Integrated specifications for abstract systems

Journal ArticleStructural specifications define an abstract object as a composition of other abstract objects. Behavioral specifications define an abstract object in terms of its associated operations. Integrated specifications are a combination of structural and behavioral specifications which are more powerful than either used alone. By providing four naming mechanisms, integrated specifications hide the details of how objects are represented and accessed on storage devices. The four naming mechanisms allow objects to be named in terms of the operations previously applied to them, the unique attributes they possess, the relationships they participate in, and the categories they belong to. Integrated specifications can specify the structure of more abstract systems than the relational database model, while also characterizing dynamic properties. Examples are given of integrated specifications for quide, symboltable and expression. These specifications are simple and guide, but do not constrain, the implementor in designing refinements. By exploiting abstract structure in specifications, common aspects of inter-object communication can be suppressed and only salient differences emphasized. Integrated specifications can make a significant contribution to the useability, reliability and efficiency of computer systems

Continuous and Reinforcement Learning Methods for First-Person Shooter Games

Machine learning is now widely studied as thebasis for artificial intelligence systems within computer games.Most existing work focuses on methods for learning staticexpert systems, typically emphasizing candidate selection. Thispaper extends this work by exploring the use of continuous andreinforcement learning techniques to develop fully-adaptivegame AI for first-person shooter bots. We begin by outlining aframework for learning static control models for tanks withinthe game BZFlag, then extend that framework using continuouslearning techniques that allow computer controlled tanks to adaptto the game style of other players, extending overall playability bythwarting attempts to infer the underlying AI. We further showhow reinforcement learning can be used to create bots that learnhow to play based solely through trial and error, providing gameengineers with a practical means to produce large numbers ofbots, each with individual intelligences and unique behaviours;all from a single initial AI model

Improved Limits on Sterile Neutrino Dark Matter using Full-Sky Fermi Gamma-Ray Burst Monitor Data

A sterile neutrino of ~keV mass is a well motivated dark matter candidate. Its decay generates an X-ray line that offers a unique target for X-ray telescopes. For the first time, we use the Gamma-ray Burst Monitor (GBM) onboard the Fermi Gamma-Ray Space Telescope to search for sterile neutrino decay lines; our analysis covers the energy range 10-25 keV (sterile neutrino mass 20-50 keV), which is inaccessible to X-ray and gamma-ray satellites such as Chandra, Suzaku, XMM-Newton, and INTEGRAL. The extremely wide field of view of the GBM enables a large fraction of the Milky Way dark matter halo to be probed. After implementing careful data cuts, we obtain ~53 days of full sky observational data. We observe an excess of photons towards the Galactic Center, as expected from astrophysical emission. We search for sterile neutrino decay lines in the energy spectrum, and find no significant signal. From this, we obtain upper limits on the sterile neutrino mixing angle as a function of mass. In the sterile neutrino mass range 25-40 keV, we improve upon previous upper limits by approximately an order of magnitude. Better understanding of detector and astrophysical backgrounds, as well as detector response, will further improve the sensitivity of a search with the GBM.Comment: 16 pages, 11 figures, references added, discussion expanded, some typos fixed, matches the published versio

A Phospho-SIM in the Antiviral Protein PML is Required for Its Recruitment to HSV-1 Genomes

Herpes simplex virus type 1 (HSV-1) is a significant human pathogen that infects a large portion of the human population. Cells deploy a variety of defenses to limit the extent to which the virus can replicate. One such factor is the promyelocytic leukemia (PML) protein, the nucleating and organizing factor of nuclear domain 10 (ND10). PML responds to a number of stimuli and is implicated in intrinsic and innate cellular antiviral defenses against HSV-1. While the role of PML in a number of cellular pathways is controlled by post-translational modifications, the effects of phosphorylation on its antiviral activity toward HSV-1 have been largely unexplored. Consequently, we mapped phosphorylation sites on PML, mutated these and other known phosphorylation sites on PML isoform I (PML-I), and examined their effects on a number of PML’s activities. Our results show that phosphorylation at most sites on PML-I is dispensable for the formation of ND10s and colocalization between PML-I and the HSV-1 regulatory protein, ICP0, which antagonizes PML-I function. However, inhibiting phosphorylation at sites near the SUMO-interaction motif (SIM) of PML-I impairs its ability to respond to HSV-1 infection. Overall, our data suggest that PML phosphorylation regulates its antiviral activity against HSV-1

Advances in direct T-cell alloreactivity: Function, avidity, biophysics and structure

Although T-cell-based adaptive immunity plays a crucial role in protection against infectious pathogens and uncontrolled outgrowth of malignant cells, a large portion of these T cells are also capable of responding to allogeneic HLA molecules, violating the paradigm of self-major histocompatibility complex (MHC) restriction. Recent studies have provided insights into the mechanisms by which these T cells recognize allogeneic targets. The role of antiviral T cells in direct alloreactivity through peptide-dependent molecular mimicry and alternate peptide-MHC docking modes has emerged as major models for the human alloresponse. Here, we review in depth recent advances in this field and discuss how molecular interactions between T cells and HLA molecules drive the activation of these effector cells and its potential implications for alloreactivity in human transplantation

Feature-based diversity optimization for problem instance classification

Parallel Problem Solving from Nature – PPSN XIVUnderstanding the behaviour of heuristic search methods is a challenge. This even holds for simple local search methods such as 2-OPT for the Traveling Salesperson problem. In this paper, we present a general framework that is able to construct a diverse set of instances that are hard or easy for a given search heuristic. Such a diverse set is obtained by using an evolutionary algorithm for constructing hard or easy instances that are diverse with respect to different features of the underlying problem. Examining the constructed instance sets, we show that many combinations of two or three features give a good classification of the TSP instances in terms of whether they are hard to be solved by 2-OPT.Wanru Gao, Samadhi Nallaperuma, and Frank Neuman

Linear criteria for gravity-wave breaking in resonant stratified flow over a ridge

Using linear theory, it is shown that, in resonant flow over a 2D mountain ridge, such as exists when a layer of uniform wind is topped by an environmental critical level, the conditions for internal gravity-wave breaking are different from those determined in previous studies for non-resonant flows. For Richardson numbers in the shear layer not exceeding 2.25, two zones of flow overturning exist, respectively below and downstream and above and upstream of the expected locations. Flow overturning occurs for values of the dimensionless height of the ridge smaller than those required for a uniform wind profile. These results may have implications for the physical understanding of high-drag states

Quantifying ice cliff evolution with multi-temporal point clouds on the debris-covered Khumbu Glacier, Nepal

Measurements of glacier ice cliff evolution are sparse, but where they do exist, they indicate that such areas of exposed ice contribute a disproportionate amount of melt to the glacier ablation budget. We used Structure from Motion photogrammetry with Multi-View Stereo to derive 3-D point clouds for nine ice cliffs on Khumbu Glacier, Nepal (in November 2015, May 2016 and October 2016). By differencing these clouds, we could quantify the magnitude, seasonality and spatial variability of ice cliff retreat. Mean retreat rates of 0.30–1.49 cm d−1 were observed during the winter interval (November 2015–May 2016) and 0.74–5.18 cm d−1 were observed during the summer (May 2016–October 2016). Four ice cliffs, which all featured supraglacial ponds, persisted over the full study period. In contrast, ice cliffs without a pond or with a steep back-slope degraded over the same period. The rate of thermo-erosional undercutting was over double that of subaerial retreat. Overall, 3-D topographic differencing allowed an improved process-based understanding of cliff evolution and cliff-pond coupling, which will become increasingly important for monitoring and modelling the evolution of thinning debris-covered glaciers

Time-Course Analysis of Brain Regional Expression Network Responses to Chronic Intermittent Ethanol and Withdrawal: Implications for Mechanisms Underlying Excessive Ethanol Consumption

Long lasting abusive consumption, dependence, and withdrawal are characteristic features of alcohol use disorders (AUD). Mechanistically, persistent changes in gene expression are hypothesized to contribute to brain adaptations leading to ethanol toxicity and AUD. We employed repeated chronic intermittent ethanol (CIE) exposure by vapor chamber as a mouse model to simulate the cycles of ethanol exposure and withdrawal commonly seen with AUD. This model has been shown to induce progressive ethanol consumption in rodents. Brain CIE-responsive expression networks were identified by microarray analysis across five regions of the mesolimbic dopamine system and extended amygdala with tissue harvested from 0-hours to 7-days following CIE. Weighted Gene Correlated Network Analysis (WGCNA) was used to identify gene networks over-represented for CIE-induced temporal expression changes across brain regions. Differential gene expression analysis showed that long-lasting gene regulation occurred 7-days after the final cycle of ethanol exposure only in prefrontal cortex (PFC) and hippocampus. Across all brain regions, however, ethanol-responsive expression changes occurred mainly within the first 8-hours after removal from ethanol. Bioinformatics analysis showed that neuroinflammatory responses were seen across multiple brain regions at early time-points, whereas co-expression modules related to neuroplasticity, chromatin remodeling, and neurodevelopment were seen at later time-points and in specific brain regions (PFC or HPC). In PFC a module containing Bdnf was identified as highly CIE responsive in a biphasic manner, with peak changes at 0 hours and 5 days following CIE, suggesting a possible role in mechanisms underlying long-term molecular and behavioral response to CIE. Bioinformatics analysis of this network and several other modules identified Let-7 family microRNAs as potential regulators of gene expression changes induced by CIE. Our results suggest a complex temporal and regional pattern of widespread gene network responses involving neuroinflammatory and neuroplasticity related genes as contributing to physiological and behavioral responses to chronic ethanol

Stakeholder perspectives on new ways of delivering unscheduled health care: the role of ownership and organisational identity

<b>Rationale, aims and objectives</b>: To explore stakeholder perspectives of the implementation of a new, national integrated nurse-led telephone advice and consultation service (NHS 24), comparing the views of stakeholders from different health care organisations. <b>Methods</b>: Semi-structured interviews with 26 stakeholders including partner organisations located in primary and secondary unscheduled care settings (general practitioner (GP) out-of-hours co-operative; accident and emergency department; national ambulance service), members of NHS 24 and national policymakers. Attendance at key meetings, documentary review and email implementation diaries provided a contextual history of events with which interview data could be compared. <b>Results</b>: The contextual history of events highlighted a fast-paced implementation process, with little time for reflection. Key areas of partner concern were increasing workload, the clinical safety of nurse triage and the lack of communication across the organisations. Concerns were most apparent within the GP out-of-hours co-operative, leading to calls for the dissolution of the partnership. Accident and emergency and ambulance service responses were more conciliatory, suggesting that such problems were to be expected within the developmental phase of a new organisation. Further exploration of these responses highlighted the sense of ownership within the GP co-operative, with GPs having both financial and philosophical ownership of the co-operative. This was not apparent within the other two partner organisations, in particular the ambulance service, which operated on a regional model very similar to that of NHS 24. <b>Conclusions</b>: As the delivery of unscheduled primary health care crosses professional boundaries and locations, different organisations and professional groups must develop new ways of partnership working, developing trust and confidence in each other. The results of this study highlight, for the first time, the key importance of understanding the professional ownership and identity of individual organisations, in order to facilitate the most effective mechanisms to enable that partnership working