Folate-targeted nanoparticles for rheumatoid arthritis therapy

Rheumatoid arthritis (RA) is the most common inflammatory rheumatic disease, affecting almost 1% of the world population. Although the cause of RA remains unknown, the complex interaction between immune mediators (cytokines and effector cells) is responsible for the joint damage that begins at the synovial membrane. Activated macrophages are critical in the pathogenesis of RA and have been shown to specifically express a receptor for the vitamin folic acid (FA), folate receptor (FR). This particular receptor allows internalization of FA-coupled cargo. In this review we will address the potential of nanoparticles as an effective drug delivery system for therapies that will directly target activated macrophages. Special attention will be given to stealth degree of the nanoparticles as a strategy to avoid clearance by macrophages of the mononuclear phagocytic system (MPS). This review summarizes the application of FA-target nanoparticles as drug delivery systems for RA and proposes prospective future directions.

Relative information entropy in cosmology: The problem of information entanglement

The necessary information to distinguish a local inhomogeneous mass density field from its spatial average on a compact domain of the universe can be measured by relative information entropy. The Kullback-Leibler (KL) formula arises very naturally in this context, however, it provides a very complicated way to compute the mutual information between spatially separated but causally connected regions of the universe in a realistic, inhomogeneous model. To circumvent this issue, by considering a parametric extension of the KL measure, we develop a simple model to describe the mutual information which is entangled via the gravitational field equations. We show that the Tsallis relative entropy can be a good approximation in the case of small inhomogeneities, and for measuring the independent relative information inside the domain, we propose the R\'enyi relative entropy formula.

Single molecule simulation of diffusion and enzyme kinetics

This work presents a molecular-scale agent-based model for the simulation of enzymatic reactions at experimentally measured concentrations. The model incorporates stochasticity and spatial dependence, using diffusing and reacting particles with physical dimensions. We developed strategies to adjust and validate the enzymatic rates and diffusion coefficients to the information required by the computational agents, i.e., collision efficiency, interaction logic between agents, the time scale associated with interactions (e.g., kinetics), and agent velocity. Also, we tested the impact of molecular location (a source of biological noise) in the speed at which the reactions take place. Simulations were conducted for experimental data on the 2-hydroxymuconate tautomerase (EC 5.3.2.6, UniProt ID Q01468) and the Steroid Delta-isomerase (EC 5.3.3.1, UniProt ID P07445). Obtained results demonstrate that our approach is in accordance to existing experimental data and long-term biophysical and biochemical assumptions.

Mobilidade social, identidade e valores: o regresso de emigrantes no Minho

Dissertação de mestrado em Sociologia (área de especialização em Políticas Comunitárias e Cooperação Territorial)