a guide, we probe the dimensional crossover between 1D and 3D. The phase separation in 1D is inverted from that in 3D, which provides a unique characteristic to distinguish between the dimensions. By varying the tunneling between tubes and the atomic interactions in a 2D optical lattice, we control whether the system is 1D, 3D, or in between. Using the properties of a 3D gas as a guide, we directly observe when the gas has crossed over from being dominated by 1D-like behavior to 3D. In this way, we have found a universal value for the dimensional crossover. The 1D-3D crossover paves the way to search for the exotic FFLO (Fulde-Ferrell-Larkin-Ovchinnikov) superconductor. While most superconductors do not coexist with magnetism, the FFLO phase requires large magnetic fields to support its pairing mechanism. Additionally, this phase is more likely to be found in lower dimensional systems. However, at low dimensions, the effect of temperature fluctuations on the phase is destabilizing, but these temperature effects are reduced with higher dimensionality. Thus, the quasi-1D regime is the optimal region of parameter space to find this phase. The search for direct evidence of FFLO continues in this regime.

Cognitive Abilities as Expressions of Three "Ways of Knowing."

ERIC Educational Resources Information Center

Diamond, Stephen R.; Royce, Joseph R.

1980-01-01

Factor analytic studies suggest that there are six replicable second order cognitive factors. These six factors lend themselves to being interpreted as aspects of Royce's three ways of knowing: conceptual, perceptual, or symbolical. This view provides a unified explanation of the second and third order factors. (Author/CTM)

Selection of UV Resins for Nanostructured Molds for Thermal-NIL.

PubMed

Jia, Zheng; Choi, Junseo; Park, Sunggook

2018-06-18

Nanoimprint molds made of soft polymeric materials have advantages of low demolding force and low fabrication cost over Si or metal-based hard molds. However, such advantages are often sacrificed by their reduced replication fidelity associated with the low mechanical strength. In this paper, we studied replication fidelity of different UV-resin molds copied from a Si master mold via UV nanoimprint lithography (NIL) and their thermal imprinting performance into a thermoplastic polymer. Four different UV resins were studied: two were high surface energy UV resins based on tripropyleneglycol diacrylate (TPGDA resin) and polypropyleneglycol diacrylate (PPGDA resin), and the other two were commercially available, low surface energy poly-urethane acrylate (PUA resin) and fluorine-containing (MD 700) UV resins. The replication fidelity among the four UV-resins during UV nanoimprint lithograph from a Si master with sharp nanostructures was in the increasing order of (poorest) PUA resin < MD 700 < PPGDA resin < TPGDA resin (best). The results show that the high surface energy and small monomer size are keys to achieving good UV resin filling into sharp nanostructures over the viscosity of the resin solution. When the four UV-resin molds were used for thermal-NIL into a thermoplastic polymer, the replication fidelity was in the increasing order of (poorest) MD 700 < TPGDA resin < PUA resin (best), which follows the same order of their Young's moduli. Our results indicate that the selection of an appropriate UV resin for NIL molds requires consideration of the replication fidelities in the mold fabrication and the subsequent thermal-NIL into thermoplastic polymers. © 2018 IOP Publishing Ltd.

Modified Veress needle decompression of tension pneumothorax: a randomized crossover animal study.

PubMed

Lubin, Dafney; Tang, Andrew L; Friese, Randall S; Martin, Matthew; Green, D J; Jones, Trevor; Means, Russell R; Ginwalla, Rashna; O'Keeffe, Terence S; Joseph, Bellal A; Wynne, Julie L; Kulvatunyou, Narong; Vercruysse, Gary; Gries, Lynn; Rhee, Peter

2013-12-01

The current prehospital standard of care using a large bore intravenous catheter for tension pneumothorax (tPTX) decompression is associated with a high failure rate. We developed a modified Veress needle (mVN) for this condition. The purpose of this study was to evaluate the effectiveness and safety of the mVN as compared with a 14-gauge needle thoracostomy (NT) in a swine tPTX model. tPTX was created in 16 adult swine via thoracic CO2 insufflation to 15 mm Hg. After tension physiology was achieved, defined as a 50% reduction of cardiac output, the swine were randomized to undergo either mVN or NT decompression. Failure to restore 80% baseline systolic blood pressure within 5 minutes resulted in crossover to the alternate device. The success rate of each device, death, and need for crossover were analyzed using χ. Forty-three tension events were created in 16 swine (24 mVN, 19 NT) at 15 mm Hg of intrathoracic pressure with a mean CO2 volume of 3.8 L. tPTX resulted in a 48% decline of systolic blood pressure from baseline and 73% decline of cardiac output, and 42% had equalization of central venous pressure with pulmonary capillary wedge pressure. All tension events randomized to mVN were successfully rescued within a mean (SD) of 70 (86) seconds. NT resulted in four successful decompressions (21%) within a mean (SD) of 157 (96) seconds. Four swine (21%) died within 5 minutes of NT decompression. The persistent tension events where the swine survived past 5 minutes (11 of 19 NTs) underwent crossover mVN decompression, yielding 100% rescue. Neither the mVN nor the NT was associated with inadvertent injuries to the viscera. Thoracic insufflation produced a reliable and highly reproducible model of tPTX. The mVN is vastly superior to NT for effective and safe tPTX decompression and physiologic recovery. Further research should be invested in the mVN for device refinement and replacement of NT in the field.

Broadband Via-Less Microwave Crossover Using Microstrip-CPW Transitions

NASA Technical Reports Server (NTRS)

Stevenson, Thomas; U-Yen, Kongpop; Wollack, Edward; Moseley, Samuel; Hsieh, Wen-Ting

2011-01-01

The front-to-back interface between microstrip and CPW (coplanar waveguide) typically requires complex fabrication or has high radiation loss. The microwave crossover typically requires a complex fabrication step. The prior art in microstrip-CPW transition requires a physical vias connection between the microstrip and CPW line on a separate layer. The via-less version of this transition was designed empirically and does not have a close form solution. The prior art of the micro wave crossover requires either additional substrate or wire bond as an air bridge to isolate two microwave lines at the crossing junction. The disadvantages are high radiation loss, no analytical solution to the problem, lengthy simulation time, and complex fabrication procedures to generate air bridges or via. The disadvantage of the prior crossover is a complex fabrication procedure, which also affects the device reliability and yield. This microstrip-CPW transition is visualized as two microstrip-slotline transitions combined in a way that the radiation from two slotlines cancels each other out. The invention is designed based on analytical methods; thus, it significantly reduces the development time. The crossover requires no extra layer to cross two microwave signals and has low radiation loss. The invention is simple to fabricate and design. It produces low radiation loss and can be designed with low insertion loss, with some tradeoff with signal isolation. The microstrip-CPW transition is used as an interface to connect between the device and the circuit outside the package. The via-less microwave crossover is used to allow two signals to cross without using an extra layer or fabrication processing step to enable this function. This design allows the solution to be determined entirely though analytical techniques. In addition, a planar via-less microwave crossover using this technique was proposed. The experimental results show that the proposed crossover at 5 GHz has a minimum isolation of 32 dB. It also has low in-band insertion loss and return loss of 1.2 dB and 18 dB, respectively, over more than 44 percent of bandwidth at room temperature. This microstrip-CPW transition requires the microstrip line to be split into two sections. Each section is connected to a microstrip quarter-wavelength openended stub. A slotline is also placed perpendicular to the microstrip section. The slot is connected to a grounded-end quarter-wavelength slotline and generates a microstrip-slotline transition. When two of these sections are placed in parallel and with the microstrip section combined at transition, a microstrip- CPW transition is formed. The slotline radiation is suppressed as two slots are excited with the electric field in an opposite direction, which cancels the radiation in far field. The invention on the crossover consists of the invented microstrip-CPW transitions combined back-to-back and a microstrip low-pass filter. One signal is crossed through to the microstrip layer, while the other signal is crossed through the CPW line located on the ground plane of the microstrip line. The microstrip low-pass filter produces a narrow line at the crossing point to enhance the system isolation. It also produces broadband response in the operating frequency band. The microstrip-CPW transition allows a microwave signal to travel from microstrip line to CPW line with low radiation loss. The crossover allows two microwave signals to cross with minimal parasitic coupling.

High-throughput state-machine replication using software transactional memory.

PubMed

Zhao, Wenbing; Yang, William; Zhang, Honglei; Yang, Jack; Luo, Xiong; Zhu, Yueqin; Yang, Mary; Luo, Chaomin

2016-11-01

State-machine replication is a common way of constructing general purpose fault tolerance systems. To ensure replica consistency, requests must be executed sequentially according to some total order at all non-faulty replicas. Unfortunately, this could severely limit the system throughput. This issue has been partially addressed by identifying non-conflicting requests based on application semantics and executing these requests concurrently. However, identifying and tracking non-conflicting requests require intimate knowledge of application design and implementation, and a custom fault tolerance solution developed for one application cannot be easily adopted by other applications. Software transactional memory offers a new way of constructing concurrent programs. In this article, we present the mechanisms needed to retrofit existing concurrency control algorithms designed for software transactional memory for state-machine replication. The main benefit for using software transactional memory in state-machine replication is that general purpose concurrency control mechanisms can be designed without deep knowledge of application semantics. As such, new fault tolerance systems based on state-machine replications with excellent throughput can be easily designed and maintained. In this article, we introduce three different concurrency control mechanisms for state-machine replication using software transactional memory, namely, ordered strong strict two-phase locking, conventional timestamp-based multiversion concurrency control, and speculative timestamp-based multiversion concurrency control. Our experiments show that speculative timestamp-based multiversion concurrency control mechanism has the best performance in all types of workload, the conventional timestamp-based multiversion concurrency control offers the worst performance due to high abort rate in the presence of even moderate contention between transactions. The ordered strong strict two-phase locking mechanism offers the simplest solution with excellent performance in low contention workload, and fairly good performance in high contention workload.

High-throughput state-machine replication using software transactional memory

PubMed Central

Yang, William; Zhang, Honglei; Yang, Jack; Luo, Xiong; Zhu, Yueqin; Yang, Mary; Luo, Chaomin

2017-01-01

State-machine replication is a common way of constructing general purpose fault tolerance systems. To ensure replica consistency, requests must be executed sequentially according to some total order at all non-faulty replicas. Unfortunately, this could severely limit the system throughput. This issue has been partially addressed by identifying non-conflicting requests based on application semantics and executing these requests concurrently. However, identifying and tracking non-conflicting requests require intimate knowledge of application design and implementation, and a custom fault tolerance solution developed for one application cannot be easily adopted by other applications. Software transactional memory offers a new way of constructing concurrent programs. In this article, we present the mechanisms needed to retrofit existing concurrency control algorithms designed for software transactional memory for state-machine replication. The main benefit for using software transactional memory in state-machine replication is that general purpose concurrency control mechanisms can be designed without deep knowledge of application semantics. As such, new fault tolerance systems based on state-machine replications with excellent throughput can be easily designed and maintained. In this article, we introduce three different concurrency control mechanisms for state-machine replication using software transactional memory, namely, ordered strong strict two-phase locking, conventional timestamp-based multiversion concurrency control, and speculative timestamp-based multiversion concurrency control. Our experiments show that speculative timestamp-based multiversion concurrency control mechanism has the best performance in all types of workload, the conventional timestamp-based multiversion concurrency control offers the worst performance due to high abort rate in the presence of even moderate contention between transactions. The ordered strong strict two-phase locking mechanism offers the simplest solution with excellent performance in low contention workload, and fairly good performance in high contention workload. PMID:29075049

Prebiotic chemistry and nucleic acid replication

NASA Technical Reports Server (NTRS)

Orgel, L. E.; Lohrmann, R.

1974-01-01

Recent work is reviewed on some reactions that could have occurred on the primitive earth and that could have played a part in the evolution of a self-replicating system. The transition from the primitive atmosphere to the simplest replicating molecules is considered in four stages: (1) the formation of a 'prebiotic soup' of organic precursors, including the purine and pyrimidine bases and the pentose sugars; (2) the condensation of these precursors and inorganic phosphate to form monomeric nucleotides and activated nucleotide derivatives; (3) the polymerization of nucleotide derivatives to oligonucleotides; and (4) the complementary replication of oligonucleotides in a template-directed process that depends on Watson-Crick base pairing.

Tombusviruses upregulate phospholipid biosynthesis via interaction between p33 replication protein and yeast lipid sensor proteins during virus replication in yeast

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barajas, Daniel; Xu, Kai; Sharma, Monika

Positive-stranded RNA viruses induce new membranous structures and promote membrane proliferation in infected cells to facilitate viral replication. In this paper, the authors show that a plant-infecting tombusvirus upregulates transcription of phospholipid biosynthesis genes, such as INO1, OPI3 and CHO1, and increases phospholipid levels in yeast model host. This is accomplished by the viral p33 replication protein, which interacts with Opi1p FFAT domain protein and Scs2p VAP protein. Opi1p and Scs2p are phospholipid sensor proteins and they repress the expression of phospholipid genes. Accordingly, deletion of OPI1 transcription repressor in yeast has a stimulatory effect on TBSV RNA accumulation andmore » enhanced tombusvirus replicase activity in an in vitro assay. Altogether, the presented data convincingly demonstrate that de novo lipid biosynthesis is required for optimal TBSV replication. Overall, this work reveals that a (+)RNA virus reprograms the phospholipid biosynthesis pathway in a unique way to facilitate its replication in yeast cells. - Highlights: • Tombusvirus p33 replication protein interacts with FFAT-domain host protein. • Tombusvirus replication leads to upregulation of phospholipids. • Tombusvirus replication depends on de novo lipid synthesis. • Deletion of FFAT-domain host protein enhances TBSV replication. • TBSV rewires host phospholipid synthesis.« less

β-Glucan and dark chocolate: a randomized crossover study on short-term satiety and energy intake.

PubMed

Akyol, Asli; Dasgin, Halil; Ayaz, Aylin; Buyuktuncer, Zehra; Besler, H Tanju

2014-09-23

The aims of this study were to adapt a traditional recipe into a healthier form by adding 3 g of oat β-glucan, substituting milk chocolate to dark chocolate with 70% cocoa, and to examine the effect of these alterations on short-term satiety and energy intake. Study subjects (n = 25) were tested in a randomized, crossover design with four products closely matched for energy content. Four different versions of a traditional recipe including milk chocolate-control (CON), oat β-glucan (B-GLU), dark chocolate (DARK) or oat β-glucan and dark chocolate (B-GLU + DARK) were given to subjects on different test days. After subjects were asked to report visual analog scale (VAS) scores on sensory outcomes and related satiety for four hours ad libitum, lunch was served and energy intake of individuals was measured. VAS scores indicated that none of the test foods exerted an improved effect on satiety feelings. However, energy intake of individuals during ad libitum lunch was significantly lower in dark chocolate groups (CON: 849.46 ± 47.45 kcal versus DARK: 677.69 ± 48.45 kcal and B-GLU + DARK: 691.08 ± 47.45 kcal, p = 0.014). The study demonstrated that substituting dark chocolate for milk chocolate is more effective in inducing satiety during subsequent food intake in healthy subjects.

What is the preferred number of consecutive night shifts? results from a crossover intervention study among police officers in Denmark.

PubMed

Nabe-Nielsen, Kirsten; Jensen, Marie Aarrebo; Hansen, Åse Marie; Kristiansen, Jesper; Garde, Anne Helene

2016-10-01

Among police officers in Denmark, we studied (i) how many consecutive night shifts participants preferred at baseline; (ii) preferences regarding three intervention conditions (two, four, and seven consecutive night shifts followed by the same number of days off/day shifts: '2 + 2', '4 + 4', '7 + 7') at follow-up; (iii) characteristics of participants preferring each of these intervention conditions. Questionnaire data from a crossover intervention study were used (baseline: n = 73; follow-up: n = 68). At baseline, 49% preferred four consecutive night shifts. At follow-up, 57% preferred '4 + 4', 26% preferred '2 + 2' and 26% preferred '7 + 7'. Participants, who preferred longer spells of night work experienced that night work was less demanding, found it easier to sleep at different times of the day, and were more frequently evening types compared with participants who preferred shorter spells of night work. The participants' preferences are likely to be influenced by their previous shift work experience. Practitioner Summary: We investigated police officers' preferences regarding the number of consecutive night shifts. The majority preferred four consecutive night shifts. Those who preferred the longer spells of night work found night work less demanding, found it easier to sleep at different times of the day, and were more frequently evening types.

β-Glucan and Dark Chocolate: A Randomized Crossover Study on Short-Term Satiety and Energy Intake

PubMed Central

Akyol, Asli; Dasgin, Halil; Ayaz, Aylin; Buyuktuncer, Zehra; Besler, H. Tanju

2014-01-01

Aim: The aims of this study were to adapt a traditional recipe into a healthier form by adding 3 g of oat β-glucan, substituting milk chocolate to dark chocolate with 70% cocoa, and to examine the effect of these alterations on short-term satiety and energy intake. Materials and Methods: Study subjects (n = 25) were tested in a randomized, crossover design with four products closely matched for energy content. Four different versions of a traditional recipe including milk chocolate-control (CON), oat β-glucan (B-GLU), dark chocolate (DARK) or oat β-glucan and dark chocolate (B-GLU + DARK) were given to subjects on different test days. After subjects were asked to report visual analog scale (VAS) scores on sensory outcomes and related satiety for four hours ad libitum, lunch was served and energy intake of individuals was measured. Results: VAS scores indicated that none of the test foods exerted an improved effect on satiety feelings. However, energy intake of individuals during ad libitum lunch was significantly lower in dark chocolate groups (CON: 849.46 ± 47.45 kcal versus DARK: 677.69 ± 48.45 kcal and B-GLU + DARK: 691.08 ± 47.45 kcal, p = 0.014). Conclusion: The study demonstrated that substituting dark chocolate for milk chocolate is more effective in inducing satiety during subsequent food intake in healthy subjects. PMID:25251294

Transient effects of transfusion and feeding advances (volumetric and caloric) on necrotizing enterocolitis development: A case-crossover study.

PubMed

Le, Vi T; Klebanoff, Mark A; Talavera, Maria M; Slaughter, Jonathan L

2017-01-01

To evaluate the short-term effects of feed fortification, feed volume increase, and PRBC transfusion on the odds of developing NEC. Case-crossover study of neonatal intensive care infants born at ≤ 32 weeks' gestation who were admitted to 5 central Ohio intensive care units from January 2012-July 2016 and developed NEC Bell Stage ≥2. Each patient served as their own control, with exposure during the 48-hour period just prior to NEC onset (hazard period) being compared to a preceding 48-hour control period, thus eliminating confounding by patient factors fixed between both intervals. NEC onset was determined by chart review as the earliest occurrence of one of the following within 24 hours of confirmatory x-ray: (1) antibiotic initiation, (2) enteral feeding cessation, (3) physician first notified of abdominal concerns, or (4) abdominal x-ray ordered. Conditional logistic regression compared exposures to feed volume increase, fortification, and PRBC transfusion during the 48-hour period prior to NEC onset to those during a preceding 48-hour control period. Analyses were stratified by gestational age and anemia (defined: hemoglobin ≤ 9.3 g/dL within 7 days of NEC onset). We included 63 infants with confirmed NEC. Acute exposure to fortification (odds ratio [OR]: 1.67, 95% confidence interval [CI]: 0.61, 4.59), feed volume increase (OR: 0.63, 95% CI: 0.28, 1.38), and PRBC transfusion (OR: 1.80, 95% CI: 0.60, 5.37) was not associated with the onset of NEC. Gestational age and anemia did not significantly modify the associations. Sensitivity testing substituting 24- and 72-hour hazard and control periods produced similar results. Using a case-crossover design, we did not detect an association between NEC development and feed fortification, feed volume increase, or PRBC transfusion within 48-hours prior to NEC-onset. Replication in a larger set of cases is needed.

Skin Cooling and Force Replication at the Ankle in Healthy Individuals: A Crossover Randomized Controlled Trial

PubMed Central

Haupenthal, Daniela Pacheco dos Santos; de Noronha, Marcos; Haupenthal, Alessandro; Ruschel, Caroline; Nunes, Guilherme S.

2015-01-01

Context Proprioception of the ankle is determined by the ability to perceive the sense of position of the ankle structures, as well as the speed and direction of movement. Few researchers have investigated proprioception by force-replication ability and particularly after skin cooling. Objective To analyze the ability of the ankle-dorsiflexor muscles to replicate isometric force after a period of skin cooling. Design Randomized controlled clinical trial. Setting Laboratory. Patients or Other Participants Twenty healthy individuals (10 men, 10 women; age = 26.8 ± 5.2 years, height = 171 ± 7 cm, mass = 66.8 ± 10.5 kg). Intervention(s) Skin cooling was carried out using 2 ice applications: (1) after maximal voluntary isometric contraction (MVIC) performance and before data collection for the first target force, maintained for 20 minutes; and (2) before data collection for the second target force, maintained for 10 minutes. We measured skin temperature before and after ice applications to ensure skin cooling. Main Outcome Measure(s) A load cell was placed under an inclined board for data collection, and 10 attempts of force replication were carried out for 2 values of MVIC (20%, 50%) in each condition (ice, no ice). We assessed force sense with absolute and root mean square errors (the difference between the force developed by the dorsiflexors and the target force measured with the raw data and after root mean square analysis, respectively) and variable error (the variance around the mean absolute error score). A repeated-measures multivariate analysis of variance was used for statistical analysis. Results The absolute error was greater for the ice than for the no-ice condition (F1,19 = 9.05, P = .007) and for the target force at 50% of MVIC than at 20% of MVIC (F1,19 = 26.01, P < .001). Conclusions The error was greater in the ice condition and at 50% of MVIC. Skin cooling reduced the proprioceptive ability of the ankle-dorsiflexor muscles to replicate isometric force. PMID:25761136

Hot-embossing replication of self-centering optical fiber alignment structures prototyped by deep proton writing

NASA Astrophysics Data System (ADS)

Ebraert, Evert; Wissmann, Markus; Guttmann, Markus; Kolew, Alexander; Worgull, Matthias; Barié, Nicole; Schneider, Marc; Hofmann, Andreas; Beri, Stefano; Watté, Jan; Thienpont, Hugo; Van Erps, Jürgen

2016-07-01

This paper presents the hot-embossing replication of self-centering fiber alignment structures for high-precision, single-mode optical fiber connectors. To this end, a metal mold insert was fabricated by electroforming a polymer prototype patterned by means of deep proton writing (DPW). To achieve through-hole structures, we developed a postembossing process step to remove the residual layer inherently present in hot-embossed structures. The geometrical characteristics of the hot-embossed replicas are compared, before and after removal of the residual layer, with the DPW prototypes. Initial measurements on the optical performance of the replicas are performed. The successful replication of these components paves the way toward low-cost mass replication of DPW-fabricated prototypes in a variety of high-tech plastics.

Effect of serial pig passages on the adaptation of an avian H9N2 influenza virus to swine.

PubMed

Mancera Gracia, Jose Carlos; Van den Hoecke, Silvie; Saelens, Xavier; Van Reeth, Kristien

2017-01-01

H9N2 avian influenza viruses are endemic in poultry in Asia and the Middle East. These viruses sporadically cause dead-end infections in pigs and humans raising concerns about their potential to adapt to mammals or reassort with human or swine influenza viruses. We performed ten serial passages with an avian H9N2 virus (A/quail/Hong Kong/G1/1997) in influenza naïve pigs to assess the potential of this virus to adapt to swine. Virus replication in the entire respiratory tract and nasal virus excretion were examined after each passage and we deep sequenced viral genomic RNA of the parental and passage four H9N2 virus isolated from the nasal mucosa and lung. The parental H9N2 virus caused a productive infection in pigs with a predominant tropism for the nasal mucosa, whereas only 50% lung samples were virus-positive. In contrast, inoculation of pigs with passage four virus resulted in viral replication in the entire respiratory tract. Subsequent passages were associated with reduced virus replication in the lungs and infectious virus was no longer detectable in the upper and lower respiratory tract of inoculated pigs at passage ten. The broader tissue tropism after four passages was associated with an amino acid residue substitution at position 225, within the receptor-binding site of the hemagglutinin. We also compared the parental H9N2, passage four H9N2 and the 2009 pandemic H1N1 (pH1N1) virus in a direct contact transmission experiment. Whereas only one out of six contact pigs showed nasal virus excretion of the wild-type H9N2 for more than four days, all six contact animals shed the passage four H9N2 virus. Nevertheless, the amount of excreted virus was significantly lower when compared to that of the pH1N1, which readily transmitted and replicated in all six contact animals. Our data demonstrate that serial passaging of H9N2 virus in pigs enhances its replication and transmissibility. However, full adaptation of an avian H9N2 virus to pigs likely requires an extensive set of mutations.

Effect of serial pig passages on the adaptation of an avian H9N2 influenza virus to swine

PubMed Central

Van den Hoecke, Silvie; Saelens, Xavier; Van Reeth, Kristien

2017-01-01

H9N2 avian influenza viruses are endemic in poultry in Asia and the Middle East. These viruses sporadically cause dead-end infections in pigs and humans raising concerns about their potential to adapt to mammals or reassort with human or swine influenza viruses. We performed ten serial passages with an avian H9N2 virus (A/quail/Hong Kong/G1/1997) in influenza naïve pigs to assess the potential of this virus to adapt to swine. Virus replication in the entire respiratory tract and nasal virus excretion were examined after each passage and we deep sequenced viral genomic RNA of the parental and passage four H9N2 virus isolated from the nasal mucosa and lung. The parental H9N2 virus caused a productive infection in pigs with a predominant tropism for the nasal mucosa, whereas only 50% lung samples were virus-positive. In contrast, inoculation of pigs with passage four virus resulted in viral replication in the entire respiratory tract. Subsequent passages were associated with reduced virus replication in the lungs and infectious virus was no longer detectable in the upper and lower respiratory tract of inoculated pigs at passage ten. The broader tissue tropism after four passages was associated with an amino acid residue substitution at position 225, within the receptor-binding site of the hemagglutinin. We also compared the parental H9N2, passage four H9N2 and the 2009 pandemic H1N1 (pH1N1) virus in a direct contact transmission experiment. Whereas only one out of six contact pigs showed nasal virus excretion of the wild-type H9N2 for more than four days, all six contact animals shed the passage four H9N2 virus. Nevertheless, the amount of excreted virus was significantly lower when compared to that of the pH1N1, which readily transmitted and replicated in all six contact animals. Our data demonstrate that serial passaging of H9N2 virus in pigs enhances its replication and transmissibility. However, full adaptation of an avian H9N2 virus to pigs likely requires an extensive set of mutations. PMID:28384328

The Factor Replicability of the Litwin and Stringer Organizational Climate Questionnaire: An Inter- and Intra-Organizational Assessment.

ERIC Educational Resources Information Center

Rogers, Evan D.; And Others

1980-01-01

Four recent factor analytic studies of the Litwin and Stringer Organizational Climate Questionnaire (LSOCQ) are compared. Although there is somewhat more intra- than inter-organizational replicability of factors, both comparisons raise considerable doubt about the validity of the Litwin and Stringer instrument. (Author)

An experimental study of catechol-o-methyltransferase Val158Met moderation of delta-9-tetrahydrocannabinol-induced effects on psychosis and cognition.

PubMed

Henquet, Cécile; Rosa, Araceli; Krabbendam, Lydia; Papiol, Sergi; Fananás, Lourdes; Drukker, Marjan; Ramaekers, Johannes G; van Os, Jim

2006-12-01

Observational studies have suggested that psychometric psychosis liability and a functional polymorphism in the catechol-O-methyltransferase (COMT Val(158)Met) gene moderate the psychosis-inducing effect of cannabis. To replicate and extend this finding, a double-blind, placebo-controlled cross-over design was used in which patients with a psychotic disorder (n=30), relatives of patients with a psychotic disorder (n=12), and healthy controls (n=32) were exposed to Delta-9-tetrahydrocannabinol (Delta-9-THC, the principal component of cannabis) or placebo, followed by cognitive assessment and assessment of current psychotic experiences. Previous expression of psychometric psychosis liability was also assessed. Models of current psychotic experiences and cognition were examined with multilevel random regression analyses to assess (i) main effects of genotype and condition, (ii) interactions between condition and genotype, and (iii) three-way interactions between condition, genotype, and psychometric psychosis liability. Carriers of the Val allele were most sensitive to Delta-9-THC-induced psychotic experiences, but this was conditional on prior evidence of psychometric psychosis liability. Delta-9-THC impacted negatively on cognitive measures. Carriers of the Val allele were also more sensitive to Delta-9-THC-induced memory and attention impairments compared to carriers of the Met allele. Experimental effects of Delta-9-THC on cognition and psychosis are moderated by COMT Val(158)Met genotype, but the effects may in part be conditional on the additional presence of pre-existing psychosis liability. The association between cannabis and psychosis may represent higher order gene-environment and gene-gene interactions.

Metabolically Coupled Replicator Systems: Overview of an RNA-world model concept of prebiotic evolution on mineral surfaces.

PubMed

Czárán, Tamás; Könnyű, Balázs; Szathmáry, Eörs

2015-09-21

Metabolically Coupled Replicator Systems (MCRS) are a family of models implementing a simple, physico-chemically and ecologically feasible scenario for the first steps of chemical evolution towards life. Evolution in an abiotically produced RNA-population sets in as soon as any one of the RNA molecules become autocatalytic by engaging in template directed self-replication from activated monomers, and starts increasing exponentially. Competition for the finite external supply of monomers ignites selection favouring RNA molecules with catalytic activity helping self-replication by any possible means. One way of providing such autocatalytic help is to become a replicase ribozyme. An additional way is through increasing monomer supply by contributing to monomer synthesis from external resources, i.e., by evolving metabolic enzyme activity. Retroevolution may build up an increasingly autotrophic, cooperating community of metabolic ribozymes running an increasingly complicated and ever more efficient metabolism. Maintaining such a cooperating community of metabolic replicators raises two serious ecological problems: one is keeping the system coexistent in spite of the different replicabilities of the cooperating replicators; the other is constraining parasitism, i.e., keeping "cheaters" in check. Surface-bound MCRS provide an automatic solution to both problems: coexistence and parasite resistance are the consequences of assuming the local nature of metabolic interactions. In this review we present an overview of results published in previous articles, showing that these effects are, indeed, robust in different MCRS implementations, by considering different environmental setups and realistic chemical details in a few different models. We argue that the MCRS model framework naturally offers a suitable starting point for the future modelling of membrane evolution and extending the theory to cover the emergence of the first protocell in a self-consistent manner. The coevolution of metabolic, genetic and membrane functions is hypothesized to follow the progressive sequestration scenario, the conceptual blueprint for the earliest steps of protocell evolution. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

PubMed

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.

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

PubMed Central

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

2017-01-01

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. PMID:28140396

Omega-3/Omega-6 Fatty Acids for Attention Deficit Hyperactivity Disorder: A Randomized Placebo-Controlled Trial in Children and Adolescents

ERIC Educational Resources Information Center

Johnson, Mats; Ostlund, Sven; Fransson, Gunnar; Kadesjo, Bjorn; Gillberg, Christopher

2009-01-01

Objective: The aim of the study was to assess omega 3/6 fatty acids (eye q) in attention deficit hyperactivity disorder (ADHD). Method: The study included a randomized, 3-month, omega 3/6 placebo-controlled, one-way crossover trial with 75 children and adolescents (8-18 years), followed by 3 months with omega 3/6 for all. Investigator-rated ADHD…

Does Branding Need Web Usability? A Value-Oriented Empirical Study

NASA Astrophysics Data System (ADS)

Bolchini, Davide; Garzotto, Franca; Sorce, Fabio

Does usability of a web-based communication artifact affect brand, i.e., the set of beliefs, emotions, attitudes, or qualities that people mentally associate to the entity behind that artifact? Intuitively, the answer is “yes”: usability is a fundamental aspect of the quality of the experience with a website, and a “good” experience with a “product” or its reifications tends to translate into “good” brand perception. To date, however, the existence of a connection between web usability and brand perception is shown through anecdotic arguments, and is not supported by published systematic research. This paper discusses a study that empirically investigates this correlation in a more rigorous, analytical, and replicable way. Our main contribution is twofold: on the one hand, we provide empirical evidence to the heuristic principle that web usability influences branding, and we do that through four between subjects controlled experiments that involved 120 subjects. On the other hand, we inform the study with a systematic value-oriented approach to the user experience, and thus provide a conceptual framework that can be reused in other experimental settings, either for replicating our study, or for designing similar studies focusing on the correlation of web branding vs. design factors other than usability.

A New Replicator: A theoretical framework for analysing replication

PubMed Central

2010-01-01

Background Replicators are the crucial entities in evolution. The notion of a replicator, however, is far less exact than the weight of its importance. Without identifying and classifying multiplying entities exactly, their dynamics cannot be determined appropriately. Therefore, it is importance to decide the nature and characteristics of any multiplying entity, in a detailed and formal way. Results Replication is basically an autocatalytic process which enables us to rest on the notions of formal chemistry. This statement has major implications. Simple autocatalytic cycle intermediates are considered as non-informational replicators. A consequence of which is that any autocatalytically multiplying entity is a replicator, be it simple or overly complex (even nests). A stricter definition refers to entities which can inherit acquired changes (informational replicators). Simple autocatalytic molecules (and nests) are excluded from this group. However, in turn, any entity possessing copiable information is to be named a replicator, even multicellular organisms. In order to deal with the situation, an abstract, formal framework is presented, which allows the proper identification of various types of replicators. This sheds light on the old problem of the units and levels of selection and evolution. A hierarchical classification for the partition of the replicator-continuum is provided where specific replicators are nested within more general ones. The classification should be able to be successfully applied to known replicators and also to future candidates. Conclusion This paper redefines the concept of the replicator from a bottom-up theoretical approach. The formal definition and the abstract models presented can distinguish between among all possible replicator types, based on their quantity of variable and heritable information. This allows for the exact identification of various replicator types and their underlying dynamics. The most important claim is that replication, in general, is basically autocatalysis, with a specific defined environment and selective force. A replicator is not valid unless its working environment, and the selective force to which it is subject, is specified. PMID:20219099

Whole-body cryotherapy (extreme cold air exposure) for preventing and treating muscle soreness after exercise in adults.

PubMed

Costello, Joseph T; Baker, Philip R A; Minett, Geoffrey M; Bieuzen, Francois; Stewart, Ian B; Bleakley, Chris

2015-09-18

Recovery strategies are often used with the intention of preventing or minimising muscle soreness after exercise. Whole-body cryotherapy, which involves a single or repeated exposure(s) to extremely cold dry air (below -100 °C) in a specialised chamber or cabin for two to four minutes per exposure, is currently being advocated as an effective intervention to reduce muscle soreness after exercise. To assess the effects (benefits and harms) of whole-body cryotherapy (extreme cold air exposure) for preventing and treating muscle soreness after exercise in adults. We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, the British Nursing Index and the Physiotherapy Evidence Database. We also searched the reference lists of articles, trial registers and conference proceedings, handsearched journals and contacted experts.The searches were run in August 2015. We aimed to include randomised and quasi-randomised trials that compared the use of whole-body cryotherapy (WBC) versus a passive or control intervention (rest, no treatment or placebo treatment) or active interventions including cold or contrast water immersion, active recovery and infrared therapy for preventing or treating muscle soreness after exercise in adults. We also aimed to include randomised trials that compared different durations or dosages of WBC. Our prespecified primary outcomes were muscle soreness, subjective recovery (e.g. tiredness, well-being) and adverse effects. Two review authors independently screened search results, selected studies, assessed risk of bias and extracted and cross-checked data. Where appropriate, we pooled results of comparable trials. The random-effects model was used for pooling where there was substantial heterogeneity. We assessed the quality of the evidence using GRADE. Four laboratory-based randomised controlled trials were included. These reported results for 64 physically active predominantly young adults (mean age 23 years). All but four participants were male. Two trials were parallel group trials (44 participants) and two were cross-over trials (20 participants). The trials were heterogeneous, including the type, temperature, duration and frequency of WBC, and the type of preceding exercise. None of the trials reported active surveillance of predefined adverse events. All four trials had design features that carried a high risk of bias, potentially limiting the reliability of their findings. The evidence for all outcomes was classified as 'very low' quality based on the GRADE criteria.Two comparisons were tested: WBC versus control (rest or no WBC), tested in four studies; and WBC versus far-infrared therapy, also tested in one study. No studies compared WBC with other active interventions, such as cold water immersion, or different types and applications of WBC.All four trials compared WBC with rest or no WBC. There was very low quality evidence for lower self-reported muscle soreness (pain at rest) scores after WBC at 1 hour (standardised mean difference (SMD) -0.77, 95% confidence interval (CI) -1.42 to -0.12; 20 participants, 2 cross-over trials); 24 hours (SMD -0.57, 95% CI -1.48 to 0.33) and 48 hours (SMD -0.58, 95% CI -1.37 to 0.21), both with 38 participants, 2 cross-over studies, 1 parallel group study; and 72 hours (SMD -0.65, 95% CI -2.54 to 1.24; 29 participants, 1 cross-over study, 1 parallel group study). Of note is that the 95% CIs also included either no between-group differences or a benefit in favour of the control group. One small cross-over trial (9 participants) found no difference in tiredness but better well-being after WBC at 24 hours post exercise. There was no report of adverse events.One small cross-over trial involving nine well-trained runners provided very low quality evidence of lower levels of muscle soreness after WBC, when compared with infrared therapy, at 1 hour follow-up, but not at 24 or 48 hours. The same trial found no difference in well-being but less tiredness after WBC at 24 hours post exercise. There was no report of adverse events. There is insufficient evidence to determine whether whole-body cryotherapy (WBC) reduces self-reported muscle soreness, or improves subjective recovery, after exercise compared with passive rest or no WBC in physically active young adult males. There is no evidence on the use of this intervention in females or elite athletes. The lack of evidence on adverse events is important given that the exposure to extreme temperature presents a potential hazard. Further high-quality, well-reported research in this area is required and must provide detailed reporting of adverse events.

Unambiguously identifying spin states of transition-metal ions in the Earth (Invited)

NASA Astrophysics Data System (ADS)

Hsu, H.

2010-12-01

The spin state of a transition-metal ion in crystalline solids, defined by the number of unpaired electrons in the ion’s incomplete 3d shell, may vary with many factors, such as temperature, pressure, strain, and the local atomic configuration, to name a few. Such a phenomenon, known as spin-state crossover, plays a crucial role in spintronic materials. Recently, the pressure-induced spin-state crossover in iron-bearing minerals has been recognized to affect the minerals’ structural and elastic properties. However, the detailed mechanism of such crossover in iron-bearing magnesium silicate perovskite, the most abundant mineral in the Earth, remains unclear. A significant part of this confusion arises from the difficulty in reliably extracting the spin state from experiments. For the same reason, the thermally-induced spin-state crossover in lanthanum cobaltite (LaCoO3) has been controversial for more than four decades. In this talk, I will discuss how first-principle calculations can help clarifying these long-standing controversies. In addition to the total energy, equation of state, and elastic properties of each spin state, first-principle calculations also predict the electric field gradient (EFG) at the nucleus of each transition-metal ion. Our calculations showed that the nuclear EFG, a quantity that can be measured via Mössbauer or nuclear magnetic resonance (NMR) spectroscopy, depends primarily on the spin state, irrespective of the concentration or configuration of transition-metal ions. Such robustness makes EFG a unique fingerprint to identify the spin state. The combination of first-principle calculations and Mössbauer/NMR spectroscopy can therefore be a reliable and efficient approach in tackling spin-state crossover problems in the Earth. This work was primarily supported by the MRSEC Program of NSF under Awards Number DMR-0212302 and DMR-0819885, and partially supported by NSF under ATM-0428774 (V-Lab), EAR-1019853, and EAR-0810272. The computations were performed mainly at the Minnesota Supercomputing Institute (MSI).

The importance of replication in wildlife research

USGS Publications Warehouse

Johnson, D.H.

2002-01-01

Wildlife ecology and management studies have been widely criticized for deficiencies in design or analysis. Manipulative experiments--with controls, randomization, and replication in space and time--provide powerful ways of learning about natural systems and establishing causal relationships, but such studies are rare in our field. Observational studies and sample surveys are more common; they also require appropriate design and analysis. More important than the design and analysis of individual studies is metareplication: replication of entire studies. Similar conclusions obtained from studies of the same phenomenon conducted under widely differing conditions will give us greater confidence in the generality of those findings than would any single study, however well designed and executed.

HPV31 Utilizes the ATR-Chk1 Pathway to Maintain Elevated RRM2 Levels and a Replication-Competent Environment in Differentiating Keratinocytes

PubMed Central

Anacker, Daniel C.; Aloor, Heather L.; Shepard, Caitlin N.; Lenzi, Gina M.; Johnson, Bryan A.; Kim, Baek; Moody, Cary A.

2016-01-01

Productive replication of human papillomaviruses (HPV) is restricted to the uppermost layers of the differentiating epithelia. How HPV ensures an adequate supply of cellular substrates for viral DNA synthesis in a differentiating environment is unclear. Here, we demonstrate that HPV31 positive cells exhibit increased dNTP pools and levels of RRM2, a component of the ribonucleotide reductase (RNR) complex, which is required for de novo synthesis of dNTPs. RRM2 depletion blocks productive replication, suggesting RRM2 provides dNTPs for viral DNA synthesis in differentiating cells. We demonstrate that HPV31 regulates RRM2 levels through expression of E7 and activation of the ATR-Chk1-E2F1 DNA damage response, which is essential to combat replication stress upon entry into S-phase, as well as for productive replication. Our findings suggest a novel way in which viral DNA synthesis is regulated through activation of ATR and Chk1 and highlight an intriguing new virus/host interaction utilized for viral replication. PMID:27764728

Effect of fungicides on sorghum anthracnose and grain mold in Burleson County, Texas, 2013

USDA-ARS?s Scientific Manuscript database

The experiment was conducted at the Texas AgriLife Experiment Station near College Station. The hybrids BH3822 and BH 5566 were planted in replicated plots and treatment arranged in a randomized, blocked factorial design. Each replicate consisted of four, 20 ft rows, with 30-in. row spacing and a ...

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

ERIC Educational Resources Information Center

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…

A Systems Approach to Effectiveness in Catholic Elementary Schools: A Replication and Extension

ERIC Educational Resources Information Center

Mitchell, Roxanne M.; Tarter, C. John

2011-01-01

This study replicated an earlier study conducted by Tarter and Hoy (2004) in which an open systems model was used to test a series of hypotheses that explained elements of school performance. Four internal system elements (structure, individual, culture, and politics) of the school were used to explain two sets of school outcomes (student…

Cognitive Mediation of Rape's Mental Health Impact: Constructive Replication of a Cross-Sectional Model in Longitudinal Data

ERIC Educational Resources Information Center

Koss, Mary P.; Figueredo, Aurelio Jose

2004-01-01

The constructive replication of a prespecified, cognitively mediated model of rape's impact on psychosocial health is reported using longitudinal data (see Koss, Figueredo, & Prince, 2002, for a summary of model development). Rape survivors (n= 59) were assessed four times, 3 to 24 months postrape. Structural equations modeling of baseline data…

Quasi-experimental designs in practice-based research settings: design and implementation considerations.

PubMed

Handley, Margaret A; Schillinger, Dean; Shiboski, Stephen

2011-01-01

Although randomized controlled trials are often a gold standard for determining intervention effects, in the area of practice-based research (PBR), there are many situations in which individual randomization is not possible. Alternative approaches to evaluating interventions have received increased attention, particularly those that can retain elements of randomization such that they can be considered "controlled" trials. Methodological design elements and practical implementation considerations for two quasi-experimental design approaches that have considerable promise in PBR settings--the stepped-wedge design, and a variant of this design, a wait-list cross-over design, are presented along with a case study from a recent PBR intervention for patients with diabetes. PBR-relevant design features include: creation of a cohort over time that collects control data but allows all participants (clusters or patients) to receive the intervention; staggered introduction of clusters; multiple data collection points; and one-way cross-over into the intervention arm. Practical considerations include: randomization versus stratification, training run in phases; and extended time period for overall study completion. Several design features of practice based research studies can be adapted to local circumstances yet retain elements to improve methodological rigor. Studies that utilize these methods, such as the stepped-wedge design and the wait-list cross-over design, can increase the evidence base for controlled studies conducted within the complex environment of PBR.

The deficit of joint position sense in the chronic unstable ankle as measured by inversion angle replication error.

PubMed

Nakasa, Tomoyuki; Fukuhara, Kohei; Adachi, Nobuo; Ochi, Mitsuo

2008-05-01

Functional instability is defined as a repeated ankle inversion sprain and a giving way sensation. Previous studies have described the damage of sensori-motor control in ankle sprain as being a possible cause of functional instability. The aim of this study was to evaluate the inversion angle replication errors in patients with functional instability after ankle sprain. The difference between the index angle and replication angle was measured in 12 subjects with functional instability, with the aim of evaluating the replication error. As a control group, the replication errors of 17 healthy volunteers were investigated. The side-to-side differences of the replication errors were compared between both the groups, and the relationship between the side-to-side differences of the replication errors and the mechanical instability were statistically analyzed in the unstable group. The side-to-side difference of the replication errors was 1.0 +/- 0.7 degrees in the unstable group and 0.2 +/- 0.7 degrees in the control group. There was a statistically significant difference between both the groups. The side-to-side differences of the replication errors in the unstable group did not statistically correlate to the anterior talar translation and talar tilt. The patients with functional instability had the deficit of joint position sense in comparison with healthy volunteers. The replication error did not correlate to the mechanical instability. The patients with functional instability should be treated appropriately in spite of having less mechanical instability.

Comparison of the Transcription and Replication Strategies of Marburg Virus and Ebola Virus by Using Artificial Replication Systems

PubMed Central

Mühlberger, Elke; Weik, Michael; Volchkov, Viktor E.; Klenk, Hans-Dieter; Becker, Stephan

1999-01-01

The members of the family Filoviridae, Marburg virus (MBGV) and Ebola virus (EBOV), are very similar in terms of morphology, genome organization, and protein composition. To compare the replication and transcription strategies of both viruses, an artificial replication system based on the vaccinia virus T7 expression system was established for EBOV. Specific transcription and replication of an artificial monocistronic minireplicon was demonstrated by reporter gene expression and detection of the transcribed and replicated RNA species. As it was shown previously for MBGV, three of the four EBOV nucleocapsid proteins, NP, VP35, and L, were essential and sufficient for replication. In contrast to MBGV, EBOV-specific transcription was dependent on the presence of the fourth nucleocapsid protein, VP30. When EBOV VP30 was replaced by MBGV VP30, EBOV-specific transcription was observed but with lower efficiency. Exchange of NP, VP35, and L between the two replication systems did not lead to detectable reporter gene expression. It was further observed that neither MBGV nor EBOV were able to replicate the heterologous minigenomes. A chimeric minigenome, however, containing the EBOV leader and the MBGV trailer was encapsidated, replicated, transcribed, and packaged by both viruses. PMID:9971816

Growth Performance, Carcass Traits and Serum Mineral Chemistry as Affected by Dietary Sodium and Sodium Salts Fed to Broiler Chickens Reared under Phase Feeding System

PubMed Central

Mushtaq, M. M. H.; Pasha, T. N.; Saima; Akram, M.; Mushtaq, T.; Parvin, R.; Farooq, U.; Mehmood, S.; Iqbal, K. J.; Hwangbo, J.

2013-01-01

A basal diet (0.8 g/kg dNa) was formulated in which each of the two sources (NaHCO3 and Na2SO4) were supplemented in such a way to attain four levels (1.7, 2.6, 3.5, and 4.4 g/kg) of total dNa, respectively, under 4×2 factorial arrangement. Eight dietary treatments were replicated four times, with 40 birds in each replicate (n = 1,280). The diets supplemented with Na2SO4 to attain higher levels of dNa showed highest BW gain and feed intake (FI) during d 1 to 10 (interaction effects) while 2.6 g/kg dNa exhibited improved BW gain and gain:feed (FG) during d 11 to 20. Linear rise in daily water intake (DWI) was associated with diets containing increasing dNa during d 1 to 42 (p≤0.036). During the first 10 d, DWI:FI was found highest in NaHCO3 diets while Na2SO4 diets showed highest DWI:FI during last 10 d of the experiment (p≤0.036). Increasing dNa and changing Na2SO4 with NaHCO3 salt increased pH and resulted in poor growth performance. Dressing weight (p≤0.001) and abdominal fat (p≤0.001; quadratic effect) were reduced, whereas breast (p≤0.001) and thigh (p<0.001) weights were aggravated with increasing dNa (linear effects). Present findings suggested higher levels of dNa from Na2SO4 as the supplemental salt in broiler diets would produce better growth performance, especially in first ten days of life, and improve carcass and body organ characteristics. PMID:25049765

Measuring DNA Replication in Hypoxic Conditions.

PubMed

Foskolou, Iosifina P; Biasoli, Deborah; Olcina, Monica M; Hammond, Ester M

2016-01-01

It is imperative that dividing cells maintain replication fork integrity in order to prevent DNA damage and cell death. The investigation of DNA replication is of high importance as alterations in this process can lead to genomic instability, a known causative factor of tumor development. A simple, sensitive, and informative technique which enables the study of DNA replication, is the DNA fiber assay, an adaptation of which is described in this chapter. The DNA fiber method is a powerful tool, which allows the quantitative and qualitative analysis of DNA replication at the single molecule level. The sequential pulse labeling of live cells with two thymidine analogues and the subsequent detection with specific antibodies and fluorescence imaging allows direct examination of sites of DNA synthesis. In this chapter, we describe how this assay can be performed in conditions of low oxygen levels (hypoxia)-a physiologically relevant stress that occurs in most solid tumors. Moreover, we suggest ways on how to overcome the technical problems that arise while using the hypoxic chambers.

Human Mitochondrial DNA Replication

PubMed Central

Holt, Ian J.; Reyes, Aurelio

2012-01-01

Elucidation of the process of DNA replication in mitochondria is in its infancy. For many years, maintenance of the mitochondrial genome was regarded as greatly simplified compared to the nucleus. Mammalian mitochondria were reported to lack all DNA repair systems, to eschew DNA recombination, and to possess but a single DNA polymerase, polymerase γ. Polγ was said to replicate mitochondrial DNA exclusively via one mechanism, involving only two priming events and a handful of proteins. In this “strand-displacement model,” leading strand DNA synthesis begins at a specific site and advances approximately two-thirds of the way around the molecule before DNA synthesis is initiated on the “lagging” strand. Although the displaced strand was long-held to be coated with protein, RNA has more recently been proposed in its place. Furthermore, mitochondrial DNA molecules with all the features of products of conventional bidirectional replication have been documented, suggesting that the process and regulation of replication in mitochondria is complex, as befits a genome that is a core factor in human health and longevity. PMID:23143808

Antiviral effect of PmRab7 knock-down on inhibition of Laem-Singh virus replication in black tiger shrimp.

PubMed

Ongvarrasopone, Chalermporn; Chomchay, Ekapol; Panyim, Sakol

2010-10-01

PmRab7 is a Penaeus monodon small GTPase protein possibly involved in replication of several shrimp viruses. In this study RNA interference (RNAi) using double-stranded RNA (dsRNA) targeting PmRab7 gene (dsRNA-PmRab7) was employed to silence the expression of PmRab7 to investigate the inhibitory effect on Laem-Singh virus (LSNV) replication. Injection of dsRNA-PmRab7 24h before challenge with the virus resulted in a drastic decrease of PmRab7 mRNA and complete inhibition of LSNV replication at 3 days post-challenge. In a therapeutic mode, shrimp injected with dsRNA-PmRab7 1 day but not at 3 or 5 days post-LSNV challenge resulted in inhibition of LSNV replication. These results pave the way to use dsRNA-PmRab7 to prevent or cure LSNV infection in shrimp. Copyright © 2010 Elsevier B.V. All rights reserved.

Small finger protein of avian and murine retroviruses has nucleic acid annealing activity and positions the replication primer tRNA onto genomic RNA.

PubMed Central

Prats, A C; Sarih, L; Gabus, C; Litvak, S; Keith, G; Darlix, J L

1988-01-01

Retrovirus virions carry a diploid genome associated with a large number of small viral finger protein molecules which are required for encapsidation. Our present results show that finger protein p12 of Rous sarcoma virus (RSV) and p10 of murine leukaemia virus (MuLV) positions replication primer tRNA on the replication initiation site (PBS) at the 5' end of the RNA genome. An RSV mutant with a Val-Pro insertion in the finger motif of p12 is able to partially encapsidate genomic RNA but is not infectious because mutated p12 is incapable of positioning the replication primer, tRNATrp. Since all known replication competent retroviruses, and the plant virus CaMV, code for finger proteins analogous to RSV p12 or MuLV p10, the initial stage of reverse transcription in avian, mammalian and human retroviruses and in CaMV is probably controlled in an analogous way. Images PMID:2458920

Small finger protein of avian and murine retroviruses has nucleic acid annealing activity and positions the replication primer tRNA onto genomic RNA.

PubMed

Prats, A C; Sarih, L; Gabus, C; Litvak, S; Keith, G; Darlix, J L

1988-06-01

Retrovirus virions carry a diploid genome associated with a large number of small viral finger protein molecules which are required for encapsidation. Our present results show that finger protein p12 of Rous sarcoma virus (RSV) and p10 of murine leukaemia virus (MuLV) positions replication primer tRNA on the replication initiation site (PBS) at the 5' end of the RNA genome. An RSV mutant with a Val-Pro insertion in the finger motif of p12 is able to partially encapsidate genomic RNA but is not infectious because mutated p12 is incapable of positioning the replication primer, tRNATrp. Since all known replication competent retroviruses, and the plant virus CaMV, code for finger proteins analogous to RSV p12 or MuLV p10, the initial stage of reverse transcription in avian, mammalian and human retroviruses and in CaMV is probably controlled in an analogous way.

Going Underground: A Field Investigation and Lab Activity on Karst Topography and Water Systems

ERIC Educational Resources Information Center

O'Dell, Gary; Gonzalez-Espada, Wilson

2011-01-01

Students learn science best with activities that mirror the way scientists work. This article describes how geologists investigate groundwater flow systems in areas of karst topography--geologic formations shaped by dissolving bedrock--and provides a way for students to replicate this research. Students also use electric current to model water…

Design, analysis, and testing of high frequency passively damped struts

NASA Technical Reports Server (NTRS)

Yiu, Y. C.; Davis, L. Porter; Napolitano, Kevin; Ninneman, R. Rory

1993-01-01

Objectives of the research are: (1) to develop design requirements for damped struts to stabilize control system in the high frequency cross-over and spill-over range; (2) to design, fabricate and test viscously damped strut and viscoelastically damped strut; (3) to verify accuracy of design and analysis methodology of damped struts; and (4) to design and build test apparatus, and develop data reduction algorithm to measure strut complex stiffness. In order to meet the stringent performance requirements of the SPICE experiment, the active control system is used to suppress the dynamic responses of the low order structural modes. However, the control system also inadvertently drives some of the higher order modes unstable in the cross-over and spill-over frequency range. Passive damping is a reliable and effective way to provide damping to stabilize the control system. It also improves the robustness of the control system. Damping is designed into the SPICE testbed as an integral part of the control-structure technology.

Double-blind evaluation of deanol in tardive dyskinesia.

PubMed

Penovich, P; Morgan, J P; Kerzner, B; Karch, F; Goldblatt, D

1978-05-12

We administered deanol acetamidobenzoate, 2.0 g/day for four weeks, a double-blind, placebo-controlled crossover trial, to 14 patients with tardive dyskineasia. The patient population included both inpatients and outpatients. The response was evaluated by subjective clinical impression and scoring of filmed sequences. Patients' conditions improved significantly from baseline scores while receiving both deanol and placebo, but there was no distinction between the two treatments.

Effect of sex, age and genetics on crossover interference in cattle

PubMed Central

Wang, Zhiying; Shen, Botong; Jiang, Jicai; Li, Jinquan; Ma, Li

2016-01-01

Crossovers generated by homologous recombination ensure proper chromosome segregation during meiosis. Crossover interference results in chiasmata being more evenly distributed along chromosomes, but the mechanism underlying crossover interference remains elusive. Based on large pedigrees of Holstein and Jersey cattle with genotype data, we extracted three-generation families, including 147,327 male and 71,687 female meioses in Holstein, and 108,163 male and 37,008 female meioses in Jersey, respectively. We identified crossovers in these meioses and fitted the Housworth-Stahl “interference-escape” model to study crossover interference patterns in the cattle genome. Our result reveals that the degree of crossover interference is stronger in females than in males. We found evidence for inter-chromosomal variation in the level of crossover interference, with smaller chromosomes exhibiting stronger interference. In addition, crossover interference levels decreased with maternal age. Finally, sex-specific GWAS analyses identified one locus near the NEK9 gene on chromosome 10 to have a significant effect on crossover interference levels. This locus has been previously associated with recombination rate in cattle. Collectively, this large-scale analysis provided a comprehensive description of crossover interference across chromosome, sex and age groups, identified associated candidate genes, and produced useful insights into the mechanism of crossover interference. PMID:27892966

Calibration Matters: Advances in Strapdown Airborne Gravimetry

NASA Astrophysics Data System (ADS)

Becker, D.

2015-12-01

Using a commercial navigation-grade strapdown inertial measurement unit (IMU) for airborne gravimetry can be advantageous in terms of cost, handling, and space consumption compared to the classical stable-platform spring gravimeters. Up to now, however, large sensor errors made it impossible to reach the mGal-level using such type IMUs as they are not designed or optimized for this kind of application. Apart from a proper error-modeling in the filtering process, specific calibration methods that are tailored to the application of aerogravity may help to bridge this gap and to improve their performance. Based on simulations, a quantitative analysis is presented on how much IMU sensor errors, as biases, scale factors, cross couplings, and thermal drifts distort the determination of gravity and the deflection of the vertical (DOV). Several lab and in-field calibration methods are briefly discussed, and calibration results are shown for an iMAR RQH unit. In particular, a thermal lab calibration of its QA2000 accelerometers greatly improved the long-term drift behavior. Latest results from four recent airborne gravimetry campaigns confirm the effectiveness of the calibrations applied, with cross-over accuracies reaching 1.0 mGal (0.6 mGal after cross-over adjustment) and DOV accuracies reaching 1.1 arc seconds after cross-over adjustment.

Self-reported smoking effects and comparative value between cigarettes and high dose e-cigarettes in nicotine-dependent cigarette smokers.

PubMed

McPherson, Sterling; Howell, Donelle; Lewis, Jennifer; Barbosa-Leiker, Celestina; Bertotti Metoyer, Patrick; Roll, John

2016-04-01

The objective of this experiment was to evaluate the comparative value of cigarettes versus high dose e-cigarettes among nicotine-dependent cigarette smokers when compared with money or use of their usual cigarette brand. The experiment used a within-subject design with four sessions. After baseline assessment, participants attended two 15-min unrestricted smoking sessions: one cigarette smoking session and one e-cigarette smoking session. Participants then attended two multiple-choice procedure (MCP) sessions: a session comparing cigarettes and money and a session comparing e-cigarettes and money. Participants (n=27) had used cigarettes regularly, had never used e-cigarettes, and were not currently attempting to quit smoking. The sample consisted primarily of males (72%), with a mean age of 34 years. When given the opportunity to choose between smoking a cigarette or an e-cigarette, participants chose the cigarette 73.9% of the time. Findings from the MCP demonstrated that after the first e-cigarette exposure sessions, the crossover value for cigarettes ($3.45) was significantly higher compared with the crossover value for e-cigarettes ($2.73). The higher participant preference, self-reported smoking effects, and higher MCP crossover points indicate that cigarettes have a higher comparative value than high dose e-cigarettes among e-cigarette naive smokers.

Exercise frequency and calcium intake predict 4-year bone changes in postmenopausal women.

PubMed

Cussler, Ellen C; Going, Scott B; Houtkooper, Linda B; Stanford, Vanessa A; Blew, Robert M; Flint-Wagner, Hilary G; Metcalfe, Lauve L; Choi, Ji-Eun; Lohman, Timothy G

2005-12-01

The aim of this study was to examine the association of exercise frequency and calcium intake (CI) with change in regional and total bone mineral density (BMD) in a group of postmenopausal women completing 4 years of progressive strength training. One hundred sixty-seven calcium-supplemented (800 mg/day) sedentary women (56.1+/-4.5 years) randomized to a progressive strength training exercise program or to control were followed for 4 years. Fifty-four percent of the women were using hormone therapy (HT) at baseline. At 1 year, controls were permitted to begin the exercise program (crossovers). The final sample included 23 controls, 55 crossovers, and 89 randomized exercisers. Exercisers were instructed to complete two sets of six to eight repetitions of exercises at 70-80% of one repetition maximum, three times weekly. BMD was measured at baseline and thereafter annually using dual-energy X-ray absorptiometry. Four-year percentage exercise frequency (ExFreq) averaged 26.8%+/-20.1% for crossovers (including the first year at 0%), and 50.4%+/-26.7% for exercisers. Four-year total CI averaged 1,635+/-367 mg/day and supplemental calcium intake, 711+/-174 mg/day. In adjusted multiple linear regression models, ExFreq was positively and significantly related to changes in femur trochanter (FT) and neck (FN), lumbar spine (LS), and total body (TB) BMD. Among HT users, FT BMD increased 1.5%, and FN and LS BMD, 1.2% (p<0.01) for each standard deviation (SD) of percentage ExFreq (29.5% or 0.9 days/week). HT non-users gained 1.9% and 2.3% BMD at FT and FN, respectively, (p<0.05) for every SD of CI. The significant, positive, association between BMD change and ExFreq supports the long-term usefulness of strength training exercise for the prevention of osteoporosis in postmenopausal women, especially HT users. The positive relationship of CI to change in BMD among postmenopausal women not using HT has clinical implications in light of recent evidence of an increased health risk associated with HT.

Reversal of apixaban anticoagulation by four-factor prothrombin complex concentrates in healthy subjects: a randomized three-period crossover study.

PubMed

Song, Y; Wang, Z; Perlstein, I; Wang, J; LaCreta, F; Frost, R J A; Frost, C

2017-11-01

Essentials Prothrombin complex concentrates (PCCs) may reverse the effect of factor Xa (FXa) inhibitors. We conducted an open-label, randomized, placebo-controlled, three-period crossover study in 15 subjects. Both PCCs rapidly reversed apixaban-mediated decreases in mean endogenous thrombin potential. Four-factor PCC administration had no effect on apixaban pharmacokinetics or anti-FXa activity. Background Currently, there is no approved reversal agent for direct activated factor Xa (FXa) inhibitors; however, several agents are under investigation, including prothrombin complex concentrates (PCCs). Objective This open-label, randomized, placebo-controlled, three-period crossover study assessed the effect of two four-factor PCCs on apixaban pharmacodynamics and pharmacokinetics in 15 healthy subjects. Methods Subjects received apixaban 10 mg twice daily for 3 days. On day 4, 3 h after apixaban, subjects received a 30-min infusion of 50 IU kg -1 Cofact, Beriplex P/N (Beriplex), or saline. Change in endogenous thrombin potential (ETP), measured with a thrombin generation assay (TGA), was the primary endpoint. Secondary endpoints included changes in other TGA parameters, prothrombin time (PT), International Normalized Ratio (INR), activated partial thromboplastin time, anti-FXa activity, apixaban pharmacokinetics, and safety. Results Apixaban-related changes in ETP and several other pharmacodynamic measures occurred following apixaban administration. Both PCCs reversed apixaban's effect on ETP; the differences in adjusted mean change from pre-PCC baseline to end of infusion were 425 nm min (95% confidence interval [CI] 219.8-630.7 nm min; P < 0.001) for Cofact, and 91 nm min (95% CI - 31.3 to 212.4 nm min; P > 0.05) for Beriplex. Both PCCs returned ETP to pre-apixaban baseline levels 4 h after PCC infusion, versus 45 h for placebo. For both PCCs, mean ETP peaked 21 h after PCC initiation, and then slowly decreased over the following 48 h. Both PCCs reversed apixaban's effect on TGA peak height, PT, and INR. Apixaban pharmacokinetic and anti-FXa profiles were consistent across treatments. Conclusions Cofact and Beriplex reversed apixaban's steady-state effects on several coagulation assessments. © 2017 International Society on Thrombosis and Haemostasis.

Variation and Evolution of the Meiotic Requirement for Crossing Over in Mammals.

PubMed

Dumont, Beth L

2017-01-01

The segregation of homologous chromosomes at the first meiotic division is dependent on the presence of at least one well-positioned crossover per chromosome. In some mammalian species, however, the genomic distribution of crossovers is consistent with a more stringent baseline requirement of one crossover per chromosome arm. Given that the meiotic requirement for crossing over defines the minimum frequency of recombination necessary for the production of viable gametes, determining the chromosomal scale of this constraint is essential for defining crossover profiles predisposed to aneuploidy and understanding the parameters that shape patterns of recombination rate evolution across species. Here, I use cytogenetic methods for in situ imaging of crossovers in karyotypically diverse house mice (Mus musculus domesticus) and voles (genus Microtus) to test how chromosome number and configuration constrain the distribution of crossovers in a genome. I show that the global distribution of crossovers in house mice is thresholded by a minimum of one crossover per chromosome arm, whereas the crossover landscape in voles is defined by a more relaxed requirement of one crossover per chromosome. I extend these findings in an evolutionary metaanalysis of published recombination and karyotype data for 112 mammalian species and demonstrate that the physical scale of the genomic crossover distribution has undergone multiple independent shifts from one crossover per chromosome arm to one per chromosome during mammalian evolution. Together, these results indicate that the chromosomal scale constraint on crossover rates is itself a trait that evolves among species, a finding that casts light on an important source of crossover rate variation in mammals. Copyright © 2017 by the Genetics Society of America.

Interferon-β 1a and SARS Coronavirus Replication

PubMed Central

Hensley, Lisa E.; Fritz, Elizabeth A.; Karp, Christopher; Huggins, John W.; Geisbert, Thomas W.

2004-01-01

A global outbreak of severe acute respiratory syndrome (SARS) caused by a novel coronavirus began in March 2003. The rapid emergence of SARS and the substantial illness and death it caused have made it a critical public health issue. Because no effective treatments are available, an intensive effort is under way to identify and test promising antiviral drugs. Here, we report that recombinant human interferon (IFN)-β 1a potently inhibits SARS coronavirus replication in vitro. PMID:15030704

Defective replication initiation results in locus specific chromosome breakage and a ribosomal RNA deficiency in yeast

PubMed Central

Sanchez, Joseph C.; Kwan, Elizabeth X.; Raghuraman, M. K.; Brewer, Bonita J.

2017-01-01

A form of dwarfism known as Meier-Gorlin syndrome (MGS) is caused by recessive mutations in one of six different genes (ORC1, ORC4, ORC6, CDC6, CDT1, and MCM5). These genes encode components of the pre-replication complex, which assembles at origins of replication prior to S phase. Also, variants in two additional replication initiation genes have joined the list of causative mutations for MGS (Geminin and CDC45). The identity of the causative MGS genetic variants strongly suggests that some aspect of replication is amiss in MGS patients; however, little evidence has been obtained regarding what aspect of chromosome replication is faulty. Since the site of one of the missense mutations in the human ORC4 alleles is conserved between humans and yeast, we sought to determine in what way this single amino acid change affects the process of chromosome replication, by introducing the comparable mutation into yeast (orc4Y232C). We find that yeast cells with the orc4Y232C allele have a prolonged S-phase, due to compromised replication initiation at the ribosomal DNA (rDNA) locus located on chromosome XII. The inability to initiate replication at the rDNA locus results in chromosome breakage and a severely reduced rDNA copy number in the survivors, presumably helping to ensure complete replication of chromosome XII. Although reducing rDNA copy number may help ensure complete chromosome replication, orc4Y232C cells struggle to meet the high demand for ribosomal RNA synthesis. This finding provides additional evidence linking two essential cellular pathways—DNA replication and ribosome biogenesis. PMID:29036220

Defective replication initiation results in locus specific chromosome breakage and a ribosomal RNA deficiency in yeast.

PubMed

Sanchez, Joseph C; Kwan, Elizabeth X; Pohl, Thomas J; Amemiya, Haley M; Raghuraman, M K; Brewer, Bonita J

2017-10-01

A form of dwarfism known as Meier-Gorlin syndrome (MGS) is caused by recessive mutations in one of six different genes (ORC1, ORC4, ORC6, CDC6, CDT1, and MCM5). These genes encode components of the pre-replication complex, which assembles at origins of replication prior to S phase. Also, variants in two additional replication initiation genes have joined the list of causative mutations for MGS (Geminin and CDC45). The identity of the causative MGS genetic variants strongly suggests that some aspect of replication is amiss in MGS patients; however, little evidence has been obtained regarding what aspect of chromosome replication is faulty. Since the site of one of the missense mutations in the human ORC4 alleles is conserved between humans and yeast, we sought to determine in what way this single amino acid change affects the process of chromosome replication, by introducing the comparable mutation into yeast (orc4Y232C). We find that yeast cells with the orc4Y232C allele have a prolonged S-phase, due to compromised replication initiation at the ribosomal DNA (rDNA) locus located on chromosome XII. The inability to initiate replication at the rDNA locus results in chromosome breakage and a severely reduced rDNA copy number in the survivors, presumably helping to ensure complete replication of chromosome XII. Although reducing rDNA copy number may help ensure complete chromosome replication, orc4Y232C cells struggle to meet the high demand for ribosomal RNA synthesis. This finding provides additional evidence linking two essential cellular pathways-DNA replication and ribosome biogenesis.

Testing crossover effects in an actor-partner interdependence model among Chinese dual-earner couples.

PubMed

Liu, Huimin; Cheung, Fanny M

2015-03-01

The purpose of the present study is to examine the crossover effects from one partner's work-family interface (work-family conflict [WFC] and work-family enrichment [WFE]) to the other partner's four outcomes (psychological strain, life satisfaction, marital satisfaction and job satisfaction) in a sample of Chinese dual-earner couples. Married couples (N = 361) completed a battery of questionnaires, including the work-family interface scale, the psychological strain scale, the life, marital, as well as job satisfaction scale. Results from the actor-partner interdependence model (APIM) analyses showed that wives' WFE was negatively associated with husbands' psychological strain, and positively associated with husbands' life, marital and job satisfaction. Furthermore, husbands' WFC was negatively related to wives' marital satisfaction, whereas husbands' WFE was positively related to wives' marital satisfaction. Theoretical and practical implications were discussed, and future research directions were provided. © 2014 International Union of Psychological Science.

How tetraquarks can generate a second chiral phase transition

DOE PAGES

Pisarski, Robert D.; Skokov, Vladimir V.

2016-09-09

We consider how tetraquarks can affect the chiral phase transition in theories like QCD, with light quarks coupled to three colors. For two flavors the tetraquark field is an isosinglet, and its effect is minimal. For three flavors, however, the tetraquark field transforms in the same representation of the chiral symmetry group as the usual chiral order parameter, and so for very light quarks there may be two chiral phase transitions, which are both of first order. In QCD, results from the lattice indicate that any transition from the tetraquark condensate is a smooth crossover. In the plane of temperature,more » T, and quark chemical potential, μ, though, a crossover line for the tetraquark condensate is naturally related to the transition line for color superconductivity. For four flavors we suggest that a triquark field, antisymmetric in both flavor and color, combine to form hexaquarks.« less

Dimensions of Temperament and Depressive Symptoms: Replicating a Three-Way Interaction

PubMed Central

Vasey, Michael W.; Harbaugh, Casaundra N.; Lonigan, Chistopher J.; Phillips, Beth M.; Hankin, Benjamin L.; Willem, Lore; Bijttebier, Patricia

2014-01-01

High negative emotionality (NE), low positive emotionality (PE), and low self-regulatory capacity (i.e., effortful control or EC) are related to depressive symptoms and furthermore, may moderate one another’s relations to such symptoms. Indeed, preliminary evidence suggests they may operate in a three-way interaction (Dinovo & Vasey, 2011), but the replicability of that finding remains unknown. Therefore, we tested this NExPExEC interaction in association with depressive symptoms in 5 independent samples. This interaction was significant in 4 of the 5 samples and a combined sample and approached significance in the fifth sample. In contrast, the NExPExEC interaction was unrelated to general anxious symptoms and thus may be specific to symptoms of depression. Implications, directions for future research, and limitations are discussed. PMID:24493906

A Short (Personal) Future History of Revolution 2.0.

PubMed

Spellman, Barbara A

2015-11-01

Crisis of replicability is one term that psychological scientists use for the current introspective phase we are in-I argue instead that we are going through a revolution analogous to a political revolution. Revolution 2.0 is an uprising focused on how we should be doing science now (i.e., in a 2.0 world). The precipitating events of the revolution have already been well-documented: failures to replicate, questionable research practices, fraud, etc. And the fact that none of these events is new to our field has also been well-documented. I suggest four interconnected reasons as to why this time is different: changing technology, changing demographics of researchers, limited resources, and misaligned incentives. I then describe two reasons why the revolution is more likely to catch on this time: technology (as part of the solution) and the fact that these concerns cut across social and life sciences-that is, we are not alone. Neither side in the revolution has behaved well, and each has characterized the other in extreme terms (although, of course, each has had a few extreme actors). Some suggested reforms are already taking hold (e.g., journals asking for more transparency in methods and analysis decisions; journals publishing replications) but the feared tyrannical requirements have, of course, not taken root (e.g., few journals require open data; there is no ban on exploratory analyses). Still, we have not yet made needed advances in the ways in which we accumulate, connect, and extract conclusions from our aggregated research. However, we are now ready to move forward by adopting incremental changes and by acknowledging the multiplicity of goals within psychological science. © The Author(s) 2015.

Initial small mammal responses to alternative pine regeneration methods in Arkansas and Oklahoma: preliminary findings

Treesearch

Ronald E. Thill; Roger W. Perry; Nancy E. Koerth; Philip A. Tappe; David G. Peitz

2004-01-01

Abstract - We studied winter small mammal communities in the Ouachita Mountains of west-central Arkansas and eastern Oklahoma using Sherman live traps in four replications of four regeneration treatments (clearcut/plant, shelterwood, single-tree selection, and group selection), plus four mature, untreated "controls." Data on relative small...

Low-cost replicable plastic HUD combiner element

NASA Astrophysics Data System (ADS)

Kress, Bernard; Raulot, Victorien; St. Hilaire, Pierre; Meyrueis, Patrick

2009-05-01

We present a novel technique to fabricate low cost mass replicable plastic HUDs for the transportation industry. HUD are implemented in numerous sectors today (in avionics, automobile, military, machinery,...). Typical implementations include an optical combiner which produces the desired virtual image while leaving the field mostly unaffected by the optics. Such combiners optics are usually implemented as cumbersome catadioptric devices in automobile, dichroic coated curved plates, or expensive volume holograms in commercial and military aviation. We propose a novel way to design, model and fabricate combiner masters which can be replicated in mass by UV casting in plastic. We review the various design techniques required for such elements and the novel mastering technology.

Self-Administered Cued Naming Therapy: A Single-Participant Investigation of a Computer-Based Therapy Program Replicated in Four Cases

ERIC Educational Resources Information Center

Ramsberger, Gail; Marie, Basem

2007-01-01

Purpose: This study examined the benefits of a self-administered, clinician-guided, computer-based, cued naming therapy. Results of intense and nonintense treatment schedules were compared. Method: A single-participant design with multiple baselines across behaviors and varied treatment intensity for 2 trained lists was replicated over 4…

Initiation preference at a yeast origin of replication.

PubMed

Brewer, B J; Fangman, W L

1994-04-12

Replication origins in the yeast Saccharomyces cerevisiae are identified as autonomous replication sequence (ARS) elements. To examine the effect of origin density on replication initiation, we have analyzed the replication of a plasmid that contains two copies of the same origin, ARS1. The activation of origins and the direction that replication forks move through flanking sequences can be physically determined by analyzing replication intermediates on two-dimensional agarose gels. We find that only one of the two identical ARSs on the plasmid initiates replication on any given plasmid molecule; that is, this close spacing of ARSs results in an apparent interference between the potential origins. Moreover, in the particular plasmid that we constructed, one of the two identical copies of ARS1 is used four times more frequently than the other one. These results show that the plasmid context is critical for determining the preferred origin. This origin preference is also exhibited when the tandem copies of ARS1 are introduced into a yeast chromosome. The sequences responsible for establishing the origin preference have been identified by deletion analysis and are found to reside in a portion of the yeast URA3 gene.

Spacetime Replication of Quantum Information Using (2 , 3) Quantum Secret Sharing and Teleportation

NASA Astrophysics Data System (ADS)

Wu, Yadong; Khalid, Abdullah; Davijani, Masoud; Sanders, Barry

The aim of this work is to construct a protocol to replicate quantum information in any valid configuration of causal diamonds and assess resources required to physically realize spacetime replication. We present a set of codes to replicate quantum information along with a scheme to realize these codes using continuous-variable quantum optics. We use our proposed experimental realizations to determine upper bounds on the quantum and classical resources required to simulate spacetime replication. For four causal diamonds, our implementation scheme is more efficient than the one proposed previously. Our codes are designed using a decomposition algorithm for complete directed graphs, (2 , 3) quantum secret sharing, quantum teleportation and entanglement swapping. These results show the simulation of spacetime replication of quantum information is feasible with existing experimental methods. Alberta Innovates, NSERC, China's 1000 Talent Plan and the Institute for Quantum Information and Matter, which is an NSF Physics Frontiers Center (NSF Grant PHY-1125565) with support of the Gordon and Betty Moore Foundation (GBMF-2644).

Genetic recombination in plant-infecting messenger-sense RNA viruses: overview and research perspectives

PubMed Central

Bujarski, Jozef J.

2013-01-01

RNA recombination is one of the driving forces of genetic variability in (+)-strand RNA viruses. Various types of RNA–RNA crossovers were described including crosses between the same or different viral RNAs or between viral and cellular RNAs. Likewise, a variety of molecular mechanisms are known to support RNA recombination, such as replicative events (based on internal or end-to-end replicase switchings) along with non-replicative joining among RNA fragments of viral and/or cellular origin. Such mechanisms as RNA decay or RNA interference are responsible for RNA fragmentation and trans-esterification reactions which are likely accountable for ligation of RNA fragments. Numerous host factors were found to affect the profiles of viral RNA recombinants and significant differences in recombination frequency were observed among various RNA viruses. Comparative analyses of viral sequences allowed for the development of evolutionary models in order to explain adaptive phenotypic changes and co-evolving sites. Many questions remain to be answered by forthcoming RNA recombination research. (1) How various factors modulate the ability of viral replicase to switch templates, (2) What is the intracellular location of RNA–RNA template switchings, (3) Mechanisms and factors responsible for non-replicative RNA recombination, (4) Mechanisms of integration of RNA viral sequences with cellular genomic DNA, and (5) What is the role of RNA splicing and ribozyme activity. From an evolutionary stand point, it is not known how RNA viruses parasitize new host species via recombination, nor is it obvious what the contribution of RNA recombination is among other RNA modification pathways. We do not understand why the frequency of RNA recombination varies so much among RNA viruses and the status of RNA recombination as a form of sex is not well documented. PMID:23533000

Genetic recombination in plant-infecting messenger-sense RNA viruses: overview and research perspectives.

PubMed

Bujarski, Jozef J

2013-01-01

RNA recombination is one of the driving forces of genetic variability in (+)-strand RNA viruses. Various types of RNA-RNA crossovers were described including crosses between the same or different viral RNAs or between viral and cellular RNAs. Likewise, a variety of molecular mechanisms are known to support RNA recombination, such as replicative events (based on internal or end-to-end replicase switchings) along with non-replicative joining among RNA fragments of viral and/or cellular origin. Such mechanisms as RNA decay or RNA interference are responsible for RNA fragmentation and trans-esterification reactions which are likely accountable for ligation of RNA fragments. Numerous host factors were found to affect the profiles of viral RNA recombinants and significant differences in recombination frequency were observed among various RNA viruses. Comparative analyses of viral sequences allowed for the development of evolutionary models in order to explain adaptive phenotypic changes and co-evolving sites. Many questions remain to be answered by forthcoming RNA recombination research. (1) How various factors modulate the ability of viral replicase to switch templates, (2) What is the intracellular location of RNA-RNA template switchings, (3) Mechanisms and factors responsible for non-replicative RNA recombination, (4) Mechanisms of integration of RNA viral sequences with cellular genomic DNA, and (5) What is the role of RNA splicing and ribozyme activity. From an evolutionary stand point, it is not known how RNA viruses parasitize new host species via recombination, nor is it obvious what the contribution of RNA recombination is among other RNA modification pathways. We do not understand why the frequency of RNA recombination varies so much among RNA viruses and the status of RNA recombination as a form of sex is not well documented.

Hey kid! Wanna build a loudspeaker? The first one's free

NASA Astrophysics Data System (ADS)

Garrett, Steven

2005-09-01

In 2000, Penn State University instituted a First Year Seminar (FYS) requirement for every entering undergraduate student. This paper describes a hands-on FYS on audio engineering that has each freshman, in a class of 20, construct and test a two-way loudspeaker system during eight 2-hour meetings. Time and resource constraints dictated that the speaker system must be assembled using only hand tools and characterized using only an oscillator and digital multimeters. Due to limitations on the funds made available for each FYS by the College of Engineering, the total cost of entire system could not exceed $65/side. Each student is provided with a woofer, tweeter, crossover components, and enclosure parts to build one speaker system. The students are offered the option of purchasing a second set of parts for $65 so that they can complete the course with a stereo pair. Ninety percent of the students exercise the stereo option. This presentation will describe the speaker system, using an enclosure made primarily from PVC plumbing parts, and the four laboratory exercises that the students perform and write up that are designed to introduce basic engineering concepts including graphing, electrical impedance, resonance, transfer functions, mechanical and gas stiffness, and nondestructive parameter measurement.

[Troubleshooting of bioinequivalence of compound valsartan tablets].

PubMed

Shao, Da; Zhang, Yi-Fan; Zhan, Yan; Chen, Xiao-Yan; Zhong, Da-Fang

2014-04-01

The study aims to evaluate the bioequivalence of valsartan hydrochlorothiazide tablets, and to investigate the potential cause of bioinequivalence. This was a single-center study with an open, randomized double-way crossover design. Test and reference preparations containing 160 mg of valsartan and 25 mg of hydrochlorothiazide were given to 36 healthy male volunteers. Plasma concentrations of valsartan and hydrochlorothiazide were determined simultaneously by LC-MS/MS. The pharmacokinetic parameters and relative bioavailability were calculated, while the bioequivalence between test and reference preparations were evaluated. The dissolution profiles of test and reference preparations in four different mediums were determined via dissolution test and HPLC. The similarity was investigated according to the similarity factors (f2). The F(o-t) and F(0-infinity) were (139.4 +/- 65.2)% and (137.5 +/- 61.2)% for valsartan of test preparations. It led to get the conclusion that test and reference preparations were not bioequivalent for valsartan. A significant difference was observed between test and reference tablets in the valsartan dissolution test of pH 1.2 hydrochloric acid solution. The key factor of the bioinequivalence might be that dissolution of valsartan in acid medium has marked difference between two preparations.

Turning lemonade into lemons: Dampening appraisals reduce positive affect and increase negative affect during positive activity scheduling.

PubMed

Burr, Leigh-Anne; Javiad, Mahmood; Jell, Grace; Werner-Seidler, Aliza; Dunn, Barnaby D

2017-04-01

The way individuals appraise positive emotions may modulate affective experience during positive activity scheduling. Individuals may either engage in dampening appraisals (e.g., think "this is too good to last") or amplifying appraisals (e.g., think "I deserve this"). A cross-over randomized design was used to examine the consequences of these appraisal styles. Participants (N = 43) rated positive affect (PA) and negative affect (NA) during four daily walks in pleasant locations, whilst following dampening, emotion-focus amplifying (focusing on how good one feels), self-focus amplifying (focusing on positive self qualities), or control instructions. There was no difference between the two amplifying and control conditions, which all increased PA and reduced NA during the walks. However, the dampening condition significantly differed from all other conditions, reducing PA and increasing NA during the walk. Individual differences in anhedonia symptoms did not significantly moderate the pattern of findings. This evidence supports the view that dampening appraisals may be one mechanism driving anhedonia and may account for why positive activity scheduling can sometimes backfire when utilized in the clinic. Copyright © 2017 Elsevier Ltd. All rights reserved.

Vildagliptin Improves Endothelium-Dependent Vasodilatation in Type 2 Diabetes

PubMed Central

van Poppel, Pleun C.M.; Netea, Mihai G.; Smits, Paul; Tack, Cees J.

2011-01-01

OBJECTIVE To investigate whether the dipeptidyl peptidase-4 inhibitor vildagliptin improves endothelium-dependent vasodilatation in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Sixteen subjects with type 2 diabetes (age 59.8 ± 6.8 years, BMI 29.1 ± 4.8 kg/m2, HbA1c 6.97 ± 0.61) on oral blood glucose–lowering treatment were included. Participants received vildagliptin 50 mg b.i.d. or acarbose 100 mg t.i.d. for four consecutive weeks in a randomized, double-blind, cross-over design. At the end of each treatment period, we measured forearm vasodilator responses to intra-arterially administered acetylcholine (endothelium-dependent vasodilator) and sodium nitroprusside (endothelium-independent vasodilator). RESULTS Infusion of acetylcholine induced a dose-dependent increase in forearm blood flow in the experimental arm, which was higher during vildagliptin (3.1 ± 0.7, 7.9 ± 1.1, and 12.6 ± 1.4 mL ⋅ dL−1 ⋅ min−1 in response to three increasing dosages of acetylcholine) than during acarbose (2.0 ± 0.7, 5.0 ± 1.2, and 11.7 ± 1.6 mL ⋅ dL−1 ⋅ min−1, respectively; P = 0.01 by two-way ANOVA). Treatment with vildagliptin did not significantly change the vascular responses to sodium nitroprusside. CONCLUSIONS Four weeks’ treatment with vildagliptin improves endothelium-dependent vasodilatation in subjects with type 2 diabetes. This observation might have favorable cardiovascular implications. PMID:21788633

Bioavailability of bromhexine tablets and preliminary pharmacokinetics in humans.

PubMed

Bechgaard, E; Nielsen, A

1982-01-01

The absorption of bromhexine from Bromhexin tablets 8 mg, DAK has been compared with that from Bisolvon tablets 8 mg, Boehringer Ingelheim, in a two-way complete crossover study. Four tablets of each of the two bromhexine products, corresponding to a single dose of 32 mg of bromhexine hydrochloride (77.6 mumol), was administered to each of the 10 volunteers. The plasma concentration was followed over the 4-hour period following each administration. By means of Pratt's test for paired data no statistically significant difference (p greater than 0.10) between the two products was found with respect to maximum plasma concentration (89 and 84 nmol.1(-1), respectively), the times for their occurrence (1.3 and 1.0 h, respectively), and the area under the plasma concentration-time curves (140 and 132 nmol.1(-1).h, respectively). It is concluded that Bromhexin, DAK and Bisolvon are bioequivalent. Provisional pharmacokinetic data for bromhexine, after oral administration, in man were obtained. The first-pass effect and the biological half-life were estimated by combining plasma and 30 h urine data from four of the volunteers. The first-pass effect was estimated to be c. 75 per cent, the biological half-life to be c. 6 h, and c. 0.1 per cent of the dose was found as unmetabolized bromhexine in the urine. The data indicate that the pharmacokinetics of bromhexine may be described as a two-compartment open model.

Effects of rabeprazole, 20 mg, or esomeprazole, 20 mg, on 24-h intragastric pH and serum gastrin in healthy subjects.

PubMed

Warrington, S; Baisley, K; Boyce, M; Tejura, B; Morocutti, A; Miller, N

2002-07-01

To compare the antisecretory effects of rabeprazole and esomeprazole in an open, randomized, two-way crossover, clinical pharmacology study. Twenty-four healthy subjects (14 men, 10 women; mean age 26.8 years) received rabeprazole 20 mg or esomeprazole 20 mg daily on days 1-5, with a 14-day 'wash-out'. Intragastric pH was recorded continuously, and serum gastrin measured, on days 0, 1 and 5. On day 0, mean intragastric pH AUC was significantly higher before the esomeprazole than before the rabeprazole treatment in four of the five time intervals analysed. On days 1 and 5, mean intragastric pH AUC was higher after rabeprazole than esomeprazole during 5-11, 14-24 and 0-24 h after dosing. Mean pH AUC in the first 5 h after dosing on day 5 was higher after esomeprazole than rabeprazole (P=0.012). On day 1, mean per cent times pH > 3 and > 4 were significantly greater after rabeprazole than esomeprazole during 0-14, 14-24 and 0-24 h. On day 5, mean serum gastrin AUC0-4 was higher (P = 0.017) after rabeprazole than esomeprazole (335 vs. 316 pg/mL.h). In this clinical pharmacology study, rabeprazole 20 mg daily was more effective than esomeprazole 20 mg daily in increasing intragastric pH and maintaining pH > 3 and > 4. On day 5, mean pH AUC was higher after esomeprazole than rabeprazole.

The efficacy of a highly concentrated fluoride dentifrice on bovine enamel subjected to erosion and abrasion.

PubMed

Rios, Daniela; Magalhães, Ana Carolina; Polo, Renata Ocon Braga; Wiegand, Annette; Attin, Thomas; Buzalaf, Marilia Afonso Rabelo

2008-12-01

Researchers have proposed the use of fluoride for the prevention of enamel wear; however, only limited information is available about the impact of fluoridated dentifrices. Because tooth wear is a well-recognized dental problem, the authors conducted an in situ, ex vivo study to assess the efficacy of a highly concentrated fluoride dentifrice on bovine enamel subjected to erosion and abrasion. The authors conducted a double-blind, crossover in situ study consisting of three phases (seven days each). In each phase, the authors tested one of the dentifrices (5,000 parts per million fluoride [F]; 1,100 ppm F; no F). They performed erosive challenges with the use of cola drink (60 seconds, four times per day) and abrasive challenges via toothbrushing (30 seconds, four times per day). The authors determined the enamel loss via profilometry. The authors tested the data by using two-way analysis of variance (P < .05). For the erosion-plus-abrasion condition, the study results showed that enamel wear was significantly higher than that with erosion alone. The findings showed no significant differences between the dentifrices regarding enamel wear. Within the in situ, ex vivo conditions of this study, the authors concluded that the highly concentrated fluoride dentifrice did not have a protective effect on enamel against erosion and erosion plus toothbrushing abrasion. Patients at risk of developing enamel erosion should benefit from preventive measures other than fluoride dentifrice, because even a highly concentrated fluoride dentifrice does not appear to prevent enamel erosion.

Effect of low-fluoride dentifrices supplemented with calcium glycerophosphate on enamel demineralization in situ.

PubMed

do Amaral, Jackeline Gallo; Sassaki, Kikue Takebayashi; Martinhon, Cleide Cristina Rodrigues; Delbem, Alberto Carlos Botazzo

2013-04-01

To evaluate whether a low-fluoride dentifrice with calcium glycerophosphate (CaGP) reduced the demineralization process in situ. A cross-over design with four treatment phases of 7 days each was used. Ten volunteers wore palatal devices containing four blocks of bovine dental enamel. The enamel was treated (ex-vivo) with a placebo, 500 microg-F/g (500), 500 microg-F/g with 0.25%CaGP (500 CaGP), and 1,100 microg-F/g (1,100) dentifrices (twice a day/1 minute) under cariogenic challenge from sucrose solution. To evaluate mineral loss, surface and cross-sectional hardness were performed. The fluoride, calcium, and phosphorus ion concentrations from enamel and dental plaque were determined. The insoluble extracellular polysaccharide (EPS) concentrations were also analyzed. The data were submitted to ANOVA (1-way) followed by the Student-Newman-Keuls test (P < 0.05). The mineral loss and EPS concentration were lowest in the 500 CaGP and 1,100 dentifrice groups. The use of the 500 CaGP and 1,100 dentifrices resulted in similar fluoride, calcium, and phosphorus concentrations in the enamel and in dental plaque (P > 0.05). The ionic activities of calcium phosphate phases for the 500 CaGP and 1,100 dentifrices were similar (P > or = 0.492). The low-fluoride dentifrice with 0.25%CaGP demonstrated efficacy similar to that of the positive control (1,100 dentifrice) with respect to in situ demineralization.

Time-dependent effects of safflower oil to improve glycemia, inflammation and blood lipids in obese, post-menopausal women with type 2 diabetes: a randomized, double-masked, crossover study.

PubMed

Asp, Michelle L; Collene, Angela L; Norris, Leigh E; Cole, Rachel M; Stout, Michael B; Tang, Szu-Yu; Hsu, Jason C; Belury, Martha A

2011-08-01

Metabolic effects of dietary fat quality in people with type 2 diabetes are not well-understood. The study objective was to evaluate effects of conjugated linoleic acid (CLA) and safflower (SAF) oils on glycemia, blood lipids, and inflammation. The hypothesis we tested is that dietary oils improve glycemia, lipids, and inflammatory markers in a time-dependent way that follows accumulation of linoleic acid and CLA isomers in serum of subjects supplemented with dietary oils. Fifty-five post-menopausal, obese women with type 2 diabetes enrolled, and 35 completed this randomized, double-masked crossover study. Treatments were 8 g daily of CLA and SAF for 16 weeks each. We used a multiple testing procedure with pre-determined steps analysis to determine the earliest time that a significant effect was detected. CLA did not alter measured metabolic parameters. SAF decreased HbA1c (-0.64 ± 0.18%, p = 0.0007) and C-reactive protein (-13.6 ± 8.2 mg/L, p = 0.0472), increased QUICKI (0.0077 ± 0.0035, p = 0.0146) with a minimum time to effect observed 16 weeks after treatment. SAF increased HDL cholesterol (0.12 ± 0.05 mmol/L, p = 0.0228) with the minimum time to detect an effect of SAF at 12 weeks. The minimum time to detect an increase of c9t11-CLA, t10c12-CLA, and linoleic acid in serum of women supplemented CLA or SAF, respectively, was four weeks. We conclude that 8 g of SAF daily improved glycemia, inflammation, and blood lipids, indicating that small changes in dietary fat quality may augment diabetes treatments to improve risk factors for diabetes-related complications. Copyright © 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Time-dependent effects of safflower oil to improve glycemia, inflammation and blood lipids in obese, post-menopausal women with type 2 diabetes: a randomized, double-masked, crossover study

PubMed Central

Asp, Michelle L.; Collene, Angela L.; Norris, Leigh E.; Cole, Rachel M.; Stout, Michael B.; Tang, Szu-Yu; Hsu, Jason C.; Belury, Martha A.

2011-01-01

Background & Aims Metabolic effects of dietary fat quality in people with type 2 diabetes are not well-understood. The study objective was to evaluate effects of conjugated linoleic acid (CLA) and safflower (SAF) oils on glycemia, blood lipids, and inflammation. The hypothesis we tested is SAF oil improves glycemic and inflammatory markers in a time dependent way that follows accumulation of linoleic acid and CLA isomers in serum of subjects supplemented with dietary oils. Methods Fifty-five post-menopausal, obese women with type 2 diabetes enrolled, and 35 completed this randomized, double-masked crossover study. Treatments were eight grams daily of CLA and SAF for 16 weeks each. We used a multiple testing procedure with predetermined step analysis to determine when the earliest time to effect was significant. Results CLA did not alter measured metabolic parameters. SAF decreased HbA1c (−0.64±0.18%, p<0.0007) and C-reactive protein (−13.6±8.2mg/L, p<0.0472), increased QUICKI (0.0077±0.0035, p<0.0146) with a minimum time to effect observed 16 weeks after treatment. SAF increased HDL cholesterol (0.12±0.05mmol/L, p<0.0228) with the minimum time to detect an effect of SAF at 12 weeks. The minimum time to detect an increase of c9t11-CLA, t10c12-CLA and linoleic acid in serum of women supplemented CLA or SAF respectively was four weeks. Conclusions We conclude that eight grams of SAF daily improved glycemia, inflammation, and blood lipids indicating that small changes in dietary fat quality may augment diabetes treatments to improve risk factors for diabetes-related complications. PMID:21295383

Randomized cross-over trial of ventilator modes during non-invasive ventilation titration in amyotrophic lateral sclerosis.

PubMed

Vrijsen, Bart; Buyse, Bertien; Belge, Catharina; Vanpee, Goele; Van Damme, Philip; Testelmans, Dries

2017-08-01

Non-invasive ventilation (NIV) improves survival, quality of life and sleep in patients with amyotrophic lateral sclerosis (ALS). Nevertheless, NIV titration is conducted in different ways. We aim to provide more insight into NIV titration by comparing the effects of a spontaneous (S) and spontaneous-timed (ST) modes on gas exchange, sleep architecture and patient-ventilator asynchronies (PVAs). After an initial night of NIV titration, patients were randomized to S or ST mode in a cross-over design. NIV was titrated using polysomnography, oximetry (oxygen saturation, SpO 2 %) and transcutaneous carbon dioxide (PtcCO 2 ) measurement. PVAs were analysed breath-by-breath. Thirteen patients were analysed after inclusion. ST mode showed better results in gas exchange (minimal SpO 2 %: 83 (80-89)% vs 87 (84-89)%; oxygen desaturation index: 15 (5-28)/h sleep vs 7 (3-9)/h sleep; PtcCO 2 >55 mm Hg: 20 (0-59)% vs 0 (0-27)% total sleep time for S and ST mode, respectively, all P < 0.05) and respiratory events (obstructive: 8.9 (1.2-18.3)/h sleep vs 1.8 (0.3-4.9)/h sleep and central: 2.6 (0.4-14.1)/h sleep vs 0.2 (0.0-1.1)/h sleep for S and ST mode, respectively, both P < 0.01). No differences in sleep architecture were found. Ineffective efforts and respiratory events were more frequently present in S mode. Nevertheless, four patients were discharged on S mode as these patients showed clinically better results for sleep architecture and PVA during the night on S mode. ST mode shows better results in gas exchange, respiratory events and PVA. Nevertheless, accurate NIV titration remains necessary as some patients show equal or better results when using the S mode. © 2017 Asian Pacific Society of Respirology.

Vitamin C metabolites, independent of smoking status, significantly enhance leukocyte, but not plasma ascorbate concentrations.

PubMed

Moyad, Mark A; Combs, Maile A; Vrablic, Angelica S; Velasquez, Janet; Turner, Benilda; Bernal, Samuel

2008-10-01

The objective of this study was to test the effects of acute doses of vitamin C alone, calcium ascorbate with vitamin C metabolites, and placebo, on total plasma and leukocyte vitamin C concentrations over 24 hours. A double-blind, placebo-controlled, four-way crossover study was performed consisting of four separate phases lasting 24 hours each and utilizing one of four oral 1000-mg preparations within each phase (one of vitamin C alone, two separate vitamin C formulations of calcium ascorbate with vitamin C metabolites, and placebo). There was a 7-day washout between phases, and blood draws at seven time points within each phase of the study for a total of 28 serologic measurements per subject and 420 total measurements for the entire clinical trial. Vitamin C concentration in plasma and leukocytes were measured by high-performance liquid chromatography at baseline and at six sequential time periods over 24 hours. Fifteen healthy males were enrolled, aged 18-39 years; nine were had never smoked and six were chronic smokers. No significant difference in plasma vitamin C levels was observed when comparing the different preparations. However, at 24 hours, calcium ascorbate with metabolites resulted in significantly higher concentrations of vitamin C in leukocytes (P<0.0001) compared with vitamin C alone. These results were similar for both metabolite formulations, and independent of smoking status. Regardless of smoking status, vitamin C metabolites may enhance leukocyte utilization of vitamin C itself, despite no consistent difference in plasma levels among the different preparations. A larger clinical investigation is warranted to confirm these preliminary findings, and to determine the clinical relevance of this impact on overall immune function.

Morning Sleep Inertia in Alertness and Performance: Effect of Cognitive Domain and White Light Conditions

PubMed Central

Santhi, Nayantara; Groeger, John A.; Archer, Simon N.; Gimenez, Marina; Schlangen, Luc J. M.; Dijk, Derk-Jan

2013-01-01

The transition from sleep to wakefulness entails a temporary period of reduced alertness and impaired performance known as sleep inertia. The extent to which its severity varies with task and cognitive processes remains unclear. We examined sleep inertia in alertness, attention, working memory and cognitive throughput with the Karolinska Sleepiness Scale (KSS), the Psychomotor Vigilance Task (PVT), n-back and add tasks, respectively. The tasks were administered 2 hours before bedtime and at regular intervals for four hours, starting immediately after awakening in the morning, in eleven participants, in a four-way cross-over laboratory design. We also investigated whether exposure to Blue-Enhanced or Bright Blue-Enhanced white light would reduce sleep inertia. Alertness and all cognitive processes were impaired immediately upon awakening (p<0.01). However, alertness and sustained attention were more affected than cognitive throughput and working memory. Moreover, speed was more affected than accuracy of responses. The light conditions had no differential effect on performance except in the 3-back task (p<0.01), where response times (RT) at the end of four hours in the two Blue-Enhanced white light conditions were faster (200 ms) than at wake time. We conclude that the effect of sleep inertia varies with cognitive domain and that it’s spectral/intensity response to light is different from that of sleepiness. That is, just increasing blue-wavelength in light may not be sufficient to reduce sleep inertia. These findings have implications for critical professions like medicine, law-enforcement etc., in which, personnel routinely wake up from night-time sleep to respond to emergency situations. PMID:24260280

The effect of food composition on serum testosterone levels after oral administration of Andriol® Testocaps®

PubMed Central

Schnabel, Peter G; Bagchus, Wilma; Lass, Holger; Thomsen, Torben; Geurts, T B Paul

2007-01-01

Objective Andriol® Testocaps® is a new oral formulation of testosterone undecanoate (TU) for treatment of hypogonadism. As TU is taken up by the intestinal lymphatic system, both the presence and the composition of food influence the absorption. The aim of this study was to investigate the effect of food composition on the pharmacokinetics of oral TU. Design An open-label, single-centre, four-way crossover study. With a washout period of 6–7 days, 80 mg TU was administered in the morning 5 min after consuming each of four different meals in a randomized order (A: 230 kcal, 0·6 g lipid; B: 220 kcal, 5 g lipid; C: 474 kcal, 19 g lipid; D: 837 kcal, 44 g lipid). Patients Twenty-four postmenopausal volunteers. Measurements Serial blood samples were collected until 24 h after dosing to determine testosterone and dihydrotestosterone (DHT) by gas chromatography-mass spectroscopy (GC-MS). Results The bioavailability of testosterone after a low-calorie meal containing 0·6 g lipid or 5 g lipid was relatively low, the area under the concentration–time curve (AUC0–tlast) for testosterone being 30·7 and 43·5 nmol h/l, respectively. The bioavailability of testosterone after a meal containing 19 g lipid was considerably higher (AUC0–tlast = 146 nmol h/l), whereas increasing the lipid content to 44 g lipid did not further increase the bioavailability of testosterone (AUC0–tlast = 154 nmol h/l). Conclusion Approximately 19 g of lipid per meal efficiently increases absorption of testosterone from oral TU. Therefore, coadministration with a normal rather than a fatty meal is sufficient to increase serum testosterone levels when using oral TU. PMID:17371478

Cancer Terminator Viruses and Approaches for Enhancing Therapeutic Outcomes

PubMed Central

Das, Swadesh K.; Sarkar, Siddik; Dash, Rupesh; Dent, Paul; Wang, Xiang-Yang; Sarkar, Devanand; Fisher, Paul B.

2015-01-01

No single or combinatorial therapeutic approach has proven effective in decreasing morbidity or engendering a cure of metastatic cancer. In principle, conditionally replication-competent adenoviruses that induce tumor oncolysis through cancer-specific replication hold promise for cancer therapy. However, a single-agent approach may not be adequate to completely eradicate cancer in a patient because most cancers arise from abnormalities in multiple genetic and signal transduction pathways and targeting disseminated metastases is difficult to achieve. Based on these considerations, a novel class of cancer destroying adenoviruses have been produced, cancer terminator viruses (CTVs), in which cancer-specific replication is controlled by the progression-elevated gene-3 promoter and replicating viruses produce a second transgene encoding an apoptosis-inducing and immunomodulatory cytokine, either melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24) or interferon-γ. This review focuses on these viruses and ways to improve their delivery systemically and enhance their therapeutic efficacy. PMID:23021240

BiP: Master Regulator of the Unfolded Protein Response and Crucial Factor in Flavivirus Biology


PubMed Central

Lewy, Tyler G.; Grabowski, Jeffrey M.; Bloom, Marshall E.

2017-01-01

Flaviviruses have an intimate relationship with their host cells, utilizing host proteins during replication. Much of viral genome replication and virion assembly occurs on and within the endoplasmic reticulum (ER). As a cellular protein folding hub, the ER provides an ideal environment for flaviviruses to replicate. Flaviviruses can interact with several ER processes, including the unfolded protein response (UPR), a cellular stress mechanism responsible for managing unfolded protein accumulation and ER stress. The UPR can alter the ER environment in several ways, including increasing ER volume and quantity of available chaperones, both of which can favor viral replication. BiP, a chaperone and master regulator of the UPR, has been demonstrated to play a key role in several flavivirus infections. Here we describe what is known in regard to BiP, its implicated role with flavivirus infection, and what remains to be discovered. PMID:28656015

BiP: Master Regulator of the Unfolded Protein Response and Crucial Factor in Flavivirus Biology
.

PubMed

Lewy, Tyler G; Grabowski, Jeffrey M; Bloom, Marshall E

2017-06-01

Flaviviruses have an intimate relationship with their host cells, utilizing host proteins during replication. Much of viral genome replication and virion assembly occurs on and within the endoplasmic reticulum (ER). As a cellular protein folding hub, the ER provides an ideal environment for flaviviruses to replicate. Flaviviruses can interact with several ER processes, including the unfolded protein response (UPR), a cellular stress mechanism responsible for managing unfolded protein accumulation and ER stress. The UPR can alter the ER environment in several ways, including increasing ER volume and quantity of available chaperones, both of which can favor viral replication. BiP, a chaperone and master regulator of the UPR, has been demonstrated to play a key role in several flavivirus infections. Here we describe what is known in regard to BiP, its implicated role with flavivirus infection, and what remains to be discovered.

Manipulating charge transfer excited state relaxation and spin crossover in iron coordination complexes with ligand substitution

DOE PAGES

Zhang, Wenkai; Kjaer, Kasper S.; Alonso-Mori, Roberto; ...

2016-08-25

Developing light-harvesting and photocatalytic molecules made with iron could provide a cost effective, scalable, and environmentally benign path for solar energy conversion. To date these developments have been limited by the sub-picosecond metal-to-ligand charge transfer (MLCT) electronic excited state lifetime of iron based complexes due to spin crossover – the extremely fast intersystem crossing and internal conversion to high spin metal-centered excited states. We revitalize a 30 year old synthetic strategy for extending the MLCT excited state lifetimes of iron complexes by making mixed ligand iron complexes with four cyanide (CN –) ligands and one 2,2'-bipyridine (bpy) ligand. This enablesmore » MLCT excited state and metal-centered excited state energies to be manipulated with partial independence and provides a path to suppressing spin crossover. We have combined X-ray Free-Electron Laser (XFEL) Kβ hard X-ray fluorescence spectroscopy with femtosecond time-resolved UV-visible absorption spectroscopy to characterize the electronic excited state dynamics initiated by MLCT excitation of [Fe(CN) 4(bpy)] 2–. The two experimental techniques are highly complementary; the time-resolved UV-visible measurement probes allowed electronic transitions between valence states making it sensitive to ligand-centered electronic states such as MLCT states, whereas the Kβ fluorescence spectroscopy provides a sensitive measure of changes in the Fe spin state characteristic of metal-centered excited states. Here, we conclude that the MLCT excited state of [Fe(CN) 4(bpy)] 2– decays with roughly a 20 ps lifetime without undergoing spin crossover, exceeding the MLCT excited state lifetime of [Fe(2,2'-bipyridine) 3] 2+ by more than two orders of magnitude.« less

Replication of Heliothis virescens ascovirus in insect cell lines.

PubMed

Asgari, S

2006-09-01

Ascoviruses (AVs) infect larvae of various insect pests belonging to the family Noctuidae. The result of AV infection in the hosts is cleavage of infected cells into vesicles, a unique feature of AV infection. Since insect cell lines facilitate the study of virus life cycles, attempts were made to analyze Heliothis virescens AV (HvAV3e) infection in several cell lines and compare cell pathology to larval infection. In this study, replication and cytopathological effects of HvAV3e on four different cell lines were investigated. HvAV3e replication was confirmed in three noctuid cell lines from Spodoptera frugiperda (Sf9) and Helicoverpa zea (BCIRL-Hz-AM1 and FB33). However, the virus did not replicate in the non-noctuid insect cell line from Pieris rapae (Pieridae). Despite replication of the virus in the three permissive cell lines, the cytopathological effects of the virus were significantly different from that of larval infection.

Specific functions of the Rep and Rep׳ proteins of porcine circovirus during copy-release and rolling-circle DNA replication.

PubMed

Cheung, Andrew K

2015-07-01

The roles of two porcine circovirus replication initiator proteins, Rep and Rep׳, in generating copy-release and rolling-circle DNA replication intermediates were determined. Rep uses the supercoiled closed-circular genome (ccc) to initiate leading-strand synthesis (identical to copy-release replication) and generates the single-stranded circular (ssc) genome from the displaced DNA strand. In the process, a minus-genome primer (MGP) necessary for complementary-strand synthesis, from ssc to ccc, is synthesized. Rep׳ cleaves the growing nascent-strand to regenerate the parent ccc molecule. In the process, a Rep׳-DNA hybrid containing the right palindromic sequence (at the origin of DNA replication) is generated. Analysis of the virus particle showed that it is composed of four components: ssc, MGP, capsid protein and a novel Rep-related protein (designated Protein-3). Copyright © 2015. Published by Elsevier Inc.

Cumulative Genetic Risk Predicts Platinum/Taxane-Induced Neurotoxicity

PubMed Central

McWhinney-Glass, Sarah; Winham, Stacey J.; Hertz, Daniel L.; Revollo, Jane Yen; Paul, Jim; He, Yijing; Brown, Robert; Motsinger-Reif, Alison A.; McLeod, Howard L.

2013-01-01

Purpose The combination of a platinum and taxane are standard of care for many cancers, but the utility is often limited due to debilitating neurotoxicity. We examined whether single nucleotide polymorphisms (SNPs) from annotated candidate genes will identify genetic risk for chemotherapy-induced neurotoxicity. Patients and Methods A candidate-gene association study was conducted to validate the relevance of 1261 SNPs within 60 candidate genes in 404 ovarian cancer patients receiving platinum/taxane chemotherapy on the SCOTROC1 trial. Statistically significant variants were then assessed for replication in a separate 404 patient replication cohort from SCOTROC1. Results Significant associations with chemotherapy-induced neurotoxicity were identified and replicated for four SNPs in SOX10, BCL2, OPRM1, and TRPV1. The Population Attributable Risk for each of the four SNPs ranged from 5–35%, with a cumulative risk of 62%. According to the multiplicative model, the odds of developing neurotoxicity increase by a factor of 1.64 for every risk genotype. Patients possessing 3 risk variants have an estimated odds ratio of 4.49 (2.36–8.54) compared to individuals with 0 risk variants. Neither the four SNPs nor the risk score were associated with progression free survival or overall survival. Conclusions This study demonstrates that SNPs in four genes have a significant cumulative association with increased risk for the development of chemotherapy-induced neurotoxicity, independent of patient survival. PMID:23963862

Newton's Investigation of the Resistance to Moving Bodies in Continuous Fluids and the Nature of "Frontier Science"

ERIC Educational Resources Information Center

Gauld, Colin F.

2010-01-01

Newton's experiments into the resistance which fluids offer to moving bodies provide some insight into the way he related theory and experiment. His theory demonstrates a way of thought typical of 17th century physics and his experiments are simple enough to be replicated by present day students. Newton's investigations using pendulums were…

Food choice ideologies: the modern manifestations of normative and humanist views of the world.

PubMed

Lindeman, M; Sirelius, M

2001-12-01

Two studies examined whether everyday food choice motives (FCMs) and abstract values constitute food choice ideologies (FCIs), whether these ideologies reflect the same normativism-humanism polarity as Tomkins' theory suggests to reflect ideologies in general, and whether various dietary groups endorse FCIs in different ways. In Study 1, 82 female participants filled in the Food Choice Questionnaire, a short version of Schwartz's Value Survey, and Tomkins' Polarity Scale. The results reflected four FCIs: ecological ideology (EI), health ideology (HI), pleasure ideology (PI) and convenience ideology (CI). Study 2 (N=144) replicated the results for ecological and health ideologies but not for pleasure and convenience ideologies. In both studies, EI, which was typical for vegetarians, was associated with a humanist view of the world, whereas HI was related to a normative view of the world. The results suggest that food choice has become a new site where one expresses one's philosophy of life.

Antibacterial and antiplaque efficacy of a commercially available octenidine-containing mouthrinse.

PubMed

Welk, Alexander; Zahedani, Maral; Beyer, Carolin; Kramer, Axel; Müller, Gerald

2016-09-01

The purpose of this clinical study was to determine the antibacterial and antiplaque efficacy of a recently introduced octenidine-containing mouthrinse (Octenidol®) in comparison with established antiseptic mouthrinses. In a 4-day plaque-regrowth study employing a four-replicate cross-over design, a 0.1 % octenidine mouthrinse (Octenidol®/OCT-MR) was compared with a 0.12 % chlorhexidine mouthrinse (Paroex®/CHX-MR), an essential oil mouthrinse (Listerine®/EO-MR), and a placebo mouthrinse/P-MR. Plaque regrowth was assessed with a modified Quigley-Hein plaque index. The antibacterial effect was assessed by taking bacterial counts from the tooth surface and oral mucosa after professional tooth cleaning and after first rinsing with the allocated mouthrinse on days 1 and 5. Sixteen volunteers suspended tooth cleaning and rinsed twice daily with the allocated mouthrinse for 4 days. All tested antiseptic mouthrinses were significantly more effective than the placebo mouthrinse in inhibiting plaque, but no significant differences were observed between OCT-MR and CHX-MR, OCT-MR and EO-MR, and CHX-MR and EO-MR. After 4 days, comparable bacterial count levels were found on both the tooth surface and mucosa applying OCT-MR and CHX-MR, which were significantly lower than that of EO-MR and P-MR. Octenidol® and Paroex® showed comparable antibacterial and antiplaque efficacy in the human oral cavity. The recently introduced octenidine-containing mouthrinse Octenidol® may become a suitable alternative to 0.12 % chlorhexidine-containing mouthrinses such as Paroex®.

A Genetic System for Clostridium ljungdahlii: a Chassis for Autotrophic Production of Biocommodities and a Model Homoacetogen

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leang, C; Ueki, T; Nevin, KP

Methods for genetic manipulation of Clostridium ljungdahlii are of interest because of the potential for production of fuels and other biocommodities from carbon dioxide via microbial electrosynthesis or more traditional modes of autotrophy with hydrogen or carbon monoxide as the electron donor. Furthermore, acetogenesis plays an important role in the global carbon cycle. Gene deletion strategies required for physiological studies of C. ljungdahlii have not previously been demonstrated. An electroporation procedure for introducing plasmids was optimized, and four different replicative origins for plasmid propagation in C. ljungdahlii were identified. Chromosomal gene deletion via double-crossover homologous recombination with a suicide vectormore » was demonstrated initially with deletion of the gene for FliA, a putative sigma factor involved in flagellar biogenesis and motility in C. ljungdahlii. Deletion of fliA yielded a strain that lacked flagella and was not motile. To evaluate the potential utility of gene deletions for functional genomic studies and to redirect carbon and electron flow, the genes for the putative bifunctional aldehyde/alcohol dehydrogenases, adhE1 and adhE2, were deleted individually or together. Deletion of adhE1, but not adhE2, diminished ethanol production with a corresponding carbon recovery in acetate. The double deletion mutant had a phenotype similar to that of the adhE1-deficient strain. Expression of adhE1 in trans partially restored the capacity for ethanol production. These results demonstrate the feasibility of genetic investigations of acetogen physiology and the potential for genetic manipulation of C. ljungdahlii to optimize autotrophic biocommodity production.« less

Treatment of fatigue with methylphenidate, modafinil and amantadine in multiple sclerosis (TRIUMPHANT-MS): Study design for a pragmatic, randomized, double-blind, crossover clinical trial.

PubMed

Nourbakhsh, Bardia; Revirajan, Nisha; Waubant, Emmanuelle

2018-01-01

Fatigue is the most common symptom of multiple sclerosis (MS). Amantadine, modafinil and amphetamine-like stimulants are commonly used in clinical practice for treatment of fatigue; however, the evidence supporting their effectiveness is sparse and conflicting. To describe the design of a trial study funded by Patient-Centered Outcome Research Institute (PCORI) that will compare the efficacy of commonly used fatigue medications in patients with MS. The study is a randomized, placebo-controlled, crossover, four-sequence, four-period, double-blind, multicenter trial of three commonly used medications for the treatment of MS-related fatigue (amantadine, modafinil, methylphenidate) versus placebo in fatigued subjects with MS. Adult patients with MS, with an Expanded Disability Status Scale of <7.0 are eligible to participate. Participants will be randomized to one of four predefined sequences of medication administration. Each sequence comprises four 6-week periods of treatment with one of the 3 study drugs or placebo, and three 2-week washout periods between medication periods. 136 participants will be randomized over two years in two academic centers in the United States starting in the Summer 2017. Complete enrollment is expected by early 2019. The primary outcome of the study is the modified fatigue impact scale (MFIS) score while participants receive the maximally tolerated dose of each study medication (or placebo). Safety and tolerability of the medications and heterogeneity of treatment effect will also be assessed. Results of the proposed study will provide evidence-based and personalized treatment options for patients affected by MS-related fatigue. Clinicaltrials.gov registration number: NCT03185065. Copyright © 2017 Elsevier Inc. All rights reserved.

Scaling Exponents in Financial Markets

NASA Astrophysics Data System (ADS)

Kim, Kyungsik; Kim, Cheol-Hyun; Kim, Soo Yong

2007-03-01

We study the dynamical behavior of four exchange rates in foreign exchange markets. A detrended fluctuation analysis (DFA) is applied to detect the long-range correlation embedded in the non-stationary time series. It is for our case found that there exists a persistent long-range correlation in volatilities, which implies the deviation from the efficient market hypothesis. Particularly, the crossover is shown to exist in the scaling behaviors of the volatilities.

Experience and challenges presented by a multicenter crossover study of combination analgesic therapy for the treatment of painful HIV-associated polyneuropathies.

PubMed

Harrison, Taylor; Miyahara, Sachiko; Lee, Anthony; Evans, Scott; Bastow, Barbara; Simpson, David; Gilron, Ian; Dworkin, Robert; Daar, Eric S; Wieclaw, Linda; Clifford, David B

2013-07-01

There is limited evidence for efficacy of analgesics as monotherapy for neuropathic pain associated with HIV-associated polyneuropathies, in spite of demonstrated efficacy in other neuropathic pain conditions. We evaluated the tolerability and analgesic efficacy of duloxetine, methadone, and the combination of duloxetine-methadone compared with placebo. This study was a phase II, randomized, double-blind, placebo-controlled, four-period crossover multicenter study of analgesic therapy for patients with at least moderate neuropathic pain due to HIV-associated polyneuropathy. Duloxetine, methadone, combination duloxetine-methadone, and placebo were administered in four different possible sequences. The primary outcome measure was mean pain intensity (MPI) measured daily in a study-supplied pain diary. A total of 15 patients were enrolled from eight study sites and eight patients completed the entire trial. Study treatments failed to show statistically significant change in MPI compared with placebo. Adverse events were frequent and associated with high rates of drug discontinuation and study dropout. Challenges with participant recruitment and poor retention precluded trial completion to its planned targets, limiting our evaluation of the analgesic efficacy of the study treatments. Challenges to successful completion of this study and lessons learned are discussed. Wiley Periodicals, Inc.

Experience and challenges presented by a multicenter crossover study of combination analgesic therapy for the treatment of painful HIV-associated polyneuropathies

PubMed Central

Harrison, Taylor; Miyahara, Sachiko; Lee, Anthony; Evans, Scott; Bastow, Barbara; Simpson, David; Gilron, Ian; Dworkin, Robert; Daar, Eric S.; Wieclaw, Linda; Clifford, David B.

2014-01-01

Objective There is limited evidence for efficacy of analgesics as monotherapy for neuropathic pain associated with HIV-associated polyneuropathies, in spite of demonstrated efficacy in other neuropathic pain conditions. We evaluated the tolerability and analgesic efficacy of duloxetine, methadone, and the combination of duloxetine-methadone compared to placebo. Design This study was a phase II, randomized, double blind, placebo-controlled, four-period crossover multi-center study of analgesic therapy for patients with at least moderate neuropathic pain due to HIV-associated polyneuropathy. Duloxetine, methadone, combination duloxetine-methadone, and placebo were administered in four different possible sequences. The primary outcome measure was mean pain intensity (MPI) measured daily in a study-supplied pain diary. Results A total of 15 patients were enrolled from 8 study sites and 8 patients completed the entire trial. Study treatments failed to show statistically significant change in MPI compared to placebo. Adverse events were frequent and associated with high rates of drug discontinuation and study drop-out. Conclusions Challenges with participant recruitment and poor retention precluded trial completion to its planned targets, limiting our evaluation of the analgesic efficacy of the study treatments. Challenges to successful completion of this study and lessons learned are discussed. PMID:23565581

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

ERIC Educational Resources Information Center

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

2018-01-01

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

Recognition of Computer Viruses by Detecting Their Gene of Self Replication

DTIC Science & Technology

2006-03-01

etection A pproach ................................................................................................. 6 1.4.1 The syntactic analysis m...Therefore a group of instructions acting together in the right order have to be identified for the gene of self-replication to be obvious in a...its first system call NtCreateFile, while the outputs of NtWriteFile become its output arguments. These four blocks form the final structure - The Gene

Brief Report: Use of an Antecedent Procedure to Decrease Night Awakening in an Infant--A Replication

ERIC Educational Resources Information Center

Cautilli, Joseph

2005-01-01

Borowski, Hunter, and Johnson (2001) found that an antecedent strategy such as white noise could decrease sleep awakenings for infants in the natural home environment. This study attempts to replicate the findings using an ABAB reversal design. A five month and one week old child, who had difficulty with waking an average of four times per night,…

Performance analysis of data intensive cloud systems based on data management and replication: a survey

DOE Office of Scientific and Technical Information (OSTI.GOV)

Malik, Saif Ur Rehman; Khan, Samee U.; Ewen, Sam J.

2015-03-14

As we delve deeper into the ‘Digital Age’, we witness an explosive growth in the volume, velocity, and variety of the data available on the Internet. For example, in 2012 about 2.5 quintillion bytes of data was created on a daily basis that originated from myriad of sources and applications including mobiledevices, sensors, individual archives, social networks, Internet of Things, enterprises, cameras, software logs, etc. Such ‘Data Explosions’ has led to one of the most challenging research issues of the current Information and Communication Technology era: how to optimally manage (e.g., store, replicated, filter, and the like) such large amountmore » of data and identify new ways to analyze large amounts of data for unlocking information. It is clear that such large data streams cannot be managed by setting up on-premises enterprise database systems as it leads to a large up-front cost in buying and administering the hardware and software systems. Therefore, next generation data management systems must be deployed on cloud. The cloud computing paradigm provides scalable and elastic resources, such as data and services accessible over the Internet Every Cloud Service Provider must assure that data is efficiently processed and distributed in a way that does not compromise end-users’ Quality of Service (QoS) in terms of data availability, data search delay, data analysis delay, and the like. In the aforementioned perspective, data replication is used in the cloud for improving the performance (e.g., read and write delay) of applications that access data. Through replication a data intensive application or system can achieve high availability, better fault tolerance, and data recovery. In this paper, we survey data management and replication approaches (from 2007 to 2011) that are developed by both industrial and research communities. The focus of the survey is to discuss and characterize the existing approaches of data replication and management that tackle the resource usage and QoS provisioning with different levels of efficiencies. Moreover, the breakdown of both influential expressions (data replication and management) to provide different QoS attributes is deliberated. Furthermore, the performance advantages and disadvantages of data replication and management approaches in the cloud computing environments are analyzed. Open issues and future challenges related to data consistency, scalability, load balancing, processing and placement are also reported.« less

Adoption of the B2SAFE EUDAT replication service by the EPOS community

NASA Astrophysics Data System (ADS)

Cacciari, Claudio; Fares, Massimo; Fiameni, Giuseppe; Michelini, Alberto; Danecek, Peter; Wittenburg, Peter

2014-05-01

B2SAFE is the EUDAT service for moving and replicating data between sites and storage systems for different purposes. The goal of B2SAFE is to keep the data from a repository safe by replicating it across different geographical and administrative zones according to a set of well-defined policies. It is also a way to store large volumes of data permanently at those sites which are providing powerful on-demand data analysis facilities. In particular, B2SAFE operates on the domain of registered data where data objects are referable via persistent identifiers (PIDs). B2SAFE is more than just copying data because the PIDs must be carefully managed when data objects are moved or replicated. The EUDAT B2SAFE Service offers functionality to replicate datasets across different data centres in a safe and efficient way while maintaining all information required to easily find and query information about the replica locations. The information about the replica locations and other important information is stored in PID records, each managed in separate administrative domains. The B2SAFE Service is implemented as an iRODS module providing a set of iRODS rules or policies to interface with the EPIC handle API and uses the iRODS middleware to replicate datasets from a source data (or community) centre to a destination data centre. The definition of the dataset(s) to replicate is flexible and up to the communities using the B2SAFE service. While the B2SAFE is internally using the EPIC handle API, communities have the choice to use any PID system they prefer to assign PIDs to their digital objects. A reference to one or more EUDAT B2SAFE PIDs is returned by the B2SAFE service when a dataset is replicated. The presentation will introduce the problem space of B2SAFE, presents the achievements that have been made during the last year for enabling communities to make use of the B2SAFE service, demonstrates a EPOS use cases, outlines the commonalities and differences between the policies for B2SAFE, presents new developments towards a common service layer interface and a data policy management framework.

Manual transmission enhances attention and driving performance of ADHD adolescent males: pilot study.

PubMed

Cox, Daniel J; Punja, Mohan; Powers, Katie; Merkel, R Lawrence; Burket, Roger; Moore, Melissa; Thorndike, Frances; Kovatchev, Boris

2006-11-01

Inattention is a major contributor to driving mishaps and is especially problematic among adolescent drivers with ADHD, possibly contributing to their 2 to 4 times higher incidence of collisions. Manual transmission has been demonstrated to be associated with greater arousal. This study tests the hypotheses that manual transmission, compared to automatic transmission, would be associated with better attention and performance on a driving simulator. Ten adolescent drivers with ADHD practice driving on the simulator in the manual and automatic mode. Employing a single-blind, cross-over design, participants drive the simulator at 19:30 and 22:30 hr for 30 min in both transmissions and rate their attention to driving. Subjectively, participants report being more attentive while driving in manual transmission mode. Objectively, participants drive safer in the manual transmission mode. Although in need of replication, this pilot study suggests a behavioral intervention to improve driving performance among ADHD adolescents.

Mechanism for Coordinated RNA Packaging and Genome Replication by Rotavirus Polymerase VP1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lu, Xiaohui; McDonald, Sarah M.; Tortorici, M. Alejandra

2009-04-08

Rotavirus RNA-dependent RNA polymerase VP1 catalyzes RNA synthesis within a subviral particle. This activity depends on core shell protein VP2. A conserved sequence at the 3' end of plus-strand RNA templates is important for polymerase association and genome replication. We have determined the structure of VP1 at 2.9 {angstrom} resolution, as apoenzyme and in complex with RNA. The cage-like enzyme is similar to reovirus {lambda}3, with four tunnels leading to or from a central, catalytic cavity. A distinguishing characteristic of VP1 is specific recognition, by conserved features of the template-entry channel, of four bases, UGUG, in the conserved 3' sequence.more » Well-defined interactions with these bases position the RNA so that its 3' end overshoots the initiating register, producing a stable but catalytically inactive complex. We propose that specific 3' end recognition selects rotavirus RNA for packaging and that VP2 activates the autoinhibited VP1/RNA complex to coordinate packaging and genome replication.« less

Influence of Layup and Curing on the Surface Accuracy in the Manufacturing of Carbon Fiber Reinforced Polymer (CFRP) Composite Space Mirrors

NASA Astrophysics Data System (ADS)

Yang, Zhiyong; Zhang, Jianbao; Xie, Yongjie; Zhang, Boming; Sun, Baogang; Guo, Hongjun

2017-12-01

Carbon fiber reinforced polymer, CFRP, composite materials have been used to fabricate space mirror. Usually the composite space mirror can completely replicate the high-precision surface of mould by replication process, but the actual surface accuracy of replicated space mirror is always reduced, still needed further study. We emphatically studied the error caused by layup and curing on the surface accuracy of space mirror through comparative experiments and analyses, the layup and curing influence factors include curing temperature, cooling rate of curing, method of prepreg lay-up, and area weight of fiber. Focusing on the four factors, we analyzed the error influence rule and put forward corresponding control measures to improve the surface figure of space mirror. For comparative analysis, six CFRP composite mirrors were fabricated and surface profile of mirrors were measured. Four guiding control measures were described here. Curing process of composite space mirror is our next focus.

Identification of novel inhibitors of non-replicating Mycobacterium tuberculosis using a carbon starvation model

PubMed Central

Grant, Sarah Schmidt; Kawate, Tomohiko; Nag, Partha P.; Silvis, Melanie R.; Gordon, Katherine; Stanley, Sarah A.; Kazyanskaya, Ed; Nietupski, Ray; Golas, Aaron; Fitzgerald, Michael; Cho, Sanghyun; Franzblau, Scott G.; Hung, Deborah T.

2013-01-01

During Mycobacterium tuberculosis infection, a population of bacteria is thought to exist in a non-replicating state, refractory to antibiotics, which may contribute to the need for prolonged antibiotic therapy. The identification of inhibitors of the non-replicating state provides tools that can be used to probe this hypothesis and the physiology of this state. The development of such inhibitors also has the potential to shorten the duration of antibiotic therapy required. Here we describe the development of a novel non-replicating assay amenable to high-throughput chemical screening coupled with secondary assays that use carbon starvation as the in vitro model. Together these assays identify compounds with activity against replicating and non-replicating M. tuberculosis as well as compounds that inhibit the transition from non-replicating to replicating stages of growth. Using these assays we successfully screened over 300,000 compounds and identified 786 inhibitors of non-replicating M. tuberculosis. In order to understand the relationship among different non-replicating models, we teste 52 of these molecules in a hypoxia model and four different chemical scaffolds in a stochastic persist model and a streptomycin dependent model. We found that compounds display varying levels of activity in different models for the non-replicating state, suggesting important differences in bacterial physiology between models. Therefore, chemical tools identified in this assay may be useful for determining the relevance of different non-replicating in vitro models to in vivo M. tuberculosis infection. Given our current limited understanding, molecules that are active across multiple models may represent more promising candidates for further development. PMID:23898841

Limits to behavioral evolution: the quantitative genetics of a complex trait under directional selection.

PubMed

Careau, Vincent; Wolak, Matthew E; Carter, Patrick A; Garland, Theodore

2013-11-01

Replicated selection experiments provide a powerful way to study how "multiple adaptive solutions" may lead to differences in the quantitative-genetic architecture of selected traits and whether this may translate into differences in the timing at which evolutionary limits are reached. We analyze data from 31 generations (n=17,988) of selection on voluntary wheel running in house mice. The rate of initial response, timing of selection limit, and height of the plateau varied significantly between sexes and among the four selected lines. Analyses of litter size and realized selection differentials seem to rule out counterposing natural selection as a cause of the selection limits. Animal-model analyses showed that although the additive genetic variance was significantly lower in selected than control lines, both before and after the limits, the decrease was not sufficient to explain the limits. Moreover, directional selection promoted a negative covariance between additive and maternal genetic variance over the first 10 generations. These results stress the importance of replication in selection studies of higher-level traits and highlight the fact that long-term predictions of response to selection are not necessarily expected to be linear because of the variable effects of selection on additive genetic variance and maternal effects. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

Control of Meiotic Crossovers: From Double-Strand Break Formation to Designation

PubMed Central

Gray, Stephen

2017-01-01

Meiosis, the mechanism of creating haploid gametes, is a complex cellular process observed across sexually reproducing organisms. Fundamental to meiosis is the process of homologous recombination, whereby DNA double-strand breaks are introduced into the genome and are subsequently repaired to generate either noncrossovers or crossovers. Although homologous recombination is essential for chromosome pairing during prophase I, the resulting crossovers are critical for maintaining homolog interactions and enabling accurate segregation at the first meiotic division. Thus, the placement, timing, and frequency of crossover formation must be exquisitely controlled. In this review, we discuss the proteins involved in crossover formation, the process of their formation and designation, and the rules governing crossovers, all within the context of the important landmarks of prophase I. We draw together crossover designation data across organisms, analyze their evolutionary divergence, and propose a universal model for crossover regulation. PMID:27648641

Investigation of iron spin crossover pressure in Fe-bearing MgO using hybrid functional

NASA Astrophysics Data System (ADS)

Cheng, Ya; Wang, Xianlong; Zhang, Jie; Yang, Kaishuai; Zhang, Chuanguo; Zeng, Zhi; Lin, Haiqin

2018-04-01

Pressure-induced spin crossover behaviors of Fe-bearing MgO were widely investigated by using an LDA  +  U functional for describing the strongly correlated Fe–O bonding. Moreover, the simulated spin crossover pressures depend on the applied U values, which are sensitive to environments and parameters. In this work, the spin crossover pressures of (Mg1‑x ,Fe x )O are investigated by using the hybrid functional with a uniform parameter. Our results indicate that the spin crossover pressures increase with increasing iron concentration. For example, the spin crossover pressure of (Mg0.03125,Fe0.96875)O and FeO was 56 GPa and 127 GPa, respectively. The calculated crossover pressures agreed well with the experimental observations. Therefore, the hybrid functional should be an effective method for describing the pressure-induced spin crossover behaviors in transition metal oxides.

The scenario on the origin of translation in the RNA world: in principle of replication parsimony

PubMed Central

2010-01-01

Background It is now believed that in the origin of life, proteins should have been "invented" in an RNA world. However, due to the complexity of a possible RNA-based proto-translation system, this evolving process seems quite complicated and the associated scenario remains very blurry. Considering that RNA can bind amino acids with specificity, it has been reasonably supposed that initial peptides might have been synthesized on "RNA templates" containing multiple amino acid binding sites. This "Direct RNA Template (DRT)" mechanism is attractive because it should be the simplest mechanism for RNA to synthesize peptides, thus very likely to have been adopted initially in the RNA world. Then, how this mechanism could develop into a proto-translation system mechanism is an interesting problem. Presentation of the hypothesis Here an explanation to this problem is shown considering the principle of "replication parsimony" --- genetic information tends to be utilized in a parsimonious way under selection pressure, due to its replication cost (e.g., in the RNA world, nucleotides and ribozymes for RNA replication). Because a DRT would be quite long even for a short peptide, its replication cost would be great. Thus the diversity and the length of functional peptides synthesized by the DRT mechanism would be seriously limited. Adaptors (proto-tRNAs) would arise to allow a DRT's complementary strand (called "C-DRT" here) to direct the synthesis of the same peptide synthesized by the DRT itself. Because the C-DRT is a necessary part in the DRT's replication, fewer turns of the DRT's replication would be needed to synthesize definite copies of the functional peptide, thus saving the replication cost. Acting through adaptors, C-DRTs could transform into much shorter templates (called "proto-mRNAs" here) and substitute the role of DRTs, thus significantly saving the replication cost. A proto-rRNA corresponding to the small subunit rRNA would then emerge to aid the binding of proto-tRNAs and proto-mRNAs, allowing the reduction of base pairs between them (ultimately resulting in the triplet anticodon/codon pair), thus further saving the replication cost. In this context, the replication cost saved would allow the appearance of more and longer functional peptides and, finally, proteins. The hypothesis could be called "DRT-RP" ("RP" for "replication parsimony"). Testing the hypothesis The scenario described here is open for experimental work at some key scenes, including the compact DRT mechanism, the development of adaptors from aa-aptamers, the synthesis of peptides by proto-tRNAs and proto-mRNAs without the participation of proto-rRNAs, etc. Interestingly, a recent computer simulation study has demonstrated the plausibility of one of the evolving processes driven by replication parsimony in the scenario. Implication of the hypothesis An RNA-based proto-translation system could arise gradually from the DRT mechanism according to the principle of "replication parsimony" --- to save the replication cost of RNA templates for functional peptides. A surprising side deduction along the logic of the hypothesis is that complex, biosynthetic amino acids might have entered the genetic code earlier than simple, prebiotic amino acids, which is opposite to the common sense. Overall, the present discussion clarifies the blurry scenario concerning the origin of translation with a major clue, which shows vividly how life could "manage" to exploit potential chemical resources in nature, eventually in an efficient way over evolution. Reviewers This article was reviewed by Eugene V. Koonin, Juergen Brosius, and Arcady Mushegian. PMID:21110883

Assessing the Use of School Public Address Systems to Deliver Nutrition Messages to Children: Shape Up Somerville--Audio Adventures

ERIC Educational Resources Information Center

Folta, Sara C.; Goldberg, Jeanne P.; Economos, Christina; Bell, Rick; Landers, Stewart; Hyatt, Raymond

2006-01-01

Given the current childhood obesity epidemic, it is especially important to find effective ways to promote healthful foods to children. School public address (PA) systems represent an inexpensive and a replicable way of reaching children with health messages. To test the effectiveness of this channel, messages were created to promote 2 dried bean…

Transparency in Distributed File Systems

DTIC Science & Technology

1989-01-01

ORGANIZATION NAME AND ADDRESS 10. PROGRAM ELEMENT. PROJECT, TASK Computer Science Department AREA & WORK UNIT NUMBERS 734 Comouter Studies Bldc . University of...sistency control , file and director) placement, and file and directory migration in a way that pro- 3 vides full network transparency. This transparency...areas of naming, replication, con- sistency control , file and directory placement, and file and directory migration in a way that pro- 3 vides full

Learning from Errors at Work: A Replication Study in Elder Care Nursing

ERIC Educational Resources Information Center

Leicher, Veronika; Mulder, Regina H.; Bauer, Johannes

2013-01-01

Learning from errors is an important way of learning at work. In this article, we analyse conditions under which elder care nurses use errors as a starting point for the engagement in social learning activities (ESLA) in the form of joint reflection with colleagues on potential causes of errors and ways to prevent them in future. The goal of our…

Roles of Long and Short Replication Initiation Proteins in the Fate of IncP-1 Plasmids

PubMed Central

Yano, Hirokazu; Deckert, Gail E.; Rogers, Linda M.

2012-01-01

Broad-host-range IncP-1 plasmids generally encode two replication initiation proteins, TrfA1 and TrfA2. TrfA2 is produced from an internal translational start site within trfA1. While TrfA1 was previously shown to be essential for replication in Pseudomonas aeruginosa, its role in other bacteria within its broad host range has not been established. To address the role of TrfA1 and TrfA2 in other hosts, efficiency of transformation, plasmid copy number (PCN), and plasmid stability were first compared between a mini-IncP-1β plasmid and its trfA1 frameshift variant in four phylogenetically distant hosts: Escherichia coli, Pseudomonas putida, Sphingobium japonicum, and Cupriavidus necator. TrfA2 was sufficient for replication in these hosts, but the presence of TrfA1 enhanced transformation efficiency and PCN. However, TrfA1 did not contribute to, and even negatively affected, long-term plasmid persistence. When trfA genes were cloned under a constitutive promoter in the chromosomes of the four hosts, strains expressing either both TrfA1 and TrfA2 or TrfA1 alone, again, generally elicited a higher PCN of an IncP1-β replicon than strains expressing TrfA2 alone. When a single species of TrfA was produced at different concentrations in E. coli cells, TrfA1 maintained a 3- to 4-fold higher PCN than TrfA2 at the same TrfA concentrations, indicating that replication mediated by TrfA1 is more efficient than that by TrfA2. These results suggest that the broad-host-range properties of IncP-1 plasmids are essentially conferred by TrfA2 and the intact replication origin alone but that TrfA1 is nonetheless important to efficiently establish plasmid replication upon transfer into a broad range of hosts. PMID:22228734

Strand-Specific Analysis of DNA Synthesis and Proteins Association with DNA Replication Forks in Budding Yeast.

PubMed

Yu, Chuanhe; Gan, Haiyun; Zhang, Zhiguo

2018-01-01

DNA replication initiates at DNA replication origins after unwinding of double-strand DNA(dsDNA) by replicative helicase to generate single-stranded DNA (ssDNA) templates for the continuous synthesis of leading-strand and the discontinuous synthesis of lagging-strand. Therefore, methods capable of detecting strand-specific information will likely yield insight into the association of proteins at leading and lagging strand of DNA replication forks and the regulation of leading and lagging strand synthesis during DNA replication. The enrichment and Sequencing of Protein-Associated Nascent DNA (eSPAN), which measure the relative amounts of proteins at nascent leading and lagging strands of DNA replication forks, is a step-wise procedure involving the chromatin immunoprecipitation (ChIP) of a protein of interest followed by the enrichment of protein-associated nascent DNA through BrdU immunoprecipitation. The isolated ssDNA is then subjected to strand-specific sequencing. This method can detect whether a protein is enriched at leading or lagging strand of DNA replication forks. In addition to eSPAN, two other strand-specific methods, (ChIP-ssSeq), which detects potential protein-ssDNA binding and BrdU-IP-ssSeq, which can measure synthesis of both leading and lagging strand, were developed along the way. These methods can provide strand-specific and complementary information about the association of the target protein with DNA replication forks as well as synthesis of leading and lagging strands genome wide. Below, we describe the detailed eSPAN, ChIP-ssSeq, and BrdU-IP-ssSeq protocols.

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

PubMed

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

1979-08-01

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

Short-term response of reptiles and amphibians to prescribed fire and mechanical fuel reduction in a southern Appalachian upland hardwood forest

Treesearch

Cathryn H. Greenberg; Thomas A. Waldrop

2008-01-01

We compared the effects of three fuel reduction techniques and a control on the relative abundance and richness of reptiles and amphibians using drift fence arrays with pitfall and funnel traps. Three replicate blocks were established at the Green River Game Land, Polk County, North Carolina. Each replicate block contained four experimental units that were each...

The City as a Teaching Device

ERIC Educational Resources Information Center

Siegert, Richard

1976-01-01

Hong Kong International School has made extensive use of city resources in teaching concepts of government, world affairs, urban geography, economic geography, and macro-economics, in ways that may be replicated in other urban centers. (MB)

The efficacy of cevimeline hydrochloride in the treatment of xerostomia in Sjögren's syndrome in southern Chinese patients: a randomised double-blind, placebo-controlled crossover study.

PubMed

Leung, K C M; McMillan, A S; Wong, M C M; Leung, W K; Mok, M Y; Lau, C S

2008-04-01

Cevimeline hydrochloride, a specific agonist of the M3 muscarinic receptor, is beneficial in the treatment of symptoms of xerostomia and xerophthalmia associated with Sjögren's syndrome (SS). Cevimeline has not been evaluated in southern Chinese patients. Furthermore, the effects of cevimeline on health-related quality of life and oral health status are not known. In this randomised, double-blind, placebo-controlled crossover study, patients received cevimeline 30 mg or matched placebo three times per day over 10 weeks followed by a 4-week washout period before treatment crossover. Participants self-completed the following questionnaires: Xerostomia Inventory (XI), the General Oral Health Assessment Index (GOHAI), the Ocular Surface Disease Index (OSDI) and the Medical Outcomes Short Form (SF-36). Clinical assessments included sialometry, examination of the oral cavity for the degree of xerostomia and dental complications of xerostomia. Fifty patients (22 primary SS and 28 secondary SS) were enrolled in the trial. Forty-four patients completed the study. There was a significant improvement in the XI and GOHAI scores as well as the objective rating of xerostomic signs of the oral cavity after treatment with cevimeline. However, there was no improvement in salivary flow rates and dry eye symptoms. SS patients had lower SF-36 scores, but these did not improve after treatment with cevimeline.

What makes a word so attractive? Disclosing the urge to read while bisecting.

PubMed

Girelli, Luisa; Previtali, Paola; Arduino, Lisa S

2018-04-22

Expert readers have been repeatedly reported to misperceive the centre of visual stimuli, shifting systematically to the left the bisection of any lines (pseudoneglect) while showing a cross-over effect while bisecting different types of orthographic strings (Arduino et al., 2010, Neuropsychologia, 48, 2140). This difference has been attributed to asymmetrical allocation of attention that visuo-verbal material receives when lexical access occurs (e.g., Fischer, 2004, Cognitive Brain Research, 4, 163). The aim of this study was to further examine which visual features guide recognition of potentially orthographic materials. To disentangle the role of orthography, heterogeneity, and visuo-perceptual discreteness, we presented Italian unimpaired adults with four experiments exploiting the bisection paradigm. The results showed that a cross-over effect emerges in most discrete strings, especially when their internal structure, that is being composed of heterogeneous elements, is suggestive of orthographically relevant material. Interestingly, the cross-over effect systematically characterized the processing of letter strings (Experiment 2) and words (Experiments 3 and 4), whether visually discrete or not. Overall, this pattern of results suggests that neither discreteness nor heterogeneity per se are responsible for activating visual scanning mechanisms implied in text exploration, although both contribute to increasing the chance of a visual stimulus undergoing a perceptual analysis dedicated to pre-lexical processing. © 2018 The British Psychological Society.

Effects of breaking up sitting on adolescents' postprandial glucose after consuming meals varying in energy: a cross-over randomised trial.

PubMed

Fletcher, Elly A; Salmon, Jo; McNaughton, Sarah A; Orellana, Liliana; Wadley, Glenn D; Bruce, Clinton; Dempsey, Paddy C; Lacy, Kathleen E; Dunstan, David W

2018-03-01

To explore the impact of uninterrupted sitting versus sitting with resistance-type activity breaks on adolescents' postprandial glucose responses while consuming a diet varying in energy. Cross-over randomised trial. Thirteen healthy participants (16.4±1.3years) completed a four-treatment cross-over trial: (1) uninterrupted sitting+high-energy diet; (2) sitting with breaks+high-energy diet; (3) uninterrupted sitting+standard-energy diet; and (4) sitting with breaks+standard-energy diet. For all four conditions, two identical meals were consumed; at 0h and 3h. A continuous glucose monitoring system (CGM) recorded interstitial glucose concentrations every five minutes. Linear mixed models examined differences in glucose positive incremental area under the curve (iAUC) and total AUC between the sitting and diet conditions for the first meal, second meal and entire trial period. Compared to the uninterrupted sitting conditions, the breaks condition elicited a 36.0mmol/L/h (95%CI 6.6-65.5) and 35.9mmol/L/h (95%CI 6.6-65.5) lower iAUC response after the first and second meal, respectively, but not for the entire trial period or for total AUC. Compared to the standard-energy diet, the high-energy diet elicited a 55.0mmol/L/h (95%CI 25.8-84.2) and 75.7mmol/L/h (95%CI 8.6-142.7) higher iAUC response after the first meal and entire trial, respectively. Similar response to the high-energy diet were observed for total AUC. According to iAUC, interrupting sitting had a significant effect on lowering postprandial glucose for both dietary conditions, however, it was not significant when examining total AUC. Larger studies are needed to confirm these findings. ACTRN12615001145594. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

How do walkers behave when crossing the way of a mobile robot that replicates human interaction rules?

PubMed

Vassallo, Christian; Olivier, Anne-Hélène; Souères, Philippe; Crétual, Armel; Stasse, Olivier; Pettré, Julien

2018-02-01

Previous studies showed the existence of implicit interaction rules shared by human walkers when crossing each other. Especially, each walker contributes to the collision avoidance task and the crossing order, as set at the beginning, is preserved along the interaction. This order determines the adaptation strategy: the first arrived increases his/her advance by slightly accelerating and changing his/her heading, whereas the second one slows down and moves in the opposite direction. In this study, we analyzed the behavior of human walkers crossing the trajectory of a mobile robot that was programmed to reproduce this human avoidance strategy. In contrast with a previous study, which showed that humans mostly prefer to give the way to a non-reactive robot, we observed similar behaviors between human-human avoidance and human-robot avoidance when the robot replicates the human interaction rules. We discuss this result in relation with the importance of controlling robots in a human-like way in order to ease their cohabitation with humans. Copyright © 2017 Elsevier B.V. All rights reserved.

Escherichia coli DinB inhibits replication fork progression without significantly inducing the SOS response.

PubMed

Mori, Tetsuya; Nakamura, Tatsuro; Okazaki, Naoto; Furukohri, Asako; Maki, Hisaji; Akiyama, Masahiro Tatsumi

2012-01-01

The SOS response is readily triggered by replication fork stalling caused by DNA damage or a dysfunctional replicative apparatus in Escherichia coli cells. E. coli dinB encodes DinB DNA polymerase and its expression is upregulated during the SOS response. DinB catalyzes translesion DNA synthesis in place of a replicative DNA polymerase III that is stalled at a DNA lesion. We showed previously that DNA replication was suppressed without exogenous DNA damage in cells overproducing DinB. In this report, we confirm that this was due to a dose-dependent inhibition of ongoing replication forks by DinB. Interestingly, the DinB-overproducing cells did not significantly induce the SOS response even though DNA replication was perturbed. RecA protein is activated by forming a nucleoprotein filament with single-stranded DNA, which leads to the onset of the SOS response. In the DinB-overproducing cells, RecA was not activated to induce the SOS response. However, the SOS response was observed after heat-inducible activation in strain recA441 (encoding a temperature-sensitive RecA) and after replication blockage in strain dnaE486 (encoding a temperature-sensitive catalytic subunit of the replicative DNA polymerase III) at a non-permissive temperature when DinB was overproduced in these cells. Furthermore, since catalytically inactive DinB could avoid the SOS response to a DinB-promoted fork block, it is unlikely that overproduced DinB takes control of primer extension and thus limits single-stranded DNA. These observations suggest that DinB possesses a feature that suppresses DNA replication but does not abolish the cell's capacity to induce the SOS response. We conclude that DinB impedes replication fork progression in a way that does not activate RecA, in contrast to obstructive DNA lesions and dysfunctional replication machinery.

Perfectionism, Burnout, and Motivation in Dance: A Replication and Test of the 2×2 Model of Perfectionism.

PubMed

Nordin-Bates, Sanna M; Raedeke, Thomas D; Madigan, Daniel J

2017-09-15

The relationships between multidimensional perfectionism, burnout, and motivation were examined. In so doing, this study aimed to replicate and extend the study by Cumming and Duda (2012). Ninety-one ballet dancers completed questionnaires assessing the target constructs. Using cluster analysis, four profiles emerged that replicated Cumming and Duda's findings and generally supported Gaudrau and Thompson's 2x2 model of perfectionism. As such, these profiles represented pure personal standards perfectionism, mixed perfectionism, pure evaluative concerns perfectionism, and non-perfectionism. Extending previous literature, the four profiles were then compared on a range of burnout symptoms and motivational regulations. It was found that the four clusters differed significantly on these constructs, in a manner partly supportive of the hypotheses associated with the 2x2 model of perfectionism. In particular, our results reflect and extend those of Cumming and Duda, in that mixed perfectionism and pure evaluative concerns perfectionism did not differ on any of the measures. Thus, the higher personal standards of dancers exhibiting mixed perfectionism did not appear to be associated with better functioning than that experienced by dancers with pure evaluative concerns perfectionism. Altogether, the study extends our current understanding of perfectionism in dance and its potential effects, including those on burnout and motivation.

Brief report: reporting practices of methodological information in four journals of pediatric and child psychology.

PubMed

Raad, Jennifer M; Bellinger, Skylar; McCormick, Erica; Roberts, Michael C; Steele, Ric G

2008-08-01

To replicate Sifers, Puddy, Warren, and Roberts (2002) examining reporting rates of demographic, methodological, and ethical information in articles published during 1997, and to compare these rates to those found in articles published during 2005, in order to determine whether and how reporting practices of these variables have changed over time. We examined reporting demographic, methodological, and ethical information in articles in four journals: Journal of Pediatric Psychology, Journal of Clinical Child and Adolescent Psychology, Journal of Abnormal Child Psychology, and Child Development. Reporting rates during 2005 were compared to articles published during 1997. These four journals improved on many of the 23 variables compared to Sifers et al. including increases in the reporting of ethnicity, attrition, child assent procedures, socioeconomic status, reliability, and reward/incentive offered to participants. Improvements in descriptive information have implications for interpretation, replication, and generalizability of research findings.

An insight into the performance of road barriers - redistribution of barrier-relevant crashes.

PubMed

Zou, Yaotian; Tarko, Andrew P

2016-11-01

Unlike most of traffic safety treatments that prevent crashes, road barriers reduce the severity of crash outcomes by replacing crashes with a high risk of severe injury and fatality (such as median crossover head-on collisions or collisions with high-hazard objects) with less risky events (such as collisions with barriers). This "crash conversion" is actually more complex than one-to-one replacement and it has not been studied yet. The published work estimated the reduction of selected types of crashes (typically, median crossover collisions) or the overall effect of barriers on crash severity. The objective of this study was to study the probabilities of various types of crash events possible under various road and barrier scenarios. The estimated probabilities are conditional given that at least one vehicle left the travelled way and the resulted crash had been recorded. The results are meant to deliver a useful insight onto the conversion of crashes by barriers from more to less risky to help better understand the mechanism of crash severity reduction. Such knowledge should allow engineers more accurate estimation of barriers' benefits and help researchers evaluate barriers' performance to improve the barrier's design. Seven barrier-relevant crash events possible after a vehicle departs the road could be identified based on the existing crash data and their probabilities estimated given the presence and location of three types of barriers: median concrete barriers, median and roadside W-beam steel guardrails, and high-tension median cable barriers. A multinomial logit model with variable outcomes was estimated based on 2049 barrier-relevant crashes occurred between 2003 and 2012 on 1258 unidirectional travelled ways in Indiana. The developed model allows calculating the changes in the probabilities of the barrier-relevant crash events. The results of this study indicated that road departures lead to less frequent crossings of unprotected (no barriers) medians 50-80ft. wide than for narrower medians 30-50ft wide. This benefit decreased with an increase in rollovers inside the median. Although our data indicated no median crossover events when a median barrier was present, the risk of crossovers, although low, is still present and could manifest itself if the sample were larger. The presence of barriers near a travelled way was associated with a higher risk of redirecting errant vehicles back to the roadway where they could collide with other vehicles continuing on the road. As expected, cable barriers installed on the far-side edge of a median were associated with a lower probability of being hit by errant vehicles and of redirecting vehicles into traffic than the nearside cable barriers. On the other hand, the probability of off-road non-barrier crashes was higher because vehicles penetrating the median from the unprotected side were exposed to median ditches and similar obstacles. The roadside guardrails were confirmed to reduce the percentage of hazardous off-road crashes. The results of this study facilitate a more transparent evaluation of the safety effect of road barriers. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evidence for Sequential and Increasing Activation of Replication Origins along Replication Timing Gradients in the Human Genome

PubMed Central

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

2011-01-01

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 model for their replication kinetics. PMID:22219720

The spatial regulation of meiotic recombination hotspots: are all DSB hotspots crossover hotspots?

PubMed

Serrentino, Maria-Elisabetta; Borde, Valérie

2012-07-15

A key step for the success of meiosis is programmed homologous recombination, during which crossovers, or exchange of chromosome arms, take place. Crossovers increase genetic diversity but their main function is to ensure accurate chromosome segregation. Defects in crossover number and position produce aneuploidies that represent the main cause of miscarriages and chromosomal abnormalities such as Down's syndrome. Recombination is initiated by the formation of programmed double strand breaks (DSBs), which occur preferentially at places called DSB hotspots. Among all DSBs generated, only a small fraction is repaired by crossover, the other being repaired by other homologous recombination pathways. Crossover maps have been generated in a number of organisms, defining crossover hotspots. With the availability of genome-wide maps of DSBs as well as the ability to measure genetically the repair outcome at several hotspots, it is becoming more and more clear that not all DSB hotspots behave the same for crossover formation, suggesting that chromosomal features distinguish different types of hotspots. Copyright © 2012. Published by Elsevier Inc.

Analysis of the antibacterial activity and plaque control benefit of colgate total dentifrice via clinical evaluation and real-time polymerase chain reaction.

PubMed

Xu, Tao; Deshmukh, Meenal; Barnes, Virginia Monsul; Trivedi, Harsh M; Du-Thumm, Laurence; Richter, Rose; Cummins, Diane

2005-01-01

This study analyzed, from a combined clinical and molecular biologic perspective, the antibacterial and antiplaque efficacy of Colgate Total dentifrice (CTD). A single-blind crossover study design utilized 11 healthy human subjects. After a one-week washout period, subjects donated dental plaque, received a dental prophylaxis, and subsequently brushed with a test product. Twenty-four hours postbrushing, dental plaque was collected and a clinical plaque score determined. Dental plaque was submitted for Real-time Polymerase Chain Reaction (Real-time PCR) analysis. The same procedure was repeated in accordance with a crossover design for the use of the second test product. Following a one-week washout, a plaque donation, prophylaxis, and brushing with the test product ensued for each subject. Twenty-four hours post-brushing, the subjects returned for a plaque score and plaque donation. Twenty-four hours after brushing, dental plaque coverage increased 17.88% +/- 8.27% with CTD, compared to 30.42% +/- 9.97% with Colgate Cavity Protection (CCP; p = 0.005). Real-time PCR found plaque collected 24 hours after brushing with CTD exhibited, on average, fewer representative periodontal pathogens (Fusobacterium nucleatum, Actinobacillus actinomycetemcomitans, Tannerella forsythensis, and Porphyromonas gingivalis) and fewer early colonizers (Actinomyces naeslundii) than plaque collected before brushing, whereas CCP showed a moderate effect on oral bacteria. The study provides clinical and molecular biological evidence to substantiate the antibacterial and plaque control benefits of Colgate Total, and suggests the value of combining a molecular biological method with clinical research to corroborate clinical benefits.

Individual and crossover effects of stress on adjustment in medical student marriages.

PubMed

Katz, J; Monnier, J; Libet, J; Shaw, D; Beach, S R

2000-07-01

High-stress individuals may benefit from social support, although their support providers may be adversely affected via stress crossover effects. Individual and crossover effects of perceived stress within medical student marriages (n = 30) were investigated. Perceived spousal support was positively associated with individuals' own marital and emotional adjustment, attenuating stress effects. With regard to crossover effects, medical students' perceived stress was significantly associated with their spouses' emotional adjustment. Further, medical students' own emotional adjustment fully mediated this crossover effect. Results suggest that the contagion of negative affect may serve as a key mechanism through which stress crossover effects operate in marriage.

Faithful replication of grating patterns in polymer through electrohydrodynamic instabilities

NASA Astrophysics Data System (ADS)

Li, H.; Yu, W.; Wang, T.; Zhang, H.; Cao, Y.; Abraham, E.; Desmulliez, M. P. Y.

2014-07-01

Electrohydrodynamic instability patterning (EHDIP) as an alternative patterning method has attracted a great deal of attention over the past decade. This article demonstrates the faithful transfer of patterns with a high aspect ratio onto a polymer film via electrohydrodynamic instabilities for a given patterned grating mask. We perform a simple mathematical analysis to determine the influence of process parameters on the pressure difference ▵P. Through numerical simulation, it is demonstrated that thick films subject to large electric fields are essential to realize this faithful replication. In particular, the influence of the material properties of the polymer on pattern replication is discussed in detail. It is found that, to achieve the smaller periodic patterns with a higher resolution, film with a larger value of the dielectric constant and smaller value of the surface tension should be chosen. In addition, an ideal replication of the mask pattern with a short evolution time is possible by reducing the viscosity of the polymer liquid. Finally, the experiments of the pattern replication with and without defects are demonstrated to compare with the numerical simulation results. It is found that experiments are in good agreement with the simulation results and prove that the numerical simulation method provides an effective way to predict faithful replication.

Implications of "Too Good to Be True" for Replication, Theoretical Claims, and Experimental Design: An Example Using Prominent Studies of Racial Bias.

PubMed

Francis, Gregory

2016-01-01

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.

Implications of “Too Good to Be True” for Replication, Theoretical Claims, and Experimental Design: An Example Using Prominent Studies of Racial Bias

PubMed Central

Francis, Gregory

2016-01-01

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. PMID:27713708

Vehicles, Replicators, and Intercellular Movement of Genetic Information: Evolutionary Dissection of a Bacterial Cell

PubMed Central

Jalasvuori, Matti

2012-01-01

Prokaryotic biosphere is vastly diverse in many respects. Any given bacterial cell may harbor in different combinations viruses, plasmids, transposons, and other genetic elements along with their chromosome(s). These agents interact in complex environments in various ways causing multitude of phenotypic effects on their hosting cells. In this discussion I perform a dissection for a bacterial cell in order to simplify the diversity into components that may help approach the ocean of details in evolving microbial worlds. The cell itself is separated from all the genetic replicators that use the cell vehicle for preservation and propagation. I introduce a classification that groups different replicators according to their horizontal movement potential between cells and according to their effects on the fitness of their present host cells. The classification is used to discuss and improve the means by which we approach general evolutionary tendencies in microbial communities. Moreover, the classification is utilized as a tool to help formulating evolutionary hypotheses and to discuss emerging bacterial pathogens as well as to promote understanding on the average phenotypes of different replicators in general. It is also discussed that any given biosphere comprising prokaryotic cell vehicles and genetic replicators may naturally evolve to have horizontally moving replicators of various types. PMID:22567533

Replicating the AC-130’s Urban Close Air Support Capabilities Around the Clock

DTIC Science & Technology

2006-12-15

Each employs four Allison T56 -15 turbo-prop engines, dual-wheel construction, steerable nose gear, two tandem-mounted main retractable landing gear...Primary Function: Close air support, air interdiction and force protection Builder: Lockheed/Boeing Corp. Power Plant: Four Allison T56 -A-15

DNA methylation epigenetically silences crossover hot spots and controls chromosomal domains of meiotic recombination in Arabidopsis.

PubMed

Yelina, Nataliya E; Lambing, Christophe; Hardcastle, Thomas J; Zhao, Xiaohui; Santos, Bruno; Henderson, Ian R

2015-10-15

During meiosis, homologous chromosomes undergo crossover recombination, which is typically concentrated in narrow hot spots that are controlled by genetic and epigenetic information. Arabidopsis chromosomes are highly DNA methylated in the repetitive centromeres, which are also crossover-suppressed. Here we demonstrate that RNA-directed DNA methylation is sufficient to locally silence Arabidopsis euchromatic crossover hot spots and is associated with increased nucleosome density and H3K9me2. However, loss of CG DNA methylation maintenance in met1 triggers epigenetic crossover remodeling at the chromosome scale, with pericentromeric decreases and euchromatic increases in recombination. We used recombination mutants that alter interfering and noninterfering crossover repair pathways (fancm and zip4) to demonstrate that remodeling primarily involves redistribution of interfering crossovers. Using whole-genome bisulfite sequencing, we show that crossover remodeling is driven by loss of CG methylation within the centromeric regions. Using cytogenetics, we profiled meiotic DNA double-strand break (DSB) foci in met1 and found them unchanged relative to wild type. We propose that met1 chromosome structure is altered, causing centromere-proximal DSBs to be inhibited from maturation into interfering crossovers. These data demonstrate that DNA methylation is sufficient to silence crossover hot spots and plays a key role in establishing domains of meiotic recombination along chromosomes. © 2015 Yelina et al.; Published by Cold Spring Harbor Laboratory Press.

An alternative approach for neural network evolution with a genetic algorithm: crossover by combinatorial optimization.

PubMed

García-Pedrajas, Nicolás; Ortiz-Boyer, Domingo; Hervás-Martínez, César

2006-05-01

In this work we present a new approach to crossover operator in the genetic evolution of neural networks. The most widely used evolutionary computation paradigm for neural network evolution is evolutionary programming. This paradigm is usually preferred due to the problems caused by the application of crossover to neural network evolution. However, crossover is the most innovative operator within the field of evolutionary computation. One of the most notorious problems with the application of crossover to neural networks is known as the permutation problem. This problem occurs due to the fact that the same network can be represented in a genetic coding by many different codifications. Our approach modifies the standard crossover operator taking into account the special features of the individuals to be mated. We present a new model for mating individuals that considers the structure of the hidden layer and redefines the crossover operator. As each hidden node represents a non-linear projection of the input variables, we approach the crossover as a problem on combinatorial optimization. We can formulate the problem as the extraction of a subset of near-optimal projections to create the hidden layer of the new network. This new approach is compared to a classical crossover in 25 real-world problems with an excellent performance. Moreover, the networks obtained are much smaller than those obtained with classical crossover operator.

Low template STR typing: effect of replicate number and consensus method on genotyping reliability and DNA database search results.

PubMed

Benschop, Corina C G; van der Beek, Cornelis P; Meiland, Hugo C; van Gorp, Ankie G M; Westen, Antoinette A; Sijen, Titia

2011-08-01

To analyze DNA samples with very low DNA concentrations, various methods have been developed that sensitize short tandem repeat (STR) typing. Sensitized DNA typing is accompanied by stochastic amplification effects, such as allele drop-outs and drop-ins. Therefore low template (LT) DNA profiles are interpreted with care. One can either try to infer the genotype by a consensus method that uses alleles confirmed in replicate analyses, or one can use a statistical model to evaluate the strength of the evidence in a direct comparison with a known DNA profile. In this study we focused on the first strategy and we show that the procedure by which the consensus profile is assembled will affect genotyping reliability. In order to gain insight in the roles of replicate number and requested level of reproducibility, we generated six independent amplifications of samples of known donors. The LT methods included both increased cycling and enhanced capillary electrophoresis (CE) injection [1]. Consensus profiles were assembled from two to six of the replications using four methods: composite (include all alleles), n-1 (include alleles detected in all but one replicate), n/2 (include alleles detected in at least half of the replicates) and 2× (include alleles detected twice). We compared the consensus DNA profiles with the DNA profile of the known donor, studied the stochastic amplification effects and examined the effect of the consensus procedure on DNA database search results. From all these analyses we conclude that the accuracy of LT DNA typing and the efficiency of database searching improve when the number of replicates is increased and the consensus method is n/2. The most functional number of replicates within this n/2 method is four (although a replicate number of three suffices for samples showing >25% of the alleles in standard STR typing). This approach was also the optimal strategy for the analysis of 2-person mixtures, although modified search strategies may be needed to retrieve the minor component in database searches. From the database searches follows the recommendation to specifically mark LT DNA profiles when entering them into the DNA database. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Inhibition of HIV-1 Replication by Secondary Metabolites From Endophytic Fungi of Desert Plants

PubMed Central

Wellensiek, Brian P.; Ramakrishnan, Rajesh; Bashyal, Bharat P.; Eason, Yvette; Gunatilaka, A. A. Leslie; Ahmad, Nafees

2013-01-01

Most antiretroviral drugs currently in use to treat an HIV-1 infection are chemically synthesized and lead to the development of viral resistance, as well as cause severe toxicities. However, a largely unexplored source for HIV-1 drug discovery is endophytic fungi that live in a symbiotic relationship with plants. These fungi produce biologically active secondary metabolites, which are natural products that are beneficial to the host. We prepared several hundred extracts from endophytic fungi of desert plants and evaluated the inhibitory effects on HIV-1 replication of those extracts that showed less than 30% cytotoxicity in T-lymphocytes. Those extracts that inhibited viral replication were fractionated in order to isolate the compounds responsible for activity. Multiple rounds of fractionation and antiviral evaluation lead to the identification of four compounds, which almost completely impede HIV-1 replication. These studies demonstrate that metabolites from endophytic fungi of desert plants can serve as a viable source for identifying potent inhibitors of HIV-1 replication. PMID:23961302

Multiple determinants controlling activation of yeast replication origins late in S phase.

PubMed

Friedman, K L; Diller, J D; Ferguson, B M; Nyland, S V; Brewer, B J; Fangman, W L

1996-07-01

Analysis of a 131-kb segment of the left arm of yeast chromosome XIV beginning 157 kb from the telomere reveals four highly active origins of replication that initiate replication late in S phase. Previous work has shown that telomeres act as determinants for late origin activation. However, at least two of the chromosome XIV origins maintain their late activation time when located on large circular plasmids, indicating that late replication is independent of telomeres. Analysis of the replication time of plasmid derivatives containing varying amounts of chromosome XIV DNA show that a minimum of three chromosomal elements, distinct from each tested origin, contribute to late activation time. These late determinants are functionally equivalent, because duplication of one set of contributing sequences can compensate for the removal of another set. Furthermore, insertion of an origin that is normally early activated into this domain results in a shift to late activation, suggesting that the chromosome XIV origins are not unique in their ability to respond to the late determinants.

Kinetic nanofriction: a mechanism transition from quasi-continuous to ballistic-like Brownian regime

PubMed Central

2012-01-01

Surface diffusion of mobile adsorbates is not only the key to control the rate of dynamical processes on solid surfaces, e.g. epitaxial growth, but also of fundamental importance for recent technological applications, such as nanoscale electro-mechanical, tribological, and surface probing devices. Though several possible regimes of surface diffusion have been suggested, the nanoscale surface Brownian motion, especially in the technologically important low friction regimes, remains largely unexplored. Using molecular dynamics simulations, we show for the first time, that a C60 admolecule on a graphene substrate exhibits two distinct regimes of nanoscale Brownian motion: a quasi-continuous and a ballistic-like. A crossover between these two regimes is realized by changing the temperature of the system. We reveal that the underlying physical origin for this crossover is a mechanism transition of kinetic nanofriction arising from distinctive ways of interaction between the admolecule and the graphene substrate in these two regimes due to the temperature change. Our findings provide insight into surface mass transport and kinetic friction control at the nanoscale. PMID:22353343

Dimensional crossover and cold-atom realization of topological Mott insulators

PubMed Central

Scheurer, Mathias S.; Rachel, Stephan; Orth, Peter P.

2015-01-01

Interacting cold-atomic gases in optical lattices offer an experimental approach to outstanding problems of many body physics. One important example is the interplay of interaction and topology which promises to generate a variety of exotic phases such as the fractionalized Chern insulator or the topological Mott insulator. Both theoretically understanding these states of matter and finding suitable systems that host them have proven to be challenging problems. Here we propose a cold-atom setup where Hubbard on-site interactions give rise to spin liquid-like phases: weak and strong topological Mott insulators. They represent the celebrated paradigm of an interacting and topological quantum state with fractionalized spinon excitations that inherit the topology of the non-interacting system. Our proposal shall help to pave the way for a controlled experimental investigation of this exotic state of matter in optical lattices. Furthermore, it allows for the investigation of a dimensional crossover from a two-dimensional quantum spin Hall insulating phase to a three-dimensional strong topological insulator by tuning the hopping between the layers. PMID:25669431

Cardio-autonomic control and wellbeing due to oscillating color light exposure.

PubMed

Grote, Vincent; Kelz, Christina; Goswami, Nandu; Stossier, Harald; Tafeit, Erwin; Moser, Maximilian

2013-04-10

We investigated the cardio-autonomic and psychological effects of colored light cycling with the wavelength of ultradian rhythms. In two consecutive experiments, an explorative, longitudinal test followed by a randomized crossover design, 20 healthy subjects each were exposed to oscillating red, green and blue light. Heart rate, heart rate variability (HRV) and subjective wellbeing were measured. Significant effects of the oscillating color light exposure were observed for heart rate and cardio-autonomic control rhythms, derived from HRV (p≤.001). These effects on HRV were replicated in the second experiment in comparison to a similar white light exposure protocol (p≤.05). Vigilance showed improvement over the two weeks (p≤.001) in the longitudinal study. External color light cycling at the wavelength of blood pressure oscillations appears to amplify the endogenous autonomic oscillations. This leads to an optimization of cardio-autonomic control; an effect that was reflected shortly after the onset of the light exposure sessions by the increase of heart rate variability. From the results, we conclude that it takes repeated light exposure session to foster the positive effects on the psychological aspects, as we observed an increase of subjectively perceived mood only in the longitudinal study, not for the crossover design study. The results of our study imply some possible health effects of a color light exposure that is adjusted to 10 s and 1 min oscillations of humans' ultradian rhythms. These novel results show possible applications of oscillating visual inputs to the activation of processes connected to physiological regulation. Copyright © 2013 Elsevier Inc. All rights reserved.

miR-30a can inhibit DNA replication by targeting RPA1 thus slowing cancer cell proliferation.

PubMed

Zou, Zhenyou; Ni, Mengjie; Zhang, Jing; Chen, Yongfeng; Ma, Hongyu; Qian, Shihan; Tang, Longhua; Tang, Jiamei; Yao, Hailun; Zhao, Chengbin; Lu, Xiongwen; Sun, Hongyang; Qian, Jue; Mao, Xiaoting; Lu, Xulin; Liu, Qun; Zen, Juping; Wu, Hanbing; Bao, Zhaosheng; Lin, Shudan; Sheng, Hongyu; Li, Yunlong; Liang, Yong; Chen, Zhiqiang; Zong, Dan

2016-07-15

Cell proliferation was inhibited following forced over-expression of miR-30a in the ovary cancer cell line A2780DX5 and the gastric cancer cell line SGC7901R. Interestingly, miR-30a targets the DNA replication protein RPA1, hinders the replication of DNA and induces DNA fragmentation. Furthermore, ataxia telangiectasia mutated (ATM) and checkpoint kinase 2 (CHK2) were phosphorylated after DNA damage, which induced p53 expression, thus triggering the S-phase checkpoint, arresting cell cycle progression and ultimately initiating cancer cell apoptosis. Therefore, forced miR-30a over-expression in cancer cells can be a potential way to inhibit tumour development. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

Chapter One---Cancer terminator viruses and approaches for enhancing therapeutic outcomes.

PubMed

Das, Swadesh K; Sarkar, Siddik; Dash, Rupesh; Dent, Paul; Wang, Xiang-Yang; Sarkar, Devanand; Fisher, Paul B

2012-01-01

No single or combinatorial therapeutic approach has proven effective in decreasing morbidity or engendering a cure of metastatic cancer. In principle, conditionally replication-competent adenoviruses that induce tumor oncolysis through cancer-specific replication hold promise for cancer therapy. However, a single-agent approach may not be adequate to completely eradicate cancer in a patient because most cancers arise from abnormalities in multiple genetic and signal transduction pathways and targeting disseminated metastases is difficult to achieve. Based on these considerations, a novel class of cancer destroying adenoviruses have been produced, cancer terminator viruses (CTVs), in which cancer-specific replication is controlled by the progression-elevated gene-3 promoter and replicating viruses produce a second transgene encoding an apoptosis-inducing and immunomodulatory cytokine, either melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24) or interferon-γ. This review focuses on these viruses and ways to improve their delivery systemically and enhance their therapeutic efficacy. Copyright © 2012 Elsevier Inc. All rights reserved.

Molecular turnover, the H3.3 dilemma and organismal aging (hypothesis)

PubMed Central

Saade, Evelyne; Pirozhkova, Iryna; Aimbetov, Rakhan; Lipinski, Marc; Ogryzko, Vasily

2015-01-01

The H3.3 histone variant has been a subject of increasing interest in the field of chromatin studies due to its two distinguishing features. First, its incorporation into chromatin is replication independent unlike the replication-coupled deposition of its canonical counterparts H3.1/2. Second, H3.3 has been consistently associated with an active state of chromatin. In accordance, this histone variant should be expected to be causally involved in the regulation of gene expression, or more generally, its incorporation should have downstream consequences for the structure and function of chromatin. This, however, leads to an apparent paradox: In cells that slowly replicate in the organism, H3.3 will accumulate with time, opening the way to aberrant effects on heterochromatin. Here, we review the indications that H3.3 is expected both to be incorporated in the heterochromatin of slowly replicating cells and to retain its functional downstream effects. Implications for organismal aging are discussed. PMID:25720734

Proton conductivity and methanol permeability of Nafion-SiO2/SiWA composite membranes

NASA Astrophysics Data System (ADS)

Thiam, Hui San; Chia, Min Yan; Cheah, Qiao Rou; Koo, Charlene Chai Hoon; Lai, Soon Onn; Chong, Kok Chung

2017-04-01

Proton exchange membranes for a direct methanol fuel cell (DMFC) were prepared by incorporating silica/silicotungstic acid (SiO2/SiWA) inorganic composite into a Nafion polymer. The effects of SiO2/SiWA content on proton conductivity of membranes were investigated by using a four-probe conductivity cell. Methanol permeability of composite membrane was also determined by using a homemade diffusion cell and gas chromatography technique. It was found that proton conductivity of the composite membranes decreased with SiO2/SiWA content, however the highest proton conductivity achieved was 11% greater than the pure recast Nafion membrane. The methanol permeability of composite membrane was much lower than that of pure recast Nafion, in a reduction of 58% which indicated a better resistance to fuel crossover. Nafion-SiO2/SiWA composite membrane showed promising advantages over pure Nafion on electrochemical properties such as proton conductivity and fuel crossover and it is potentially attractive for use in DMFC.

Differential-Evolution Control Parameter Optimization for Unmanned Aerial Vehicle Path Planning

PubMed Central

Kok, Kai Yit; Rajendran, Parvathy

2016-01-01

The differential evolution algorithm has been widely applied on unmanned aerial vehicle (UAV) path planning. At present, four random tuning parameters exist for differential evolution algorithm, namely, population size, differential weight, crossover, and generation number. These tuning parameters are required, together with user setting on path and computational cost weightage. However, the optimum settings of these tuning parameters vary according to application. Instead of trial and error, this paper presents an optimization method of differential evolution algorithm for tuning the parameters of UAV path planning. The parameters that this research focuses on are population size, differential weight, crossover, and generation number. The developed algorithm enables the user to simply define the weightage desired between the path and computational cost to converge with the minimum generation required based on user requirement. In conclusion, the proposed optimization of tuning parameters in differential evolution algorithm for UAV path planning expedites and improves the final output path and computational cost. PMID:26943630

The pharmacokinetic profile of a novel fixed-dose combination tablet of ibuprofen and paracetamol

PubMed Central

2010-01-01

Background Ibuprofen and paracetamol differ in their mode of action and related therapeutic effects, suggesting that combined administration may offer improved analgesia. Reported here are the results of two studies on the pharmacokinetic properties of a novel ibuprofen (200 mg) and paracetamol (500 mg) fixed-dose combination tablet. Methods Both studies were open-label, randomised studies in healthy volunteers: Study 1 was a four-way crossover, single-dose study; Study 2 was a two-way cross-over, repeat-dose study. Results Pharmacokinetic parameters for ibuprofen and paracetamol were similar for the combination and monotherapy tablets (values falling within the 80% to 125% acceptable bioequivalence range) except for the rate of absorption of paracetamol from the combination (tmax), which was significantly faster compared with monotherapy (median difference 10 minutes; p < 0.05). Mean plasma concentrations of both drugs were higher, earlier, following administration of the combination tablet compared with monotherapy. Mean plasma levels at 10 and 20 minutes were 6.64 μg.mL-1 and 16.81 μg.mL-1, respectively, for ibuprofen from the combination, compared with 0.58 μg.mL-1 and 9.00 μg.mL-1, respectively, for monotherapy. For paracetamol, mean plasma levels at 10 and 20 minutes were 5.43 μg.mL-1 and 14.54 μg.mL-1, respectively, for the combination compared with 0.33 μg.mL-1 and 9.19 μg.mL-1, respectively, for monotherapy. The rate of absorption of both ibuprofen and paracetamol was significantly delayed when the combination tablet was administered in the fed versus fasted state; median delay was 25 minutes for ibuprofen (p > 0.05) and 55 minutes for paracetamol (p < 0.001). The pharmacokinetic parameters were comparable irrespective of whether the combination tablet was given twice or three times daily; systemic exposure was, however, approximately 1.4 times greater for both drugs when given three times daily. Conclusions Administration of ibuprofen and paracetamol in a fixed-dose combination tablet does not significantly alter the pharmacokinetic profiles of either drug, except for enhancing the rate of paracetamol absorption, offering potential therapeutic benefits in relation to the onset of analgesia. Concentrations of both drugs reached previously reported therapeutic levels when the combination tablet was administrated in the fed or fasted state. Three times daily dosing may offer enhanced therapeutic effect for longer than twice daily dosing. PMID:20602760

Tunable Magnetic Alignment between Trapped Exciton-Polariton Condensates.

PubMed

Ohadi, H; Del Valle-Inclan Redondo, Y; Dreismann, A; Rubo, Y G; Pinsker, F; Tsintzos, S I; Hatzopoulos, Z; Savvidis, P G; Baumberg, J J

2016-03-11

Tunable spin correlations are found to arise between two neighboring trapped exciton-polariton condensates which spin polarize spontaneously. We observe a crossover from an antiferromagnetic to a ferromagnetic pair state by reducing the coupling barrier in real time using control of the imprinted pattern of pump light. Fast optical switching of both condensates is then achieved by resonantly but weakly triggering only a single condensate. These effects can be explained as the competition between spin bifurcations and spin-preserving Josephson coupling between the two condensates, and open the way to polariton Bose-Hubbard ladders.

Promotion of Hendra Virus Replication by MicroRNA 146a

PubMed Central

Marsh, Glenn A.; Jenkins, Kristie A.; Gantier, Michael P.; Tizard, Mark L.; Middleton, Deborah; Lowenthal, John W.; Haining, Jessica; Izzard, Leonard; Gough, Tamara J.; Deffrasnes, Celine; Stambas, John; Robinson, Rachel; Heine, Hans G.; Pallister, Jackie A.; Foord, Adam J.; Bean, Andrew G.; Wang, Lin-Fa

2013-01-01

Hendra virus is a highly pathogenic zoonotic paramyxovirus in the genus Henipavirus. Thirty-nine outbreaks of Hendra virus have been reported since its initial identification in Queensland, Australia, resulting in seven human infections and four fatalities. Little is known about cellular host factors impacting Hendra virus replication. In this work, we demonstrate that Hendra virus makes use of a microRNA (miRNA) designated miR-146a, an NF-κB-responsive miRNA upregulated by several innate immune ligands, to favor its replication. miR-146a is elevated in the blood of ferrets and horses infected with Hendra virus and is upregulated by Hendra virus in human cells in vitro. Blocking miR-146a reduces Hendra virus replication in vitro, suggesting a role for this miRNA in Hendra virus replication. In silico analysis of miR-146a targets identified ring finger protein (RNF)11, a member of the A20 ubiquitin editing complex that negatively regulates NF-κB activity, as a novel component of Hendra virus replication. RNA interference-mediated silencing of RNF11 promotes Hendra virus replication in vitro, suggesting that increased NF-κB activity aids Hendra virus replication. Furthermore, overexpression of the IκB superrepressor inhibits Hendra virus replication. These studies are the first to demonstrate a host miRNA response to Hendra virus infection and suggest an important role for host miRNAs in Hendra virus disease. PMID:23345523

Ecology and Evolution in the RNA World Dynamics and Stability of Prebiotic Replicator Systems.

PubMed

Szilágyi, András; Zachar, István; Scheuring, István; Kun, Ádám; Könnyű, Balázs; Czárán, Tamás

2017-11-27

As of today, the most credible scientific paradigm pertaining to the origin of life on Earth is undoubtedly the RNA World scenario. It is built on the assumption that catalytically active replicators (most probably RNA-like macromolecules) may have been responsible for booting up life almost four billion years ago. The many different incarnations of nucleotide sequence (string) replicator models proposed recently are all attempts to explain on this basis how the genetic information transfer and the functional diversity of prebiotic replicator systems may have emerged, persisted and evolved into the first living cell. We have postulated three necessary conditions for an RNA World model system to be a dynamically feasible representation of prebiotic chemical evolution: (1) it must maintain and transfer a sufficient diversity of information reliably and indefinitely, (2) it must be ecologically stable and (3) it must be evolutionarily stable. In this review, we discuss the best-known prebiotic scenarios and the corresponding models of string-replicator dynamics and assess them against these criteria. We suggest that the most popular of prebiotic replicator systems, the hypercycle, is probably the worst performer in almost all of these respects, whereas a few other model concepts (parabolic replicator, open chaotic flows, stochastic corrector, metabolically coupled replicator system) are promising candidates for development into coherent models that may become experimentally accessible in the future.

Ecology and Evolution in the RNA World Dynamics and Stability of Prebiotic Replicator Systems

PubMed Central

Szilágyi, András; Kun, Ádám; Könnyű, Balázs; Czárán, Tamás

2017-01-01

As of today, the most credible scientific paradigm pertaining to the origin of life on Earth is undoubtedly the RNA World scenario. It is built on the assumption that catalytically active replicators (most probably RNA-like macromolecules) may have been responsible for booting up life almost four billion years ago. The many different incarnations of nucleotide sequence (string) replicator models proposed recently are all attempts to explain on this basis how the genetic information transfer and the functional diversity of prebiotic replicator systems may have emerged, persisted and evolved into the first living cell. We have postulated three necessary conditions for an RNA World model system to be a dynamically feasible representation of prebiotic chemical evolution: (1) it must maintain and transfer a sufficient diversity of information reliably and indefinitely, (2) it must be ecologically stable and (3) it must be evolutionarily stable. In this review, we discuss the best-known prebiotic scenarios and the corresponding models of string-replicator dynamics and assess them against these criteria. We suggest that the most popular of prebiotic replicator systems, the hypercycle, is probably the worst performer in almost all of these respects, whereas a few other model concepts (parabolic replicator, open chaotic flows, stochastic corrector, metabolically coupled replicator system) are promising candidates for development into coherent models that may become experimentally accessible in the future. PMID:29186916

50 CFR 660.320 - Open access fishery-crossover provisions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 50 Wildlife and Fisheries 13 2014-10-01 2014-10-01 false Open access fishery-crossover provisions... West Coast Groundfish-Open Access Fisheries § 660.320 Open access fishery—crossover provisions. The crossover provisions listed at § 660.60(h)(7), apply to vessels fishing in the open access fishery. [76 FR...

50 CFR 660.320 - Open access fishery-crossover provisions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 50 Wildlife and Fisheries 13 2013-10-01 2013-10-01 false Open access fishery-crossover provisions... West Coast Groundfish-Open Access Fisheries § 660.320 Open access fishery—crossover provisions. The crossover provisions listed at § 660.60(h)(7), apply to vessels fishing in the open access fishery. [76 FR...

50 CFR 660.320 - Open access fishery-crossover provisions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 50 Wildlife and Fisheries 13 2012-10-01 2012-10-01 false Open access fishery-crossover provisions... West Coast Groundfish-Open Access Fisheries § 660.320 Open access fishery—crossover provisions. The crossover provisions listed at § 660.60(h)(7), apply to vessels fishing in the open access fishery. [76 FR...

An approach to checking case-crossover analyses based on equivalence with time-series methods.

PubMed

Lu, Yun; Symons, James Morel; Geyh, Alison S; Zeger, Scott L

2008-03-01

The case-crossover design has been increasingly applied to epidemiologic investigations of acute adverse health effects associated with ambient air pollution. The correspondence of the design to that of matched case-control studies makes it inferentially appealing for epidemiologic studies. Case-crossover analyses generally use conditional logistic regression modeling. This technique is equivalent to time-series log-linear regression models when there is a common exposure across individuals, as in air pollution studies. Previous methods for obtaining unbiased estimates for case-crossover analyses have assumed that time-varying risk factors are constant within reference windows. In this paper, we rely on the connection between case-crossover and time-series methods to illustrate model-checking procedures from log-linear model diagnostics for time-stratified case-crossover analyses. Additionally, we compare the relative performance of the time-stratified case-crossover approach to time-series methods under 3 simulated scenarios representing different temporal patterns of daily mortality associated with air pollution in Chicago, Illinois, during 1995 and 1996. Whenever a model-be it time-series or case-crossover-fails to account appropriately for fluctuations in time that confound the exposure, the effect estimate will be biased. It is therefore important to perform model-checking in time-stratified case-crossover analyses rather than assume the estimator is unbiased.

Meiotic recombination protein Rec12: functional conservation, crossover homeostasis and early crossover/non-crossover decision

PubMed Central

Kan, Fengling; Davidson, Mari K.; Wahls, Wayne P.

2011-01-01

In fission yeast and other eukaryotes, Rec12 (Spo11) is thought to catalyze the formation of dsDNA breaks (DSBs) that initiate homologous recombination in meiosis. Rec12 is orthologous to the catalytic subunit of topoisomerase VI (Top6A). Guided by the crystal structure of Top6A, we engineered the rec12 locus to encode Rec12 proteins each with a single amino acid substitution in a conserved residue. Of 21 substitutions, 10 significantly reduced or abolished meiotic DSBs, gene conversion, crossover recombination and the faithful segregation of chromosomes. Critical residues map within the metal ion-binding pocket toprim (E179A, D229A, D231A), catalytic region 5Y-CAP (R94A, D95A, Y98F) and the DNA-binding interface (K201A, G202E, R209A, K242A). A subset of substitutions reduced DSBs but maintained crossovers, demonstrating crossover homeostasis. Furthermore, a strong separation of function mutation (R304A) suggests that the crossover/non-crossover decision is established early by a protein–protein interaction surface of Rec12. Fission yeast has multiple crossovers per bivalent, and chromosome segregation was robust above a threshold of about one crossover per bivalent, below which non-disjunction occurred. These results support structural and functional conservation among Rec12/Spo11/Top6A family members for the catalysis of DSBs, and they reveal how Rec12 regulates other features of meiotic chromosome dynamics. PMID:21030440

DNA Replication Dynamics of the GGGGCC Repeat of the C9orf72 Gene.

PubMed

Thys, Ryan Griffin; Wang, Yuh-Hwa

2015-11-27

DNA has the ability to form a variety of secondary structures in addition to the normal B-form DNA, including hairpins and quadruplexes. These structures are implicated in a number of neurological diseases and cancer. Expansion of a GGGGCC repeat located at C9orf72 is associated with familial amyotrophic lateral sclerosis and frontotemporal dementia. This repeat expands from two to 24 copies in normal individuals to several hundreds or thousands of repeats in individuals with the disease. Biochemical studies have demonstrated that as little as four repeats have the ability to form a stable DNA secondary structure known as a G-quadruplex. Quadruplex structures have the ability to disrupt normal DNA processes such as DNA replication and transcription. Here we examine the role of GGGGCC repeat length and orientation on DNA replication using an SV40 replication system in human cells. Replication through GGGGCC repeats leads to a decrease in overall replication efficiency and an increase in instability in a length-dependent manner. Both repeat expansions and contractions are observed, and replication orientation is found to influence the propensity for expansions or contractions. The presence of replication stress, such as low-dose aphidicolin, diminishes replication efficiency but has no effect on instability. Two-dimensional gel electrophoresis analysis demonstrates a replication stall with as few as 20 GGGGCC repeats. These results suggest that replication of the GGGGCC repeat at C9orf72 is perturbed by the presence of expanded repeats, which has the potential to result in further expansion, leading to disease. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Proof of Monogamy of non-local correlations in three and four qubit states

NASA Astrophysics Data System (ADS)

Sharma, Santosh Shelly; Sharma, Naresh Kumar

2015-03-01

Recently, we used the process of selective construction of invariants to obtain physically meaningful polynomial invariants for three and four qubit pure states. In this article, we report the exact relations between the concurrence of a two qubit reduced state and corresponding three or four qubit pure state invariants. Firstly, we obtain an analytical expression for concurrence of a given mixed state of two qubits in terms of determinants of negativity fonts in the three or four qubit pure state. For three qubits, a comparison with three tangle and squared negativity expressed in terms of determinants of negativity fonts leads to three relations. These three conditions satisfied by the two-way and three-way correlations sum together and lead to well known CKW inequality. When a qubit pair is part of a four qubit pure state, it may be entangled to the rest of the system through two-way, three-way and four-way correlations. Monogamy equalities, satisfied by two-way, three-way and four-way non-local quantum correlatios are presented for states belonging to classes of four qubit pure states with distinct entanglement types. We gratefully acknowledge financial support from CNPq and Capes Brazil.

Actual drawing of histological images improves knowledge retention.

PubMed

Balemans, Monique C M; Kooloos, Jan G M; Donders, A Rogier T; Van der Zee, Catharina E E M

2016-01-01

Medical students have to process a large amount of information during the first years of their study, which has to be retained over long periods of nonuse. Therefore, it would be beneficial when knowledge is gained in a way that promotes long-term retention. Paper-and-pencil drawings for the uptake of form-function relationships of basic tissues has been a teaching tool for a long time, but now seems to be redundant with virtual microscopy on computer-screens and printers everywhere. Several studies claimed that, apart from learning from pictures, actual drawing of images significantly improved knowledge retention. However, these studies applied only immediate post-tests. We investigated the effects of actual drawing of histological images, using randomized cross-over design and different retention periods. The first part of the study concerned esophageal and tracheal epithelium, with 384 medical and biomedical sciences students randomly assigned to either the drawing or the nondrawing group. For the second part of the study, concerning heart muscle cells, students from the previous drawing group were now assigned to the nondrawing group and vice versa. One, four, and six weeks after the experimental intervention, the students were given a free recall test and a questionnaire or drawing exercise, to determine the amount of knowledge retention. The data from this study showed that knowledge retention was significantly improved in the drawing groups compared with the nondrawing groups, even after four or six weeks. This suggests that actual drawing of histological images can be used as a tool to improve long-term knowledge retention. © 2015 American Association of Anatomists.

Alcohol calibration of tests measuring skills related to car driving.

PubMed

Jongen, Stefan; Vuurman, Eric; Ramaekers, Jan; Vermeeren, Annemiek

2014-06-01

Medication and illicit drugs can have detrimental side effects which impair driving performance. A drug's impairing potential should be determined by well-validated, reliable, and sensitive tests and ideally be calibrated by benchmark drugs and doses. To date, no consensus has been reached on the issue of which psychometric tests are best suited for initial screening of a drug's driving impairment potential. The aim of this alcohol calibration study is to determine which performance tests are useful to measure drug-induced impairment. The effects of alcohol are used to compare the psychometric quality between tests and as benchmark to quantify performance changes in each test associated with potentially impairing drug effects. Twenty-four healthy volunteers participated in a double-blind, four-way crossover study. Treatments were placebo and three different doses of alcohol leading to blood alcohol concentrations (BACs) of 0.2, 0.5, and 0.8 g/L. Main effects of alcohol were found in most tests. Compared with placebo, performance in the Divided Attention Test (DAT) was significantly impaired after all alcohol doses and performance in the Psychomotor Vigilance Test (PVT) and the Balance Test was impaired with a BAC of 0.5 and 0.8 g/L. The largest effect sizes were found on postural balance with eyes open and mean reaction time in the divided attention and the psychomotor vigilance test. The preferable tests for initial screening are the DAT and the PVT, as these tests were most sensitive to the impairing effects of alcohol and being considerably valid in assessing potential driving impairment.

Pharmacokinetics and pharmacodynamics of GSK961081, a novel inhaled muscarinic antagonist β2 -agonist, and fluticasone propionate administered alone, concurrently and as a combination blend formulation in healthy volunteers.

PubMed

Norris, Virginia; Ambery, Claire; Riley, Trevor

2014-07-01

To investigate the pharmacokinetics and pharmacodynamics of inhaled GSK961081 and fluticasone propionate (FP) given alone, concurrently and as a combination blend formulation. The study was double-blind, double-dummy, four-way crossover. Twenty-four healthy volunteers took single doses of the following in randomized order: (1) GSK961081 800 µg; (2) FP 500 µg; (3) GSK961081 800 µg and FP 500 µg as a blend formulation; and (4) GSK961081 800 µg and FP 500 µg concurrently via separate inhalers. The eLung breathing simulator was also used for the in vitro characterization of the formulations. There was no pharmacokinetic interaction when GSK961081 and FP were administered concurrently. Mean Cmax and AUC(0-t) of GSK961081 were lower (∼20%) and mean Cmax and AUC(0-t) of FP were higher (two fold) following GSK961081/FP blend formulation compared to concurrent or the individual components alone. There was an increase in the FP in vitro ex-throat dose for the GSK961081/FP blend from the eLung breathing simulator. Serum cortisol suppression was greater with GSK961081/FP blend, with lower (∼10%) cortisol levels than after GSK961081 + FP concurrent or FP alone. GSK961081/FP blend formulation was associated with an increase in FP systemic exposure and greater serum cortisol suppression. © 2014, The American College of Clinical Pharmacology.

Grapefruit juice reduces the oral bioavailability of fexofenadine but not desloratadine.

PubMed

Banfield, Christopher; Gupta, Samir; Marino, Mark; Lim, Josephine; Affrime, Melton

2002-01-01

Certain foods, such as grapefruit juice, are known to substantially alter the bioavailability of some drugs. These effects may be mediated by interactions with enzyme systems, such as cytochrome P450, or with active transporter systems, such as P-glycoprotein and organic anion transporting polypeptides. To assess the effect of consumption of grapefruit juice on the oral bioavailability of two nonsedating antihistamines, fexofenadine and desloratadine. Non-blinded, randomised, single-dose, four-way crossover study. Twenty-four healthy adult volunteers. Single oral doses of desloratadine 5mg and fexofenadine 60mg taken without and with grapefruit juice (pretreatment with 240ml of double-strength juice three times daily for 2 days prior to administration of study drug, plus the same amount simultaneously with, and 2 hours after, the drug dose). Each treatment was separated by at least 10 days. Log-transformed pharmacokinetic parameters [peak plasma concentration (C(max)) and area under the curve (AUC)], time to maximum concentration, elimination half-life and electrocardiographic (ECG) parameters. Comparing the ratio of the pharmacokinetic parameter means (C(max) and AUC) with and without grapefruit juice (expressed as a percentage), the rate (C(max)) and extent (AUC) of absorption of fexofenadine were reduced by 30% by consumption of grapefruit juice. In contrast, the bioavailability of desloratadine was unaffected by grapefruit juice. No clinically significant changes in ECG parameters were observed following coadministration of grapefruit juice with desloratadine or fexofenadine compared with either antihistamine given alone. The bioavailability of drugs that do not undergo significant intestinal or hepatic metabolism, such as fexofenadine, may be altered when administered with agents that influence drug transport mechanisms.

On the cross-cultural replicability of the resilient, undercontrolled, and overcontrolled personality types.

PubMed

Alessandri, Guido; Vecchione, Michele; Donnellan, Brent M; Eisenberg, Nancy; Caprara, Gian Vittorio; Cieciuch, Jan

2014-08-01

Personality types reflect typical configurations of personality attributes within individuals. Over the last 20 years, researchers have identified a set of three replicable personality types: resilient (R), undercontrolled (U), and overcontrolled (O) types. In this study, we examined the cross-cultural replicability of the RUO types in Italy, Poland, Spain, and the United States. Personality types were identified using cluster analyses of Big Five profiles in large samples of college students from Italy (n = 322), the United States (n = 499), Spain (n = 420), and Poland (n = 235). Prior to clustering the profiles, the measurement invariance of the Big Five measure across samples was tested. We found evidence for the RUO types in all four samples. The three-cluster solution showed a better fit over alternative solutions and had a relatively high degree of cross-cultural generalizability. The RUO types are evident in samples from four countries with distinct linguistic and cultural traditions. Results were discussed in light of the importance of considering how traits are organized within individuals for advancing contemporary personality psychology. © 2013 Wiley Periodicals, Inc.

Social learning and the replication process: an experimental investigation.

PubMed

Derex, Maxime; Feron, Romain; Godelle, Bernard; Raymond, Michel

2015-06-07

Human cultural traits typically result from a gradual process that has been described as analogous to biological evolution. This observation has led pioneering scholars to draw inspiration from population genetics to develop a rigorous and successful theoretical framework of cultural evolution. Social learning, the mechanism allowing information to be transmitted between individuals, has thus been described as a simple replication mechanism. Although useful, the extent to which this idealization appropriately describes the actual social learning events has not been carefully assessed. Here, we used a specifically developed computer task to evaluate (i) the extent to which social learning leads to the replication of an observed behaviour and (ii) the consequences it has for fitness landscape exploration. Our results show that social learning does not lead to a dichotomous choice between disregarding and replicating social information. Rather, it appeared that individuals combine and transform information coming from multiple sources to produce new solutions. As a consequence, landscape exploration was promoted by the use of social information. These results invite us to rethink the way social learning is commonly modelled and could question the validity of predictions coming from models considering this process as replicative. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Chromosome dynamics in the yeast interphase nucleus.

PubMed

Heun, P; Laroche, T; Shimada, K; Furrer, P; Gasser, S M

2001-12-07

Little is known about the dynamics of chromosomes in interphase nuclei. By tagging four chromosomal regions with a green fluorescent protein fusion to lac repressor, we monitored the movement and subnuclear position of specific sites in the yeast genome, sampling at short time intervals. We found that early and late origins of replication are highly mobile in G1 phase, frequently moving at or faster than 0.5 micrometers/10 seconds, in an energy-dependent fashion. The rapid diffusive movement of chromatin detected in G1 becomes constrained in S phase through a mechanism dependent on active DNA replication. In contrast, telomeres and centromeres provide replication-independent constraint on chromatin movement in both G1 and S phases.

Towards Self-Replicating Chemical Systems Based on Cytidylic and Guanylic Acids

NASA Technical Reports Server (NTRS)

Kanavarioti, Anastassia

1999-01-01

This project was aimed towards a better understanding of template-directed reactions and, based on this, towards the development of efficient non-enzymatic RNA replicating systems. These systems could serve as models for the prebiotic synthesis of an RNA world. The major objectives of this project are: (a) To elucidate the mechanistic aspects of template-directed (TD) chemistry and (b) to identify active boundary regions, or conditions, environmental and other, that favor "organized chemistry" and stereo-selective polymerization of nucleotides. "Organized chemistry" may lead to enhanced polymerization efficiency which in turn is expected to facilitate the road towards a self-replicating chemical system based on all four nucleic acid bases.

New multifunctional Escherichia coli-Streptomyces shuttle vectors allowing blue-white screening on XGal plates.

PubMed

Wehmeier, U F

1995-11-07

Four new shuttle vectors for Escherichia coli (Ec) and Streptomyces, pUWL218, pUWL219, pUWL-SK and pUWL-KS, which permit recognition of recombinant (re-) plasmids on XGal plates in Ec, were constructed. These vectors contain the replication functions of the Streptomyces wide-host-range multicopy plasmid pIJ101, the tsr gene conferring resistance to thiostrepton in Streptomyces, the ColEI origin of replication from the pUC plasmids for replication in Ec and the bla gene conferring resistance to ampicillin in Ec. They possess multiple cloning sites with a number of unique restriction sites and allow direct sequencing of re-derivatives using the pUC sequencing primers.

What's Mine Is Yours: The Crossover of Day-Specific Self-Esteem

ERIC Educational Resources Information Center

Neff, Angela; Sonnentag, Sabine; Niessen, Cornelia; Unger, Dana

2012-01-01

This diary study examines the daily crossover of self-esteem within working couples. By integrating self-esteem research into the crossover framework, we hypothesized that the day-specific self-esteem experienced by one partner after work crosses over to the other partner. Furthermore, we proposed that this daily crossover process is moderated by…

Studies on the individual and combined diuretic effects of four Vietnamese traditional herbal remedies (Zea mays, Imperata cylindrica, Plantago major and Orthosiphon stamineus).

PubMed

Doan, D D; Nguyen, N H; Doan, H K; Nguyen, T L; Phan, T S; van Dau, N; Grabe, M; Johansson, R; Lindgren, G; Stjernström, N E

1992-06-01

Herbal remedies are widely used in Vietnam alongside modern drugs. We assessed the diuretic effect of four traditional Vietnamese herbal remedies from Zea mays, Imperata cylindrica, Plantago major and Orthosiphon stamineus, all claimed to produce an increase of diuresis. No influence was recorded for the 12- and 24-h urine output or on the sodium excretion for any of the drugs when tested under standardized conditions in a placebo controlled double-blind crossover model. The present study indicates the need for critical review of the present recommendations regarding therapy with plant materials in countries relying on empiric traditions.

Individual responses to methylphenidate and caffeine in children with minimal brain dysfunction.

PubMed Central

Garfinkel, B. D.; Webster, C. D.; Sloman, L.

1975-01-01

Eight children with minimal brain dysfunction were studied for their individual responses to two stimulant medications--methylphenidate hydrochloride and caffeine citrate. Four types of behavioural responses were observed in the double-blind crossover experiment: four children responded favourably to both psychostimulants, one responded to methylphenidate alone and two responded to the placebo. The behaviour of one child deteriorated while he was taking methylphenidate and caffeine. In general, methylphenidate was superior to caffeine in diminishing hyperactive and aggressive behaviour. It is apparent that such stimulant medication exerts its therapeutic effects in these two areas primarily and would therefore be useful as one aspect of a complete treatment program for children with this syndrome. PMID:803184

The Crossover Time as an Evaluation of Ocean Models Against Persistence

NASA Astrophysics Data System (ADS)

Phillipson, L. M.; Toumi, R.

2018-01-01

A new ocean evaluation metric, the crossover time, is defined as the time it takes for a numerical model to equal the performance of persistence. As an example, the average crossover time calculated using the Lagrangian separation distance (the distance between simulated trajectories and observed drifters) for the global MERCATOR ocean model analysis is found to be about 6 days. Conversely, the model forecast has an average crossover time longer than 6 days, suggesting limited skill in Lagrangian predictability by the current generation of global ocean models. The crossover time of the velocity error is less than 3 days, which is similar to the average decorrelation time of the observed drifters. The crossover time is a useful measure to quantify future ocean model improvements.

Initial bird responses to alternative pine regeneration methods in Arkansas and Oklahoma: preliminary findings

Treesearch

Ronald E. Thill; Roger W. Perry; Nancy E. Koerth; Philip A. Tappe; David G. Peitz

2004-01-01

Abstract - We studied spring songbird communities in a predominantly forested landscape in the Ouachita Mountains of west-central Arkansas and eastern Oklahoma. Relative bird abundance, species richness, diversity, and evenness values are presented for the first, third, and fifth years following harvesting in four replications of four regeneration...

Sequential structures provide insights into the fidelity of RNA replication.

PubMed

Ferrer-Orta, Cristina; Arias, Armando; Pérez-Luque, Rosa; Escarmís, Cristina; Domingo, Esteban; Verdaguer, Nuria

2007-05-29

RNA virus replication is an error-prone event caused by the low fidelity of viral RNA-dependent RNA polymerases. Replication fidelity can be decreased further by the use of mutagenic ribonucleoside analogs to a point where viral genetic information can no longer be maintained. For foot-and-mouth disease virus, the antiviral analogs ribavirin and 5-fluorouracil have been shown to be mutagenic, contributing to virus extinction through lethal mutagenesis. Here, we report the x-ray structure of four elongation complexes of foot-and-mouth disease virus polymerase 3D obtained in presence of natural substrates, ATP and UTP, or mutagenic nucleotides, ribavirin triphosphate and 5-fluorouridine triphosphate with different RNAs as template-primer molecules. The ability of these complexes to synthesize RNA in crystals allowed us to capture different successive replication events and to define the critical amino acids involved in (i) the recognition and positioning of the incoming nucleotide or analog; (ii) the positioning of the acceptor base of the template strand; and (iii) the positioning of the 3'-OH group of the primer nucleotide during RNA replication. The structures identify key interactions involved in viral RNA replication and provide insights into the molecular basis of the low fidelity of viral RNA polymerases.

Comparative Evaluation of Vacuum-based Surface Sampling ...

EPA Pesticide Factsheets

Journal Article Following a biological contamination incident, collection of surface samples is necessary to determine the extent and level of contamination, and to deem an area safe for reentry upon decontamination. Current sampling strategies targeting Bacillus anthracis spores prescribe vacuum-based methods for rough and/or porous surfaces. In this study, four commonly-used B. anthracis spore sampling devices (vacuum socks, 37 mm 0.8 µm MCE filter cassettes, 37 mm 0.3 µm PTFE filter cassettes, and 3MTM forensic filters) were comparatively evaluated for their ability to recover surface-associated spores. The vacuum sock device was evaluated at two sampling speeds (slow and fast), resulting in five total methods evaluated. Aerosolized spores (~105 cm-2) of a surrogate Bacillus species (Bacillus atrophaeus) were allowed to settle onto three material types (concrete, carpet, and upholstery). Ten replicate samples were collected using each vacuum method, from each of the three material types. In addition, stainless steel (i.e., nonporous) surfaces inoculated simultaneously were sampled with pre-moistened wipes. Recoveries from wipes of steel surfaces were utilized to verify the inoculum, and to normalize vacuum-based recoveries across trials. Recovery (CFU cm-2) and relative recovery (vacuum recovery/wipe recovery) were determined for each method and material type. Relative recoveries were compared by one-way and three-way ANOVA. Data analysis by one-

Recent H1N1 viruses (A/USSR/90/77, A/Fiji/15899/83, A/Firenze/13/83) replicate poorly in ferret bronchial epithelium. Brief report.

PubMed

Sweet, C; Bird, R A; Coates, D M; Overton, H A; Smith, H

1985-01-01

Three recent wild-type H1N1 influenza virus isolates (A/USSR/90/77, A/Fiji/15899/83 and A/Firenze/13/83) replicated poorly in organ cultures of ferret bronchial tissue compared with the replication of an H3N2 wild-type virus (A/England/939/69). All four viruses replicated well in nasal turbinate tissue. Examination of one H1N1 virus (A/USSR/90/77) in vivo showed heavy infection in the upper respiratory tract of ferrets but little in the lower respiratory tract. These results raise the possibility that the mildness of human influenza arising from the H1N1 strains may be due to lack of capacity to attack the lower respiratory tract as well as the presence of antibody in previously exposed persons.

The role of technical assistance in the replication of effective HIV interventions.

PubMed

O'Donnell, L; Scattergood, P; Adler, M; Doval, A S; Barker, M; Kelly, J A; Kegeles, S M; Rebchook, G M; Adams, J; Terry, M A; Neumann, M S

2000-01-01

This article examines the role of technical assistance (TA) in supporting the replication of proven HIV interventions. A case study of the replication of the VOICES/VOCES intervention elucidates the level and types of TA provided to support new users through the adoption process. TA included help in garnering administrative support, identifying target audiences, recruiting groups for sessions, maintaining fidelity to the intervention's core elements, tailoring the intervention to meet clients' needs, strengthening staff members' facilitation skills, troubleshooting challenges, and devising strategies to sustain the intervention. Two to four hours per month of TA were provided to each agency adopting the intervention, at an estimated monthly cost of $206 to $412. Findings illustrate how TA supports replication by establishing a conversation between the researcher TA providers experienced with the intervention and new users. This communication helps preserve key program elements and contributes to ongoing refinement of the intervention.

Palatability of a Novel Oral Formulation of Prednisone in Healthy Young Adults

PubMed Central

Bai, Shasha; Dormer, Nathan; Shoults, Catherine; Meyer, Amanda; Pierce, Carol D'Ann; Neville, Kathleen A.; Kearns, Gregory L.

2017-01-01

Objectives Prednisone is a widely used anti-inflammatory for a variety of conditions. While oral liquid formulations of prednisone enable weight-based dosing, children frequently find them to be objectionable due to bitter taste. This limitation of prednisone can adversely impact patient acceptance and may result in non-compliance. Efforts to mask flavors often result in poorly controlled, heterogeneous particle distributions and can provide ineffective taste masking. The present work utilized a novel drug delivery technology developed by Orbis Biosciences, Inc., to create an oral taste-masked formulation of prednisone. Methods The study examined the palatability of Orbis’ microsphere prednisone formulation in healthy young adults (n=24). Four test articles were used in the study including a reference formulation (Roxane Laboratories), a control, and the test formulation (Orbis) prepared in two different ways. Study participants were randomized in a crossover design. Key Findings Results indicated that the test prednisone formulation was indistinguishable from the control, and both were preferable to the reference formulation in every category of palatability assessed using a validated 9-point Hedonic Scale. The data also suggested that preparing the microsphere suspension immediately prior to administration results in the most ideal palatability properties. Conclusions In conclusion, the novel microsphere formulation technology was effective in taste-masking prednisone. PMID:28271493

The influence of modulation of P-glycoprotein and /or cytochrome P450 3A on the pharmacokinetics and pharmacodynamics of orally administered morphine in dogs.

PubMed

Gadeyne, C; Van der Heyden, S; Gasthuys, F; Croubels, S; Schauvliege, S; Polis, I

2011-10-01

The influence of pretreatment with ketoconazole [cytochrome P450 3A (CYP3A) + P-glycoprotein (P-gp) inhibitor], elacridar (selective P-gp inhibitor) and rifampicin (CYP3A + P-gp inducer) on oral morphine pharmacokinetics and pharmacodynamics was investigated in experimental dogs. Seven beagles were used in a four-way crossover design. Morphine hydrochloride was administered orally (2.5 mg/kg) alone (control group CON) or after pretreatment with ketoconazole (group KETO), elacridar (group ELA) or rifampicin (group RIF). Morphine plasma concentrations were analysed by liquid chromatography-tandem mass spectrometry. Sedation scores (none, mild, moderate or severe) were evaluated subjectively. Dogs were significantly (P < 0.05) more sedated after ketoconazole pretreatment. There were no significant differences between group CON and the other pretreatment groups in pharmacokinetic parameters taking both sexes into account. Sex differences were apparent in some pharmacokinetic parameters of morphine. The area under the plasma concentration time curve (AUC(0-∞) ) was significantly higher, and the total body clearance was significantly lower in male compared to female dogs in all treatment groups. Ketoconazole, rifampicin and elacridar pretreatment had no significant effects on morphine pharmacokinetics, although dogs in the ketoconazole group showed higher sedation scores. © 2011 Blackwell Publishing Ltd.

Effects of fexofenadine and hydroxyzine on brake reaction time during car-driving with cellular phone use.

PubMed

Tashiro, Manabu; Horikawa, Etsuo; Mochizuki, Hideki; Sakurada, Yumiko; Kato, Motohisa; Inokuchi, Takatoshi; Ridout, Fran; Hindmarch, Ian; Yanai, Kazuhiko

2005-10-01

Antihistamines are a mainstay treatment for allergic rhinitis; however, many older agents cause adverse events, including sedation and central nervous system (CNS) impairment. Research has shown sedating effects of antihistamines on driving; currently, no known study has examined whether cellular phone usage while driving further compounds impairment in individuals administered antihistamines. The aim of this study was to examine this endpoint. In a randomized, double-blind, placebo-controlled, three-way crossover study, healthy volunteers received fexofenadine HCl 120 mg, hydroxyzine HCl 30 mg and placebo. Brake reaction time (BRT) was used to examine driving performance across four conditions: driving only; driving while completing simple calculations; complex calculations; and conversing on a cellular phone. Subjective sedation assessments were also conducted. Brake reaction time with and without cellular phone usage in fexofenadine-treated subjects did not differ significantly from placebo in any condition. In contrast, hydroxyzine-treated subjects were significantly more sedated and had slower BRTs, suggesting slower hazard recognition and brake application, compared with the fexofenadine and placebo groups in all conditions. Importantly, cellular phone operation was an additive factor, increasing BRTs in hydroxyzine-treated volunteers. Fexofenadine did not impair CNS function in subjects involved in a divided attention task of driving and cellular phone operation. Copyright (c) 2005 John Wiley & Sons, Ltd.

Acute and subchronic effects of bilastine (20 and 40 mg) and hydroxyzine (50 mg) on actual driving performance in healthy volunteers.

PubMed

Conen, Silke; Theunissen, Eef L; Van Oers, Anita C M; Valiente, Román; Ramaekers, Johannes G

2011-11-01

Bilastine is a new second-generation H1 antagonist. Although bilastine has been demonstrated to produce little or no performance impairment in laboratory tests, it cannot be excluded that it produces impairments in real-life performance such as driving. This study aims to assess the effects of two doses of bilastine (20 and 40 mg) on actual driving after single and repeated administration. Hydroxyzine 50 mg was included as an active control. Twenty-two participants (11 females, 11 males) were tested in a placebo-controlled, randomized, double-blind, four-way cross-over design. Participants were treated with once-daily doses for eight consecutive days. On day 1 and 8 of each treatment period participants performed an actual highway driving test. The primary variable was standard deviation of lateral position (SDLP), a measure of weaving. Results demonstrated that hydroxyzine significantly increased SDLP on days 1 and 8 of treatment. Bilastine did not affect SDLP. It is concluded that hydroxyzine produces severe driving impairment after single doses and that this impairment only partly mitigates over time due to a lack of complete tolerance. Bilastine did not produce any driving impairment after single and repeated doses and can be safely used in traffic in doses up to 40 mg.

Effects of the Red Bull energy drink on cognitive function and mood in healthy young volunteers.

PubMed

Wesnes, Keith A; Brooker, Helen; Watson, Anthony W; Bal, Wendy; Okello, Edward

2017-02-01

The present study compared the cognitive and mood effects of two commercially available products, Red Bull energy drink 250 mL and Red Bull Sugarfree energy drink 250 mL, together with a matching placebo 250 mL. Twenty-four healthy young volunteers took part in a randomised, placebo controlled, double-blind, three-way cross-over study. Cognitive function was assessed using an integrated set of nine computerised tests of attention, working and episodic memory. On each study day the volunteers received a standardised breakfast prior to completing a baseline performance on cognitive tests and mood scales, followed by the consumption of the study drink. The cognitive tests and scales were then re-administered at 30, 60 and 90 min post-dose. Red Bull was found to produce significant improvements over both the Sugarfree version and the placebo drink on two composite scores from the six working and episodic memory tests; one combining the 12 accuracy measures from the six tasks and the other the average speed of correct responses from the working memory and episodic recognition memory tasks. These improvements were in the range of a medium effect size, which reflects a substantial enhancement to memory in young volunteers.

The effect of breed and sex on sulfamethazine, enrofloxacin, fenbendazole and flunixin meglumine pharmacokinetic parameters in swine.

PubMed

Howard, J T; Baynes, R E; Brooks, J D; Yeatts, J L; Bellis, B; Ashwell, M S; Routh, P; O'Nan, A T; Maltecca, C

2014-12-01

Drug use in livestock has received increased attention due to welfare concerns and food safety. Characterizing heterogeneity in the way swine populations respond to drugs could allow for group-specific dose or drug recommendations. Our objective was to determine whether drug clearance differs across genetic backgrounds and sex for sulfamethazine, enrofloxacin, fenbendazole and flunixin meglumine. Two sires from each of four breeds were mated to a common sow population. The nursery pigs generated (n = 114) were utilized in a random crossover design. Drugs were administered intravenously and blood collected a minimum of 10 times over 48 h. A non-compartmental analysis of drug and metabolite plasma concentration vs. time profiles was performed. Within-drug and metabolite analysis of pharmacokinetic parameters included fixed effects of drug administration date, sex and breed of sire. Breed differences existed for flunixin meglumine (P-value<0.05; Cl, Vdss ) and oxfendazole (P-value<0.05, AUC0→∞ ). Sex differences existed for oxfendazole (P-value < 0.05; Tmax ) and sulfamethazine (P-value < 0.05, Cl). Differences in drug clearance were seen, and future work will determine the degree of additive genetic variation utilizing a larger population. © 2014 John Wiley & Sons Ltd.

Acute neuropsychological effects of MDMA and ethanol (co-)administration in healthy volunteers.

PubMed

Dumont, G J H; Wezenberg, E; Valkenberg, M M G J; de Jong, C A J; Buitelaar, J K; van Gerven, J M A; Verkes, R J

2008-04-01

In Western societies, a considerable percentage of young people expose themselves to 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy"). Commonly, ecstasy is used in combination with other substances, in particular alcohol (ethanol). MDMA induces both arousing as well as hallucinogenic effects, whereas ethanol is a general central nervous system depressant. The aim of the present study is to assess the acute effects of single and co-administration of MDMA and ethanol on executive, memory, psychomotor, visuomotor, visuospatial and attention function, as well as on subjective experience. We performed a four-way, double-blind, randomised, crossover, placebo-controlled study in 16 healthy volunteers (nine male, seven female) between the ages of 18-29. MDMA was given orally (100 mg) and blood alcohol concentration was maintained at 0.6 per thousand by an ethanol infusion regime. Co-administration of MDMA and ethanol was well tolerated and did not show greater impairment of performance compared to the single-drug conditions. Impaired memory function was consistently observed after all drug conditions, whereas impairment of psychomotor function and attention was less consistent across drug conditions. Co-administration of MDMA and ethanol did not exacerbate the effects of either drug alone. Although the impairment of performance by all drug conditions was relatively moderate, all induced significant impairment of cognitive function.

Glucose response to exercise in the post-prandial period is independent of exercise intensity.

PubMed

Shambrook, P; Kingsley, M I; Wundersitz, D W; Xanthos, P D; Wyckelsma, V L; Gordon, B A

2018-03-01

This study investigated the acute glucose response to low-intensity, moderate-intensity, and high-intensity interval exercise compared to no-exercise in healthy insufficiently active males using a four-arm, randomized, crossover design. Ten males (age: 37.3 ± 7.3 years, BMI: 29.3 ± 6.5 kg·m -2 ) completed four 30-minute interventions at weekly intervals comprising low-intensity exercise (LIE) at ~35% V˙O 2 R, moderate-intensity exercise (MIE) at ~50% V˙O 2 R, high-intensity interval exercise (HIIE) at ~80% V˙O 2 R, and a no-exercise control. Participants performed cycle ergometer exercise 30 minutes after finishing breakfast. Glucose response was assessed using a continuous glucose monitor under free-living conditions with dietary intake replicated. A significant effect for intensity on energy expenditure was identified (P < .001) with similar energy cost in MIE (mean ± SD: 869 ± 148 kJ) and HIIE (806 ± 145 kJ), which were both greater than LIE (633 ± 129 kJ). The pattern of glucose response between the interventions over time was different (P = .02). Glucose was lower 25 minutes into each of the HIIE, MIE and LIE trials respectively (mean difference ± SD: -0.7 ± 1.1; -0.9 ± 1.1; -0.6 ± 0.9 mmol·L -1 ; P < .05) than in the no-exercise trial. Glucose response was not different between exercise intensities (P > .05). Twenty-four-hour AUC was not affected by exercise intensity (P = .75). There was a significant effect for exercise enjoyment (P = .02), with LIE (69 ± 4) preferred less than HIIE (mean ± SD: 84 ± 14; P = .02), MIE (73 ± 5; P = .03), and no-exercise (75 ± 4; P = .03). Exercise at any intensity 30 minutes after a meal affects glycemic regulation equally in insufficiently active males. Moderate to vigorous exercise intensities were preferred, and therefore, the exercise guidelines appear appropriate for the prevention of cardiometabolic disease. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Rhombic-Shaped Nanostructures and Mechanical Properties of 2D DNA Origami Constructed with Different Crossover/Nick Designs.

PubMed

Ma, Zhipeng; Huang, Yunfei; Park, Seongsu; Kawai, Kentaro; Kim, Do-Nyun; Hirai, Yoshikazu; Tsuchiya, Toshiyuki; Yamada, Hirofumi; Tabata, Osamu

2018-01-01

DNA origami methods enable the fabrication of various nanostructures and nanodevices, but their effective use depends on an understanding of their structural and mechanical properties and the effects of basic structural features. Frequency-modulation atomic force microscopy is introduced to directly characterize, in aqueous solution, the crossover regions of sets of 2D DNA origami based on different crossover/nick designs. Rhombic-shaped nanostructures formed under the influence of flexible crossovers placed between DNA helices are observed in DNA origami incorporating crossovers every 3, 4, or 6 DNA turns. The bending rigidity of crossovers is determined to be only one-third of that of the DNA helix, based on interhelical electrostatic forces reported elsewhere, and the measured pitches of the 3-turn crossover design rhombic-shaped nanostructures undergoing negligible bending. To evaluate the robustness of their structural integrity, they are intentionally and simultaneously stressed using force-controlled atomic force microscopy. DNA crossovers are verified to have a stabilizing effect on the structural robustness, while the nicks have an opposite effect. The structural and mechanical properties of DNA origami and the effects of crossovers and nicks revealed in this paper can provide information essential for the design of versatile DNA origami structures that exhibit specified and desirable properties. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Restrictions to cross species transmission of lentiviral infection gleaned from studies of FIV

PubMed Central

Troyer, Jennifer; Poss, Mary

2009-01-01

More than 40 species of primates and over 20 species of cats harbor antibodies that sero-react to lentiviral antigens. In nearly all cases where viral genetic analysis has been conducted, each host species is infected with a unique lentivirus. Though lentivirus clades within a species can be substantially divergent, they are typically monophyletic within that species. A notable significant departure from this observation is apparent cross-species transmission of FIV between bobcats (Lynx rufus) and pumas (Puma concolor) in southern California that has occurred at least three times; evidence from one bobcat sequence suggests this cross-over may have also occurred in Florida between bobcats and the endangered Florida panther. Several other isolated reports demonstrate cross-species transmission of FIV isolates among captive animals housed in close proximity, and it is well established that HIV-1 and HIV-2 arose from human contact with SIV-infected nonhuman primates. Using an experimental model, we have determined that domestic cats (Felis catus) are susceptible to FIVs originating from pumas or lions. While infections are initially replicative, and animals seroconvert, within a relatively short period of time circulating virus is reduced to nearly undetectable levels in a majority of animals. This diminution of viral load is proportional to initial viral peak. Although viral reservoirs can be identified in gastrointestinal tissues, most viral genomes recovered peripherally are highly mutated, suggesting that the non-adapted host successfully inhibits normal viral replication, leading to replication incompetent viral progeny. Mechanisms possible for such restriction of cross-species infections in natural settings include: 1. Lack of contact conducive to lentiviral transmission between infected and shedding animals of different species; 2. Lack of suitable receptor repertoire to allow viral entry to susceptible cells of a new species; 3. Cellular machinery in the new host sufficiently divergent from the primary host to support viral replication (ie passive unfacilitated viral replication); 4. Intracellular restriction mechanisms present in the new host that is able to limit viral replication (i.e. active interrupted viral replication. These include factors that limit uncoating, replication, packaging, and virion release); 5. Unique ability of new host to raise sterilizing adaptive immunity, resulting in aborted infection and inability to spread infections among con-specifics; or, 6. Production of defective or non-infectious viral progeny that lack cellular cofactors to render them infectious to conspecifics (i.e. particles lacking appropriate cellular components in viral Env to render them infectious to other animals of the same species). Data to support or refute the relative importance of each of these possibilities is described in this review. Insights based on our in vivo cross-species model suggest intracellular restriction mechanisms effectively inhibit rapid inter-specific transmission of lentiviruses. Further, limited contact both within and between species in natural populations is highly relevant to limiting the opportunity for spread of FIV strains. Studies of naturally-occurring SIV and innate host restriction systems suggest these same two mechanisms are significant factors inhibiting widespread cross-species transmission of lentiviruses among primate species as well. PMID:19896218

Hospice use among nursing home and non-nursing home patients.

PubMed

Unroe, Kathleen T; Sachs, Greg A; Dennis, M E; Hickman, Susan E; Stump, Timothy E; Tu, Wanzhu; Callahan, Christopher M

2015-02-01

For nursing home patients, hospice use and associated costs have grown dramatically. A better understanding of hospice in all care settings, especially how patients move across settings, is needed to inform debates about appropriateness of use and potential policy reform. Our aim was to describe characteristics and utilization of hospice among nursing home and non-nursing home patients. Medicare, Medicaid and Minimum Data Set data, 1999-2008, were merged for 3,771 hospice patients aged 65 years and above from a safety net health system. Patients were classified into four groups who received hospice: 1) only in nursing homes; 2) outside of nursing homes; 3) crossover patients utilizing hospice in both settings; and 4) "near-transition" patients who received hospice within 30 days of a nursing home stay. Differences in demographics, hospice diagnoses and length of stay, utilization and costs are presented with descriptive statistics. Nursing home hospice patients were older, and more likely to be women and to have dementia (p < 0.0001). Nearly one-third (32.3 %) of crossover patients had hospice stays > 6 months, compared with the other groups (16 % of nursing home hospice only, 10.7 % of non-nursing home hospice and 7.6 % of those with near transitions) (p < 0.0001). Overall, 27.7 % of patients had a hospice stay <1 week, but there were marked differences between groups-48 % of near-transition patients vs. 7.4 % of crossover patients had these short hospice stays (p < 0.0001). Crossover and near-transition hospice patients had higher costs to Medicare compared to other groups (p < 0.05). Dichotomizing hospice users only into nursing home vs. non-nursing home patients is difficult, due to transitions across settings. Hospice patients with transitions accrue higher costs. The impact of changes to the hospice benefit on patients who live or move through nursing homes near the end of life should be carefully considered.

The risk of acute liver injury among users of antibiotic medications: a comparison of case-only studies.

PubMed

Brauer, Ruth; Ruigómez, Ana; Klungel, Olaf; Reynolds, Robert; Feudjo Tepie, Maurille; Smeeth, Liam; Douglas, Ian

2016-03-01

The aims of this study were two-fold: (i) to investigate the effect of exposure to antibiotic agents on the risk of acute liver injury using a self-controlled case series and case-crossover study and (ii) to compare the results between the case-only studies. For the self-controlled case series study relative incidence ratios (IRR) were calculated by dividing the rate of acute liver injury experienced during patients' periods of exposure to antibiotics to patients' rate of events during non-exposed time using conditional Poisson regression. For the case-crossover analysis we calculated Odds Ratios (OR) using conditional logistic regression by comparing exposure during 14- and 30-day risk windows with exposure during control moments. Using the self-controlled case series approach, the IRR was highest during the first 7 days after receipt of a prescription (10.01, 95% CI 6.59-15.18). Omitting post-exposure washout periods lowered the IRR to 7.2. The highest estimate in the case-crossover analysis was found when two 30-day control periods 1 year prior to the 30-day ALI risk period were retained in the analysis: OR = 6.5 (95% CI, 3.95-10.71). The lowest estimate was found when exposure in the 14-day risk period was compared to exposure in four consecutive 14-day control periods immediately prior to the risk period (OR = 3.05, 95% CI, 2.06-4.53). An increased relative risk of acute liver injury was consistently observed using both self-controlled case series and case-crossover designs. Case-only designs can be used as a viable alternative study design to study the risk of acute liver injury, albeit with some limitations. © 2015 The Authors Pharmacoepidemiology and Drug Safety Published by John Wiley & Sons Ltd.

Inhaled concentrated ambient particles are associated with hematologic and bronchoalveolar lavage changes in canines.

PubMed Central

Clarke, R W; Coull, B; Reinisch, U; Catalano, P; Killingsworth, C R; Koutrakis, P; Kavouras, I; Murthy, G G; Lawrence, J; Lovett, E; Wolfson, J M; Verrier, R L; Godleski, J J

2000-01-01

Pulmonary inflammatory and hematologic responses of canines were studied after exposure to concentrated ambient particles (CAPs) using the Harvard ambient particle concentrator (HAPC). For pulmonary inflammatory studies, normal dogs were exposed in pairs to either CAPs or filtered air (paired studies) for 6 hr/day on 3 consecutive days. For hematologic studies, dogs were exposed for 6 hr/day for 3 consecutive days with one receiving CAPs while the other was simultaneously exposed to filtered air; crossover of exposure took place the following week (crossover studies). Physicochemical characterization of CAPs exposure samples included measurements of particle mass, size distribution, and composition. No statistical differences in biologic responses were found when all CAPs and all sham exposures were compared. However, the variability in biologic response was considerably higher with CAPs exposure. Subsequent exploratory graphical analyses and mixed linear regression analyses suggested associations between CAPs constituents and biologic responses. Factor analysis was applied to the compositional data from paired and crossover experiments to determine elements consistently associated with each other in CAPs samples. In paired experiments, four factors were identified; in crossover studies, a total of six factors were observed. Bronchoalveolar lavage (BAL) and hematologic data were regressed on the factor scores. Increased BAL neutrophil percentage, total peripheral white blood cell (WBC) counts, circulating neutrophils, and circulating lymphocytes were associated with increases in the aluminum/silicon factor. Increased circulating neutrophils and increased BAL macrophages were associated with the vanadium/nickel factor. Increased BAL neutrophils were associated with the bromine/lead factor when only the compositional data from the third day of CAPs exposure were used. Significant decreases in red blood cell counts and hemoglobin levels were correlated with the sulfur factor. BAL or hematologic parameters were not associated with increases in total CAPs mass concentration. These data suggest that CAPs inhalation is associated with subtle alterations in pulmonary and systemic cell profiles, and specific components of CAPs may be responsible for these biologic responses. PMID:11133399

49 CFR 213.353 - Turnouts, crossovers, and lift rail assemblies or other transition devices on moveable bridges.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Turnouts, crossovers, and lift rail assemblies or... SAFETY STANDARDS Train Operations at Track Classes 6 and Higher § 213.353 Turnouts, crossovers, and lift... shall be at least 11/2 inches wide. (d) For all turnouts and crossovers, and lift rail assemblies or...

49 CFR 213.353 - Turnouts, crossovers, and lift rail assemblies or other transition devices on moveable bridges.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Turnouts, crossovers, and lift rail assemblies or... SAFETY STANDARDS Train Operations at Track Classes 6 and Higher § 213.353 Turnouts, crossovers, and lift... shall be at least 11/2 inches wide. (d) For all turnouts and crossovers, and lift rail assemblies or...

How Crossover Speeds up Building Block Assembly in Genetic Algorithms.

PubMed

Sudholt, Dirk

2017-01-01

We reinvestigate a fundamental question: How effective is crossover in genetic algorithms in combining building blocks of good solutions? Although this has been discussed controversially for decades, we are still lacking a rigorous and intuitive answer. We provide such answers for royal road functions and OneMax, where every bit is a building block. For the latter, we show that using crossover makes every ([Formula: see text]+[Formula: see text]) genetic algorithm at least twice as fast as the fastest evolutionary algorithm using only standard bit mutation, up to small-order terms and for moderate [Formula: see text] and [Formula: see text]. Crossover is beneficial because it can capitalize on mutations that have both beneficial and disruptive effects on building blocks: crossover is able to repair the disruptive effects of mutation in later generations. Compared to mutation-based evolutionary algorithms, this makes multibit mutations more useful. Introducing crossover changes the optimal mutation rate on OneMax from [Formula: see text] to [Formula: see text]. This holds both for uniform crossover and k-point crossover. Experiments and statistical tests confirm that our findings apply to a broad class of building block functions.

Transcription and Recombination: When RNA Meets DNA

PubMed Central

Aguilera, Andrés; Gaillard, Hélène

2014-01-01

A particularly relevant phenomenon in cell physiology and proliferation is the fact that spontaneous mitotic recombination is strongly enhanced by transcription. The most accepted view is that transcription increases the occurrence of double-strand breaks and/or single-stranded DNA gaps that are repaired by recombination. Most breaks would arise as a consequence of the impact that transcription has on replication fork progression, provoking its stalling and/or breakage. Here, we discuss the mechanisms responsible for the cross talk between transcription and recombination, with emphasis on (1) the transcription–replication conflicts as the main source of recombinogenic DNA breaks, and (2) the formation of cotranscriptional R-loops as a major cause of such breaks. The new emerging questions and perspectives are discussed on the basis of the interference between transcription and replication, as well as the way RNA influences genome dynamics. PMID:25085910

The cost of copy number in a selfish genetic element: the 2-μm plasmid of Saccharomyces cerevisiae.

PubMed

Harrison, Ellie; Koufopanou, V; Burt, A; MacLean, R C

2012-11-01

Many autonomously replicating genetic elements exist as multiple copies within the cell. The copy number of these elements is often assumed to have important fitness consequences for both element and host, yet the forces shaping its evolution are not well understood. The 2 μm is a multicopy plasmid of Saccharomyces yeasts, encoding just four genes that are solely involved in plasmid replication. One simple model for the fitness relationship between yeasts and 2 μm is that plasmid copy number evolves as a trade-off between selection for increased vertical transmission, favouring high copy number, and selection for decreased virulence, favouring low copy number. To test this model, we experimentally manipulated the copy number of the plasmid and directly measured the fitness cost, in terms of growth rate reduction, associated with high plasmid copy number. We find that the fitness burden imposed by the 2 μm increases with plasmid copy number, such that each copy imposes a fitness burden of 0.17% (± 0.008%), greatly exceeding the cost expected for it to be stably maintained in yeast populations. Our results demonstrate the crucial importance of copy number in the evolution of yeast per 2 μm associations and pave the way for future studies examining how selection can shape the cost of multicopy elements. © 2012 The Authors. Journal of Evolutionary Biology © 2012 European Society For Evolutionary Biology.

The kinetochore prevents centromere-proximal crossover recombination during meiosis

PubMed Central

Vincenten, Nadine; Kuhl, Lisa-Marie; Lam, Isabel; Oke, Ashwini; Kerr, Alastair RW; Hochwagen, Andreas; Fung, Jennifer; Keeney, Scott; Vader, Gerben; Marston, Adèle L

2015-01-01

During meiosis, crossover recombination is essential to link homologous chromosomes and drive faithful chromosome segregation. Crossover recombination is non-random across the genome, and centromere-proximal crossovers are associated with an increased risk of aneuploidy, including Trisomy 21 in humans. Here, we identify the conserved Ctf19/CCAN kinetochore sub-complex as a major factor that minimizes potentially deleterious centromere-proximal crossovers in budding yeast. We uncover multi-layered suppression of pericentromeric recombination by the Ctf19 complex, operating across distinct chromosomal distances. The Ctf19 complex prevents meiotic DNA break formation, the initiating event of recombination, proximal to the centromere. The Ctf19 complex independently drives the enrichment of cohesin throughout the broader pericentromere to suppress crossovers, but not DNA breaks. This non-canonical role of the kinetochore in defining a chromosome domain that is refractory to crossovers adds a new layer of functionality by which the kinetochore prevents the incidence of chromosome segregation errors that generate aneuploid gametes. DOI: http://dx.doi.org/10.7554/eLife.10850.001 PMID:26653857

Magnetization reversal dynamics in Co nanowires with competing magnetic anisotropies

NASA Astrophysics Data System (ADS)

Pal, Semanti; Saha, Susmita; Polley, Debanjan; Barman, Anjan

2011-12-01

We present the magnetization reversal dynamics of Co nanowires with competing magnetic anisotropies. The aspect ratio ( R) of the nanowires is varied between 2.5 and 60, and we observe a cross-over of the directions of the magnetic easy and hard axes at R=6.8. Micromagnetic simulations qualitatively reproduce the observed cross-over and give detailed insight into the reversal mechanisms associated with the cross-over. The reversal mechanism for a field applied along the long axis of the nanowire exhibits a quasi-coherent rotation mode and a corkscrew-like mode, respectively, above and below the cross-over, with the formation of a Bloch domain near the cross-over region. For a field applied along the short axis, the reversal occurs by nucleation and propagation of reversed domains from the two ends of the nanowires for very high values of the aspect ratio down to the cross-over region, but it transforms into quasi-coherent rotation mode for smaller aspect ratios (below the cross-over region).

Factors affecting in-hospital heat-related mortality: a multi-city case-crossover analysis.

PubMed

Stafoggia, M; Forastiere, F; Agostini, D; Caranci, N; de'Donato, F; Demaria, M; Michelozzi, P; Miglio, R; Rognoni, M; Russo, A; Perucci, C A

2008-03-01

Several studies have identified strong effects of high temperatures on mortality at population level; however, individual vulnerability factors associated with heat-related in-hospital mortality are largely unknown. The objective of the study was to evaluate heat-related in-hospital mortality using a multi-city case-crossover analysis. We studied residents of four Italian cities, aged 65+ years, who died during 1997-2004. For 94,944 individuals who died in hospital and were hospitalised two or more days before death, demographics, chronic conditions, primary diagnoses of last event and hospital wards were considered. A city-specific case-crossover analysis was performed to evaluate the association between apparent temperature and mortality. Pooled odds ratios (OR) of dying on a day with a temperature of 30 degrees C compared to a day with a temperature of 20 degrees C were estimated with a random-effects meta-analysis. We estimated an overall OR of 1.32 (95% confidence interval: 1.25, 1.39). Age, marital status and hospital ward were important risk indicators. Patients in general medicine were at higher risk than those in high and intensive care units. A history of psychiatric disorders and cerebrovascular diseases gave a higher vulnerability. Mortality was greater among patients hospitalised for heart failure, stroke and chronic pulmonary diseases. In-hospital mortality is strongly associated with high temperatures. A comfortable temperature in hospitals and increased attention to vulnerable patients during heatwaves, especially in general medicine, are necessary preventive measures.

Making Friends With Yourself: A Mixed Methods Pilot Study of a Mindful Self-Compassion Program for Adolescents

PubMed Central

Bluth, Karen; Gaylord, Susan A.; Campo, Rebecca A.; Mullarkey, Michael C.; Hobbs, Lorraine

2015-01-01

The aims of this mixed-method pilot study were to determine the feasibility, acceptability, and preliminary psychosocial outcomes of “Making Friends with Yourself: A Mindful Self-Compassion Program for Teens” (MFY), an adaptation of the adult Mindful Self-Compassion program. Thirty-four students age 14–17 enrolled in this waitlist controlled crossover study. Participants were randomized to either the waitlist or intervention group and administered online surveys at baseline, after the first cohort participated in the intervention, and after the waitlist crossovers participated in the intervention. Attendance and retention data were collected to determine feasibility, and audiorecordings of the 6-week class were analyzed to determine acceptability of the program. Findings indicated that MFY is a feasible and acceptable program for adolescents. Compared to the waitlist control, the intervention group had significantly greater self-compassion and life satisfaction and significantly lower depression than the waitlist control, with trends for greater mindfulness, greater social connectedness and lower anxiety. When waitlist crossovers results were combined with that of the first intervention group, findings indicated significantly greater mindfulness and self-compassion, and significantly less anxiety, depression, perceived stress and negative affect post-intervention. Additionally, regression results demonstrated that self-compassion and mindfulness predicted decreases in anxiety, depression, perceived stress, and increases in life satisfaction post-intervention. MFY shows promise as a program to increase psychosocial wellbeing in adolescents through increasing mindfulness and self-compassion. Further testing is needed to substantiate the findings. PMID:27110301

Regulation of human retinal blood flow by endothelin-1.

PubMed

Polak, Kaija; Luksch, Alexandra; Frank, Barbara; Jandrasits, Kerstin; Polska, Elzbieta; Schmetterer, Leopold

2003-05-01

There is evidence from in vitro and animal studies that endothelin is a major regulator of retinal blood flow. We set out to characterize the role of the endothelin-system in the blood flow control of the human retina. Two studies in healthy subjects were performed. The study design was randomized, placebo-controlled, double-masked, balanced, two-way crossover in protocol A and three way-way crossover in protocol B. In protocol A 18 healthy male subjects received intravenous endothelin-1 (ET-1) in a dose of 2.5 ng kg (-1)min(-1) for 30 min or placebo on two different study days and retinal vessel diameters were measured. In protocol B 12 healthy male subjects received ET-1 in stepwise increasing doses of 0, 1.25, 2.5 and 5 ng kg (-1)min(-1) (each infusion step over 20 min) in co-infusion with the specific ET(A)-receptor antagonist BQ123 (60 microg min (-1)) or placebo or BQ123 alone investigating retinal vessel diameters, retinal blood velocity and retinal blood flow. Measurements of retinal vessel size were done with the Zeiss retinal vessel analyzer. Measurements of blood velocities were done with bi-directional laser Doppler velocimetry. From these measurements retinal blood flow was calculated. In protocol A exogenous ET-1 tended to decrease retinal arterial diameter, but this effect was not significant versus placebo. No effect on retinal venous diameter was seen. In protocol B retinal venous blood velocity and retinal blood flow was significantly reduced after administration of exogenous ET-1. These effects were significantly blunted when BQ-123 was co-administered. By contrast, BQ-123 alone had no effect on retinal hemodynamic parameters. Concluding, BQ123 antagonizes the effects of exogenously administered ET-1 on retinal blood flow in healthy subjects. In addition, the results of the present study are compatible with the hypothesis that ET-1 exerts its vasoconstrictor effects in the retina mainly on the microvessels.

Levothyroxine soft capsules demonstrate bioequivalent pharmacokinetic exposure with the European reference tablets in healthy volunteers under fasting conditions.

PubMed

Al-Numani, Dina; Scarsi, Claudia; Ducharme, Murray P

2016-02-01

To assess the bioequivalence (BE) potential under fasting conditions between levothyroxine soft capsules and the European reference tablet formulation. Two studies were conducted to assess the BE potential as per European regulations. Study 1 was a two-way crossover BE study comparing a high strength of levothyroxine soft capsules versus levothyroxine tablets (200 μg), while study 2 was a three-way crossover dosage form proportionality study between low, medium, and high strengths of soft capsules. 70 healthy adult subjects participated in the two studies. Each treatment consisted of a 600-μg dose of levothyroxine sodium, administered under fasting conditions. Blood samples were collected for levothyroxine (T4) assay prior to dosing and up to 72 hours post dose. A washout of 35 days separated treatments in each study. Pharmacokinetics was assessed using noncompartmental methods. A total of 61 subjects completed the studies. Baseline-adjusted total T4 ratios (test/reference) and 90% confidence intervals (CIs) between soft capsules and tablets were within 80.00 - 125.00%. Comparison of the three strengths of soft capsules indicated pharmacokinetic equivalence between them (ratios and 90% CIs were contained within 80.00 - 125.00%). Overall, levothyroxine sodium was well tolerated with all products when given as single oral doses of 600 μg, except for 1 serious adverse event of secondary bacteremia reported in study 2, deemed not to be related to treatment. Levothyroxine soft capsules meet BE criteria in terms of systemic exposure when compared to a European reference tablet under fasting conditions in healthy volunteers.

Stepped wedge designs: insights from a design of experiments perspective.

PubMed

Matthews, J N S; Forbes, A B

2017-10-30

Stepped wedge designs (SWDs) have received considerable attention recently, as they are potentially a useful way to assess new treatments in areas such as health services implementation. Because allocation is usually by cluster, SWDs are often viewed as a form of cluster-randomized trial. However, since the treatment within a cluster changes during the course of the study, they can also be viewed as a form of crossover design. This article explores SWDs from the perspective of crossover trials and designed experiments more generally. We show that the treatment effect estimator in a linear mixed effects model can be decomposed into a weighted mean of the estimators obtained from (1) regarding an SWD as a conventional row-column design and (2) a so-called vertical analysis, which is a row-column design with row effects omitted. This provides a precise representation of "horizontal" and "vertical" comparisons, respectively, which to date have appeared without formal description in the literature. This decomposition displays a sometimes surprising way the analysis corrects for the partial confounding between time and treatment effects. The approach also permits the quantification of the loss of efficiency caused by mis-specifying the correlation parameter in the mixed-effects model. Optimal extensions of the vertical analysis are obtained, and these are shown to be highly inefficient for values of the within-cluster dependence that are likely to be encountered in practice. Some recently described extensions to the classic SWD incorporating multiple treatments are also compared using the experimental design framework. Copyright © 2017 John Wiley & Sons, Ltd.

Preventing gastric sieving by blending a solid/water meal enhances satiation in healthy humans.

PubMed

Marciani, Luca; Hall, Nicholas; Pritchard, Susan E; Cox, Eleanor F; Totman, John J; Lad, Mita; Hoad, Caroline L; Foster, Tim J; Gowland, Penny A; Spiller, Robin C

2012-07-01

Separation of solids and liquids within the stomach allows faster gastric emptying of liquids compared with solids, a phenomenon known as sieving. We tested the hypothesis that blending a solid and water meal would abolish sieving, preventing the early rapid decrease in gastric volume and thereby enhancing satiety. We carried out 2 separate studies. Study 1 was a 2-way, crossover, satiety study of 22 healthy volunteers who consumed roasted chicken and vegetables with a glass of water (1008 kJ) or the same blended to a soup. They completed satiety visual analogue scales at intervals for 3 h. Study 2 was a 2-way, crossover, mechanistic study of 18 volunteers who consumed the same meals and underwent an MRI to assess gastric emptying, gallbladder contraction, and small bowel water content (SBWC) at intervals for 3 h. In Study 1, the soup meal was associated with reduced hunger (P = 0.02). In Study 2, the volume of the gastric contents after the soup meal decreased more slowly than after the solid/liquid meal (P = 0.0003). The soup meal caused greater gallbladder contraction (P < 0.04). SBWC showed a biphasic response with an initial "gastric" phase during which SBWC was greater when the solid/liquid meal was consumed (P < 0.001) and a later "small bowel" phase when SBWC was greater when the soup meal was consumed (P < 0.01). Blending the solid/liquid meal to a soup delayed gastric emptying and increased the hormonal response to feeding, which may contribute to enhanced postprandial satiety.

Relationship between the acid-inhibitory effects of two proton pump inhibitors and CYP2C19 genotype in Japanese subjects: a randomized two-way crossover study.

PubMed

Furuta, K; Adachi, K; Ohara, S; Morita, T; Tanimura, T; Koshino, K; Kinoshita, Y

2010-01-01

This two-way crossover study investigated possible differences between the proton pump inhibitors, omeprazole and rabeprazole, in their effect on gastric acid secretion in Japanese subjects with differing cytochrome P450, family 2, subfamily C, polypeptide 19 (CYP2C19) genotypes. A total of 23 Helicobacter pylori-negative healthy volunteers received omeprazole 20 mg/day and rabeprazole 10 mg/day. Each drug treatment was given for a continuous 7-day period allocated in random order, with an interval of at least 1 week between drug treatment periods to allow for wash-out. Intragastric pH was measured on days 1 and 7. Overall median intragastric pH levels at 7 and 8 h after the first administration were significantly higher with omeprazole. There was no significant difference in intragastric pH in homozygous extensive metabolizers, whereas intragastric pH was significantly higher with omeprazole in combined data from heterozygous extensive metabolizers and poor metabolizers at 6, 7 and 8 h after the first drug administration. There were no significant differences in intragastric pH between omeprazole and rabeprazole irrespective of genotype on day 7 of administration. In conclusion, on day 1 the time to onset of the antisecretory action of 20 mg/day omeprazole was more rapid than that of 10 mg/day rabeprazole in Japanese individuals who have a higher incidence of the CYP2C19 poor metabolizer genotype, however by day 7 no difference in antisecretory effect was found, regardless of genotype.

Evaluation of a 12-Hour Sustained-Release Acetaminophen (Paracetamol) Formulation: A Randomized, 3-Way Crossover Pharmacokinetic and Safety Study in Healthy Volunteers.

PubMed

Yue, Yong; Collaku, Agron; Liu, Dongzhou J

2018-01-01

Acetaminophen (paracetamol) is a first-line treatment for mild and moderate pain. A twice-daily sustained-release (SR) formulation may be more convenient for chronic users than standard immediate-release (IR) acetaminophen. This randomized, 3-way crossover study evaluated pharmacokinetics and safety of single-dose 1500- and 2000-mg SR acetaminophen formulations and 2 doses of IR acetaminophen 1000 mg given 6 hours apart in healthy adults (n = 14). Primary outcome was time that plasma acetaminophen concentration was ≥4 μg/mL (T C≥4μg/mL ). Key secondary outcomes were area under the plasma concentration-time curve (AUC) from time 0 to time t, when plasma acetaminophen was detectable (AUC 0-t ), AUC from 0 to infinity (AUC 0-inf ), and maximum plasma acetaminophen concentration (C max ). T C≥4μg/mL from 2000-mg SR acetaminophen was similar to that from 2 doses of IR acetaminophen, whereas T C≥4μg/mL for 1500-mg SR acetaminophen was significantly shorter than that for IR acetaminophen (P = .004). The extent of acetaminophen absorption from 2000-mg SR and 2 doses of the IR formulation was similar and within bioequivalence limits with regard to AUC 0-12 , AUC 0-t , and AUC 0-inf . The extent of acetaminophen absorption from 1500-mg SR was significantly lower than that from IR acetaminophen. The 2000-mg SR represents a potential candidate formulation for 12-hour dosing with acetaminophen. © 2017, The American College of Clinical Pharmacology.

Recruitment of Mcm10 to Sites of Replication Initiation Requires Direct Binding to the Minichromosome Maintenance (MCM) Complex*

PubMed Central

Douglas, Max E.

2016-01-01

Mcm10 is required for the initiation of eukaryotic DNA replication and contributes in some unknown way to the activation of the Cdc45-MCM-GINS (CMG) helicase. How Mcm10 is localized to sites of replication initiation is unclear, as current models indicate that direct binding to minichromosome maintenance (MCM) plays a role, but the details and functional importance of this interaction have not been determined. Here, we show that purified Mcm10 can bind both DNA-bound double hexamers and soluble single hexamers of MCM. The binding of Mcm10 to MCM requires the Mcm10 C terminus. Moreover, the binding site for Mcm10 on MCM includes the Mcm2 and Mcm6 subunits and overlaps that for the loading factor Cdt1. Whether Mcm10 recruitment to replication origins depends on CMG helicase assembly has been unclear. We show that Mcm10 recruitment occurs via two modes: low affinity recruitment in the absence of CMG assembly (“G1-like”) and high affinity recruitment when CMG assembly takes place (“S-phase-like”). Mcm10 that cannot bind directly to MCM is defective in both modes of recruitment and is unable to support DNA replication. These findings indicate that Mcm10 is localized to replication initiation sites by directly binding MCM through the Mcm10 C terminus. PMID:26719337

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

PubMed

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

2016-01-01

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. 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"). 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%. 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. The differences in reliability between biological psychiatry, neurology and somatic diseases suggest that there is room for improvement, at least in some subdomains.

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

PubMed Central

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 between biological psychiatry, neurology and somatic diseases suggest that there is room for improvement, at least in some subdomains. PMID:27336301

DAMe: a toolkit for the initial processing of datasets with PCR replicates of double-tagged amplicons for DNA metabarcoding analyses.

PubMed

Zepeda-Mendoza, Marie Lisandra; Bohmann, Kristine; Carmona Baez, Aldo; Gilbert, M Thomas P

2016-05-03

DNA metabarcoding is an approach for identifying multiple taxa in an environmental sample using specific genetic loci and taxa-specific primers. When combined with high-throughput sequencing it enables the taxonomic characterization of large numbers of samples in a relatively time- and cost-efficient manner. One recent laboratory development is the addition of 5'-nucleotide tags to both primers producing double-tagged amplicons and the use of multiple PCR replicates to filter erroneous sequences. However, there is currently no available toolkit for the straightforward analysis of datasets produced in this way. We present DAMe, a toolkit for the processing of datasets generated by double-tagged amplicons from multiple PCR replicates derived from an unlimited number of samples. Specifically, DAMe can be used to (i) sort amplicons by tag combination, (ii) evaluate PCR replicates dissimilarity, and (iii) filter sequences derived from sequencing/PCR errors, chimeras, and contamination. This is attained by calculating the following parameters: (i) sequence content similarity between the PCR replicates from each sample, (ii) reproducibility of each unique sequence across the PCR replicates, and (iii) copy number of the unique sequences in each PCR replicate. We showcase the insights that can be obtained using DAMe prior to taxonomic assignment, by applying it to two real datasets that vary in their complexity regarding number of samples, sequencing libraries, PCR replicates, and used tag combinations. Finally, we use a third mock dataset to demonstrate the impact and importance of filtering the sequences with DAMe. DAMe allows the user-friendly manipulation of amplicons derived from multiple samples with PCR replicates built in a single or multiple sequencing libraries. It allows the user to: (i) collapse amplicons into unique sequences and sort them by tag combination while retaining the sample identifier and copy number information, (ii) identify sequences carrying unused tag combinations, (iii) evaluate the comparability of PCR replicates of the same sample, and (iv) filter tagged amplicons from a number of PCR replicates using parameters of minimum length, copy number, and reproducibility across the PCR replicates. This enables an efficient analysis of complex datasets, and ultimately increases the ease of handling datasets from large-scale studies.

Revealing Long-Range Interconnected Hubs in Human Chromatin Interaction Data Using Graph Theory

NASA Astrophysics Data System (ADS)

Boulos, R. E.; Arneodo, A.; Jensen, P.; Audit, B.

2013-09-01

We use graph theory to analyze chromatin interaction (Hi-C) data in the human genome. We show that a key functional feature of the genome—“master” replication origins—corresponds to DNA loci of maximal network centrality. These loci form a set of interconnected hubs both within chromosomes and between different chromosomes. Our results open the way to a fruitful use of graph theory concepts to decipher DNA structural organization in relation to genome functions such as replication and transcription. This quantitative information should prove useful to discriminate between possible polymer models of nuclear organization.

Ways of learning: Observational studies versus experiments

USGS Publications Warehouse

Shaffer, T.L.; Johnson, D.H.

2008-01-01

Manipulative experimentation that features random assignment of treatments, replication, and controls is an effective way to determine causal relationships. Wildlife ecologists, however, often must take a more passive approach to investigating causality. Their observational studies lack one or more of the 3 cornerstones of experimentation: controls, randomization, and replication. Although an observational study can be analyzed similarly to an experiment, one is less certain that the presumed treatment actually caused the observed response. Because the investigator does not actively manipulate the system, the chance that something other than the treatment caused the observed results is increased. We reviewed observational studies and contrasted them with experiments and, to a lesser extent, sample surveys. We identified features that distinguish each method of learning and illustrate or discuss some complications that may arise when analyzing results of observational studies. Findings from observational studies are prone to bias. Investigators can reduce the chance of reaching erroneous conclusions by formulating a priori hypotheses that can be pursued multiple ways and by evaluating the sensitivity of study conclusions to biases of various magnitudes. In the end, however, professional judgment that considers all available evidence is necessary to render a decision regarding causality based on observational studies.

DNA polymerases eta and kappa exchange with the polymerase delta holoenzyme to complete common fragile site synthesis.

PubMed

Barnes, Ryan P; Hile, Suzanne E; Lee, Marietta Y; Eckert, Kristin A

2017-09-01

Common fragile sites (CFSs) are inherently unstable genomic loci that are recurrently altered in human tumor cells. Despite their instability, CFS are ubiquitous throughout the human genome and associated with large tumor suppressor genes or oncogenes. CFSs are enriched with repetitive DNA sequences, one feature postulated to explain why these loci are inherently difficult to replicate, and sensitive to replication stress. We have shown that specialized DNA polymerases (Pols) η and κ replicate CFS-derived sequences more efficiently than the replicative Pol δ. However, we lacked an understanding of how these enzymes cooperate to ensure efficient CFS replication. Here, we designed a model of lagging strand replication with RFC loaded PCNA that allows for maximal activity of the four-subunit human Pol δ holoenzyme, Pol η, and Pol κ in polymerase mixing assays. We discovered that Pol η and κ are both able to exchange with Pol δ stalled at repetitive CFS sequences, enhancing Normalized Replication Efficiency. We used this model to test the impact of PCNA mono-ubiquitination on polymerase exchange, and found no change in polymerase cooperativity in CFS replication compared with unmodified PCNA. Finally, we modeled replication stress in vitro using aphidicolin and found that Pol δ holoenzyme synthesis was significantly inhibited in a dose-dependent manner, preventing any replication past the CFS. Importantly, Pol η and κ were still proficient in rescuing this stalled Pol δ synthesis, which may explain, in part, the CFS instability phenotype of aphidicolin-treated Pol η and Pol κ-deficient cells. In total, our data support a model wherein Pol δ stalling at CFSs allows for free exchange with a specialized polymerase that is not driven by PCNA. Copyright © 2017 Elsevier B.V. All rights reserved.

Sleeping Beauty transposon-based system for rapid generation of HBV-replicating stable cell lines.

PubMed

Wu, Yong; Zhang, Tian-Ying; Fang, Lin-Lin; Chen, Zi-Xuan; Song, Liu-Wei; Cao, Jia-Li; Yang, Lin; Yuan, Quan; Xia, Ning-Shao

2016-08-01

The stable HBV-replicating cell lines, which carry replication-competent HBV genome stably integrated into the genome of host cell, are widely used to evaluate the effects of antiviral agents. However, current methods to generate HBV-replicating cell lines, which are mostly dependent on random integration of foreign DNA via plasmid transfection, are less-efficient and time-consuming. To address this issue, we constructed an all-in-one Sleeping Beauty transposon system (denoted pTSMP-HBV vector) for robust generation of stable cell lines carrying replication-competent HBV genome of different genotype. This vector contains a Sleeping Beauty transposon containing HBV 1.3-copy genome with an expression cassette of the SV40 promoter driving red fluorescent protein (mCherry) and self-cleaving P2A peptide linked puromycin resistance gene (PuroR). In addition, a PGK promoter-driven SB100X hyperactive transposase cassette is placed in the outside of the transposon in the same plasmid.The HBV-replicating stable cells could be obtained from pTSMP-HBV transfected HepG2 cells by red fluorescence-activated cell sorting and puromycin resistant cell selection within 4-week. Using this system, we successfully constructed four cell lines carrying replication-competent HBV genome of genotypes A-D. The replication and viral protein expression profiles of these cells were systematically characterized. In conclusion, our study provides a high-efficiency strategy to generate HBV-replicating stable cell lines, which may facilitate HBV-related virological study. Copyright © 2016. Published by Elsevier B.V.

Comprehensive Analysis of the Effects of Ordinary Nutrients on Hepatitis C Virus RNA Replication in Cell Culture▿

PubMed Central

Yano, Masahiko; Ikeda, Masanori; Abe, Ken-ichi; Dansako, Hiromichi; Ohkoshi, Shogo; Aoyagi, Yutaka; Kato, Nobuyuki

2007-01-01

To date, only a limited number of studies have reported finding an influence of ordinary nutrients on hepatitis C virus (HCV) RNA replication. However, the effects of other nutrients on HCV RNA replication remain largely unknown. We recently developed a reporter assay system for genome-length HCV RNA replication in hepatoma-derived HuH-7 cells (OR6). Here, using this OR6 assay system, we comprehensively examined 46 nutrients from four nutrient groups: vitamins, amino acids, fatty acids, and salts. We found that three nutrients—β-carotene, vitamin D2, and linoleic acid—inhibited HCV RNA replication and that their combination caused additive and/or synergistic effects on HCV RNA replication. In addition, combined treatment with each of the three nutrients and interferon alpha or beta or fluvastatin inhibited HCV RNA replication in an additive manner, while combined treatment with cyclosporine synergistically inhibited HCV RNA replication. In contrast, we found that vitamin E enhanced HCV RNA replication and negated the effects of the three anti-HCV nutrients and cyclosporine but not those of interferon or fluvastatin. These results will provide useful information for the treatment of chronic hepatitis C patients who also take anti-HCV nutrients as an adjunctive therapy in combination with interferon. In conclusion, among the ordinary nutrients tested, β-carotene, vitamin D2, and linoleic acid possessed anti-HCV activity in a cell culture system, and these nutrients are therefore considered to be potential candidates for enhancing the effects of interferon therapy. PMID:17420205

Solving chromatographic challenges in comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry using multivariate curve resolution-alternating least squares.

PubMed

Parastar, Hadi; Radović, Jagoš R; Bayona, Josep M; Tauler, Roma

2013-07-01

Multivariate curve resolution-alternating least squares (MCR-ALS) analysis is proposed to solve chromatographic challenges during two-dimensional gas chromatography-time-of-flight mass spectrometry (GC × GC-TOFMS) analysis of complex samples, such as crude oil extract. In view of the fact that the MCR-ALS method is based on the fulfillment of the bilinear model assumption, three-way and four-way GC × GC-TOFMS data are preferably arranged in a column-wise superaugmented data matrix in which mass-to-charge ratios (m/z) are in its columns and the elution times in the second and first chromatographic columns are in its rows. Since m/z values are common for all measured spectra in all second-column modulations, unavoidable chromatographic challenges such as retention time shifts within and between GC × GC-TOFMS experiments are properly handled. In addition, baseline/background contributions can be modeled by adding extra components to the MCR-ALS model. Another outstanding aspect of MCR-ALS analysis is its extreme flexibility to consider all samples (standards, unknowns, and replicates) in a single superaugmented data matrix, allowing joint analysis. In this way, resolution, identification, and quantification results can be simultaneously obtained in a very fast and reliable way. The potential of MCR-ALS analysis is demonstrated in GC × GC-TOFMS analysis of a North Sea crude oil extract sample with relative errors in estimated concentrations of target compounds below 6.0 % and relative standard deviations lower than 7.0 %. The results obtained, along with reasonable values for the lack of fit of the MCR-ALS model and high values of the reversed match factor in mass spectra similarity searches, confirm the reliability of the proposed strategy for GC × GC-TOFMS data analysis.

Analyses of a whole-genome inter-clade recombination map of hepatitis delta virus suggest a host polymerase-driven and viral RNA structure-promoted template-switching mechanism for viral RNA recombination

PubMed Central

Chao, Mei; Wang, Tzu-Chi; Lin, Chia-Chi; Yung-Liang Wang, Robert; Lin, Wen-Bin; Lee, Shang-En; Cheng, Ying-Yu; Yeh, Chau-Ting; Iang, Shan-Bei

2017-01-01

The genome of hepatitis delta virus (HDV) is a 1.7-kb single-stranded circular RNA that folds into an unbranched rod-like structure and has ribozyme activity. HDV redirects host RNA polymerase(s) (RNAP) to perform viral RNA-directed RNA transcription. RNA recombination is known to contribute to the genetic heterogeneity of HDV, but its molecular mechanism is poorly understood. Here, we established a whole-genome HDV-1/HDV-4 recombination map using two cloned sequences coexisting in cultured cells. Our functional analyses of the resulting chimeric delta antigens (the only viral-encoded protein) and recombinant genomes provide insights into how recombination promotes the genotypic and phenotypic diversity of HDV. Our examination of crossover distribution and subsequent mutagenesis analyses demonstrated that ribozyme activity on HDV genome, which is required for viral replication, also contributes to the generation of an inter-clade junction. These data provide circumstantial evidence supporting our contention that HDV RNA recombination occurs via a replication-dependent mechanism. Furthermore, we identify an intrinsic asymmetric bulge on the HDV genome, which appears to promote recombination events in the vicinity. We therefore propose a mammalian RNAP-driven and viral-RNA-structure-promoted template-switching mechanism for HDV genetic recombination. The present findings improve our understanding of the capacities of the host RNAP beyond typical DNA-directed transcription. PMID:28977829

Computer Analysis of 400 HZ Aircraft Electrical Generator Test Data.

DTIC Science & Technology

1980-06-01

Data Acquisition System. ............ 6 3 Voltage Waveform with Data Points. ....... 19 14 Zero Crossover Interpolation. ........ 20 5 Numerical...difference between successive positive-sloped zero crossovers of the waveform. However, the exact time of zero crossover is not known. This is because...data sampling and the generator output are not synchronized. This unsynchronization means that data points which correspond with an exact zero crossover

Expression of a single siRNA against a conserved region of NP gene strongly inhibits in vitro replication of different Influenza A virus strains of avian and swine origin.

PubMed

Stoppani, Elena; Bassi, Ivan; Dotti, Silvia; Lizier, Michela; Ferrari, Maura; Lucchini, Franco

2015-08-01

Influenza A virus is the principal agent responsible of the respiratory tract's infections in humans. Every year, highly pathogenic and infectious strains with new antigenic assets appear, making ineffective vaccines so far developed. The discovery of RNA interference (RNAi) opened the way to the progress of new promising drugs against Influenza A virus and also to the introduction of disease resistance traits in genetically modified animals. In this paper, we show that Madin-Darby Canine Kidney (MDCK) cell line expressing short hairpin RNAs (shRNAs) cassette, designed on a specific conserved region of the nucleoprotein (NP) viral genome, can strongly inhibit the viral replication of four viral strains sharing the target sequence, reducing the viral mRNA respectively to 2.5×10(-4), 7.5×10(-5), 1.7×10(-3), 1.9×10(-4) compared to the control, as assessed by real-time PCR. Moreover, we demonstrate that during the challenge with a viral strain bearing a single mismatch on the target sequence, although a weaker inhibition is observed, viral mRNA is still lowered down to 1.2×10(-3) folds in the shRNA-expressing clone compared to the control, indicating a broad potential use of this approach. In addition, we developed a highly predictive and fast screening test of siRNA sequences based on dual-luciferase assay, useful for the in vitro prediction of the potential effect of viral inhibition. In conclusion, these findings reveal new siRNA sequences able to inhibit Influenza A virus replication and provide a basis for the development of siRNAs as prophylaxis and therapy for influenza infection both in humans and animals. Copyright © 2015 Elsevier B.V. All rights reserved.

Baculovirus LEF-11 nuclear localization signal is important for viral DNA replication.

PubMed

Chen, Tingting; Dong, Zhanqi; Hu, Nan; Hu, Zhigang; Dong, Feifan; Jiang, Yaming; Li, Jun; Chen, Peng; Lu, Cheng; Pan, Minhui

2017-06-15

Baculovirus LEF-11 is a small nuclear protein that is involved in viral late gene transcription and DNA replication. However, the characteristics of its nuclear localization signal and its impact on viral DNA replication are unknown. In the present study, systemic bioinformatics analysis showed that the baculovirus LEF-11 contains monopartite and bipartite classical nuclear localization signal sequences (cNLSs), which were also detected in a few alphabaculovirus species. Localization of representative LEF-11 proteins of four baculovirus genera indicated that the nuclear localization characteristics of baculovirus LEF-11 coincided with the predicted results. Moreover, Bombyx mori nucleopolyhedrovirus (BmNPV) LEF-11 could be transported into the nucleus during viral infection in the absence of a cNLSs. Further investigations demonstrated that the NLS of BmNPV LEF-11 is important for viral DNA replication. The findings of the present study indicate that the characteristics of the baculovirus LEF-11 protein and the NLS is essential to virus DNA replication and nuclear transport mechanisms. Copyright © 2017 Elsevier B.V. All rights reserved.

Chaotic interactions of self-replicating RNA.

PubMed

Forst, C V

1996-03-01

A general system of high-order differential equations describing complex dynamics of replicating biomolecules is given. Symmetry relations and coordinate transformations of general replication systems leading to topologically equivalent systems are derived. Three chaotic attractors observed in Lotka-Volterra equations of dimension n = 3 are shown to represent three cross-sections of one and the same chaotic regime. Also a fractal torus in a generalized three-dimensional Lotka-Volterra Model has been linked to one of the chaotic attractors. The strange attractors are studied in the equivalent four-dimensional catalytic replicator network. The fractal torus has been examined in adapted Lotka-Volterra equations. Analytic expressions are derived for the Lyapunov exponents of the flow in the replicator system. Lyapunov spectra for different pathways into chaos has been calculated. In the generalized Lotka-Volterra system a second inner rest point--coexisting with (quasi)-periodic orbits--can be observed; with an abundance of different bifurcations. Pathways from chaotic tori, via quasi-periodic tori, via limit cycles, via multi-periodic orbits--emerging out of periodic doubling bifurcations--to "simple" chaotic attractors can be found.

The Obligate Human Pathogen, Neisseria gonorrhoeae, Is Polyploid

PubMed Central

Tobiason, Deborah M; Seifert, H. Steven

2006-01-01

We show using several methodologies that the Gram-negative, diplococcal-bacterium Neisseria gonorrhoeae has more than one complete genome copy per cell. Gene dosage measurements demonstrated that only a single replication initiation event per chromosome occurs per round of cell division, and that there is a single origin of replication. The region containing the origin does not encode any genes previously associated with bacterial origins of replication. Quantitative PCR results showed that there are on average three genome copies per coccal cell unit. These findings allow a model for gonococcal DNA replication and cell division to be proposed, in which a minimum of two chromosomal copies exist per coccal unit within a monococcal or diplococcal cell, and these chromosomes replicate in unison to produce four chromosomal copies during cell division. Immune evasion via antigenic variation is an important mechanism that allows these organisms to continually infect a high risk population of people. We propose that polyploidy may be necessary for the high frequency gene conversion system that mediates pilin antigenic variation and the propagation of N. gonorrhoeae within its human hosts. PMID:16719561

Experimental history: swinging pendulums and melting shellac.

PubMed

Palmieri, Paolo

2009-09-01

Four hundred years ago Galileo Galilei aimed a telescope at the sky. He revolutionized astronomy. Equally revolutionary were his experiments in physics. Unlike his astronomical observations the experiments remain difficult to understand and replicate even today. Two centuries after Galileo, Augustin Coulomb demonstrated experimentally the law of electrostatic force. It has never been successfully replicated. Yet both Galileo and Coulomb were exquisite experimentalists. The fact is that revolutionary experiments in physics are never finished. They are open for investigation for generations to come.

Teaching Real Science with a Microcomputer.

ERIC Educational Resources Information Center

Naiman, Adeline

1983-01-01

Discusses various ways science can be taught using microcomputers, including simulations/games which allow large-scale or historic experiments to be replicated on a manageable scale in a brief time. Examples of several computer programs are also presented, including "Experiments in Human Physiology,""Health Awareness…

Repressor logic modules assembled by rolling circle amplification platform to construct a set of logic gates

PubMed Central

Wei, Hua; Hu, Bo; Tang, Suming; Zhao, Guojie; Guan, Yifu

2016-01-01

Small molecule metabolites and their allosterically regulated repressors play an important role in many gene expression and metabolic disorder processes. These natural sensors, though valuable as good logic switches, have rarely been employed without transcription machinery in cells. Here, two pairs of repressors, which function in opposite ways, were cloned, purified and used to control DNA replication in rolling circle amplification (RCA) in vitro. By using metabolites and repressors as inputs, RCA signals as outputs, four basic logic modules were constructed successfully. To achieve various logic computations based on these basic modules, we designed series and parallel strategies of circular templates, which can further assemble these repressor modules in an RCA platform to realize twelve two-input Boolean logic gates and a three-input logic gate. The RCA-output and RCA-assembled platform was proved to be easy and flexible for complex logic processes and might have application potential in molecular computing and synthetic biology. PMID:27869177

Tax Compliance Inventory: TAX-I Voluntary tax compliance, enforced tax compliance, tax avoidance, and tax evasion

PubMed Central

Kirchler, Erich; Wahl, Ingrid

2010-01-01

Surveys on tax compliance and non-compliance often rely on ad hoc formulated items which lack standardization and empirical validation. We present an inventory to assess tax compliance and distinguish between different forms of compliance and non-compliance: voluntary versus enforced compliance, tax avoidance, and tax evasion. First, items to measure voluntary and enforced compliance, avoidance, and evasion were drawn up (collected from past research and newly developed), and tested empirically with the aim of producing four validated scales with a clear factorial structure. Second, findings from the first analyses were replicated and extended to validation on the basis of motivational postures. A standardized inventory is provided which can be used in surveys in order to collect data which are comparable across research focusing on self-reports. The inventory can be used in either of two ways: either in its entirety, or by applying the single scales independently, allowing an economical and fast assessment of different facets of tax compliance. PMID:20502612

Tools for Basic Statistical Analysis

NASA Technical Reports Server (NTRS)

Luz, Paul L.

2005-01-01

Statistical Analysis Toolset is a collection of eight Microsoft Excel spreadsheet programs, each of which performs calculations pertaining to an aspect of statistical analysis. These programs present input and output data in user-friendly, menu-driven formats, with automatic execution. The following types of calculations are performed: Descriptive statistics are computed for a set of data x(i) (i = 1, 2, 3 . . . ) entered by the user. Normal Distribution Estimates will calculate the statistical value that corresponds to cumulative probability values, given a sample mean and standard deviation of the normal distribution. Normal Distribution from two Data Points will extend and generate a cumulative normal distribution for the user, given two data points and their associated probability values. Two programs perform two-way analysis of variance (ANOVA) with no replication or generalized ANOVA for two factors with four levels and three repetitions. Linear Regression-ANOVA will curvefit data to the linear equation y=f(x) and will do an ANOVA to check its significance.

The Role of Psychometrics in Individual Differences Research in Cognition: A Case Study of the AX-CPT

PubMed Central

Cooper, Shelly R.; Gonthier, Corentin; Barch, Deanna M.; Braver, Todd S.

2017-01-01

Investigating individual differences in cognition requires addressing questions not often thought about in standard experimental designs, especially regarding the psychometric properties of the task. Using the AX-CPT cognitive control task as a case study example, we address four concerns that one may encounter when researching the topic of individual differences in cognition. First, we demonstrate the importance of variability in task scores, which in turn directly impacts reliability, particularly when comparing correlations in different populations. Second, we demonstrate the importance of variability and reliability for evaluating potential failures to replicate predicted correlations, even within the same population. Third, we demonstrate how researchers can turn to evaluating psychometric properties as a way of evaluating the feasibility of utilizing the task in new settings (e.g., online administration). Lastly, we show how the examination of psychometric properties can help researchers make informed decisions when designing a study, such as determining the appropriate number of trials for a task. PMID:28928690

Tax Compliance Inventory: TAX-I Voluntary tax compliance, enforced tax compliance, tax avoidance, and tax evasion.

PubMed

Kirchler, Erich; Wahl, Ingrid

2010-06-01

Surveys on tax compliance and non-compliance often rely on ad hoc formulated items which lack standardization and empirical validation. We present an inventory to assess tax compliance and distinguish between different forms of compliance and non-compliance: voluntary versus enforced compliance, tax avoidance, and tax evasion. First, items to measure voluntary and enforced compliance, avoidance, and evasion were drawn up (collected from past research and newly developed), and tested empirically with the aim of producing four validated scales with a clear factorial structure. Second, findings from the first analyses were replicated and extended to validation on the basis of motivational postures. A standardized inventory is provided which can be used in surveys in order to collect data which are comparable across research focusing on self-reports. The inventory can be used in either of two ways: either in its entirety, or by applying the single scales independently, allowing an economical and fast assessment of different facets of tax compliance.

Validation of the BESS TRS-P Structure with an Independent Sample of Teacher Ratings

ERIC Educational Resources Information Center

DiStefano, Christine; Greer, Fred; Liu, Jin

2016-01-01

The underlying structure of the Behavioral and Emotional Screening System, Teacher Rating Scale-Preschool was investigated with a replication sample. Ratings from more than 3,000 students were used and four alternative models were investigated. As with prior research, a bifactor model with four factors was identified. The results supported an…

Evaluation of fungicide rotations and MELCAST for management of Phytophthora fruit rot of watermelon, 2014

USDA-ARS?s Scientific Manuscript database

The experiment was conducted at the U.S. Vegetable Laboratory farm in Charleston, SC. The soil was Yonges loamy fine sand, and for the past 5 years, the field has been infested with Phytophthora capsici. The experimental design was a randomized complete block with four replications. Four-week-old...

Validation of a Four-Factor Model of Career Indecision

ERIC Educational Resources Information Center

Brown, Steven D.; Hacker, Jason; Abrams, Matthew; Carr, Andrea; Rector, Christopher; Lamp, Kristen; Telander, Kyle; Siena, Anne

2012-01-01

Two studies were designed to explore whether a meta-analytically derived four-factor model of career indecision (Brown & Rector, 2008) could be replicated at the primary and secondary data levels. In the first study, an initial pool of 167 items was written based on 35 different instruments whose scores had loaded saliently on at least one…

Long term growth responses of loblolly pine to optimal nutrient and water resource availability

Treesearch

Timothy J. Albaugh; H. Lee Allen; Phillip M. Dougherty; Kurt H. Johnsen

2004-01-01

A factorial combination of four treatments (control (CW), optimal growing season water availability (IW), optimum nutrient availability (FW), and combined optimum water and nutrient availability (FIW)) in four replications were initiated in an 8-year- old Pinus taeda stand growing on a droughty, nutrient-poor, sandy site in Scotland County, NC and...

Tip moth control and loblolly pine growth in intensive pine culture: four year results

Treesearch

David L. Kulhavy; Jimmie L. Yeiser; L. Allen Smith

2006-01-01

Twenty-two treatments replicated four times were applied to planted loblolly pine, Pinus taeda L., on bedded industrial forest land in east Texas for measurement of growth impact of Nantucket pine tip moth (NPTM), Rhyacionia frustrana Comstock, and effects on pine growth over 2 years. Treatments were combinations of Velpar®,...

New ways in creating pixelgram images

NASA Astrophysics Data System (ADS)

Malureanu, Radu; Di Fabrizio, Enzo

2006-09-01

Since the diffraction gratings were invented, their use in various security systems has been exploited. Their big advantage is the low production cost and, in the same time, the difficulty of replicating them. Most of the nowadays security systems are using those gratings to prove their originality. They can be seen on all the CDs, DVDs, most of the major credit cards and even on the wine bottles. In this article we present a new way of making such gratings without changing the production steps but generating an even more difficult to be replicated item. This new way consists not only in changing the grating period so that various false colours can be seen, but also their orientation so that for a complete check of the grating it should be seen under a certain solid angle. In the same time, one can also keep the possibility to change the grating period so this way various colours can be seen for each angle variation. By combining these two techniques (changing period and changing the angle ones) one can indeed create different images for each view angle and thus increasing the security of the object. In the same time, as can be seen, from the fabrication point of view no further complications appear. The production steps are identical, the only difference being the pattern. The resolution of the grating is not increased necessarily so neither from this point of view will complications appear.

Calorimetric indications of a cooperativity onset in the crossover region of dynamic glass transition for benzoin isobutylether

NASA Astrophysics Data System (ADS)

Kahle, S.; Schröter, K.; Hempel, E.; Donth, E.

1999-10-01

Heat capacity spectroscopy (HCS), dielectric spectroscopy, and shear viscosity data are reported for liquid benzoin isobutylether (BIBE). Dielectric and viscosity peculiarities indicate the crossover region of dynamic glass transition at T=(-8±8) °C where the extrapolated Johari Goldstein β relaxation intersects the main transition trace in an Arrhenius plot. Although HCS does not reach the crossover frequency of order ω=2×106 rad/s, the linear decrease of the square root of cooperativity as calculated from HCS data at lower frequencies indicates a cooperativity onset in the crossover temperature-frequency range. As BIBE belongs to another dielectric crossover scenario as the substances where such an onset could previously be observed, it seems that the cooperativity onset is a general property of the crossover region.

Crossover ensembles of random matrices and skew-orthogonal polynomials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kumar, Santosh, E-mail: skumar.physics@gmail.com; Pandey, Akhilesh, E-mail: ap0700@mail.jnu.ac.in

2011-08-15

Highlights: > We study crossover ensembles of Jacobi family of random matrices. > We consider correlations for orthogonal-unitary and symplectic-unitary crossovers. > We use the method of skew-orthogonal polynomials and quaternion determinants. > We prove universality of spectral correlations in crossover ensembles. > We discuss applications to quantum conductance and communication theory problems. - Abstract: In a recent paper (S. Kumar, A. Pandey, Phys. Rev. E, 79, 2009, p. 026211) we considered Jacobi family (including Laguerre and Gaussian cases) of random matrix ensembles and reported exact solutions of crossover problems involving time-reversal symmetry breaking. In the present paper we givemore » details of the work. We start with Dyson's Brownian motion description of random matrix ensembles and obtain universal hierarchic relations among the unfolded correlation functions. For arbitrary dimensions we derive the joint probability density (jpd) of eigenvalues for all transitions leading to unitary ensembles as equilibrium ensembles. We focus on the orthogonal-unitary and symplectic-unitary crossovers and give generic expressions for jpd of eigenvalues, two-point kernels and n-level correlation functions. This involves generalization of the theory of skew-orthogonal polynomials to crossover ensembles. We also consider crossovers in the circular ensembles to show the generality of our method. In the large dimensionality limit, correlations in spectra with arbitrary initial density are shown to be universal when expressed in terms of a rescaled symmetry breaking parameter. Applications of our crossover results to communication theory and quantum conductance problems are also briefly discussed.« less

Enzyme Kinetics of the Mitochondrial Deoxyribonucleoside Salvage Pathway Are Not Sufficient to Support Rapid mtDNA Replication

PubMed Central

Gandhi, Vishal V.; Samuels, David C.

2011-01-01

Using a computational model, we simulated mitochondrial deoxynucleotide metabolism and mitochondrial DNA replication. Our results indicate that the output from the mitochondrial salvage enzymes alone is inadequate to support a mitochondrial DNA replication duration of as long as 10 hours. We find that an external source of deoxyribonucleoside diphosphates or triphosphates (dNTPs), in addition to those supplied by mitochondrial salvage, is essential for the replication of mitochondrial DNA to complete in the experimentally observed duration of approximately 1 to 2 hours. For meeting a relatively fast replication target of 2 hours, almost two-thirds of the dNTP requirements had to be externally supplied as either deoxyribonucleoside di- or triphosphates, at about equal rates for all four dNTPs. Added monophosphates did not suffice. However, for a replication target of 10 hours, mitochondrial salvage was able to provide for most, but not all, of the total substrate requirements. Still, additional dGTPs and dATPs had to be supplied. Our analysis of the enzyme kinetics also revealed that the majority of enzymes of this pathway prefer substrates that are not precursors (canonical deoxyribonucleosides and deoxyribonucleotides) for mitochondrial DNA replication, such as phosphorylated ribonucleotides, instead of the corresponding deoxyribonucleotides. The kinetic constants for reactions between mitochondrial salvage enzymes and deoxyribonucleotide substrates are physiologically unreasonable for achieving efficient catalysis with the expected in situ concentrations of deoxyribonucleotides. PMID:21829339

Genetic variations in the DNA replication origins of human papillomavirus family correlate with their oncogenic potential.

PubMed

Yilmaz, Gulden; Biswas-Fiss, Esther E; Biswas, Subhasis B

2018-04-01

Human papillomaviruses (HPVs) encompass a large family of viruses that range from benign to highly carcinogenic. The crucial differences between benign and carcinogenic types of HPV remain unknown, except that the two HPV types differ in the frequency of DNA replication. We have systematically analyzed the mechanism of HPV DNA replication initiation in low-risk and high-risk HPVs. Our results demonstrate that HPV-encoded E2 initiator protein and its four binding sites in the replication origin play pivotal roles in determining the destiny of the HPV-infected cell. We have identified strain-specific single nucleotide variations in E2 binding sites found only in the high-risk HPVs. We have demonstrated that these variations result in attenuated formation of the E2-DNA complex. E2 binding to these sites is linked to the activation of the DNA replication origin as well as initiation of DNA replication. Both electrophoretic mobility shift assay and atomic force microscopy studies demonstrated that binding of E2 from either low- or high-risk HPVs with variant binding sequences lacked multimeric E2-DNA complex formation in vitro. These results provided a molecular basis of differential DNA replication in the two types of HPVs and pointed to a correlation with the development of cancer. Copyright © 2017. Published by Elsevier B.V.

Injection and injection-compression moulding replication capability for the production of polymer lab-on-a-chip with nano structures

NASA Astrophysics Data System (ADS)

Calaon, M.; Tosello, G.; Garnaes, J.; Hansen, H. N.

2017-10-01

The manufacturing precision and accuracy in the production of polymer lab-on-a-chip components with 100-130 nm deep nanochannels are evaluated using a metrological approach. Replication fidelity on corresponding process fingerprint test nanostructures over different substrates (nickel tool and polymer part) is quantified through traceable atomic force microscope measurements. Dimensions of injection moulded (IM) and injection-compression moulded (ICM) thermoplastic cyclic olefin copolymer nanofeatures are characterized depending on process parameters and four different features positions on a 30  ×  80 mm2 area. Replication capability of IM and ICM technologies are quantified and the products tolerance at the nanometre dimensional scale verified.

Design, Analysis, and Reporting of Crossover Trials for Inclusion in a Meta-Analysis.

PubMed

Li, Tianjing; Yu, Tsung; Hawkins, Barbara S; Dickersin, Kay

2015-01-01

To evaluate the characteristics of the design, analysis, and reporting of crossover trials for inclusion in a meta-analysis of treatment for primary open-angle glaucoma and to provide empirical evidence to inform the development of tools to assess the validity of the results from crossover trials and reporting guidelines. We searched MEDLINE, EMBASE, and Cochrane's CENTRAL register for randomized crossover trials for a systematic review and network meta-analysis we are conducting. Two individuals independently screened the search results for eligibility and abstracted data from each included report. We identified 83 crossover trials eligible for inclusion. Issues affecting the risk of bias in crossover trials, such as carryover, period effects and missing data, were often ignored. Some trials failed to accommodate the within-individual differences in the analysis. For a large proportion of the trials, the authors tabulated the results as if they arose from a parallel design. Precision estimates properly accounting for the paired nature of the design were often unavailable from the study reports; consequently, to include trial findings in a meta-analysis would require further manipulation and assumptions. The high proportion of poorly reported analyses and results has the potential to affect whether crossover data should or can be included in a meta-analysis. There is pressing need for reporting guidelines for crossover trials.

Circuit Design Optimization Using Genetic Algorithm with Parameterized Uniform Crossover

NASA Astrophysics Data System (ADS)

Bao, Zhiguo; Watanabe, Takahiro

Evolvable hardware (EHW) is a new research field about the use of Evolutionary Algorithms (EAs) to construct electronic systems. EHW refers in a narrow sense to use evolutionary mechanisms as the algorithmic drivers for system design, while in a general sense to the capability of the hardware system to develop and to improve itself. Genetic Algorithm (GA) is one of typical EAs. We propose optimal circuit design by using GA with parameterized uniform crossover (GApuc) and with fitness function composed of circuit complexity, power, and signal delay. Parameterized uniform crossover is much more likely to distribute its disruptive trials in an unbiased manner over larger portions of the space, then it has more exploratory power than one and two-point crossover, so we have more chances of finding better solutions. Its effectiveness is shown by experiments. From the results, we can see that the best elite fitness, the average value of fitness of the correct circuits and the number of the correct circuits of GApuc are better than that of GA with one-point crossover or two-point crossover. The best case of optimal circuits generated by GApuc is 10.18% and 6.08% better in evaluating value than that by GA with one-point crossover and two-point crossover, respectively.

Changing Racial/Ethnic Disparities in Heavy Drinking Trajectories Through Young Adulthood: A Comparative Cohort Study.

PubMed

Williams, Edwina; Mulia, Nina; Karriker-Jaffe, Katherine J; Lui, Camillia K

2018-01-01

There is evidence of racial/ethnic differences in the age at which young adults age out of heavy drinking. Some studies have found Black and Hispanic drinkers engage in more frequent heavy drinking than White people beyond adulthood. Yet, the alcohol-related disparities literature has produced contradictory findings on whether an age-crossover effect is evident among racial/ethnic groups; that is, whether racial/ethnic minorities' drinking levels or trajectories are lower than White people at young ages but later exceed (or crossover) those of White people. This study extends this scant literature by assessing whether racial/ethnic differences in heavy drinking have changed over time (possibly accounting for mixed findings from prior research); and tests for an age-crossover effect in heavy drinking using longitudinal data from 2 cohorts born 20 years apart. Data are from the 1979 (n = 10,963) and 1997 (n = 8,852) cohorts of the National Longitudinal Survey of Youth (NLSY). Generalized estimating equations were used to model trajectories of heavy drinking frequency from ages 17 to 31. Racial/ethnic differences were determined using sex-stratified models and 3-way interactions of race/ethnicity with age, age-squared, and cohort. Racial/ethnic differences in heavy drinking trajectories have changed over time in men and women. In the older NLSY cohort, Hispanic men and Black women surpassed White men's and women's heavy drinking frequency by age 31. This crossover was absent in the younger cohort, where trajectories of all racial-sex groups converged by age 31. Normative trajectories have changed in Hispanics and White people of both sexes, with a delay in age of peak frequency, and greater levels of heavy drinking in the younger cohort of women. Changes in heavy drinking trajectories over time suggest the need for targeted interventions during young adulthood. While disparities in young adult heavy drinking were no longer apparent in the more recent birth cohort, continued monitoring is important. Copyright © 2017 by the Research Society on Alcoholism.

Molecular turnover, the H3.3 dilemma and organismal aging (hypothesis).

PubMed

Saade, Evelyne; Pirozhkova, Iryna; Aimbetov, Rakhan; Lipinski, Marc; Ogryzko, Vasily

2015-06-01

The H3.3 histone variant has been a subject of increasing interest in the field of chromatin studies due to its two distinguishing features. First, its incorporation into chromatin is replication independent unlike the replication-coupled deposition of its canonical counterparts H3.1/2. Second, H3.3 has been consistently associated with an active state of chromatin. In accordance, this histone variant should be expected to be causally involved in the regulation of gene expression, or more generally, its incorporation should have downstream consequences for the structure and function of chromatin. This, however, leads to an apparent paradox: In cells that slowly replicate in the organism, H3.3 will accumulate with time, opening the way to aberrant effects on heterochromatin. Here, we review the indications that H3.3 is expected both to be incorporated in the heterochromatin of slowly replicating cells and to retain its functional downstream effects. Implications for organismal aging are discussed. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Effect of temperature on replicative aging of the budding yeast Saccharomyces cerevisiae.

PubMed

Molon, Mateusz; Zadrag-Tecza, Renata

2016-04-01

The use of the budding yeast Saccharomyces cerevisiae in gerontological studies was based on the assumption that the reproduction limit of a single cell (replicative aging) is a consequence of accumulation of a hypothetical universal "senescence factor" within the mother cell. However, some evidence suggests that molecules or structures proposed as the "aging factor", such as rDNA circles, oxidatively damaged proteins (with carbonyl groups) or mitochondria, have little effect on replicative lifespan of yeast cells. Our results also suggest that protein aggregates associated with Hsp104, treated as a marker of yeast aging, do not seem to affect the numeric value of replicative lifespan of yeast. What these results indicate, however, is the need for finding a different way of expressing age and longevity of yeast cells instead of the commonly used number of daughters produced over units of time, as in the case of other organisms. In this paper, we show that the temperature has a stronger influence on the time of life (the total lifespan) than on the reproductive potential of yeast cells.

Truncated Cross Effect Dynamic Nuclear Polarization: An Overhauser Effect Doppelgänger.

PubMed

Equbal, Asif; Li, Yuanxin; Leavesley, Alisa; Huang, Shengdian; Rajca, Suchada; Rajca, Andrzej; Han, Songi

2018-05-03

The discovery of a truncated cross-effect (CE) in dynamic nuclear polarization (DNP) NMR that has the features of an Overhauser-effect DNP (OE-DNP) is reported here. The apparent OE-DNP, where minimal μw power achieved optimum enhancement, was observed when doping Trityl-OX063 with a pyrroline nitroxide radical that possesses electron-withdrawing tetracarboxylate substituents (tetracarboxylate-ester-pyrroline or TCP) in vitrified water/glycerol at 6.9 T and at 3.3 to 85 K, in apparent contradiction to expectations. While the observations are fully consistent with OE-DNP, we discover that a truncated cross-effect ( tCE) is the underlying mechanism, owing to TCP's shortened T 1e . We take this observation as a guideline and demonstrate that a crossover from CE to tCE can be replicated by simulating the CE of a narrow-line (Trityl-OX063) and a broad-line (TCP) radical pair, with a significantly shortened T 1e of the broad-line radical.

Double-blind cross-over investigation of the effectiveness and safety of two doses of indoprofen compared with an ASA preparation and placebo in patients suffering from osteoarthritis.

PubMed

Valtonen, E; Bergamini, N; Groppi, W; Mandelli, V

1981-01-01

Eighty patients suffering from osteoarthritis of the large joints were admitted to the study and randomly allocated to a 4-treatment sequence, according to a multiple replication of a 4 x 4 Latin square design, with proper balancing of treatments, of periods and of the residual effects of drugs. Each treatment (indoprofen 300 or 600 mg/day, ASA 1500 + diazepam 6 mg/day, and matching placebo) was administered for 7 days. Examinations were carried out on admission, after a 3-4 day wash-out period, and then repeated at the end of each treatment period. Treatment with active drugs was significantly better than placebo in relieving overall pain, and in patient's and investigator's opinion on effectiveness. Treatment with indoprofen, at both dosages, was preferred more frequently than others. The incidence of adverse events during each period did not seem to depend either on the treatment being given during that period or on the previous one.

Does switching to a tobacco-free waterpipe product reduce toxicant intake? A crossover study comparing CO, NO, PAH, volatile aldehydes, tar and nicotine yields

PubMed Central

Shihadeh, Alan; Salman, Rola; Jaroudi, Ezzat; Saliba, Najat; Sepetdjian, Elizabeth; Blank, Melissa D.; Cobb, Caroline O.; Eissenberg, Thomas

2012-01-01

Waterpipe (hookah, narghile, shisha) use has become a global phenomenon, with numerous product variations. One variation is a class of products marketed as “tobacco-free” alternatives for the “health conscious user”. In this study toxicant yields from waterpipes smoked using conventional tobacco-based and tobacco-free preparations were compared. A human-mimic waterpipe smoking machine was used to replicate the puffing sequences of 31 human participants who completed two double-blind ad libitum smoking sessions in a controlled clinical setting: once with a tobacco-based product of their choosing and once with a flavor-matched tobacco-free product. Outcome measures included yields of carbon monoxide, nitric oxide, volatile aldehydes, nicotine, tar, and polycyclic aromatic hydrocarbons. Smoke from both waterpipe preparations contained substantial quantities of toxicants. Nicotine yield was the only outcome that differed significantly between preparations. These findings contradict advertising messages that “herbal” waterpipe products are a healthy alternative to tobacco products. PMID:22406330

Quantifiers more or less quantify online: ERP evidence for partial incremental interpretation

PubMed Central

Urbach, Thomas P.; Kutas, Marta

2010-01-01

Event-related brain potentials were recorded during RSVP reading to test the hypothesis that quantifier expressions are incrementally interpreted fully and immediately. In sentences tapping general knowledge (Farmers grow crops/worms as their primary source of income), Experiment 1 found larger N400s for atypical (worms) than typical objects (crops). Experiment 2 crossed object typicality with non-logical subject-noun phrase quantifiers (most, few). Off-line plausibility ratings exhibited the crossover interaction predicted by full quantifier interpretation: Most farmers grow crops and Few farmers grow worms were rated more plausible than Most farmers grow worms and Few farmers grow crops. Object N400s, although modulated in the expected direction, did not reverse. Experiment 3 replicated these findings with adverbial quantifiers (Farmers often/rarely grow crops/worms). Interpretation of quantifier expressions thus is neither fully immediate nor fully delayed. Furthermore, object atypicality was associated with a frontal slow positivity in few-type/rarely quantifier contexts, suggesting systematic processing differences among quantifier types. PMID:20640044

Using an innovative multiple regression procedure in a cancer population (Part II): fever, depressive affect, and mobility problems clarify an influential symptom pair (pain-fatigue/weakness) and cluster (pain-fatigue/weakness-sleep problems).

PubMed

Francoeur, Richard B

2015-01-01

Most patients with advanced cancer experience symptom pairs or clusters among pain, fatigue, and insomnia. However, only combinations where symptoms are mutually influential hold potential for identifying patient subgroups at greater risk, and in some contexts, interventions with "cross-over" (multisymptom) effects. Improved methods to detect and interpret interactions among symptoms, signs, or biomarkers are needed to reveal these influential pairs and clusters. I recently created sequential residual centering (SRC) to reduce multicollinearity in moderated regression, which enhances sensitivity to detect these interactions. I applied SRC to moderated regressions of single-item symptoms that interact to predict outcomes from 268 palliative radiation outpatients. I investigated: 1) the hypothesis that the interaction, pain × fatigue/weakness × sleep problems, predicts depressive affect only when fever presents, and 2) an exploratory analysis, when fever is absent, that the interaction, pain × fatigue/weakness × sleep problems × depressive affect, predicts mobility problems. In the fever context, three-way interactions (and derivative terms) of the four symptoms (pain, fatigue/weakness, fever, sleep problems) are tested individually and simultaneously; in the non-fever context, a single four-way interaction (and derivative terms) is tested. Fever interacts separately with fatigue/weakness and sleep problems; these comoderators each magnify the pain-depressive affect relationship along the upper or full range of pain values. In non-fever contexts, fatigue/weakness, sleep problems, and depressive affect comagnify the relationship between pain and mobility problems. Different mechanisms contribute to the pain × fatigue/weakness × sleep problems interaction, but all depend on the presence of fever, a sign/biomarker/symptom of proinflammatory sickness behavior. In non-fever contexts, depressive affect is no longer an outcome representing malaise from the physical symptoms of sickness, but becomes a fourth symptom of the interaction. In outpatient subgroups at heightened risk, single interventions could potentially relieve multiple symptoms when fever accompanies sickness malaise and in non-fever contexts with mobility problems. SRC strengthens insights into symptom pairs/clusters.

Local chromosome context is a major determinant of crossover pathway biochemistry during budding yeast meiosis.

PubMed

Medhi, Darpan; Goldman, Alastair Sh; Lichten, Michael

2016-11-18

The budding yeast genome contains regions where meiotic recombination initiates more frequently than in others. This pattern parallels enrichment for the meiotic chromosome axis proteins Hop1 and Red1. These proteins are important for Spo11-catalyzed double strand break formation; their contribution to crossover recombination remains undefined. Using the sequence-specific VMA1 -derived endonuclease (VDE) to initiate recombination in meiosis, we show that chromosome structure influences the choice of proteins that resolve recombination intermediates to form crossovers. At a Hop1-enriched locus, most VDE-initiated crossovers, like most Spo11-initiated crossovers, required the meiosis-specific MutLγ resolvase. In contrast, at a locus with lower Hop1 occupancy, most VDE-initiated crossovers were MutLγ-independent. In pch2 mutants, the two loci displayed similar Hop1 occupancy levels, and VDE-induced crossovers were similarly MutLγ-dependent. We suggest that meiotic and mitotic recombination pathways coexist within meiotic cells, and that features of meiotic chromosome structure determine whether one or the other predominates in different regions.

Efficacy of denture adhesives in maxillary dentures using gnathodynamometry: a comparative study.

PubMed

Polyzois, Gregory; Lagouvardos, Panagiotis; Frangou, Maria; Stefaniotis, Theodoros

2011-07-01

The purpose of this study was to investigate the effect of four commercially available denture adhesives on the incisal and premolar dislodgement forces of maxillary complete dentures by using an electronic and disposable gnathodynamometer and compare the measured incisal forces for differences. This study was conducted with 12 complete maxillary denture wearers. Four commercially available denture adhesives Super Corega(®), Corega Ultra(®), Super Corega Powder(®) and Fittydent Cationic(®) were investigated. Testing protocol and sequence included baseline measurements without adhesives (control) for previous and new dentures and then replications of measurements with the four adhesives. Maximum dislodgement forces were recorded in two sites between central incisors and the left 2nd premolars by using an electronic and disposable gnathodynamometer. To estimate the effect of the different adhesives on the dislodgement forces, data were analyzed by a 2- and 3-way ANOVA, while for estimating the agreement of the two devices a Bland-Altman and Mountain plots were used. ANOVAs indicated significant differences between adhesives (p < 0.05), denture types (p < 0.05) and biting sites (p < 0.05) with both devices. Bland-Altman plot and Mountain plots indicated a poor agreement of the two devices. It was concluded that denture adhesives increase the denture dislodgement forces, but with differences among them. The two devices do not highly agree with each other, but each one alone is useful in estimating dislodgement forces in clinical practice and research.

Knemometry Assessment of Short-term Growth in Children With Asthma Receiving Fluticasone Furoate for 2 Weeks: A Randomized, Placebo-controlled, Crossover Trial.

PubMed

Wolthers, Ole D; Stone, Sally; Bareille, Philippe; Tomkins, Susan; Khindri, Sanjeev

2017-06-01

A dry powder inhaler formulation of the inhaled corticosteroid fluticasone furoate (FF) is being evaluated for use in children. An important potential risk associated with the use of inhaled corticosteroids in children is growth suppression. Therefore, the aim of this study was to assess the short-term lower leg growth in children with asthma treated for 2 weeks with inhaled FF versus placebo from the ELLIPTA inhaler. Prepubertal children with persistent asthma (n = 60; aged 5 to <12 years) were recruited into a randomized, double-blind, placebo-controlled, 2-way crossover, noninferiority study. The study consisted of four 2-week periods: run-in, 2 treatment periods, 1 washout period, and a 1-week follow-up period. Interventions were FF 50 µg and placebo once daily in the evening. Lower leg length was measured by using knemometry. The randomized ITT population comprised 36 boys and 24 girls with a mean age of 8.7 (standard deviation, 1.5; range, 5-11) years; 58% had a duration of asthma ≥5 years. Fifty-eight subjects completed both treatment periods. The least squares mean growth rate was 0.31 mm/week during treatment with FF and 0.36 mm/week during the placebo period. The difference in adjusted least squares mean growth rates between FF and placebo was -0.052 mm/week with a 95% CI of -0.122 to 0.018. This finding was greater than the prespecified noninferiority margin of -0.20 mm/week. The overall incidence of adverse events was 35% with placebo and 22% with FF. Inhaled FF 50 µg provided once daily for 2 weeks was noninferior to placebo in terms of effects on short-term lower leg growth in children with asthma. To further quantify the risk of growth suppression in children, intermediate-term growth studies should be conducted. Inhaled FF 50 µg was well tolerated in this study population. ClinicalTrials.gov identifier: NCT02502734. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

The Analysis of Leaf Shape Using Fractal Geometry.

ERIC Educational Resources Information Center

Hartvigsen, Gregg

2000-01-01

Describes ways to examine leaf structure and shape using fractal geometry. Students can test hypotheses using the leaves of replicated plants to look for non-linear trends in leaf shape along the stems of plants, across species, and under different environmental growth conditions. (SAH)

Therapeutic assessment for preadolescent boys with oppositional defiant disorder: a replicated single-case time-series design.

PubMed

Smith, Justin D; Handler, Leonard; Nash, Michael R

2010-09-01

The Therapeutic Assessment (TA) model is a relatively new treatment approach that fuses assessment and psychotherapy. The study examines the efficacy of this model with preadolescent boys with oppositional defiant disorder and their families. A replicated single-case time-series design with daily measures is used to assess the effects of TA and to track the process of change as it unfolds. All 3 families benefitted from participation in TA across multiple domains of functioning, but the way in which change unfolded was unique for each family. These findings are substantiated by the Behavior Assessment System for Children (Reynolds & Kamphaus, 2004). The TA model is shown to be an effective treatment for preadolescent boys with oppositional defiant disorder and their families. Further, the time-series design of this study illustrated how this empirically grounded case-based methodology reveals when and how change unfolds during treatment in a way that is usually not possible with other research designs.

Sweet/Dessert Foods Are More Appealing to Adolescents after Sleep Restriction

PubMed Central

Simon, Stacey L.; Field, Julie; Miller, Lauren E.; DiFrancesco, Mark; Beebe, Dean W.

2015-01-01

Study Objective Examine the effect of experimental sleep restriction (SR) on adolescents’ subjective hunger and perceived appeal of sweet/dessert foods versus other foods. A secondary goal was to replicate previous findings on the effects of SR on dietary intake. Design Randomized cross-over sleep restriction-extension paradigm. Setting Sleep was obtained and monitored at home. Outcome measures were gathered during office visits. Participants 31 typically-developing adolescents aged 14–17 years. Interventions The three-week protocol consisted of a baseline week, followed randomly by five consecutive nights of SR (6.5 hours in bed) versus healthy sleep duration (HS; 10 hours in bed), a 2-night wash-out period, and a 5-night cross-over. Measurements Sleep was monitored via actigraphy. The morning after each experimental condition, teens rated their hunger, underwent a 24-hour diet recall interview, and rated the appeal of a series of pictures of sweet/dessert foods (e.g., ice cream, candy) and non-sweets (meat, eggs, fruits, vegetables). Results Teens rated pictures of sweet/dessert foods to be more appealing after SR than after HS (Cohen’s d = .41, t = 2.07, p = .045). The sleep manipulation did not affect self-reported hunger or the appeal of non-sweet foods (p >.10). Consistent with our prior work, intake of overall calories was 11% higher and consumption of sweet/dessert servings was 52% greater during SR than HS. Conclusions Adolescent SR appears to increase the subjective appeal of sweet/dessert foods, indicating a potential mechanism by which SR might contribute to weight gain and the risk for obesity and chronic illness. PMID:25706861

Low-dose naltrexone for the treatment of fibromyalgia: findings of a small, randomized, double-blind, placebo-controlled, counterbalanced, crossover trial assessing daily pain levels.

PubMed

Younger, Jarred; Noor, Noorulain; McCue, Rebecca; Mackey, Sean

2013-02-01

To determine whether low dosages (4.5 mg/day) of naltrexone reduce fibromyalgia severity as compared with the nonspecific effects of placebo. In this replication and extension study of a previous clinical trial, we tested the impact of low-dose naltrexone on daily self-reported pain. Secondary outcomes included general satisfaction with life, positive mood, sleep quality, and fatigue. Thirty-one women with fibromyalgia participated in the randomized, double-blind, placebo-controlled, counterbalanced, crossover study. During the active drug phase, participants received 4.5 mg of oral naltrexone daily. An intensive longitudinal design was used to measure daily levels of pain. When contrasting the condition end points, we observed a significantly greater reduction of baseline pain in those taking low-dose naltrexone than in those taking placebo (28.8% reduction versus 18.0% reduction; P = 0.016). Low-dose naltrexone was also associated with improved general satisfaction with life (P = 0.045) and with improved mood (P = 0.039), but not improved fatigue or sleep. Thirty-two percent of participants met the criteria for response (defined as a significant reduction in pain plus a significant reduction in either fatigue or sleep problems) during low-dose naltrexone therapy, as contrasted with an 11% response rate during placebo therapy (P = 0.05). Low-dose naltrexone was rated equally tolerable as placebo, and no serious side effects were reported. The preliminary evidence continues to show that low-dose naltrexone has a specific and clinically beneficial impact on fibromyalgia pain. The medication is widely available, inexpensive, safe, and well-tolerated. Parallel-group randomized controlled trials are needed to fully determine the efficacy of the medication. Copyright © 2013 by the American College of Rheumatology.

An acute, double-blind, placebo-controlled cross-over study of 320 mg and 640 mg doses of Bacopa monnieri (CDRI 08) on multitasking stress reactivity and mood.

PubMed

Benson, Sarah; Downey, Luke A; Stough, Con; Wetherell, Mark; Zangara, Andrea; Scholey, Andrew

2014-04-01

Little research exists in humans concerning the anxiolytic, antidepressant, sedative, and adaptogenic actions the traditional Ayurvedic medicine Bacopa monnieri (BM) possesses in addition to its documented cognitive-enhancing effects. Preclinical work has identified a number of acute anxiolytic, nootropic, and adaptogenic effects of BM that may also co-occur in humans. The current double-blind, placebo-controlled cross-over study assessed the acute effects of a specific extract of BM (KeenMind® - CDRI 08) in normal healthy participants during completion of a multitasking framework (MTF). Seventeen healthy volunteers completed the MTF, at baseline, then 1 h and 2 h after consuming a placebo, 320 mg BM and 640 mg of BM. Treatments were separated by a 7-day washout with order determined by Latin Square. Outcome measures included cognitive outcomes from the MTF, with mood and salivary cortisol measured before and after each completion of the MTF. Change from baseline scores indicated positive cognitive effects, notably at both 1 h post and 2 h post BM consumption on the Letter Search and Stroop tasks, suggesting an earlier nootropic effect of BM than previously investigated. There were also some positive mood effects and reduction in cortisol levels, pointing to a physiological mechanism for stress reduction associated with BM consumption. It was concluded that acute BM supplementation produced some adaptogenic and nootropic effects that need to be replicated in a larger sample and in isolation from stressful cognitive tests in order to quantify the magnitude of these effects. The study was registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12612000834853). Copyright © 2013 John Wiley & Sons, Ltd.

Hypoglycemia Risk Related to Double Dose Is Markedly Reduced with Basal Insulin Peglispro Versus Insulin Glargine in Patients with Type 2 Diabetes Mellitus in a Randomized Trial: IMAGINE 8.

PubMed

Harris, Cynthia; Forst, Thomas; Heise, Tim; Plum-Mörschel, Leona; Watkins, Elaine; Zhang, Qianyi; Fan, Ludi; Garhyan, Parag; Porksen, Niels

2017-08-01

Basal insulin peglispro (BIL) has a peripheral-to-hepatic distribution of action that resembles endogenous insulin and a prolonged duration of action with a flat pharmacokinetic/pharmacodynamic profile at steady state, characteristics that tend to reduce hypoglycemia risk compared to insulin glargine (GL). The primary objective was to demonstrate that clinically significant hypoglycemia (blood glucose ≤54 mg/dL [3.0 mmol/L] or symptoms of severe hypoglycemia) occurred less frequently within 84 h after a double dose (DD) of BIL than a DD of GL. This was a randomized, double-blind, two-period crossover study in patients with type 2 diabetes (T2D) previously treated with insulin (N = 68). For the first 3 weeks of each of the two crossover periods, patients received an individualized dose of BIL or GL once nightly (stable dose for 2 weeks/period). Then, during a 7-day inpatient stay with frequent blood glucose monitoring and standardized meals, one DD of study insulin was given. Glucose was infused if blood glucose was ≤54 mg/dL (3.0 mmol/L) or for symptoms of severe hypoglycemia. Within 84 h after the DD, a significantly smaller proportion of patients experienced clinically significant hypoglycemia with BIL compared to GL (BIL, 6.6%; GL, 35.5%; odds ratio for BIL/GL 0.13 [95% confidence interval 0.04-0.39]; P < 0.001). Adverse event profiles were similar for the two insulins. Serum alanine aminotransferase and triglyceride levels were significantly higher with BIL versus GL. BIL has a markedly lower risk of hypoglycemia than GL when replicating a double-dose error in patients with T2D.

Using gait parameters to detect fatigue and responses to ice slurry during prolonged load carriage.

PubMed

Tay, Cheryl S; Lee, Jason K W; Teo, Ya S; Foo, Phildia Q Z; Tan, Pearl M S; Kong, Pui W

2016-01-01

This study examined (1) if changes in gait characteristics could indicate the exertional heat stress experienced during prolonged load carriage, and (2) if gait characteristics were responsive to a heat mitigation strategy. In an environmental chamber replicating tropical climatic conditions (ambient temperature 32°C, 70% relative humidity), 16 males aged 21.8 (1.2) years performed two trials of a work-rest cycle protocol consisting two bouts of 4-km treadmill walks with 30-kg load at 5.3km/h separated by a 15-min rest period. Ice slurry (ICE) or room temperature water (29°C) as a control (CON) was provided in 200-ml aliquots. The fluids were given 10min before the start, at the 15(th) and 30(th) min of each work cycle, and during each rest period. Spatio-temporal gait characteristics were obtained at the start and end of each work-rest cycle using a floor-based photocell system (OptoGait) and a high-speed video camera at 120Hz. Repeated-measure analysis of variance (trial×time) showed that with time, step width decreased (p=.024) while percent crossover steps increased (p=.008) from the 40(th) min onwards. Reduced stance time variability (-11.1%, p=.029) step width variability (-8.2%, p=.001), and percent crossover step (-18.5%, p=.010) were observed in ICE compared with CON. No differences in step length and most temporal variables were found. In conclusion, changes in frontal plane gait characteristics may indicate exertional heat stress during prolonged load carriage, and some of these changes may be mitigated with ice slurry ingestion. Copyright © 2015 Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ono, Shota, E-mail: shota-o@gifu-u.ac.jp; Department of Physics, Graduate School of Engineering, Yokohama National University, Yokohama 240-8501; Tanikawa, Kousei

Revealing a universal relation between geometrical structures and electronic properties of capped carbon nanotubes (CNTs) is one of the current objectives in nanocarbon community. Here, we investigate the local curvature of capped CNTs and define the cap region by a crossover behavior of the curvature energy versus the number of carbon atoms integrated from the tip to the tube region. Clear correlations among the energy gap of the cap localized states, the curvature energy, the number of carbon atoms in the cap region, and the number of specific carbon clusters are observed. The present analysis opens the way to understandmore » the cap states.« less

Semiotic systems with duality of patterning and the issue of cultural replicators.

PubMed

Schaden, Gerhard; Patin, Cédric

2017-11-14

Two major works in recent evolutionary biology have in different ways touched upon the issue of cultural replicators in language, namely Dawkins' Selfish Gene and Maynard Smith and Szathmáry's Major Transitions in Evolution. In the latter, the emergence of language is referred to as the last major transition in evolution (for the time being), a claim we argue to be derived from a crucial property of language, called Duality of Patterning. Prima facie, this property makes natural language look like a structural equivalent to DNA, and its peer in terms of expressive power. We will argue that, if one takes seriously Maynard Smith and Szathmáry's outlook and examines what has been proposed as linguistic replicators, amongst others phonemes and words, the analogy meme-gene becomes problematic. A key issue is the fact that genes and memes are assumed to carry and transmit information, while what has been described as the best candidate for replicatorhood in language, i.e. the phoneme, does by definition not carry meaning. We will argue that semiotic systems with Duality of Pattering (like natural languages) force us to reconsider either the analogy between replicators in the biological and the cultural domain, or what it is to be a replicator in linguistics.

Analysis of host response to bacterial infection using error model based gene expression microarray experiments

PubMed Central

Stekel, Dov J.; Sarti, Donatella; Trevino, Victor; Zhang, Lihong; Salmon, Mike; Buckley, Chris D.; Stevens, Mark; Pallen, Mark J.; Penn, Charles; Falciani, Francesco

2005-01-01

A key step in the analysis of microarray data is the selection of genes that are differentially expressed. Ideally, such experiments should be properly replicated in order to infer both technical and biological variability, and the data should be subjected to rigorous hypothesis tests to identify the differentially expressed genes. However, in microarray experiments involving the analysis of very large numbers of biological samples, replication is not always practical. Therefore, there is a need for a method to select differentially expressed genes in a rational way from insufficiently replicated data. In this paper, we describe a simple method that uses bootstrapping to generate an error model from a replicated pilot study that can be used to identify differentially expressed genes in subsequent large-scale studies on the same platform, but in which there may be no replicated arrays. The method builds a stratified error model that includes array-to-array variability, feature-to-feature variability and the dependence of error on signal intensity. We apply this model to the characterization of the host response in a model of bacterial infection of human intestinal epithelial cells. We demonstrate the effectiveness of error model based microarray experiments and propose this as a general strategy for a microarray-based screening of large collections of biological samples. PMID:15800204

The joy of six: how to control your crossovers.

PubMed

Globus, Samuel T; Keeney, Scott

2012-03-30

Meiotic cells tightly regulate the number and distribution of crossovers to promote accurate chromosome segregation. Yokoo and colleagues uncover a metazoan-specific, cyclin-like protein that is crucial for crossover formation. They utilize this protein's unique properties to explore a remarkable example of biological numerology, whereby nearly every meiotic cell in C. elegans makes precisely six crossovers, one for each of its six chromosome pairs. Copyright © 2012 Elsevier Inc. All rights reserved.

An improved genetic algorithm and its application in the TSP problem

NASA Astrophysics Data System (ADS)

Li, Zheng; Qin, Jinlei

2011-12-01

Concept and research actuality of genetic algorithm are introduced in detail in the paper. Under this condition, the simple genetic algorithm and an improved algorithm are described and applied in an example of TSP problem, where the advantage of genetic algorithm is adequately shown in solving the NP-hard problem. In addition, based on partial matching crossover operator, the crossover operator method is improved into extended crossover operator in order to advance the efficiency when solving the TSP. In the extended crossover method, crossover operator can be performed between random positions of two random individuals, which will not be restricted by the position of chromosome. Finally, the nine-city TSP is solved using the improved genetic algorithm with extended crossover method, the efficiency of whose solution process is much higher, besides, the solving speed of the optimal solution is much faster.

Diverged composition and regulation of the Trypanosoma brucei origin recognition complex that mediates DNA replication initiation

PubMed Central

Marques, Catarina A.; Tiengwe, Calvin; Lemgruber, Leandro; Damasceno, Jeziel D.; Scott, Alan; Paape, Daniel; Marcello, Lucio; McCulloch, Richard

2016-01-01

Abstract Initiation of DNA replication depends upon recognition of genomic sites, termed origins, by AAA+ ATPases. In prokaryotes a single factor binds each origin, whereas in eukaryotes this role is played by a six-protein origin recognition complex (ORC). Why eukaryotes evolved a multisubunit initiator, and the roles of each component, remains unclear. In Trypanosoma brucei, an ancient unicellular eukaryote, only one ORC-related initiator, TbORC1/CDC6, has been identified by sequence homology. Here we show that three TbORC1/CDC6-interacting factors also act in T. brucei nuclear DNA replication and demonstrate that TbORC1/CDC6 interacts in a high molecular complex in which a diverged Orc4 homologue and one replicative helicase subunit can also be found. Analysing the subcellular localization of four TbORC1/CDC6-interacting factors during the cell cycle reveals that one factor, TbORC1B, is not a static constituent of ORC but displays S-phase restricted nuclear localization and expression, suggesting it positively regulates replication. This work shows that ORC architecture and regulation are diverged features of DNA replication initiation in T. brucei, providing new insight into this key stage of eukaryotic genome copying. PMID:26951375

Sequence selection by dynamical symmetry breaking in an autocatalytic binary polymer model

NASA Astrophysics Data System (ADS)

Fellermann, Harold; Tanaka, Shinpei; Rasmussen, Steen

2017-12-01

Template-directed replication of nucleic acids is at the essence of all living beings and a major milestone for any origin of life scenario. We present an idealized model of prebiotic sequence replication, where binary polymers act as templates for their autocatalytic replication, thereby serving as each others reactants and products in an intertwined molecular ecology. Our model demonstrates how autocatalysis alters the qualitative and quantitative system dynamics in counterintuitive ways. Most notably, numerical simulations reveal a very strong intrinsic selection mechanism that favors the appearance of a few population structures with highly ordered and repetitive sequence patterns when starting from a pool of monomers. We demonstrate both analytically and through simulation how this "selection of the dullest" is caused by continued symmetry breaking through random fluctuations in the transient dynamics that are amplified by autocatalysis and eventually propagate to the population level. The impact of these observations on related prebiotic mathematical models is discussed.

Transcription and recombination: when RNA meets DNA.

PubMed

Aguilera, Andrés; Gaillard, Hélène

2014-08-01

A particularly relevant phenomenon in cell physiology and proliferation is the fact that spontaneous mitotic recombination is strongly enhanced by transcription. The most accepted view is that transcription increases the occurrence of double-strand breaks and/or single-stranded DNA gaps that are repaired by recombination. Most breaks would arise as a consequence of the impact that transcription has on replication fork progression, provoking its stalling and/or breakage. Here, we discuss the mechanisms responsible for the cross talk between transcription and recombination, with emphasis on (1) the transcription-replication conflicts as the main source of recombinogenic DNA breaks, and (2) the formation of cotranscriptional R-loops as a major cause of such breaks. The new emerging questions and perspectives are discussed on the basis of the interference between transcription and replication, as well as the way RNA influences genome dynamics. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

Chk1 and Cds1: linchpins of the DNA damage and replication checkpoint pathways

PubMed Central

Rhind, Nicholas; Russell, Paul

2010-01-01

SUMMARY Recent work on the mechanisms of DNA damage and replication cell cycle checkpoints has revealed great similarity between the checkpoint pathways of organisms as diverse as yeasts, flies and humans. However, there are differences in the ways these organisms regulate their cell cycles. To connect the conserved checkpoint pathways with various cell cycle targets requires an adaptable link that can target different cell cycle components in different organisms. The Chk1 and Cds1 protein kinases, downstream effectors in the checkpoint pathways, seem to play just such roles. Perhaps more surprisingly, the two kinases not only have different targets in different organisms but also seem to respond to different signals in different organisms. So, whereas in fission yeast Chk1 is required for the DNA damage checkpoint and Cds1 is specifically involved in the replication checkpoint, their roles seem to be shuffled in metazoans. PMID:11058076

Expected precision of Europa Clipper gravity measurements

NASA Astrophysics Data System (ADS)

Verma, Ashok K.; Margot, Jean-Luc

2018-11-01

The primary gravity science objective of NASA's Clipper mission to Europa is to confirm the presence or absence of a global subsurface ocean beneath Europa's Icy crust. Gravity field measurements obtained with a radio science investigation can reveal much about Europa's interior structure. Here, we conduct extensive simulations of the radio science measurements with the anticipated spacecraft trajectory and attitude (17F12v2) and assets on the spacecraft and the ground, including antenna orientations and beam patterns, transmitter characteristics, and receiver noise figures. In addition to two-way Doppler measurements, we also include radar altimeter crossover range measurements. We concentrate on ± 2 h intervals centered on the closest approach of each of the 46 flybys. Our covariance analyses reveal the precision with which the tidal Love number k2, second-degree gravity coefficients Cbar20 and Cbar22 , and higher-order gravity coefficients can be determined. The results depend on the Deep Space Network (DSN) assets that are deployed to track the spacecraft. We find that some DSN allocations are sufficient to conclusively confirm the presence or absence of a global ocean. Given adequate crossover range performance, it is also possible to evaluate whether the ice shell is hydrostatic.

A pilot study assessing the effectiveness of a glycerin suppository in controlled colostomy emptying.

PubMed

McClees, Nancy; Mikolaj, Eda L; Carlson, Sharon L; Pryor-McCann, Joan

2004-01-01

The focus of this research was to explore another way for the patient to manage their colostomy. It was hoped that by inserting a glycerin suppository into the colostomy one would be able to evacuate the lower large intestine more effectively and efficiently. To determine if persons with a sigmoid colostomy could obtain fecal continence by instituting a daily self-administered bowel-stimulating suppository. Randomized crossover comparative study comparing usual ostomy emptying practice with emptying with a glycerine suppository to stimulate controlled emptying. Adult males and females with a sigmoid colostomy were studied in their homes. The instruments included a profile questionnaire, a take-home diary, crossover and end-of-study questionnaires, and an exit questionnaire. Subjects were randomized to their usual pouching method or to the experimental suppository method for 14 days each. There was no difference in fecal output, fecal volume, or flatus between the 2 groups. The action of the suppository was affected by its failure to remain in the bowel for an adequate amount of time. Further research is needed to determine if an adjunct device/method to hold the suppository in place would produce successful results.

In silico modelling of directed evolution: Implications for experimental design and stepwise evolution.

PubMed

Wedge, David C; Rowe, William; Kell, Douglas B; Knowles, Joshua

2009-03-07

We model the process of directed evolution (DE) in silico using genetic algorithms. Making use of the NK fitness landscape model, we analyse the effects of mutation rate, crossover and selection pressure on the performance of DE. A range of values of K, the epistatic interaction of the landscape, are considered, and high- and low-throughput modes of evolution are compared. Our findings suggest that for runs of or around ten generations' duration-as is typical in DE-there is little difference between the way in which DE needs to be configured in the high- and low-throughput regimes, nor across different degrees of landscape epistasis. In all cases, a high selection pressure (but not an extreme one) combined with a moderately high mutation rate works best, while crossover provides some benefit but only on the less rugged landscapes. These genetic algorithms were also compared with a "model-based approach" from the literature, which uses sequential fixing of the problem parameters based on fitting a linear model. Overall, we find that purely evolutionary techniques fare better than do model-based approaches across all but the smoothest landscapes.

The effect of glucose dose and fasting interval on cognitive function: a double-blind, placebo-controlled, six-way crossover study.

PubMed

Owen, Lauren; Scholey, Andrew B; Finnegan, Yvonne; Hu, Henglong; Sünram-Lea, Sandra I

2012-04-01

Previous research has identified a number of factors that appear to moderate the behavioural response to glucose administration. These include physiological state, dose, types of cognitive tasks used and level of cognitive demand. Another potential moderating factor is the length of the fasting interval prior to a glucose load. Therefore, we aimed to examine the effect of glucose dose and fasting interval on mood and cognitive function. The current study utilised a double-blind, placebo-controlled, balanced, six period crossover design to examine potential interactions between length of fasting interval (2 versus 12 hours) and optimal dose for cognition enhancement. Results demonstrated that the higher dose (60 g) increased working memory performance following an overnight fast, whereas the lower dose (25 g) enhanced working memory performance following a 2-h fast. The data suggest that optimal glucose dosage may differ under different conditions of depleted blood glucose resources. In addition, glucoregulation was observed to be a moderating factor. However, further research is needed to develop a model of the moderating and mediating factors under which glucose facilitation is best achieved.

Increased Erythrocyte Eicosapentaenoic Acid and Docosahexaenoic Acid Are Associated With Improved Attention and Behavior in Children With ADHD in a Randomized Controlled Three-Way Crossover Trial.

PubMed

Milte, Catherine M; Parletta, Natalie; Buckley, Jonathan D; Coates, Alison M; Young, Ross M; Howe, Peter R C

2015-11-01

To investigate effects of omega-3 polyunsaturated fatty acids (n-3 PUFA) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on attention, literacy, and behavior in children with ADHD. Ninety children were randomized to consume supplements high in EPA, DHA, or linoleic acid (control) for 4 months each in a crossover design. Erythrocyte fatty acids, attention, cognition, literacy, and Conners' Parent Rating Scales (CPRS) were measured at 0, 4, 8, 12 months. Fifty-three children completed the treatment. Outcome measures showed no significant differences between the three treatments. However, in children with blood samples (n = 76-46), increased erythrocyte EPA + DHA was associated with improved spelling (r = .365, p < .001) and attention (r = -.540, p < .001) and reduced oppositional behavior (r = -.301, p < .003), hyperactivity (r = -.310, p < .001), cognitive problems (r = -.326, p < .001), Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) hyperactivity (r = -.270, p = .002) and DSM-IV inattention (r = -.343, p < .001). Increasing erythrocyte DHA and EPA via dietary supplementation may improve behavior, attention, and literacy in children with ADHD. © The Author(s) 2013.

Nonlocal equation for the superconducting gap parameter

NASA Astrophysics Data System (ADS)

Simonucci, S.; Strinati, G. Calvanese

2017-08-01

The properties are considered in detail of a nonlocal (integral) equation for the superconducting gap parameter, which is obtained by a coarse-graining procedure applied to the Bogoliubov-de Gennes (BdG) equations over the whole coupling-versus-temperature phase diagram associated with the superfluid phase. It is found that the limiting size of the coarse-graining procedure, which is dictated by the range of the kernel of this integral equation, corresponds to the size of the Cooper pairs over the whole coupling-versus-temperature phase diagram up to the critical temperature, even when Cooper pairs turn into composite bosons on the BEC side of the BCS-BEC crossover. A practical method is further implemented to solve numerically this integral equation in an efficient way, which is based on a novel algorithm for calculating the Fourier transforms. Application of this method to the case of an isolated vortex, throughout the BCS-BEC crossover and for all temperatures in the superfluid phase, helps clarifying the nature of the length scales associated with a single vortex and the kinds of details that are in practice disposed off by the coarse-graining procedure on the BdG equations.

Engineering of DNA polymerase I from Thermus thermophilus using compartmentalized self-replication.

PubMed

Aye, Seaim Lwin; Fujiwara, Kei; Ueki, Asuka; Doi, Nobuhide

2018-05-05

Although compartmentalized self-replication (CSR) and compartmentalized partnered replication (CPR) are powerful tools for directed evolution of proteins and gene circuits, limitations remain in the emulsion PCR process with the wild-type Taq DNA polymerase used so far, including long run times, low amounts of product, and false negative results due to inhibitors. In this study, we developed a high-efficiency mutant of DNA polymerase I from Thermus thermophilus HB27 (Tth pol) suited for CSR and CPR. We modified the wild-type Tth pol by (i) deletion of the N-terminal 5' to 3' exonuclease domain, (ii) fusion with the DNA-binding protein Sso7d, (iii) introduction of four known effective point mutations from other DNA polymerase mutants, and (iv) codon optimization to reduce the GC content. Consequently, we obtained a mutant that provides higher product yields than the conventional Taq pol without decreased fidelity. Next, we performed four rounds of CSR selection with a randomly mutated library of this modified Tth pol and obtained mutants that provide higher product yields in fewer cycles of emulsion PCR than the parent Tth pol as well as the conventional Taq pol. Copyright © 2018 Elsevier Inc. All rights reserved.

Interplay Among Constitutes of Ebola Virus: Nucleoprotein, Polymerase L, Viral Proteins

NASA Astrophysics Data System (ADS)

Zhang, Minchuan; He, Peiming; Su, Jing; Singh, Dadabhai T.; Su, Hailei; Su, Haibin

Ebola virus is a highly lethal filovirus, claimed thousands of people in its recent outbreak. Seven viral proteins constitute ebola viral structure, and four of them (nucleoprotein (NP), polymerase L, VP35 and VP30) participate majorly in viral replication and transcription. We have elucidated a conformation change of NP cleft by VP35 NP-binding protein domains through superimposing two experimental NP structure images and discussed the function of this conformation change in the replication and transcription with polymerase complex (L, VP35 and VP30). The important roles of VP30 in viral RNA synthesis have also been discussed. A “tapping” model has been proposed in this paper for a better understanding of the interplay among the four viral proteins (NP, polymerase L, VP35 and VP30). Moreover, we have pinpointed some key residue changes on NP (both NP N- and C-terminal) and L between Reston and Zaire by computational studies. Together, this paper provides a description of interactions among ebola viral proteins (NP, L, VP35, VP30 and VP40) in viral replication and transcription, and sheds light on the complex system of viral reproduction.

Evidence for Protection against Chronic Hepatitis C Virus Infection in Chimpanzees by Immunization with Replicating Recombinant Vaccinia Virus▿

PubMed Central

Youn, Jin-Won; Hu, Yu-Wen; Tricoche, Nancy; Pfahler, Wolfram; Shata, Mohamed Tarek; Dreux, Marlene; Cosset, François-Loic; Folgori, Antonella; Lee, Dong-Hun; Brotman, Betsy; Prince, Alfred M.

2008-01-01

Given the failures of nonreplicating vaccines against chronic hepatitis C virus (HCV) infection, we hypothesized that a replicating viral vector may provide protective immunity. Four chimpanzees were immunized transdermally twice with recombinant vaccinia viruses (rVV) expressing HCV genes. After challenge with 24 50% chimpanzee infective doses of homologous HCV, the two control animals that had received only the parental VV developed chronic HCV infection. All four immunized animals resolved HCV infection. The difference in the rate of chronicity between the immunized and the control animals was close to statistical significance (P = 0.067). Immunized animals developed vigorous gamma interferon enzyme-linked immunospot responses and moderate proliferative responses. To investigate cross-genotype protection, the immunized recovered chimpanzees were challenged with a pool of six major HCV genotypes. During the acute phase after the multigenotype challenge, all animals had high-titer viremia in which genotype 4 dominated (87%), followed by genotype 5 (13%). However, after fluctuating low-level viremia, the viremia finally turned negative or persisted at very low levels. This study suggests the potential efficacy of replicating recombinant vaccinia virus-based immunization against chronic HCV infection. PMID:18753204

A comparison of four different blood gas analysers.

PubMed

Kofstad, J

1981-06-01

Four automatic blood gas analysers from four different manufactures were evaluated and compared. The measurements were performed on blood representing respiratory acidosis and hypoxemia, normal conditions, and respiratory alkalosis and hyperoxemia. On each level nine complete runs were carried out, each run consisting of six replicates of each parameter (pH, Pco2 and Po2) on each instrument (six rounds). Only the directly measured parameters (pH, Pco2, Po2) were compared. The main conclusion is that the four instruments can be used alternatively, and that the differences between the values measured by the four instruments are of little clinical significance.

Cross-over endocytosis of claudins is mediated by interactions via their extracellular loops.

PubMed

Gehne, Nora; Lamik, Agathe; Lehmann, Martin; Haseloff, Reiner F; Andjelkovic, Anuska V; Blasig, Ingolf E

2017-01-01

Claudins (Cldns) are transmembrane tight junction (TJ) proteins that paracellularly seal endo- and epithelial barriers by their interactions within the TJs. However, the mechanisms allowing TJ remodeling while maintaining barrier integrity are largely unknown. Cldns and occludin are heterophilically and homophilically cross-over endocytosed into neighboring cells in large, double membrane vesicles. Super-resolution microscopy confirmed the presence of Cldns in these vesicles and revealed a distinct separation of Cldns derived from opposing cells within cross-over endocytosed vesicles. Colocalization of cross-over endocytosed Cldn with the autophagosome markers as well as inhibition of autophagosome biogenesis verified involvement of the autophagosomal pathway. Accordingly, cross-over endocytosed Cldns underwent lysosomal degradation as indicated by lysosome markers. Cross-over endocytosis of Cldn5 depended on clathrin and caveolin pathways but not on dynamin. Cross-over endocytosis also depended on Cldn-Cldn-interactions. Amino acid substitutions in the second extracellular loop of Cldn5 (F147A, Q156E) caused impaired cis- and trans-interaction, as well as diminished cross-over endocytosis. Moreover, F147A exhibited an increased mobility in the membrane, while Q156E was not as mobile but enhanced the paracellular permeability. In conclusion, the endocytosis of TJ proteins depends on their ability to interact strongly with each other in cis and trans, and the mobility of Cldns in the membrane is not necessarily an indicator of barrier permeability. TJ-remodeling via cross-over endocytosis represents a general mechanism for the degradation of transmembrane proteins in cell-cell contacts and directly links junctional membrane turnover to autophagy.

How reaction to cigarette packet health warnings influence quitting: Findings from the ITC Four Country survey

PubMed Central

Borland, Ron; Yong, Hua-Hie; Wilson, Nick; Fong, Geoffrey T.; Hammond, David; Michael Cummings, K.; Hosking, Warwick; McNeill, Ann

2015-01-01

Objectives To examine prospectively the impact of health warnings on quitting activity. Design Five waves (2002–2006) of a cohort survey where reactions to health warnings at one survey wave are used to predict cessation activity at the next wave, controlling for country (proxy for warning differences) and other factors. These analyses were replicated on four wave-to-wave transitions. Setting and participants Smokers from Australia, Canada, the UK and USA. Samples were Waves 1–2: n=6525; Waves 2–3: n=5257; Waves 3–4:n=4439; and Waves 4–5: n=3993. Measures Warning salience, cognitive responses (thoughts of harm and of quitting), forgoing of cigarettes and avoidance of warnings were examined as predictors of quit attempts, and of quitting success among those who tried (1 month sustained abstinence), replicated across four wave-to-wave transitions. Results All four responses to warnings were independently predictive of quitting activity in bivariate analyses. In multivariate analyses, forgoing cigarettes and cognitive responses to the warnings both prospectively predicted making quit attempts in all replications. However, avoiding warnings did not consistently add predictive value, and there was no consistent pattern for warning salience. There were no interactions by country. Some, but not all, of the effects were mediated by quitting intentions. There were no consistent effects on quit success. Conclusions This study adds to the evidence that forgoing cigarettes as a result of noticing warnings and quit-related cognitive reactions to warnings are consistent prospective predictors of making quit attempts. This work strengthens the evidence base for governments to go beyond the FCTC to mandate health warnings on tobacco products that stimulate the highest possible levels of these reactions. PMID:19215595

Selective Modification of Adenovirus Replication Can Be Achieved through Rational Mutagenesis of the Adenovirus Type 5 DNA Polymerase

PubMed Central

Capella, Cristina; Beltejar, Michael-John; Brown, Caitlin; Fong, Vincent; Daddacha, Waaqo; Kim, Baek

2012-01-01

Mutations that reduce the efficiency of deoxynucleoside (dN) triphosphate (dNTP) substrate utilization by the HIV-1 DNA polymerase prevent viral replication in resting cells, which contain low dNTP concentrations, but not in rapidly dividing cells such as cancer cells, which contain high levels of dNTPs. We therefore tested whether mutations in regions of the adenovirus type 5 (Ad5) DNA polymerase that interact with the dNTP substrate or DNA template could alter virus replication. The majority of the mutations created, including conservative substitutions, were incompatible with virus replication. Five replication-competent mutants were recovered from 293 cells, but four of these mutants failed to replicate in A549 lung carcinoma cells and Wi38 normal lung cells. Purified polymerase proteins from these viruses exhibited only a 2- to 4-fold reduction in their dNTP utilization efficiency but nonetheless could not be rescued, even when intracellular dNTP concentrations were artificially raised by the addition of exogenous dNs to virus-infected A549 cells. The fifth mutation (I664V) reduced biochemical dNTP utilization by the viral polymerase by 2.5-fold. The corresponding virus replicated to wild-type levels in three different cancer cell lines but was significantly impaired in all normal cell lines in which it was tested. Efficient replication and virus-mediated cell killing were rescued by the addition of exogenous dNs to normal lung fibroblasts (MRC5 cells), confirming the dNTP-dependent nature of the polymerase defect. Collectively, these data provide proof-of-concept support for the notion that conditionally replicating, tumor-selective adenovirus vectors can be created by modifying the efficiency with which the viral DNA polymerase utilizes dNTP substrates. PMID:22811532

A randomized, double-blind, crossover, placebo-controlled comparative clinical trial of arginine aspartate plus adenosine monophosphate for the intermittent treatment of male erectile dysfunction.

PubMed

Neuzillet, Y; Hupertan, V; Cour, F; Botto, H; Lebret, T

2013-03-01

Efficacy and safety of l-arginine aspartate 8 g combined with 200 mg of adenosine monophosphate (AA) with placebo (PL) alone for intermittent treatment of mild-to-moderate erectile dysfunction (ED) were compared. The study design was a double-blind, PL-controlled, two-way crossover randomized clinical trial with 26 patients. Efficacy was assessed by International Index of Erectile Function (IIEF) and two additional validated questionnaires [the Erection Hardness Score (EHS) and the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS). During each crossover period, separated by a 2-week wash-out period, drugs were administered orally, 1-2 h before sexual intercourse. Primary endpoint was a change in the IIEF. Secondary endpoints were patient and investigator assessments of treatment success. Investigators' and patients' assessment of efficacy was significantly improved by the combination vs. PL (p = 0.01 and p = 0.04 respectively]. EHS and EDITS questionnaires were both improved by the combination (p = 0.015 and p = 0.017 respectively). There was no significant difference in terms of tolerance between AA and PL or severe adverse events. ED patients demonstrated significant improvements in all IIEF domains with the exception of the Sexual Desire and Orgasmic Domains when treated with AA compared with PL. This pilot phase II study showed that the on-demand oral administration at a high dosage of l-arginine aspartate-adenosine monophosphate combination may be effective in patients with mild-to-moderate ED, is very well tolerated and could be tested as a safe first-line therapy in a larger size phase III study. © 2012 American Society of Andrology and European Academy of Andrology.

Menstrual cycle phase and single tablet antiretroviral medication adherence in women with HIV.

PubMed

Hessol, Nancy A; Holman, Susan; Minkoff, Howard; Cohen, Mardge H; Golub, Elizabeth T; Kassaye, Seble; Karim, Roksana; Sosanya, Oluwakemi; Shaheen, Christopher; Merhi, Zaher

2016-01-01

Suboptimal adherence to antiretroviral (ARV) therapy among HIV-infected individuals is associated with increased risk of progression to AIDS and the development of HIV resistance to ARV medications. To examine whether the luteal phase of the menstrual cycle is independently associated with suboptimal adherence to single tablet regimen (STR) ARV medication, data were analyzed from a multicenter cohort study of HIV-infected women who reported regular menstrual cycles and were taking an STR. In a cross-sectional analysis, suboptimal adherence to an STR among women in their follicular phase was compared with suboptimal adherence among women in their luteal phase. In two-way crossover analyses, whereby the same woman was assessed for STR medication adherence in both her follicular and luteal phases, the estimated exact conditional odds of non-adherence to an STR was measured. In adjusted logistic regression analysis of the cross-sectional data (N=327), women with ≤12 years of education were more than three times more likely to have suboptimal adherence (OR=3.6, p=.04) compared to those with >12 years of education. Additionally, women with Center for Epidemiological Studies Depression Scale (CES-D) scores ≥23 were 2.5-times more likely to have suboptimal adherence (OR=2.6, p=.02) compared to those with CES-D scores <23. In conditional logistic regression analyses of the crossover data (N=184), having childcare responsibilities was associated with greater odds of ≤95% adherence. Menstrual cycle phase was not associated with STR adherence in either the cross-sectional or crossover analyses. The lack of association between phase of the menstrual cycle and adherence to an STR in HIV-infected women means attention can be given to other more important risk factors for suboptimal adherence, such as depression, level of education, and childcare responsibilities.

The new insight into dynamic crossover in glass forming liquids from the apparent enthalpy analysis

NASA Astrophysics Data System (ADS)

Martinez-Garcia, Julio Cesar; Martinez-Garcia, Jorge; Rzoska, Sylwester J.; Hulliger, Jürg

2012-08-01

One of the most intriguing phenomena in glass forming systems is the dynamic crossover (TB), occurring well above the glass temperature (Tg). So far, it was estimated mainly from the linearized derivative analysis of the primary relaxation time τ(T) or viscosity η(T) experimental data, originally proposed by Stickel et al. [J. Chem. Phys. 104, 2043 (1996), 10.1063/1.470961; Stickel et al. J. Chem. Phys. 107, 1086 (1997)], 10.1063/1.474456. However, this formal procedure is based on the general validity of the Vogel-Fulcher-Tammann equation, which has been strongly questioned recently [T. Hecksher et al. Nature Phys. 4, 737 (2008), 10.1038/nphys1033; P. Lunkenheimer et al. Phys. Rev. E 81, 051504 (2010), 10.1103/PhysRevE.81.051504; J. C. Martinez-Garcia et al. J. Chem. Phys. 134, 024512 (2011)], 10.1063/1.3514589. We present a qualitatively new way to identify the dynamic crossover based on the apparent enthalpy space (H_a^' = {{dln τ }/{d({1/T})}}) analysis via a new plot ln H_a^' vs. 1/T supported by the Savitzky-Golay filtering procedure for getting an insight into the noise-distorted high order derivatives. It is shown that depending on the ratio between the "virtual" fragility in the high temperature dynamic domain (mhigh) and the "real" fragility at Tg (the low temperature dynamic domain, m = mlow) glass formers can be splitted into two groups related to f < 1 and f > 1, (f = mhigh/mlow). The link of this phenomenon to the ratio between the apparent enthalpy and activation energy as well as the behavior of the configurational entropy is indicated.

Elevated mutation rate during meiosis in Saccharomyces cerevisiae.

PubMed

Rattray, Alison; Santoyo, Gustavo; Shafer, Brenda; Strathern, Jeffrey N

2015-01-01

Mutations accumulate during all stages of growth, but only germ line mutations contribute to evolution. While meiosis contributes to evolution by reassortment of parental alleles, we show here that the process itself is inherently mutagenic. We have previously shown that the DNA synthesis associated with repair of a double-strand break is about 1000-fold less accurate than S-phase synthesis. Since the process of meiosis involves many programmed DSBs, we reasoned that this repair might also be mutagenic. Indeed, in the early 1960's Magni and Von Borstel observed elevated reversion of recessive alleles during meiosis, and found that the revertants were more likely to be associated with a crossover than non-revertants, a process that they called "the meiotic effect." Here we use a forward mutation reporter (CAN1 HIS3) placed at either a meiotic recombination coldspot or hotspot near the MAT locus on Chromosome III. We find that the increased mutation rate at CAN1 (6 to 21 -fold) correlates with the underlying recombination rate at the locus. Importantly, we show that the elevated mutation rate is fully dependent upon Spo11, the protein that introduces the meiosis specific DSBs. To examine associated recombination we selected for random spores with or without a mutation in CAN1. We find that the mutations isolated this way show an increased association with recombination (crossovers, loss of crossover interference and/or increased gene conversion tracts). Polζ appears to contribute about half of the mutations induced during meiosis, but is not the only source of mutations for the meiotic effect. We see no difference in either the spectrum or distribution of mutations between mitosis and meiosis. The correlation of hotspots with elevated mutagenesis provides a mechanism for organisms to control evolution rates in a gene specific manner.

Deltoid Injections of Risperidone Long-acting Injectable in Patients with Schizophrenia

PubMed Central

Quiroz, Jorge A.; Rusch, Sarah; Thyssen, An; Kushner, Stuart

2011-01-01

Background Risperidone long-acting injectable was previously approved for treatment of schizophrenia as biweekly injections in the gluteal muscle only. We present data on local injection-site tolerability and safety of risperidone long-acting injectable and comparability of systemic exposure of deltoid versus gluteal injections. Methods Risperidone long-acting injectable was administered in an open-label, single-dose, two-way crossover study, with patients randomized to receive either 25mg gluteal/37.5mg deltoid crossover in two treatment periods or 50mg gluteal/50mg deltoid injections crossover; each treatment period was separated by an 85-day observation period (Study 1) and an open-label, multiple-dose study (4 sequential 37.5mg or 50mg deltoid injections every 2 weeks) (Study 2). The pharmacokinetic results from both the studies have already been published. Results In Study 1 (n=170), the majority of patients had no local injection-site findings, based on investigator and patient-rated evaluations. In Study 2 (n=53), seven of the 51 patients who received at least two deltoid injections discontinued (primary endpoint). However, none of the discontinuations were due to injection-site related reasons. The 90-percent upper confidence limit of the true proportion of injection-site issue withdrawals was 5.7 percent. No moderate or severe injection-site reactions were reported. Conclusion Intramuscular injections via the deltoid and gluteal sites are equivalent routes of administration of risperidone long-acting injectable with respect to local injection-site tolerability. The overall safety and tolerability profile of risperidone long-acting injectable was comparable when administered as an intramuscular injection in the deltoid (37.5mg and 50mg) and gluteal (25mg and 50mg) sites. PMID:21779538

Classical-to-Quantum Transition with Broadband Four-Wave Mixing

NASA Astrophysics Data System (ADS)

Vered, Rafi Z.; Shaked, Yaakov; Ben-Or, Yelena; Rosenbluh, Michael; Pe'er, Avi

2015-02-01

A key question of quantum optics is how nonclassical biphoton correlations at low power evolve into classical coherence at high power. Direct observation of the crossover from quantum to classical behavior is desirable, but difficult due to the lack of adequate experimental techniques that cover the ultrawide dynamic range in photon flux from the single photon regime to the classical level. We investigate biphoton correlations within the spectrum of light generated by broadband four-wave mixing over a large dynamic range of ˜80 dB in photon flux across the classical-to-quantum transition using a two-photon interference effect that distinguishes between classical and quantum behavior. We explore the quantum-classical nature of the light by observing the interference contrast dependence on internal loss and demonstrate quantum collapse and revival of the interference when the four-wave mixing gain in the fiber becomes imaginary.

Topoisomerase II Mediates Meiotic Crossover Interference

PubMed Central

Zhang, Liangran; Wang, Shunxin; Yin, Shen; Hong, Soogil; Kim, Keun P.; Kleckner, Nancy

2014-01-01

Summary Spatial patterning is a ubiquitous feature of biological systems. Meiotic crossovers provide an interesting example, defined by the classical phenomenon of crossover interference. Here, analysis of crossover patterns in budding yeast identifies a molecular pathway for interference. Topoisomerase II (Topo II) plays a central role, thus identifying a new function for this critical molecule. SUMOylation [of TopoII and axis component Red1] and ubiquitin-mediated removal of SUMOylated proteins are also required. These and other findings support the hypothesis that crossover interference involves accumulation, relief and redistribution of mechanical stress along the protein/DNA meshwork of meiotic chromosome axes, with TopoII required to adjust spatial relationships among DNA segments. PMID:25043020

Genetic Difference in Height Growth and Survival of Cottonwood Full-Sib Families

Treesearch

D. T. Cooper; W. K. Randall

1973-01-01

Sixteen full-sib families from crosses between four fast-growing female and four fast-growing male clones of cottonwood (Populus deltoides Bartr.) were clonally evaluated for 1 year in a replicated field test. Seedling size had no effect on clonal performance. Approximately 70 percent of the genetic variance for height and 20 percent of that for...

Vector competence of Malaysian Aedes albopictus with and without Wolbachia to four dengue virus serotypes.

PubMed

Joanne, Sylvia; Vythilingam, Indra; Teoh, Boon-Teong; Leong, Cherng-Shii; Tan, Kim-Kee; Wong, Meng-Li; Yugavathy, Nava; AbuBakar, Sazaly

2017-09-01

To determine the susceptibility status of Aedes albopictus with and without Wolbachia to the four dengue virus serotypes. Two newly colonised colonies of Ae. albopictus from the wild were used for the study. One colony was naturally infected with Wolbachia while in the other Wolbachia was removed by tetracycline treatment. Both colonies were orally infected with dengue virus-infected fresh blood meal. Dengue virus load was measured using quantitative RT-PCR at four-time intervals in the salivary glands, midguts and ovaries. Wolbachia did not significantly affect Malaysian Ae. albopictus dengue infection or the dissemination rate for all four dengue virus serotypes. Malaysian Ae. albopictus had the highest replication kinetics for DENV-1 and the highest salivary gland and midgut infection rate for DENV-4. Wolbachia, which naturally exists in Malaysian Ae. albopictus, does not significantly affect dengue virus replication. Malaysian Ae. albopictus is susceptible to dengue virus infections and capable of transmitting dengue virus, especially DENV-1 and DENV-4. Removal of Wolbachia from Malaysian Ae. albopictus would not reduce their susceptibility status. © 2017 John Wiley & Sons Ltd.

The fission yeast meiosis-specific Dmc1 recombinase mediates formation and branch migration of Holliday junctions by preferentially promoting strand exchange in a direction opposite to that of Rad51

PubMed Central

Murayama, Yasuto; Tsutsui, Yasuhiro; Iwasaki, Hiroshi

2011-01-01

Homologous recombination proceeds via the formation of several intermediates including Holliday junctions (HJs), which are important for creating crossover products. DNA strand exchange is a core reaction that produces these intermediates that is directly catalyzed by RecA family recombinases, of which there are two types in eukaryotes: universal Rad51 and meiosis-specific Dmc1. We demonstrated previously that Rad51 promotes four-strand exchange, mimicking the formation and branch migration of HJs. Here we show that Dmc1 from fission yeast has a similar activity, which requires ATP hydrolysis and is independent of an absolute requirement for the Swi5–Sfr1 complex. These features are critically different from three-strand exchange mediated by Dmc1, but similar to those of four-strand exchange mediated by Rad51, suggesting that strand exchange reactions between duplex–duplex and single-duplex DNAs are mechanistically different. Interestingly, despite similarities in protein structure and in reaction features, the preferential polarities of Dmc1 and Rad51 strand exchange are different (Dmc1 promotes exchange in the 5′-to-3′ direction and Rad51 promotes exchange in the 3′-to-5′ direction relative to the ssDNA region of the DNA substrate). The significance of the Dmc1 polarity is discussed within the context of the necessity for crossover production. PMID:21363965

Effects of Chlorogenic Acid-Enriched and Hydroxyhydroquinone-Reduced Coffee on Postprandial Fat Oxidation and Antioxidative Capacity in Healthy Men: A Randomized, Double-Blind, Placebo-Controlled, Crossover Trial

PubMed Central

Katada, Shun; Watanabe, Takuya; Mizuno, Tomohito; Kobayashi, Shinichi; Takeshita, Masao; Osaki, Noriko; Kobayashi, Shigeru; Katsuragi, Yoshihisa

2018-01-01

Chlorogenic acids (CGAs) reduce blood pressure and body fat, and enhance fat metabolism. In roasted coffee, CGAs exist together with the oxidant component hydroxyhydroquinone (HHQ). HHQ counteracts the antihypertensive effects of CGA, but its effects on CGA-induced fat oxidation (FOX) are unknown. Here we assessed the effects of CGA-enriched and HHQ-reduced coffee on FOX. Fifteen healthy male volunteers (age: 38 ± 8 years (mean ± SD); BMI: 22.4 ± 1.5 kg/m2) participated in this crossover study. Subjects consumed the test beverage (coffee) containing the same amount of CGA with HHQ (CGA-HHQ(+)) or without HHQ (CGA-HHQ(−)) for four weeks. Postprandial FOX and the ratio of the biological antioxidant potential (BAP) to the derivatives of reactive oxygen metabolites (d-ROMs) as an indicator of oxidative stress were assessed. After the four-week intervention, postprandial FOX and the postprandial BAP/d-ROMs ratio were significantly higher in the CGA-HHQ(−) group compared with the CGA-HHQ(+) group (4 ± 23 mg/min, group effect: p = 0.040; 0.27 ± 0.74, group effect: p = 0.007, respectively). In conclusion, reducing the amount of HHQ facilitated the postprandial FOX effects of CGA in coffee. Our findings also suggest that the mechanism underlying the inhibition of FOX by HHQ is related to postprandial oxidative stress. PMID:29690626

Double-blind, placebo-controlled study of vigabatrin (gamma-vinyl GABA) in drug-resistant epilepsy.

PubMed

Loiseau, P; Hardenberg, J P; Pestre, M; Guyot, M; Schechter, P J; Tell, G P

1986-01-01

Vigabatrin (GVG) (3 g/day) and placebo were compared as an add-on to standard therapy in therapy-resistant epileptic patients using a double-blind crossover design with randomized treatment allocation. Twenty-three patients entered the trial, with four dropping out due to either increased seizure frequency following the cross-over from GVG to placebo (n = 1), intolerance to GVG therapy (n = 2), or poor seizure record (n = 1). Of the 19 patients who completed the study, 17 had partial seizures, eight of whom had secondary generalization and two who had primary generalized seizures. Compared with placebo, GVG was associated with a significant reduction in seizure frequency (p less than 0.01), with 11 of 19 patients experiencing greater than 50% reduction in weekly seizure occurrence, two showing a 25-50% reduction, four unchanged, and two showing an increase in seizures. Global efficacy ratings were greater in the GVG period for 15 patients (p less than 0.05) compared with one in whom there was no period difference and two in whom ratings were higher in the placebo period. Fourteen of the 19 patients indicated a preference for the GVG period. Adverse effects observed during GVG treatment were generally mild and consisted of drowsiness, confusion, nausea, irritability, and constipation. No clinically significant alterations in laboratory test results were observed. No treatment-related changes in plasma concentrations of concomitant antiepileptic drugs were noted. These results confirm the antiepileptic efficacy of oral GVG in refractory epileptics.

Crossover versus mutation: a comparative analysis of the evolutionary strategy of genetic algorithms applied to combinatorial optimization problems.

PubMed

Osaba, E; Carballedo, R; Diaz, F; Onieva, E; de la Iglesia, I; Perallos, A

2014-01-01

Since their first formulation, genetic algorithms (GAs) have been one of the most widely used techniques to solve combinatorial optimization problems. The basic structure of the GAs is known by the scientific community, and thanks to their easy application and good performance, GAs are the focus of a lot of research works annually. Although throughout history there have been many studies analyzing various concepts of GAs, in the literature there are few studies that analyze objectively the influence of using blind crossover operators for combinatorial optimization problems. For this reason, in this paper a deep study on the influence of using them is conducted. The study is based on a comparison of nine techniques applied to four well-known combinatorial optimization problems. Six of the techniques are GAs with different configurations, and the remaining three are evolutionary algorithms that focus exclusively on the mutation process. Finally, to perform a reliable comparison of these results, a statistical study of them is made, performing the normal distribution z-test.

Crossover versus Mutation: A Comparative Analysis of the Evolutionary Strategy of Genetic Algorithms Applied to Combinatorial Optimization Problems

PubMed Central

Osaba, E.; Carballedo, R.; Diaz, F.; Onieva, E.; de la Iglesia, I.; Perallos, A.

2014-01-01

Since their first formulation, genetic algorithms (GAs) have been one of the most widely used techniques to solve combinatorial optimization problems. The basic structure of the GAs is known by the scientific community, and thanks to their easy application and good performance, GAs are the focus of a lot of research works annually. Although throughout history there have been many studies analyzing various concepts of GAs, in the literature there are few studies that analyze objectively the influence of using blind crossover operators for combinatorial optimization problems. For this reason, in this paper a deep study on the influence of using them is conducted. The study is based on a comparison of nine techniques applied to four well-known combinatorial optimization problems. Six of the techniques are GAs with different configurations, and the remaining three are evolutionary algorithms that focus exclusively on the mutation process. Finally, to perform a reliable comparison of these results, a statistical study of them is made, performing the normal distribution z-test. PMID:25165731

Chitosan and alginate types of bio-membrane in fuel cell application: An overview

NASA Astrophysics Data System (ADS)

Shaari, N.; Kamarudin, S. K.

2015-09-01

The major problems of polymer electrolyte membrane fuel cell technology that need to be highlighted are fuel crossovers (e.g., methanol or hydrogen leaking across fuel cell membranes), CO poisoning, low durability, and high cost. Chitosan and alginate-based biopolymer membranes have recently been used to solve these problems with promising results. Current research in biopolymer membrane materials and systems has focused on the following: 1) the development of novel and efficient biopolymer materials; and 2) increasing the processing capacity of membrane operations. Consequently, chitosan and alginate-based biopolymers seek to enhance fuel cell performance by improving proton conductivity, membrane durability, and reducing fuel crossover and electro-osmotic drag. There are four groups of chitosan-based membranes (categorized according to their reaction and preparation): self-cross-linked and salt-complexed chitosans, chitosan-based polymer blends, chitosan/inorganic filler composites, and chitosan/polymer composites. There are only three alginate-based membranes that have been synthesized for fuel cell application. This work aims to review the state-of-the-art in the growth of chitosan and alginate-based biopolymer membranes for fuel cell applications.

Effects of chocolate-based products intake on blood glucose, insulin and ghrelin levels and on satiety in young people: a cross-over experimental study.

PubMed

Zhang, Cai-Xia; Long, Wei-Qing; Ye, Yan-Bin; Lu, Min-Shan; Zhang, Nai-Qi; Xu, Ming; Huang, Jing; Su, Yi-Xiang

2018-02-19

This cross-over experimental study aimed to examine the effects of filled chocolate consumption on blood glucose, insulin and ghrelin levels in 20 volunteers. After a one-week run-in period, study participants consumed two chocolate-based products, the tested biscuit or water for 21 days as a morning snack. After a two-week wash-out period, participants consumed another tested food for another 21 days. Each participant consumed all four test foods within an 18-week period. The participants' blood insulin increased slowly after two chocolate-based products intakes on the first day and satiety levels after eating chocolate-based products and the tested biscuit were the same. Chocolate consumption for three weeks had no adverse effects on blood glucose, insulin or ghrelin levels. In conclusion, compared to eating the tested biscuit, 21-day consumption of the tested chocolate-based products had no adverse effects on the blood glucose, insulin and ghrelin levels. This trial is registered with chictr.org.cn: ChiCTR-IOR-16009525.

Towards the GEOSAT Follow-On Precise Orbit Determination Goals of High Accuracy and Near-Real-Time Processing

NASA Technical Reports Server (NTRS)

Lemoine, Frank G.; Zelensky, Nikita P.; Chinn, Douglas S.; Beckley, Brian D.; Lillibridge, John L.

2006-01-01

The US Navy's GEOSAT Follow-On spacecraft (GFO) primary mission objective is to map the oceans using a radar altimeter. Satellite laser ranging data, especially in combination with altimeter crossover data, offer the only means of determining high-quality precise orbits. Two tuned gravity models, PGS7727 and PGS7777b, were created at NASA GSFC for GFO that reduce the predicted radial orbit through degree 70 to 13.7 and 10.0 mm. A macromodel was developed to model the nonconservative forces and the SLR spacecraft measurement offset was adjusted to remove a mean bias. Using these improved models, satellite-ranging data, altimeter crossover data, and Doppler data are used to compute both daily medium precision orbits with a latency of less than 24 hours. Final precise orbits are also computed using these tracking data and exported with a latency of three to four weeks to NOAA for use on the GFO Geophysical Data Records (GDR s). The estimated orbit precision of the daily orbits is between 10 and 20 cm, whereas the precise orbits have a precision of 5 cm.