Linkage disequilibrium under recurrent bottlenecks

Understanding patterns of selectively neutral genetic variation is essential in order to model deviations from neutrality, caused for example by different forms of selection. Best understood is neutral genetic variation at a single locus, but additional insights can be gained by investigating genetic variation at multiple loci. The corresponding patterns of variation reflect linkage disequilibrium and provide information about the underlying multi-locus gene genealogies. The statistical properties of two-locus genealogies have been intensively studied for populations of constant census size, as well as for simple demographic histories such as exponential population growth, and single bottlenecks. By contrast, the combined effect of recombination and sustained demographic fluctuations is poorly understood. Addressing this issue, we study a two-locus Wright-Fisher model of a population subject to recurrent bottlenecks. We derive coalescent approximations for the covariance of the times to the most recent common ancestor at two loci. We find, first, that an effective population-size approximation describes the numerically observed linkage disequilibrium provided that recombination occurs either much faster or much more slowly than the population size changes. Second, when recombination occurs frequently between bottlenecks but rarely within bottlenecks, we observe long-range linkage disequilibrium. Third, we show that in the latter case, a commonly used measure of linkage disequilibrium, sigma_d^2 (closely related to r^2), fails to capture long-range linkage disequilibrium because constituent terms, each reflecting long-range linkage disequilibrium, cancel. Fourth, we analyse a limiting case in which long-range linkage disequilibrium can be described in terms of a Xi-coalescent process allowing for simultaneous multiple mergers of ancestral lines.Comment: 34 pages, 7 figure

Genetic Correlations Greatly Increase Mutational Robustness and Can Both Reduce and Enhance Evolvability.

Mutational neighbourhoods in genotype-phenotype (GP) maps are widely believed to be more likely to share characteristics than expected from random chance. Such genetic correlations should strongly influence evolutionary dynamics. We explore and quantify these intuitions by comparing three GP maps-a model for RNA secondary structure, the HP model for protein tertiary structure, and the Polyomino model for protein quaternary structure-to a simple random null model that maintains the number of genotypes mapping to each phenotype, but assigns genotypes randomly. The mutational neighbourhood of a genotype in these GP maps is much more likely to contain genotypes mapping to the same phenotype than in the random null model. Such neutral correlations can be quantified by the robustness to mutations, which can be many orders of magnitude larger than that of the null model, and crucially, above the critical threshold for the formation of large neutral networks of mutationally connected genotypes which enhance the capacity for the exploration of phenotypic novelty. Thus neutral correlations increase evolvability. We also study non-neutral correlations: Compared to the null model, i) If a particular (non-neutral) phenotype is found once in the 1-mutation neighbourhood of a genotype, then the chance of finding that phenotype multiple times in this neighbourhood is larger than expected; ii) If two genotypes are connected by a single neutral mutation, then their respective non-neutral 1-mutation neighbourhoods are more likely to be similar; iii) If a genotype maps to a folding or self-assembling phenotype, then its non-neutral neighbours are less likely to be a potentially deleterious non-folding or non-assembling phenotype. Non-neutral correlations of type i) and ii) reduce the rate at which new phenotypes can be found by neutral exploration, and so may diminish evolvability, while non-neutral correlations of type iii) may instead facilitate evolutionary exploration and so increase evolvability.This work was funded under EP/P504287/1 by the Engineering and Physical Sciences Research Council (https://www.epsrc.ac.uk). SEA is supported by The Royal Society (https://royalsociety.org/).This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.pcbi.100477

Surgery groups of the fundamental groups of hyperplane arrangement complements

Using a recent result of Bartels and Lueck (arXiv:0901.0442) we deduce that the Farrell-Jones Fibered Isomorphism conjecture in L-theory is true for any group which contains a finite index strongly poly-free normal subgroup, in particular, for the Artin full braid groups. As a consequence we explicitly compute the surgery groups of the Artin pure braid groups. This is obtained as a corollary to a computation of the surgery groups of a more general class of groups, namely for the fundamental group of the complement of any fiber-type hyperplane arrangement in the complex n-space.Comment: 11 pages, AMSLATEX file, revised following referee's comments and suggestions, to appear in Archiv der Mathemati

Seroepidemiological survey for canine angiostrongylosis in dogs from Germany and the UK using combined detection of Angiostrongylus vasorum antigen and specific antibodies

Dogs infected with Angiostrongylus vasorum, a potentially lethal parasite parasitizing the heart and pulmonary arteries, may present severe respiratory, haematological and neurological signs. In this first large-scale seroepidemiological survey, 4003 sera originating from Germany and 4030 from the UK were tested by an ELISA for the detection of circulating antigen of A. vasorum, and by a separate ELISA detecting specific antibodies. In Germany, where mainly western federal states were sampled, 0·3% (n = 13, CI: 0·2-0·6%) of dogs were positive in both ELISAs, whereas in total 0·5% (n = 20, CI: 0·3-0·8%) were antigen-positive and 2·25% (n = 90, CI: 1·8-2·8%) were positive for specific antibodies. Regions with antigen- and antibody-positive animals were overlapping. In the UK, where mainly the south of the country was sampled, 0·97% (n = 39, CI: 0·7-1·3%) of dogs were antigen- and antibody positive. In total, 1·32% (n = 53, CI: 1·0-1·7%) were antigen-positive, and 3·2% (n = 129, CI: 2·7-3·8%) were positive for specific antibodies, again in overlapping regions. These results confirm the occurrence of A. vasorum in a random dog population originating from large parts of the countries investigated. The use of the tests alone or in combination was considered as a function of their sensitivities and specificities, in order to guide efficient clinical and epidemiological applicatio

Process Analysis and Physical Simulation of Electromagnetic Joining of Thin-Walled parts

To avoid typical problems when connecting different metallic materials as aluminum and titanium as e.g. the formation of intermetallic phases, electromagnetic welding represents an alternative technology to conventional (i.e. usually thermal) joining processes. Although feasibility and potential of this technique are already proved, the fundamental correlations of part- and process-parameters have not yet been investigated systematically. As an approach to examine these, the performance of model experiments and supplementary technological tests is suggested. The resulting connection quality is evaluated using metallographic methods

ИССЛЕДОВАНИЕ ВОЗДЕЙСТВИЯ АПОЛЯРНЫХ РЕАГЕНТОВ НА ТЕКУЧЕСТЬ ВОДОУГОЛЬНЫХ СУСПЕНЗИЙ

В последнее время возник интерес к поведению водоугольных суспензий в связи с поиском альтернативных видов энергоресурсов [1-4]. Повышенный интерес к водо угольному топливу вызван ростом цен на нефть и нефтепродукты и ограниченностью запасов этого сырья. Водоугольные смеси широко изучаются в различных странах мира, так как они могут заменить и традиционное пылевидное топливо, перед которым имеют ряд существенных преимуществ. Особенности горения водоугольного топлива позволяют относить его к разряду экологически чистых видов топлива. При сжигании угля в виде водоугольной суспензии увеличивается скорость выгорания углерода, снижаются выбросы вредных веществ в атмосферу и образование оксидов азота

Design and Analysis of a Deep Drawing and Inprocess Electromagnetic Sheet Metal Forming Process

The design as well as the subsequent analysis of a deep drawing and in-process electromagnetic sheet metal forming calibration will be described in this paper. Due to the quite different forming processes concerning the occurred strain rates, an investigation on the microstructure of the formed workpieces will be pointed out. Furthermore, the design steps regarding the integrated tool coil will be presented and the resulting examples discussed. Finally, the setup of the integrated process as well as the feasibility will be shown on an exemplary semi-industrial workpiece

Adhesion of HVOF-sprayed WC-Co coatings on 316L substrates processed by SLM

Different studies have been demonstrated that the surface integrity of substrate bulk materials to be coated has a significant impact on the adhesion of thermally sprayed coatings. It is known that the surface integrity of parts processed by selective laser melting (SLM) differs from those obtained from bulk materials. Although 316L stainless steel is among the most investigated material for SLM, the adhesion of thermally sprayed coatings on 316L stainless steel substrates processed by SLM has not been studied yet. This study aims at evaluating the effect of various mechanical pre-treatments onto 316L stainless steel substrates processed by SLM and their effect on the adhesion of high velocity oxy-fuel (HVOF)-sprayed WC-Co coatings. To differentiate between topographical effects and residual stress-related phenomena, a stress-relief heat treatment of the SLM substrates served as a reference throughout the investigations. The differently pre-treated SLM substrates were investigated with regard to the surface roughness and residual stresses. For the HVOF-sprayed SLM composites, Vickers interfacial indentation tests were conducted to assess the resulting coating adhesion. The findings demonstrated that the HVOF-sprayed WC-Co coatings predominantly exhibit good adhesion to the SLM 316L substrates. However, it was found that the stress state in the SLM 316L substrate surface is more likely to affect the adhesion of the WC-Co coating, while the substrate surface roughness showed a marginal effect