300 research outputs found

    "The Collecting Itself Feels Good": Towards Collection Interfaces for Digital Game Objects

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    © Lennart Nacke, 2016. This is the author’s version of the work. It is posted here for your personal use. Not for redistribution. The definitive version was published in CHI PLAY Companion '16 Proceedings of the 2016 Annual Symposium on Computer-Human Interaction in Play Companion Extended Abstracts, https://doi.org/10.1145/2967934.2968088Digital games offer a variety of collectible objects. We investigate players' collecting behaviors in digital games to determine what digital game objects players enjoyed collecting and why they valued these objects. Using this information, we seek to inform the design of future digital game object collection interfaces. We discuss the types of objects that players prefer, the reasons that players value digital game objects, and how collection behaviors may guide play. Through our findings, we identify design implications for digital game object collection interfaces: enable object curation, preserve rules and mechanics, preserve context of play, and allow players to share their collections with others. Digital game object collection interfaces are applicable to the design of digital games, gamified applications, and educational software.Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada Social Sciences and Humanities Research Council of CanadaPeer-reviewe

    A robust and rapid xenograft model to assess efficacy of chemotherapeutic agents for human acute myeloid leukemia

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    International audienceRelevant preclinical mouse models are crucial to screen new therapeutic agents for acute myeloid leukemia (AML). Current in vivo models based on the use of patient samples are not easy to establish and manipulate in the laboratory. Our objective was to develop robust xenograft models of human AML using well-characterized cell lines as a more accessible and faster alternative to those incorporating the use of patient-derived AML cells. Five widely used AML cell lines representing various AML subtypes were transplanted and expanded into highly immunodeficient non-obese diabetic/LtSz-severe combined immunodeficiency IL2R gamma(null)(c) mice (for example, cell line-derived xenografts). We show here that bone marrow sublethal conditioning with busulfan or irradiation has equal efficiency for the xenotransplantation of AML cell lines. Although higher number of injected AML cells did not change tumor engraftment in bone marrow and spleen, it significantly reduced the overall survival in mice for all tested AML cell lines. On the basis of AML cell characteristics, these models also exhibited a broad range of overall mouse survival, engraftment, tissue infiltration and aggressiveness. Thus, we have established a robust, rapid and straightforward in vivo model based on engraftment behavior of AML cell lines, all vital prerequisites for testing new therapeutic agents in preclinical studies

    Materializing digital collecting: an extended view of digital materiality

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    If digital objects are abundant and ubiquitous, why should consumers pay for, much less collect them? The qualities of digital code present numerous challenges for collecting, yet digital collecting can and does occur. We explore the role of companies in constructing digital consumption objects that encourage and support collecting behaviours, identifying material configuration techniques that materialise these objects as elusive and authentic. Such techniques, we argue, may facilitate those pleasures of collecting otherwise absent in the digital realm. We extend theories of collecting by highlighting the role of objects and the companies that construct them in materialising digital collecting. More broadly, we extend theories of digital materiality by highlighting processes of digital material configuration that occur in the pre-objectification phase of materialisation, acknowledging the role of marketing and design in shaping the qualities exhibited by digital consumption objects and consequently related consumption behaviours and experiences

    The transport and vertical distribution of microplastics in the Mekong River, SE Asia

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    Rivers are primary vectors of plastic debris to oceans, but sources, transport mechanisms, and fate of fluvial microplastics (<5 mm) remain poorly understood, impeding accurate predictions of microplastic flux, ecological risk and socio-economic impacts. We report on microplastic concentrations, characteristics and dynamics in the Mekong River, one of the world's largest and polluting rivers, in Cambodia and Vietnam. Sampling throughout the water column at multiple localities detected an average of 24 microplastics m−3 (0.073 mg l−1). Concentrations increased downstream from rural Kampi, Cambodia (344 km from river mouth; 2 microplastics m−3, 0.006 mg l−1), to Can Tho, Vietnam (83 km from river mouth; 64 microplastics m−3, 0.182 mg l−1) with most microplastics being fibres (53 %), followed by fragments (44 %) and the most common polymer being polyethylene terephthalate (PET) or polyester. Pathways of microplastic pollution are expected to be from urban wastewater highlighting the need for improved wastewater treatment in this region. On average, 86 % of microplastics are transported within the water column and consequently we identified an optimum sampling depth capturing a representative flux value, highlighting that sampling only the water surface substantially biases microplastic concentration predictions. Additionally, microplastic abundance does not linearly follow discharge changes during annual monsoonal floods or mirror siliciclastic sediment transport, as microplastic concentrations decrease rapidly during higher monsoon flows. The findings reveal complex microplastic transport in large rivers and call for improved sampling methods and predictive models to better assess environmental risk and guide policy

    A corpus-assisted study of the discourse marker well as an indicator of judges' institutional roles in court cases with litigants in person

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    In this paper, I concentrate on court cases with litigants in person (lay people who act on their own behalf in legal proceedings without a counsel or solicitor) and discuss the challenges of building a corpus of courtroom discourse where it is crucial to distinguish between speakers due to their distinct institutional roles. The corpus incorporates seven sub-corpora of verbatim transcripts from different court cases with litigants in person and comprises over eleven-million tokens. The focus of this paper is on the interplay between the legal and lay discourse types and how judges project their institutional roles through well-initiated turns directed at litigants in person and counsels. As a versatile discourse marker, well provides a good opportunity to explore how judges have to adapt their roles to ensure lay litigants in person receive the necessary support and that their lack of competence does not impede on the fairness of the proceedings. Given the breadth and importance of the topic of litigation in person, I discuss how the tools and approaches of corpus linguistics can be helpful in this multi-disciplinary area where multiple functions and uses of individual linguistic features need to be explored in depth

    Increased immunogenicity of surviving tumor cells enables cooperation between liposomal doxorubicin and IL-18

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    <p>Abstract</p> <p>Background</p> <p>Liposomal doxorubicin (Doxil) is a cytotoxic chemotherapy drug with a favorable hematologic toxicity profile. Its active drug, doxorubicin, has interesting immunomodulatory properties. Here, the effects of Doxil on surviving tumor cell immunophenotype were investigated.</p> <p>Methods</p> <p>Using ID8 murine ovarian cancer cells, the immunomodulatory effects of Doxil were studied by measuring its impact on ovarian cancer cell expression of MHC class-I and Fas, and susceptibility to immune attack <it>in vitro</it>. To evaluate the ability of Doxil to cooperate with cancer immunotherapy, the interaction between Doxil and Interleukin 18 (IL-18), a pleiotropic immunostimulatory cytokine, was investigated <it>in vivo </it>in mice bearing ID8-Vegf tumors.</p> <p>Results</p> <p>While Doxil killed ID8 tumor cells in a dose-dependent manner, tumor cells escaping Doxil-induced apoptosis upregulated surface expression of MHC-I and Fas, and were sensitized to CTL killing and Fas-mediated death <it>in vitro</it>. We therefore tested the hypothesis that the combination of immunotherapy with Doxil provides positive interactions. Combination IL-18 and Doxil significantly suppressed tumor growth compared with either monotherapy <it>in vivo </it>and uniquely resulted in complete tumor regression and long term antitumor protection in a significant proportion of mice.</p> <p>Conclusion</p> <p>These data demonstrate that Doxil favorably changes the immunophenotype of a large fraction of the tumor that escapes direct killing thus creating an opportunity to expand tumor killing by immunotherapy, which can be capitalized through addition of IL-18 <it>in vivo</it>.</p

    Cronicidad y uso de servicios sanitarios: la formación entre iguales de la Escuela de Pacientes

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    RESUMEN Objetivo: Evaluar el impacto de la estrategia formativa de la Escuela de Pacientes en el uso de servicios sanitarios entre las personas con enfermedades crónicas. Método: Diseño cuantitativo de evaluación pretest y postest con una población de 3350 pacientes crónicos de la Escuela de Pacientes (Andalucía, 2013-2015). Se empleó un cuestionario adaptado de la Universidad de Stanford, que midió: salud autopercibida, número de visitas médicas y nivel de confianza y comunicación con el personal sanitario. Se realizó estudio descriptivo y bivariante, estudio de correlación y análisis de ganancias netas pretest/postest. Resultados: Participaron 964 pacientes (28,8% de la población): el 18,8% hombres, edad media 56 años. La formación aumentó la confianza en el personal de Atención Primaria (AP) y Atención Hospitalaria (AH) (0,44 y 0,65 puntos), descendieron las visitas médicas en un 25% y los ingresos hospitalarios en un 51%, con diferencias estadísticamente significativas por sexo y enfermedad. El índice de correlación entre confianza con profesionales y uso de servicios sanitarios fue de −0,215. Conclusión: La estrategia formativa tuvo un impacto positivo en el uso de servicios sanitarios y confianza con personal sanitario, detectándose áreas de mejora a partir de las cuales se establecen recomendaciones

    Distinct Effects of IL-18 on the Engraftment and Function of Human Effector CD8+ T Cells and Regulatory T Cells

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    IL-18 has pleotropic effects on the activation of T cells during antigen presentation. We investigated the effects of human IL-18 on the engraftment and function of human T cell subsets in xenograft mouse models. IL-18 enhanced the engraftment of human CD8+ effector T cells and promoted the development of xenogeneic graft versus host disease (GVHD). In marked contrast, IL-18 had reciprocal effects on the engraftment of CD4+CD25+Foxp3+ regulatory T cells (Tregs) in the xenografted mice. Adoptive transfer experiments indicated that IL-18 prevented the suppressive effects of Tregs on the development of xenogeneic GVHD. The IL-18 results were robust as they were observed in two different mouse strains. In addition, the effects of IL-18 were systemic as IL-18 promoted engraftment and persistence of human effector T cells and decreased Tregs in peripheral blood, peritoneal cavity, spleen and liver. In vitro experiments indicated that the expression of the IL-18Rα was induced on both CD4 and CD8 effector T cells and Tregs, and that the duration of expression was less sustained on Tregs. These preclinical data suggest that human IL-18 may have use as an adjuvant for immune reconstitution after cytotoxic therapies, and to augment adoptive immunotherapy, donor leukocyte infusions, and vaccine strategies

    Engineering HIV-Resistant Human CD4+ T Cells with CXCR4-Specific Zinc-Finger Nucleases

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    HIV-1 entry requires the cell surface expression of CD4 and either the CCR5 or CXCR4 coreceptors on host cells. Individuals homozygous for the ccr5Δ32 polymorphism do not express CCR5 and are protected from infection by CCR5-tropic (R5) virus strains. As an approach to inactivating CCR5, we introduced CCR5-specific zinc-finger nucleases into human CD4+ T cells prior to adoptive transfer, but the need to protect cells from virus strains that use CXCR4 (X4) in place of or in addition to CCR5 (R5X4) remains. Here we describe engineering a pair of zinc finger nucleases that, when introduced into human T cells, efficiently disrupt cxcr4 by cleavage and error-prone non-homologous DNA end-joining. The resulting cells proliferated normally and were resistant to infection by X4-tropic HIV-1 strains. CXCR4 could also be inactivated in ccr5Δ32 CD4+ T cells, and we show that such cells were resistant to all strains of HIV-1 tested. Loss of CXCR4 also provided protection from X4 HIV-1 in a humanized mouse model, though this protection was lost over time due to the emergence of R5-tropic viral mutants. These data suggest that CXCR4-specific ZFNs may prove useful in establishing resistance to CXCR4-tropic HIV for autologous transplant in HIV-infected individuals
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