1,933 research outputs found

    The Anthropocene Hypothesis

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    Plot-based urbanism and urban morphometrics : measuring the evolution of blocks, street fronts and plots in cities

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    Generative urban design has been always conceived as a creation-centered process, i.e. a process mainly concerned with the creation phase of a spatial transformation. We argue that, though the way we create a space is important, how that space evolves in time is ways more important when it comes to providing livable places gifted by identity and sense of attachment. We are presenting in this paper this idea and its major consequences for urban design under the title of “Plot-Based Urbanism”. We will argue that however, in order for a place to be adaptable in time, the right structure must be provided “by design” from the outset. We conceive urban design as the activity aimed at designing that structure. The force that shapes (has always shaped) the adaptability in time of livable urban places is the restless activity of ordinary people doing their own ordinary business, a kind of participation to the common good, which has hardly been acknowledged as such, that we term “informal participation”. Investigating what spatial components belong to the spatial structure and how they relate to each other is of crucial importance for urban design and that is the scope of our research. In this paper a methodology to represent and measure form-related properties of streets, blocks, plots and buildings in cities is presented. Several dozens of urban blocks of different historic formation in Milan (IT) and Glasgow (UK) are surveyed and analyzed. Effort is posed to identify those spatial properties that are shared by clusters of cases in history and therefore constitute the set of spatial relationships that determine the morphological identity of places. To do so, we investigate the analogy that links the evolution of urban form as a cultural construct to that of living organisms, outlining a conceptual framework of reference for the further investigation of “the DNA of places”. In this sense, we identify in the year 1950 the nominal watershed that marks the first “speciation” in urban history and we find that factors of location/centrality, scale and street permeability are the main drivers of that transition towards the entirely new urban forms of contemporary cities

    Il finanziamento pubblico ai partiti e lo sviluppo dei Partiti Europei

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    The aim of this paper is to investigate the effects on European political party organisations (PPELs), and on their party system, of Reg. 2004/2003’s implementation. Regulation (EC) 2004/2003 defines the role of PPELs and the requirements needed for party eligibility to receive funding from the European Union. The provisions of the Regulation may well be able to consolidate more effectively the various party components operating at European level. However, while the literature on the funding of party organisations suggests that rules and regulations have a tendency to promote organisational convergence, the EU regulation set only a generic organisational pre-requisite for PPELs. In addition, the generally positive picture provided by the Statute is counter-balanced by two provisions, one contained directly in the Statute, and the other in its implementation rules, which keep the federations in a subordinate position with respect to their national components and the parliamentary groups. Our investigation follows two main trajectories: 1) an in-depth comparative analysis of PPEL statutes and internal regulations, by focusing on three different aspects of party organisations, i.e., party membership, party deliberative/executive organs, financial rules; 2) a critic review of Regulation 2004/2003 provisions and its impacts on the balance of powers between PPELs and national political parties. The goal of this contribution is to shed some light over the state of the art of the building process of a more effective and autonomous transnational party system

    Liquid Biopsy in Rare Cancers: Lessons from Hemangiopericytoma

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    Hemangiopericytoma (HPT) is a rare mesenchymal tumor of fibroblastic type and for its rarity is poorly studied. The most common sites of metastatic disease in patients with intracranial HPT are the bone, liver, and lung, suggestive for an hematogenous dissemination; for this reason, we investigated, for the first time, the presence of circulating tumor cells (CTCs) in hemangiopericytoma patient by CellSearch® and SceenCell® devices. Peripheral blood samples were drawn and processed by CellSearch, an EpCAM-dependent device, and ScreenCell®, a device size based. We found nontypical CTCs by CellSearch system and the immunofluorescence analysis performed on CTCs isolate by ScreenCell demonstrated the presence of single CTCs and CTC clusters. The molecular characterization of single CTCs and CTC clusters, using antibodies directed against EpCAM, CD34, cytokeratins (8, 18, and 19), and CD45, showed a great heterogeneity in CTC clusters. We believe that the present study may open a new scenario in the rare tumors: the introduction of the liquid biopsy and the molecular characterization of circulating tumor cells could lead to personalized targeted treatments and also for rare tumors

    THEORETICAL AND METHODOLOGICAL FRAMEWORK TO IDENTIFYING STRATEGIC CATEGORIES IN THE BRAZILIAN MOBILE PHONE SECTOR (BMPS): TOWARDS THEORY DEVELOPMENT

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    El Sector de Telefonia Móvil en Brasil (BMPS) ha enfrentado, en los últimos años, diversos cambios teconológicos y estructurales que tuvieron un impacto directo sobre cuestiones estratégicas que deben ser consideradas por las empresas de este sector. Este artículo propone tres objetivos principales: primero, explorar algunas categorías estratégicas de BPM; segundo, construir un modelo teórico y metodologico a partir de estas categorías; tercero, presentar un modelo de valor agregado de apoyo al desarrollo teórico. Para lograr estos objetivos, construimos un marco teórico que abarca la estrategia competitiva, innovación teconológica y teoría de stakeholdres, y desarrollamos una investigación empírica acompañada de entrevistas con expertos brasileños en el sector. Estas entrevistas fueron analizadas desde el punto de vista del análisis de contenido. El resultado central de dicho estudio se refiere al propio modelo teórico y metodológico para BMPS, que puede ser concebido como una contribución de valor agregado para la teoría. Es interesante observar que hay algunos avances respecto de los enfoques tradicionales del desarrollo de modelos así como de determinados procedimientos del análisis de contenido.The Brazilian Mobile Phone Sector (BMPS) has been through a series of technological and structural changes in the past few years, which have directly impacted strategic issues that should be taken into consideration by companies in this sector. This article addresses three main objectives: the first is to explore some strategic BMPS categories; the second is to build a theoretical and methodological framework from them; and the third is to present a value-added model supporting theory development. Towards that aim, we build on a theoretical approach to competitive strategy, technological innovation and stakeholders theory, and perform an empirical research supported by interviews with Brazilian experts from the sector; the interviews were further analyzed from a content analysis perspective. The key result from this study concerns the very theoretical and methodological framework for the BMPS, and such a framework can be conceived as a value-added contribution to theory. It is worth noting that some advances over traditional approaches to framework development are made, as well as regarding particular content analysis procedures

    The Learning Process in Interorganizational Relationships

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    This study was inspired by the proposition developed by Karthik (2002) and applied to a context of horizontal interorganizational relations. Our main objective was to understand how the learning process between organizations inserted in networks occurs, from the perspective of the evolution of relationships over time. This study has a qualitative and exploratory nature, and the method adopted is the case study with multiple units of analysis. The research was carried out in a network of thirteen supermarket companies in the State of Rio Grande do Sul, Brazil. The data was collected through individual interviews, questionnaires, documental sources and histories of learning. As the main contribution, we highlight the critical discussion made of the model proposed by Karthik (2002) as it is applied in horizontal networks: contradicting the author’s suggestion, the results of this research reveal that there was a predominance of mutual learning in the initial stages of the companies' relationships and, as the relationships evolved, there was a predominance of unilateral learning. This change can be seen in the adoption of opportunist behavior and the predominance of structural characteristics of trust in the relationships established by the companies involved

    How to Create a Transnational Party System

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    This study has been prepared by the Observatory on Political Parties and Representation (OPPR), part of the European Democracy Observatory (EUDO) at the European University Institute (EUI). It covers four aspects: 1) An analysis of the political doctrine and programme of major political parties in several Member States. 2) An examination of current procedures applied to political parties to choose leaders for European Office. 3) The development of proposals on how to help a European political party system evolve from national structures strongly influenced by historical traditions and cultural factors. 4) Suggestions regarding the extent to which the European electoral system and different systems of party financing would have to be revised in order to facilitate the above objectives

    An Integrated Geometric and Material Survey for the Conservation of Heritage Masonry Structures

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    This paper reports the knowledge process and the analyses performed to assess the seismic behavior of a heritage masonry building. The case study is a three-story masonry building that was the house of the Renaissance architect and painter Giorgio Vasari (the Vasari’s House museum). An interdisciplinary approach was adopted, following the Italian “Guidelines for the assessment and mitigation of the seismic risk of the cultural heritage”. This document proposes a methodology of investigation and analysis based on three evaluation levels (EL1, analysis at territorial level; EL2, local analysis and EL3, global analysis), according to an increasing level of knowledge on the building. A comprehensive knowledge process, composed by a 3D survey by Terrestrial Laser Scanning (TLS) and experimental in situ tests, allowed us to identify the basic structural geometry and to assess the value of mechanical parameters subsequently needed to perform a reliable structural assessment. The museum represents a typology of masonry building extremely diffused in the Italian territory, and the assessment of its seismic behavior was performed by investigating its global behavior through the EL1 and the EL3 analyses

    Long-term insulin independence following repeated islet transplantation in totally pancreatectomized diabetic pigs.

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    Clinical islet transplantation (Tx) in type I diabetic patients has been successful so far only in a minority of cases, probably because of multiple factors, partly immunologic and partly nonimmunologic in nature. Pre-clinical studies of islet Tx in large animals are still needed to clarify the reasons and find possible solutions. In this study, we tested the feasibility of noninvasive, repeated intrahepatic allo-Tx of porcine pancreatic islets obtained from multiple donors, in pigs rendered diabetic by total pancreatectomy (Pct). In group I Yucatan miniature swine (n = 6), after induction of diabetes by Pct, repeated islet allo-Tx of ≥80% pure islets was performed. Islets obtained from two pigs of the Hanford breed were injected twice a week, half freshly isolated and half 48-h cultured, over a period of 11 days, for a total of 23,647 ± 1617 islet equivalents (IE)/kg recipient body weight (BW). In group II Yucatan miniature swine (n = 3), after Pct, a single allo-Tx of ≥80% pure islets, previously obtained from two donors of the Hanford breed, was performed, using a total of 22,416 ± 1124 IE/kg BW. In group III Yucatan miniature swine (n = 3), auto-Tx of 60–75% pure islets, averaging 2980 ± 424 IE/kg BW, was performed a few hours after Pct. Group IV Yucatan mini pigs (n = 3) underwent Pct and were used as diabetic controls. Group V animals (n = 3) were normal control Yucatan mini pigs. Porcine islets were isolated by a modification of the standard collagenase digestion and Ficoll gradient purification method. Donors and recipients were chosen on the basis of moderate to high mutual alloreactivity in mixed lymphocyte culture (MLC). In groups I and II, cyclosporine A (CsA) was started 4 days before allo-Tx, at the dose of 15 mg/kg IM, and then gradually reduced to 4 mg/kg IM. In all group I animals, normal fasting blood glucose (FBG) was restored within 2–3 weeks. Two normoglycemic pigs died of acute pneumonia at 33 and 112 days, respectively, and one animal became progressively hyperglycemic at 100 days. After 3 months, discontinuation of CsA treatment resulted in FBG increase in two group I animals. In one pig, CsA was stopped after 151 days, and normoglycemia persisted until euthanasia, after 8 months. In group II pigs, normoglycemia lasted 4–20 days, with a progressive increase of insulin requirement thereafter. In group III animals, after islet auto-Tx, normoglycemia lasted 7–10 days, while insulin daily requirement progressively increased thereafter, stabilizing at 0.4 IU/kg/day, corresponding to about one third of the amount required in diabetic controls. The single most important result in this series of experiments is that intraportal allo-Tx of a sufficient islet mass, divided in multiple subtherapeutic doses, produced a better metabolic long-term control in comparison to a single injection of the same amount of islets. The technique of multiple-donor repeated islet Tx may prove useful to overcome the problem of primary nonfunction or early graft failure, currently limiting the success of clinical islet Tx in most cases

    529. Lentiviral Vectors with a Reduced Splicing Interference Potential Have a Significantly Improved Safety Profile In Vivo

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    Genotoxicity assays based on systemic vector injection into newborn tumor-prone Cdkn2a−/− and Cdkn2a+/− mice has shown that self-inactivating (SIN) lentiviral vector (LV) harboring strong or moderate enhancer/promoters in internal position caused acceleration in hematopoietic tumor onset compared to control mice. Integration site (IS) analysis in vector-induced tumors showed that oncogene activation or tumor suppressor inactivation occurs by mechanisms of aberrant splicing and/or enhancer-mediated overexpression of cellular genes. Although oncogene activation may be reduced by the use of SIN design, moderate cellular promoters and insulator sequences, how to reduce genotoxic splicing-capture events and aberrant transcript formation triggered by vector integration is still unclear. Here, we specifically designed SINLVs harboring sequences complementary to microRNAs (mirT sequence) which are active in hematopoietic cells (mir223 and mir142-3p) within the SIN LTR (mirsT-LTR.LV) or in the vector backbone and outside the gene expression cassette (mirT-LV). In our rationale, the mirT sequences when incorporated in an aberrantly generated mRNA would be selectively degraded through the miRNA pathway. Thus, by taking advantage of our in vivo models, we assessed the genotoxicity of these LVs with mirT sequences. Systemic injection of mirsT-LTR.LV (N=34) and mirT-LV (N=39) in Cdkn2a−/− mice did not cause any significant acceleration in hematopoietic tumor onset compared to un-injected mice (N=37) or mice injected with a SINLV that does not harbor mirT sequences (N=24). Similar results have been obtained after injection of the same vectors in Cdkn2a+/− mice (N=29 mirsT-LTR.LV, N=25 mirT-LV, N=40 un-injected and N=15 injected control mice). To gain additional information on the safety profile of these vectors, we performed IS analysis (N>10,000) in tumor-derived DNA. By this analysis, we previously found that Map3k8 activation by LV insertions was the major mechanism of genotoxicity when prototypical SINLVs were injected into Cdkn2a−/− mice. Now, we found that mice treated with mirsT-LTR.LV and mirT-LV did not show any Map3k8 activating insertions, suggesting that the new vectors are efficient in preventing its activation and confirming their superior safety profile. Furthermore, as expected, Pten was the most frequently targeted gene in tumors derived from Cdkn2a−/− mice injected with the LVs harboring mirT sequences. Pten insertions mainly targeted exons, suggesting the potential inactivation of its transcription unit. Finally, we found that Sfi1 was the major Common Insertion Site (CIS) in Cdkn2a+/− mice injected with LVs harboring mirT sequences. This CIS gene however appears to be the product of an intrinsic bias of LV integration, rather than the result of a selection process. Overall, our studies showed that these new advanced design LVs have a significantly improved safety profile and could represent the vector design of choice in future gene therapy applications
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