Currently in the Royal Navy, any training feedback provided during a team training exercise at sea or in the full training simulator is delivered by a human instructor “as required”, with the majority of feedback provided in a post-exercise debrief. An automated embedded training system would enable the provision of feedback in real-time during a training session to be standardised, but could provide an almost unlimited amount of feedback. The aim of this research is therefore to identify the benefits of providing on-line feedback, and to develop guidelines for future advanced training systems. This paper describes work that has been carried out to identify existing feedback principles, and to evaluate their utility in the context of a complex, real-time computer-based task. A series of experiments was conducted using a simulation of elements of a Naval Anti-Air Warfare decision making task, with Naval operators as participants. This paper describes the experimental test-bed and provides an overview of the experimental programme. Preliminary results from the first experiment are reported, comparing trainee performance and retention when on-line feedback is provided, with a control condition of no feedback.
The commercial adoption of transgenic Bacillus thuringiensis (Bt) cotton (Bollgard II®) reduced the use of insecticides to control Helicoverpa spp. However, the ineffectiveness of the Bt toxin against sucking pests such as silverleaf whiteflies (Bemisia tabaci) resulted in a marked increase in B. tabaci populations and in the use of insecticides to control this pest. The effect of the entomopathogenic fungus Aspergillus sp. BC 639 on B. tabaci and beneficial insects (predominantly predatory insects) was studied in commercial cotton field trials. The results showed that oil-based extracts of the entomopathogenic fungus BC 639 control the number of B. tabaci adults and nymphs in commercial transgenic cotton crops. The BC 639 fungus caused 60.0%, 67.2%, and 68.8% mortality in adults, and 54.6%, 62.3%, and 51.7% in nymphs at 7, 14, and 21 days after treatment, respectively, relative to the unsprayed controls. The effect of BC 639 at concentrations of 125, 250, and 500 ml/ha on low-density B. tabaci (∼10 nymphs/leaf) did not differ significantly from that of the commercial insecticide (pyriproxifen). However, at higher densities (>50 nymphs per leaf), low concentrations of BC 639 (125 and 250 ml/ha) were not as effective as 500 ml/ha BC 639 in successfully controlling the pest. A simple graphic analysis suggested that the more B. tabaci nymphs per leaf, the fewer adults per leaf, and that once the number of nymphs increased to ∼70 per leaf, a negative feedback regulatory effect reduced the survivorship of the nymphs and adults and/or caused the emigration of the adults from the contaminated leaves in search of new resources. Therefore, the ability of BC 639 to control B. tabaci adults and nymphs with minimal effects on predatory insects indicates its potential utility in supplementing integrated pest management programmes for cotton crops.
Abstract The chapter evaluates dialogue between the UK courts and the European Court of Human Rights and the European Court of Justice. It explains how the different constitutional relationship between these two different European courts and UK courts means that they facilitate different forms of inter-institutional interactions. This is particularly the case given the principle of the primacy of directly effective European Union law, and the lack of an established doctrine of the margin of appreciation in European Union law. The chapter evaluates interactions between the UK courts and these European courts, providing a framework of interactions that are more likely to facilitate democratic dialogue.
Abstract Background An association between neuroinflammation and age-related neurologic disorders has been established but the molecular mechanisms and cell types involved have not been thoroughly characterized. Activity of the proinflammatory NLRP3 inflammasome is implicated in Alzheimer’s and Parkinson’s disease and our recent studies in patients suggest that dopaminergic neurons within the degenerating mesencephalon express NLRP3 throughout the progression of PD. Here, we directly test the impact of enhanced inflammasome activity in mesencephalic neurons by characterizing motor function, tissue integrity, and neuroinflammation in aging mice harboring hyper-activating mutations within the endogenous murine Nlrp3 locus, enabled only in cells expressing the dopamine neuron specific Slc6a3 promoter. Methods We compared mice harboring inducible alleles encoding the cryopyrin-associated periodic syndrome activating mutations Nlrp3A350V and Nlrp3L351P inserted into the endogenous mouse Nlrp3 locus. Tissue specific expression was driven by breeding these animals with mice expressing Cre recombinase under the control of the dopamine neuron specific Slc6a3 promoter. The experimental mice, designed to express hyperactive NLRP3 only when the endogenous mouse Nlrp3 promotor is active in dopaminergic neurons, were analyzed throughout 18 months of aging using longitudinal motor function assessments. Biochemical and histologic analyses of mesencephalic tissues were conducted in 1- and 18-month old animals. Results We observed progressive and significant deficits in motor function in animals expressing Nlrp3L351P, compared with animals expressing Nlrp3WT and Nlrp3A350V. Age-dependent neuroinflammatory changes in the mesencephalon were noted in all animals. Analysis of GFAP-immunoreactive astrocytes in the substantia nigra revealed a significant increase in astrocyte number in animals expressing Nlrp3L351P compared with Nlrp3WT and Nlrp3A350V. Further analysis of Nlrp3L351P striatal tissues indicated genotype specific gliosis, elevated Il1b expression, and both morphologic and gene expression indicators of proinflammatory A1 astrocytes. Conclusions Dopaminergic neurons have the potential to accumulate NLRP3 inflammasome activators with age, including reactive oxygen species, dopamine metabolites, and misfolded proteins. Results indicate the Nlrp3 locus is active in dopaminergic neurons in aging mice, and that the hyperactive Nlrp3L351P allele can drive neuroinflammatory changes in association with progressive behavioral deficits. Findings suggest neuronal NLRP3 inflammasome activity may contribute to neuroinflammation observed during normal aging and the progression of neurologic disorders.
Cells isolated from many types of human cancers express heparin-binding growth factors (HBGFs) that drive tumor growth, metastasis, and angiogenesis. The heparan sulfate proteoglycan glypican-1 (GPC1) is a coreceptor for HBGFs. Here we show that both cancer cell-derived and host-derived GPC1 are crucial for efficient growth, metastasis, and angiogenesis of human and mouse cancer cells. Thus downregulation of GPC1 in the human pancreatic cancer cell line PANC-1, using antisense approaches, resulted in prolonged doubling times and decreased anchorage-independent growth in vitro as well as attenuated tumor growth, angiogenesis, and metastasis when these cells were transplanted into athymic mice. Moreover, athymic mice that lacked GPC1 exhibited decreased tumor angiogenesis and metastasis following intrapancreatic implantation with either PANC-1 or T3M4 human pancreatic cancer cells and fewer pulmonary metastases following intravenous injection of murine B16-F10 melanoma cells. In addition, hepatic endothelial cells isolated from these mice exhibited an attenuated mitogenic response to VEGF-A. These data indicate that cancer cell- and host-derived GPC1 are crucial for full mitogenic, angiogenic, and metastatic potential of cancer cells. Thus targeting GPC1 might provide new avenues for cancer therapy and for the prevention of cancer metastasis.
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