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.

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.

On representing chemical environments

We review some recently published methods to represent atomic neighbourhood environments, and analyse their relative merits in terms of their faithfulness and suitability for fitting potential energy surfaces. The crucial properties that such representations (sometimes called descriptors) must have are differentiability with respect to moving the atoms, and invariance to the basic symmetries of physics: rotation, reflection, translation, and permutation of atoms of the same species. We demonstrate that certain widely used descriptors that initially look quite different are specific cases of a general approach, in which a finite set of basis functions with increasing angular wave numbers are used to expand the atomic neighbourhood density function. Using the example system of small clusters, we quantitatively show that this expansion needs to be carried to higher and higher wave numbers as the number of neighbours increases in order to obtain a faithful representation, and that variants of the descriptors converge at very different rates. We also propose an altogether new approach, called Smooth Overlap of Atomic Positions (SOAP), that sidesteps these difficulties by directly defining the similarity between any two neighbourhood environments, and show that it is still closely connected to the invariant descriptors. We test the performance of the various representations by fitting models to the potential energy surface of small silicon clusters and the bulk crystal.

Discriminative language model adaptation for Mandarin broadcast speech transcription and translation

This paper investigates unsupervised test-time adaptation of language models (LM) using discriminative methods for a Mandarin broadcast speech transcription and translation task. A standard approach to adapt interpolated language models to is to optimize the component weights by minimizing the perplexity on supervision data. This is a widely made approximation for language modeling in automatic speech recognition (ASR) systems. For speech translation tasks, it is unclear whether a strong correlation still exists between perplexity and various forms of error cost functions in recognition and translation stages. The proposed minimum Bayes risk (MBR) based approach provides a flexible framework for unsupervised LM adaptation. It generalizes to a variety of forms of recognition and translation error metrics. LM adaptation is performed at the audio document level using either the character error rate (CER), or translation edit rate (TER) as the cost function. An efficient parameter estimation scheme using the extended Baum-Welch (EBW) algorithm is proposed. Experimental results on a state-of-the-art speech recognition and translation system are presented. The MBR adapted language models gave the best recognition and translation performance and reduced the TER score by up to 0.54% absolute. © 2007 IEEE.