223 research outputs found

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

    Get PDF
    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

    Acute Insulin Stimulation Induces Phosphorylation of the Na-Cl Cotransporter in Cultured Distal mpkDCT Cells and Mouse Kidney

    Get PDF
    The NaCl cotransporter (NCC) is essential for sodium reabsorption at the distal convoluted tubules (DCT), and its phosphorylation increases its transport activity and apical membrane localization. Although insulin has been reported to increase sodium reabsorption in the kidney, the linkage between insulin and NCC phosphorylation has not yet been investigated. This study examined whether insulin regulates NCC phosphorylation. In cultured mpkDCT cells, insulin increased phosphorylation of STE20/SPS1-related proline-alanine-rich kinase (SPAK) and NCC in a dose-dependent manner. This insulin-induced phosphorylation of NCC was suppressed in WNK4 and SPAK knockdown cells. In addition, Ly294002, a PI3K inhibitor, decreased the insulin effect on SPAK and NCC phosphorylation, indicating that insulin induces phosphorylation of SPAK and NCC through PI3K and WNK4 in mpkDCT cells. Moreover, acute insulin administration to mice increased phosphorylation of oxidative stress-responsive kinase-1 (OSR1), SPAK and NCC in the kidney. Time-course experiments in mpkDCT cells and mice suggested that SPAK is upstream of NCC in this insulin-induced NCC phosphorylation mechanism, which was confirmed by the lack of insulin-induced NCC phosphorylation in SPAK knockout mice. Moreover, insulin administration to WNK4 hypomorphic mice did not increase phosphorylation of OSR1, SPAK and NCC in the kidney, suggesting that WNK4 is also involved in the insulin-induced OSR1, SPAK and NCC phosphorylation mechanism in vivo. The present results demonstrated that insulin is a potent regulator of NCC phosphorylation in the kidney, and that WNK4 and SPAK are involved in this mechanism of NCC phosphorylation by insulin

    Evaluation of molecular descriptors for antitumor drugs with respect to noncovalent binding to DNA and antiproliferative activity

    Get PDF
    34 pages, 6 additional files, 5 tables, 4 figures.[Background ] Small molecules that bind reversibly to DNA are among the antitumor drugs currently used in chemotherapy. In the pursuit of a more rational approach to cancer chemotherapy based upon these molecules, it is necessary to exploit the interdependency between DNA-binding affinity, sequence selectivity and cytotoxicity. For drugs binding noncovalently to DNA, it is worth exploring whether molecular descriptors, such as their molecular weight or the number of potential hydrogen acceptors/donors, can account for their DNA-binding affinity and cytotoxicity.[Results] Fifteen antitumor agents, which are in clinical use or being evaluated as part of the National Cancer Institute’s drug screening effort, were analyzed in silico to assess the contribution of various molecular descriptors to their DNA-binding affinity, and the capacity of the descriptors and DNA-binding constants for predicting cell cytotoxicity. Equations to predict drug-DNA binding constants and growth-inhibitory concentrations were obtained by multiple regression following rigorous statistical procedures.[Conclusions] For drugs binding reversibly to DNA, both their strength of binding and their cytoxicity are fairly predicted from molecular descriptors by using multiple regression methods. The equations derived may be useful for rational drug design. The results obtained agree with that compounds more active across the National Cancer Institute’s 60-cell line data set tend to have common structural features.Supported by a grant from the former Spanish Ministry of Education and Science (BFU2007-60998) and the FEDER program of the European Community.Peer reviewe

    Co-producing across organizational boundaries: promoting asylum seeker integration in Scotland

    Get PDF
    This paper questions whether asylum seeker integration is promoted through inter-organisational relationships between non-profit and voluntary organisations (NPVOs) and government agencies. It focuses particularly on the role of NPVOs in service delivery (co-management) and in the delivery and planning of public services (co-governance). It presents a research study on the public services provided to asylum seekers in Glasgow and asks the following questions: What role do NPVOs play in the planning and delivery of public services? When planning and delivering public services, to what extent do NPVOs work across organisational boundaries and what kind of relationships exist? And in practice, what makes inter-organisational relationships work? This paper offers new empirical evidence and also contributes to the theoretical debate around the integration of asylum seekers

    The Intracellular Threonine of Amyloid Precursor Protein That Is Essential for Docking of Pin1 Is Dispensable for Developmental Function

    Get PDF
    Background: Processing of Ab-precursor protein (APP) plays an important role in Alzheimer’s Disease (AD) pathogenesis. Thr residue at amino acid 668 of the APP intracellular domain (AID) is highly conserved. When phosphorylated, this residue generates a binding site for Pin1. The interaction of APP with Pin1 has been involved in AD pathogenesis. Methodology/Principal Findings: To dissect the functions of this sequence in vivo, we created an APP knock-in allele, in which Thr 668 is replaced by an Ala (T 668 A). Doubly deficient APP/APP-like protein 2 (APLP2) mice present postnatal lethality and neuromuscular synapse defects. Previous work has shown that the APP intracellular domain is necessary for preventing early lethality and neuromuscular junctions (NMJ) defects. Crossing the T 668 A allele into the APLP2 knockout background showed that mutation of Thr 668 does not cause a defective phenotype. Notably, the T 668 A mutant APP is able to bind Mint1. Conclusions/Significance: Our results argue against an important role of the Thr 668 residue in the essential function of APP in developmental regulation. Furthermore, they indicate that phosphorylation at this residue is not functionally involved i

    Influence of the central-to-peripheral arterial stiffness gradient on the timing and amplitude of wave reflections

    Get PDF
    In individuals with compliant aortas, peripheral muscular artery stiffness exceeds central elastic artery stiffness. With ageing, central stiffness increases, with little change in peripheral stiffness, resulting in a reversal of the normal stiffness gradient. This reversal may reduce wave reflection amplitude, due to movement of the major “effective” reflection site further from the heart. To test this, we investigated the relationship among arterial stiffness gradients (normal and reversed), wave reflection amplitude and reflection site distance. Subjects aged ≥50years were recruited from the Anglo-Cardiff Collaborative Trial. Central stiffness was assessed by carotid-femoral pulse wave velocity (cfPWV). In study 1, peripheral PWV was also measured in the arm (carotid-radial, crPWV), and in study 2 in the leg (femoral- dorsalis pedis, fpPWV). Reflection site distance was calculated from cfPWV and reflected wave travel time. Subjects were dichotomized into those with a normal stiffness gradient (peripheral>central PWV), or a reversed gradient (peripheral<central PWV). In study 1, reflection site distance was greater in subjects with a reversed gradient (P<0.01), whereas time to reflection was lower (P<0.001). Both augmentation pressure (P<0.001) and augmentation index (P<0.05) were greater in subjects with a reversed gradient. In study 2, augmentation pressure, augmentation index and reflection site distance were greater in subjects with a reversed stiffness gradient (P<0.01, P<0.05 and P<0.01, respectively), and time to reflection was not different between groups. A reversed arterial stiffness gradient is associated with increased reflection site distance and a paradoxical increase in reflected wave amplitude, and augmentation index

    Network capitalism and the role of strategy, contracts and performance expectations for Asia-Pacific innovation partnerships

    Full text link
    © Springer Nature Singapore Pte Ltd. 2018. With the growth of emerging economies in Asia-Pacific over the last three decades collaboration with the aim of innovation between firms within and with partners outside the region have developed substantially. Not always have such partnerships fulfilled their anticipated strategic objectives. The literature suggests that the nature of market arrangements and the role of government within that system play a role, but also innate contracting practices and governance of innovation partnerships are related. Yet, our understanding about the specific relationships between these factors and the emerging partnership innovation culture that facilitates joint business activities in an Asia-Pacific context remains vague. In this conceptual chapter we suggest how characteristics of so called network capitalism in conjunction with the nature of contractual agreements between partners, the alignment of their innovation objectives and the ambiguity inherent in their mutual contributions to the partnership can be interpreted as indicators of joint innovation culture. However, while innovation partnerships generally may result to be bureaucratic, market, clan, or adhocracy, we discuss how in an Asia Pacific context, innovation partnerships are limited by the extent of codification and diffusion of information and the social embeddedness of economic transactions
    corecore