THE EXTERNAL ELECTRON BEAM OF THE CAMBRIDGE ELECTRON ACCELERATOR

The resonant beam extraction system of Cambridge Synchrotron is described, and measurements of the extraction efficiency and extracted beam properties are compared with values predicted by calculations. (auth

Long-term heart transplant survival by targeting the ionotropic purinergic receptor P2X7

Background: Heart transplantation is a lifesaving procedure for patients with end-stage heart failure. Despite much effort and advances in the field, current immunosuppressive regimens are still associated with poor long-term cardiac allograft outcomes, and with the development of complications, including infections and malignancies, as well. The development of a novel, short-term, and effective immunomodulatory protocol will thus be an important achievement. The purine ATP, released during cell damage/activation, is sensed by the ionotropic purinergic receptor P2X7 (P2X7R) on lymphocytes and regulates T-cell activation. Novel clinical-grade P2X7R inhibitors are available, rendering the targeting of P2X7R a potential therapy in cardiac transplantation. Methods and Results: We analyzed P2X7R expression in patients and mice and P2X7R targeting in murine recipients in the context of cardiac transplantation. Our data demonstrate that P2X7R is specifically upregulated in graft-infiltrating lymphocytes in cardiac-transplanted humans and mice. Short-term P2X7R targeting with periodate-oxidized ATP promotes long-term cardiac transplant survival in 80% of murine recipients of a fully mismatched allograft. Long-term survival of cardiac transplants was associated with reduced T-cell activation, T-helper cell 1/T-helper cell 17 differentiation, and inhibition of STAT3 phosphorylation in T cells, thus leading to a reduced transplant infiltrate and coronaropathy. In vitro genetic upregulation of the P2X7R pathway was also shown to stimulate T-helper cell 1/T-helper cell 17 cell generation. Finally, P2X7R targeting halted the progression of coronaropathy in a murine model of chronic rejection as well. Conclusions: P2X7R targeting is a novel clinically relevant strategy to prolong cardiac transplant survival. \ua9 2012 American Heart Association, Inc

Co-creating value in urban public policy contexts: a different approach

Urban areas face daunting economic challenges that have increased in scope in recent years. At the same time, cities provide for opportunities for growth and value creation. The interplay of these challenges and opportunities represents an area of intervention for policymakers and researchers. However, traditional approaches to urban policy deriving from managerial and economic policy theories present difficulties mainly related to capacities to counterbalance the interests and expectations of a multitude of stakeholders participating in the value co-creation process and to allow different components to synergically contribute to the sustainability of a system. The author proposes an innovative approach to urban public policy that involves adopting the theoretical corpus of the viable systems approach (“VSA”). Urban planning is particularly analyzed as systemic components of urban areas with the aim of investigating decision-making processes that support an integrated, efficient, effective and sustainable management of territories as multidimensional, multisectoral and multi-stakeholder entities. By recovering different settings, the VSA is designed for the co-creation of value as the capacity for viable systems to increase their chances of survival in their own contexts. Value derives first from strategic decisions made to find both dyadic and context consonance. Through its strategic decisions, the governing body of the territory develops a specific system as an overall synthesis of all possible systems organized within a specific area, identifying patterns of development agreed upon by the several stakeholders of the given territory. In the dynamics of value co-creation in systemic multi-subjective organizations where levels of complexity are particularly high, research on consonance among different stakeholders is particularly important to achieve the most value for a territory. In this respect, the VSA may constitute a valid tool for finding necessary capacities to imagine evolutionary paths toward new competencies