Inflammation of the Hypothalamus Leads to Defective Pancreatic Islet Function

Type 2 diabetes mellitus results from the complex association of insulin resistance and pancreatic beta-cell failure. Obesity is the main risk factor for type 2 diabetes mellitus, and recent studies have shown that, in diet-induced obesity, the hypothalamus becomes inflamed and dysfunctional, resulting in the loss of the perfect coupling between caloric intake and energy expenditure. Because pancreatic beta-cell function is, in part, under the control of the autonomic nervous system, we evaluated the role of hypothalamic inflammation in pancreatic islet function. In diet-induced obesity, the earliest markers of hypothalamic inflammation are present at 8 weeks after the beginning of the high fat diet; similarly, the loss of the first phase of insulin secretion is detected at the same time point and is restored following sympathectomy. Intracerebroventricular injection of a low dose of tumor necrosis factor a leads to a dysfunctional increase in insulin secretion and activates the expression of a number of markers of apoptosis in pancreatic islets. In addition, the injection of stearic acid intracerebroventricularly, which leads to hypothalamic inflammation through the activation of tau-like receptor-4 and endoplasmic reticulum stress, produces an impairment of insulin secretion, accompanied by increased expression of markers of apoptosis. The defective insulin secretion, in this case, is partially dependent on sympathetic signal-induced peroxisome proliferator receptor-gamma coactivator Delta a and uncoupling protein-2 expression and is restored after sympathectomy or following PGC1 alpha expression inhibition by an antisense oligonucleotide. Thus, the autonomic signals generated in concert with hypothalamic inflammation can impair pancreatic islet function, a phenomenon that may explain the early link between obesity and defective insulin secretion.

Gene optimization leads to robust expression of human respiratory syncytial virus nucleoprotein and phosphoprotein in human cells and induction of humoral immunity in mice

Human respiratory syncytial virus (HRSV) is the major pathogen leading to respiratory disease in infants and neonates worldwide. An effective vaccine has not yet been developed against this virus, despite considerable efforts in basic and clinical research. HRSV replication is independent of the nuclear RNA processing constraints, since the virus genes are adapted to the cytoplasmic transcription, a process performed by the viral RNA-dependent RNA polymerase. This study shows that meaningful nuclear RNA polymerase II dependent expression of the HRSV nucleoprotein (N) and phosphoprotein (F) proteins can only be achieved with the optimization of their genes, and that the intracellular localization of N and P proteins changes when they are expressed out of the virus replication context. Immunization tests performed in mice resulted in the induction of humoral immunity using the optimized genes. This result was not observed for the non-optimized genes. In conclusion, optimization is a valuable tool for improving expression of HRSV genes in DNA vaccines. (c) 2009 Elsevier B.V. All rights reserved.

Ab Initio Calculations of Structural Evolution and Conductance of Benzene-1,4-dithiol on Gold Leads

By performing at) initio density functional theory (DFT) calculations and electronic transport simulations based on the OFT nonequilibrium Green`s functions method we investigate how the conformational changes of a benzene-1,4-dithiol molecule bonded to gold affect the molecular transport as the electrodes are separated from each other. In particular we consider the full evolution of the stretching process until the Junction breaking point and compare results obtained with a standard semilocal exchange and correlation functional to those computed with a self-interaction corrected method. We conclude that the inclusion of self-interaction corrections is fundamental for describing both the molecule conductance and its stability against conformational fluctuations.

Long-term intermittent feeding, but not caloric restriction, leads to redox imbalance, insulin receptor nitration, and glucose intolerance

Calorie restriction is a dietary intervention known to improve redox state, glucose tolerance, and animal life span. Other interventions have been adopted as study models for caloric restriction, including nonsupplemented food restriction and intermittent, every-other-day feedings. We compared the short- and long-term effects of these interventions to ad libitum protocols and found that, although all restricted diets decrease body weight, intermittent feeding did not decrease intra-abdominal adiposity. Short-term calorie restriction and intermittent feeding presented similar results relative to glucose tolerance. Surprisingly, long-term intermittent feeding promoted glucose intolerance, without a loss in insulin receptor phosphorylation. Intermittent feeding substantially increased insulin receptor nitration in both intra-abdominal adipose tissue and muscle, a modification associated with receptor inactivation. All restricted diets enhanced nitric oxide synthase levels in the insulin-responsive adipose tissue and skeletal muscle. However, whereas calorie restriction improved tissue redox state, food restriction and intermittent feedings did not. In fact, long-term intermittent feeding resulted in largely enhanced tissue release of oxidants. Overall, our results show that restricted diets are significantly different in their effects on glucose tolerance and redox state when adopted long-term. Furthermore, we show that intermittent feeding can lead to oxidative insulin receptor inactivation and glucose intolerance. (C) 2011 Elsevier Inc. All rights reserved.

The impact of big-boxes on local retail : What happens when IKEA comes to town?

The development of large discount retailers, or big-boxes as they are sometimes referred to, are often subject to heated debate and their entry on a market is greeted with either great enthusiasm or dread. For instance, the world’s largest retailer Wal-Mart (Forbes 2014) has a number of anti- and pro-groups dedicated to its being and the event of a Wal-Mart entry tends to be met with protests and campaigns (Decamme 2013) but also welcomed by, for instance, consumers (Davis & DeBonis 2013). Also in Sweden, the entry of a big box is a hot topic and before IKEA’s opening i Borlänge 2013, the first in Sweden in more than five years, great expectations were mixed with worry (Västerbottens-Kuriren 2011).The presence of large scale discount retailers is not, however, a novel phenomenon but a part of a long-term change in retailing that has taken place globally over the past couple of decades (Taylor & Smalling, 2005). As noted by Dawson (2006), the trend in Europe has over the past few decades gone towards an increasing concentration of large firms along with a decrease of smaller firms.This trend is also detectable in the Swedish retail industry. Over the past decade, the retailing industry in Sweden has increased by around 190 Billion SEK, and its share of GDP has risen from 2,7% to 2,9%, while the number of employees have increased from 200 000 to 250 000 (HUI 2013). This growth, however, has not been distributed evenly but rather it has been oriented mainly towards out-of-town retail clusters. Parallel to this development, the number of large retailers has risen at the expense of market shares of smaller independent firms (Rämme et al 2010). Thereby, the presence of large scale retailers is simply part of a changing retail landscape.The effects of this development, where large scale retailing agents relocate shopping to out-of-town shopping areas, have been heavily debated. On the one hand, the big-boxes are accused of displacing independent small retail businesses in the city-centers and the residential areas, resulting in, to some extent, reduced employment opportunities and less availability for the consumers - especially the elderly (Ljungberg et al 2006). In addition, as access to shopping now tends to require some sort of a motorized vehicle, environmental aspects to the discussion have emerged. Ultimately these types of concerns have resulted in calls for regulations against this development (Olsson 2010). On the other hand, the proponents of the new shopping landscape argue that this evolution implies productivity gains, the benefits of lower prices and an increased variety of products (Maican & Orth 2012). Moreover it is argued that it leads to, for instance, better services (such as longer opening hours) and a creative destruction transformation pressure on retailers, which brings about a renewal of city-centerIIretail and services, increasing their attractivity (Bergström 2010). The belief in benefits of a big box entry can be exemplified by the attractivity of IKEA, and the fact that municipalities are prepared to commit to expenses amounting up to hundreds of millions in order to attract the entry of this big-box. Borlänge municipality, for instance, agreed to expenses of about 350 million SEK in order to secure the entry of IKEA, which opened in 2013 (Blomgren 2009).Against this backdrop, the overall effects of large discount retailers become important: Are the economic benefits enough to warrant subsidies or are there, on the contrary, some very compelling grounds for regulations against these types of establishments? In other words; how is overall retail in a region where a store like IKEA enters affected? And how are local retail firms affected?In order to answer these questions, the purpose of this thesis is to study how entry of a big-box retailer affects the entry region. The object of this study is IKEA - one of the world’s largest retailers, with 345 stores, active in over 40 countries and with profits of about 3.3 billion (IKEA 2013; IKEA 2014). By studying the effects of IKEA-entry, both on an aggregated level and on firm level, this thesis intends to find indications of how large discount retail establishments in general can be expected to affect the economic development both in a region overall, but also on the local firm level, something which is of interest to both policymakers as well as the retailing industry in general.The first paper examines the effects of IKEA on retail revenues and employment in the municipalities that IKEA chose to enter between 2000 and 2011; Gothenburg, Haparanda, Kalmar and Karlstad. By means of a matching method we first identify non-entry municipalities that have a similar probability of IKEA entry as the true entry municipalities. Then, using these non-entry municipalities as a control group, the causal effects of IKEA entry can be estimated using a treatment-control approach. We also extend the analysis to examine the spatial impact of IKEA by estimating the effects on retail in neighboring municipalities. It is found that a new IKEA store increases revenues in durable goods trade with 20% in the entry municipality and the number of employees with 17%. Only small, and in most cases statistically insignificant, negative effects were found in neighboring municipalities.It appears that there is a positive net effect on durables retail sales and employment in the entry municipality. However, the analysis is based on data on an aggregated municipality level and thereby it remains unclear if and how the effects vary within the entry municipalities. In addition, the data used in the first study includes the sales and employment of IKEA itself, which could account for the majority of the increases in employment and retail. Thereby the potential spillover effects on incumbent retailers in the entry municipalities cannot be discerned in the first study.IIITo examine effects of IKEA entry on incumbent retail firms, the second paper in this thesis analyses how IKEA entry affects the revenues and employment of local retail firms in three municipalities; Haparanda, Kalmar and Karlstad, which experienced entry by IKEA between 2000 and 2010. In this second study, we exclude Gothenburg due to the fact that big-box entry appears to have weaker effects in metropolitan areas (as indicated by Artz & Stone 2006). By excluding Gothenburg we aim to reduce the geographical heterogeneity in our study. We obtain control municipalities that are as similar as possible to the three entry municipalities using the same method as in the previous study, but including a slightly different set of variables in the selection equation. Using similar retail firms in the control municipalities as our comparison group, we estimate the impact of IKEA entry on revenues and employment for retail firms located at varying distances from the IKEA entry site.The results generated in this study imply that entry by IKEA increases revenues in incumbent retail firms by, on average, 11% in the entry municipalities. In addition, we do not find any significant impact on retail revenues in the city centers of the entry municipalities. However, we do find that retail firms within 1 km of the IKEA experience increases in revenues of about 26%, which indicates large spillover effects in the area nearby the entry site. As expected, this impact decreases as we expand the buffer zone: firms located between 0-2 km experiences a 14% increase and firms in 2-5 km experiences an increase of 10%. We do not find any significant impacts on retail employment.

The impact of price changes on volume sales of alcoholic beverages in Sweden, 2006-2013

We evaluate whether price elasticities on registered alcohol have changed in the last ten years in Sweden, in particular with regard to the investigation by Asplund et al (2007). We also investigate the fiscal effects of such changes. According to our estimates, price elasticities have increased, and these increases may have substantial effects on estimated changes in tax revenues when commodity tax rates are changed. In particular, commodity tax rates on spirits may have reached “Laffer territory” where tax increases may actually lower tax revenues.

O canal de distribuição para produtos cosméticos em Porto Alegre : uma análise com foco nos salões de beleza

As empresas estão participando de um mercado cada vez mais competitivo. Esta disputa acirrada das empresas pelos clientes tem propiciado canais alternativos de distribuição dos produtos aos diferentes segmentos de mercado. Os canais de distribuição estão adquirindo uma importância cada vez maior aos olhos dos fabricantes e dos clientes, principalmente na questão de serviços. De acordo com Ballou (2001, p.44), “o serviço ao cliente, inclui disponibilidade de estoques, rapidez na entrega, rapidez e acuracidade no preenchimento de pedidos”. A esses serviços pode ser somada uma gama variada de outros serviços a serem prestados pelos participantes do canal de distribuição ou pelos fabricantes. A empresa Ravel Produtos Cosméticos e Dermatológicos será a principal usuária dos resultados obtidos com este estudo, pois é fabricante de produtos cosméticos e tem seu foco de atuação principal na cidade de Porto Alegre. O objetivo deste trabalho foi analisar o canal de distribuição para produtos cosméticos destinados a consumidores de alta renda no mercado de Porto Alegre, procurando identificar os aspectos de serviços demandados, produtos utilizados e mix de produtos comercializados pelo canal de distribuição: salões de beleza. O estudo foi realizado através de pesquisa qualitativa, com entrevistas individuais junto aos proprietários dos salões, ou junto às pessoas que decidem o mix de produtos a ser utilizado ou comercializado pelos salões. O mix de produtos comercializados pelos salões de beleza em Porto Alegre conforme a pesquisa realizada, é o seguinte: xampus, cremes, máscaras, hidratantes, fluidos e géis. Entre as respostas das entrevistas, foram encontrados os seguintes serviços demandados pelos salões de beleza: amostras de produtos, entregas rápidas, frete cif, suporte técnico do fabricante, prazos elásticos de pagamento e exclusividade como canal de distribuição para as linhas que comercializa.

The behavior of temporary sales in a macroeconomic context

Nós investigamos promoções temporárias usando uma base de dados detalhada de 13 anos sobre preços ao consumidor no Brasil, com cotações de preços coletadas decendialmente. Nós encontramos forte evidências da existência de relação entre a frequência e tamanho de promoções e as variáveis macroeconômicas. A crença comum na literatura de que promoções não reagem a mudanças nas variáveis macroeconômicas pode ser devido a baixa volatilidade do cenário macro- econômico nos países analisados até o presente momento.

Determinantes da intenção de uso de serviços pessoais : um estudo em assessoria esportiva e salões de beleza

A intenção de uso categoria de serviços e seu modelo vêm recebendo relativo interesse no meio acadêmico tanto como preditora do comportamento de compra, quanto como alternativa aos modelos de comportamento, os quais presumem que o indivíduo se recorda de suas experiências prévias com prestadores de serviços. Por acreditarem nesta premissa, normalmente os profissionais de marketing focam suas ações e esforços no nível de escolha do prestador do serviço, não atentando para as fases anteriores e aos antecedentes da compra do serviço, os quais têm um papel importante sobre a intenção de uso da categoria de serviço. Elementos relacionados ao serviço como qualidade e preço estarão relacionadas às percepções do consumidor sobre a categoria e somadas à sua experiência prévia, expectativa de benefícios e condição financeira alterarão a intenção deste se comportar a favor ou contra a contratação do prestador de serviço. Com objetivo de entender tal dinâmica esta dissertação avalia empiricamente duas categorias de serviços pessoais (salão de beleza e assessoria esportiva) evidenciando a importância dos antecedentes à intenção de uso. A adição de variáveis como qualidade prévia percebida e comunicação boca-a-boca como preditoras da intenção foram suportadas, sugerindo mudanças no estado atual da teoria de intenção de uso.

"We sold a million units": the role of advertising past-sales

In a market where past-sales embed information about consumers’ tastes (quality), we analyze the seller’s incentives to invest in a costly advertising campaign to report them under two informational assumptions. In the …rst scenario, a pooling equilibrium with past-sales advertising is derived. Information revelation only occurs when the seller bene…ciates from the herding behaviour that the advertising campaign induces on the part of consumers. In the second informational regime, a separating equilibrium with past-sales advertising is computed. Information revelation always happens, either through prices or through costly advertisements.

Endogenous collateral: arbitrage and equilibrium without bounded short sales

We study the implications of the absence of arbitrage in an two period economy where default is allowed and assets are secured by collateral choosen by the borrowers. We show that non arbitrage sale prices of assets are submartingales, whereas non arbitrage purchase prices of the derivatives (secured by the pool of collaterals) are supermartingales. We use these non arbitrage conditions to establish existence of equilibrium, without imposing bounds on short sales. The nonconvexity of the budget set is overcome by considering a continuum of agents. Our results are particularly relevant for the collateralized mortgage obligations(CMO) markets.

Fundamentos da ordem republicana : repensando o pacto de Campos Sales

Resumo não disponível.

Essays on price dynamics

Esta tese tem como objetivo principal aproximar a evidencia empirica existente sobre os agregados macroeconomicos com as novas evidencias empiricas baseadas nos micro dados de precos ao consumidor, tendo como base os modelos padroes de rigidez de preco utilizados na literatura de politica monetaria. Para isso, esta tese utiliza a base de dados individuais de precos ao consumidor no Brasil fornecida pela Fundacao Getulio Vargas. Especificamente, esta tese foca em tres temas principais: a existencia de variac˜oes temporararias de precos, a heterogeneidade na rigidez de precos entre firmas de um mesmo setor e o formato das func˜oes hazard. Os resultados mostram que: existe de fato uma correlac˜ao entre as variaveis referentes as mudancas temporararias de precos e os agregados macroeconomicos; a heterogeneidade na rigidez de precos entre firmas de um mesmo setor apresenta efeitos significativos sobre a dinamica dos agregados macroeconomicos; e por fim, o formato mais geral da func˜ao hazard proposta nesta tese possibilita novas dinamicas dos agregados macroeconomicos.

Políticas públicas, conselhos municipais e agricultura familiar : representações sobre o rural em Roca Sales/RS e a emergência da noção de multifuncionalidade da agricultura

Esta dissertação trata inicialmente de questões relativas ao papel das políticas públicas voltadas à modernização da agricultura nos contextos internacional e brasileiro. Com efeito, procurou-se evidenciar como foram concebidos os processos de modernização agrícola assentados no produtivismo. A propósito, os problemas sócio-ambientais gerados por estas políticas propiciaram o início do debate sobre a multifuncionalidade da agricultura. No caso brasileiro, a contestação das políticas de modernização conservadora da agricultura chegando levou ao Programa Nacional de Fortalecimento da Agricultura Familiar (PRONAF), cujo público-alvo, os agricultores familiares, estiveram, em grande medida, alijados até então das políticas públicas modernizantes. Num segundo momento, chamou-se a atenção para a emergência da noção de multifuncionalidade da agricultura, particularmente no que ela pode vir a transformar os rumos do desenvolvimento rural brasileiro, além da questão da produção. Traçando paralelos com o debate da multifuncionalidade, dedicou-se um capítulo sobre a evolução das concepções em torno da propriedade fundiária: de um direito irrestrito à sua função sócio-ambiental. Na atualidade, a incorporação de demandas ambientais reorientaram essa discussão. Por outro lado, a dissertação permite também discutir o lugar do Conselho de Desenvolvimento Rural (CMDR) de Roca Sales, a partir de uma interpretação fundada nas lógicas de seu funcionamento. Destacou-se a dependência do conselho em relação a programas estaduais e federais cuja alocação de recursos exige a caução dos conselheiros do desenvolvimento rural. Enfim, procurou-se discutir as representações sociais dos atores locais, de alguma maneira implicados no conselho, sobre a agricultura e o mundo rural. Notadamente, tentou-se examinar em qual medida as preocupações com o desenvolvimento rural consideram funções não produtivas da agricultura, principalmente nas dimensões da: reprodução socioeconômica das famílias; promoção da segurança alimentar da sociedade e das próprias famílias rurais; manutenção do tecido social e cultural e preservação dos recursos naturais e da paisagem rural. Nesse sentido, puderam-se apreender nas visões dos atores locais percepções que se aproximam dos fundamentos da noção de multifuncionalidade da agricultura, principalmente quando relacionados à temas como: agroindustrialização familiar, diversificação, profissionalização do agricultor, segurança alimentar, autoconsumo e turismo rural. Com efeito, as preocupações com o desenvolvimento rural revelam propensões dos atores locais em considerar as funções não mercantis da agricultura.

Effect of price and in-store promotion on sales: a study of distinct regions in an emerging market

Increasing competition caused by globalization, high growth of some emerging markets and stagnation of developed economies motivate Consumer Packaged Goods (CPGs) manufacturers to drive their attention to emerging markets. These companies are expected to adapt their marketing activities to the particularities of these markets in order to succeed. In a country classified as emerging market, regions are not alike and some contrasts can be identified. In addition, divergences of marketing variables effect can also be observed in the different retail formats. The retail formats in emerging markets can be segregated in chain self-service and traditional full-service. Thus, understanding the effectiveness of marketing mix not only in country aggregated level data can be an important contribution. Inasmuch as companies aim to generate profits from emerging markets, price is an important marketing variable in the process of creating competitive advantage. Along with price, promotional variables such as in-store displays and price cut are often viewed as temporary incentives to increase short-term sales. Managers defend the usage of promotions as being the most reliable and fastest manner to increase sales and then short-term profits. However, some authors alert about sales promotions disadvantages; mainly in the long-term. This study investigates the effect of price and in-store promotions on sales volume in different regions within an emerging market. The database used is at SKU level for juice, being segregated in the Brazilian northeast and southeast regions and corresponding to the period from January 2011 to January 2013. The methodological approach is descriptive quantitative involving validation tests, application of multivariate and temporal series analysis method. The Vector-Autoregressive (VAR) model was used to perform the analysis. Results suggest similar price sensitivity in the northeast and southeast region and greater in-store promotion sensitivity in the northeast. Price reductions show negative results in the long-term (persistent sales in six months) and in-store promotion, positive results. In-store promotion shows no significant influence on sales in chain self-service stores while price demonstrates no relevant impact on sales in traditional full-service stores. Hence, this study contributes to the business environment for companies wishing to manage price and sales promotions for consumer brands in regions with different features within an emerging market. As a theoretical contribution, this study fills an academic gap providing a dedicated price and sales promotion study to contrast regions in an emerging market.