The three-dimensional structure of a protein, formed as a result of amino-acid sequences folding into compact domains, is regarded as a key factor in its biological function. How and why proteins fold into specific topologies, remain the key focus of scientific research in the field of biophysics. By stripping down complex reactions down to the most basic elements, biophysicists aim to develop simplified models for biological phenomena such as antibody discrimination, viral fusion or self-assembly. Focusing on small model peptide systems, rather than the full proteins from which they were derived, was hoped to result in accurate structural measurements and provide a more transparent comparison between simulation and experiment. The aim of this research was therefore to investigate how accurate these models were when compared against experiment. Furthermore, while breaking down the complex biological phenomena into simple models, there was also a conscious effort to ensure that the models were representative of real biological systems, and a major focus was therefore aimed at determining whether any meaningful biomedical insight may be extrapolated from such models. Peptides found in hormones (human chorionic gonadotropin, luteinizing hormone), viruses (HIV) and amyloid diseases (transthyretin) were selected in order to probe a variety of questions in relation to the aforementioned biological phenomena. Namely, how the primary sequence influenced the three-dimensional structure (and thus its biological function), how its environment could influence such a confirmation, and how these systems aggregated. This doctoral study has made use of a combination of computer simulations and experimental techniques to investigate a selection of biologically relevant peptides; utilising classical atomistic molecular dynamics (MD) simulations to characterise the free-energy landscapes of the chosen peptides, and compare these findings with the secondary structure content predicted by spectroscopic methods such as circular dichroism and infrared spectroscopy. The peptide systems studied within, were found to be characterised by rugged free-energy landscapes unlike their protein counterparts (defined by singular, deep minima). Furthermore, these landscapes were found to be highly plastic and sensitive to changes in the local environment.

[pt] A incerteza é um fator relevante na modelagem de variáveis macroeconômi-cas, especialmente em países emergentes. Neste estudo, tentamos entender se me-didas de incerteza oriundas do mercado brasileiro podem melhorar as projeções de PIB do país. Traçando uma curva IS da forma mais simples possível: relacionando o hiato do produto a suas primeiras defasagens e aos juros reais ex-ante, podemos adicionar medidas de incerteza e atestar se estas melhoram as projeções de hiato realizadas para o período imediatamente subsequente. Como medidas de incerte-za, utilizamos a dispersão de expectativas do boletim Focus para PIB e inflação; a volatilidade implícita dos contratos futuros de câmbio; o VIX; a volatilidade observada nas empresas mais relevantes do índice Bovespa e o Índice de Incerteza Econômica (IIE-Br). Conseguimos demonstrar com um exercício de backtest que a previsão de hiatos do PIB se torna melhor com a inclusão de variáveis de incerteza na curva IS. / [en] Uncertainty is a relevant matter when modelling economic variables, especially in emerging countries. Here, we try to understand if measures of uncertainty observed in the Brazilian market allow us to improve GDP forecasting. By defining an IS curve as simply as possible: relating current output gap with its lags and the economy s ex-ante real interest rate, it is possible to introduce an uncertainty measure and examine if the forecasting exercise improves in the next period. As proxies for uncertainty, we shall use dispersion of financial markets expectations for future inflation and future output growth; FX future contracts implied volatility; VIX Index; observed volatility in Brazil s most relevant companies stock prices, and; the Economy Uncertainty Index (IIE-Br). We were able to demonstrate through a backtest exercise that the insertion of uncertainty measures in the IS curve improves the output gap forecasting.

This doctoral thesis considers the automatic verification of parameterized systems, i.e. systems with an arbitrary number of communicating components, such as mutual exclusion protocols, cache coherence protocols or heap manipulating programs. The components may be organized in various topologies such as words, multisets, rings, or trees. The task is to show correctness regardless of the size of the system and we consider two methods to prove safety:(i) a backward reachability analysis, using the well-quasi ordered framework and monotonic abstraction, and (ii) a forward analysis which only needs to inspect a small number of components in order to show correctness of the whole system. The latter relies on an abstraction function that views the system from the perspective of a fixed number of components. The abstraction is used during the verification procedure in order to dynamically detect cut-off points beyond which the search of the state-space need not continue. Our experimentation on a variety of benchmarks demonstrate that the method is highly efficient and that it works well even for classes of systems with undecidable property. It has been, for example, successfully applied to verify a fine-grained model of Szymanski's mutual exclusion protocol. Finally, we applied the methods to solve the complex problem of verifying highly concurrent data-structures, in a challenging setting: We do not a priori bound the number of threads, the size of the data-structure, the domain of the data to store nor do we require the presence of a garbage collector. We successfully verified the concurrent Treiber's stack and Michael & Scott's queue, in the aforementioned setting. To the best of our knowledge, these verification problems have been considered challenging in the parameterized verification community and could not be carried out automatically by other existing methods.