Dimension reduction and parameter estimation for additive index models *

In this paper, we consider simultaneous model selection and estimation for the additive index model. The additive index model is a class of structured nonparametric models that can be expressed as additive models of a set of unknown linear transformation of the original predictor variables. We introduce a penalized least squares estimator and discuss how it can be efficiently computed in practice. Both theoretical and empirical properties of the estimate are presented to demonstrate its merits. Extensions to more general prediction framework are also discussed

Heat shock transcription factor 1 preserves cardiac angiogenesis and adaptation during pressure overload

To examine how heat shock transcription factor 1 (HSF1) protects against maladaptive hypertrophy during pressure overload, we subjected HSF1 transgenic (TG), knockout (KO) and wild type (WT) mice to a constriction of transverse aorta (TAC), and found that cardiac hypertrophy, functions and angiogenesis were well preserved in TG mice but were decreased in KO mice compared to WT ones at 4 weeks, which was related to HIF-1 and p53 expression. Inhibition of angiogenesis suppressed cardiac adaptation in TG mice while overexpression of angiogenesis factors improved maladaptive hypertrophy in KO mice. In vitro formation of vasculatures by microvascular endothelial cells was higher in TG mice but lower in KO mice than in WT ones. A siRNA of p53 but not a HIF-1 gene significantly reversed maladaptive hypertrophy in KO mice whereas a siRNA of HIF-1 but not a p53 gene induced maladaptive hypertrophy in TG mice. Heart microRNA analysis showed that miR-378 and miR-379 were differently changed among the three mice after TAC, and miR-378 or siRNA of miR-379 could maintain cardiac adaptation in WT mice. These results indicate that HSF1 preserves cardiac adaptation during pressure overload through p53-HIF-1-associated angiogenesis, which is controlled by miR-378 and miR-379

PM2.5 Pollution: Health and Economic Effect Assessment Based on a Recursive Dynamic Computable General Equilibrium Model

At present particulate matter (PM₂.₅) pollution represents a serious threat to the public health and the national economic system in China. This paper optimizes the whitening coefficient in a grey Markov model by a genetic algorithm, predicts the concentration of fine particulate matter (PM₂.₅), and then quantifies the health effects of PM₂.₅ pollution by utilizing the predicted concentration, computable general equilibrium (CGE), and a carefully designed exposure–response model. Further, the authors establish a social accounting matrix (SAM), calibrate the parameter values in the CGE model, and construct a recursive dynamic CGE model under closed economy conditions to assess the long-term economic losses incurred by PM₂.₅ pollution. Subsequently, an empirical analysis was conducted for the Beijing area: Despite the reduced concentration trend, PM₂.₅ pollution continued to cause serious damage to human health and the economic system from 2013 to 2020, as illustrated by various facts, including: (1) the estimated premature deaths and individuals suffering haze pollution-related diseases are 156,588 (95% confidence intervals (CI): 43,335–248,914)) and six million, respectively; and (2) the accumulated labor loss and the medical expenditure negatively impact the regional gross domestic product, with an estimated loss of 3062.63 (95% CI: 1,168.77–4671.13) million RMB. These findings can provide useful information for governmental agencies to formulate relevant environmental policies and for communities to promote prevention and rescue strategies

17β-Estradiol Enhances Schwann Cell Differentiation via the ERβ-ERK1/2 Signaling Pathway and Promotes Remyelination in Injured Sciatic Nerves

Remyelination is critical for nerve regeneration. However, the molecular mechanism involved in remyelination is poorly understood. To explore the roles of 17β-estradiol (E2) for myelination in the peripheral nervous system, we used a co-culture model of rat dorsal root ganglion (DRG) explants and Schwann cells (SCs) and a regeneration model of the crushed sciatic nerves in ovariectomized (OVX) and non-ovariectomized (non-OVX) rats for in vitro and in vivo analysis. E2 promoted myelination by facilitating the differentiation of SCs in vitro, which could be inhibited by the estrogen receptors (ER) antagonist ICI182780, ERβ antagonist PHTPP, or ERK1/2 antagonist PD98059. This suggests that E2 accelerates SC differentiation via the ERβ-ERK1/2 signaling. Furthermore, E2 promotes remyelination in crushed sciatic nerves of both OVX and non-OVX rats. Interestingly, E2 also significantly increased the expression of the lysosome membrane proteins LAMP1 and myelin protein P0 in the regenerating nerves. Moreover, P0 has higher degree of colocalization with LAMP1 in the regenerating nerves. Taking together, our results suggest that E2 enhances Schwann cell differentiation and further myelination via the ERβ-ERK1/2 signaling and that E2 increases the expression of myelin proteins and lysosomes in SCs to promotes remyelination in regenerating sciatic nerves