Efficient inference for genetic association studies with multiple outcomes

Combined inference for heterogeneous high-dimensional data is critical in modern biology, where clinical and various kinds of molecular data may be available from a single study. Classical genetic association studies regress a single clinical outcome on many genetic variants one by one, but there is an increasing demand for joint analysis of many molecular outcomes and genetic variants in order to unravel functional interactions. Unfortunately, most existing approaches to joint modelling are either too simplistic to be powerful or are impracticable for computational reasons. Inspired by Richardson et al. (2010, Bayesian Statistics 9), we consider a sparse multivariate regression model that allows simultaneous selection of predictors and associated responses. As Markov chain Monte Carlo (MCMC) inference on such models can be prohibitively slow when the number of genetic variants exceeds a few thousand, we propose a variational inference approach which produces posterior information very close to that of MCMC inference, at a much reduced computational cost. Extensive numerical experiments show that our approach outperforms popular variable selection methods and tailored Bayesian procedures, dealing within hours with problems involving hundreds of thousands of genetic variants and tens to hundreds of clinical or molecular outcomes

Signal and noise in helioseismic holography

Helioseismic holography is an imaging technique used to study heterogeneities and flows in the solar interior from observations of solar oscillations at the surface. Holograms contain noise due to the stochastic nature of solar oscillations. We provide a theoretical framework for modeling signal and noise in Porter-Bojarski helioseismic holography. The wave equation may be recast into a Helmholtz-like equation, so as to connect with the acoustics literature and define the holography Green's function in a meaningful way. Sources of wave excitation are assumed to be stationary, horizontally homogeneous, and spatially uncorrelated. Using the first Born approximation we calculate holograms in the presence of perturbations in sound-speed, density, flows, and source covariance, as well as the noise level as a function of position. This work is a direct extension of the methods used in time-distance helioseismology to model signal and noise. To illustrate the theory, we compute the hologram intensity numerically for a buried sound-speed perturbation at different depths in the solar interior. The reference Green's function is obtained for a spherically-symmetric solar model using a finite-element solver in the frequency domain. Below the pupil area on the surface, we find that the spatial resolution of the hologram intensity is very close to half the local wavelength. For a sound-speed perturbation of size comparable to the local spatial resolution, the signal-to-noise ratio is approximately constant with depth. Averaging the hologram intensity over a number $N$ of frequencies above 3 mHz increases the signal-to-noise ratio by a factor nearly equal to the square root of $N$. This may not be the case at lower frequencies, where large variations in the holographic signal are due to the individual contributions of the long-lived modes of oscillation.Comment: Submitted to Astronomy and Astrophysic

Séquence sédimentaire du secteur aval de la rivière Coppermine, Territoires du Nord-Ouest

L'étude des sédiments exposés dans 31 coupes le long du cours inférieur de la rivière Coppermine, entre les monts September et Coppermine et le golfe du Couronnement, a permis de reconstituer l'évolution postglaciaire de la région. Après le retrait des glaces, Ia mer a envahi la zone côtière déprimée par glacio-isostasie sous le niveau marin. La déglaciation a aussi permis à la rivière Coppermine de reprendre son cours vers le nord. Or, celle-ci transportait d'énormes quantités de sédiments qui lui étaient fournies d'une part par les eaux de fonte provenant des masses de glace en décrépitude et, d'autre part, par le remaniement des sédiments du lac glaciaire Coppermine. La sédimentation dans les parties relativement profondes de la mer postglaciaire est représentée par d'importants dépôts de silt et d'argile rythmés. Ces rythmites résultent d'une mise en place par des courants de turbidité. Un diamicton de plus de 30 m d'épaisseur est intercalé dans les rythmites marines. On l'interprète comme étant le résultat d'une série de coulées boueuses provoquées par la liquéfaction des varves du lac glaciaire Coppermine. Ces dépôts ont été recouverts graduellement par des sédiments de plus en plus grossiers de plage ou de delta. Il s'agit donc d'une séquence sédimentaire inverse, caractéristique d'une sédimentation dans une mer en régression. Les datations indiquent que la mer postglaciaire a envahi la région avant 10 000 ans BP.The study of 31 sections along the Coppermine River, between September and Coppermine mountains and Coronation Gulf, makes it possible to understand the postglacial history of the area. Following déglaciation, the sea invaded the depressed coastal lowlands and the Coppermine River resumed its course northward. Its high sediment load originating from the sediment-laden glacial meltwaters and the reworked Glacial Lake Coppermine deposits resulted in an important sedimentation in the postglacial sea. Sedimentation in the deeper areas of the sea left thick deposits of silt and clay rythmites. These rythmites owe their origin to turbidity currents. A 30 m-thick diamicton is interbedded with the rythmites. It is interpreted as the result of a number of debris flows generated by liquefaction of Glacial Lake Coppermine varves early in the region's postglacial history. These deposits are gradually overlaid by coarser beach or deltaic sediments, up to gravel and boulder size. This coarsening-upward sequence is typical of sedimentation in an offlap marine phase. The 14C dates suggest a minimum age of 10,000 BP for the postglacial marine phase

Substrate-specific clades of active marine methylotrophs associated with a phytoplankton bloom in a temperate coastal environment

Marine microorganisms that consume one-carbon (C1) compounds are poorly described, despite their impact on global climate via an influence on aquatic and atmospheric chemistry. This study investigated marine bacterial communities involved in the metabolism of C1 compounds. These communities were of relevance to surface seawater and atmospheric chemistry in the context of a bloom that was dominated by phytoplankton known to produce dimethylsulfoniopropionate. In addition to using 16S rRNA gene fingerprinting and clone libraries to characterize samples taken from a bloom transect in July 2006, seawater samples from the phytoplankton bloom were incubated with 13C-labeled methanol, monomethylamine, dimethylamine, methyl bromide, and dimethyl sulfide to identify microbial populations involved in the turnover of C1 compounds, using DNA stable isotope probing. The [13C]DNA samples from a single time point were characterized and compared using denaturing gradient gel electrophoresis (DGGE), fingerprint cluster analysis, and 16S rRNA gene clone library analysis. Bacterial community DGGE fingerprints from 13C-labeled DNA were distinct from those obtained with the DNA of the nonlabeled community DNA and suggested some overlap in substrate utilization between active methylotroph populations growing on different C1 substrates. Active methylotrophs were affiliated with Methylophaga spp. and several clades of undescribed Gammaproteobacteria that utilized methanol, methylamines (both monomethylamine and dimethylamine), and dimethyl sulfide. rRNA gene sequences corresponding to populations assimilating 13C-labeled methyl bromide and other substrates were associated with members of the Alphaproteobacteria (e.g., the family Rhodobacteraceae), the Cytophaga-Flexibacter-Bacteroides group, and unknown taxa. This study expands the known diversity of marine methylotrophs in surface seawater and provides a comprehensive data set for focused cultivation and metagenomic analyses in the future

Dynamical Signatures of Edge-State Magnetism on Graphene Nanoribbons

We investigate the edge-state magnetism of graphene nanoribbons using projective quantum Monte Carlo simulations and a self-consistent mean-field approximation of the Hubbard model. The static magnetic correlations are found to be short ranged. Nevertheless, the correlation length increases with the width of the ribbon such that already for ribbons of moderate widths we observe a strong trend towards mean-field-type ferromagnetic correlations at a zigzag edge. These correlations are accompanied by a dominant low-energy peak in the local spectral function and we propose that this can be used to detect edge-state magnetism by scanning tunneling microscopy. The dynamic spin structure factor at the edge of a ribbon exhibits an approximately linearly dispersing collective magnonlike mode at low energies that decays into Stoner modes beyond the energy scale where it merges into the particle-hole continuum.Comment: 4+ pages including 4 figure

Off-equilibrium corrections to energy and conserved charge densities in the relativistic fluid in heavy-ion collisions

Dissipative processes in relativistic fluids are known to be important in the analyses of the hot QCD matter created in high-energy heavy-ion collisions. In this work, I consider dissipative corrections to energy and conserved charge densities, which are conventionally assumed to be vanishing but could be finite. Causal dissipative hydrodynamics is formulated in the presence of those dissipative currents. The relation between hydrodynamic stability and transport coefficients is discussed. I then study their phenomenological consequences on the observables of heavy-ion collisions in numerical simulations. It is shown that particle spectra and elliptic flow can be visibly modified.Comment: 10 pages, 5 figures; title changed, references added, conclusions unchange

A Partial Bison (Bison cf. B. latifrons) Skeleton from Chuchi Lake, and its Implications for the Middle Wisconsinan Environment of Central British Columbia

Fragmentary but massive left and right horncores, found with eight post-cranial bones, from a clay unit underlying a diamicton of the last (Fraser) glaciation at Chuchi Lake, British Columbia probably represents an individual giant bison (Bison cf. B. latifrons). A sample of bone from one of the horncores yielded an accelerator mass spectrometry (AMS) radiocarbon date of 30 740 ± 220 BP, whereas overlapping dates from two other laboratories on an associated humerus are 34 800 ± 420 BP and 35 480 ± 1080 BP. Despite the discrepancy between horncore and humerus dates, they are in accord with the suspected stratigraphie age of the clay unit whence they came. Analysis of pollen from that clay unit indicates that bison with massive horns once occupied an open forest in the vicinity. Probably giant bison and Columbian mammoths (incorporating paleoenvironmental evidence found with the nearby, penecontemporaneous Babine Lake mammoth) shared lake-dotted open forest to shrub tundra range in what is now central British Columbia toward the close of the Middle Wisconsinan (Olympia Nonglacial Interval). The Chuchi Lake specimen is important because it is the first indication of giant bison from British Columbia, and it appears to be one of the latest known survivors of this species.On a trouvé au lac Chuchi dans une unité d'argile recouverte d'un diamicton de la dernière glaciation (Fraser), des fragments de noyaux de cornes droite et gauche et des ossements postcrâniens qui pourraient provenir du bison géant (Bison cf. B. latifrons). Un échantillon d'un des noyaux de corne a été daté au radiocarbone par spectrométrie de masse par accélérateur à 30 740 ± 220 BP, alors qu'un humérus du même horizon a été daté dans deux différents laboratoires à 34 800 ± 420 BP et 35 480 ± 1080 BP. Malgré la différence entre les dates du noyau de corne et de l'humérus, celles-ci concordent avec l'âge stratigraphique présumé de l'unité d'argile où les ossements ont été trouvés. L'analyse du pollen de la même unité d'argile indique que le bison vivait dans une forêt ouverte. Selon les données paléoenvironnementales du Babine Lake, où on a trouvé un mammouth du même âge, il est probable que le bison et le mammouth colombien partageaient un milieu variant entre la forêt ouverte et la toundra arbustive parsemée de lacs, au centre de la Colombie-Britannique, pendant le Wisconsinien moyen (intervalle non glaciaire de l'Olympia). La découverte du spécimen du Chuchi Lake est d'autant plus importante qu'il constitue le premier indice de la présence du bison géant en Colombie-Britannique; il pourrait être parmi les derniers survivants de cette espèce.Fragmentarische aber massive linke und rechte Hornkerne zusammen mit acht Hinterschâdelknochen, die man in einer Lehm-Einheit unter einem Diamikton der letzten Vereisung (Fraser) am See Chuchi, British Columbia, gefunden hat, kônnten wohl von einem einzelnen Riesenbison stammen (Bison ci. B. latifrons). Fur eine Knochenprobe von einem der Hornkerne wurde mittels Massenspek-trometrie durch Beschleuniger ein Radiokarbondatum von 30 740 ± 220 v.u.Z. ermittelt, wâhrend zwei andere Labore sich ùberschneidende Daten auf einem damit in Verbindung gebrachten Oberarmknochen ermittelten: 34 800 ± 420 v.u.Z. und 35 480 ± 1080 v.u.Z. Trotz der Diskrepanz zwischen den Hornkern- und Oberarmknochendaten, stimmen sie mit dem vermuteten stratigraphischen Alter der Lehmeinheit, aus der sie stammen, ûberein. Die Pollen-Analyse von dieser Lehmeinheit zeigt, daf3 ehemals Bisons mit massiven Hôrnern in einem offenen WaId in der Nàhe lebten. Gegen Ende des mittleren Wisconsiniums (nichtglaziales Intervall von Olympia) teilten sich wahrscheinlich Riesenbisons und kolumbianische Mammuts (wenn man die Palàoumweltbelege von Babine Lake berùcksichtigt, wo man ein Mammut des gleichen Alters gefunden hat) ein Gebiet, das von Seen durchsetzten offenen WaId bis zur Buschtundra enthielt und dem heutigen Zentrum von British Columbia entspricht. Das Exemplar von Chuchi Lake ist wichtig, weil es der erste Hinweis auf Riesenbison von British Columbia ist, und es scheint eines der letzten bekannten Ùberlebenden dieser Art zu sein

On Motives Associated to Graph Polynomials

The appearance of multiple zeta values in anomalous dimensions and $\beta$-functions of renormalizable quantum field theories has given evidence towards a motivic interpretation of these renormalization group functions. In this paper we start to hunt the motive, restricting our attention to a subclass of graphs in four dimensional scalar field theory which give scheme independent contributions to the above functions.Comment: 54

Modelling Ductile Stable Crack Growth in a C-Mn Steel with Local Approaches

JR-resistance curves obtained on a C-Mn steel with different specimens are compared. The experiments confirm a geometrical dependence of the fracture toughness. An attempt is made to explain these results in terms of models derived from the local approach to fracture. Two types of model are presented where the damage is, either uncoupled or coupled to the material behaviour. The uncoupled model with the Tai-Yang approach and the coupled model with the Rousselier potential give results in good agreement with the experiments