Evaluation of a Bayesian inference network for ligand-based virtual screening

Background Bayesian inference networks enable the computation of the probability that an event will occur. They have been used previously to rank textual documents in order of decreasing relevance to a user-defined query. Here, we modify the approach to enable a Bayesian inference network to be used for chemical similarity searching, where a database is ranked in order of decreasing probability of bioactivity. Results Bayesian inference networks were implemented using two different types of network and four different types of belief function. Experiments with the MDDR and WOMBAT databases show that a Bayesian inference network can be used to provide effective ligand-based screening, especially when the active molecules being sought have a high degree of structural homogeneity; in such cases, the network substantially out-performs a conventional, Tanimoto-based similarity searching system. However, the effectiveness of the network is much less when structurally heterogeneous sets of actives are being sought. Conclusion A Bayesian inference network provides an interesting alternative to existing tools for ligand-based virtual screening

Impaired mitochondrial biogenesis contributes to depletion of functional mitochondria in chronic MPP+ toxicity: dual roles for ERK1/2

The regulation of mitochondrial quality has emerged as a central issue in neurodegeneration, diabetes, and cancer. We utilized repeated low-dose applications of the complex I inhibitor 1-methyl-4-phenylpyridinium (MPP+) over 2 weeks to study cellular responses to chronic mitochondrial stress. Chronic MPP+ triggered depletion of functional mitochondria resulting in diminished capacities for aerobic respiration. Inhibiting autophagy/mitophagy only partially restored mitochondrial content. In contrast, inhibiting activation of extracellular signal-regulated protein kinases conferred complete cytoprotection with full restoration of mitochondrial functional and morphological parameters, enhancing spare respiratory capacity in MPP+ co-treated cells above that of control cells. Reversal of mitochondrial injury occurred when U0126 was added 1 week after MPP+, implicating enhanced repair mechanisms. Chronic MPP+ caused a >90% decrease in complex I subunits, along with decreases in complex III and IV subunits. Decreases in respiratory complex subunits were reversed by co-treatment with U0126, ERK1/2 RNAi or transfection of dominant-negative MEK1, but only partially restored by degradation inhibitors. Chronic MPP+ also suppressed the de novo synthesis of mitochondrial DNA-encoded proteins, accompanied by decreased expression of the mitochondrial transcription factor TFAM. U0126 completely reversed each of these deficits in mitochondrial translation and protein expression. These data indicate a key, limiting role for mitochondrial biogenesis in determining the outcome of injuries associated with elevated mitophagy

Experimental study of strain rate effects on normal weight concrete after exposure to elevated temperature

© 2016, RILEM. The effects of strain rate ranging from 10-4 to 300 s-1 on normal weight concrete after exposure to elevated temperature up to 1000 °C were experimentally investigated using a servo-hydraulic testing machine and a split Hopkinson pressure bar. The casted cylinder concrete specimens were firstly heated in a microwave oven, and then cooled down to the ambient temperature with control. Experimental results proved that the normal weight concrete after high temperature exposure still showed significant strain rate dependency. The dynamic increase factor(DIF) for compressive strength decreased with the exposed elevated temperature from 600 to 800 °C, and increased from 800 to 1000 °C. The DIF of concrete after exposure to elevated temperature is smaller than that at the ambient temperature according to CEB code. The larger the compressive strength is, the smaller the DIF of normal weight concrete after high temperature exposure will be. In addition, further comparison showed that the DIF after high temperature exposure is larger than that exactly at the same high temperature. An empirical model of DIF for normal weight concrete after elevated temperature exposure was proposed based on the experimental data. It obviously benefits the assessment of blast resistant capacity of post-fired concrete structures, as well as referred retrofitting techniques

An exploratory analysis on Agritech policies, innovations and funding for climate change mitigation

Climate change mitigation technologies (CCMT) have significantly been developed for the last decade to mitigate the consequences of mega global challenges, such as climate risk and threatened food security. International agreements such as the Kyoto Protocol and Paris Agreement are the driving framework for developing policies and fostering research and innovation. However, the proportionality of technological innovation, funding, and policy development is very skewed towards energy-intensive sectors like transport, industry and energy and ignores sectors like agriculture and waste. This paper aims to explore three dimensions that drive the development of CCMT in the agriculture sector: innovation, policy and funding. We have used a mixed-method approach where we have collected open-source data, using text mining techniques for filtering CCMT and agriculture concerning regulations and projects, and applied a descriptive analysis. The findings of this study show that there is no precise alignment of the three dimensions and confirm that only 2.3% of the EU financial contribution goes to the agriculture sector. Moreover, most of the climate change policies or regulations are intended for energy-intensive sectors and not explicitly focused on agriculture. Finally, the analysis reveals that the constricted development of CCMT in the agricultural sector is not only due to the limited financial investment but also due to conflicting policies, decisions, and regulatory cooperation