Uncovering regulatory pathways that affect hematopoietic stem cell function using 'genetical genomics'

We combined large-scale mRNA expression analysis and gene mapping to identify genes and loci that control hematopoietic stem cell (HSC) function. We measured mRNA expression levels in purified HSCs isolated from a panel of densely genotyped recombinant inbred mouse strains. We mapped quantitative trait loci (QTLs) associated with variation in expression of thousands of transcripts. By comparing the physical transcript position with the location of the controlling QTL, we identified polymorphic cis-acting stem cell genes. We also identified multiple trans-acting control loci that modify expression of large numbers of genes. These groups of coregulated transcripts identify pathways that specify variation in stem cells. We illustrate this concept with the identification of candidate genes involved with HSC turnover. We compared expression QTLs in HSCs and brain from the same mice and identified both shared and tissue-specific QTLs. Our data are accessible through WebQTL, a web-based interface that allows custom genetic linkage analysis and identification of coregulated transcripts.

Graph theoretical approach to study eQTL: a case study of Plasmodium falciparum

Motivation: Analysis of expression quantitative trait loci (eQTL) significantly contributes to the determination of gene regulation programs. However, the discovery and analysis of associations of gene expression levels and their underlying sequence polymorphisms continue to pose many challenges. Methods are limited in their ability to illuminate the full structure of the eQTL data. Most rely on an exhaustive, genome scale search that considers all possible locus–gene pairs and tests the linkage between each locus and gene

Is there an association between ACTN3 R577X polymorphism and muscle power phenotypes in young, non-athletic adults?

We investigated the association between ACTN3 R577X polymorphism and jumping (vertical squat and counter-movement jump tests) and sprint ability (30 m dash) in non-athletic, healthy young adults [N=284 (217 male), mean (SD) age: 21 (2) years]. We analyzed the differences in the study phenotypes among ACTN3 R577X genotypes by one-way analysis of covariance before and after adjusting for sex, age, weight and height (confounders). We also compared the genotype and allele frequencies between those with the best and worst results in the aforementioned tests (≥90th vs 0.05). In summary, α-actinin-3 deficiency does not negatively influence the ability to generate explosive leg muscle power in a young non-athletic population

ACTN3 R577X Polymorphism does not Influence Explosive Leg Muscle Power in Elite Volleyball Players

We examined the association of R577X polymorphism (rs1815739) in the α-actinin-3 (ACTN3) gene with “explosive” leg muscle power performance in a group of male and female elite volleyball players (n=66, 31 men, 35 women) and in a group of non-athletic male and female young adults (n=334, 243 men, 91 women). We assessed power performance by means of the vertical squat and counter-movement jump tests. We also determined whether the genotypic frequencies of the ACTN3 R577X genotypes differed between groups. We did not observe any effect of the ACTN3 R577X polymorphism on study phenotypes in both groups, regardless of gender (all P>0.05). Genotype frequencies were similar between volleyball and control groups (P=0.095). Moreover, we did not find an association between the ACTN3 R577X polymorphism and the likelihood of being an elite volleyball player using the dominant (RR vs RX+XX) and the recessive model (RR+RX vs XX). In summary, these findings suggest that the ACTN3 R577X polymorphism does not influence explosive leg muscle power in elite volleyball players

Genetical genomics: spotlight on QTL hotspots

No abstract available

Reconstruction of the gravitational wave signal h(t)h(t) during the Virgo science runs and independent validation with a photon calibrator

The Virgo detector is a kilometer-scale interferometer for gravitational wave detection located near Pisa (Italy). About 13 months of data were accumulated during four science runs (VSR1, VSR2, VSR3 and VSR4) between May 2007 and September 2011, with increasing sensitivity. In this paper, the method used to reconstruct, in the range 10 Hz-10 kHz, the gravitational wave strain time series $h(t)$ from the detector signals is described. The standard consistency checks of the reconstruction are discussed and used to estimate the systematic uncertainties of the $h(t)$ signal as a function of frequency. Finally, an independent setup, the photon calibrator, is described and used to validate the reconstructed $h(t)$ signal and the associated uncertainties. The uncertainties of the $h(t)$ time series are estimated to be 8% in amplitude. The uncertainty of the phase of $h(t)$ is 50 mrad at 10 Hz with a frequency dependence following a delay of 8 $\mu$s at high frequency. A bias lower than $4\,\mathrm{\mu s}$ and depending on the sky direction of the GW is also present.Comment: 35 pages, 16 figures. Accepted by CQ

Virgo calibration and reconstruction of the gravitational wave strain during VSR1

Virgo is a kilometer-length interferometer for gravitational waves detection located near Pisa. Its first science run, VSR1, occured from May to October 2007. The aims of the calibration are to measure the detector sensitivity and to reconstruct the time series of the gravitational wave strain h(t). The absolute length calibration is based on an original non-linear reconstruction of the differential arm length variations in free swinging Michelson configurations. It uses the laser wavelength as length standard. This method is used to calibrate the frequency dependent response of the Virgo mirror actuators and derive the detector in-loop response and sensitivity within ~5%. The principle of the strain reconstruction is highlighted and the h(t) systematic errors are estimated. A photon calibrator is used to check the sign of h(t). The reconstructed h(t) during VSR1 is valid from 10 Hz up to 10 kHz with systematic errors estimated to 6% in amplitude. The phase error is estimated to be 70 mrad below 1.9 kHz and 6 micro-seconds above.Comment: 8 pages, 8 figures, proceedings of Amaldi 8 conference, to be published in Journal of Physics Conference Series (JPCS). Second release: correct typo

Calibration and sensitivity of the Virgo detector during its second science run

The Virgo detector is a kilometer-length interferometer for gravitational wave detection located near Pisa (Italy). During its second science run (VSR2) in 2009, six months of data were accumulated with a sensitivity close to its design. In this paper, the methods used to determine the parameters for sensitivity estimation and gravitational wave reconstruction are described. The main quantities to be calibrated are the frequency response of the mirror actuation and the sensing of the output power. Focus is also put on their absolute timing. The monitoring of the calibration data as well as the parameter estimation with independent techniques are discussed to provide an estimation of the calibration uncertainties. Finally, the estimation of the Virgo sensitivity in the frequency-domain is described and typical sensitivities measured during VSR2 are shown.Comment: 30 pages, 23 figures, 1 table. Published in Classical and Quantum Gravity (CQG), Corrigendum include

The variable finesse locking technique

Virgo is a power recycled Michelson interferometer, with 3 km long Fabry-Perot cavities in the arms. The locking of the interferometer has been obtained with an original lock acquisition technique. The main idea is to lock the instrument away from its working point. Lock is obtained by misaligning the power recycling mirror and detuning the Michelson from the dark fringe. In this way, a good fraction of light escapes through the antisymmetric port and the power build-up inside the recycling cavity is extremely low. The benefit is that all the degrees of freedom are controlled when they are almost decoupled, and the linewidth of the recycling cavity is large. The interferometer is then adiabatically brought on to the dark fringe. This technique is referred to as variable finesse, since the recycling cavity is considered as a variable finesse Fabry-Perot. This technique has been widely tested and allows us to reach the dark fringe in few minutes, in an essentially deterministic way

A Cross-correlation method to search for gravitational wave bursts with AURIGA and Virgo

We present a method to search for transient GWs using a network of detectors with different spectral and directional sensitivities: the interferometer Virgo and the bar detector AURIGA. The data analysis method is based on the measurements of the correlated energy in the network by means of a weighted cross-correlation. To limit the computational load, this coherent analysis step is performed around time-frequency coincident triggers selected by an excess power event trigger generator tuned at low thresholds. The final selection of GW candidates is performed by a combined cut on the correlated energy and on the significance as measured by the event trigger generator. The method has been tested on one day of data of AURIGA and Virgo during September 2005. The outcomes are compared to the results of a stand-alone time-frequency coincidence search. We discuss the advantages and the limits of this approach, in view of a possible future joint search between AURIGA and one interferometric detector.Comment: 11 pages, 6 figures, submitted to CQG special issue for Amaldi 7 Proceeding