Of mice and men: Sparse statistical modeling in cardiovascular genomics

In high-throughput genomics, large-scale designed experiments are becoming common, and analysis approaches based on highly multivariate regression and anova concepts are key tools. Shrinkage models of one form or another can provide comprehensive approaches to the problems of simultaneous inference that involve implicit multiple comparisons over the many, many parameters representing effects of design factors and covariates. We use such approaches here in a study of cardiovascular genomics. The primary experimental context concerns a carefully designed, and rich, gene expression study focused on gene-environment interactions, with the goals of identifying genes implicated in connection with disease states and known risk factors, and in generating expression signatures as proxies for such risk factors. A coupled exploratory analysis investigates cross-species extrapolation of gene expression signatures--how these mouse-model signatures translate to humans. The latter involves exploration of sparse latent factor analysis of human observational data and of how it relates to projected risk signatures derived in the animal models. The study also highlights a range of applied statistical and genomic data analysis issues, including model specification, computational questions and model-based correction of experimental artifacts in DNA microarray data.Comment: Published at http://dx.doi.org/10.1214/07-AOAS110 in the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Creation and validation of the 4-item BriefPCS-chronic through methodological triangulation

© 2020 The Author(s). Background: The Pain Catastrophizing Scale (PCS) is a widely used self-report tool to evaluate pain related catastrophizing. The PCS was developed using classical test theory and has been shown to be psychometrically sound among various populations. However, it\u27s current three subscales are rarely used in clinical practice, offering potential for an abbreviated version that reduces administrative burden and can be used to estimate full scale scores, yet is not bound by the inclusion of items from each subscale. Hence, the aim of the current study was to develop a unidimensional abbreviated version of the PCS through findings from qualitative, classical test theory, and newer Rasch analysis. Methods: The current cross-sectional study used data from the Quebec Pain Registry (n = 5646) to obtain PCS scores of people seeking care at tertiary chronic pain centres. To develop an abbreviated unidimensional tool, items were removed based on triangulation of qualitative review of each item and response, corrected item-total correlations, and Rasch analysis. Confirmatory factor analysis was conducted on the final remaining items to confirm the tool was assessing a single latent construct (catastrophizing). Fit was assessed using the cumulative fit index (CFI), Tucker Lewis Index (TLI), and root-mean-squared error of approximation (RMSEA). Results: After triangulation, a final abbreviated 4-item scale showed adequate model fit with a strong correlation (r \u3e 0.95) with the original scale and properties that were stable across age, sex, cause, and medicolegal status. Additionally, the brief version addressed some problematic wording on some items on the original scale. Both the original and new abbreviated tool were associated with the Beck Depression Inventory and the Brief Pain Inventory at the same magnitude. Conclusion: The abbreviated scale may allow for a decrease in administrator burden and greater clinical uptake when a quick screen for exaggerated negative orientation towards pain is needed

Current oscillations in Vanadium Dioxide: evidence for electrically triggered percolation avalanches

In this work, we experimentally and theoretically explore voltage controlled oscillations occurring in micro-beams of vanadium dioxide. These oscillations are a result of the reversible insulator to metal phase transition in vanadium dioxide. Examining the structure of the observed oscillations in detail, we propose a modified percolative-avalanche model which allows for voltage-triggering. This model captures the periodicity and waveshape of the oscillations as well as several other key features. Importantly, our modeling shows that while temperature plays a critical role in the vanadium dioxide phase transition, electrically induced heating cannot act as the primary instigator of the oscillations in this configuration. This realization leads us to identify electric field as the most likely candidate for driving the phase transition

Improving Cosmological Distance Measurements by Reconstruction of the Baryon Acoustic Peak

The baryon acoustic oscillations are a promising route to the precision measure of the cosmological distance scale and hence the measurement of the time evolution of dark energy. We show that the non-linear degradation of the acoustic signature in the correlations of low-redshift galaxies is a correctable process. By suitable reconstruction of the linear density field, one can sharpen the acoustic peak in the correlation function or, equivalently, restore the higher harmonics of the oscillations in the power spectrum. With this, one can achieve better measurements of the acoustic scale for a given survey volume. Reconstruction is particularly effective at low redshift, where the non-linearities are worse but where the dark energy density is highest. At z=0.3, we find that one can reduce the sample variance error bar on the acoustic scale by at least a factor of 2 and in principle by nearly a factor of 4. We discuss the significant implications our results have for the design of galaxy surveys aimed at measuring the distance scale through the acoustic peak.Comment: 5 pages, LaTeX. Submitted to the Astrophysical Journa

Syntaphilin Ubiquitination Regulates Mitochondrial Dynamics and Tumor Cell Movements.

Syntaphilin (SNPH) inhibits the movement of mitochondria in tumor cells, preventing their accumulation at the cortical cytoskeleton and limiting the bioenergetics of cell motility and invasion. Although this may suppress metastasis, the regulation of the SNPH pathway is not well understood. Using a global proteomics screen, we show that SNPH associates with multiple regulators of ubiquitin-dependent responses and is ubiquitinated by the E3 ligase CHIP (or STUB1) on Lys111 and Lys153 in the microtubule-binding domain. SNPH ubiquitination did not result in protein degradation, but instead anchored SNPH on tubulin to inhibit mitochondrial motility and cycles of organelle fusion and fission, that is dynamics. Expression of ubiquitination-defective SNPH mutant Lys111!Arg or Lys153!Arg increased the speed and distance traveled by mitochondria, repositioned mitochondria to the cortical cytoskeleton, and supported heightened tumor chemotaxis, invasion, and metastasis in vivo. Interference with SNPH ubiquitination activated mitochondrial dynamics, resulting in increased recruitment of the fission regulator dynamin-related protein-1 (Drp1) to mitochondria and Drp1-dependent tumor cell motility. These data uncover nondegradative ubiquitination of SNPH as a key regulator of mitochondrial trafficking and tumor cell motility and invasion. In this way, SNPH may function as a unique, ubiquitination-regulated suppressor of metastasis

Characterizing Solid Electrolyte Interphase on Sn Anode in Lithium Ion Battery

Tin (Sn) nanoparticle electrodes have been prepared and battery cycling performance has been investigated with 1.2 M LiPF6 in ethylene carbonate (EC) / diethyl carbonate (DEC) electrolyte (1:1, w/w) with and without added vinylene carbonate (VC) or fluoroethylene carbonate (FEC). Incorporation of either VC or FEC improves the capacity retention of Sn nanoparticle electrodes although incorporation of VC also results in a significant increase in cell impedance. The best electrochemical performance was observed with electrolyte containing 10% of added FEC. In order to develop a better understanding of the role of the electrolyte in capacity retention and solid electrolyte interface (SEI) structure, ex-situ surface analysis has been performed on cycled electrodes with infrared (IR) spectroscopy, X-ray photoelectron spectroscopy (XPS), and Hard XPS (HAXPES). The ex-situ analysis reveals a correlation between electrochemical performance, electrolyte composition, and SEI structure