It is increasingly recognized that social interaction and collaboration rely on the participants' abilities to access and use a range of resources including objects and artifacts from within the immediate environment. In recent years, system support for remote collaboration has begun to address this issue, and we have witnessed the emergence of a number of technologies designed to provide remote participants with access to (features of) each others' environment. In this article we examine the use of one such system, an innovative mixed media environment designed to enable participants to refer to and point at objects and artifacts within each other's remote environment. The article addresses the ways in which participants use the system to undertake various collaborative activities and discusses the problems and issues that emerge, for the participants' themselves, in coordinating action with and through objects. We then consider these issues with regard to interaction and collaboration in more conventional environments such as work settings, and we discuss the ways in which the interpretation and production of action are inextricably embedded within the immediate environment, an environment of action that is inadvertently fractured in even this more sophisticated media space.
Previous high throughput screening studies led to the discovery of two novel, nonlipid-like chemotypes as Toll-like receptor 4 (TLR4) agonists. One of these chemotypes, the pyrimido[5,4-b]indoles, was explored for structure–activity relationship trends relative to production of TLR4 dependent cytokines/chemokines, resulting in a semioptimized lead (compound 1) that provided a starting point for further optimization studies. In this report, compounds belonging to three areas of structural modification were evaluated for biological activity using murine and human TLR4 reporter cells, primary murine bone marrow derived dendritic cells, and human peripheral blood mononuclear cells. The compounds bearing certain aryl groups at the C8 position, such as phenyl (36) and β-naphthyl (39), had potencies significantly greater than compound 1. Compound 36 displayed human TLR4 agonist activity at submicromolar concentrations. The computational analysis suggests that the improved potency of these C8-aryl derivatives may be the result of additional binding interactions at the interface of the TLR4/myeloid differentiation protein-2 (MD-2) complex.
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