Embracing polygenicity: a review of methods and tools for psychiatric genetics research.

The availability of genome-wide genetic data on hundreds of thousands of people has led to an equally rapid growth in methodologies available to analyse these data. While the motivation for undertaking genome-wide association studies (GWAS) is identification of genetic markers associated with complex traits, once generated these data can be used for many other analyses. GWAS have demonstrated that complex traits exhibit a highly polygenic genetic architecture, often with shared genetic risk factors across traits. New methods to analyse data from GWAS are increasingly being used to address a diverse set of questions about the aetiology of complex traits and diseases, including psychiatric disorders. Here, we give an overview of some of these methods and present examples of how they have contributed to our understanding of psychiatric disorders. We consider: (i) estimation of the extent of genetic influence on traits, (ii) uncovering of shared genetic control between traits, (iii) predictions of genetic risk for individuals, (iv) uncovering of causal relationships between traits, (v) identifying causal single-nucleotide polymorphisms and genes or (vi) the detection of genetic heterogeneity. This classification helps organise the large number of recently developed methods, although some could be placed in more than one category. While some methods require GWAS data on individual people, others simply use GWAS summary statistics data, allowing novel well-powered analyses to be conducted at a low computational burden

Correlation functions in the factorization approach of nonextensive quantum statistics

We study the long range behavior of a gas whose partition function depends on a parameter q and it has been claimed to be a good approximation to the partition function proposed in the formulation of nonextensive statistical mechanics. We compare our results, at large temperatures and at the critical point, with the case of Boltzmann-Gibbs thermodynamics for the case of a Bose-Einstein gas. In particular, we find that for all temperatures the long range correlations in a Bose gas decrease when the value of q departs from the standard value q=1.Comment: revtex file, 10 pages, two eps style figures, packaged as a single tar.gz fil

Neutron depolarization studies of Pd-Ni-Fe-P alloy

Bulk metallic glasses based on the quaternary alloy Pd-Ni-Fe-P exhibit interesting phase behavior depending on temperature and applied magnetic field. Previous work has suggested that a range of magnetic phases including paramagnetic, superparamagnetic, ferromagnetic and spin glass can be observed in this system. We have applied one dimensional neutron depolarization to explore the correlation of magnetic moments in Pd40Ni22.5Fe17.5P20 alloy as a function of temperature and applied magnetic field. The results provided evidence for correlation lengths of ~ 200 Å. The nature of the correlations and the formation mechanism of the induced ferromagnetic phase are discusse

Effect of local Coulomb interactions on the electronic structure and exchange interactions in Mn12 magnetic molecules

We have studied the effect of local Coulomb interactions on the electronic structure of the molecular magnet Mn12-acetate within the LDA+U approach. The account of the on-site repulsion results in a finite energy gap and an integer value of the molecule's magnetic moment, both quantities being in a good agreement with the experimental results. The resulting magnetic moments and charge states of non-equivalent manganese ions agree very well with experiments. The calculated values of the intramolecular exchange parameters depend on the molecule's spin configuration, differing by 25-30% between the ferrimagnetic ground state and the completely ferromagnetic configurations. The values of the ground-state exchange coupling parameters are in reasonable agreement with the recent data on the magnetization jumps in megagauss magnetic fields. Simple estimates show that the obtained exchange parameters can be applied, at least qualitatively, to the description of the spin excitations in Mn12-acetate.Comment: RevTeX, LaTeX2e, 4 EPS figure

A Hybrid Artificial Bee Colony Algorithm for Graph 3-Coloring

The Artificial Bee Colony (ABC) is the name of an optimization algorithm that was inspired by the intelligent behavior of a honey bee swarm. It is widely recognized as a quick, reliable, and efficient methods for solving optimization problems. This paper proposes a hybrid ABC (HABC) algorithm for graph 3-coloring, which is a well-known discrete optimization problem. The results of HABC are compared with results of the well-known graph coloring algorithms of today, i.e. the Tabucol and Hybrid Evolutionary algorithm (HEA) and results of the traditional evolutionary algorithm with SAW method (EA-SAW). Extensive experimentations has shown that the HABC matched the competitive results of the best graph coloring algorithms, and did better than the traditional heuristics EA-SAW when solving equi-partite, flat, and random generated medium-sized graphs

Replicated analysis of the genetic architecture of quantitative traits in two wild great tit populations

Currently, there is much debate on the genetic architecture of quantitative traits in wild populations. Is trait variation influenced by many genes of small effect or by a few genes of major effect? Where is additive genetic variation located in the genome? Do the same loci cause similar phenotypic variation in different populations? Great tits (Parus major) have been studied extensively in long-term studies across Europe and consequently are considered an ecological ‘model organism’. Recently, genomic resources have been developed for the great tit, including a custom SNP chip and genetic linkage map. In this study, we used a suite of approaches to investigate the genetic architecture of eight quantitative traits in two long-term study populations of great tits—one in the Netherlands and the other in the United Kingdom. Overall, we found little evidence for the presence of genes of large effects in either population. Instead, traits appeared to be influenced by many genes of small effect, with conservative estimates of the number of contributing loci ranging from 31 to 310. Despite concordance between population-specific heritabilities, we found no evidence for the presence of loci having similar effects in both populations. While population-specific genetic architectures are possible, an undetected shared architecture cannot be rejected because of limited power to map loci of small and moderate effects. This study is one of few examples of genetic architecture analysis in replicated wild populations and highlights some of the challenges and limitations researchers will face when attempting similar molecular quantitative genetic studies in free-living populations

Performance of nano-structured multilayer PVD coating TiAlN/VN in dry high speed milling of aerospace aluminium 7010-T7651

A low-friction and wear resistant TiAlN/VN multilayer coating with TiAlN/VN bilayer thickness 3 nm has been grown by using the combined cathodic arc etching and unbalanced magnetron sputtering deposition on high speed steel tools for dry cutting of aluminium alloys. In this paper, in-lab and industrial high speed milling tests have been performed on an aerospace aluminium alloy 7010-T7651. The results show that the TiAlN/VN coated tools achieved lower cutting forces, lower metal surface roughness, and significantly longer tool lifetime by three times over the uncoated tools as a result of the low friction and eliminated tool-metal adhesion. Under the same conditions, a TiAlN based multicomponent coating TiAlCrYN also increased the tool lifetime by up to 100% despite the high cutting forces measured

A controlled evaluation of an enhanced self-directed behavioural family intervention for parents of children with conduct problems in rural and remote areas.

Few studies have examined the impact of parenting interventions for families in rural and isolated areas who have children with conduct problems, where-access to professional services can be difficult. The present investigation compared the effects of three conditions, two levels of self-directed behavioral family intervention: an enhanced self-directed program that combined a self-help program using written materials and a weekly telephone consultation (ESD), a self-help program (SD) and a waitlist control group (WL). At postintervention the ESD group reported significantly lower levels of disruptive behaviour, and lower levels of dysfunctional parenting than the SD and WL controls, and higher levels of consumer satisfaction. At 6 months follow-up the main effects for the ESD group had been maintained. The SD group continued to evidence improvement from postintervention to follow-up such that 65% of children in the ESD condition and 57% of children in the SD condition showed clinical reliable change on measures of disruptive behaviour. Implications of findings and directions for future research are discussed

First and second order optimality conditions for optimal control problems of state constrained integral equations

This paper deals with optimal control problems of integral equations, with initial-final and running state constraints. The order of a running state constraint is defined in the setting of integral dynamics, and we work here with constraints of arbitrary high orders. First and second-order necessary conditions of optimality are obtained, as well as second-order sufficient conditions

Covariant anomaly and Hawking radiation from the modified black hole in the rainbow gravity theory

Recently, Banerjee and Kulkarni (R. Banerjee, S. Kulkarni, arXiv:0707.2449 [hep-th]) suggested that it is conceptually clean and economical to use only the covariant anomaly to derive Hawking radiation from a black hole. Based upon this simplified formalism, we apply the covariant anomaly cancellation method to investigate Hawking radiation from a modified Schwarzschild black hole in the theory of rainbow gravity. Hawking temperature of the gravity's rainbow black hole is derived from the energy-momentum flux by requiring it to cancel the covariant gravitational anomaly at the horizon. We stress that this temperature is exactly the same as that calculated by the method of cancelling the consistent anomaly.Comment: 5 page