Inflammation-mediated fibroblast activation and immune dysregulation in collagen VII-deficient skin

Inflammation is known to play a critical role in all stages of tumorigenesis; however, less is known about how it predisposes the tissue microenvironment preceding tumor formation. Recessive dystrophic epidermolysis bullosa (RDEB), a skin-blistering disease secondary to COL7A1 mutations and associated with chronic wounding, inflammation, fibrosis, and cutaneous squamous cell carcinoma (cSCC), models this dynamic. Here, we used single-cell RNA sequencing (scRNAseq) to analyze gene expression patterns in skin cells from a mouse model of RDEB. We uncovered a complex landscape within the RDEB dermal microenvironment that exhibited altered metabolism, enhanced angiogenesis, hyperproliferative keratinocytes, infiltration and activation of immune cell populations, and inflammatory fibroblast priming. We demonstrated the presence of activated neutrophil and Langerhans cell subpopulations and elevated expression of PD-1 and PD-L1 in T cells and antigen-presenting cells, respectively. Unsupervised clustering within the fibroblast population further revealed two differentiation pathways in RDEB fibroblasts, one toward myofibroblasts and the other toward a phenotype that shares the characteristics of inflammatory fibroblast subsets in other inflammatory diseases as well as the IL-1-induced inflammatory cancer-associated fibroblasts (iCAFs) reported in various cancer types. Quantitation of inflammatory cytokines indicated dynamic waves of IL-1α, TGF-β1, TNF, IL-6, and IFN-γ concentrations, along with dermal NF-κB activation preceding JAK/STAT signaling. We further demonstrated the divergent and overlapping roles of these cytokines in inducing inflammatory phenotypes in RDEB patients as well as RDEB mouse-derived fibroblasts together with their healthy controls. In summary, our data have suggested a potential role of inflammation, driven by the chronic release of inflammatory cytokines such as IL-1, in creating an immune-suppressed dermal microenvironment that underlies RDEB disease progression

The Project Planning of Urban Decongestion

This study introduces a methodology for the evaluation, among a set of  possible plans and/or policies, of a transport system which could reduce the  effects of the network congestion on an urban area. Hence it is proposed a  procedure which contains a new element compared with the current  methodologies that is the final useris evaluation of the examined system by  turning to the application of the contingent valuation method, a technique like  stated preferences. The approach we propose is based on the necessity for a  determination of an optimal solution to the urban congestion to be established  on the politic acceptability by the final user. Solutions which result virtually  feasible for a public administration both on a technique and economic point of  view often meet hostility by individuals. Consequently, it would be interesting  for policy makers to adopt a process of valuation which could let to  understand the useris sensitivity and hostility towards specific configurations  of the system, chosen as solution to decongestion (traffic calming, roadpricing, auto-free zones) and consequently to make less unpleasant the  strategy to be carried out to control congestion (Harrington et al., 2001). In  this way, a user does not judge the implementation of a set of projects made  by a decision-maker as imposition and he is willing to pay in order to fulfil the  chosen scenario. Finally we describe an application of the proposed  methodology relating the definition of the integrated transport system in the  metropolitan area of Bari, chief town of Apulia. 

Interni per la produzione 4.0

Gli spazi della produzione industriale e manifatturiera, nei quali ogni giorno sono rea- lizzati tutti i prodotti che in piccola o larga scala vengono consumati da gran parte della popo- lazione mondiale, costituiscono lo scenario di una recente trasformazione radicale: la quarta Rivoluzione industriale. Questo cambiamento profondo dei sistemi industriali si fonda sull’af- fermarsi di un nuovo modello di produzione, responsivo e adattivo, denominato Industria 4.01 che, non solo è stato in grado di scardinare i modelli organizzativi e produttivi precedenti, ma ha generato nuovi spazi per la produzione dei beni: le smart factory, fabbriche intelligenti. In- terni altamente ingegnerizzati, connessi e proiettati al futuro, sempre più sostenibili, silenziosi e asettici, in cui le persone, sempre meno, che vi lavorano si relazionano con cobots, robots collaborativi, e intelligenza artificiale

Optimization of Choice Modelling in Complex Urban Contexts - Applications in planning for sustainable development

This paper focuses on the capabilities of choice models in assisting planners in the development of transport policies and interventions for strategic transport planning for urban systems. Models are looked at as part of a decision support system for the development of transport measures for sustainable mobility. The use of participation is looked at as a tool for the understanding of the real needs in terms of mobility in the complex contemporary society and for the construction of the future transport scenarios and transport alternatives

Sustainable cities: Innovative solutions for mobility and logistics

The content of this Special Issue can be summarised by stating that moving towards more Sustainable Cities require a flexible, co-modal, approach in the use of more oil-independent and shared vehicles in daily mobility as well as an integrated vision of the transport planning process that have to considered different elements of the land-use and technology dominoes such as transport policies, travel demand management, shared and environmental friendly mobility, new management models for city logistics and transport terminals, innovativetechnologies. The synergy of these possible approaches could help the decision makers to determine the most sustainable and cost-effective solutions to the overcome the critical points our cities: loss of space, pollution, safety

Concealed interiors for production in the Age of Industry 4.0

The aim of the paper is to investigate the hidden dimension of smart factories from the perspective of the interior, with relevant case studies that test the definition of the new factory: transparent, hybrid spaces, that relocate the individual in the midst of production[1], and are focused on the integration of the site of production with the city. The paper presents the ongoing research “Spaces for Production in the Age of industry 4.0: the Man at the Centre of the Factory” developed by the authors at the Department of Design - Politecnico di Milano in collaboration with Senaf for Mecspe 2019

Methods for infrastructure planning in areas close to hospitals at the regional level

Healthcare emergency management is also an infrastructure problem, in terms of accessibility and safety but nowadays there is lack of consolidated method to solve this issue. Concerning accessibility, the access to the nearest hospital should be guaranteed from each city in the region in an acceptable time. Concerning safety, road arterials travelled by emergency vehicles should have high safety standards, for emergency vehicles and the reduction of congestion due to traffic crashes.This study aims at providing a methodological framework (tested in the case of Apulia, Italy) to conduct accessibility and safety assessments at the regional level, in case of existing and new hospitals. Accessibility and safety were studied setting specific metrics, like time to reach the hospital and accident analysis at macroscopic level to plan safety interventions. The least safe road sites in the ranking obtained by applying the proposed indicators for new and existing hospitals can be improved