A synchronous program algebra: a basis for reasoning about shared-memory and event-based concurrency

This research started with an algebra for reasoning about rely/guarantee concurrency for a shared memory model. The approach taken led to a more abstract algebra of atomic steps, in which atomic steps synchronise (rather than interleave) when composed in parallel. The algebra of rely/guarantee concurrency then becomes an instantiation of the more abstract algebra. Many of the core properties needed for rely/guarantee reasoning can be shown to hold in the abstract algebra where their proofs are simpler and hence allow a higher degree of automation. The algebra has been encoded in Isabelle/HOL to provide a basis for tool support for program verification. In rely/guarantee concurrency, programs are specified to guarantee certain behaviours until assumptions about the behaviour of their environment are violated. When assumptions are violated, program behaviour is unconstrained (aborting), and guarantees need no longer hold. To support these guarantees a second synchronous operator, weak conjunction, was introduced: both processes in a weak conjunction must agree to take each atomic step, unless one aborts in which case the whole aborts. In developing the laws for parallel and weak conjunction we found many properties were shared by the operators and that the proofs of many laws were essentially the same. This insight led to the idea of generalising synchronisation to an abstract operator with only the axioms that are shared by the parallel and weak conjunction operator, so that those two operators can be viewed as instantiations of the abstract synchronisation operator. The main differences between parallel and weak conjunction are how they combine individual atomic steps; that is left open in the axioms for the abstract operator.Comment: Extended version of a Formal Methods 2016 paper, "An algebra of synchronous atomic steps

Malignant Transformation and Antineoplastic Actions of Nonsteroidal Antiinflammatory Drugs (Nsaids) on Cyclooxygenase-Null Embryo Fibroblasts

In this study, we use primary embryonic fibroblasts derived from cyclooxygenase-deficient transgenic embryos to further investigate the role of the two cyclooxygenases, cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2), in the process of neoplastic transformation. Cells with either, neither, or both of the cyclooxygenases were transformed by Ha-ras and/or SV40. Our results show that when a cyclooxygenase enzyme is present, the transformed cells have marked increases in COX-2 and/or COX-1 expression. Nevertheless, each type of cell, deficient in either or both cyclooxygenases, can be readily transformed at almost equal efficiency. Different nonsteroidal antiinflammatory drugs (NSAIDs) were used to examine their possible antineoplastic effects on the transformed cells, which have various levels of expression of COX-1 or COX-2. Our results show that NSAIDs suppress the colony formation in soft agar in a dosage-dependent manner in the absence of the cyclooxygenase(s). Thymidine incorporation and apoptosis analyses further demonstrate that the NSAIDs are effective in the cyclooxygenase-null cells. Our findings with cyclooxygenase knockout cells confirm recent reports that some of the antiproliferative and antineoplastic effects of NSAIDs are independent of the inhibition of either COX-1 or COX-2. They also show that transformation is independent of the status of cyclooxygenase expression, suggesting that the involvement of the cyclooxygenases in tumorigenesis may occur at later steps

Hydrodynamically Guided Hierarchical Self-Assembly of Peptide-Protein Bioinks

Effective integration of molecular self-assembly and additive manufacturing would provide a technological leap in bioprinting. This article reports on a biofabrication system based on the hydrodynamically guided co-assembly of peptide amphiphiles (PAs) with naturally occurring biomolecules and proteins to generate hierarchical constructs with tuneable molecular composition and structural control. The system takes advantage of droplet-on-demand (DoD) inkjet printing to exploit interfacial fluid forces and guide molecular self-assembly into aligned or disordered nanofibers, hydrogel structures of different geometries and sizes, surface topographies and higherordered constructs bound by molecular diffusion. PAs were designed to co-assemble during printing in cell diluent conditions with a range of extracellular matrix (ECM) proteins and biomolecules including fibronectin, collagen, keratin, elastin-like proteins (ELPs) and hyaluronic acid. Using combinations of these molecules, NIH-3T3 and adipose derived stem cells were bioprinted within complex structures while exhibiting high cell viability (> 88 %). By integrating self-assembly with 3D-bioprinting, the study introduces a novel biofabrication platform capable of encapsulating and spatially distributing multiple cell types within tuneable pericellular environments. In this way, the work demonstrates the potential of the approach to generate complex bioactive scaffolds for applications such as tissue engineering, in vitro models, and drug screening

Prevention of child mental health problems through parenting interventions in Southeastern Europe (RISE): study protocol for a multi-site randomised controlled trial

Background: Childhood adversities, such as poor parental practices, exposure to violence, and risk behaviours strongly impact children’s future mental and behavioural problems. Adversities affect families living in disadvantaged environments and low- and middle-income countries (LMICs) to a greater extent than in high-income countries. Parenting programmes are an effective way to alleviate them, although their outreach and scalability is still limited in LMICs. Methods/design: A multi-site randomised controlled trial will be conducted in North Macedonia, Republic of Moldova and Romania to test the efficacy and cost-effectiveness of an optimised version of the promising Parenting for Lifelong Health Programme for Young Children (PLH-YC, 5 sessions), against a standard lecture on parenting issues (control group, 1 session). At least 864 participants who report having children between 2 and 9 years old who display elevated levels of behavioural difficulties will be randomised on a 1:1 basis to the intervention and control groups. The primary outcome will consist of parent report of child oppositional aggressive behaviour. Post-test (four months) and follow-up (12 months) assessments will provide information on short- and longer-term effects of PLH-YC compared to the parenting lecture in the control group. Discussion: This randomised trial will test the efficacy of PLH-YC in alleviating child behavioural problems and assess the cost-effectiveness, transportability across three different cultural contexts, and potential for scalability of the programme. Trial registration: ClinicalTrials.gov., Registration number: NCT04721730 (https://clinicaltrials.gov/ct2/show/NCT04721730). Registered 13.01.202

The Red Sea under the Caliphal Dynasties, c. 639–1171

Students of world history will be familiar with the Red Sea as a strategic communications corridor linking the Mediterranean to the Indian Ocean. This paper examines the Red Sea region between the seventh and twelfth centuries, when it was ruled by a succession of Islamic caliphal dynasties, namely, the Umayyads, ʿAbbāsids, and Fāṭimids. It first sets out a sketch of the political history of the Red Sea and its constituent hinterland polities, including particularly Egypt, Sudan, al‐Ḥijāz, and Yemen, drawing attention to episodes and processes in which the Red Sea was significant. A section on Africa and Arabia explores the Red Sea as a zone of economic and social interaction; another section deals with the historic shift of Indian Ocean trade from the ʿAbbāsid Persian Gulf to the Fāṭimid Red Sea. Finally, the impact of the Red Sea on its constituent hinterland polities and the wider sweep of Islamic history is considered

Design and Deploying Tools to ‘Actively Engaging Nature’: The My Naturewatch Project as an Agent for Engagement

‘Shifting Baseline Syndrome’ is highly apparent in the context of generational shifts in work and life patterns that reduce interaction with and knowledge of the natural world, and therefore expectations of it. This is exacerbated by changes in the natural world itself due to climate change, biodiversity decline and a range of anthropogenic factors. Distributed and accessible technologies, and grass roots approaches provide fresh opportunities for interactions, which enable active engagement in ecological scenarios. The My NatureWatch project uses digital devices to collect visual content about UK wildlife, promoting ‘active engagements with nature’. The project embodies Inclusive Design in the Digital Age, as the activity; engages a wide demographic community, can be used by all, provided user led agency and produced methodological design lessons. The article frames My Naturewatch as an agent for active designed engagements with nature. The research objective is to comprehend ‘how to design tools for positive nature engagement’ holding value for; (1) academic communities as validated methodologies (2) the public through access to enabling technologies, content and knowledge (3) industry in the form of new; experiences, engagements and commerce. The approach is specifically designed to yield insights from a multitude of engagements, through the deployment of accessible, lowcost products. Project reporting documents the benefits, pitfalls and opportunities in the aforementioned engagement uncovered through design-led approaches. Insights are gathered from public/community facing workshops, wildlife experts, ecologists, economists, educators and wildlife NGO’s. The engagement methodologies are compared highlighting which initiative yielded ‘Active Engagement with Nature’

Hormone response to repeated electroconvulsive therapy: Effects of naloxone

Plasma prolactin (PRL), cortisol, and growth hormone (GH) were measured before, and at 15-min intervals for 1 hr after, electroconvulsive therapy (ECT). This was repeated over a series of 6 consecutive treatments for each of 12 depressed drug-free inpatients. Patients received naloxone, 2 mg or 20 mg, by intravenous infusion before the third and fifth treatment. ECT was consistently followed by a release of PRL and cortisol, although two patterns of PRL response could be distinguished. In eight patients, the PRL response did not change significantly with repeated ECT, whereas in four patients, the plasma PRL increased tenfold after the first treatment and decreased after each successive treatment. The GH level varied widely, with no evidence of a reliable response to ECT. Opiate receptor blockade with low- or high-dose naloxone did not alter the release of PRL or cortisol after ECT. These findings demonstrate a reliable PRL and cortisol response to ECT, but do not support a role for endogenous opiates in these hormonal changes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25658/1/0000210.pd