Feature selection for chemical sensor arrays using mutual information

We address the problem of feature selection for classifying a diverse set of chemicals using an array of metal oxide sensors. Our aim is to evaluate a filter approach to feature selection with reference to previous work, which used a wrapper approach on the same data set, and established best features and upper bounds on classification performance. We selected feature sets that exhibit the maximal mutual information with the identity of the chemicals. The selected features closely match those found to perform well in the previous study using a wrapper approach to conduct an exhaustive search of all permitted feature combinations. By comparing the classification performance of support vector machines (using features selected by mutual information) with the performance observed in the previous study, we found that while our approach does not always give the maximum possible classification performance, it always selects features that achieve classification performance approaching the optimum obtained by exhaustive search. We performed further classification using the selected feature set with some common classifiers and found that, for the selected features, Bayesian Networks gave the best performance. Finally, we compared the observed classification performances with the performance of classifiers using randomly selected features. We found that the selected features consistently outperformed randomly selected features for all tested classifiers. The mutual information filter approach is therefore a computationally efficient method for selecting near optimal features for chemical sensor arrays

Lung Cancer in Pulmonary Fibrosis: Tales of Epithelial Cell Plasticity

Lung epithelial cells exhibit a high degree of plasticity. Alterations to lung epithelial cell function are critically involved in several chronic lung diseases such as pulmonary fibrosis. Pulmonary fibrosis is characterized by repetitive injury and subsequent impaired repair of epithelial cells, which leads to aberrant growth factor activation and fibroblast accumulation. Increased proliferation and hyper- and metaplasia of epithelial cells upon injury have also been observed in pulmonary fibrosis; this epithelial cell activation might represent the basis for lung cancer development. Indeed, several studies have provided histopathological evidence of an increased incidence of lung cancer in pulmonary fibrosis. The mechanisms involved in the development of cancer in pulmonary fibrosis, however, remain poorly understood. This review highlights recently uncovered molecular mechanisms shared between lung cancer and fibrosis, which extend the current evidence of a common trait of cancer and fibrosis, as provided by histopathological observations. Copyright (C) 2011 S. Karger AG, Base

Aptamer-based multiplexed proteomic technology for biomarker discovery

Interrogation of the human proteome in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology. We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 [mu]L of serum or plasma). Our current assay allows us to measure ~800 proteins with very low limits of detection (1 pM average), 7 logs of overall dynamic range, and 5% average coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding DNA aptamer concentration signature, which is then quantified with a DNA microarray. In essence, our assay takes advantage of the dual nature of aptamers as both folded binding entities with defined shapes and unique sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to discover unique protein signatures characteristic of various disease states. More generally, we describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine

Wealth and sexual behaviour among men in Cameroon

BACKGROUND: The 2004 Demographic and Health Survey (DHS) in Cameroon revealed a higher prevalence of HIV in richest and most educated people than their poorest and least educated compatriots. It is not certain whether the higher prevalence results partly or wholly from wealthier people adopting more unsafe sexual behaviours, surviving longer due to greater access to treatment and care, or being exposed to unsafe injections or other HIV risk factors. As unsafe sex is currently believed to be the main driver of the HIV epidemic in sub-Saharan Africa, we designed this study to examine the association between wealth and sexual behaviour in Cameroon. METHODS: We analysed data from 4409 sexually active men aged 15–59 years who participated in the Cameroon DHS using logistic regression models, and have reported odds ratios (OR) with confidence intervals (CI). RESULTS: When we controlled for the potential confounding effects of marital status, place of residence, religion and age, men in the richest third of the population were less likely to have used a condom in the last sex with a non-spousal non-cohabiting partner (OR 0.43, 95% CI 0.32–0.56) and more likely to have had at least two concurrent sex partners in the last 12 months (OR 1.38, 95% CI 1.12–1.19) and more than five lifetime sex partners (OR 1.97, 95% CI 1.60–2.43). However, there was no difference between the richest and poorest men in the purchase of sexual services. Regarding education, men with secondary or higher education were less likely to have used a condom in the last sex with a non-spousal non-cohabiting partner (OR 0.24, 95% CI 0.16–0.38) and more likely to have started sexual activity at age 17 years or less (OR 2.73, 95% CI 2.10–3.56) and had more than five lifetime sexual partners (OR 2.59, 95% CI 2.02–3.31). There was no significant association between education and multiple concurrent sexual partnerships in the last 12 months or purchase of sexual services. CONCLUSION: Wealthy men in Cameroon are more likely to start sexual activity early and have both multiple concurrent and lifetime sex partners, and are less likely to (consistently) use a condom in sex with a non-spousal non-cohabiting partner. These unsafe sexual behaviours may explain the higher HIV prevalence among wealthier men in the country. While these findings do not suggest a redirection of HIV prevention efforts from the poor to the wealthy, they do call for efforts to ensure that HIV prevention messages get across all strata of society

Ethics takes time, but not that long

© 2007 Hansson et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

The impact of family structure and disruption on intergenerational emotional exchange in Eastern Europe

Demographic trends across Europe involve a decrease in fertility and mortality rates, and an increase in divorce and stepfamily formation. Life courses and living arrangements have become less standardized and the structure of families has changed. In this article, we examine to what extent contemporary family structure and composition resulting from demographic changes affect emotional exchange between children and their parents, both from adult child to parent and from parent to child. Because the general level of well-being has been shown to be lower in Eastern Europe, thereby potentially affecting emotional exchange within families, we focus our research on Eastern Europe. We use the “conservation of resources theory” to derive hypotheses on how family structure may affect intergenerational emotional exchange. Family ties are assumed to be important resources of affection that people want to obtain and retain throughout their lives. Data from the Generations and Gender Survey (GGS) are used to test our hypotheses. In general, our data offer more support for the idea that families are resilient than for the often heard assumption that families are in decline as a consequence of the changed family structure and composition

Reverse Engineering the Yeast RNR1 Transcriptional Control System

Transcription is controlled by multi-protein complexes binding to short non-coding regions of genomic DNA. These complexes interact combinatorially. A major goal of modern biology is to provide simple models that predict this complex behavior. The yeast gene RNR1 is transcribed periodically during the cell cycle. Here, we present a pilot study to demonstrate a new method of deciphering the logic behind transcriptional regulation. We took regular samples from cell cycle synchronized cultures of Saccharomyces cerevisiae and extracted nuclear protein. We tested these samples to measure the amount of protein that bound to seven different 16 base pair sequences of DNA that have been previously identified as protein binding locations in the promoter of the RNR1 gene. These tests were performed using surface plasmon resonance. We found that the surface plasmon resonance signals showed significant variation throughout the cell cycle. We correlated the protein binding data with previously published mRNA expression data and interpreted this to show that transcription requires protein bound to a particular site and either five different sites or one additional sites. We conclude that this demonstrates the feasibility of this approach to decipher the combinatorial logic of transcription

Robustness of Learning That Is Based on Covariance-Driven Synaptic Plasticity

It is widely believed that learning is due, at least in part, to long-lasting modifications of the strengths of synapses in the brain. Theoretical studies have shown that a family of synaptic plasticity rules, in which synaptic changes are driven by covariance, is particularly useful for many forms of learning, including associative memory, gradient estimation, and operant conditioning. Covariance-based plasticity is inherently sensitive. Even a slight mistuning of the parameters of a covariance-based plasticity rule is likely to result in substantial changes in synaptic efficacies. Therefore, the biological relevance of covariance-based plasticity models is questionable. Here, we study the effects of mistuning parameters of the plasticity rule in a decision making model in which synaptic plasticity is driven by the covariance of reward and neural activity. An exact covariance plasticity rule yields Herrnstein's matching law. We show that although the effect of slight mistuning of the plasticity rule on the synaptic efficacies is large, the behavioral effect is small. Thus, matching behavior is robust to mistuning of the parameters of the covariance-based plasticity rule. Furthermore, the mistuned covariance rule results in undermatching, which is consistent with experimentally observed behavior. These results substantiate the hypothesis that approximate covariance-based synaptic plasticity underlies operant conditioning. However, we show that the mistuning of the mean subtraction makes behavior sensitive to the mistuning of the properties of the decision making network. Thus, there is a tradeoff between the robustness of matching behavior to changes in the plasticity rule and its robustness to changes in the properties of the decision making network

Meta-analysis of epigenome-wide association studies of carotid intima-media thickness

Common carotid intima-media thickness (cIMT) is an index of subclinical atherosclerosis that is associated with ischemic stroke and coronary artery disease (CAD). We undertook a cross-sectional epigenome-wide association study (EWAS) of measures of cIMT in 6400 individuals. Mendelian randomization analysis was applied to investigate the potential causal role of DNA methylation in the link between atherosclerotic cardiovascular risk factors and cIMT or clinical cardiovascular disease. The CpG site cg05575921 was associated with cIMT (beta = -0.0264, p value = 3.5 × 10-8) in the discovery panel and was replicated in replication panel (beta = -0.07, p value = 0.005). This CpG is located at chr5:81649347 in the intron 3 of the aryl hydrocarbon receptor repressor gene (AHRR). Our results indicate that DNA methylation at cg05575921 might be in the pathway between smoking, cIMT and stroke. Moreover, in a region-based analysis, 34 differentially methylated regions (DMRs) were identified of which a DMR upstream of ALOX12 showed the strongest association with cIMT (p value = 1.4 × 10-13). In conclusion, our study suggests that DNA methylation may play a role in the link between cardiovascular risk factors, cIMT and clinical cardiovascular disease

The morphometry of soft tissue insertions on the tibial plateau: Data acquisition and statistical shape analysis

This study characterized the soft tissue insertion morphometrics on the tibial plateau and their inter-relationships as well as variabilities. The outlines of the cruciate ligament and meniscal root insertions along with the medial and lateral cartilage on 20 cadaveric tibias (10 left and 10 right knees) were digitized and co-registered with corresponding CT-based 3D bone models. Generalized Procrustes Analysis was employed in conjunction with Principal Components Analysis to first create a geometric consensus based on tibial cartilage and then determine the means and variations of insertion morphometrics including shape, size, location, and inter-relationship measures. Step-wise regression analysis was conducted in search of parsimonious models relating the morphometric measures to the tibial plateau width and depth, and basic anthropometric and gender factors. The analyses resulted in statistical morphometric representations for Procrustes-superimposed cruciate ligament and meniscus insertions, and identified only a few moderate correlations (R 2: 0.37-0.49). The study provided evidence challenging the isometric scaling based on a single dimension frequently employed in related morphometric studies, and data for evaluating cruciate ligament reconstruction strategies in terms of re-creating the native anatomy and minimizing the risk of iatrogenic injury. It paved the way for future development of computer-aided personalized orthopaedic surgery applications improving the quality of care and patient safety, and biomechanical models with a better population or average representation