Genome-wide association study of behavioural and psychiatric features in human prion disease.

Prion diseases are rare neurodegenerative conditions causing highly variable clinical syndromes, which often include prominent neuropsychiatric symptoms. We have recently carried out a clinical study of behavioural and psychiatric symptoms in a large prospective cohort of patients with prion disease in the United Kingdom, allowing us to operationalise specific behavioural/psychiatric phenotypes as traits in human prion disease. Here, we report exploratory genome-wide association analysis on 170 of these patients and 5200 UK controls, looking for single-nucleotide polymorphisms (SNPs) associated with three behavioural/psychiatric phenotypes in the context of prion disease. We also specifically examined a selection of candidate SNPs that have shown genome-wide association with psychiatric conditions in previously published studies, and the codon 129 polymorphism of the prion protein gene, which is known to modify various aspects of the phenotype of prion disease. No SNPs reached genome-wide significance, and there was no evidence of altered burden of known psychiatric risk alleles in relevant prion cases. SNPs showing suggestive evidence of association (P<10(-5)) included several lying near genes previously implicated in association studies of other psychiatric and neurodegenerative diseases. These include ANK3, SORL1 and a region of chromosome 6p containing several genes implicated in schizophrenia and bipolar disorder. We would encourage others to acquire phenotype data in independent cohorts of patients with prion disease as well as other neurodegenerative and neuropsychiatric conditions, to allow meta-analysis that may shed clearer light on the biological basis of these complex disease manifestations, and the diseases themselves

Pointwise consistency of the kriging predictor with known mean and covariance functions

This paper deals with several issues related to the pointwise consistency of the kriging predictor when the mean and the covariance functions are known. These questions are of general importance in the context of computer experiments. The analysis is based on the properties of approximations in reproducing kernel Hilbert spaces. We fix an erroneous claim of Yakowitz and Szidarovszky (J. Multivariate Analysis, 1985) that the kriging predictor is pointwise consistent for all continuous sample paths under some assumptions.Comment: Submitted to mODa9 (the Model-Oriented Data Analysis and Optimum Design Conference), 14th-19th June 2010, Bertinoro, Ital

Constraining the Kahler Moduli in the Heterotic Standard Model

Phenomenological implications of the volume of the Calabi-Yau threefolds on the hidden and observable M-theory boundaries, together with slope stability of their corresponding vector bundles, constrain the set of Kaehler moduli which give rise to realistic compactifications of the strongly coupled heterotic string. When vector bundles are constructed using extensions, we provide simple rules to determine lower and upper bounds to the region of the Kaehler moduli space where such compactifications can exist. We show how small these regions can be, working out in full detail the case of the recently proposed Heterotic Standard Model. More explicitely, we exhibit Kaehler classes in these regions for which the visible vector bundle is stable. On the other hand, there is no polarization for which the hidden bundle is stable.Comment: 28 pages, harvmac. Exposition improved, references and one figure added, minor correction

Andreev reflection and order parameter symmetry in heavy-fermion superconductors: the case of CeCoIn5_5

We review the current status of Andreev reflection spectroscopy on the heavy fermions, mostly focusing on the case of CeCoIn$_5$, a heavy-fermion superconductor with a critical temperature of 2.3 K. This is a well-established technique to investigate superconducting order parameters via measurements of the differential conductance from nanoscale metallic junctions. Andreev reflection is clearly observed in CeCoIn$_5$ as in other heavy-fermion superconductors. The measured Andreev signal is highly reduced to the order of maximum $\sim$ 13% compared to the theoretically predicted value (100%). Analysis of the conductance spectra using the extended BTK model provides a qualitative measure for the superconducting order parameter symmetry, which is determined to be $d_{x^2-y^2}$-wave in CeCoIn$_5$. A phenomenological model is proposed employing a Fano interference effect between two conductance channels in order to explain both the conductance asymmetry and the reduced Andreev signal. This model appears plausible not only because it provides good fits to the data but also because it is highly likely that the electrical conduction occurs via two channels, one into the heavy electron liquid and the other into the conduction electron continuum. Further experimental and theoretical investigations will shed new light on the mechanism of how the coherent heavy-electron liquid emerges out of the Kondo lattice, a prototypical strongly correlated electron system. Unresolved issues and future directions are also discussed.Comment: Topical Review published in JPCM (see below), 28 pages, 9 figure

CMB photons shedding light on dark matter

The annihilation or decay of Dark Matter (DM) particles could affect the thermal history of the universe and leave an observable signature in Cosmic Microwave Background (CMB) anisotropies. We update constraints on the annihilation rate of DM particles in the smooth cosmological background, using WMAP7 and recent small-scale CMB data. With a systematic analysis based on the Press-Schechter formalism, we also show that DM annihilation in halos at small redshift may explain entirely the reionization patterns observed in the CMB, under reasonable assumptions concerning the concentration and formation redshift of halos. We find that a mixed reionization model based on DM annihilation in halos as well as star formation at a redshift z~6.5 could simultaneously account for CMB observations and satisfy constraints inferred from the Gunn-Peterson effect. However, these models tend to reheat the inter-galactic medium (IGM) well above observational bounds: by including a realistic prior on the IGM temperature at low redshift, we find stronger cosmological bounds on the annihilation cross-section than with the CMB alone.Comment: 35 pages, 14 figures; version accepted in JCAP after minor revision

Assessment of Existing Steel Structures - Recommendations for Estimation of the Remaining Fatigue Life

Due to the demand for freight volume on rail and road, traffic has increased significantly in the past years leading to an increasing number of heavy vehicles in the traffic flows and greater exploitation of their loading capacities. Because of environmental considerations there is also a tendency to further enhance the admissible loads in the design of new heavy vehicles (e.g. by increasing axle loads or using road trains). This all may affect the safety, serviceability and durability of existing bridges. Bridge authorities are therefore interested in agreed methods to assess the safety and durability of existing bridges and to make appropriate provisions for more refined maintenance methods, possible restriction of traffic, bridge-rehabilitation or substitution of old bridges by new ones where necessary. For steel bridges including the old riveted ones there are numerous approaches to such assessments, partly standardized by national codes or recommendations. In the light of the development of the European single market for construction works and engineering services there is thus a need to harmonize them and to develop agreed European technical recommendations for the safety and durability assessment of existing structures. These recommendations should follow the principles and application rules in the Eurocodes and provide a scheme with different levels of analysis: a basic level with general methods and further levels with higher sophistication that call for specific expertise. This technical report on ¿Recommendations for the estimation of remaining fatigue life¿ supported by the ECCS could be used as a basis for harmonizing National procedures and for the further evolution of the Eurocodes.JRC.G.5-European laboratory for structural assessmen

Numerical solution to the hermitian Yang-Mills equation on the Fermat quintic

We develop an iterative method for finding solutions to the hermitian Yang-Mills equation on stable holomorphic vector bundles, following ideas recently developed by Donaldson. As illustrations, we construct numerically the hermitian Einstein metrics on the tangent bundle and a rank three vector bundle on P^2. In addition, we find a hermitian Yang-Mills connection on a stable rank three vector bundle on the Fermat quintic.Comment: 25 pages, 2 figure

The nature of the different zero-temperature phases in discrete two-dimensional spin glasses: Entropy, universality, chaos and cascades in the renormalization group flow

The properties of discrete two-dimensional spin glasses depend strongly on the way the zero-temperature limit is taken. We discuss this phenomenon in the context of the Migdal-Kadanoff renormalization group. We see, in particular, how these properties are connected with the presence of a cascade of fixed points in the renormalization group flow. Of particular interest are two unstable fixed points that correspond to two different spin-glass phases at zero temperature. We discuss how these phenomena are related with the presence of entropy fluctuations and temperature chaos, and universality in this model.Comment: 14 pages, 5 figures, 2 table

Critical behavior of the random-anisotropy model in the strong-anisotropy limit

We investigate the nature of the critical behavior of the random-anisotropy Heisenberg model (RAM), which describes a magnetic system with random uniaxial single-site anisotropy, such as some amorphous alloys of rare earths and transition metals. In particular, we consider the strong-anisotropy limit (SRAM), in which the Hamiltonian can be rewritten as the one of an Ising spin-glass model with correlated bond disorder. We perform Monte Carlo simulations of the SRAM on simple cubic L^3 lattices, up to L=30, measuring correlation functions of the replica-replica overlap, which is the order parameter at a glass transition. The corresponding results show critical behavior and finite-size scaling. They provide evidence of a finite-temperature continuous transition with critical exponents $\eta_o=-0.24(4)$ and $\nu_o=2.4(6)$. These results are close to the corresponding estimates that have been obtained in the usual Ising spin-glass model with uncorrelated bond disorder, suggesting that the two models belong to the same universality class. We also determine the leading correction-to-scaling exponent finding $\omega = 1.0(4)$.Comment: 24 pages, 13 figs, J. Stat. Mech. in pres