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In this paper, we propose a re-routing strategy for connected and automated vehicles (CAVs), considering coordination and control of all the CAVs in the network. The objective for each CAV is to find the route that minimizes the total travel time of all CAVs. We coordinate CAVs at signal-free intersections to accurately predict the travel time for the routing problem. While it is possible to find a system-optimal solution by comparing all the possible combinations of the routes, this may impose a computational burden. Thus, we instead find a person-by-person optimal solution to reduce computational time while still deriving a better solution than selfish routing. We validate our framework through simulations in a grid network.more » « less
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Wang, Jichuan ; Aldahamsheh, Osama ; Ferrena, Alexander ; Borjihan, Hasibagan ; Singla, Amit ; Yaguare, Simon ; Singh, Swapnil ; Viscarret, Valentina ; Tingling, Janet ; Zi, Xiaolin ; et al ( , Annals of the New York Academy of Sciences)
Abstract Osteosarcoma is a highly aggressive malignancy for which treatment has remained essentially unchanged for years. Our previous studies found that the F‐box protein SKP2 is overexpressed in osteosarcoma, acting as a proto‐oncogene; p27Kip1(p27) is an inhibitor of cyclin‐dependent kinases and a downstream substrate of SKP2‐mediated ubiquitination. Overexpression of SKP2 and underexpression of p27 are common characteristics of cancer cells. The SCFSKP2E3 ligase ubiquitinates Thr187‐phosphorylated p27 for proteasome degradation, which can be abolished by a Thr187Ala knock‐in (p27T187AKI) mutation.
RB1 andTP53 are two major tumor suppressors commonly coinactivated in osteosarcoma. We generated a mouse model with a double knockout (DKO) ofRb1 andTrp53 within cells of the osteoblastic lineage, which developed osteosarcoma with full penetrance. When p27T187AKI mice were crossed on to the DKO background, p27T187Aprotein was found to accumulate in osteosarcoma tumor tissues. Furthermore, p27T187Apromoted apoptosis in DKO tumors, slowed disease progression, and significantly prolonged overall survival. RNA sequencing analysis also linked the SCFSKP2–p27T187Aaxis to potentially reduced cancer stemness. Given thatRB1 andTP53 loss or coinactivation is common in human osteosarcoma, our study suggests that inhibiting the SKP2–p27 axis may represent a desirable therapeutic strategy for this cancer.