Translation initiation is the rate-limiting step of protein synthesis that is downregulated during the Integrated Stress Response (ISR). Previously, we demonstrated that most human mRNAs that are resistant to this inhibition possess translated upstream open reading frames (uORFs), and that in some cases a single uORF is sufficient for the resistance. Here we developed a computational model of Initiation Complexes Interference with Elongating Ribosomes (ICIER) to gain insight into the mechanism. We explored the relationship between the flux of scanning ribosomes upstream and downstream of a single uORF depending on uORF features. Paradoxically, our analysis predicts that reducing ribosome flux upstream of certain uORFs increases initiation downstream. The model supports the derepression of downstream translation as a general mechanism of uORF-mediated stress resistance. It predicts that stress resistance can be achieved with long slowly decoded uORFs that do not favor translation reinitiation and that start with initiators of low leakiness.
Operation regimes of a two section monolithic quantum dot (QD) mode-locked laser are studied experimentally with InGaAs lasers and theoretically, using a model that takes into account carrier exchange between QD ground state and two-dimensional reservoir of a QD-in-a-well structure. It is shown analytically and numerically that, when the absorber section is long enough, the laser exhibits bistability between laser off state and different mode-locking regimes. The Q-switching instability leading to slow modulation of the mode-locked pulse peak intensity is completely eliminated in this case. When, on the contrary, the absorber length is rather short, in addition to usual Q-switched mode-locking, pure Q-switching regimes are predicted theoretically and observed experimentally.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.