1,983 research outputs found

    The theory of international business: the role of economic models

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    This paper reviews the scope for economic modelling in international business studies. It argues for multi-level theory based on classic internalisation theory. It present a systems approach that encompasses both firm-level and industry-level analysis

    Gene expression drives the evolution of dominance.

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    Dominance is a fundamental concept in molecular genetics and has implications for understanding patterns of genetic variation, evolution, and complex traits. However, despite its importance, the degree of dominance in natural populations is poorly quantified. Here, we leverage multiple mating systems in natural populations of Arabidopsis to co-estimate the distribution of fitness effects and dominance coefficients of new amino acid changing mutations. We find that more deleterious mutations are more likely to be recessive than less deleterious mutations. Further, this pattern holds across gene categories, but varies with the connectivity and expression patterns of genes. Our work argues that dominance arises as a consequence of the functional importance of genes and their optimal expression levels

    The LKB1-salt-inducible kinase pathway functions as a key gluconeogenic suppressor in the liver

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    LKB1 is a master kinase that regulates metabolism and growth through adenosine monophosphate-activated protein kinase (AMPK) and 12 other closely related kinases. Liver-specific ablation of LKB1 causes increased glucose production in hepatocytes in vitro and hyperglycaemia in fasting mice in vivo. Here we report that the salt-inducible kinases (SIK1, 2 and 3), members of the AMPK-related kinase family, play a key role as gluconeogenic suppressors downstream of LKB1 in the liver. The selective SIK inhibitor HG-9-91-01 promotes dephosphorylation of transcriptional co-activators CRTC2/3 resulting in enhanced gluconeogenic gene expression and glucose production in hepatocytes, an effect that is abolished when an HG-9-91-01-insensitive mutant SIK is introduced or LKB1 is ablated. Although SIK2 was proposed as a key regulator of insulin-mediated suppression of gluconeogenesis, we provide genetic evidence that liver-specific ablation of SIK2 alone has no effect on gluconeogenesis and insulin does not modulate SIK2 phosphorylation or activity. Collectively, we demonstrate that the LKB1-SIK pathway functions as a key gluconeogenic gatekeeper in the liver

    Prevalence of Risk Factors for Adverse Pregnancy Outcomes During Pregnancy and the Preconception Period—United States, 2002–2004

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    Objectives: To assess the prevalence of risk factors for adverse pregnancy outcome during the preconception stage and during pregnancy, and to assess differences between women in preconception and pregnancy. Methods: Data from the 2002 and 2004 Behavioral Risk Factor Surveillance System, United States, were used to estimate the prevalence of selected risk factors among women 18–44 in the preconception period (women who wanted a baby in the next 12 months, and were not using contraception, not sterile and not already pregnant) with women who reported that they were pregnant at the time of interview. Results: Major health risks were reported by substantial proportions of women in the preconceptional period and were also reported by many pregnant women, although pregnant women tended to report lower levels of risk than preconception women. For example, 54.5% of preconception women reported one or more of 3 risk factors (frequent drinking, current smoking, and absence of an HIV test), compared with 32.0% of pregnant women (p < .05). The difference in the prevalence of these three risk factors between preconception and pregnancy was significant for women with health insurance (52.5% in preconception vs. 29.4% in pregnancy, p < .05), but not for women without insurance (63.4% vs. 52.7%, p > .05). Conclusions: Women appear to be responding to messages regarding behaviors that directly affect pregnancy such as smoking, alcohol consumption and taking folic acid, but many remain unaware of the benefits of available interventions to prevent HIV transmission and birth defects. Although it appears that some women reduce their risk for adverse pregnancy outcomes after learning of their pregnancy, the data suggest that a substantial proportion of women do not. Furthermore, if such change occurs it is often too late to affect outcomes, such as birth defects resulting from alcohol consumption during the periconception period. Preconception interventions are recommended to achieve a more significant reduction in risk and further improvement in perinatal outcomes

    Methodological challenges in online trials: an update and insights from the REACT trial

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    There has been a growth in the number of web-based trials of web-based interventions, adding to an increasing evidence base for their feasibility and effectiveness. However, there are challenges associated with such trials, which researchers must address. This discussion paper follows the structure of the Down Your Drink trial methodology paper, providing an update from the literature for each key trial parameter (recruitment, registration eligibility checks, consent and participant withdrawal, randomization, engagement with a web-based intervention, retention, data quality and analysis, spamming, cybersquatting, patient and public involvement, and risk management and adverse events), along with our own recommendations based on designing the Relatives Education and Coping Toolkit randomized controlled trial for relatives of people with psychosis or bipolar disorder. The key recommendations outlined here are relevant for future web-based and hybrid trials and studies using iterative development and test models such as the Accelerated Creation-to-Sustainment model, both within general health research and specifically within mental health research for relatives. Researchers should continue to share lessons learned from conducting web-based trials of web-based interventions to benefit future studies

    How managers can build trust in strategic alliances: a meta-analysis on the central trust-building mechanisms

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    Trust is an important driver of superior alliance performance. Alliance managers are influential in this regard because trust requires active involvement, commitment and the dedicated support of the key actors involved in the strategic alliance. Despite the importance of trust for explaining alliance performance, little effort has been made to systematically investigate the mechanisms that managers can use to purposefully create trust in strategic alliances. We use Parkhe’s (1998b) theoretical framework to derive nine hypotheses that distinguish between process-based, characteristic-based and institutional-based trust-building mechanisms. Our meta-analysis of 64 empirical studies shows that trust is strongly related to alliance performance. Process-based mechanisms are more important for building trust than characteristic- and institutional-based mechanisms. The effects of prior ties and asset specificity are not as strong as expected and the impact of safeguards on trust is not well understood. Overall, theoretical trust research has outpaced empirical research by far and promising opportunities for future empirical research exist

    Correcting the Site Frequency Spectrum for Divergence-Based Ascertainment

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    Comparative genomics based on sequenced referenced genomes is essential to hypothesis generation and testing within population genetics. However, selection of candidate regions for further study on the basis of elevated or depressed divergence between species leads to a divergence-based ascertainment bias in the site frequency spectrum within selected candidate loci. Here, a method to correct this problem is developed that obtains maximum-likelihood estimates of the unascertained allele frequency distribution using numerical optimization. I show how divergence-based ascertainment may mimic the effects of natural selection and offer correction formulae for performing proper estimation into the strength of selection in candidate regions in a maximum-likelihood setting

    Abundance, rarity and invasion debt among exotic species in a patchy ecosystem

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    Community assembly through species invasions is a long-term process, for which vital information regarding future trends can be contained in current patterns. Using comparative analyses of native and exotic plant assemblages from meadow patches on islands in British Columbia, Canada, we examined multiple lines of evidence for ‘invasion debt’, a latent expansion of exotic species populations. We show that: (1) short-dispersing species are underrepresented compared to their long-dispersing counterparts in exotic species only; (2) among species that are invasive elsewhere in North America, a greater proportion of long dispersers are common in the study area and a greater proportion of short dispersers are rare; and (3) time since arrival in the study region is positively related to number of occurrences in exotic species. In addition, we show that a suite of exotic species possesses the facility of rapid long-distance dispersal and ability to establish viable populations on even the most isolated and least disturbed patches. While some highly-dispersive exotic species can rapidly colonize new areas, short dispersers appear to exhibit invasion debt, with their potential distributions only being realized in the long term. Removing or even reducing populations of many rapid colonizers could be extremely difficult; however, for species exhibiting patterns most consistent with invasion debt, an opportunity exists for monitoring and removal to help reduce potential competition with native species

    Extensive Copy-Number Variation of Young Genes across Stickleback Populations

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    MM received funding from the Max Planck innovation funds for this project. PGDF was supported by a Marie Curie European Reintegration Grant (proposal nr 270891). CE was supported by German Science Foundation grants (DFG, EI 841/4-1 and EI 841/6-1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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