User equilibrium traffic network assignment with stochastic travel times and late arrival penalty

The classical Wardrop user equilibrium (UE) assignment model assumes traveller choices are based on fixed, known travel times, yet these times are known to be rather variable between trips, both within and between days; typically, then, only mean travel times are represented. Classical stochastic user equilibrium (SUE) methods allow the mean travel times to be differentially perceived across the population, yet in a conventional application neither the UE or SUE approach recognises the travel times to be inherently variable. That is to say, there is no recognition that drivers risk arriving late at their destinations, and that this risk may vary across different paths of the network and according to the arrival time flexibility of the traveller. Recent work on incorporating risky elements into the choice process is seen either to neglect the link to the arrival constraints of the traveller, or to apply only to restricted problems with parallel alternatives and inflexible travel time distributions. In the paper, an alternative approach is described based on the ‘schedule delay’ paradigm, penalising late arrival under fixed departure times. The approach allows flexible travel time densities, which can be fitted to actual surveillance data, to be incorporated. A generalised formulation of UE is proposed, termed a Late Arrival Penalised UE (LAPUE). Conditions for the existence and uniqueness of LAPUE solutions are considered, as well as methods for their computation. Two specific travel time models are then considered, one based on multivariate Normal arc travel times, and an extended model to represent arc incidents, based on mixture distributions of multivariate Normals. Several illustrative examples are used to examine the sensitivity of LAPUE solutions to various input parameters, and in particular its comparison with UE predictions. Finally, paths for further research are discussed, including the extension of the model to include elements such as distributed arrival time constraints and penalties

Cell fate reprogramming by control of intracellular network dynamics

Identifying control strategies for biological networks is paramount for practical applications that involve reprogramming a cell's fate, such as disease therapeutics and stem cell reprogramming. Here we develop a novel network control framework that integrates the structural and functional information available for intracellular networks to predict control targets. Formulated in a logical dynamic scheme, our approach drives any initial state to the target state with 100% effectiveness and needs to be applied only transiently for the network to reach and stay in the desired state. We illustrate our method's potential to find intervention targets for cancer treatment and cell differentiation by applying it to a leukemia signaling network and to the network controlling the differentiation of helper T cells. We find that the predicted control targets are effective in a broad dynamic framework. Moreover, several of the predicted interventions are supported by experiments.Comment: 61 pages (main text, 15 pages; supporting information, 46 pages) and 12 figures (main text, 6 figures; supporting information, 6 figures). In revie