O quadro de resistência à insulina em humanos está fortemente relacionado ao acumulo de lipídeos intracelulares, a inatividade física e ao aumento de espécies reativas de oxigênio (ERO). O objetivo deste estudo foi verificar se o aumento na oferta de nutrientes incluindo glicose e ácido graxo palmítico pode alterar o potencial de membrana mitocondrial, a respiração, a produção de espécies reativas de oxigênio e a resposta a insulina em células do tecido muscular. Nossos resultados mostram que a exposição de células musculares a elevada disponibilidade de substratos resultou em diminuição do potencial de membrana mitocondrial, e aumento da respiração no estado IV e da expressão do RNAm da proteína desacopladora mitocondrial UCP-3. Mostrando a existência de um mecanismo de desacoplamento intrínseco em células do músculo esquelético ativado em situações de elevada oferta de nutrientes. Nessas condições observamos redução do acoplamento e da eficiência termodinâmica mitocondrial. Interessantemente, essa capacidade de desacoplamento parece ser perdida cronicamente como indicado pelos nossos resultados de consumo de oxigênio no período de 48h favorecendo uma menor atividade mitocondrial, aumento de EROs e redução da razão GSH/GSSG. Imagens de microscopia eletrônica em cultura primária e expressão gênica do PGC1-, um reconhecido gene regulador da biogênese mitocondrial, não demonstraram diferença entre controle e tratamento com palmitato. O ácido palmito resultou na redução da fosforilação de Akt, bem como, na captação de glicose estimulada por insulina. Nossos achados, portanto, sugerem que uma redução do acoplamento termodinâmico mitocondrial e do sistema antioxidante, juntamente com aumento do peróxido de hidrogênio, estão fortemente relacionados a redução da resposta a insulina. Deste modo, nosso estudo sugere um papel importante da mitocôndria na resposta a insulina. / The insulin resistance in human framework is strongly related to the accumulation of intracellular lipids, physical inactivity and increased reactive oxygen species (ROS). The aim of this study was to determine whether the increase in nutrient supply including glucose and palmitic fatty acid can change the mitochondrial membrane potential, respiration, production of reactive oxygen species and the insulin response in muscle tissue cells. Our results show that exposure of muscle cells to high availability of the substrate resulted in decreased mitochondrial membrane potential, in increased respiration in the state IV and mRNA expression of mitochondrial uncoupling protein UCP-3. Showing the existence of an intrinsic uncoupling mechanism of skeletal muscle cells activated in situations of high supply of nutrients. However, under these conditions we observed a reduction of the coupling and mitochondrial thermodynamic efficiency. Interestingly, this decoupling capacity was chronically lost as indicated by our results in the 48 hours period favoring a lower mitochondrial activity, increase of ROS and reduced GSH / GSSG ratio. Images from electron microscopy and gene expression of PGC1-, a recognized regulatory gene of mitochondrial biogenesis, showed no difference between control and treatment with palmitate. The palm acid resulted in reduced phosphorylation of Akt, as well as glucose uptake stimulated by insulin. Our findings thus suggest that a reduction in mitochondrial antioxidant and thermodynamic coupling system, along with increase in the hydrogen peroxide, are closely related to reducing insulin response. Thus, our findings suggest a role of mitochondria in insulin response.

O pinhão é a semente comestível da Araucaria angustifolia, sendo consumido no sul e sudeste do Brasil. Possui excelentes características nutritivas e energéticas. As sementes têm uma atividade de água muito elevada (>0,98), o que facilita o desenvolvimento de fungos durante a estocagem, dificultando a sua comercialização. A literatura sobre os seus aspectos nutricionais e tecnológicos é muito escassa. O objetivo principal deste trabalho foi determinar aspectos tecnológicos e de engenharia relacionados com o processamento e armazenamento do pinhão. Foi estudada a vida de prateleira do pinhão cru a 25°C (5 dias), 5°C (3 meses) e –18°C (mais de 8 meses) através de análises fisicoquímicas, microbiológicas e sensoriais. Foram propostas as seguintes operações preliminares para preservar a qualidade da semente comercializada: recepção, limpeza, seleção, classificação e armazenamento. Foram determinadas as isotermas de desorção do pinhão cru e cozido e de adsorção da farinha de pinhão cru em diferentes temperaturas (entre 10 e 40°C) sendo ajustados modelos da literatura e calculadas a entalpia e entropia diferenciais. Para os três casos o modelo que melhor se ajustou aos dados foi o de Chirife e a teoria compensatória foi aplicada. Foi avaliada também a cinética de secagem do pinhão cru e cozido em secador de bandeja a 55, 70 e 85°C. Os dados foram ajustados a modelos de secagem e calculadas as difusividades efetivas, sendo que a difusividade do pinhão cozido (1,18 a 3,17 x10-10 m2s-1) foi menor do que a do pinhão cru (1,64 a 4,52 x10-10 m2s-1), provavelmente devido à gelatinização do amido. Um dos processos empregados pela tecnologia de alimentos, com a finalidade de obter produtos estáveis a partir de sementes, é a produção de farinhas. Neste trabalho foi produzida farinha de pinhão variando as seguintes condições de processo: utilização de pinhão cru e cozido e diferentes temperaturas de secagem (55, 70 e 85°C). As farinhas produzidas com pinhão cozido apresentaram cor mais escura, com uma luminosidade menor (Lmédia= 75.8) e coordenada de cromaticidade maior (amédia= 6.9), quando comparadas com as farinhas de pinhão cru (Lmédia= 89.0, amédia= 2.1). A temperatura de secagem também influenciou a cor das farinhas produzidas com pinhão cru. Através de análise multivariada dos dados foi possível agrupar as amostras. A partir dos resultados da análise sensorial constatou-se que o suflê produzido com a farinha de pinhão cozido apresentou maior aceitação, obtendo-se um produto que une praticidade, inovação e apelo regional. Por último, como uma forma de aproveitamento da casca do pinhão, foi estudada a extração de compostos fenólicos da casca, como uma nova fonte de antioxidantes. Foram determinadas as melhores condições em termos de volume e concentração de solvente (etanol) e temperatura de extração, utilizando a metodologia de superfície de resposta. / The seeds of Araucaria angustifolia, named pinhão, are consumed in the South and Southeast of Brazil. Pinhão has good nutritious and energetic characteristics. Since the seeds have a high water activity (>0,98), they can be easily contaminated by mushrooms during the stockpiling, hindering its commercialisation. The literature about nutritional and technological aspects of pinhão is very scarce. The main objective of this work was to determine technological and engineering aspects of the processing and storage of pinhão. The Shelf life of raw pinhão was studied at 25°C (5 days), 5°C (3 months) and -18°C (more than 8 months) using physiochemical, microbiological and sensorial analyses. The following preliminary operations were proposed to preserve the quality of the seed for commercialisation: reception, cleaning, selection, classification and storage. Desorption of raw and cooked pinhão and adsorption isotherms of raw pinhão flour were determined at different temperatures (between 10 and 40°C), modelled using well know isotherm models and differential enthalpy and entropy were calculated. Results show that the Chirife model most appropriately represents the experimental data for the three cases and the enthalpy-entropy compensation theory was applied. Drying behavior of raw and cooked pinhão was studied at 55, 70 and 85°C. The data were adjusted to drying models and effective diffusivity were calculated. Values for cooked pinhão (1,18 to 3,17 x10-10 m2s-1) were smaller than values for raw pinhão (1,64 to 4,52 x10-10 m2s-1), probably due to starch gelatinisation. One of the processes used by food technology with the purpose of obtaining stable products from seeds, it is the production of flours. In this work pinhão flour was produced varying the following process conditions: use of raw or cooked pinhão and different drying temperatures (55, 70 and 85°C). Flours produced with cooked pinhão presented darker colour, with a smaller brightness (Lmean = 75.8) and larger coordinate of chromaticity (amean = 6.9), when compared with raw pinhão flours (Lmean = 89.0, amean = 2.1). Drying temperature also influenced the colour of flours produced with raw pinhão. Through multivariate analysis of the data it was possible to cluster the samples. Results of sensorial analysis show that soufflé produced with cooked pinhão flour presented larger acceptance, being obtained a new product with regional appeal. The extraction of phenolic compounds of pinhão coats was also studied as a new source of antioxidants. The best condition of solvent volume, ethanol concentration and temperature, using factorial design and response surface methodology, were obtained.

Submitted by Jorge Silva (jorgelmsilva@ufrrj.br) on 2018-11-21T16:44:58Z No. of bitstreams: 1 2013 - Beatriz Autullo Ramos.pdf: 1610426 bytes, checksum: c3defc33414fda5b010152756fc0f0ce (MD5) / Made available in DSpace on 2018-11-21T16:45:00Z (GMT). No. of bitstreams: 1 2013 - Beatriz Autullo Ramos.pdf: 1610426 bytes, checksum: c3defc33414fda5b010152756fc0f0ce (MD5) Previous issue date: 2013-08-29 / CAPES / FAPERJ / The aim of this study was to obtain the sorption isotherms, analyze the kinetics of drying jatropha seeds, perform mathematical modeling of sorption isotherms and kinetic experiments, and to study the thermodynamics of the process. Seeds with initial moisture content of 8-10%, dry basis, were used. The sorption isotherms were found using two experimental devices: a water activity meter and a thermal bath with temperatures adjusted at 30, 40 and 50 ?C for the first apparatus and 40, 50 and 60 ?C for the second one. To obtain the sorption isotherms with a thermal bath the method of saturated saline solutions of MgCl2, K2CO3, KI, NaCl, and NaBrO3 was applied and the time to reach equilibrium was, generally, 20 days. Nine kinetic experiments were performed setting temperatures at 30, 40 and 50 ?C, and the superficial gas velocity at 397, 794 and 1190 cm/min, with duration of three hundred and sixty minutes. Oswin's mathematical model was the best to describe the hygroscopic behavior of the isotherms found with the water activity meter, while Caurie's model was the best for the thermal bath data, because they showed the lowest deviations and the highest coefficients of determination. ANOVA indicated that only the water activity has significant influence over the equilibrium moisture on the sorption isotherm experiments, in both equipments. Nine mathematical models were tested to simulate the kinetics and the ?two exponential terms? model presented the lowest deviations and highest coefficients of determination. It was observed that the temperature and superficial gas velocity did not significantly influence the kinetic experiments. For calculation of the thermodynamic properties the models that best fitted the data of the two experiments to obtain the sorption isotherms were used. The positive values of the differential enthalpy and entropy for both studies showed that the sorption process of jatropha seeds is endothermic and irreversible. The negative values of the Gibbs free energy variation for both studies indicated that the sorption process occurs spontaneously for the temperature conditions evaluated. The enthalpy-entropy compensation theory was applied satisfactorily and Krug?s test showed that the isokinetic temperature was different from the harmonic mean temperature in both studies. / O objetivo deste trabalho foi obter as isotermas de sor??o, analisar a cin?tica de secagem da semente do pinh?o-manso, realizar a modelagem matem?tica dos experimentos da isoterma de equil?brio e de cin?tica, e o estudo termodin?mico do processo. Utilizaram-se sementes com teor de umidade inicial de 8 a 10 %, em base seca. Os experimentos de determina??o da isoterma de equil?brio foram realizados utilizando dois equipamentos: o medidor de atividade de ?gua e o banho t?rmico, com faixas de temperatura de 30, 40 e 50 ?C, para o primeiro, e de 40, 50 e 60 ?C, para o segundo. As isotermas obtidas pelo banho t?rmico foram obtidas atrav?s do m?todo das solu??es salinas saturadas de MgCl2, K2CO3, KI, NaCl e NaBrO3 e o tempo para atingir o equil?brio foi, em geral, de 20 dias. Foram realizados nove experimentos de cin?tica, nas temperaturas de 30, 40 e 50 ?C, com velocidade superficial do g?s de 397, 794 e 1190 cm/min, com dura??o de trezentos e sessenta minutos. O melhor modelo matem?tico selecionado para descrever o comportamento higrosc?pico das isotermas foi o Oswin, para o medidor de atividade de ?gua, e o de Caurie, para o banho t?rmico, pois apresentaram os menores desvios e os maiores coeficientes de determina??o. Atrav?s da ANOVA verificou-se que somente a atividade de ?gua apresentou influencia significativa sobre a umidade de equil?brio para os experimentos de isoterma, em ambos os equipamentos. Nove modelos matem?ticos foram testados para a simula??o da cin?tica sendo que o modelo de ?Dois termos exponenciais? apresentou os menores desvios e os maiores coeficientes de determina??o. Observou-se que a temperatura e a velocidade superficial do g?s n?o influenciaram significativamente os experimentos de cin?tica. Para os c?lculos das propriedades termodin?micas foram utilizados os modelos que melhor ajustaram os dados dos dois experimentos para obten??o das isotermas de sor??o. Os valores positivos de entalpia e entropia diferencial, para ambos os estudos, mostraram que o processo de sor??o de ?gua nos gr?os de pinh?o-manso ? endot?rmico e irrevers?vel. Os valores negativos da varia??o da energia livre de Gibbs, para os dois estudos, indicaram que o processo de sor??o ocorre de forma espont?nea para as condi??es de temperatura avaliadas. A teoria compensat?ria entalpia-entropia foi aplicada de forma satisfat?ria, e o teste de Krug mostrou que a temperatura isocin?tica foi diferente da temperatura m?dia harm?nica nos dois estudos realizados.

Esse trabalho apresenta um modelo termodinâmico de uma bomba multifásica do tipo duplo parafuso. Para uma dada condição de operação, o modelo calcula a potência consumida, as condições do fluido na descarga e o perfil de pressão ao longo da bomba. Ao invés de simular diretamente o escoamento dentro da bomba, simulou-se os processos que ocorrem dentro das suas câmaras. Para tanto, dividiu-se o processo de bombeamento multifásico em uma seqüência de processos simples, facilitando-se a construção do modelo no simulador de processos Hysys.Process v2.1. Os resultados de potência e temperatura de descarga obtidos com a simulação mostram uma boa concordância com valores experimentais, principalmente para FVG’s baixos. Para FVG’s elevados, o modelo passa a superestimar a potência consumida indicando que as fendas, nesses casos, já não se encontram totalmente preenchidas com líqüido. Dos resultados obtidos para o refluxo, conclui-se que, das equações sugeridas na literatura, aquelas para escoamento turbulento liso são mais adequadas para os números de Reynolds envolvidos. O perfil de pressão e a vazão de refluxo quando o escoamento é multifásico aproxima-se qualitativamente das medições experimentais. Estudou-se a influência de diversos parâmetros na eficiência exergética da bomba. Os resultados mostram que a otimização da eficiência depende das condições de operação da bomba: FVG, tipo de líqüido, diferença de pressão, entre outros. / The goal of this project was to develop a thermodynamic model of a twin-screw multiphase pump. With given operation conditions the model can determine the absorbed power, discharge conditions and the pressure profile along the screw. An alternative approach was suggested to overcome the complex flow problem and the processes inside the pump were simulated instead of direct simulation of the flow. For this purpose, the multiphase pumping process was divided in a sequence of simple processes so the model could be developed in an easier way. The power and temperature values calculated by the model are in good agreement with experimental data, mainly when the gas fraction is low. With higher gas fractions, the model overestimates the absorbed power indicating that screw gaps are not completely filled with liquid anymore. Concerning about the backflow rate, the results show that the equations for turbulent flow in smooth ducts fits better the Reynolds number range in the gaps. The pressure profile and backflow rate for multiphase flow agree qualitatively with experimental results. The influence of several parameters in the exergetic eficiency of the pump were analysed and results show that the efficiency optimization depends on pump operation conditions: gas fraction, liquid type, pressure difference and others.

Fundamental thermodynamic investigations have been carried out regarding the phase equilibria of La0.8Sr0.2MnO3±δ (LSM), a cathode of a solid oxide fuel cell (SOFC), utilizing the CALculation of PHAse Diagram (CALPHAD) approach. The assessed thermodynamic databases developed for LSM perovskite in contact with YSZ fluorite and the other species have been discussed. The application of computational thermodynamics to the cathode is comprehensively explained in detail, including the defect chemistry analysis as well as the quantitative Brouwer diagrams, electronic conductivity, cathode/electrolyte interface stability, thermomechanical properties of the cathode and the impact of gas impurities, such as CO2 as well as humidity, on the phase stability of the cathode. The quantitative Brouwer diagrams for LSM at different temperatures are developed and the detailed analysis of the Mn3+ charge disproportionation behavior and the electronic conductivity in the temperature range of 1000-1200°C revealed a good agreement with the available experimental observations. The effects of temperature, CO2 partial pressure, O2 partial pressure, humidity level and the cathode composition on the formation of secondary phases have been investigated and correlated with the available experimental results found in the literature. It has been indicated that the CO2 exposure does not change the electronic/ionic carriers’ concentration in the perovskite phase. The observed electrical conductivity drop is predicted to occur due to the formation of secondary phases such as LaZr2O7, SrZrO3, SrCO3 and Mn oxides at the LSM/YSZ interface, resulting in the blocking of the electron/ion transfer paths. For the thermo-mechanical properties of LSM, a new weight loss Mechanism for (La0.8Sr0.2)0.98MnO3±δ using the La-Sr-Mn-O thermodynamic database is modeled with respect to the compound energy formalism model. This newly proposed mechanism comprehensively explains the defect formation as a result of volume/weight change during the thermal cycles. According to the proposed mechanism the impact of cation vacancies regarding the volume change of cathode was explained.

Dans ce travail, nous avons présenté notre contribution portant sur la modélisation et le contrôle a priori de congestion des réseaux de carrefours signalisés. De point de vue de la modélisation, nous avons introduit un nouveau regard sur les systèmes de transport en proposant un premier travail sur la manière dont les liens se tissent entre ces systèmes et la thermodynamique. Le point de vue dominant est l'assimilation des véhicules à l'énergie fournie ou/et échangée entre les intersections signalisées. L'avantages majeur de la modélisation thermodynamique est l'introduction de la notion d'entropie du transport mesurant le désordre du système. Elle peut être considérée non seulement comme un moyen pour la compréhension des phénomènes du trafic, mais aussi comme un outil d'évaluation surtout lorsqu'il s'agit de traiter des réseaux de grande taille. De point de vue du contrôle, nous nous sommes intéressés essentiellement à un travail en amont permettant d'éviter la congestion en forçant les files d'attente à ne pas dépasser le niveau du trafic correspondant à l'optimum opérationnel des lignes. Nous avons traité le problème de deux façons différentes. La première fait appel à l’approche de la commande dissipative. Nous avons exploité cet outil pour arriver à des résultats théoriques dont la vérification permet de conclure sur la possibilité de dissiper les véhicules au moyen d'une action de la commande adéquate. L'existence d'une commande dissipative est caractérisée par la faisabilité de certaines inégalités matricielles linéaires (LMI). La deuxième façon de traiter notre problème de commande fait appel à la commande H∞. Nous avons tiré profit de cet outil pour développer des résultats assurant l'invariance positive en boucle fermée d'un domaine ellipsoïdal contenu dans l'ensemble des contraintes. Le test d'existence et le calcul d'une loi de commande robuste par retour d'état peut alors se faire de façon simple par la résolution d'un problème de programmation linéaire convexe. Enfin, ses travaux ont été appliqués sur deux types de réseaux de carrefours, artériel et en grille afin de montrer l'intérêt des résultats. / In this work, we have presented a thermodynamic point of view for the transportation network. Analogies have been drawn between thermodynamic and transportation systems by considering traffic lanes as thermodynamic sub-systems and the vehicles as the abstract energy supplied to them. In addition, the concepts of thermal capacity and temperature are also introduced into transportation context to correspond to lane capacity and occupancy respectively. Then, it has been demonstrated that the first law of thermodynamics corresponds to the conservation of vehicles. It is also demonstrated that the transportation network can have a similar notion of entropy. Such transportation entropy is a measure of disorder of the system and hence may provide deep insight in the analysis of transportation control problems. In particular, this work has presented a dissipativity phenomenon of transportation entropy that reduces the system disorder and hence renders the system better organized. Though this phenomenon doesn’t exist naturally in transportation context, the ways to construct feedback control strategies have been proposed to achieve such objective by means of Linear Matrix Inequalities (LMIs). However, since transportation systems involve massive complex human activities, there exist substantial unpredictable uncertainties of the traffic demands. In this context, we have proposed a robust controller for disturbance attenuation of transportation network. The errors between input flows and the nominal ones are considered as disturbances and a constrained H∞ control has been formulated in terms of maximization of the tolerance under control constraints. The problem of disturbance attenuation is solved by means of a convex optimization with Linear Matrix Inequality. Finally, two types of networks (arterial and grid) are carried out to illustrate the performances of our strategies.

<p>The increased use of biomass and recovered waste fuels in favor of fossil fuels for heat and power production is an important step towards a sustainable future. Combustion of waste fuels also offers several advantages over traditional landfilling, such as substantial volume reduction, detoxification of pathological wastes, and reduction of toxic leaches and greenhouse gas (methane) formation from landfills. However, combustion of recovered waste fuels emits more harmful trace elements than combustion of other fuels. These elements are distributed between bottom ash, fly ash and flue gas, depending on the elements partitioning and enrichment behavior. Volatilized harmful trace elements are mainly enriched in the submicron fly ash fraction. If emitted to the atmosphere, submicron particles can penetrate deep into the alveoli of the lungs, causing severe impacts on human health. Consequently, to reduce ash related problems and to control the emissions to the atmosphere, there is an increased need for understanding the physicochemical processes involved in ash transformation, including particle formation.</p><p>The objective of this thesis was to carefully and systematically study the fate of trace elements during combustion, i.e. the chemical form of the elements and the partitioning behavior, by means of chemical equilibrium model calculations, X-ray diffraction, microscopy techniques and various spectroscopy methods. The influence of some fuel additives was also analyzed. Primarily, the elements copper, chromium and arsenic were studied.</p><p>An initial review and evaluation of the content of thermodynamical data in commercial thermochemical databases used for chemical equilibrium model calculations showed that there was a significant difference in number of included phases and species between databases. Thermodynamical data also differed between databases, although in general less for condensed phases than for gaseous species. A state-of-the-art database for Cu, Cr and As was compiled and used for further chemical equilibrium model calculations. The fate of Cu, Cr and As was determined in combustion experiments on wood impregnated with copper, chromium and arsenic (CCA) in a bench scale reactor (15 kW). The results showed that global chemical equilibrium model calculations predicted the overall fate of Cu, Cr and As in bottom ash and ash particles quite well. However, compared to the experimental results the global model overpredicted the formation of refractory calcium arsenates, thus the arsenic volatilization was found to be higher then the predicted volatilization. In terms of chromium volatility, copper was found to be an important refractory element forming stable CuCrO₂(s) and CuCr₂O₄(s) that suppressed the formation of CrO₂(OH)₂(g). The retention and speciation of Cu, Cr and As in bottom ash was further determined from combustion experiments of CCA wood fuel particles in a single particle reactor. Local chemical equilibrium model calculations were performed to simulate the combustion stages of a burning CCA treated wood fuel particle: drying, devolatilization, char burning and post-combustion. The results from the work showed that a mix of global and local chemical equilibrium model calculations is needed to describe the reality and that the combustion stages are partially overlapping. The fate of harmful trace elements, including Cu, Cr and As, was finally studied in full scale (65 MW) combustion experiments. Particles from the raw flue gas emissions were sampled and analyzed. The comparison with chemical equilibrium model calculations showed that the model explained the results well, but due to lack of thermodynamic data for K₂ZnCl₄(s), the formation of this phase could not be predicted.</p>

In the Mars atmosphere, reactivity of trace components is as relevant as that of the major compounds if formation of complex molecules is considered. These are of great importance concerning the existence of a past or future life on Mars. In this context, the gas-phase chemistry of alkylcarbonate and alkyloxalate ions and radicals, ROCOO–/• and ROCOCOO–/•, is investigated for different alkyl substituents R (H, CH3, C2H5, i-C3H7, and t-C4H9). This study describes the structures, stability, and unimolecular dissociation behavior of these species and is achieved by means of mass spectrometric methods and ab initio calculations. Standard heats of formation of the ions and radicals are determined via computational methods, using atomization energies and bond-separation reactions. Vertical charge-transfer experiments are performed to provide evidence for the existence of the radicals under study and the NIDD (ion and neutral decomposition difference) method is employed to determine their reactivity. Typical processes observed involve direct bond cleavages leading to elimination of carbon dioxide. Concerning anionic compounds, classical metastable ion (MI) and collisional activation (CA) experiments enable the determination of their gas-phase behavior. This, in contrast to radicals, is not only constituted by direct bond cleavages, but also by hydride-transfer reaction or carbon monoxide expulsion involving formation of ion-neutral complexes as intermediates. Translational energy loss spectra are also employed to gain more insights concerning the dissociation energetics of CH3OCOO• and CH3OCOO+ formed by vertical charge-transfer of methylcarbonate. This rather unusual method for such study implies a careful evaluation of the error caused by the instrument which may otherwise generate dramatic deviations of the results compared to theory.

Aggregation of the Amyloid β (Aβ) peptide to amyloid fibrils is associated with the outbreak of Alzheimer’s disease. Early aggregation intermediates in form of soluble oligomers are of special interest as they are believed to be the major toxic components in the process. These oligomers are of disordered and transient nature. Therefore, their detailed molecular structure is difficult to access experimentally and often remains unknown. In the present work extensive, fully atomistic replica exchange molecular dynamics simulations were performed to study the preaggregated, monomer states and early aggregation intermediates (dimers, trimers) of Aβ(25-35) and Aβ(10-35)-NH2 in aqueous solution. The folding and aggregation of Aβ(25-35) were studied at neutral pH and 293 K. Aβ(25-35) monomers mainly adopt β-hairpin conformations characterized by a β-turn formed by residues G29 and A30, and a β-sheet between residues N27–K28 and I31–I32 in equilibrium with coiled conformations. The β-hairpin conformations served as initial configurations to model spontaneous aggregation of Aβ(25-35). As expected, within the Aβ(25-35) dimer and trimer ensembles many different poorly populated conformations appear. Nevertheless, we were able to distinguish between disordered and fibril-like oligomers. Whereas disordered oligomers are rather compact with few intermolecular hydrogen bonds (HBs), fibril-like oligomers are characterized by the formation of large intermolecular β-sheets. In most of the fibril-like dimers and trimers individual peptides are fully extended forming in- or out-of-register antiparallel β-sheets. A small amount of fibril-like trimers contained V-shaped peptides forming parallel β-sheets. The dimensions of extended and V-shaped oligomers correspond well to the diameters of two distinct morphologies found for Aβ(25-35) fibrils. The transition from disordered to fibril-like Aβ(25-35) dimers is unfavorable but driven by energy. The lower energy of fibril-like dimers arises from favorable intermolecular HBs and other electrostatic interactions which compete with a loss in entropy. Approximately 25 % of the entropic cost correspond to configurational entropy. The rest relates to solvent entropy, presumably caused by hydrophobic and electrostatic effects. In contrast to the transition towards fibril-like dimers the first step of aggregation is driven by entropy. Here, we compared structural and thermodynamic properties of the individual monomer, dimer and trimer ensembles to gain qualitative information about the aggregation process. The β-hairpin conformation observed for monomers is successively dissolved in dimer and trimer ensembles while instead intermolecular β-sheets are formed. As expected upon aggregation the configurational entropy decreases. Additionally, the solvent accessible surface area (SASA), especially the hydrophobic SASA, decreases yielding a favorable solvation free energy which overcompensates the loss in configurational entropy. In summary, the hydrophobic effect, possibly combined with electrostatic effects, yields an increase in solvent entropy which is believed to be one major driving force towards aggregation. Spontaneous folding of the Aβ(10-35)-NH2 monomer was modeled using two force fields, GROMOS96 43a1 and OPLS/AA, and compared to primary NMR data collected at pH 5.6 and 283 K taken from the literature. Unexpectedly, the two force fields yielded significantly different main conformations. Comparison between experimental and calculated nuclear Overhauser effect (NOE) distances is not sufficient to distinguish between the different force fields. Additionally, the comparison with scalar coupling constants suggest that the chosen protonation in both simulations corresponds to a pH lower than in the experiment. Based on this analysis we were unable to determine which force field yields a better description of this system. Dimerization of Aβ(10-35)-NH2 was studied at neutral pH and 300 K. Dimer conformations arrange in many distinct, poorly populated and rather complex alignments or interlocking patterns which are rather stabilized by side chain interactions than by specific intermolecular hydrogen bonds. Similar to Aβ(25-35) dimers, transition towards β-sheet-rich, fibril-like Aβ(10-35) dimers is driven by energy competing with a loss in entropy. Here, transition is mediated by favorable peptide-solvent and solvent-solvent interactions mainly arising from electrostatic interactions. / Die Aggregation des Amyloid β (Aβ) Peptids zu Amyloidfibrillen wird mit dem Ausbruch der Alzheimer Krankheit in Verbindung gebracht. Die toxische Wirkung auf Zellen wird vor allem den zeitigen Intermediaten in Form von löslichen Oligomeren zugeschrieben. Aufgrund deren ungeordneter und flüchtiger Natur kann die molekulare Struktur solcher zeitigen Oligomere oft experimentell nicht aufgelöst werden. In der vorliegenden Arbeit wurden aufwendige atomistische Replica-Exchange-Molekulardynamik-Simulationen durchgeführt, um die molekulare Struktur von Monomeren und Oligomeren der Fragmente Aβ(25-35) und Aβ(10-35)-NH2 in Wasser zu untersuchen. Die Faltung und Aggregation von Aβ(25-35) wurde bei neutralem pH und 293 K untersucht. Monomere dieses Fragments bilden hauptsächlich β-Haarnadelkonformationen im Gleichgewicht mit Knäulstrukturen. Innerhalb der β-Haarnadelkonformationen bilden die Residuen G29 und A30 einen β-turn, während N27–K28 and I31–I32 ein β-Faltblatt bilden. Diese β-Haarnadelkonformationen bildeten den Ausgangspunkt zur Modellierung spontaner Aggregation. Wie zu erwarten, bilden sich eine Vielzahl verschiedener, gering besetzter Dimer- und Trimerkonformationen. Mit Hilfe einer gröberen Einteilung können diese in ungeordnete und fibrillähnliche Oligomere unterteilt werden. Ungeordnete Oligomere bilden kompakte Strukturen, die nur durch wenige intermolekulare Wasserstoffbrückenbindungen (HBB) stabilisiert sind. Typisch für fibrillähnliche Oligomere ist hingegen die Ausbildung großer intermolekularer β-Faltblätter. In vielen dieser Oligomere finden wir antiparallele, in- oder out-of-register β-Faltblätter gebildet durch vollständig ausgestreckte Peptide. Ein kleiner Teil der fibrillähnlichen Trimere bildet parallele, V-förmige β-Faltblätter. Die Ausdehnungen ausgestreckter und V-förmiger Oligomere entspricht in etwa den Durchmessern von zwei verschiedenen, experimentell gefundenen Fibrillmorphologien für Aβ(25-35). Die Umwandlung von ungeordneten zu fibrillähnlichen Aβ(25-35) Dimeren ist energetisch begünstigt, läuft aber nicht freiwillig ab. Fibrillähnliche Dimere haben eine geringere Energie aufgrund günstiger Peptidwechselwirkungen (HBB, Salzbrücken), welche durch den Verlust an Entropie kompensiert wird. Etwa 25 % entsprechen dem Verlust an Konfigurationsentropie. Der restliche Anteil wird einem Verlust an Lösungsmittelentropie aufgrund von hydrophoben und elektrostatischen Effekten zugesprochen. Im Gegensatz zur Umwandlung in fibrillähnliche Dimere, ist die Assoziation von Monomeren oder Oligomeren entropisch begünstigt. Beim Vergleich thermodynamischer Eigenschaften der Monomer-, Dimer- und Trimersysteme zeigt sich im Verlauf der Aggregation, wie erwartet, eine Abnahme der Konfigurationsentropie. Zusätzlich nimmt die dem Lösungsmittel zugängliche Oberfläche (SASA), insbesondere die hydrophobe SASA, ab. In Verbindung damit beobachten wir eine Abnahme der freien Solvatisierungsenergie, welche den Verlust an Konfigurationsentropie kompensiert. Mit anderen Worten, der hydrophobe Effekt in Kombination mit elektrostatischen Wechselwirkungen führt zu einem Ansteigen der Lösungsmittelentropie und begünstigt damit die Aggegation. Die spontane Faltung des Aβ(10-35)-NH2 Monomers wurde für zwei verschiedene Proteinkraftfelder, GROMOS96 43a1 und OPLS/AA, untersucht und mit primären NMR-Daten aus der Literatur, gemessen bei pH 5.6 und 283 K, verglichen. Beide Kraftfelder generieren unterschiedliche Hauptkonformationen. Der Vergleich zwischen experimentellen und berechneten Kern-Overhauser-Effekt (NOE) Abständen ist nicht ausreichend, um zwischen beiden Kraftfeldern zu unterscheiden. Der Vergleich mit Kopplungskonstanten aus Experiment und Simulation zeigt, dass beide Simulationen einem pH-Wert geringer als 5.6 ensprechen. Basierend auf den bisherigen Ergebnissen können wir nicht entscheiden, welches Kraftfeld eine bessere Beschreibung für dieses System liefert. Die Dimerisierung von Aβ(10-35)-NH2 wurde bei neutralem pH und 300 K untersucht. Wir finden eine Vielzahl verschiedener, gering besetzter Dimerstrukturen, welche eher durch Seitenkettenkontakte als durch spezifische HBB stabilisiert sind. Wie bei den Aβ(25-35) Dimeren, ist die Umwandlung zu β-Faltblattreichen, fibrillähnlichen Aβ(10-35) Dimeren energetisch begünstigt, konkurriert aber mit einem Entropieverlust. Die Umwandlung wird in diesem Fall durch elektrostatische Wechselwirkungen zwischen Peptid und Lösungsmittel und innerhalb des Lösungsmittels bestimmt.

In view of the important applications of carbides and carbo-nitrides of transition metals in the heat-resistant and hard materials industries, the thermodynamic activities of Cr and Mn in the Cr-C, Fe-Cr-C, Mn-Ni-C and Mn-Ni-C-N systems have been studied in the present work by the use of the galvanic cell technique. CaF2single crystals were used as the solid electrolyte. The phase relationships in selected regions of the systems in question were investigated by the use of the equilibration technique. The phase compositions and microstructures of the alloys were analysed by X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM). In the Cr-C system, the Gibbs energy of formation of Cr3C2 were obtained from ElectroMotive Force (EMF) measurements conducted in the temperature range 950-1150 K. The values of the enthalpy of formation of Cr3C2 were evaluated by the third-law method. The ground-state energy of the hypothetic end-member compound CrC3, in the bcc structure at 0 K, was calculated by use of the Ab-initio method. Based on the obtained results the Cr-C system was reassessed by use of the CALPHAD approach. In the Fe-Cr-C system, 16 different alloys were quenched at 1223 K and their equilibrium phases identified by XRD. The experimental results show that the substitution of Cr by Fe in the (Cr,Fe)7C3 carbide changes the lattice parameters of the phase. A slight decrease of the lattice parameters with an increase in the Fe content was established. The lattice parameters of the γ-phase in the Fe-Cr solid solution did also show a decrease with an increase of the Fe content. The activities of chromium in Fe-Cr-C alloys were investigated in the temperature range 940-1155 K. The activity of chromium decreases with an increase in the Fe content when the ratio of C/(Cr+C) was constant. It was also established that the activity of chromium decreases with an increase of the carbon content when the iron content was constant. The experimental results obtained were compared with the data calculated by use of the Thermo-Calc software. In the Mn-Ni-C system the phase relationships were investigated at 1073 K as well as at 1223 K. The experimental results obtained showed that the site fraction of Ni in the metallic sublattice of the carbides M23C6, M7C3 and M5C2 (M=Mn and Ni) was quite low (approximately 2~3 percent). The activities of manganese in Mn-Ni-C alloys were investigated in the temperature range 940-1165 K. The three-phase region γ/M7C3/graphite was partly constructed at 1073 K. In the Mn-Ni-C-N system, nitrogen was introduced into Mn-Ni-C alloys by equilibrating with N2 gas. It was established that the solubility of nitrogen in the investigated alloys was effected by the carbon content, and that a (Mn,Ni)4(N,C) compound was formed in the nitrided alloys. EMF measurements were performed on Mn-Ni-C-N alloys in the temperature interval 940-1127 K. The addition of nitrogen to Mn-Ni-C alloys was found to decrease the activity of manganese. The negative effect of nitrogen on the activity of manganese was found to decrease as the carbon content increased. Keywords: Thermodynamic activity; Galvanic cell technique; Transition metal carbides; Transition metal nitrides; Phase equilibrium; Thermodynamics; Differential thermal analysis; Scanning electron microscopy; Transmission electron microscopy; Ab-initio calculations; CALPHAD approach;