Consumption of cocoa and dark chocolate products has been associated with positive health outcomes including reduced onset of cardiovascular disease, inflammation, diabetes, obesity, and platelet disorders. Cocoa polyphenols, putatively responsible for these beneficial activities, are highly impacted by cocoa variety, agronomic effects and processing history. However, the difference in polyphenol concentration and composition between cocoa products originating from different hybrid clones (selected for high yield) or from different fermentation conditions is not fully understood. Detailed polyphenol characterization including determination of total polyphenol and total procyanidin concentrations, and qualitative and quantitative analysis of (mean) degree of polymerization was conducted. Significant differences in total polyphenol and procyanidin concentrations were observed between five genetic clones grown by the USDA-ARS Cocoa Germplasm Repository located in Mayagüez, Puerto Rico. To facilitate cocoa fermentation research in laboratories distant from cocoa harvesting sites, a laboratory-scale cocoa fermentation model system was developed in this study. This model system used dried, unfermented, cocoa beans and simulated pulp medium as the starting material. The model system supported growth of the essential succession of cocoa fermenting microorganisms and generated similar chemical changes to those observed in on-farm cocoa fermentation. Using this model system, the impact of inoculation with proprietary yeast strains Saccharomyces cerevisiae Lev F and Saccharomyces cerevisiae Lev B on cocoa polyphenol concentration and composition was evaluated. Inoculation with both yeast strains resulted in increased fermentation rate and Lev B inoculation resulted in higher total polyphenol and procyandin contents at the end of fermentation. Overall, the present work addressed the influence of cocoa variety selection and fermentation process conditions on the composition and concentration of polyphenols. These findings will contribute to continued efforts to develop cocoa products with optimized bioactivity and maximum disease preventative effects. / PHD / Annual worldwide cocoa production exceeds four million tons and the cocoa market impacts not only cocoa growing regions, but also countries producing cocoa products. Consumption of cocoa and dark chocolate products has been associated with positive health outcomes including reduced onset of cardiovascular disease, inflammation, diabetes, obesity, and platelet disorders. Cocoa polyphenols, compounds increasingly associated with health benefits, are highly impacted by the variety and processing history of cocoa. However, the extent to which cocoa genetic variety and processing conditions impact polyphenol concentration and composition is not fully understood. Polyphenol characterization was conducted for five genetic varieties sourced from the USDA cocoa germplasm repository located in Mayagüez, Puerto Rico and it was found that genetic variance could contribute to differences in polyphenol concentration. The main focus in this thesis was to develop laboratory cocoa fermentation model system to facilitate cocoa research in laboratories distant from the cocoa growing region. This model system used dried, unfermented cocoa beans and simulated pulp medium as the starting material. The model system was effective in that it supported growth of the essential succession of coca fermenting microorganisms and generated similar chemical changes to those observed in on-farm cocoa fermentation. This model system could be further applied to test the impact of fermentation conditions on cocoa bean quality. The potential for using yeast starter cultures to improve control and consistency of cocoa fermentation was evaluated using the model fermentation system. Yeast inoculation improved fermentation rate, and polyphenol concentration in fermented beans was higher when cocoa fermentation was inoculated with the yeast strain Saccharomyces cerevisiae Lev B. Overall, the present work addressed the influence of cocoa variety selection and fermentation process conditions on the composition and concentration of polyphenols. These findings will contribute to continued efforts to develop cocoa products optimized for maximum health benefits.

For manufacturers of complex interdisciplinary system solutions, the Digital Thread is an essential element that serves as the backbone of technical and organizational data flows. This study proposes a graph-based Digital Thread that integrates a Digital Model and a derived Digital Twin in a native graph database in a polyglot architecture. The approach includes dynamic processes such as advanced interdisciplinary change management and additional data from different lifecycle phases, using objects and relations described by attributes to minimize redundancy while enabling view creation and filtering. Companies often have discipline-oriented IT landscapes that create data silos and prevent contextbased integration of data and process models. The Digital Thread as a backbone represents an approach to overcome these silos as a system lifecycle-spanning system.

<p>Cilj &ndash; Prvi cilj istraživanja je kreiranje modela podataka i implementacija informacionog sistema zasnovanog na modelu za potrebe vrednovanja publikovanih naučno-istraživačkih rezultata. Model bi bio primenjen u CRIS UNS informacionom sistemu, kao podr&scaron;ka sistemu vrednovanja.<br />Drugi cilj istraživanja je utvrđivanje u kojoj meri i na koji način se može automatizovati proces evaluacije koji se zasniva na različitim pravilima i pravilnicima.<br />Metodologija &ndash; Kako bi se definisalo pro&scaron;irenje CERIF modela neophodno je bilo identifikovati različite aspekte podataka koji su prisutni u evaluaciji naučno-istraživačkih publikacija. Stoga, zarad potreba istraživanja, odabrana su i analizirana su dokumenta koja predstavljaju različite nacionalne pravilnike, okvire i smernice za evaluaciju.<br />Za modelovanje specifikacije arhitekture sistema za vrednovanje kori&scaron;ćeni su CASE alati koji su bazirani na objektno-orijentisanoj metodologiji (UML 2.0). Za implementaciju pro&scaron;irenja CERIF modela u CRIS UNS sistemu kori&scaron;ćena je Java platforma i tehnologije koji olak&scaron;avaju kreiranje veb aplikacija kao &scaron;to su AJAX, RichFaces, JSF itd. Pored navedene op&scaron;te metodologije za razvoj softverskih sistema kori&scaron;ćeni su primeri dobre prakse u razvoju informacionih sistema. To se pre svega odnosi na principe kori&scaron;ćene u razvoju institucionalnih repozitorijuma, bibliotečkih informacionih sistema, informacionih sistema naučno-istraživačke delatnosti, CRIS sistema, sistema koji omogućuju evaluaciju podataka itd.<br />Ekspertski sistem koji bi podržao automatizaciju procesa evaluacije po različitim pravilnicima odabran je na osnovu analize postojećih re&scaron;enja za sisteme bazirane na pravilima i pregleda naučne literature.<br />Rezultati &ndash; Analizom nacionalnih pravilnika i smernica dobijen je skup podataka na osnovu kojeg je moguće evaluirati publikovane rezultate po odabranim pravilnicima.<br />Razvijen je model podataka kojim se predstavljaju svi podaci koji učestvuju u procesu evaluacije i koji je kompatibilan sa CERIF modelom podataka.<br />Predloženi model je moguće implementirati u CERIF kompatibilnim CRIS sistemima, &scaron;to je potvrđeno implementacijom informacionog sistema za vrednovanje publikovanih naučno-istraživačkih rezultata u okviru CRIS UNS.<br />Ekspertski sistem baziran na pravilima može biti iskori&scaron;ćen za potrebe automatizacije procesa evaluacije, &scaron;to je potvrđeno predstavom i implementacijom SRB pravilnika u Jess sistemu baziranom na pravilima.<br />Praktična primena &ndash;Zaključci proiza&scaron;li iz analize pravilnika (npr. poređenje sistema i definisanje metapodataka za vrednovanje) se mogu primeniti pri definisanju modela podataka za CERIF sisteme i za sisteme koji nisu CERIF orijentisani.<br />Sistem za podr&scaron;ku vrednovanju publikovanih naučno-istraživačkih rezultata je implementiran kao deo CRIS UNS sistema koji se koristi na Univerzitetu u Novom Sadu čime je obezbeđeno vrednovanje publikovanih naučno-istraživačkih rezultata za različite potrebe (npr. promocije u naučna i istraživačka zvanja, dodele nagrada i materijalnih sredstava, finansiranje projekata, itd.), po različitim pravilnicima i komisijama.<br />Vrednost &ndash; Dati su metapodaci na osnovu kojih se vr&scaron;i vrednovanje publikovanih rezultat istraživanja po raznim nacionalnim pravilnicima i smernicama. Dat je model podataka i pro&scaron;irenje CERIF modela podataka kojim se podržava vrednovanje rezultata istraživanja u CRIS sistemima. Posebna prednost pomenutih modela je nezavisnost istih od implementacije sistema za vrednovanje rezultata istraživanja. Primena predloženog pro&scaron;irenje CERIF modela u CRIS sistemima praktično je pokazana u CRIS sistemu Univerziteta u Novom Sadu. Sistem za vrednovanje koji se bazira na pro&scaron;irenju CERIF modela pruža i potencijalnu interoperabilnost sa sistemima koji CERIF model podržavaju. Implementacijom informacionog sistema za vrednovanje, vrednovanje naučnih publikacija je postalo olak&scaron;ano i transparentnije. Potvrda koncepata da se ekspertski sistemi bazirani na pravilima mogu koristiti za automatizaciju vrednovanja, otvara totalno novi okvir za implementaciju informacionih sistema za podr&scaron;ku vrednovanja postignutih rezultata istraživanja.</p> / <p>Aim &ndash; The first aim of the research was creation of data model and implementation of information system based on the proposed model for the purpose of evaluation of published research outputs. The model is applied in CRIS information system to support the system for evaluation.<br />The second objective was determination of the manner and extent in which the evaluation process that is based on different rules and different rulebooks could be automated.<br />Methodology - In order to define the extension of the CERIF model, it was necessary to identify the various aspects of data which is relevant in evaluation of scientific research publications. Therefore, documents representing different national regulations, frameworks and guidelines for evaluations were selected and analyzed.<br />For the modeling of the system architecture, CASE tools were used, which are based on object-oriented methodology (UML 2.0). To implement the extension of the CERIF model within the CRIS UNS system, JAVA platform and technologies that facilitate creation of web applications such as AXAJ and RichFaces were used. In addition to this general methodology for development of software systems, best practice examples from the information systems development are also used. This primary refers to the principles used in development of institutional repositories, library information systems, information systems of the scientific-research domain, CRIS systems, systems that enable evaluation of data, etc.<br />The expert system that supports automation of the evaluation process by different rulebooks was selected based on analysis of the existing solutions for rule based systems and examination of scientific literature.<br />Results - By analysis of the national rulebooks and guidelines, a pool of data was gathered, which served as a basis for evaluation of published results by any analyzed rulebook.<br />A data model was developed, by which all data involved in the evaluation process can be represented. The proposed model is CERIF compatible.<br />The proposed model can be implemented in CERIF compatible CRIS systems, which was confirmed by the implementation of an information system for evaluation of published scientific research results in CRIS UNS.<br />An expert system based on rules can be used for the needs of automation of the evaluation process, which was confirmed by the presentation and implementation of the Serbian Rulebook by Jess.<br />Practical application - The conclusions raised from the analysis of rulebooks (e.g. Comparison of systems and defining metadata for evaluation) can be applied in defining the data model for CERIF systems and for systems that are not CERIF oriented.<br />The system for support of evaluation of published scientific research results was implemented as part of the CRIS UNS system used at the University of Novi Sad, thus providing evaluation of published scientific research results for different purposes (e.g. promotion in scientific and research titles, assignment of awards and material resources, financing of projects, etc.), according to different rulebooks and commissions.<br />Value &ndash; Metadata is provided on which basis the evaluation of published research results by various national rulebooks and guidelines is conducted. A data model and an expansion of the CERIF data model that supports the evaluation of the research results within CRIS systems are given. A special advantage of these models is their independence of the implementation of the system for evaluation of research results. The application of the proposed extension of the CERIF model into CRIS systems practically is demonstrated in the CRIS system of the University of Novi Sad. The system that implements an expansion of the CERIF model provides a potential interoperability with systems that support CERIF model. After the implementation of the information system for evaluation, the evaluation of scientific publications becomes easier and more transparent. A confirmation of the concept that the expert systems based on rules can be used in automation of the evaluation process opens a whole new framework for implementation of information systems for evaluation.</p>

No description available.

Un défi majeur en oncologie clinique est de caractériser avec précision la réponse des patients aux agents thérapeutiques. Actuellement, il n'existe pas de modèles et de tests fiables capable de reproduire précisément une tumeur primaire dans toute sa complexité. Or, ce paramètre est essentiel pour mettre en œuvre une stratégie de médecine personnalisée capable d'identifier le régime de traitement le plus approprié pour un patient particulier dans un délai cliniquement pertinent. Pour répondre à ce besoin, notre groupe a développé un nouveau modèle 3D ex vivo qui repose sur la micro-dissection d'un échantillon de tumeur (MDT) d'un patient et l'utilisation de technologies microfluidiques pour maintenir la viabilité du tissu et le microenvironnement tumoral naturel afin d’évaluer la sensibilité aux traitements dans un délai adapté à la prise de décision clinique. Cette approche permettrait de sélectionner les thérapies les plus efficaces tout en réduisant l'administration de traitements inefficaces associés à des effets secondaires indésirables, ainsi que les coûts de prise en charge des patients. Des travaux précédemment publiés par notre équipe ont montré que la viabilité des cellules cancéreuses situées dans notre modèle de tumeur ex vivo pouvait être caractérisée par microscopie confocale sur l’intégralité du MDT ou par cytométrie de flux sur les MDTs après dissociation enzymatique des cellules. Cependant, ces techniques présentent des limitations en termes de résolution visuelle pour la microscopie confocale et de sensibilité et information spatiale pour la cytométrie de flux. Nous proposons ici d’associer notre modèle 3D de MDTs en microfluidiques à des techniques d’immuno-histopathologie, dans le but d’offrir une évaluation moléculaire, spatiale et quantitative de la réponse de la tumeur au traitement. Pour cela, nous avons optimisé une procédure de lithographie en paraffine de nos systèmes microfluidiques, permettant la production de blocs de micro-étalages micro-réseaux de tissus micro-disséqués (MDTMA). afin de permettre une coloration morphologique du tissu et un marquage de protéines spécifiques pour analyser l'architecture tissulaire, la prolifération et l’apoptose cellulaire au sein des échantillons traités. En outre, nous avons montré que le modèle ex vivo est comparable et corrélé au système de modèle de souris in vivo de référence pour l'essai de chimio-sensibilité. Suite à l’optimisation de ce modèle, nous avons collecté 25 échantillons de tumeurs de patientes atteintes de cancer de l’ovaire, pour réaliser des MDTs et des cultures de cellules primaires afin de comparer les profils transcriptomiques de ces deux modèles avec celui de la tumeur d’origine, et d'analyser les réponses aux traitements et le microenvironnement tumoral. Les données transcriptomiques obtenues par micropuces ARN nous ont permis d'effectuer une analyse bio-informatique des voies de signalisation incluant un groupement hiérarchique non supervisé. Nos résultats montrent que les MDT à chaque point de temps (jour 0, 8 et 15) sont génétiquement similaires à la tumeur primaire par opposition aux cultures cellulaires primaires, et que les principales voies dérégulées sont impliquées dans la réponse cellulaire au stress. Nous avons observé une viabilité élevée des cellules au sein des MDT sur une période de culture de 15 jours. En outre, nous avons déterminé qu'un régime de chimiothérapie (carboplatine et paclitaxel) consistant en une induction thérapeutique de 10 heures suivie d'une période de récupération de 14 heures était idéal pour caractériser la réponse au traitement. Notre analyse de prédiction de la réponse des patients montre que nous avons une corrélation positive élevée d'une efficacité de 95 % entre la réponse ex vivo et la réponse clinique pour les patients appariés. En général, nos résultats suggèrent que notre technique fournit un modèle plus sophistiqué et précis pour récapituler la réponse de la tumeur primaire dans un laps de temps cliniquement adapté, et pourrait servir de plateforme pour tester de nouvelles thérapeutiques, et d'outil d'orientation clinique pour la réponse des patients. / A major challenge in clinical oncology is the inability to accurately predict the patients’ response to therapeutic agents. Currently, there are no reliable models and assays available that reiterate the immense complexity of a primary tumor. These factors are important to implement a personalized medicine strategy capable of identifying the most suitable treatment regimen for a particular patient in a clinically relevant timeframe. To answer this need, our group has developed a novel ex vivo 3D model that relies on the micro-dissection of a patient’s tumor specimen and the utilization of microfluidic technologies to monitor drug sensitivity within a time-frame suitable for clinical decision-making. This approach would allow for better selection of effective therapies and limit the administration of ineffective treatments, further improving treatment outcome of patients while reducing cost and drug-induced toxicities. Previously published work studied that the viability of cancer cells located within the tumor was characterized using two imaging modalities: confocal microscopy and flow cytometry. However, each technique has its own disadvantage, limiting their ability to molecularly characterize the effect of therapeutic agents on cancer cells. Thus, we hypothesize that our 3D ex vivo tumor-derived model coupled to a pathology-like tool would allow for a more comprehensive approach to evaluate tumor response to treatment, providing a readout system to closely mirror the patient’s response, and evaluating molecular mechanisms involved in response to drugs. To address this hypothesis, we optimized a paraffin-embedding lithography procedure allowing the production of micro-dissected tissue micro-array (MDTMA) block to allow morphological and protein-specific staining to analyze the cellular integrity and tissue architecture of treated samples. In addition, we showed that ex vivo model is comparable and correlated to the gold standard in vivo mouse model system for chemosensitivity assay. Moreover, we collected, following informed consent, 25 post-surgical OC patient tumor samples, to form micro-dissected tissues (MDTs), and primary cell cultures for micro-array analysis and characterization of the TME and response prediction. The micro-array data allowed us to perform unsupervised hierarchical clustering and pathway analysis showing that the MDTs at each time-point (day 0, 8 and 15) are genetically similar to the primary tumor as opposed to the primary cell cultures and that main deregulated pathways are involved in cellular response to stress. We observed a high viability of cells within MDTs over a culture period of 15 days. In addition, we determined that a treatment regimen consisting of a 10-hour therapy induction followed by a 14-hour recovery period was ideal for characterizing carboplatin treatment response. Our response prediction analysis of patients shows that we have a high positive correlation of 95% efficiency between ex vivo and clinical response for matched patients. In general, our results suggest that our ex vivo drug response model provides a more sophisticated model to recapitulate primary tumor response in a clinically suitable timeframe that can be exploited further serving, in part, as a platform to test new therapeutics and as a clinical guidance tool for patient response.

In dieser Arbeit werden mit einem Raumtemperatur-Modellsystem die Wechselwirkungen und Überlagerungen der verschiedenen Einflussparameter auf die Partikelabscheidung in keramischen Tiefenfiltern dargestellt. Aussagen zum zeitlichen Beladungsverhalten, dem Einfluss der Strukturparameter und der Oberflächenrauheit der Filter auf die Abscheidung werden diskutiert. Außerdem wird die Abscheideeffizienz in Abhängigkeit der Eigenschaften der Verunreinigungen (Größe, Agglomeratzustand, Dichte), sowie dem Vorhandensein von Mikro- oder Nanogasblasen untersucht. Mit Hilfe der Computertomografie können die im Filter abgeschiedenen Verunreinigungen lokal abgebildet werden, was zum Verständnis der in schaumkeramischen Filtern ablaufenden Prozesse bei der Aluminium-Schmelzefiltration beiträgt. Ergebnisse einer dynamischen Bildanalyse lassen Rückschlüsse auf den Fraktionsabscheidegrad der Filter zu.

The research in the field of travel demand modeling is driven by the need to understand individuals’ behavior in the context of travel-related decisions as accurately as possible. In this regard, the activity-based approach to modeling travel demand has received substantial attention in the past decade, both in the research arena as well as in practice. At the same time, recent efforts have been focused on more fully realizing the potential of activity-based models by explicitly recognizing the multi-dimensional nature of activity-travel decisions. However, as more behavioral elements/dimensions are added, the dimensionality of the model systems tends to explode, making the estimation of such models all but infeasible using traditional inference methods. As a result, analysts and practitioners often trade-off between recognizing attributes that will make a model behaviorally more representative (from a theoretical viewpoint) and being able to estimate/implement a model (from a practical viewpoint). An alternative approach to deal with the estimation complications arising from multi-dimensional choice situations is the technique of composite marginal likelihood (CML). This is an estimation technique that is gaining substantial attention in the statistics field, though there has been relatively little coverage of this method in transportation and other fields. The CML approach is a conceptually and pedagogically simpler simulation-free procedure (relative to traditional approaches that employ simulation techniques), and has the advantage of reproducibility of the results. Under the usual regularity assumptions, the CML estimator is consistent, unbiased, and asymptotically normally distributed. The discussion above indicates that the CML approach has the potential to contribute in the area of travel demand modeling in a significant way. For example, the approach can be used to develop conceptually and behaviorally more appealing models to examine individuals’ travel decisions in a joint framework. The overarching goal of the current research work is to demonstrate the applicability of the CML approach in the area of activity-travel demand modeling and to highlight the enhanced features of the choice models estimated using the CML approach. The goal of the dissertation is achieved in three steps as follows: (1) by evaluating the performance of the CML approach in multivariate situations, (2) by developing multidimensional choice models using the CML approach, and (3) by demonstrating applications of the multidimensional choice models developed in the current dissertation. / text

I started writing this thesis not only to obtain a doctoral degree, but also to compile in a particular way all the work that I have done during this time. The articles published during these years can only give a short overview of my research task. I decided to give my own perspective of the things I have learned and the results I have obtained. Some sections are directly the published articles, but some other are not and contain a significant amount of unpublished data. Even in some cases the published plots have been modified / altered to provide more insight or to maintain consistency. Historical perspectives often provide a deep understanding of the problems and have been briefly discussed in some chapters. This thesis contains theoretical and computer simulation studies to under-stand effects of spatial correlation on dynamics in several complex systems. Based on the different phenomena studied, the thesis has been divided into three major parts: I. Pair hydrophobicity, composition-dependent anomalies and structural trans-formations in aqueous binary mixtures II. Microscopic analysis of hydrophobic force law in a two dimensional (2D) water-like model system III. Diffusion of a tagged particle on a rugged energy landscape with spatial correlations The three parts have been further divided into ten chapters. In the following we provide part-wise and chapter-wise outline of the thesis. Part I consists of six chapters, where we focus on several important aqueous binary mixtures of amphiphilic molecules. To start with, Chapter 1 provides an introduction to non-ideality often encountered in aqueous binary mixtures. Here we briefly discuss the existing ideas of structural transformations associated with solvation of a foreign molecule in water, with particular emphasis on the classic “iceberg” model. Over the last decade, several investigations, especially neutron scattering and diffraction experiments, have questioned the validity of existing theories and have given rise to an alternate molecular picture involving micro aggregation of amphiphilic co-solvents in their aqueous binary mixtures. Such microheterogeneity was also supported by other experiments and simulations. In Chapter 2, we present our calculation of the separation dependence of potential of mean force (PMF) between two methane molecules in water-dimethyl sulfoxide (DMSO) mixture, using constrained molecular dynamics simulation. It helps us to understand the composition-dependence of pair hydrophobicity in this binary solvent. We find that pair hydrophobicity in the medium is surprisingly enhanced at DMSO mole fraction xDMSO ≈ 0.15, which explains several anomalous properties of this binary mixture – including the age-old mystery of DMSO being a protein stabilizer at lower concentration and protein destabilizer at higher concentration. Chapter 3 starts with discussion of non-monotonic composition dependence of several other properties in water-DMSO binary mixture, like diffusion coefficient, local composition fluctuation and fluctuations in total dipole moment of the system. All these properties exhibit weak to strong anomalies at low solute concentration. We attempt to provide a physical interpretation of such anomalies. Previous analyses often suggested occurrence of a “structural transformation” (or, microheterogeneity) in aqueous binary mixtures of amphiphilic molecules. We show that this structural transformation can be characterized and better understood under the purview of percolation theory. We define the self-aggregates of DMSO as clusters. Analysis of fractal dimension and cluster size distribution with reference to corresponding “universal” scaling exponents, combined with calculation of weight-averaged fraction of largest cluster and cluster size weight average, reveal a percolation transition of the clusters of DMSO in the anomalous concentration range. The percolation threshold appears at xDMSO ≈ 0.15. The molecular picture suggests that DMSO molecules form segregated islands or micro-aggregates at concentrations below the percolation threshold. Close to the critical concentration, DMSO molecules start forming a spanning cluster which gives rise to a bi-continuous phase (of water-rich region and DMSO-rich region) beyond the threshold of xDMSO ≈ 0.15. This percolation transition might be responsible for composition-dependent anomalies of the binary mixture in this low concentration regime. Similar phenomenon is observed for another amphiphilic molecule – ethanol, as discussed in Chapter 4. We again find composition dependent anomalies in several thermophysical properties, such as local composition fluctuation, radial distribution function of ethyl groups and self-diffusion co-efficient of ethanol. Earlier experiments often suggested distinct structural regimes in water-ethanol mixture at different concentrations. Using the statistical mechanical techniques introduced in the previous chapter, we show that ethanol clusters undergo a percolation transition in the anomalous concentration range. Despite the lack of a precise determination of the percolation threshold, estimate lies in the ethanol mole fraction range xEtOH ≈ 0.075 - 0.10. This difficulty is probably due to transient nature of the clusters (as will be discussed in Chapter 6) and finite size of the system. The scaling of ethanol cluster size distribution and the fractal behavior of ethanol clusters, however, conclusively demonstrate their “spanning” nature. To develop a unified understanding, we further study the composition-dependent anomalies and structural transformations in another amphiphilic molecule, tertiary butyl alcohol (TBA) in Chapter 5. Similar to the above-mentioned aqueous binary mixtures of DMSO and ethanol, we demonstrate here that the anomalies occur due to local structural changes involving self-aggregation of TBA molecules and percolation transition of TBA clusters at xTBA ≈ 0.05. At this percolation threshold, we observe a lambda-type divergence in the fluctuation of the size of the largest TBA cluster, reminiscent of a critical point. Interestingly, water molecules themselves exhibit a reverse percolation transition at higher TBA concentration ≈ 0.45, where large spanning water clusters now break-up into small clusters. This is accompanied by significant divergence of the fluctuations in the size of the largest water cluster. This second transition gives rise to another set of anomalies around. We conclude this part of the thesis with Chapter 6, where we introduce a novel method for understanding the stability of fluctuating clusters of DMSO, ethanol and TBA in their respective aqueous binary mixtures. We find that TBA clusters are the most stable, whereas ethanol clusters are the most transient among the three representative amphiphilic co-solvents. This correlates well with the amplitude of anomalies observed in these three binary mixtures. Part II deals with the topic of hydrophobic force law in water. In the introductory Chapter 7 of this part, we briefly discuss the concept of hydrophobicity which is believed to be of importance in understanding / explaining the initial processes involved in protein folding. We also discuss the experimental observations of Israelachvili (on the force between hydrophobic plates) and the empirical hydrophobic force law. We briefly touch upon the theoretical back-ground, including Lum-Chandler-Weeks theory. We conclude this chapter with a brief account of relevant and important in silico studies so far. In Chapter 8, we present our studies on Mercedes-Benz (MB) model – a two dimensional model system where circular disks interact with an anisotropic potential. This model was introduced by Ben-Naim and was later parametrized by Dill and co-workers to reproduce many of the anomalous properties of water. Using molecular dynamics simulation, we show that hydrophobic force law is indeed observed in MB model, with a correlation length of ξ=3.79. The simplicity of the model enables us to unravel the underlying physics that leads to this long range force between hydrophobic plates. In accordance with Lum-Chandler-Weeks theory, density fluctuation of MB particles (leading to cavitation) between the hydrophobic rods is clearly distinguishable – but it is not sufficiently long ranged, with density correlation extending only up to ζ=2.45. We find that relative orientation of MB molecules plays an important role in the origin of the hydrophobic force in long range. We define appropriate order parameters to capture the role of orientation, and briefly discuss a plausible approach of an orientation-dependent theory to explain this phenomenon. Part III consists of two chapters and focuses on the diffusion of a Brownian particle on a Gaussian random energy landscape. We articulate the rich history of the problem in the introductory Chapter 9. Despite broad applicability and historical importance of the problem, we have little knowledge about the effect of ruggedness on diffusion at a quantitative level. Every study seems to use the expression of Zwanzig [Proc. Natl. Acad. U.S.A, 85, 2029 (1988)] who derived the effective diffusion coefficient, Deff =D0 exp (-β2ε2 )for a Gaussian random surface with variance ε, but validity of the same has never been tested rigorously. In Chapter 10, we introduce two models of Gaussian random energy surface – a discrete lattice and a continuous field. Using computer simulation and theoretical analyses, we explore many different aspects of the diffusion process. We show that the elegant expression of Zwanzig can be reproduced ex-actly by Rosenfeld diffusion-entropy scaling relationship. Our simulations show that Zwanzig’s expression overestimates diffusion in the uncorrelated Gaussian random lattice – differing even by more than an order of magnitude at moderately high ruggedness (ε>3.0). The disparity originates from the presence of “three-site traps” (TST) on the landscape – which are formed by deep minima flanked by high barriers on either side. Using mean first passage time (MFPT) formalism, we derive an expression for the effective diffusion coefficient, Deff =D0 exp ( -β2ε2)[1 +erf (βε/2)]−1 in the presence of TSTs. This modified expression reproduces the simulation results accurately. Further, in presence of spatial correlation we derive a general expression, which reduces to Zwanzig’s form in the limit of infinite spatial correlation and to the above-mentioned equation in absence of correlation. The Gaussian random field has an inherent spatial correlation. Diffusion coefficient obtained from the Gaussian field – both by simulations and analytical methods – establish the effect of spatial correlation on random walk. We make special note of the fact that presence of TSTs at large ruggedness gives rise to an apparent breakdown of ergodicity of the type often encountered in glassy liquids. We characterize the same using non-Gaussian order parameter, and show that this “breakdown” scales with ruggedness following an asymptotic power law. We have discussed the scope of future work at the end of each chapter when-ever appropriate.

In the present work a simulation model for examining the fundamental dynamic behaviour of a servo driven powertrain is developed. This powertrain consists of a permanent magnet synchronous motor, a cycloidal gearbox and a torque motor to apply a load. On basis of this model the selection of components for the design of a test rig is possible. This leads to the constructive draft of the test rig. In order to model the system, the fundamentals give a brief overview of the components incorporated in the test rig system. With ais of the specified task the simulation purpose is defined and the modelling process enabled. The subsequent system analysis is performed intensively to decompose the system into subsystems, which are then investigated to find the optimal modelling approach for the given simulation task. Particular emphasis is put on the investigation of the cycloidal gearbox subsystem and it shows, that approaches for modelling the dynamic behaviour of the gearbox as a whole have only been published partially. Therefore, the available modelling approaches are analysed and suitable models are developed as conceptual models. Those will be formalised and implemented in Matlab/Simulink. The model is verified and simulation experiments are performed, that help in the selection of suitable test rig components. On basis of a flexible test rig, finally the constructive draft is presented.:1 Introduction 1.1 Motivation 1.2 Procedure 2 Fundamentals 2.1 Definitions 2.2 Modelling 2.3 Servo Drive 2.3.1 Introduction 2.3.2 Permanent Magnet Synchronous Motor 2.3.3 Servo Inverter 2.3.4 Control System 2.4 Torque Motor 2.5 Gearbox 3 Specified Task 4 System Analysis 4.1 Introduction 4.2 Servo Inverter 4.3 Control System 4.4 Servo Motor 4.5 Transmission Elements 4.6 Cycloidal Gearbox 5 Model Formalisation 5.1 Introduction 5.2 Servo Inverter 5.3 Control System 5.4 Servo Motor 5.5 Transmission Elements 5.6 Cycloidal Gearbox 6 Model Implementation 6.1 Introduction 6.2 Servo Inverter 6.3 Control System 6.4 Servo Motor 6.5 Transmission Elements 6.6 Cycloidal Gearbox 7 Simulation 7.1 Introduction 7.2 Solver 7.3 Verification 7.4 System Evaluation 7.4.1 Sensitivity Analysis 7.4.2 Stability Analysis 8 Design of the Test Rig 8.1 Selection of the components 8.2 Constructive Draft 9 Summary and Outlook

In the present hypercompetitive market environment of car producers established especially at the developed west european markets is very difficult to gain new customers and increase the market share. The car producing companies have to build and increase customer loyalty to ensure the sustainable growth of market share in the future. One possibility how to improve customer's loyality to brand is to provide the highest standard at both sales and service department and carefully monitor the customer satisfaction. From the satisfaction and performance indicators of the car producing company is possible to construct a mathematical model producing the market share in a given country as an output. Key indikators of customer satisfaction, sales and service and also the macroeconomical data has been used as the inputs for the model. As a target market for my analysis has been chosen Germany. This thesis presents a set of recommendations and proposals, whose implementation should ensure the improvement of the market share of the given brand on german market. The recommendation does not include only the tips for improvement of the key indicators but it also gives the overview of how to make the marketing strategy more efficient using Customer relationship management.