Grain Dynamics in a Two-dimensional Granular Flow

We have used particle tracking methods to study the dynamics of individual balls comprising a granular flow in a small-angle two-dimensional funnel. We statistically analyze many ball trajectories to examine the mechanisms of shock propagation. In particular, we study the creation of, and interactions between, shock waves. We also investigate the role of granular temperature and draw parallels to traffic flow dynamics.Comment: 17 pages, 24 figures. To appear in Phys.Rev.E. High res./color figures etc. on http://www.nbi.dk/CATS/Granular/GrainDyn.htm

PASSion: a pattern growth algorithm-based pipeline for splice junction detection in paired-end RNA-Seq data

Motivation: RNA-seq is a powerful technology for the study of transcriptome profiles that uses deep-sequencing technologies. Moreover, it may be used for cellular phenotyping and help establishing the etiology of diseases characterized by abnormal splicing patterns. In RNA-Seq, the exact nature of splicing events is buried in the reads that span exon–exon boundaries. The accurate and efficient mapping of these reads to the reference genome is a major challenge

Methods to study splicing from high-throughput RNA Sequencing data

The development of novel high-throughput sequencing (HTS) methods for RNA (RNA-Seq) has provided a very powerful mean to study splicing under multiple conditions at unprecedented depth. However, the complexity of the information to be analyzed has turned this into a challenging task. In the last few years, a plethora of tools have been developed, allowing researchers to process RNA-Seq data to study the expression of isoforms and splicing events, and their relative changes under different conditions. We provide an overview of the methods available to study splicing from short RNA-Seq data. We group the methods according to the different questions they address: 1) Assignment of the sequencing reads to their likely gene of origin. This is addressed by methods that map reads to the genome and/or to the available gene annotations. 2) Recovering the sequence of splicing events and isoforms. This is addressed by transcript reconstruction and de novo assembly methods. 3) Quantification of events and isoforms. Either after reconstructing transcripts or using an annotation, many methods estimate the expression level or the relative usage of isoforms and/or events. 4) Providing an isoform or event view of differential splicing or expression. These include methods that compare relative event/isoform abundance or isoform expression across two or more conditions. 5) Visualizing splicing regulation. Various tools facilitate the visualization of the RNA-Seq data in the context of alternative splicing. In this review, we do not describe the specific mathematical models behind each method. Our aim is rather to provide an overview that could serve as an entry point for users who need to decide on a suitable tool for a specific analysis. We also attempt to propose a classification of the tools according to the operations they do, to facilitate the comparison and choice of methods.Comment: 31 pages, 1 figure, 9 tables. Small corrections adde

HMMSplicer: A Tool for Efficient and Sensitive Discovery of Known and Novel Splice Junctions in RNA-Seq Data

Background: High-throughput sequencing of an organism’s transcriptome, or RNA-Seq, is a valuable and versatile new strategy for capturing snapshots of gene expression. However, transcriptome sequencing creates a new class of alignment problem: mapping short reads that span exon-exon junctions back to the reference genome, especially in the case where a splice junction is previously unknown. Methodology/Principal Findings: Here we introduce HMMSplicer, an accurate and efficient algorithm for discovering canonical and non-canonical splice junctions in short read datasets. HMMSplicer identifies more splice junctions than currently available algorithms when tested on publicly available A. thaliana, P. falciparum, and H. sapiens datasets without a reduction in specificity. Conclusions/Significance: HMMSplicer was found to perform especially well in compact genomes and on genes with low expression levels, alternative splice isoforms, or non-canonical splice junctions. Because HHMSplicer does not rely on prebuilt gene models, the products of inexact splicing are also detected. For H. sapiens, we find 3.6 % of 39 splice sites and 1.4% of 59 splice sites are inexact, typically differing by 3 bases in either direction. In addition, HMMSplicer provides a score for every predicted junction allowing the user to set a threshold to tune false positive rates depending on the needs of the experiment. HMMSplicer is implemented in Python. Code and documentation are freely available a

RNA-seq analyses of blood-induced changes in gene expression in the mosquito vector species, Aedes aegypti

<p>Abstract</p> <p>Background</p> <p>Hematophagy is a common trait of insect vectors of disease. Extensive genome-wide transcriptional changes occur in mosquitoes after blood meals, and these are related to digestive and reproductive processes, among others. Studies of these changes are expected to reveal molecular targets for novel vector control and pathogen transmission-blocking strategies. The mosquito <it>Aedes aegypti </it>(Diptera, Culicidae), a vector of Dengue viruses, Yellow Fever Virus (YFV) and Chikungunya virus (CV), is the subject of this study to look at genome-wide changes in gene expression following a blood meal.</p> <p>Results</p> <p>Transcriptional changes that follow a blood meal in <it>Ae. aegypti </it>females were explored using RNA-seq technology. Over 30% of more than 18,000 investigated transcripts accumulate differentially in mosquitoes at five hours after a blood meal when compared to those fed only on sugar. Forty transcripts accumulate only in blood-fed mosquitoes. The list of regulated transcripts correlates with an enhancement of digestive activity and a suppression of environmental stimuli perception and innate immunity. The alignment of more than 65 million high-quality short reads to the <it>Ae. aegypti </it>reference genome permitted the refinement of the current annotation of transcript boundaries, as well as the discovery of novel transcripts, exons and splicing variants. <it>Cis</it>-regulatory elements (CRE) and <it>cis</it>-regulatory modules (CRM) enriched significantly at the 5'end flanking sequences of blood meal-regulated genes were identified.</p> <p>Conclusions</p> <p>This study provides the first global view of the changes in transcript accumulation elicited by a blood meal in <it>Ae. aegypti </it>females. This information permitted the identification of classes of potentially co-regulated genes and a description of biochemical and physiological events that occur immediately after blood feeding. The data presented here serve as a basis for novel vector control and pathogen transmission-blocking strategies including those in which the vectors are modified genetically to express anti-pathogen effector molecules.</p

Polymorphism of the catechol-O-methyltransferase gene in Han Chinese patients with psoriasis vulgaris

Psoriasis vulgaris is defined by a series of linked cellular changes in the skin: hyperplasia of epidermal keratinocytes, vascular hyperplasia and ectasia, and infiltration of T lymphocytes, neutrophils and other types of leukocytes in the affected skin. Catechol-O-methyltransferase (COMT) 158 polymorphism can reduce the activity of the COMT enzyme that may trigger defective differentiation of keratinocytes in psoriasis. Immunocytes can degrade and inactivate catecholamines via monamine oxidase (MAO) and COMT in the cells. We hypothesized that the COMT-158G > A polymorphism was associated with the risk of psoriasis vulgaris in Han Chinese people. In a hospital-based case-control study, 524 patients with psoriasis vulgaris and 549 psoriasis-free controls were studied. COMT-158 G > A polymorphism was genotyped using the PCR sequence-specific primer (PCR-SSP) technique. We found no statistically significant association between the COMT-158 allele A and the risk of psoriasis vulgaris (p = 0.739 adjusted OR = 1.03; 95% CI = 0.81-1.31). This suggests that the COMT-158 G > A polymorphism may not contribute to the etiology of psoriasis vulgaris in the Han Chinese population

The influence of care home managers on the implementation of a complex intervention: Findings from the process evaluation of a randomised controlled trial of Dementia Care Mapping

Background: Many people with dementia live in care homes, where staff can struggle to meet their complex needs. Successful practice improvement interventions in these settings require strong managerial support, but little is known about how managers can support implementation in practice, or what factors support or hinder care home managers in providing this support. Using Dementia Care Mapping™ (DCM) as an example, this study explored how care home managers can support the implementation of complex interventions, and identified factors affecting their ability to provide this support. Methods: We undertook interviews with 48 staff members (managers and intervention leads) from care homes participating in the intervention arm of the DCM EPIC trial of DCM implementation. Results: Managerial support played a key role in facilitating the implementation of a complex intervention in care home settings. Managers could provide practical and financial support in many forms. However, managerial support and leadership approaches towards implementation were highly variable in practice, and implementation was easily de-stabilised by management changes or competing managerial priorities. How well managers understood, valued and engaged with the intervention, alongside the leadership style they adopted to support implementation, were key influences on implementation success. Conclusions: For care home managers to effectively support interventions they must fully understand the proposed intervention and its potential value. This is especially important during times of managerial or practice changes, when managers lack the skills required to effectively support implementation, or when the intervention is complex. It may be unfeasible to successfully implement new interventions during times of managerial or practice instability