The selectivity and structural determinants of peptide antagonists at the CGRP receptor of rat, L6 myocytes

1. Potency orders were determined for a series of agonists and antagonists on the calcitonin gene-related peptide (CGRP) receptor of rat L6 myocytes. The agents tested were all shown to have been active against CGRP, amylin or adrenomedullin receptors. 2. AC187 had a PIC50 Of 6.8 ± 0.10, making it 14 fold less potent as an antagonist than CGRP8-37 (PIC50, 7.95 ± 0.14). Amyline8-37 was equipotent to AC187 (PIC50, 6.6 ± 0.16) and CGRP19-37 was a fold less potent than either (pIC50 6.1 ± 0.24). 3. [Ala11]-CGRP8-37 was 6 fold less potent than CGRP8-37, (pIC50 7.13 ± 0.14), whereas [Ala18] CGRP8-37 was approximately equipotent to CGRP8-37 (pIC50, 7.52 ± 0.15). However, [Ala11,Ala18]- CGRP8-37 was over 300 fold less potent than CGRP8-37 (pIC50, 5.30 ± 0.04). 4. [Tyr0]-CGRP28-37, amylin19-37 and adrenomedullin22-52 were inactive as antagonists at concentrations of up to 1 μM. 5. Biotinyl-human α-CGRP was 150 fold less potent than human α-CGRP itself (EC50 values of 48 ± 17 nM and 0.31 ± 0.13 nM, respectively). At 1 μM, [Cys(acetomethoxy)(2'7)]-CGRP was inactive as an agonist. 6. These results confirm a role for Arg11 in maintaining the high affinity binding of CGRP8-37. Arg18 is of less direct significance for high affinity binding, but it may be important in maintaining the amphipathic nature of CGRP and its analogues.

Dietary habits are major determinants of the plasma antioxidant status in healthy elderly subjects

Previous studies indicate that regular consumption of a diet rich in fruits and vegetables is associated with a lower risk for age-related diseases. The aim of the present study was to evaluate whether the often-reported age-related decrease of plasma antioxidants in man depends on differences in dietary intake or on other age- and gender-related factors. In this observational case-control study, thirty-nine community-dwelling healthy subjects aged 65 years and older consuming high intakes of fruits and vegetables daily (HI) and forty-eight healthy subjects aged 65 and older consuming low intakes of fruit and vegetables daily (LI) were enrolled. Plasma levels of retinol, tocopherols, carotenoids and malondialdehyde (MDA) as well as content of protein carbonyls in Ig G were measured. Plasma levels of retinol, tocopherols and carotenoids were significantly higher in group HI than in group LI subjects independent of age and gender. MDA levels were inversely correlated with vitamin A and α-carotene. Protein carbonyls were inversely correlated with γ-tocopherol. In the elderly, a higher daily intake of fruits and vegetables is associated with an improved antioxidant status in comparison to subjects consuming diets poor in fruits and vegetables. Modification of nutritional habits among other lifestyle changes should be encouraged to lower prevalence of disease risk factors in later life. © The Authors 2005.

Determinants of inward investment in the UK, a panel analysis

This paper develops an inter-industry model of inward investment, using a fixed effects approach. This demonstrates that when inward investment is investigated in such a framework, previous findings, relating to the specification of measures of location advantage and ownership advantages no longer hold. This also shows that there are some industries that have attracted significant inward investment over time, and continue to do so, while others are noticeably less successful. Reasons for this, and potential policy measures are briefly discussed.

Determinants of entry and exit in the foreign owned sector of UK manufacturing

This paper examines the extent to which foreign entry and exit in the UK is related to domestic industry characteristics. The units of analysis are firm numbers, and thus entry and exit at the industry level are treated as being generated by Poisson processes. This therefore uses quasimaximum likelihood estimation, to estimate entry and exit functions simultaneously. The results demonstrate that foreign entry is attracted by industry level profitability and performance, but that firm specific 'ownership' advantages are also important. The results also demonstrate that inward investors that are motivated by the desire to exploit firm-specific assets, are unlikely to be more transient than domestic firms. This however, cannot be said of those foreign entrants who are attracted to the UK by location advantage or investment incentives.

Sales manager and sales team determinants of salesperson ethical behaviour

Purpose – The purpose of this paper is to develop and test a model of the role managers and peers play in shaping salespeople's ethical behaviour. The model specifies that sales manager personal moral philosophies, whether sales managers themselves are rewarded according to the outcomes or behaviours of their salespeople, sales team job security, intra-team cooperation, and sales team tactical performance all influence sales team ethical standards. In turn, ethical standards influence the probability that sales team members will behave (un)ethically when faced with ethical dilemmas. Design/methodology/approach – The model is tested on a sample of 154 Finnish sales managers. Data were collected via mail survey. Analysis was undertaken using structural equation modelling. Findings – Ethical standards appear to be shaped by several factors; behaviour-based management controls increase ethical standards, relativist managers tend to manage less ethically-minded sales teams, job insecurity impedes the development of ethical standards, and sales teams' cooperation activity increases ethical standards. Sales teams are less likely to engage in unethical behaviour when the teams have strong ethical standards. Research limitations/implications – Cross-sectional data limits generalisability; single country data may limit the ability to generalise to different sales environments; additional measure development is needed; identification of additional antecedent factors would be beneficial. Practical implications – Sales managers should consciously develop high ethical standards in sales teams if they wish to reduce unethical behaviour. Ethical standards can be improved if sales managers change their own outward behaviour (exhibit a less relativistic ethical philosophy), foster cooperation amongst salespeople, and develop perceptions of job security. How sales managers are rewarded may shape how they approach the management of ethical behaviour in their sales teams. Originality/value – This paper appears to be the first to simultaneously examine both sales manager-specific and sales team-specific antecedents to sales team ethical standards and behaviours. As such, it provides an important base for research in this critical area.

The determinants of export performance:evidence for manufacturing plants in Ireland and Northern Ireland

The dramatic GDP and export growth of Ireland over the last decade forms a marked contrast with that of its nearest neighbour Northern Ireland. In Ireland, export volume growth averaged 15.5% p.a. from 1991 to 1999 compared with 6.3% from Northern Ireland. Using data on individual manufacturing plants this paper considers the determinants of export performance in the two areas. Larger, externally owned plants with higher skill levels are found to have the highest export propensities in both areas. Other influences (plant age, R&D, etc.) prove more strongly conditional on location, plant size, and ownership. Structural factors (e.g. ownership, industry) explain almost all of the difference in export propensity between larger plants in Northern Ireland and Ireland but only around one-third of that between smaller plants. Significant differences are also evident between plants in terms of their sources of new technology. For indigenously owned plants, inhouse R&D is important. For externally owned plants, R&D conducted elsewhere in the group - typically outside Ireland and Northern Ireland - proves more significant. This external dependency and lower than expected export propensity on the part of small plants in Northern Ireland represent significant policy challenges for the future.© 2006 Scottish Economic Society. Published by Blackwell Publishing Ltd.

Macro determinants of FDI inflows to Japan:an analysis of source country characteristics

This paper examines the source country determinants of FDI into Japan. The paper highlights certain methodological and theoretical weaknesses in the previous literature and offers some explanations for hitherto ambiguous results. Specifically, the paper highlights the importance of panel data analysis, and the identification of fixed effects in the analysis rather than simply pooling the data. Indeed, we argue that many of the results reported elsewhere are a feature of this mis-specification. To this end, pooled, fixed effects and random effects estimates are compared. The results suggest that FDI into Japan is inversely related to trade flows, such that trade and FDI are substitutes. Moreover, the results also suggest that FDI increases with home country political and economic stability. The paper also shows that previously reported results, regarding the importance of exchange rates, relative borrowing costs and labour costs in explaining FDI flows, are sensitive to the econometric specification and estimation approach. The paper also discusses the importance of these results within a policy context. In recent years Japan has sought to attract FDI, though many firms still complain of barriers to inward investment penetration in Japan. The results show that cultural and geographic distance are only of marginal importance in explaining FDI, and that the results are consistent with the market-seeking explanation of FDI. As such, the attitude to risk in the source country is strongly related to the size of FDI flows to Japan. © 2007 The Authors Journal compilation © 2007 Blackwell Publishing Ltd.

The determinants of firms' performance:can finance constraints improve technical efficiency?

This paper analyses the mechanisms through which binding finance constraints can induce debt-constrained firms to improve technical efficiency to guarantee positive profits. This hypothesis is tested on a sample of firms belonging to the Italian manufacturing. Technical efficiency scores are computed by estimating parametric production frontiers using the one stage approach as in Battese and Coelli [Battese, G., Coelli, T., 1995. A model for technical efficiency effects in a stochastic frontier production function for panel data. Empirical Economics 20, 325-332]. The results support the hypothesis that a restriction in the availability of financial resources can affect positively efficiency. © 2004 Elsevier B.V. All rights reserved.

The microstructure of the foreign exchange market:the determinants of bid-ask spreads in the foreign exchange market

The purpose of this thesis is to shed more light in the FX market microstructure by examining the determinants of bid-ask spread for three currencies pairs, the US dollar/Japanese yen, the British pound/US dollar and the Euro/US dollar in different time zones. I examine the commonality in liquidity with the elaboration of FX market microstructure variables in financial centres across the world (New York, London, Tokyo) based on the quotes of three exchange rate currency pairs over a ten-year period. I use GARCH (1,1) specifications, ICSS algorithm, and vector autoregression analysis to examine the effect of trading activity, exchange rate volatility and inventory holding costs on both quoted and relative spreads. ICSS algorithm results show that intraday spread series are much less volatile compared to the intraday exchange rate series as the number of change points obtained from ICSS algorithm is considerably lower. GARCH (1,1) estimation results of daily and intraday bid-ask spreads, show that the explanatory variables work better when I use higher frequency data (intraday results) however, their explanatory power is significantly lower compared to the results based on the daily sample. This suggests that although daily spreads and intraday spreads have some common determinants there are other factors that determine the behaviour of spreads at high frequencies. VAR results show that there are some differences in the behaviour of the variables at high frequencies compared to the results from the daily sample. A shock in the number of quote revisions has more effect on the spread when short term trading intervals are considered (intra-day) compared to its own shocks. When longer trading intervals are considered (daily) then the shocks in the spread have more effect on the future spread. In other words, trading activity is more informative about the future spread when intra-day trading is considered while past spread is more informative about the future spread when daily trading is considered

An empirical investigation of the effect of rights issue announcements on share returns and the determinants of abnormal returns on the Kuala Lumpur Stock Exchange

This thesis examines the effect of rights issue announcements on stock prices by companies listed on the Kuala Lumpur Stock Exchange (KLSE) between 1987 to 1996. The emphasis is to report whether the KLSE is semi strongly efficient with respect to the announcement of rights issues and to check whether the implications of corporate finance theories on the effect of an event can be supported in the context of an emerging market. Once the effect is established, potential determinants of abnormal returns identified by previous empirical work and corporate financial theory are analysed. By examining 70 companies making clean rights issue announcements, this thesis will hopefully shed light on some important issues in long term corporate financing. Event study analysis is used to check on the efficiency of the Malaysian stock market; while cross-sectional regression analysis is executed to identify possible explanators of the rights issue announcements' effect. To ensure the results presented are not contaminated, econometric and statistical issues raised in both analyses have been taken into account. Given the small amount of empirical research conducted in this part of the world, the results of this study will hopefully be of use to investors, security analysts, corporate financial managements, regulators and policy makers as well as those who are interested in capital market based research of an emerging market. It is found that the Malaysian stock market is not semi strongly efficient since there exists a persistent non-zero abnormal return. This finding is not consistent with the hypothesis that security returns adjust rapidly to reflect new information. It may be possible that the result is influenced by the sample, consisting mainly of below average size companies which tend to be thinly traded. Nevertheless, these issues have been addressed. Another important issue which has emerged from the study is that there is some evidence to suggest that insider trading activity existed in this market. In addition to these findings, when the rights issue announcements' effect is compared to the implications of corporate finance theories in predicting the sign of abnormal returns, the signalling model, asymmetric information model, perfect substitution hypothesis and Scholes' information hypothesis cannot be supported.

An exploration of the determinants of innovation:the top management team, organisational climate and organisational learning

Some researchers argue that the top team, rather than the CEO, is a better predictor of an organisation’s fate (Finkelstein & Hambrick, 1996; Knight et al., 1999). However, others suggest that the importance of the top management team (TMT) composition literature is exaggerated (West & Schwenk, 1996). This has stimulated a need for further research on TMTs. While the importance of TMT is well documented in the innovation literature, the organisational environment also plays a key role in determining organisational outcomes. Therefore, the inclusion of both TMT characteristics and organisational variables (climate and organisational learning) in this study provides a more holistic picture of innovation. The research methodologies employed includes (i) interviews with TMT members in 35 Irish software companies (ii) a survey completed by managerial respondents and core workers in these companies (iii) in-depth interviews with TMT members from five companies. Data were gathered in two phases, time 1 (1998-2000) and time 2 (2003). The TMT played an important part in fostering innovation. However, it was a group process, rather than team demography, that was most strongly associated with innovation. Task reflexivity was an important predictor of innovation time 1, time 2). Only one measure of TMT diversity was associated with innovation - tenure diversity -in time 2 only. Organisational context played an important role in determining innovation. This was positively associated with innovation - but with one dimension of organisational learning only. The ability to share information (access to information) was not associated with innovation but the motivation to share information was (perceiving the sharing of information to be valuable). Innovative climate was also associated with innovation. This study suggests that this will lead to innovative outcomes if employees perceive the organisation to support risk, experimentation and other innovative behaviours.

Determinants of sales performance in insurance industry:a cross-cultural comparison between the UK and Malaysia

This thesis is concerned with an empirical investigation of the factors that predict a successful salesperson, using a cross-cultural comparison of two countries: the UK and Malaysia. Besides collecting quantitative data, qualitative data on organisational, environmental and cultural factors were also collected through interviews, personal and case observations. The quantitative data consist of sixteen independent factors and three dependent factors. The independent variables include self-efficacy, self-esteem, locus of control, self-monitoring, extrinsic motivation, intrinsic motivation, experience, training perception, role ambiguity, role conflict, role inaccuracy, gender, age, education, race and religion. The dependent variables are performance target achieved, performance earnings and performance ratings. Questionnaires were distributed to about 500 salespersons in each country, from three insurance companies in the UK and two insurance companies in Malaysia. Response rates were 75 and 50 percent from the UK and Malaysia respectively. The survey results indicated that a salesperson's performance in the UK is predicted by self-efficacy, internal locus of control, self-esteem, extrinsic motivation, experience, training perceptions, role conflict and gender. In Malaysia, a salesperson's performance is predicted by self-efficacy, self-monitoring, experience, role conflict, role ambiguity, education, gender, race and religion. Self-efficacy, experience, role conflict and gender are common predictors of salespersons' performance in both cultures. The likely explanation for these results is culture differences, i.e. UK has a homogeneous culture, while Malaysia has a heterogeneous one. Results from the case observations, such as organisational and environmental factors, give supporting evidence in explaining the empirical results. Implications from the findings are discussed from two aspects: (1) theoretical implications for divergence/convergence theory, Hofstede's model, Churchill's model, and (2) managerial implications for selection, training, motivation and appraisal.

Determinants of sponsorship fit:a multilevel analysis

Sponsorship fit is frequently mentioned and empirically examined as a success factor of sponsorship. While sponsorship fit has been considered as a determinant of sponsorship success, little knowledge exists about the antecedents of sponsorship fit. In the present paper, individual and firm-level antecedents of sponsorship fit are examined in a single hierarchical linear model. Results show that sponsorship fit is influenced by the perception of benefits, the firm’s regional identification, sincerity, relatedness to the sponsored activity, and its dominance. On a partnership level, results show that contract length contributes to sponsorship fit while contract value is found to be unrelated.