770 research outputs found

    Mathematical model of a serine integrase-controlled toggle switch with a single input

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    Dual-state genetic switches that can change their state in response to input signals can be used in synthetic biology to encode memory and control gene expression. A transcriptional toggle switch (TTS), with two mutually repressing transcription regulators, was previously used for switching between two expression states. In other studies, serine integrases have been used to control DNA inversion switches that can alternate between two different states. Both of these switches use two different inputs to switch ON or OFF. Here, we use mathematical modelling to design a robust one-input binary switch, which combines a TTS with a DNA inversion switch. This combined circuit switches between the two states every time it receives a pulse of a single-input signal. The robustness of the switch is based on the bistability of its TTS, while integrase recombination allows single-input control. Unidirectional integrase-RDF-mediated recombination is provided by a recently developed integrase-RDF fusion protein. We show that the switch is stable against parameter variations and molecular noise, making it a promising candidate for further use as a basic element of binary counting devices

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    Does a powerlifting inspired exercise programme better compliment pain education compared to bodyweight exercise for people with chronic low back pain? A multicentre, single-blind, randomised controlled trial

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    Background Contemporary management of chronic low back pain involves combined exercise and pain education. Currently, there is a gap in the literature for whether any exercise mode better pairs with pain education. The purpose of this study was to compare general callisthenic exercise with a powerlifting style programme, both paired with consistent pain education, for chronic low back pain. We hypothesised powerlifting style training may better compliment the messages of pain education. Methods An 8-week single-blind randomised controlled trial was conducted comparing bodyweight exercise (n  =  32) with powerlifting (n  =  32) paired with the same education, for people with chronic low back pain. Exercise sessions were one-on-one and lasted 60-min, with the last 5–15 min comprising pain education. Pain, disability, fear, catastrophizing, self-efficacy, anxiety, and depression were measured at baseline, 8-weeks, 3-months, and 6-months. Results No significant between-group differences were observed for pain (p≥0.40), or disability (p≥0.45) at any time-point. Within-group differences were significantly improved for pain (p ≤ 0.04) and disability (p ≤ 0.04) at all time-points for both groups, except 6-month disability in the bodyweight group (p  =  0.1). Behavioural measures explained 39–60% of the variance in changes in pain and disability at each time-point, with fear and self-efficacy emerging as significant in these models (p ≤ 0.001) Conclusions Both powerlifting and bodyweight exercise were safe and beneficial when paired with pain education for chronic low back pain, with reductions in pain and disability associated with improved fear and self-efficacy. This study provides opportunity for practitioners to no longer be constrained by systematic approaches to chronic low back pain

    Patterns of Urban Violent Injury: A Spatio-Temporal Analysis

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    Injury related to violent acts is a problem in every society. Although some authors have examined the geography of violent crime, few have focused on the spatio-temporal patterns of violent injury and none have used an ambulance dataset to explore the spatial characteristics of injury. The purpose of this study was to describe the combined spatial and temporal characteristics of violent injury in a large urban centre.Using a geomatics framework and geographic information systems software, we studied 4,587 ambulance dispatches and 10,693 emergency room admissions for violent injury occurrences among adults (aged 18–64) in Toronto, Canada, during 2002 and 2004, using population-based datasets. We created kernel density and choropleth maps for 24-hour periods and four-hour daily time periods and compared location of ambulance dispatches and patient residences with local land use and socioeconomic characteristics. We used multivariate regressions to control for confounding factors. We found the locations of violent injury and the residence locations of those injured were both closely related to each other and clearly clustered in certain parts of the city characterised by high numbers of bars, social housing units, and homeless shelters, as well as lower household incomes. The night and early morning showed a distinctive peak in injuries and a shift in the location of injuries to a “nightlife” district. The locational pattern of patient residences remained unchanged during those times.Our results demonstrate that there is a distinctive spatio-temporal pattern in violent injury reflected in the ambulance data. People injured in this urban centre more commonly live in areas of social deprivation. During the day, locations of injury and locations of residences are similar. However, later at night, the injury location of highest density shifts to a “nightlife” district, whereas the residence locations of those most at risk of injury do not change

    Rfam: annotating non-coding RNAs in complete genomes

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    Rfam is a comprehensive collection of non-coding RNA (ncRNA) families, represented by multiple sequence alignments and profile stochastic context-free grammars. Rfam aims to facilitate the identification and classification of new members of known sequence families, and distributes annotation of ncRNAs in over 200 complete genome sequences. The data provide the first glimpses of conservation of multiple ncRNA families across a wide taxonomic range. A small number of large families are essential in all three kingdoms of life, with large numbers of smaller families specific to certain taxa. Recent improvements in the database are discussed, together with challenges for the future. Rfam is available on the Web at http://www.sanger.ac.uk/Software/Rfam/ and http://rfam.wustl.edu/
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