Purpose of the Review Mitochondrial dysfunction has long been proposed to play a crucial role in the pathogenesis of a considerable number of disorders, such as neurodegeneration, cancer, cardiovascular, and metabolic disorders, including obesity-related insulin resistance and non-alcoholic fatty liver disease (NAFLD). Mitochondria are highly dynamic organelles that undergo functional and structural adaptations to meet the metabolic requirements of the cell. Alterations in nutrient availability or cellular energy needs can modify their formation through biogenesis and the opposite processes of fission and fusion, the fragmentation, and connection of mitochondrial network areas respectively. Herein, we review and discuss the current literature on the significance of mitochondrial adaptations in obesity and metabolic dysregulation, emphasizing on the role of hepatocyte mitochondrial flexibility in obesity and NAFLD. Recent Findings Accumulating evidence suggests the involvement of mitochondrial morphology and bioenergetics dysregulations to the emergence of NAFLD and its progress to non-alcoholic steatohepatitis (NASH). Summary Most relevant data suggests that changes in liver mitochondrial dynamics and bioenergetics hold a key role in the pathogenesis of NAFLD. During obesity and NAFLD, oxidative stress occurs due to the excessive production of ROS, leading to mitochondrial dysfunction. As a result, mitochondria become incompetent and uncoupled from respiratory chain activities, further promoting hepatic fat accumulation, while leading to liver inflammation, insulin resistance, and disease’s deterioration. Elucidation of the mechanisms leading to dysfunctional mitochondrial activity of the hepatocytes during NAFLD is of predominant importance for the development of novel therapeutic approaches towards the treatment of this metabolic disorder.

In next generation wireless networks such as 4G- LTE and WiMax, the demand for high data rates, the scarcity of wireless resources and the time varying channel conditions has led to the adoption of more sophisticated and robust techniques in PHY such as orthogonal frequency division multiplexing (OFDM) and the corresponding access technique known as orthogonal frequency division multiplexing access (OFDMA). Cross-layer schedulers have been developed in order to describe the procedure of resource allocation in OFDMA wireless networks. The resource allocation in OFDMA wireless networks has received great attention in research, by proposing many different ways for frequency diversity exploitation and system’s optimization. Many cross-layer proposals for dynamic resource allocation have been investigated in literature approaching the optimization problem from different viewpoints i.e. maximizing total data rate, minimizing total transmit power, satisfying minimum users’ requirements or providing fairness amongst users. The design of a cross-layer scheduler for OFDMA wireless networks is the topic of this research. The scheduler utilizes game theory in order to make decisions for subcarrier and power allocation to the users with the main concern being to maintain fairness as well as to maximize overall system’s performance. A very well known theorem in cooperative game theory, the Nash Bargaining Solution (NBS), is employed and solved in a close form way, resulting in a Pareto optimal solution. Two different cases are proposed. The first one is the symmetric NBS (S-NBS) where all users have the same weight and therefore all users have the same opportunity for resources and the second one, is the asymmetric NBS (A-NBS), where users have different weights, hence different priorities where the scheduler favours users with higher priorities at expense of lower priority users. As MAC layer is vital for cross-layer, the scheduler is combined with a queuing model based on Markov chain in order to describe more realistically the incoming procedure from the higher layers.

The present work seeks to incorporate a popular descriptive, empirically grounded model of human preference under risk, prospect theory, into the equilibrium theory of noncooperative games. Three primary, candidate definitions are systematically identified on the basis of classical characterizations of Nash Equilibrium; in addition, three equilibrium subtypes are defined for each primary definition, in order to enable modeling of players' reference points as exogenous and fixed, slowly and myopically adaptive, highly flexible and non-myopically adaptive. Each primary equilibrium concept was analyzed both theoretically and empirically; for the theoretical analyses, prospect theory, game theory, and computational complexity theory were all summoned to analysis. In chapter 1, the reader is provided with background on each of these theoretical underpinnings of the current work, the scope of the project is described, and its conclusions briefly summarized. In chapters 2 and 3, each of the three equilibrium concepts is analyzed theoretically, with emphasis placed on issues of classical interest (e.g. existence, dominance, rationalizability) and computational complexity (i.e, assessing how difficult each concept is to apply in algorithmic practice, with particular focus on comparison to classical Nash Equilibrium). This theoretical analysis leads us to discard the first of our three equilibrium concepts as unacceptable. In chapter 4, our remaining two equilibrium concepts are compared empirically, using average-level data originally aggregated from a number of studies by Camerer and Selten and Chmura; the results suggest that PT preferences may improve on the descriptive validity of NE, and pose some interesting questions about the nature of the PT weighting function (2003, Ch. 3). Chapter 5 concludes, systematically summarizes theoretical and empirical differences and similarities between the three equilibrium concepts, and offers some thoughts on future work.

We present an in-depth analysis of the music industry and use our findings to judge the practical assumptions and design of an original theoretical model. The model is in three stages, where, in a Hotelling-type framework, the last agents to act are consumers who choose between copying, purchasing, or staying out of the market for music. Prior to the last stage, the record label chooses its profit maximizing price and, in the first stage, we incorporate the artist-label bargaining agreement into a theoretical framework using the Nash cooperative bargaining solution. The current structure of the music industry is a combination of the oligopoly and monopolistic competition models, consisting of five major labels and many independents. Despite major labels' advantage in large-scale distribution, we argue that digital downloading has the potential to radically alter the current industry structure, and that artists would be unable to sell their music in such an environment without enforceable copyrights. Our model assumes that the most important determinants of CD and copy demand are consumers' tastes and transaction costs of copying, CD prices, and the substitutability between CDs and copies. We hypothesize that Internet file-sharing has been undertaken by both consumers who were previously not in the market, and by those who decided to copy rather than buy. In regard to firm strategy, the model suggests that labels could increase the sales of CDs by trying to increase consumers' taste for music, perhaps by reducing the price of CDs. Our model also predicts a positive relationship between artists' optimal share of album sales and their bargaining power, as well as a negative relationship between artists' optimal share and their risk aversion. Since lowering the reliance on labels for distribution would increase artists' bargaining power, our model predicts that artists' share of profits should increase as legitimate digital distribution gains prominence. We also provide empirical testing of our hypothesis that some music file-sharing has been done by consumers frequently not in the market. After examining consumers' expenditures and aggregate industry sales, we are unable to reject our hypothesis

Thesis advisor: Hideo Konishi / My doctoral dissertation contains three essays on menu auction and its related applications. The first chapter is a theoretical generalization of classical menu auction model, and the second and the third chapters are applications to a resource allocation problem and an industrial organization problem. Menu auction (Bernheim and Whinston, 1986) is a first-price package auction with complete information. They show that every Nash equilibrium under some refinements always leads to an efficient outcome. Therefore, this becomes a natural efficiency benchmark for package auction designs (e.g., Ausubel and Milgrom 2002). Menu auction can also be viewed as a model of economic influence where the auctioneer is going to choose an action which affects bidders' payoff so that each bidder tries to influence the outcome by monetary transfer to the auctioneer. This framework is widely adopted in political lobbying models where the special interest groups lobbying the government over trade policies (e.g., Grossman and Helpman 1994). However, the applicability is limited by quasi-linear preferences and the absence of budget constraints. In my first chapter, ``Menu Auctions with Non-Transferable Utilities and Budget Constraints'', I extends Bernheim and Whinston's (1986) menu auction model under transferable utilities to a framework with non-transferable utilities and budget constraints. Under appropriate definitions of equilibria consistent with subgame perfection, it is shown that every truthful Nash equilibrium (TNE) is a coalition-proof Nash equilibrium (CPNE) and that the set of TNE payoffs and the set of CPNE payoffs are equivalent, as in a transferable utility framework. The existence of a CPNE is assured in contrast with the possible non-existence of Nash equilibrium under the definition by Dixit, Grossman, and Helpman (1997). Moreover, the set of CPNE payoffs is equivalent to the bidder-optimal weak core. The second chapter relates menu auction to a resource allocation problem. Kelso and Crawford (1982) propose a wage-adjustment mechanism resulting in a stable matching between heterogeneous firms and workers. Instead of a benevolent social planner, in ``Profit-Maximizing Matchmaker'' (w. Hideo Konishi), we consider a profit-maximizing auctioneer to solve this many-to-one assignment problem. If firms can only use individualized price, then the auctioneer can only earn zero profit in every Nash equilibrium and the sets of stable assignments and strong Nash equilibria are equivalent. Otherwise, the auctioneer might earn positive profit even in a coalition-proof Nash equilibrium. This reinforces Milgrom's (2010) argument on the benefit of using simplified message spaces that it not only reduces information requirement but also improves resource allocation. The third chapter applies menu auction in an industrial organization problem. In ``Choosing a Licensee from Heterogeneous Rivals'' (w. Hideo Konishi and Anthony Creane), we consider a firm licensing its production technology to rivals when firms with heterogeneous in production costs competing in a Cournot market. While Katz and Shapiro (1986) show that a complete transfer in duopoly can be joint-profit reducing, we show that it is always joint-profit improving provided that at least three firms remain in the industry after transfer. While transfers between similarly efficient firms may reduce welfare, the social welfare must increase if the licensor is the most efficient in the industry, contrast with Katz and Shapiro (1985) in the duopoly environment. This has an important implication in competition regulation. Then we investigate relative efficiency of the licensee under different licensing auction mechanisms. With natural refinement of equilibria, we show that a menu auction licensee, a standard first-price auction licensee, and a joint-profit maximizing licensee are in (weakly) descending order of efficiency. / Thesis (PhD) — Boston College, 2012. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Economics.

Analisamos a ação da liraglutida na flora intestinal e perda de peso de dois modelos de obesidade: por dieta hiperlipidica (HFD) e obesidade genética (ob/ob). Os modelos foram tratados com o fármaco durante duas semanas. Perfis metabólicos foram feitos por meio de testes glicêmicos e insulínicos, histologia do fígado, região cecal e coxins gordurosos, ingestão alimentar, peso corporal e metagenômica do conteúdo cecal. O tratamento induziu perda de peso com melhora dos níveis glicêmicos e redução da inflamação na região cecal e do fígado e foi capaz de reduzir o acúmulo de gordura hepática promovendo a redução da EHNA. A metagenômica mostrou mudança taxonômica geral, bem como a abundância relativa de bactérias envolvidas com peso e controle glicêmico:redução de Proteobacterias e aumento de Akkermansia muciniphila. Apresentamos evidências do fármaco revertendo DGHNA/EHNA e a perda de peso associados às mudanças da microbiota. Sugerimos uma lista de alvos bacterianos que podem interferir no metabolismo energético para o controle clinico de doenças metabólicas. / The study analyzed the effects of liraglutide on gut microbiota and weight-loss in two obesity model: induced by high fat diet (HFD) and genetic obese mice (ob/ob). Models were treated with liraglutide for two weeks. Metabolic profiles were measured by glycemic and insulin test, histological liver, cecal region and fat pad morphologies, food intake, body weight and metagenomic of cecal contents. The treatment induced weight-loss, improvement of glycemic parameters and reduction of inflammatory cells in the cecum and the liver and reduced fat accumulation in liver reverting NASH. The metagenomic showed a general changed in taxonomic structure as well the relative abundance of weight-relevant:reduction of Proteobacteria and increases of Akkermansia muciniphila. We showed evidences that liraglutide leads to improvement of NASH and weight loss associated with changes in microbiota. Moreover, by the profile of the gut microbiota, we present a bacterial target list that may affect energetic metabolism inducing a metabolic clinical controlled profile.

The results section of my thesis includes three chapters. The first two chapters are on theoretical game theory. In both chapters, by mathematical modelling and game theoretical tools, I am predicting the behaviour of the players in some real world issues. Hoteling-Downs model plays an important role in the modern political interpretations. The first chapter of this study investigates an extension of Hoteling-Downs model to have multi-dimensional strategy space and asymmetric candidates. Chapter 3 looks into the inspection game where the inspections are not the same in the series of sequential inspections. By modelling the game as a series of recursive zero-sum games I find the optimal strategy of the players in the equilibrium. The forth chapter investigates direct optimization methods for large scale problems. Using Matlab implementations of Genetic and Nelder-Mead algorithms, I compare the efficiency and accuracy of the most famous direct optimization methods for unconstraint optimization problems based on differing number of variables.

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Typescript (photocopy). / Digitized by Kansas Correctional Industries

Es werden verschiedene Verfahren zur Lösung verallgemeinerter Nash-Gleichgewichtsprobleme mit dem Schwerpunkt auf deren globaler Konvergenz entwickelt. Ein globalisiertes Newton-Verfahren zur Berechnung normalisierter Lösungen, ein nichtglattes Optimierungsverfahren basierend auf einer unrestringierten Umformulierung des spieltheoretischen Problems, und ein Minimierungsansatz sowei eine Innere-Punkte-Methode zur Lösung der gemeinsamen Karush-Kuhn-Tucker-Bedingungen der Spieler werden theoretisch untersucht und numerisch getestet. Insbesondere das Innere-Punkte Verfahren erweist sich als das zur Zeit wohl beste Verfahren zur Lösung verallgemeinerter Nash-Gleichgewichtsprobleme. / In this thesis different algorithms for the solution of generalized Nash equilibrium problems with the focus on global convergence properties are developed. A globalized Newton method for the computation of normalized solutions, a nonsmooth algorithm based on an optimization reformulation of the game-theoretic problem, and a merit function approach and an interior point method for the solution of the concatenated Karush-Kuhn-Tucker-system are analyzed theoretically and numerically. The interior point method turns out to be one of the best existing methods for the solution of generalized Nash equilibrium problems.