Study of the Aerosol Indirect Effect by Large-Eddy Simulation of Marine Stratocumulus

A total of 98 three-dimensional large-eddy simulations (LESs) of marine stratocumulus clouds covering both nighttime and daytime conditions were performed to explore the response of cloud optical depth (τ) to various aerosol number concentrations (Na = 50–2500 cm−3) and the covarying meteorological conditions (large-scale divergence rate and SST). The idealized First International Satellite Cloud Climatology Project (ISCCP) Regional Experiment (FIRE) and the Atlantic Stratocumulus Transition Experiment (ASTEX) Lagrangian 1 sounding profiles were used to represent the lightly and heavily drizzling cases, respectively. The first and second aerosol indirect effects are identified. Through statistical analysis, τ is found be to both positively correlated with Na and cloud liquid water path (LWP) with a higher correlation associated with LWP, which is predominantly regulated by large-scale subsidence and SST. Clouds with high LWP occur under low SST or weak large-scale subsidence. Introduction of a small amount of giant sea salt aerosol into the simulation lowers the number of cloud droplets activated, results in larger cloud droplets, and initiates precipitation for nondrizzling polluted clouds or precedes the precipitation process for drizzling clouds. However, giant sea salt aerosol is found to have a negligible effect on τ for lightly precipitating cases, while resulting in a relative reduction of τ of 3%–77% (increasing with Na, for Na = 1000–2500 cm−3) for heavily precipitating cases, suggesting that the impact of giant sea salt is only important for moist and potentially convective clouds. Finally, a regression analysis of the simulations shows that the second indirect effect is more evident in clear than polluted cases. The second indirect effect is found to enhance (reduce) the overall aerosol indirect effect for heavily (lightly) drizzling clouds; that is, τ is larger (smaller) for the same relative change in Na than considering the Twomey (first indirect) effect alone. The aerosol indirect effect (on τ) is lessened in the daytime afternoon conditions and is dominated by the Twomey effect; however, the effect in the early morning is close but slightly smaller than that in the nocturnal run. Diurnal variations of the aerosol indirect effect should be considered to accurately assess its magnitude

REDOX-REGULATED RELB-AR AXIS MEDIATES PROSTATE SPECIFIC ANTIGEN EXPRESSION: INSIGHT IN PROSTATE CANCER RESPONSE TO RADIATION THERAPY

Although the prostate specific antigen (PSA) test is widely used in clinical settings for prostate cancer (PCa) diagnosis and post-treatment follow-up monitoring, false positive PSA test results, which contribute to over-diagnosis of PCa, and false negative results, which miss some patients with aggressive PCa, remain problems of clinical importance. Our study demonstrates that radiation therapy, which is widely used for treatment of localized PCa, generates TNF-α in tumor cells and stromal fibroblasts, redox dependently. Interestingly, TNF-α rapidly and transiently triggers the RelA-mediated NF-κB canonical pathway, but its effect on RelB expression is more robust and long lasting, which leads to sustainable suppression of PSA expression. TNF-α further amplifies endogenous reactive oxygen species (ROS) partially through NADPH oxidase activation and mediates redox-dependent downstream signaling pathways. Addition of the NADPH oxidase inhibitor or ROS scavengers such as superoxide dismutase (SOD) mimetic can abrogate TNF-α-mediated suppression of PSA expression by inhibiting the RelB-AR axis. Treatment with TNF-α suppresses PSA expression and it confers minor yet statistically significant protection to LNCap cells against irradiation, indicating that radiation-induced TNF-α may not only interfere with the PSA-based PCa diagnosis and post-treatment monitoring but may also diminish the efficacy of radiotherapy. In addition, we uncover a role for RelB in suppressing PSA expression at the advanced stage of PCa, which could be a mechanism for the low PSA level in some patients bearing aggressive PCa. Experiments with both RelB overexpression and siRNA knockdown indicate that RelB negatively regulates androgen receptor (AR) and PSA levels in human prostate cancer, LNCap, cells. RelB directly interacts with AR to form a complex on the enhancer elements of the PSA promoter. Thus, the RelB-AR axis is an important contributor to PSA suppression at the advanced stage of PCa. Overall, this study is the first to reveal a redox-mediated association among radiation-generated TNF-α, activation of the RelB-mediated alternative NF-kappaB pathway and PSA suppression. This mechanistic information provides new insights with practical and clinical implications for PSA-based PCa diagnosis and post-treatment monitoring as well as redox intervention in radiation therapy