100 research outputs found

    The Effects of the Environment and Linear Actuators on Robot Morphologies

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    The field of evolutionary robotics uses principles of natural evolution to design robots. In this paper, we study the effect of adding a new module inspired by the skeletal muscle to the existing RoboGen framework: the linear actuator. Additionally, we investigate how robots evolved in a plain environment differ from robots evolved in a rough environment. We consider the task of directed locomotion for comparing evolved robot morphologies. The results show that the addition of the linear actuator does not have a significant impact on the performance and morphologies of robots evolved in a plain environment. However, we find significant differences in the morphologies of robots evolved in a plain environment and robots evolved in a rough environment. We find that more complex behavior and morphologies emerge when we change the terrain of the environment

    Residency-as-method: a process-based approach to developing artistic ways of knowing within sites of informal learning

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    This study makes the proposition that an artist’s residency-is-method. By method, I mean a specific way of doing research. Residency I define as an artist working within a practice within a site. I identify the relations between personal art practice and its agency through telling the story of an experiment in research-creation that crosses three sites. The study builds a platform and in so doing creates a territory where multiple trajectories collide. The study employs propositions from the field of research-creation as an approach that pays attention to the individual subjective and a singular arts practice. The intention is to acknowledge the difficulties and contradictions that emerge when artistic ways of thinking are diffracted through the lens of research methods and brought to written language. This study is written for artists and researchers who are working on cross-disciplinary research projects that are not located within university fine art departments. It contributes from an individual and personal perspective to the growing fields of research-creation in that it pragmatically layers the approach into the complex relation of work within sites of collective community action. Where necessary the study draws on theoretical and ontological thinking of post-philosophies, specifically Deleuze and Guattari’s concepts of assemblage and the nomadic. However, it remains deeply immersed in the thinking-making-doing process of art within the ongoing creative-event. It applies research-creation as an approach to open a space for art to do things differently and enunciate newsense challenging multiple disciplinary boundaries and sedimented ways of knowing. This study interrogates thoughts, observations and the concepts that emerged from the interactions between doing research and maintaining an artist's identity through thinking-making-doing within multiple sites of practice. I recognise that the work of this study is a further ravelling and as such a coming together. It is not a systematic untangling, the undoing of knots, or an unravelling. There are no conclusions, only thoughts and movement in process

    The Open Linguistics Working Group: developing the Linguistic Linked Open Data cloud

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    The Open Linguistics Working Group (OWLG) brings together researchers from various fields of linguistics, natural language processing, and information technology to present and discuss principles, case studies, and best practices for representing, publishing and linking linguistic data collections. A major outcome of our work is the Linguistic Linked Open Data (LLOD) cloud, an LOD (sub-)cloud of linguistic resources, which covers various linguistic databases, lexicons, corpora, terminologies, and metadata repositories. We present and summarize five years of progress on the development of the cloud and of advancements in open data in linguistics, and we describe recent community activities. The paper aims to serve as a guideline to orient and involve researchers with the community and/or Linguistic Linked Open Data

    ADCC responses and blocking of EGFR-mediated signaling and cell growth by combining the anti-EGFR antibodies imgatuzumab and cetuximab in NSCLC cells

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    Imgatuzumab is a novel glycoengineered anti-epidermal growth factor receptor (EGFR) monoclonal antibody optimized to induce both antibody-dependent cellular cytotoxicity (ADCC) and EGFR signal transduction inhibition. We investigated antiEGFR monoclonal antibodies imgatuzumab and cetuximab-induced internalization and membranous turnover of EGFR, and whether this affected imgatuzumab-mediated ADCC responses and growth inhibition of non-small cell lung cancer (NSCLC) cells. In a panel of wild-type EGFR expressing human NSCLC cell lines, membranous and total EGFR levels were downregulated more effectively by imgatuzumab when compared with cetuximab. Imgatuzumab plus cetuximab enhanced EGFR internalization and reduced membranous turnover of EGFR, resulting in an even stronger downregulation of EGFR. Immunofluorescent analysis showed that combined treatment increased clustering of receptor-antibody complexes and directed internalized EGFR to lysosomes. The antibody combination potently inhibited intracellular signaling and epidermal growth factor (EGF)-dependent cell proliferation. More importantly, robust EGFR downregulation after 72 hours with the antibody combination did not impair ADCC responses. In conclusion, imgatuzumab plus cetuximab leads to a strong downregulation of EGFR and superior cell growth inhibition in vitro without affecting antibody-induced ADCC responses. These findings support further clinical exploration of the antibody combination in EGFR wild-type NSCLC

    Goldstraw, K,. Macmillan, A,. Mort, H,. Pahl, K., Pool, S., Rafiq, Z., Rasool, Z (2020) Co-Producing Artistic Approaches to Social Cohesion Research for All

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    This paper examines the potential of co-produced arts-based methodologies through the lens of a social cohesion project, from the perspectives of five artists. Arts methodologies can be useful in working across different disciplines and across university and community boundaries to create equitable knowledge production processes. The ways in which art is used in community settings as a mode of collaboration are explored, using the reflections from five artists who were involved in the social cohesion project together. This paper argues that co-producing artistic approaches to social cohesion is a complex, multilayered and sometimes fragile process, but that recognizing and discussing understandings of the role of power and voice within co-produced projects enables effective team communication

    (89)Zr-mAb3481 PET for HER3 tumor status assessment during lapatinib treatment

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    Treatment of human epidermal growth factor receptor 2 (HER2)-driven breast cancer with tyrosine kinase inhibitor lapatinib can induce a compensatory HER3 increase, which may attenuate antitumor efficacy. Therefore, we explored in vivo HER3 tumor status assessment after lapatinib treatment with zirconium-89 ((89)Zr)-labeled anti-HER3 antibody mAb3481 positron emission tomography (PET). Lapatinib effects on HER3 cell surface expression and mAb3481 internalization were evaluated in human breast (BT474, SKBR3) and gastric (N87) cancer cell lines using flow cytometry. Next, in vivo effects of daily lapatinib treatment on(89)Zr-mAb3481 BT474 and N87 xenograft tumor uptake were studied. PET-scans (BT474 only) were made after daily lapatinib treatment for 9 days, starting 3 days prior to (89)Zr-mAb3481 administration. Subsequently, ex vivo (89)Zr-mAb3481 organ distribution analysis was performed and HER3 tumor levels were measured with Western blot and immunohistochemistry. In vitro, lapatinib increased membranous HER3 in BT474, SKBR3 and N87 cells, and consequently mAb3481 internalization 1.7-fold (BT474), 1.4-fold (SKBR3) and 1.4-fold (N87). (89)Zr-mAb3481 BT474 tumor uptake was remarkably high at SUVmean 5.6±0.6 (51.8±7.7%ID/g) using a 10 μg (89)Zr-mAb3481 protein dose in vehicle-treated mice. However, compared to vehicle, lapatinib did not affect (89)Zr-mAb3481 ex vivo uptake in BT474 and N87 tumors, while HER3 tumor expression remained unchanged. In conclusion, lapatinib increased in vitro HER3 tumor cell expression, but not when these cells were xenografted. (89)Zr-mAb3481 PET accurately reflected HER3 tumor status. (89)Zr-mAb3481 PET showed high, HER3-specific tumor uptake, and such an approach might sensitively assess HER3 tumor heterogeneity and treatment response in patients

    ElecSim: Monte-Carlo Open-Source Agent-Based Model to Inform Policy for Long-Term Electricity Planning

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    Due to the threat of climate change, a transition from a fossil-fuel based system to one based on zero-carbon is required. However, this is not as simple as instantaneously closing down all fossil fuel energy generation and replacing them with renewable sources -- careful decisions need to be taken to ensure rapid but stable progress. To aid decision makers, we present a new tool, ElecSim, which is an open-sourced agent-based modelling framework used to examine the effect of policy on long-term investment decisions in electricity generation. ElecSim allows non-experts to rapidly prototype new ideas. Different techniques to model long-term electricity decisions are reviewed and used to motivate why agent-based models will become an important strategic tool for policy. We motivate why an open-source toolkit is required for long-term electricity planning. Actual electricity prices are compared with our model and we demonstrate that the use of a Monte-Carlo simulation in the system improves performance by 52.5%52.5\%. Further, using ElecSim we demonstrate the effect of a carbon tax to encourage a low-carbon electricity supply. We show how a {\pounds}40 ($50\$50) per tonne of CO2 emitted would lead to 70% renewable electricity by 2050.Comment: e-Energy '19 Proceedings of the Tenth ACM International Conference on Future Energy System

    Extracellular domain shedding influences specific tumor uptake and organ distribution of the EGFR PET tracer 89Zr-imgatuzumab

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    Preclinical positron emission tomography (PET) imaging revealed a mismatch between in vivo epidermal growth factor receptor (EGFR) expression and EGFR antibody tracer tumor uptake. Shed EGFR ectodomain (sEGFR), which is present in cancer patient sera, can potentially bind tracer and therefore influence tracer kinetics. To optimize EGFR-PET, we examined the influence of sEGFR levels on tracer kinetics and tumor uptake of EGFR monoclonal antibody Zr-89-imgatuzumab in varying xenograft models. Human cancer cell lines A431 (EGFR overexpressing, epidermoid), A549 and H441 (both EGFR medium expressing, non-small cell lung cancer) were xenografted in mice. Xenografted mice received 10, 25 or 160 mu g Zr-89-imgatuzumab, co-injected with equal doses In-111-IgG control. MicroPET scans were made 24, 72 and 144 h post injection, followed by biodistribution analysis. sEGFR levels in liver and plasma samples were determined by ELISA. Zr-89-imgatuzumab uptake in A431 tumors was highest (29.8 +/- 5.4 % ID/g) in the 160 mu g dose group. Contrary, highest uptake in A549 and H441 tumors was found at the lowest (10 mu g) Zr-89-imgatuzumab dose. High Zr-89-imgatuzumab liver accumulation was found in A431 xenografted mice, which decreased with antibody dose increments. Zr-89-imgatuzumab liver uptake in A549 and H441 xenografted mice was low at all doses. sEGFR levels in liver and plasma of A431 bearing mice were up to 1000-fold higher than levels found in A549, H441 and non-tumor xenografted mice. Zr-89-imgatuzumab effectively visualizes EGFR-expressing tumors. High sEGFR levels can redirect Zr-89-imgatuzumab to the liver, in which case tumor visualization can be improved by increasing tracer antibody dose

    Expressed sequence tag analysis of adult human optic nerve for NEIBank: Identification of cell type and tissue markers

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    <p>Abstract</p> <p>Background</p> <p>The optic nerve is a pure white matter central nervous system (CNS) tract with an isolated blood supply, and is widely used in physiological studies of white matter response to various insults. We examined the gene expression profile of human optic nerve (ON) and, through the NEIBANK online resource, to provide a resource of sequenced verified cDNA clones. An un-normalized cDNA library was constructed from pooled human ON tissues and was used in expressed sequence tag (EST) analysis. Location of an abundant oligodendrocyte marker was examined by immunofluorescence. Quantitative real time polymerase chain reaction (qRT-PCR) and Western analysis were used to compare levels of expression for key calcium channel protein genes and protein product in primate and rodent ON.</p> <p>Results</p> <p>Our analyses revealed a profile similar in many respects to other white matter related tissues, but significantly different from previously available ON cDNA libraries. The previous libraries were found to include specific markers for other eye tissues, suggesting contamination. Immune/inflammatory markers were abundant in the new ON library. The oligodendrocyte marker QKI was abundant at the EST level. Immunofluorescence revealed that this protein is a useful oligodendrocyte cell-type marker in rodent and primate ONs. L-type calcium channel EST abundance was found to be particularly low. A qRT-PCR-based comparative mammalian species analysis reveals that L-type calcium channel expression levels are significantly lower in primate than in rodent ON, which may help account for the class-specific difference in responsiveness to calcium channel blocking agents. Several known eye disease genes are abundantly expressed in ON. Many genes associated with normal axonal function, mRNAs associated with axonal transport, inflammation and neuroprotection are observed.</p> <p>Conclusion</p> <p>We conclude that the new cDNA library is a faithful representation of human ON and EST data provide an initial overview of gene expression patterns in this tissue. The data provide clues for tissue-specific and species-specific properties of human ON that will help in design of therapeutic models.</p

    Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

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    Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts
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