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This paper presents a data-driven approach to estimate incident-induced delays (IIDs) using probe vehicle data while accounting for missing data. The proposed approach is applied to evaluate the effectiveness of a safety service patrol (SSP) program. Existing data-driven methods for IID estimation usually rely on complete data sets. The proposed approach employs a random forest-based classification model and an interpolation method to estimate IIDs when real-time data are completely or partially missing during the incident-impacted time period. It also identifies reference profiles from the closest spatial-temporal road segments to improve data availability. The case study shows that the SSP program in the Quad Cities area of Iowa reduces IIDs associated with various incidents by 15%-91%. This data-driven evaluation framework can be applied to other traffic incident management programs, allowing more accurate and objective evaluations of their effectiveness., Author(s): Minsoo Oh [1]; Jing Dong-O'Brien (corresponding author) [1] 1. Introduction Incidents, such as collisions and stalled vehicles, can significantly affect the traffic flow, causing significant travel delays, especially during [...]

Abstract: Accumulated evidence suggests that aberrant regulation of δ-catenin leads to pathological consequences such as mental retardation and cognitive dysfunction. This study revealed that 14-3-3ɛ/ζ stabilizes δ-catenin, with different binding regions involved in the interaction. Furthermore, the specific inhibition of the interaction of 14-3-3 with δ-catenin reduced levels of δ-catenin and significantly impaired the capacity of δ-catenin to induce dendritic branching in both NIH3T3 fibroblasts and primary hippocampal neurons. However, the S1094A δ-catenin mutant, which cannot interact with 14-3-3ζ, still retained the capability of inducing dendrogenesis. Taken together, these results elucidate the underlying events that regulate the stability of δ-catenin and δ-catenin-induced dendrogenesis. [Copyright &y& Elsevier]

Delta-catenin was first identified because of its interaction with presenilin-1, and its aberrant expression has been reported in various human tumors and in patients with Cri-du-Chat syndrome, a form of mental retardation. However, the mechanism whereby delta-catenin is regulated in cells has not been fully elucidated. We investigated the possibility that glycogen-synthase kinase-3 (GSK-3) phosphorylates delta-catenin and thus affects its stability. Initially, we found that the level of delta-catenin was greater and the half-life of delta-catenin was longer in GSK-3beta(-/-) fibroblasts than those in GSK-3beta(+/+) fibroblasts. Furthermore, four different approaches designed to specifically inhibit GSK-3 activity, i.e. GSK-3-specific chemical inhibitors, Wnt-3a conditioned media, small interfering RNAs, and GSK-3alpha and -3beta kinase dead constructs, consistently showed that the levels of endogenous delta-catenin in CWR22Rv-1 prostate carcinoma cells and primary cortical neurons were increased by inhibiting GSK-3 activity. In addition, it was found that both GSK-3alpha and -3beta interact with and phosphorylate delta-catenin. The phosphorylation of DeltaC207-delta-catenin (lacking 207 C-terminal residues) and T1078A delta-catenin by GSK-3 was noticeably reduced compared with that of wild type delta-catenin, and the data from liquid chromatography-tandem mass spectrometry analyses suggest that the Thr(1078) residue of delta-catenin is one of the GSK-3 phosphorylation sites. Treatment with MG132 or ALLN, specific inhibitors of proteosome-dependent proteolysis, increased delta-catenin levels and caused an accumulation of ubiquitinated delta-catenin. It was also found that GSK-3 triggers the ubiquitination of delta-catenin. These results suggest that GSK-3 interacts with and phosphorylates delta-catenin and thereby negatively affects its stability by enabling its ubiquitination/proteosome-mediated proteolysis.

delta-Catenin is a member of the p120-catenin subfamily of armadillo proteins. Here, we describe distinctive features of delta-catenin localization and its association with E-cadherin in HEK293 epithelial cells. In HEK293 cells maintained in low cell densities, approximately 15% of cells overexpressing delta-catenin showed dendrite-like process formation, but there was no detectable change in RhoA activity. In addition, delta-catenin was localized mainly in the cytoplasm and was associated with p190RhoGEF. However, at high cell densities, delta-catenin localization was shifted to the plasma membrane. The association of delta-catenin with E-cadherin was strengthened, whereas its interaction with p190RhoGEF was weakened. In mouse embryonic fibroblast cell, ectopic expression of E-cadherin decreased the effect of delta-catenin on the reduction of RhoA activity as well as on dendrite-like process formation. These results suggest that delta-catenin is more dominantly bound to E-cadherin than to p190RhoGEF, and that delta-catenin's function is dependent on its cellular binding partner.

delta-Catenin is upregulated in human carcinomas. However, little is known about the potential transcriptional factors that regulate delta-catenin expression in cancer. Using a human delta-catenin reporter system, we have screened several nuclear signaling modulators to test whether they can affect delta-catenin transcription. Among beta-catenin/LEF-1, Notch1, and E2F1, E2F1 dramatically increased delta-catenin-luciferase activities while beta-catenin/LEF-1 induced only a marginal increase. Rb suppressed the upregulation of delta-catenin-luciferase activities induced by E2F1 but did not interact with delta-catenin. RT-PCR and Western blot analyses in 4 different prostate cancer cell lines revealed that regulation of delta-catenin expression is controlled mainly at the transcriptional level. Interestingly, the effects of E2F1 on delta-catenin expression were observed only in human cancer cells expressing abundant endogenous delta-catenin. These studies identify E2F1 as a positive transcriptional regulator for delta-catenin, but further suggest the presence of strong negative regulator(s) for delta-catenin in prostate cancer cells with minimal endogenous delta-catenin expression.

Nuclear beta-catenin affects the developmental process and progression of tumors. However, the precise mechanism for the nuclear export of beta-catenin is not completely understood. We found that beta-catenin can bind directly to CRM1 through its central armadillo (ARM) repeats region, independently of the adenomatous polyposis coli (APC) protein. CRM1 overexpression transports nuclear beta-catenin into the cytoplasm and decreases LEF-1/beta-catenin-dependent transcriptional activity, which is also affected by the co-overexpression of E-cadherin. CRM1 competed with E-cadherin and LEF-1 for binding to beta-catenin. beta-catenin could interact directly with APC through its essential sequences between amino acids 342 and 350. The site-directed beta-catenin mutant (NES2(-)), which could interact with CRM1, but not with APC, still retained its ability to export from the nucleus and its transactivational activity. This suggests that CRM1 can function as an efficient nuclear exporter for beta-catenin independently of APC. These results strongly suggest that the CRM1-mediated pathway is involved in the efficient transport of nuclear beta-catenin in the nucleus of cells.

Delta-catenin was first identified through its interaction with Presenilin-1 and has been implicated in the regulation of dendrogenesis and cognitive function. However, the molecular mechanisms by which delta-catenin promotes dendritic morphogenesis were unclear. In this study, we demonstrated delta-catenin interaction with p190RhoGEF, and the importance of Akt1-mediated phosphorylation at Thr-454 residue of delta-catenin in this interaction. We have also found that delta-catenin overexpression decreased the binding between p190RhoGEF and RhoA, and significantly lowered the levels of GTP-RhoA but not those of GTP-Rac1 and -Cdc42. Delta-catenin T454A, a defective form in p190RhoGEF binding, did not decrease the binding between p190RhoGEF and RhoA. Delta-catenin T454A also did not lower GTP-RhoA levels and failed to induce dendrite-like process formation in NIH 3T3 fibroblasts. Furthermore, delta-catenin T454A significantly reduced the length and number of mature mushroom shaped spines in primary hippocampal neurons. These results highlight signaling events in the regulation of delta-catenin-induced dendrogenesis and spine morphogenesis.