6,242 research outputs found

    Practical tools for exploring data and models

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    The Optimisation of Stochastic Grammars to Enable Cost-Effective Probabilistic Structural Testing

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    The effectiveness of probabilistic structural testing depends on the characteristics of the probability distribution from which test inputs are sampled at random. Metaheuristic search has been shown to be a practical method of optimis- ing the characteristics of such distributions. However, the applicability of the existing search-based algorithm is lim- ited by the requirement that the software’s inputs must be a fixed number of numeric values. In this paper we relax this limitation by means of a new representation for the probability distribution. The repre- sentation is based on stochastic context-free grammars but incorporates two novel extensions: conditional production weights and the aggregation of terminal symbols represent- ing numeric values. We demonstrate that an algorithm which combines the new representation with hill-climbing search is able to effi- ciently derive probability distributions suitable for testing software with structurally-complex input domains

    Ultrafine carbon nanoparticles activate inflammasome signaling and cell death in murine macrophages

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    Carbon black (CB) is the primary nanoparticulate component of air pollution from fossil fuel combustion. This work examines the cellular impact of ultrafine carbon (carbon black, CB) nanoparticles, that range in size down to 30 nm, upon murine macrophages. The size analysis of the carbon black nanoparticles was performed using atomic force microscopy (AFM) and transmission electron microscopy (TEM) techniques. RAW246.7 macrophage cells were exposed to CB doses ranging from 50 – 200 ug/ml in complete media. Analysis of cell survival over time revealed elevated rates of significant nuclear degradation and cell lifting after 48 hours of exposure, and in a dose dependent pattern. Live cell imaging of cells exposed to nanoparticles revealed a visible uptake of nanoparticles with accumulation over time. To assess inflammasome signaling, both caspase-1 activation and IL-1b production were observed in whole cell lysates. Caspase-1 activation was measured as the appearance of the active (cleaved) form of the protease appearing in immunoblot analysis. The analysis revealed significant activation of caspase-1 with 48-hour CB exposures at doses of 100-200 ug/ml. Similarly, levels of IL-1b were significantly induced by CB exposure, with maximal induction observed after a 48 hour exposure. Macrophage cells were assessed for accumulation of LC3, a marker for autophagosome vesicle accumulation. Immunoblot analysis revealed a significant accumulation of LC3 in response to CB exposure and in response to chloroquine, which inhibits autophagosome/lysosome fusion. Taken together, these results support a model in which CB exposure activates the inflammasome and disrupts autophagy in macrophages

    IFRS: Approaching A State Of Convergence

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    In this paper we will discuss the underlying differences that currently exist between IFRS and US GAAP. Our paper is presented with the belief that convergence is within reach at this point, and no longer an unfeasible event. The systematic rules-based approach and the conceptual principles-based approach are important models for this paper, and we refer to them when discussing the differences and developing our beliefs. The differences that we have chosen to discuss are ones, we feel, that could lead to comparability complications once IFRS is acceptable among US firms and International firms with US subsidiaries. Areas of concern involve items regarding financial statement presentation, revenue recognition, expense recognition, assets, and liabilities. Although there are a great deal of similarities between the US GAAP and IFRS reporting requirements, the specific items presented within this paper need to be addressed before commonly accepted accounting standards are used among encompassing countries

    Star Electronics, Inc.: An Excel Based Case Using Financial Statement Analysis To Detect Fraud

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    The demand for forensic accounting within the corporate world is continually increasing. The services performed by forensic accountants help detect and prevent fraud within companies. This case is a study of forensic accounting that utilizes fraud methodology and detection techniques through a simulation engagement. Those who complete this case will proceed through a series of procedures that will lead to the formulation of potential fraudulent activity within the discussed company. The addressed procedures include: understanding the business, determining the areas that may be susceptible to fraud, performing analytical procedures to detect fraud, and creating a report to the board of directors as a follow up to any potential red flags found during the performed testing

    Positive Autoregulation Shapes Response Timing and Intensity in Two-component Signal Transduction Systems

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    Positive feedback loops are regulatory elements that can modulate expression output, kinetics and noise in genetic circuits. Transcriptional regulators participating in such loops are often expressed from two promoters, one constitutive and one autoregulated. Here, we investigate the interplay of promoter strengths and the intensity of the stimulus activating the transcriptional regulator in defining the output of a positively autoregulated genetic circuit. Using a mathematical model of twocomponent regulatory systems, which are present in all domains of life, we establish that positive feedback strongly affects the steady-state output levels at both low and high levels of stimulus if the constitutive promoter of the regulator is weak. By contrast, the effect of positive feedback is negligible when the constitutive promoter is sufficiently strong, unless the stimulus intensity is very high. Furthermore, we determine that positive feedback can affect both transient and steady state output levels even in the simplest genetic regulatory systems. We tested our modeling predictions by abolishing the positive feedback loop in the two-component regulatory system PhoP/PhoQ of Salmonella enterica, which resulted in diminished induction of PhoP-activated genes

    Social group size affects Mycobacterium bovis infection in European badgers (Meles meles)

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    1. In most social animals, the prevalence of directly transmitted pathogens increases in larger groups and at higher population densities. Such patterns are predicted by models of Mycobacterium bovis infection in European badgers (Meles meles). 2. We investigated the relationship between badger abundance and M. bovis prevalence, using data on 2696 adult badgers in 10 populations sampled at the start of the Randomized Badger Culling Trial. 3. M. bovis prevalence was consistently higher at low badger densities and in small social groups. M. bovis prevalence was also higher among badgers whose genetic profiles suggested that they had immigrated into their assigned social groups. 4. The association between high M. bovis prevalence and small badger group size appeared not to have been caused by previous small-scale culling in study areas, which had been suspended, on average, 5 years before the start of the current study. 5. The observed pattern of prevalence might occur through badgers in smaller groups interacting more frequently with members of neighbouring groups; detailed behavioural data are needed to test this hypothesis. Likewise, longitudinal data are needed to determine whether the size of infected groups might be suppressed by disease-related mortality. 6. Although M. bovis prevalence was lower at high population densities, the absolute number of infected badgers was higher. However, this does not necessarily mean that the risk of M. bovis transmission to cattle is highest at high badger densities, since transmission risk depends on badger behaviour as well as on badger density

    The Lives of Young Fathers: A Review of Selected Evidence

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    While young fathers have been neglected in social research in the UK, over the past fifteen years a small but growing body of empirical evidence has emerged across a range of studies. This review article draws selectively on this literature to document the characteristics of young fathers in the UK and their lived experiences. It presents compelling evidence for the desire of young fathers to be engaged as parents, despite the sometimes multiple challenges that they face. The article begins with a demographic profile of young fathers and documents what is known of young fathers’ relationships with their children, the child's mother and wider kin. It goes on to consider a range of practical issues facing young fathers. The article concludes with a consideration of young fathers’ support needs and experiences of professional support, drawing out the implications for policy and professional practice

    A clinical prediction model for long-term functional outcome after traumatic spinal cord injury based on acute clinical and imaging factors.

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    To improve clinicians\u27 ability to predict outcome after spinal cord injury (SCI) and to help classify patients within clinical trials, we have created a novel prediction model relating acute clinical and imaging information to functional outcome at 1 year. Data were obtained from two large prospective SCI datasets. Functional independence measure (FIM) motor score at 1 year follow-up was the primary outcome, and functional independence (score ≥ 6 for each FIM motor item) was the secondary outcome. A linear regression model was created with the primary outcome modeled relative to clinical and imaging predictors obtained within 3 days of injury. A logistic model was then created using the dichotomized secondary outcome and the same predictor variables. Model validation was performed using a bootstrap resampling procedure. Of 729 patients, 376 met the inclusion criteria. The mean FIM motor score at 1 year was 62.9 (±28.6). Better functional status was predicted by less severe initial American Spinal Injury Association (ASIA) Impairment Scale grade, and by an ASIA motor score \u3e50 at admission. In contrast, older age and magnetic resonance imaging (MRI) signal characteristics consistent with spinal cord edema or hemorrhage predicted worse functional outcome. The linear model predicting FIM motor score demonstrated an R-square of 0.52 in the original dataset, and 0.52 (95% CI 0.52,0.53) across the 200 bootstraps. Functional independence was achieved by 148 patients (39.4%). For the logistic model, the area under the curve was 0.93 in the original dataset, and 0.92 (95% CI 0.92,0.93) across the bootstraps, indicating excellent predictive discrimination. These models will have important clinical impact to guide decision making and to counsel patients and families
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