Microglial activation plays a pivotal role in the development and progression of neurodegenerative diseases. Thus, anti-inflammatory agents that control microglial activation can serve as potential therapeutic agents for neurodegenerative diseases. Here, we designed and synthesized α-galactosylceramide (α-GalCer) analogs to exert anti-inflammatory effects in activated microglia. We performed biological evaluations of 25 α-GalCer analogs and observed an interesting preliminary structure-activity relationship in their inhibitory influence on NO release and TNF-α production in LPS-stimulated BV2 microglial cells. After identification of 4d and 4e as hit compounds, we further investigated the underlying mechanism of their anti-inflammatory effects using RT-PCR analysis. We confirmed that 4d and 4e regulate the expression of iNOS, COX-2, IL-1β, and IL-6 at the mRNA level and the expression of TNF-α at the post-transcriptional level. In addition, both 4d and 4e inhibited LPS-induced DNA binding activities of NF-κB and AP-1 and phosphorylation of p38 MAPK without affecting other MAP kinases. When we examined the anti-inflammatory effect of a p38 MAPK-specific inhibitor, SB203580, on microglial activation, we observed an identical inhibitory pattern as that of 4d and 4e, not only on NO and TNF-α production but also on the DNA binding activities of NF-κB and AP-1. Taken together, these results suggest that p38 MAPK plays an important role in the anti-inflammatory effects of 4d and 4e via the modulation of NF-κB and AP-1 activities.

A merging section on a freeway is a typical bottleneck where congestion easily occurs due to interference caused by vehicles entering the mainline from the ramp. To achieve higher speeds and/or yield to merging vehicles, drivers on the mainline often change lanes while continuously examining the circumstances ahead that are within their sight. This individual lane‐changing behaviour is somewhat myopic and could cause an imbalance in lane use, resulting in earlier onset of congestion and a more severe capacity drop than with balanced lane use. This study proposes a feedback‐based lane‐changing control strategy that balances lane flow at merge bottlenecks to mitigate capacity drop under a connected vehicle environment. The proposed Proportional‐Integral‐Derivative feedback controller examines the traffic state of the inner lanes and systematically governs the number of lane‐changing vehicles to prevent possible excessive disturbance. The proposed strategy is evaluated using microscopic simulation. For the hypothetical network, the strategy reduces the imbalance in lane flows and improves discharge flow rate as well as travel time. For the real‐world network, the strategy can also effectively relieve congestion in a possible scenario of connected automated vehicle adoption. These results indicate that the proposed strategy can improve flow efficiency for high‐volume traffic.

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