2,145 research outputs found

    Towards insect inspired visual sensors for robots

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    Flying insects display a repertoire of complex behaviours that are facilitated by their non-standard visual system that if understood would offer solutions for weight- and power- constrained robotic platforms such as micro unmanned aerial vehicles (MUAVs). Crucial to this goal is revealing the specific features of insect eyes that engineered solutions would benefit from possessing, however progress in exploration of the design space has been limited by challenges in accurately replicating insect vision. Here we propose that emerging ray-tracing technologies are ideally placed to realise the high-fidelity replication of the insect visual perspective in a rapid, modular and adaptive framework allowing development of technical specifications for a new class of bio-inspired sensor. A proof-of-principle insect eye renderer is shown and insights into research directions it affords discussed

    Sport and austerity in the UK: an insight into Liverpool 2014

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    The UK’s Comprehensive Spending Review (CSR) in 2010, outlined £81 billion of cuts across government departments by 2014/15. The Conservative-Liberal Democrat reform was premised on the ‘Big Society’ making up for their austere cuts to the state. In this piece, we debate the impact of this on sports development, taking the case study of inner city Liverpool. This example is marked because, on the one hand, it presents cuts to municipal sports facilities which are threatened with closure as a result of shrinking local authority budgets, and on the other this role is partially taken on by an offshoot of Everton Football Club (EFC). The points we debate are: 1) is the change in responsibility from the local authority to a private enterprise, staffed by volunteers, a new turn in sport policy?; and 2) what are the consequences of this on grassroots sport participation

    The Effects of Combination Treatment Using Phenoxodiol and Docetaxel, and Phenoxodiol and Secreted Frizzled-related Protein 4 on Prostate Cancer Cell Lines

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    Although much progress has been made for the treatment of prostate cancer, patients with advanced prostate cancer still have a poor 5 year survival rate. Current practices for hormone-refractory/castrate resistant, metastatic prostate cancer involve the use of taxanes. Docetaxel, in particular, is being incorporated in numerous current clinical trials either as a single or combination agent against androgen-independent prostate cancer. Combination therapies have the potential to increase the effectiveness of drug treatments while simultaneously increasing quality of life by reducing side effects, lowering effective dosage rates, or by increasing effectiveness of one compound once combined with another. Using three diverse human prostate cancer cell lines, LNCap, DU145, and PC3, we studied the effect of the novel prostate cancer drug phenoxodiol in combination with docetaxel by utilizing isobolograms, and found that docetaxelinduced cell death was attenuated by co-treatment or pre-treatment of cells with phenoxodiol. This attenuation is associated with the prevention of cells from entering the G2/M phase of the cell cycle where docetaxel is functional in damaging the spindle fibers, and potentially due to p21WAF1 mediated cell survival after docetaxel treatment.We also investigated the use of the Wnt signaling pathway antagonist secreted frizzled-related protein 4 (sFRP4) to increase the effectiveness of phenoxodiol treatment. We found that, through stabilization of the GSK3β molecule, sFRP4 induces degradation of active β-catenin, which causes an increased sensitivity to isoflavone cytotoxic induction by increasing p21WAF1 expression and decreasing expression of c-Myc, Cyclin-D1, and other potent oncogenes. Phenoxodiol induces significant cytotoxicity when combined with a Wnt/β-catenin receptor blocker such as sFRP4. This promotes the concept that combination therapy of a Wnt inhibitor with phenoxodiol might increase the effectiveness of phenoxodiol and give a subset population of prostate cancer sufferers a more effective treatment regime

    Low Carbon Cities: Is Ambitious Action Affordable?

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    Research has begun to uncover the extent that greenhouse gas emissions can be attributed to cities, as well as the scope for cities to contribute to emissions reduction. But assessments of the economics of urban climate mitigation are lacking, and are currently based on selective case studies or specific sectors. Further analysis is crucial to enable action at the urban level. Here we consider the investment needs associated with 11 clusters of low carbon measures that could be deployed across the world’s urban areas in a way that is consistent with a broader 2°C target. Economic assessment of these low carbon measures finds that they could be deployed around the world with investments of c1trillionperyearbetween2015and2050(equivalentto1.31 trillion per year between 2015 and 2050 (equivalent to 1.3% of global GDP in 2014). When the direct savings that emerge from these measures due to avoided energy costs are considered, under the central scenario these investments have a net present value of c16.6 trillion USD in the period to 2050. However, discount rates, energy prices and rates of technological learning are key to the economic feasibility of climate action, with the NPV of these measures ranging from -1.1trillionUSDto1.1 trillion USD to 65.2 trillion USD under different conditions

    Circulating tumour DNA (ctDNA) as a biomarker in metachronous melanoma and colorectal cancer- a case report

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    Background: Circulating tumour DNA (ctDNA) has emerged as a promising blood-based biomarker for monitoring disease status of patients with advanced cancers. The presence of ctDNA in the blood is a result of biological processes, namely tumour cell apoptosis and/or necrosis, and can be used to monitor different cancers by targeting cancer-specific mutation. Case presentation: We present the case of a 67 year old Caucasian male that was initially treated with BRAF inhibitors followed by anti-CTLA4 and then anti-PD1 immunotherapy for metastatic melanoma but later developed colorectal cancer. The kinetics of ctDNA derived from each cancer type were monitored targeting BRAF V600R (melanoma) and KRAS G13D (colon cancer), specifically reflected the status of the patient\u27s tumours. In fact, the discordant pattern of BRAF and KRAS ctDNA was significantly correlated with the clinical response of melanoma to pembrolizumab treatment and progression of colorectal cancer noted by PET and/or CT scan. Based on these results, ctDNA can be used to specifically clarify disease status of patients with metachronous cancers. Conclusions: Using cancer-specific mutational targets, we report here for the first time the efficacy of ctDNA to accurately provide a comprehensive outlook of the tumour status of two different cancers within one patient. Thus, ctDNA analysis has a potential clinical utility to delineate clinical information in patients with multiple cancer types

    Static Ricci-flat 5-manifolds admitting the 2-sphere

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    We examine, in a purely geometrical way, static Ricci-flat 5-manifolds admitting the 2-sphere and an additional hypersurface-orthogonal Killing vector. These are widely studied in the literature, from different physical approaches, and known variously as the Kramer - Gross - Perry - Davidson - Owen solutions. The 2-fold infinity of cases that result are studied by way of new coordinates (which are in most cases global) and the cases likely to be of interest in any physical approach are distinguished on the basis of the nakedness and geometrical mass of their associated singularities. It is argued that the entire class of solutions has to be considered unstable about the exceptional solutions: the black string and soliton cases. Any physical theory which admits the non-exceptional solutions as the external vacuua of a collapsing object has to accept the possibility of collapse to zero volume leaving behind the weakest possible, albeit naked, geometrical singularities at the origin.Finally, it is pointed out that these types of solutions generalize, in a straightforward way, to higher dimensions.Comment: Generalize, in a straightforward way, to higher dimension

    Advances in personalized targeted treatment of metastatic melanoma and non-invasive tumor monitoring

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    Despite extensive scientific progress in the melanoma field, treatment of advanced stage melanoma with chemotherapeutics and biotherapeutics has rarely provided response rates higher than 20%. In the past decade, targeted inhibitors have been developed for metastatic melanoma, leading to the advent of more personalized therapies of genetically characterized tumors. Here we review current melanoma treatments and emerging targeted molecular therapies. In particular we discuss the mutant BRAF inhibitors Vemurafenib and Dabrafenib, which markedly inhibit tumor growth and advance patients’ overall survival. However this response is almost inevitably followed by complete tumor relapse due to drug resistance hampering the encouraging initial responses. Several mechanisms of resistance within and outside the MAPK pathway have now been uncovered and have paved theway for clinical trials of combination therapies to try and overcome tumor relapse. It is apparent that personalized treatment management will be required in this new era of targeted treatment. Circulating tumor cells (CTCs) provide an easily accessible means of monitoring patient relapse and several new approaches are available for the molecular characterization of CTCs. Thus CTCs provide a monitoring tool to evaluate treatment efficacy and early detection of drug resistance in real time.We detail here how advances in the molecular analysis of CTCs may provide insight into new avenues of approaching therapeutic options that would benefit personalized melanoma management

    Tectonic synthesis and contextual setting for the Central North Sea and adjacent onshore areas, 21CXRM Palaeozoic Project

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    This report is designed simply to provide a summary tectonic outline and contextual setting against which offshore seismic and well data relating to the Devono-Carboniferous evolution of the Central North Sea, Forth Approaches, and adjacent UK onshore region can be considered. This summary is intended to help better frame the questions that will arise during interrogation of that data; the findings that result from that analysis are presented elsewhere in the report series (Arsenikos et al., 2015; Kimbell & Williamson, 2015; Monaghan et al., 2015). Apparently contradictory, wrench- or extension-dominated patterns of Lower Carboniferous basin development are recorded in the Forth Approaches, Quadrant 29, North Dogger and Silverpit basins of the Central North Sea, as well as the Midland Valley of Scotland (MVS) and Northumberland and Solway basins onshore. Partitioning Carboniferous deformation across inherited pre-existing Caledonian or Tornquist structures is likely to be an important control on the tectonic architecture developed in these regions during intervals of the geological record in the Carboniferous. Onshore, spatially separate but contemporaneous domains of extension-dominated tectonics versus wrench-dominated tectonics explain the contrasting tectonic framework of the MVS/Forth Approaches region (wrench-dominated) compared with Northumberland Basin (classic ‘stags head’ structure). NE-SW trending Caledonian inheritance strongly controls the domain boundaries and the patterns of deformation created in each of these domains. Offshore, in the Devono-Carboniferous basins of the Central North Sea, the likelihood that strain is partitioned in a similar way across features inherited from the NW-SE Tornquist trend is proposed and examined. The data currently under consideration suggests that a NW-SE trending wrench-dominated domain is spatially associated with the region underlain by the Dogger Granite pluton; domains affected by extension-dominated tectonics appear to be arranged on either side of that feature, namely the Quadrant 29 and North Dogger basins to the NE, and the Silverpit Basin to the SW. Extension is expressed as a NE-SW directed stretch in both of these domains. Patterns of broadly N-S trending fold axes need to be carefully assessed in terms of their structural setting, as folding cannot implicitly be linked with inversion/compression when partitioned strains are developed. Superficially similar features can develop in the MVS in dextral transpression, in north Northumberland buttressed around the Cheviot Granite in overall dextral wrench, and as superimposed late compressional folds in end-Variscan convergence, for example in the Boldon syncline of County Durham. Offshore, similar inversion effects can be seen in the patterns of transpressive faulting associated with features such as the Murdoch Ridge, and with examples of superimposed NE-SW trending extensional faults active in the latest Carboniferous to early Permian

    Opportunities and Challenges for the development of 'Core Outcome Sets' in Neuro-Oncology

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    Core Outcome Sets (COS) define minimum outcomes to be measured and reported in clinical effectiveness trials for a particular health condition/health area. Despite recognition as critical to clinical research design for other health areas, none have been developed for neuro-oncology. COS development projects should carefully consider: scope (how the COS should be used), stakeholders involved in development (including patients as both research partners and participants), and consensus methodologies used (typically a Delphi survey and consensus meeting), as well as dissemination plans. Developing COS for neuro-oncology is potentially challenging due to extensive tumor subclassification (including molecular stratification), different symptoms related to anatomical tumor location, and variation in treatment options. Development of a COS specific to tumor subtype, in a specific location, for a particular intervention may be too narrow and would be unlikely to be used. Equally, a COS that is applicable across a wider area of neuro-oncology may be too broad and therefore lack specificity. This review describes why and how a COS may be developed, and discusses challenges for their development, specific to neuro-oncology. The COS under development are briefly described, including: adult glioma, incidental/untreated meningioma, meningioma requiring intervention, and adverse events from surgical intervention for pediatric brain tumors. Keywords: clinical trial; core outcome set; effectiveness; glioma; meningioma
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