Emerging technology and management research in the container terminals: Trends and the COVID-19 pandemic impacts.

Despite the significant fluctuations in global trend due to the rising trade friction and the COVID19 pandemic, the container terminals are continuously working in three technology areas including automation, electrification and digitalization. This study reviewed recent technology trends as well as relevant research topics related to the container terminals, and investigated how the trends and topics would facilitate the terminals to achieve their strategic objectives. We also studied the trends in the container terminal industry before and after the pandemic outbreak. Recent progress shows that generally the long-term plans remain unchanged while there are some changes in timeline and priorities. The findings suggest that despite the common interest in long-term plans, gaps are still identified between academia and industry interests. Future directions are discussed for these technology areas, particularly in the context of the post-pandemic world, where the limited resources should be invested to the most urgent areas.

Activation of the GLP-1 receptor by a non-peptidic agonist.

Class B G-protein-coupled receptors are major targets for the treatment of chronic diseases, including diabetes and obesity1. Structures of active receptors reveal peptide agonists engage deep within the receptor core, leading to an outward movement of extracellular loop 3 and the tops of transmembrane helices 6 and 7, an inward movement of transmembrane helix 1, reorganization of extracellular loop 2 and outward movement of the intracellular side of transmembrane helix 6, resulting in G-protein interaction and activation2-6. Here we solved the structure of a non-peptide agonist, TT-OAD2, bound to the glucagon-like peptide-1 (GLP-1) receptor. Our structure identified an unpredicted non-peptide agonist-binding pocket in which reorganization of extracellular loop 3 and transmembrane helices 6 and 7 manifests independently of direct ligand interaction within the deep transmembrane domain pocket. TT-OAD2 exhibits biased agonism, and kinetics of G-protein activation and signalling that are distinct from peptide agonists. Within the structure, TT-OAD2 protrudes beyond the receptor core to interact with the lipid or detergent, providing an explanation for the distinct activation kinetics that may contribute to the clinical efficacy of this compound series. This work alters our understanding of the events that drive the activation of class B receptors.

Modelling the impact of liner shipping network perturbations on container cargo routing: Southeast Asia to Europe application.

Understanding how container routing stands to be impacted by different scenarios of liner shipping network perturbations such as natural disasters or new major infrastructure developments is of key importance for decision-making in the liner shipping industry. The variety of actors and processes within modern supply chains and the complexity of their relationships have previously led to the development of simulation-based models, whose application has been largely compromised by their dependency on extensive and often confidential sets of data. This study proposes the application of optimisation techniques less dependent on complex data sets in order to develop a quantitative framework to assess the impacts of disruptive events on liner shipping networks. We provide a categorization of liner network perturbations, differentiating between systemic and external and formulate a container assignment model that minimises routing costs extending previous implementations to allow feasible solutions when routing capacity is reduced below transport demand. We develop a base case network for the Southeast Asia to Europe liner shipping trade and review of accidents related to port disruptions for two scenarios of seismic and political conflict hazards. Numerical results identify alternative routing paths and costs in the aftermath of port disruptions scenarios and suggest higher vulnerability of intra-regional connectivity.

Network science approach to modelling the topology and robustness of supply chain networks: a review and perspective.

Due to the increasingly complex and interconnected nature of global supply chain networks (SCNs), a recent strand of research has applied network science methods to model SCN growth and subsequently analyse various topological features, such as robustness. This paper provides: (1) a comprehensive review of the methodologies adopted in literature for modelling the topology and robustness of SCNs; (2) a summary of topological features of the real world SCNs, as reported in various data driven studies; and (3) a discussion on the limitations of existing network growth models to realistically represent the observed topological characteristics of SCNs. Finally, a novel perspective is proposed to mimic the SCN topologies reported in empirical studies, through fitness based generative network models.

Development of a high-throughput assay for aldosterone synthase inhibitors using high-performance liquid chromatography-tandem mass spectrometry.

Aldosterone plays a key role in the pathogenesis of hypertension, congestive heart failure, and chronic kidney disease. Aldosterone biosynthesis involves three membrane-bound enzymes: aldosterone synthase, adrenodoxin, and adrenodoxin reductase. Here, we report the development of a mass spectrometry-based high-throughput whole cell-based assay for aldosterone synthesis. A human adrenal carcinoma cell line (H295R) overexpressing human aldosterone synthase cDNA was established. The production of aldosterone in these cells was initiated with the addition of 11-deoxycorticosterone, the immediate substrate of aldosterone synthase. An automatic liquid handler was used to gently distribute cells uniformly to well plates. The adaption of a second automated liquid handling system to extract aldosterone from the cell culture medium into organic solvent enabled the development of 96- and 384-well plate formats for this cellular assay. A high-performance liquid chromatography-tandem mass spectrometry method was established for the detection of aldosterone. Production of aldosterone was linear with time and saturable with increasing substrate concentration. The assay was highly reproducible with an overall average Z' value=0.49. This high-throughput assay would enable high-throughput screening for inhibitors of aldosterone biosynthesis.

GluK1 antagonists from 6-(carboxy)phenyl decahydroisoquinoline derivatives. SAR and evaluation of a prodrug strategy for oral efficacy in pain models.

The synthesis and structure-activity relationship of decahydroisoquinoline derivatives with various benzoic acid substitutions as GluK1 antagonists are described. Potent and selective antagonists were selected for a tailored prodrug approach in order to facilitate the evaluation of the new compounds in pain models after oral administration. Several diester prodrugs allowed for acceptable amino acid exposure and moderate efficacy in vivo.

GluK1 antagonists from 6-(tetrazolyl)phenyl decahydroisoquinoline derivatives: in vitro profile and in vivo analgesic efficacy.

We have explored the decahydroisoquinoline scaffold, bearing a phenyl tetrazole, as GluK1 antagonists with potential as oral analgesics. We have established the optimal linker atom between decahydroisoquinoline and phenyl rings and demonstrated an improvement of both the affinity for the GluK1 receptor and the selectivity against the related GluA2 receptor with proper phenyl substitution. In this Letter, we also disclose in vivo data that led to the discovery of LY545694·HCl, a compound with oral efficacy in two persistent pain models.

The kinematic features of motorcycles in congested urban networks.

The aim of this paper is to compare the kinematic features of motorcycles with those of passenger cars in urban traffic. The hypothesis that motorcycles' capability to swerve in urban traffic contributes to their seemingly assertive behaviour is examined. Data for this study were collected in afternoon peak hours at Central London using video recorders. Detailed information on the trajectories of 2109 vehicles (including 477 motorcycles and 1293 passenger cars) was extracted from the video images and the observable kinematic features were analysed. In addition, a model describing the longitudinal following behaviour of motorcycles was employed to analyse the impacts of motorcycles' swerving behaviour. The model was calibrated using Markov Chain Monte Carlo (MCMC) numerical methods. The observable kinematic features show that in comparison to passenger cars, motorcycles have shorter safety gaps, higher speeds and severer acceleration and deceleration rates reflecting their generally much higher power to weight ratios and usage of available braking power. However, the data also support the hypothesis that motorcyclists maintain a considerable safety margin as they have the ability to avoid a collision by swerving away.

(S)-N-{3-[1-cyclopropyl-1-(2,4-difluoro-phenyl)-ethyl]-1H-indol-7-yl}-methanesulfonamide: a potent, nonsteroidal, functional antagonist of the mineralocorticoid receptor.

A novel, potent series of indole analogs were recently developed as MR antagonists, culminating in 14. This compound represents the first MR antagonist in this class of molecules, exhibiting picomolar binding affinity and in vivo blood pressure lowering at pharmaceutically relevant doses.

Potent benzimidazolone based human beta(3)-adrenergic receptor agonists.

The synthesis and biological evaluation of a series of benzimidazolone beta(3) adrenergic receptor agonists are described. A trend toward the reduction of rat atrial tachycardia upon increasing steric bulk at the 3-position of the benzimidazolone moiety was observed.

Two prodrugs of potent and selective GluR5 kainate receptor antagonists actives in three animal models of pain.

Amino acids 5 and 7, two potent and selective competitive GluR5 KA receptor antagonists, exhibited high GluR5 receptor affinity over other glutamate receptors. Their ester prodrugs 6 and 8 were orally active in three models of pain: reversal of formalin-induced paw licking, carrageenan-induced thermal hyperalgesia, and capsaicin-induced mechanical hyperalgesia.

Ethyl (3S,4aR,6S,8aR)-6-(4-ethoxycar- bonylimidazol-1-ylmethyl)decahydroiso-quinoline-3-carboxylic ester: a prodrug of a GluR5 kainate receptor antagonist active in two animal models of acute migraine.

Amino diacid 3, a highly selective competitive GluR5 kainate receptor antagonist, exhibited high GluR5 receptor affinity and selectivity over other glutamate receptors. Its diethyl ester prodrug 4 was orally active in two models of migraine: the neurogenic dural plasma protein extravasation model and the nucleus caudalis c-fos expression model. These data suggest that a GluR5 kainate receptor antagonist might be an efficacious antimigraine therapy with a novel mechanism of action.