Multi-Scale Modeling of HIV Infection in vitro and APOBEC3G-Based Anti-Retroviral Therapy

The human APOBEC3G is an innate restriction factor that, in the absence of Vif, restricts HIV-1 replication by inducing excessive deamination of cytidine residues in nascent reverse transcripts and inhibiting reverse transcription and integration. To shed light on impact of A3G-Vif interactions on HIV replication, we developed a multi-scale computational system consisting of intracellular (single-cell), cellular and extracellular (multicellular) events by using ordinary differential equations. The single-cell model describes molecular-level events within individual cells (such as production and degradation of host and viral proteins, and assembly and release of new virions), whereas the multicellular model describes the viral dynamics and multiple cycles of infection within a population of cells. We estimated the model parameters either directly from previously published experimental data or by running simulations to find the optimum values. We validated our integrated model by reproducing the results of in vitro T cell culture experiments. Crucially, both downstream effects of A3G (hypermutation and reduction of viral burst size) were necessary to replicate the experimental results in silico. We also used the model to study anti-HIV capability of several possible therapeutic strategies including: an antibody to Vif; upregulation of A3G; and mutated forms of A3G. According to our simulations, A3G with a mutated Vif binding site is predicted to be significantly more effective than other molecules at the same dose. Ultimately, we performed sensitivity analysis to identify important model parameters. The results showed that the timing of particle formation and virus release had the highest impacts on HIV replication. The model also predicted that the degradation of A3G by Vif is not a crucial step in HIV pathogenesis

The case for adaptive theory for investigation meaning in the workplace

Most qualitative research studies in business utilise case studies, which on their own can fail to integrate wider, structural factors which may have shaped the observed events at the local level. This paper outlines the use of adaptive theory (Layder 1997, 1998) as a means of combining agency research (case studies of individual experiences and phenomological research) with structural research (broader theories, surveys of societal issues). The paper focuses on the application of adaptive theory on a study of workplace conflict resolution. The findings indicate that adaptive theory would be most suitable for studies dealing with corruption, HR processes (training, performance development, organisational change) and other areas in which an individual’s perception is required relating to workplace practices

The engagement of academics at work : a research strategy

Employee engagement stems from a body of research focusing upon the ‘human’ aspect of production. Research has provided clear links between organisational investment in human capital and greater productivity. The term ‘engagement’ stems from the work of Kahn (1990) who distinguished between being engaged and disengaged at work. Since Kahn’s study, a number of other factors have been linked to engagement leading to an overlap and confusion of the definition. The aim of this paper is provide a research strategy to investigate the interrelated factors of employee engagement and the extent to which they contribute to engagement. From this, a more inclusive definition and theory of employee engagement may be developed using the Higher Education Sector as the testing ground

Reshaping the role of the tribunal as third party in Australian workplace conflict resolution

In common with courts and tribunals in other developed countries, Australia has experienced the rise of the self-represented litigant. This chapter examines innovations in the approaches taken by the Australian Fair Work Commission (FWC), the national employment relations tribunal, in responding to the growing number of self-represented employers and employees appearing before it or seeking redress. In particular, the chapter explores and discusses the shift towards alternative dispute resolution (ADR) and an increasing number of self-help initiatives in the context of the growing individualization of the Australian labour market and the consequent rise of self-represented litigants before the tribunal. These changes are reshaping the role of the tribunal as a third party in Australian workplace conflict resolution. © The Editor(s) (if applicable) and The Author(s) 2016