Pharmacological activation of FOXO3 suppresses triple-negative breast cancer in vitro and in vivo

Triple-negative breast cancer (TNBC) is the most lethal form of breast cancer. Lacking effective therapeutic options hinders treatment of TNBC. Here, we show that bepridil (BPD) and trifluoperazine (TFP), which are FDA-approved drugs for treatment of schizophrenia and angina respectively, inhibit Akt-pS473 phosphorylation and promote FOXO3 nuclear localization and activation in TNBC cells. BPD and TFP inhibit survival and proliferation in TNBC cells and suppress the growth of TNBC tumors, whereas silencing FOXO3 reduces the BPD- and TFP-mediated suppression of survival in TNBC cells. While BPD and TFP decrease the expression of oncogenic c-Myc, KLF5, and dopamine receptor DRD2 in TNBC cells, silencing FOXO3 diminishes BPD- and TFP-mediated repression of the expression of these proteins in TNBC cells. Since c-Myc, KLF5, and DRD2 have been suggested to increase cancer stem cell-like populations in various tumors, reducing these proteins in response to BPD and TFP suggests a novel FOXO3-dependent mechanism underlying BPD- and TFP-induced apoptosis in TNBC cells

Public Transportation Service Evaluations Utilizing Seoul Transportation Card Data

AbstractThis study evaluated transit service performance in Seoul using data collected from the Automatic Fare Collection (AFC) system in Seoul. The distance-based fare system in Seoul allows a maximum of four transfers with no additional charges to encourage transit ridership. In order to analyze the transit transfers, this study developed quantitative indicators for public transportation evaluations differentiated from those of previous studies by the fact that it utilizes data mining techniques which incorporate massive amounts of data (over 10 million transits per day) derived from the smart card system. This study not only carried out an evaluation to improve public transportation quality but provided comparative analysis of the mobility handicapped and an evaluation of public transportation users’ regional equity. This evaluative analysis of Level of Services (LOS) for various items is expected to be adopted for analyzing LOS status and generating improvement priorities and to be utilized as an objective database for public transportation policy decisions

Estimation and uncertainty analysis of impacts of future heat waves on mortality in the Eastern United States

Background: Climate change is anticipated to influence heat-related mortality in the future. However, estimates of excess mortality attributable to future heat waves are subject to large uncertainties and have not been projected under the latest greenhouse gas emission scenarios. Objectives: We estimated future heat wave mortality in the eastern United States (approximately 1,700 counties) under two Representative Concentration Pathways (RCPs) and investigated sources of uncertainty. Methods: Using dynamically downscaled hourly temperature projections for 2057–2059, we projected heat wave days that were defined using four heat wave metrics and estimated the excess mortality attributable to them. We apportioned the sources of uncertainty in excess mortality estimates using a variance-decomposition method. Results: Estimates suggest that excess mortality attributable to heat waves in the eastern United States would result in 200–7,807 deaths/year (mean 2,379 deaths/year) in 2057–2059. Average excess mortality projections under RCP4.5 and RCP8.5 scenarios were 1,403 and 3,556 deaths/year, respectively. Excess mortality would be relatively high in the southern states and eastern coastal areas (excluding Maine). The major sources of uncertainty were the relative risk estimates for mortality on heat wave versus non–heat wave days, the RCP scenarios, and the heat wave definitions. Conclusions: Mortality risks from future heat waves may be an order of magnitude higher than the mortality risks reported in 2002–2004, with thousands of heat wave–related deaths per year in the study area projected under the RCP8.5 scenario. Substantial spatial variability in county-level heat mortality estimates suggests that effective mitigation and adaptation measures should be developed based on spatially resolved data