211 research outputs found

    Emulating Human Play in a Leading Mobile Card Game

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    Monte Carlo Tree Search (MCTS) has become a popular solution for game AI, capable of creating strong game playing opponents. However, the emergent playstyle of agents using MCTS is not neces- sarily human-like, believable or enjoyable. AI Factory Spades, currently the top rated Spades game in the Google Play store, uses a variant of MCTS to control AI allies and opponents. In collaboration with the developers, we showed in a previous study that the playstyle of human players significantly differed from that of the AI players [1]. This article presents a method for player modelling using gameplay data and neural networks that does not require domain knowledge, and a method of biasing MCTS with such a player model to create Spades playing agents that emulate human play whilst maintaining strong, competitive performance. The methods of player modelling and biasing MCTS presented in this study are applied to the commercial codebase of AI Factory Spades, and are transferable to MCTS implementations for discrete-action games where relevant gameplay data is available

    Disease causing mutations in inverted formin 2 regulate its binding to G-actin, F-actin capping protein (CapZ α-1) and profilin 2

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    Focal segmental glomerulosclerosis (FSGS) is a devastating form of nephrotic syndrome which ultimately leads to end stage renal failure (ESRF). Mutations in inverted formin 2 (INF2), a member of the formin family of actin-regulating proteins, have recently been associated with a familial cause of nephrotic syndrome characterized by FSGS. INF2 is a unique formin that can both polymerize and depolymerize actin filaments. How mutations in INF2 lead to disease is unknown. In the present study, we show that three mutations associated with FSGS, E184K, S186P and R218Q, reduce INF2 auto-inhibition and increase association with monomeric actin. Furthermore using a combination of GFP–INF2 expression in human podocytes and GFP-Trap purification coupled with MS we demonstrate that INF2 interacts with profilin 2 and the F-actin capping protein, CapZ α-1. These interactions are increased by the presence of the disease causing mutations. Since both these proteins are involved in the dynamic turnover and restructuring of the actin cytoskeleton these changes strengthen the evidence that aberrant regulation of actin dynamics underlies the pathogenesis of disease

    Counterparts: Clothing, value and the sites of otherness in Panapompom ethnographic encounters

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    This is an Author's Accepted Manuscript of an article published in Anthropological Forum, 18(1), 17-35, 2008 [copyright Taylor & Francis], available online at: http://www.tandfonline.com/10.1080/00664670701858927.Panapompom people living in the western Louisiade Archipelago of Milne Bay Province, Papua New Guinea, see their clothes as indices of their perceived poverty. ‘Development’ as a valued form of social life appears as images that attach only loosely to the people employing them. They nevertheless hold Panapompom people to account as subjects to a voice and gaze that is located in the imagery they strive to present: their clothes. This predicament strains anthropological approaches to the study of Melanesia that subsist on strict alterity, because native self‐judgments are located ‘at home’ for the ethnographer. In this article, I develop the notion of the counterpart as a means to explore these forms of postcolonial oppression and their implications for the ethnographic encounter

    Compton scattering beyond the impulse approximation

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    We treat the non-relativistic Compton scattering process in which an incoming photon scatters from an N-electron many-body state to yield an outgoing photon and a recoil electron, without invoking the commonly used frameworks of either the impulse approximation (IA) or the independent particle model (IPM). An expression for the associated triple differential scattering cross section is obtained in terms of Dyson orbitals, which give the overlap amplitudes between the N-electron initial state and the (N-1) electron singly ionized quantum states of the target. We show how in the high energy transfer regime, one can recover from our general formalism the standard IA based formula for the cross section which involves the ground state electron momentum density (EMD) of the initial state. Our formalism will permit the analysis and interpretation of electronic transitions in correlated electron systems via inelastic x-ray scattering (IXS) spectroscopy beyond the constraints of the IA and the IPM.Comment: 7 pages, 1 figur

    Adeno-associated virus gene therapy prevents progression of kidney disease in genetic models of nephrotic syndrome

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    Gene therapy for kidney diseases has proven challenging. Adeno-associated virus (AAV) is used as a vector for gene therapy targeting other organs, with particular success demonstrated in monogenic diseases. We aimed to establish gene therapy for the kidney by targeting a monogenic disease of the kidney podocyte. The most common cause of childhood genetic nephrotic syndrome is mutations in the podocyte gene NPHS2, encoding podocin. We used AAV-based gene therapy to rescue this genetic defect in human and mouse models of disease. In vitro transduction studies identified the AAV-LK03 serotype as a highly efficient transducer of human podocytes. AAV-LK03–mediated transduction of podocin in mutant human podocytes resulted in functional rescue in vitro, and AAV 2/9–mediated gene transfer in both the inducible podocin knockout and knock-in mouse models resulted in successful amelioration of kidney disease. A prophylactic approach of AAV 2/9 gene transfer before induction of disease in conditional knockout mice demonstrated improvements in albuminuria, plasma creatinine, plasma urea, plasma cholesterol, histological changes, and long-term survival. A therapeutic approach of AAV 2/9 gene transfer 2 weeks after disease induction in proteinuric conditional knock-in mice demonstrated improvement in urinary albuminuria at days 42 and 56 after disease induction, with corresponding improvements in plasma albumin. Therefore, we have demonstrated successful AAV-mediated gene rescue in a monogenic renal disease and established the podocyte as a tractable target for gene therapy approaches

    The RING-CH ligase K5 antagonizes restriction of KSHV and HIV-1 particle release by mediating ubiquitin-dependent endosomal degradation of tetherin

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    Tetherin (CD317/BST2) is an interferon-induced membrane protein that inhibits the release of diverse enveloped viral particles. Several mammalian viruses have evolved countermeasures that inactivate tetherin, with the prototype being the HIV-1 Vpu protein. Here we show that the human herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) is sensitive to tetherin restriction and its activity is counteracted by the KSHV encoded RING-CH E3 ubiquitin ligase K5. Tetherin expression in KSHV-infected cells inhibits viral particle release, as does depletion of K5 protein using RNA interference. K5 induces a species-specific downregulation of human tetherin from the cell surface followed by its endosomal degradation. We show that K5 targets a single lysine (K18) in the cytoplasmic tail of tetherin for ubiquitination, leading to relocalization of tetherin to CD63-positive endosomal compartments. Tetherin degradation is dependent on ESCRT-mediated endosomal sorting, but does not require a tyrosine-based sorting signal in the tetherin cytoplasmic tail. Importantly, we also show that the ability of K5 to substitute for Vpu in HIV-1 release is entirely dependent on K18 and the RING-CH domain of K5. By contrast, while Vpu induces ubiquitination of tetherin cytoplasmic tail lysine residues, mutation of these positions has no effect on its antagonism of tetherin function, and residual tetherin is associated with the trans-Golgi network (TGN) in Vpu-expressing cells. Taken together our results demonstrate that K5 is a mechanistically distinct viral countermeasure to tetherin-mediated restriction, and that herpesvirus particle release is sensitive to this mode of antiviral inhibition

    Unique, non‐Earthlike, meteoritic ion behavior in upper atmosphere of Mars

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    Interplanetary dust particles have long been expected to produce permanent ionospheric metal ion layers at Mars, as on Earth, but the two environments are so different that uncertainty existed as to whether terrestrial-established understanding would apply to Mars. The Mars Atmosphere and Volatile EvolutioN (MAVEN) mission made the first in situ detection of the continuous presence of Na+, Mg+, and Fe+ at Mars and indeed revealed non-Earthlike features/processes. There is no separation of the light Mg+ and the heavy Fe+ with increasing altitude as expected for gravity control. The metal ions are well-mixed with the neutral atmosphere at altitudes where no mixing process is expected. Isolated metal ion layers mimicking Earth's sporadic E layers occur despite the lack of a strong magnetic field as required at Earth. Further, the metal ion distributions are coherent enough to always show atmospheric gravity wave signatures. All features and processes are unique to Mars

    The rise of consumer health wearables: promises and barriers

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    Will consumer wearable technology ever be adopted or accepted by the medical community? Patients and practitioners regularly use digital technology (e.g., thermometers and glucose monitors) to identify and discuss symptoms. In addition, a third of general practitioners in the United Kingdom report that patients arrive with suggestions for treatment based on online search results. However, consumer health wearables are predicted to become the next “Dr Google.” One in six (15%) consumers in the United States currently uses wearable technology, including smartwatches or fitness bands. While 19 million fitness devices are likely to be sold this year, that number is predicted to grow to 110 million in 2018. As the line between consumer health wearables and medical devices begins to blur, it is now possible for a single wearable device to monitor a range of medical risk factors. Potentially, these devices could give patients direct access to personal analytics that can contribute to their health, facilitate preventive care, and aid in the management of ongoing illness. However, how this new wearable technology might best serve medicine remains unclea
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