This paper reviews studies from the past 30 years that use operations research methods to tackle containership routing and scheduling problems at the strategic, tactical, and operational planning levels. These problems are first classified and summarized, with a focus on model formulations, assumptions, and algorithm design. The paper then gives an overview of studies on containership fleet size and mix, alliance strategy, and network design (at the strategic level); frequency determination, fleet deployment, speed optimization, and schedule design (at the tactical level); and container booking and routing and ship rescheduling (at the operational level). The paper further elaborates on the needs of the liner container shipping industry and notes the gap between existing academic studies and industrial practices. Research on containership routing and scheduling lags behind practice, especially in the face of the fast growth of the container shipping industry and the advancement of operations research and computer technology. The purpose of this paper is to stimulate more practically relevant research in this emerging area.

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Multidrug efflux pumps actively expel a wide range of toxic substrates from the cell and play a major role in intrinsic and acquired drug resistance. In Gram-negative bacteria, these pumps form tripartite assemblies that span the cell envelope. However, the in situ structure and assembly mechanism of multidrug efflux pumps remain unknown. Here we report the in situ structure of the Escherichia coli AcrAB-TolC multidrug efflux pump obtained by electron cryo-tomography and subtomogram averaging. The fully assembled efflux pump is observed in a closed state under conditions of antibiotic challenge and in an open state in the presence of AcrB inhibitor. We also observe intermediate AcrAB complexes without TolC and discover that AcrA contacts the peptidoglycan layer of the periplasm. Our data point to a sequential assembly process in living bacteria, beginning with formation of the AcrAB subcomplex and suggest domains to target with efflux pump inhibitors.

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