Operationalizing the circular city model for naples' city-port: A hybrid development strategy

The city-port context involves a decisive reality for the economic development of territories and nations, capable of significantly influencing the conditions of well-being and quality of life, and of making the Circular City Model (CCM) operational, preserving and enhancing seas and marine resources in a sustainable way. This can be achieved through the construction of appropriate production and consumption models, with attention to relations with the urban and territorial system. This paper presents an adaptive decision-making process for Naples (Italy) commercial port's development strategies, aimed at re-establishing a sustainable city-port relationship and making Circular Economy (CE) principles operative. The approach has aimed at implementing a CCM by operationalizing European recommendations provided within both the Sustainable Development Goals (SDGs) framework-specifically focusing on goals 9, 11 and 12-and the Maritime Spatial Planning European Directive 2014/89, to face conflicts about the overlapping areas of the city-port through multidimensional evaluations' principles and tools. In this perspective, a four-step methodological framework has been structured applying a place-based approach with mixed evaluation methods, eliciting soft and hard knowledge domains, which have been expressed and assessed by a core set of Sustainability Indicators (SI), linked to SDGs. The contribution outcomes have been centred on the assessment of three design alternatives for the East Naples port and the development of a hybrid regeneration scenario consistent with CE and sustainability principles. The structured decision-making process has allowed us to test how an adaptive approach can expand the knowledge base underpinning policy design and decisions to achieve better outcomes and cultivate a broad civic and technical engagement, that can enhance the legitimacy and transparency of policies

Interleukin-6 trans-signaling is a candidate mechanism to drive progression of human DCCs during clinical latency

Although thousands of breast cancer cells disseminate and home to bone marrow until primary surgery, usually less than a handful will succeed in establishing manifest metastases months to years later. To identify signals that support survival or outgrowth in patients, we profile rare bone marrow-derived disseminated cancer cells (DCCs) long before manifestation of metastasis and identify IL6/PI3K-signaling as candidate pathway for DCC activation. Surprisingly, and similar to mammary epithelial cells, DCCs lack membranous IL6 receptor expression and mechanistic dissection reveals IL6 trans-signaling to regulate a stem-like state of mammary epithelial cells via gp130. Responsiveness to IL6 trans-signals is found to be niche-dependent as bone marrow stromal and endosteal cells down-regulate gp130 in premalignant mammary epithelial cells as opposed to vascular niche cells. PIK3CA activation renders cells independent from IL6 trans-signaling. Consistent with a bottleneck function of microenvironmental DCC control, we find PIK3CA mutations highly associated with late-stage metastatic cells while being extremely rare in early DCCs. Our data suggest that the initial steps of metastasis formation are often not cancer cell-autonomous, but also depend on microenvironmental signals. Metastatic dissemination in breast cancer patients occurs early in malignant transformation, raising questions about how disseminated cancer cells (DCC) progress at distant sites. Here, the authors show that DCCs in bone marrow are activated via IL6-trans-signaling and thereby acquire stemness traits relevant for metastasis formation