Variable Selection for Nonparametric Varying-Coefficient Models for Analysis of Repeated Measurements

Nonparametric varying-coefficient models are commonly used for analysis of data measured repeatedly over time, including longitudinal and functional responses data. While many procedures have been developed for estimating the varying-coefficients, the problem of variable selection for such models has not been addressed. In this article, we present a regularized estimation procedure for variable selection for such nonparametric varying-coefficient models using basis function approximations and a group smoothly clipped absolute deviation penalty (gSCAD). This gSCAD procedure simultaneously selects significant variables with time-varying effects and estimates unknown smooth functions using basis function approximations. With appropriate selection of the tuning parameters, we have established the oracle property of the procedure and the consistency of the function estimation. The methods are illustrated with simulations and an application to analysis of microarray time-course gene expression data to in order to identify the transcription factors that are related to yeast cell cycle process

A Unified Approach to Robust Inference for Genetic Covariance

Genome-wide association studies (GWAS) have identified thousands of genetic variants associated with complex traits. Many complex traits are found to have shared genetic etiology. Genetic covariance is defined as the underlying covariance of genetic values and can be used to measure the shared genetic architecture. The data of two outcomes may be collected from the same group or different groups of individuals and the outcomes can be of different types or collected based on different study designs. This paper proposes a unified approach to robust estimation and inference for genetic covariance of general outcomes that may be associated with genetic variants nonlinearly. We provide the asymptotic properties of the proposed estimator and show that our proposal is robust under certain model mis-specification. Our method under linear working models provides robust inference for the narrow-sense genetic covariance, even when both linear models are mis-specified. Various numerical experiments are performed to support the theoretical results. Our method is applied to an outbred mice GWAS data set to study the overlapping genetic effects between the behavioral and physiological phenotypes. The real data results demonstrate the robustness of the proposed method and reveal interesting genetic covariance among different mice developmental traits

Group SCAD Regression Analysis for Microarray Time Course Gene Expression Data

Since many important biological systems or processes are dynamic systems, it is important to study the gene expression patterns over time in a genomic scale in order to capture the dynamic behavior of gene expression. Microarray technologies have made it possible to measure the gene expression levels of essentially all the genes during a given biological process. In order to determine the transcriptional factors involved in gene regulation during a given biological process, we propose to develop a functional response model with varying coefficients in order to model the transcriptional effects on gene expression levels and to develop a group smoothly clipped absolute deviation (SCAD) regression procedure for selecting the transcriptional factors with varying coefficients that are involved in gene regulation during a biological process. Simulation studies indicated that such a procedure is quite effective in selecting the relevant variables with time-varying coefficients and in estimating the coefficients. Application to the yeast cell cycle microarray time course gene expression data set identified 19 of the 21 known transcriptional factors related to the cell cycle process. In addition, we have identified another 52 TFs that also have periodic transcriptional effects on gene expression during the cell cycle process. Compared to simple linear regression analysis at each time point, our procedure identified more known cell cycle related transcriptional factors. The proposed group SCAD regression procedure is very effective for identifying variables with time-varying coefficients, in particular, for identifying the transcriptional factors that are related to gene expression over time. By identifying the transcriptional factors that are related to gene expression variations over time, the procedure can potentially provide more insight into the gene regulatory networks

Acoustic Trauma Increases Cochlear and Hair Cell Uptake of Gentamicin

Exposure to intense sound or high doses of aminoglycoside antibiotics can increase hearing thresholds, induce cochlear dysfunction, disrupt hair cell morphology and promote hair cell death, leading to permanent hearing loss. When the two insults are combined, synergistic ototoxicity occurs, exacerbating cochlear vulnerability to sound exposure. The underlying mechanism of this synergism remains unknown. In this study, we tested the hypothesis that sound exposure enhances the intra-cochlear trafficking of aminoglycosides, such as gentamicin, leading to increased hair cell uptake of aminoglycosides and subsequent ototoxicity.Juvenile C57Bl/6 mice were exposed to moderate or intense sound levels, while fluorescently-conjugated or native gentamicin was administered concurrently or following sound exposure. Drug uptake was then examined in cochlear tissues by confocal microscopy.Prolonged sound exposure that induced temporary threshold shifts increased gentamicin uptake by cochlear hair cells, and increased gentamicin permeation across the strial blood-labyrinth barrier. Enhanced intra-cochlear trafficking and hair cell uptake of gentamicin also occurred when prolonged sound, and subsequent aminoglycoside exposure were temporally separated, confirming previous observations. Acute, concurrent sound exposure did not increase cochlear uptake of aminoglycosides.Prolonged, moderate sound exposures enhanced intra-cochlear aminoglycoside trafficking into the stria vascularis and hair cells. Changes in strial and/or hair cell physiology and integrity due to acoustic overstimulation could increase hair cell uptake of gentamicin, and may represent one mechanism of synergistic ototoxicity

Junior high school students’ perception of physical factors in the classroom based on the Online Q Method

 Students spend a lot of time in the classroom, and the physical environment in the classroom plays an important role in the development of students. It is necessary to scientifically investigate students' views and opinions on the physical factors in the classroom. Due to the COVID-19 pandemic, this study used the Q method online and allowed 40 junior high school students to rank 32 physical factors in the classrooms according to their own perspectives. The results can provide a reference for the reconstruction and construction of classrooms in middle schools and contribute to the design of learner-oriented humanized classrooms

A conserved but plant-specific CDK-mediated regulation of DNA replication protein A2 in the precise control of stomatal terminal division

The R2R3-MYB transcription factor FOUR LIPS (FLP) controls the stomatal terminal division through transcriptional repression of the cell cycle genes CYCLIN-DEPENDENT KINASE (CDK) B1s (CDKB1s), CDKA; 1, and CYCLIN A2s (CYCA2s). We mutagenized the weak mutant allele flp-1 seeds with ethylmethane sulfonate and screened out a flp-1 suppressor 1 (fsp1) that suppressed the flp-1 stomatal cluster phenotype. FSP1 encodes RPA2a subunit of Replication Protein A (RPA) complexes that play important roles in DNA replication, recombination, and repair. Here, we show that FSP1/RPA2a functions together with CDKB1s and CYCA2s in restricting stomatal precursor proliferation, ensuring the stomatal terminal division and maintaining a normal guard-cell size and DNA content. Furthermore, we provide direct evidence for the existence of an evolutionarily conserved, but plant-specific, CDK-mediated RPA regulatory pathway. Serine-11 and Serine-21 at the N terminus of RPA2a are CDK phosphorylation target residues. The expression of the phosphorylation-mimic variant RPA2a(S11,21/D) partially complemented the defective cell division and DNA damage hypersensitivity in cdkb1;1 1;2 mutants. Thus, our study provides a mechanistic understanding of the CDK-mediated phosphorylation of RPA in the precise control of cell cycle and DNA repair in plants