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

Microscopic description of d-wave superconductivity by Van Hove nesting in the Hubbard model

We devise a computational approach to the Hubbard model that captures the strong coupling dynamics arising when the Fermi level is at a Van Hove singularity in the density of states. We rely on an approximate degeneracy among the many-body states accounting for the main instabilities of the system (antiferromagnetism, d-wave superconductivity). The Fermi line turns out to be deformed in a manner consistent with the pinning of the Fermi level to the Van Hove singularity. For a doping rate $\delta \sim 0.2$, the ground state is characterized by d-wave symmetry, quasiparticles gapped only at the saddle-points of the band, and a large peak at zero momentum in the d-wave pairing correlations.Comment: 4 pages, 2 Postscript figure

Conceptual Foundations for a Service-oriented Knowledge and Learning Architecture: Supporting Content, Process and Ontology Maturing

Abstract: The knowledge maturing model views learning activities as embedded into, interwoven with, and even indistinguishable from everyday work processes. Learning is understood as an inherently social and collaborative activity. The Knowledge Maturing Process Model structures this process into five phases: expressing ideas, distributing in communities, formalizing, ad-hoc learning and standardization. It is applicable not only for content but also to process knowledge and semantics. In the MATURE IP two toolsets will be develop that support the maturing process: a personal learning environment and an organisation learning environment integrating the levels of individuals, communities and organisation. The development is guided by the SER theory of seeding, evolutionary growth and reseeding and is based on generally applicable maturing services

Mesoscopic models for DNA stretching under force: new results and comparison to experiments

Single molecule experiments on B-DNA stretching have revealed one or two structural transitions, when increasing the external force. They are characterized by a sudden increase of DNA contour length and a decrease of the bending rigidity. It has been proposed that the first transition, at forces of 60--80 pN, is a transition from B to S-DNA, viewed as a stretched duplex DNA, while the second one, at stronger forces, is a strand peeling resulting in single stranded DNAs (ssDNA), similar to thermal denaturation. But due to experimental conditions these two transitions can overlap, for instance for poly(dA-dT). We derive analytical formula using a coupled discrete worm like chain-Ising model. Our model takes into account bending rigidity, discreteness of the chain, linear and non-linear (for ssDNA) bond stretching. In the limit of zero force, this model simplifies into a coupled model already developed by us for studying thermal DNA melting, establishing a connexion with previous fitting parameter values for denaturation profiles. We find that: (i) ssDNA is fitted, using an analytical formula, over a nanoNewton range with only three free parameters, the contour length, the bending modulus and the monomer size; (ii) a surprisingly good fit on this force range is possible only by choosing a monomer size of 0.2 nm, almost 4 times smaller than the ssDNA nucleobase length; (iii) mesoscopic models are not able to fit B to ssDNA (or S to ss) transitions; (iv) an analytical formula for fitting B to S transitions is derived in the strong force approximation and for long DNAs, which is in excellent agreement with exact transfer matrix calculations; (v) this formula fits perfectly well poly(dG-dC) and $\lambda$-DNA force-extension curves with consistent parameter values; (vi) a coherent picture, where S to ssDNA transitions are much more sensitive to base-pair sequence than the B to S one, emerges.Comment: 14 pages, 9 figure

High-spin isomers and three-neutron valence configurations in 211Pb

Deep-inelastic reactions between a beam of 1360 MeV 208Pb ions and a thick 238U target have been used to populate the neutron-rich nucleus 211Pb. The observation of its γ decay has allowed identification of excited states up to the highest spin which can be formed from the three valence neutrons, including identification of three high-spin isomers. Level energies and transition strengths are compared to shell-model calculations with empirical interactions and predictions are made for the expected behaviour of more neutron-rich lead isotopes. The evidence for a possible increase in the neutron effective charge moving away from the N=126 shell gap is evaluated

Magnetic Field Amplification in Galaxy Clusters and its Simulation

We review the present theoretical and numerical understanding of magnetic field amplification in cosmic large-scale structure, on length scales of galaxy clusters and beyond. Structure formation drives compression and turbulence, which amplify tiny magnetic seed fields to the microGauss values that are observed in the intracluster medium. This process is intimately connected to the properties of turbulence and the microphysics of the intra-cluster medium. Additional roles are played by merger induced shocks that sweep through the intra-cluster medium and motions induced by sloshing cool cores. The accurate simulation of magnetic field amplification in clusters still poses a serious challenge for simulations of cosmological structure formation. We review the current literature on cosmological simulations that include magnetic fields and outline theoretical as well as numerical challenges.Comment: 60 pages, 19 Figure

Heavy quarkonium: progress, puzzles, and opportunities

A golden age for heavy quarkonium physics dawned a decade ago, initiated by the confluence of exciting advances in quantum chromodynamics (QCD) and an explosion of related experimental activity. The early years of this period were chronicled in the Quarkonium Working Group (QWG) CERN Yellow Report (YR) in 2004, which presented a comprehensive review of the status of the field at that time and provided specific recommendations for further progress. However, the broad spectrum of subsequent breakthroughs, surprises, and continuing puzzles could only be partially anticipated. Since the release of the YR, the BESII program concluded only to give birth to BESIII; the $B$-factories and CLEO-c flourished; quarkonium production and polarization measurements at HERA and the Tevatron matured; and heavy-ion collisions at RHIC have opened a window on the deconfinement regime. All these experiments leave legacies of quality, precision, and unsolved mysteries for quarkonium physics, and therefore beg for continuing investigations. The plethora of newly-found quarkonium-like states unleashed a flood of theoretical investigations into new forms of matter such as quark-gluon hybrids, mesonic molecules, and tetraquarks. Measurements of the spectroscopy, decays, production, and in-medium behavior of c\bar{c}, b\bar{b}, and b\bar{c} bound states have been shown to validate some theoretical approaches to QCD and highlight lack of quantitative success for others. The intriguing details of quarkonium suppression in heavy-ion collisions that have emerged from RHIC have elevated the importance of separating hot- and cold-nuclear-matter effects in quark-gluon plasma studies. This review systematically addresses all these matters and concludes by prioritizing directions for ongoing and future efforts.Comment: 182 pages, 112 figures. Editors: N. Brambilla, S. Eidelman, B. K. Heltsley, R. Vogt. Section Coordinators: G. T. Bodwin, E. Eichten, A. D. Frawley, A. B. Meyer, R. E. Mitchell, V. Papadimitriou, P. Petreczky, A. A. Petrov, P. Robbe, A. Vair

High-spin yrast structure of Hg 204 from the decay of a four-hole, 22+ isomer

A high-spin isomer with τ>700 ns has been found in Hg204, populated in reactions of 1360-MeV Pb208 and 330-MeV Ca48 beams with a thick U238 target and a 1450-MeV Pb208 beam on a thick Pb208 target. The observed γ-ray decay of the isomer has established the yrast states below it, including another isomer with τ=33(3) ns. The experimental results are compared with shell-model calculations that include four holes in the configuration space between Sn132 and Pb208. The available spectroscopic information, including transition strengths, total conversion, and angular correlation coefficients, together with the observed agreement with the calculations, allows spin, parity, and configuration assignments to be proposed for the experimental states. The τ>700 ns isomer is the 22+ state of maximum spin available from the alignment of the four valence holes with the configuration πh11/2-2νi13/2-2