An efficient algorithm to perform multiple testing in epistasis screening

Background: Research in epistasis or gene-gene interaction detection for human complex traits has grown over the last few years. It has been marked by promising methodological developments, improved translation efforts of statistical epistasis to biological epistasis and attempts to integrate different omics information sources into the epistasis screening to enhance power. The quest for gene-gene interactions poses severe multiple-testing problems. In this context, the maxT algorithm is one technique to control the false-positive rate. However, the memory needed by this algorithm rises linearly with the amount of hypothesis tests. Gene-gene interaction studies will require a memory proportional to the squared number of SNPs. A genome-wide epistasis search would therefore require terabytes of memory. Hence, cache problems are likely to occur, increasing the computation time. In this work we present a new version of maxT, requiring an amount of memory independent from the number of genetic effects to be investigated. This algorithm was implemented in C++ in our epistasis screening software MBMDR-3.0.3. We evaluate the new implementation in terms of memory efficiency and speed using simulated data. The software is illustrated on real-life data for Crohn’s disease. Results: In the case of a binary (affected/unaffected) trait, the parallel workflow of MBMDR-3.0.3 analyzes all gene-gene interactions with a dataset of 100,000 SNPs typed on 1000 individuals within 4 days and 9 hours, using 999 permutations of the trait to assess statistical significance, on a cluster composed of 10 blades, containing each four Quad-Core AMD Opteron(tm) Processor 2352 2.1 GHz. In the case of a continuous trait, a similar run takes 9 days. Our program found 14 SNP-SNP interactions with a multiple-testing corrected p-value of less than 0.05 on real-life Crohn’s disease (CD) data. Conclusions: Our software is the first implementation of the MB-MDR methodology able to solve large-scale SNP-SNP interactions problems within a few days, without using much memory, while adequately controlling the type I error rates. A new implementation to reach genome-wide epistasis screening is under construction. In the context of Crohn’s disease, MBMDR-3.0.3 could identify epistasis involving regions that are well known in the field and could be explained from a biological point of view. This demonstrates the power of our software to find relevant phenotype-genotype higher-order associations.

A Canonical Genetic Algorithm for Blind Inversion of Linear Channels

It is well known the relationship between source separation and blind deconvolution: If a filtered version of an unknown i.i.d. signal is observed, temporal independence between samples can be used to retrieve the original signal, in the same manner as spatial independence is used for source separation. In this paper we propose the use of a Genetic Algorithm (GA) to blindly invert linear channels. The use of GA is justified in the case of small number of samples, where other gradient-like methods fails because of poor estimation of statistics.

A hybrid algorithm combining metaheuristic with Monte Carlo simulation for solving the Stochastic Flow Shop problem

In this paper, a hybrid simulation-based algorithm is proposed for the StochasticFlow Shop Problem. The main idea of the methodology is to transform the stochastic problem into a deterministic problem and then apply simulation to the latter. In order to achieve this goal, we rely on Monte Carlo Simulation and an adapted version of a deterministic heuristic. This approach aims to provide flexibility and simplicity due to the fact that it is not constrained by any previous assumption and relies in well-tested heuristics.

A hybrid algorithm combining metaheuristic with Monte Carlo simulation for solving the Stochastic Flow Shop problem

In this paper, a hybrid simulation-based algorithm is proposed for the StochasticFlow Shop Problem. The main idea of the methodology is to transform the stochastic problem into a deterministic problem and then apply simulation to the latter. In order to achieve this goal, we rely on Monte Carlo Simulation and an adapted version of a deterministic heuristic. This approach aims to provide flexibility and simplicity due to the fact that it is not constrained by any previous assumption and relies in well-tested heuristics.

Relation between plaque type, plaque thickness, blood shear stress, and plaque stress in coronary arteries assessed by X-ray Angiography and Intravascular Ultrasound

Purpose: Atheromatic plaque progression is affected, among others phenomena, by biomechanical, biochemical, and physiological factors. In this paper, the authors introduce a novel framework able to provide both morphological (vessel radius, plaque thickness, and type) and biomechanical (wall shear stress and Von Mises stress) indices of coronary arteries. Methods: First, the approach reconstructs the three-dimensional morphology of the vessel from intravascular ultrasound(IVUS) and Angiographic sequences, requiring minimal user interaction. Then, a computational pipeline allows to automatically assess fluid-dynamic and mechanical indices. Ten coronary arteries are analyzed illustrating the capabilities of the tool and confirming previous technical and clinical observations. Results: The relations between the arterial indices obtained by IVUS measurement and simulations have been quantitatively analyzed along the whole surface of the artery, extending the analysis of the coronary arteries shown in previous state of the art studies. Additionally, for the first time in the literature, the framework allows the computation of the membrane stresses using a simplified mechanical model of the arterial wall. Conclusions: Circumferentially (within a given frame), statistical analysis shows an inverse relation between the wall shear stress and the plaque thickness. At the global level (comparing a frame within the entire vessel), it is observed that heavy plaque accumulations are in general calcified and are located in the areas of the vessel having high wall shear stress. Finally, in their experiments the inverse proportionality between fluid and structural stresses is observed.

Genetic algorithm for sequencing in midex model non-permutation flowshops using constrained buffers

Este trabajo presenta un Algoritmo Genético (GA) del problema de secuenciar unidades en una línea de producción. Se tiene en cuenta la posibilidad de cambiar la secuencia de piezas mediante estaciones con acceso a un almacén intermedio o centralizado. El acceso al almacén además está restringido, debido al tamaño de las piezas.AbstractThis paper presents a Genetic Algorithm (GA) for the problem of sequencing in a mixed model non-permutation flowshop. Resequencingis permitted where stations have access to intermittent or centralized resequencing buffers. The access to a buffer is restricted by the number of available buffer places and the physical size of the products.

Kumar's algorithm for solving Toeplitz systems of equations over finite fields

Adaptació de l'algorisme de Kumar per resoldre sistemes d'equacions amb matrius de Toeplitz sobre els reals a cossos finits en un temps 0 (n log n).

Implementation of the Rijndael-AES algorithm on a Sage-Math worksheet

La principal motivació d'aquest treball ha estat implementar l'algoritme Rijndael-AES en un full Sage-math, paquet de software matemàtic de lliure distribució i en actual desenvolupament, aprofitant les seves eines i funcionalitats integrades.

The star forming region Monoceros R2 as a gamma-ray source

After the release of the gamma-ray source catalog produced by the Fermi satellite during its first two years of operation, a significant fraction of sources still remain unassociated at lower energies. In addition to well-known high-energy emitters (pulsars, blazars, supernova remnants, etc.), theoretical expectations predict new classes of gamma-ray sources. In particular, gamma-ray emission could be associated with some of the early phases of stellar evolution, but this interesting possibility is still poorly understood. Aims: The aim of this paper is to assess the possibility of the Fermi gamma-ray source 2FGL J0607.5-0618c being associated with the massive star forming region Monoceros R2. Methods: A multi-wavelength analysis of the Monoceros R2 region is carried out using archival data at radio, infrared, X-ray, and gamma-ray wavelengths. The resulting observational properties are used to estimate the physical parameters needed to test the different physical scenarios. Results: We confirm the 2FGL J0607.5-0618c detection with improved confidence over the Fermi two-year catalog. We find that a combined effect of the multiple young stellar objects in Monoceros R2 is a viable picture for the nature of the source.

The changing milliarcsecond radio morphology of the gamma-ray binary LS 5039

LS 5039 is one of the few TeV emitting X-ray binaries detected so far. The powering source of its multiwavelength emission can be accretion in a microquasar scenario or wind interaction in a young nonaccreting pulsar scenario. Aims.To present new high-resolution radio images and compare them with the expected behavior in the different scenarios. Methods.We analyze Very Long Baseline Array (VLBA) radio observations that provide morphological and astrometric information at milliarcsecond scales. Results.We detect a changing morphology between two images obtained five days apart. In both runs there is a core component with a constant flux density, and an elongated emission with a position angle (PA) that changes by 12 $\pm$ $3\degr$ between both runs. The source is nearly symmetric in the first run and asymmetric in the second one. The astrometric results are not conclusive. Conclusions.A simple and shockless microquasar scenario cannot easily explain the observed changes in morphology. An interpretation within the young nonaccreting pulsar scenario requires the inclination of the binary system to be very close to the upper limit imposed by the absence of X-ray eclipses.

Spectral energy distribution of the gamma-ray microquasar LS 5039

The microquasar LS 5039 has recently been detected as a source of very high energy (VHE) $\gamma$-rays. This detection, that confirms the previously proposed association of LS 5039 with the EGRET source 3EG~J1824$-$1514, makes of LS 5039 a special system with observational data covering nearly all the electromagnetic spectrum. In order to reproduce the observed spectrum of LS 5039, from radio to VHE $\gamma$-rays, we have applied a cold matter dominated jet model that takes into account accretion variability, the jet magnetic field, particle acceleration, adiabatic and radiative losses, microscopic energy conservation in the jet, and pair creation and absorption due to the external photon fields, as well as the emission from the first generation of secondaries. The radiative processes taken into account are synchrotron, relativistic Bremsstrahlung and inverse Compton (IC). The model is based on a scenario that has been characterized with recent observational results, concerning the orbital parameters, the orbital variability at X-rays and the nature of the compact object. The computed spectral energy distribution (SED) shows a good agreement with the available observational data.

Relation between plaque type, plaque thickness, blood shear stress, and plaque stress in coronary arteries assessed by X-ray Angiography and Intravascular Ultrasound

Purpose: Atheromatic plaque progression is affected, among others phenomena, by biomechanical, biochemical, and physiological factors. In this paper, the authors introduce a novel framework able to provide both morphological (vessel radius, plaque thickness, and type) and biomechanical (wall shear stress and Von Mises stress) indices of coronary arteries. Methods: First, the approach reconstructs the three-dimensional morphology of the vessel from intravascular ultrasound(IVUS) and Angiographic sequences, requiring minimal user interaction. Then, a computational pipeline allows to automatically assess fluid-dynamic and mechanical indices. Ten coronary arteries are analyzed illustrating the capabilities of the tool and confirming previous technical and clinical observations. Results: The relations between the arterial indices obtained by IVUS measurement and simulations have been quantitatively analyzed along the whole surface of the artery, extending the analysis of the coronary arteries shown in previous state of the art studies. Additionally, for the first time in the literature, the framework allows the computation of the membrane stresses using a simplified mechanical model of the arterial wall. Conclusions: Circumferentially (within a given frame), statistical analysis shows an inverse relation between the wall shear stress and the plaque thickness. At the global level (comparing a frame within the entire vessel), it is observed that heavy plaque accumulations are in general calcified and are located in the areas of the vessel having high wall shear stress. Finally, in their experiments the inverse proportionality between fluid and structural stresses is observed.

Radio Imaging of the Very-High-Energy γ-Ray Emission Region in the Central Engine of a Radio Galaxy

The accretion of matter onto a massive black hole is believed to feed the relativistic plasma jets found in many active galactic nuclei (AGN). Although some AGN accelerate particles to energies exceeding 1012 electron volts and are bright sources of very-high-energy (VHE) γ-ray emission, it is not yet known where the VHE emission originates. Here we report on radio and VHE observations of the radio galaxy Messier 87, revealing a period of extremely strong VHE γ-ray flares accompanied by a strong increase of the radio flux from its nucleus. These results imply that charged particles are accelerated to very high energies in the immediate vicinity of the black hole.

Gamma-ray emission from microquasars: a numerical model for LSI+61º303

We explore the possible association between the microquasar LSI +61°303 and the EGRET source 2CG 135+01/3EG J0241+6103 by studying, with a detailed numerical model, whether this system can produce the emission and the variability detected by EGRET (>100 MeV) through inverse Compton (IC) scattering. Our numerical approach considers a population of relativistic electrons entrained in a cylindrical inhomogeneous jet, interacting with both the radiation and the magnetic fields, taking into account the Thomson and Klein-Nishina regimes of interaction. Our results reproduce the observed spectral characteristics and variability at γ-rays, thus strengthening the identification of LSI +61°303 as a high-energy γ-ray source.

Efficacy of the fluorescent dyes Fast Blue, Fluoro-Gold, and Diamidino Yellow for retrograde tracing to dorsal root ganglia after subcutaneous injection

The present study was designed to investigate the efficacy of the fluorescent dyes Fast Blue (FB), Fluoro-Gold (FG), and Diamidino Yellow (DY) for retrograde tracing of lumbar dorsal root ganglia after their subcutaneous injection into different hindlimb digits. Injection of equal volumes (0.5 mu l) of 5% FB or 2% FG resulted in similar mean numbers of sensory neurones labelled by each tracer. Injection of equal volumes (0.5 mu l) of FB or FG in a single digit followed 10 days later by a second injection of the same volume of 5% DY into the same digit resulted in similar mean numbers of labelled sensory neurones for each of the three tracers. Furthermore, on average, 75% of all the FB-labelled cells and 74% of all FC-labelled cells also contained DY. Repeating the same experiment with an increased volume of DY (1.5 mu l) resulted in an increase in the mean number of double-labelled profiles to 82 and 84% for FB and FG, respectively. The results show that FB, FG and DY label similar numbers of cutaneous afferents and that a high level of double labelling may be obtained after sequential injections in digits. These properties make them suitable candidates in investigations where a combination of tracers with similar labelling efficacies is needed.