89 research outputs found

    Predictive text entry methods for mobile phones

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    This paper reports initial user tests comparing text entry methods, analysis of word clashes with dictionary based methods and keystroke level modelling of the different input methods

    The work of community gardens: reclaiming place for community in the city

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    The growth of community gardens has become the source of much academic debate regarding their role in community empowerment in the contemporary city. In this article, we focus upon the work being done in community gardens, using gardening in Glasgow as a case study. We argue that while community gardening cannot be divorced from more regressive underlying economic and social processes accompanying neoliberal austerity policies, it does provide space for important forms of work that address social needs and advance community empowerment. In developing this argument we use recent geographical scholarship concerning the generative role of place in bringing together individuals and communities in new collective forms of working. Community gardens are places that facilitate the recovery of individual agency, construction of new forms of knowledge and participation, and renewal of reflexive and proactive communities that provide broader lessons for building more progressive forms of work in cities

    Military maladaptation : counterinsurgency and the politics of failure

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    Tactical learning is critical to battlefield success, especially in a counterinsurgency. This article tests the existing model of military adaption against a ‘most-likely’ case: the British Army’s counterinsurgency in the Southern Cameroons (1960–61). Despite meeting all preconditions thought to enable adaptation – decentralization, leadership turnover, supportive leadership, poor organizational memory, feedback loops, and a clear threat – the British still failed to adapt. Archival evidence suggests politicians subverted bottom-up adaptation, because winning came at too high a price in terms of Britain’s broader strategic imperatives. Our finding identifies an important gap in the extant adaptation literature: it ignores politics.PostprintPeer reviewe

    Epigenetic Reprogramming Sensitizes CML Stem Cells to Combined EZH2 and Tyrosine Kinase Inhibition.

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    UNLABELLED: A major obstacle to curing chronic myeloid leukemia (CML) is residual disease maintained by tyrosine kinase inhibitor (TKI)-persistent leukemic stem cells (LSC). These are BCR-ABL1 kinase independent, refractory to apoptosis, and serve as a reservoir to drive relapse or TKI resistance. We demonstrate that Polycomb Repressive Complex 2 is misregulated in chronic phase CML LSCs. This is associated with extensive reprogramming of H3K27me3 targets in LSCs, thus sensitizing them to apoptosis upon treatment with an EZH2-specific inhibitor (EZH2i). EZH2i does not impair normal hematopoietic stem cell survival. Strikingly, treatment of primary CML cells with either EZH2i or TKI alone caused significant upregulation of H3K27me3 targets, and combined treatment further potentiated these effects and resulted in significant loss of LSCs compared to TKI alone, in vitro, and in long-term bone marrow murine xenografts. Our findings point to a promising epigenetic-based therapeutic strategy to more effectively target LSCs in patients with CML receiving TKIs. SIGNIFICANCE: In CML, TKI-persistent LSCs remain an obstacle to cure, and approaches to eradicate them remain a significant unmet clinical need. We demonstrate that EZH2 and H3K27me3 reprogramming is important for LSC survival, but renders LSCs sensitive to the combined effects of EZH2i and TKI. This represents a novel approach to more effectively target LSCs in patients receiving TKI treatment. Cancer Discov; 6(11); 1248-57. ©2016 AACR.See related article by Xie et al., p. 1237This article is highlighted in the In This Issue feature, p. 1197

    Mammalian BTBD12 (SLX4) Protects against Genomic Instability during Mammalian Spermatogenesis

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    The mammalian ortholog of yeast Slx4, BTBD12, is an ATM substrate that functions as a scaffold for various DNA repair activities. Mutations of human BTBD12 have been reported in a new sub-type of Fanconi anemia patients. Recent studies have implicated the fly and worm orthologs, MUS312 and HIM-18, in the regulation of meiotic crossovers arising from double-strand break (DSB) initiating events and also in genome stability prior to meiosis. Using a Btbd12 mutant mouse, we analyzed the role of BTBD12 in mammalian gametogenesis. BTBD12 localizes to pre-meiotic spermatogonia and to meiotic spermatocytes in wildtype males. Btbd12 mutant mice have less than 15% normal spermatozoa and are subfertile. Loss of BTBD12 during embryogenesis results in impaired primordial germ cell proliferation and increased apoptosis, which reduces the spermatogonial pool in the early postnatal testis. During prophase I, DSBs initiate normally in Btbd12 mutant animals. However, DSB repair is delayed or impeded, resulting in persistent γH2AX and RAD51, and the choice of repair pathway may be altered, resulting in elevated MLH1/MLH3 focus numbers at pachynema. The result is an increase in apoptosis through prophase I and beyond. Unlike yeast Slx4, therefore, BTBD12 appears to function in meiotic prophase I, possibly during the recombination events that lead to the production of crossovers. In line with its expected regulation by ATM kinase, BTBD12 protein is reduced in the testis of Atm−/− males, and Btbd12 mutant mice exhibit increased genomic instability in the form of elevated blood cell micronucleus formation similar to that seen in Atm−/− males. Taken together, these data indicate that BTBD12 functions throughout gametogenesis to maintain genome stability, possibly by co-ordinating repair processes and/or by linking DNA repair events to the cell cycle via ATM

    Endogenous formaldehyde is a hematopoietic stem cell genotoxin and metabolic carcinogen

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    Endogenous formaldehyde is produced by numerous biochemical pathways fundamental to life, and it can crosslink both DNA and proteins. However, the consequences of its accumulation are unclear. Here we show that endogenous formaldehyde is removed by the enzyme alcohol dehydrogenase 5 (ADH5/GSNOR), and Adh5−/− mice therefore accumulate formaldehyde adducts in DNA. The repair of this damage is mediated by FANCD2, a DNA crosslink repair protein. Adh5−/−Fancd2−/− mice reveal an essential requirement for these protection mechanisms in hematopoietic stem cells (HSCs), leading to their depletion and precipitating bone marrow failure. More widespread formaldehyde-induced DNA damage also causes karyomegaly and dysfunction of hepatocytes and nephrons. Bone marrow transplantation not only rescued hematopoiesis but, surprisingly, also preserved nephron function. Nevertheless, all of these animals eventually developed fatal malignancies. Formaldehyde is therefore an important source of endogenous DNA damage that is counteracted in mammals by a conserved protection mechanism

    Glasgow's Community Gardens: Sustainable Communities of Care

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    Drawing upon new approaches to thinking about care this research set out to explore the inter-relationships between sustainability, health, well-being and the urban environment. Through actively engaging with existing grassroots projects involved in community gardening in Glasgow, the project goes beyond existing top-down public policy initiatives, to explore bottom-up and collaborative models of urban regeneration. The research project underpinning this report was designed in collaboration with grassroots community garden groups in the city. Bringing together the experiences and opinions of volunteers and staff working in these gardens and a number of experts and activists in the related areas of Urban Agriculture (UA) and urban green space use, the report identifies a number of ways in which gardens benefit communities. It also assesses a number of challenges faced by community groups as they try to construct a sustainable future for community gardening in Glasgow. After a brief introduction to community gardening in Glasgow, this report outlines a range of benefits accrued to individuals that participate in community garden activities and the wider communities that live in relative proximity to the gardens. The report then considers the main challenges faced by community garden groups in the city

    Gait phase effects in mobile interaction

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    One problem evaluating mobile and wearable devices is that they are used in mobile settings, making it hard to collect usability data. We present a study of tap-based selection of on-screen targets whilst walking and sitting, using a PocketPC instrumented with an accelerometer to collect information about user activity at the time of each tap. From these data the user’s gait can be derived, and this is then used to investigate preferred tapping behaviour relative to gait phase, and associated tap accuracy. Results showed that users were more accurate sitting than walking. When walking there were phase regions with significantly increased tap likelihood, and these regions had significantly lower error rates, and lower error variability. This work represents an example of accelerometer-instrumented mobile usability analysis, and the results give a quantitative understanding of the detailed interactions taking place when on the move, allowing us to develop better mobile interfaces. Author Keywords Accelerometer, targeting, pen-based interfaces, mobile devices

    The Design and Evaluation of a Haptic Veterinary Palpation Training Simulator

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    Virtual Reality (VR) simulators have the potential to offer a new training paradigm for improving the practical skills of novice doctors and veterinarians. They provide a training environment where novices can make mistakes and learn from these mistakes without consequences to the patient. However, if adoption of VR medical simulators is to become widespread it is essential that they are shown to provide benefit in areas that have previously been difficult or dangerous to train for. They must show benefit over existing methods, and more importantly show that they provide the expected training benefits to the user. This thesis follows through the design and evaluation of a veterinary medical palpation simulator. It is structured around three main areas. Firstly, it examines the integration of a simulator into an existing veterinary medical course and demonstrates the benefits of using accepted computer aided learning design techniques. Secondly, it examines the problem of evaluation of a simulator. A thorough, structured evaluation is performed that examines different aspects of the training environment developed. Finally, methods of augmenting a simulation are discussed. Multimodal cues are introduced as a method of providing guidance and assessing the performance of users on th

    A review of the influence of corporate governance on the banking crises in the United Kingdom and Germany

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    Purpose - The purpose of this paper is to provide an overview of corporate governance structures in the UK and Germany addressing the extent to which corporate governance structures may have been a contributory factor to the recent banking crisis. Following a review of shareholder and stakeholder theories of corporate governance and a comparative overview of corporate governance codes in the UK and Germany, we provide some country level macroeconomic data and performance related data for a small number of large banks in the UK and Germany. Findings suggest that while corporate governance in banks would appear to have been a significant factor in the recent banking crisis, based on the performance data, it cannot be said that a corporate governance approach based on either shareholder capitalism (UK) or stakeholder capitalism (Germany) is more at fault than the other. However, it is clear that UK and German corporate governance structures were not adequate to prevent the recent banking crisis and only time will tell whether the remedial actions taken have been sufficient.Design/methodology/approach - The rest of this paper is structured as follows. Section 2 reviews the existing literature that underpins the stakeholder vs. shareholder debate within corporate governance. In section 3 the current codes of conduct and governance structures implemented by UK and German banks is reviewed. An analysis of the extent to which the banking crises can be attributed to failures in governance is presented in section 4 and finally some conclusions and recommendations are outlined in section 5. Findings - Our findings, in line with those presented in the Walker report (2009) suggest that the codes of conduct in both countries were not adequate to deal with the complex issues caused by the financial crisis and that changes need to be implemented. We fully acknowledge that corporate governance only played a part in the financial crisis and in order to try to stop a repeat of this, the whole regulatory environment in both countries needs to be strengthened. Research limitations/implications - There main limitation of the study lies with a lack of complex analysis undertaken to support the findings. Practical implications - The findings from the study suggest that, regardless of the type of governance in operation, current corporate governance rules were not adequate and that a new set of rules are need in both the UK and Germany. The findings also suggest that the stakeholder/shareholder debate may not be as important as previously claimed and that regulators need to find good governance rules, regardless of theoretical underpinnings.Originality/value - The paper is original as it is the first attempt to discuss the corporate governance failing and the banking crises from a shareholder/stakeholder perspective
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