461 research outputs found
Genetic Dissection of Cardiac Remodeling in an Isoproterenol-Induced Heart Failure Mouse Model.
We aimed to understand the genetic control of cardiac remodeling using an isoproterenol-induced heart failure model in mice, which allowed control of confounding factors in an experimental setting. We characterized the changes in cardiac structure and function in response to chronic isoproterenol infusion using echocardiography in a panel of 104 inbred mouse strains. We showed that cardiac structure and function, whether under normal or stress conditions, has a strong genetic component, with heritability estimates of left ventricular mass between 61% and 81%. Association analyses of cardiac remodeling traits, corrected for population structure, body size and heart rate, revealed 17 genome-wide significant loci, including several loci containing previously implicated genes. Cardiac tissue gene expression profiling, expression quantitative trait loci, expression-phenotype correlation, and coding sequence variation analyses were performed to prioritize candidate genes and to generate hypotheses for downstream mechanistic studies. Using this approach, we have validated a novel gene, Myh14, as a negative regulator of ISO-induced left ventricular mass hypertrophy in an in vivo mouse model and demonstrated the up-regulation of immediate early gene Myc, fetal gene Nppb, and fibrosis gene Lgals3 in ISO-treated Myh14 deficient hearts compared to controls
Correcting for serial dependence in studies of respiratory dynamics
Understanding the physiological impact of drug treatments on patients is important in assessing their performance and determining possible side effects. While this effect might be best determined in individual subjects, conventional methods assess treatment performance by averaging a physiological measure of interest before and after drug administration for n subjects. Summarizing large numbers of time-series observations in two means for each subject in this way results in significant information loss. Treatment effect can instead be analyzed in individual subjects. Because serial dependence of observations from the same animal must then be considered, methods that assume independence of observations, such as the t-test and z-test, cannot be used. We address this issue in the case of respiratory data collected from anesthetized rats that were injected with a dopamine agonist. In order to accurately assess treatment effect in time-series data, we begin by formulating a method of conditional likelihood maximization to estimate the parameters of a first-order autoregressive (AR) process. We show that treatment effect of a dopamine agonist can be determined while incorporating serial effect into the analysis. In addition, while maximum likelihood estimators of a large sample with independent observations may converge to an asymptotically normal distribution, this result of large sample theory may not hold when observations are serially dependent. In this case, a parametric bootstrap comparison can be used to approximate an appropriate measure of uncertainty.National Institutes of Health (U.S.) (Grant DP1-OD003646)National Institutes of Health (U.S.) (Grant K08-GM094394)National Institutes of Health (U.S.) (Grant K08-GM083216
Semiconducting Polymer Photodetectors with Electron and Hole Blocking Layers: High Detectivity in the Near-Infrared
Sensing from the ultraviolet-visible to the infrared is critical for a variety of industrial and scientific applications. Photodetectors with broad spectral response, from 300 nm to 1,100 nm, were fabricated using a narrow-band gap semiconducting polymer blended with a fullerene derivative. By using both an electron-blocking layer and a hole-blocking layer, the polymer photodetectors, operating at room temperature, exhibited calculated detectivities greater than 1013 cm Hz1/2/W over entire spectral range with linear dynamic range approximately 130 dB. The performance is comparable to or even better than Si photodetectors
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Improved Constraints on Sterile Neutrino Mixing from Disappearance Searches in the MINOS, MINOS+, Daya Bay, and Bugey-3 Experiments.
Searches for electron antineutrino, muon neutrino, and muon antineutrino disappearance driven by sterile neutrino mixing have been carried out by the Daya Bay and MINOS+ collaborations. This Letter presents the combined results of these searches, along with exclusion results from the Bugey-3 reactor experiment, framed in a minimally extended four-neutrino scenario. Significantly improved constraints on the θ_{μe} mixing angle are derived that constitute the most constraining limits to date over five orders of magnitude in the mass-squared splitting Δm_{41}^{2}, excluding the 90% C.L. sterile-neutrino parameter space allowed by the LSND and MiniBooNE observations at 90% CL_{s} for Δm_{41}^{2}<13 eV^{2}. Furthermore, the LSND and MiniBooNE 99% C.L. allowed regions are excluded at 99% CL_{s} for Δm_{41}^{2}<1.6 eV^{2}
Structure of hadron resonances with a nearby zero of the amplitude
We discuss the relation between the analytic structure of the scattering
amplitude and the origin of an eigenstate represented by a pole of the
amplitude.If the eigenstate is not dynamically generated by the interaction in
the channel of interest, the residue of the pole vanishes in the zero coupling
limit. Based on the topological nature of the phase of the scattering
amplitude, we show that the pole must encounter with the
Castillejo-Dalitz-Dyson (CDD) zero in this limit. It is concluded that the
dynamical component of the eigenstate is small if a CDD zero exists near the
eigenstate pole. We show that the line shape of the resonance is distorted from
the Breit-Wigner form as an observable consequence of the nearby CDD zero.
Finally, studying the positions of poles and CDD zeros of the KbarN-piSigma
amplitude, we discuss the origin of the eigenstates in the Lambda(1405) region.Comment: 7 pages, 3 figures, v2: published versio
New measurement of via neutron capture on hydrogen at Daya Bay
This article reports an improved independent measurement of neutrino mixing
angle at the Daya Bay Reactor Neutrino Experiment. Electron
antineutrinos were identified by inverse -decays with the emitted
neutron captured by hydrogen, yielding a data-set with principally distinct
uncertainties from that with neutrons captured by gadolinium. With the final
two of eight antineutrino detectors installed, this study used 621 days of data
including the previously reported 217-day data set with six detectors. The
dominant statistical uncertainty was reduced by 49%. Intensive studies of the
cosmogenic muon-induced Li and fast neutron backgrounds and the
neutron-capture energy selection efficiency, resulted in a reduction of the
systematic uncertainty by 26%. The deficit in the detected number of
antineutrinos at the far detectors relative to the expected number based on the
near detectors yielded in the
three-neutrino-oscillation framework. The combination of this result with the
gadolinium-capture result is also reported.Comment: 26 pages, 23 figure
A new measurement of antineutrino oscillation with the full detector configuration at Daya Bay
We report a new measurement of electron antineutrino disappearance using the
fully-constructed Daya Bay Reactor Neutrino Experiment. The final two of eight
antineutrino detectors were installed in the summer of 2012. Including the 404
days of data collected from October 2012 to November 2013 resulted in a total
exposure of 6.910 GW-ton-days, a 3.6 times increase over
our previous results. Improvements in energy calibration limited variations
between detectors to 0.2%. Removal of six Am-C radioactive
calibration sources reduced the background by a factor of two for the detectors
in the experimental hall furthest from the reactors. Direct prediction of the
antineutrino signal in the far detectors based on the measurements in the near
detectors explicitly minimized the dependence of the measurement on models of
reactor antineutrino emission. The uncertainties in our estimates of
and were halved as a result of these
improvements. Analysis of the relative antineutrino rates and energy spectra
between detectors gave and eV in the three-neutrino
framework.Comment: Updated to match final published versio
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