Distributions associated with general runs and patterns in hidden Markov models

This paper gives a method for computing distributions associated with patterns in the state sequence of a hidden Markov model, conditional on observing all or part of the observation sequence. Probabilities are computed for very general classes of patterns (competing patterns and generalized later patterns), and thus, the theory includes as special cases results for a large class of problems that have wide application. The unobserved state sequence is assumed to be Markovian with a general order of dependence. An auxiliary Markov chain is associated with the state sequence and is used to simplify the computations. Two examples are given to illustrate the use of the methodology. Whereas the first application is more to illustrate the basic steps in applying the theory, the second is a more detailed application to DNA sequences, and shows that the methods can be adapted to include restrictions related to biological knowledge.Comment: Published in at http://dx.doi.org/10.1214/07-AOAS125 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Dynamic filtering of static dipoles in magnetoencephalography

We consider the problem of estimating neural activity from measurements of the magnetic fields recorded by magnetoencephalography. We exploit the temporal structure of the problem and model the neural current as a collection of evolving current dipoles, which appear and disappear, but whose locations are constant throughout their lifetime. This fully reflects the physiological interpretation of the model. In order to conduct inference under this proposed model, it was necessary to develop an algorithm based around state-of-the-art sequential Monte Carlo methods employing carefully designed importance distributions. Previous work employed a bootstrap filter and an artificial dynamic structure where dipoles performed a random walk in space, yielding nonphysical artefacts in the reconstructions; such artefacts are not observed when using the proposed model. The algorithm is validated with simulated data, in which it provided an average localisation error which is approximately half that of the bootstrap filter. An application to complex real data derived from a somatosensory experiment is presented. Assessment of model fit via marginal likelihood showed a clear preference for the proposed model and the associated reconstructions show better localisation

Viewing the efficiency of chaos control

This paper aims to cast some new light on controlling chaos using the OGY- and the Zero-Spectral-Radius methods. In deriving those methods we use a generalized procedure differing from the usual ones. This procedure allows us to conveniently treat maps to be controlled bringing the orbit to both various saddles and to sources with both real and complex eigenvalues. We demonstrate the procedure and the subsequent control on a variety of maps. We evaluate the control by examining the basins of attraction of the relevant controlled systems graphically and in some cases analytically

Critical mutation rate has an exponential dependence on population size for eukaryotic-length genomes with crossover

The critical mutation rate (CMR) determines the shift between survival-of-the-fittest and survival of individuals with greater mutational robustness (“flattest”). We identify an inverse relationship between CMR and sequence length in an in silico system with a two-peak fitness landscape; CMR decreases to no more than five orders of magnitude above estimates of eukaryotic per base mutation rate. We confirm the CMR reduces exponentially at low population sizes, irrespective of peak radius and distance, and increases with the number of genetic crossovers. We also identify an inverse relationship between CMR and the number of genes, confirming that, for a similar number of genes to that for the plant Arabidopsis thaliana (25,000), the CMR is close to its known wild-type mutation rate; mutation rates for additional organisms were also found to be within one order of magnitude of the CMR. This is the first time such a simulation model has been assigned input and produced output within range for a given biological organism. The decrease in CMR with population size previously observed is maintained; there is potential for the model to influence understanding of populations undergoing bottleneck, stress, and conservation strategy for populations near extinction

Environmental pleiotropy and demographic history direct adaptation under antibiotic selection

Evolutionary rescue following environmental change requires mutations permitting population growth in the new environment. If change is severe enough to prevent most of the population reproducing, rescue becomes reliant on mutations already present. If change is sustained, the fitness effects in both environments, and how they are associated—termed ‘environmental pleiotropy’—may determine which alleles are ultimately favoured. A population’s demographic history—its size over time—influences the variation present. Although demographic history is known to affect the probability of evolutionary rescue, how it interacts with environmental pleiotropy during severe and sustained environmental change remains unexplored. Here, we demonstrate how these factors interact during antibiotic resistance evolution, a key example of evolutionary rescue fuelled by pre-existing mutations with pleiotropic fitness effects. We combine published data with novel simulations to characterise environmental pleiotropy and its effects on resistance evolution under different demographic histories. Comparisons among resistance alleles typically revealed no correlation for fitness—i.e., neutral pleiotropy—above and below the sensitive strain’s minimum inhibitory concentration. Resistance allele frequency following experimental evolution showed opposing correlations with their fitness effects in the presence and absence of antibiotic. Simulations demonstrated that effects of environmental pleiotropy on allele frequencies depended on demographic history. At the population level, the major influence of environmental pleiotropy was on mean fitness, rather than the probability of evolutionary rescue or diversity. Our work suggests that determining both environmental pleiotropy and demographic history is critical for predicting resistance evolution, and we discuss the practicalities of this during in vivo evolution

Opposing effects of final population density and stress on Escherichia coli mutation rate

Evolution depends on mutations. For an individual genotype, the rate at which mutations arise is known to increase with various stressors (stress-induced mutagenesis-SIM) and decrease at high final population density (density-associated mutation-rate plasticity-DAMP). We hypothesised that these two forms of mutation-rate plasticity would have opposing effects across a nutrient gradient. Here we test this hypothesis, culturing Escherichia coli in increasingly rich media. We distinguish an increase in mutation rate with added nutrients through SIM (dependent on error-prone polymerases Pol IV and Pol V) and an opposing effect of DAMP (dependent on MutT, which removes oxidised G nucleotides). The combination of DAMP and SIM results in a mutation rate minimum at intermediate nutrient levels (which can support 7 × 10  cells ml ). These findings demonstrate a strikingly close and nuanced relationship of ecological factors-stress and population density-with mutation, the fuel of all evolution

Spin-Parity Analysis of the Centrally produced KsKs system at 800 GeV

Results are presented of the spin-parity analysis on a sample of centrally produced mesons in the reaction (p p -> p_{slow} K_s K_s p_{fast}) with 800 GeV protons on liquid hydrogen. The spin-parity analysis in the mass region between threshold and 1.58 GeV/c^2 shows that the (K_s K_s) system is produced mainly in S-wave. The f_0(1500) is clearly observed in this region. Above 1.58 GeV/c^2 two solutions are possible, one with mainly S-wave and another with mainly D-wave. This ambiguity prevents a unique determination of the spin of the f_J(1710) meson.Comment: 6 pages, including 6 figures. LaTex, uses 'espcrc2.sty'. To appear in LEAP'96 proceeding

Studying Kaon-pion S-wave scattering in K-matrix formalism

We generalize our previous work on \pi\pi scattering to K\pi scattering, and re-analyze the experiment data of K\pi scattering below 1.6 GeV. Without any free parameter, we explain K\pi I=3/2 S-wave phase shift very well by using t-channel rho and u-channel K^* meson exchange. With the t-channel and u-channel meson exchange fixed as the background term, we fit the K\pi I=1/2 S-wave data of the LASS experiment quite well by introducing one or two s-channel resonances. It is found that there is only one s-channel resonance between K\pi threshold and 1.6 GeV, i.e., K_0^*(1430) with a mass around 1438~1486 MeV and a width about 346 MeV, while the t-channel rho exchange gives a pole at (450-480i) MeV for the amplitude.Comment: REVTeX4 file, 11 pages and 3 figure

Spontaneous mutation rate is a plastic trait associated with population density across domains of life

Rates of random, spontaneous mutation can vary plastically, dependent upon the environment. Such plasticity affects evolutionary trajectories and may be adaptive. We recently identified an inverse plastic association between mutation rate and population density at 1 locus in 1 species of bacterium. It is unknown how widespread this association is, whether it varies among organisms, and what molecular mechanisms of mutagenesis or repair are required for this mutation-rate plasticity. Here, we address all 3 questions. We identify a strong negative association between mutation rate and population density across 70 years of published literature, comprising hundreds of mutation rates estimated using phenotypic markers of mutation (fluctuation tests) from all domains of life and viruses. We test this relationship experimentally, determining that there is indeed density-associated mutation-rate plasticity (DAMP) at multiple loci in both eukaryotes and bacteria, with up to 23-fold lower mutation rates at higher population densities. We find that the degree of plasticity varies, even among closely related organisms. Nonetheless, in each domain tested, DAMP requires proteins scavenging the mutagenic oxidised nucleotide 8-oxo-dGTP. This implies that phenotypic markers give a more precise view of mutation rate than previously believed: having accounted for other known factors affecting mutation rate, controlling for population density can reduce variation in mutation-rate estimates by 93%. Widespread DAMP, which we manipulate genetically in disparate organisms, also provides a novel trait to use in the fight against the evolution of antimicrobial resistance. Such a prevalent environmental association and conserved mechanism suggest that mutation has varied plastically with population density since the early origins of life

Final State Interactions in Hadronic D decays

We show that the large corrections due to final state interactions (FSI) in the D^+\to \pi^-\pi^+\pi^+, D^+_s\to \pi^-\pi^+\pi^+, and D^+\to K^-\pi^+\pi^+ decays can be accounted for by invoking scattering amplitudes in agreement with those derived from phase shifts studies. In this way, broad/overlapping resonances in S-waves are properly treated and the phase motions of the transition amplitudes are driven by the corresponding scattering matrix elements determined in many other experiments. This is an important step forward in resolving the puzzle of the FSI in these decays. We also discuss why the \sigma and \kappa resonances, hardly visible in scattering experiments, are much more prominent and clearly visible in these decays without destroying the agreement with the experimental \pi\pi and K\pi low energy S-wave phase shifts.Comment: 22 pages, 6 figures, 5 tables. Minor changes. We extend the discusion when quoting a reference and we include a new one. Some typos are fixe