A Role for Cadherin-5 in Regulation of Vascular Endothelial Growth Factor Receptor 2 Activity in Endothelial Cells

FLK-1/vascular endothelial growth factor receptor 2 (VEGFR-2) is one of the receptors for VEGF. In this study we examined the effect of cell density on activation of VEGFR-2. VEGF induces only very slight tyrosine phosphorylation of VEGFR-2 in confluent (95–100% confluent) pig aortic endothelial (PAE) cells. In contrast, robust VEGF-dependent tyrosine phosphorylation of VEGFR-2 was observed in cells plated in sparse culture conditions (60–65% confluent). A similar cell density-dependent phenomenon was observed in different endothelial cells but not in NIH-3T3 fibroblast cells expressing VEGFR-2. Stimulating cells with high concentrations of VEGF or replacing the extracellular domain of VEGFR-2 with that of the colony-stimulating factor 1 receptor did not alleviate the sensitivity of VEGFR-2 to cell density, indicating that the confluent cells were probably not secreting an antagonist to VEGF. Furthermore, in PAE cells, ectopically introduced platelet-derived growth factor α receptor could be activated at both high and low cell density conditions, indicating that the density effect was not universal for all receptor tyrosine kinases expressed in endothelial cells. In addition to lowering the density of cells, removing divalent cations from the medium of confluent cells potentiated VEGFR-2 phosphorylation in response to VEGF. These findings suggested that cell–cell contact may be playing a role in regulating the activation of VEGFR-2. To this end, pretreatment of confluent PAE cells with a neutralizing anti-cadherin-5 antibody potentiated the response of VEGFR-2 to VEGF. Our data demonstrate that endothelial cell density plays a critical role in regulating VEGFR-2 activity, and that the underlying mechanism appears to involve cadherin-5.

Human fatty acid synthase: Role of interdomain in the formation of catalytically active synthase dimer

The human and animal fatty acid synthases are dimers of two identical multifunctional proteins (Mr 272,000) arranged in an antiparallel configuration. This arrangement generates two active centers for fatty acid synthesis separated by interdomain (ID) regions and predicts that two appropriate halves of the monomer should be able to reconstitute an active fatty acid synthesizing center. This prediction was confirmed by the reconstitution of the synthase active center by using two heterologously expressed halves of the monomer protein. Each of these recombinant halves of synthase monomer contains half of the ID regions. We show here that the fatty acid synthase activity could not be reconstituted when the ID sequences present in the two recombinant halves are deleted, suggesting that these ID sequences are essential for fatty acid synthase dimer formation. Further, we confirm that the ID sequences are the only regions of fatty acid synthase monomers that showed significant dimer formation, by using the yeast two-hybrid system. These results are consistent with the proposal that the ID region, which has no known catalytic activity, associates readily and holds together the two dynamic active centers of the fatty acid synthase dimer, therefore playing an important role in the architecture of catalytically active fatty acid synthase.

Resonant tectorial membrane motion in the inner ear: its crucial role in frequency tuning.

The tectorial membrane has long been postulated as playing a role in the exquisite sensitivity of the cochlea. In particular, it has been proposed that the tectorial membrane provides a second resonant system, in addition to that of the basilar membrane, which contributes to the amplification of the motion of the cochlear partition. Until now, technical difficulties had prevented vibration measurements of the tectorial membrane and, therefore, precluded direct evidence of a mechanical resonance. In the study reported here, the vibration of the tectorial membrane was measured in two orthogonal directions by using a novel method of combining laser interferometry with a photodiode technique. It is shown experimentally that the motion of the tectorial membrane is resonant at a frequency of 0.5 octave (oct) below the resonant frequency of the basilar membrane and polarized parallel to the reticular lamina. It is concluded that the resonant motion of the tectorial membrane is due to a parallel resonance between the mass of the tectorial membrane and the compliance of the stereocilia of the outer hair cells. Moreover, in combination with the contractile force of outer hair cells, it is proposed that inertial motion of the tectorial membrane provides the necessary conditions to allow positive feedback of mechanical energy into the cochlear partition, thereby amplifying and tuning the cochlear response.

Alterações dos estados de ânimo presentes de jovens atletas de futebol em função do decurso temporal durante um período competitivo

São escassos os estudos que analisam o contínuo temporal dos estados de ânimo ao longo de um período competitivo esportivo. Embora os estados de ânimo pareçam estáveis ao longo do tempo, diferentes estímulos e contextos presentes modificam a intensidade e a valência desses estados. Além disso, há fenômenos psicológicos como decaimento, em que traços de informação perdem sua ativação devido, principalmente, à passagem do tempo e a expectativa, que é a espera pela ocorrência de um evento em um determinado tempo. O objetivo desse estudo foi examinar as alterações dos estados de ânimo em jovens atletas de futebol, separados por posição e função, que ocorreram num período competitivo, em função do decurso temporal. Assim, processos como decaimento dos estados de ânimo e a influência da expectativa pela ocorrência jogo foram analisados, bem como a influência do contexto nas variações dos estados de ânimo dos atletas. Participaram deste estudo 18 jovens atletas (média de 15,4 anos ± 0,266) de um clube de futebol que estava disputando um campeonato estadual. Para o acesso aos estados de ânimo, foi utilizada a versão reduzida da Lista de Estados de Ânimo Presentes (LEAP), juntamente com um formulário de instruções de preenchimento, aplicada minutos antes de alguns treinamentos e jogos. Foram calculados os valores de presença de cada Fator da LEAP em cada evento para cada participante. Os dados foram coletados em três tipos de Eventos: antes do último treino antecedente ao jogo (Treino-Pré), antes do jogo (Pré-jogo) e antes do primeiro treino subsequente ao jogo (Treino-Pós). Os 18 jogadores foram divididos em dois grupos: Ações Defensivas (AD) e Ações Ofensivas (AO). Foram encontrados padrões de alteração dos estados de ânimo, representados pelos Fatores II (Fadiga), VII (Interesse) e XII (Serenidade) da LEAP, em função do decurso temporal, permitindo a análise dos processos de decaimento desses estados de ânimo e a influência da expectativa nessas alterações. Também foi encontrado que alguns estados de ânimo diferiram seus padrões de alteração de acordo com um intervalo temporal (Fatores IV Limerência/Empatia e; VII Interesse), bem como tiveram valores de presença diferentes na comparação entre esses intervalos. Além disso, os Fatores III (Esperança), V (Fisiológico) e XI (Receptividade) apresentaram padrões de alteração em função do decurso temporal em diferentes intervalos temporais. Variáveis contextuais, como o resultado das partidas e a competição esportiva em si, também foram influentes nessas alterações. Fadiga, esperança, empatia, estados ligados à propriocepção, interesse, receptividade e serenidade foram os estados de ânimo presentes durante todo o estudo. Ressalta-se a importância de incluir a temporalidade como variável influente nos modelos de variação de processos neurobiológicos, sobretudo nas investigações acerca de aspectos subjetivos como os estados de ânimo.

International financial regulation: A role for the Eurozone? EU Diplomacy Paper 08/2012, October 2012

The deepest financial crisis to strike the global economy since the Great Depression has unceremoniously called into question the very foundations of the Western economic model. The liberalisation of capital flows and the growing internationalisation of financial markets outpaced global regulatory and supervisory efforts. The repercussions of the financial crisis have given new dynamism to the reform of financial regulation both globally and within the European Union (EU). The Eurozone, by way of its own failings, has emerged as a stronger conceptual and legitimate entity since the onset of the crisis, but to what extent does this equate to a greater external role, in particular in the reform of international financial regulation? This paper argues that the Eurozone is currently not in a position to play an important role in the reform of international financial regulation, as it is a weak actor in the context of the EU financial architecture, which is still largely characterised by differing national regimes, a prevailing influence from the UK and fragmented external representation. The key finding from this study is that internal tensions in the EU are at the very heart of the Eurozone’s difficulties in playing a role in the reform of international financial regulation. Surmounting these tensions is a pre-requisite for the Eurozone if it is to overcome its structural weakness in international financial politics. However, the implications of such evolutions to the Eurozone, as an entity, and to European integration are far-reaching.

Will the Transatlantic Trade and Investment Partnership be a game-changer? EU Centre Singapore Policy Brief No. 5, April 2013

In February 2013, US President Barrack Obama, European Council President Herman Van Rompuy and President of the European Commission José Manuel Barroso announced the decision to go for an ambitious and comprehensive trade and investment agreement between the US and the EU. To be called the Transatlantic Trade and Investment Partnership (TTIP), this agreement would lead to a new stage in the transatlantic relationship and be a much needed boost to the lacklustre economic recovery so far. Some analysts have even argued that TTIP would be a “game changer” – besides the economic gains, it would serve a bigger strategic purpose of promoting EU-US common objective to set higher standards of trade liberalisation, and thereby level the playing field in China and other key emerging markets. This policy brief examines the reasons behind the current push towards TTIP and the possible contents of such an agreement. It also discusses the possible obstacles to the realisation of TTIP, and at the same time, looks into what a successful conclusion of TTIP would mean for Asia and beyond.

Game of zones. The quest for influence in Europe’s neighbourhood. Egmont Paper No. 67, June 2014

Introduction. Russia’s annexation of the Crimea and subsequent meddling in Ukraine does not constitute a game-changer. It is just a reminder that at least since the war with Georgia in 2008 Russia has been and still is playing the same game: a “game of zones”, aimed at (re)establishing an exclusive sphere of influence. Many of us Europeans had forgotten that, or had pushed it to the back of our minds, preferring to believe that we were not engaged in a zero-sum game in our eastern neighbourhood. While we were dealing with Ukraine, we tended also to forget the crises still going on in our southern neighbourhood, in Libya, Mali, Syria and now Iraq. Spilling over from Syria, extremist militias may establish their own “zone” in the Middle East, which would de-stabilize the entire region. In order to prevent that game-changer from materializing, another game-changer may be necessary: a rapprochement with Iran. Europe must assume responsibility for security in its entire neighbourhood, both east and south. The challenge is great – but so are Europe’s means.

New Techniques in Deep Representation Learning

Thesis (Ph.D.)--University of Washington, 2016-06

Role of culture in gambling and problem gambling

There has been a significant gap in the gambling literature regarding the role of culture in gambling and problem gambling (PG). This paper aims to reduce this gap by presenting a systematic review of the cultural variations in gambling and PG as well as a discussion of the role cultural variables can play in the initiation and maintenance of gambling in order to stimulate further research. The review shows that although studies investigating prevalence rates of gambling and PG among different cultures are not plentiful, evidence does suggest certain cultural groups are more vulnerable to begin gambling and to develop PG. Significant factors including familial/genetic, sociological, and individual factors have been found in the Western gambling literature as playing important roles in the development and maintenance of PG. These factors need to be examined now in other cultural groups so we can better understand the etiological processes involved in PG and design culturally sensitive treatments. In addition, variables, such as cultural values and beliefs, the process of acculturation, and the influence of culturally determined help-seeking behaviors need to be also examined in relation to the role they could play in the initiation of and maintenance of gambling. Understanding the contribution of cultural variables will allow us to devise better prevention and treatment options for PG. Methodological problems in this area of research are highlighted, and suggestions for future research are included. (C) 2004 Elsevier Ltd. All rights reserved.

The role of different sources of communication and trust in reducing change-related uncertainties during organisational change

The current paper presents a qualitadve study of the role of different sources of communicadon in reducing change-related uncertaintj' experienced by employees during organisadonal change. The paper examines the role of trust in influencing how employees' appraise informadon from different sources within organisadons. Interviews with 19 employees from a range of organisadons idendfy the different types of change-related uncertaindes experienced during change. In addidon, the different sources of communicadon utilised by employees are idendfied and the role each source plays in reducing the different t}'pes of uncertaint}' invesdgated. From employee responses it is evident that t)'pically supervisors are the best source of change informadon, while communicadon from senior management usually focuses on strategic issues. Employees indicate that communicadon with coworkers operates as a support mechanism providing an avenue to share grievances arising from the change. Finally, trust is idendfied as playing an important role in influencing who employees go to for informadon when experiencing uncertainty'. ImpUcadons for change management research in addidon to pracdcal implicadons are discussed.

Hardware gimmick or cultural innovation? Technological, cultural, and social foundations of the Japanese video game industry

This paper examines the role of creative resources in the emergence of the Japanese video game industry. We argue that creative resources nurtured by popular cartoons and animation sector, combined with technological knowledge accumulated in the consumer electronics industry, facilitated the emergence of successful video game industry in Japan. First we trace the development of the industry from its origin to the rise of platform developers and software publishers. Then, knowledge and creative foundations that influenced the developmental trajectory of this industry are analyzed, with links to consumer electronics and in regards to cartoons and animation industry.

The role of line managers in employee career management:an attachment theory perspective

Line managers increasingly play a key role in organizational career development systems, yet few studies have examined the nature of this role or its implications for employee career attitudes and behaviors. In two studies, we used attachment theory to explore this issue. In Study 1, in-depth interviews (N = 20) showed that employees viewed career management as a relational process in which line managers are expected to act as ‘caregiver’ to support individualized career development. Study 2 was a large-scale international survey (N = 891). Participants scoring higher on attachment avoidance in their line manager relationships reported more negative perceptions of career growth opportunities, lower participation in organizational career development activities and higher turnover intentions. Trust in the organization partially mediated the relationship. Theoretical and practical implications for HRM are discussed.

Employee perceptions of interpersonal justice:the moderating role of attachment and cultural values

This study investigated the moderating role of national culture in the relationship between attachment orientations and employee perceptions of interpersonal justice. Three hundred and forty individuals from countries categorized (by GLOBE) as either low collectivistic ‘Anglo’ (e.g. UK, Australia, US; N = 205) or high collectivistic ‘South Asian’ (e.g. India, Malaysia, Indonesia; N = 135), responded to an online questionnaire. Attachment anxiety and avoidance were negatively related to perceptions of interpersonal justice, as expected, but against expectations the direct relationship between attachment orientations and interpersonal justice did not differ between cultures. However, supplementary analysis revealed a significant 3-way interaction. When attachment anxiety was high, avoidance was a stronger predictor of interpersonal justice perceptions but the direction of this association differed by culture. The findings suggest the importance of fit between employee attachment orientations and cultural relational values in the workplace. Practical and theoretical implications are discussed.