184 research outputs found

    Developing a gamified peer-reviewed bug bounty programme

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    Bug bounty processes have remained broadly unchanged since their inception. Existing literature recognises that current methods generate intensive resource demands, impacting upon programme effectiveness. This paper proposes a novel implementation which aims to alleviate resource demands and mitigate inherent issues through gamification. This incorporates the use of additional crowdsourcing of vulnerability verification and reproduction by peers, allowing the client organisation to reduce overheads at the cost of rewarding participants. The system has the potential to be used in Higher Education Institutions which typically face resource and budget constraints

    'They're battle scars, I wear them well': A phenomenological exploration of young women's experiences of building resilience following adversity in adolescence

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    This is an Author's Accepted Manuscript of an article published in Journal of Youth Studies, 13(3), 273 - 290, 2010 [copyright Taylor & Francis], available online at: http://www.tandfonline.com/10.1080/13676260903520886.This phenomenological study explored young women's accounts of building resilience following chains of adverse life experiences in adolescence. Six participants were interviewed, aged 20–25 years. Most had, or were receiving, a university education. They described their recovery from adversity as starting with certain pivotal moments, followed by both short-term and longer-term strategies. Short-term strategies tended to offer respite from distress and emotional comfort, increased clarity about their experiences and social affirmation. Recovery involved gaining new perspectives on their adverse situation and recovering a positive self-image through three longer-term strategies. These involved making visible progress in their education, rebuilding relationships with family and friends, and participating in the ‘normalizing’ activities and developmental projects of adolescence. Participants believed that they were stronger and more compassionate although positive achievements co-existed with some regrets. Most perceived the adversity as catalyzing personal growth. These accounts of resilience revealed the complex psychosocial processes and resources available to some adolescents

    Loss of LKB1-NUAK1 signalling enhances NF-ÎșB activity in a spheroid model of high-grade serous ovarian cancer

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    High-grade serous ovarian cancer (HGSOC) is an aggressive malignancy often diagnosed at an advanced stage. Although most HGSOC patients respond initially to debulking surgery combined with cytotoxic chemotherapy, many ultimately relapse with platinum-resistant disease. Thus, improving outcomes requires new ways of limiting metastasis and eradicating residual disease. We identified previously that Liver kinase B1 (LKB1) and its substrate NUAK1 are implicated in EOC spheroid cell viability and are required for efficient metastasis in orthotopic mouse models. Here, we sought to identify additional signalling pathways altered in EOC cells due to LKB1 or NUAK1 loss-of-function. Transcriptome analysis revealed that inflammatory signalling mediated by NF-ÎșB transcription factors is hyperactive due to LKB1-NUAK1 loss in HGSOC cells and spheroids. Upregulated NF-ÎșB signalling due to NUAK1 loss suppresses reactive oxygen species (ROS) production and sustains cell survival in spheroids. NF-ÎșB signalling is also activated in HGSOC precursor fallopian tube secretory epithelial cell spheroids, and is further enhanced by NUAK1 loss. Finally, immunohistochemical analysis of OVCAR8 xenograft tumors lacking NUAK1 displayed increased RelB expression and nuclear staining. Our results support the idea that NUAK1 and NF-ÎșB signalling pathways together regulate ROS and inflammatory signalling, supporting cell survival during each step of HGSOC pathogenesis. We propose that their combined inhibition may be efficacious as a novel therapeutic strategy for advanced HGSOC

    Disaggregated N2O emission factors in China based on cropping parameters create a robust approach to the IPCC Tier 2 methodology

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    Acknowledgements This work was funded by Chinese Ministry of Agriculture and the United Kingdom Department for Environment, Food and Rural Affairs (DEFRA), UK under the UK-China Sustainable Agriculture Innovation Network (SAIN; Project DC09-06). Rothamsted Research receives strategic funding by the Biotechnology and Biological Sciences Research Council (BBSRC).Peer reviewedPublisher PD

    A novel role for NUAK1 in promoting ovarian cancer metastasis through regulation of fibronectin production in Spheroids

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    Epithelial ovarian cancer (EOC) has a unique mode of metastasis, where cells shed from the primary tumour, form aggregates called spheroids to evade anoikis, spread through the peritoneal cavity, and adhere to secondary sites. We previously showed that the master kinase Liver kinase B1 (LKB1) is required for EOC spheroid viability and metastasis. We have identified novel (nua) kinase 1 (NUAK1) as a top candidate LKB1 substrate in EOC cells and spheroids using a multiplex inhibitor beads-mass spectrometry approach. We confirmed that LKB1 maintains NUAK1 phosphorylation and promotes its stabilization. We next investigated NUAK1 function in EOC cells. Ectopic NUAK1-overexpressing EOC cell lines had increased adhesion, whereas the reverse was seen in OVCAR8-NUAK1KO cells. In fact, cells with NUAK1 loss generate spheroids with reduced integrity, leading to increased cell death after long-term culture. Following transcriptome analysis, we identified reduced enrichment for cell interaction gene expression pathways in OVCAR8-NUAK1KO spheroids. In fact, the FN1 gene, encoding fibronectin, exhibited a 745-fold decreased expression in NUAK1KO spheroids. Fibronectin expression was induced during native spheroid formation, yet this was completely lost in NUAK1KO spheroids. Co-incubation with soluble fibronectin restored the compact spheroid phenotype to OVCAR8-NUAK1KO cells. In a xenograft model of intraperitoneal metastasis, NUAK1 loss extended survival and reduced fibronectin expression in tumours. Thus, we have identified a new mechanism controlling EOC metastasis, through which LKB1-NUAK1 activity promotes spheroid formation and secondary tumours via fibronectin production
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