Genome-wide co-expression analysis in multiple tissues

Expression quantitative trait loci (eQTLs) represent genetic control points of gene expression, and can be categorized as cis- and trans-acting, reflecting local and distant regulation of gene expression respectively. Although there is evidence of co-regulation within clusters of trans-eQTLs, the extent of co-expression patterns and their relationship with the genotypes at eQTLs are not fully understood. We have mapped thousands of cis- and trans-eQTLs in four tissues (fat, kidney, adrenal and left ventricle) in a large panel of rat recombinant inbred (RI) strains. Here we investigate the genome-wide correlation structure in expression levels of eQTL transcripts and underlying genotypes to elucidate the nature of co-regulation within cis- and trans-eQTL datasets. Across the four tissues, we consistently found statistically significant correlations of cis-regulated gene expression to be rare (<0.9% of all pairs tested). Most (>80%) of the observed significant correlations of cis-regulated gene expression are explained by correlation of the underlying genotypes. In comparison, co-expression of trans-regulated gene expression is more common, with significant correlation ranging from 2.9%-14.9% of all pairs of trans-eQTL transcripts. We observed a total of 81 trans-eQTL clusters (hot-spots), defined as consisting of > or =10 eQTLs linked to a common region, with very high levels of correlation between trans-regulated transcripts (77.2-90.2%). Moreover, functional analysis of large trans-eQTL clusters (> or =30 eQTLs) revealed significant functional enrichment among genes comprising 80% of the large clusters. The results of this genome-wide co-expression study show the effects of the eQTL genotypes on the observed patterns of correlation, and suggest that functional relatedness between genes underlying trans-eQTLs is reflected in the degree of co-expression observed in trans-eQTL clusters. Our results demonstrate the power of an integrative, systematic approach to the analysis of a large gene expression dataset to uncover underlying structure, and inform future eQTL studies

Simulation, Experiment, and Evolution: Understanding Nucleation in Protein S6 Folding

In this study, we explore nucleation and the transition state ensemble of the ribosomal protein S6 using a Monte Carlo Go model in conjunction with restraints from experiment. The results are analyzed in the context of extensive experimental and evolutionary data. The roles of individual residues in the folding nucleus are identified and the order of events in the S6 folding mechanism is explored in detail. Interpretation of our results agrees with, and extends the utility of, experiments that shift f-values by modulating denaturant concentration and presents strong evidence for the realism of the mechanistic details in our Monte Carlo Go model and the structural interpretation of experimental f-values. We also observe plasticity in the contacts of the hydrophobic core that support the specific nucleus. For S6, which binds to RNA and protein after folding, this plasticity may result from the conformational flexibility required to achieve biological function. These results present a theoretical and conceptual picture that is relevant in understanding the mechanism of nucleation in protein folding.Comment: PNAS in pres

Direct Josephson coupling between superconducting flux qubits

We have demonstrated strong antiferromagnetic coupling between two three-junction flux qubits based on a shared Josephson junction, and therefore not limited by the small inductances of the qubit loops. The coupling sign and magnitude were measured by coupling the system to a high-quality superconducting tank circuit. Design modifications allowing to continuously tune the coupling strength and/or make the coupling ferromagnetic are discussed.Comment: REVTeX 4, 4 pages, 5 figures; v2: completely rewritten, added finite-temperature results and proposals for ferromagnetic galvanic couplin

Electron g-Factor Anisotropy in Symmetric (110)-oriented GaAs Quantum Wells

We demonstrate by spin quantum beat spectroscopy that in undoped symmetric (110)-oriented GaAs/AlGaAs single quantum wells even a symmetric spatial envelope wavefunction gives rise to an asymmetric in-plane electron Land\'e-g-factor. The anisotropy is neither a direct consequence of the asymmetric in-plane Dresselhaus splitting nor of the asymmetric Zeeman splitting of the hole bands but is a pure higher order effect that exists as well for diamond type lattices. The measurements for various well widths are very well described within 14 x 14 band k.p theory and illustrate that the electron spin is an excellent meter variable to map out the internal -otherwise hidden- symmetries in two dimensional systems. Fourth order perturbation theory yields an analytical expression for the strength of the g-factor anisotropy, providing a qualitative understanding of the observed effects

Geometric observation for the Bures fidelity between two states of a qubit

In this Brief Report, we present a geometric observation for the Bures fidelity between two states of a qubit.Comment: 4 pages, 1 figure, RevTex, Accepted by Phys. Rev.

The Aladin2 experiment: sensitivity study

Aladin2 is an experiment devoted to the first measurement of variations of Casimir energy in a rigid body. The main short-term scientific motivation relies on the possibility of the first demonstration of a phase transition influenced by vacuum fluctuations while, in the long term and in the mainframe of the cosmological constant problem, it can be regarded as the first step towards a measurement of the weight of vacuum energy. In this paper, after a presentation of the guiding principle of the measurement, the experimental apparatus and sensitivity studies on final cavities will be presented