Identification of a novel ligand binding motif in the transthyretin channel

The design of therapeutic compounds targeting transthyretin (TTR) is challenging due to the low specificity of interaction in the hormone binding site. Such feature is highlighted by the interactions of TTR with diclofenac, a compound with high affinity for TTR, in two dissimilar modes, as evidenced by crystal structure of the complex. We report here structural analysis of the interactions of TTR with two small molecules, 1-amino-5-naphthalene sulfonate (1,5-AmNS) and 1-anilino-8-naphthalene sulfonate (1,8-ANS). Crystal structure of TTR: 1,8-ANS complex reveals a peculiar interaction, through the stacking of the naphthalene ring between the side-chain of Lys15 and Leu17. The sulfonate moiety provides additional interaction with Lys15` and a water-mediated hydrogen bond with Thr119`. The uniqueness of this mode of ligand recognition is corroborated by the crystal structure of TTR in complex with the weak analogue 1,5-AmNS, the binding of which is driven mainly by hydrophobic partition and one electrostatic interaction between the sulfonate group and the Lys15. The ligand binding motif unraveled by 1,8-ANS may open new possibilities to treat TTR amyloid diseases by the elucidation of novel candidates for a more specific pharmacophoric pattern. (C) 2009 Published by Elsevier Ltd.

Redox regulation of the mitochondrial K(ATP) channel in cardioprotection

The mitochondrial ATP-sensitive potassium channel (mK(ATP)) is important in the protective mechanism of ischemic preconditioning (IPC). The channel is reportedly sensitive to reactive oxygen and nitrogen species, and the aim of this study was to compare such species in parallel, to build a more comprehensive picture of mK(ATP) regulation. mK(ATP) activity was measured by both osmotic swelling and Tl(+) flux assays, in isolated rat heart mitochondria. An isolated adult rat cardiomyocyte model of ischemia-reperfusion (IR) injury was also used to determine the role of mK(ATP) in cardioprotection by nitroxyl. Key findings were as follows: (i) mK(ATP) was activated by O(2)(center dot-) and H(2)O(2) but not other peroxides. (ii) mK(ATP) was inhibited by NADPH. (iii) mK(ATP) was activated by S-nitrosothiols, nitroxyl, and nitrolinoleate. The latter two species also inhibited mitochondrial complex II. (iv) Nitroxyl protected cardiomyocytes against IR injury in an mK(ATP)-dependent manner. Overall, these results suggest that the mK(ATP) channel is activated by specific reactive oxygen and nitrogen species, and inhibited by NADPH. The redox modulation of mK(ATP) may be an underlying mechanism for its regulation in the context of IPC. This article is part of a Special Issue entitled: Mitochondria and Cardioprotection. (C) 2010 Elsevier B.V. All rights reserved.

Effects of a high fat diet on liver mitochondria: increased ATP-sensitive K(+) channel activity and reactive oxygen species generation

High fat diets are extensively associated with health complications within the spectrum of the metabolic syndrome. Some of the most prevalent of these pathologies, often observed early in the development of high-fat dietary complications, are non-alcoholic fatty liver diseases. Mitochondrial bioenergetics and redox state changes are also widely associated with alterations within the metabolic syndrome. We investigated the mitochondrial effects of a high fat diet leading to non-alcoholic fatty liver disease in mice. We found that the diet does not substantially alter respiratory rates, ADP/O ratios or membrane potentials of isolated liver mitochondria. However, H(2)O(2) release using different substrates and ATP-sensitive K(+) transport activities are increased in mitochondria from animals on high fat diets. The increase in H(2)O(2) release rates was observed with different respiratory substrates and was not altered by modulators of mitochondrial ATP-sensitive K(+) channels, indicating it was not related to an observed increase in K(+) transport. Altogether, we demonstrate that mitochondria from animals with diet-induced steatosis do not present significant bioenergetic changes, but display altered ion transport and increased oxidant generation. This is the first evidence, to our knowledge, that ATP-sensitive K(+) transport in mitochondria can be modulated by diet.

Factors influencing the choice of a bank : An international student perspective

Purpose: The purposeof this thesis is to identify what factors influence international students in their choice of a bank.Literature review: A review of previous research about bank selection criteria related to students as well as a few examples of bank choice studies in the general population is presented. The review consists of studies from different years to illustrate criteria that reoccur in order to decrease the chances of overlooking important criteria that may be of importance for today‘s customers. Method: The thesis is based upon empirical data gathering through a non-probability sampling technique by distributing questionnaires through the Internet and in person. The data was analyzedwith the help of exploratory factor analysis (EFA). Conclusion: We found thatfive factors influence the choice of bank for international students. These factors are: cost of the bank services, use of technology, convenience, banks‘ reputation and marketing communication effectiveness. These factors could be helpful for banks who want to gain customers from international students, which are a relatively unexploited customer segment.

Are central bank independence reforms necessary for achieving low and stable inflation?

Using data on the occurence of central bank independence (CBI) reforms in 131 countries during 1980-2005, we test whether they were important in reducing inflation and maintaining price stability. CBI reforms are found to have reduced inflation on average 3.31% when countries with historically high inflation rates are included. But countries with lower inflation have reduced it without institutional reforms granting central banks more independence, undermining the theoretical time-inconsistency case for CBI. There is furthermore no evidence that CBI reforms have helped reduce inflation variability.

Determinants and effects of central bank independence reforms

This thesis consists of four empirically oriented papers on central bank independence (CBI) reforms.    Paper [1] is an investigation of why politicians around the world have chosen to give up power to independent central banks, thereby reducing their ability to control the economy. A new data-set, including the possible occurrence of CBI-reforms in 132 countries during 1980-2005, was collected. Politicians in non-OECD countries were more likely to delegate power to independent central banks if their country had been characterized by high variability in inflation and if they faced a high probability of being replaced. No such effects were found for OECD countries.    Paper [2], using a difference-in-difference approach, studies whether CBI reform matters for inflation performance. The analysis is based on a dataset including the possible occurrence of CBI-reforms in 132 countries during the period of 1980-2005. CBI reform is found to have contributed to bringing down inflation in high-inflation countries, but it seems unrelated to inflation performance in low-inflation countries.    Paper [3] investigates whether CBI-reforms are important in reducing inflation and maintaining price stability, using a random-effects random-coefficients model to account for heterogeneity in the effects of CBI-reforms on inflation. CBI-reforms are found to have reduced inflation on average by 3.31 percent, but the effect is only present when countries with historically high inflation rates are included in the sample. Countries with more modest inflation rates have achieved low inflation without institutional reforms that grant central banks more independence, thus undermining the time-inconsistency theory case for CBI. There is furthermore no evidence that CBI-reforms have contributed to lower inflation variability    Paper [4] studies the relationship between CBI and a suggested trade-off between price variability and output variability using data on CBI-levels, and data the on implementation dates of CBI-reforms. The results question the existence of such a trade-off, but indicate that there may still be potential gains in stabilization policy from CBI-reforms.

Effects of central bank independence reforms on inflation in different parts of the world

The purpose of this study is to analyze the effect of CBI-reforms on inflation in different parts of the world from a theoretical and empirical perspective. Compared to previous studies, this study focuses on whether CBI-reforms have different effects on reducing inflation in different parts of the world. The study is based on a 132 country data-set from 1980 to 2005 compiled by Daunfeldt et al. (2008). The result indicates that the reduction in inflation due to the CBI-reforms varies between 2.2 and 12.32 percentage points in Asia, Europe, South America and Oceania, supporting the claim that implementing CBI-reforms can be successful in reducing inflation in most of the parts of the world.

A Study On The Flow Characteristics Influenced By Hydraulic Structure At A Channel Junction

Natural riversare consisting of various networks as junction andstreams. And sediment and erosion are occurred by specific stream condition. When flood season,large discharge flew in the river and river bed changed by high flow velocity. Especially junction area’s flow characteristics are very complex. The purpose of this study is to analyze the flow characteristics in channel junction, which are most influenced by large discharge like flooding and input water from tributary. We investigate the flow characteristics by using hydrodynamics and transport module in MIKE 3 FM. MIKE 3 FM model was helpful tool to analysis 3D hydrodynamics, erosion and sediment effect from channel bed. We analyze flow characteristics at channel junction. Also we consider hydraulic structures like a bridge pier which is influencing flow characteristics like a flow velocity, water level, erosion and scour depth in channel bed. In the model, we controlled discharge condition according to Froude Number and reflect various grain diameter size and flow ratio change in main stream and tributary. In the result, flow velocity, water level, erosion and sediment depth are analyzed. Additionally, we suggest a these result relationship with equations. This study will help the understand flow characteristics and influence of hydraulic structure in channel junction. Acknowledgments This research was supported by a grant (12-TI-C01) from Advanced Water Management Research Program funded by Ministry of Land, Infrastructure and Transport of Korean government.

Money with Bank Networks

Rio de Janeiro

What happens after the central bank of Brazil increases the target interbank rate by 1%?

I start presenting an explicit solution to Taylorís (2001) model, in order to illustrate the link between the target interest rate and the overnight interest rate prevailing in the economy. Next, I use Vector Auto Regressions to shed some light on the evolution of key macroeconomic variables after the Central Bank of Brazil increases the target interest rate by 1%. Point estimates show a four-year accumulated output loss ranging from 0:04% (whole sample, 1980 : 1-2004 : 2; quarterly data) to 0:25% (Post-Real data only) with a Örst-year peak output response between 0:04% and 1:0%; respectively. Prices decline between 2% and 4% in a 4-year horizon. The accumulated output response is found to be between 3:5 and 6 times higher after the Real Plan than when the whole sample is considered. The 95% confidence bands obtained using bias-corrected bootstrap always include the null output response when the whole sample is used, but not when the data is restricted to the Post-Real period. Innovations to interest rates explain between 4:9% (whole sample) and 9:2% (post-Real sample) of the forecast error of GDP.

Canal de crédito: um estudo sobre a influência das questões regulatórias no mercado de crédito brasileiro

A literatura econômica discute há algum tempo as influências da política monetária no nível de produto e emprego de longo-prazo. Paralelo a este debate seminal, surgiram ao longo dos últimos anos discussões sobre os canais de transmissão de política monetária. Dentre o conjunto de canais sugeridos pela literatura, o canal de crédito é um dos que mais tem motivado estudiosos a aprofundarem o conhecimento sobre a sua forma de interação com a economia monetária e real. Por esta razão, este trabalho busca evidências da presença de um canal de crédito no Brasil que funciona através de alterações endógenas no mercado de crédito, mais propriamente através da alteração das condições do balanço dos agentes e de mudanças nos seus custos de agência, que motivam uma queda dos saldos de crédito concedidos a estes. Mas mais do que isto, através dos testes empíricos desenvolvidos, procura-se evidenciar que a presença de um canal de crédito no Brasil é reforçado por exigências regulatórias impostas aos bancos, que os tornam mais conservadores na oferta de crédito marginal ao conjunto de tomadores novos e com operações de crédito já contratadas. Em especial, o teste toma como variável a série de saldos de crédito concedidos ao longo do tempo, baseada em resoluções do Banco Central que normatizam sobre o provisionamento de crédito, em que se supõe que um choque monetário seja capaz de piorar a qualidade do balanço dos agentes, forçando as instituições financeiras a reclassificarem-os para piores classes de risco. Esta reclassificação, por sua vez, deve aumentar a base de crédito sobre a qual residem os maiores percentuais de provisionamento, o que torna os banqueiros mais conservadores e menos desejosos em ofertar crédito para o conjunto de tomadores de maior risco e para os tomadores como um todo.

Escassez de crédito bancário no Brasil: comparação internacional e evidência recente

O objetivo deste trabalho é estudar o nível de crédito bancário no Brasil no período pós implantação do Plano Real. Para isso, o trabalho utiliza a metodologia de Barajas e Steiner (2002) mas utilizando uma amostra maior de países (além da economia brasileira, nove países da América Latina e quarenta não América Latina). Os resultados encontrados mostram que o crédito bancário historicamente não cresceu como o esperado e ainda é tão volátil quanto a média América latina. O sistema bancário não mostrou-se menor do que o esperado para a economia brasileira, mas é menos propenso ao crédito ao setor privado. O crédito ao setor público ainda ocupa uma fatia muito relevante no balanço do agregado bancário e sobre esse respeito o trabalho mostra que um aumento na securitização e cessão de crédito aumenta significativamente o crédito ao setor privado.