Mechanisms of gene silencing by double-stranded RNA

Double-stranded RNA (dsRNA) is an important regulator of gene expression in many eukaryotes. It triggers different types of gene silencing that are collectively referred to as RNA silencing or RNA interference. A key step in known silencing pathways is the processing of dsRNAs into short RNA duplexes of characteristic size and structure. These short dsRNAs guide RNA silencing by specific and distinct mechanisms. Many components of the RNA silencing machinery still need to be identified and characterized, but a more complete understanding of the process is imminent.     

Forecast Combinations in a DSGE‐VAR Lab

We explore the benefits of forecast combinations based on forecast‐encompassing tests compared to simple averages and to Bates–Granger combinations. We also consider a new combination algorithm that fuses test‐based and Bates–Granger weighting. For a realistic simulation design, we generate multivariate time series samples from a macroeconomic DSGE‐VAR (dynamic stochastic general equilibrium–vector autoregressive) model. Results generally support Bates–Granger over uniform weighting, whereas benefits of test‐based weights depend on the sample size and on the prediction horizon. In a corresponding application to real‐world data, simple averaging performs best. Uniform averages may be the weighting scheme that is most robust to empirically observed irregularities. Copyright © 2016 John Wiley & Sons, Ltd.     

The usefulness of heuristic N(E)RLS algorithms for combining forecasts

There exists theoretical and empirical evidence on the efficiency and robustness of Non-negativity Restricted Least Squares combinations of forecasts. However, the computational complexity of the method hinders its widespread use in practice. We examine various optimizing and heuristic computational algorithms for estimating NRLS combination models and provide certain CPU-time reducing implementations. We empirically compare the combination weights identified by the alternative algorithms and their computational demands based on a total of more than 66,000 models estimated to combine the forecasts of 37 firm-specific accounting earnings series. The ex ante prediction accuracies of combined forecasts from the optimizing versus heuristic algorithms are compared. The effects of fit sample size, model specification, multicollinearity, correlations of forecast errors, and series and forecast variances on the relative accuracy of the optimizing versus heuristic algorithms are analysed. The results reveal that, in general, the computationally simple heuristic algorithms perform as well as the optimizing algorithms. No generalizable conclusions could be reached, however, about which algorithm should be used based on series and forecast characteristics. © 1997 John Wiley & Sons, Ltd.     

N-step combinations of forecasts

While there is general agreement that a linear combination of forecasts can outperform the individual forecasts, there is controversy about the appropriateness of the combination method to be used in a given situation. Hence, in any given application it may be more beneficial to combine different sets of combined forecasts rather than picking one of them. This paper introduces the concept of N-step combinations of forecasts which involves combining the combined forecasts obtained from different combination procedures used at the preceding step. Using quarterly GNP data, evidence supporting the increase in the accuracy of the one-period-ahead ex-ante forecasts as the combination step increases is provided. The MSE, MAE, MAPE and their corresponding standard deviations are used to evaluate the accuracy of the forecasts obtained.     

流程工业中的优化技术及应用研究

提出了流程工业中的静态优化、动态优化和生产结构优化问题的命题和数学描述,及目前解决这些问题的优化方法和常用的工具。对正交配置离散化结合序贯二次规划优化计算的动态优化方法进行了详细的介绍。以热集成精馏系统以能耗最低为操作目标的优化为例,说明动态优化技术在流程工业中的应用。     

The environment and schizophrenia

Psychotic syndromes can be understood as disorders of adaptation to social context. Although heritability is often emphasized, onset is associated with environmental factors such as early life adversity, growing up in an urban environment, minority group position and cannabis use, suggesting that exposure may have an impact on the developing 'social' brain during sensitive periods. Therefore heritability, as an index of genetic influence, may be of limited explanatory power unless viewed in the context of interaction with social effects. Longitudinal research is needed to uncover gene-environment interplay that determines how expression of vulnerability in the general population may give rise to more severe psychopathology.     

Structural basis for 5'-end-specific recognition of guide RNA by the A. fulgidus Piwi protein

RNA interference (RNAi) is a conserved sequence-specific gene regulatory mechanism mediated by the RNA-induced silencing complex (RISC), which is composed of a single-stranded guide RNA and an Argonaute protein. The PIWI domain, a highly conserved motif within Argonaute, has been shown to adopt an RNase H fold critical for the endonuclease cleavage activity of RISC. Here we report the crystal structure of Archaeoglobus fulgidus Piwi protein bound to double-stranded RNA, thereby identifying the binding pocket for guide-strand 5'-end recognition and providing insight into guide-strand-mediated messenger RNA target recognition. The phosphorylated 5' end of the guide RNA is anchored within a highly conserved basic pocket, supplemented by the carboxy-terminal carboxylate and a bound divalent cation. The first nucleotide from the 5' end of the guide RNA is unpaired and stacks over a conserved tyrosine residue, whereas successive nucleotides form a four-base-pair RNA duplex. Mutation of the corresponding amino acids that contact the 5' phosphate in human Ago2 resulted in attenuated mRNA cleavage activity. Our structure of the Piwi-RNA complex, and that determined elsewhere, provide direct support for the 5' region of the guide RNA serving as a nucleation site for pairing with target mRNA and for a fixed distance separating the RISC-mediated mRNA cleavage site from the anchored 5' end of the guide RNA.