Stochastic analysis of the VEGF receptor response curve

Recently, an analysis of the response curve of the vascular endothelial growth factor (VEGF) receptor and its application to cancer therapy was described in [T. Alarcón, and K. Page, J. R. Soc. Lond. Interface 4, 283–304 (2007)]. The analysis is significantly extended here by demonstrating that an alternative computational strategy, namely the Krylov FSP algorithm for the direct solution of the chemical master equation, is feasible for the study of the receptor model. The new method allows us to further investigate the hypothesis of symmetry in the stochastic fluctuations of the response. Also, by augmenting the original model with a single reversible reaction we formulate a plausible mechanism capable of realizing a bimodal response, which is reported experimentally but which is not exhibited by the original model. The significance of these findings for mechanisms of tumour resistance to antiangiogenic therapy is discussed.

Pharmacological consequence of the A118G μ opioid receptor polymorphism on morphine-and fentanyl-mediated modulation of Ca2+ channels in humanized mouse sensory neurons

Background: The most common functional single nucleotide polymorphism of the human OPRM1 gene, A118G, has been shown to be associated with interindividual differences in opioid analgesic requirements, particularly with morphine, in patients with acute postoperative pain. The purpose of this study was to examine whether this polymorphism would modulate the morphine and fentanyl pharmacological profile of sensory neurons isolated from a humanized mouse model homozygous for either the 118A or 118G allele. Methods: The coupling of wild-type and mutant μ opioid receptors to voltage-gated Ca channels after exposure to either ligand was examined by employing the whole cell variant of the patch-clamp technique in acutely dissociated trigeminal ganglion neurons. Morphine-mediated antinociception was measured in mice carrying either the 118AA or 118GG allele. RESULTS:: The biophysical parameters (cell size, current density, and peak current amplitude potential) measured from both groups of sensory neurons were not significantly different. In 118GG neurons, morphine was approximately fivefold less potent and 26% less efficacious than that observed in 118AA neurons. On the other hand, the potency and efficacy of fentanyl were similar for both groups of neurons. Morphine-mediated analgesia in 118GG mice was significantly reduced compared with the 118AA mice. Conclusions: This study provides evidence to suggest that the diminished clinical effect observed with morphine in 118G carriers results from an alteration of the receptor's pharmacology in sensory neurons. In addition, the impaired analgesic response with morphine may explain why carriers of this receptor variant have an increased susceptibility to become addicted to opioids. © 2011 the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins. Anesthesiology.

Project management deployment : the role of cultural factors

This paper investigates the role of cultural factors as possible partial explanation of the disparity in terms of project management deployment observed between various studied countries. The topic of culture has received increasing attention in the management literature in general during the last decades and in the project management literature in particular during the last few years. The globalization of businesses and worldwide Governmental/International organizations collaborations drives this interest in the national culture to increase more and more. Based on Hofstede national culture framework, the study hypothesizes and tests the impact of the culture and development of the country on the PM deployment. Seventy-four countries are selected to conduct a correlation and regression analysis between Hofstede’s national culture dimensions and the used PM deployment indicator. The results show the relations between various national culture dimensions and development indicator (GDP/Capita) on the project management deployment levels of the considered countries.

The two dimensions of virtual and collocated project teams or what project team members WANT and GET : an empirical study

The current paper compares and investigates the discrepancies in motivational drives of project team members with respect to their project environment in collocated and distributed (virtual) project teams. The set of factors, which in this context are called ‘Sense of Ownership’, is used as a scale to measure these discrepancies using one tailed t tests. These factors are abstracted from theories of motivation, team performance, and team effectiveness and are related to ‘Nature of Work’, ‘Rewards’, and ‘Communication’. It has been observed that ‘virtual ness’ does not seem to impact the motivational drives of the project team members or the way the project environments provide or support those motivational drives in collocated and distributed projects. At a more specific level in terms of the motivational drives of the project team (‘WANT’) and the ability of the project environment to provide or support those factors (‘GET’), in collocated project teams, significant discrepancies were observed with respect to financial and non financial rewards, learning opportunities, nature of work and project specific communication, while in distributed teams, significant discrepancies with respect to project centric communication, followed by financial rewards and nature of work. Further, distributed project environments seem to better support the team member motivation than collocated project environments. The study concludes that both the collocated and distributed project environments may not be adequately supporting the motivational drives of its project team members, which may be frustrating to them. However, members working in virtual team environments may be less frustrated than their collocated counterparts as virtual project environments are better aligned with the motivational drives of their team members vis-à-vis the collocated project environments.

The two dimensions of virtual and collocated project teams or what project team members WANT and GET : empirical evidence

The current paper compares and investigates the discrepancies in motivational drives of project team members with respect to their project environment in collocated and distributed (virtual) project teams. The set of factors, which in this context are called ‘Sense of Ownership’, is used as a scale to measure these discrepancies using one tailed t tests. These factors are abstracted from theories of motivation, team performance, and team effectiveness and are related to ‘Nature of Work’, ‘Rewards’, and ‘Communication’. It has been observed that ‘virtualness’ does not seem to impact the motivational drives of the project team members or the way the project environments provide or support those motivational drives in collocated and distributed projects. At a more specific level in terms of the motivational drives of the project team (‘WANT’) and the ability of the project environment to provide or support those factors (‘GET’), in collocated project teams, significant discrepancies were observed with respect to financial and non financial rewards, learning opportunities, nature of work and project specific communication, while in distributed teams, significant discrepancies with respect to project centric communication, followed by financial rewards and nature of work. Further, distributed project environments seem to better support the team member motivation than collocated project environments. The study concludes that both the collocated and distributed project environments may not be adequately supporting the motivational drives of its project team members, which may be frustrating to them. However, members working in virtual team environments may be less frustrated than their collocated counterparts as virtual project environments are better aligned with the motivational drives of their team members vis-à-vis the collocated project environments.

Internal and external motivation factors in virtual and collocated project environments : a principal component investigation

In this study, we explore motivation in collocated and virtual project teams. The literature on motivation in a project set.,ting reveals that motivation is closely linked to team performance. Based on this literature, we propose a set., of variables related to the three dimensions of ‘Nature of work’, ‘Rewards’, and ‘Communication’. Thirteen original variables in a sample size of 66 collocated and 66 virtual respondents are investigated using one tail t test and principal component analysis. We find that there are minimal differences between the two groups with respect to the above mentioned three dimensions. (p= .06; t=1.71). Further, a principal component analysis of the combined sample of collocated and virtual project environments reveals two factors- ‘Internal Motivating Factor’ related to work and work environment, and ‘External Motivating Factor’ related to the financial and non-financial rewards that explain 59.8% of the variance and comprehensively characterize motivation in collocated and virtual project environments. A ‘sense check’ of our interpretation of the results shows conformity with the theory and existing practice of project organization

Profiling work motivation of project workers

The purpose of this study is to understand the constructs of work motivation in project—based organizations. We first juxtapose work motivation in traditional and project—based organizations to put forward an operational definition of work motivation for our study. We then present the research methodology where we profile work motivation as perceived by project workers using principal component analysis. We obtain a five factor structure of work motivation. Finally, we discuss these results by putting them within the project management perspective and suggest managerial implications.

Project management deployment : the role of cultural factors

This paper investigates the role of cultural factors as possible partial explanation of the disparity in terms of Project Management Deployment observed between various studied countries. The topic of culture has received increasing attention in the management literature in general during the last decades and in the Project Management literature in particular during the last few years. The globalization of businesses and worldwide Governmental / International organizations collaborations drives this interest in the national culture to increase more and more. Based on Hofstede national culture framework, the study hypothesizes and tests the impact of the culture and development of the country on the PM Deployment. 74 countries are selected to conduct a correlation and regression analysis between Hofstede’s national culture dimensions and the used PM Deployment indicator. The results show the relations between various national culture dimensions and development indicator (GDP/Capita) on the Project Management Deployment levels of the considered countries.