Varying Index Coefficient Models Ma, Shujie; Song, Peter X.-K.
Journal of the American Statistical Association,
03/2015, Volume:
110, Issue:
509
Journal Article
Peer reviewed
Open access
It has been a long history of using interactions in regression analysis to investigate alterations in covariate-effects on response variables. In this article, we aim to address two kinds of new ...challenges arising from the inclusion of such high-order effects in the regression model for complex data. The first kind concerns a situation where interaction effects of individual covariates are weak but those of combined covariates are strong, and the other kind pertains to the presence of nonlinear interactive effects directed by low-effect covariates. We propose a new class of semiparametric models with varying index coefficients, which enables us to model and assess nonlinear interaction effects between grouped covariates on the response variable. As a result, most of the existing semiparametric regression models are special cases of our proposed models. We develop a numerically stable and computationally fast estimation procedure using both profile least squares method and local fitting. We establish both estimation consistency and asymptotic normality for the proposed estimators of index coefficients as well as the oracle property for the nonparametric function estimator. In addition, a generalized likelihood ratio test is provided to test for the existence of interaction effects or the existence of nonlinear interaction effects. Our models and estimation methods are illustrated by simulation studies, and by an analysis of child growth data to evaluate alterations in growth rates incurred by mother's exposures to endocrine disrupting compounds during pregnancy. Supplementary materials for this article are available online.
Abstract
Study Objectives:
While short and poor quality sleep among training physicians has long been recognized as problematic, the longitudinal relationships among sleep, work hours, mood, and work ...performance are not well understood. Here, we prospectively characterize the risk of depression and medical errors based on preinternship sleep disturbance, internship-related sleep duration, and duty hours.
Methods:
Survey data from 1215 nondepressed interns were collected at preinternship baseline, then 3 and 6 months into internship. We examined how preinternship sleep quality and internship sleep and work hours affected risk of depression at 3 months, per the Patient Health Questionnaire 9. We then examined the impact of sleep loss and work hours on depression persistence from 3 to 6 months. Finally, we compared self-reported errors among interns based on nightly sleep duration (≤6 hr vs. >6 hr), weekly work hours (<70 hr vs. ≥70 hr), and depression (non- vs. acutely vs. chronically depressed).
Results:
Poorly sleeping trainees obtained less sleep and were at elevated risk of depression in the first months of internship. Short sleep (≤6 hr nightly) during internship mediated the relationship between sleep disturbance and depression risk, and sleep loss led to a chronic course for depression. Depression rates were highest among interns with both sleep disturbance and short sleep. Elevated medical error rates were reported by physicians sleeping ≤6 hr per night, working ≥ 70 weekly hours, and who were acutely or chronically depressed.
Conclusions:
Sleep disturbance and internship-enforced short sleep increase risk of depression development and chronicity and medical errors. Interventions targeting sleep problems prior to and during residency hold promise for curbing depression rates and improving patient care.
To elucidate the cytotoxicity mechanism of Garnoderma triterpenes, a chemoproteomic study using five purified ganoderic acids, ganoderic acid F (GAF), ganoderic acid K (GAK), ganoderic B (GAB), ...ganoderic acid D (GAD) and ganoderic acid AM1 (GAAM1) was conducted. GAF, GAK, GAB, GAD and GAAM1 treatment for 48 h inhibited the proliferation of HeLa human cervical carcinoma cells with IC
50 values of 19.5±0.6
μM, 15.1±0.5
μM, 20.3±0.4
μM, 17.3±0.3
μM, 19.8±0.7
μM, respectively. The protein expression profiles of HeLa cells treated with each ganoderic acid at dose of 15
μM for 48
h were checked using two-dimensional electrophoresis (2-DE). The possible target-related proteins of ganoderic acids, i.e. proteins with same change tendency in all five ganoderic acids-treated groups compared with control, were identified using MALDI-TOF MS/MS. Twelve proteins including human interleukin-17E, eukaryotic translation initiation factor 5A (eIF5A), peroxiredoxin 2, ubiquilin 2, Cu/Zn-superoxide dismutase, 14-3-3 beta/alpha, TPM4-ALK fusion oncoprotein type 2, PP2A subunit A PR65-alpha isoform, nucleobindin-1, heterogeneous nuclear ribonucleoprotein K, reticulocalbin 1 and chain A of DJ-1 protein were identified. Ganoderic acids might exert their cytotoxicity by altering proteins involved in cell proliferation and/or cell death, carcinogenosis, oxidative stress, calcium signaling and ER stress.
Background
Digital Image Correlation (DIC) is a widely employed full-field measurement technique in the realm of experimental mechanics. Nevertheless, mitigating measurement errors, particularly in ...fields with large strain gradients, remains a challenge.
Objective
The Gaussian window is employed to weight the correlation criterion in order to enhance measurement accuracy, and this method is called Gaussian window weighted DIC (GW-DIC). However, the optimization of the weighted correlation criterion does not guarantee that the displacement vector iterates to its optimal solution as the Gaussian window parameter changes during the iteration.
Methods
A new power window and the power window weighted DIC (PW-DIC) are proposed. The parameters of this power window keep constant during the iteration, and can be selected by given self-adaptive strategy for accuracy or preset according to the presumed deformation of the region of interest (ROI) for efficiency.
Results
The calculation example of synthetic images with imposed homogeneous deformation indicates that, the proposed power window is more effective than the Gaussian window when weighting the correlation criterion. For multi-directional deformation fields, both the displacement and strain accuracy of PW-DIC with self-adaptive parameters are at least 18% superior to those of conventional DIC. The tensile experimental dataset indicates that PW-DIC is more accurate and stable than GW-DIC.
Conclusions
PW-DIC with self-adaptive parameters is better suited for strain measurement in fields with large strain gradients. The weighted correlation criterion with preset parameters can potentially serve as a substitute for conventional correlation criterion.
The aim of this study was to construct a stable and efficient eukaryotic expression system for the secretion of biologically active recombinant human hepatocyte growth factor (rhHGF). The eukaryotic ...expression vector pGAPZα A was chosen to express rhHGF. To ensure the presence of the secondary structure, we inserted the enterokinase sequence between Arg494 and Val495. After digesting the rhHGF and pGAPZα A plasmid with Xho I and Xba I, we connected and transformed them into
E. coli
Trans10 competent cells. This resulted in the successful construction of the shuttle plasmid, pGAPZα A-rhHGF. After sequencing, we transformed the linearized pGAPZα A-rhHGF plasmid into
Pichia pastoris
GS115 using electroporation for subsequent protein expression. The expressed rhHGF samples were collected at 0, 24, 48, 72 and 96 h, purified by affinity chromatography, and tested using Western blotting. As a result, the pGAPZα A-rhHGF shuttle plasmid was constructed successfully. A positive band of approximately 80 kDa was observed in the Western blotting indicating successful expression of rhHGF. The highest expression abundance of rhHGF protein was observed at 48 h. Furthermore, we isolated and cultured primary rat hepatocytes, the harvested rhHGF protein exhibited high biological activity. This research provides experimental evidence for the eukaryotic expression of rhHGF protein and theoretical support for large-scale manufacturing.
Summary Objective This study aimed to investigate the role of the Wnt/β-catenin signaling pathway and E-cadherin/β-catenin complex in intermittent cyclic mechanical tension (ICMT)-induced endplate ...cartilage degeneration. Design β-Catenin expression was measured in disc samples obtained from patients with disc degeneration and those with cervical vertebrae fracture or dislocation. Histological staining was performed to examine the disc tissue morphology and extracellular matrix after application of ICMT in vitro and in vivo. Multiple strategies were employed to examine activation of Wnt/β-catenin signaling after ICMT application in vivo and in vitro . Co-immunoprecipitation was performed to examine the interaction between E-cadherin and β-catenin. Pathway-specific inhibitors and an E-cadherin expression plasmid were used to regulate Wnt/β-catenin signaling and E-cadherin expression. Results β-Catenin protein expression was elevated significantly, whereas cartilaginous genes were down-regulated in endplate cartilage samples obtained from patients with disc degeneration. ICMT loading led to Wnt/β-catenin signaling activation and the loss of the chondrogenic phenotype of endplate chondrocytes in both an in vivo rabbit model and in vitro endplate chondrocyte culture system. Inhibition of Wnt/β-catenin signaling suppressed the decrease in ICMT-induced cartilaginous gene expression. Furthermore, E-cadherin expression was inhibited by ICMT stimulation, resulting in a decrease in the interaction between E-cadherin and β-catenin proteins. Over-expression of E-cadherin rescued the cartilaginous gene expression by enhancing the interaction between E-cadherin and β-catenin proteins. Conclusions ICMT promotes endplate cartilage degeneration via activation of Wnt/β-catenin signaling and suppression of physical protein–protein interactions between E-cadherin and β-catenin.
Spatial‐clustered data refer to high‐dimensional correlated measurements collected from units or subjects that are spatially clustered. Such data arise frequently from studies in social and health ...sciences. We propose a unified modeling framework, termed as GeoCopula, to characterize both large‐scale variation, and small‐scale variation for various data types, including continuous data, binary data, and count data as special cases. To overcome challenges in the estimation and inference for the model parameters, we propose an efficient composite likelihood approach in that the estimation efficiency is resulted from a construction of over‐identified joint composite estimating equations. Consequently, the statistical theory for the proposed estimation is developed by extending the classical theory of the generalized method of moments. A clear advantage of the proposed estimation method is the computation feasibility. We conduct several simulation studies to assess the performance of the proposed models and estimation methods for both Gaussian and binary spatial‐clustered data. Results show a clear improvement on estimation efficiency over the conventional composite likelihood method. An illustrative data example is included to motivate and demonstrate the proposed method.
Summary
Regulatory T cells (Tregs) are specialized in immune suppression and play a dominant role in peripheral immune tolerance. Treg cell lineage development and function maintenance is determined ...by the forkhead box protein 3 (FoxP3) transcriptional factor, whose activity is fine‐tuned by its post‐translational modifications (PTMs) and interaction partners. In this review, we summarize current studies in the crystal structures, the PTMs and interaction partners of FoxP3 protein, and discuss how these insights may provide a roadmap for new approaches to modulate Treg suppression, and new therapies to enhance immune tolerance in autoimmune diseases.
FOXP3 is the master transcription factor in regulating Treg cell development and function. The forkhead domain of FOXP3 forms a domain‐swapped dimer which can bridge two long‐range FOXP3‐targeted genes (a). The zinc‐finger and leucine‐zipper domain forms oligomerization through the hydrophobic coiled‐coil surface (b). Acetylation of K250 and K252 located in the coiled‐coil region changes the conformation of FOXP3, which implies a structure‐based regulation of the conformation and activity of FOXP3 by integration of posttranslational modifications may modulate Treg function. Understanding the molecular and structural features of Foxp3 helps to design rational therapeutic strategies against autoimmune diseases.
Transition metal–based materials have become significant family of electrocatalysts for hydrogen and oxygen evolution because of their low cost, various compositions and structures, and their ...excellent electronic transfer ability. Because of their tunable compositions and diverse structures, polyoxometalates (POMs) are promising catalytic components and are promising precursors for the fabrication of early transition metal–based materials, especially for Mo and W, for hydrogen and oxygen evolution electrocatalysis. By incorporating POMs into metal–organic frameworks (MOFs) , the target POM/MOF will promote the dispersion of POMs and increase the compositional and structural complexity of the derived materials. In this review, recent relevant research fruits focusing on POM/MOF composites and their derivatives (such as carbides, oxides, phosphides, sulfides, and selenides) are summarized. Their designable synthesis, structure modulation, and electrocatalytic performance in HER and OER are highlighted to figure out the structure-property relationship. The existing problems of POM/MOF materials and their derivatives in electrocatalysis are also discussed. Then we propose the future prospective, providing a brand new vision of design and development of other POM/MOF-based/derived advanced electrocatalysts for water splitting.
This review will highlight the recent progress of polyoxometalate (POM)/metal–organic framework (MOF) hybrids and their derived functional materials, including metal carbides, oxides, phosphides, and chalcogenides, for hydrogen and oxygen evolution electrocatalysis. It will also focus on the structure modulation to boost the activity and figure out the structure–property relationship. This review will provide insightful guidance for design and development of other POM/MOF-based/derived advanced electrocatalysts for water splitting. Display omitted
•The applications of polyoxometalate / metal–organic framework hybrids and their derivatives in both hydrogen evolution reaction and oxygen evolution reaction are discussed.•Heterostructure, hollow structure, core/shell structure, carbon coating, and heteroatoms doping are summarized.•The synthesis and structure design strategies and the structure–activity relationship are figured out.•Mo- and W-based materials are focused.
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