The Effect of Four-Lane to Three-Lane Conversion on the Number of Crashes and Crash Rates in Iowa Roads, June 2005

We analyze crash data collected by the Iowa Department of Transportation using Bayesian methods. The data set includes monthly crash numbers, estimated monthly traffic volumes, site length and other information collected at 30 paired sites in Iowa over more than 20 years during which an intervention experiment was set up. The intervention consisted in transforming 15 undivided road segments from four-lane to three lanes, while an additional 15 segments, thought to be comparable in terms of traffic safety-related characteristics were not converted. The main objective of this work is to find out whether the intervention reduces the number of crashes and the crash rates at the treated sites. We fitted a hierarchical Poisson regression model with a change-point to the number of monthly crashes per mile at each of the sites. Explanatory variables in the model included estimated monthly traffic volume, time, an indicator for intervention reflecting whether the site was a “treatment” or a “control” site, and various interactions. We accounted for seasonal effects in the number of crashes at a site by including smooth trigonometric functions with three different periods to reflect the four seasons of the year. A change-point at the month and year in which the intervention was completed for treated sites was also included. The number of crashes at a site can be thought to follow a Poisson distribution. To estimate the association between crashes and the explanatory variables, we used a log link function and added a random effect to account for overdispersion and for autocorrelation among observations obtained at the same site. We used proper but non-informative priors for all parameters in the model, and carried out all calculations using Markov chain Monte Carlo methods implemented in WinBUGS. We evaluated the effect of the four to three-lane conversion by comparing the expected number of crashes per year per mile during the years preceding the conversion and following the conversion for treatment and control sites. We estimated this difference using the observed traffic volumes at each site and also on a per 100,000,000 vehicles. We also conducted a prospective analysis to forecast the expected number of crashes per mile at each site in the study one year, three years and five years following the four to three-lane conversion. Posterior predictive distributions of the number of crashes, the crash rate and the percent reduction in crashes per mile were obtained for each site for the months of January and June one, three and five years after completion of the intervention. The model appears to fit the data well. We found that in most sites, the intervention was effective and reduced the number of crashes. Overall, and for the observed traffic volumes, the reduction in the expected number of crashes per year and mile at converted sites was 32.3% (31.4% to 33.5% with 95% probability) while at the control sites, the reduction was estimated to be 7.1% (5.7% to 8.2% with 95% probability). When the reduction in the expected number of crashes per year, mile and 100,000,000 AADT was computed, the estimates were 44.3% (43.9% to 44.6%) and 25.5% (24.6% to 26.0%) for converted and control sites, respectively. In both cases, the difference in the percent reduction in the expected number of crashes during the years following the conversion was significantly larger at converted sites than at control sites, even though the number of crashes appears to decline over time at all sites. Results indicate that the reduction in the expected number of sites per mile has a steeper negative slope at converted than at control sites. Consistent with this, the forecasted reduction in the number of crashes per year and mile during the years after completion of the conversion at converted sites is more pronounced than at control sites. Seasonal effects on the number of crashes have been well-documented. In this dataset, we found that, as expected, the expected number of monthly crashes per mile tends to be higher during winter months than during the rest of the year. Perhaps more interestingly, we found that there is an interaction between the four to three-lane conversion and season; the reduction in the number of crashes appears to be more pronounced during months, when the weather is nice than during other times of the year, even though a reduction was estimated for the entire year. Thus, it appears that the four to three-lane conversion, while effective year-round, is particularly effective in reducing the expected number of crashes in nice weather.

Generation of short-term murine natural killer cell clones to analyze Ly49 gene expression.

Natural killer (NK) cellsexpress receptors specific for class I major histocompatibility complex (MHC) molecules. In the mouse, the class I specific receptors identified to date belong to the polymorphic Ly49 receptor family. Engagement of Ly49 receptors with their respective MHC ligands results in negative regulation of NK cell effector functions, consistent with a critical role of these receptors in "missing self" recognition. The Ly49 receptors analyzed so far are clonally distributed such that multiple distinct Ly49 receptors can be expressed by individual NK cells (for review see refs. 1-3). The finding that most NK cells that express the Ly49A receptor do so from a single Ly49A allele (whereby expression can occur from the maternal or the paternal chromosome) may thus reflect a putative receptor distribution process that restricts the number of Ly49 receptors expressed in a single NK cell (3-5).

Avalanches in a fluctuationless first-order phase transition in a random-bond Ising model

We study the behavior of the random-bond Ising model at zero temperature by numerical simulations for a variable amount of disorder. The model is an example of systems exhibiting a fluctuationless first-order phase transition similar to some field-induced phase transitions in ferromagnetic systems and the martensitic phase transition appearing in a number of metallic alloys. We focus on the study of the hysteresis cycles appearing when the external field is swept from positive to negative values. By using a finite-size scaling hypothesis, we analyze the disorder-induced phase transition between the phase exhibiting a discontinuity in the hysteresis cycle and the phase with the continuous hysteresis cycle. Critical exponents characterizing the transition are obtained. We also analyze the size and duration distributions of the magnetization jumps (avalanches).

Finite-size scaling analysis of the avalanches in the three-dimensional Gaussian random-field Ising model with metastable dynamics

A numerical study is presented of the third-dimensional Gaussian random-field Ising model at T=0 driven by an external field. Standard synchronous relaxation dynamics is employed to obtain the magnetization versus field hysteresis loops. The focus is on the analysis of the number and size distribution of the magnetization avalanches. They are classified as being nonspanning, one-dimensional-spanning, two-dimensional-spanning, or three-dimensional-spanning depending on whether or not they span the whole lattice in different space directions. Moreover, finite-size scaling analysis enables identification of two different types of nonspanning avalanches (critical and noncritical) and two different types of three-dimensional-spanning avalanches (critical and subcritical), whose numbers increase with L as a power law with different exponents. We conclude by giving a scenario for avalanche behavior in the thermodynamic limit.

Hysteresis and avalanches in the T=0 random field ising model with 2-spin flip dynamics

We study the nonequilibrium behavior of the three-dimensional Gaussian random-field Ising model at T=0 in the presence of a uniform external field using a two-spin-flip dynamics. The deterministic, history-dependent evolution of the system is compared with the one obtained with the standard one-spin-flip dynamics used in previous studies of the model. The change in the dynamics yields a significant suppression of coercivity, but the distribution of avalanches (in number and size) stays remarkably similar, except for the largest ones that are responsible for the jump in the saturation magnetization curve at low disorder in the thermodynamic limit. By performing a finite-size scaling study, we find strong evidence that the change in the dynamics does not modify the universality class of the disorder-induced phase transition.

Diluted three-dimensional random field Ising model at zero temperature with metastable dynamics.

The influence of vacancy concentration on the behavior of the three-dimensional random field Ising model with metastable dynamics is studied. We have focused our analysis on the number of spanning avalanches which allows us a clear determination of the critical line where the hysteresis loops change from continuous to discontinuous. By a detailed finite-size scaling analysis we determine the phase diagram and numerically estimate the critical exponents along the whole critical line. Finally, we discuss the origin of the curvature of the critical line at high vacancy concentration.

A non-random chromosome abnormality found in precursor-B lineage acute lymphoblastic leukaemia: dic(9;20)(p1?3;q11).

A comparison of cytogenetical data on acute lymphoblastic leukaemia studied at four large European centres has revealed a non-random dicentric chromosome abnormality: dic(9;20) (p1?3;q11) in 10 patients, nine of whom were children. All had early precursor-B lineage ALL, and eight children had a non-standard risk clinical presentation. The origin of the dicentric chromosome was demonstrated using a range of chromosome banding techniques. This was confirmed by FISH using paints and centromeric probes for chromosomes 9 and 20, together with a number of cosmid probes. The follow-up time of these patients is presently too short and the number of patients too few to determine the prognostic significant of this chromosome abnormality.

An analytical approach to sorting in periodic and random potentials

There has been a recent revolution in the ability to manipulate micrometer-sized objects on surfaces patterned by traps or obstacles of controllable configurations and shapes. One application of this technology is to separate particles driven across such a surface by an external force according to some particle characteristic such as size or index of refraction. The surface features cause the trajectories of particles driven across the surface to deviate from the direction of the force by an amount that depends on the particular characteristic, thus leading to sorting. While models of this behavior have provided a good understanding of these observations, the solutions have so far been primarily numerical. In this paper we provide analytic predictions for the dependence of the angle between the direction of motion and the external force on a number of model parameters for periodic as well as random surfaces. We test these predictions against exact numerical simulations.

Occupancy of a single site by many random walkers

We consider an infinite number of noninteracting lattice random walkers with the goal of determining statistical properties of the time, out of a total time T, that a single site has been occupied by n random walkers. Initially the random walkers are assumed uniformly distributed on the lattice except for the target site at the origin, which is unoccupied. The random-walk model is taken to be a continuous-time random walk and the pausing-time density at the target site is allowed to differ from the pausing-time density at other sites. We calculate the dependence of the mean time of occupancy by n random walkers as a function of n and the observation time T. We also find the variance for the cumulative time during which the site is unoccupied. The large-T behavior of the variance differs according as the random walk is transient or recurrent. It is shown that the variance is proportional to T at large T in three or more dimensions, it is proportional to T3/2 in one dimension and to TlnT in two dimensions.

Simulations in Evolution. III. Randomness as a Generator of Opportunities.

In Neo-Darwinism, variation and natural selection are the two evolutionary mechanisms which propel biological evolution. Our previous reports presented a histogram model to simulate the evolution of populations of individuals classified into bins according to an unspecified, quantifiable phenotypic character, and whose number in each bin changed generation after generation under the influence of fitness, while the total population was maintained constant. The histogram model also allowed Shannon entropy (SE) to be monitored continuously as the information content of the total population decreased or increased. Here, a simple Perl (Practical Extraction and Reporting Language) application was developed to carry out these computations, with the critical feature of an added random factor in the percent of individuals whose offspring moved to a vicinal bin. The results of the simulations demonstrate that the random factor mimicking variation increased considerably the range of values covered by Shannon entropy, especially when the percentage of changed offspring was high. This increase in information content is interpreted as facilitated adaptability of the population.

Probe-specific mixed-model approach to detect copy number differences using multiplex ligation-dependent probe amplification (MLPA)

Background: MLPA method is a potentially useful semi-quantitative method to detect copy number alterations in targeted regions. In this paper, we propose a method for the normalization procedure based on a non-linear mixed-model, as well as a new approach for determining the statistical significance of altered probes based on linear mixed-model. This method establishes a threshold by using different tolerance intervals that accommodates the specific random error variability observed in each test sample.Results: Through simulation studies we have shown that our proposed method outperforms two existing methods that are based on simple threshold rules or iterative regression. We have illustrated the method using a controlled MLPA assay in which targeted regions are variable in copy number in individuals suffering from different disorders such as Prader-Willi, DiGeorge or Autism showing the best performace.Conclusion: Using the proposed mixed-model, we are able to determine thresholds to decide whether a region is altered. These threholds are specific for each individual, incorporating experimental variability, resulting in improved sensitivity and specificity as the examples with real data have revealed.

Identification and validation of copy number variants using SNP genotyping arrays from a large clinical cohort.

BACKGROUND: Genotypes obtained with commercial SNP arrays have been extensively used in many large case-control or population-based cohorts for SNP-based genome-wide association studies for a multitude of traits. Yet, these genotypes capture only a small fraction of the variance of the studied traits. Genomic structural variants (GSV) such as Copy Number Variation (CNV) may account for part of the missing heritability, but their comprehensive detection requires either next-generation arrays or sequencing. Sophisticated algorithms that infer CNVs by combining the intensities from SNP-probes for the two alleles can already be used to extract a partial view of such GSV from existing data sets. RESULTS: Here we present several advances to facilitate the latter approach. First, we introduce a novel CNV detection method based on a Gaussian Mixture Model. Second, we propose a new algorithm, PCA merge, for combining copy-number profiles from many individuals into consensus regions. We applied both our new methods as well as existing ones to data from 5612 individuals from the CoLaus study who were genotyped on Affymetrix 500K arrays. We developed a number of procedures in order to evaluate the performance of the different methods. This includes comparison with previously published CNVs as well as using a replication sample of 239 individuals, genotyped with Illumina 550K arrays. We also established a new evaluation procedure that employs the fact that related individuals are expected to share their CNVs more frequently than randomly selected individuals. The ability to detect both rare and common CNVs provides a valuable resource that will facilitate association studies exploring potential phenotypic associations with CNVs. CONCLUSION: Our new methodologies for CNV detection and their evaluation will help in extracting additional information from the large amount of SNP-genotyping data on various cohorts and use this to explore structural variants and their impact on complex traits.

Linear relations between writhe and minimal crossing number in Conway families of ideal knots and links

We showed earlier how to predict the writhe of any rational knot or link in its ideal geometric configuration, or equivalently the average of the 3D writhe over statistical ensembles of random configurations of a given knot or link (Cerf and Stasiak 2000 Proc. Natl Acad. Sci. USA 97 3795). There is no general relation between the minimal crossing number of a knot and the writhe of its ideal geometric configuration. However, within individual families of knots linear relations between minimal crossing number and writhe were observed (Katritch et al 1996 Nature 384 142). Here we present a method that allows us to express the writhe as a linear function of the minimal crossing number within Conway families of knots and links in their ideal configuration. The slope of the lines and the shift between any two lines with the same

Variable queen number in ant colonies: no impact on queen turnover, inbreeding, and population genetic differentiation in the ant Formica selysi.

Variation in queen number alters the genetic structure of social insect colonies, which in turn affects patterns of kin-selected conflict and cooperation. Theory suggests that shifts from single- to multiple-queen colonies are often associated with other changes in the breeding system, such as higher queen turnover, more local mating, and restricted dispersal. These changes may restrict gene flow between the two types of colonies and it has been suggested that this might ultimately lead to sympatric speciation. We performed a detailed microsatellite analysis of a large population of the ant Formica selysi, which revealed extensive variation in social structure, with 71 colonies headed by a single queen and 41 by multiple queens. This polymorphism in social structure appeared stable over time, since little change in the number of queens per colony was detected over a five-year period. Apart from queen number, single- and multiple-queen colonies had very similar breeding systems. Queen turnover was absent or very low in both types of colonies. Single- and multiple-queen colonies exhibited very small but significant levels of inbreeding, which indicates a slight deviation from random mating at a local scale and suggests that a small proportion of queens mate with related males. For both types of colonies, there was very little genetic structuring above the level of the nest, with no sign of isolation by distance. These similarities in the breeding systems were associated with a complete lack of genetic differentiation between single- and multiple-queen colonies, which provides no support for the hypothesis that change in queen number leads to restricted gene flow between social forms. Overall, this study suggests that the higher rates of queen turnover, local mating, and population structuring that are often associated with multiple-queen colonies do not appear when single- and multiple-queen colonies still coexist within the same population, but build up over time in populations consisting mostly of multiple-queen colonies.

Inferring the mode of origin of polyploid species from next-generation sequence data.

Many eukaryote organisms are polyploid. However, despite their importance, evolutionary inference of polyploid origins and modes of inheritance has been limited by a need for analyses of allele segregation at multiple loci using crosses. The increasing availability of sequence data for nonmodel species now allows the application of established approaches for the analysis of genomic data in polyploids. Here, we ask whether approximate Bayesian computation (ABC), applied to realistic traditional and next-generation sequence data, allows correct inference of the evolutionary and demographic history of polyploids. Using simulations, we evaluate the robustness of evolutionary inference by ABC for tetraploid species as a function of the number of individuals and loci sampled, and the presence or absence of an outgroup. We find that ABC adequately retrieves the recent evolutionary history of polyploid species on the basis of both old and new sequencing technologies. The application of ABC to sequence data from diploid and polyploid species of the plant genus Capsella confirms its utility. Our analysis strongly supports an allopolyploid origin of C. bursa-pastoris about 80 000 years ago. This conclusion runs contrary to previous findings based on the same data set but using an alternative approach and is in agreement with recent findings based on whole-genome sequencing. Our results indicate that ABC is a promising and powerful method for revealing the evolution of polyploid species, without the need to attribute alleles to a homeologous chromosome pair. The approach can readily be extended to more complex scenarios involving higher ploidy levels.