This thesis reports on brand repositioning, i.e. changing a position of a brand. The theoretical approaches are described in the first part, the second one focuses on an analysis of the Scholl brand repositioning. This brand offers shoes of a supreme quality and design. The main goal of this paper is to evaluate the continous results of the repositioning activities accomplished since 2009, compare them with the specified goals for this mission, and based on the findings, formulate recommendations for Scholl, how to proceed in order to achive those goals.

The neuropathological process in Alzheimer's disease (AD) is characterized by both intra and extracellular Aβ42 aggregates. The neuropathological process of AD is complex and the exact cause of Aβ aggregation leading towards neuronal death is yet unknown. Several events are implicated towards the development of AD including changes within the proteome. With more than 30 million people currently affected with AD, there is still no cure for AD. In this project we seek to identify differential protein profiles by undertaking a comparative analysis of the intracellular and extracellular effects of Aβ on the human proteome using two cellular neuronal models: MC65 and SHSY5Y cells, to understand the biochemical pathology underlying AD. We also initiated a compound screening approach which not only identified several small molecules and peptides inhibiting the Aβ cytotoxicity, but also identified several known compounds from the LOPAC library acting as potential inhibitors of intra and extracellular Aβ42 cytotoxicity, thus highlighting the importance of drug repositioning to identify novel compounds in the therapeutic regime of AD which could be categorized as Aβ toxicity inhibitors. A comparative qualitative proteomics approach was undertaken using OFFGEL fractionation. The MS data was analysed through GO, biological pathway and protein interaction analysis using various databases such as UniProtKB, DAVID v6.7, KEGG and String 9.0 for the SHSY5Y cells treated with extracellular Aβ42 and MC65 cells which conditionally express intracellular C99, that is further cleaved to intracellular Aβ. This was followed by validation of 8 proteins by in-cell Western assay (ICW) undertaken using the LI-COR Infrared Imaging System for the cell lysates of control and Aβ42 treated SH-SY5Y as well as Aβ induced MC65 cells. We have also screened a library of 1280 LOPAC compounds on both the cell lines and 9 other compounds previously known as Aβ toxicity inhibitors on MC65 cells. The lead compounds were further characterized using MTT, LDH, ThT and ICW assays. The proteomics methodology undertaken through this project identified several novel proteins specific to intracellular and extracellular Aβ aggregation. The GO, biological pathway analysis and the functional interaction study helped to identify proteins associated from the proteasome pathway to be affected as an effect of Aβ aggregation for both the cells exposed with intra and extracellular Aβ aggregation. The compound screening study also identified several compounds as inhibitors of Aβ cytotoxicity. A-77636, a D1 dopamine receptor agonist was identified as a lead compound to reduce the extracellular Aβ42 cytotoxicity at nM concentration. Moreover, 1,3-Diethyl-8-phenylxanthine and Arecaidine propargyl ester hydrobromide also proved successful in attenuating the extracellular Aβ42 cytotoxicity. Apart from this; SEN1000, SEN304 and Scylloinositol were able to completely attenuate the intracellular Aβ cytotoxicity, whereas two other compounds, 1,3-Dipropyl-8-p-sulfophenylxanthine and 3-Bromo-7-nitroindazole from the LOPAC library proved effective in acting as partial inhibitors of intracellular Aβ aggregation induced cytotoxicity. The ADME profile for most of these compounds is acceptable, therefore these can be considered as therapeutic leads for AD in the future.

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¡@¡@In 2001, when American Marketing Association selected ¡§the most influential thoughts in history of American marketing¡¨, the positioning theory won this special honor. The positioning theory was proposed by Jack Trout and Al Ries in 1969, and its related concepts has deeply been influenced many people¡¦s marketing viewpoint, moreover, it is widely apply for a variety of fields such as marketing, advertising, design and product development. Since the marketing strategy of the five-star hotels always focus on customers¡¦ need, they have to take advantages of the strategies of target market segmentation and positioning. However, daily fierce market competition, the customers¡¦ need is highly uncertain, and therefore the original position strategy of a five-star hotel might not always be suitable for its customers. Sometimes, a five-star hotel have to change and make a new repositioning strategy for maintaining its competition advantage. The theory of positioning or repositioning is easy to understand; however, the feelings and cognitions of the customers are very hard to express by words because of communication gaps. This research uses Canton Court of Ambassador Hotel Kaohsiung as a case study. The result of the analysis shows that there is significantly different between the customers' satisfactions of product, service, environment, place and price, and the impact on it has positive correlation. ¡@¡@The original terms of the repositioning strategy of the case are newly made, instant availability, new taste of tea and hospitality with great passion. After study, the new terms from customers' experiences and viewpoints are Lover River, feast enjoyed, the culture of Dim Sum, warm feeling and freshly made.

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There is a lot of possible points of view on the brand repositioning. One of them are the changes which take place in the society.

The problem of developing drugs that can be used to cure diseases is important and requires a careful approach. Since pursuing the wrong candidate drug for a particular disease could be very costly in terms of time and money, there is a strong interest in minimizing such risks. Drug repositioning has become a hot topic of research, as it helps reduce these risks significantly at the early stages of drug development by reusing an approved drug for the treatment of a different disease. Still, finding new usage for a drug is non-trivial, as it is necessary to find out strong supporting evidence that the proposed new uses of drugs are plausible. Many computational approaches were developed to narrow the list of possible candidate drug-target interactions (DTIs) before any experiments are done. However, many of these approaches suffer from unacceptable levels of false positives. We developed two novel methods based on graph mining networks of drugs and targets. The first method (DASPfind) finds all non-cyclic paths that connect a drug and a target, and using a function that we define, calculates a score from all the paths. This score describes our confidence that DTI is correct. We show that DASPfind significantly outperforms other state-of-the-art methods in predicting the top ranked target for each drug. We demonstrate the utility of DASPfind by predicting 15 novel DTIs over a set of ion channel proteins, and confirming 12 out of these 15 DTIs through experimental evidence reported in literature and online drug databases. The second method (DASPfind+) modifies DASPfind in order to increase the confidence and reliability of the resultant predictions. Based on the structure of the drug-target interaction (DTI) networks, we introduced an optimization scheme that incrementally alters the network structure locally for each drug to achieve more robust top 1 ranked predictions. Moreover, we explored effects of several similarity measures between the targets on the prediction accuracy and proposed an enhanced strategy for DTI prediction. Our results show significant improvements of the accuracy of the top ranked DTI prediction over the current state-of-the-art methods.

The empty railcars repositioning strategy generates no income but is crucial for a good service quality, it should then satisfy two main objectives: fullling the customer demand and generating as little expense as possible. Moreover, because of breakdown or heavy traffic, variation on travel times happens to be the main cause of uncertainty in railroad scheduling and must be taken into account to suggest a robust planning. This thesis presents the linear program used in a prototype tool for the optimization of empty railcar repositioning strategy designed for the SNCF¹. The resulting schedule is computed with CPLEX and minimizes moving cost, delay and unfulllment penalties. Substitutions of railcar categories are also permitted and eventually penalized. In addition, uncertainty on travel times is handled by considering the expected cost of a move (regarding delay probability and possible penalties) and by adding slack periods at the end of moves. The robustness can be modulated through the use of a cursor. Finally, the model enforces a decision making process previously dened by the SNCF to ensure that the suggested planning can be easily grasped and trusted by users. Schedules have then been generated based on randomly generated data and simulated. Results show a potential saves of 10% on considered costs and a good range of use of the robustness cursor is suggested. Finally, paths for improvement of this prototype are proposed to meet the eventual schedulers' further needs in order to move forward the production of this tool at the company scale. ¹Société Nationale des Chemins de fer Français (French National Railways) / Master of Science

Lured by the promise of bigger sales, companies are increasingly looking to raise the volume of international trade. Consequently, the amount of bulk products carried in containers and transported overseas exploded because of the flexibility and reliability of this type of transportation. However, minimizing the logistics costs arising from the container flow management across different terminals has emerged asa major problem that companies and affiliated third-party logistics firms face routinely. The empty tankcontainer allocation problem occurs in the context of intermodal distribution systems management and transportation operations carried out by logistic service provider companies. This paper considers the time-evolving supply chain system of an international logistic service provider company that transports bulk products loaded in tank containers via road, rail and sea. In such system, unbalanced movements of loaded tank containers forces the company to reposition empty tank containers. The purpose of this paper is to develop a mathematical model that supports tactical decisions for flow management of empty tank containers. The problem involves dispatching empty tank containers of various types to the meet on-time delivery requirements and repositioning the other tank containers to storage facilities, depots and cleaning stations. To this aim, a mixed-integer linear programming (MILP) multiperiod optimization model is developed. The model is analyzed and developed step by step, and its functionality is demonstrated by conducting experiments on the network from our case study problem, within the boarders of Europe. The case study constitutes three different scenarios of empty tank container allocation. The computational experiments show that the model finds good quality solutions, and demonstrate that cost and modality improvements can be achieved in the network The sensitivity analysis employs a set of data from our case study and randomly selected data to highlight certain features of the model and provide some insights regarding the model’s behavior.

Previously, the rich customers bought expensive luxury goods, the impoverished customers bought cheap low quality merchandise and the middle class customers stayed true and loyal to the middle market. However, today there has been a change in the customer shopping behaviour, especially among the middle class customers who no longer want to be stuck in mediocrity. Either the customers “trade up”, which means that they buy goods with higher price and quality; or they “trade down”, which means that they buy cheaper low quality goods. This has created a change, which means that around the world, premium and no-frills products are squeezing middle-of-the-road products and services. Sales in the middle market are pressed while sales on both the top end and the bottom end of the market are rapidly growing. The market conditions are changing and this thesis is written with the purpose to analyse the given market situation - giving companies, primarily in the fashion industry, an opportunity to overview the possibilities for positioning on a market where the gap between discount and premium brands is getting bigger. Obviously, the phenomenon of market polarization will continue and the pressure on the companies to change will increase. This thesis discus therefore how a company can position and reposition itself in the emerging and ever changing environment. Three companies have been researched – Helly Hansen, Pennyblack and Nova Star. The choice of the companies have been made on the basis of all being active on the Scandinavian middle market practicing in three different parts of the fashion industry, which gives this study a broader approach. The study is qualitative and based on interviews with representatives from each company. After conducting the interviews and analysing the empirical framework, the conclusions suggest that the most beneficial way for a company to position itself on the current saturated market is by differentiating themselves, providing something that the competitors cannot offer. Nevertheless, the differentiation has nowadays become more complex and convoluted. This happened since the saturation has made attributes that previously have been seen as unique - such as for example, superior quality and design, to be mainly common. The saturated market leads to more and more tough competition between the companies. The study shows that this actually is the reason making the companies to try to make profit everywhere, attempting to reach people that should not fall within their targeted segment. On the contrary, it is more beneficial to target as narrowly as possible, specifically aiming at the consumers that would actually benefit form the products a company offers. Lastly, the results indicate that the International brands attempting to enter the Scandinavian market should be prepared to adjust their strategies, since the Scandinavian market seems to be different from the rest of the world. / Program: Master in Fashion Management with specialisation in Fashion Marketing and Retailing