Anti-adipogenesis by 6-thioinosine is mediated by downregulation of PPAR γ through JNK-dependent upregulation of iNOS

Adipocyte dysfunction is associated with the development of obesity. This study shows that 6-thioinosine inhibits adipocyte differentiation. The mRNA levels of PPAR γ and C/EBPα, but not C/EBPβ and δ, were reduced by 6-thioinosine. Moreover, the mRNA levels of PPAR γ target genes (LPL, CD36, aP2, and LXRα) were down-regulated by 6-thioinosine. We also demonstrated that 6-thioinosine inhibits the transactivation activity and the mRNA level of PPAR γ. Additionally, attempts to elucidate a possible mechanism underlying the 6-thioinosine-mediated effects revealed that 6-thioinosine induced iNOS gene expression without impacting eNOS expression, and that this was mediated through activation of AP-1, especially, JNK. In addition, 6-thioinosine was found to operate upstream of MEKK-1 in JNK activation signaling. Taken together, these findings suggest that the inhibition of adipocyte differentiation by 6-thioinosine occurs primarily through the reduced expression of PPAR γ, which is mediated by upregulation of iNOS via the activation of JNK.     

Time series forecasting using functional partial least square regression with stochastic volatility,GARCH, and exponential smoothing

We propose a method for improving the predictive ability of standard forecasting models used in financial economics. Our approach is based on the functional partial least squares (FPLS) model, which is capable of avoiding multicollinearity in regression by efficiently extracting information from the high‐dimensional market data. By using its well‐known ability, we can incorporate auxiliary variables that improve the predictive accuracy. We provide an empirical application of our proposed methodology in terms of its ability to predict the conditional average log return and the volatility of crude oil prices via exponential smoothing, Bayesian stochastic volatility, and GARCH (generalized autoregressive conditional heteroskedasticity) models, respectively. In particular, what we call functional data analysis (FDA) traces in this article are obtained via the FPLS regression from both the crude oil returns and auxiliary variables of the exchange rates of major currencies. For forecast performance evaluation, we compare out‐of‐sample forecasting accuracy of the standard models with FDA traces to the accuracy of the same forecasting models with the observed crude oil returns, principal component regression (PCR), and least absolute shrinkage and selection operator (LASSO) models. We find evidence that the standard models with FDA traces significantly outperform our competing models. Finally, they are also compared with the test for superior predictive ability and the reality check for data snooping. Our empirical results show that our new methodology significantly improves predictive ability of standard models in forecasting the latent average log return and the volatility of financial time series.     

浅析足球守门员扑“单刀球”技术及训练方法

根据足球守门员扑球技术 ,分析了扑“单刀球”技术特点和出击时机 ,提出了对守门员训练方法     

Autistic-like social behaviour in Shank2-mutant mice improved by restoring NMDA receptor function

Autism spectrum disorder (ASD) is a group of conditions characterized by impaired social interaction and communication, and restricted and repetitive behaviours. ASD is a highly heritable disorder involving various genetic determinants. Shank2 (also known as ProSAP1) is a multi-domain scaffolding protein and signalling adaptor enriched at excitatory neuronal synapses, and mutations in the human SHANK2 gene have recently been associated with ASD and intellectual disability. Although ASD-associated genes are being increasingly identified and studied using various approaches, including mouse genetics, further efforts are required to delineate important causal mechanisms with the potential for therapeutic application. Here we show that Shank2-mutant (Shank2(-/-)) mice carrying a mutation identical to the ASD-associated microdeletion in the human SHANK2 gene exhibit ASD-like behaviours including reduced social interaction, reduced social communication by ultrasonic vocalizations, and repetitive jumping. These mice show a marked decrease in NMDA (N-methyl-D-aspartate) glutamate receptor (NMDAR) function. Direct stimulation of NMDARs with D-cycloserine, a partial agonist of NMDARs, normalizes NMDAR function and improves social interaction in Shank2(-/-) mice. Furthermore, treatment of Shank2(-/-) mice with a positive allosteric modulator of metabotropic glutamate receptor 5 (mGluR5), which enhances NMDAR function via mGluR5 activation, also normalizes NMDAR function and markedly enhances social interaction. These results suggest that reduced NMDAR function may contribute to the development of ASD-like phenotypes in Shank2(-/-) mice, and mGluR modulation of NMDARs offers a potential strategy to treat ASD.     

Effect of prolonged inhibition of histidine decarboxylase on tissue histamine concentrations

In rats, chronic infusion of alpha-fluoromethyl histidine, a selective irreversible inhibitor of mammalian histidine decarboxylase, caused a marked depletion of histamine in all tissues examined. There were no gross pharmacological effects associated with this depletion.     

Relationship Between Measured Friction Coefficients and Two Tread Groove Design Parameters for Footwear Pads

Introduction Slips and falls are common phenomena both in work- places and leisure activities. The coefficient of fric- tion (COF) between footwear and the floor is regarded as the most critical item determining the occurrence of a slip. It is commonly ac…     

管状曲面的奇点

研究管状曲面和它的平行曲面的奇点问题.所谓管状曲面,是沿着E3里一条曲线的双参数空间运动产生的.选定曲线的Frenet向量T作为旋转轴,用不同的方法得到了运动管状曲面的特征.然后,给出管状曲面奇点的一些定理和结果.