Dans cette thèse, les propriétés optiques de biomolécules importantes ont été étudiées en utilisant une approche théorique et, dans un cas, aussi expérimentale. La Théorie de la fonctionnelle de la densité (DFT) et la timedependent-DFT (TD-DFT) sont les principales méthodes de chimie quantique utilisées dans cette thèse. Plusieurs spectroscopies ont été étudiées (au niveau théorique et, dans certains cas, également au niveau expérimental) : absorption électronique linéaire (absorption à un photon, OPA) et non-linéaire (absorption à deux ou trois photons, TPA et 3PA), dichroïsme circulaire électronique (DCE) et spectroscopie de fluorescence. Les effets de l’environnement, particulièrement importants dans des systèmes biologiques, ont été pris en compte, pour les propriétés de l’état fondamental et des états excités en utilisant une méthode multi-échelles QM/MM appelée Polarizable Embedding (PE). L’échantillonnage des conformations a été pris en compte avec des simulations de dynamique moléculaire (MD) qui sont basées sur la mécanique classique. Deux thématiques ont été étudiées dans cette thèse : le cholestérol et le design in silico de ses analogues fluorescents ainsi que la caractérisation des coudes de type β dans différentes conformations grâce à la simulation des spectres DCE. La simulation de plus d’une spectroscopie a été importante dans l’étude des états excités du cholestérol dans des solutions organiques. Le design in silico a suggéré un nouveau stérol-polyénique (P-stérol) qui montre despropriétés optiques améliorées pour le mécanisme d’excitation à trois photons par rapport au déhydroergostérol (DHE), une sonde du cholestérol déjà très utilisée. Ce nouveau P-stérol a été suggéré pour la synthèse. L’étude des spectres de DCE des coudes β en différentes conformations a mené une double conclusion : même si deux allures de DCE pour les conformations des coudes β étudiées (4) ont été trouvées (dans la majorité des cas), la spectroscopie de DCE doit toujours être associée à d’autres techniques spectroscopiques dans la caractérisation en solution des coudes β. / In this thesis, the optical properties of important biomolecules were studied using a theoretical approach and, in one case, also an experimental one. Density Functional Theory (DFT) and time-dependent-DFT (TD-DFT), were the principal quantum chemical methods adopted in this thesis.Various spectroscopies were studied (theoretically and, in some cases, also experimentally) : linear (one-photon, OPA) and non-linear (two- and three-photon, TPA and 3PA) electronic absorption, electronic circular dichroism (ECD) and fluorescence spectroscopy. The environment effects, which are particularly important in biological systems, were taken into account, for both ground and excited states properties, using a multiscale QM/MM method called Polarizable Embedding (PE). The sampling of conformations was addressed by Molecular Dynamic (MD) simulations based on classical mechanics. Two topics were studied in this thesis: cholesterol and the in-silico design of its fluorescent analogues, and the characterization of β-turns in different conformations by simulations of their ECD spectra in aqueous solutions. The simulation of more than one spectroscopy resulted to be important when studying the electronic excited states of cholesterol in organic solutions. The in-silico design study suggested a novel polyene-sterol (P-sterol) which shows improved optical properties for the three-photon excitation mechanism with respect to dehydroergosterol (DHE), an already widely used cholesterol probe. This new P-sterol was thus suggested for synthesis. The achievement from the study of ECD spectra for different β-turn conformations is two-fold: even if two ECD patterns for the β-turn conformations studied (4) were found (in most of cases), ECD spectroscopy should be always associated with other spectroscopic techniques when trying to characterize the β-turn conformations in solutions.

Anecdotal data affirms that companies applying Lean Six Sigma in their operations not only deliver higher quality products and services, but also obtain superior financial results. The goal of this research was to empirically verify anecdotal data. The study proposed to analyze a group of publicly traded manufacturing companies with the intent of verifying if a correlation exists between companies being lean and the attainment of superior returns on investments. The researcher performed a series of statistical tests comparing key Financial Performance Indicators (FPI) extracted from annual reports (10-K) from a large pool of companies. The outcome of this study showed that superior financial rewards result from a systematic application of lean and quality tools. At the conclusion of this thesis we verified that companies having a business model that stimulates a high level of communication between them and their markets - because they are lean - obtained substantially higher financial advantages when compared to companies that still followed a more traditional mode of production. The results also revealed that lean companies obtained on average Return on Invested Capital (ROIC) 10% higher than mass producers. Therefore, companies wanting to strategically invest their capital should consider Lean Six Sigma as a source of competitive advantage. Another strategic insight derived from this study was the recognition of signs of a smart business. Potential investors should look for the presence of lean and quality improvement programs as one sign that capital is being wisely invested to generate value. Another sign is how well historically ROIC have performed against Weighted Average Cost of Capital (WACC). The research revealed that, on average, lean companies had ROIC of 16%. Assuming that the hurdle rate (WACC) for most companies is near 10%, having ROIC of 16% is an incentive to become lean, thus allowing such companies to create value for their shareholders. Finally, we learned that many factors affect ROIC, namely, brand equity, market positioning, patents, core competency, innovation, leadership, etc. However, the presence of a Lean Six Sigma program in a manufacturing business was a strong positive factor impacting ROIC.

The productivity advances generated from lean manufacturing are self-evident. Plants that adopt lean are more capable of achieving high levels of quality, shorter lead times, and less waste in the system. While it seems logical that higher levels of productivity and quality, as is common in lean companies, should result in positive financial performance, the research community has failed to establish the financial profitability of lean. Those researchers who have studied the financial returns issue report varying results. The goal of this research was to determine if a connection exists between lean and financial success and to discover why so many researchers are finding mixed results. Information Velocity (IV) was theorized to provide the solidifying link between lean and financial performance. Measured by combining the environmental volatility with a company's leanness, IV measures how fast a company can transmit information from the market into a customer-satisfying product in the hands of the consumer. This study analyzed over 530 publicly-traded manufacturing companies to validate the following hypotheses: 1) there is a positive relationship between leanness and financial returns, 2) there is a negative relationship between environmental volatility and financial returns, and 3) there is a positive relationship between IV and financial returns. Regression models were run in various combinations to determine the effect of lean, environmental instability, environmental unpredictability, and IV on financial performance indicators such as return on sales (ROS), return on assets (ROA), and quarter-closing stock price. The outcome of this study showed that financial rewards do result from lean, which positively affected financial performance in almost all scenarios. Environmental instability always negatively correlated with financial returns, and IV mostly shows a positive effect, but with mixed results. Lastly, IV does not explain why researchers find mixed results on the profitability measures of lean. The results of this thesis highlight the significance of implementing lean manufacturing, especially in a dynamic environment. As the instability in the environment increases, profitability decreases. Therefore, an increase in leanness by boosting inventory turns can compensate for the volatility and create enhanced productivity measures and financial results.