In multiple biological systems, vital intracellular signaling processes occur locally in minute periplasmic subspaces often referred to as signaling microdomains. The number of signaling molecules in these microdomains is small enough to render the notion of continuous concentration changes invalid, such that signaling events are better described using stochastic rather than deterministic methods. Of particular interest is the dyadic cleft in the cardiac myocyte, where short-lived, local increases in intracellular Ca2+ known as Ca2+ sparks regulate excitation-contraction coupling. The geometry of dyadic spaces can alter in disease and development and display significant interspecies variability. We created and studied a 3D Monte Carlo model of the dyadic cleft, specifying the spatial localization of L-type Ca2+ channels and ryanodine receptors. Our analysis revealed how reaction specificity and efficiency are regulated by microdomain geometry as well as the physical separation of signaling molecules into functional complexes. The spark amplitude and rise time were found to be highly dependent on the concentration of activated channels per dyadic cleft and on the intermembrane separation, but not very sensitive to other cleft dimensions. The role of L-type Ca2+ channel and ryanodine receptor phosphorylation was also examined. We anticipate that this modeling approach may be applied to other systems (e.g., neuronal growth cones and chemotactic cells) to create a general description of stochastic events in Ca2+ signaling.

Team production is ubiquitous in the economy, but managing teams effectively remains a challenge for many organizations. This paper studies how familiarity among teammates influences the performance of specialist teams, relative to nonspecialist teams. Applying theories of team production to contexts where team members coordinate interdependent activities extemporaneously, we develop predictions about factors that shift the marginal returns to specialization along two dimensions of familiarity: social familiarity and functional familiarity. We test our hypotheses in the context of Defence of the Ancients 2 (DOTA2), a major e-sports game where, in some formats, players are exogenously assigned to five-person teams. After analyzing nearly 6.5 million matches, we find that specialist teams are relatively more successful when members are more socially and functionally familiar with one another. The results suggest that the plug-and-play perspective on specialist teams is incomplete; rather, specialization and familiarity are complements in dynamic environments where team members coordinate extemporaneously. Funded: Financial support from the UCL School of Management and Worcester Polytechnic Institute is gratefully acknowledged.

No abstract

This paper explores entrepreneurial strategy by analyzing the Internet video industry.

No abstract