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- What drives an amyloid protein precursor from an amyloidogenic to a native-like aggregation pathway?Publication . Quintas, AlexandreConformational disorders such as Alzheimer’s, Parkinson’s, familial amyloidotic polyneuropathy and spongiform encephalopaties are a consequence of protein misfolding and aggregation predominantly in the form of amyloid fibrils. These pathologies represent a major health problem, which most probably will overwhelm the health systems of developed countries in the near future. Significant progress has been made recently to understanding the underlying mechanism of protein misfolding and aggregation. The current picture of protein aggregation is a phenomenon resulting from protein conformational fluctuations leading to misfolded intermediates prone to form non-native interactions with other intermediates, resulting in amyloid fibril formation. Fortunately just a small group of proteins are associated with human conformational disorders. The primary causes that lead this group of proteins to misfolding and aggregation are point mutations, protein over-expression and failure of protein quality-control system. Beside amyloid formation, there are other types of aggregation available to a misfold-disease-related polypeptide chain in the proteinfree energy landscape. Among them, native-like aggregation is becoming a widely studied topic of research.
- Computing Repairs from Active Integrity ConstraintsPublication . Cruz-Filipe, L.; Engrácia, P.; Nunes, I.; Gaspar, G.Repairing an inconsistent knowledge base is a well known problem for which several solutions have been proposed and implemented in the past. In this paper, we start by looking at databases with active integrity constraints - consistency requirements that also indicate how the database should be updated when they are not met - as introduced by Caroprese et al.We show that the different kinds of repairs considered by those authors can be effectively computed by searching for leaves of specific kinds of trees. Although these computations are in general not very efficient (deciding the existence of a repair for a given database with active integrity constraints is NP-complete), on average the algorithms we present make significant reductions on the number of nodes in the search tree. Finally, these algorithms also give an operational characterization of different kinds of repairs that can be used when we extend the concept of active integrity constraints to the more general setting of knowledge bases.