972 resultados para Russell, Stephen


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Single-strand DNA (ssDNA)-binding proteins (SSBs) are ubiquitous and essential for a wide variety of DNA metabolic processes, including DNA replication, recombination, DNA damage detection and repair1. SSBs have multiple roles in binding and sequestering ssDNA, detecting DNA damage, stimulating nucleases, helicases and strand-exchange proteins, activating transcription and mediating protein–protein interactions. In eukaryotes, the major SSB, replication protein A (RPA), is a heterotrimer1. Here we describe a second human SSB (hSSB1), with a domain organization closer to the archaeal SSB than to RPA. Ataxia telangiectasia mutated (ATM) kinase phosphorylates hSSB1 in response to DNA double-strand breaks (DSBs). This phosphorylation event is required for DNA damage-induced stabilization of hSSB1. Upon induction of DNA damage, hSSB1 accumulates in the nucleus and forms distinct foci independent of cell-cycle phase. These foci co-localize with other known repair proteins. In contrast to RPA, hSSB1 does not localize to replication foci in S-phase cells and hSSB1 deficiency does not influence S-phase progression. Depletion of hSSB1 abrogates the cellular response to DSBs, including activation of ATM and phosphorylation of ATM targets after ionizing radiation. Cells deficient in hSSB1 exhibit increased radiosensitivity, defective checkpoint activation and enhanced genomic instability coupled with a diminished capacity for DNA repair. These findings establish that hSSB1 influences diverse endpoints in the cellular DNA damage response.

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Background: The enthesis of the plantar fascia is thought to play an important role in stress dissipation. However, the potential link between entheseal thickening characteristic of enthesopathy and the stress-dissipating properties of the intervening plantar fat pad have not been investigated. Purpose: This study was conducted to identify whether plantar fat pad mechanics explain variance in the thickness of the fascial enthesis in individuals with and without plantar enthesopathy. Study Design: Case-control study; Level of evidence, 3. Methods: The study population consisted of 9 patients with unilateral plantar enthesopathy and 9 asymptomatic, individually matched controls. The thickness of the enthesis of the symptomatic, asymptomatic, and a matched control limb was acquired using high-resolution ultrasound. The compressive strain of the plantar fat pad during walking was estimated from dynamic lateral radiographs acquired with a multifunction fluoroscopy unit. Peak compressive stress was simultaneously acquired via a pressure platform. Principal viscoelastic parameters were estimated from subsequent stress-strain curves. Results: The symptomatic fascial enthesis (6.7 ± 2.0 mm) was significantly thicker than the asymptomatic enthesis (4.2 ± 0.4 mm), which in turn was thicker than the enthesis (3.3 ± 0.4 mm) of control limbs (P < .05). There was no significant difference in the mean thickness, peak stress, peak strain, or secant modulus of the plantar fat pad between limbs. However, the energy dissipated by the fat pad during loading and unloading was significantly lower in the symptomatic limb (0.55 ± 0.17) when compared with asymptomatic (0.69 ± 0.13) and control (0.70 ± 0.09) limbs (P < .05). The sonographic thickness of the enthesis was correlated with the energy dissipation ratio of the plantar fat pad (r = .72, P < .05), but only in the symptomatic limb. Conclusion: The energy-dissipating properties of the plantar fat pad are associated with the sonograpic appearance of the enthesis in symptomatic limbs, providing a previously unidentified link between the mechanical behavior of the plantar fat pad and enthesopathy.

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The field of Business ProcessManagement (BPM) has evolved considerably over the past decade. Many proposals for business process modelling and/or execution have emerged and some of these have faded into oblivion again. The Workflow Patterns Initiative aimed at achieving a more structured approach to language comparison and development. The patterns that were distilled served as the basis for YAWL (Yet AnotherWorkflow Language). In this paper YAWL is positioned with respect to historical developments in BPM and current challenges in the field.

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Traditional workflow systems focus on providing support for the control-flow perspective of a business process, with other aspects such as data management and work distribution receiving markedly less attention. A guide to desirable workflow characteristics is provided by the well-known workflow patterns which are derived from a comprehensive survey of contemporary tools and modelling formalisms. In this paper we describe the approach taken to designing the newYAWL workflow system, an offering that aims to provide comprehensive support for the control-flow, data and resource perspectives based on the workflow patterns. The semantics of the newYAWL workflow language are based on Coloured Petri Nets thus facilitating the direct enactment and analysis of processes described in terms of newYAWL language constructs. As part of this discussion, we explain how the operational semantics for each of the language elements are embodied in the newYAWL system and indicate the facilities required to support them in an operational environment. We also review the experiences associated with developing a complete operational design for an offering of this scale using formal techniques.

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As governments around the world adopt a marketing orientation, the importance of consumer satisfaction to the effectiveness of the organization is being recognized. While some investigation of satisfaction with a government agencies' service has occurred, there is little examination of satisfaction with a government agency that acts as a third-party on the behalf of consumers to gain marketplace redress. Given the number of third-party complaints is increasing as a result of internet access to complaint channels, this research is a timely investigation. This study reports the findings of a survey of 454 complainants to an Australian Government agency: the Office of Fair Trading (OFT). The findings show that satisfaction with the service was subjectively experienced, based around individual expectations of the redress and satisfaction levels were higher when the redress sought was financial compared with non-financial forms of redress such as apology.

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With over 100,000 alcohol-related hospitalisations every year, risky drinking within Australia is a major health issue (Pascal, Chikritzhs, & Jones, 2009). Typically health advocates focus on parental and peer influence as a source of excessive drinking; leaving out the often overlooked role of siblings. Using consumer socialisation theory (Ward, 1974), the adoption of alcohol related behaviours between siblings was examined. Using a sample of 257 young adults alcohol behaviours were examined between sibship groups. The results revealed that alcohol type similarity was significant for siblings of who were of the same gender, but not significant for siblings of opposite genders. The results suggest that in order for an older sibling to influence a younger brother or sister they must be of the same gender and that there must be a relatively large age gap between them. This suggests that power in sibling relationships could play an important factor in alcohol behaviours.

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Despite substantial investment by governments in social marketing campaigns and the introduction of various legislative and supply controls on alcohol, the binge drinking phenomenon amongst young people continues unabated in many countries and appears to be spreading to others. This paper examines drinking behaviour amongst university students from 50 countries across Europe, North America and the Asia Pacific region and argues that more needs to be done in understanding socio-cultural factors. To date, little is known of the specific socio-cultural factors that are common in countries that have high drinking behaviour compared to countries that have moderate bingedrinking behaviour. Using a marketing systems approach, this exploratory study identifies two key themes that distinguish these countries, namely family influences and peer influences.

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This research investigated the role of mother-centred issues that influence breastfeeding behaviours. The need for social marketing research for breastfeeding is indicated by the fact that despite evidence of the health benefits to both the infant and mother of longer breastfeeding duration, rates in developed countries have failed to increase in recent decades. Breastfeeding is a complex behaviour that for many women involves barriers that influence their commitment to continue breastfeeding. Structural equation modelling was used on a sample of 405 respondents to an online survey. The analysis revealed that personal social support had a significant impact on breastfeeding self-efficacy, which in turn had a significant impact on breastfeeding behaviour. The findings and implications for both social marketing theory and practice are discussed.

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The field of workflow technology has burgeoned in recent years providing a variety of means of automating business processes. It is a great source of opportunity for organisations seeking to streamline and optimise their operations. Despite these advantages however, the current generation of workflow technologies are subject to a variety of criticisms, in terms of their restricted view of what comprises a business process, their imprecise definition and their general inflexibility. As a remedy to these potential difficulties, in this paper we propose a series of development goals for the next generation of workflow technology. We also present newYAWL, a formally defined, multi-perspective reference language for workflow systems.

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This third edition of Laying down the criminal law: A handbook for youth workers is essential to understanding young people’s experiences with criminal justice in Queensland. The text comprises detailed scenarios of situations where a young person would have contact with the system, and young people ‘in trouble’ (for example, being excluded from school). The text discusses how workers support the young person in talking to police, going to court, or being a victim of crime. One scenario notes how a youth worker responds to 15 year old Stephen staying at a youth shelter after leaving home and having contact with police. Scenarios are supplemented with information about confidentiality and negligence, and how workers consider these concepts supporting young people...

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The terms ‘literacy’ and ‘technology’ remain highly contentious within the field of education. What is meant by ‘literacy’ and the methods used to measure it vary quite markedly in educational and historical contexts across the world. Similarly, while there is a shared concern to research the potential impact of new information and communication technologies (ICTs) on patterns of teaching and learning, there are major discrepancies about which aspects and uses of these technologies should be incorporated into formal learning environments and how this can be accomplished. While government policy makers tend to regard ICTs in relation to ideas of ‘smartness’, efficiency, and the ‘knowledge’ (or ‘new’) economy, educators and educational researchers promote them as offering new tools for learning and critical thinking and the development of new literacies and socio-cultural identities. This clearly has ramifications for the ways literacy is taught and conceptualised throughout the years of schooling, K-12. Outside school, meanwhile, students engage with ICTs on another level entirely, as tools for the maintenance of social networks, for leisure, and for learning and participating in the cultures of their peers. Whatever the differences in perspective, it remains the case that a society’s dominant understandings about literacy and technology will have significant implications for the development of school curriculum.

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The project is working towards building an understanding of the personal interests and experiences of children with the aim of designing appropriate, usable and, most importantly, inspirational educational technology. kidprobe, an adaptation of the technology probe concept, has been used as a lightweight method of gaining contextual information about children's interactions with 'fun' technology. kidprobe has produced design inspiration which focuses primarily on the social and emotional connections children made. The use of kidprobe has generated some important ideas for improving the use of probes with children. It is an important first step in understanding how to effectively adapt probing techniques to inspire the design of technology for children.

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Background and purpose: The appropriate fixation method for hemiarthroplasty of the hip as it relates to implant survivorship and patient mortality is a matter of ongoing debate. We examined the influence of fixation method on revision rate and mortality.----- ----- Methods: We analyzed approximately 25,000 hemiarthroplasty cases from the AOA National Joint Replacement Registry. Deaths at 1 day, 1 week, 1 month, and 1 year were compared for all patients and among subgroups based on implant type.----- ----- Results: Patients treated with cemented monoblock hemiarthroplasty had a 1.7-times higher day-1 mortality compared to uncemented monoblock components (p < 0.001). This finding was reversed by 1 week, 1 month, and 1 year after surgery (p < 0.001). Modular hemiarthroplasties did not reveal a difference in mortality between fixation methods at any time point.----- ----- Interpretation: This study shows lower (or similar) overall mortality with cemented hemiarthroplasty of the hip.