Mapping Dynamic Histone Acetylation Patterns to Gene Expression in Nanog-depleted Murine Embryonic Stem Cells

Embryonic stem cells (ESC) have the potential to self-renew indefinitely and to differentiate into any of the three germ layers. The molecular mechanisms for self-renewal, maintenance of pluripotency and lineage specification are poorly understood, but recent results point to a key role for epigenetic mechanisms. In this study, we focus on quantifying the impact of histone 3 acetylation (H3K9,14ac) on gene expression in murine embryonic stem cells. We analyze genome-wide histone acetylation patterns and gene expression profiles measured over the first five days of cell differentiation triggered by silencing Nanog, a key transcription factor in ESC regulation. We explore the temporal and spatial dynamics of histone acetylation data and its correlation with gene expression using supervised and unsupervised statistical models. On a genome-wide scale, changes in acetylation are significantly correlated to changes in mRNA expression and, surprisingly, this coherence increases over time. We quantify the predictive power of histone acetylation for gene expression changes in a balanced cross-validation procedure. In an in-depth study we focus on genes central to the regulatory network of Mouse ESC, including those identified in a recent genome-wide RNAi screen and in the PluriNet, a computationally derived stem cell signature. We find that compared to the rest of the genome, ESC-specific genes show significantly more acetylation signal and a much stronger decrease in acetylation over time, which is often not reflected in an concordant expression change. These results shed light on the complexity of the relationship between histone acetylation and gene expression and are a step forward to dissect the multilayer regulatory mechanisms that determine stem cell fate.Comment: accepted at PLoS Computational Biolog

Maintenance Strategies to Reduce Downtime Due to Machine Positional Errors

Manufacturing strives to reduce waste and increase Overall Equipment Effectiveness (OEE). When managing machine tool maintenance a manufacturer must apply an appropriate decision technique in order to reveal hidden costs associated with production losses, reduce equipment downtime competently and similarly identify the machines’ performance. Total productive maintenance (TPM) is a maintenance program that involves concepts for maintaining plant and equipment effectively. OEE is a powerful metric of manufacturing performance incorporating measures of the utilisation, yield and efficiency of a given process, machine or manufacturing line. It supports TPM initiatives by accurately tracking progress towards achieving “perfect production.” This paper presents a review of maintenance management methodologies and their application to positional error calibration decision-making. The purpose of this review is to evaluate the contribution of maintenance strategies, in particular TPM, towards improving manufacturing performance, and how they could be applied to reduce downtime due to inaccuracy of the machine. This is to find a balance between predictive calibration, on-machine checking and lost production due to inaccuracy. This work redefines the role of maintenance management techniques and develops a framework to support the process of implementing a predictive calibration program as a prime method to supporting the change of philosophy for machine tool calibration decision making. Keywords—maintenance strategies, down time, OEE, TPM, decision making, predictive calibration

Dispersal and extrapolation on the accuracy of temporal predictions from distribution models for the Darwin's frog

Indexación: Web of Science; Scopus.Climate change is a major threat to biodiversity; the development of models that reliably predict its effects on species distributions is a priority for conservation biogeography. Two of the main issues for accurate temporal predictions from Species Distribution Models (SDM) are model extrapolation and unrealistic dispersal scenarios. We assessed the consequences of these issues on the accuracy of climate-driven SDM predictions for the dispersal-limited Darwin's frog Rhinoderma darwinii in South America. We calibrated models using historical data (1950-1975) and projected them across 40 yr to predict distribution under current climatic conditions, assessing predictive accuracy through the area under the ROC curve (AUC) and True Skill Statistics (TSS), contrasting binary model predictions against temporal-independent validation data set (i.e., current presences/absences). To assess the effects of incorporating dispersal processes we compared the predictive accuracy of dispersal constrained models with no dispersal limited SDMs; and to assess the effects of model extrapolation on the predictive accuracy of SDMs, we compared this between extrapolated and no extrapolated areas. The incorporation of dispersal processes enhanced predictive accuracy, mainly due to a decrease in the false presence rate of model predictions, which is consistent with discrimination of suitable but inaccessible habitat. This also had consequences on range size changes over time, which is the most used proxy for extinction risk from climate change. The area of current climatic conditions that was absent in the baseline conditions (i.e., extrapolated areas) represents 39% of the study area, leading to a significant decrease in predictive accuracy of model predictions for those areas. Our results highlight (1) incorporating dispersal processes can improve predictive accuracy of temporal transference of SDMs and reduce uncertainties of extinction risk assessments from global change; (2) as geographical areas subjected to novel climates are expected to arise, they must be reported as they show less accurate predictions under future climate scenarios. Consequently, environmental extrapolation and dispersal processes should be explicitly incorporated to report and reduce uncertainties in temporal predictions of SDMs, respectively. Doing so, we expect to improve the reliability of the information we provide for conservation decision makers under future climate change scenarios.http://onlinelibrary.wiley.com/doi/10.1002/eap.1556/abstract;jsessionid=1E2084FF99600D0EEC9FA358A3DBC2A3.f02t0

A Survey of Prediction and Classification Techniques in Multicore Processor Systems

In multicore processor systems, being able to accurately predict the future provides new optimization opportunities, which otherwise could not be exploited. For example, an oracle able to predict a certain application\u27s behavior running on a smart phone could direct the power manager to switch to appropriate dynamic voltage and frequency scaling modes that would guarantee minimum levels of desired performance while saving energy consumption and thereby prolonging battery life. Using predictions enables systems to become proactive rather than continue to operate in a reactive manner. This prediction-based proactive approach has become increasingly popular in the design and optimization of integrated circuits and of multicore processor systems. Prediction transforms from simple forecasting to sophisticated machine learning based prediction and classification that learns from existing data, employs data mining, and predicts future behavior. This can be exploited by novel optimization techniques that can span across all layers of the computing stack. In this survey paper, we present a discussion of the most popular techniques on prediction and classification in the general context of computing systems with emphasis on multicore processors. The paper is far from comprehensive, but, it will help the reader interested in employing prediction in optimization of multicore processor systems