The work presented in this thesis has contributed with knowledge to several aspects of protein-protein interaction involving PDZ domains. A substantial amount of our proteome contains regions that are intrinsically disordered but fold upon ligand interaction. The mechanism by which disordered regions bind to their ligands is one important piece of the puzzle to understand why disorder is beneficial. A region in the PDZ domain of nNOS undergoes such a disorder-to-order transition to form a b-sheet in the binding pocket of its partner. By studying the kinetics of interaction, in combination with mutations that modulate the stability of the aforementioned region, we demonstrate that the binding mechanism consists of multiple steps in which the native binding interactions of the b-sheet are formed cooperatively after the rate-limiting transition state. These mechanistic aspects may be general for the binding reactions of intrinsically disordered protein regions, at least upon formation of β-sheets.               The second part of this thesis deals with the engineering of proteins for increasing affinity in protein-protein interaction. Infection by high-risk human papillomavirus (hrHPV) can lead to cancer, and the viral E6 protein is an attractive drug target. E6 from hrHPV natively interacts with the well-characterized PDZ2 domain in SAP97, which we used as a scaffold to develop a high affinity bivalent binder of hrHPV E6. We initially increased PDZ2's affinity for E6 6-fold, but at the cost of decreased specificity. Attaching a helix that binds E6 at a distant site, increasing the affinity another14-fold, completed the design.             The final work of this thesis investigates if binding studies conducted with isolated PDZ domains is representative of the full-length proteins they belong to. It has been suggested that ligand binding in PDZ domains can be influenced by factors such as adjacent domains and interactions outside of the binding pocket. We studied these aspects for the three PDZ domains of PSD-95 and found that they on the whole function in an independent manner with short peptides as ligands, but that interactions outside of the PDZ binding-pocket may be present. The representative length of the PDZ interaction partner should therefore be considered.

Esta tese apresenta a formalização, construção e validação experimental de um mecanismo de interação entre agentes baseado em valores de troca. Através do mecanismo de interação, os agentes são capazes de estabelecer, avaliar e regular os balanços de troca de suas interações, com o objetivo de alcançar resultados que eles valorizem, i.e., considerem adequados. Na formalização do mecanismo de interação são considerados diversos aspectos abordados nas Ciências Sociais, na Psicologia e em Teorias Utilitaristas. No mecanismo são observados, igualmente, os aspectos sociais e psicológicos que podem influenciar os resultados das interações entre os agentes. Desse modo, o mecanismo leva em consideração que os agentes podem construir suas estratégias levando em consideração as informações relacionadas com o “poder social” e as “atitudes” de interação. No mecanismo de interação recorre-se aos diálogos de argumentação com a finalidade de permitir que os agentes possam influenciar os seus parceiros em relação ao estabelecimento de acordos sobre os serviços e aos valores de troca envolvidos nas interações. Na validação experimental, o cenário utilizado foi o dos “Robôs Coletores de Lixo em Marte”. Através dos resultados obtidos, pode-se observar que o mecanismo de interação considera os valores de troca no processo de formação da cooperação, auxiliando os agentes na escolha de futuros parceiros. / This thesis presents the formalization, construction and validation of an interaction mechanism based on exchange values. Through the interaction mechanism, the agents are capable to establish, to evaluate and to regulate the balances of exchange of their interactions, with the objective of reaching the results that they consider adequate. In the formalization of the mechanism several aspects of Social Sciences, Psychology and Utilitarian Theories are considered. In the mechanism are observed the social and psychological aspects that can influence the results of the interactions between the agents. In this manner, the mechanism considers that the agents can build their strategies considering the information related to the social power and to interaction attitudes. In the mechanism the argument dialogs are used with the purpose to allow the agents to influence their partners in relation to the establishment of agreements about the services and about the exchange values involved in the interactions. In the validation, the scenario used was the “Garbage Collector Robots in Mars”. Through the obtained results, it was possible to observe that the interaction mechanism considers the values of exchange in the process of formation of the cooperation, helping the agents to choose their future partners.

The research aims at modeling and analyzing the interactions among functional process variables (FPVs) for process control in semiconductor manufacturing. Interaction is a universal phenomenon and different interaction patterns among system components might characterize the system conditions. To monitor and control the system, process variables are normally collected for observation which could vary with time and present in a functional form. These FPVs interact with each other and contain rich information regarding the process conditions. As an example in one of the semiconductor manufacturing processes, changes of interactions among FPVs like temperature and coefficient of friction (COF) might characterize different process conditions. This dissertation systematically developed a methodology to study interaction among FPVs through statistical and physical modeling. Three main topics are discussed in this dissertation: (1) Interaction patterns of FPVs under varying process conditions are studied both through experiments and statistical approaches. A method based on functional canonical correlation analysis (FCCA) is employed to extract the interaction patterns between FPVs and experiments of wafer polishing processes are conducted to verify the patterns of FPVs under varying process conditions. (2) Interaction among FPVs is further studied based on physics for process condition diagnosis. A mathematical model based on nonlinear dynamics is developed to study the strength of interaction and their directionalities, and advanced statistical control charts followed by this nonlinear dynamics model are established for process monitoring. (3) Complex interaction structures among multiple FPVs are analyzed based on nonlinear dynamics for a better understanding of process mechanism. An approach with extended nonlinear dynamics model is proposed to characterize process conditions, and combined engineering knowledge, complex interaction structure patterns are concluded accordingly for interpretation of process mechanism. The main contribution of this dissertation is to propose a novel methodology based on nonlinear dynamics, which could investigate interactions between components of systems and provide physical understanding of process mechanism for process monitoring and diagnosis. Through studies on interaction among FPVs in semiconductor manufacturing, this research provides guidance for improvement of manufacturing processes. Not limited to manufacturing, the developed methodology can be applied to other areas such as healthcare delivery.

Esta tese apresenta a formalização, construção e validação experimental de um mecanismo de interação entre agentes baseado em valores de troca. Através do mecanismo de interação, os agentes são capazes de estabelecer, avaliar e regular os balanços de troca de suas interações, com o objetivo de alcançar resultados que eles valorizem, i.e., considerem adequados. Na formalização do mecanismo de interação são considerados diversos aspectos abordados nas Ciências Sociais, na Psicologia e em Teorias Utilitaristas. No mecanismo são observados, igualmente, os aspectos sociais e psicológicos que podem influenciar os resultados das interações entre os agentes. Desse modo, o mecanismo leva em consideração que os agentes podem construir suas estratégias levando em consideração as informações relacionadas com o “poder social” e as “atitudes” de interação. No mecanismo de interação recorre-se aos diálogos de argumentação com a finalidade de permitir que os agentes possam influenciar os seus parceiros em relação ao estabelecimento de acordos sobre os serviços e aos valores de troca envolvidos nas interações. Na validação experimental, o cenário utilizado foi o dos “Robôs Coletores de Lixo em Marte”. Através dos resultados obtidos, pode-se observar que o mecanismo de interação considera os valores de troca no processo de formação da cooperação, auxiliando os agentes na escolha de futuros parceiros. / This thesis presents the formalization, construction and validation of an interaction mechanism based on exchange values. Through the interaction mechanism, the agents are capable to establish, to evaluate and to regulate the balances of exchange of their interactions, with the objective of reaching the results that they consider adequate. In the formalization of the mechanism several aspects of Social Sciences, Psychology and Utilitarian Theories are considered. In the mechanism are observed the social and psychological aspects that can influence the results of the interactions between the agents. In this manner, the mechanism considers that the agents can build their strategies considering the information related to the social power and to interaction attitudes. In the mechanism the argument dialogs are used with the purpose to allow the agents to influence their partners in relation to the establishment of agreements about the services and about the exchange values involved in the interactions. In the validation, the scenario used was the “Garbage Collector Robots in Mars”. Through the obtained results, it was possible to observe that the interaction mechanism considers the values of exchange in the process of formation of the cooperation, helping the agents to choose their future partners.

Esta tese apresenta a formalização, construção e validação experimental de um mecanismo de interação entre agentes baseado em valores de troca. Através do mecanismo de interação, os agentes são capazes de estabelecer, avaliar e regular os balanços de troca de suas interações, com o objetivo de alcançar resultados que eles valorizem, i.e., considerem adequados. Na formalização do mecanismo de interação são considerados diversos aspectos abordados nas Ciências Sociais, na Psicologia e em Teorias Utilitaristas. No mecanismo são observados, igualmente, os aspectos sociais e psicológicos que podem influenciar os resultados das interações entre os agentes. Desse modo, o mecanismo leva em consideração que os agentes podem construir suas estratégias levando em consideração as informações relacionadas com o “poder social” e as “atitudes” de interação. No mecanismo de interação recorre-se aos diálogos de argumentação com a finalidade de permitir que os agentes possam influenciar os seus parceiros em relação ao estabelecimento de acordos sobre os serviços e aos valores de troca envolvidos nas interações. Na validação experimental, o cenário utilizado foi o dos “Robôs Coletores de Lixo em Marte”. Através dos resultados obtidos, pode-se observar que o mecanismo de interação considera os valores de troca no processo de formação da cooperação, auxiliando os agentes na escolha de futuros parceiros. / This thesis presents the formalization, construction and validation of an interaction mechanism based on exchange values. Through the interaction mechanism, the agents are capable to establish, to evaluate and to regulate the balances of exchange of their interactions, with the objective of reaching the results that they consider adequate. In the formalization of the mechanism several aspects of Social Sciences, Psychology and Utilitarian Theories are considered. In the mechanism are observed the social and psychological aspects that can influence the results of the interactions between the agents. In this manner, the mechanism considers that the agents can build their strategies considering the information related to the social power and to interaction attitudes. In the mechanism the argument dialogs are used with the purpose to allow the agents to influence their partners in relation to the establishment of agreements about the services and about the exchange values involved in the interactions. In the validation, the scenario used was the “Garbage Collector Robots in Mars”. Through the obtained results, it was possible to observe that the interaction mechanism considers the values of exchange in the process of formation of the cooperation, helping the agents to choose their future partners.

台灣觀光外匯的成長力度高，外國旅客來台灣包車旅遊的需求漸增，因應而生的包車平台興起，本研究期望針對既有個案探討包車平台如何去設定付費方與被捕貼方，並且提供其他同質性平台商業模式設計更多元的思考方式。 透過黃勇及周學春提出之平台商業模式研究之框架及陳威如及余卓軒提出的平台補貼策略之考慮因素，以質性研究方式，選取UTAXI、台灣小旅行、DingTAXI叮叮包車三個包車平台個案進行訪談與分析。 UTAXI媒合“旅客-司機”，致力“您的專屬司機”，選擇司機作為付費方，自由行旅客為被補貼方，定價較市場平均價格高；台灣小旅行媒合“旅客-司機”，致力“體驗台灣在地感動，訴說土地故事”，選擇自由行旅客作為付費方，計程車學院協會司機為被補貼方，定價為市場平均價格；DingTAXI叮叮包車媒合“旅客-車隊“，致力”解決自由行旅客交通困擾“，選擇自由行旅客作為付費方，合作車行、車隊為被補貼方。 本研究得知個案其各自商業模式之創建、如何選擇付費方與被補貼方以及包車平台之定價策略，也可從個案中得知，思考角度與立場不同，運用補貼模式的準則得出之結果也截然不同，提供未來同質性平台於發展時多元的思考方式及依據。 / From 2007 to 2015, visitors to Taiwan increased from 3.71 million to more than 10 million. As a result, foreign exchange earnings from tourism surged by 2.6 times, from NT$17.12 billion (US$521.95 million) to an estimated NT$44.50 billion (US$1.36 billion). These results and reviews demonstrate that Taiwan is becoming a major destination for travelers worldwide. Car carter service become a popular way for visitors to explore Taiwan on their own, therefore more and more online car carter service platforms are being set up. Platform pricing model is not set up by user charge alone, how users interact on the platform is also considered. Platform controller attract users who can cause positive cross-side network effect by offering them better price so that they can attract users who are willing to pay the fee. This research depends on two-side market theory to explain how online car carter platforms attract users to enter their platforms, design interaction mechanism and set rules to allow users to use platforms easily. Depending on different point of views, every online car carter service platform has its own design. Therefore, this research also depends on the business model and the eco-system on platform theory to analyze car carter service platform. After understanding how platforms design interaction mechanism, platform pricing model is then discussed. Every platform has its own pricing model, because of different design. This research analyzes platform pricing model by subsidy rules from previous studies. By analyzing three online car carter service platform cases, this research concludes that platforms have different interacting mechanisms because of website design purpose and user dating purpose. This research demonstrates which subsidy rules are used on online dating platform and how these platform create their own eco-system to maintain the platform.

近年來平台商業模式與網路交友的盛行，使得許多網路交友平台應運而生。平台的收費模式不以傳統使用者付費的觀念建立，而是以整體平台的互動作為收費的考量，以較優惠或是免費的方式來吸引會引起正向跨邊網路效應的使用者加入，讓他們作為平台的被補貼方，藉此吸引平台的付費方群體加入。 本研究以雙邊平台的觀點來研究網路交友平台是如何設計讓使用者願意加入此平台、如何設計互動機制讓平台上雙方群體進行互動，如何訂定合適的管制讓使用者能方便使用並信任此平台上使用者的真實性，讓適當的顧客匯集。即使同為網路交友平台，其交友的目的、交友的模式也有所不同，因此本研究先探討各交友平台是如何設計互動模式，來促進使用者間的交流，並比較各平台的不同之處。 理解平台的互動機制後，接著探討平台的補貼準則。因為各網路交友平台的設計不同也使得補貼準則有所差異，透過文獻裡所述的補貼準則來分析平台是透過哪種方式來向使用者進行收費，以及分析使用者願意支付費用的原因。 透過幾個交友平台的個案分析，本研究觀察到雖都為網路交友平台，但是其交友的機制都會因其設計理念、交友目的而有所不同。因此本研究整理出哪些補貼準則被應用在網路交友平台上，而各交友平台如何設計收費時機在互動模式上，以理解網路交友平台的整個收費訂價的方式。 / Platform business model and online dating has become popular in recent years, therefore more and more online dating platforms are being set up. Platform pricing model is not set up by user charge alone, how users interact on the platform is also considered. Platform controller attract users who can cause positive cross-side network effect by offering them better price so that they can attract users who are willing to pay the fee. This research depends on two-side market theory to explain how online dating platforms attract users to enter their platforms, design interaction mechanism and set rules to allow users to use platforms easily. Depending on different dating purposes, every online dating platform has its own design. Therefore, this research discusses how different online dating platforms design interaction mechanism and compare the differences between them. After understanding how platforms design interaction mechanism, platform pricing model is then discussed. Every platform has its own pricing model, because of different design. This research analyzes platform pricing model by subsidy rules from previous studies, and why users are willing to pay. By analyzing several online dating platform cases, this research concludes that platforms have different interacting mechanisms because of website design purpose and user dating purpose. This research demonstrates which subsidy rules are used on online dating platform and how these platform design charge timing in order to understand online dating platform pricing model.

Dissertation thesis is a 5-publications' collection concerning characterization and application potential of cyclodextrins, polysaccharides and macrocyclic antibiotics based chiral stationary phases. The effects of stationary phase and mobile phase are studied. This approach ensures the complex insight into separation systems studied. Systems with different nature of chiral selector were studied by HPLC. Namely, macrocyclic antibiotics and derivatized polysaccharides were used for experiments. Former ones provided better results for enantioseparation of non-coded amino acids than latter ones. Dynamic coating procedure was used for preparation of a new chiral stationary phase. Characterization of new cationic cyclodextrin based chiral stationary phase was performed. Linear free energy relationship method was used for characterization of two different separation systems, i.e. newly prepared stationary phase and commercially available stationary phase. Based on results obtained, newly prepared stationary phase showed better results for separation of different achiral groups of analysts. New stationary phase prepared by dynamic coating was compared with chromatographic system, in which the chiral selector was used as a mobile phase additive. The chiral selector used for the two different approaches was...

Ziel dieser Arbeit war es, die mechanistischen Abläufe bei der Papierleimung mit ASA besser zu verstehen und weiter aufzuklären, um vor allem Wechselwirkungen mit Füllstoffen und anderen chemischen Additiven zu minimieren. Dazu sollten analytische Verfahrensmethoden entwickelt werden, welche die bilanztechnische Verfolgung von ASA und dessen Reaktionsprodukten ermöglichen, um anschließend den Einfluss und die Wechselwirkungen verschiedenster Parameter auf die ASA-Leimung untersuchen zu können. Weiterhin sollte bei Untersuchungen zur Emulgierung versucht werden, die wichtigsten Einflussgrößen auf die Partikelgröße, Stabilität und Hydrolyse des ASA aufzuzeigen. Im ersten Teil der Arbeit konnten bei den Untersuchungen zur Emulgierung wichtige Einflussgrößen auf die Partikelgröße, Stabilität und Hydrolyse von ASA-Emulsionen aufgeklärt werden. Weiterhin wurde eine Methode zur genauen Bestimmung der Reaktionskinetik der ASA-Hydrolyse sowie der Ablagerungsneigung entwickelt. Bei den Untersuchungen zur analytischen Bestimmung wurde über die NIR-Spektroskopie ein einfaches Analyseverfahren zur exakten quantitativen Bestimmung von ASA und AKD entwickelt. Es wurde gefunden, dass eine quantitative Erfassung von synthetischen Leimungsmitteln (ASA / AKD) mittels NIR in den Regionen der CH2-Schwingungen um 4300 cm-1 und 5750 cm-1 mit hoher statistischer Genauigkeit möglich ist. Der Methodenfehler für die Bestimmung von AKD liegt bei ± 0,010 % und bei ± 0,013 % für ASA. Dadurch ist eine wesentlich genauere Bewertung von Wechselwirkungen bei der Leimung als bisher möglich, da nicht nur die Leimungswirkung, sondern über NIR auch Menge und Art (gebunden / ungebunden) an Leimungsmittel in einer bisher nicht erreichbaren Messzeit betrachtet werden können. Mittels HPLC und Pyrolyse-GC/MS konnten die erstellten NIR-Kalibrationen erfolgreich validiert werden. Im letzten Teil der Arbeit wurden Wechselwirkungen von ASA mit Füllstoffen und chemischen Additiven aufgeklärt, sowie mechanistische Grundlagen zur Leimung mit ASA erarbeitet. Hier hat sich gezeigt, dass der Mechanismus der ASA-Leimung nicht nur, wie oft in der Literatur beschrieben, auf eine Veresterung mit den Hydroxylgruppen der Cellulose zurückzuführen ist. Vielmehr ist die optimale Wirkung von Leimungsmitteln sehr stark von deren Verteilung, Mobilität und Orientierung abhängig. Weiterhin konnte festgestellt werden, dass der größte Anteil des Leimungsmittels im Papier in ungebundener (hydrolisierter) Form vorliegt und somit zur Wanderung (Migration) durch das Papiergefüge befähigt ist. Trotzdem kann der hydrolisierte Anteil deutlich zur Hydrophobierung des Papiers beitragen, wenn dieser richtig orientiert und fein verteilt ist. Schlecht orientierte Leimungsmittel tragen nicht zur Leimung bei bzw. können diese sogar reduzieren. In der vorliegenden Arbeit wurden unter Einsatz moderner Methoden wichtige Grundlagen zur Papierleimung mit ASA erarbeitet. Dabei wurden insbesondere Beiträge zu den Themen Emulgierung, Hydrolyse- und Ablagerungsneigung, analytische Bestimmung, Wechselwirkungen sowie Mechanismen von ASA geleistet. Diese Ergebnisse zeigen Möglichkeiten auf, wie in Unternehmen der Papierindustrie zukünftig ASA-Leimungsmittel gezielter dosiert, Produktionsstörungen vermieden und Kosten reduziert werden können. / The purpose of this work was to develop a deeper understanding of the mechanisms in ASA sizing and to minimise interactions with fillers and other chemical additives. Therefore analytical test methods were developed, to enable a simple mass balance approach for ASA and its reaction products. Afterwards, the influence of various factors affecting ASA sizing and retention could be investigated and explained. Furthermore, the most important factors which influence particle size, stability, and hydrolysis of ASA emulsions had to be determined. In the first part of this work, studies regarding the emulsification of ASA were carried out. Here, the most important factors with regard to particle size, stability, and hydrolysis of ASA emulsions were investigated. Furthermore, a method for the exact determination of ASA hydrolysis as well as the agglomeration tendency was developed. For the investigations regarding the analytical determination, a fast and easy-to-use method for the quantification of ASA and AKD has been developed. The investigations have shown that a quantitative determination of synthetic sizing agents (ASA / AKD) is possible using NIR spectroscopy. With the help of multivariate data analysis and PLS regression, mainly the region of the CH2-bands around 4300 cm-1 and 5750 cm-1 were evaluated. The prediction error (RMSEP) for the determination of AKD is 0.01 %, and 0.013 % for ASA. Even an analysis of the percentage of bound and unbound ASA / AKD is possible by NIR spectroscopy of extracted paper samples. Thus, a fast and detailed investigation of mechanisms as regards sizing is possible. The developed NIR methods were validated using HPLC and Pyrolysis-GC/MS. In the last part of the work, interactions of ASA with fillers and chemical additives were investigated, and mechanisms of ASA sizing were studied. It was shown that the mechanism of ASA sizing - as often described in the literature - can not only be attributed to the esterification with the hydroxyl groups of the cellulose. In fact, the optimal effect of sizing agents is much more dependant on a fine distribution, mobility and orientation of ASA molecules. It was observed that the main part of the ASA is present in an unbound (hydrolysed) form and therefore is able to migrate through the paper structure. However, the hydrolysed ASA can significantly contribute to sizing when it is finely distributed and well orientated. Sizing agents orientated in the opposite do not contribute to sizing but they can even decrease the existing sizing level. To summarize, it can be concluded that, in this work important fundamentals as regards ASA sizing were developed using modern test methods. Thereby important contributions were made to the topics of emulsification, hydrolysis- and emulsion-stability, analytical determination, interactions and mechanisms of ASA. These results show possibilities how ASA sizing agents can be used more effectively, process disturbances avoided, and costs reduced.