cAMP inhibits TGFβ1-induced in vitro angiogenesis

AbstractTransforming growth factor-β (TGFβ1) is a proangiogenic factor both, in vitro and in vivo, that is mainly involved in the later phases of angiogenesis. In an attempt to identify genes that participate in this effect, we found that TGFβ1 down-regulates expression of adenylate cyclase VI. In addition, cAMP analogs (8-Bromo-cAMP) and forskolin (an adenylate cyclase activator) also reduced TGFβ1-induced in vitro angiogenesis in mouse endothelial cell lines and in primary cultures of human umbilical vein endothelial cells on collagen gels. Induction of Ets-1 and plasminogen activator inhibitor-1 (PAI-1) by TGFβ1 was blocked by these cAMP agonists and activators, in the absence of effects on endothelial cell viability. Moreover, the signal transduction pathways stimulated by TGFβ1 were unaffected. Thus, Smad2 was normally phosphorylated and translocated to the nucleus in the presence of forskolin. In contrast, transfection studies using the PAI-1-promoter indicated that these cAMP analogues inhibit transcriptional stimulation by TGFβ1. Electrophoretic mobility shift assay showed that Smad2/3 were bound normally to a TGFβ1-response region in the presence of the cAMP analogs. In all, these data suggest that the cAMP pathway inhibits the transcriptional activity of Smads, that could be responsible for the block of the TGFβ1-induced in vitro angiogenesis caused by this second messenger

Octanol-water partition coefficients of highly hydrophobic photodynamic therapy drugs: a computational study

Photodynamic therapy is a novel treatment for solid tumorsbased on the selective induction of cell death by the generation of cytotoxic reactive oxygen species within neoplastic tissues. Oxygen photosensitization is promoted as a consequence of the activation (using light) of a photosensitizer, which must reach the desired tissue by cellular transport. Hydrophobicity (expressed as the logarithm of octanol/water partition coefficient, logP), becomes a key factor in these processes. Unfortunately, there is no computational method to unambiguously predict the logP value for high hydrophobic photosensitizers. In this study, a total of 12 computational methods have been tested for predicting the logP value of tetrapyrrolic derivatives. Furthermore, in the attempt to correlate logP with experimental HPLC measurements (log(k’)), validation of the results leads to the proposal of a sigmoidal regression for the two parameters (log(k’) and logP)

Disseny eficient de xarxes de transport públic col·lectiu en zones urbanes

Aquest treball presenta i valida un mètode de disseny de xarxes de transport públic d’altes prestacions. El mètode proposa diferents esquemes conceptuals de xarxes per idealitzacions geomètriques d'una ciutat particular, que després són adaptades a les condicions reals. Aquests esquemes conceptuals són caracteritzats per mitjà de quatre variables de decisió: la separació de línies, separació de parades, interval de pas i la grandària d’una zona central amb millor cobertura espaial. El millor esquema per a una aplicació específica es tria a través de l'optimització. La funció objectiu es compon de fórmules analítiques per al cost de l’operador i les prestacions als usuaris. El disseny òptim proposat per a la ciutat de Barcelona planteja la utilització d’un terç dels recursos per a oferir un menor temps de viatge en relació a la xarxa actual d’autobusos.Peer Reviewe

Cálculo y dimensionamiento de una nave industrial para almacenaje

El present treball de fi de grau realitzat tracta de dissenyar una nau industrial estructuralment metàl·lica amb la finalitat d’utilitzar-la com magatzem. Es farà a partir del software CYPE amb l’objectiu de poder aprendre a fer ús d’aquest programa, poder dimensionar els perfils perquè suportin la càrrega calculada i primordialment poder ampliar els meus coneixements sobre el món de les estructures i construcció. Juntament amb l’estructura també es calculen les instal·lacions per donar servei a un annex integrat a la nau industrial perquè els futurs treballadors tinguin una zona de descans i lavabos fent ús de diferents programes de càlcul d’instal·lacions com DM ELECT, Dialux evo i altres. Per la realització del treball s’ha respectat la normativa vigent, tant europea com estatal, per al correcte funcionament i la legalització de l’estructura i de les instal·lacions en aquest projecte. El projecte inclou perquè sigui més complet, a part del càlcul estructural i instal·lacions, un pressupost del total del projecte, un plec de condicions i plànols d’estructura i instal·lacions.El presente trabajo de fin de grado realizado trata de diseñar una nave industrial estructuralmente metálica con el fin de usarla como almacén. Se hará a partir del software CYPE con el objetivo de poder aprender a utilizar este programa, poder dimensionar los perfiles para que soporten la carga calculada y primordialmente poder ampliar mis conocimientos más sobre el mundo de las estructuras y construcción. Juntamente a la estructura también se calculan las instalaciones para dar servicio a un anexo integrado en la nave industrial para que los futuros trabajadores tengan una zona de descanso y aseos utilizando diversos programas de cálculo de instalaciones como DM ELECT, Dialux evo y otros. Para la realización del trabajo se ha respetado la normativa vigente, tanto normativa europea como estatal, para el correcto funcionamiento y legalización de la estructura y de las instalaciones en este proyecto. El proyecto incluye para que sea más completo, a parte del cálculo estructural e instalaciones, un presupuesto del proyecto en total, un pliego de condiciones y planos de estructura e instalaciones.This end-of-degree project is about the design of an industrial building made of structural steel to be used as a warehouse. It will be done using CYPE software with the aim of learning how to use this programme, to be able to dimension the profiles to support the calculated load and, above all, to be able to broaden my knowledge of the world of structures and construction. Together with the structure, the installations are also calculated to provide service to an annexe integrated into the industrial building so that future workers have a rest area and toilets using various installation calculation programmes such as DM ELECT, Dialux evo and others. The work has been carried out in accordance with the current regulations, both European and national, for the correct functioning and legalization of the structure and installations in this project. The project includes, in order to make it more complete, apart from the structural calculation and installations, a budget for the project in total, a set of specifications and plans of the structure and installations

Bus network structure and mobility pattern: a monocentric analytical approach on a grid street layout

This study discusses which transit network structure is the best option to serve urban mobility. As a consequence of the evolution of urban form, cities have undergone a process of dispersion of their activities that has caused a change in mobility needs in the last few decades. Mobility networks and services should progressively adapt to the new demand patterns, especially the bus transit network, which has more flexibility to absorb the changes. We compare four base transit network structures: a radial scheme, a direct trip-based network, and a transfer-based system by means of either a complete grid or a hybrid structure. An analytical model is used to estimate the behavior of these structures for idealized monocentric mobility patterns with several degrees of concentration. The purpose is to determine the right range of situations for the applicability of each bus transit structure, and to determine guidelines about the transit network planning process. It turns out that the best structure is not always the same, and depends on the mobility spatial pattern. A radial network is the best alternative in very concentrated cities; however, a direct trip-based system is more suitable for intermediate degrees of dispersion. A transfer-based structure is the best option when the activities are more decentralized. Nevertheless, the decentralization degree that justifies a specific transit structure is not constant. This degree depends on the characteristics of the city, transport technology and users.Peer ReviewedPostprint (author's final draft

Spatial analysis of public transportation infrastructure in Santiago, Chile, using the continuous approximation method

Santiago, the capital city of Chile, has seven million inhabitants in an area of 850 km2. This city has a metro network with seven lines extending 140 kilometers and transports approximately 2.6 million people daily. The bus system has undergone significant transformations over the last three decades. The most relevant change having been Transantiago, the public transportation system implemented in 2007 for Santiago, Child, which combines the use of Metro and buses (BRT). Metropolitan Mobility Network (called Red) is the latest version of the public transportation plan. This paper aims to analyze the current subway infrastructure using the continuous approximation method for Santiago, Chile. We previously proposed a macroscopic methodology to identify the needs for an adequate level of service in urban mobility and transportation, and we applied it to Santiago’s Metro network. Our work focuses on functionality and demand distribution. Santiago’s demand varies spatially in volume and extension throughout the city. Using the latest origin-destination survey from 2012, we deduct the critical components in this current network structure. It is worth mentioning that the Metro design bases its network on a ring-radial structure. With our macroscopic model applied to Santiago, Chile, we have detected infrastructure needs in the current transit network. The supply of infrastructure should increase for two reasons: first, to achieve balanced cost levels between users and the agency and second, to reduce subway occupations. The optimal model outcomes for Santiago define the optimal network in which the system requires five rings and ten end-to-end longitudinal lines (20 radial routes), including lower levels of occupation. The obtained results are a good preliminary solution, considering the subway infrastructure supply could be sub-estimated in the public transportation plan.The authors had support from the Barcelona Innovative Transportation (BIT) Research Group. Moreover, the first author's work was supported by Chile's National Agency for Research and Development (ANID) / Becas-Chile Doctoral Scholarship Program No. 72160291. The first author had support from the Project 092112MT of the DICYT of the University of Santiago of Chile (USACH).Postprint (published version

Modeling public transportation networks for a circular city: the role of urban subcenters and mobility density

The concentration of both employment and services in a specific area of a town generates positive effects, but also impacts (congestion, transit issues, and others). Urban subcenters seek to approach economic activities to residents in peripheral urban spaces. The objective of this research is to evaluate the contribution to the mobility of implementing urban subcenters in a city. The model has a total cost function (users and agency costs) on a circular city (ring and radial routes) formulated using the continuous approximation method. The model solution addresses with mathematical optimization. The model evaluates a BRT network applied to scenarios of urban subcenters. The results of the modeling show that the implementation of subcenters obtains savings of 3.5% in rush hour. Thus, this strategy of urban planning generates improvements in the functioning of a public transportation system. Moreover, the maximum benefits are obtained in medium-sized subcenters in comparison to the CBD, which allows balancing user and agency costs. Therefore, the outcomes may be better with an urban pattern with subcenters, and a transit scheme adapted to the demand needs.The authors are members of BIT-Barcelona Innovative Transportation research group at BarcelonaTech. The work of the first author was also supported by CONICYT PFCHA/BCH 72160291 scholarship. This study had support from the Project 061312MT of the Departamento de Investigaciones Científicas y Tecnológicas (DICYT) of the Vicerrectoría de Investigación, Desarrollo e Innovación of the Universidad de Santiago de Chile (USACH).Peer ReviewedPostprint (published version

Night deliveries and carrier-led consolidation strategies to improve urban goods distribution

Night distribution and consolidation strategies have been proposed in many cities to increase the efficiency of the urban goods distribution system and to reduce the external effects that it causes in terms of emissions. However, the deployment of these initiatives presents a new reallocation of costs and incomes among collaborative stakeholders that take part in. In this paper, an analytical model to estimate the new economic effects caused by these strategies on the involved agents is presented, based on continuous approximations. This model allows decision makers to estimate the transportation cost and emissions savings that will be obtained by each strategy as well as the range of retailer demand in which these strategies are not economically feasible. The results show that night distribution generally outperforms the carrier cost reduction and emissions savings, especially when large vehicles are used in night periods.Peer ReviewedPostprint (published version

Public transport policies in Europe: implementing bus rapid transit systems in major European cities

Policies promoting Bus Rapid Transit implementation in Europe might take advantage of its low budget requirements and high capacity to provide a much more efficient transport system.Postprint (published version