257 research outputs found
Genomic landscapes of Chinese hamster ovary cell lines as revealed by the Cricetulus griseus draft genome.
Wheels, skills and thrills: A social marketing trial to reduce aggressive driving from young men in deprived areas
Young men from poorer backgrounds are associated with high road traffic collision levels. However, solving this problem has proven very difficult. Hence this paper summarises the findings of a UK government funded two-year trial of a cross-discipline intervention to reduce aggressive driving amongst this group. The intervention reported on here departed from traditional approaches such as fear appeals, standalone educational approaches, or punitive measures. Instead, the discipline of social marketing was used to provide overarching direction and structure for the trial, with a key focus on motivation and engagement. The project rested on a strong education and training platform and included a bespoke coaching programme, incentives, and an in-vehicle measurement and feedback device. The project had three development phases leading to the final trial. First, a literature and case study review identified possible design strategies. Second, these strategies were explored using primary research in the form of a qualitative inquiry. Third, a pre-trial design phase sought to introduce key components of the intervention to the trial cohort, retaining some flexibility before committing to the final design. Young males with a history of challenging behaviour (e.g. criminal records, driving convictions) from an economically deprived area within a UK city were recruited. Of 42 recruits, 23 successfully completed the trial. Behaviour changes were measured pre-, during and post-trial through a combination of driver performance data measured by in-vehicle data recorders (IVDRs), assessments of driving undertaken by trained observers, and self-assessment surveys and interviews with trial participants. Results indicate a significant average improvement in driving skills amongst participants who completed the trial. Given the difficulty in engaging and changing behaviour of this specific group, this is regarded as a significant finding. In summary the study provides an indication of proof of concept for the intervention in improving driving skills. However the limited sample size and lack of control group mean that further work will be required to validate these findings. It is recommended that a feasibility study with higher cohort volumes is undertaken, before attempting a full scale trial. © 2013 Elsevier Ltd. All rights reserved
The twilight of the Liberal Social Contract? On the Reception of Rawlsian Political Liberalism
This chapter discusses the Rawlsian project of public reason, or public justification-based 'political' liberalism, and its reception. After a brief philosophical rather than philological reconstruction of the project, the chapter revolves around a distinction between idealist and realist responses to it. Focusing on political liberalism’s critical reception illuminates an overarching question: was Rawls’s revival of a contractualist approach to liberal legitimacy a fruitful move for liberalism and/or the social contract tradition? The last section contains a largely negative answer to that question. Nonetheless the chapter's conclusion shows that the research programme of political liberalism provided and continues to provide illuminating insights into the limitations of liberal contractualism, especially under conditions of persistent and radical diversity. The programme is, however, less receptive to challenges to do with the relative decline of the power of modern states
p53 activates the PANK1/miRNA-107 gene leading to downregulation of CDK6 and p130 cell cycle proteins
The tumor suppressor p53 is a central regulator of cell-cycle arrest and apoptosis by acting as a transcription factor to regulate numerous genes. We identified all human p53-regulated mRNAs by microarray analyses and searched for protein-coding genes which contain intronic miRNAs. Among others, this analysis yielded the panthothenate kinase 1 (PANK1) gene and its intronic miRNA-107. We showed that miRNA-107 and PANK1 are coregulated by p53 in different cell systems. The PANK1 protein, which catalyzes the rate-limiting step of coenzyme A biosynthesis, is also upregulated by p53. We observed that p53 directly activates PANK1 and miRNA-107 transcription through a binding site in the PANK1 promoter. Furthermore, p53 is recruited to the PANK1 promoter after DNA damage. In order to get more insight into miRNA-107 function we investigated its potential target genes. Cell-cycle regulators are significantly enriched among predicted miRNA-107 targets. We found miRNA-107-dependent regulation of two important regulators of G1/S progression, CDK6 and the RB-related 2 gene RBL2 (p130). CDK6 and p130 proteins are downregulated upon miRNA-107 expression. Our results uncover a novel miRNA-dependent signaling pathway which leads to downregulation of cell cycle proteins in the absence of transcriptional repression
Drivers and technology-related obstacles in moving to multichannel retailing
Today, multichannel retailing is a key strategic issue for most retailers. Yet, while there are many drivers associated with retailers going multichannel so too are there technology-related obstacles, however, few prior empirical studies explore these themes. In light of this, by using a multi-case approach to understand the key drivers and technology-related obstacles associated with retailers moving to multichannel retailing our study makes two key contributions. First, we extend prior theory by providing novel empirical insights into the main drivers underpinning retailers using a multichannel strategy. We find that meeting customer needs and increasing sales were the primary drivers behind retailers using the strategy, although there is diversity in the way retailers respond to these motives. Second, we provide empirical support for a proposed theoretical framework which summarises the key technology-related obstacles retailers encounter when going multichannel, by stage of implementation. The framework reveals that retailers face technology-related obstacles when implementing a multichannel strategy due to the need to switch/acquire resources and achieve channel integration. Furthermore, the framework highlights that these resource and channel integration issues are often interrelated with each other and with other staff engagement and cultural issues, vary by retailer and stage of implementation, and pose greater obstacles to retailers using new and multiple channels than the extant literature suggests
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Rapid Seeding of the Viral Reservoir Prior to SIV Viremia in Rhesus Monkeys
The viral reservoir represents a critical challenge facing HIV-1 eradication strategies1–5. However, it remains unclear when and where the viral reservoir is seeded during acute infection and the extent to which it is susceptible to early antiretroviral therapy (ART). Here we show that the viral reservoir is seeded very early following mucosal SIV infection of rhesus monkeys and prior to systemic viremia. We initiated suppressive ART in groups of monkeys on days 3, 7, 10, and 14 following intrarectal SIVmac251 infection. Treatment on day 3 blocked the emergence of viral RNA and proviral DNA in peripheral blood and also substantially reduced levels of proviral DNA in lymph nodes and gastrointestinal mucosa as compared with treatment at later timepoints. In addition, treatment on day 3 abrogated the induction of SIV-specific humoral and cellular immune responses. Nevertheless, following discontinuation of ART after 24 weeks of fully suppressive therapy, virus rebounded in all animals, although animals treated on day 3 exhibited a delayed viral rebound as compared with animals treated on days 7, 10 and 14. The time to viral rebound correlated with total viremia during acute infection and with proviral DNA at the time of ART discontinuation. These data demonstrate that the viral reservoir is seeded very early following intrarectal SIV infection of rhesus monkeys, during the “eclipse” phase, and prior to viremia. This strikingly early seeding of the refractory viral reservoir raises important new challenges for HIV-1 eradication strategies
Philosophy of action
The philosophical study of human action begins with Plato and Aristotle. Their influence in late antiquity and the Middle Ages yielded sophisticated theories of action and motivation, notably in the works of Augustine and Aquinas.1 But the ideas that were dominant in 1945 have their roots in the early modern period, when advances in physics and mathematics reshaped philosophy
Social exclusion, vulnerable groups and driving forces: Towards a social research based policy on car mobility
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