Computational alignment of goals and scenarios for complex systems

The purpose of requirements validation is to determine whether a large requirements set will lead to the achievement of system-related goals under different conditions - a task that needs automation if it is to be performed quickly and accurately. One reason for the current lack of software tools to undertake such validation is the absence of the computational mechanisms needed to associate scenario, system specification and goal analysis tools. Therefore, in this paper, we report first research experiments in developing these new capabilities, and demonstrate them with a non-trivial example associated with a Rolls Royce aircraft engine software component

Longitudinal variation in SARS-CoV-2 antibody levels and emergence of viral variants:a serological analysis

BACKGROUND: Serological assays are being used to monitor antibody responses in individuals who had SARS-CoV-2 infection and those who received a COVID-19 vaccine. We aimed to determine whether such assays can predict neutralising antibody titres as antibody levels wane and viral variants emerge. METHODS: We measured antibody levels in serum samples from a cohort of 112 participants with SARS-CoV-2 infection using ten high-throughput serological tests and functional neutralisation assays. Serum samples were taken at baseline and at up to four subsequent visits. We assessed the effects of time and spike protein sequence variation on the performance and predictive value of the various assays. We did correlation analyses for individual timepoints using non-parametric Spearman correlation, and differences between timepoints were determined by use of a two-tailed Wilcoxon matched-pairs signed rank test. FINDINGS: Neutralising antibody titres decreased over the first few months post-infection but stabilised thereafter, at about 30% of the level observed shortly after infection. Serological assays commonly used to measure antibodies against SARS-CoV-2 displayed a range of sensitivities that declined to varying extents over time. Quantitative measurements generated by serological assays based on the spike protein were better at predicting neutralising antibody titres than those based on nucleocapsid, but performance was variable, and manufacturer positivity thresholds were not able to predict the presence or absence of detectable neutralising activity. Although we observed some deterioration in correlation between serological measurements and functional neutralisation activity, some assays maintained an ability to predict neutralising titres, even against variants of concern. INTERPRETATION: The ability of high-throughput serological assays to predict neutralising antibody titres is likely to be crucial for evaluation of immunity at the population scale. These data can facilitate the selection of the most suitable assays as surrogates of functional neutralising activity and suggest that such measurements might be useful in clinical practice. FUNDING: US National Institutes of Health and National Health Service Research Scotland BioResource

Close Encounters: Intimate service interactions in lap dancing work as a nexus of ‘self-others-things’

Drawing on ethnographic research on lap dancing work, this paper focuses on how the subjectivities, interactions and settings that constitute the lap dancing industry come into being through three interrelated processes of encoding, embodying and embedding. In considering how these processes combine to ‘enact’ the industry, the paper draws on Merleau Ponty’s understanding of the world as a dynamic nexus of ‘self-others-things’. Focusing on how this nexus shapes lived experiences of intimate service interactions, the analysis considers how dancers continually negotiate customers’ expectations of the service encounter given the ways in which these are: (i) encoded in depictions of lap dancing work in marketing and advertising materials on club websites; (ii) embodied by lap dancers through their interactions with customers; and (iii) embedded within the materiality of lap dancing clubs. The paper shows how intimate service encounters can be understood as the outcome of a nexus of ‘self-others-things’ through which particular organizational subjectivities and settings are brought into being through these three interrelated processes

Regulatory T cell-derived extracellular vesicles modify dendritic cell function

Regulatory T cells (Treg) are a subpopulation of T cells that maintain tolerance to self and limit other immune responses. They achieve this through different mechanisms including the release of extracellular vesicles (EVs) such as exosomes as shown by us, and others. One of the ways that Treg derived EVs inhibit target cells such as effector T cells is via the transfer of miRNA. Another key target for the immunoregulatory function of Tregs is the dendritic cells (DCs). In this study we demonstrate directly, and for the first time, that miRNAs are transferred from Tregs to DCs via Treg derived EVs. In particular two miRNAs, namely miR-150-5p and miR-142-3p, were increased in DCs following their interaction with Tregs and Treg derived exosomes. One of the consequences for DCs following the acquisition of miRNAs contained in Treg derived EVs was the induction of a tolerogenic phenotype in these cells, with increased IL-10 and decreased IL-6 production being observed following LPS stimulation. Altogether our findings provide data to support the idea that intercellular transfer of miRNAs via EVs may be a novel mechanism by which Tregs regulate DC function and could represent a mechanism to inhibit immune reactions in tissues

Do Toxoplasma gondii RH strain tachyzoites evolve during continuous passage?

Aim: To examine three lineages of Toxoplasma gondii RH strain in terms of performance in the dye test, culture, and gene expression. Methods: Historical data (culture growth and performance in the dye test) from three lineages of RH strain tachyzoites (B, J, and Q) that had been continuously cultured in HeLa cells was assessed. Tachyzoite harvests obtained during continuous cell culture were retrieved from liquid nitrogen and cultured in HeLa cells, providing mRNA that was extracted and used to study gene expression using random amplified polymorphic DNA analysis at different stages of lineage adaptation to continuous culture. Results: The B and Q lineages consistently produced tachyzoites that were successfully used in the dye test and their gene expression was stable after multiple passages. The J lineage had unpredictable growth, tachyzoites unsuitable for use in the dye test, and changing gene expression with multiple passage. Conclusion: This study has explained some anomalies in the performance of different stocks of T gondii, and suggests that lineages that are still evolving in cell culture should be avoided