1000 resultados para Sulfuryl transfer


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Human SULT1A1 is primarily responsible for sulfonation of xenobiotics, including the activation of promutagens, and it has been implicated in several forms of cancer. Human SULT1A3 has been shown to be the major sulfotransferase that sulfonates dopamine. These two enzymes shares 93% amino acid sequence identity and have distinct but overlapping substrate preferences. The resolution of the crystal structures of these two enzymes has enabled us to elucidate the mechanisms controlling their substrate preferences and inhibition. The presence of two p-nitrophenol (pNP) molecules in the crystal structure of SULT1A1 was postulated to explain cooperativity at low and inhibition at high substrate concentrations, respectively. In SULT1A1, substrate inhibition occurs with pNP as the substrate but not with dopamine. For SULT1A3, substrate inhibition is found for dopamine but not with pNP. We investigated how substrate inhibition occurs in these two enzymes using molecular modeling, site-directed mutagenesis, and kinetic analysis. The results show that residue Phe-247 of SULT1A1, which interacts with both p-nitrophenol molecules in the active site, is important for substrate inhibition. Mutation of phenylalanine to leucine at this position in SULT1A1 results in substrate inhibition by dopamine. We also propose, based on modeling and kinetic studies, that substrate inhibition by dopamine in SULT1A3 is caused by binding of two dopamine molecules in the active site. © 2004 by The American Society for Biochemistry and Molecular Biology, Inc.

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Two dimensional flow of a micropolar fluid in a porous channel is investigated. The flow is driven by suction or injection at the channel walls, and the micropolar model due to Eringen is used to describe the working fluid. An extension of Berman's similarity transform is used to reduce the governing equations to a set of non-linear coupled ordinary differential equations. The latter are solved for large mass transfer via a perturbation analysis where the inverse of the cross-flow Reynolds number is used as the perturbing parameter. Complementary numerical solutions for strong injection are also obtained using a quasilinearisation scheme, and good agreement is observed between the solutions obtained from the perturbation analysis and the computations.

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Knowledge has been recognised as an important organisational asset that increases in value when shared; the opposite to other organisational assets which decrease in value during their exploitation. Effective knowledge transfer in organisations helps to achieve and maintain competitive advantage and ultimately organisational success. So far, the research on knowledge transfer has focused on traditional (functional) organisations. Only recently has attention been directed towards knowledge transfer in projects. Existing research on project learning has recognised the need for knowledge transfer within and across projects in project-based organisations (PBOs). Most projects can provide valuable new knowledge from unexpected actions, approaches or problems experienced during the project phases. The aim of this paper is to demonstrate the impact of unique projects characteristics on knowledge transfer in PBO. This is accomplished through review of the literature and a series of interviews with senior project practitioners. The interviews complement the findings from the literature. Knowledge transfer in projects occurs by social communication and transfer of lessons learned where project management offices (PMOs) and project managers play significant roles in enhancing knowledge transfer and communication within the PBO and across projects. They act as connectors between projects and the PBO ‘hub’. Moreover, some project management processes naturally facilitate knowledge transfer across projects. On the other hand, PBOs face communication challenges due to unique and temporary characteristics of projects. The distance between projects and the lack or weakness of formal links across projects, create communication problems that impede knowledge transfer across projects. The main contribution of this paper is to demonstrate that both social communication and explicit informational channels play important role in inter-project knowledge transfer. Interviews also revealed the important role organisational culture play in knowledge transfer in PBOs.

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This paper uses the case study of a hybrid public-private strategic alliance as data to complement and contrast with the traditional views on knowledge transfer and learning between alliance partners. In particular, the paper explores whether the concept of competitive collaboration conceptualized by Hamel (1991) in his seminal work holds true for all forms of strategic alliances. Conceptualizing the knowledge boundaries of organisations in alliances as a ‘collaborative membrane’, we focus attention on the permeability of these boundaries rather than the actual location of the boundaries. In this vein, we present a case study of a major public sector organization that illustrates how these principles have allowed it to start rebuilding its internal capabilities adopting a more collaborative stance and ensuring their knowledge boundaries are highly porous as they move more major projects into hybrid public private alliance contracts.