Optimization of production of anti-cancer vaccines based on dendritic cells

Cancer remains as one of the top killing diseases in first world countries. It’s not a single, but a set of various diseases for which different treatment approaches have been taken over the years. Cancer immunotherapy comes as a “new” breath on cancer treatment, taking use of the patients’ immune system to induce anti-cancer responses. Dendritic Cell (DC) vaccines use the extraordinary capacity of DCs’ antigen presentation so that specific T cell responses may be generated against cancer. In this work, we report the ex vivo generation of DCs from precursors isolated from clinical-grade cryopreserved umbilical cord blood (UCB) samples. After the thawing protocol for cryopreserved samples was optimized, the generation of DCs from CD14+ monocytes, i.e., moDCs, or CD34+ hematopoietic stem cells (HSCs), i.e, CD34-derived DCs, was followed and their phenotype and function evaluated. Functional testing included the ability to respond to maturation stimuli (including enzymatic removal of surface sialic acids), Ovalbumin-FITC endocytic capacity, cytokine secretion and T cell priming ability. In order to evaluate the feasibility of using DCs derived from UCB precursors to induce immune responses, they were compared to peripheral blood (PB) moDCs. We observed an increased endocytosis capacity after moDCs were differentiated from monocyte precursors, but almost 10-fold lower than that of PB moDCs. Maturation markers were absent, low levels of inflammatory cytokines were seen and T cell stimulatory capacity was reduced. Sialidase enzymatic treatment was able to mature these cells, diminishing endocytosis and promoting higher T cell stimulation. CD34-derived DCs showed higher capacity for both maturation and endocytic capacity than moDCs. Although much more information was acquired from moDCs than from CD34-derived DCs, we conclude the last as probably the best suited for generating an immune response against cancer, but of course much more research has to be performed.

Experimental analysis of the cyclic response of traditional timber joints and their influence on the seismic capacity of timber frame structures

Timber connections represent the crucial part of a timber structure and a great variability exists in terms of types of connections and mechanisms. Taking as case study the widespread traditional timber frame structures, in particular the Portuguese Pombalino buildings, one of the most common timber connection is the half-lap joint. Connections play a major role in the overall behaviour of a structure, particularly when assessing their seismic response, since damage is concentrated at the connections. For this reason, an experimental campaign was designed and distinct types of tests were carried out on traditional half-lap joints to assess their in-plane response. In particular, pull-out and in-plane cyclic tests were carried out on real scale unreinforced connections. Subsequently, the connections were retrofitted, using strengthening techniques such as self-tapping screws, steel plates and GFRP sheets. The tests chosen were meant to capture the hysteretic behaviour and dissipative capacity of the connections and characterise their response and, therefore, their influence on the seismic response of timber frame walls, particularly concerning their uplifting and rotation capacity, that could lead to rocking in the walls. In this paper, the results of the experimental campaign are presented in terms of hysteretic curves, dissipated energy and equivalent viscous damping ratio. Moreover, recommendations are provided on the most appropriate retrofitting solutions.

Numerical Assessment of the out-of-plane response of a brick masonry structure without box behaviour

This paper presents the assessment of the out-of-plane response due to seismic loading of a masonry structure without rigid diaphragm. This structure corresponds to real scale brick masonry specimen with a main façade connected to two return walls. Two modelling approaches were defined for this evaluation. The first one consisted on macro modelling, whereas the second one on simplified micro modelling. As a first step of this study, static nonlinear analyses were conducted to the macro model aiming at evaluating the out-of-plane response and failure mechanism of the masonry structure. A sensibility analyses was performed in order to assess the mesh size and material model dependency. In addition, the macro models were subjected to dynamic nonlinear analyses with time integration in order to assess the collapse mechanism. Finally, these analyses were also applied to a simplified micro model of the masonry structure. Furthermore, these results were compared to experimental response from shaking table tests. It was observed that these numerical techniques simulate correctly the in-plane behaviour of masonry structures. However, the

Effect of environmental ageing on the numerical response of FRP-strengthened masonry walls

Recent durability studies have shown the susceptibility of bond in fiber-reinforced polymer (FRP) strengthened masonry components to hygrothermal exposures. However, it is not clear how this local material degradation affects the global behavior of FRP-strengthened masonry structures. This study addresses this issue by numerically investigating the nonlinear behavior of FRP-masonry walls after aging in two different environmental conditions. A numerical modeling strategy is adopted and validated with existing experimental tests on FRP-strengthened masonry panels. The model, once validated, is used for modeling of four hypothetical FRP-strengthened masonry walls with different boundary conditions, strengthening schemes, and reinforcement ratios. The nonlinear behavior of the walls is then simulated before and after aging in two different environmental conditions. The degradation data are taken from previous accelerated aging tests. The changes in the failure mode and nonlinear response of the walls after aging are presented and discussed.