A Java Distributed Computation Library

This paper describes the design and development of a Java Distributed Computation Library, which provides a simple development platform for developers who wish to quickly implement a distributed computation in the context of an SPMD architecture (Single Program, Multiple Data). The need for this research arose out of the realisation that the currently available distributed computation libraries and systems do not adequately meet certain criteria, such as ease of development, dynamic changes to system behaviour, and easy deployment of distributed software. The proposed solution to this problem was to produce a Java-based distributed computation library which enables developers to use the Java language to quickly and easily implement a distributed computation. The results of experiments conducted using DCL are also presented, as a means of showing that DCL met its design goals

The Marginal Enumeration Bayesian Cramer-Rao Bound for Jump Markov Systems

A marginal version of the enumeration Bayesian Cramer-Rao Bound (EBCRB) for jump Markov systems is proposed. It is shown that the proposed bound is at least as tight as EBCRB and the improvement stems from better handling of the nonlinearities. The new bound is illustrated to yield tighter results than BCRB and EBCRB on a benchmark example

Accuracy and simultaneous selection gains for grain yield and earliness in tropical maize lines

Winter maize is sown between January and March in Brazil. Although this maize is sown in unfavorable weather conditions, many farmers are successful, and winter maize has become an important crop. The sowing of early hybrids is a strategy to reduce the effects of stress on yield; however, low yields may result from earliness. Thus, the objectives in this study were to investigate tropical maize lines for the possibility of simultaneous selection for yield and earliness and to compare the differences among the simultaneous selection methods. Therefore, 64 lines were evaluated in two locations for grain yield, days to female flowering and grain moisture at harvest. The genotypic values for these traits were predicted using Restricted Maximum Likelihood/Best Linear Unbiased Predictor (REML/BLUP) single-trait (univariate) and multi-trait (multivariate) methods. Using three simultaneous selection methods (i.e., Additive index, Mulamba-Mock index and Independent culling levels) with two methods of prediction for genotypic values (single-trait and multi-trait), six simultaneous selection scenarios were considered and then compared for selection gains and accuracy. Because of the low correlation between these traits, the pre- dictions of genotypic values were similar for single-trait and multi-trait methods. Thus, single-trait analysis should be prioritized because of its practicality. The Additive index obtained the highest selection gain for grain yield and simultaneously achieved good gains for days to female flowering and grain moisture at harvest. Therefore, the Additive index, using the single-trait prediction method, is the best simultaneous selection method for yield and earliness in tropical maize lines

Effects of RAF inhibitors on PI3K/AKT signalling depend on mutational status of the RAS/RAF signalling axis

Targeted therapies within the RAS/RAF/MEK/ERK signalling axis become increasingly popular, yet cross-talk and feedbacks in the signalling network lead to unexpected effects. Here we look systematically into how inhibiting RAF and MEK with clinically relevant inhibitors result in changes in PI3K/AKT activation. We measure the signalling response using a bead-based ELISA, and use a panel of three cell lines, and isogenic cell lines that express mutant forms of the oncogenes KRAS and BRAF to interrogate the effects of the MEK and RAF inhibitors on signalling. We find that treatment with the RAF inhibitors have opposing effects on AKT phosphorylation depending on the mutational status of two important oncogenes, KRAS and BRAF. If these two genes are in wildtype configuration, RAF inhibitors reduce AKT phosphorylation. In contrast, if BRAF or KRAS are mutant, RAF inhibitors will leave AKT phosphorylation unaffected or lead to an increase of AKT phosphorylation. Down-regulation of phospho-AKT by RAF inhibitors also extends to downstream transcription factors, and correlates with apoptosis induction. Our results show that oncogenes rewire signalling such that targeted therapies can have opposing effects on parallel pathways, which depend on the mutational status of the cell

An immediate-late gene expression module decodes ERK signal duration

The RAF-MEK-ERK signalling pathway controls fundamental, often opposing cellular processes such as proliferation and apoptosis. Signal duration has been identified to play a decisive role in these cell fate decisions. However, it remains unclear how the different early and late responding gene expression modules can discriminate short and long signals. We obtained both protein phosphorylation and gene expression time course data from HEK293 cells carrying an inducible construct of the proto-oncogene RAF By mathematical modelling, we identified a new gene expression module of immediate-late genes (ILGs) distinct in gene expression dynamics and function. We find that mRNA longevity enables these ILGs to respond late and thus translate ERK signal duration into response amplitude. Despite their late response, their GC-rich promoter structure suggested and metabolic labelling with 4SU confirmed that transcription of ILGs is induced immediately. A comparative analysis shows that the principle of duration decoding is conserved in PC12 cells and MCF7 cells, two paradigm cell systems for ERK signal duration. Altogether, our findings suggest that ILGs function as a gene expression module to decode ERK signal duration