A Hierarchical Bayesian Approach to Multi-Trait Clinical Quantitative Trait Locus Modeling

Recent advances in high-throughput genotyping and transcript profiling technologies have enabled the inexpensive production of genome-wide dense marker maps in tandem with huge amounts of expression profiles. These large-scale data encompass valuable information about the genetic architecture of important phenotypic traits. Comprehensive models that combine molecular markers and gene transcript levels are increasingly advocated as an effective approach to dissecting the genetic architecture of complex phenotypic traits. The simultaneous utilization of marker and gene expression data to explain the variation in clinical quantitative trait, known as clinical quantitative trait locus (cQTL) mapping, poses challenges that are both conceptual and computational. Nonetheless, the hierarchical Bayesian (HB) modeling approach, in combination with modern computational tools such as Markov chain Monte Carlo (MCMC) simulation techniques, provides much versatility for cQTL analysis. Sillanpää and Noykova (2008) developed a HB model for single-trait cQTL analysis in inbred line cross-data using molecular markers, gene expressions, and marker-gene expression pairs. However, clinical traits generally relate to one another through environmental correlations and/or pleiotropy. A multi-trait approach can improve on the power to detect genetic effects and on their estimation precision. A multi-trait model also provides a framework for examining a number of biologically interesting hypotheses. In this paper we extend the HB cQTL model for inbred line crosses proposed by Sillanpää and Noykova to a multi-trait setting. We illustrate the implementation of our new model with simulated data, and evaluate the multi-trait model performance with regard to its single-trait counterpart. The data simulation process was based on the multi-trait cQTL model, assuming three traits with uncorrelated and correlated cQTL residuals, with the simulated data under uncorrelated cQTL residuals serving as our test set for comparing the performances of the multi-trait and single-trait models. The simulated data under correlated cQTL residuals were essentially used to assess how well our new model can estimate the cQTL residual covariance structure. The model fitting to the data was carried out by MCMC simulation through OpenBUGS. The multi-trait model outperformed its single-trait counterpart in identifying cQTLs, with a consistently lower false discovery rate. Moreover, the covariance matrix of cQTL residuals was typically estimated to an appreciable degree of precision under the multi-trait cQTL model, making our new model a promising approach to addressing a wide range of issues facing the analysis of correlated clinical traits

Charge sensitivity of the Inductive Single-Electron Transistor

We calculate the charge sensitivity of a recently demonstrated device where the Josephson inductance of a single Cooper-pair transistor is measured. We find that the intrinsic limit to detector performance is set by oscillator quantum noise. Sensitivity better than $10^{-6}$e$/\sqrt{\mathrm{Hz}}$ is possible with a high $Q$-value $\sim 10^3$, or using a SQUID amplifier. The model is compared to experiment, where charge sensitivity $3 \times 10^{-5}$e$/\sqrt{\mathrm{Hz}}$ and bandwidth 100 MHz are achieved.Comment: 3 page

Sonoelectrochemical degradation of formic acid using Ti/Ta2O5-SnO2 electrodes

AbstractAdvanced oxidation processes (AOPs) are modern methods using highly reactive hydroxyl radicals for the oxidation of persistent organic (sometimes inorganic) compounds in aqueous phase. Among AOPs, sonoelectrochemical degradation is a technique employing electrochemistry and ultrasound as the main source of energy without the need for additional chemicals for the process. The annual production of formic acid (FA) is around 800,000tons and is a constituent in wastewaters from tannery, chemical, pharmaceutical, dyeing industries etc. Thus far sonoelectrochemical methods have never been applied to FA decomposition. The aim of this paper is to investigate the sonoelectrochemical decomposition of FA, optimize the sonochemical and electrochemical parameters involved in FA degradation and compare the results with other existing AOPs. Sonoelectrochemical degradation of FA was found to be either comparable or better than other AOPs in terms of time and degradation efficiency. The highest 97% mineralization of FA was obtained using 1176kHz ultrasonic irradiation combined with 20mA electrolysis in 120min. The fastest FA degradation kinetics with a rate constant of 0.0374min−1 were generated at 381kHz at 20mA at an ultrasonic power of 0.02W/cm3

Graphene Optomechanics Realized at Microwave Frequencies

Cavity optomechanics has served as a platform for studying the interaction between light and micromechanical motion via radiation pressure. Here we observe such phenomena with a graphene mechanical resonator coupled to an electromagnetic mode. We measure thermal motion and backaction cooling in a bilayer graphene resonator coupled to a microwave on-chip cavity. We detect the lowest flexural mode at 24 MHz down to 60 mK, corresponding to 50±6 mechanical quanta, which represents a phonon occupation that is nearly 3 orders of magnitude lower than that which has been recorded to date with graphene resonators.Peer reviewe

Long-term changes in the incidence of childhood epilepsy. A population study from Finland

BackgroundThe incidence of childhood epilepsy has changed during the past decades, but it is unclear whether it increased or decreased.MethodsChanges in drug-treated childhood epilepsy between 1968 and 2012 were evaluated using the Finnish nationwide register of all children, aged ≤ 15 years, on antiepileptic drugs (AEDs) prescribed for the treatment of epilepsy. The first registered entitlement to full-refundable AEDs was used as a proxy for newly diagnosed epilepsy. Incidence densities were calculated as ratios of annual new cases per 100,000 person-years in each calendar year during 1968 to 2012.ResultsThe annual incidence density of newly treated childhood epilepsy increased from 35 in the 1960s to 87 per 100,000 person-years in the 1990s and decreased thereafter to 61 per 100,000 person-years. Since 1996, the incidence density decreased 1–2% per year in children aged ConclusionThe incidence of drug-treated childhood epilepsy from the late 1960s to the early 1990s distinctly increased. The reasons for the increase are not fully understood but may include increasing ascertainment through improved diagnosis and a wider acceptance of AED treatment. Since the 1990s, a slight decline can be seen, probably reflecting the recent improvement in child health and safety.</p

Squeezing of Quantum Noise of Motion in a Micromechanical Resonator

Peer reviewe

Direct Observation of Josephson Capacitance

The effective capacitance has been measured in the split Cooper pair box (CPB) over its phase-gate bias plane. Our low-frequency reactive measurement scheme allows to probe purely the capacitive susceptibility due to the CPB band structure. The data are quantitatively explained using parameters determined independently by spectroscopic means. In addition, we show in practice that the method offers an efficient way to do non-demolition readout of the CPB quantum state.Comment: 4 page

Observation of shot-noise-induced asymmetry in the Coulomb blockaded Josephson junction

We have investigated the influence of shot noise on the IV-curves of a single mesoscopic Josephson junction. We observe a linear enhancement of zero-bias conductance of the Josephson junction with increasing shot noise power. Moreover, the IV-curves become increasingly asymmetric. Our analysis on the asymmetry shows that the Coulomb blockade of Cooper pairs is strongly influenced by the non-Gaussian character of the shot noise.Comment: 4 pages, 5 figures, RevTE