ALBERT

Description: We investigate how the choice of injection mode impacts transport properties in kilometer-scale three-dimensional discrete fracture networks (DFN). The choice of injection mode, resident or flux-weighted, is designed to mimic different physical phenomena. It has been hypothesized that solute plumes injected under resident conditions evolve to behave similarly to solutes injected under flux-weighted conditions. Previously, computational limitations have prohibited the large scale simulations required to investigate this hypothesis. We investigate this hypothesis by using a high performance DFN suite, dfnWorks , to simulate flow in kilometer-scale three-dimensional DFNs based on fractured granite at the Forsmark site in Sweden, and adopt a Lagrangian approach to simulate transport therein. Results show that after traveling through a pre-equilibrium region both injection methods exhibit linear scaling of the first moment of travel time and power law scaling of the breakthrough curve with similar exponents, slightly larger than two. The physical mechanisms behind this evolution appear to be the combination of in-network channeling of mass into larger fractures, which offer reduced resistance to flow, and in-fracture channeling, which results from the topology of the DFN. This article is protected by copyright. All rights reserved.

Description: Hydrologic ensemble forecasts driven by atmospheric ensemble prediction systems need statistical post-processing in order to account for systematic errors in terms of both location and spread. Runoff is an inherently multivariate process with typical events lasting from hours in case of floods to weeks or even months in case of droughts. This calls for multivariate post-processing techniques that yield well calibrated forecasts in univariate terms and ensure a realistic temporal dependence structure at the same time. To this end, the univariate ensemble model output statistics (EMOS) post-processing method is combined with two different copula approaches that ensure multivariate calibration throughout the entire forecast horizon. The domain of this study covers three sub-catchments of the river Rhine that represent different sizes and hydrological regimes: the Upper Rhine up to the gauge Maxau, the river Moselle up to the gauge Trier, and the river Lahn up to the gauge Kalkofen. In this study the two approaches to model the temporal dependence structure are ensemble copula coupling (ECC), which preserves the dependence structure of the raw ensemble, and a Gaussian copula approach (GCA), which estimates the temporal correlations from training observations. The results indicate that both methods are suitable for modelling the temporal dependencies of probabilistic hydrologic forecasts. This article is protected by copyright. All rights reserved.

Description: A three-dimensional mathematical model that describes transport of contaminant in a horizontal aquifer with simultaneous diffusion into a fractured clay formation is proposed. A group of semi-analytical solutions is derived based on specific initial and boundary conditions as well as various source functions. The analytical model solutions are evaluated by numerical Laplace inverse transformation and analytical Fourier inverse transformation. The model solutions can be used to study the fate and transport in a three-dimensional spatial domain in which a non-aqueous phase liquid exists as a pool atop a fractured low permeability clay layer. The non-aqueous phase liquid gradually dissolves into the groundwater flowing past the pool, while simultaneously diffusing into the fractured clay formation below the aquifer. Mass transfer of the contaminant into the clay formation is demonstrated to be significantly enhanced by the existence of the fractures, even though the volume of fractures is relatively small compared to the volume of the clay matrix. The model solution is a useful tool in assessing contaminant attenuation processes in a confined aquifer underlain by a fractured clay formation. This article is protected by copyright. All rights reserved.

Description: World Health Organization reports that methicillin-resistant Staphylococcus aureus (MRSA) is the origin of higher proportion of hospital acquired infections. In order to combat the effect of MRSA infection, an ideal drug should stimulate the allosteric exposure of active site, prompting penicillin binding proteins (PBP2a) to bind with that particular compound. Ceftaroline shows high binding affinity towards PBP2a and also confers resistance against degrading enzymes. Recently, two amino acid alterations in the allosteric site of PBP2a, asparagine (N) to lysine (K) at position 146 and glutamic acid (E) to lysine at position 150 are reported to confer resistance against ceftaroline resulting in the rise of ceftaroline-resistant MRSA strains. The present study focuses on the identification of potential ligands that can effectively bind with allosteric site of PBP2a, that leads to the access of active site and entry of a β-lactam antibiotic for effective inhibition. The results obtained from our study will be useful for designing effective compounds with potential therapeutic effects against ceftaroline resistant MRSA strains. This article is protected by copyright. All rights reserved

Description: The human protein kinase X gene (PRKX) and cAMP-dependent protein kinase (PKA) are both c-AMP-dependent serine/threonine protein kinases within the protein kinase AGC subgroup. Of all the protein kinases in this group, PRKX is the least studied. PRKX has been isolated from patients with chondrodysplasia punctate and is involved in numerous processes, including sexual differentiation and fertilization, normal kidney development, and autosomal dominant polycystic kidney disease (ADPKD), blood maturation, neural development and angiogenesis in vitro. Although the role of PRKX in development and disease has been reported recently, the underlying mechanism of PRKX activity is largely unknown. In addition, based on the expression pattern of PRKX and the extensive role of PKA in disease and development, PRKX might have additional crucial functions that have not been addressed in the literature. In this review, we summarize the characteristics and developmental functions of PRKX that have been reported by recent studies. In particular, we elucidate the structural and functional differences between PRKX and PKA, as well as the possible roles of PRKX in development and related diseases. Finally, we propose future studies that could lead to important discoveries of more PRKX functions and the underlying mechanisms involved. This article is protected by copyright. All rights reserved

Description: Several key transcription factors regulate cell growth, survival, and differentiation during neural crest and melanoblast development in the embryo, and these same pathways may be reactivated in tumors arising from the progenitors of these cells. The transcription factors PAX3 and FOXD3 have essential roles in melanoblasts and melanoma. In this study, we define a regulatory pathway where FOXD3 promotes the expression of PAX3. Both factors are expressed in melanoma cells and there is a positive correlation between the transcript levels of PAX3 and FOXD3. The PAX3 gene contains two FOX binding motifs within highly conserved enhancer regulatory elements that are essential for neural crest development. FOXD3 binds to both of these motifs in vitro but only one of these sites is preferentially utilized in melanoma cells. Overexpression of FOXD3 upregulates PAX3 levels while inhibition of FOXD3 function does not alter PAX3 protein levels, supporting that FOXD3 is sufficient but not necessary to drive PAX3 expression in melanoma cells. Here, we identify a molecular pathway where FOXD3 upregulates PAX3 expression and therefore contributes to melanoma progression. This article is protected by copyright. All rights reserved

Description: Metabolic networks are significantly altered in neoplastic cells. This altered metabolic program leads to increased glycolysis and lipogenesis and decreased dependence on oxidative phosphorylation and oxygen consumption. Despite their limited mitochondrial respiration, cancer cells, nonetheless, derive sufficient energy from alternative carbon sources and metabolic pathways to maintain cell proliferation. They do so, in part, by utilizing fatty acids, amino acids, ketone bodies and acetate, in addition to glucose. The alternative pathways used in the metabolism of these carbon sources provide opportunities for therapeutic manipulation. Acetate, in particular, has garnered increased attention in the context of cancer as both an epigenetic regulator of posttranslational protein modification, and as a carbon source for cancer cell biomass accumulation. However, to date, the data have not provided a clear understanding of the precise roles that protein acetylation and acetate oxidation play in carcinogenesis, cancer progression or treatment. This review highlights some of the major issues, discrepancies and opportunities associated with the manipulation of acetate metabolism and acetylation-based signaling in cancer development and treatment. This article is protected by copyright. All rights reserved

Description: Adipogenesis comprises a complex network of signaling pathways and transcriptional cascades; the GSK3β-C/EBPβ- srebf1a axis is a critical signaling pathway at early stages leading to the expression of PPARγ2, the master regulator of adipose differentiation. Previous work has demonstrated that retinoic acid inhibits adipogenesis affecting different signaling pathways. Here, we evaluated the anti-adipogenic effect of retinoic acid on the adipogenic transcriptional cascade, and the expression of adipogenic genes cebpb , srebf1a , srebf1c , pparg2 , and cebpa . Our results demonstrate that retinoic acid blocks adipose differentiation during commitment, returning cells to an apparent non-committed state, since they have to be newly induced to adipose conversion after the retinoid is removed from the culture medium. Retinoic acid down regulates the expression of the adipogenic genes, srebf1a, srebf1c , pparg2 , and cebpa . Retinoic acid did not down regulate the expression of cebpb , but it inhibited C/EBPβ phosphorylation at Thr188, a critical step for the progression of the adipogenic program. We also found that RA inhibition of adipogenesis did not increase the expression of dlk1 , the gene encoding for Pref1, a well-known anti-adipogenic transcription factor. This article is protected by copyright. All rights reserved

Description: ABSTRACT Platelets are important in hemostasis, but also detect particles and pathogens in the circulation. Phagocytic and endocytic activities of platelets are widely recognized, however, receptors and mechanisms involved remain poorly understood. We previously demonstrated that platelets internalize and store phospholipid microvesicles enriched in human tissue factor (TF + MVs) and that platelet-associated TF enhances thrombus formation at sites of vascular damage. Here we investigate the mechanisms implied in the interactions of TF + MVs with platelets and the effects of specific inhibitory strategies. Aggregometry and electron microscopy were used to assess platelet activation and TF + MVs uptake. Cytoskeletal assembly and activation of phosphoinositide 3-kinase (PI3K) and RhoA were analyzed by western blot and ELISA. Exposure of platelets to TF + MVs caused reversible platelet aggregation, actin polymerization and association of contractile proteins to the cytoskeleton being maximal at 1 min. The same kinetics were observed for activation of PI3K and translocation of RhoA to the cytoskeleton. Inhibitory strategies to block glycoprotein IIb-IIIa (GPIIb-IIIa), scavenger receptor CD36, serotonin transporter (SERT) and PI3K, fully prevented platelet aggregation by TF + MVs. Ultrastructural techniques revealed that uptake of TF + MVs was efficiently prevented by anti-CD36 and SERT inhibitor, but only moderately interfered by GPIIb-IIIa blockade. We conclude that internalization of TF + MVs by platelets occurs independently of receptors related to their main hemostatic function (GPIIb-IIIa), involves the scavenger receptor CD36, SERT and engages PI3-Kinase activation and cytoskeletal assembly. CD36 and SERT appear as potential therapeutic targets to interfere with the association of TF + MVs with platelets and possibly downregulate their prothrombotic phenotype. This article is protected by copyright. All rights reserved

Description: Human pancreatic and prostate cancers metastasize along nerve axons during perineural invasion. The extracellular matrix laminin class of proteins is an abundant component of both myelinated and non-myelinated nerves. Analysis of human pancreatic and prostate tissue revealed both perineural and endoneural invasion with Schwann cells surrounded or disrupted by tumor, respectively. Tumor and nerve cell co-culture conditions were used to determine if myelinating or non-myelinating Schwann cell (S16 and S16Y, respectively) phenotype was equally likely to promote integrin-dependent cancer cell invasion and migration on laminin. Conditioned medium from S16 cells increased tumor cell (DU145, PC3, and CFPAC1) invasion into laminin approximately 1.3 to 2.0 fold compared to fetal bovine serum (FBS) treated cells. Integrin function (e.g., ITGA6p formation) increased up to 1.5 fold in prostate (DU145, PC3, RWPE-1) and pancreatic (CFPAC1) cells, and invasion was dependent on ITGA6p formation and ITGB1 as determined by function-blocking antibodies. In contrast, conditioned medium isolated from S16Y cells (non-myelinating phenotype) decreased constitutive levels of ITGA6p in the tumor cells by 50% compared to untreated cells and decreased ITGA6p formation 3.0 fold compared to S16 treated cells. Flow cytometry and western blot analysis revealed loss of ITGA6p formation as reversible and independent of overall loss of ITGA6 expression. These results suggest that the myelinating phenotype of Schwann cells within the tumor microenvironment increased integrin-dependent tumor invasion on laminin. This article is protected by copyright. All rights reserved

Description: This work focuses on the implementation of a Shallow Water-Exner model for compound natural channels with complex geometry and movable bed within the finite volume framework. The model is devised for compound channels modeling: cross-section overbanks are treated with fixed bed conditions, while the main channel is left free to modify its morphology. A capacitive approach is used for bedload transport modeling, in which the solid flow rates are estimated with bedload transport formulas. The model equations pose some numerical issues in the case of natural channels, where bedload transport may occur for both subcritical and supercritical flows and geometry varies in space. An explicit path-conservative scheme, designed to overcome all these issues, is presented in the paper. The scheme solves liquid and solid phases dynamics in a coupled manner, in order to correctly model near critical currents/channel interactions and is well-balanced, that is able to properly reproduce steady states. The Roe and Osher Riemann solvers are implemented, so as to take into account the spatial geometry variations of natural channels. The scheme reaches up to 2 nd order accuracy. Validation is performed with fixed and movable bed test cases whose analytical solution is known, and with flume experimental data. An application of the model to a real case study is also shown. This article is protected by copyright. All rights reserved.

Description: In this paper we use a physical modelling approach to explore the effect of lateral confinement on gravel bed river planform style, bed morphology, and sediment transport processes. A set of 27 runs was performed in a large flume (25 m long, 2.9 m wide), with constant longitudinal slope (0.01) and uniform grain size (1 mm), changing the water discharge (1.5 to 2.5 l/s) and the channel width (0.15 m to 1.5 m) to model a wide range of channel configurations, from narrow, straight, embanked channels to wide braided networks. The outcomes of each run were characterized by a detailed digital elevation model describing channel morphology, a map of dry areas and areas actively transporting sediment within the channel, and continuous monitoring of the amount of sediment transported through the flume outlet. Analysis reveals strong relationships between unit stream power and parameters describing the channel morphology. In particular, a smooth transition is observed between narrow channels with an almost rectangular cross section profile (with sediment transport occurring across the entire channel width) and complex braided networks where only a limited proportion (30%) of the bed is active. This transition is captured by descriptors of the bed elevation frequency distribution, e.g. standard deviation, skewness and kurtosis. These summary statistics represent potentially useful indicators of bed morphology that are compared with other commonly used summary indicators such as the braiding index and the type and number of bars. This article is protected by copyright. All rights reserved.

Description: We believe that there are too many models in hydrology and we should ask ourselves the question, if we are currently wasting time and effort in developing another model again instead of focusing on the development of a community hydrological model. In other fields this kind of models have been quite successful, but due to several reasons, no single community model has been developed in the field of hydrology yet. The concept, strength and weakness of a community model was discussed at the Chapman Conference on Catchment Spatial Behaviour and Complex Organisation held in Luxembourg in September 2014. This discussion as well as out own opinions about the potential of a community models, or at least the necessary discussion to establish one are debated in this commentary. This article is protected by copyright. All rights reserved.

Description: Soil surface sealing is a widespread natural process occurring frequently in bare soil areas between vegetation patches. The low hydraulic conductivity that characterizes the seal layer reduces both infiltration and evaporation fluxes from the soil, and thus has the potential to affect local vegetation water uptake (VWU). This effect is investigated here using experimental data, 2D physically based modelling and a long-term climatic dataset from three dry sites presenting a climatic gradient in the Negev Desert, Israel. The Feddes VWU parameters for the dominant shrub at the study site ( Sarcopoterium spinosum ) were acquired using lysimeter experiments. The results indicate that during the season surface sealing could either increase or decrease VWU depending on initial soil water content, rainfall intensity, and the duration of the subsequent drying intervals. These factors have a marked effect on inter-annual variability of the seal layer effect on VWU, which on average was found to be 26% higher under sealed conditions than in the case of unsealed soil surfaces. The seal layer was found to reduce the period where the vegetation was under water stress by 31% compared with unsealed conditions. This effect was more pronounced for seasons with total rainfall depth higher than 10 cm/y, and was affected by interseasonal climatic variability. These results shed light on the importance of surface sealing in dry environments and its contribution to the resilience of woody vegetation. This article is protected by copyright. All rights reserved.

Description: Female salmonids bury and lay their eggs in streambeds by digging a pit, which is then covered with sediment from a second pit. The spawning process alters streambed topography, winnows fine sediment, and mixes sediment in the active layer. The resulting egg nests (redds) contain coarser and looser sediments than those of unspawned streambed areas, and display a dune-like shape with an amplitude and length that vary with fish size, substrate conditions, and flow conditions. Redds increase local bed surface roughness (〈10 −1 channel width, W ), but may reduce the size of macro-bedforms by eroding reach scale topography (10 ° -10 1 W ). Research has suggested that spawning may increase flow resistance due to redd form drag, resulting in lower grain shear stress and less particle mobility. Spawning however also prevents streambed armoring through surface and subsurface material mixing, potentially increasing particle mobility. Here, we use 2-dimensional hydraulic modeling with detailed pre- and post-spawning bathymetries and field observations to test the effect of small spawning salmonids on sediment transport. Our results show that topographical roughness added by small-bodied salmon redds has negligible effects on shear stress at the reach-unit scale, and limited effects at the local scale. Conversely, our results indicate sediment mixing reduces armoring and enhances sediment mobility, which increases potential bed load transport by subsequent floods. River restoration in fish-bearing streams should take into consideration the effects of redd excavation on channel stability. This is particularly important for streams that historically supported salmonids, and at present are the focus of habitat restoration actions. This article is protected by copyright. All rights reserved.

Description: Floods are a natural hazard that affect communities worldwide, but to date the vast majority of flood hazard research and mapping has been undertaken by wealthy developed nations. As populations and economies have grown across the developing world, so too has demand from governments, businesses and NGOs for modelled flood hazard data in these data-scarce regions. We identify six key challenges faced when developing a flood hazard model that can be applied globally, and present a framework methodology that leverages recent cross-disciplinary advances to tackle each challenge. The model produces return period flood hazard maps at ∼90 m resolution for the whole terrestrial land surface between 56˚S and 60˚N, and results are validated against high resolution government flood hazard datasets from the UK and Canada. The global model is shown to capture between two thirds and three quarters of the area determined to be at risk in the benchmark data without generating excessive false positive predictions. When aggregated to ∼1 km, mean absolute error in flooded fraction falls to ∼5%. The full complexity global model contains an automatically parameterised subgrid channel network, and comparison to both a simplified 2D only variant and an independently developed pan-European model shows the explicit inclusion of channels to be a critical contributor to improved model performance. Whilst careful processing of existing global terrain datasets enables reasonable model performance in urban areas, adoption of forthcoming next-generation global terrain datasets will offer the best prospect for a step-change improvement in model performance. This article is protected by copyright. All rights reserved.

Description: Understanding how channel bed morphology affects flow conditions (and vice versa) is important for a wide range of fluvial processes and practical applications. We investigated interactions between bed roughness and flow velocity in a steep, glacier-fed mountain stream (Riedbach, Ct. Valais, Switzerland) with almost flume-like boundary conditions. Bed gradient increases along the 1-km study reach by roughly one order of magnitude ( S =3-41%), with a corresponding increase in streambed roughness, while flow discharge and width remain approximately constant due to the glacial runoff regime. Streambed roughness was characterized by semi-variograms and standard deviations of point clouds derived from terrestrial laser scanning. Reach-averaged flow velocity was derived from dye tracer breakthrough curves measured by 10 fluorometers installed along the channel. Commonly used flow resistance approaches (Darcy-Weisbach equation and dimensionless hydraulic geometry) were used to relate the measured bulk velocity to bed characteristics. As a roughness measure, D 84 yielded comparable results to more laborious measures derived from point clouds. Flow resistance behavior across this large range of steep slopes agreed with patterns established in previous studies for both lower-gradient and steep reaches, regardless of which roughness measures were used. We linked empirical critical shear stress approaches to the variable power equation for flow resistance to investigate the change of bed roughness with channel slope. The predicted increase in D 84 with increasing channel slope was in good agreement with field observations. This article is protected by copyright. All rights reserved.

Description: Large wood governs channel morphology, as well as the availability of in-stream habitat, in many forested streams. In this paper we use a stochastic, physically based model to simulate wood recruitment and in-stream geomorphic processes, in order to explore the influence of disturbance history on the availability of aquatic habitat. Specifically, we consider the effects of fire on a range of stream sizes by varying the rate of tree toppling over time in a simulated forest characterized by a tree height of 30 m. We also consider the effects of forest harvesting with various riparian buffer sizes, by limiting the lateral extent of the riparian stand. Our results show that pulsed inputs of wood increase the availability and variability of physical habitat in the post-fire period; reach-averaged pool area and deposit area double in small streams, while side-channels increase by over 50% in intermediate-sized channels. By contrast, forest harvesting reduces the availability of habitat within the reach, though the effects diminish with increasing buffer size or stream width; in laterally stable streams the effects are minimal so long as buffer width is large enough for key pieces to be recruited to the reach. This research emphasizes the importance of natural disturbance in creating and maintaining habitat heterogeneity and shows that scenario-based numerical modeling provides a useful tool for assessing the historical range of variability associated with natural disturbance, as well as changes in habitat relevant to fish. It can be also used to inform forest harvesting and management. This article is protected by copyright. All rights reserved.

Description: Spreading of conservative solutes in groundwater due to aquifer heterogeneity is quantified by the macrodispersivity, which was found to be scale dependent. It increases with travel distance, stabilizing eventually at a constant value. However, the question of its asymptotic behaviour at very large scale is still a matter of debate. It was surmised in the literature that macrodispersivity scales up following a unique scaling law. Attempts to define such a law were made by fitting a regression line in the log-log representation of an ensemble of macrodispersivities from multiple experiments. The functional relationships differ among the authors, based on the choice of data. Our study revisits the data basis, used for inferring unique scaling, through a detailed analysis of literature marcodispersivities. In addition, values were collected from the most recent tracer tests reported in the literature. We specified a system of criteria for reliability and re-evaluated the reliability of the reported values. The final collection of reliable estimates of macrodispersivity does not support a unique scaling law relationship. On the contrary, our results indicate, that the field data can be explained as a collection of macrodispersivities of aquifers with varying degree of heterogeneity where each exhibits its own constant asymptotic value. Our investigation concludes that transport, and particularly the macrodispersivity, is formation-specific, and that modeling of transport cannot be relegated to a unique scaling law. Instead, transport requires characterization of aquifer properties, e.g. spatial distribution of hydraulic conductivity, and the use of adequate models. This article is protected by copyright. All rights reserved.

Description: For the past few decades, heat has been used to estimate river-aquifer exchange flux at discrete locations by comparison of river and groundwater temperature. In recent years, heat has also been employed to estimate reach-scale river-aquifer exchange flux based only on river temperature. However, there are many more parameters that govern heat exchange and transport in surface water than in groundwater. In this study, we analyzed the sensitivities of surface water temperature to various parameters and assessed the accuracy of temperature-based estimates of exchange flux in two synthetic rivers and in a field setting. For the large synthetic river with a flow rate of 63 m 3 s −1 (i.e., 5.44 × 10 6 m 3 d −1 ), the upper and lower bounds of the groundwater inflow rate can be determined when the actual groundwater inflow is around 100 m 2 d −1 . For higher and lower fluxes, only minimum and maximum bounds respectively can be determined. For the small synthetic river with the flow rate of 0.63 m 3 s −1 (i.e., 5.44 × 10 4 m 3 d −1 ), the bounds of the groundwater inflow rate can only be estimated when the actual groundwater inflow rate is near 10 m 2 d −1 . In the field setting, results show that the inflow rate must be less than 100 m 2 d −1 , but a lower bound for groundwater inflow cannot be determined. The large ranges of estimated groundwater inflow rates in both theoretical and field settings indicate the need to reduce parameter errors and combine heat measurements with other isotopic and/or chemical methods. This article is protected by copyright. All rights reserved.

Description: Climate state can be an important predictor of future hydrologic conditions. In ensemble streamflow forecasting, where historical weather inputs or streamflow observations are used to generate the ensemble, climate index weighting is one way to represent the influence of climate state. Using a climate index, each forecast variable member of the ensemble is selectively weighted to reflect the climate state at the time of the forecast. A new approach to climate index weighting of ensemble forecasts is presented. The method is based on a sampling-resampling approach for Bayesian updating. The original hydrologic ensemble members define a sample drawn from the prior distribution; the relationship between the climate index and the ensemble member forecast variable is used to estimate a likelihood function. Given an observation of the climate index at the time of the forecast, the estimated likelihood function is then used to assign weights to each ensemble member. The weights define the probability of each ensemble member outcome given the observed climate index. The weighted ensemble forecast is then used to estimate the posterior distribution of the forecast variable conditioned on the climate index. The Bayesian climate index weighting approach is easy to apply to hydrologic ensemble forecasts; its parameters do not require calibration with hindcasts, and it adapts to the strength of the relation between climate and the forecast variable, defaulting to equal weighting of ensemble members when no relationship exists. A hydrologic forecasting application illustrates the approach and contrasts it with traditional climate index weighting approaches. This article is protected by copyright. All rights reserved.

Description: Profilin (Pfn1) regulates cytoskeletal reorganization and migration, but its role in osteoblasts is not known. BMPs (bone morphogenetic proteins) aree a multifunctional cytokine involved in osteoblastic differentiation and promote bone regeneration and repair. Although several molecules are known to modulate BMP signaling, mechanisms that determine the levels of BMP action in osteoblastic function are still incompletely understood. We therefore examine the expression of Pfn1 in osteoblasts and its role in BMP-induced differentiation in osteoblasts. In osteoblastic MC3T3-E1(MC) cells, Pfn1 mRNA is expressed constitutively and its expression levels are declined during the culture in a time dependent manner in contrast to the increase in alkaline phosphatase activity revealing that Pfn1 expression is down regulated along with differentiation. To test the effects of osteoblastic differentiation on Pfn1expression further, MC cells are treated with BMP. BMP treatment suppresses the levels of Pfn1 mRNA. This suppressive effect of BMP is time dependent and further down regulation of Pfn1 mRNA levels is observed when the BMP treatment is continued for a longer period of time. Pfn1mRNA knock down (KD) by siRNAs enhances BMP-induced increase in alkaline phosphatase (Alp) activity in MC cells. To analyze the regulatory mechanism, Alp mRNA levels are examined and Pfn1 KD enhances the BMP-induced increase in the levels of Alp mRNA expression. Furthermore, Pfn1 KD enhances BMP-induced transcriptional expression of luciferase reporter activity via BMP response element in osteoblasts. These data indicate that Pfn1 is a novel target of BMP and suppresses BMP-induced differentiation of osteoblasts at least in part via transcriptional event. This article is protected by copyright. All rights reserved

Description: Field hydrology is on the decline. Meanwhile, the need for new field-derived insight into the age, origin and pathway of water in the headwaters, where most runoff is generated, is more needed than ever. Water Resources Research (WRR) has included some of the most influential papers in field-based runoff process understanding, particularly in the formative years when the knowledge base was developing rapidly. Here, we take advantage of this 50 th anniversary of the journal to highlight a few of these important field-based papers and show how field scientists have posed strong and sometimes outrageous hypotheses—approaches so needed in an era of largely model-only research. We chronicle the decline in field work and note that it is not only the quantity of field work that is diminishing but its character is changing too: from discovery science to data collection for model parameterisation. While the latter is a necessary activity, the loss of the former is a major concern if we are to advance the science of watershed hydrology. We outline a vision for field research to seek new fundamental understanding, new mechanistic explanations of how watershed systems work, particularly outside the regions of traditional focus. This article is protected by copyright. All rights reserved.

Description: One of the major features of neurodegenerative disease is the selective vulnerability of different neuronal populations that are affected in a progressive and often stereotyped manner. Despite the susceptible neuronal population varies between diseases, oxidative stress is implicated as the major pathogenic process in all of them. Natural Extract of Castanea sativa Mill . bark (ENC), recently characterized in its phenolic composition, acts as antioxidant and cardioprotective agent. Its neuroprotettive properties, however, have never been investigated. The aim of this study was to assess neuroprotection of ENC in in vitro models of oxidative-stress-mediate injury. Human neuroblastoma SH-SY5Y cells treated with glutamate (50 mM for 24h) or hydrogen peroxide (25 µM for 1h followed by 24 with medium) were used. The results showed that the addition of ENC (1-50 µg/ml) to cell medium before the neuronal damage provided neuroprotection in both experimental models used, while its addition after the injury was ineffective. In conclusion, the present results suggest that ENC could be a valuable support as dietary supplement, combining beneficial preventive neuroprotettive effects with a high antioxidant activity. This article is protected by copyright. All rights reserved

Description: PKR-like ER-resident kinase (PERK) phosphorylates eukaryotic translation initiation factor 2 alpha (eIF2α) under endoplasmic reticulum (ER) stress; this results in repression of general translation and induction of specific gene expression, such as activating transcription factor 4 (ATF4). We previously showed that, upon ER stress, transducin (beta)-like 2 (TBL2) was an ER-localized transmembrane protein and interacted with PERK and that TBL2 was involved in ATF4 expression and cell survival. Here, we show that TBL2 is able to associate with ATF4 mRNA and regulate its translation. The RNA-immunoprecipitation analysis using several TBL2 deletion mutants revealed that the WD40 domain was essential for association with ATF4 mRNA. Importantly, suppression of TBL2 by knockdown or overexpression of the TBL2 mutant with a defective WD40 domain diminished ATF4 induction at the translational level. Thus, our findings indicate that, under ER stress, TBL2 participates in ATF4 translation through its association with the mRNA. This article is protected by copyright. All rights reserved

Description: Toll-like receptor 2 (TLR2)-mediated signaling cascades and gene regulation are mainly involved in diseases such as immunity and inflammation. In this study microarray analysis was performed using bone marrow-derived macrophages (BMDM) and Raw 264.7 cells to identify novel proteins involved in the TLR2-mediated cellular response. We found that pleckstrin homology-like domain family, member 1 (PHLDA1) is a novel gene up-regulated by TLR2 stimulation and determined the unique signaling pathway for its expression. Treatment with TLR2 agonist Pam 3 CSK 4 increased mRNA, protein, and fluorescence staining of PHLDA1. Induction of PHLDA1 by TLR2 stimulation disappeared from TLR2 KO mice-derived BMDM. Among janus kinase (JAK) family members, JAK2 was involved in TLR2-stimulated PHLDA1 expression. Signal transducer and activator of transcription 3 (STAT3) also participated in PHLDA1 expression downstream of the JAK2. Interestingly, ERK1/2 was an intermediate between JAK2 and STAT3. In silico analysis revealed the presence of highly conserved γ-activated sites within mouse PHLDA1 promoter and confirmed the JAK2-STAT3 pathway is important to Pam 3 CSK 4 -induced PHLDA1 transcription. These findings suggest that the JAK2-ERK1/2-STAT3 pathway is an important signaling pathway for PHLDA1 expression and that these proteins may play a critical role in eliciting TLR2-mediated immune and inflammatory response. This article is protected by copyright. All rights reserved

Description: Autophagy is a catabolic cellular mechanism involving lysosomal degradation of unwanted cellular components. Interaction between Beclin-1 and Bcl-2 proteins is known to play a critical role in the initiation of autophagy. We report that malignantly transformed lung epithelial cells are resistant to autophagy, and express lower basal levels of autophagic proteins Beclin-1 and LC3-II as compared to non-tumorigenic cells. Additionally, increased levels of nitric oxide (NO) and Bcl-2 were observed in transformed cells. NO was found to negatively regulate autophagy initiation and autophagic flux by nitrosylating Bcl-2 and stabilizing its interaction with Beclin-1, resulting in inhibition of Beclin-1 activity. An increase in the apoptotic initiator caspase-9 and the apoptosis and autophagy-associated kinase p38/MAPK in both cell types indicated possible autophagy-apoptosis crosstalk. Pre-treatments with ABT-737 (Bcl-2 inhibitor) and aminoguanidine (NO inhibitor), and transfection with a non-nitrosylable Bcl-2 cysteine double-mutant plasmid resulted in increased autophagic flux (LC3-II/p62 upregulation) corresponding with decreased S -nitrocysteine expression, thus corroborating the regulatory role of Bcl-2 S -nitrosylation in autophagy. In conclusion, our study reveals a novel mechanism of autophagy resistance via post-translational modification of Bcl-2 protein by NO, which may be critical in driving cellular tumorigenesis. This article is protected by copyright. All rights reserved

Description: We present a novel inverse modeling strategy to estimate spatially distributed parameters of nonlinear models. The maximum a posteriori (MAP) estimators of these parameters are based on a likelihood functional, which contains spatially discrete measurements of the system parameters and spatio-temporally discrete measurements of the transient system states. The piecewise continuity prior for the parameters is expressed via Total Variation (TV) regularization. The MAP estimator is computed by minimizing a non-quadratic objective equipped with the TV operator. We apply this inversion algorithm to estimate hydraulic conductivity of a synthetic confined aquifer from measurements of conductivity and hydraulic head. The synthetic conductivity field is composed of a low-conductivity heterogeneous intrusion into a high-conductivity heterogeneous medium. Our algorithm accurately reconstructs the location, orientation and extent of the intrusion from the steady-state data only. Addition of transient measurements of hydraulic head improves the parameter estimation, accurately reconstructing the conductivity field in the vicinity of observation locations. This article is protected by copyright. All rights reserved.

Description: Human societies are increasingly altering the water and biogeochemical cycles to both improve ecosystem productivity and reduce risks associated with the unpredictable variability of climatic drivers. These alterations, however, often cause large negative environmental consequences, raising the question as to how societies can ensure a sustainable use of natural resources for the future. Here we discuss how ecohydrological modeling may address these broad questions with special attention to agroecosystems. The challenges related to modeling the two-way interaction between society and environment are illustrated by means of a dynamical model in which soil and water quality supports the growth of human society but is also degraded by excessive pressure, leading to critical transitions and sustained societal growth-collapse cycles. We then focus on the coupled dynamics of soil water and solutes (nutrients or contaminants), emphasizing the modeling challenges, presented by the strong nonlinearities in the soil and plant system and the unpredictable hydro-climatic forcing, that need to be overcome to quantitatively analyze problems of soil water sustainability in both natural and agricultural ecosystems. We discuss applications of this framework to problems of irrigation, soil salinization, and fertilization and emphasize how optimal solutions for large-scale, long-term planning of soil and water resources in agroecosystems under uncertainty could be provided by methods from stochastic control, informed by physically and mathematically sound descriptions of ecohydrological and biogeochemical interactions. This article is protected by copyright. All rights reserved.

Description: Water resource management (WRM) through dams or reservoirs is worldwide necessary to support key human-related activities, ranging from hydropower production to water allocation and flood risk mitigation. Designing of reservoir operations aims primarily to fulfil the main purpose (or purposes) for which the structure has been built. However, it is well known that reservoirs strongly influence river geomorphic processes, causing sediment deficits downstream, altering water and sediment fluxes, leading to river bed incision and causing infrastructure instability and ecological degradation. We propose a framework that, by combining physically based modelling, surrogate modelling techniques and Multi-Objective (MO) optimization, allows to include fluvial geomorphology into MO optimization whose main objectives is the maximization of hydropower revenue and the minimization of river bed degradation. The case study is a run-of-the-river power plant on the River Po (Italy). A 1D mobile-bed hydro-morphological model simulated the river bed evolution over a ten year horizon for alternatives operation rules of the power plant. The knowledge provided by such a physically based model is integrated into a MO optimization routine via surrogate modelling using the response surface methodology. Hence, this framework overcomes the high computational costs that so far hindered the integration of river geomorphology into WRM. We provided numerical proof that river morphologic processes and hydropower production are indeed in conflict, but that the conflict may be mitigated with appropriate control strategies. This article is protected by copyright. All rights reserved.

Description: This paper addresses how much flood water can be conserved for use after the flood season through the operation of reservoir by taking into account the residual flood control capacity (the difference between flood conveyance capacity and the expected inflow in a lead time). A two-stage model for dynamic control of the flood limited water level (the maximum allowed water level during the flood season, DC-FLWL) is established considering forecast uncertainty and acceptable flood risk. It is found that DC-FLWL is applicable when the reservoir inflow ranges from small to medium levels of the historical records, while both forecast uncertainty and acceptable risk in the downstream affect the feasible space of DC-FLWL. As forecast uncertainty increases (under a given risk level) or as acceptable risk level decreases (under a given forecast uncertainty level), the minimum required safety margin for flood control increases, and the chance for DC-FLWL decreases. The derived hedging rules from the modeling framework illustrate either the dominant role of water conservation or flood control or the tradeoff between the two objectives under different levels of forecast uncertainty and acceptable risk. These rules may provide useful guidelines for conserving water from flood, especially in the area with heavy water stress. The analysis is illustrated via a case study with a real-world reservoir in northeastern China. This article is protected by copyright. All rights reserved.

Description: Although the mechanism which regulates transcription in the 5'-UTR of the mu opioid receptor (MOR) gene (OPRM1) in lymphocytes has been well studied, a question remains as to whether there is post-transcriptional regulation of MOR gene OPRM1 gene in lymphocytes. In this study, we describe both the role played by miRNAs and the impact of SIVmac239 infection on post-transcriptional regulation of MOR gene OPRM1 gene in CEM x174 cells. Our results show that miR-16 is able to bind the target site in the range of 8699-8719 nt from the stop coden in MOR gene MOR-1 mRNA 3'-UTR and suppress the expression of MOR OPRM1 gene. Mutation of this target site reduces the effect of miR-16. Morphine (1 µM) inhibites the expression of miR-16, and this effect is reversed by the antagonist naloxone. Thus, morphine may up-regulate MOR receptor level by both stimulating MOR OPRM1 gene transcription and stabilizing its mRNA. SIVmac239 infection results in an apparent elevation of miR-16 and gradual reduction of MOR OPRM1 gene expression. The inverse correlation of elevated miR-16 and reduced MOR OPRM1 gene expression under viral loading confirmed the effect of SIVmac239 on post-transcriptional regulation of MOR OPRM1 gene in lymphocytes. We conclude that miR-16 is a primary factor in post-transcriptional regulation of MOR OPRM1 gene. SIVmac239 upregulates miR-16 levels and consequently suppresses MOR OPRM1 gene expression. This finding will be helpful for full understanding of the regulatory mechanism of MOR OPRM1 gene in lymphocytes, as well as the synergistic mechanism of HIV infection and morphine addiction in the pathogenesis of AIDS.

Description: Structural stability of Oldenlandia affinis cyclotide, kalata B1 of native (1NB1) and two mutants 2F2I ([P20D, V21K] kB1) and 2F2J ([W19K, P20N, V21K] kB1) was investigated. Single model analysis showed high number of intra-molecular interactions followed by more proportion of beta sheet contents in [P20D, V21K] kB1 as compared to that of native and the other mutant of kalata B1. Further, the modern conformational sampling approach, an alternate to classical molecular dynamics was introduced, which revealed that the [P20D, V21K] kB1 was identified as structurally stable one, substantiated by various structural events viz., root mean square deviation, root mean square fluctuation and angular deviation by Ramachandran plot. Moreover, the statistically validated contours of polar surface area, hydrogen bond distribution and the distance of disulfide bridges also supported the priority of [P20D, V21K] kB1 with respect to stability. From this work, it is proposed that the [P20D, V21K] kB1 (2F2I) could be the best template for scaffolding peptide based drug design.

Description: Inhibition of metabolic features which distinguish cancer cells from their non-malignant counterparts is a promising approach to cancer treatment. Energy support for drug extrusion in multidrug resistance (MDR) is a potential target for metabolic inhibition. Two major sources of ATP-based metabolic energy are partial (glycolysis) and complete (mitochondrial oxidative phosphorylation) oxidation of metabolic fuels. In cancer cells, the balance between them tends to be shifted towards glycolysis; this shift is considered to be characteristic of the cancer metabolic phenotype. Numerous earlier studies, conducted with cells cultured in a monolayer (2-D model), suggested inhibition of glycolytic ATP production as an efficient tool to suppress MDR in cancer cells. Yet, more recent work challenged the appropriateness of the 2-D model for such studies and suggested that a more clinically relevant approach would utilize a more advanced cellular model such as a 3-D model. Here we show that the transition from the 2-D model (cultured monolayer) to a 3-D model (cultured spheroids) introduces essential changes into the concept of energetic suppression of MDR. The 3-D cell organization leads to the formation of a discrete cell subpopulation (not formed in the 2-D model) with elevated MDR transport capacity. This subpopulation has a specific metabolic phenotype (mixed glycolytic/oxidative MDR support) different from that of cells cultured in the 2-D model. Finally, the shift to the oxidative phenotype becomes greater when the spheroids are grown under conditions of lactic acidosis that are typical for solid tumors. The potential clinical significance of these findings is discussed.

Description: We investigated the effects of exogenous sodium pyruvate (SP) on adipocyte differentiation, lipid accumulation, and the mRNA expression levels of adipogenesis-related genes in 3T3-L1 pre-adipocytes. Differentiation of pre-adipocytes was induced by MDI (3-isobutyl-1-methylxanthine: IBMX, dexamethasone: DEX, and insulin), in the presence or absence of SP. Adipogenesis was stimulated by SP in a concentration-dependent manner. SP also induced the expression of genes encoding aP2, GLUT4, and adiponectin, but had no effect on cell proliferation. Exogenous glucose did not promote adipogenesis or lipid accumulation. 2-deoxy-D-glucose inhibited adipogenesis initiated by MDI, but failed to influence the effects of SP on adipogenesis, whereas 3-bromopyruvate inhibited adipogenesis regardless of whether SP was present. The pro-adipogenic properties of SP were limited to the early events of adipogenesis. To determine whether SP mimics the adipogenic action of dexamethasone or insulin, we examined the effects of SP on adipogenesis with combinations of IBMX, DEX, and insulin. SP did not improve incomplete lipid accumulation observed in cells grown under IBMX-, DEX-, or insulin-free conditions. Insulin-stimulated ERK1/2 phosphorylation was diminished by SP, while phosphorylation of Akt was increased, correlating with increased glucose uptake in response to insulin. We also observed that SP stimulated immediate early expression of C/EBPβ and C/EBPδ. The PPARγ antagonist GW9662 inhibited adipogenesis. Our findings highlight the adipogenic function of exogenous SP by stimulating early events of adipogenesis.

Description: Diabetic nephropathy is characterized by inordinate secretion of extracellular matrix (ECM) proteins from mesangial cells (MCs), which is tightly associated with excessive activation of TGF-β signaling. The forkhead transcription factor O1 (FoxO1) protects mesangial cells from hyperglycemia-induced oxidative stress, which may be involved in ameliorating the redundant secretion of ECM proteins under high glucose conditions. Here we reported that high glucose elevated the level of p-Akt to attenuate endogenous FoxO1 bioactivities in MCs, accompanied with decreases in the mRNA expressions of catalase (CAT) and superoxide dismutase 2 (SOD2). Meanwhile, the expression of major ECM proteins-FN and Col I- increased under high glucose condition, in consistent with the activation of TGF-β/Smad signaling. By contrast, overexpression of nucleus-localized FoxO1 (insensitive to Akt phosphorylation) directly up-regulated the expressions of anti-oxidative enzymes, accompanied with inactivation of TGF-β/Smad3 pathway, as well as decreases of extracellular matrix proteins. Moreover, similar to those MCs overexpressed of nucleus-localized FoxO1 in high glucose conditions, MCs with down-regulation of FoxO1 by small interference-RNA under normal glucose conditions showed increased FN level and activated TGF-β/Smad3 pathway. Our findings link the anti-oxidative activity of FoxO1 and the TGF-β-induced secretion of ECM proteins, indicating the novel role of FoxO1 in protecting MCs under high glucose conditions.

Description: We present a co-evolutionary view of hydrologic systems, revolving around feedbacks between environmental and social processes operating across different time scales. This brings to the fore an emphasis on emergent phenomena in changing water systems, such as the levee effect, adaptation to change, system lock-in, and system collapse due to resource depletion. Changing human values play a key role in the emergence of these phenomena and should therefore be considered as internal to the system. Guidance is provided for the framing and modeling of these phenomena to test alternative hypotheses about how they arose. A plurality of co-evolutionary models, from stylized to comprehensive system-of-system models, may assist strategic water management for long time scales through facilitating stakeholder participation, exploring the possibility space of alternative futures, and helping to synthesize the observed dynamics in a wide range of case studies. Future research opportunities lie in exploring emergent phenomena arising from time scale interactions through historical, comparative and process studies of human-water feedbacks. This article is protected by copyright. All rights reserved.

Description: ABSTRACT Multiphase-fluid distribution and flow is inherent in numerous areas of hydrology. Yet, pore-scale characterization of transitions between two and three immiscible-fluids is limited. The objective of this study was to examine the impact of such transitions on the pore-scale configuration of organic liquid in a multi-fluid system comprising natural porous media. Three-dimensional images of an organic liquid (trichloroethene) in two-phase (organic-liquid/water) and three-phase (air/organic-liquid/water) systems were obtained using X-ray microtomography before and after drainage and imbibition. Upon transition from a two-phase to a three-phase system, a significant portion of the organic liquid (intermediate wetting fluid) was observed to exist as lenses and films in contact with air (nonwetting fluid). In these cases, the air was either encased by or contiguous to the organic liquid. The presence of air resulted in an increase in the surface-area-to-volume ratios for the organic-liquid blobs. Upon imbibition, the air was displaced downgradient, and concomitantly, the morphology of the organic-liquid blobs no longer in contact with air reverted to that characteristic of a two-phase distribution (i.e., more spherical blobs and ganglia). This change in morphology resulted in a reduction in the surface-area-to-volume ratio. These results illustrate the impact of transitions between two-phase and three-phase conditions on fluid configuration, and they demonstrate the malleable nature of fluid configuration under dynamic, multiphase-flow conditions. The results have implications for characterizing and modeling pore-scale flow and mass-transfer processes. This article is protected by copyright. All rights reserved.

Description: We performed power-spectral analyses on 133 globally distributed lake-level time series after removing annual variability. Lake-level power spectra are found to be power-law functions of frequency over the range of 20 days -1 to 27 years -1 , suggesting that lake levels are globally a f -β -type noise. The spectral exponent (β), i.e. the best-fit slope of the logarithm of the power spectrum to the logarithm of frequency, is a nonlinear function of lake surface area, indicating that lake size is an important control on the magnitude of water-level variability over the range of time scales we considered. A simple cellular model for lake-level fluctuations that reproduces the observed spectral-scaling properties is presented. The model (an adaptation of a surface-growth model with random deposition and relaxation) is based on the equations governing flow in an unconfined aquifer with stochastic inputs and outputs of water (e.g. random storms). The agreement between observation and simulation suggests that lake surface area, spatio-temporal stochastic forcing, and diffusion of the groundwater table are the primary factors controlling lake water-level variability in natural (unmanaged) lakes. Water-level variability is generally considered to be a manifestation of climate trends or climate change, yet our work shows that an input with short or no memory (i.e. weather) gives rise to a long-memory non-stationary output (lake water-level). This work forms the basis for a null hypothesis of lake water-level variability that should be disproven before water-level trends are to be attributed to climate. This article is protected by copyright. All rights reserved.

Description: Describing convective nonwetting phase flow in unsaturated porous media requires knowledge of the nonwetting phase relative permeability. This study was conducted to formulate and derive a generalized expression for the nonwetting phase relative permeability via combining with the Kosugi water retention function. This generalized formulation is then used to flexibly investigate the Burdine, Mualem and Alexander and Skaggs models' prediction accuracy for relative nonwetting phase permeability. The model and data comparison results show that these three permeability models, if used in their original form, but applied to the nonwetting phase, could not predict the experimental data well. The optimum pore tortuosity and connectivity value is thus obtained for the improved prediction of relative nonwetting phase permeability. As a result, the effective parametrization of (α,β,η) parameters in the modified Burdine, modified Mualem and modified Alexander and Skaggs permeability models were found to be (2.5, 2, 1), (2, 1, 2) and (2.5, 1, 1), respectively. These three suggested models display the highest accuracy among the nine relative permeability models investigated in this study. However, the corresponding discontinuous nonwetting phase and the liquid film flow should be accounted for in future for the improved prediction of nonwetting phase relative permeability at very high and very low water saturation range, respectively. This article is protected by copyright. All rights reserved.

Description: A new optical remote sensing technique for estimating water depth from an oblique camera view is described. The water surface and the bed were imaged simultaneously to create time-dependent maps of the water surface velocities and the bed elevations that can be used to validate numerical models at high spatial and temporal resolution. The technique was applied in a sandy meander bend at the University of Minnesota Saint Anthony Falls Laboratory Outdoor StreamLab. The root mean square differences between optical estimates of the bed and in situ observations ranged between 0.01 and 0.03 m. Mean bedform wavelength was 0.73 m and mean crest height was 0.07 m, but both varied with distance around the meander bend. Bedform classification varied with distance downstream, and sinuosity of bedforms varied with local radius of curvature. Bedform roughness scaled similarly to other natural riverine environments although wavelength and height magnitude and variability were larger than predicted by empirical formulations for straight reaches. Bedform translation rate varied between 1 and 5 mm s −1 . Estimates of velocity from particle image velocimetry (PIV) on the water surface were ∼10% higher than in situ observations collected ∼0.05 m below the water surface. Using the PIV observations to drive simple equations for bedload sediment flux, we explained up to 72% of the observed variance in downstream sediment flux. The new methodology described here provides non-intrusive, high spatial and temporal resolution measurements of both the bed and the flow. This article is protected by copyright. All rights reserved.

Description: We study the influence of topography on groundwater fluxes and water table depths across the Contiguous United States (CONUS). Groundwater tables are often conceptualized as subdued replicas of topography. While it is well known that groundwater configuration is also controlled by geology and climate, nonlinear interactions between these drivers within large real world systems are not well understood and are difficult to characterize given sparse groundwater observations. We address this limitation using the fully integrated physical hydrology model ParFlow to directly simulate groundwater fluxes and water table depths within a complex heterogeneous domain that incorporates all three primary groundwater drivers. Analysis is based on a first of its kind, continental scale, high-resolution (1km), groundwater-surface water simulation spanning more than 6.3 million km 2 . Results show that groundwater fluxes are most strongly driven by topographic gradients (as opposed to gradients in pressure head) in humid regions with small topographic gradients or low conductivity. These regions are generally consistent with the topographically controlled groundwater regions identified in previous studies. However, we also show that areas where topographic slopes drive groundwater flux do not generally have strong correlations between water table depth and elevation. Nonlinear relationships between topography and water table depth are consistent with groundwater flow systems that are dominated by local convergence and could also be influenced by local variability in geology and climate. One of the strengths of the numerical modeling approach is its ability to evaluate continental scale groundwater behavior at a high resolution not possible with other techniques. This article is protected by copyright. All rights reserved.

Description: Hydrology is an integrative discipline linking the broad array of water-related research with physical, ecological, and social sciences. The increasing breadth of hydrological research, often where subdisciplines of hydrology partner with related sciences, reflects the central importance of water to environmental science, while highlighting the fractured nature of the discipline itself. This lack of coordination among hydrologic subdisciplines has hindered the development of hydrologic theory and integrated models capable of predicting hydrologic partitioning across time and space. The recent development of the concept of the critical zone (CZ), an open system extending from the top of the canopy to the base of groundwater, brings together multiple hydrological subdisciplines with related physical and ecological sciences. Observations obtained by CZ researchers provide a diverse range of complementary process and structural data to evaluate both conceptual and numerical models. Consequently, a cross-site focus on “critical zone hydrology” has potential to advance the discipline of hydrology and to facilitate the transition of CZ observatories into a research network with immediate societal relevance. Here we review recent work in catchment hydrology and hydrochemistry, hydrogeology, and ecohydrology that highlights a common knowledge gap in how precipitation is partitioned in the critical zone: “ how is the amount, routing, and residence time of water in the subsurface related to the biogeophysical structure of the CZ? ” Addressing this question will require coordination among hydrologic subdisciplines and interfacing sciences, and catalyze rapid progress in understanding current CZ structure and predicting how climate and land cover changes will affect hydrologic partitioning. This article is protected by copyright. All rights reserved.

Description: The effect of targeted expression of an anabolic isoform of basic fibroblast growth factor (FGF2) in osteoblastic lineage on tibial fracture healing was assessed in mice. Closed fracture of the tibiae was performed in Col3.6-18kDa Fgf2 -IRES-GFPsaph mice in which a 3.6 kb fragment of type I collagen promoter (Col3.6) drives the expression of only the 18kD isoform of FGF2 (18kDa Fgf2/ LMW) with green fluorescent protein-sapphire (GFPsaph) as well as Vector mice (Col3.6-IRES-GFPsaph, Vector) that did not harbor the FGF2 transgene. Radiographic, micro-CT, DEXA and histologic analysis of fracture healing of tibiae harvested at 3, 10 and 20 days showed a smaller fracture callus but accelerated fracture healing in LMWTg compared with Vector mice. At post fracture day 3, FGF receptor 3 and Sox 9 mRNA were significantly increased in LMWTg compared with Vector. Accelerated fracture healing was associated with higher FGF receptor 1, platelet derived growth factors B, C and D, type X collagen, vascular endothelial cell growth factor, matrix metalloproteinase 9, tartrate resistant acid phosphatase, cathepsin K, runt-related transcription factor-2, Osterix and Osteocalcin and lower Sox9, and type 2 collagen expression at 10 days post fracture. We postulate that overexpression of LMW FGF2 accelerated the fracture healing process due to its effects on factors that are important in chondrocyte and osteoblast differentiation and vascular invasion. This article is protected by copyright. All rights reserved

Description: In the last decades significant technological advances together with improved modeling capabilities fostered a rapid development of geophysical monitoring techniques in support of hydrological modeling. Geophysical monitoring offers the attractive possibility to acquire spatially distributed information on state variables. These provide complementary information about the functioning of the hydrological system to that provided by standard hydrological measurements, which are either intrinsically local or the result of a complex spatial averaging process. Soil water content is an example of state variable, which is relatively simple to measure pointwise (locally) but with a vanishing constraining effect on catchment-scale modeling, while streamflow data, the typical hydrological measurement, offer limited possibility to disentangle the controlling processes. The objective of this work is to analyze the advantages offered by coupling traditional hydrological data with unconventional geophysical information in inverse modeling of hydrological systems. In particular, we explored how the use of time-lapse, spatially distributed microgravity measurements may improve the conceptual model identification of a topographically complex Alpine catchment (the Vermigliana catchment, South-Eastern Alps, Italy). The inclusion of microgravity data resulted in a better constraint of the inversion procedure and an improved capability to identify limitations of concurring conceptual models to a level that would be impossible relying only on streamflow data. This allowed for a better identification of model parameters and a more reliable description of the controlling hydrological processes, with a significant reduction of uncertainty in water storage dynamics with respect to the case when only streamflow data are used. This article is protected by copyright. All rights reserved.

Description: TCERG1 was characterized previously as a repressor of the transcription factor C/EBPα through a mechanism that involved relocalization of TCERG1 from nuclear speckles to pericentromeric regions. The inhibitory activity as well as the relocalization activity has been demonstrated to lie in the amino terminal half of the protein, which contains several discrete motifs including an imperfect glutamine-alanine (QA) repeat. In the present study, we showed that deletion of this domain completely abrogated the ability of TCERG1 to inhibit the growth arrest activity of C/EBPα. Moreover, the QA repeat deletion mutant of TCERG1 lost the ability to be relocalized from nuclear speckles to pericentromeric regions, and caused an increase in the average size of individual speckles. We also showed that deletion of the QA repeat abrogated the complex formation between TCERG1 and C/EBPα. Examination of mutants with varying numbers of QA repeats indicated that a minimal number of repeats are required for inhibitory activity as well as relocalization ability. These data contribute to our overall understanding of how TCERG1 can have gene-specific effects in addition to its more general roles in coordinating transcription elongation and splicing. This article is protected by copyright. All rights reserved

Description: We present new measurements of bedload tracer transport in a mountain stream over several snowmelt seasons. Cumulative displacements were measured using passive tracers, which consisted of gravel and cobbles embedded with radio frequency identification tags. The timing of bedload motion during eleven transporting events was quantified with active tracers, i.e., accelerometer-embedded cobbles. Probabilities of cobble transport increased with discharge above a threshold, and exhibited slight to moderate hysteresis during snowmelt hydrographs. Dividing cumulative displacements by the number of movements recorded by each active tracer constrained average step lengths. Average step lengths increased with discharge, and distributions of average step lengths and cumulative displacements were thin-tailed. Distributions of rest times followed heavy-tailed power law scaling. Rest time scaling varied somewhat with discharge and with the degree to which tracers were incorporated into the stream bed. The combination of thin-tailed displacement distributions and heavy-tailed rest time distributions predict superdiffusive dispersion. This article is protected by copyright. All rights reserved.

Description: Gas transfer processes are fundamental to the biogeochemical and water quality functions of wetlands, yet there is limited knowledge of the rates and pathways of soil - atmosphere exchange for gases other than oxygen and methane (CH 4 ). In this study we use a novel push-pull technique with sulfur hexafluoride (SF 6 ) and helium (He) as dissolved gas tracers to quantify the kinetics of root-mediated gas transfer, which is a critical efflux pathway for gases from wetland soils. This tracer approach disentangles the effects of physical transport from simultaneous reaction in saturated, vegetated wetland soils. We measured significant seasonal variation in first-order gas exchange rate constants, with smaller spatial variations between different soil depths and vegetation zones in a New Jersey tidal marsh. Gas transfer rates for most biogeochemical trace gases are expected to be bracketed by the rate constants for SF 6 and He, which ranged from ∼10 −2 to 2x10 −1 h −1 at our site. A modified Damköhler number analysis is used to evaluate the balance between biochemical reaction and root-driven gas exchange in governing the fate of environmental trace gases in rooted, anaerobic soils. This approach confirmed the importance of plant gas transport for CH 4 , and showed that root-driven transport may affect nitrous oxide (N 2 O) balances in settings where N 2 O reduction rates are slow This article is protected by copyright. All rights reserved.

Description: Measuring vertically nested temperatures at the streambed interface poses practical challenges that are addressed here with a new discrete subsurface temperature profiling probe. We describe a new temperature probe and its application for heat as a tracer investigations to demonstrate the probe's utility. Accuracy and response time of temperature measurements made at 6 discrete depths in the probe were analyzed in the laboratory using temperature bath experiments. We find the temperature probe to be an accurate and robust instrument that allows for easily installation and long-term monitoring in highly variable environments. Because the probe is inexpensive and versatile, it is useful for many environmental applications that require temperature data collection for periods of several months in environments that are difficult to access or require minimal disturbance. This article is protected by copyright. All rights reserved.

Description: Nanoparticle deposition behavior observed at the Darcy scale represents an average of the processes occurring at the pore scale. Hence, the effect of various pore-scale parameters on nanoparticle deposition can be understood by studying nanoparticle transport at pore scale and upscaling the results to the Darcy scale. In this work, correlation equations for the deposition rate coefficients of nanoparticles in a cylindrical pore are developed as a function of nine pore-scale parameters: the pore radius, nanoparticle radius, mean flow velocity, solution ionic strength, viscosity, temperature, solution dielectric constant, and nanoparticle and collector surface potentials. Based on dominant processes, the pore space is divided into three different regions, namely, bulk, diffusion, and potential regions. Advection-diffusion equations for nanoparticle transport are prescribed for the bulk and diffusion regions, while the interaction between the diffusion and potential regions is included as a boundary condition. This interaction is modeled as a first-order reversible kinetic adsorption. The expressions for the mass transfer rate coefficients between the diffusion and the potential regions are derived in terms of the interaction energy profile. Among other effects, we account for nanoparticle-collector interaction forces on nanoparticle deposition. The resulting equations are solved numerically for a range of values of pore-scale parameters. The nanoparticle concentration profile obtained for the cylindrical pore is averaged over a moving averaging volume within the pore in order to get the 1D concentration field. The latter is fitted to the 1D advection-dispersion equation with an equilibrium or kinetic adsorption model to determine the values of the average deposition rate coefficients. In this study, pore-scale simulations are performed for three values of Péclet number, Pe = 0.05, 5 and 50. We find that under unfavorable conditions, the nanoparticle deposition at pore scale is best described by an equilibrium model at low Péclet numbers ( Pe = 0.05), and by a kinetic model at high Péclet numbers ( Pe = 50). But, at an intermediate Pe (e.g., near Pe = 5), both equilibrium and kinetic models fit the 1D concentration field. Correlation equations for the pore-averaged nanoparticle deposition rate coefficients under unfavorable conditions are derived by performing a multiple-linear regression analysis between the estimated deposition rate coefficients for a single pore and various pore-scale parameters. The correlation equations, which follow a power law relation with nine pore-scale parameters, are found to be consistent with the column-scale and pore-scale experimental results, and qualitatively agree with the colloid filtration theory. These equations can be incorporated into pore network models to study the effect of pore-scale parameters on nanoparticle deposition at larger length scales such as Darcy scale. This article is protected by copyright. All rights reserved.

Description: Safe drinking water is critical to human health and development. In rural sub-Saharan Africa, most improved water sources are boreholes with handpumps; studies suggest that up to one third of these handpumps are non-functional at any given time. This work presents findings from a secondary analysis of cross-sectional data from 1509 water sources in 570 communities in the rural Greater Afram Plains (GAP) region of Ghana; one of the largest studies of its kind. 79.4% of enumerated water sources were functional when visited; in multivariable regressions, functionality depended on source age, management, the number of other sources in the community, and the district. A Bayesian network (BN) model developed using the same dataset found strong dependencies of functionality on implementer, pump type, management, and the availability of tools, with synergistic effects from management determinants on functionality, increasing the likelihood of a source being functional from a baseline of 72% to more than 97% with optimal management and available tools. We suggest that functionality may be a dynamic equilibrium between regular breakdowns and repairs, with management a key determinant of repair rate. Management variables may interact synergistically in ways better captured by BN analysis than by logistic regressions. These qualitative findings may prove generalizable beyond the study area, and may offer new approaches to understanding and increasing handpump functionality and safe water access. This article is protected by copyright. All rights reserved.

Description: Process controls on water, sediment, nutrient and organic carbon exports from the landscape through runoff are not fully understood. This paper provides analyses from 446 sites worldwide to evaluate the impact of environmental factors (MAP and MAT: mean annual precipitation and temperature; CLAY and BD: soil clay content and bulk density; S: slope gradient and LU: land use) on annual exports (R C : runoff coefficients; SL: sediment loads; TOC L : organic carbon losses; TN L : nitrogen losses and TP L : phosphorus losses) from different spatial scales. R C was found to increase, on average, from 18% at local scale (in headwaters), 25% at micro and subcatchment scale (mid-reaches) to 41% at catchment scale (lower reaches of river basins) in response to multiple factors. SL increased from microplots (468 g m −2 yr −1 ) to plots (901 g m −2 yr −1 ), accompanied by decreasing TOC L and TN L . Climate was a major control masking the effects of other factors. For example, R C , SL, TOC L , TN L and TP L tended to increase with MAP at all spatial scales. These variables, however, decreased with MAT. The impact of CLAY, BD, LU and S on erosion variables was largely confined to the hillslope scale, where R C, SL and TOC L decreased with CLAY, while TNL and TP L increased. The results contribute to better understanding of water, nutrient and carbon cycles in terrestrial ecosystems, and should inform river basin modelling and ecosystem management. The important role of spatial climate variability points to a need for comparative research in specific environments at nested spatio-temporal scales. This article is protected by copyright. All rights reserved.

Description: G-protein-coupled receptor 30 (GPR30) is an estrogen receptor that initiates several rapid, non-genomic signaling events triggered by E2. GPR30 has recently been identified in C2C12 cells; however, little is known about the intracelular distribution and its role in C2C12 myoblasts and myotubes. By western blotting and immunohistochemistry, we evidenced expression of GPR30. While in C2C12 myoblasts the receptor was present in nucleus, mitochondria and endoplasmic reticulum, in C2C12 myotubes it was additionally found in cytoplasm. Using trypan blue uptake assay to determine cellular death and fluorescent microscopy to evaluate picnotic nuclei and mitochondrial distribution, we demonstated that treatment of C2C12 myoblasts with G1 (GPR30 agonist) did not protect the cells against apoptosis induced by H 2 O 2 as E2. However, when G15 (GPR30 antagonist) was used, E2 could not prevent the damage caused by the oxidative stress. Further, some of the molecular mechanisms involved were investigated by wertern blot assays. Thus, E2 was able to induce AKT phosphorylation in apoptotic conditions and ERK phosphorylation in proliferating C2C12 cells but not when the cultures were incubated with G15. Additionally, using G15 antagonist we have found that GPR30 participates in the myogenin expression and creatine kinase activity stimulated by E2 in the first steps of C2C12 differentiation. Althogether these findings provide evidences showing that GPR30 is expressed in diverse intracellular compartments in undifferentiated and differentiated C2C12 cells and mediates E2 actions. This article is protected by copyright. All rights reserved

Description: Chd5 is an essential factor for neuronal differentiation and spermatogenesis, and known as a tumor suppressor. H3K27me3 and H3K4un are modifications recognized by Chd5; however, it remains unclear how Chd5 remodels chromatin structure. We completely disrupted the Chd5 locus using the CRISPR-Cas9 system to generate a 52 kbp long deletion, and analyzed Chd5 function in mouse embryonic stem cells. Our findings show that Chd5 represses murine endogenous retrovirus-L (MuERV-L/MERVL), an endogenous retrovirus-derived retrotransposon, by regulating H3K27me3 and H3.1/H3.2 function. This article is protected by copyright. All rights reserved

Description: Previous studies have shown that promyelocytic leukemia zinc finger (PLZF), chemokine (C-X-C motif) receptor 4 (CXCR4) and mir146a were associated with the self-renewal of mouse spermatogonial stem cells (SSCs); however, there is little information on their effects on the fate of livestock SSCs. Here, we have identified a regulatory pathway in dairy goat mGSCs, involving PLZF, mir146a and the SDF-1 receptor CXCR4. PLZF overexpression downregulated mir146a and simultaneously upregulated the expression of CXCR4 protein, whereas PLZF knockdown (siPLZF) induced the specifically opposite effects. The in vitro assays demonstrated that PLZF specifically interacts with and suppresses the mir146a promoter, and mir146a targets CXCR4 to impede its translation. The levels of ERK1/2 phosphorylation in the mGSCs overexpressed CXCR4 and PLZF were upregulated, respectively, whereas mir146a expression was decreased and CXCR4 protein was increased. Mir146a overexpression and siPLZF impaired mGSC proliferation and differentiation, however, Mir146a knockdown induced the opposite effects. The effects of PLZF and mir146a were mediated regulation by mir146a and CXCR4, respectively. Overexpression of CXCR4 or addition of CXCL12 in cultures of dairy goat mGSCs resulted in the upregulation of their signaling, and the phosphorylation of ERK1/2 was increased. Collectively, these findings indicate that PLZF is an important transcription factor in the regulation of the expression of CXCR4 to promote dairy goat mGSC proliferation by targeting mir146a. This article is protected by copyright. All rights reserved

Description: Bacterial lipopolysaccharide (LPS) is the most important contributing factor in pathogenesis of bacterial infection in male accessory glands; and it has shown to inhibit testicular steroidogenesis and induce apoptosis. The present study demonstrates that LPS causes mitochondrial dysfunction via suppression of sirtuin 4 (SIRT4); which in turn affects Leydig cell function by modulating steroidogenesis and apoptosis. LC-540 Leydig cells treated with LPS (10µg/ml) showed impaired steroidogenesis and increased cellular apoptosis. The mRNA and protein expression of SIRT4 were decreased in LPS treated cells when compared to controls. The obtained data suggest that the c-Jun N-terminal kinase (JNK) activation suppresses SIRT4 expression in LPS treated Leydig cells. Furthermore, the overexpression of SIRT4 prevented LPS induced impaired steroidogenesis and cellular apoptosis by improving mitochondrial function. These findings provide valuable information that SIRT4 regulates LPS mediated Leydig cell dysfunction. This article is protected by copyright. All rights reserved

Description: Ketamine, a dissociative anesthetic, is misused and abused worldwide as an illegal recreational drug. In addition to its neuropathic toxicity, ketamine abuse has numerous effects, including renal failure; however, the underlying mechanism is poorly understood. The process called epithelial phenotypic changes (EPCs) causes the loss of cell-cell adhesion and cell polarity in renal diseases, as well as the acquisition of migratory and invasive properties. Madin-Darby canine kidney cells, an in vitro cell model, were subjected to experimental manipulation to investigate whether ketamine could promote EPCs. Our data showed that ketamine dramatically decreased transepithelial electrical resistance and increased paracellular permeability and junction disruption, which were coupled to decreased levels of apical junctional proteins (ZO-1, Occludin and E-cadherin). Consistent with the downregulation of epithelial markers, the mesenchymal markers N-cadherin, Fibronectin and Vimentin were markedly upregulated following ketamine stimulation. Of the E-cadherin repressor complexes tested, the mRNA levels of Snail, Slug, Twist, and ZEB1 were elevated. Moreover, ketamine significantly enhanced migration and invasion. Ketamine-mediated changes were at least partly caused by the inhibition of GSK-3β activity through Ser-9 phosphorylation by the PI3K/Akt pathway. Inhibiting PI3K/Akt with LY294002 reactivated GSK-3β and suppressed ketamine-enhanced permeability, EPCs and motility. These findings were recapitulated by the inactivation of GSK-3β using the inhibitor 3F8. Taken together, these results provide evidence that ketamine induces renal distal tubular EPCs through the downregulation of several junction proteins, the upregulation of mesenchymal markers, the activation of Akt, and the inactivation of GSK-3β. This article is protected by copyright. All rights reserved

Description: CCN2/connective tissue growth factor (CTGF) is a multifunctional molecule that promotes harmonized development and regeneration of cartilage through its matricellular interaction with a variety of extracellular biomolecules. Thus, deficiency in CCN2 supply profoundly affects a variety of cellular activities including basic metabolism. A previous study showed that the expression of a number of ribosomal protein genes was markedly enhanced in Ccn2 -null chondrocytes. Therefore, in this study, we analyzed the impact of CCN2 on amino acid and protein metabolism in chondrocytes. Comparative metabolome analysis of the amino acids in Ccn2 -null and wild type mouse chondrocytes revealed stable decreases in the cellular levels of all of the essential amino acids. Unexpectedly, uptake of such amino acids was rather enhanced in Ccn2 -null chondrocytes, and the addition of exogenous CCN2 to human chondrocytic cells resulted in decreased amino acid uptake. However, as expected, amino acid consumption by protein synthesis was also accelerated in Ccn2 -null chondrocytes. Furthermore, we newly found that expression of 2 genes encoding 2 glycolytic enzymes, as well as the previously reported Eno 1 gene, was repressed in those cells. Considering the impaired glycolysis and retained mitochondrial membrane potential in Ccn2 -null chondrocytes, these findings suggest that Ccn2 deficiency induces amino acid shortage in chondrocytes by accelerated amino acid consumption through protein synthesis and acquisition of aerobic energy. Interestingly, CCN2 was found to capture such free amino acids in vitro . Under physiological conditions, CCN2 may be regulating the levels of free amino acids in the extracellular matrix of cartilage. This article is protected by copyright. All rights reserved

Description: ABSTRACT Some cord blood banks freeze entire pieces of UC (mixed cord, MC) which after post-thaw yields mixed heterogeneous populations of mesenchymal stem cells (MSCs) from all its microanatomical compartments. Freezing of such entire tissues results in sub-optimal post-thaw cell recovery because of poor cryoprotectant diffusion and intracellular ice-formation, heat and water transport issues and damage to intercellular junctions. To develop a simple method of harvesting pure homogeneous MSCs for cord blood banks we compared the post-thaw behavior of three groups of frozen UC tissues (i) freshly harvested WJ without cell separation, (ii) MSCs isolated from WJ (WJSC) and (iii) MC. WJ and WJSC produced high post-thaw cell survival rates (93.52 ± 6.12% to 90.83 ± 4.51%) and epithelioid monolayers within 24h in primary culture whereas post-thaw MC explants showed slow growth with mixed epithelioid and fibroblastic cell outgrowths after several days. Viability and proliferation rates of post-thawed WJ and hWJSC were significantly greater than MC. Post-thaw WJ and WJSC produced significantly greater CD24 + and CD108 + fluorescence intensities and significantly lower CD40 + contaminants. Post-thaw WJ and WJSC produced significantly lesser annexin-V-positive and sub-G1 cells and greater degrees of osteogenic and chondrogenic differentiation compared to MC. qRT-PCR analysis of post-thaw MC showed significant decreases in anti-apoptotic gene expression (SURVIVIN, BCL2) and increases in pro-apoptotic (BAX) and cell cycle regulator genes (P53, P21, ROCK 1) compared to WJ and WJSC. We conclude that freezing of fresh WJ is a simple and reliable method of generating large numbers of clinically utilizable MSCs for cell-based therapies. This article is protected by copyright. All rights reserved

Description: The Wnt ligands are a family of secreted signaling proteins which play key roles in a number of cellular processes under physiological and pathological conditions. Wnts bind to their membrane receptors and initiate a signaling cascade which leads to the nuclear localization and transcriptional activity of β-catenin. The development of purified recombinant Wnt ligands has greatly aided in our understanding of Wnt signaling and its functions in development and disease. In the current study, we identified non-Wnt related signaling activities which were present in commercially available preparations of recombinant Wnt3a. Specifically, we found that treatment of cultured fibroblasts with recombinant Wnt3a induced immediate activation of TGF-β and BMP signaling and this activity appeared to be independent of the Wnt ligand itself. Therefore, while purified recombinant Wnt ligands continue to be a useful tool for studying this signaling pathway, one must exercise a degree of caution when analyzing the results of experiments that utilize purified recombinant Wnt ligands. This article is protected by copyright. All rights reserved

Description: The wettability of CO 2 -brine-rock systems will have a major impact on the management of carbon sequestration in subsurface geological formations. Recent contact angle measurement studies have reported sensitivity in wetting behaviour of this system to pressure, temperature and brine salinity. We report observations of the impact of reservoir conditions on the capillary pressure characteristic curve and and relative permeability of a single Berea sandstone during drainage - CO 2 displacing brine - through effects on the wetting state. Eight reservoir condition drainage capillary pressure characteristic curves were measured using CO 2 and brine in a single fired Berea sandstone at pressures (5 to 20 MPa), temperatures (25 to 50°C) and ionic strengths (0 to 5 mol kg −1 NaCl). A ninth measurement using a N 2 -water system provided a benchmark for capillarity with a strongly water wet system. The capillary pressure curves from each of the tests were found to be similar to the N 2 -water curve when scaled by the interfacial tension. Reservoir conditions were not found to have a significant impact on the capillary strength of the CO 2 -brine system during drainage through a variation in the wetting state. Two steady-state relative permeability measurements with CO 2 and brine and one with N 2 and brine similarly show little variation between conditions, consistent with the observation that the CO 2 -brine-sandstone system is water wetting and multiphase flow properties invariant across a wide range of reservoir conditions. This article is protected by copyright. All rights reserved.

Description: Hillslope-scale rainfall-runoff processes leading to a fast catchment response are not explicitly included in land surface models (LSMs) for use in earth system models (ESMs) due to computational constraints. This study presents a hybrid-3D hillslope hydrological model (h3D) that couples a 1D vertical soil column model with a lateral pseudo-2D saturated zone and overland flow model for use in ESMs. By representing vertical and lateral responses separately at different spatial resolutions, h3D is computationally efficient. The h3D model was first tested for three different hillslope planforms (uniform, convergent and divergent). We then compared h3D (with single and multiple soil columns) with a complex physically-based 3D model and a simple 1D soil moisture model coupled with an unconfined aquifer (as typically used in LSMs). It is found that simulations obtained by the simple 1D model vary considerably from the complex 3D model and are not able to represent hillslope-scale variations in the lateral flow response. In contrast, the single soil column h3D model shows a much better performance and saves computational time by 2-3 orders of magnitude compared with the complex 3D model. When multiple vertical soil columns are implemented, the resulting hydrological responses (soil moisture, water table depth, and baseflow along the hillslope) from h3D are nearly identical to those predicted by the complex 3D model, but still saves computational time. As such, the computational efficiency of the h3D model provides a valuable and promising approach to incorporating hillslope-scale hydrological processes into continental and global-scale ESMs. This article is protected by copyright. All rights reserved.

Description: We investigated potential source areas of dissolved organic carbon (DOC) in headwater streams by examining DOC concentrations in lysimeter, shallow well, and streamwater samples from a reference catchment at the Hubbard Brook Experimental Forest. These observations were then compared to high frequency temporal variations in fluorescent dissolved organic matter (FDOM) at the catchment outlet and the predicted spatial extent of shallow groundwater in soils throughout the catchment. While near-stream soils are generally considered a DOC source in forested catchments, DOC concentrations in near-stream groundwater were low (mean = 2.4 mg/L, standard error = 0.6 mg/L), less than hillslope groundwater farther from the channel (mean = 5.7 mg/L, standard error = 0.4 mg/L). Furthermore, water tables in near-stream soils did not rise into the carbon rich upper B or O horizons even during events. In contrast, soils below bedrock outcrops near channel heads where lateral soil formation processes dominate had much higher DOC concentrations. Soils immediately downslope of bedrock areas had thick eluvial horizons indicative of leaching of organic materials, Fe, and Al and had similarly high DOC concentrations in groundwater (mean = 14.5 mg/L, standard error = 0.8 mg/L). Flow from bedrock outcrops partially covered by organic soil horizons produced the highest groundwater DOC concentrations (mean = 20.0 mg/L, standard error = 4.6 mg/L) measured in the catchment. Correspondingly, streamwater in channel heads sourced in part by shallow soils and bedrock outcrops had the highest stream DOC concentrations measured in the catchment. Variation in FDOM concentrations at the catchment outlet followed water table fluctuations in shallow to bedrock soils near channel heads. We show that shallow hillslope soils receiving runoff from organic matter-covered bedrock outcrops may be a major source of DOC in headwater catchments in forested mountainous regions where catchments have exposed or shallow bedrock near channel heads. This article is protected by copyright. All rights reserved.

Description: ABSTRACT Multiple scenarios of upward CO 2 migration driven by both injection-induced pressure and buoyancy force were investigated in a horizontally and vertically stratified core utilizing a core-flooding system with a 2D X-ray scanner. Two reservoir type scenarios were considered: (1) the terrestrial reservoir scenario (10 MPa and 50°C), where CO 2 exists in a supercritical state and (2) the deep-sea sediment reservoir scenario (28 MPa and 25°C), where CO 2 is stored in the liquid phase. The core-flooding experiments showed a 36% increase in migration rate in the vertical core setting compared with the horizontal setting, indicating the significance of the buoyancy force under the terrestrial reservoir scenario. Under both reservoir conditions, the injected CO 2 tended to find a preferential flow path (low capillary entry pressure and high-permeability (high- k ) path) and bypass the unfavorable pathways, leaving low CO 2 saturation in the low-permeability (low- k ) layers. No distinctive fingering was observed as the CO 2 moved upward, and the CO 2 movement was primarily controlled by media heterogeneity. The CO 2 saturation in the low- k layers exhibited a more sensitive response to injection rates, implying that the increase in CO 2 injection rates could be more effective in terms of storage capacity in the low- k layers in a stratified reservoir. Under the deep-sea sediment condition, the storage potential of liquid CO 2 was more than twice as high as that of supercritical CO 2 under the terrestrial reservoir scenario. In the end, multiphase transport simulations were conducted to assess the effects of heterogeneity on the spatial variation of pressure build-up, CO 2 saturation and CO 2 flux. Finally, we showed that a high gravity number () tended to be more influenced by the heterogeneity of the porous media. This article is protected by copyright. All rights reserved.