Generalized binomial Tau-leap method for biochemical kinetics incorporating both delay and intrinsic noise

The delay stochastic simulation algorithm (DSSA) by Barrio et al. [Plos Comput. Biol.2, 117–E (2006)] was developed to simulate delayed processes in cell biology in the presence of intrinsic noise, that is, when there are small-to-moderate numbers of certain key molecules present in a chemical reaction system. These delayed processes can faithfully represent complex interactions and mechanisms that imply a number of spatiotemporal processes often not explicitly modeled such as transcription and translation, basic in the modeling of cell signaling pathways. However, for systems with widely varying reaction rate constants or large numbers of molecules, the simulation time steps of both the stochastic simulation algorithm (SSA) and the DSSA can become very small causing considerable computational overheads. In order to overcome the limit of small step sizes, various τ-leap strategies have been suggested for improving computational performance of the SSA. In this paper, we present a binomial τ- DSSA method that extends the τ-leap idea to the delay setting and avoids drawing insufficient numbers of reactions, a common shortcoming of existing binomial τ-leap methods that becomes evident when dealing with complex chemical interactions. The resulting inaccuracies are most evident in the delayed case, even when considering reaction products as potential reactants within the same time step in which they are produced. Moreover, we extend the framework to account for multicellular systems with different degrees of intercellular communication. We apply these ideas to two important genetic regulatory models, namely, the hes1 gene, implicated as a molecular clock, and a Her1/Her 7 model for coupled oscillating cells.

The measurement of information system use: preliminary considerations

The concept of system use has suffered from a "too simplistic definition" (DeLone and McLean [9], p. 16). This paper reviews various attempts at conceptualization and measurement of system use and then proposes a re-conceptualization of it as "the level of incorporation of an information system within a user's processes." We then go on to develop the concept of a Functional Interface Point and four dimensions of system usage: automation level, the proportion of the business process encoded by the information system; extent, the proportion of the FIPs used by the business process; frequency, the rate at which FIPs are used by the participants in the process; and thoroughness, the level of use of information/functionality provided by the system at an FIP. The article concludes with a discussion of some implications of this re-conceptualization and areas for follow on research.