Paula Milheiro-Oliveira

Comparative effects of bevacizumab, ranibizumab and pegaptanib at intravitreal dose range on endothelial cells.

Anti-VEGF therapy proved to be useful against several ocular pathological situations, including choroidal neovascularization and proliferative retinopathies. Ranibizumab (Ran), Pegaptanib (Peg) and Bevacizumab (Bev) are the pharmacological agents more frequently used in clinical practice by intravitreal injection. However, their exact effects on the angiogenic process have not been accurately established in a comparative study. The aim of the present study was to elucidate the precise effects of Ran, Peg and Bev on the multiple steps of the angiogenic process. Human umbilical vein endothelial cells (HUVEC) were incubated with each agent within the clinically established concentration range, or identical amounts of the excipients; cell cytotoxicity, proliferation, apoptosis, migration and vessel assembly were assessed. No cytotoxic effects were found for any of the agents studied at any concentration tested. At the clinical dose, cell proliferation was significantly reduced by Bev and Ran, whereas no difference was observed after Peg treatment. In addition, HUVEC apoptosis was effectively increased by Bev and Ran. Cell migration was reduced after incubation with every agent analyzed, though only reaching statistical significance upon Ran intravitreal dose. At clinical doses, capillary assembly was only affected by Bev. In agreement with these data, the active form of VEGF receptor-2 expression was decreased after incubation with Bev (to 66% of control values), Ran (78%) and Peg (86%) relative to controls. These findings indicate that these three agents display distinct effects on endothelial cells.

Robust SCC Mixes through Mix Design

AbstractOne of the main obstacles to a wider use of self-compacting concrete (SCC) is its sensitivity to small variations of the constituent materials, mix proportions, and other external factors. The main objective of this paper is to illustrate how to evaluate and compare the robustness of SCC mixtures optimized according to various economic criteria while maintaining the water/cement ratio and fresh state target properties. The optimization is derived from numerical models, and a central composite design is developed to mathematically model the influence of mixture parameters and their coupled effects on deformability, passing and filling abilities, and compressive strength. The strategies to increase the robustness of SCC mixtures and the existing methodologies to assess it are presented and discussed. By applying these methodologies, it is shown that robustness can be enhanced by changing only the proportions of materials in mixtures. Minimizing the superplasticizer dosage and, consequently, increasi...

Modeling and Simulation of Traffic Movements at Semiactuated Signalized Intersections

This work presents a microscopic stochastic simulation model that emulates the traffic movements at signalized intersections with semiactuated signal operation. This model uses the Awesim simulation language to implement and facilitate the evaluation of numerous operating scenarios associated with vehicle-actuated control strategies at isolated signalized intersections. A validation procedure was carried out, field data were collected, and delays and green times observed in the field were compared with those estimated by the simulation program. The adequacy of this model to represent real-world systems is shown. The structure of the model and the steps that were followed for its implementation are described. The relationship between simulated delays and the delays obtained from applying the Highway Capacity Manual model is analyzed. The impact of the maximum green time and the unit extension of green time assigned by the actuated system to each phase is also assessed. The model outputs include measures of...

BAYESIAN STATISTICAL METHODS FOR MODELING AND PREDICTION OF MAJOR LANDSLIDES IN COASTAL CLIFFS

The ability to predict coastline evolution in the long term is of great importance to coastal managers for social, economic and environmental risk assessment purposes. A Bayesian statistical approach to the problem of modeling and predicting the occurrence of major failure events in soft coasted cliffs is presented. This approach combines available data with expert judgement about the behavior of the cliff under study. Expert judgement is described in the form of expected values for cliff failure occurrences, confidence or degree of belief and subjective probability of occurrence of extremes. WinBUGS software is used to derive predictive probabilities, estimates of the rate of failure and standard deviations, which combine all information. The statistical method is illustrated in the cases of cliffs situated in Herne Bay and Scarborough, UK. The results can be used in a risk-based assessment of coastal cliff recession.

Queues with Server Vacations as a Model for Pretimed Signalized Urban Traffic

A queuing system resulting from a signalized intersection regulated by pretimed control in a network of urban traffic is considered. Modeling the queue length and the delay of vehicles is crucial to evaluate the performance of intersections equipped with traffic signals. Air quality and rational use of energy also depend on an efficient management of the intersections. These traffic systems have the specificity that the server (green signal) is deactivated (red signal) during a fixed period of time. In the present work, an M/D/1 queue with a server that occasionally takes vacations is analyzed. The mean delays of vehicles and the mean queue length are computed and compared with those obtained by using a detailed simulation model in a case study. We find that, in general, the mean delays of vehicles given by the proposed queuing model provide a good approximation, but the model can provide slightly smaller values than those obtained in the simulation model for large traffic flows. This result is of interes...

Application of a Particular Class of Markov Chains in the Assessment of Semi-actuated Signalized Intersections

We investigate a queuing model for a signalized intersection regulated by semi-actuated control in a urban traffic network. Modelling the queue length and the delay of vehicles for this type of traffic, characterized by variable durations of the green signal, is crucial to evaluate the performance of traffic intersections. Additionally, determining the size of the extensions of the green signal is also relevant. The traffic systems addressed in the paper have the particularity that the server remains active (green signal) for a period of time that depends on the number of vehicles waiting at the intersection. This gives rise to an M/D/1 queuing system with a server that occasionally takes vacations (red signal), for which we compute the long-run mean delay of vehicles, mean queue length and mean duration of the green signal. We consider a case study and compare the results obtained from the proposed queueing model with those obtained by using a microsimulation model. The formulas derived for the performance measures are of interest for traffic engineers, since the existing alternative formulas are subject to strong criticism.

Efficiency of an approximate filter for a particular class of nonlinear diffusions with observations corrupted by small noise

The asymptotic behaviour of a nonlinear continuous time approximate filter when the variance of the observation noise tends to 0 is investigated. We consider a particular class of signals modeled by a two-dimensional quasi-linear diffusion from which only one of the components is noisy, and we assume that a one-dimensional linear function of the signal, depending only of the unnoisy component, is observed in a low noise channel. Under some detectability assumptions the unobserved signal can be restored by means of an approximate nonlinear filter. We establish that the filtering error converges to 0 and we give an upper bound for the convergence rate. The efficiency of the approximate filter is compared with the efficiency of the optimal filter and the order of magnitude of the error between the two filters, as the observation noise vanishes, is obtained. A more general case is briefly presented.