[1] The effect of retention time on redox sequences along the hydrological flow path of groundwater discharging through low-relief coastal stream sediments and the subsequent impact on the fate of NO 3 À carried in the groundwater was examined in two intact cores. Rates of denitrification were determined for the organic-rich streambed sediments, and a macroscopic, multispecies, reactive transport model based on multiple Monod kinetics was developed to interpret and extend the experimental results. Regionalized sensitivity analysis and parameter estimation were used to determine a set of parameters that best describe the experimental data for one column. The calibrated model successfully replicated the spatial profiles of nitrate under both steady and transient conditions in the second column operated under different conditions. A dimensionless form of the model was used to examine how coupled biogeochemical reactions and hydrological transport processes operate within the stream sediments could be understood in terms of Peclet (ratio of advection to dispersion) and Damkohler numbers (the ratio of the characteristic time of transport to the characteristic time for reaction). At the study site, the Peclet number and the Damkohler numbers for both oxygen and nitrate are high (Pe = 25, Da N = 47.5, and Da O = 40). When Pe > 5, Damkohler numbers explain observed variations in nitrate removal rates; as the flow rate increases, the solute residence time in the reactive zone is shortened resulting in a lesser extent of reaction, such that more NO 3 À is delivered to the stream water.

[1] Hyporheic exchanges in riparian zones induced by stream stage fluctuations, referred to as bank storage, can influence contaminant transport and transformation when mixing of groundwater and surface waters with distinct chemical signatures occur, which might lead to a high biochemical activity. The effect of bank storage on nutrient transport was analyzed here using a two-dimensional, variably saturated and multispecies reactive transport model, which accounted for the water flow and solute transport and reactions within riparian zones. After verification with field observations, our model demonstrated that high biogeochemical activities occurred at the near-stream riparian zone during stage fluctuation, a process referred to as bank storage hot moment (BSHM). We used Monte Carlo simulations to study the uncertainty of BSHM and related nutrient dynamics to biogeochemical and hydrological factors. À5 and SD ¼ 2.4 Â 10 À4 m min À1 ) was comparable to that of in-stream transient storage from the literature. This result suggests that BSHM may be a significant process contributing to the nutrient budget at the ecosystem level. Finally, a theoretical framework representing the coupled hydrobiogeochemical controls on riparian hot spots was developed to help predicting when BSHM can become important in a particular stream.

[1] The development and initial application of a mechanistic model (TOUGHREACT-N) designed to characterize soil nitrogen (N) cycling and losses are described. The model couples advective and diffusive nutrient transport, multiple microbial biomass dynamics, and equilibrium and kinetic chemical reactions. TOUGHREACT-N was calibrated and tested against field measurements to assess pathways of N loss as either gas emission or solute leachate following fertilization and irrigation in a Central Valley, California, agricultural field as functions of fertilizer application rate and depth, and irrigation water volume. Our results, relative to the period before plants emerge, show that an increase in fertilizer rate produced a nonlinear response in terms of N losses. An increase of irrigation volume produced NO 2 À and NO 3 À leaching, whereas an increase in fertilization depth mainly increased leaching of all N solutes. In addition, nitrifying bacteria largely increased in mass with increasing fertilizer rate. Increases in water application caused nitrifiers and denitrifiers to decrease and increase their mass, respectively, while nitrifiers and denitrifiers reversed their spatial stratification when fertilizer was applied below 15 cm depth. Coupling aqueous advection and diffusion, and gaseous diffusion with biological processes, closely captured actual conditions and, in the system explored here, significantly clarified interpretation of field measurements.

Key Points• Wogonoside induces cell cycle arrest and differentiation. • Wogonoside acts by changing PLSCR1 expression and subcellular localization in the nucleus and by PLSCR1-related molecular events.Wogonoside is the main flavonoid component derived from the root of Scutellaria baicalensis Georgi. It is a popular Chinese herbal medicine with the potential to treat hematologic malignancies. In this study, we investigated the anticancer effects of wogonoside in acute myeloid leukemia (AML) cell lines and primary patient-derived AML cells. Wogonoside exerted antiproliferative properties both in vitro and in vivo. Furthermore, it efficiently inhibited the proliferation of U937 and HL-60 cells through the induction of G 1 phase arrest and the promotion of differentiation. We also demonstrated that wogonoside significantly increased the transcription of phospholipid scramblase 1 (PLSCR1) due to its influence on the expression of cell cycle-and differentiation-related genes, including the upregulation of p21waf1/cip1 and downregulation of the oncogenic protein c-Myc. Wogonoside also promoted PLSCR1 trafficking into the nucleus and facilitated its binding to the inositol 1,4,5-trisphosphate receptor 1 (IP3R1) promoter, thus increasing the expression of IP3R1. Finally, inhibition of PLSCR1 expression with small interfering RNA partially blocked wogonoside-induced cell cycle arrest and differentiation and disturbed the wogonosideassociated molecular events. The results of this study therefore suggest that wogonoside may represent a therapeutic candidate for the treatment of AML. (Blood. 2013;121(18):3682-3691) Introduction Acute myeloid leukemia (AML) comprises a genetically and clinically heterogeneous group of aggressive hematological neoplasms. 1Continuing research into the pathogenesis and heterogeneity of AML has resulted in the development of several potentially useful therapeutic agents.2 However, despite some advances in the treatment of AML, therapies have not changed significantly in the past 20 years. Further research is thus warranted to identify effective agents and develop new therapeutic strategies for the treatment of this deadly disease. Flavonoids possess diverse biological and pharmaceutical properties and have been subjected to extensive investigations as likely candidates for cancer treatment. Scutellaria baicalensis Georgi (huang qin) is 1 of the most popular and multipurpose traditional Chinese medicinal herbs, and it has a high flavonoid content. 4 Wogonin, a flavonoid extracted from S. baicalensis, has several biological effects including antioxidant, anti-inflammatory, antiviral, neuroprotective, anxiolytic, and anticancer activities. 5 It has been shown to possess antitumor effects in various cancer cells, 6 including antiproliferation, cell cycle arrest, induction of apoptosis and differentiation, inhibition of angiogenesis, anti-invasion, and increased sensitivity to apoptosis. Moreover, wogonin has shown therapeutic potential for the treatment of hematologic malignancies. 7 Flavonoid agl...