Urban policies and planning approaches for a safer and climate friendlier mobility in cities: Strategies, initiatives and some analysis

How can urban policies and planning approaches help in achieving a safer mobility and carbon reduction in the transport sector? The attention of planners and policy makers towards the promotion of sustainability and reduction of environmental impacts has grown in recent years. This paper investigates the role that Urban Planning plays in the long term towards a safer and climate friendlier mobility, highlighting the need for integrated approaches gathering spatial planning and mobility management. After a review of several urban policies and planning strategies, initiatives, and approaches, mainly based on the urban scale, the paper presents an urban regeneration case study leading to an increase of pedestrian accessibility at the neighborhood level. This can be seen as a support tool to foster sustainable, safe, and climate friendly mobility in cities. The results of the performed analysis show a dependency of accessibility from two different factors: the distribution of services and the capillarity of the soft mobility network, which can contribute to creating a more walkable space

Permeability-enhancing effects of three laurate-disaccharide monoesters across isolated rat intestinal mucosae

Laurate (C12)-sucrose esters are established intestinal epithelial permeation enhancers (PEs) with potential for use in oral delivery. Most studies have examined blends of ester rather than specific monoesters, with little variation on the sugar moiety. To investigate the influence of varying the sugar moiety on monoester performance, we compared three monoesters: C12-sucrose, C12-lactose, and C12-trehalose. The assays were: critical micellar concentration (CMC) in Krebs-Henseleit buffer, MTS and lactate dehydrogenase assays in Caco-2 cells, transepithelial electrical resistance (TEER) and apparent permeability coefficient (Papp) of [14C] mannitol across isolated rat intestinal mucosae, and tissue histology. For CMC, the rank order was C12-trehalose (0.21 mM) < C12-sucrose (0.34 mM) < C12-lactose (0.43 mM). Exposure to Caco-2 cells for 120 min produced TC50 values in the MTS assay from 0.1 to 0.4 mM. Each ester produced a concentration-dependent decrease in TEER across rat mucosae with 80% reduction seen with 8 mM in 5 min, but C12-trehalose was less potent. C12-sucrose and C12-lactose increased the Papp of [14C] mannitol across mucosae with similar potency and efficacy, whereas C12-trehalose was not as potent or efficacious, even though it still increased flux. In the presence of the three esters, gross intestinal histology was unaffected except at 8 mM for C12-sucrose and C12-lactose. In conclusion, the three esters enhanced permeability likely via tight junction modulation in rat intestinal tissue. C12-trehalose was not quite as efficacious, but neither did it damage tissue to the same extent. All three can be considered as potential PEs to be included in oral formulations

Multiple Integrated Non-clinical Studies Predict the Safety of Lentivirus-Mediated Gene Therapy for \u3b2-Thalassemia

Gene therapy clinical trials require rigorous non-clinical studies in the most relevant models to assess the benefit-to-risk ratio. To support the clinical development of gene therapy for \u3b2-thalassemia, we performed in vitro and in vivo studies for prediction of safety. First we developed newly GLOBE-derived vectors that were tested for their transcriptional activity and potential interference with the expression of surrounding genes. Because these vectors did not show significant advantages, GLOBE lentiviral vector (LV) was elected for further safety characterization. To support the use of hematopoietic stem cells (HSCs) transduced by GLOBE LV for the treatment of \u3b2-thalassemia, we conducted toxicology, tumorigenicity, and biodistribution studies in compliance with the OECD Principles of Good Laboratory Practice. We demonstrated a lack of toxicity and tumorigenic potential associated with GLOBE LV-transduced cells. Vector integration site (IS) studies demonstrated that both murine and human transduced HSCs retain self-renewal capacity and generate new blood cell progeny in the absence of clonal dominance. Moreover, IS analysis showed an absence of enrichment in cancer-related genes, and the genes targeted by GLOBE LV in human HSCs are well known sites of integration, as seen in other lentiviral gene therapy trials, and have not been associated with clonal expansion. Taken together, these integrated studies provide safety data supporting the clinical application of GLOBE-mediated gene therapy for \u3b2-thalassemia

Giant quartz orebodies: structural, mineralogical and geochemical evolution

Quartz veins are frequent but giant quartz-only orebodies,mostly mined for metallurgy and ceramic industry, are not so common and their origin and mechanisms of emplacemen are not completely understood (e.g., see [1] for a geologicalstructural model). At the location of Sondalo, in the Central Alpine Belt (Northern Italy), a huge orebody of pure quartz is emplaced in high-grade continental basement of the Austroalpine Languard-Campo Nappe. The orebody, currently extensively mined and in development, is open ended at depth. It has never been studied. The orebody is irregularly tubularshaped, and is in direct, brecciated to faulted contact with basement migmatites, garnet-biotite-sillimanite gneisses and amphibolites as well as with a Permian gabbro intrusion(Sondalo Gabbro)emplaced in the basement. The orebody consists of extremely hard, highly deformed, varicoloured(white, light pink, grey, black) quartz. Muscovite and tourmaline are the rare but coarser accessory minerals near the margins of the body, although sub-micrometric accessory phases variably disseminated throughout the body were observed. Fluid inclusions are locally abundant.3D meso- and micro-structural relationships between orebody and basement and thermo-barometric estimates suggest emplacement of the quartz intrusion later than Permian but before Alpine convergence, at T >750\ub0C and P 48 0.7 Gpa. However unusual, coarse skeletal biotite and orthopyroxene intergrowths in reaction rims of breccia fragments also suggest a remarkably high thermal regime of the quartz emplacement, at T > 670\ub0C (biotite-opx thermometer). During the emplacement widespread brittle deformation occurred likely associated with hydrofracturing mechanisms. Quartz also bears evidences of intense plastic deformation with localized annealing, in addition to widespread mm- to cm-spaced late-stage fracturing. At the mesoscale highly strained portions of the orebody may show impressive colour variations from pure white to black. Selected trace elements, Al, B, Ba, Fe, Ge, P, Ti were analyzed for evaluating colour variations and provenance of quartz based on mechanisms of Si replacement in the quartz lattice in pegmatite-like contexts (see [2,3]). The trace element composition of the Sondalo quartz revealed unusually high values of Si-substituting Ge, P Ti and Al contents and related ratios relative to pegmatite-related quartz, as well as high contents in Ba. Trace elements show roughly zoned, coherent distribution patterns and show some relationships with colour variations. Coupled Ba and Ti enrichments may also cope the occurrence of phases like benitoite (revealed only in XRD patterns) among the submicrometric accessory phases. Coupling of structural and geochemical mineralogical investigations of orebody and wall rock may give additional clues on the still poorly understood nature, mechanisms of formation and emplacement of huge quartz-only bodies in orogens. [1] Bons, P.D. (2001) Tectonophysics, 336, 1-17. [2] Larsen, R.B. et al. (2004) Contrib. Miner. Petrol., 147, 615-628. [3] G\uf6tze, J. et al. (2004) Geochim. Cosmochim. Ac., 68, 3741-3759

Gli effetti delle previsioni urbanistiche sulla rigenerazione urbana diffusa. Il caso di Brescia

Obiettivo del presente lavoro è quello di indagare gli effetti che l’attuazione delle previsioni urbanistiche può avere in termini di rigenerazione diffusa, partendo dal caso studio della città di Brescia, che nell’ultimo quinquennio è stata interessata da numerose trasformazioni dell’assetto urbanistico. Trasformazioni che hanno in qualche misura segnato l’uscita dalla crisi che nell’ultimo decennio ha colpito pesantemente il mercato immobiliare. In queste trasformazioni urbanistiche, che interessano per la gran parte aree di proprietà privata, e solo in misura minore aree di proprietà comunale, l’iniziativa arriva da soggetti privati, ma il comune assume un fondamentale ruolo di regia nello sviluppo e nell’attuazione dell’intervento, e soprattutto nel definire le prestazioni pubbliche attese e, di conseguenza, le opere di urbanizzazione primaria e secondaria da prevedere nelle convenzioni urbanistiche dei piani attuativi. Le trasformazioni che interessano le aree private, unitamente alle opere di urbanizzazione da esse originate, raggiungono così il duplice effetto di recuperare le aree dismesse e degradate, e rigenerare lo spazio pubblico adiacente, attraverso un’azione di rammendo del tessuto urbano consolidato, anche mediante l’inserimento di servizi che possono aumentare la vitalità di alcune parti dei quartieri, e generando così l’effetto sociale di rafforzare il senso di comunità e favorire l’integrazione. Questo lavoro presenta una metodologia di analisi che, partendo dalla disamina delle delibere assunte negli ultimi 5 anni dal Settore Urbanistica del Comune di Brescia, mette in relazione trasformazioni urbanistiche e qualità dello spazio pubblico. La metodologia si basa sull’utilizzo di un software GIS, che consente di mappare, categorizzare e quantificare le trasformazioni, con la finalità di costruire una base informativa che permetta nel tempo di monitorare gli effetti delle trasformazioni urbanistiche sulla dimensione socio-economica oltre che sulla qualità dello spazio urbano

Comunita' minori in ambiti svantaggiati: verso una visione globale attraverso analisi locali in differenti contesti europei

La promozione di un sviluppo sostenibile di comunità minori in ambiti svantaggiati può trarre giovamento dalla condivisione della conoscenza di esperienze in realtà analoghe. Ciò rende utile individuare processi metodologici che permettano di confrontare realtà anche molto lontane geograficamente, e non solo, ma che hanno in comune alcune caratteristiche territoriali, sociali, economiche, ed alcune dinamiche in atto, prima fra tutte il pericolo di scomparire a causa del forte decremento di popolazione, col rischio che vadano persi valori storici e culturali, o che non vengano valorizzate potenzialità, quali quelle paesaggistiche, ambientali o turistiche, con la finalità ultima di individuare “buone pratiche” di governo del territorio trasferibili al altri contesti territoriali