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

The ABC Effect in Double-Pionic Nuclear Fusion and a pn Resonance as its Possible Origin

The ABC effect -- a long-standing puzzle in double-pionic fusion -- has been reexamined by the first exclusive and kinematically complete measurements of solid statistics for the fusion reactions $pn \to d\pi^0\pi^0$, $pd \to ^3$He$\pi\pi$ and $dd \to ^4$He$\pi\pi$ using the WASA detector, first at CELSIUS and recently at COSY -- the latter with a statistics increased by another two orders of magnitude. In all cases we observe a huge low-mass enhancement in the $\pi\pi$-invariant mass accompanied by a pronounced $\Delta\Delta$ excitation. For the most basic fusion reaction, the $pn \to d\pi^0\pi^0$ reaction, we observe in addition a very pronounced resonance-like energy dependence in the total cross section with a maximum 90 MeV below the $\Delta\Delta$ mass and a width of only 50 MeV, which is five times smaller than expected from a conventional $t$-channel $\Delta\Delta$ excitation. This reveals the ABC effect to be the consequence of a s-channel resonance with the formfactor of this dibaryonic state being reflected in the low-mass enhancement of the $\pi\pi$-invariant mass. From the fusion reactions to $^3$He and $^4$He we learn that this resonance is robust enough to survive even in nuclei.Comment: conference proceedings PANIC 0

Systematic Study of Two-Pion Production in NN Collisions -- from Single-Baryon to Di-Baryon Excitations

The two-pion production in nucleon-nucleon collisions has been studied by exclusive and kinematically complete experiments from threshold up to $T_p$ = 1.36 GeV at CELSIUS-WASA. At near-threshold energies the total and differential distributions for the $\pi^+\pi^-$ and $\pi^0\pi^0$ channels are dominated by Roper excitation and its decay into $N\sigma$ and $\Delta\pi$ channels. At beam energies $T_p >$ 1.1 GeV the $\Delta\Delta$ excitation governs the two-pion production process. In the $\pi^+\pi^+$ channel evidence is found for the excitation of a higher-lying I=3/2 resonance, favorably the $\Delta(1600)$. The isovector fusion processes leading to the deuteron and to quasi-stable $^2$He, respectively, %with the production of an isovector pion-pair exhibit no or only a modest ABC-effect, {\it i.e.} low-mass enhancement in the $\pi\pi$-invariant mass spectrum, and can be described by conventional $t$-channel $\Delta\Delta$ excitation. On the other hand, the isoscalar fusion process to the deuteron %with the production of an isoscalar pion-pair exhibits a dramatic ABC-effect correlated with a narrow resonance-like energy dependence in the total cross section with a width of only 50 MeV and situated at a mass 90 MeV below the $\Delta\Delta$ mass.Comment: Proceedings HADRON0

Glycosidase-catalyzed synthesis of glycosylated nutraceutical ingredients

Hydroxyphenyl propenoic acids (hydroxycinnamic acids) and their alcohol derivatives are common components of the human diet which often occur in plants in the form of various glycosides. As the diets rich in polyphenols have repeatedly been related to low incidence of cardiovascular, neurodegenerative, and oncological diseases, various food supplements containing these compounds are becoming increasingly popular among the general population. In quest of a biocatalytic route to structurally complex phenolic glycosides, we built a sustainable and convenient, one-pot two-enzyme method for the glucosylation of arylalkyl alcohols based on the synthetic exploitation of a fungal rutinosidase from A. niger and rhamnosidase from A. terreus. Both these enzymes were available to us as heterologous proteins produced by a recombinant strain of P. pastoris. As an example, the -glucoside salidroside, a compound endowed with various pharmacological effects and commercialized in Rhodiola rosea nutraceutical formulations, was obtained in high isolated yield and purity from tyrosol thanks to our one-pot enzymatic process. Furthermore, during the course of our investigation, we found that the rutinosidase from A. niger not only efficiently converted hydroxylated aromatic acids (e.g. coumaric and ferulic acids) into the respective phenolic rutinosides, but surprisingly could also catalyze the formation of the respective glycosyl esters. Here the results of our systematic study about the glycosidase-based biocatalytic preparation of lycosylated nutraceutical ingredients, which lead us to the discovery of a unique enzymatic entry to naturally occurring glycosyl esters, are reported

A Hot Dynamic Seal Rig for Measuring Hypersonic Engine Seal Durability and Flow Performance

A test fixture for measuring the dynamic performance of candidate high-temperature engine seal concepts was installed at NASA Lewis Research Center. The test fixture was designed to evaluate seal concepts under development for advanced hypersonic engines, such as those being considered for the National Aerospace Plane (NASP). The fixture can measure dynamic seal leakage performance from room temperature up to 840 C (1550 F) and air pressure differentials up to 690 kPa (100 psi). Performance of the seals can be measured while sealing against flat or distorted walls. In the fixture two seals are preloaded against the sides of a 30 cm (1 ft) long saber that slides transverse to the axis of the seals, simulating the scrubbing motion anticipated in these engines. The capabilities of this test fixture along with preliminary data showing the dependence of seal leakage performance on high temperature cycling are addressed

Hot dynamic test rig for measuring hypersonic engine seal flow and durability

A test fixture for measuring the dynamic performance of candidate high-temperature engine seal concepts was developed. The test fixture was developed to evaluate seal concepts under development for advanced hypersonic engines, such as those being considered for the National Aerospace Plane (NASP). The fixture can measure dynamic seal leakage performance from room temperature up to 840 C and air pressure differentials of to 0.7 MPa. Performance of the seals can be measured while sealing against flat or engine-simulated distorted walls. In the fixture, two seals are preloaded against the sides of a 0.3 m long saber that slides transverse to the axis of the seals, simulating the scrubbing motion anticipated in these engines. The capabilities of this text fixture along with preliminary data showing the dependence of seal leakage performance on high temperature cycling are covered

Anisotropy in the pion angular distribution of the reaction pp -> pp pi0 at 400 MeV

The reaction pp -> pp pi0 was studied with the WASA detector at the CELSIUS storage ring. The center of mass angular distribution of the pi0 was obtained by detection of the gamma decay products together with the two outgoing protons, and found to be anisotropic with a negative second derivative slope, in agreement with the theoretical predictions from a microscopic calculation.Comment: Revtex 4 style, 5 pages 7 figures, PACS numbers:13.60.Le, 13.75.Cs, 21.45.+v, 25.10.+

The Effects of Reputation and Ethics on Budgetary Slack

This experimental study tests the effects on budgetary slack of two potential controls for opportunistic self-interestóreputation and ethics. I manipulate the level of information asymmetry between the subordinate and the superior regarding productive capability and measure the subordinateís reputation and ethical concerns regarding budgetary slack. In this setting, I examine how information asymmetry affects reputation and ethical concerns, and test the effects of these concerns on budgetary slack. Consistent with prior findings, subordinates restrict the slack in their budgets to well below the maximum under a slackinducing pay scheme, even after five periods of experience. Budgetary slack is negatively associated with a measure of ethical responsibility from a pre-experiment personality questionnaire as well as reputation and ethical concerns expressed in an exit questionnaire. Subordinates express lower reputation concerns as information asymmetry regarding productive capability increases, thereby reducing the superiorís ability to monitor the slack in their budget. Ethical concerns, however, are not diminished with increases in information asymmetry. These results suggest that reputation is a socially mediated control, whereas ethics is an internally mediated control for opportunistic self-interest