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PubMed2006

Mean crossover functions for uniaxial three-dimensional Ising-like systems.

We give simple expressions for the mean of the max and min bounds of the critical-to-classical crossover functions, previously calculated [Bagnuls and Bervillier, Phys. Rev. E 65, 066132 (2002)] within the massive renormalization scheme of the Phi(d)4(n) model in three dimensions (d = 3) and scalar order parameter (n = 1) of the Ising-like universality class. The mean functions are determined relying on the properties of the theoretical functions in the two limiting three-dimensional (3D) Ising-like and mean-field-like descriptions close to the Wilson-Fisher fixed point and to the Gaussian fixed point, respectively. Such descriptions correspond to the preasymptotic domains near each fixed point where a Wegner expansion restricted to two terms (leading and first confluent terms) is valid. The Ising-like preasymptotic domain description includes the correlations between parameters due to the error-bar determination of the exponents and amplitude combinations very close to the Wilson-Fisher fixed point. Adding the equivalent description of the mean field preasymptotic domain close to the Gaussian fixed point leads to define each mean crossover function with three calculated parameters. Fixing a unique value of one parameter whatever the selected mean crossover function, we use this parameter as a relative sensor to estimate the dominant nature, either (Ising-like) critical, or (mean-field-like) classical, of the crossover behavior. Finally, we obtain an explicit criterion to measure the extension of the Ising-like preasymptotic domain which can then permit to coherently account for measurements performed in systems where the asymptotical approach to the critical point remains finite, using a well-controlled number of system-dependent parameters (like in the subclass of one-component fluids).

Journal Article↗

PubMed2005

The crossover design to evaluate the efficacy of plaque removal in tooth-brushing studies.

OBJECTIVES: To evaluate the crossover clinical trial design to assess plaque removal efficacy of the Sonicare Elite. MATERIAL AND METHODS: A single-cohort, 12-week, two-treatment, single-blind, crossover clinical trial recruited 45 subjects. Plaque was recorded using the modified Quigley and Hein index plaque index (PI). After screening, subjects used the toothbrush for 2 weeks and were reminded to abstain from tooth cleaning 12-18 h prior to appointments. At visit two, subjects were randomized to 2 or 2(1/2) min. brushing time. PIs was recorded pre- and post-brushing. Subjects brushed for the allocated time for a further 2 weeks. At visit 3, PIs were recorded pre- and post-brushing. Two weeks later, at visit 4, the subjects crossed over and the protocol was repeated. RESULTS: There was no evidence of a learning effect within each arm of the crossover. A significant period effect was detected; however, no significant treatment by period effect was found. 2(1/2) min. brushing removed more plaque at full mouth (p=0.037), smooth (p=0.012) and lingual (p=0.002) sites compared with 2 min. CONCLUSION: The crossover design is a valid model for assessing plaque removal efficacy in tooth-brushing studies where no carry-over effect is clinically plausible.

Adolescent↗

PubMedDate not supplied

Problems associated with simulated light sensitometry for low-crossover medical x-ray films.

Over the past ten years the evolution of medical x-ray films has been toward films with reduced intensifying-screen light crossover in order to reduce blur and obtain higher spatial resolution. For films with very low crossover, misleading and incorrect sensitometric data may be obtained for film contrast evaluation and processor control if a simulated light sensitometer with a single-sided, light-exposing device is used. Screen light exposures were made using an inverse square, intensity-scale sensitometer. Simulated light exposures were made using a widely used single-sided, simulated-light sensitometer commonly used for film processor quality control, and a new simulated-light sensitometer capable of producing either single- or double-sided sensitometric exposures. The films used included one single-emulsion film and three double-emulsion medical x-ray films with light-crossover values ranging from approximately 3% to 30%. Sensitometric data showed a significant distortion (bump) in the characteristic curve for the 3% light-crossover film exposed with the single-sided, simulated-light sensitometer.

Light↗

PubMed1995

Efficient system of homologous RNA recombination in brome mosaic virus: sequence and structure requirements and accuracy of crossovers.

Brome mosaic virus (BMV), a tripartite positive-stranded RNA virus of plants engineered to support intersegment RNA recombination, was used for the determination of sequence and structural requirements of homologous crossovers. A 60-nucleotide (nt) sequence, common between wild-type RNA2 and mutant RNA3, supported efficient repair (90%) of a modified 3' noncoding region in the RNA3 segment by homologous recombination with wild-type RNA2 3' noncoding sequences. Deletions within this sequence in RNA3 demonstrated that a nucleotide identity as short as 15 nt can support efficient homologous recombination events, while shorter (5-nt) sequence identity resulted in reduced recombination frequency (5%) within this region. Three or more mismatches within a downstream portion of the common 60-nt RNA3 sequence affected both the incidence of recombination and the distribution of crossover sites, suggesting that besides the length, the extent of sequence identity between two recombining BMV RNAs is an important factor in homologous recombination. Site-directed mutagenesis of the common sequence in RNA3 did not reveal a clear correlation between the stability of predicted secondary structures and recombination activity. This indicates that homologous recombination does not require similar secondary structures between two recombining RNAs at the sites of crossovers. Nearly 20% of homologous recombinants were imprecise (aberrant), containing either nucleotide mismatches, small deletions, or small insertions within the region of crossovers. This implies that homologous RNA recombination is not as accurate as proposed previously. Our results provide experimental evidence that the requirements and thus the mechanism of homologous recombination in BMV differ from those of previously described heteroduplex-mediated nonhomologous recombination (P. D. Nagy and J. J. Bujarski, Proc. Natl. Acad. Sci. USA 90:6390-6394, 1993).

Base Sequence↗

PubMed2005

Homologous crossovers among molecules of brome mosaic bromovirus RNA1 or RNA2 segments in vivo.

Previously we demonstrated frequent homologous crossovers among molecules of the RNA3 segment in the tripartite brome mosaic bromovirus (BMV) RNA genome (A. Bruyere, M. Wantroba, S. Flasinski, A. Dzianott, and J. J. Bujarski, J. Virol. 74:4214-4219, 2000). To further our knowledge about mechanisms of viral RNA genome variability, in this paper we have studied homologous recombination in BMV RNA1 and RNA2 components during infection. We have found that basal RNA-RNA crossovers could occur within coding regions of both RNAs, although recombination frequencies slightly varied at different RNA sections. In all cases, the frequencies were much lower than the rate observed for the intercistronic recombination hot spot in BMV RNA3. Probability calculations accounted for at least one homologous crossover per RNA molecule per replication cycle. In addition, we have demonstrated an efficient repair of mutations within the conserved 3' and 5' noncoding regions, most likely due to error-prone BMV RNA replication. Overall, our data verify that homologous crossovers are common events a during virus life cycle, and we discuss their importance for viral RNA genetics.

Bromovirus↗

PubMed1989

Sodium restriction and blood pressure in hypertensive type II diabetics: randomised blind controlled and crossover studies of moderate sodium restriction and sodium supplementation.

OBJECTIVE: To determine the effect of moderate dietary sodium restriction on the hypertension of non-insulin-dependent (type II) diabetes. DESIGN: Randomised parallel controlled study of moderate sodium restriction for three months compared with usual diabetic diet, followed by randomised double blind crossover trial of sustained release preparation of sodium for one month versus placebo for one month in patients continuing with sodium restriction. SETTING: Patients attending diabetic outpatient clinic of city hospital. PATIENTS: Thirty four patients with established type II diabetes complicated by mild hypertension (systolic blood pressure greater than 160 mm Hg or diastolic pressure greater than 95 mm Hg on three consecutive occasions). Patients already taking antihypertensive agents (but not diuretics) not barred from study provided that criteria for mild hypertension still met. Conditions precluding patients from study were diabetic or hypertensive nephropathy, cardiac failure, and pregnancy. INTERVENTIONS: After run in phase with recordings at seven weeks, three weeks, and time zero patients were allocated at random to receive moderate dietary sodium restriction for three months (n = 17) or to continue with usual diabetic diet. Subsequently nine patients in sodium restriction group continued with regimen for a further two months, during which they completed a randomised double blind crossover trial of sustained release preparation of sodium (Slow Sodium 80 mmol daily) for one month versus matching placebo for one month. END POINT: Reduction in blood pressure in type II diabetics with mild hypertension. MEASUREMENTS AND MAIN RESULTS: Supine and erect blood pressure, body weight, and 24 hour urinary sodium and potassium excretion measured monthly during parallel group and double blind crossover studies. After parallel group study sodium restriction group showed significant reduction in systolic blood pressure (supine 19.2 mm Hg, erect 21.4 mm Hg; p less than 0.001) and mean daily urinary sodium excretion (mean reduction 60 mmol/24 h). There were no appreciable changes in weight, diabetic control, or diastolic pressure. No significant changes occurred in controls. In double blind crossover study mean supine systolic blood pressure rose significantly (p less than 0.005) during sodium supplementation (to 171 mm Hg) compared with value after three months of sodium restriction alone (159.9 mm Hg) and after one month of placebo (161.8 mm Hg). CONCLUSIONS: Moderate dietary restriction of sodium has a definite hypotensive effect, which may be useful in mild hypertension of type II diabetes.

Clinical Trials as Topic↗

PubMed2000

Should we use a case-crossover design?

The first decade of experience with case-crossover studies has shown that the design applies best if the exposure is intermittent, the effect on risk is immediate and transient, and the outcome is abrupt. However, this design has been used to study single changes in exposure level, gradual effects on risk, and outcomes with insidious onsets. To estimate relative risk, the exposure frequency during a window just before outcome onset is compared with exposure frequencies during control times rather than in control persons. One or more control times are supplied by each of the cases themselves, to control for confounding by constant characteristics and self-confounding between the trigger's acute and chronic effects. This review of published case-crossover studies is designed to help the reader prepare a better research proposal by understanding triggers and deterrents, target person times, alternative study bases, crossover cohorts, induction times, effect and hazard periods, exposure windows, the exposure opportunity fallacy, a general likelihood formula, and control crossover analysis.

Acute Disease↗

PubMed1994

Balance of carbohydrate and lipid utilization during exercise: the "crossover" concept.

The "crossover" concept represents a theoretical means by which one can understand the effects of exercise intensity and prior endurance training on the balance of carbohydrate (CHO) and lipid metabolism during sustained exercise. According to the crossover concept, endurance training results in muscular biochemical adaptations that enhance lipid oxidation as well as decrease the sympathetic nervous system responses to given submaximal exercise stresses. These adaptations promote lipid oxidation during mild- to moderate-intensity exercise. In contrast, increases in exercise intensity are conceived to increase contraction-induced muscle glycogenolysis, alter the pattern of fiber type recruitment, and increase sympathetic nervous system activity. Therefore the pattern of substrate utilization in an individual at any point in time depends on the interaction between exercise intensity-induced responses (which increase CHO utilization) and endurance training-induced responses (which promote lipid oxidation). The crossover point is the power output at which energy from CHO-derived fuels predominates over energy from lipids, with further increases in power eliciting a relative increment in CHO utilization and a decrement in lipid oxidation. The contemporary literature contains data indicating that, after endurance training, exercise at low intensities (< or = 45% maximal O2 uptake) is accomplished with lipid as the main substrate. In contrast, the literature also contains reports that are interpreted to indicate that during hard-intensity exercise (approximately 75% maximal O2 uptake) CHO is the predominant substrate. Seen within the context of the crossover concept these apparently divergent results are, in fact, consistent.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1999

Crossover accelerates evolution in GAs with a Babel-like fitness landscape: mathematical analyses.

The effectiveness of crossover in accelerating evolution in genetic algorithms (GAs) is studied with a haploid finite population of bit sequences. A Babel-like fitness landscape is assumed. There is a single bit sequence (schema) that is significantly more advantageous than all the others. We study the time until domination of the advantageous schema (Τ&subd;). Evolution proceeds with appearance, spread, and domination of the advantageous schema. The most important process determining Τ&subd; is the appearance (creation) of the advantageous schema. Crossover helps this creation process and enhances the rate of evolution. To study this effect, we first establish an analytical method to estimate Τ&subd; with or without crossover. Then, we conduct a numerical analysis using the frequency vector representation of the population with the recurrence relations formulated after GA operations. Finally, we carry out direct computer simulations with simple GAs operating on a population of binary strings directly prepared in the computer memory to examine the performance of the two analytical methods. It is shown that Τ&subd; is reduced greatly by crossover with a mildly high rate when the mutation rate is adjusted to a moderate value and that an advantageous schema has a fairly larger order (the number of bits). From these observations, we can determine implementation criteria for GAs, which are useful when we are applying GAs to engineering problems having a conspicuously discontinuous fitness landscape.

Algorithms↗

PubMed1994

Bayesian analyses of two-treatment crossover studies.

This review covers Bayesian analyses of two-treatment crossover studies. The main emphasis is placed on the analysis of continuous data although we also consider dichotomous responses. Studies discussed include (1) the simple two-period, two-treatment crossover, (2) the two-period crossover with one baseline measurement, (3) the two-period crossover with two baselines and (4) the extra-period design with two treatment sequences.

Bayes Theorem↗

PubMed2002

Distinct functions of S. pombe Rec12 (Spo11) protein and Rec12-dependent crossover recombination (chiasmata) in meiosis I; and a requirement for Rec12 in meiosis II.

BACKGROUND: In most organisms proper reductional chromosome segregation during meiosis I is strongly correlated with the presence of crossover recombination structures (chiasmata); recombination deficient mutants lack crossovers and suffer meiosis I nondisjunction. We report that these functions are separable in the fission yeast Schizosaccharomyces pombe. RESULTS: Intron mapping and expression studies confirmed that Rec12 is a member of the Spo11/Top6A topoisomerase family required for the formation of meiotic dsDNA breaks and recombination. rec12-117, rec12-D15 (null), and rec12-Y98F (active site) mutants lacked most crossover recombination and chromosomes segregated abnormally to generate aneuploid meiotic products. Since S. pombe contains only three chromosome pairs, many of those aneuploid products were viable. The types of aberrant chromosome segregation were inferred from the inheritance patterns of centromere linked markers in diploid meiotic products. The rec12-117 and rec12-D15 mutants manifest segregation errors during both meiosis I and meiosis II. Remarkably, the rec12-Y98F (active site) mutant exhibited essentially normal meiosis I segregation patterns, but still exhibited meiosis II segregation errors. CONCLUSIONS: Rec12 is a 345 amino acid protein required for most crossover recombination and for chiasmatic segregation of chromosomes during meiosis I. Rec12 also participates in a backup distributive (achiasmatic) system of chromosome segregation during meiosis I. In addition, catalytically-active Rec12 mediates some signal that is required for faithful equational segregation of chromosomes during meiosis II.

Journal Article↗

PubMed2005

Drosophila ERCC1 is required for a subset of MEI-9-dependent meiotic crossovers.

Drosophila MEI-9 is the catalytic subunit of a DNA structure-specific endonuclease required for nucleotide excision repair (NER). The enzymatic activity of this endonuclease during NER requires the presence of a second, noncatalytic subunit called ERCC1. In addition to its role in NER, MEI-9 is required for the generation of most meiotic crossovers. To better understand the role of MEI-9 in crossover formation, we report here the characterization of the Drosophila Ercc1 gene. We created an Ercc1 mutant through homologous gene targeting. We find that Ercc1 mutants are identical to mei-9 mutants in sensitivity to DNA-damaging agents, but have a less severe reduction in the number of meiotic crossovers. MEI-9 protein levels are reduced in Ercc1 mutants; however, overexpression of MEI-9 is not sufficient to restore meiotic crossing over in Ercc1 mutants. We conclude that MEI-9 can generate some meiotic crossovers in an ERCC1-independent manner.

Alleles↗

PubMed2005

Crossover interference on nucleolus organizing region-bearing chromosomes in Arabidopsis.

In most eukaryotes, crossovers are not independently distributed along the length of a chromosome. Instead, they appear to avoid close proximity to one another--a phenomenon known as crossover interference. Previously, for three of the five Arabidopsis chromosomes, we measured the strength of interference and suggested a model wherein some crossovers experience interference while others do not. Here we show, using the same model, that the fraction of interference-insensitive crossovers is significantly smaller on the remaining two chromosomes. Since these two chromosomes bear the Arabidopsis NOR domains, the possibility that these chromosomal regions influence interference is discussed.

Arabidopsis↗

PubMed1999

Control for seasonal variation and time trend in case-crossover studies of acute effects of environmental exposures.

The case-crossover study design is used to study the triggers of acute outcomes in populations. It controls for all measured and unmeasured time-invariant confounders by design. Studies of environmental triggers of morbidity are potentially confounded by temporal trends in the outcome owing to omitted covariates. We conducted a simulation study of the case-crossover design's ability to control for temporal confounding patterns by design rather than through modeling. We compared five case-crossover control sampling strategies including the matched pair, a symmetric bi-directional, a total history approach, and two approaches proposed by Navidi (Biometrics 1998;54:596-605). We simulated true relative risks (RR) of 1.10 and 2.00 and induced confounding by seasonal patterns as well as linear and nonlinear long-term trends to yield estimated RR values as high as 3.18. The symmetric bi-directional approach was compared across four lag times and controlled for temporal confounding best when the lag was shortest. With a 1-week lag, it estimated the RR values as 1.10 and 2.01. The four other approaches failed to control for the temporal trends. Our simulations show that the symmetric bi-directional case-crossover design can substantially control for temporal confounding by design although it is not as efficient (66%) as Poisson regression analysis.

Computer Simulation↗

PubMed1999

[The crossover effect of the propositional text representation and the mental model:the role of individual differences in spatial imagery ability].

The crossover effect (Mani & Johnson-Laird, 1982) predicts that a mental model is more likely to be available after reading a determinate description of a spatial scene than after reading an indeterminate description whereas the reverse should apply to the propositional text representation. Although attempts to replicate this pattern were less than convincing, the crossover effect has often been stated as evidence justifying the differentiation of propositional representations and mental models. In an experiment with 44 adult, German-speaking participants, it was investigated whether the crossover effect is moderated by individual differences in spatial imagery ability. Participants read 6 determinate and 6 indeterminate descriptions of schematic, non-schematic, or schema-incompatible spatial scenes. Recognition data showed a crossover effect only in participants with lower ability. In the high-ability group the propositional text representation was less available than in the low-ability group, independent of whether or not a mental model could be constructed. The results explain why earlier replications might have failed. Consequences for current mental model theories of text comprehension are discussed.

Adult↗

PubMed2000

A case-crossover analysis of a case-control study of alcohol consumption and coronary events: the effects of exposure definition and the use of control data.

BACKGROUND: Case-crossover studies can be used to assess the effects of transient exposures in acute events by comparing cases' exposures at the time of the event against their usual exposure. Cases from a case-control study can also be analysed by this method if appropriate information is obtained. METHODS: We apply the case-crossover method to data collected in a case-control study of acute coronary events, to estimate the risk of alcohol consumption in the 24 h before a coronary event. Two questions, concerning the usual frequency of consuming alcohol and how much was consumed, were used in the analysis. The sensitivity of effect estimates to the two questions and to different ways of eliciting probabilities from them, are examined. The cases and controls were both analysed in the same way, assigning controls a 'pseudo-event' time at random. It is suggested that controls may provide a benchmark to establish whether bias exists in the case-series analysis. RESULTS: We find that the case-crossover analysis is sensitive to how exposure probabilities are assigned. Adopting a Poisson model for exposures leads to inflated risk estimates. The bias is removed if the control series is used to adjust estimates. There appears to be a small protective effect from alcohol consumption. CONCLUSION: Case-crossover designs have considerable potential, but reliable information on usual exposure limits their applicability. More research is required on how best to elicit exposure probabilities.

Alcohol Drinking↗

PubMed2002

A randomized crossover study to evaluate LDL-cholesterol lowering effect of a generic product of simvastatin (Unison Company) compared to simvastatin (Zocor) in hypercholesterolemic subjects.

It is agreed that people with a high blood LDL-cholesterol level will have a higher risk of coronary heart disease (CAD) than those with low blood LDL-cholesterol level. Because of the present National Drug Strategy of Thailand, the promotion of "in-country production" of a generic drug has been established. Simvastatin is one of the drugs in this strategy. In this, the primary report of a randomized crossover study with washout period for a cholesterol lowering effect in a generic product of simvastatin (Unison company) which was compared to the original simvastatin (Zocor) hypercholesterolemic to the subjects were presented. Simvastatin used in this study were derived from two sources. The first group was the original product (Zocor), dosage 10 mg, Lot No IC4/36(N) from Merck Sharp & Dohme Company and the second group was a generic product, dosage 10 mg, Lot No T05/080 and T06/109 from Unison Company. All simvastatin tablets from the first and second sources were inserted into closed capsule of the same shape and called drug A and drug B, respectively. Both the physician in-charge and the subjects in this study were blinded for the content inside the capsule (Double blind). Thirty drug capsules were put into a sachet and distributed to the subject at each visit. The interval between each visit was 4 weeks. All subjects were asked to bring back the residual capsule within the sachet to the researcher at each visit in order to evaluate the subject's compliance. All subjects had physical examination and blood tests at each visit. Furthermore, all subjects were advised to practice diet control and regular in-take of the drug capsule daily after their evening meal. All 48 subjects were randomly allocated into 2 groups. This study was run as a randomized crossover study. After taking the drugs for the first 8 weeks, no statistically significant difference of blood LDL-cholesterol between the first and second group was detected. After a 4 week washout period, crossover and taking the drugs for the last 8 weeks, no statistically significant difference of blood LDL-cholesterol between the first and second group was detected. At the end of this study, comparing both groups by ANOVA crossover test, no statistically significant difference of blood LDL-cholesterol between the first and second group was detected.

Adult↗

PubMed2002

[Lampbrush chromosomes in the japanese quail Coturnix coturnix japonica: cytological maps of macro chromosomes and meiotic crossover frequency in females].

Cytological maps of lampbrush macrobivalents of the Japanese quail (Coturnix coturnix japonica) were constructed. Investigation of chiasmata allowed determination of the meiotic frequency of reciprocal genetic recombination (crossing over) in Japanese quail females. The total chiasma number in bivalents of Japanese quail oocyte nuclei was determined to be 53-58. Macrobivalents 1-5 and Z of the Japanese quail had on average 3.3 chiasmata per bivalent, and microbivalents, 1.0-1.1 chiasmata per bivalent. The chiasmata (crossover) frequency in Japanese quail females was lower than in chicks. In macrochromosomes of Japanese quail females, one crossover occurred per 43.9 Mb, and in chicken, per 30.0 Mb. Judging from chiasma frequency, the genetic length of the Japanese quail genome is likely to be 2650-2900 cM. Crossover frequency in the species was 0.023 per Mb in macrobivalents and 0.07-0.08 Mb in microbivalents and for the total genome, 0.041 crossovers per Mb. The genetic length of one Mb (theta) in female Japanese quails was 1.14 cM in macrochromosomes, 3.60-4.12 cM in microchromosomes, and about 1.96-2.15 cM averaged over the genome.

Animals↗