108 research outputs found

    Multi-attribute classification of housing conservation status in urban regeneration actions

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    Urban regeneration is more and more a “universal issue” and a crucial factor in the new trends of urban planning. It is no longer only an area of study and research; it became part of new urban and housing policies. Urban regeneration involves complex decisions as a consequence of the multiple dimensions of the problems that include special technical requirements, safety concerns, socio-economic, environmental, aesthetic, and political impacts, among others. This multi-dimensional nature of urban regeneration projects and their large capital investments justify the development and use of state-of-the-art decision support methodologies to assist decision makers. This research focuses on the development of a multi-attribute approach for the evaluation of building conservation status in urban regeneration projects, thus supporting decision makers in their analysis of the problem and in the definition of strategies and priorities of intervention. The methods presented can be embedded into a Geographical Information System for visualization of results. A real-world case study was used to test the methodology, whose results are also presented.This work has been framed under the Energy for Sustainability Initiative of the University of Coimbra and supported by Energy and Mobility for Sustainable Regions (EMSURE) Project CENTRO-07-0224-FEDER-002004 and Fundação para a Ciência e a Tecnologia (FCT) under PEst-C/EEI/UI0308/2011

    Metodologia em ambiente SIG para localizar dispositivos de auxílio ao ciclista em cidades declivosas

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    Preocupações de sustentabilidade relacionadas com o uso intensivo de energia, e o congestionamento de tráfego, têm levado decisores a procurar soluções alternativas, e à emergência de uma mudança para modos de transporte suaves/ativos. A bicicleta é um modo de transporte suave e muito eficiente. No entanto, há também fatores dissuasores do uso da bicicleta - entre estes, é reconhecida a importância do declive na escolha deste modo. Uma das formas de contornar esta limitação consiste na construção de dispositivos mecânicos de auxílio (e.g. elevadores, teleféricos). Apresenta-se neste trabalho uma metodologia que, usando tecnologia SIG, ajuda a identificar potenciais locais para a colocação desses dispositivos, de forma a não só minorar a extensão e número destes, mas também conseguir uma maior permeabilidade da cidade à bicicleta. A metodologia, baseada essencialmente na obtenção de áreas de serviço adequadas, permitirá também identificar arcos críticos à conexão ciclável da rede viária urbana. Acompanha a abordagem um estudo de caso para a cidade de Coimbra, Portugal, onde, para além da aplicação da metodologia, se considera um circuito para bicicletas e se estuda a permeabilidade ciclável da rede com e sem elevadores, com o circuito, bem como formas de acesso ao local mais importante da cidade.Sustainability worries related to the intensive use of energy by automobiles, and traffic congestion issues, have encouraged decision makers to look for alternative solutions and to an emerging shift towards soft/active transport modes. The bicycle, a very efficient mode of transport, is one such soft travel mode. Cycling however also has its deterrents - among these, it is recognized that slopes play an important role in influencing the choice for this mode. One of the ways to mitigate this limitation consists in constructing hard aid devices (e.g. elevators). In this work a methodology is presented that uses GIS technology to identify potential locations for these connecting devices, such that not only their span and number are minimized but also a greater cycling permeability for the city is acheived. The methodology, which is based in obtaining suitable service areas, will also pinpoint arcs that are critical to the cyclable connectivity of the urban network. A case study for the city of Coimbra, Portugal, is presented, where along with the methodology’s application, a bicycling circuit is considered and the network’s cycling permeability is studied, with and without devices, with the circuit, as well as means of accessing the city’s most important place.Este trabalho foi parcialmente financiado pela Fundação Portuguesa para a Ciência e Tecnologia (FCT) sob a Refª “PEst-OE/EEI/UI308/2014”, pelo projeto Energy and Mobility for Sustainable Regions (EMSURE) - Refª CENTRO-07-0224-FEDER-002004, e enquadra-se na iniciativa Energy for Sustainability da Universidade de Coimbra

    Building a bicycle suitability map for Coimbra

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    The adoption of faster modes of transportation (mainly the private car) has changed profoundly the spatial organisation of cities. The increase in distance covered due to increased speed of travel and to urban sprawl leads to an increase in energy consumption, being the transportation sector a huge consumer responsible for 61.5% of total world oil consumption and a global final energy consumption of 31.6% in EU-27 (2007). Due to unsustainable transportation conditions, many cities suffer from congestion and various other traffic problems. Such situations get worse with solutions mostly seen in the development of new infrastructure for motorized modes of transportation, and construction of car parking structures. The bicycle, considered the most efficient among all modes of transportation including walking, is a travel mode that can be adopted in most cities contributing for urban sustainability given the associated environmental, economic and social advantages. In many nations a large number of policy initiatives have focused on discouraging the use of private cars, encouraging the use of sustainable modes of transportation, like public transportation and other forms such as bicycling. Given the importance of developing initiatives that favour the use of bicycle as an urban transportation mode, an analysis of city suitability, including distances and slopes of street network, is crucial in order to help decision-makers to plan the city for bicycle. In this research Geographical Information Systems (GIS) technology was used for this purpose and some results are presented concerning the city of Coimbra.This work has been framed under the Energy for Sustainability Initiative of the University of Coimbra and supported by Energy and Mobility for Sustainable Regions (EMSURE) Project CENTRO-07-0224-FEDER-002004 and Fundação para a Ciência e a Tecnologia (FCT) under PEst-C/EEI/UI0308/2011

    Design of bicycling suitability maps for hilly cities

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    Sustainability worries related to the intensive use of energy by automobiles and traffic congestion issues have encouraged decision makers to look for alternative solutions, leading to an emerging shift towards soft/active transport modes. The bicycle, a very efficient mode of transport, is a soft travel mode that can be adopted in most cities, contributing to urban sustainability given the associated environmental, economic and social advantages. Cycling, however, also has its deterrents. Among these, it is recognised that slopes play an important role in influencing the choice for this mode of travel. The purpose of this paper is to present methods to analyse a hilly city’s suitability for cycling, in what concerns relief, with the aim of identifying locations for implementation of hard aid devices that restore connectivity between most parts, or even the whole, of the city. The methodology proposed makes use of appropriate service areas. Geographical information systems technology was used to implement the methodology and the approach is demonstrated with a case study for the city of Coimbra, Portugal. This combined approach helps decision makers to plan the city in a sustainable way

    Analytical properties of a stochastic teletraffic system with MMPP input and an access function, Journal of Telecommunications and Information Technology, 2002, nr 3

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    Stochastic modeling of teletraffic systems with restricted availability and correlated input arrival rates is of great interest in GoS (grade of service) analysis and design of certain telecommunication networks. This paper presents some analytical properties of a recursive nature, associated with the infinitesimal generator of the Markov process which describes the state of a teletraffic system with MMPP (Markov modulated Poisson process) input traffic, negative exponentially distributed service times, finite queue and restricted availability defined through a loss function. Also the possible application of the derived properties to a direct method of resolution of the linear system, which gives the stationary probability distribution of the system, will be discussed

    Decorin deficiency promotes hepatic carcinogenesis

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    Hepatocellular carcinoma represents one of the most-rapidly spreading cancers in the world. In the majority of cases, an inflammation-driven fibrosis or cirrhosis precedes the development of the tumor. During malignant transformation, the tumor microenvironment undergoes qualitative and quantitative changes that modulate the behavior of the malignant cells. A key constituent for the hepatic microenvironment is the small leucine-rich proteoglycan decorin, known to interfere with cellular events of tumorigenesis mainly by blocking various receptor tyrosine kinases (RTK) such as EGFR, Met, IGF-IR, PDGFR and VEGFR2. In this study, we characterized cell signaling events evoked by decorin deficiency in two experimental models of hepatocarcinogenesis using thioacetamide or diethyl nitrosamine as carcinogens. Genetic ablation of decorin led to enhanced tumor occurrence as compared to wild-type animals. These findings correlated with decreased levels of the cyclin-dependent kinase inhibitor p21WAF1/CIP1 and a concurrent elevation in retinoblastoma protein phosphorylation via cyclin dependent kinase 4. Decreased steady state p21Waf1/Cip1 levels correlated with enhanced expression of transcription factor AP4, a known transcriptional repressor of p21Waf1/Cip1, and enhanced c-Myc protein levels. In addition, translocation of beta-catenin was a typical event in diethyl nitrosamine-evoked tumors. In parallel, decreased phosphorylation of both c-Myc and beta-catenin was observed in Dcn-/- livers likely due to the hindered GSK3beta-mediated targeting of these proteins to proteasomal degradation. We discovered that in a genetic background lacking decorin, four RTKs were constitutively activated (phosphorylated), including three known targets of decorin such as PDGFRalpha, EGFR, IGF-IR, and a novel RTK MSPR/RON. Our findings provide powerful genetic evidence for a crucial in vivo role of decorin during hepatocarcinogenesis as lack of decorin in the liver and hepatic stroma facilitates experimental carcinogenesis by providing an environment devoid of this potent pan-RTK inhibitor. Thus, our results support future utilization of decorin as an antitumor agent in liver cancer

    A highly efficient, stable, and rapid approach for ex vivo human liver gene therapy via a FLAP lentiviral vector

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    Allogenic hepatocyte transplantation or autologous transplantation of genetically modified hepatocytes has been used successfully to correct congenital or acquired liver diseases and can be considered as an alternative to orthotopic liver transplantation. However, hepatocytes are neither easily maintained in culture nor efficiently genetically modified and are very sensitive to dissociation before their reimplantation into the recipient. These difficulties have greatly limited the use of an ex vivo approach in clinical trials. In the present study, we have shown that primary human and rat hepatocytes can be efficiently transduced with a FLAP lentiviral vector without the need for plating and culture. Efficient transduction of nonadherent primary hepatocytes was achieved with a short period of contact with vector particles, without modifying hepatocyte viability, and using reduced amounts of vector. We also showed that the presence of the DNA FLAP in the vector construct was essential to reach high levels of transduction. Moreover, transplanted into uPA/SCID mouse liver, lentivirally transduced primary human hepatocytes extensively repopulated their liver and maintained a differentiated and functional phenotype as assessed by the stable detection of human albumin and antitrypsin in the serum of the animals for months. In conclusion, the use of FLAP lentiviral vectors allows, in a short period of time, a high transduction efficiency of human functional and reimplantable hepatocytes. This work therefore opens new perspectives for the development of human clinical trials based on liver-directed ex vivo gene therapy.info:eu-repo/semantics/publishedVersio

    Impact of Preoperative Chemotherapy Features on Patient Outcomes after Hepatectomy for Initially Unresectable Colorectal Cancer Liver Metastases: A LiverMetSurvey Analysis

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    Background: Prognostic factors have been extensively reported after resection of colorectal liver metastases (CLM); however, specific analyses of the impact of preoperative systemic anticancer therapy (PO-SACT) features on outcomes is lacking. Methods: For this real-world evidence study, we used prospectively collected data within the international surgical LiverMetSurvey database from all patients with initially-irresectable CLM. The main outcome was Overall Survival (OS) after surgery. Disease-free (DFS) and hepatic-specific relapse-free survival (HS-RFS) were secondary outcomes. PO-SACT features included duration (cumulative number of cycles), choice of the cytotoxic backbone (oxaliplatin- or irinotecan-based), fluoropyrimidine (infusional or oral) and addition or not of targeted monoclonal antibodies (anti-EGFR or anti-VEGF). Results: A total of 2793 patients in the database had received PO-SACT for initially irresectable diseases. Short (<7 or <13 cycles in 1st or 2nd line) PO-SACT duration was independently associated with longer OS (HR: 0.85 p = 0.046), DFS (HR: 0.81; p = 0.016) and HS-RFS (HR: 0.80; p = 0.05). All other PO-SACT features yielded basically comparable results. Conclusions: In this international cohort, provided that PO-SACT allowed conversion to resectability in initially irresectable CLM, surgery performed as soon as technically feasible resulted in the best outcomes. When resection was achieved, our findings indicate that the choice of PO-SACT regimen had a marginal if any, impact on outcomes.info:eu-repo/semantics/publishedVersio

    Co-Depletion of Cathepsin B and uPAR Induces G0/G1 Arrest in Glioma via FOXO3a Mediated p27Kip1 Upregulation

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    Cathepsin B and urokinase plasminogen activator receptor (uPAR) are both known to be overexpressed in gliomas. Our previous work and that of others strongly suggest a relationship between the infiltrative phenotype of glioma and the expression of cathepsin B and uPAR. Though their role in migration and adhesion are well studied the effect of these molecules on cell cycle progression has not been thoroughly examined.Cathepsin B and uPAR single and bicistronic siRNA plasmids were used to downregulate these molecules in SNB19 and U251 glioma cells. FACS analysis and BrdU incorporation assay demonstrated G0/G1 arrest and decreased proliferation with the treatments, respectively. Immunoblot and immunocyto analysis demonstrated increased expression of p27(Kip1) and its nuclear localization with the knockdown of cathepsin B and uPAR. These effects could be mediated by alphaVbeta3/PI3K/AKT/FOXO pathway as observed by the decreased alphaVbeta3 expression, PI3K and AKT phosphorylation accompanied by elevated FOXO3a levels. These results were further confirmed with the increased expression of p27(Kip1) and FOXO3a when treated with Ly294002 (10 microM) and increased luciferase expression with the siRNA and Ly294002 treatments when the FOXO binding promoter region of p27(Kip1) was used. Our treatment also reduced the expression of cyclin D1, cyclin D2, p-Rb and cyclin E while the expression of Cdk2 was unaffected. Of note, the Cdk2-cyclin E complex formation was reduced significantly.Our study indicates that cathepsin B and uPAR knockdown induces G0/G1 arrest by modulating the PI3K/AKT signaling pathway and further increases expression of p27(Kip1) accompanied by the binding of FOXO3a to its promoter. Taken together, our findings provide molecular mechanism for the G0/G1 arrest induced by the downregulation of cathepsin B and uPAR in SNB19 and U251 glioma cells
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