Dual modulation of cell survival and cell death by β2-adrenergic signaling in adult mouse cardiac myocytes

The goal of this study was to determine whether β1-adrenergic receptor (AR) and β2-AR differ in regulating cardiomyocyte survival and apoptosis and, if so, to explore underlying mechanisms. One potential mechanism is that cardiac β2-AR can activate both Gs and Gi proteins, whereas cardiac β1-AR couples only to Gs. To avoid complicated crosstalk between β-AR subtypes, we expressed β1-AR or β2-AR individually in adult β1/β2-AR double knockout mouse cardiac myocytes by using adenoviral gene transfer. Stimulation of β1-AR, but not β2-AR, markedly induced myocyte apoptosis, as indicated by increased terminal deoxynucleotidyltransferase-mediated UTP end labeling or Hoechst staining positive cells and DNA fragmentation. In contrast, β2-AR (but not β1-AR) stimulation elevated the activity of Akt, a powerful survival signal; this effect was fully abolished by inhibiting Gi, Gβγ, or phosphoinositide 3 kinase (PI3K) with pertussis toxin, βARK-ct (a peptide inhibitor of Gβγ), or LY294002, respectively. This indicates that β2-AR activates Akt via a Gi-Gβγ-PI3K pathway. More importantly, inhibition of the Gi-Gβγ-PI3K-Akt pathway converts β2-AR signaling from survival to apoptotic. Thus, stimulation of a single class of receptors, β2-ARs, elicits concurrent apoptotic and survival signals in cardiac myocytes. The survival effect appears to predominate and is mediated by the Gi-Gβγ-PI3K-Akt signaling pathway.

SMART, a simple modular architecture research tool: Identification of signaling domains

Accurate multiple alignments of 86 domains that occur in signaling proteins have been constructed and used to provide a Web-based tool (SMART: simple modular architecture research tool) that allows rapid identification and annotation of signaling domain sequences. The majority of signaling proteins are multidomain in character with a considerable variety of domain combinations known. Comparison with established databases showed that 25% of our domain set could not be deduced from SwissProt and 41% could not be annotated by Pfam. SMART is able to determine the modular architectures of single sequences or genomes; application to the entire yeast genome revealed that at least 6.7% of its genes contain one or more signaling domains, approximately 350 greater than previously annotated. The process of constructing SMART predicted (i) novel domain homologues in unexpected locations such as band 4.1-homologous domains in focal adhesion kinases; (ii) previously unknown domain families, including a citron-homology domain; (iii) putative functions of domain families after identification of additional family members, for example, a ubiquitin-binding role for ubiquitin-associated domains (UBA); (iv) cellular roles for proteins, such predicted DEATH domains in netrin receptors further implicating these molecules in axonal guidance; (v) signaling domains in known disease genes such as SPRY domains in both marenostrin/pyrin and Midline 1; (vi) domains in unexpected phylogenetic contexts such as diacylglycerol kinase homologues in yeast and bacteria; and (vii) likely protein misclassifications exemplified by a predicted pleckstrin homology domain in a Candida albicans protein, previously described as an integrin.

Coleta de dados pessoais e paradoxo da privacidade: um estudo entre usuários de aplicativos móveis

Aplicativos móveis de celulares que coletam dados pessoais estão cada vez mais presentes na rotina do cidadão comum. Associado a estas aplicações, há polêmicas sobre riscos de segurança e de invasão de privacidade, que podem se tornar entraves para aceitação destes sistemas por parte dos usuários. Por outro lado, discute-se o Paradoxo da Privacidade, em que os consumidores revelam mais informações pessoais voluntariamente, apesar de declarar que reconhecem os riscos. Há pouco consenso, nas pesquisas acadêmicas, sobre os motivos deste paradoxo ou mesmo se este fenômeno realmente existe. O objetivo desta pesquisa é analisar como a coleta de informações sensíveis influencia a escolha de aplicativos móveis. A metodologia é o estudo de aplicativos disponíveis em lojas virtuais para celulares através de técnicas qualitativas e quantitativas. Os resultados indicam que os produtos mais populares da loja são aqueles que coletam mais dados pessoais. Porém, em uma análise minuciosa, observa-se que aqueles mais buscados também pertencem a empresas de boa reputação e possuem mais funcionalidades, que exigem maior acesso aos dados privativos do celular. Na survey realizada em seguida, nota-se que os consumidores reduzem o uso dos aplicativos quando consideram que o produto coleta dados excessivamente, mas a estratégia para proteger essas informações pode variar. No grupo dos usuários que usam aplicativos que coletam dados excessivamente, conclui-se que o motivo primordial para compartilhar informações pessoais são as funcionalidades. Além disso, esta pesquisa confirma que comparar os dados solicitados pelos aplicativos com a expectativa inicial do consumidor é um constructo complementar para avaliar preocupações com privacidade, ao invés de simplesmente analisar a quantidade de informações coletadas. O processo desta pesquisa também ilustrou que, dependendo do método utilizado para análise, é possível chegar a resultados opostos sobre a ocorrência ou não do paradoxo. Isso pode dar indícios sobre os motivos da falta de consenso sobre o assunto

Library of high-resolution UES echelle spectra of F, G, K and M field dwarf stars

We present a library of Utrecht echelle spectrograph (UES) observations of a sample of F, G, K and M field dwarf stars covering the spectral range from 4800 Å to 10600 Å with a resolution of 55000. These spectra include some of the spectral lines most widely used as optical and near-infrared indicators of chromospheric activity such as Hβ, Mg I b triplet, Na I D_1, D_2, He I D_3, Hα, and Ca II IRT lines, as well as a large number of photospheric lines which can also be affected by chromospheric activity. The spectra have been compiled with the aim of providing a set of standards observed at high-resolution to be used in the application of the spectral subtraction technique to obtain the active-chromosphere contribution to these lines in chromospherically active single and binary stars. This library can also be used for spectral classification purposes. A digital version with all the spectra is available via ftp and the World Wide Web (WWW) in both ASCII and FITS formats.

Desempenho propulsivo de embarcações de pesca: estudo aplicado à melhoria das embarcações do Espírito Santo.

Este trabalho apresenta um procedimento simples e robusto para avaliação e análise do desempenho de instalações propulsoras de embarcações de pesca operando no Estado do Espírito Santo. O objetivo é verificar se as embarcações estão operando com baixa eficiência propulsiva, portanto, com consumo de combustível maior do que o desejável, e identificar possíveis ações de melhoria desta eficiência que poderiam ser implementadas com baixo custo. Tendo em vista as condições artesanais da construção e operação das embarcações de pesca no Espírito Santo, o procedimento foi desenvolvido de forma a poder ser aplicado com relativa facilidade pelas pessoas envolvidas na atividade pesqueira artesanal neste Estado. O procedimento envolve o levantamento de informações sobre a geometria do casco, as características da instalação propulsora existente e sobre alguns aspectos do desempenho das embarcações. Para este levantamento são propostos métodos e técnicas suficientemente simples para que possam ser facilmente aplicadas nos estaleiros. Com base nestes dados levantados implementou-se no procedimento proposto diversos algoritmos que permitem determinar o coeficiente propulsivo das embarcações de pesca e a perda de energia útil que ocorre tanto no motor, por conta de condições inadequadas de operação, quanto na transmissão desta energia para o hélice. Para a validação dos métodos e técnicas envolvidos neste procedimento e dos resultados fornecidos por ele, o mesmo foi aplicado em alguns cascos de embarcações de pesca disponíveis em estaleiros visitados no Estado. Para uma destas embarcações o procedimento foi aplicado em sua totalidade, permitindo identificar a baixa eficiência da instalação propulsora e algumas das possíveis causas que provocam a perda de energia útil no sistema. Finalmente, com base nesse exemplo de aplicação, um estudo de possíveis melhorias na instalação propulsora é apresentado ao final do trabalho.

E-CRM e a influência da digital analytics.

O mercado consumidor passou por diversas transformações ao longo do tempo devido principalmente à evolução tecnológica. A evolução tecnológica proporcionou ao consumidor a possibilidade de escolher por produtos e marcas, e permite a oportunidade de colaborar e influenciar a opinião de outros consumidores através do compartilhamento de experiências, principalmente através da utilização de plataformas digitais. O CRM (gerenciamento do relacionamento com o consumidor) é a forma utilizada pelas empresas para conhecerem o consumidor e criar um relacionamento satisfatório entre empresa e consumidor. Esse relacionamento tem o intuito de satisfazer e fidelizar o consumidor, evitando que ele deixe de consumir a marca e evitando que ele influencie negativamente outros consumidores. O e-CRM é o gerenciamento eletrônico do relacionamento com o consumidor, que possui todas as tradicionais características do CRM, porém com o incremento do ambiente digital. O ambiente digital diminuiu a distância entre pessoas e empresas e se tornou um meio colaborativo de baixo custo de interação com o consumidor. Por outro lado, este é um meio onde o consumidor deixa de ser passivo e se torna ativo, o que o torna capaz de influenciar não só um pequeno grupo de amigos, mas toda uma rede de consumidores. A digital analytics é a medição, coleta, análise e elaboração de relatórios de dados digitais para os propósitos de entendimento e otimização da performance em negócios. A utilização de dados digitais auxilia no desenvolvimento do e-CRM através da compreensão do comportamento do consumidor em um ambiente onde o consumidor é ativo. O ambiente digital permite um conhecimento mais detalhado dos consumidores, baseado não somente nos hábitos de compra, mas também nos interesses e interações. Este estudo tem como objetivo principal compreender como as empresas aplicam os conceitos do e-CRM em suas estratégias de negócios, compreendendo de que forma a digital analytics contribui para o desenvolvimento do e-CRM, e compreendendo como os fatores críticos de sucesso (humano, tecnológico e estratégico) impactam na implantação e desenvolvimento do e-CRM. Quatro empresas de diferentes segmentos foram estudadas através da aplicação de estudo de caso. As empresas buscam cada vez mais explorar as estratégias de e-CRM no ambiente digital, porém existem limitações identificadas devido à captação, armazenamento e análise de informações multicanais, principalmente considerando os canais digitais. Outros fatores como o apoio da alta direção e a compreensão de funcionários para lidar com estratégias focadas no consumidor único também foram identificados neste estudo. O estudo foi capaz de identificar as informações mais relevantes para a geração de estratégias de gerenciamento eletrônico do relacionamento com o consumidor e identificou os aspectos mais relevantes dos fatores críticos de sucesso.

Dhoā:māhādhinje:ćhañṭe:vijaṇjī : manuscript, 1778-1865

Local paper. Beginning and end folios in brittle and poor condition, several folios repaired, many folios water-stained.

Regional government and the "New Europe"

Introduction. Regional government in contemporary western Europe corresponds to a type of society and economy variously labeled "post-industrial", "post-bourgeois" or merely "the New Europe."l This New Europe evolved historically from the interconnected strands of capitalism; industrialism and pluralistic democracy. It resembles in many respects the type of economy and society familiar to us in North America. Regional government in such a society is thus merely an adaptation on the scale of half a continent of forms of social and economic organization which evolved historically at the national level. Regional government in the New Europe is the institutional and political recognition that societies have changed dramatically since 1945, so dramatically that they cannot be adequately described in the doctrines and ideologies made familiar by nineteenth and early twentieth century political thought. Hence the New Europe and its regional government is the future of that part of history which has also been aptly described as "the end of ideology."

The SRM and the dream to resolve banks without public money. CEPS Commentary, 19 December 2013

In his assessment of the compromise agreement reached on the Single Resolution Mechanisn (SRM), Daniel Gros finds that the popular perception that the periphery has the most to gain from the establishment of a unified resolution regime might have gotten it backwards. In reality, he finds that Germany and other surplus countries have a bigger interest in tying the hands of their national resolution authorities, which have a tendency to be too generous.

The Sovereign Debt Crisis: Placing a curb on growth. CEPS Paperbacks. May 2012

To ward off the threat of a worldwide depression that loomed at the end of the 2000s, governments opted to run up substantial fiscal deficits. In doing so, they sowed the seeds of the sovereign debt crisis. Saddled with often high debt burdens and modest growth prospects, developed countries’ governments must now rebalance their budgets. Doing so too rapidly, however, will choke growth. Faced with this dilemma, Japan and the United States have pursued growth policies while the euro area members are quickly trying to rebalance their budgets. This book explores the respective risks associated with these two strategies. It further investigates the consequences for the international monetary and financial system of developing countries’ public debts ceasing to be risk-free.

Lisbon Treaty: Year I

The completion of the ratification of the Lisbon Treaty (from now on the Treaty) in November and its entry into force on 1 December 2009 marked the end of an extraordinary and unprecedented lengthy process of institutional change of the European Union. The Treaty had been signed on 13 December 2007, almost two years before its entry into force, by no means an excessive duration compared to the ratification of previous modifications of the Treaties. But the Treaty – in strictly legal terms a substantial set of amendments to two previous treaties renamed in the process – has a long history. Initial proposals for institutional reform date back to the German reunification in 1989-1990. They went through lengthy debates that eventually led to the European Convention and the 'Draft Treaty establishing a Constitution for Europe' of 20031 and from there to the 'Treaty establishing a Constitution for Europe' of 20042. If the current form of the Treaty is a clear consequence of the difficulties of the ratification process of the Constitution, the ideas that provide the substance can be traced back to the final years of the past century. The pages that follow are not a legal analysis but an attempt to identify changes and to assess their significance3.

Ukrainian economy overshadowed by war. OSW Commentary No. 148, 08.10.2014

Ukraine’s financial results over the past few months prove that the economic crisis which has been ongoing since mid 2012 has exacerbated. According to data from the Ukrainian Ministry of Economy, Gross Domestic Product for the first six months of 2014 shrank by 3%. In the second quarter, it fell by 4.6%1 and may further be reduced by as much as 8–10% over the year as a whole. After the first six months of this year, the balance of payments deficit reached US$4.3 billion. After deflation last year, prices grew by 12%, and the hryvnia dropped to a historic low. Although a surplus was seen in Ukrainian foreign trade in goods and services, reaching over US$3 billion at the end of June, its trade volume is shrinking. The main reason behind this deteriorating situation is the actions taken by Russia. Moscow has been fomenting the conflict in Donbas since April, has consistently imposed embargoes on imports of more and more Ukrainian goods and cut gas supplies to Ukraine in June. This has forced the government to focus on the current management of state finances and to carry out budget sequestration twice this year. The government has also used this as an excuse not to implement necessary systemic reforms. The increasing share of military expenditure, the shrinking exports (-5% in the first six months), including in particular to Russia, which until recently was Ukraine’s key trade partner, and the rapid fall in industrial production and investments have all made the situation even worse. All that saves Ukraine from an economic collapse is the loan from the International Monetary Fund and higher taxes, which allows the government to maintain budget liquidity. However, if the conflict in Donbas lasts longer and if Russia continues its economic blackmail, including withholding gas supplies, the economic crisis may prove to be long-lasting.

The Second Phase of the Common European Asylum System: A Step Forward in the Protection of Asylum Seekers? IES WORKING PAPER 7/2013

The aim of this paper is to analyse what is the impact of the second phase of the creation of the Common European Asylum System (CEAS) in the protection of rights of Asylum Seekers in the European Union. The establishment of a CEAS has been always a part of the development of the Area of Freedom, Security and Justice. Its implementation was planned in two phases: the first one, focused on the harmonisation of internal legislation on minimum common standards; the second, based on the result of an evaluation of the effectiveness of the agreed legal instruments, should improve the effectiveness of the protection granted. The five instruments adopted between 2002 and 2005, three Directives, on Qualification, Reception Conditions and Asylum Procedures, and two Regulations, the so-called “Dublin System”, were subjected to an extensive evaluation and modification, which led to the end of the recasting in 2013. The paper discusses briefly the international obligations concerning the rights of asylum seekers and continues with the presentation of the legal basis of the CEAS and its development, together with the role of the Charter of Fundamental Rights of the European Union in asylum matters. The research will then focus on the development in the protection of asylum seekers after the recasting of the legislative instruments mentioned above. The paper will note that the European standards result now improved, especially concerning the treatment of vulnerable people, the quality of the application procedure, the effectiveness of the appeal, the treatment of gender issues in decision concerning procedures and reception. However, it will be also highlighted that Member States maintained a wide margin of appreciation in many fields, which can lead to the compression of important guarantees. This margin concerns, for example, the access to free legal assistance, the definition of the material support to be granted to each applicant for international protection, the access to labour market, the application of the presumptions of the “safety” of a third country. The paper will therefore stress that the long negotiations that characterised the second phase of the CEAS undoubtedly led to some progress in the protection of Asylum Seekers in the EU. However, some provisions are still in open contrast with the international obligations concerning rights of asylum seekers, while others require to the Member State consider carefully its obligation in the choice of internal policies concerning asylum matters.

The long road towards the European single market. Bruegel Working Paper 2015/01, March 2015

The single market is often perceived as the panacea for Europe’s economic troubles. It is believed that completing the single market would boost welfare, stimulate growth and increase European competitiveness. • However, identifying and quantifying the channels through which market integration is expected to engender growth is methodologically complex. Although the overwhelming prediction from the literature is for single market integration to generate positive and significant aggregate effects, we conclude that the impact so far has fallen short of initial expectations, because: (1) Barriers continue to prevail in the EU, preventing the exploitation of the potential benefits of full market integration (2) ‘Complementary policies’ to support the single market were not, or were insufficiently, put in place (3) The single market project has not sufficiently been framed as a key part of the process of creative destruction that Europe needs to embrace to successfully modernise its economy. • That single market integration generates positive and significant aggregate effects does not imply that its effects are positive and significant for every sector. There is therefore an important role for European Union and national distributional policies to ensure that losers are sufficiently compensated by the winners, and to overcome political resistance to completing the single market.

"Where is the Wealth?" Echoing the King's 2014 speech in light of the delay in the implementation of the new Constitution. Arab Citizenship Review No. 16, 19 February 2016

In Morocco, the new Constitution promised by King Mohammed VI in 2011 has raised high expectations regarding the improvement of socio-economic standards in the country and the possible redistribution of national wealth in a more transparent and democratic way. Just like Tunisia and Egypt, Moroccan demonstrators of the 20 February Movement had taken to the streets to ask for more freedom and democracy, but also to call for social equality and an end to corruption. Many of the grievances and the claims raised by demonstrators fell within the domain of socio-economic rights. Even though it might still be early to take stock, five years down the road, it is possible to provide a fist assessment of the major changes in Morocco in the socio-economic area. The attempt is to analyse whether the improvements introduced by the new Constitution have met the expectations of the people standing up for their rights in the wake of the Arab Spring, or whether the Kingdom of Morocco has fallen short on its promise to undertake structural change.