O mercado automotivo global em 2008 sofreu uma queda drástica na produção e nas vendas após a eclosão da crise do subprime nos Estados Unidos. Em todo o mundo, políticas de fomento foram sendo implementadas sob as mais variadas formas para recuperar o setor. Presumivelmente, em resposta à crise, o governo brasileiro resolveu agir decretando a política anticíclica de redução do IPI ao mercado automobilístico em 2008, sendo está repetida em 2012. Neste mesmo ano também ocorreu a modificação do acordo automotivo Brasil/México, e em 2013 foi implantado o INOVAR-AUTO. Sendo assim, o objetivo do presente estudo, será avaliar o efeito da diminuição do IPI sobre o comportamento da demanda, da oferta e os efeitos líquidos sobre os agentes de mercado. O estudo se relaciona com uma literatura que busca avaliar os efeitos de reformas tributárias em indústrias com produtos diferenciados, como Fershtman, Gandal e Markovich (1999) e Verboven (2002). É empregado o modelo logit aninhado de McFadden et al. (1973) e estendido por Berry (1994), combinado com uma estrutura de competição oligopolista pressupondo equilíbrio nos preços, segundo Nevo (1998), do tipo Nash-Bertrand. Adicionalmente, é elaborado uma análise econométrica preliminar de preços hedônicos, seguindo Griliches (1961), formulado num painel de efeitos fixos que avaliará o comportamento dos preços médios dos veículos novos nos períodos de modificação do IPI. Os resultados dos modelos de apreçamento hedônico demonstram que as montadoras não remanejaram os preços médios no mesmo percentual efetivo da queda do IPI. As variações dos preços foram mais baixas do que a da alíquota. Na metodologia discreta, os resultados apontam que empresas que detém maiores poderes de mercado possuem elasticidades preço próprias baixas. Lucros mais elevados estão associados a marcas que no grosso de suas vendas comercializam automóveis de menor porte que embutem uma alta relação markup preço-custo. Montadoras nacionais tiveram melhor desempenho que suas contrapartes importadoras. A carga tributária altíssima é o principal vilão para o desempenho ruim dos importados. Os excedentes gerados com a modificação do IPI foram positivos para todos os agentes. Consumidores, produtores e governo ganharam com a medida. Ou seja, há espaço para reduções de impostos com aumento da arrecadação do governo. / The global automotive market in 2008 saw a sharp drop in production and sales following the outbreak of the subprime crisis in the United States. Throughout the world, development policies have been implemented in a variety of ways to recover the sector. Presumably, in response to the crisis, the Brazilian government decided to act by decreeing the anti-cyclical policy of reducing the IPI to the automobile market in 2008, and is repeated in 2012. In 2012 also occurred the modification of the automotive agreement Brazil / Mexico, and in 2013 was implanted the INOVAR-AUTO. Therefore, the objective of the present study will be to evaluate the effect of the reduction of IPI on the behavior of demand, supply and net effects on market agents. The study is related to a literature that seeks to evaluate the effects of tax reforms in industries with differentiated products, such as Fershtman, Gandal e Markovich (1999) and Verboven (2002). The nested logit model of McFadden et al. (1973) and extended by Berry (1994), combined with an oligopolistic competition structure presupposing price equilibrium, according to Nevo (1998), of the Nash-Bertrand type, is used. Additionally, a preliminary econometric analysis of hedonic prices is elaborated, following Griliches (1961), formulated in a panel of fixed effects that will evaluate the behavior of the average prices of new vehicles in the periods of modification of the IPI. The results of the hedonic pricing models show that the automakers did not change average prices in the same effective percentage of the IPI fall. Price changes were lower than the rate. In the discrete methodology, the results indicate that companies that have greater market power have lower price elasticities. Higher profits are associated with brands that in the bulk of their sales market smaller automobiles that embody a high price-cost markup ratio. National car manufacturers performed better than their importing counterparts. The very high tax burden is the main villain for the poor performance of imported. The surpluses generated with the IPI change were positive for all agents. Consumers, producers and government won with the measure. That is, there is room for tax cuts with increased government revenue.

This thesis considers resource management issues in wireless sensor networks (WSNs), wireless local area networks (WLANs), and cognitive radio (CR) networks. Since energy is a critical resource in WSNs, we consider energy minimization techniques based on explicit node cooperation and distributed source coding (DSC). The explicit node cooperation based on space time block codes (STBC) improves energy efficiency of WSNs, by reducing the energy consumption per bit of each sensor node. The DSC on the other hand exploits the spatial correlation in WSNs, and thus reduces the data generated in a WSN. For the purpose of our analysis, we model the spatial correlation according to a linear Gauss-Markov model. Through our numerical results, we observe that the node cooperation combined with DSC can improve energy efficiency for many cases of interest. A unique aspect of our work is we obtain important structural results using the concepts from monotone comparative statics. These structural results provide insights into the general design of WSNs. Through our numerical results, we also demonstrate that, the cooperation based transmission can achieve better mutual information (MI)-energy tradeoff than the non-cooperation based transmission scheme. From the perspective of WLANs, we propose a price based approach to regulate the channel occupancy of low rate users, which is known to be the primary cause for low overall throughput in WLANs. Owing to the decentralized nature of WLANs we use non-cooperative game theory as a tool for analysis. Specifically, we use supermodular game theory. Through our analysis, we show that an increase in price leads to an increase in rate of WLAN users. We also prove that the best response dynamics indeed converge to the Nash equilibrium of the underlying non-cooperative game. Through our numerical results, we demonstrate that by proper tuning of the price, the proposed price based approach can lead to an improvement in overall throughput of a WLAN. Finally from the perspective of CR networks, we consider the impact of number of channels captured by a secondary user on its transmission control protocol (TCP) throughput. From our simulation results it was found that, there exists a definite optimal number of channels a secondary user needs to capture, to maximize its TCP throughput. / Applied Science, Faculty of / Electrical and Computer Engineering, Department of / Graduate

Nonalcoholic steatohepatitis (NASH) is a severe liver disorder characterized by triglyceride accumulation, severe inflammation, and fibrosis. With the recent increase in prevalence, NASH is now the leading cause of liver transplantation, with no approved therapeutics available. Despite years of research, the exact molecular mechanism of NASH progression is not well understood, but fat accumulation is believed to be the primary driver of the disease. Therefore, diacylglycerol O-acyltransferase 2 (DGAT2), a key enzyme in triglyceride synthesis, has been explored as a NASH target. RNAi-based therapeutics is revolutionizing the treatment of liver diseases, with recent chemical advances supporting long term gene silencing with single subcutaneous administration. Here we identified a hyper-functional, fully chemically stabilized GalNAc conjugated siRNA targeting DGAT2 (Dgat2-1473) that upon injection elicits up to three months of DGAT2 silencing (>80-90%, p<0.0001) in wild-type and NSG-PiZ “humanized” mice. Using an obesity-driven mouse model of NASH (ob/ob-GAN), Dgat2-1473 administration prevents and reverses triglyceride accumulation (> 50%, p:0.0008), resulting in significant improvement of the fatty liver phenotype. However, surprisingly, the reduction in liver fat didn’t translate into a similar impact on inflammation and fibrosis. Thus, while Dgat2-1473 is a practical, long-lasting silencing agent for potential therapeutic attenuation of liver steatosis, combinatorial targeting of a second pathway may be necessary for therapeutic efficacy against NASH.

V této práci je vytvořen model rozhodovací situace v odpadovém hospodářství využívající metody teorie her. Model tvoří nekooperativní hra pro reprezentaci konfliktu zpracovatelů odpadu a kooperativní hra pro reprezentaci konfliktu producentů odpadu. Pro konflikt zpracovatelů odpadu je k nalezení strategií při volbě cen na bráně využit koncept Nashovy rovnováhy, takto nalezené stabilní strategie mohou sloužit jako předpověď budoucí situace. Pro zpřesnění množin strategií jsou určeny dolní a horní meze. Pro konflikt producentů odpadu se uvažuje spolupráce všech producentů a určuje se pro ni přerozdělení nákladů pomocí Shapleyho hodnoty a nucleolu. Pro konflikt více producentů jsou vyvinuty aproximační algoritmy pro Shapleyho hodnotu i nucleolus. Tyto algoritmy jsou založeny na předpokladu, že se vzdálení hráči vzájemně neovlivňují. Model je aplikován na situaci v České republice. Pro konflikt zpracovatelů odpadu je nalezen jeden bod Nashovy rovnováhy. Pro konflikt producentů odpadu jsou určeni někteří producenti s vysokým kooperativním potenciálem.

Die Nicht-alkoholische Steatohepatitis (NASH), gehörig zu der Gruppe der chronischen Lebererkrankungen als eine schwere Form der Nicht-alkoholischen Fettleber-erkrankungen (NAFLD), nimmt in ihrer Prävalenz ständig zu. Gründe dafür sind u.a. eine gesteigerte Nahrungsaufnahme sowie Veränderungen der Nahrungszusammen-setzung. Es kommt zur Ausbildung einer Steatose, die sich unter Mitwirkung verschie-dener Einflussfaktoren zur Steatohepatitis weiterentwickeln kann, wobei die Pathoge-nese noch nicht genau verstanden ist. Die Nicht-alkoholische Steatohepatitis geht oft einher mit Insulinresistenz und starkem Übergewicht. Die Folgen für die Leber sind Funktionseinschränkungen und –verlust, hervorgerufen durch eine massive Akkumula-tion von Triglyzeriden in den Hepatozyten, Entzündungsprozesse sowie einem fibro-tischen Umbau der Leber. Im fortgeschritten Stadium wird eine Lebertransplantation unausweichlich, die jedoch aufgrund des zunehmenden Mangels an Spenderorganen oft nicht möglich ist. Eine Alternative bietet die Transplantation mesenchymaler Stammzellen (MSC). MSC können in vitro in leberzellähnliche Zellen differenziert wer-den und weisen dabei essentielle hepatozytäre Eigenschaften auf, wodurch sie als möglicher Ersatz bzw. als Überbrückungstherapie bis zur Lebertransplantation in Frage kommen. Die vorliegende Arbeit beschäftigte sich mit dieser Fragestellung. Dazu wur-de ein Tiermodell der NASH mittels Methionin-Cholin-defizienter Diät (MCD-Diät) etab-liert und die Transplantation von hepatozytär differenzierten MSC durchgeführt. An-hand spezifischer zellulärer und biochemischer Marker der NASH konnte die Wirkung des Zelltransplantats auf die Empfängerleber analysiert werden. Es hat sich gezeigt, dass die MSC einen anti-inflammatorischen, anti-fibrotischen und pro-proliferativen Einfluss auf das Empfängerparenchym hatten und somit zur Verbesserung der Symptomatik der NASH beitrugen.

<div>This study explores the vertical relationships in the supply chain at three different levels, namely, firm-consumer interface, supplier-buyer interface, and firm-government interface. We provide a brief description of the results obtained for the specific problems considered in this study.</div><div><br></div><div><div>The firm-consumer interface is examined in Chapter 2. We explore firms’ selling strategy when dynamically competing for a common stream of consumers. In the situation of pure price competition, a commonly studied case, it is known that the </div><div>seller with a higher stock level can compete more effectively by forcing the seller with a lower stock level to sell out first and enjoy a monopoly power afterward. We show that when the sellers are open to price bargaining as a way of attracting buyers, the </div><div>competition equilibrium can exhibit different outcomes. When the overall stock held by the sellers is limited, there is a good chance that both sellers deplete the inventories before the end of the selling season. In this case, an incoming buyer would prefer a</div><div>high inventory seller, with whom he can bargain down the price. Interestingly, such a phenomenon only appears when the length of selling season is long enough. Thus, our study highlights the unique role of bargaining in consumer markets, as well as the importance of time horizon in characterizing equilibrium for dynamic games.</div></div><div><br></div><div>The supplier-buyer interface is studied in Chapter 3. In recent years, an increasing number of studies have applied the Nash bargaining (NB) solution to study channel relationships. However, this solution concept builds on an unrealistic axiom of independence of irrelevant alternatives. We demonstrate that, indeed, the NB solution can produce unreasonable outcomes in vertical negotiations. For example, a supplier negotiating with a monopoly retailer can end up making a higher profit than the one negotiating with a retailer facing potential competitions. To address this issue, we examine the Kalai-Smorodinsky (KS) solution as an alternative. Our analysis suggests that in competing supply chains, the KS solution appropriately captures the negotiation power shift induced by the decision ownership, the negotiation sequence, the vertical relationship, the competition intensity, the contract contingency, and the contract type. This is the first time the KS solution concept is applied to supply chain negotiations.<br></div><div><br></div><div>The firm-government interface is explored in Chapter 4. From the policymakers’ perspective, incentives firms actions toward increasing the product consumption for the needy group or increasing social welfare has a major influence in many supply chains. For example, agricultural products are subsidized by many governments. In this study, we analyze the design of government subsidy programs to induce socially improved firm decisions. We show that subsidizing on production input can lead to a more balanced distribution of market shares and firm profits than subsidizing on production output. Moreover, firms with efficient production technology prefer output subsidy, while those with inefficient production technology favor input subsidy<br></div>

No description available.

Thesis / Doctor of Philosophy (PhD)

Overweight has become a major health care problem in Western societies and is accompanied by an increasing incidence and prevalence of non-alcoholic fatty liver disease (NAFLD). The progression from NAFLD to non-alcoholic steatohepatitis (NASH) marks a crucial tipping point in the progression of severe and irreversible liver diseases. This study aims to gain further insight into the molecular processes leading to the evolution from steatosis to steatohepatitis. Steatosis was induced in cultures of primary human hepatocytes by continuous five-day exposure to free fatty acids (FFAs). The kinetics of lipid accumulation, lipotoxicity, and oxidative stress were measured. Additionally, ER stress was evaluated by analyzing the protein expression profiles of its key players: PERK, IRE1a, and ATF6a. Our data revealed that hepatocytes are capable of storing enormous amounts of lipids without showing signs of lipotoxicity. Prolonged lipid accumulation did not create an imbalance in hepatocyte redox homeostasis or a reduction in antioxidative capacity. However, we observed an FFA-dependent increase in ER stress, revealing thresholds for triggering the activation of pathways associated with lipid stress, inhibition of protein translation, and apoptosis. Our study clearly showed that even severe lipid accumulation can be attenuated by cellular defenses, but regenerative capacities may be reduced.

Lean Startup is a widely adopted method nowadays, which contains a consistent approach to unveil a valid business model in a scenario of extreme uncertainty. This process involves a significant amount of effectual reasoning. On the other hand, established companies use planning strategies for their operations where causal reasoning drives the decision-making process based on future market predictions. There is clearly a gap on how growing startups that have discovered a working business model shift their initial effectual methodologies to more causal methods while they grow. In this thesis, common effectual and causal methodologies are explained and mapped against existing frameworks used in the industry. Furthermore, an analysis of how companies can include causality into the effectual methodologies initially used is done, in particular using the Lean Startup framework. Furthermore, the intrusion of causal components in effectual frameworks leads to a question of balancing between the causal and effectual components. A simple method to detect whether a startup needs one or the other during its evolution is presented and explained using game theory. Through non-cooperative game strategies, i.e. Nash equilibrium, a simple rule to evaluate the current balance between causation and effectuation can be used.