Structure, dynamics, and energetics of siRNA-cationic vector complexation:a molecular dynamics study

The design and synthesis of safe and efficient nonviral vectors for gene delivery has attracted significant attention in recent years. Previous experiments have revealed that the charge density of a polycation (the carrier) plays a crucial role in complexation and the release of the gene from the complex in the cytosol. In this work, we adopt an atomistic molecular dynamics simulation approach to study the complexation of short strand duplex RNA with six cationic carrier systems of varying charge and surface topology. The simulations reveal detailed molecular-level pictures of the structures and dynamics of the RNA-polycation complexes. Estimates for the binding free energy indicate that electrostatic contributions are dominant followed by van der Waals interactions. The binding free energy between the 8(+)polymers and the RNA is found to be larger than that of the 4(+)polymers, in general agreement with previously published data. Because reliable binding free energies provide an effective index of the ability of the polycationic carrier to bind the nucleic acid and also carry implications for the process of gene release within the cytosol, these novel simulations have the potential to provide us with a much better understanding of key mechanistic aspects of gene-polycation complexation and thereby advance the rational design of nonviral gene delivery systems.

Board composition, ownership structure and dividend policies in an emerging market: further evidence from CASE 50

Purpose – The purpose of this study is to examine dividend policies in an emerging capital market, in a country undergoing a transitional period. Design/methodology/approach – Using pooled cross-sectional observations from the top 50 listed Egyptian firms between 2003 and 2005, this study examines the effect of board of directors’ composition and ownership structure on dividend policies in Egypt. Findings – It is found that there is a significant positive association between institutional ownership and firm performance, and both dividend decision and payout ratio. The results confirm that firms with a higher return on equity and a higher institutional ownership distribute higher levels of dividend. No significant association was found between board composition and dividend decisions or ratios. Originality/value – This study provides additional evidence of the applicability of the signalling model in the emerging market of Egypt. It was found that despite the high institutional ownership and the closely held nature of the firms, which imply lower agency costs, the payment of higher dividend was considered necessary to attract capital during this transitional period.

Corporate social responsibility in China:impact of regulations, market orientation and ownership structure

Purpose – This paper aims to report on a study that contributes to the understanding of the determinants of corporate social responsibility (CSR) in the largest emerging market, namely China. Design/methodology/approach – The approach is a survey of 600 hotels that resulted in 143 returned responses from top managers. Findings – Market orientation is the most significant predicator of CSR followed by government regulations. In contrast, ownership structure is found to have little effect. Originality/value – Previous research on CSR focuses on its nature and impact on business performance, and is carried out mainly in developed countries. This research contributes to one's understanding of the determinants of CSR in emerging markets like China. © 2007, Emerald Group Publishing Limited

Effects of government regulations, market orientation and ownership structure on corporate social responsibility in China:an empirical study

Previous research on corporate social responsibility mainly focuses on its nature and impact on business performance. This paper reports on a study that contributes to our understanding of the determinants of corporate social responsibility by focusing specifically on the role played by three strategically important variables, namely government regulation, ownership structure and market orientation. Results of a survey of 586 general managers of hotels in China suggest that the market orientation is the most significant predicator of corporate social responsibility followed by government regulation. In contrast, the ownership structure is found to have little effect. The implications of the findings for managers in China are discussed.

The impact of regulation and ownership structure on market orientation in the tourism industry in China

The nature of market orientation and its impact on business performance and other related outcomes have been extensively researched in a range of service contexts including tourism. In contrast, our understanding of the factors that influence market orientation is still limited. This paper reports on a study that contributes to our understanding of the determinants of market orientation within the tourism sector by focusing specifically on the role played by two strategically important variables, namely government regulation and ownership structure. The study analyses two national samples of hotels and travel services in the rapidly growing tourism industry in China. The hotel sector has been open to foreign investment for two decades and has a diversified ownership structure, whereas the travel services sector has been dominated by government owned firms and relatively closed to foreign investment. The results of the survey suggest that of the two new antecedents, only government regulation has a significant role to play in driving market orientation. Internally, access to appropriate managerial and marketing capabilities was identified as a significant predictor of the development of market orientation.

Capital markets and the market structure of foreign investments

Contrary to the long-received theory of FDI, interest rates or rates of return can motivate foreign direct investment (FDI) in concert with the benefits of direct ownership. Thus, access to investor capital and capital markets is a vital component of the multinational’s competitive market structure. Moreover, multinationals can use their superior financial capacity as a competitive advantage in exploiting FDI opportunities in dynamic markets. They can also mitigate higher levels of foreign business risks under dynamic conditions by shifting more financial risk to creditors in the host economy. Furthermore, the investor’s expectation of foreign business risk necessarily commands a risk premium for exposing their equity to foreign market risk. Multinationals can modify the profit maximization strategy of their foreign subsidiaries to maximize growth or profits to generate this risk premium. In this context, we investigate how foreign subsidiaries manage their capital funding, business risk, and profit strategies with a diverse sample of 8,000 matched parents and foreign subsidiary accounts from multiple industries in 38 countries.We find that interest rates, asset prices, and expectations in capital markets have a significant effect on the capital movements of foreign subsidiaries. We also find that foreign subsidiaries mitigate their exposure to foreign business risk by modifying their capital structure and debt maturity. Further, we show how the operating strategy of foreign subsidiaries affects their preference for growth or profit maximization. We further show that superior shareholder value, which is a vital link for access to capital for funding foreign expansion in open market economies, is achieved through maintaining stability in the rate of growth and good asset utilization.

Chain-store pricing and the structure of retail markets

This paper investigates competition between chain-stores and independents in the UK opticians' industry, using the relationship between the number of outlets present in a local market and the market size. Chain-stores are shown to have a significant effect on local market competition. In addition, the empirical approach is extended to allow inferences on the nature and extent of product differentiation. The results are broadly consistent with a model of vertical product differentiation in which chain-stores adopt national pricing strategies. The evidence suggests that the nature of competition between independent retailers depends on whether a chain-store is present.

A survey of some small firms in the rural areas of England: their structure and functions, with special reference to factors that affect their development

This study was concerned with the structure, functions and development, especially the performance, of some rural small firms associated with the Council for Small Industries in Rural Areas (C?SIRA) of England. Forty firms were used as the main basis of analysis. For some aspects of the investigation, however, data from another 54 firms, obtained indirectly through nine CoSIRA Organisers, were also used. For performance-analysis, the 40 firms were firstly ranked according to their growth and profitability rates which were calculated from their financial data. Then each of the variables hypothesised to be related to performance was tested to ascertain its relationship with performance, using the Spearman's Rank Correlation technique. The analysis indicated that each of the four factors .. the principal, the firm itself, its management, and the environment - had a bearing upon the performance of the firm. Within the first factor, the owner-manager's background and attitudes were found to be most important; in the second, the firm's size, age and scope of activities were also found to be correlated with performance; with respect to the third, it was revealed that firms which practised some forms of systems in planning, control and costing performed better than those which did not and, finally with respect to the fourth factor, it was found that some of the services provided by CoSIRA, especially credit finance, were facilitative to the firm's performance. Another significant facet of the firms highlighted by the study was their multifarious roles. These, meeting economic, psychological, sociological and political needs, were considered to be most useful to man and his society. Finally, the study has added light to the structural characteristics of the sampled firms, including various aspects of their development, orientation and organisation, as well as their various structural strengths and weakness. ' .

The discourse of biology lectures : aspects of its mode and text structure

The present thesis investigates mode related aspects in biology lecture discourse and attempts to identify the position of this variety along the spontaneous spoken versus planned written language continuum. Nine lectures (of 43,000 words) consisting of three sets of three lectures each, given by the three lecturers at Aston University, make up the corpus. The indeterminacy of the results obtained from the investigation of grammatical complexity as measured in subordination motivates the need to take the analysis beyond sentence level to the study of mode related aspects in the use of sentence-initial connectives, sub-topic shifting and paraphrase. It is found that biology lecture discourse combines features typical of speech and writing at sentence as well as discourse level: thus, subordination is more used than co-ordination, but one degree complexity sentence is favoured; some sentence initial connectives are only found in uses typical of spoken language but sub-topic shift signalling (generally introduced by a connective) typical of planned written language is a major feature of the lectures; syntactic and lexical revision and repetition, interrupted structures are found in the sub-topic shift signalling utterance and paraphrase, but the text is also amenable to analysis into sentence like units. On the other hand, it is also found that: (1) while there are some differences in the use of a given feature, inter-speaker variation is on the whole not significant; (2) mode related aspects are often motivated by the didactic function of the variety; and (3) the structuring of the text follows a sequencing whose boundaries are marked by sub-topic shifting and the summary paraphrase. This study enables us to draw four theoretical conclusions: (1) mode related aspects cannot be approached as a simple dichotomy since a combination of aspects of both speech and writing are found in a given feature. It is necessary to go to the level of textual features to identify mode related aspects; (2) homogeneity is dominant in this sample of lectures which suggests that there is a high level of standardization in this variety; (3) the didactic function of the variety is manifested in some mode related aspects; (4) the features studied play a role in the structuring of the text.

The dyslexia candidate locus on 2p12 is associated with general cognitive ability and white matter structure

Independent studies have shown that candidate genes for dyslexia and specific language impairment (SLI) impact upon reading/language-specific traits in the general population. To further explore the effect of disorder-associated genes on cognitive functions, we investigated whether they play a role in broader cognitive traits. We tested a panel of dyslexia and SLI genetic risk factors for association with two measures of general cognitive abilities, or IQ, (verbal and non-verbal) in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort (N>5,000). Only the MRPL19/C2ORF3 locus showed statistically significant association (minimum P = 0.00009) which was further supported by independent replications following analysis in four other cohorts. In addition, a fifth independent sample showed association between the MRPL19/C2ORF3 locus and white matter structure in the posterior part of the corpus callosum and cingulum, connecting large parts of the cortex in the parietal, occipital and temporal lobes. These findings suggest that this locus, originally identified as being associated with dyslexia, is likely to harbour genetic variants associated with general cognitive abilities by influencing white matter structure in localised neuronal regions.

Structure-activity relationships for α-calcitonin gene-related peptide

Calcitonin gene-related peptide (CGRP) is a member of the calcitonin (CT) family of peptides. It is a widely distributed neuropeptide implicated in conditions such as neurogenic inflammation. With other members of the CT family, it shares an N-terminal disulphide-bonded ring which is essential for biological activity, an area of potential α-helix, and a C-terminal amide. CGRP binds to the calcitonin receptor-like receptor (CLR) in complex with receptor activity-modifying protein 1 (RAMP1), a member of the family B (or secretin-like) GPCRs. It can also activate other CLR or calcitonin-receptor/RAMP complexes. This 37 amino acid peptide comprises the N-terminal ring that is required for receptor activation (residues 1-7); an α-helix (residues 8-18), a region incorporating a β-bend (residues 19-26) and the C-terminal portion (residues 27-37), that is characterized by bends between residues 28-30 and 33-34. A few residues have been identified that seem to make major contributions to receptor binding and activation, with a larger number contributing either to minor interactions (which collectively may be significant), or to maintaining the conformation of the bound peptide. It is not clear if CGRP follows the pattern of other family B GPCRs in binding largely as an α-helix. Linked Articles This article is part of a themed section on Neuropeptides. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.170.issue-7 © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Hsc70-induced changes in clathrin-auxilin cage structure suggest a role for clathrin light chains in cage disassembly

The molecular chaperone, Hsc70, together with its cofactor, auxilin, facilitates the ATP-dependent removal of clathrin during clathrin-mediated endocytosis in cells. We have used cryo-electron microscopy to determine the 3D structure of a complex of clathrin, auxilin401-910 and Hsc70 at pH 6 in the presence of ATP, frozen within 20 seconds of adding Hsc70 in order to visualize events that follow the binding of Hsc70 to clathrin and auxilin before clathrin disassembly. In this map,we observe density beneath the vertex of the cage that we attribute to bound Hsc70. This density emerges asymmetrically from the clathrin vertex, suggesting preferential binding by Hsc70 for one of the three possible sites at the vertex. Statistical comparison with a map of whole auxilin and clathrin previously published by us reveals the location of statistically significant differences which implicate involvement of clathrin light chains in structural rearrangements which occur after Hsc70 is recruited. Clathrin disassembly assays using light scattering suggest that loss of clathrin light chains reduces the efficiency with which auxilin facilitates this reaction. These data support a regulatory role for clathrin light chains in clathrin disassembly in addition to their established role in regulating clathrin assembly. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Institutions and equity structure of foreign affiliates

Question/Issue: We combine agency and institutional theory to explain the division of equity shares between the foreign (majority) and local (minority) partners within foreign affiliates. We posit that once the decision to invest is made, the ownership structure is arranged so as to generate appropriate incentives to local partners, taking into account both the institutional environment and the firm-specific difficulty in monitoring. Research Findings/Insights: Using a large firm-level dataset for the period 2003-2011 from 16 Central and Eastern European countries and applying selectivity corrected estimates, we find that both weaker host country institutions and higher share of intangible assets in total assets in the firm imply higher minority equity share of local partners. The findings hold when controlling for host country effects and when the attributes of the institutional environment are instrumented. Theoretical/Academic Implications: The classic view is that weak institutions lead to concentrated ownership, yet it leaves the level of minority equity shares unexplained. Our contribution uses a firm-level perspective combined with national-level variation in the institutional environment, and applies agency theory to explain the minority local partner share in foreign affiliates. In particular, we posit that the information asymmetry and monitoring problem in firms are exacerbated by weak host country institutions, but also by the higher share of intangible assets in total assets. Practitioner/Policy Implications: Assessing investment opportunities abroad, foreign firms need to pay attention not only to features directly related to corporate governance (e.g., bankruptcy codes) but also to the broad institutional environment. In weak institutional environments, foreign parent firms need to create strong incentives for local partners by offering them significant minority shares in equity. The same recommendation applies to firms with higher shares of intangible assets in total assets. © 2014 The Authors.

Board composition, ownership structure and dividend policies in an emerging market: further evidence from CASE 50

Purpose – The purpose of this study is to examine dividend policies in an emerging capital market, in a country undergoing a transitional period. Design/methodology/approach – Using pooled cross-sectional observations from the top 50 listed Egyptian firms between 2003 and 2005, this study examines the effect of board of directors’ composition and ownership structure on dividend policies in Egypt. Findings – It is found that there is a significant positive association between institutional ownership and firm performance, and both dividend decision and payout ratio. The results confirm that firms with a higher return on equity and a higher institutional ownership distribute higher levels of dividend. No significant association was found between board composition and dividend decisions or ratios. Originality/value – This study provides additional evidence of the applicability of the signalling model in the emerging market of Egypt. It was found that despite the high institutional ownership and the closely held nature of the firms, which imply lower agency costs, the payment of higher dividend was considered necessary to attract capital during this transitional period.

Optimization of DFB fiber laser performance based on a superimposed cavities structure

A simple technique based on superimposed cavities structure for direct real-time assessment of a DFB fiber laser mode condition during operation is demonstrated and used to provide a cavity mode conditioning feedback mechanism to optimize output performance. Significant improvements to the output performance and robustness are achieved over the entire pump power range without ambient isolation.