Towards a directed homotopy type theory

In this paper, we present a directed homotopy type theory for reasoning synthetically about (higher) categories, directed homotopy theory, and its applications to concurrency. We specify a new `homomorphism' type former for Martin-L\"of type theory which is roughly analogous to the identity type former originally introduced by Martin-L\"of. The homomorphism type former is meant to capture the notions of morphism (from the theory of categories) and directed path (from directed homotopy theory) just as the identity type former is known to capture the notions of isomorphism (from the theory of groupoids) and path (from homotopy theory). Our main result is an interpretation of these homomorphism types into Cat, the category of small categories. There, the interpretation of each homomorphism type hom(a,b) is indeed the set of morphisms between the objects a and b of a category C. We end the paper with an analysis of the interpretation in Cat with which we argue that our homomorphism types are indeed the directed version of Martin-L\"of's identity types

The connexin mimetic peptide Gap27 and Cx43-Knockdown reveal differential roles for Connexin43 in wound closure events in skin model systems

In the epidermis, remodelling of Connexin43 is a key event in wound closure. However, controversy between the role of connexin channel and non-channel functions exist. We compared the impact of SiRNA targeted to Connexin43 and the connexin mimetic peptide Gap27 on scrape wound closure rates and hemichannel signalling in adult keratinocytes (AK) and fibroblasts sourced from juvenile foreskin (JFF), human neonatal fibroblasts (HNDF) and adult dermal tissue (ADF). The impact of these agents, following 24 h exposure, on (encoding Connexin43), and gene expression, and Connexin43 and pSmad3 protein expression levels, were examined by qPCR and Western Blot respectively. In all cell types Gap27 (100-100 μM) attenuated hemichannel activity. In AK and JFF cells, Gap27 (100 nM-100 μM) enhanced scrape wound closure rates by ~50% but did not influence movement in HNDF or ADF cells. In both JF and AK cells, exposure to Gap27 for 24 h reduced the level of Cx43 protein expression but did not affect the level in ADF and HNDF cells. Connexin43-SiRNA enhanced scrape wound closure in all the cell types under investigation. In HDNF and ADF, Connexin43-SiRNA enhanced cell proliferation rates, with enhanced proliferation also observed following exposure of HDNF to Gap27. By contrast, in JFF and AK cells no changes in proliferation occurred. In JFF cells, Connexin43-SiRNA enhanced levels and in JFF and ADF cells both Connexin43-SiRNA and Gap27 enhanced pSmad3 protein expression levels. We conclude that Connexin43 signalling plays an important role in cell migration in keratinocytes and foreskin derived fibroblasts, however, different pathways are evoked and in dermal derived adult and neonatal fibroblasts, inhibition of Connexin43 signalling plays a more significant role in regulating cell proliferation than cell migration

Connexin 43 plays a role in pulmonary vascular reactivity in mice

Pulmonary arterial hypertension (PAH) is a chronic condition characterized by vascular remodeling and increased vaso-reactivity. PAH is more common in females than in males (~3:1). Connexin (Cx)43 has been shown to be involved in cellular communication within the pulmonary vasculature. Therefore, we investigated the role of Cx43 in pulmonary vascular reactivity using Cx43 heterozygous (Cx43+/−) mice and 37,43Gap27, which is a pharmacological inhibitor of Cx37 and Cx43. Contraction and relaxation responses were studied in intra-lobar pulmonary arteries (IPAs) derived from normoxic mice and hypoxic mice using wire myography. IPAs from male Cx43+/− mice displayed a small but significant increase in the contractile response to endothelin-1 (but not 5-hydroxytryptamine) under both normoxic and hypoxic conditions. There was no difference in the contractile response to endothelin-1 (ET-1) or 5-hydroxytryptamine (5-HT) in IPAs derived from female Cx43+/−mice compared to wildtype mice. Relaxation responses to methacholine (MCh) were attenuated in IPAs from male and female Cx43+/− mice or by pre-incubation of IPAs with 37,43Gap27. Nω-Nitro-L-arginine methyl ester (l-NAME) fully inhibited MCh-induced relaxation. In conclusion, Cx43 is involved in nitric oxide (NO)-induced pulmonary vascular relaxation and plays a gender-specific and agonist-specific role in pulmonary vascular contractility. Therefore, reduced Cx43 signaling may contribute to pulmonary vascular dysfunction

Towards a practical ecclesiology for urban Scotland

This research is praxiological in nature, arising out of committed action and leading to more informed urban ecclesiological practice in Scotland. It acknowledges the current haemorrhaging of membership and influence facing the Church of Scotland - felt most acutely in the poorest parts of the country - and seeks to plot a practical urban ecclesiology which takes seriously both the urban context and also the gospel priority towards the poorest and most marginalised. Chapter One provides an autobiographical backcloth to the research and highlights the three core principles underlying it: a preferential option for the poor; an understanding of knowledge as situated; and a commitment to an abductive research process. Chapter Two outlines the research methodology and, in particular, justifies the use of Case Studies, with Focus Groups and semi-structured Interviews, as an appropriate research model. Chapter Three focuses on the nature of the post-industrial city. It highlights globalisation, environmentalism and the collapse of western-style democracy as three of the key issues in the current urban context. It considers post-war urban regeneration, highlighting the failings of a model substantially dominated by buildings and a top-down strategy. Chapter Four is concerned with the nature of poverty in Scotland today, including how such poverty can be defined and measured. The causes of poverty are understood structurally and a particular critique of New Labour's social inclusion policies is offered, based on an analysis of their underlying political philosophy of communitarianism and the Third Way. Chapter Five draws on the different theological and ecclesiological responses to the urban and to poverty and, in particular, upon Latin American Liberation Theology and Urban Theology in Britain since 1985. Through an exploration of Pentecostalism, it highlights the need to develop appropriate ecclesiological models which take the nature of rooted hybrid spirituality more seriously. In Chapter Six the focus of the research narrows down to look at Glasgow, giving consideration to both the effectiveness of the city's place-marketing strategy and also some of the patterns of church life in the city. Chapter Seven focuses upon four Case Studies. These affirm and inform the conclusions reached in previous chapters, highlighting the failure of urban policy to adequately address poverty and the need of the Church to move beyond a 'project-based' response. The research also highlights the importance of church buildings as places of sanctuary and of the 'cultural sectarianism' which continues to pervade the culture of west central Scotland. Chapter Eight represents an attempt to return to informed practice, highlighting how some of the key concepts and findings within the research are informing the developing strategy and practice of the Church of Scotland's Priority Areas Committee

Probability as a physical motive

Recent theoretical progress in nonequilibrium thermodynamics, linking the physical principle of Maximum Entropy Production ("MEP") to the information-theoretical "MaxEnt" principle of scientific inference, together with conjectures from theoretical physics that there may be no fundamental causal laws but only probabilities for physical processes, and from evolutionary theory that biological systems expand "the adjacent possible" as rapidly as possible, all lend credence to the proposition that probability should be recognized as a fundamental physical motive. It is further proposed that spatial order and temporal order are two aspects of the same thing, and that this is the essence of the second law of thermodynamics.Comment: Replaced at the request of the publisher. Minor corrections to references and to Equation 1 added

The evolution of harm: effect of sexual conflicts and population size

Conflicts of interest between mates can lead to the evolution of male traits reducing female fitness and to coevolution between the sexes. The rate of adaptation and counter-adaptation is constrained by the intensity of selection and its efficiency, which depends on drift and genetic variability. This leads to the largely untested prediction that coevolutionary adaptations such as those driven by sexual conflict should evolve faster in large populations where the response to selection is stronger and sexual selection is more intense. We test this using the bruchid beetle Callosobruchus maculatus, a species with well documented male harm. Whilst most experimental evolution studies remove sexual conflicts, we reintroduce sexual conflict in populations where it has been experimentally removed. Both population size and standing genetic variability were manipulated in a factorial experimental design. After 90 generations of relaxed conflict (monogamy), the reintroduction of sexual conflicts for 30 generations favoured males that harmed females and females more resistant to the genital damage inflicted by males. Large population size rather than high initial genetic variation allowed males to evolve faster and become more harmful. Sexual selection thus creates conditions where males benefit from harming females and this selection is more effective in larger populations