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Inappropriate activation of mast cells via the FcεRI receptor leads to the release of inflammatory mediators and symptoms of allergic disease. Calcium influx is a critical regulator of mast cell signaling and is required for exocytosis of preformed mediators and for synthesis of eicosanoids, cytokines and chemokines. Studies in rodent and human mast cells have identified Orai calcium channels as key contributors to FcεRI-initiated mediator release. However, until now the role of TRPC calcium channels in FcεRI-mediated human mast cell signaling has not been published. Here, we show evidence for the expression of Orai 1,2, and 3 and TRPC1 and 6 in primary human lung mast cells and the LAD2 human mast cell line but, we only find evidence of functional contribution of Orai and not TRPC channels to FcεRI-mediated calcium entry. Calcium imaging experiments, utilizing an Orai selective antagonist (Synta66) showed the contribution of Orai to FcεRI-mediated signaling in human mast cells. Although, the use of a TRPC3/6 selective antagonist and agonist (GSK-3503A and GSK-2934A, respectively) did not reveal evidence for TRPC6 contribution to FcεRI-mediated calcium signaling in human mast cells. Similarly, inactivation of STIM1-regulated TRPC1 in human mast cells (as tested by transfecting cells with STIM1-KK(684-685)EE - TRPC1 gating mutant) failed to alter FcεRI-mediated calcium signaling in LAD2 human mast cells. Mediator release assays confirm that FcεRI-mediated calcium influx through Orai is necessary for histamine and TNFα release but is differentially involved in the generation of cytokines and eicosanoids.

The case for heat decarbonisation is widely acknowledged, with studies showing that it is more cost effective to tackle CO2 emissions from buildings than cutting more deeply in other sectors.The real challenge is establishing new heating solutions that substantially remove natural gas use from homes whilst making the solutions financially viable and attractive to consumers. Around 20,000 homes each week will need new heating system installations between 2025 and 2050 to meet decarbonisation targets; a rate fifty times greater than achieved to date.The current market will not deliver at scale for residential low carbon heat transition given: unappealing consumer propositions, a fragmented industry structure, a lack economic drivers and need for holistic policy framework.The Energy Technology Institute commissioned theEnergy Systems Catapult to deliver a business model development project to develop a number of specific business propositions that could stimulate new thinking for models to be introduced into the market from just before 2020 through to the late 2020’s.This report outlines five promising consumer business models to transform low carbon heating and well-being in the home.. This aims to stimulate new thinking for business models to be introduced into the market from 2020 that are attractive to customers and investors, to test thinking about wider policy and market development and provide options for future demonstration projects within the Smart Systems and Heat

The case for heat decarbonisation is widely acknowledged, with studies showing that it is more cost effective to tackle CO2 emissions from buildings than cutting more deeply in other sectors.The real challenge is establishing new heating solutions that substantially remove natural gas use from homes whilst making the solutions financially viable and attractive to consumers. Around 20,000 homes each week will need new heating system installations between 2025 and 2050 to meet decarbonisation targets; a rate fifty times greater than achieved to date.The current market will not deliver at scale for residential low carbon heat transition given: unappealing consumer propositions, a fragmented industry structure, a lack economic drivers and need for holistic policy framework.The Energy Technology Institute commissioned theEnergy Systems Catapult to deliver a business model development project to develop a number of specific business propositions that could stimulate new thinking for models to be introduced into the market from just before 2020 through to the late 2020’s.Five complementary business models are considered in order to stimulate new thinking on addressing affordability and engagement in residential low carbon heating for all homes and consumers, including the fuel poor:Home Service CompanyHome Comfort ContractHome ModerniserNeighbourhood Heat and ElectricityUrban RenewalAnalysis suggests that the most significant Enablers would be Policy, ICT and Standardisation. It is notable that none of the business models depends on new clean technology per se and that financing typical for other sectors could be sufficient to move the market forward. Trading of energy was deemed to have aminor impact in the value or cost of the home heating provision.

Interventions to support livelihoods in Fragile and Conflict-Affected Situations (FCAS) are seen by many as subsidiary to the primary (relief-based) imperative to save lives. For others, FCAS interventions remain “stuck” for too long in relief mode, and the potential to get back into support for livelihoods is lost. This paper examines how livelihoods models, initially used in development, not relief, contexts, have been adapted to suit FCAS, and asks what evidence we have on how livelihoods have changed under FCAS and why. It also asks how far efforts to support livelihoods in FCAS have been effective. To provide effective livelihoods support is complex, requiring understanding of how people link into distant opportunities outside the FCAS, how they perceive and respond to risk, and how their livelihoods are affected by power relations, by restrictions on the movement of people and goods, and by reduced capacity to enforce the rule of law in relation to e.g. contracts and the ownership of and access to resources.

The dramatic changes in land use observed in Europe in the last fifty years have generally resulted in improvement of human welfare and economic development. On the other hand, they have caused serious environmental problems. There is therefore a need for approaches that help to understand in an integrative way the economic, environmental and societal impacts that land use changes have on sustainability. Sustainability Impact Assessment (SIA), which assesses the impact of policies on sustainability, addresses this challenge. SIA partly builds on the concept of the multifunctionality of land which helps to deal with the complexity of interactions between different land uses, their temporal and spatial changes, and finally how policies might steer those changes towards sustainability. Following this need for true integration of economic, environmental and societal issues across policy areas at a meaningful spatial scale, an nterdisciplinary team in the SENSOR project has developed an innovative conceptual framework to assess the impact of policies on land sustainability at various levels of spatial aggregation i.e. the Land Use Functions (LUFs) framework. LUFs are the goods and services provided by the different land uses that summarise the most relevant economic, environmental and societal issues of a region. The LUFs framework integrates the changes observed in a large set of impact indicators into nine Land Use Functions (LUFs), which are balanced among the three pillars of sustainability. The LUFs framework makes it possible for policy makers, scientists and stakeholders to identify at a glance those functions of the land which are hindered or enhanced under various scenarios of land use change, and makes it possible to explore the trade-offs between them. The LUFs framework allows therefore the building of assessment across disciplines, sectors and the three sustainability dimensions. It has proved to be very helpful for the systematisation of relevant sustainability indicators within SENSOR and is intended to be further used in other projects as a tool for Sustainability Impact Assessment. The rationale leading to the LUFs concept, its definition and the conceptual framework is described in this chapter. We conclude that the concept of LUFs allows users to make explicit the analytical links between multifunctional land use and sustainable development, and therefore to look at multifunctionality as a way towards sustainability.; Dans le cadre du projet SENSOR, une équipe interdisciplinaire a développé un cadre conceptuel pour l'évaluation des impacts des politiques sur la durabilité des usages de l'espace. Il repose sur l'identification de diverses fonctions assurées par l'espace et permet d'évaluer les effets des changements des usages de l'espace sur ces fonctions. Le concept permet de mettre en relation la multifonctionnalité des usages de l'espace et la durabilité du développement : maintenir la première conditionne la seconde.