Dissecting Arabidopsis thaliana DICER function in small RNA processing, gene silencing and DNA methylation patterning.

Small RNAs have several important biological functions. MicroRNAs (miRNAs) and trans-acting small interfering RNAs (tasiRNAs) regulate mRNA stability and translation, and siRNAs cause post-transcriptional gene silencing of transposons, viruses and transgenes and are important in both the establishment and maintenance of cytosine DNA methylation. Here, we study the role of the four Arabidopsis thaliana DICER-LIKE genes (DCL1-DCL4) in these processes. Sequencing of small RNAs from a dcl2 dcl3 dcl4 triple mutant showed markedly reduced tasiRNA and siRNA production and indicated that DCL1, in addition to its role as the major enzyme for processing miRNAs, has a previously unknown role in the production of small RNAs from endogenous inverted repeats. DCL2, DCL3 and DCL4 showed functional redundancy in siRNA and tasiRNA production and in the establishment and maintenance of DNA methylation. Our studies also suggest that asymmetric DNA methylation can be maintained by pathways that do not require siRNAs.

Statistical gear health analysis which is robust to fluctuating loads and operating speeds

Condition-based maintenance is concerned with the collection and interpretation of data to support maintenance decisions. The non-intrusive nature of vibration data enables the monitoring of enclosed systems such as gearboxes. It remains a significant challenge to analyze vibration data that are generated under fluctuating operating conditions. This is especially true for situations where relatively little prior knowledge regarding the specific gearbox is available. It is therefore investigated how an adaptive time series model, which is based on Bayesian model selection, may be used to remove the non-fault related components in the structural response of a gear assembly to obtain a residual signal which is robust to fluctuating operating conditions. A statistical framework is subsequently proposed which may be used to interpret the structure of the residual signal in order to facilitate an intuitive understanding of the condition of the gear system. The proposed methodology is investigated on both simulated and experimental data from a single stage gearbox. © 2011 Elsevier Ltd. All rights reserved.

Policy as a struggle for meaning: disentangling knowledge translation across international health contexts

Over the last decade, research in medical science has focused on knowledge translation and diffusion of best practices to enable improved health outcomes. However, there has been less attention given to the role of policy in influencing the translation of best practice across different national contexts. This paper argues that the underlying set of public discourses of healthcare policy significantly influences its development with implications for the dissemination of best practices. Our research uses Critical Discourse Analysis to examine the policy discourses surrounding the treatment of stroke across Canada and the U.K. It focuses in specific on how concepts of knowledge translation, user empowerment, and service innovation construct different accounts of the health service in the two countries. These findings provide an important yet overlooked starting point for understanding the role of policy development in knowledge transfer and the translation of science into health practice. © 2011 Operational Research Society. All rights reserved.

A Bayesian approach to tracking in single molecule fluorescence microscopy

Using fluorescence microscopy with single molecule sensitivity it is now possible to follow the movement of individual fluorophore tagged molecules such as proteins and lipids in the cell membrane with nanometer precision. These experiments are important as they allow many key biological processes on the cell membrane and in the cell, such as transcription, translation and DNA replication, to be studied at new levels of detail. Computerized microscopes generate sequences of images (in the order of tens to hundreds) of the molecules diffusing and one of the challenges is to track these molecules to obtain reliable statistics such as speed distributions, diffusion patterns, intracellular positioning, etc. The data set is challenging because the molecules are tagged with a single or small number of fluorophores, which makes it difficult to distinguish them from the background, the fluorophore bleaches irreversibly over time, the number of tagged molecules are unknown and there is occasional loss of signal from the tagged molecules. All these factors make accurate tracking over long trajectories difficult. Also the experiments are technically difficulty to conduct and thus there is a pressing need to develop better algorithms to extract the maximum information from the data. For this purpose we propose a Bayesian approach and apply our technique to synthetic and a real experimental data set.