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Water table depth (WTD) has a substantial impact on the connection between groundwater dynamics and land surface processes. Due to the scarcity of WTD observations, physically‐based groundwater models are growing in their ability to map WTD at large scales; however, they are still challenged to represent simulated WTD compared to well observations. In this study, we develop a purely data‐driven approach to estimating WTD at continental scale. We apply a random forest (RF) model to estimate WTD over most of the contiguous United States (CONUS) based on available WTD observations. The estimated WTD are in good agreement with well observations, with a Pearson correlation coefficient (r) of 0.96 (0.81 during testing), a Nash‐Sutcliffe efficiency (NSE) of 0.93 (0.65 during testing), and a root mean square error (RMSE) of 6.87 m (15.31 m during testing). The location of each grid cell is rated as the most important feature in estimating WTD over most of the CONUS, which might be a surrogate for spatial information. In addition, the uncertainty of the RF model is quantified using quantile regression forests. High uncertainties are generally associated with locations having a shallow WTD. Our study demonstrates that the RF model can produce reasonable WTD estimates over most of the CONUS, providing an alternative to physics‐based modeling for modeling large‐scale freshwater resources. Since the CONUS covers many different hydrologic regimes, the RF model trained for the CONUS may be transferrable to other regions with a similar hydrologic regime and limited observations. [ABSTRACT FROM AUTHOR]

The use of optical imaging and bipolar electrochemical arrays is a powerful approach for optically monitoring as well as spatially and temporally resolving heterogeneous electron-transfer processes. Previous studies, however, have been largely limited to the study of slower or steady-state redox processes. In this work, we use electrochemiluminescence (ECL) to demonstrate the ability to optically record transient collision events of single platinum nanoparticles on a carbon ultramicroelectrode (UME). The electrocatalytic signal of a Pt nanoparticle on a cathodic pole of a bipolar electrode is coupled to the ECL signal on the anodic pole generating a transient optical signal. Correlated amperometric (i-t) and ECL (count-t) traces are then compared to determine critical parameters which influence the accurate temporal resolution of these rapid events. Our results suggest that ECL can be an effective means for spatially and temporally resolving transient redox processes when used on arrays of closed bipolar electrodes. [ABSTRACT FROM AUTHOR]

Increased airway smooth muscle (ASM) cell mass and secretory functions are characteristics of airway inflammatory diseases, such as asthma. To date, there are no effective therapies to combat ASM cell proliferation, which contributes to bronchoconstriction and airway obstruction. Growth factors such as platelet-derived growth factor (PDGF) and the activation of the ERK1/2 are major regulators of ASM cell proliferation and airway remodeling in asthma. However, given the ubiquitous expression and multiple functions of ERK1/2, complete inhibition of ERK1/2 using ATP-competitive inhibitors may lead to unwanted off-target effects. Alternatively, we have identified compounds that are designed to target substrate docking sites and act as function-selective inhibitors of ERK1/2 signaling. Here, we show that both function-selective and ATP-competitive ERK1/2 inhibitors are effective at inhibiting PDGF-mediated proliferation, collagen production, and IL-6 secretion in ASM cells. Proteomic analysis revealed that both types of inhibitors had similar effects on reducing proteins related to TGF-β and IL-6 signaling that are relevant to airway remodeling. However, function-selective ERK1/2 inhibitors caused fewer changes in protein expression compared with ATP-competitive inhibitors. These studies provide a molecular basis for the development of function-selective ERK1/2 inhibitors to mitigate airway remodeling in asthma with defined regulation of ERK1/2 signaling. [ABSTRACT FROM AUTHOR]

R682 --> 793.13 --> ATP synthase is a membrane protein complex that synthesizes adenosine triphosphate (ATP), an integral molecule that provides energy to all forms of life. The complex is comprised of two rotary motors, the soluble F1 sector and the membrane embedded Fo sector. ATP synthesis is catalyzed by conformational changes within F1, which are driven by the rotation of the c‐ring (rotor) of Fo. The Fo motor is powered by the electrochemical gradient of H+ across the cell membrane, and movement of H+ through Fo is facilitated by two aqueous half‐channels within subunit a (stator) and at the rotor‐stator interface. The mechanism of how H+‐driven rotation in Fo is generated is not fully understood. Cryo‐electron microscopy has revealed structures of E. coli F1Fo ATP synthase, but inconsistencies between this structural data and previous cross‐linking data within subunit a suggest the existence of multiple conformations. In order to gain insight into suspected conformational dynamics of the stator, we have utilized site‐directed spin labeling and electron paramagnetic resonance (EPR) spectroscopy to observe backbone mobility at several points in subunit a. We demonstrate the feasibility of membrane extraction using mixed micelles of dodecylmaltoside/phosphatidylcholine or styrene maleic acid lipid particles (SMALPs). Furthermore, we found high backbone mobility at sites on the cytoplasmic surface of the subunit a stator. [ABSTRACT FROM AUTHOR]

Protein kinase C (PKC) is a heterogeneous family of serine/threonine protein kinases that have different biological effects in normal and neoplastic melanocytes (MCs). To explore the mechanism behind their differential response to PKC activation, we analyzed the expression profile of all nine PKC isoforms in normal human MCs, HPV16 E6/E7 immortalized MCs, and a panel of melanoma cell lines. We found reduced PKCβ and increased PKCζ and PKCι expression at both the protein and mRNA levels in immortalized MCs and melanoma lines. We focused on PKCβ as it has been functionally linked to melanin production and oxidative stress response. Re-expression of PKCβ in melanoma cells inhibited colony formation in soft agar, indicating that PKCβ loss in melanoma is important for melanoma growth. PKCβII, but not PKCβI, was localized to the mitochondria, and inhibition of PKCβ significantly reduced UV-induced reactive oxygen species (ROS) in MCs with high PKCβ expression. Thus alterations in PKCβ expression in melanoma contribute to their neoplastic phenotype, possibly by reducing oxidative stress, and may constitute a selective therapeutic target. [ABSTRACT FROM AUTHOR]

Vitamin A deficiency has been shown to exacerbate allergic asthma. Previous studies have postulated that retinoic acid (RA), an active metabolite of vitamin A and high-affinity ligand for RA receptor (RAR), is reduced in airway inflammatory condition and contributes to multiple features of asthma including airway hyperresponsiveness and excessive accumulation of airway smooth muscle (ASM) cells. In this study, we directly quantified RA and examined the molecular basis for reduced RA levels and RA-mediated signaling in lungs and ASM cells obtained from asthmatic donors and in lungs from allergen-challenged mice. Levels of RA and retinol were significantly lower in lung tissues from asthmatic donors and house dust mite (HDM)-challenged mice compared to non-asthmatic human lungs and PBS-challenged mice, respectively. Quantification of mRNA and protein expression revealed dysregulation in the first step of RA biosynthesis consistent with reduced RA including decreased protein expression of retinol dehydrogenase (RDH)-10 and increased protein expression of RDH11 and dehydrogenase/reductase (DHRS)-4 in asthmatic lung. Proteomic profiling of non-asthmatic and asthmatic lungs also showed significant changes in the protein expression of AP-1 targets consistent with increased AP-1 activity. Further, basal RA levels and RA biosynthetic capabilities were decreased in asthmatic human ASM cells. Treatment of human ASM cells with all-trans RA (ATRA) or the RARγ-specific agonist (CD1530) resulted in the inhibition of mitogen-induced cell proliferation and AP-1-dependent transcription. These data suggest that RA metabolism is decreased in asthmatic lung and that enhancing RAR signaling using ATRA or RARγ agonists may mitigate airway remodeling associated with asthma. [ABSTRACT FROM AUTHOR]

Ionogels are an emerging class of soft materials that exhibit ionic conductivity and thermal stability without the need to replenish ions or the addition of conductive particle fillers. An ionogel ink is reported for direct‐write 3D printing to fabricate conductive structures that can vary in the printed object geometries. This approach relies on a shear‐thinning ionogel ink that can be extruded to afford self‐supporting constructs. After a brief UV cure, the printed construct is transformed into a mechanically tough, transparent structure that is ionically conductive. Upon application of stretching and twisting loads, the 3D‐printed objects exhibit detectable changes in conductivity. To demonstrate the versatility of rapid prototyping with the ionogel inks, an auxetic structure is 3D printed and tested as a strain sensor. The printed auxetic structure exhibits an electrical response to strain, but also demonstrates increased extensibility and operational range in comparison to a casted bulk film with the same outer dimensions. [ABSTRACT FROM AUTHOR]