1,297 research outputs found

    Evaluating Singleplayer and Multiplayer in Human Computation Games

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    Human computation games (HCGs) can provide novel solutions to intractable computational problems, help enable scientific breakthroughs, and provide datasets for artificial intelligence. However, our knowledge about how to design and deploy HCGs that appeal to players and solve problems effectively is incomplete. We present an investigatory HCG based on Super Mario Bros. We used this game in a human subjects study to investigate how different social conditions---singleplayer and multiplayer---and scoring mechanics---collaborative and competitive---affect players' subjective experiences, accuracy at the task, and the completion rate. In doing so, we demonstrate a novel design approach for HCGs, and discuss the benefits and tradeoffs of these mechanics in HCG design.Comment: 10 pages, 4 figures, 2 table

    Large Animal Studies to Reduce the Foreign Body Reaction in Brain-Computer Interfaces: A Systematic Review.

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    Brain-computer interfaces (BCI) are reliant on the interface between electrodes and neurons to function. The foreign body reaction (FBR) that occurs in response to electrodes in the brain alters this interface and may pollute detected signals, ultimately impeding BCI function. The size of the FBR is influenced by several key factors explored in this review; namely, (a) the size of the animal tested, (b) anatomical location of the BCI, (c) the electrode morphology and coating, (d) the mechanics of electrode insertion, and (e) pharmacological modification (e.g., drug eluting electrodes). Trialing methods to reduce FBR in vivo, particularly in large models, is important to enable further translation in humans, and we systematically reviewed the literature to this effect. The OVID, MEDLINE, EMBASE, SCOPUS and Scholar databases were searched. Compiled results were analysed qualitatively. Out of 8388 yielded articles, 13 were included for analysis, with most excluded studies experimenting on murine models. Cats, rabbits, and a variety of breeds of minipig/marmoset were trialed. On average, over 30% reduction in inflammatory cells of FBR on post mortem histology was noted across intervention groups. Similar strategies to those used in rodent models, including tip modification and flexible and sinusoidal electrode configurations, all produced good effects in histology; however, a notable absence of trials examining the effect on BCI end-function was noted. Future studies should assess whether the reduction in FBR correlates to an improvement in the functional effect of the intended BCI

    Influence of calcium fortification on physicochemical properties of whey protein concentrate solutions enriched in α-lactalbumin

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    In this study, three whey protein concentrate systems enriched in α-lactalbumin, produced using membrane filtration (LAC-M), selective precipitation (LAC-P) and ion-exchange chromatography (LAC-IE), were fortified with calcium chloride (CaCl2) at 0–5 mM and changes in physicochemical properties studied. Binding of calcium (Ca2+) occurred for LAC-P in the range 0.00–2.00 mM, with an affinity constant (Kd) of 1.63 × 10−7, resulting in a proportion of total protein-bound calcium of 81.8% at 2 mM CaCl2. At 5 mM CaCl2, LAC-P had volume mean diameter (VMD) of 638 nm, while LAC-M and LAC-IE had VMD of 204 and 3.87 nm, respectively. Changes in physicochemical properties were dependent on the approach used to enrich α-lactalbumin and concentrations of other macromolecules (e.g., phospholipid). The results obtained in this study provide fundamental insights into the influence of fortification with soluble calcium salts on the physicochemical stability of next-generation whey protein ingredients enriched in α-lactalbumin

    Flow cytometry of bone marrow aspirates from neuroblastoma patients is a highly sensitive technique for quantification of low-level neuroblastoma [version 2; peer review: 2 approved]

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    Background: Bone marrow involvement is an important aspect of determining staging of disease and treatment for childhood neuroblastoma. Current standard of care relies on microscopic examination of bone marrow trephine biopsies and aspirates respectively, to define involvement. Flow cytometric analysis of disaggregated tumour cells, when using a panel of neuroblastoma specific markers, allows for potentially less subjective determination of the presence of tumour cells. Methods: A retrospective review of sequential bone marrow trephine biopsies and aspirates, performed at Great Ormond Street Hospital, London, between the years 2015 and 2018, was performed to assess whether the addition of flow cytometric analysis to these standard of care methods provided concordant or additional information. Results: There was good concurrence between all three methods for negative results 216/302 (72%). Positive results had a concordance of 52/86 (61%), comparing samples positive by flow cytometry and positive by either or both cytology and histology. Of the remaining samples, 20/86 (23%) were positive by either or both cytology and histology, but negative by flow cytometry. Whereas 14/86 (16%) of samples were positive only by flow cytometry. Conclusions: Our review highlights the ongoing importance of expert cytological and histological assessment of bone marrow results. Flow cytometry is an objective, quantitative method to assess the level of bone marrow disease in aspirates. In this study, flow cytometry identified low-level residual disease that was not detected by cytology or histology. The clinical significance of this low-level disease warrants further investigation

    Academic neurosurgery in the UK: present and future directions.

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    Academic neurosurgery encompasses basic science and clinical research efforts to better understand and treat diseases of relevance to neurosurgical practice, with the overall aim of improving treatment and outcome for patients. In this article, we provide an overview of the current and future directions of British academic neurosurgery. Training pathways are considered together with personal accounts of experiences of structured integrated clinical academic training and unstructured academic training. Life as an academic consultant is also described. Funding is explored, for the specialty as a whole and at the individual level. UK academic neurosurgical organisations are highlighted. Finally, the UK's international standing is considered

    Band-gaps in long Josephson junctions with periodic phase-shifts

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    We investigate analytically and numerically a long Josephson junction on an infnite domain, having arbitrary periodic phase shift of k, that is, the so-called 0-k long Josephson junction. The system is described by a one-dimensional sine-Gordon equation and has relatively recently been proposed as artificial atom lattices. We discuss the existence of periodic solutions of the system and investigate their stability both in the absence and presence of an applied bias current. We find critical values of the phase-discontinuity and the applied bias current beyond which a solution switches to its complementary counterpart. Due to the periodic discontinuity in the phase, the system admits regions of allowed and forbidden bands. We perturbatively investigate the Arnold tongues that separate the region of allowed and forbidden bands, and discuss the effect of an applied bias current on the band-gap structure. We present numerical simulations to support our analytical results

    Short-term variability in euphotic zone biogeochemistry and primary productivity at Station ALOHA : a case study of summer 2012

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    Author Posting. © American Geophysical Union, 2015. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Global Biogeochemical Cycles 29 (2015): 1145–1164, doi:10.1002/2015GB005141.Time-series observations are critical to understand the structure, function, and dynamics of marine ecosystems. The Hawaii Ocean Time-series program has maintained near-monthly sampling at Station ALOHA (22°45′N, 158°00′W) in the oligotrophic North Pacific Subtropical Gyre (NPSG) since 1988 and has identified ecosystem variability over seasonal to interannual timescales. To further extend the temporal resolution of these near-monthly time-series observations, an extensive field campaign was conducted during July–September 2012 at Station ALOHA with near-daily sampling of upper water-column biogeochemistry, phytoplankton abundance, and activity. The resulting data set provided biogeochemical measurements at high temporal resolution and documents two important events at Station ALOHA: (1) a prolonged period of low productivity when net community production in the mixed layer shifted to a net heterotrophic state and (2) detection of a distinct sea-surface salinity minimum feature which was prominent in the upper water column (0–50 m) for a period of approximately 30 days. The shipboard observations during July–September 2012 were supplemented with in situ measurements provided by Seagliders, profiling floats, and remote satellite observations that together revealed the extent of the low productivity and the sea-surface salinity minimum feature in the NPSG.NOAA Climate Observation Division; National Science Foundation (NSF) Center for Microbial Oceanography: Research and Education (C-MORE) Grant Numbers: EF0424599, OCE-1153656, OCE-1260164; Gordon and Betty Moore Foundation Marine Microbiology Investigator2016-02-1

    Solid Organ Transplantation During COVID-19 Pandemic: An International Web-based Survey on Resources’ Allocation

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    Background. Solid organ transplants (SOTs) are life-saving interventions, recently challenged by coronavirus disease 2019 (COVID-19). SOTs require a multistep process, which can be affected by COVID-19 at several phases. Methods. SOT-specialists, COVID-19-specialists, and medical ethicists designed an international survey according to CHERRIES guidelines. Personal opinions about continuing SOTs, safe managing of donors and recipients, as well as equity of resources' allocation were investigated. The survey was sent by e-mail. Multiple approaches were used (corresponding authors from Scopus, websites of scientific societies, COVID-19 webinars). After the descriptive analysis, univariate and multivariate ordinal regression analysis was performed. Results. There were 1819 complete answers from 71 countries. The response rate was 49%. Data were stratified according to region, macrospecialty, and organ of interest. Answers were analyzed using univariate- multivariate ordinal regression analysis and thematic analysis. Overall, 20% of the responders thought SOTs should not stop (continue transplant without restriction); over 70% suggested SOTs should selectively stop, and almost 10% indicated they should completely stop. Furthermore, 82% agreed to shift resources from transplant to COVID-19 temporarily. Briefly, main reason for not stopping was that if the transplant will not proceed, the organ will be wasted. Focusing on SOT from living donors, 61% stated that activity should be restricted only to "urgent"cases. At the multivariate analysis, factors identified in favor of continuing transplant were Italy, ethicist, partially disagreeing on the equity question, a high number of COVID-19- related deaths on the day of the answer, a high IHDI country. Factors predicting to stop SOTs were Europe except-Italy, public university hospital, and strongly agreeing on the equity question. Conclusions. In conclusion, the majority of responders suggested that transplant activity should be continued through the implementation of isolation measures and the adoption of the COVID-19-free pathways. Differences between professional categories are less strong than supposed

    PTPA variants and impaired PP2A activity in early-onset parkinsonism with intellectual disability

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    The protein phosphatase 2A complex (PP2A), the major Ser/Thr phosphatase in the brain, is involved in a number of signalling pathways and functions, including the regulation of crucial proteins for neurodegeneration, such as alpha-synuclein, tau and LRRK2. Here, we report the identification of variants in the PTPA/PPP2R4 gene, encoding a major PP2A activator, in two families with early-onset parkinsonism and intellectual disability. We carried out clinical studies and genetic analyses, including genome-wide linkage analysis, whole-exome sequencing, and Sanger sequencing of candidate variants. We next performed functional studies on the disease-associated variants in cultured cells and knock-down of ptpa in Drosophila melanogaster. We first identified a homozygous PTPA variant, c.893T&gt;G (p.Met298Arg), in patients from a South African family with early-onset parkinsonism and intellectual disability. Screening of a large series of additional families yielded a second homozygous variant, c.512C&gt;A (p.Ala171Asp), in a Libyan family with a similar phenotype. Both variants co-segregate with disease in the respective families. The affected subjects display juvenile-onset parkinsonism and intellectual disability. The motor symptoms were responsive to treatment with levodopa and deep brain stimulation of the subthalamic nucleus. In overexpression studies, both the PTPA p.Ala171Asp and p.Met298Arg variants were associated with decreased PTPA RNA stability and decreased PTPA protein levels; the p.Ala171Asp variant additionally displayed decreased PTPA protein stability. Crucially, expression of both variants was associated with decreased PP2A complex levels and impaired PP2A phosphatase activation. PTPA orthologue knock-down in Drosophila neurons induced a significant impairment of locomotion in the climbing test. This defect was age-dependent and fully reversed by L-DOPA treatment. We conclude that bi-allelic missense PTPA variants associated with impaired activation of the PP2A phosphatase cause autosomal recessive early-onset parkinsonism with intellectual disability. Our findings might also provide new insights for understanding the role of the PP2A complex in the pathogenesis of more common forms of neurodegeneration.</p
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