28 research outputs found

    Design Frictions for Mindful Interactions: The Case for Microboundaries

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    Design frictions, a term found in popular media articles about user experience design, refer to points of difficulty occurring during interaction with technology. Such articles often argue that these frictions should be removed from interaction flows in order to reduce the risk of user frustration and disengagement. In this paper we argue that, in many scenarios, designing friction into interactions through the introduction of microboundaries, can, in fact, have positive effects. Design frictions can disrupt "mindless" automatic interactions, prompting moments of reflection and more "mindful" interaction. The potential advantages of intentionally introduced frictions are numerous: from reducing the likelihood of errors in data-entry tasks, to supporting health-behaviour change

    Bottom pressure signals at the TAG deep-sea hydrothermal field : evidence for short-period, flow-induced ground deformation

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    Author Posting. © American Geophysical Union, 2009. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geophysical Research Letters 36 (2009): L19301, doi:10.1029/2009GL040006.Bottom pressure measurements acquired from the TAG hydrothermal field on the Mid-Atlantic Ridge (26°N) contain clusters of narrowband spectral peaks centered at periods from 22 to 53.2 minutes. The strongest signal at 53.2 min corresponds to 13 mm of water depth variation. Smaller, but statistically significant, signals were also observed at periods of 22, 26.5, 33.4, and 37.7 min (1–4 mm amplitude). These kinds of signals have not previously been observed in the ocean, and they appear to represent vertical motion of the seafloor in response to hydrothermal flow - similar in many ways to periodic terrestrial geysers. We demonstrate that displacements of 13 mm can be produced by relatively small flow-induced pressures (several kPa) if the source region is less than ∼100 m below the seafloor. We suggest that the periodic nature of the signals results from a non-linear relationship between fluid pore pressure and crustal permeability

    Evaluation of Musical Creativity and Musical Metacreation Systems

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    The field of computational creativity, including musical metacreation, strives to develop artificial systems that are capable of demonstrating creative behavior or producing creative artefacts. But the claim of creativity is often assessed, subjectively only on the part of the researcher and not objectively at all. This article provides theoretical motivation for more systematic evaluation of musical metacreation and computationally creative systems and presents an overview of current methods used to assess human and machine creativity that may be adapted for this purpose. In order to highlight the need for a varied set of evaluation tools, a distinction is drawn among three types of creative systems: those that are purely generative, those that contain internal or external feedback, and those that are capable of reflection and self-reflection. To address the evaluation of each of these aspects, concrete examples of methods and techniques are suggested to help researchers (1) evaluate their systems' creative process and generated artefacts, and test their impact on the perceptual, cognitive, and affective states of the audience, and (2) build mechanisms for reflection into the creative system, including models of human perception and cognition, to endow creative systems with internal evaluative mechanisms to drive self-reflective processes. The first type of evaluation can be considered external to the creative system and may be employed by the researcher to both better understand the efficacy of their system and its impact and to incorporate feedback into the system. Here we take the stance that understanding human creativity can lend insight to computational approaches, and knowledge of how humans perceive creative systems and their output can be incorporated into artificial agents as feedback to provide a sense of how a creation will impact the audience. The second type centers around internal evaluation, in which the system is able to reason about its own behavior and generated output. We argue that creative behavior cannot occur without feedback and reflection by the creative/metacreative system itself. More rigorous empirical testing will allow computational and metacreative systems to become more creative by definition and can be used to demonstrate the impact and novelty of particular approaches

    Mitochondrial physiology

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    As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

    Mitochondrial physiology

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    As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

    31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

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    Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival
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