Aging Shapes the Population-Mean and -Dispersion of Gene Expression in Human Brains

Human aging is associated with cognitive decline and an increased risk of neurodegenerative disease. Our objective for this study was to evaluate potential relationships between age and variation in gene expression across different regions of the brain. We analyzed the Genotype-Tissue Expression (GTEx) data from 54 to 101 tissue samples across 13 brain regions in post-mortem donors of European descent aged between 20 and 70 years at death. After accounting for the effects of covariates and hidden confounding factors, we identified 1446 protein-coding genes whose expression in one or more brain regions is correlated with chronological age at a false discovery rate of 5%. These genes are involved in various biological processes including apoptosis, mRNA splicing, amino acid biosynthesis, and neurotransmitter transport. The distribution of these genes among brain regions is uneven, suggesting variable regional responses to aging. We also found that the aging response of many genes, e.g., TP37 and C1QA, depends on individuals' genotypic backgrounds. Finally, using dispersion-specific analysis, we identified genes such as IL7R, MS4A4E, and TERF1/TERF2 whose expressions are differentially dispersed by aging, i.e., variances differ between age groups. Our results demonstrate that age-related gene expression is brain region-specific, genotype-dependent, and associated with both mean and dispersion changes. Our findings provide a foundation for more sophisticated gene expression modeling in the studies of age-related neurodegenerative diseases

Structure and microstructure evolution of Al-Mg-Si alloy processed by equal-channel angular pressing

An ultrafine grained Al–Mg–Si alloy was prepared by severe plastic deformation using the equal-channel angular pressing (ECAP) method. Samples were ECAPed through a die with an inner angle of F = 90° and outer arc of curvature of ¿ = 37° from 1 to 12 ECAP passes at room temperature following route Bc. To analyze the evolution of the microstructure at increasing ECAP passes, X-ray diffraction and electron backscatter diffraction analyses were carried out. The results revealed two distinct processing regimes, namely (i) from 1 to 5 passes, the microstructure evolved from elongated grains and sub-grains to a rather equiaxed array of ultrafine grains and (ii) from 5 to 12 passes where no change in the morphology and average grain size was noticed. In the overall behavior, the boundary misorientation angle and the fraction of high-angle boundaries increase rapidly up to 5 passes and at a lower rate from 5 to 12 passes. The crystallite size decreased down to about 45 nm with the increase in deformation. The influence of deformation on precipitate evolution in the Al–Mg–Si alloy was also studied by differential scanning calorimetry. A significant decrease in the peak temperature associated to the 50% of recrystallization was observed at increasing ECAP passes.Peer ReviewedPreprin

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

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}

New measurement of θ13\theta_{13} via neutron capture on hydrogen at Daya Bay

This article reports an improved independent measurement of neutrino mixing angle $\theta_{13}$ at the Daya Bay Reactor Neutrino Experiment. Electron antineutrinos were identified by inverse $\beta$-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 $^9$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 $\sin^22\theta_{13} = 0.071 \pm 0.011$ 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 6.9$\times$10$^5$ GW$_{\rm th}$-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 $^{241}$Am-$^{13}$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 $\sin^{2}2\theta_{13}$ and $|\Delta m^2_{ee}|$ were halved as a result of these improvements. Analysis of the relative antineutrino rates and energy spectra between detectors gave $\sin^{2}2\theta_{13} = 0.084\pm0.005$ and $|\Delta m^{2}_{ee}|= (2.42\pm0.11) \times 10^{-3}$ eV$^2$ in the three-neutrino framework.Comment: Updated to match final published versio