141,630 research outputs found
Inferring processes of cultural transmission: the critical role of rare variants in distinguishing neutrality from novelty biases
Neutral evolution assumes that there are no selective forces distinguishing
different variants in a population. Despite this striking assumption, many
recent studies have sought to assess whether neutrality can provide a good
description of different episodes of cultural change. One approach has been to
test whether neutral predictions are consistent with observed progeny
distributions, recording the number of variants that have produced a given
number of new instances within a specified time interval: a classic example is
the distribution of baby names. Using an overlapping generations model we show
that these distributions consist of two phases: a power law phase with a
constant exponent of -3/2, followed by an exponential cut-off for variants with
very large numbers of progeny. Maximum likelihood estimations of the model
parameters provide a direct way to establish whether observed empirical
patterns are consistent with neutral evolution. We apply our approach to a
complete data set of baby names from Australia. Crucially we show that analyses
based on only the most popular variants, as is often the case in studies of
cultural evolution, can provide misleading evidence for underlying transmission
hypotheses. While neutrality provides a plausible description of progeny
distributions of abundant variants, rare variants deviate from neutrality.
Further, we develop a simulation framework that allows for the detection of
alternative cultural transmission processes. We show that anti-novelty bias is
able to replicate the complete progeny distribution of the Australian data set
Genome-wide association study of electrocardiographic and heart rate variability traits: the Framingham Heart Study
BACKGROUND: Heritable electrocardiographic (ECG) and heart rate variability (HRV) measures, reflecting pacemaking, conduction, repolarization and autonomic function in the heart have been associated with risks for cardiac arrhythmias. Whereas several rare monogenic conditions with extreme phenotypes have been noted, few common genetic factors contributing to interindividual variability in ECG and HRV measures have been identified. We report the results of a community-based genomewide association study of six ECG and HRV intermediate traits. METHODS: Genotyping using Affymetrix 100K GeneChip was conducted on 1345 related Framingham Heart Study Original and Offspring cohort participants. We analyzed 1175 Original and Offspring participants with ECG data (mean age 52 years, 52% women) and 548 Offspring participants with HRV data (mean age 48 years, 51% women), in relation to 70,987 SNPs with minor allele frequency ≥ 0.10, call rate ≥ 80%, Hardy-Weinberg p-value ≥ 0.001. We used generalized estimating equations to test association of SNP alleles with multivariable-adjusted residuals for QT, RR, and PR intervals, the ratio of low frequency to high frequency power (LF/HFP), total power (TP) and the standard deviation of normal RR intervals (SDNN). RESULTS: Associations at p < 10-3 were found for 117 (QT), 105 (RR), 111 (PR), 102 (LF/HF), 121 (TP), and 102 (SDNN) SNPs. Several common variants in NOS1AP (4 SNPs with p-values < 10-3; lowest p-value, rs6683968, p = 1 × 10-4) were associated with adjusted QT residuals, consistent with our previously reported finding for NOS1AP in an unrelated sample of FHS Offspring and other cohorts. All results are publicly available at NCBI's dbGaP at. CONCLUSION: In the community-based Framingham Heart Study none of the ECG and HRV results individually attained genomewide significance. However, the presence of bona fide QT-associated SNPs among the top 117 results for QT duration supports the importance of efforts to validate top results from the reported scans. Finding genetic variants associated with ECG and HRV quantitative traits may identify novel genes and pathways implicated in arrhythmogenesis and allow for improved recognition of individuals at high risk for arrhythmias in the general population.National Institutes of Health (K23 N01-HC25195); Doris Duke Charitable Foundation Clinical Scientist Developement Award; Pfizer; National Institutes of Health National Center for Research Resources Shared Instrumentation grant (1S10RR163736-01A1
On the microCHP scheduling problem
In this paper both continuous and discrete models for the microCHP (Combined Heat and Power) scheduling problem are derived. This problem consists of the decision making to plan runs for a specific type of distributed electricity\ud
generators, the microCHP. As a special result, one model variant of the problem, named n-DSHSP-restricted, is proven to be NP-complete in the strong sense. This shows the necessity of the development of heuristics for the scheduling of microCHPs, in case multiple generators are combined in a so-called fleet
Detecting simultaneous variant intervals in aligned sequences
Given a set of aligned sequences of independent noisy observations, we are
concerned with detecting intervals where the mean values of the observations
change simultaneously in a subset of the sequences. The intervals of changed
means are typically short relative to the length of the sequences, the subset
where the change occurs, the "carriers," can be relatively small, and the sizes
of the changes can vary from one sequence to another. This problem is motivated
by the scientific problem of detecting inherited copy number variants in
aligned DNA samples. We suggest a statistic based on the assumption that for
any given interval of changed means there is a given fraction of samples that
carry the change. We derive an analytic approximation for the false positive
error probability of a scan, which is shown by simulations to be reasonably
accurate. We show that the new method usually improves on methods that analyze
a single sample at a time and on our earlier multi-sample method, which is most
efficient when the carriers form a large fraction of the set of sequences. The
proposed procedure is also shown to be robust with respect to the assumed
fraction of carriers of the changes.Comment: Published in at http://dx.doi.org/10.1214/10-AOAS400 the Annals of
Applied Statistics (http://www.imstat.org/aoas/) by the Institute of
Mathematical Statistics (http://www.imstat.org
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