Human alterations of the terrestrial water cycle through land management

This study quantifies current and potential future changes in transpiration, evaporation, interception loss and river discharge in response to land use change, irrigation and climate change, by performing several distinct simulations within the consistent hydrology and biosphere modeling framework LPJmL (Lund-Potsdam-Jena managed Land). We distinguished two irrigation simulations: a water limited one in which irrigation was restricted by local renewable water resources (ILIM), and a potential one in which no such limitation was assumed but withdrawals from deep groundwater or remote rivers allowed (IPOT). We found that the effect of historical land use change as compared to potential natural vegetation was pronounced, including a reduction in interception loss and transpiration by 25.9% and 10.6%, respectively, whereas river discharge increased by 6.6% (climate conditions of 1991–2000). Furthermore, we estimated that about 1170 km<sup>3</sup>yr<sup>−1</sup> of irrigation water could be withdrawn from local renewable water resources (in ILIM), which resulted in a reduction of river discharge by 1.5%. However, up to 1660 km<sup>3</sup>yr<sup>−1</sup> of water withdrawals were required in addition under the assumption that optimal growth of irrigated crops was sustained (IPOT), which resulted in a slight net increase in global river discharge by 2.0% due to return flows. Under the HadCM3 A2 climate and emission scenario, climate change alone will decrease total evapotranspiration by 1.5% and river discharge by 0.9% in 2046–2055 compared to 1991–2000 average due to changes in precipitation patterns, a decrease in global precipitation amount, and the net effect of CO<sub>2</sub> fertilization. A doubling of agricultural land in 2046–2055 compared to 1991–2000 average as proposed by the IMAGE land use change scenario will result in a decrease in total evapotranspiration by 2.5% and in an increase in river discharge by 3.9%. That is, the effects of land use change in the future will be comparable in magnitude to the effects of climate change in this particular scenario. On present irrigated areas future water withdrawal will increase especially in regions where climate changes towards warmer and dryer conditions will be pronounced

Dendrimer Conjugation Enhances Tumor Penetration and Cell Kill of Doxorubicin in 3D Coculture Lung Cancer Models

Background: Doxorubicin (DOX) is a potent chemotherapeutic widely used for solid tumors (1). Despite high efficacy in 2D cell culture, DOX efficacy does not translate to in vivo lung cancer models (2). Major side effects such as cardiotoxicity may be alleviated with nano-based drug delivery systems (nanoDDS). However, tumor penetration of DOX and DOX-nanoDDS is largely unknown and is an additional barrier to effective clinical therapy (3). Here we describe a nanoDDS capable of enhancing the penetration of DOX. Methods: DOX was conjugated to generation 4 poly(amido-amine) dendrimers through (GFLG) tumor- liable bond. G4SA-GFLG-DOX was synthesized/characterized. spheroids were formed of (A549) lung adenocarcinoma cells and (3T3) fibroblasts. Spheroids were characterized for ECM components with immunohistochemistry. Confocal microscopy was used to evaluate the penetration, internalization, and colocalization of DOX and G4SA-GFLG-DOX. MTT assay and Caspase 3/7 to assess 2D and 3D cytotoxicity. Flow cytometry to determine cells uptake. Results: DOX conjugation to dendrimer resulted in G4SA-GFLG-DOX with ~5.5 DOX, 10±1 nm hydrodynamic diameter, and a -17±3 mV zeta-potential. Spheroids of (A549:3T3) were ECM- rich, developed ECM containing collagen-I, hyaluronan, laminin, and fibronectin. While DOX and G4SA-GFLG-DOX had similar toxicities in 2D model, G4SA-GFLG-DOX demonstrated a 3.1-fold greater penetration into spheroids compared to DOX and correlated to a greater efficacy as measured by caspase 3/7 activity. Also, flow cytometry showed higher uptake of G4SA- GFLG-DOX in cancer cells compared to fibroblasts. Conclusion: The work demonstrates enhanced penetration of DOX, via dendrimer conjugation, into an ECM- rich 3D lung cancer model. The enhanced penetration of G4SA-GFLG-DOX correlated with greater antitumor efficacy. Acknowledgements: We acknowledge partial financial support from the Center for Pharmaceutical Engineering and Sciences - School of Pharmacy at VCU. This study was supported by VCU Quest for Distinction and NSF (DRM #1508363). Microscopy was performed at the VCU Microscopy Facility, supported, in part, by funding from NIH-NCI Cancer Center Support Grant P30 CA016059. RA would like to acknowledge King Faisal University (KFU) and Saudi Arabian Cultural Mission (SACM) for a scholarship.https://scholarscompass.vcu.edu/gradposters/1091/thumbnail.jp

An Analytical Perspective on Determination of Free Base Nicotine in E-Liquids

In electronic cigarette users, nicotine delivery to lungs depends on various factors. One of the important factors is e-liquid nicotine concentration. Nicotine concentration in e-liquids ranges from 0 to \u3e50 mg/mL. Furthermore, nicotine exists in protonated and unprotonated (“free base”) forms. The two forms are believed to affect the nicotine absorption in body. Therefore, in addition to total nicotine concentration, e-liquids should be characterized for their free base nicotine yield. Two approaches are being used for the determination of free base nicotine in e-liquids. The first is applying a dilution to e-liquids followed by two methods: Henderson–Hasselbalch theory application or a Liquid-Liquid Extraction. The second is the without-dilution approach followed by 1H NMR method. Here, we carried out controlled experiments using five e-liquids of different flavors using these two approaches. In the dilution approach, the Henderson–Hasselbalch method was tested using potentiometric titration. The accuracy was found to be \u3e98% for all five e-liquid samples (n = 3). A Liquid-Liquid Extraction was carried out using toluene or hexane as extraction solvent. The Liquid-Liquid Extraction technique was found to be limited by solvent interactions with flavors. Solvent extractions resulted in flavor dependent inaccuracies in free base nicotine determination (5 to 277% of calculated values). The without-dilution approach was carried out using 1H NMR as described by Duell et al. This approach is proposed to offer an independent and alternative scale. None of the methods have established a strong correlation between pre- and postvaporization free base nicotine yield. Here we present comparative results of two approaches using analytical techniques. Such a comparison would be helpful in establishing a standardized method for free base nicotine determination of e-liquids