Towards a Java Subtyping Operad

The subtyping relation in Java exhibits self-similarity. The self-similarity in Java subtyping is interesting and intricate due to the existence of wildcard types and, accordingly, the existence of three subtyping rules for generic types: covariant subtyping, contravariant subtyping and invariant subtyping. Supporting bounded type variables also adds to the complexity of the subtyping relation in Java and in other generic nominally-typed OO languages such as C# and Scala. In this paper we explore defining an operad to model the construction of the subtyping relation in Java and in similar generic nominally-typed OO programming languages. Operads, from category theory, are frequently used to model self-similar phenomena. The Java subtyping operad, we hope, will shed more light on understanding the type systems of generic nominally-typed OO languages.Comment: 13 page

Environmental regulation in transition: Policy officials’ views of regulatory instruments and their mapping to environmental risks

This study re-analysed 14 semi-structured interviews with policy officials from the UK Department for Environment, Food and Rural Affairs (Defra) to explore the use of a variety of regulatory instruments and different levels of risk across 14 policy domains and 18 separately named risks. Interviews took place within a policy environment of a better regulation agenda and of broader regulatory reform. Of 619 (n) coded references to 5 categories of regulatory instrument, ‘command and control’ regulation (n = 257) and support mechanisms (n = 118) dominated the discussions, with a preference for ‘command and control’ cited in 8 of the policy domains. A framing analysis revealed officials' views on instrument effectiveness, including for sub-categories of the 5 key instruments. Views were mixed, though notably positive for economic instruments including taxation, fiscal instruments and information provision. An overlap analysis explored officials' mapping of public environmental risks to instrument types suited to their management. While officials frequently cite risk concepts generally within discussions, the extent of overlap for risks of specific significance was low across all risks. Only ‘command and control’ was mapped to risks of moderate significance in likelihood and impact severity. These results show that policy makers still prefer ‘command and control’ approaches when a certainty of outcome is sought and that alternative means are sought for lower risk situations. The detailed reasons for selection, including the mapping of certain instruments to specific risk characteristics, is still developing

Critical evaluation of ecosystem changes from an offshore wind farm: producing natural capital asset and risk registers

Offshore wind infrastructure modifies benthic habitats, affecting ecosystem services. A natural capital approach allows risks to nature-based assets and ecosystem benefits to be assessed. The UK Natural Capital Committee produced guidance for conducting natural capital assessments to aid decision making processes. Development of an asset register and risk register are key components of this methodology. The former provides an inventory of NC stocks, and the latter considers the likelihood of changes and the scale of their impact on delivery of ecosystem services. In this study, suitability of the methodology in a marine environment context was critically evaluated. Natural capital stocks before and after installation of Greater Gabbard offshore wind farm were compared and risks to delivery of ecosystem services were assessed. It was demonstrated that incorporating an assessment of impacts on natural capital assets in planning and management decisions (as an extension to traditional environmental impact assessment approaches) could further facilitate sustainable use of marine ecosystems. For example, by preventing access to bottom-trawl fisheries activities, wind farms may promote recovery and increase value of seabed natural capital assets. By also introducing aquaculture systems loss of food provision (from reduced fishing activity) could be offset whilst allowing benthic natural capital assets to recover. Natural capital assessment is relevant to the marine context. However, application of the Natural Capital Committee’s methodology was constrained by the limited coverage of standard benthic sampling tools. Given the scale of wind energy plans across the marine environment it is recommended that these shortcomings are appropriately addressed

Recombinant Newcastle disease virus immunotherapy drives oncolytic effects and durable systemic antitumor immunity

A recombinant Newcastle Disease Virus (NDV), encoding either a human (NDVhuGM-CSF, MEDI5395) or murine (NDVmuGM-CSF) GM-CSF transgene, combined broad oncolytic activity with ability to significantly modulate genes related to immune functionality in human tumor cells. Replication in murine tumor lines was significantly diminished relative to human tumor cells. Nonetheless, intratumoral injection of NDVmuGM-CSF conferred antitumor effects in three syngeneic models in vivo; with efficacy further augmented by concomitant treatment with anti-PD-1/L-1 or T cell agonists. Ex vivo immune-profiling, including TCRseq, revealed profound immune-contexture changes; consistent with priming and potentiation of adaptive immunity and tumor-microenvironment (TME) re-programming towards an immune-permissive state. CRISPR modifications rendered CT26 significantly more permissive to NDV replication, and in this setting NDVmuGM-CSF confers immune-mediated¬¬¬¬¬¬ effects in the non-injected tumor in vivo. Taken together the data supports the thesis that MEDI5395 primes and augments cell mediated antitumor immunity and has significant utility as a combination partner with other immunomodulatory cancer treatments