Institute of Fundamental Technological Research

Dynamic cellular systems reprogram gene expression to ensure appropriate cellular fate responses to specific extracellular cues. Here we demonstrate that the dynamics of Nuclear Factor kappa B (NF-κB) signalling and the cell cycle are prioritised differently depending on the timing of an inflammatory signal. Using iterative experimental and computational analyses, we show physical and functional interactions between NF-κB and the E2 Factor 1 (E2F-1) and E2 Factor 4 (E2F-4) cell cycle regulators. These interactions modulate the NF-κB response. In S-phase, the NF-κB response was delayed or repressed, while cell cycle progression was unimpeded. By contrast, activation of NF-κB at the G1/S boundary resulted in a longer cell cycle and more synchronous initial NF-κB responses between cells. These data identify new mechanisms by which the cellular response to stress is differentially controlled at different stages of the cell cycle.

A theoretical and experimental investigation into the higher modal dynamic plastic response of fully clamped beams is reported herein. It is shown that the influence of geometry changes or finite-deflections is important which agrees with previous studies on the dynamic plastic behavior of uniformly loaded beams. It appears that the higher modal response of beams is a more efficient means of absorbing a given magnitude of kinetic energy than a single modal response.