Evidence that interaction between conserved residues in transmembrane helices 2, 3, and 7 are crucial for human VPAC1 receptor activation

The VPAC(1) receptor belongs to family B of G protein-coupled receptors (GPCR-B) and is activated upon binding of the vasoactive intestinal peptide (VIP). Despite the recent determination of the structure of the N terminus of several members of this receptor family, little is known about the structure of the transmembrane (TM) region and about the molecular mechanisms leading to activation. In the present study, we designed a new structural model of the TM domain and combined it with experimental mutagenesis experiments to investigate the interaction network that governs ligand binding and receptor activation. Our results suggest that this network involves the cluster of residues Arg(188) in TM2, Gln(380) in TM7, and Asn(229) in TM3. This cluster is expected to be altered upon VIP binding, because Arg(188) has been shown previously to interact with Asp(3) of VIP. Several point mutations at positions 188, 229, and 380 were experimentally characterized and were shown to severely affect VIP binding and/or VIP-mediated cAMP production. Double mutants built from reciprocal residue exchanges exhibit strong cooperative or anticooperative effects, thereby indicating the spatial proximity of residues Arg(188), Gln(380), and Asn(229). Because these residues are highly conserved in the GPCR-B family, they can moreover be expected to have a general role in mediating function.

An examination of the calcium and strontium site distribution in bioactive glasses through isomorphic neutron diffraction, X-ray diffraction, EXAFS and multinuclear solid state NMR.

Strontium has been substituted for calcium in the glass series (SiO2)49.46(Na2O)26.38(P2O5)1.07(CaO)23.08x(SrO)x (where x = 0, 11.54, 23.08) to elucidate their underlying atomic-scale structural characteristics as a basis for understanding features related to the bioactivity. These bioactive glasses have been investigated using isomorphic neutron and X-ray diffraction, Sr K-edge EXAFS and solid state 17O, 23Na, 29Si, 31P and 43Ca magic-angle-spinning (MAS) NMR. An effective isomorphic substitution first-order difference function has been applied to the neutron diffraction data, confirming that Ca and Sr behave in a similar manner within the glass network, with residual differences attributed to solely the variation in ionic radius between the two species. The diffraction data provides the first direct experimental evidence of split Ca–O nearest-neighbour correlations in these melt quench bioactive glasses, together with an analogous splitting of the Sr–O correlations; the correlations are attributed to the metal ions correlated either to bridging or to non-bridging oxygen atoms. Triple quantum (3Q) 43Ca MAS NMR corroborates the split Ca–O correlations. Successful simplification of the 2 < r (A) < 3 region via the difference method has also revealed two distinct Na environments. These environments are attributed to sodium correlated either to bridging or to nonbridging oxygen atoms. Complementary multinuclear MAS NMR, Sr K-edge EXAFS and X-ray diffraction data supports the structural model presented. The structural sites present will be intimately related to their release properties in physiological fluids such as plasma and saliva, and hence the bioactivity of the material. Detailed structural knowledge is therefore a prerequisite for optimising material design.

Tacit collusion, firm asymmetries and numbers:evidence from EC merger cases

The purpose of this paper is to identify empirically the implicit structural model, especially the roles of size asymmetries and concentration, used by the European Commission to identify mergers with coordinated effects (i.e. collective dominance). Apart from its obvious policy-relevance, the paper is designed to shed empirical light on the conditions under which tacit collusion is most likely. We construct a database relating to 62 candidate mergers and find that, in the eyes of the Commission, tacit collusion in this context virtually never involves more than two firms and requires close symmetry in the market shares of the two firms.

The definition, theoretical modelling and empirical research of front-line service employee corporate identity within a UK national grocery retailer:determining the FLE corporate brand identification construct

Over the past forty years the corporate identity literature has developed to a point of maturity where it currently contains many definitions and models of the corporate identity construct at the organisational level. The literature has evolved by developing models of corporate identity or in considering corporate identity in relation to new and developing themes, e.g. corporate social responsibility. It has evolved into a multidisciplinary domain recently incorporating constructs from other literature to further its development. However, the literature has a number of limitations. It remains that an overarching and universally accepted definition of corporate identity is elusive, potentially leaving the construct with a lack of clear definition. Only a few corporate identity definitions and models, at the corporate level, have been empirically tested. The corporate identity construct is overwhelmingly defined and theoretically constructed at the corporate level, leaving the literature without a detailed understanding of its influence at an individual stakeholder level. Front-line service employees (FLEs), form a component in a number of corporate identity models developed at the organisational level. FLEs deliver the services of an organisation to its customers, as well as represent the organisation by communicating and transporting its core defining characteristics to customers through continual customer contact and interaction. This person-to-person contact between an FLE and the customer is termed a service encounter, where service encounters influence a customer’s perception of both the service delivered and the associated level of service quality. Therefore this study for the first time defines, theoretically models and empirically tests corporate identity at the individual FLE level, termed FLE corporate identity. The study uses the services marketing literature to characterise an FLE’s operating environment, arriving at five potential dimensions to the FLE corporate identity construct. These are scrutinised against existing corporate identity definitions and models to arrive at a definition for the construct. In reviewing the corporate identity, services marketing, branding and organisational psychology literature, a theoretical model is developed for FLE corporate identity, which is empirically and quantitatively tested, with FLEs in seven stores of a major national retailer. Following rigorous construct reliability and validity testing, the 601 usable responses are used to estimate a confirmatory factor analysis and structural equation model for the study. The results for the individual hypotheses and the structural model are very encouraging, as they fit the data well and support a definition of FLE corporate identity. This study makes contributions to the branding, services marketing and organisational psychology literature, but its principal contribution is to extend the corporate identity literature into a new area of discourse and research, that of FLE corporate identity

Essays on international macroeconomics and conflict analysis

This dissertation addressed two broad problems in international macroeconomics and conflict analysis. The first problem in the first chapter looked at the behavior of exchange rate and its interaction with industry-level tradable goods prices for three countries, USA, UK and Japan. This question has important monetary policy implications. Here, I computed to what extent changes in exchange rate affected prices of consumer, producer, and export goods. I also studied the timing of these changes in these prices. My results, based on thirty-four industrial prices for USA, UK and Japan, supported the view that changes in exchange rates significantly affect prices of industrial and consumer goods. It also provided an insight to the underlying economic process that led to changes in relative prices. ^ In the second chapter, I explored the predictability of future inflation by incorporating shocks to exchange rates and clearly specified the transmission mechanisms that link exchange rates to industry-level consumer and producer prices. Employing a variety of linear and state-of-the-art nonlinear models, I also predicted growth rates of future prices. Comparing levels of inflation obtained from the above approaches showed superiority of the structural model incorporating the exchange rate pass-through effect. ^ The second broad issue addressed in the third chapter of the dissertation investigated the economic motives for conflict, manifested by rebellion and civil war for seventeen Latin American countries. Based on the analytical framework of Garfinkel, Skaperdas and Syropoulos (2004), I employed ordinal regressions and Markov switching for a panel of seventeen countries to identify trade and openness factors responsible for conflict occurrence and intensity. The results suggested that increased trade openness reduced high intensity domestic conflicts but overdependence on agricultural exports, along with a lack of income earning opportunities lead to more conflicts. Thereafter, using the Cox Proportional Hazard model I studied “conflict duration” and found that over-reliance on agricultural exports explained a major part of the length of conflicts in addition to various socio-political factors. ^

Relational predictors of condom use among adolescents in outpatient substance abuse treatment

Past HIV interventions have been critiqued for their failure to incorporate relational factors linked to condom use. Furthermore, few studies have focused on the relational context of sexual risk behavior among adolescents at elevated risk for HIV/STI exposure in the context of substance use. Therefore, this study evaluated the influence of three key relational factors (rejection sensitivity, intimacy dating goals, intercourse-related anxiety) salient for understanding condom use among adolescents in outpatient substance abuse treatment in South Florida. Structural equation modeling was used to test relational factors as direct and indirect predictors of condom use. Specifically, the current study investigated the influence of rejection sensitivity and intimacy dating goals on percentage of protected intercourse, with intercourse-related anxiety modeled as a mediator of this association. ^ Results obtained from the hypothesized structural model suggest rejection sensitivity and intimacy dating goals are significant predictors of percentage of protected intercourse. As expected, rejection sensitivity was related to lower levels of percentage of protected intercourse via heightened levels of intercourse-related anxiety and was not related directly to percentage of protected intercourse. Intercourse-related anxiety was indicated as a partial mediator between rejection sensitivity and percentage of protected intercourse. In contrast, intimacy dating goals was related to lower levels of percentage of protected intercourse directly. The findings demonstrate the importance of relational factors in condom use among adolescents in outpatient substance abuse treatment. Levels of protected intercourse are likely to increase when relational factors are targeted among adolescents in this high-risk population. Implications for prevention strategies targeting this high-risk subgroup of adolescents are discussed. ^

Relations between acculturation and alcohol use among international students

In the current study, 226 international students attending Florida International University responded to an Web-based questionnaire that assessed self-reported scores for: acculturation, acculturative stress, alcohol use patterns, perceived peer alcohol use, and perceived injunctive social norms for alcohol use. The purpose of the study was to evaluate structural relations among this set of variables using Structural Equation Modeling (SEM) via AMOS 17.0. The results of SEM analyses documented acceptable fit of a model which hypothesized that relations between acculturation and alcohol use variables are mediated partially by acculturative stress, perceived peer alcohol use, and perceived injunctive social norms. While significant path coefficients were documented for paths between (a) acculturation and acculturative stress and (b) acculturative stress and alcohol use, the coefficients had negative signs, contrary to existing studies investigating these relations among immigrant youth. While paths between (a) perceived peer alcohol use or (b) perceived injunctive social norms and participants’ alcohol use were significant, path coefficients between acculturation and either (a) perceived peer alcohol use or (b) perceived injunctive social norms were not statistically significant. In addition, multiple-group comparisons suggested that social support had a significant moderating influence on several significant paths in the structural model. Specifically, international students reporting higher social support reported lower scores for acculturative stress and alcohol use, in contrast to their counterparts who reported lower scores for social support.

What makes online grocers work? A case study analysis of factors contributing to online grocery store profitability

This research examined the factors contributing to the performance of online grocers prior to, and following, the 2000 dot.com collapse. The primary goals were to assess the relationship between a company’s business model(s) and its performance in the online grocery channel and to determine if there were other company and/or market related factors that could account for company performance. ^ To assess the primary goals, a case based theory building process was utilized. A three-way cross-case analysis comprising Peapod, GroceryWorks, and Tesco examined the common profit components, the structural category (e.g., pure-play, partnership, and hybrid) profit components, and the idiosyncratic profit components related to each specific company. ^ Based on the analysis, it was determined that online grocery store business models could be represented at three distinct, but hierarchically, related levels. The first level was termed the core model and represented the basic profit structure that all online grocers needed in order to conduct operations. The next model level was termed the structural model and represented the profit structure associated with the specific business model configuration (i.e., pure-play, partnership, hybrid). The last model level was termed the augmented model and represented the company’s business model when idiosyncratic profit components were included. In relation to the five company related factors, scalability, rate of expansion, and the automation level were potential candidates for helping to explain online grocer performance. In addition, all the market structure related factors were deemed possible candidates for helping to explain online grocer performance. ^ The study concluded by positing an alternative hypothesis concerning the performance of online grocers. Prior to this study, the prevailing wisdom was that the business models were the primary cause of online grocer performance. However, based on the core model analysis, it was hypothesized that the customer relationship activities (i.e., advertising, promotions, and loyalty program tie-ins) were the real drivers of online grocer performance. ^

The effects of parental nurturance and involvement on peer relationships and psychosocial functioning of young adults

This study examined peer relationships and psychosocial functioning as a function of maternal and paternal involvement and nurturance along with the moderating effects of gender, family form, and ethnicity. Prior research has shown the influence of mother’s involvement on peer relationship quality but not of fathers. Further, previous studies did not examine moderation by family form, gender, or ethnicity. The sample consisted of 1359 students who identified their biological mother and father as the most influential parental figures in their lives. Their ages ranged from 18 to 26; Sixty-one percent of the sample was Hispanic, 13% non-Hispanic Black, 25% non-Hispanic White; 76% female and 70% from intact families. The analytical strategy included using bivariate correlations and structural equation modeling to examine these relationships. ^ All dimensions of maternal and paternal nurturing and involvement were positively related to positive characteristics of peer relationships, self-esteem and life satisfaction consistent with the multicultural findings of PARTheory (Rohner, Khalique, & Cournoyer, 2005). A structural model was developed that was able to adequately account for the relationship between parental influence, peer relationships, and psychosocial functioning. These effects of both maternal and paternal influence were strongly moderated by culture, family form, and gender. Finally, a differential effect was found among parental influence with fathers having a greater influence on friendship quality and importance than mothers, despite greater maternal involvement. ^ These findings have theoretical, clinical, and social implications as they call for a socially based theoretical perspective within which to study these relationships. Such a perspective would better inform clinicians when using impaired social functioning as indicative of axial diagnosis, and for the implementation of social policy to encourage paternal involvement. ^

Examining argumentative coherence in essays by undergraduate students of English as a foreign language in Mainland China and their English speaking peers in the United States

I conducted this study to provide insights toward deepening understanding of association between culture and writing by building, assessing, and refining a conceptual model of second language writing. To do this, I examined culture and coherence as well as the relationship between them through a mixed methods research design. Coherence has been an important and complex concept in ESL/EFL writing. I intended to study the concept of coherence in the research context of contrastive rhetoric, comparing the coherence quality in argumentative essays written by undergraduates in Mainland China and their U.S. peers. In order to analyze the complex concept of coherence, I synthesized five linguistic theories of coherence: Halliday and Hasan's cohesion theory, Carroll's theory of coherence, Enkvist's theory of coherence, Topical Structure Analysis, and Toulmin's Model. Based upon the synthesis, 16 variables were generated. Across these 16 variables, Hotelling t-test statistical analysis was conducted to predict differences in argumentative coherence between essays written by two groups of participants. In order to complement the statistical analysis, I conducted 30 interviews of the writers in the studies. Participants' responses were analyzed with open and axial coding. By analyzing the empirical data, I refined the conceptual model by adding more categories and establishing associations among them. The study found that U.S. students made use of more pronominal reference. Chinese students adopted more lexical devices of reiteration and extended paralleling progression. The interview data implied that the difference may be associated with the difference in linguistic features and rhetorical conventions in Chinese and English. As far as Toulmin's Model is concerned, Chinese students scored higher on data than their U.S. peers. According to the interview data, this may be due to the fact that Toulmin's Model, modified as three elements of arguments, have been widely and long taught in Chinese writing instruction while U.S. interview participants said that they were not taught to write essays according to Toulmin's Model. Implications were generated from the process of textual data analysis and the formulation of structural model defining coherence. These implications were aimed at informing writing instruction, assessment, peer-review, and self-revision.

Relations Between Acculturation And Alcohol Use Among International Students

In the current study, 226 international students attending Florida International University responded to an Web-based questionnaire that assessed self-reported scores for: acculturation, acculturative stress, alcohol use patterns, perceived peer alcohol use, and perceived injunctive social norms for alcohol use. The purpose of the study was to evaluate structural relations among this set of variables using Structural Equation Modeling (SEM) via AMOS 17.0. The results of SEM analyses documented acceptable fit of a model which hypothesized that relations between acculturation and alcohol use variables are mediated partially by acculturative stress, perceived peer alcohol use, and perceived injunctive social norms. While significant path coefficients were documented for paths between (a) acculturation and acculturative stress and (b) acculturative stress and alcohol use, the coefficients had negative signs, contrary to existing studies investigating these relations among immigrant youth. While paths between (a) perceived peer alcohol use or (b) perceived injunctive social norms and participants’ alcohol use were significant, path coefficients between acculturation and either (a) perceived peer alcohol use or (b) perceived injunctive social norms were not statistically significant. In addition, multiple-group comparisons suggested that social support had a significant moderating influence on several significant paths in the structural model. Specifically, international students reporting higher social support reported lower scores for acculturative stress and alcohol use, in contrast to their counterparts who reported lower scores for social support.

Essays on Energy Economics and Industrial Organization

The dissertation consists of three chapters related to the low-price guarantee marketing strategy and energy efficiency analysis. The low-price guarantee is a marketing strategy in which firms promise to charge consumers the lowest price among their competitors. Chapter 1 addresses the research question "Does a Low-Price Guarantee Induce Lower Prices'' by looking into the retail gasoline industry in Quebec where there was a major branded firm which started a low-price guarantee back in 1996. Chapter 2 does a consumer welfare analysis of low-price guarantees to drive police indications and offers a new explanation of the firms' incentives to adopt a low-price guarantee. Chapter 3 develops the energy performance indicators (EPIs) to measure energy efficiency of the manufacturing plants in pulp, paper and paperboard industry.

Chapter 1 revisits the traditional view that a low-price guarantee results in higher prices by facilitating collusion. Using accurate market definitions and station-level data from the retail gasoline industry in Quebec, I conducted a descriptive analysis based on stations and price zones to compare the price and sales movement before and after the guarantee was adopted. I find that, contrary to the traditional view, the stores that offered the guarantee significantly decreased their prices and increased their sales. I also build a difference-in-difference model to quantify the decrease in posted price of the stores that offered the guarantee to be 0.7 cents per liter. While this change is significant, I do not find the response in comeptitors' prices to be significant. The sales of the stores that offered the guarantee increased significantly while the competitors' sales decreased significantly. However, the significance vanishes if I use the station clustered standard errors. Comparing my observations and the predictions of different theories of modeling low-price guarantees, I conclude the empirical evidence here supports that the low-price guarantee is a simple commitment device and induces lower prices.

Chapter 2 conducts a consumer welfare analysis of low-price guarantees to address the antitrust concerns and potential regulations from the government; explains the firms' potential incentives to adopt a low-price guarantee. Using station-level data from the retail gasoline industry in Quebec, I estimated consumers' demand of gasoline by a structural model with spatial competition incorporating the low-price guarantee as a commitment device, which allows firms to pre-commit to charge the lowest price among their competitors. The counterfactual analysis under the Bertrand competition setting shows that the stores that offered the guarantee attracted a lot more consumers and decreased their posted price by 0.6 cents per liter. Although the matching stores suffered a decrease in profits from gasoline sales, they are incentivized to adopt the low-price guarantee to attract more consumers to visit the store likely increasing profits at attached convenience stores. Firms have strong incentives to adopt a low-price guarantee on the product that their consumers are most price-sensitive about, while earning a profit from the products that are not covered in the guarantee. I estimate that consumers earn about 0.3% more surplus when the low-price guarantee is in place, which suggests that the authorities should not be concerned and regulate low-price guarantees. In Appendix B, I also propose an empirical model to look into how low-price guarantees would change consumer search behavior and whether consumer search plays an important role in estimating consumer surplus accurately.

Chapter 3, joint with Gale Boyd, describes work with the pulp, paper, and paperboard (PP&PB) industry to provide a plant-level indicator of energy efficiency for facilities that produce various types of paper products in the United States. Organizations that implement strategic energy management programs undertake a set of activities that, if carried out properly, have the potential to deliver sustained energy savings. Energy performance benchmarking is a key activity of strategic energy management and one way to enable companies to set energy efficiency targets for manufacturing facilities. The opportunity to assess plant energy performance through a comparison with similar plants in its industry is a highly desirable and strategic method of benchmarking for industrial energy managers. However, access to energy performance data for conducting industry benchmarking is usually unavailable to most industrial energy managers. The U.S. Environmental Protection Agency (EPA), through its ENERGY STAR program, seeks to overcome this barrier through the development of manufacturing sector-based plant energy performance indicators (EPIs) that encourage U.S. industries to use energy more efficiently. In the development of the energy performance indicator tools, consideration is given to the role that performance-based indicators play in motivating change; the steps necessary for indicator development, from interacting with an industry in securing adequate data for the indicator; and actual application and use of an indicator when complete. How indicators are employed in EPA’s efforts to encourage industries to voluntarily improve their use of energy is discussed as well. The chapter describes the data and statistical methods used to construct the EPI for plants within selected segments of the pulp, paper, and paperboard industry: specifically pulp mills and integrated paper & paperboard mills. The individual equations are presented, as are the instructions for using those equations as implemented in an associated Microsoft Excel-based spreadsheet tool.

Building an index of well-being for children living in Ireland: conceptual, measurement and policy considerations

This study conceptualised and measured children’s well-being in Ireland and considered how such conceptualisations and approaches to the measurement of well-being might inform social policy for children and families living in Ireland. This research explored what is meant by children’s well-being and how it can be conceptualised and measured so as to reflect the multi-dimensionality of the concept. The study developed an index of well-being that was both theoretically and methodologically robust and could be meaningfully used to inform social policy developments for children and their families. For the first time, an index of well-being for children was developed using an explicitly articulated unifying theory of children’s well-being. Moreover, for the first time an index of wellbeing was developed for 13-year old children living in Ireland using data from Wave 2 of the national longitudinal study of children. The Structural Model of Child Well-being (SMCW), the theoretical framework that underpins the development of this study’s index, offers a comprehensive understanding of well-being. The SMCW builds on, and integrates, a range of already-established theories concerning children’s development, their agency, rights and capabilities into a unifying theory that explains well-being in its entirety. This conceptualisation of well-being moves beyond the narrow focus on child development adopted in some recent studies of children’s well-being and which perpetuate individualised and self-responsibilising conceptualisations of well-being. This study found that the SMCW can be meaningfully applied, both theoretically and operationally, to the construction of an index of well-being for children. While it was not the purpose of this study to validate the SMCW, in the process of developing the index, I concluded that there was a theoretical ‘fit’ between the conceptual orientation of the SMCW and the wider children’s well-being literature. The ‘nested’ structure of the SMCW facilitated the identification of domains, sub-domains and indicators of well-being reflecting typical conventions of index construction. The findings from the resulting index, in both its categorical and continuous forms, demonstrated how a comprehensive theory of well-being can be used to illustrate how children are faring and which children are experiencing poorer or better well-being. Furthermore, this study demonstrated how the SMCW and the resultant index can be meaningfully used to support the implementation and review of the national policy framework for children and young people in Ireland.

What Makes Online Grocers Work? A Case Study Analysis of Factors Contributing to Online Grocery Store Profitability

This research examined the factors contributing to the performance of online grocers prior to, and following, the 2000 dot.com collapse. The primary goals were to assess the relationship between a company’s business model(s) and its performance in the online grocery channel and to determine if there were other company and/or market related factors that could account for company performance. To assess the primary goals, a case based theory building process was utilized. A three-way cross-case analysis comprising Peapod, GroceryWorks, and Tesco examined the common profit components, the structural category (e.g., pure-play, partnership, and hybrid) profit components, and the idiosyncratic profit components related to each specific company. Based on the analysis, it was determined that online grocery store business models could be represented at three distinct, but hierarchically, related levels. The first level was termed the core model and represented the basic profit structure that all online grocers needed in order to conduct operations. The next model level was termed the structural model and represented the profit structure associated with the specific business model configuration (i.e., pure-play, partnership, hybrid). The last model level was termed the augmented model and represented the company’s business model when idiosyncratic profit components were included. In relation to the five company related factors, scalability, rate of expansion, and the automation level were potential candidates for helping to explain online grocer performance. In addition, all the market structure related factors were deemed possible candidates for helping to explain online grocer performance. The study concluded by positing an alternative hypothesis concerning the performance of online grocers. Prior to this study, the prevailing wisdom was that the business models were the primary cause of online grocer performance. However, based on the core model analysis, it was hypothesized that the customer relationship activities (i.e., advertising, promotions, and loyalty program tie-ins) were the real drivers of online grocer performance.

A proposal for a corresponsible intervention on sexual harassment at work

Sexual harassment at work is a form of gender violence barely made visible but still present in labor organizations, where it keeps generating high levels of suffering, discrimination and inequality mainly affecting women. To address it properly it is necessary an organizational change towards equity arising from the knowledge of the subjective meanings that stakeholders (staff, union representatives, employers, public administration, etc.) attribute to that reality. In this article we present the main findings of a qualitative study on the social perception of sexual harassment. The work highlights the existence of many strategies aimed at legitimize and minimize the relevance of the problem, blaming the victim, justifying the lack of support from the environment and / or the involvement of the organization in the solutions. Among the conclusions we underline the need for new models of business management involving all stakeholders in the prevention and control of the in a responsible way.